Nonionizing radiation , like ultraviolet light , is not energetic enough to initiate these types of chemical changes . <hl> <hl> However , nonionizing radiation can induce dimer formation between two adjacent pyrimidine bases , commonly two thymines , within a nucleotide strand . <hl> During thymine dimer formation , the two adjacent thymines become covalently linked and , if left unrepaired , both DNA replication and transcription are stalled at this point . DNA polymerase may proceed and replicate the dimer incorrectly , potentially leading to frameshift or point mutations .\",\n \"hl_sentences\": \"Nonionizing radiation , like ultraviolet light , is not energetic enough to initiate these types of chemical changes . However , nonionizing radiation can induce dimer formation between two adjacent pyrimidine bases , commonly two thymines , within a nucleotide strand .\",\n \"question\": {\n \"cloze_format\": \"The formation of pyrimidine dimers results from ___ .\",\n \"normal_format\": \"The formation of pyrimidine dimers results from which of the following?\",\n \"question_choices\": [\n \"spontaneous errors by DNA polymerase\",\n \"exposure to gamma radiation\",\n \"exposure to ultraviolet radiation\",\n \"exposure to intercalating agents\"\n ],\n \"question_id\": \"fs-id1167660170738\",\n \"question_text\": \"The formation of pyrimidine dimers results from which of the following?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Deletions and insertions also cause various effects . <hl> <hl> Because codons are triplets of nucleotides , insertions or deletions in groups of three nucleotides may lead to the insertion or deletion of one or more amino acids and may not cause significant effects on the resulting protein ’ s functionality . <hl> <hl> However , frameshift mutation s , caused by insertions or deletions of a number of nucleotides that are not a multiple of three are extremely problematic because a shift in the reading frame results ( Figure 11.18 ) . <hl> Because ribosomes read the mRNA in triplet codons , frameshift mutations can change every amino acid after the point of the mutation . The new reading frame may also include a stop codon before the end of the coding sequence . Consequently , proteins made from genes containing frameshift mutations are nearly always nonfunctional .\",\n \"hl_sentences\": \"Deletions and insertions also cause various effects . Because codons are triplets of nucleotides , insertions or deletions in groups of three nucleotides may lead to the insertion or deletion of one or more amino acids and may not cause significant effects on the resulting protein ’ s functionality . However , frameshift mutation s , caused by insertions or deletions of a number of nucleotides that are not a multiple of three are extremely problematic because a shift in the reading frame results ( Figure 11.18 ) .\",\n \"question\": {\n \"cloze_format\": \"___ is an example of a frameshift mutation.\",\n \"normal_format\": \"Which of the following is an example of a frameshift mutation?\",\n \"question_choices\": [\n \"a deletion of a codon\",\n \"missense mutation\",\n \"silent mutation\",\n \"deletion of one nucleotide\"\n ],\n \"question_id\": \"fs-id1167662885968\",\n \"question_text\": \"Which of the following is an example of a frameshift mutation?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The direct repair ( also called light repair ) of thymine dimers occurs through the process of photoreactivation in the presence of visible light . <hl> <hl> An enzyme called photolyase recognizes the distortion in the DNA helix caused by the thymine dimer and binds to the dimer . <hl> <hl> Then , in the presence of visible light , the photolyase enzyme changes conformation and breaks apart the thymine dimer , allowing the thymines to again correctly base pair with the adenines on the complementary strand . <hl> Photoreactivation appears to be present in all organisms , with the exception of placental mammals , including humans . Photoreactivation is particularly important for organisms chronically exposed to ultraviolet radiation , like plants , photosynthetic bacteria , algae , and corals , to prevent the accumulation of mutations caused by thymine dimer formation .\",\n \"hl_sentences\": \"The direct repair ( also called light repair ) of thymine dimers occurs through the process of photoreactivation in the presence of visible light . An enzyme called photolyase recognizes the distortion in the DNA helix caused by the thymine dimer and binds to the dimer . Then , in the presence of visible light , the photolyase enzyme changes conformation and breaks apart the thymine dimer , allowing the thymines to again correctly base pair with the adenines on the complementary strand .\",\n \"question\": {\n \"cloze_format\": \"___ is the type of DNA repair in which thymine dimers are directly broken down by the enzyme photolyase.\",\n \"normal_format\": \"Which of the following is the type of DNA repair in which thymine dimers are directly broken down by the enzyme photolyase?\",\n \"question_choices\": [\n \"direct repair\",\n \"nucleotide excision repair\",\n \"mismatch repair\",\n \"proofreading\"\n ],\n \"question_id\": \"fs-id1167662907611\",\n \"question_text\": \"Which of the following is the type of DNA repair in which thymine dimers are directly broken down by the enzyme photolyase?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The Ames test , developed by Bruce Ames ( 1928 – ) in the 1970s , is a method that uses bacteria for rapid , inexpensive screening of the carcinogenic potential of new chemical compounds . <hl> The test measures the mutation rate associated with exposure to the compound , which , if elevated , may indicate that exposure to this compound is associated with greater cancer risk . The Ames test uses as the test organism a strain of Salmonella typhimurium that is a histidine auxotroph , unable to synthesize its own histidine because of a mutation in an essential gene required for its synthesis . <hl> After exposure to a potential mutagen , these bacteria are plated onto a medium lacking histidine , and the number of mutants regaining the ability to synthesize histidine is recorded and compared with the number of such mutants that arise in the absence of the potential mutagen ( Figure 11.25 ) . <hl> <hl> Chemicals that are more mutagenic will bring about more mutants with restored histidine synthesis in the Ames test . <hl> Because many chemicals are not directly mutagenic but are metabolized to mutagenic forms by liver enzymes , rat liver extract is commonly included at the start of this experiment to mimic liver metabolism . After the Ames test is conducted , compounds identified as mutagenic are further tested for their potential carcinogenic properties by using other models , including animal models like mice and rats .\",\n \"hl_sentences\": \"The Ames test , developed by Bruce Ames ( 1928 – ) in the 1970s , is a method that uses bacteria for rapid , inexpensive screening of the carcinogenic potential of new chemical compounds . After exposure to a potential mutagen , these bacteria are plated onto a medium lacking histidine , and the number of mutants regaining the ability to synthesize histidine is recorded and compared with the number of such mutants that arise in the absence of the potential mutagen ( Figure 11.25 ) . Chemicals that are more mutagenic will bring about more mutants with restored histidine synthesis in the Ames test .\",\n \"question\": {\n \"cloze_format\": \"Regarding the Ames test it is true that ___.\",\n \"normal_format\": \"Which of the following regarding the Ames test is true?\",\n \"question_choices\": [\n \"It is used to identify newly formed auxotrophic mutants.\",\n \"It is used to identify mutants with restored biosynthetic activity.\",\n \"It is used to identify spontaneous mutants.\",\n \"It is used to identify mutants lacking photoreactivation activity.\"\n ],\n \"question_id\": \"fs-id1167662483823\",\n \"question_text\": \"Which of the following regarding the Ames test is true?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"Viruses that infect bacteria ( bacteriophages ) may also move short pieces of chromosomal DNA from one bacterium to another in a process called transduction ( see Figure 6.9 ) . <hl> Recall that in generalized transduction , any piece of chromosomal DNA may be transferred to a new host cell by accidental packaging of chromosomal DNA into a phage head during phage assembly . <hl> <hl> By contrast , specialized transduction results from the imprecise excision of a lysogenic prophage from the bacterial chromosome such that it carries with it a piece of the bacterial chromosome from either side of the phage ’ s integration site to a new host cell . <hl> As a result , the host may acquire new properties . This process is called lysogenic conversion . Of medical significance , a lysogenic phage may carry with it a virulence gene to its new host . Once inserted into the new host ’ s chromosome , the new host may gain pathogenicity . Several pathogenic bacteria , including Corynebacterium diphtheriae ( the causative agent of diphtheria ) and Clostridium botulinum ( the causative agent of botulism ) , are virulent because of the introduction of toxin-encoding genes by lysogenic bacteriophages , affirming the clinical relevance of transduction in the exchange of genes involved in infectious disease . Archaea have their own viruses that translocate genetic material from one individual to another .\",\n \"hl_sentences\": \"Recall that in generalized transduction , any piece of chromosomal DNA may be transferred to a new host cell by accidental packaging of chromosomal DNA into a phage head during phage assembly . By contrast , specialized transduction results from the imprecise excision of a lysogenic prophage from the bacterial chromosome such that it carries with it a piece of the bacterial chromosome from either side of the phage ’ s integration site to a new host cell .\",\n \"question\": {\n \"cloze_format\": \"___ is the mechanism by which improper excision of a prophage from a bacterial chromosome results in packaging of bacterial genes near the integration site into a phage head.\",\n \"normal_format\": \"Which is the mechanism by which improper excision of a prophage from a bacterial chromosome results in packaging of bacterial genes near the integration site into a phage head?\",\n \"question_choices\": [\n \"conjugation\",\n \"generalized transduction\",\n \"specialized transduction\",\n \"transformation\"\n ],\n \"question_id\": \"fs-id1167663653549\",\n \"question_text\": \"Which is the mechanism by which improper excision of a prophage from a bacterial chromosome results in packaging of bacterial genes near the integration site into a phage head?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> In transformation , the prokaryote takes up naked DNA found in its environment and that is derived from other cells that have lysed on death and released their contents , including their genome , into the environment . <hl> Many bacteria are naturally competent , meaning that they actively bind to environmental DNA , transport it across their cell envelopes into their cytoplasm , and make it single stranded . Typically , double-stranded foreign DNA within cells is destroyed by nucleases as a defense against viral infection . However , these nucleases are usually ineffective against single-stranded DNA , so this single-stranded DNA within the cell has the opportunity to recombine into the bacterial genome . A molecule of DNA that contains fragments of DNA from different organisms is called recombinant DNA . ( Recombinant DNA will be discussed in more detail in Microbes and the Tools of Genetic Engineering . ) If the bacterium incorporates the new DNA into its own genome through recombination , the bacterial cell may gain new phenotypic properties . For example , if a nonpathogenic bacterium takes up DNA for a toxin gene from a pathogen and then incorporates it into its chromosome , it , too , may become pathogenic . Plasmid DNA may also be taken up by competent bacteria and confer new properties to the cell . Overall , transformation in nature is a relatively inefficient process because environmental DNA levels are low because of the activity of nucleases that are also released during cellular lysis . Additionally , genetic recombination is inefficient at incorporating new DNA sequences into the genome .\",\n \"hl_sentences\": \"In transformation , the prokaryote takes up naked DNA found in its environment and that is derived from other cells that have lysed on death and released their contents , including their genome , into the environment .\",\n \"question\": {\n \"cloze_format\": \"___ refers to the uptake of naked DNA from the surrounding environment.\",\n \"normal_format\": \"Which of the following refers to the uptake of naked DNA from the surrounding environment?\",\n \"question_choices\": [\n \"conjugation\",\n \"generalized transduction\",\n \"specialized transduction\",\n \"transformation\"\n ],\n \"question_id\": \"fs-id1167661743528\",\n \"question_text\": \"Which of the following refers to the uptake of naked DNA from the surrounding environment?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> In conjugation , DNA is directly transferred from one prokaryote to another by means of a conjugation pilus , which brings the organisms into contact with one another . <hl> <hl> In E . coli , the genes encoding the ability to conjugate are located on a bacterial plasmid called the F plasmid , also known as the fertility factor , and the conjugation pilus is called the F pilus . <hl> The F-plasmid genes encode both the proteins composing the F pilus and those involved in rolling circle replication of the plasmid . Cells containing the F plasmid , capable of forming an F pilus , are called F + cell s or donor cell s , and those lacking an F plasmid are called F − cell s or recipient cell s .\",\n \"hl_sentences\": \"In conjugation , DNA is directly transferred from one prokaryote to another by means of a conjugation pilus , which brings the organisms into contact with one another . In E . coli , the genes encoding the ability to conjugate are located on a bacterial plasmid called the F plasmid , also known as the fertility factor , and the conjugation pilus is called the F pilus .\",\n \"question\": {\n \"cloze_format\": \"The F plasmid is involved in the process of ___ .\",\n \"normal_format\": \"The F plasmid is involved in which of the following processes?\",\n \"question_choices\": [\n \"conjugation\",\n \"transduction\",\n \"transposition\",\n \"transformation\"\n ],\n \"question_id\": \"fs-id1167663963908\",\n \"question_text\": \"The F plasmid is involved in which of the following processes?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"Transposons may carry with them additional genes , moving these genes from one location to another with them . For example , bacterial transposons can relocate antibiotic resistance genes , moving them from chromosomes to plasmids . <hl> This mechanism has been shown to be responsible for the colocalization of multiple antibiotic resistance genes on a single R plasmid in Shigella strains causing bacterial dysentery . <hl> <hl> Such an R plasmid can then be easily transferred among a bacterial population through the process of conjugation . <hl>\",\n \"hl_sentences\": \"This mechanism has been shown to be responsible for the colocalization of multiple antibiotic resistance genes on a single R plasmid in Shigella strains causing bacterial dysentery . Such an R plasmid can then be easily transferred among a bacterial population through the process of conjugation .\",\n \"question\": {\n \"cloze_format\": \"___ refers to the mechanism of horizontal gene transfer naturally responsible for the spread of antibiotic resistance genes within a bacterial population.\",\n \"normal_format\": \"Which of the following refers to the mechanism of horizontal gene transfer naturally responsible for the spread of antibiotic resistance genes within a bacterial population?\",\n \"question_choices\": [\n \"conjugation\",\n \"generalized transduction\",\n \"specialized transduction\",\n \"transformation\"\n ],\n \"question_id\": \"fs-id1167663637654\",\n \"question_text\": \"Which of the following refers to the mechanism of horizontal gene transfer naturally responsible for the spread of antibiotic resistance genes within a bacterial population?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"Prokaryotic operons are commonly controlled by the binding of repressors to operator regions , thereby preventing the transcription of the structural genes . Such operons are classified as either repressible operon s or inducible operons . <hl> Repressible operons , like the tryptophan ( trp ) operon , typically contain genes encoding enzymes required for a biosynthetic pathway . <hl> <hl> As long as the product of the pathway , like tryptophan , continues to be required by the cell , a repressible operon will continue to be expressed . <hl> However , when the product of the biosynthetic pathway begins to accumulate in the cell , removing the need for the cell to continue to make more , the expression of the operon is repressed . Conversely , inducible operon s , like the lac operon of E . coli , often contain genes encoding enzymes in a pathway involved in the metabolism of a specific substrate like lactose . These enzymes are only required when that substrate is available , thus expression of the operons is typically induced only in the presence of the substrate .\",\n \"hl_sentences\": \"Repressible operons , like the tryptophan ( trp ) operon , typically contain genes encoding enzymes required for a biosynthetic pathway . As long as the product of the pathway , like tryptophan , continues to be required by the cell , a repressible operon will continue to be expressed .\",\n \"question\": {\n \"cloze_format\": \"An operon of genes encoding enzymes in a biosynthetic pathway is likely to be ___.\",\n \"normal_format\": \"An operon of genes encoding enzymes in a biosynthetic pathway is likely to be which of the following?\",\n \"question_choices\": [\n \"inducible\",\n \"repressible\",\n \"constitutive\",\n \"monocistronic\"\n ],\n \"question_id\": \"fs-id1167661296201\",\n \"question_text\": \"An operon of genes encoding enzymes in a biosynthetic pathway is likely to be which of the following?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"In prokaryotes , there are examples of operons whose gene products are required rather consistently and whose expression , therefore , is unregulated . <hl> Such operons are constitutively expressed , meaning they are transcribed and translated continuously to provide the cell with constant intermediate levels of the protein products . <hl> Such genes encode enzymes involved in housekeeping functions required for cellular maintenance , including DNA replication , repair , and expression , as well as enzymes involved in core metabolism . In contrast , there are other prokaryotic operons that are expressed only when needed and are regulated by repressors , activators , and inducers .\",\n \"hl_sentences\": \"Such operons are constitutively expressed , meaning they are transcribed and translated continuously to provide the cell with constant intermediate levels of the protein products .\",\n \"question\": {\n \"cloze_format\": \"An operon encoding genes that are transcribed and translated continuously to provide the cell with constant intermediate levels of the protein products is said to be ___.\",\n \"normal_format\": \"An operon encoding genes that are transcribed and translated continuously to provide the cell with constant intermediate levels of the protein products is said to be which of the following?\",\n \"question_choices\": [\n \"repressible\",\n \"inducible\",\n \"constitutive\",\n \"activated\"\n ],\n \"question_id\": \"fs-id1167663631279\",\n \"question_text\": \"An operon encoding genes that are transcribed and translated continuously to provide the cell with constant intermediate levels of the protein products is said to be which of the following?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The lac operon is an example of an inducible operon that is also subject to activation in the absence of glucose ( Figure 11.34 ) . <hl> The lac operon encodes three structural genes necessary to acquire and process the disaccharide lactose from the environment , breaking it down into the simple sugars glucose and galactose . <hl> For the lac operon to be expressed , lactose must be present . <hl> <hl> This makes sense for the cell because it would be energetically wasteful to create the enzymes to process lactose if lactose was not available . <hl>\",\n \"hl_sentences\": \"The lac operon is an example of an inducible operon that is also subject to activation in the absence of glucose ( Figure 11.34 ) . For the lac operon to be expressed , lactose must be present . This makes sense for the cell because it would be energetically wasteful to create the enzymes to process lactose if lactose was not available .\",\n \"question\": {\n \"cloze_format\": \"The conditions that lead to maximal expression of the lac operon are ___ .\",\n \"normal_format\": \"Which of the following conditions leads to maximal expression of the lac operon?\",\n \"question_choices\": [\n \"lactose present, glucose absent\",\n \"lactose present, glucose present\",\n \"lactose absent, glucose absent\",\n \"lactose absent, glucose present\"\n ],\n \"question_id\": \"fs-id1167661750541\",\n \"question_text\": \"Which of the following conditions leads to maximal expression of the lac operon?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> In eukaryotes , the DNA molecules or associated histones can be chemically modified in such a way as to influence transcription ; this is called epigenetic regulation . <hl> Methylation of certain cytosine nucleotides in DNA in response to environmental factors has been shown to influence use of such DNA for transcription , with DNA methylation commonly correlating to lowered levels of gene expression . Additionally , in response to environmental factors , histone proteins for packaging DNA can also be chemically modified in multiple ways , including acetylation and deacetylation , influencing the packaging state of DNA and thus affecting the availability of loosely wound DNA for transcription . These chemical modifications can sometimes be maintained through multiple rounds of cell division , making at least some of these epigenetic changes heritable .\",\n \"hl_sentences\": \"In eukaryotes , the DNA molecules or associated histones can be chemically modified in such a way as to influence transcription ; this is called epigenetic regulation .\",\n \"question\": {\n \"cloze_format\": \"(The) ___ is/are a type of regulation of gene expression unique to eukaryotes.\",\n \"normal_format\": \"Which of the following is a type of regulation of gene expression unique to eukaryotes?\",\n \"question_choices\": [\n \"attenuation\",\n \"use of alternate σ factor\",\n \"chemical modification of histones\",\n \"alarmones\"\n ],\n \"question_id\": \"fs-id1167663959876\",\n \"question_text\": \"Which of the following is a type of regulation of gene expression unique to eukaryotes?\"\n },\n \"references_are_paraphrase\": 0\n }\n]","isConversational":false},"chapter":{"kind":"number","value":11,"string":"11"},"chapter_text":{"kind":"string","value":" 11.1 The Functions of Genetic Material \n\n Learning Objectives \n\n Explain the two functions of the genome \n\n Explain the meaning of the central dogma of molecular biology \n\n Differentiate between genotype and phenotype and explain how environmental factors influence phenotype \n\n Clinical Focus Part 1 Mark is 60-year-old software engineer who suffers from type II diabetes, which he monitors and keeps under control largely through diet and exercise. One spring morning, while doing some gardening, he scraped his lower leg while walking through blackberry brambles. He continued working all day in the yard and did not bother to clean the wound and treat it with antibiotic ointment until later that evening. For the next 2 days, his leg became increasingly red, swollen, and warm to the touch. It was sore not only on the surface, but deep in the muscle. After 24 hours, Mark developed a fever and stiffness in the affected leg. Feeling increasingly weak, he called a neighbor, who drove him to the emergency department. \n\n Did Mark wait too long to seek medical attention? At what point do his signs and symptoms warrant seeking medical attention? \n\n What types of infections or other conditions might be responsible for Mark’s symptoms? \n\n Jump to the next Clinical Focus box. \n\n DNA serves two essential functions that deal with cellular information. First, DNA is the genetic material responsible for inheritance and is passed from parent to offspring for all life on earth. To preserve the integrity of this genetic information, DNA must be replicated with great accuracy, with minimal errors that introduce changes to the DNA sequence. A genome contains the full complement of DNA within a cell and is organized into smaller, discrete units called gene s that are arranged on chromosome s and plasmid s. The second function of DNA is to direct and regulate the construction of the proteins necessary to a cell for growth and reproduction in a particular cellular environment. \n\n A gene is composed of DNA that is “read” or transcribed to produce an RNA molecule during the process of transcription . One major type of RNA molecule, called messenger RNA (mRNA), provides the information for the ribosome to catalyze protein synthesis in a process called translation . The processes of transcription and translation are collectively referred to as gene expression . Gene expression is the synthesis of a specific protein with a sequence of amino acids that is encoded in the gene. The flow of genetic information from DNA to RNA to protein is described by the central dogma ( Figure 11.2 ). This central dogma of molecular biology further elucidates the mechanism behind Beadle and Tatum ’s “one gene-one enzyme” hypothesis (see Using Microorganisms to Discover the Secrets of Life ). Each of the processes of replication, transcription, and translation includes the stages of 1) initiation, 2) elongation (polymerization), and 3) termination. These stages will be described in more detail in this chapter. \n\n A cell’s genotype is the full collection of genes it contains, whereas its phenotype is the set of observable characteristics that result from those genes. The phenotype is the product of the array of proteins being produced by the cell at a given time, which is influenced by the cell’s genotype as well as interactions with the cell’s environment. Genes code for proteins that have functions in the cell. Production of a specific protein encoded by an individual gene often results in a distinct phenotype for the cell compared with the phenotype without that protein. For this reason, it is also common to refer to the genotype of an individual gene and its phenotype. Although a cell’s genotype remains constant, not all genes are used to direct the production of their proteins simultaneously. Cells carefully regulate expression of their genes, only using genes to make specific proteins when those proteins are needed ( Figure 11.3 ). \n\n Check Your Understanding \n\n What are the two functions of DNA? \n\n Distinguish between the genotype and phenotype of a cell. \n\n How can cells have the same genotype but differ in their phenotype? \n\n Eye on Ethics Use and Abuse of Genome Data Why can some humans harbor opportunistic pathogens like Haemophilus influenzae , Staphylococcus aureus , or Streptococcus pyogenes , in their upper respiratory tracts but remain asymptomatic carriers, while other individuals become seriously ill when infected? There is evidence suggesting that differences in susceptibility to infection between patients may be a result, at least in part, of genetic differences between human hosts. For example, genetic differences in human leukocyte antigens (HLAs) and red blood cell antigens among hosts have been implicated in different immune responses and resulting disease progression from infection with H. influenzae . \n\n Because the genetic interplay between pathogen and host may contribute to disease outcomes, understanding differences in genetic makeup between individuals may be an important clinical tool. Ecological genomics is a relatively new field that seeks to understand how the genotypes of different organisms interact with each other in nature. The field answers questions about how gene expression of one organism affects gene expression of another. Medical applications of ecological genomics will focus on how pathogens interact with specific individuals, as opposed to humans in general. Such analyses would allow medical professionals to use knowledge of an individual’s genotype to apply more individualized plans for treatment and prevention of disease. \n\n With the advent of next-generation sequencing, it is relatively easy to obtain the entire genomic sequences of pathogens; a bacterial genome can be sequenced in as little as a day. 1 The speed and cost of sequencing the human genome has also been greatly reduced and, already, individuals can submit samples to receive extensive reports on their personal genetic traits, including ancestry and carrier status for various genetic diseases. As sequencing technologies progress further, such services will continue to become less expensive, more extensive, and quicker. 1 D.J. Edwards, K.E. Holt. “Beginner’s Guide to Comparative Bacterial Genome Analysis Using Next-Generation Sequence Data.” Microbial Informatics and Experimentation 3 no. 1 (2013):2. \n\n However, as this day quickly approaches, there are many ethical concerns with which society must grapple. For example, should genome sequencing be a standard practice for everybody? Should it be required by law or by employers if it will lower health-care costs? If one refuses genome sequencing, does he or she forfeit his or her right to health insurance coverage? For what purposes should the data be used? Who should oversee proper use of these data? If genome sequencing reveals predisposition to a particular disease, do insurance companies have the right to increase rates? Will employers treat an employee differently? Knowing that environmental influences also affect disease development, how should the data on the presence of a particular disease-causing allele in an individual be used ethically? The Genetic Information Nondiscrimination Act of 2008 (GINA) currently prohibits discriminatory practices based on genetic information by both health insurance companies and employers. However, GINA does not cover life, disability, or long-term care insurance policies. Clearly, all members of society must continue to engage in conversations about these issues so that such genomic data can be used to improve health care while simultaneously protecting an individual’s rights. \n 11.2 DNA Replication \n\n Learning Objectives \n\n Explain the meaning of semiconservative DNA replication \n\n Explain why DNA replication is bidirectional and includes both a leading and lagging strand \n\n Explain why Okazaki fragments are formed \n\n Describe the process of DNA replication and the functions of the enzymes involved \n\n Identify the differences between DNA replication in bacteria and eukaryotes \n\n Explain the process of rolling circle replication \n\n The elucidation of the structure of the double helix by James Watson and Francis Crick in 1953 provided a hint as to how DNA is copied during the process of replication . Separating the strands of the double helix would provide two templates for the synthesis of new complementary strands, but exactly how new DNA molecules were constructed was still unclear. In one model, semiconservative replication , the two strands of the double helix separate during DNA replication, and each strand serves as a template from which the new complementary strand is copied; after replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. There were two competing models also suggested: conservative and dispersive, which are shown in Figure 11.4 . \n\n Matthew Meselson (1930–) and Franklin Stahl (1929–) devised an experiment in 1958 to test which of these models correctly represents DNA replication ( Figure 11.5 ). They grew E. coli for several generations in a medium containing a “heavy” isotope of nitrogen ( 15 N) that was incorporated into nitrogenous bases and, eventually, into the DNA. This labeled the parental DNA. The E. coli culture was then shifted into a medium containing 14 N and allowed to grow for one generation. The cells were harvested and the DNA was isolated. The DNA was separated by ultracentrifugation, during which the DNA formed bands according to its density. DNA grown in 15 N would be expected to form a band at a higher density position than that grown in 14 N. Meselson and Stahl noted that after one generation of growth in 14 N, the single band observed was intermediate in position in between DNA of cells grown exclusively in 15 N or 14 N. This suggested either a semiconservative or dispersive mode of replication. Some cells were allowed to grow for one more generation in 14 N and spun again. The DNA harvested from cells grown for two generations in 14 N formed two bands: one DNA band was at the intermediate position between 15 N and 14 N, and the other corresponded to the band of 14 N DNA. These results could only be explained if DNA replicates in a semiconservative manner. Therefore, the other two models were ruled out. As a result of this experiment, we now know that during DNA replication, each of the two strands that make up the double helix serves as a template from which new strands are copied. The new strand will be complementary to the parental or “old” strand. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells. \n\n Check Your Understanding \n\n What would have been the conclusion of Meselson and Stahl’s experiment if, after the first generation, they had found two bands of DNA? \n\n DNA Replication in Bacteria \n\n DNA replication has been well studied in bacteria primarily because of the small size of the genome and the mutants that are available. E. coli has 4.6 million base pairs (Mbp) in a single circular chromosome and all of it is replicated in approximately 42 minutes, starting from a single origin of replication and proceeding around the circle bidirectionally (i.e., in both directions). This means that approximately 1000 nucleotides are added per second. The process is quite rapid and occurs with few errors. \n\n DNA replication uses a large number of proteins and enzymes ( Table 11.1 ). One of the key players is the enzyme DNA polymerase , also known as DNA pol. In bacteria, three main types of DNA polymerases are known: DNA pol I, DNA pol II, and DNA pol III. It is now known that DNA pol III is the enzyme required for DNA synthesis; DNA pol I and DNA pol II are primarily required for repair. DNA pol III adds deoxyribonucleotides each complementary to a nucleotide on the template strand, one by one to the 3’-OH group of the growing DNA chain. The addition of these nucleotides requires energy. This energy is present in the bonds of three phosphate groups attached to each nucleotide (a triphosphate nucleotide), similar to how energy is stored in the phosphate bonds of adenosine triphosphate (ATP) ( Figure 11.6 ). When the bond between the phosphates is broken and diphosphate is released, the energy released allows for the formation of a covalent phosphodiester bond by dehydration synthesis between the incoming nucleotide and the free 3’-OH group on the growing DNA strand. \n\n Initiation \n\n The initiation of replication occurs at specific nucleotide sequence called the origin of replication , where various proteins bind to begin the replication process. E. coli has a single origin of replication (as do most prokaryotes), called oriC , on its one chromosome. The origin of replication is approximately 245 base pairs long and is rich in adenine-thymine (AT) sequences. \n\n Some of the proteins that bind to the origin of replication are important in making single-stranded regions of DNA accessible for replication. Chromosomal DNA is typically wrapped around histones (in eukaryotes and archaea) or histone-like proteins (in bacteria), and is supercoiled , or extensively wrapped and twisted on itself. This packaging makes the information in the DNA molecule inaccessible. However, enzymes called topoisomerases change the shape and supercoiling of the chromosome. For bacterial DNA replication to begin, the supercoiled chromosome is relaxed by topoisomerase II , also called DNA gyrase . An enzyme called helicase then separates the DNA strands by breaking the hydrogen bonds between the nitrogenous base pairs. Recall that AT sequences have fewer hydrogen bonds and, hence, have weaker interactions than guanine-cytosine (GC) sequences. These enzymes require ATP hydrolysis. As the DNA opens up, Y-shaped structures called replication forks are formed. Two replication forks are formed at the origin of replication, allowing for bidirectional replication and formation of a structure that looks like a bubble when viewed with a transmission electron microscope; as a result, this structure is called a replication bubble . The DNA near each replication fork is coated with single-stranded binding proteins to prevent the single-stranded DNA from rewinding into a double helix. \n\n Once single-stranded DNA is accessible at the origin of replication, DNA replication can begin. However, DNA pol III is able to add nucleotides only in the 5’ to 3’ direction (a new DNA strand can be only extended in this direction). This is because DNA polymerase requires a free 3’-OH group to which it can add nucleotides by forming a covalent phosphodiester bond between the 3’-OH end and the 5’ phosphate of the next nucleotide. This also means that it cannot add nucleotides if a free 3’-OH group is not available, which is the case for a single strand of DNA. The problem is solved with the help of an RNA sequence that provides the free 3’-OH end. Because this sequence allows the start of DNA synthesis, it is appropriately called the primer . The primer is five to 10 nucleotides long and complementary to the parental or template DNA. It is synthesized by RNA primase , which is an RNA polymerase . Unlike DNA polymerases, RNA polymerases do not need a free 3’-OH group to synthesize an RNA molecule. Now that the primer provides the free 3’-OH group, DNA polymerase III can now extend this RNA primer, adding DNA nucleotides one by one that are complementary to the template strand ( Figure 11.4 ). \n\n Elongation \n\n During elongation in DNA replication , the addition of nucleotides occurs at its maximal rate of about 1000 nucleotides per second. DNA polymerase III can only extend in the 5’ to 3’ direction, which poses a problem at the replication fork. The DNA double helix is antiparallel; that is, one strand is oriented in the 5’ to 3’ direction and the other is oriented in the 3’ to 5’ direction (see Structure and Function of DNA ). During replication, one strand, which is complementary to the 3’ to 5’ parental DNA strand, is synthesized continuously toward the replication fork because polymerase can add nucleotides in this direction. This continuously synthesized strand is known as the leading strand . The other strand, complementary to the 5’ to 3’ parental DNA, grows away from the replication fork, so the polymerase must move back toward the replication fork to begin adding bases to a new primer, again in the direction away from the replication fork. It does so until it bumps into the previously synthesized strand and then it moves back again ( Figure 11.7 ). These steps produce small DNA sequence fragments known as Okazaki fragments , each separated by RNA primer. Okazaki fragments are named after the Japanese research team and married couple Reiji and Tsuneko Okazaki , who first discovered them in 1966. The strand with the Okazaki fragments is known as the lagging strand , and its synthesis is said to be discontinuous. \n\n The leading strand can be extended from one primer alone, whereas the lagging strand needs a new primer for each of the short Okazaki fragments. The overall direction of the lagging strand will be 3’ to 5’, and that of the leading strand 5’ to 3’. A protein called the sliding clamp holds the DNA polymerase in place as it continues to add nucleotides. The sliding clamp is a ring-shaped protein that binds to the DNA and holds the polymerase in place. Beyond its role in initiation, topoisomerase also prevents the overwinding of the DNA double helix ahead of the replication fork as the DNA is opening up; it does so by causing temporary nicks in the DNA helix and then resealing it. As synthesis proceeds, the RNA primers are replaced by DNA. The primers are removed by the exonuclease activity of DNA polymerase I, and the gaps are filled in. The nicks that remain between the newly synthesized DNA (that replaced the RNA primer) and the previously synthesized DNA are sealed by the enzyme DNA ligase that catalyzes the formation of covalent phosphodiester linkage between the 3’-OH end of one DNA fragment and the 5’ phosphate end of the other fragment, stabilizing the sugar-phosphate backbone of the DNA molecule. \n\n Termination \n\n Once the complete chromosome has been replicated, termination of DNA replication must occur. Although much is known about initiation of replication, less is known about the termination process. Following replication, the resulting complete circular genomes of prokaryotes are concatenated, meaning that the circular DNA chromosomes are interlocked and must be separated from each other. This is accomplished through the activity of bacterial topoisomerase IV, which introduces double-stranded breaks into DNA molecules, allowing them to separate from each other; the enzyme then reseals the circular chromosomes. The resolution of concatemers is an issue unique to prokaryotic DNA replication because of their circular chromosomes. Because both bacterial DNA gyrase and topoisomerase IV are distinct from their eukaryotic counterparts, these enzymes serve as targets for a class of antimicrobial drugs called quinolones . \n\n The Molecular Machinery Involved in Bacterial DNA Replication \n\n Enzyme or Factor \n\n Function \n\n DNA pol I \n\n Exonuclease activity removes RNA primer and replaces it with newly synthesized DNA \n\n DNA pol III \n\n Main enzyme that adds nucleotides in the 5’ to 3’ direction \n\n Helicase \n\n Opens the DNA helix by breaking hydrogen bonds between the nitrogenous bases \n\n Ligase \n\n Seals the gaps between the Okazaki fragments on the lagging strand to create one continuous DNA strand \n\n Primase \n\n Synthesizes RNA primers needed to start replication \n\n Single-stranded binding proteins \n\n Bind to single-stranded DNA to prevent hydrogen bonding between DNA strands, reforming double-stranded DNA \n\n Sliding clamp \n\n Helps hold DNA pol III in place when nucleotides are being added \n\n Topoisomerase II (DNA gyrase) \n\n Relaxes supercoiled chromosome to make DNA more accessible for the initiation of replication; helps relieve the stress on DNA when unwinding, by causing breaks and then resealing the DNA \n\n Topoisomerase IV \n\n Introduces single-stranded break into concatenated chromosomes to release them from each other, and then reseals the DNA \n\n Table 11.1 \n\n Check Your Understanding \n\n Which enzyme breaks the hydrogen bonds holding the two strands of DNA together so that replication can occur? \n\n Is it the lagging strand or the leading strand that is synthesized in the direction toward the opening of the replication fork? \n\n Which enzyme is responsible for removing the RNA primers in newly replicated bacterial DNA? \n\n DNA Replication in Eukaryotes \n\n Eukaryotic genomes are much more complex and larger than prokaryotic genomes and are typically composed of multiple linear chromosomes ( Table 11.2 ). The human genome , for example, has 3 billion base pairs per haploid set of chromosomes, and 6 billion base pairs are inserted during replication. There are multiple origins of replication on each eukaryotic chromosome ( Figure 11.8 ); the human genome has 30,000 to 50,000 origins of replication. The rate of replication is approximately 100 nucleotides per second—10 times slower than prokaryotic replication. \n\n The essential steps of replication in eukaryotes are the same as in prokaryotes. Before replication can start, the DNA has to be made available as a template. Eukaryotic DNA is highly supercoiled and packaged, which is facilitated by many proteins, including histone s (see Structure and Function of Cellular Genomes ). At the origin of replication , a prereplication complex composed of several proteins, including helicase , forms and recruits other enzymes involved in the initiation of replication, including topoisomerase to relax supercoiling, single-stranded binding protein, RNA primase , and DNA polymerase . Following initiation of replication, in a process similar to that found in prokaryotes, elongation is facilitated by eukaryotic DNA polymerases. The leading strand is continuously synthesized by the eukaryotic polymerase enzyme pol δ, while the lagging strand is synthesized by pol ε. A sliding clamp protein holds the DNA polymerase in place so that it does not fall off the DNA. The enzyme ribonuclease H ( RNase H ), instead of a DNA polymerase as in bacteria, removes the RNA primer, which is then replaced with DNA nucleotides. The gaps that remain are sealed by DNA ligase . \n\n Because eukaryotic chromosomes are linear, one might expect that their replication would be more straightforward. As in prokaryotes, the eukaryotic DNA polymerase can add nucleotides only in the 5’ to 3’ direction. In the leading strand, synthesis continues until it reaches either the end of the chromosome or another replication fork progressing in the opposite direction. On the lagging strand, DNA is synthesized in short stretches, each of which is initiated by a separate primer. When the replication fork reaches the end of the linear chromosome, there is no place to make a primer for the DNA fragment to be copied at the end of the chromosome. These ends thus remain unpaired and, over time, they may get progressively shorter as cells continue to divide. \n\n The ends of the linear chromosomes are known as telomere s and consist of noncoding repetitive sequences. The telomeres protect coding sequences from being lost as cells continue to divide. In humans, a six base-pair sequence, TTAGGG, is repeated 100 to 1000 times to form the telomere. The discovery of the enzyme telomerase ( Figure 11.9 ) clarified our understanding of how chromosome ends are maintained. Telomerase contains a catalytic part and a built-in RNA template. It attaches to the end of the chromosome, and complementary bases to the RNA template are added on the 3’ end of the DNA strand. Once the 3’ end of the lagging strand template is sufficiently elongated, DNA polymerase can add the nucleotides complementary to the ends of the chromosomes. In this way, the ends of the chromosomes are replicated. In humans, telomerase is typically active in germ cells and adult stem cells; it is not active in adult somatic cells and may be associated with the aging of these cells. Eukaryotic microbes including fungi and protozoans also produce telomerase to maintain chromosomal integrity. For her discovery of telomerase and its action, Elizabeth Blackburn (1948–) received the Nobel Prize for Medicine or Physiology in 2009. \n\n Comparison of Bacterial and Eukaryotic Replication \n\n Property \n\n Bacteria \n\n Eukaryotes \n\n Genome structure \n\n Single circular chromosome \n\n Multiple linear chromosomes \n\n Number of origins per chromosome \n\n Single \n\n Multiple \n\n Rate of replication \n\n 1000 nucleotides per second \n\n 100 nucleotides per second \n\n Telomerase \n\n Not present \n\n Present \n\n RNA primer removal \n\n DNA pol I \n\n RNase H \n\n Strand elongation \n\n DNA pol III \n\n pol δ, pol ε \n\n Table 11.2 \n\n Link to Learning \n\n This animation compares the process of prokaryotic and eukaryotic DNA replication. \n\n Check Your Understanding \n\n How does the origin of replication differ between eukaryotes and prokaryotes? \n\n What polymerase enzymes are responsible for DNA synthesis during eukaryotic replication? \n\n What is found at the ends of the chromosomes in eukaryotes and why? \n\n DNA Replication of Extrachromosomal Elements: Plasmids and Viruses \n\n To copy their nucleic acids, plasmids and viruses frequently use variations on the pattern of DNA replication described for prokaryote genomes. For more information on the wide range of viral replication strategies, see The Viral Life Cycle . \n\n Rolling Circle Replication \n\n Whereas many bacterial plasmids (see Unique Characteristics of Prokaryotic Cells ) replicate by a process similar to that used to copy the bacterial chromosome, other plasmids, several bacteriophages , and some viruses of eukaryotes use rolling circle replication ( Figure 11.10 ). The circular nature of plasmids and the circularization of some viral genomes on infection make this possible. Rolling circle replication begins with the enzymatic nicking of one strand of the double-stranded circular molecule at the double-stranded origin (dso) site . In bacteria, DNA polymerase III binds to the 3’-OH group of the nicked strand and begins to unidirectionally replicate the DNA using the un-nicked strand as a template, displacing the nicked strand as it does so. Completion of DNA replication at the site of the original nick results in full displacement of the nicked strand, which may then recircularize into a single-stranded DNA molecule. RNA primase then synthesizes a primer to initiate DNA replication at the single-stranded origin (sso) site of the single-stranded DNA (ssDNA) molecule, resulting in a double-stranded DNA (dsDNA) molecule identical to the other circular DNA molecule. \n\n Check Your Understanding \n\n Is there a lagging strand in rolling circle replication? Why or why not? \n 11.3 RNA Transcription \n\n Learning Objectives \n\n Explain how RNA is synthesized using DNA as a template \n\n Distinguish between transcription in prokaryotes and eukaryotes \n\n During the process of transcription , the information encoded within the DNA sequence of one or more genes is transcribed into a strand of RNA, also called an RNA transcript . The resulting single-stranded RNA molecule, composed of ribonucleotides containing the bases adenine (A), cytosine (C), guanine (G), and uracil (U), acts as a mobile molecular copy of the original DNA sequence. Transcription in prokaryotes and in eukaryotes requires the DNA double helix to partially unwind in the region of RNA synthesis. The unwound region is called a transcription bubble . Transcription of a particular gene always proceeds from one of the two DNA strands that acts as a template, the so-called antisense strand . The RNA product is complementary to the template strand of DNA and is almost identical to the nontemplate DNA strand, or the sense strand . The only difference is that in RNA, all of the T nucleotides are replaced with U nucleotides; during RNA synthesis, U is incorporated when there is an A in the complementary antisense strand. \n\n Transcription in Bacteria \n\n Bacteria use the same RNA polymerase to transcribe all of their genes. Like DNA polymerase, RNA polymerase adds nucleotides one by one to the 3’-OH group of the growing nucleotide chain. One critical difference in activity between DNA polymerase and RNA polymerase is the requirement for a 3’-OH onto which to add nucleotides: DNA polymerase requires such a 3’-OH group, thus necessitating a primer, whereas RNA polymerase does not. During transcription, a ribonucleotide complementary to the DNA template strand is added to the growing RNA strand and a covalent phosphodiester bond is formed by dehydration synthesis between the new nucleotide and the last one added. In E. coli , RNA polymerase comprises six polypeptide subunits, five of which compose the polymerase core enzyme responsible for adding RNA nucleotides to a growing strand. The sixth subunit is known as sigma (σ). The σ factor enables RNA polymerase to bind to a specific promoter, thus allowing for the transcription of various genes. There are various σ factors that allow for transcription of various genes. \n\n Initiation \n\n The initiation of transcription begins at a promoter , a DNA sequence onto which the transcription machinery binds and initiates transcription. The nucleotide pair in the DNA double helix that corresponds to the site from which the first 5’ RNA nucleotide is transcribed is the initiation site. Nucleotides preceding the initiation site are designated “upstream,” whereas nucleotides following the initiation site are called “downstream” nucleotides. In most cases, promoters are located just upstream of the genes they regulate. Although promoter sequences vary among bacterial genomes, a few elements are conserved. At the –10 and –35 positions within the DNA prior to the initiation site (designated +1), there are two promoter consensus sequences, or regions that are similar across all promoters and across various bacterial species. The –10 consensus sequence, called the TATA box , is TATAAT. The –35 sequence is recognized and bound by σ. \n\n Elongation \n\n The elongation in transcription phase begins when the σ subunit dissociates from the polymerase, allowing the core enzyme to synthesize RNA complementary to the DNA template in a 5’ to 3’ direction at a rate of approximately 40 nucleotides per second. As elongation proceeds, the DNA is continuously unwound ahead of the core enzyme and rewound behind it ( Figure 11.11 ). \n\n Termination \n\n Once a gene is transcribed, the bacterial polymerase must dissociate from the DNA template and liberate the newly made RNA. This is referred to as termination of transcription . The DNA template includes repeated nucleotide sequences that act as termination signals, causing RNA polymerase to stall and release from the DNA template, freeing the RNA transcript. \n\n Check Your Understanding \n\n Where does σ factor of RNA polymerase bind DNA to start transcription? \n\n What occurs to initiate the polymerization activity of RNA polymerase? \n\n Where does the signal to end transcription come from? \n\n Transcription in Eukaryotes \n\n Prokaryotes and eukaryotes perform fundamentally the same process of transcription, with a few significant differences (see Table 11.3 ). Eukaryotes use three different polymerases, RNA polymerases I, II, and III, all structurally distinct from the bacterial RNA polymerase . Each transcribes a different subset of genes. Interestingly, archaea contain a single RNA polymerase that is more closely related to eukaryotic RNA polymerase II than to its bacterial counterpart. Eukaryotic mRNAs are also usually monocistronic, meaning that they each encode only a single polypeptide, whereas prokaryotic mRNAs of bacteria and archaea are commonly polycistronic , meaning that they encode multiple polypeptides. \n\n The most important difference between prokaryotes and eukaryotes is the latter’s membrane-bound nucleus, which influences the ease of use of RNA molecules for protein synthesis. With the genes bound in a nucleus, the eukaryotic cell must transport protein-encoding RNA molecules to the cytoplasm to be translated. Protein-encoding primary transcript s, the RNA molecules directly synthesized by RNA polymerase, must undergo several processing steps to protect these RNA molecules from degradation during the time they are transferred from the nucleus to the cytoplasm and translated into a protein. For example, eukaryotic mRNAs may last for several hours, whereas the typical prokaryotic mRNA lasts no more than 5 seconds. \n\n The primary transcript (also called pre-mRNA) is first coated with RNA-stabilizing proteins to protect it from degradation while it is processed and exported out of the nucleus. The first type of processing begins while the primary transcript is still being synthesized; a special 7-methylguanosine nucleotide, called the 5’ cap , is added to the 5’ end of the growing transcript. In addition to preventing degradation, factors involved in subsequent protein synthesis recognize the cap, which helps initiate translation by ribosomes. Once elongation is complete, another processing enzyme then adds a string of approximately 200 adenine nucleotides to the 3’ end, called the poly-A tail . This modification further protects the pre-mRNA from degradation and signals to cellular factors that the transcript needs to be exported to the cytoplasm. \n\n Eukaryotic genes that encode polypeptides are composed of coding sequences called exon s ( ex -on signifies that they are ex pressed) and intervening sequences called intron s ( int -ron denotes their int ervening role). Transcribed RNA sequences corresponding to introns do not encode regions of the functional polypeptide and are removed from the pre-mRNA during processing. It is essential that all of the intron-encoded RNA sequences are completely and precisely removed from a pre-mRNA before protein synthesis so that the exon-encoded RNA sequences are properly joined together to code for a functional polypeptide. If the process errs by even a single nucleotide, the sequences of the rejoined exons would be shifted, and the resulting polypeptide would be nonfunctional. The process of removing intron-encoded RNA sequences and reconnecting those encoded by exons is called RNA splicing and is facilitated by the action of a spliceosome containing small nuclear ribonucleo proteins (snRNPs). Intron-encoded RNA sequences are removed from the pre-mRNA while it is still in the nucleus. Although they are not translated, introns appear to have various functions, including gene regulation and mRNA transport. On completion of these modifications, the mature transcript , the mRNA that encodes a polypeptide, is transported out of the nucleus, destined for the cytoplasm for translation. Introns can be spliced out differently, resulting in various exons being included or excluded from the final mRNA product. This process is known as alternative splicing . The advantage of alternative splicing is that different types of mRNA transcripts can be generated, all derived from the same DNA sequence. In recent years, it has been shown that some archaea also have the ability to splice their pre-mRNA. \n\n Comparison of Transcription in Bacteria Versus Eukaryotes \n\n Property \n\n Bacteria \n\n Eukaryotes \n\n Number of polypeptides encoded per mRNA \n\n Monocistronic or polycistronic \n\n Exclusively monocistronic \n\n Strand elongation \n\n core + σ = holoenzyme \n\n RNA polymerases I, II, or III \n\n Addition of 5’ cap \n\n No \n\n Yes \n\n Addition of 3’ poly-A tail \n\n No \n\n Yes \n\n Splicing of pre-mRNA \n\n No \n\n Yes \n\n Table 11.3 \n\n Link to Learning \n\n Visualize how mRNA splicing happens by watching the process in action in this video. See how introns are removed during RNA splicing here. \n\n Check Your Understanding \n\n In eukaryotic cells, how is the RNA transcript from a gene for a protein modified after it is transcribed? \n\n Do exons or introns contain information for protein sequences? \n\n Clinical Focus Part 2 In the emergency department, a nurse told Mark that he had made a good decision to come to the hospital because his symptoms indicated an infection that had gotten out of control. Mark’s symptoms had progressed, with the area of skin affected and the amount of swelling increasing. Within the affected area, a rash had begun, blistering and small gas pockets underneath the outermost layer of skin had formed, and some of the skin was becoming gray. Based on the putrid smell of the pus draining from one of the blisters, the rapid progression of the infection, and the visual appearance of the affected skin, the physician immediately began treatment for necrotizing fasciitis. Mark’s physician ordered a culture of the fluid draining from the blister and also ordered blood work, including a white blood cell count. \n\n Mark was admitted to the intensive care unit and began intravenous administration of a broad-spectrum antibiotic to try to minimize further spread of the infection. Despite antibiotic therapy, Mark’s condition deteriorated quickly. Mark became confused and dizzy. Within a few hours of his hospital admission, his blood pressure dropped significantly and his breathing became shallower and more rapid. Additionally, blistering increased, with the blisters intensifying in color to purplish black, and the wound itself seemed to be progressing rapidly up Mark’s leg. \n\n What are possible causative agents of Mark’s necrotizing fasciitis? \n\n What are some possible explanations for why the antibiotic treatment does not seem to be working? \n\n Jump to the next Clinical Focus box. Go back to the previous Clinical Focus box. \n 11.4 Protein Synthesis (Translation) \n\n Learning Objectives \n\n Describe the genetic code and explain why it is considered almost universal \n\n Explain the process of translation and the functions of the molecular machinery of translation \n\n Compare translation in eukaryotes and prokaryotes \n\n The synthesis of proteins consumes more of a cell’s energy than any other metabolic process. In turn, proteins account for more mass than any other macromolecule of living organisms. They perform virtually every function of a cell, serving as both functional (e.g., enzymes) and structural elements. The process of translation , or protein synthesis , the second part of gene expression, involves the decoding by a ribosome of an mRNA message into a polypeptide product. \n\n The Genetic Code \n\n Translation of the mRNA template converts nucleotide-based genetic information into the “language” of amino acids to create a protein product. A protein sequence consists of 20 commonly occurring amino acids . Each amino acid is defined within the mRNA by a triplet of nucleotides called a codon . The relationship between an mRNA codon and its corresponding amino acid is called the genetic code . \n\n The three-nucleotide code means that there is a total of 64 possible combinations (4 3 , with four different nucleotides possible at each of the three different positions within the codon). This number is greater than the number of amino acids and a given amino acid is encoded by more than one codon ( Figure 11.12 ). This redundancy in the genetic code is called degeneracy . Typically, whereas the first two positions in a codon are important for determining which amino acid will be incorporated into a growing polypeptide, the third position, called the wobble position , is less critical. In some cases, if the nucleotide in the third position is changed, the same amino acid is still incorporated. \n\n Whereas 61 of the 64 possible triplets code for amino acids, three of the 64 codons do not code for an amino acid; they terminate protein synthesis, releasing the polypeptide from the translation machinery. These are called stop codon s or nonsense codon s . Another codon, AUG, also has a special function. In addition to specifying the amino acid methionine, it also typically serves as the start codon to initiate translation. The reading frame , the way nucleotides in mRNA are grouped into codons, for translation is set by the AUG start codon near the 5’ end of the mRNA. Each set of three nucleotides following this start codon is a codon in the mRNA message. \n\n The genetic code is nearly universal. With a few exceptions, virtually all species use the same genetic code for protein synthesis, which is powerful evidence that all extant life on earth shares a common origin. However, unusual amino acids such as selenocysteine and pyrrolysine have been observed in archaea and bacteria. In the case of selenocysteine, the codon used is UGA (normally a stop codon). However, UGA can encode for selenocysteine using a stem-loop structure (known as the selenocysteine insertion sequence, or SECIS element), which is found at the 3’ untranslated region of the mRNA. Pyrrolysine uses a different stop codon, UAG. The incorporation of pyrrolysine requires the pylS gene and a unique transfer RNA (tRNA) with a CUA anticodon. \n\n Check Your Understanding \n\n How many bases are in each codon? \n\n What amino acid is coded for by the codon AAU? \n\n What happens when a stop codon is reached? \n\n The Protein Synthesis Machinery \n\n In addition to the mRNA template, many molecules and macromolecules contribute to the process of translation . The composition of each component varies across taxa; for instance, ribosomes may consist of different numbers of ribosomal RNAs (rRNAs) and polypeptides depending on the organism. However, the general structures and functions of the protein synthesis machinery are comparable from bacteria to human cells. Translation requires the input of an mRNA template, ribosomes, tRNAs, and various enzymatic factors. \n\n Ribosomes \n\n A ribosome is a complex macromolecule composed of catalytic rRNAs (called ribozyme s) and structural rRNA s, as well as many distinct polypeptides. Mature rRNAs make up approximately 50% of each ribosome. Prokaryotes have 70S ribosomes, whereas eukaryotes have 80S ribosomes in the cytoplasm and rough endoplasmic reticulum, and 70S ribosomes in mitochondria and chloroplasts . Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation . In E. coli , the small subunit is described as 30S (which contains the 16S rRNA subunit), and the large subunit is 50S (which contains the 5S and 23S rRNA subunits), for a total of 70S (Svedberg units are not additive). Eukaryote ribosomes have a small 40S subunit (which contains the 18S rRNA subunit) and a large 60S subunit (which contains the 5S, 5.8S and 28S rRNA subunits), for a total of 80S. The small subunit is responsible for binding the mRNA template, whereas the large subunit binds tRNAs (discussed in the next subsection). \n\n Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5’ to 3’ and synthesizing the polypeptide from the N terminus to the C terminus. The complete structure containing an mRNA with multiple associated ribosomes is called a polyribosome (or polysome ). In both bacteria and archaea , before transcriptional termination occurs, each protein-encoding transcript is already being used to begin synthesis of numerous copies of the encoded polypeptide(s) because the processes of transcription and translation can occur concurrently, forming polyribosomes ( Figure 11.13 ). The reason why transcription and translation can occur simultaneously is because both of these processes occur in the same 5’ to 3’ direction, they both occur in the cytoplasm of the cell, and because the RNA transcript is not processed once it is transcribed. This allows a prokaryotic cell to respond to an environmental signal requiring new proteins very quickly. In contrast, in eukaryotic cells, simultaneous transcription and translation is not possible. Although polyribosomes also form in eukaryotes, they cannot do so until RNA synthesis is complete and the RNA molecule has been modified and transported out of the nucleus. \n\n Transfer RNAs \n\n Transfer RNAs (tRNAs) are structural RNA molecules and, depending on the species, many different types of tRNAs exist in the cytoplasm. Bacterial species typically have between 60 and 90 types. Serving as adaptors, each tRNA type binds to a specific codon on the mRNA template and adds the corresponding amino acid to the polypeptide chain. Therefore, tRNAs are the molecules that actually “translate” the language of RNA into the language of proteins. As the adaptor molecules of translation, it is surprising that tRNAs can fit so much specificity into such a small package. The tRNA molecule interacts with three factors: aminoacyl tRNA synthetases, ribosomes, and mRNA. \n\n Mature tRNAs take on a three-dimensional structure when complementary bases exposed in the single-stranded RNA molecule hydrogen bond with each other ( Figure 11.14 ). This shape positions the amino-acid binding site, called the CCA amino acid binding end , which is a cytosine-cytosine-adenine sequence at the 3’ end of the tRNA, and the anticodon at the other end. The anticodon is a three-nucleotide sequence that bonds with an mRNA codon through complementary base pairing. \n\n An amino acid is added to the end of a tRNA molecule through the process of tRNA “charging,” during which each tRNA molecule is linked to its correct or cognate amino acid by a group of enzymes called aminoacyl tRNA synthetase s. At least one type of aminoacyl tRNA synthetase exists for each of the 20 amino acids. During this process, the amino acid is first activated by the addition of adenosine monophosphate (AMP) and then transferred to the tRNA, making it a charged tRNA , and AMP is released. \n\n Check Your Understanding \n\n Describe the structure and composition of the prokaryotic ribosome. \n\n In what direction is the mRNA template read? \n\n Describe the structure and function of a tRNA. \n\n The Mechanism of Protein Synthesis \n\n Translation is similar in prokaryotes and eukaryotes. Here we will explore how translation occurs in E. coli , a representative prokaryote, and specify any differences between bacterial and eukaryotic translation. \n\n Initiation \n\n The initiation of protein synthesis begins with the formation of an initiation complex. In E. coli , this complex involves the small 30S ribosome, the mRNA template, three initiation factors that help the ribosome assemble correctly, guanosine triphosphate (GTP) that acts as an energy source, and a special initiator tRNA carrying N -formyl-methionine (fMet-tRNA fMet ) ( Figure 11.15 ). The initiator tRNA interacts with the start codon AUG of the mRNA and carries a formylated methionine (fMet). Because of its involvement in initiation, fMet is inserted at the beginning (N terminus) of every polypeptide chain synthesized by E. coli . In E. coli mRNA, a leader sequence upstream of the first AUG codon, called the Shine-Dalgarno sequence (also known as the ribosomal binding site AGGAGG), interacts through complementary base pairing with the rRNA molecules that compose the ribosome. This interaction anchors the 30S ribosomal subunit at the correct location on the mRNA template. At this point, the 50S ribosomal subunit then binds to the initiation complex, forming an intact ribosome. \n\n In eukaryotes, initiation complex formation is similar, with the following differences: \n\n The initiator tRNA is a different specialized tRNA carrying methionine, called Met-tRNAi \n\n Instead of binding to the mRNA at the Shine-Dalgarno sequence, the eukaryotic initiation complex recognizes the 5’ cap of the eukaryotic mRNA, then tracks along the mRNA in the 5’ to 3’ direction until the AUG start codon is recognized. At this point, the 60S subunit binds to the complex of Met-tRNAi, mRNA, and the 40S subunit. \n\n Elongation \n\n In prokaryotes and eukaryotes, the basics of elongation of translation are the same. In E. coli , the binding of the 50S ribosomal subunit to produce the intact ribosome forms three functionally important ribosomal sites: The A (aminoacyl) site binds incoming charged aminoacyl tRNAs. The P (peptidyl) site binds charged tRNAs carrying amino acids that have formed peptide bonds with the growing polypeptide chain but have not yet dissociated from their corresponding tRNA. The E (exit) site releases dissociated tRNAs so that they can be recharged with free amino acids. There is one notable exception to this assembly line of tRNAs: During initiation complex formation, bacterial fMet−tRNA fMet or eukaryotic Met-tRNAi enters the P site directly without first entering the A site, providing a free A site ready to accept the tRNA corresponding to the first codon after the AUG. \n\n Elongation proceeds with single-codon movements of the ribosome each called a translocation event. During each translocation event, the charged tRNAs enter at the A site, then shift to the P site, and then finally to the E site for removal. Ribosomal movements, or steps, are induced by conformational changes that advance the ribosome by three bases in the 3’ direction. Peptide bonds form between the amino group of the amino acid attached to the A-site tRNA and the carboxyl group of the amino acid attached to the P-site tRNA. The formation of each peptide bond is catalyzed by peptidyl transferase , an RNA-based ribozyme that is integrated into the 50S ribosomal subunit. The amino acid bound to the P-site tRNA is also linked to the growing polypeptide chain. As the ribosome steps across the mRNA, the former P-site tRNA enters the E site, detaches from the amino acid, and is expelled. Several of the steps during elongation, including binding of a charged aminoacyl tRNA to the A site and translocation, require energy derived from GTP hydrolysis, which is catalyzed by specific elongation factors. Amazingly, the E. coli translation apparatus takes only 0.05 seconds to add each amino acid, meaning that a 200 amino-acid protein can be translated in just 10 seconds. \n\n Termination \n\n The termination of translation occurs when a nonsense codon (UAA, UAG, or UGA) is encountered for which there is no complementary tRNA. On aligning with the A site, these nonsense codons are recognized by release factors in prokaryotes and eukaryotes that result in the P-site amino acid detaching from its tRNA, releasing the newly made polypeptide. The small and large ribosomal subunits dissociate from the mRNA and from each other; they are recruited almost immediately into another translation initiation complex. In summary, there are several key features that distinguish prokaryotic gene expression from that seen in eukaryotes. These are illustrated in Figure 11.16 and listed in Figure 11.17 . \n\n Protein Targeting, Folding, and Modification \n\n During and after translation, polypeptides may need to be modified before they are biologically active. Post-translational modifications include: \n\n removal of translated signal sequences—short tails of amino acids that aid in directing a protein to a specific cellular compartment \n\n proper “folding” of the polypeptide and association of multiple polypeptide subunits, often facilitated by chaperone proteins, into a distinct three-dimensional structure \n\n proteolytic processing of an inactive polypeptide to release an active protein component, and \n\n various chemical modifications (e.g., phosphorylation, methylation, or glycosylation) of individual amino acids. \n\n Check Your Understanding \n\n What are the components of the initiation complex for translation in prokaryotes? \n\n What are two differences between initiation of prokaryotic and eukaryotic translation? \n\n What occurs at each of the three active sites of the ribosome? \n\n What causes termination of translation? \n 11.5 Mutations \n\n Learning Objectives \n\n Compare point mutations and frameshift mutations \n\n Describe the differences between missense, nonsense, and silent mutations \n\n Describe the differences between light and dark repair \n\n Explain how different mutagens act \n\n Explain why the Ames test can be used to detect carcinogens \n\n Analyze sequences of DNA and identify examples of types of mutations \n\n A mutation is a heritable change in the DNA sequence of an organism. The resulting organism, called a mutant , may have a recognizable change in phenotype compared to the wild type , which is the phenotype most commonly observed in nature. A change in the DNA sequence is conferred to mRNA through transcription, and may lead to an altered amino acid sequence in a protein on translation. Because proteins carry out the vast majority of cellular functions, a change in amino acid sequence in a protein may lead to an altered phenotype for the cell and organism. \n\n Effects of Mutations on DNA Sequence \n\n There are several types of mutations that are classified according to how the DNA molecule is altered. One type, called a point mutation , affects a single base and most commonly occurs when one base is substituted or replaced by another. Mutations also result from the addition of one or more bases, known as an insertion , or the removal of one or more bases, known as a deletion . \n\n Check Your Understanding \n\n What type of a mutation occurs when a gene has two fewer nucleotides in its sequence? \n\n Effects of Mutations on Protein Structure and Function \n\n Point mutations may have a wide range of effects on protein function ( Figure 11.18 ). As a consequence of the degeneracy of the genetic code, a point mutation will commonly result in the same amino acid being incorporated into the resulting polypeptide despite the sequence change. This change would have no effect on the protein’s structure, and is thus called a silent mutation . A missense mutation results in a different amino acid being incorporated into the resulting polypeptide. The effect of a missense mutation depends on how chemically different the new amino acid is from the wild-type amino acid. The location of the changed amino acid within the protein also is important. For example, if the changed amino acid is part of the enzyme’s active site , then the effect of the missense mutation may be significant. Many missense mutations result in proteins that are still functional, at least to some degree. Sometimes the effects of missense mutations may be only apparent under certain environmental conditions; such missense mutations are called conditional mutation s. Rarely, a missense mutation may be beneficial. Under the right environmental conditions, this type of mutation may give the organism that harbors it a selective advantage. Yet another type of point mutation, called a nonsense mutation , converts a codon encoding an amino acid (a sense codon) into a stop codon (a nonsense codon). Nonsense mutations result in the synthesis of proteins that are shorter than the wild type and typically not functional. \n\n Deletions and insertions also cause various effects. Because codons are triplets of nucleotides, insertions or deletions in groups of three nucleotides may lead to the insertion or deletion of one or more amino acids and may not cause significant effects on the resulting protein’s functionality. However, frameshift mutation s, caused by insertions or deletions of a number of nucleotides that are not a multiple of three are extremely problematic because a shift in the reading frame results ( Figure 11.18 ). Because ribosomes read the mRNA in triplet codons, frameshift mutations can change every amino acid after the point of the mutation. The new reading frame may also include a stop codon before the end of the coding sequence. Consequently, proteins made from genes containing frameshift mutations are nearly always nonfunctional. \n\n Check Your Understanding \n\n What are the reasons a nucleotide change in a gene for a protein might not have any effect on the phenotype of that gene? \n\n Is it possible for an insertion of three nucleotides together after the fifth nucleotide in a protein-coding gene to produce a protein that is shorter than normal? How or how not? \n\n Micro Connections A Beneficial Mutation Since the first case of infection with human immunodeficiency virus (HIV) was reported in 1981, nearly 40 million people have died from HIV infection, 2 the virus that causes acquired immune deficiency syndrome (AIDS). The virus targets helper T cells that play a key role in bridging the innate and adaptive immune response, infecting and killing cells normally involved in the body’s response to infection. There is no cure for HIV infection, but many drugs have been developed to slow or block the progression of the virus. Although individuals around the world may be infected, the highest prevalence among people 15–49 years old is in sub-Saharan Africa, where nearly one person in 20 is infected, accounting for greater than 70% of the infections worldwide 3 ( Figure 11.19 ). Unfortunately, this is also a part of the world where prevention strategies and drugs to treat the infection are the most lacking. 2 World Health Organization. “ Global Health Observatory (GHO) Data, HIV/AIDS.” http://www.who.int/gho/hiv/en/. Accessed August 5, 2016. 3 World Health Organization. “ Global Health Observatory (GHO) Data, HIV/AIDS.” http://www.who.int/gho/hiv/en/. Accessed August 5, 2016. \n\n In recent years, scientific interest has been piqued by the discovery of a few individuals from northern Europe who are resistant to HIV infection. In 1998, American geneticist Stephen J. O’Brien at the National Institutes of Health (NIH) and colleagues published the results of their genetic analysis of more than 4,000 individuals. These indicated that many individuals of Eurasian descent (up to 14% in some ethnic groups) have a deletion mutation, called CCR5-delta 32, in the gene encoding CCR5. CCR5 is a coreceptor found on the surface of T cells that is necessary for many strains of the virus to enter the host cell. The mutation leads to the production of a receptor to which HIV cannot effectively bind and thus blocks viral entry. People homozygous for this mutation have greatly reduced susceptibility to HIV infection, and those who are heterozygous have some protection from infection as well. \n\n It is not clear why people of northern European descent, specifically, carry this mutation, but its prevalence seems to be highest in northern Europe and steadily decreases in populations as one moves south. Research indicates that the mutation has been present since before HIV appeared and may have been selected for in European populations as a result of exposure to the plague or smallpox. This mutation may protect individuals from plague (caused by the bacterium Yersinia pestis ) and smallpox (caused by the variola virus) because this receptor may also be involved in these diseases. The age of this mutation is a matter of debate, but estimates suggest it appeared between 1875 years to 225 years ago, and may have been spread from Northern Europe through Viking invasions. \n\n This exciting finding has led to new avenues in HIV research, including looking for drugs to block CCR5 binding to HIV in individuals who lack the mutation. Although DNA testing to determine which individuals carry the CCR5-delta 32 mutation is possible, there are documented cases of individuals homozygous for the mutation contracting HIV. For this reason, DNA testing for the mutation is not widely recommended by public health officials so as not to encourage risky behavior in those who carry the mutation. Nevertheless, inhibiting the binding of HIV to CCR5 continues to be a valid strategy for the development of drug therapies for those infected with HIV. \n\n Causes of Mutations \n\n Mistakes in the process of DNA replication can cause spontaneous mutation s to occur. The error rate of DNA polymerase is one incorrect base per billion base pairs replicated. Exposure to mutagen s can cause induced mutation s , which are various types of chemical agents or radiation ( Table 11.4 ). Exposure to a mutagen can increase the rate of mutation more than 1000-fold. Mutagens are often also carcinogen s , agents that cause cancer. However, whereas nearly all carcinogens are mutagenic, not all mutagens are necessarily carcinogens. \n\n Chemical Mutagens \n\n Various types of chemical mutagens interact directly with DNA either by acting as nucleoside analogs or by modifying nucleotide bases. Chemicals called nucleoside analog s are structurally similar to normal nucleotide bases and can be incorporated into DNA during replication ( Figure 11.20 ). These base analogs induce mutations because they often have different base-pairing rules than the bases they replace. Other chemical mutagens can modify normal DNA bases, resulting in different base-pairing rules. For example, nitrous acid deaminates cytosine, converting it to uracil. Uracil then pairs with adenine in a subsequent round of replication, resulting in the conversion of a GC base pair to an AT base pair. Nitrous acid also deaminates adenine to hypoxanthine, which base pairs with cytosine instead of thymine, resulting in the conversion of a TA base pair to a CG base pair. \n\n Chemical mutagens known as intercalating agent s work differently. These molecules slide between the stacked nitrogenous bases of the DNA double helix, distorting the molecule and creating atypical spacing between nucleotide base pairs ( Figure 11.21 ). As a result, during DNA replication, DNA polymerase may either skip replicating several nucleotides (creating a deletion ) or insert extra nucleotides (creating an insertion ). Either outcome may lead to a frameshift mutation . Combustion products like polycyclic aromatic hydrocarbons are particularly dangerous intercalating agents that can lead to mutation-caused cancers. The intercalating agents ethidium bromide and acridine orange are commonly used in the laboratory to stain DNA for visualization and are potential mutagens. \n\n Radiation \n\n Exposure to either ionizing or nonionizing radiation can each induce mutations in DNA, although by different mechanisms. Strong ionizing radiation like X-rays and gamma rays can cause single- and double-stranded breaks in the DNA backbone through the formation of hydroxyl radicals on radiation exposure ( Figure 11.22 ). Ionizing radiation can also modify bases; for example, the deamination of cytosine to uracil, analogous to the action of nitrous acid. 4 Ionizing radiation exposure is used to kill microbes to sterilize medical devices and foods, because of its dramatic nonspecific effect in damaging DNA, proteins, and other cellular components (see Using Physical Methods to Control Microorganisms ). 4 K.R. Tindall et al. “Changes in DNA Base Sequence Induced by Gamma-Ray Mutagenesis of Lambda Phage and Prophage.” Genetics 118 no. 4 (1988):551–560. \n\n Nonionizing radiation, like ultraviolet light, is not energetic enough to initiate these types of chemical changes. However, nonionizing radiation can induce dimer formation between two adjacent pyrimidine bases, commonly two thymines, within a nucleotide strand. During thymine dimer formation, the two adjacent thymines become covalently linked and, if left unrepaired, both DNA replication and transcription are stalled at this point. DNA polymerase may proceed and replicate the dimer incorrectly, potentially leading to frameshift or point mutations. \n\n A Summary of Mutagenic Agents \n\n Mutagenic Agents \n\n Mode of Action \n\n Effect on DNA \n\n Resulting Type of Mutation \n\n Nucleoside analogs \n\n 2-aminopurine \n\n Is inserted in place of A but base pairs with C \n\n Converts AT to GC base pair \n\n Point \n\n 5-bromouracil \n\n Is inserted in place of T but base pairs with G \n\n Converts AT to GC base pair \n\n Point \n\n Nucleotide-modifying agent \n\n Nitrous oxide \n\n Deaminates C to U \n\n Converts GC to AT base pair \n\n Point \n\n Intercalating agents \n\n Acridine orange, ethidium bromide, polycyclic aromatic hydrocarbons \n\n Distorts double helix, creates unusual spacing between nucleotides \n\n Introduces small deletions and insertions \n\n Frameshift \n\n Ionizing radiation \n\n X-rays, γ-rays \n\n Forms hydroxyl radicals \n\n Causes single- and double-strand DNA breaks \n\n Repair mechanisms may introduce mutations \n\n X-rays, γ-rays \n\n Modifies bases (e.g., deaminating C to U) \n\n Converts GC to AT base pair \n\n Point \n\n Nonionizing radiation \n\n Ultraviolet \n\n Forms pyrimidine (usually thymine) dimers \n\n Causes DNA replication errors \n\n Frameshift or point \n\n Table 11.4 \n\n Check Your Understanding \n\n How does a base analog introduce a mutation? \n\n How does an intercalating agent introduce a mutation? \n\n What type of mutagen causes thymine dimers? \n\n DNA Repair \n\n The process of DNA replication is highly accurate, but mistakes can occur spontaneously or be induced by mutagens. Uncorrected mistakes can lead to serious consequences for the phenotype. Cells have developed several repair mechanisms to minimize the number of mutations that persist. \n\n Proofreading \n\n Most of the mistakes introduced during DNA replication are promptly corrected by most DNA polymerase s through a function called proofreading. In proofreading , the DNA polymerase reads the newly added base, ensuring that it is complementary to the corresponding base in the template strand before adding the next one. If an incorrect base has been added, the enzyme makes a cut to release the wrong nucleotide and a new base is added. \n\n Mismatch Repair \n\n Some errors introduced during replication are corrected shortly after the replication machinery has moved. This mechanism is called mismatch repair . The enzymes involved in this mechanism recognize the incorrectly added nucleotide, excise it, and replace it with the correct base. One example is the methyl-directed mismatch repair in E. coli . The DNA is hemimethylated. This means that the parental strand is methylated while the newly synthesized daughter strand is not. It takes several minutes before the new strand is methylated. Proteins MutS, MutL, and MutH bind to the hemimethylated site where the incorrect nucleotide is found. MutH cuts the nonmethylated strand (the new strand). An exonuclease removes a portion of the strand (including the incorrect nucleotide). The gap formed is then filled in by DNA pol III and ligase. \n\n Repair of Thymine Dimers \n\n Because the production of thymine dimer s is common (many organisms cannot avoid ultraviolet light), mechanisms have evolved to repair these lesions. In nucleotide excision repair (also called dark repair), enzymes remove the pyrimidine dimer and replace it with the correct nucleotides ( Figure 11.23 ). In E. coli , the DNA is scanned by an enzyme complex. If a distortion in the double helix is found that was introduced by the pyrimidine dimer, the enzyme complex cuts the sugar-phosphate backbone several bases upstream and downstream of the dimer, and the segment of DNA between these two cuts is then enzymatically removed. DNA pol I replaces the missing nucleotides with the correct ones and DNA ligase seals the gap in the sugar-phosphate backbone. \n\n The direct repair (also called light repair) of thymine dimers occurs through the process of photoreactivation in the presence of visible light. An enzyme called photolyase recognizes the distortion in the DNA helix caused by the thymine dimer and binds to the dimer. Then, in the presence of visible light, the photolyase enzyme changes conformation and breaks apart the thymine dimer, allowing the thymines to again correctly base pair with the adenines on the complementary strand. Photoreactivation appears to be present in all organisms, with the exception of placental mammals, including humans. Photoreactivation is particularly important for organisms chronically exposed to ultraviolet radiation , like plants, photosynthetic bacteria, algae, and corals, to prevent the accumulation of mutations caused by thymine dimer formation. \n\n Check Your Understanding \n\n During mismatch repair, how does the enzyme recognize which is the new and which is the old strand? \n\n What type of mutation does photolyase repair? \n\n Identifying Bacterial Mutants \n\n One common technique used to identify bacterial mutants is called replica plating . This technique is used to detect nutritional mutants, called auxotroph s, which have a mutation in a gene encoding an enzyme in the biosynthesis pathway of a specific nutrient, such as an amino acid. As a result, whereas wild-type cells retain the ability to grow normally on a medium lacking the specific nutrient, auxotrophs are unable to grow on such a medium. During replica plating ( Figure 11.24 ), a population of bacterial cells is mutagenized and then plated as individual cells on a complex nutritionally complete plate and allowed to grow into colonies. Cells from these colonies are removed from this master plate, often using sterile velvet. This velvet, containing cells, is then pressed in the same orientation onto plates of various media. At least one plate should also be nutritionally complete to ensure that cells are being properly transferred between the plates. The other plates lack specific nutrients, allowing the researcher to discover various auxotrophic mutants unable to produce specific nutrients. Cells from the corresponding colony on the nutritionally complete plate can be used to recover the mutant for further study. \n\n Check Your Understanding \n\n Why are cells plated on a nutritionally complete plate in addition to nutrient-deficient plates when looking for a mutant? \n\n The Ames Test \n\n The Ames test , developed by Bruce Ames (1928–) in the 1970s, is a method that uses bacteria for rapid, inexpensive screening of the carcinogenic potential of new chemical compounds. The test measures the mutation rate associated with exposure to the compound, which, if elevated, may indicate that exposure to this compound is associated with greater cancer risk. The Ames test uses as the test organism a strain of Salmonella typhimurium that is a histidine auxotroph, unable to synthesize its own histidine because of a mutation in an essential gene required for its synthesis. After exposure to a potential mutagen, these bacteria are plated onto a medium lacking histidine, and the number of mutants regaining the ability to synthesize histidine is recorded and compared with the number of such mutants that arise in the absence of the potential mutagen ( Figure 11.25 ). Chemicals that are more mutagenic will bring about more mutants with restored histidine synthesis in the Ames test. Because many chemicals are not directly mutagenic but are metabolized to mutagenic forms by liver enzymes, rat liver extract is commonly included at the start of this experiment to mimic liver metabolism. After the Ames test is conducted, compounds identified as mutagenic are further tested for their potential carcinogenic properties by using other models, including animal models like mice and rats. \n\n Check Your Understanding \n\n What mutation is used as an indicator of mutation rate in the Ames test? \n\n Why can the Ames test work as a test for carcinogenicity? \n 11.6 How Asexual Prokaryotes Achieve Genetic Diversity \n\n Learning Objectives \n\n Compare the processes of transformation, transduction, and conjugation \n\n Explain how asexual gene transfer results in prokaryotic genetic diversity \n\n Explain the structure and consequences for bacterial genetic diversity of transposons \n\n Typically, when we consider genetic transfer, we think of vertical gene transfer , the transmission of genetic information from generation to generation. Vertical gene transfer is by far the main mode of transmission of genetic information in all cells. In sexually reproducing organisms, crossing-over events and independent assortment of individual chromosomes during meiosis contribute to genetic diversity in the population. Genetic diversity is also introduced during sexual reproduction , when the genetic information from two parents, each with different complements of genetic information, are combined, producing new combinations of parental genotypes in the diploid offspring. The occurrence of mutations also contributes to genetic diversity in a population. Genetic diversity of offspring is useful in changing or inconsistent environments and may be one reason for the evolutionary success of sexual reproduction. \n\n When prokaryotes and eukaryotes reproduce asexually, they transfer a nearly identical copy of their genetic material to their offspring through vertical gene transfer. Although asexual reproduction produces more offspring more quickly, any benefits of diversity among those offspring are lost. How then do organisms whose dominant reproductive mode is asexual create genetic diversity? In prokaryotes, horizontal gene transfer (HGT) , the introduction of genetic material from one organism to another organism within the same generation, is an important way to introduce genetic diversity. HGT allows even distantly related species to share genes, influencing their phenotypes. It is thought that HGT is more prevalent in prokaryotes but that only a small fraction of the prokaryotic genome may be transferred by this type of transfer at any one time. As the phenomenon is investigated more thoroughly, it may be revealed to be even more common. Many scientists believe that HGT and mutation are significant sources of genetic variation, the raw material for the process of natural selection, in prokaryotes. Although HGT is more common among evolutionarily related organisms, it may occur between any two species that live together in a natural community. \n\n HGT in prokaryotes is known to occur by the three primary mechanisms that are illustrated in Figure 11.26 : \n\n Transformation: naked DNA is taken up from the environment \n\n Transduction: genes are transferred between cells in a virus (see The Viral Life Cycle ) \n\n Conjugation: use of a hollow tube called a conjugation pilus to transfer genes between cells \n\n Check Your Understanding \n\n What are three ways sexual reproduction introduces genetic variation into offspring? \n\n What is a benefit of asexual reproduction? \n\n What are the three mechanisms of horizontal gene transfer in prokaryotes? \n\n Transformation \n\n Frederick Griffith was the first to demonstrate the process of transformation . In 1928, he showed that live, nonpathogenic Streptococcus pneumoniae bacteria could be transformed into pathogenic bacteria through exposure to a heat-killed pathogenic strain. He concluded that some sort of agent, which he called the “transforming principle,” had been passed from the dead pathogenic bacteria to the live, nonpathogenic bacteria. In 1944, Oswald Avery (1877–1955), Colin MacLeod (1909–1972), and Maclyn McCarty (1911–2005) demonstrated that the transforming principle was DNA (see Using Microorganisms to Discover the Secrets of Life ). \n\n In transformation , the prokaryote takes up naked DNA found in its environment and that is derived from other cells that have lysed on death and released their contents, including their genome, into the environment. Many bacteria are naturally competent, meaning that they actively bind to environmental DNA, transport it across their cell envelopes into their cytoplasm, and make it single stranded. Typically, double-stranded foreign DNA within cells is destroyed by nucleases as a defense against viral infection. However, these nucleases are usually ineffective against single-stranded DNA, so this single-stranded DNA within the cell has the opportunity to recombine into the bacterial genome. A molecule of DNA that contains fragments of DNA from different organisms is called recombinant DNA . (Recombinant DNA will be discussed in more detail in Microbes and the Tools of Genetic Engineering .) If the bacterium incorporates the new DNA into its own genome through recombination, the bacterial cell may gain new phenotypic properties. For example, if a nonpathogenic bacterium takes up DNA for a toxin gene from a pathogen and then incorporates it into its chromosome, it, too, may become pathogenic. Plasmid DNA may also be taken up by competent bacteria and confer new properties to the cell. Overall, transformation in nature is a relatively inefficient process because environmental DNA levels are low because of the activity of nucleases that are also released during cellular lysis. Additionally, genetic recombination is inefficient at incorporating new DNA sequences into the genome. \n\n In nature, bacterial transformation is an important mechanism for the acquisition of genetic elements encoding virulence factor s and antibiotic resistance . Genes encoding resistance to antimicrobial compounds have been shown to be widespread in nature, even in environments not influenced by humans. These genes, which allow microbes living in mixed communities to compete for limited resources, can be transferred within a population by transformation, as well as by the other processes of HGT. In the laboratory, we can exploit the natural process of bacterial transformation for genetic engineering to make a wide variety of medicinal products, as discussed in Microbes and the Tools of Genetic Engineering . \n\n Check Your Understanding \n\n Why does a bacterial cell make environmental DNA brought into the cell into a single-stranded form? \n\n Transduction \n\n Viruses that infect bacteria ( bacteriophages ) may also move short pieces of chromosomal DNA from one bacterium to another in a process called transduction (see Figure 6.9 ). Recall that in generalized transduction , any piece of chromosomal DNA may be transferred to a new host cell by accidental packaging of chromosomal DNA into a phage head during phage assembly. By contrast, specialized transduction results from the imprecise excision of a lysogenic prophage from the bacterial chromosome such that it carries with it a piece of the bacterial chromosome from either side of the phage’s integration site to a new host cell. As a result, the host may acquire new properties. This process is called lysogenic conversion. Of medical significance, a lysogenic phage may carry with it a virulence gene to its new host. Once inserted into the new host’s chromosome, the new host may gain pathogenicity. Several pathogenic bacteria, including Corynebacterium diphtheriae (the causative agent of diphtheria) and Clostridium botulinum (the causative agent of botulism), are virulent because of the introduction of toxin-encoding genes by lysogenic bacteriophages, affirming the clinical relevance of transduction in the exchange of genes involved in infectious disease. Archaea have their own viruses that translocate genetic material from one individual to another. \n\n Check Your Understanding \n\n What is the agent of transduction of prokaryotic cells? \n\n In specialized transduction, where does the transducing piece of DNA come from? \n\n Case in Point The Clinical Consequences of Transduction Paul, a 23-year-old relief worker from Atlanta, traveled to Haiti in 2011 to provide aid following the 2010 earthquake. After working there for several weeks, he suddenly began experiencing abdominal distress, including severe cramping, nausea, vomiting, and watery diarrhea. He also began to experience intense muscle cramping. At a local clinic, the physician suspected that Paul’s symptoms were caused by cholera because there had been a cholera outbreak after the earthquake. Because cholera is transmitted by the fecal-oral route, breaches in sanitation infrastructure, such as often occur following natural disasters, may precipitate outbreaks. The physician confirmed the presumptive diagnosis using a cholera dipstick test. He then prescribed Paul a single dose of doxycycline, as well as oral rehydration salts, instructing him to drink significant amounts of clean water. \n\n Cholera is caused by the gram-negative curved rod Vibrio cholerae ( Figure 11.27 ). Its symptoms largely result from the production of the cholera toxin (CT), which ultimately activates a chloride transporter to pump chloride ions out of the epithelial cells into the gut lumen. Water then follows the chloride ions, causing the prolific watery diarrhea characteristic of cholera. The gene encoding the cholera toxin is incorporated into the bacterial chromosome of V . cholerae through infection of the bacterium with the lysogenic filamentous CTX phage, which carries the CT gene and introduces it into the chromosome on integration of the prophage. Thus, pathogenic strains of V. cholerae result from horizontal gene transfer by specialized transduction. \n\n Why are outbreaks of cholera more common as a result of a natural disaster? \n\n Why is muscle cramping a common symptom of cholera? Why is treatment with oral rehydration salts so important for the treatment of cholera? \n\n In areas stricken by cholera, what are some strategies that people could use to prevent disease transmission? \n\n Conjugation \n\n In conjugation , DNA is directly transferred from one prokaryote to another by means of a conjugation pilus , which brings the organisms into contact with one another. In E. coli , the genes encoding the ability to conjugate are located on a bacterial plasmid called the F plasmid , also known as the fertility factor , and the conjugation pilus is called the F pilus . The F-plasmid genes encode both the proteins composing the F pilus and those involved in rolling circle replication of the plasmid. Cells containing the F plasmid, capable of forming an F pilus, are called F + cell s or donor cell s , and those lacking an F plasmid are called F − cell s or recipient cell s . \n\n Conjugation of the F Plasmid \n\n During typical conjugation in E. coli , the F pilus of an F + cell comes into contact with an F – cell and retracts, bringing the two cell envelopes into contact ( Figure 11.28 ). Then a cytoplasmic bridge forms between the two cells at the site of the conjugation pilus. As rolling circle replication of the F plasmid occurs in the F + cell, a single-stranded copy of the F plasmid is transferred through the cytoplasmic bridge to the F − cell, which then synthesizes the complementary strand, making it double stranded. The F − cell now becomes an F + cell capable of making its own conjugation pilus. Eventually, in a mixed bacterial population containing both F + and F − cells, all cells will become F + cells. Genes on the E. coli F plasmid also encode proteins preventing conjugation between F + cells. \n\n Conjugation of F’ and Hfr Cells \n\n Although typical conjugation in E. coli results in the transfer of the F-plasmid DNA only, conjugation may also transfer chromosomal DNA. This is because the F plasmid occasionally integrates into the bacterial chromosome through recombination between the plasmid and the chromosome, forming an Hfr cell ( Figure 11.29 ). “Hfr” refers to the high frequency of recombination seen when recipient F − cells receive genetic information from Hfr cells through conjugation. Similar to the imprecise excision of a prophage during specialized transduction , the integrated F plasmid may also be imprecisely excised from the chromosome, producing an F’ plasmid that carries with it some chromosomal DNA adjacent to the integration site. On conjugation, this DNA is introduced to the recipient cell and may be either maintained as part of the F’ plasmid or be recombined into the recipient cell’s bacterial chromosome. \n\n Hfr cells may also treat the bacterial chromosome like an enormous F plasmid and attempt to transfer a copy of it to a recipient F − cell. Because the bacterial chromosome is so large, transfer of the entire chromosome takes a long time ( Figure 11.30 ). However, contact between bacterial cells during conjugation is transient, so it is unusual for the entire chromosome to be transferred. Host chromosomal DNA near the integration site of the F plasmid, displaced by the unidirectional process of rolling circle replication, is more likely to be transferred and recombined into a recipient cell’s chromosome than host genes farther away. Thus, the relative location of bacterial genes on the Hfr cell’s genome can be mapped based on when they are transferred through conjugation. As a result, prior to the age of widespread bacterial genome sequencing, distances on prokaryotic genome maps were often measured in minutes. \n\n Consequences and Applications of Conjugation \n\n Plasmids are an important type of extrachromosomal DNA element in bacteria and, in those cells that harbor them, are considered to be part of the bacterial genome. From a clinical perspective, plasmid s often code for genes involved in virulence. For example, genes encoding proteins that make a bacterial cell resistant to a particular antibiotic are encoded on R plasmids . R plasmids, in addition to their genes for antimicrobial resistance, contain genes that control conjugation and transfer of the plasmid. R plasmids are able to transfer between cells of the same species and between cells of different species. Single R plasmids commonly contain multiple genes conferring resistance to multiple antibiotics. \n\n Genes required for the production of various toxins and molecules important for colonization during infection may also be found encoded on plasmids. For example, verotoxin-producing strains of E. coli ( VTEC ) appear to have acquired the genes encoding the Shiga toxin from its gram-negative relative Shigella dysenteriae through the acquisition of a large plasmid encoding this toxin. VTEC causes severe diarrheal disease that may result in hemolytic uremic syndrome (HUS), which may be lead to kidney failure and death. \n\n In nonclinical settings, bacterial genes that encode metabolic enzymes needed to degrade specialized atypical compounds like polycyclic aromatic hydrocarbons (PAHs) are also frequently encoded on plasmids. Additionally, certain plasmids have the ability to move from bacterial cells to other cell types, like those of plants and animals, through mechanisms distinct from conjugation. Such mechanisms and their use in genetic engineering are covered in Modern Applications of Microbial Genetics . \n\n Link to Learning \n\n Click through this animation to learn more about the process of conjugation. \n\n Check Your Understanding \n\n What type of replication occurs during conjugation? \n\n What occurs to produce an Hfr E. coli cell? \n\n What types of traits are encoded on plasmids? \n\n Transposition \n\n Genetic elements called transposons (transposable elements), or “ jumping genes ,” are molecules of DNA that include special inverted repeat sequences at their ends and a gene encoding the enzyme transposase ( Figure 11.31 ). Transposons allow the entire sequence to independently excise from one location in a DNA molecule and integrate into the DNA elsewhere through a process called transposition . Transposons were originally discovered in maize (corn) by American geneticist Barbara McClintock (1902–1992) in the 1940s. Transposons have since been found in all types of organisms, both prokaryotes and eukaryotes. Thus, unlike the three previous mechanisms discussed, transposition is not prokaryote-specific. Most transposons are nonreplicative, meaning they move in a “cut-and-paste” fashion. Some may be replicative, however, retaining their location in the DNA while making a copy to be inserted elsewhere (“copy and paste”). Because transposons can move within a DNA molecule, from one DNA molecule to another, or even from one cell to another, they have the ability to introduce genetic diversity. Movement within the same DNA molecule can alter phenotype by inactivating or activating a gene. \n\n Transposons may carry with them additional genes, moving these genes from one location to another with them. For example, bacterial transposons can relocate antibiotic resistance genes, moving them from chromosomes to plasmids. This mechanism has been shown to be responsible for the colocalization of multiple antibiotic resistance genes on a single R plasmid in Shigella strains causing bacterial dysentery. Such an R plasmid can then be easily transferred among a bacterial population through the process of conjugation. \n\n Check Your Understanding \n\n What are two ways a transposon can affect the phenotype of a cell it moves to? \n\n Table 11.5 summarizes the processes discussed in this section. \n\n Summary of Mechanisms of Genetic Diversity in Prokaryotes \n\n Term \n\n Definition \n\n Conjugation \n\n Transfer of DNA through direct contact using a conjugation pilus \n\n Transduction \n\n Mechanism of horizontal gene transfer in bacteria in which genes are transferred through viral infection \n\n Transformation \n\n Mechanism of horizontal gene transfer in which naked environmental DNA is taken up by a bacterial cell \n\n Transposition \n\n Process whereby DNA independently excises from one location in a DNA molecule and integrates elsewhere \n\n Table 11.5 \n\n Clinical Focus Part 3 Despite continued antibiotic treatment, Mark’s infection continued to progress rapidly. The infected region continued to expand, and he had to be put on a ventilator to help him breathe. Mark’s physician ordered surgical removal of the infected tissue. Following an initial surgery, Mark’s wound was monitored daily to ensure that the infection did not return, but it continued to spread. \n\n After two additional rounds of surgery, the infection finally seemed to be contained. A few days later, Mark was removed from the ventilator and was able to breathe on his own. However, he had lost a great deal of skin and soft tissue on his lower leg. \n\n Why does the removal of infected tissue stem the infection? \n\n What are some likely complications of this method of treatment? \n\n Jump to the next Clinical Focus box. Go back to the previous Clinical Focus box. \n 11.7 Gene Regulation: Operon Theory \n\n Learning Objectives \n\n Compare inducible operons and repressible operons \n\n Describe why regulation of operons is important \n\n Each nucleated cell in a multicellular organism contains copies of the same DNA. Similarly, all cells in two pure bacterial cultures inoculated from the same starting colony contain the same DNA, with the exception of changes that arise from spontaneous mutations. If each cell in a multicellular organism has the same DNA, then how is it that cells in different parts of the organism’s body exhibit different characteristics? Similarly, how is it that the same bacterial cells within two pure cultures exposed to different environmental conditions can exhibit different phenotypes? In both cases, each genetically identical cell does not turn on, or express, the same set of genes. Only a subset of proteins in a cell at a given time is expressed. \n\n Genomic DNA contains both structural gene s, which encode products that serve as cellular structures or enzymes, and regulatory gene s, which encode products that regulate gene expression. The expression of a gene is a highly regulated process. Whereas regulating gene expression in multicellular organisms allows for cellular differentiation, in single-celled organisms like prokaryotes, it primarily ensures that a cell’s resources are not wasted making proteins that the cell does not need at that time. \n\n Elucidating the mechanisms controlling gene expression is important to the understanding of human health. Malfunctions in this process in humans lead to the development of cancer and other diseases. Understanding the interaction between the gene expression of a pathogen and that of its human host is important for the understanding of a particular infectious disease. Gene regulation involves a complex web of interactions within a given cell among signals from the cell’s environment, signaling molecules within the cell, and the cell’s DNA. These interactions lead to the expression of some genes and the suppression of others, depending on circumstances. \n\n Prokaryotes and eukaryotes share some similarities in their mechanisms to regulate gene expression; however, gene expression in eukaryotes is more complicated because of the temporal and spatial separation between the processes of transcription and translation. Thus, although most regulation of gene expression occurs through transcriptional control in prokaryotes, regulation of gene expression in eukaryotes occurs at the transcriptional level and post-transcriptionally (after the primary transcript has been made). \n\n Prokaryotic Gene Regulation \n\n In bacteria and archaea , structural proteins with related functions are usually encoded together within the genome in a block called an operon and are transcribed together under the control of a single promoter , resulting in the formation of a polycistronic transcript ( Figure 11.32 ). In this way, regulation of the transcription of all of the structural genes encoding the enzymes that catalyze the many steps in a single biochemical pathway can be controlled simultaneously, because they will either all be needed at the same time, or none will be needed. For example, in E. coli , all of the structural genes that encode enzymes needed to use lactose as an energy source lie next to each other in the lactose (or lac ) operon under the control of a single promoter, the lac promoter. French scientists François Jacob (1920–2013) and Jacques Monod at the Pasteur Institute were the first to show the organization of bacterial genes into operons, through their studies on the lac operon of E. coli . For this work, they won the Nobel Prize in Physiology or Medicine in 1965. Although eukaryotic genes are not organized into operons, prokaryotic operons are excellent models for learning about gene regulation generally. There are some gene clusters in eukaryotes that function similar to operons. Many of the principles can be applied to eukaryotic systems and contribute to our understanding of changes in gene expression in eukaryotes that can result pathological changes such as cancer. \n\n Each operon includes DNA sequences that influence its own transcription; these are located in a region called the regulatory region. The regulatory region includes the promoter and the region surrounding the promoter, to which transcription factors , proteins encoded by regulatory genes, can bind. Transcription factors influence the binding of RNA polymerase to the promoter and allow its progression to transcribe structural genes. A repressor is a transcription factor that suppresses transcription of a gene in response to an external stimulus by binding to a DNA sequence within the regulatory region called the operator , which is located between the RNA polymerase binding site of the promoter and the transcriptional start site of the first structural gene. Repressor binding physically blocks RNA polymerase from transcribing structural genes. Conversely, an activator is a transcription factor that increases the transcription of a gene in response to an external stimulus by facilitating RNA polymerase binding to the promoter. An inducer , a third type of regulatory molecule, is a small molecule that either activates or represses transcription by interacting with a repressor or an activator. \n\n In prokaryotes, there are examples of operons whose gene products are required rather consistently and whose expression, therefore, is unregulated. Such operons are constitutively expressed , meaning they are transcribed and translated continuously to provide the cell with constant intermediate levels of the protein products. Such genes encode enzymes involved in housekeeping functions required for cellular maintenance, including DNA replication, repair, and expression, as well as enzymes involved in core metabolism. In contrast, there are other prokaryotic operons that are expressed only when needed and are regulated by repressors, activators, and inducers. \n\n Check Your Understanding \n\n What are the parts in the DNA sequence of an operon? \n\n What types of regulatory molecules are there? \n\n Regulation by Repression \n\n Prokaryotic operons are commonly controlled by the binding of repressors to operator regions, thereby preventing the transcription of the structural genes. Such operons are classified as either repressible operon s or inducible operons. Repressible operons, like the tryptophan ( trp ) operon, typically contain genes encoding enzymes required for a biosynthetic pathway. As long as the product of the pathway, like tryptophan, continues to be required by the cell, a repressible operon will continue to be expressed. However, when the product of the biosynthetic pathway begins to accumulate in the cell, removing the need for the cell to continue to make more, the expression of the operon is repressed. Conversely, inducible operon s , like the lac operon of E. coli , often contain genes encoding enzymes in a pathway involved in the metabolism of a specific substrate like lactose. These enzymes are only required when that substrate is available, thus expression of the operons is typically induced only in the presence of the substrate. \n\n The trp Operon: A Repressible Operon \n\n E. coli can synthesize tryptophan using enzymes that are encoded by five structural genes located next to each other in the trp operon ( Figure 11.33 ). When environmental tryptophan is low, the operon is turned on. This means that transcription is initiated, the genes are expressed, and tryptophan is synthesized. However, if tryptophan is present in the environment, the trp operon is turned off. Transcription does not occur and tryptophan is not synthesized. \n\n When tryptophan is not present in the cell, the repressor by itself does not bind to the operator; therefore, the operon is active and tryptophan is synthesized. However, when tryptophan accumulates in the cell, two tryptophan molecules bind to the trp repressor molecule, which changes its shape, allowing it to bind to the trp operator. This binding of the active form of the trp repressor to the operator blocks RNA polymerase from transcribing the structural genes, stopping expression of the operon. Thus, the actual product of the biosynthetic pathway controlled by the operon regulates the expression of the operon. \n\n Link to Learning \n\n Watch this video to learn more about the trp operon. \n\n The lac Operon: An Inducible Operon \n\n The lac operon is an example of an inducible operon that is also subject to activation in the absence of glucose ( Figure 11.34 ). The lac operon encodes three structural genes necessary to acquire and process the disaccharide lactose from the environment, breaking it down into the simple sugars glucose and galactose. For the lac operon to be expressed, lactose must be present. This makes sense for the cell because it would be energetically wasteful to create the enzymes to process lactose if lactose was not available. \n\n In the absence of lactose, the lac repressor is bound to the operator region of the lac operon, physically preventing RNA polymerase from transcribing the structural genes. However, when lactose is present, the lactose inside the cell is converted to allolactose. Allolactose serves as an inducer molecule, binding to the repressor and changing its shape so that it is no longer able to bind to the operator DNA. Removal of the repressor in the presence of lactose allows RNA polymerase to move through the operator region and begin transcription of the lac structural genes. \n\n The lac Operon: Activation by Catabolite Activator Protein \n\n Bacteria typically have the ability to use a variety of substrates as carbon sources. However, because glucose is usually preferable to other substrates, bacteria have mechanisms to ensure that alternative substrates are only used when glucose has been depleted. Additionally, bacteria have mechanisms to ensure that the genes encoding enzymes for using alternative substrates are expressed only when the alternative substrate is available. In the 1940s, Jacques Monod was the first to demonstrate the preference for certain substrates over others through his studies of E. coli ’s growth when cultured in the presence of two different substrates simultaneously. Such studies generated diauxic growth curves, like the one shown in Figure 11.35 . Although the preferred substrate glucose is used first, E. coli grows quickly and the enzymes for lactose metabolism are absent. However, once glucose levels are depleted, growth rates slow, inducing the expression of the enzymes needed for the metabolism of the second substrate, lactose. Notice how the growth rate in lactose is slower, as indicated by the lower steepness of the growth curve. \n\n The ability to switch from glucose use to another substrate like lactose is a consequence of the activity of an enzyme called Enzyme IIA (EIIA). When glucose levels drop, cells produce less ATP from catabolism (see Catabolism of Carbohydrates ), and EIIA becomes phosphorylated. Phosphorylated EIIA activates adenylyl cyclase, an enzyme that converts some of the remaining ATP to cyclic AMP (cAMP) , a cyclic derivative of AMP and important signaling molecule involved in glucose and energy metabolism in E. coli . As a result, cAMP levels begin to rise in the cell ( Figure 11.36 ). \n\n The lac operon also plays a role in this switch from using glucose to using lactose. When glucose is scarce, the accumulating cAMP caused by increased adenylyl cyclase activity binds to catabolite activator protein (CAP) , also known as cAMP receptor protein (CRP). The complex binds to the promoter region of the lac operon ( Figure 11.37 ). In the regulatory regions of these operons, a CAP binding site is located upstream of the RNA polymerase binding site in the promoter. Binding of the CAP-cAMP complex to this site increases the binding ability of RNA polymerase to the promoter region to initiate the transcription of the structural genes. Thus, in the case of the lac operon, for transcription to occur, lactose must be present (removing the lac repressor protein) and glucose levels must be depleted (allowing binding of an activating protein). When glucose levels are high, there is catabolite repression of operons encoding enzymes for the metabolism of alternative substrates. Because of low cAMP levels under these conditions, there is an insufficient amount of the CAP-cAMP complex to activate transcription of these operons. See Table 11.6 for a summary of the regulation of the lac operon. \n\n Conditions Affecting Transcription of the lac Operon \n\n Glucose \n\n CAP binds \n\n Lactose \n\n Repressor binds \n\n Transcription \n\n + \n\n – \n\n – \n\n + \n\n No \n\n + \n\n – \n\n + \n\n – \n\n Some \n\n – \n\n + \n\n – \n\n + \n\n No \n\n – \n\n + \n\n + \n\n – \n\n Yes \n\n Table 11.6 \n\n Link to Learning \n\n Watch an animated tutorial about the workings of lac operon here. \n\n Check Your Understanding \n\n What affects the binding of the trp operon repressor to the operator? \n\n How and when is the behavior of the lac repressor protein altered? \n\n In addition to being repressible, how else is the lac operon regulated? \n\n Global Responses of Prokaryotes \n\n In prokaryotes, there are also several higher levels of gene regulation that have the ability to control the transcription of many related operons simultaneously in response to an environmental signal. A group of operons all controlled simultaneously is called a regulon . \n\n Alarmones \n\n When sensing impending stress, prokaryotes alter the expression of a wide variety of operon s to respond in coordination. They do this through the production of alarmones , which are small intracellular nucleotide derivatives. Alarmones change which genes are expressed and stimulate the expression of specific stress-response genes. The use of alarmones to alter gene expression in response to stress appears to be important in pathogenic bacteria. On encountering host defense mechanisms and other harsh conditions during infection, many operons encoding virulence genes are upregulated in response to alarmone signaling. Knowledge of these responses is key to being able to fully understand the infection process of many pathogens and to the development of therapies to counter this process. \n\n Alternate σ Factors \n\n Since the σ subunit of bacterial RNA polymerase confers specificity as to which promoters should be transcribed, altering the σ factor used is another way for bacteria to quickly and globally change what regulons are transcribed at a given time. The σ factor recognizes sequences within a bacterial promoter , so different σ factors will each recognize slightly different promoter sequences. In this way, when the cell senses specific environmental conditions, it may respond by changing which σ factor it expresses, degrading the old one and producing a new one to transcribe the operons encoding genes whose products will be useful under the new environmental condition. For example, in sporulating bacteria of the genera Bacillus and Clostridium (which include many pathogens), a group of σ factors controls the expression of the many genes needed for sporulation in response to sporulation-stimulating signals. \n\n Check Your Understanding \n\n What is the name given to a collection of operons that can be regulated as a group? \n\n What type of stimulus would trigger the transcription of a different σ factor? \n\n Additional Methods of Regulation in Bacteria: Attenuation and Riboswitches \n\n Although most gene expression is regulated at the level of transcription initiation in prokaryotes, there are also mechanisms to control both the completion of transcription as well as translation concurrently. Since their discovery, these mechanisms have been shown to control the completion of transcription and translation of many prokaryotic operons. Because these mechanisms link the regulation of transcription and translation directly, they are specific to prokaryotes, because these processes are physically separated in eukaryotes. \n\n One such regulatory system is attenuation , whereby secondary stem-loop structure s formed within the 5’ end of an mRNA being transcribed determine if transcription to complete the synthesis of this mRNA will occur and if this mRNA will be used for translation. Beyond the transcriptional repression mechanism already discussed, attenuation also controls expression of the trp operon in E. coli ( Figure 11.38 ). The trp operon regulatory region contains a leader sequence called trpL between the operator and the first structural gene, which has four stretches of RNA that can base pair with each other in different combinations. When a terminator stem-loop forms, transcription terminates, releasing RNA polymerase from the mRNA. However, when an antiterminator stem-loop forms, this prevents the formation of the terminator stem-loop, so RNA polymerase can transcribe the structural genes. \n\n A related mechanism of concurrent regulation of transcription and translation in prokaryotes is the use of a riboswitch , a small region of noncoding RNA found within the 5’ end of some prokaryotic mRNA molecules ( Figure 11.39 . A riboswitch may bind to a small intracellular molecule to stabilize certain secondary structures of the mRNA molecule. The binding of the small molecule determines which stem-loop structure forms, thus influencing the completion of mRNA synthesis and protein synthesis. \n\n Other Factors Affecting Gene Expression in Prokaryotes and Eukaryotes \n\n Although the focus on our discussion of transcriptional control used prokaryotic operons as examples, eukaryotic transcriptional control is similar in many ways. As in prokaryotes, eukaryotic transcription can be controlled through the binding of transcription factors including repressor s and activator s. Interestingly, eukaryotic transcription can be influenced by the binding of proteins to regions of DNA, called enhancer s, rather far away from the gene, through DNA looping facilitated between the enhancer and the promoter ( Figure 11.40 ). Overall, regulating transcription is a highly effective way to control gene expression in both prokaryotes and eukaryotes. However, the control of gene expression in eukaryotes in response to environmental and cellular stresses can be accomplished in additional ways without the binding of transcription factors to regulatory regions. \n\n DNA-Level Control \n\n In eukaryotes, the DNA molecules or associated histones can be chemically modified in such a way as to influence transcription; this is called epigenetic regulation . Methylation of certain cytosine nucleotides in DNA in response to environmental factors has been shown to influence use of such DNA for transcription, with DNA methylation commonly correlating to lowered levels of gene expression. Additionally, in response to environmental factors, histone proteins for packaging DNA can also be chemically modified in multiple ways, including acetylation and deacetylation, influencing the packaging state of DNA and thus affecting the availability of loosely wound DNA for transcription. These chemical modifications can sometimes be maintained through multiple rounds of cell division, making at least some of these epigenetic changes heritable. \n\n Link to Learning \n\n This video describes how epigenetic regulation controls gene expression. \n\n Check Your Understanding \n\n What stops or allows transcription to proceed when attenuation is operating? \n\n What determines the state of a riboswitch? \n\n Describe the function of an enhancer. \n\n Describe two mechanisms of epigenetic regulation in eukaryotes. \n\n Clinical Focus Resolution Although Mark survived his bout with necrotizing fasciitis, he would now have to undergo a skin-grafting surgery, followed by long-term physical therapy. Based on the amount of muscle mass he lost, it is unlikely that his leg will return to full strength, but his physical therapist is optimistic that he will regain some use of his leg. \n\n Laboratory testing revealed the causative agent of Mark’s infection was a strain of Staphylococcus aureus . As required by law, Mark’s case was reported to the state health department and ultimately to the Centers for Disease Control and Prevention (CDC). At the CDC, the strain of Staphylococcus aureus strep isolated from Mark was analyzed more thoroughly for methicillin resistance. \n\n Methicillin resistance is genetically coded and is increasing among strains of S. aureus through horizontal gene transfer. Strains of S. aureus that are resistant to methicillin are typically resistant to virtually all beta-lactam antibiotics and other classes of antibiotics as well. In necrotizing fasciitis, blood flow to the infected area is typically limited because of the action of various genetically encoded bacterial toxins. This is why there is typically little to no bleeding as a result of the incision test. Unfortunately, these bacterial toxins limit the effectiveness of intravenous antibiotics in clearing infection from the skin and underlying tissue, meaning that antibiotic resistance alone does not explain the ineffectiveness of Mark’s treatment. Nevertheless, intravenous antibiotic therapy was warranted to help minimize the possible outcome of sepsis, which is a common outcome of necrotizing fasciitis. Through genomic analysis by the CDC of the strain isolated from Mark, several of the important virulence genes were shown to be encoded within pathogenicity islands that were associated with prophages. Horizontal transfer of pathogenicity island-encoded virulence factors between strains of S. aureus has been shown to occur through induction of prophage and can be induced by treatment with antibiotics. \n\n Go back to the previous Clinical Focus box. "}}},{"rowIdx":176,"cells":{"bname":{"kind":"string","value":"principles_of_accounting,_volume_1:_financial_accounting"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":" Summary 2.1 Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate \n\n Financial statements provide financial information to stakeholders to help them in making decisions. \n\n There are four financial statements: income statement, statement of owner’s equity, balance sheet, and statement of cash flows. \n\n The income statement measures the financial performance of the organization for a period of time. The income statement lists revenues, expenses, gains, and losses, which make up net income (or net loss). \n\n The statement of owner’s equity shows how the net worth of the organization changes for a period of time. In addition to showing net income or net loss, the statement of owner’s equity shows the investments by and distributions to owners. \n\n The balance sheet shows the organization’s financial position on a given date. The balance sheet lists assets, liabilities, and owners’ equity. \n\n The statement of cash flows shows the organization’s cash inflows and cash outflows for a given period of time. The statement of cash flows is necessary because financial statements are usually prepared using accrual accounting, which records transactions when they occur rather than waiting until cash is exchanged. \n\n 2.2 Define, Explain, and Provide Examples of Current and Noncurrent Assets, Current and Noncurrent Liabilities, Equity, Revenues, and Expenses \n\n Assets and liabilities are categorized into current and noncurrent, based on when the item will be settled. Assets and liabilities that will be settled in one year or less are classified as current; otherwise, the items are classified as noncurrent. \n\n Assets are also categorized based on whether or not the asset has physical substance. Assets with physical substance are considered tangible assets, while intangible assets lack physical substance. \n\n The distinction between current and noncurrent assets and liabilities is important because it helps financial statement users assess the timing of the transactions. \n\n Three broad categories of legal business structures are sole proprietorship, partnership, and corporation, with each structure having advantages and disadvantages. \n\n The accounting equation is Assets = Liabilities + Owner’s Equity. It is important to the study of accounting because it shows what the organization owns and the sources of (or claims against) those resources. \n\n Owners’ equity can also be thought of as the net worth or value of the business. There are many factors that influence equity, including net income or net loss, investments by and distributions to owners, revenues, gains, losses, expenses, and comprehensive income. \n\n 2.3 Prepare an Income Statement, Statement of Owner’s Equity, and Balance Sheet \n\n There are ten financial statement elements: revenues, expenses, gains, losses, assets, liabilities, equity, investments by owners, distributions to owners, and comprehensive income. \n\n There are standard conventions for the order of preparing financial statements (income statement, statement of owner’s equity, balance sheet, and statement of cash flows) and for the format (three-line heading and columnar structure). \n\n Financial ratios, which are calculated using financial statement information, are often beneficial to aid in financial decision-making. Ratios allow for comparisons between businesses and determining trends between periods within the same business. \n\n Liquidity ratios assess the firm’s ability to convert assets into cash. \n\n Working Capital (Current Assets – Current Liabilities) is a liquidity ratio that measures a firm’s ability to meet current obligations. \n\n The Current Ratio (Current Assets/Current Liabilities) is similar to Working Capital but allows for comparisons between firms by determining the proportion of current assets to current liabilities. "},"intro":{"kind":"string","value":" Chapter Outline 2.1 Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate 2.2 Define, Explain, and Provide Examples of Current and Noncurrent Assets, Current and Noncurrent Liabilities, Equity, Revenues, and Expenses 2.3 Prepare an Income Statement, Statement of Owner’s Equity, and Balance Sheet Why It Matters \n\n As a teenager, Derek loves computers. He also enjoys giving back to the community by helping others. Derek understands that many senior citizens live far away from their families, resulting in infrequent visits and loneliness. This summer he is considering combining both things he enjoys by working with the local retirement center. His idea is to have workshops to show the senior citizens how to connect with their families through the use of technology. The director of the retirement center is enthused about Derek’s idea and has agreed to pay him for the services. During his visits, he will set up tablets and then show the seniors how to use them. Since he lives nearby, he will also provide support on an as-needed basis. \n\n While he is excited about this opportunity, he is also trying to save up money for college. Although the retirement center will pay him for the workshops, he knows the investment in providing tablets will be expensive, and he wants to ensure he can cover his costs. A neighbor who works in banking suggests that Derek get a small loan to cover the costs of the tablets and use the income he earns to repay the loan. Derek is excited by the idea but is anxious when his neighbor mentions he will have to provide the bank monthly financial information, such as checking account and other financial statements. While he enjoys technology and helping others, he is unfamiliar with financial statements. Derek decides to learn more about how financial statements will help both him and the bank make sound financial decisions. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"In Describe the Income Statement , Statement of Owner ’ s Equity , Balance Sheet , and Statement of Cash Flows , and How They Interrelate , we discussed the function of and the basic characteristics of the statement of cash flows . This fourth and final financial statement lists the cash inflows and cash outflows for the business for a period of time . <hl> It was created to fill in some informational gaps that existed in the other three statements ( income statement , owner ’ s equity / retained earnings statement , and the balance sheet ) . <hl> A full demonstration of the creation of the statement of cash flows is presented in Statement of Cash Flows . <hl> The fourth and final financial statement prepared is the statement of cash flows , which is a statement that lists the cash inflows and cash outflows for the business for a period of time . <hl> At first glance , this may seem like a redundant financial statement . <hl> We know the income statement also reports the inflows and outflows for the business for a period of time . <hl> <hl> In addition , the statement of owner ’ s equity and the balance sheet help to show the other activities , such as investments by and distributions to owners that are not included in the income statement . <hl> To understand why the statement of cash flows is necessary , we must first understand the two bases of accounting used to prepare the financial statements . The changes in cash within this statement are often referred to as sources and uses of cash . A source of cash lets one see where cash is coming from . For example , is cash being generated from sales to customers , or is the cash a result of an advance in a large loan . Use of cash looks at what cash is being used for . Is cash being used to make an interest payment on a loan , or is cash being used to purchase a large piece of machinery that will expand business capacity ? The two bases of accounting are the cash basis and the accrual basis , briefly introduced in Describe the Income Statement , Statement of Owner ’ s Equity , Balance Sheet , and Statement of Cash Flows , and How They Interrelate .","hl_sentences":"It was created to fill in some informational gaps that existed in the other three statements ( income statement , owner ’ s equity / retained earnings statement , and the balance sheet ) . The fourth and final financial statement prepared is the statement of cash flows , which is a statement that lists the cash inflows and cash outflows for the business for a period of time . We know the income statement also reports the inflows and outflows for the business for a period of time . In addition , the statement of owner ’ s equity and the balance sheet help to show the other activities , such as investments by and distributions to owners that are not included in the income statement .","question":{"cloze_format":"The statement that is not one of the financial statements is the ___.","normal_format":"Which of these statements is not one of the financial statements?","question_choices":["income statement","balance sheet","statement of cash flows","statement of owner investments"],"question_id":"fs-idm385189632","question_text":"Which of these statements is not one of the financial statements?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"competitors"},"bloom":null,"hl_context":"Before exploring the specific financial statements , it is important to know why these are important documents . To understand this , you must first understand who the users of financial statements are . Users of the information found in financial statements are called stakeholders . <hl> A stakeholder is someone affected by decisions made by a company ; this can include groups or individuals affected by the actions or policies of an organization , including include investors , creditors , employees , managers , regulators , customers , and suppliers . <hl> <hl> The stakeholder ’ s interest sometimes is not directly related to the entity ’ s financial performance . <hl> <hl> Examples of stakeholders include lenders , investors / owners , vendors , employees and management , governmental agencies , and the communities in which the businesses operate . <hl> Stakeholders are interested in the performance of an organization for various reasons , but the common goal of using the financial statements is to understand the information each contains that is useful for making financial decisions . For example , a banker may be interested in the financial statements to decide whether or not to lend the organization money .","hl_sentences":"A stakeholder is someone affected by decisions made by a company ; this can include groups or individuals affected by the actions or policies of an organization , including include investors , creditors , employees , managers , regulators , customers , and suppliers . The stakeholder ’ s interest sometimes is not directly related to the entity ’ s financial performance . Examples of stakeholders include lenders , investors / owners , vendors , employees and management , governmental agencies , and the communities in which the businesses operate .","question":{"cloze_format":"Stakeholders are less likely to include ___.","normal_format":"Stakeholders are less likely to include which of the following groups?","question_choices":["owners","employees","community leaders","competitors"],"question_id":"fs-idm370303680","question_text":"Stakeholders are less likely to include which of the following groups?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"In accounting , this example illustrates an income statement , a financial statement that is used to measure the financial performance of an organization for a particular period of time . <hl> We use the simple landscaping account example to discuss the elements of the income statement , which are revenues , expenses , gains , and losses . <hl> Together , these determine whether the organization has net income ( where revenues and gains are greater than expenses and losses ) or net loss ( where expenses and losses are greater than revenues and gains ) . Revenues , expenses , gains , and losses are further defined here .","hl_sentences":"We use the simple landscaping account example to discuss the elements of the income statement , which are revenues , expenses , gains , and losses .","question":{"cloze_format":"The correct components of the income statement can be listed as ___.","normal_format":"What are the correct components of the income statement?","question_choices":["revenues, losses, expenses, and gains","assets, liabilities, and owner’s equity","revenues, expenses, investments by owners, distributions to owners","assets, liabilities, and dividends"],"question_id":"fs-idm359834736","question_text":"Identify the correct components of the income statement."},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"assets, liabilities, and investments by owners"},"bloom":null,"hl_context":"Knowing the difference between the cash basis and accrual basis of accounting is necessary to understand the need for the statement of cash flows . <hl> Stakeholders need to know the financial performance ( as measured by the income statement — that is , net income or net loss ) and financial position ( as measured by the balance sheet — that is , assets , liabilities , and owners ’ equity ) of the business . <hl> This information is provided in the income statement , statement of owner ’ s equity , and balance sheet . However , since these financial statements are prepared using accrual accounting , stakeholders do not have a clear picture of the business ’ s cash activities . The statement of cash flows solves this inadequacy by specifically focusing on the cash inflows and cash outflows . 2.2 Define , Explain , and Provide Examples of Current and Noncurrent Assets , Current and Noncurrent Liabilities , Equity , Revenues , and Expenses","hl_sentences":"Stakeholders need to know the financial performance ( as measured by the income statement — that is , net income or net loss ) and financial position ( as measured by the balance sheet — that is , assets , liabilities , and owners ’ equity ) of the business .","question":{"cloze_format":"The balance sheet lists ___.","normal_format":"The balance sheet lists which of the following?","question_choices":["assets, liabilities, and owners’ equity","revenues, expenses, gains, and losses","assets, liabilities, and investments by owners","revenues, expenses, gains, and distributions to owners"],"question_id":"fs-idm384816368","question_text":"The balance sheet lists which of the following?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"Tangible assets have physical substance."},"bloom":null,"hl_context":"Another thing you might have recognized when reviewing your list of coffee shop assets is that all of the items were something you could touch or move , each of which is known as a tangible asset . However , as you also learned in Describe the Income Statement , Statement of Owner ’ s Equity , Balance Sheet , and Statement of Cash Flows , and How They Interrelate , not all assets are tangible . <hl> An asset could be an intangible asset , meaning the item lacks physical substance — it cannot be touched or moved . <hl> Take a moment to think about your favorite type of shoe or a popular type of farm tractor . Would you be able to recognize the maker of that shoe or the tractor by simply seeing the logo ? Chances are you would . These are examples of intangible assets , trademarks to be precise . A trademark has value to the organization that created ( or purchased ) the trademark , and the trademark is something the organization controls — others cannot use the trademark without permission . An asset can also be categorized as a tangible asset or an intangible asset . <hl> Tangible assets have a physical nature , such as trucks or many inventory items , while intangible assets have value but often lack a physical existence or corpus , such as insurance policies or trademarks . <hl>","hl_sentences":"An asset could be an intangible asset , meaning the item lacks physical substance — it cannot be touched or moved . Tangible assets have a physical nature , such as trucks or many inventory items , while intangible assets have value but often lack a physical existence or corpus , such as insurance policies or trademarks .","question":{"cloze_format":"The statement that is true is that ___.","normal_format":"Which of the following statements is true?","question_choices":["Tangible assets lack physical substance.","Tangible assets will be consumed in a year or less.","Tangible assets have physical substance.","Tangible assets will be consumed in over a year."],"question_id":"fs-idm406688976","question_text":"Which of the following statements is true?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> A corporation is a legal business structure involving one or more individuals ( owners ) who are legally distinct ( separate ) from the business . <hl> A primary benefit of a corporate legal structure is the owners of the organization have limited liability . That is , a corporation is “ stand alone , ” conducting business as an entity separate from its owners . Under the corporate structure , owners delegate to others ( called agents ) the responsibility to make day-to-day decisions regarding the operations of the business . Other benefits of the corporate legal structure include relatively easy access to large amounts of capital by obtaining loans or selling ownership ( stock ) , and since the stock is easily sold or transferred to others , the business operates beyond the life of the shareholders . A major disadvantage of a corporate legal structure is double taxation — the business pays income tax and the owners are taxed when distributions ( also called dividends ) are received .","hl_sentences":"A corporation is a legal business structure involving one or more individuals ( owners ) who are legally distinct ( separate ) from the business .","question":{"cloze_format":"Under the legal business structure of ___, owners have no personal liability. ","normal_format":"Owners have no personal liability under which legal business structure?","question_choices":["a corporation","a partnership","a sole proprietorship","There is liability in every legal business structure."],"question_id":"fs-idm369250368","question_text":"Owners have no personal liability under which legal business structure?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"Assets = Liabilities + Owner’s Equity"},"bloom":null,"hl_context":"Your Turn The Accounting Equation On a sheet of paper , use three columns to create your own accounting equation . <hl> In the first column , list all of the things you own ( assets ) . <hl> <hl> In the second column , list any amounts owed ( liabilities ) . <hl> <hl> In the third column , using the accounting equation , calculate , you guessed it , the net amount of the asset ( equity ) . <hl> When finished , total the columns to determine your net worth . Hint : do not forget to subtract the liability from the value of the asset .","hl_sentences":"In the first column , list all of the things you own ( assets ) . In the second column , list any amounts owed ( liabilities ) . In the third column , using the accounting equation , calculate , you guessed it , the net amount of the asset ( equity ) .","question":{"cloze_format":"The accounting equation is expressed as ________.","normal_format":"What is the accounting equation?","question_choices":["Assets + Liabilities = Owner’s Equity","Assets – Noncurrent Assets = Liabilities","Assets = Liabilities + Investments by Owners","Assets = Liabilities + Owner’s Equity"],"question_id":"fs-idm369458480","question_text":"The accounting equation is expressed as ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"<hl> The elements of the financial statements shown on the statement of owner ’ s equity include investments by owners as well as distributions to owners . <hl> Investments by owners and distributions to owners are two activities that impact the value of the organization ( increase and decrease , respectively ) . <hl> In addition , net income or net loss affects the value of the organization ( net income increases the value of the organization , and net loss decreases it ) . <hl> Net income ( or net loss ) is also shown on the statement of owner ’ s equity ; this is an example of how the statements are interrelated . Note that the word owner ’ s ( singular for a sole owner ) changes to owners ’ ( plural , for a group of owners ) when preparing this statement for an entity with multiple owners versus a sole proprietorship .","hl_sentences":"The elements of the financial statements shown on the statement of owner ’ s equity include investments by owners as well as distributions to owners . In addition , net income or net loss affects the value of the organization ( net income increases the value of the organization , and net loss decreases it ) .","question":{"cloze_format":"___ decreases owner’s equity.","normal_format":"Which of the following decreases owner’s equity?","question_choices":["investments by owners","losses","gains","short-term loans"],"question_id":"fs-idm380967216","question_text":"Which of the following decreases owner’s equity?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"no impact on equity"},"bloom":null,"hl_context":"<hl> Exchanges of assets for assets <hl> As you continue to develop your understanding of accounting , you will encounter many types of transactions involving different elements of the financial statements . The previous examples highlighted elements that change the equity of an organization . Not all transactions , however , ultimately impact equity . <hl> For example , the following do not impact the equity or net worth of the organization : 10 10 SFAC No . <hl> 6 , p . 20 .","hl_sentences":"Exchanges of assets for assets For example , the following do not impact the equity or net worth of the organization : 10 10 SFAC No .","question":{"cloze_format":"The effect on equity that exchanges of assets for assets have is that (they (have)) ___.","normal_format":"Exchanges of assets for assets have what effect on equity?","question_choices":["increase equity","no impact on equity","decrease equity","There is no relationship between assets and equity."],"question_id":"fs-idm381340624","question_text":"Exchanges of assets for assets have what effect on equity?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> Acquisitions of assets by incurring liabilities <hl> As you continue to develop your understanding of accounting , you will encounter many types of transactions involving different elements of the financial statements . The previous examples highlighted elements that change the equity of an organization . Not all transactions , however , ultimately impact equity . <hl> For example , the following do not impact the equity or net worth of the organization : 10 10 SFAC No . <hl> 6 , p . 20 .","hl_sentences":"Acquisitions of assets by incurring liabilities For example , the following do not impact the equity or net worth of the organization : 10 10 SFAC No .","question":{"cloze_format":"All of the following increase owner’s equity except ___","normal_format":"All of the following increase owner’s equity except for which one?","question_choices":["gains","investments by owners","revenues","acquisitions of assets by incurring liabilities"],"question_id":"fs-idm395691424","question_text":"All of the following increase owner’s equity except for which one?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"future potential sales price of inventory"},"bloom":null,"hl_context":"<hl> Elements of the Financial Statements <hl> <hl> The statement of owner ’ s equity , which is the second financial statement created by accountants , is a statement that shows how the equity ( or value ) of the organization has changed over time . <hl> Similar to the income statement , the statement of owner ’ s equity is for a specific period of time , typically one year . Recall that another way to think about equity is net worth , or value . So , the statement of owner ’ s equity is a financial statement that shows how the net worth , or value , of the business has changed for a given period of time . In essence , the overall purpose of financial statements is to evaluate the performance of a company , governmental entity , or not-for-profit entity . This chapter illustrates this through a company , which is considered to be in business to generate a profit . <hl> Each financial statement we examine has a unique function , and together they provide information to determine whether a company generated a profit or loss for a given period ( such as a month , quarter , or year ); the assets , which are resources of the company , and accompanying liabilities , which are obligations of the company , that are used to generate the profit or loss ; owner interest in profits or losses ; and the cash position of the company at the end of the period . <hl>","hl_sentences":"Elements of the Financial Statements The statement of owner ’ s equity , which is the second financial statement created by accountants , is a statement that shows how the equity ( or value ) of the organization has changed over time . Each financial statement we examine has a unique function , and together they provide information to determine whether a company generated a profit or loss for a given period ( such as a month , quarter , or year ); the assets , which are resources of the company , and accompanying liabilities , which are obligations of the company , that are used to generate the profit or loss ; owner interest in profits or losses ; and the cash position of the company at the end of the period .","question":{"cloze_format":"___ is not an element of the financial statements.","normal_format":"Which of the following is not an element of the financial statements?","question_choices":["future potential sales price of inventory","assets","liabilities","equity"],"question_id":"fs-idm339789968","question_text":"Which of the following is not an element of the financial statements?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"In this example using a fictitious company , Cheesy Chuck ’ s , we began with the account balances and demonstrated how to prepare the financial statements for the month of June , the first month of operations for the business . <hl> It will be helpful to revisit the process by summarizing the information we started with and how that information was used to create the four financial statements : income statement , statement of owner ’ s equity , balance sheet , and statement of cash flows . <hl>","hl_sentences":"It will be helpful to revisit the process by summarizing the information we started with and how that information was used to create the four financial statements : income statement , statement of owner ’ s equity , balance sheet , and statement of cash flows .","question":{"cloze_format":"___ is the correct order of preparing the financial statements.","normal_format":"Which of the following is the correct order of preparing the financial statements?","question_choices":["income statement, statement of cash flows, balance sheet, statement of owner’s equity","income statement, statement of owner’s equity, balance sheet, statement of cash flows","income statement, balance sheet, statement of owner’s equity, statement of cash flows","income statement, balance sheet, statement of cash flows, statement of owner’s equity"],"question_id":"fs-idm383825312","question_text":"Which of the following is the correct order of preparing the financial statements?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"company, statement title, time period of report"},"bloom":null,"hl_context":"<hl> The last line indicates the time frame of the financial statement . <hl> Do not forget the income statement is for a period of time ( the month of June in our example ) . <hl> The middle line indicates the financial statement that is being presented . <hl> <hl> The first line lists the business name . <hl> <hl> The heading of the income statement includes three lines . <hl>","hl_sentences":"The last line indicates the time frame of the financial statement . The middle line indicates the financial statement that is being presented . The first line lists the business name . The heading of the income statement includes three lines .","question":{"cloze_format":"The three heading lines of financial statements typically include ___ .","normal_format":"The three heading lines of financial statements typically include which of the following?","question_choices":["company, statement title, time period of report","company headquarters, statement title, name of preparer","statement title, time period of report, name of preparer","name of auditor, statement title, fiscal year end"],"question_id":"fs-idm374265504","question_text":"The three heading lines of financial statements typically include which of the following?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"<hl> Knowing the difference between the cash basis and accrual basis of accounting is necessary to understand the need for the statement of cash flows . <hl> <hl> Stakeholders need to know the financial performance ( as measured by the income statement — that is , net income or net loss ) and financial position ( as measured by the balance sheet — that is , assets , liabilities , and owners ’ equity ) of the business . <hl> This information is provided in the income statement , statement of owner ’ s equity , and balance sheet . However , since these financial statements are prepared using accrual accounting , stakeholders do not have a clear picture of the business ’ s cash activities . The statement of cash flows solves this inadequacy by specifically focusing on the cash inflows and cash outflows . 2.2 Define , Explain , and Provide Examples of Current and Noncurrent Assets , Current and Noncurrent Liabilities , Equity , Revenues , and Expenses <hl> The fourth and final financial statement prepared is the statement of cash flows , which is a statement that lists the cash inflows and cash outflows for the business for a period of time . <hl> At first glance , this may seem like a redundant financial statement . We know the income statement also reports the inflows and outflows for the business for a period of time . In addition , the statement of owner ’ s equity and the balance sheet help to show the other activities , such as investments by and distributions to owners that are not included in the income statement . To understand why the statement of cash flows is necessary , we must first understand the two bases of accounting used to prepare the financial statements . The changes in cash within this statement are often referred to as sources and uses of cash . A source of cash lets one see where cash is coming from . For example , is cash being generated from sales to customers , or is the cash a result of an advance in a large loan . Use of cash looks at what cash is being used for . Is cash being used to make an interest payment on a loan , or is cash being used to purchase a large piece of machinery that will expand business capacity ? The two bases of accounting are the cash basis and the accrual basis , briefly introduced in Describe the Income Statement , Statement of Owner ’ s Equity , Balance Sheet , and Statement of Cash Flows , and How They Interrelate .","hl_sentences":"Knowing the difference between the cash basis and accrual basis of accounting is necessary to understand the need for the statement of cash flows . Stakeholders need to know the financial performance ( as measured by the income statement — that is , net income or net loss ) and financial position ( as measured by the balance sheet — that is , assets , liabilities , and owners ’ equity ) of the business . The fourth and final financial statement prepared is the statement of cash flows , which is a statement that lists the cash inflows and cash outflows for the business for a period of time .","question":{"cloze_format":"The financial statement that shows the financial performance of the company on a cash basis is called the ___.","normal_format":"Which financial statement shows the financial performance of the company on a cash basis?","question_choices":["balance sheet","statement of owner’s equity","statement of cash flows","income statement"],"question_id":"fs-idm347423312","question_text":"Which financial statement shows the financial performance of the company on a cash basis?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"balance sheet"},"bloom":null,"hl_context":"<hl> The third financial statement created is the balance sheet , which shows the company ’ s financial position on a given date . <hl> Cheesy Chuck ’ s balance sheet is shown in Figure 2.13 . <hl> The balance sheet summarizes the financial position of the business on a given date . <hl> Meaning , because of the financial performance over the past twelve months , for example , this is the financial position of the business as of December 31 . Think of the balance sheet as being similar to a team ’ s overall win / loss record — to a certain extent a team ’ s strength can be perceived by its win / loss record .","hl_sentences":"The third financial statement created is the balance sheet , which shows the company ’ s financial position on a given date . The balance sheet summarizes the financial position of the business on a given date .","question":{"cloze_format":"The financial statement that shows the financial position of the company is the ___ .","normal_format":"Which financial statement shows the financial position of the company?","question_choices":["balance sheet","statement of owner’s equity","statement of cash flows","income statement"],"question_id":"fs-idm374579344","question_text":"Which financial statement shows the financial position of the company?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"<hl> The starting point for understanding liquidity ratios is to define working capital — current assets minus current liabilities . <hl> Recall that current assets and current liabilities are amounts generally settled in one year or less . <hl> Working capital ( current assets minus current liabilities ) is used to assess the dollar amount of assets a business has available to meet its short-term liabilities . <hl> A positive working capital amount is desirable and indicates the business has sufficient current assets to meet short-term obligations ( liabilities ) and still has financial flexibility . A negative amount is undesirable and indicates the business should pay particular attention to the composition of the current assets ( that is , how liquid the current assets are ) and to the timing of the current liabilities . It is unlikely that all of the current liabilities will be due at the same time , but the amount of working capital gives stakeholders of both small and large businesses an indication of the firm ’ s ability to meet its short-term obligations .","hl_sentences":"The starting point for understanding liquidity ratios is to define working capital — current assets minus current liabilities . Working capital ( current assets minus current liabilities ) is used to assess the dollar amount of assets a business has available to meet its short-term liabilities .","question":{"cloze_format":"Working capital is an indication of the firm’s ________.","normal_format":"Working capital is an indication of the firm’s which of the following?","question_choices":["asset utilization","amount of noncurrent liabilities","liquidity","amount of noncurrent assets"],"question_id":"fs-idm377566608","question_text":"Working capital is an indication of the firm’s ________."},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"In Describe the Income Statement , Statement of Owner ’ s Equity , Balance Sheet , and Statement of Cash Flows , and How They Interrelate , we discussed the function of and the basic characteristics of the statement of cash flows . This fourth and final financial statement lists the cash inflows and cash outflows for the business for a period of time . <hl> It was created to fill in some informational gaps that existed in the other three statements ( income statement , owner ’ s equity / retained earnings statement , and the balance sheet ) . <hl> A full demonstration of the creation of the statement of cash flows is presented in Statement of Cash Flows . <hl> The fourth and final financial statement prepared is the statement of cash flows , which is a statement that lists the cash inflows and cash outflows for the business for a period of time . <hl> At first glance , this may seem like a redundant financial statement . <hl> We know the income statement also reports the inflows and outflows for the business for a period of time . <hl> <hl> In addition , the statement of owner ’ s equity and the balance sheet help to show the other activities , such as investments by and distributions to owners that are not included in the income statement . <hl> To understand why the statement of cash flows is necessary , we must first understand the two bases of accounting used to prepare the financial statements . The changes in cash within this statement are often referred to as sources and uses of cash . A source of cash lets one see where cash is coming from . For example , is cash being generated from sales to customers , or is the cash a result of an advance in a large loan . Use of cash looks at what cash is being used for . Is cash being used to make an interest payment on a loan , or is cash being used to purchase a large piece of machinery that will expand business capacity ? The two bases of accounting are the cash basis and the accrual basis , briefly introduced in Describe the Income Statement , Statement of Owner ’ s Equity , Balance Sheet , and Statement of Cash Flows , and How They Interrelate .\",\n \"hl_sentences\": \"It was created to fill in some informational gaps that existed in the other three statements ( income statement , owner ’ s equity / retained earnings statement , and the balance sheet ) . The fourth and final financial statement prepared is the statement of cash flows , which is a statement that lists the cash inflows and cash outflows for the business for a period of time . We know the income statement also reports the inflows and outflows for the business for a period of time . In addition , the statement of owner ’ s equity and the balance sheet help to show the other activities , such as investments by and distributions to owners that are not included in the income statement .\",\n \"question\": {\n \"cloze_format\": \"The statement that is not one of the financial statements is the ___.\",\n \"normal_format\": \"Which of these statements is not one of the financial statements?\",\n \"question_choices\": [\n \"income statement\",\n \"balance sheet\",\n \"statement of cash flows\",\n \"statement of owner investments\"\n ],\n \"question_id\": \"fs-idm385189632\",\n \"question_text\": \"Which of these statements is not one of the financial statements?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"competitors\"\n },\n \"bloom\": null,\n \"hl_context\": \"Before exploring the specific financial statements , it is important to know why these are important documents . To understand this , you must first understand who the users of financial statements are . Users of the information found in financial statements are called stakeholders . <hl> A stakeholder is someone affected by decisions made by a company ; this can include groups or individuals affected by the actions or policies of an organization , including include investors , creditors , employees , managers , regulators , customers , and suppliers . <hl> <hl> The stakeholder ’ s interest sometimes is not directly related to the entity ’ s financial performance . <hl> <hl> Examples of stakeholders include lenders , investors / owners , vendors , employees and management , governmental agencies , and the communities in which the businesses operate . <hl> Stakeholders are interested in the performance of an organization for various reasons , but the common goal of using the financial statements is to understand the information each contains that is useful for making financial decisions . For example , a banker may be interested in the financial statements to decide whether or not to lend the organization money .\",\n \"hl_sentences\": \"A stakeholder is someone affected by decisions made by a company ; this can include groups or individuals affected by the actions or policies of an organization , including include investors , creditors , employees , managers , regulators , customers , and suppliers . The stakeholder ’ s interest sometimes is not directly related to the entity ’ s financial performance . Examples of stakeholders include lenders , investors / owners , vendors , employees and management , governmental agencies , and the communities in which the businesses operate .\",\n \"question\": {\n \"cloze_format\": \"Stakeholders are less likely to include ___.\",\n \"normal_format\": \"Stakeholders are less likely to include which of the following groups?\",\n \"question_choices\": [\n \"owners\",\n \"employees\",\n \"community leaders\",\n \"competitors\"\n ],\n \"question_id\": \"fs-idm370303680\",\n \"question_text\": \"Stakeholders are less likely to include which of the following groups?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"In accounting , this example illustrates an income statement , a financial statement that is used to measure the financial performance of an organization for a particular period of time . <hl> We use the simple landscaping account example to discuss the elements of the income statement , which are revenues , expenses , gains , and losses . <hl> Together , these determine whether the organization has net income ( where revenues and gains are greater than expenses and losses ) or net loss ( where expenses and losses are greater than revenues and gains ) . Revenues , expenses , gains , and losses are further defined here .\",\n \"hl_sentences\": \"We use the simple landscaping account example to discuss the elements of the income statement , which are revenues , expenses , gains , and losses .\",\n \"question\": {\n \"cloze_format\": \"The correct components of the income statement can be listed as ___.\",\n \"normal_format\": \"What are the correct components of the income statement?\",\n \"question_choices\": [\n \"revenues, losses, expenses, and gains\",\n \"assets, liabilities, and owner’s equity\",\n \"revenues, expenses, investments by owners, distributions to owners\",\n \"assets, liabilities, and dividends\"\n ],\n \"question_id\": \"fs-idm359834736\",\n \"question_text\": \"Identify the correct components of the income statement.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"assets, liabilities, and investments by owners\"\n },\n \"bloom\": null,\n \"hl_context\": \"Knowing the difference between the cash basis and accrual basis of accounting is necessary to understand the need for the statement of cash flows . <hl> Stakeholders need to know the financial performance ( as measured by the income statement — that is , net income or net loss ) and financial position ( as measured by the balance sheet — that is , assets , liabilities , and owners ’ equity ) of the business . <hl> This information is provided in the income statement , statement of owner ’ s equity , and balance sheet . However , since these financial statements are prepared using accrual accounting , stakeholders do not have a clear picture of the business ’ s cash activities . The statement of cash flows solves this inadequacy by specifically focusing on the cash inflows and cash outflows . 2.2 Define , Explain , and Provide Examples of Current and Noncurrent Assets , Current and Noncurrent Liabilities , Equity , Revenues , and Expenses\",\n \"hl_sentences\": \"Stakeholders need to know the financial performance ( as measured by the income statement — that is , net income or net loss ) and financial position ( as measured by the balance sheet — that is , assets , liabilities , and owners ’ equity ) of the business .\",\n \"question\": {\n \"cloze_format\": \"The balance sheet lists ___.\",\n \"normal_format\": \"The balance sheet lists which of the following?\",\n \"question_choices\": [\n \"assets, liabilities, and owners’ equity\",\n \"revenues, expenses, gains, and losses\",\n \"assets, liabilities, and investments by owners\",\n \"revenues, expenses, gains, and distributions to owners\"\n ],\n \"question_id\": \"fs-idm384816368\",\n \"question_text\": \"The balance sheet lists which of the following?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"Tangible assets have physical substance.\"\n },\n \"bloom\": null,\n \"hl_context\": \"Another thing you might have recognized when reviewing your list of coffee shop assets is that all of the items were something you could touch or move , each of which is known as a tangible asset . However , as you also learned in Describe the Income Statement , Statement of Owner ’ s Equity , Balance Sheet , and Statement of Cash Flows , and How They Interrelate , not all assets are tangible . <hl> An asset could be an intangible asset , meaning the item lacks physical substance — it cannot be touched or moved . <hl> Take a moment to think about your favorite type of shoe or a popular type of farm tractor . Would you be able to recognize the maker of that shoe or the tractor by simply seeing the logo ? Chances are you would . These are examples of intangible assets , trademarks to be precise . A trademark has value to the organization that created ( or purchased ) the trademark , and the trademark is something the organization controls — others cannot use the trademark without permission . An asset can also be categorized as a tangible asset or an intangible asset . <hl> Tangible assets have a physical nature , such as trucks or many inventory items , while intangible assets have value but often lack a physical existence or corpus , such as insurance policies or trademarks . <hl>\",\n \"hl_sentences\": \"An asset could be an intangible asset , meaning the item lacks physical substance — it cannot be touched or moved . Tangible assets have a physical nature , such as trucks or many inventory items , while intangible assets have value but often lack a physical existence or corpus , such as insurance policies or trademarks .\",\n \"question\": {\n \"cloze_format\": \"The statement that is true is that ___.\",\n \"normal_format\": \"Which of the following statements is true?\",\n \"question_choices\": [\n \"Tangible assets lack physical substance.\",\n \"Tangible assets will be consumed in a year or less.\",\n \"Tangible assets have physical substance.\",\n \"Tangible assets will be consumed in over a year.\"\n ],\n \"question_id\": \"fs-idm406688976\",\n \"question_text\": \"Which of the following statements is true?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> A corporation is a legal business structure involving one or more individuals ( owners ) who are legally distinct ( separate ) from the business . <hl> A primary benefit of a corporate legal structure is the owners of the organization have limited liability . That is , a corporation is “ stand alone , ” conducting business as an entity separate from its owners . Under the corporate structure , owners delegate to others ( called agents ) the responsibility to make day-to-day decisions regarding the operations of the business . Other benefits of the corporate legal structure include relatively easy access to large amounts of capital by obtaining loans or selling ownership ( stock ) , and since the stock is easily sold or transferred to others , the business operates beyond the life of the shareholders . A major disadvantage of a corporate legal structure is double taxation — the business pays income tax and the owners are taxed when distributions ( also called dividends ) are received .\",\n \"hl_sentences\": \"A corporation is a legal business structure involving one or more individuals ( owners ) who are legally distinct ( separate ) from the business .\",\n \"question\": {\n \"cloze_format\": \"Under the legal business structure of ___, owners have no personal liability. \",\n \"normal_format\": \"Owners have no personal liability under which legal business structure?\",\n \"question_choices\": [\n \"a corporation\",\n \"a partnership\",\n \"a sole proprietorship\",\n \"There is liability in every legal business structure.\"\n ],\n \"question_id\": \"fs-idm369250368\",\n \"question_text\": \"Owners have no personal liability under which legal business structure?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"Assets = Liabilities + Owner’s Equity\"\n },\n \"bloom\": null,\n \"hl_context\": \"Your Turn The Accounting Equation On a sheet of paper , use three columns to create your own accounting equation . <hl> In the first column , list all of the things you own ( assets ) . <hl> <hl> In the second column , list any amounts owed ( liabilities ) . <hl> <hl> In the third column , using the accounting equation , calculate , you guessed it , the net amount of the asset ( equity ) . <hl> When finished , total the columns to determine your net worth . Hint : do not forget to subtract the liability from the value of the asset .\",\n \"hl_sentences\": \"In the first column , list all of the things you own ( assets ) . In the second column , list any amounts owed ( liabilities ) . In the third column , using the accounting equation , calculate , you guessed it , the net amount of the asset ( equity ) .\",\n \"question\": {\n \"cloze_format\": \"The accounting equation is expressed as ________.\",\n \"normal_format\": \"What is the accounting equation?\",\n \"question_choices\": [\n \"Assets + Liabilities = Owner’s Equity\",\n \"Assets – Noncurrent Assets = Liabilities\",\n \"Assets = Liabilities + Investments by Owners\",\n \"Assets = Liabilities + Owner’s Equity\"\n ],\n \"question_id\": \"fs-idm369458480\",\n \"question_text\": \"The accounting equation is expressed as ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The elements of the financial statements shown on the statement of owner ’ s equity include investments by owners as well as distributions to owners . <hl> Investments by owners and distributions to owners are two activities that impact the value of the organization ( increase and decrease , respectively ) . <hl> In addition , net income or net loss affects the value of the organization ( net income increases the value of the organization , and net loss decreases it ) . <hl> Net income ( or net loss ) is also shown on the statement of owner ’ s equity ; this is an example of how the statements are interrelated . Note that the word owner ’ s ( singular for a sole owner ) changes to owners ’ ( plural , for a group of owners ) when preparing this statement for an entity with multiple owners versus a sole proprietorship .\",\n \"hl_sentences\": \"The elements of the financial statements shown on the statement of owner ’ s equity include investments by owners as well as distributions to owners . In addition , net income or net loss affects the value of the organization ( net income increases the value of the organization , and net loss decreases it ) .\",\n \"question\": {\n \"cloze_format\": \"___ decreases owner’s equity.\",\n \"normal_format\": \"Which of the following decreases owner’s equity?\",\n \"question_choices\": [\n \"investments by owners\",\n \"losses\",\n \"gains\",\n \"short-term loans\"\n ],\n \"question_id\": \"fs-idm380967216\",\n \"question_text\": \"Which of the following decreases owner’s equity?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"no impact on equity\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Exchanges of assets for assets <hl> As you continue to develop your understanding of accounting , you will encounter many types of transactions involving different elements of the financial statements . The previous examples highlighted elements that change the equity of an organization . Not all transactions , however , ultimately impact equity . <hl> For example , the following do not impact the equity or net worth of the organization : 10 10 SFAC No . <hl> 6 , p . 20 .\",\n \"hl_sentences\": \"Exchanges of assets for assets For example , the following do not impact the equity or net worth of the organization : 10 10 SFAC No .\",\n \"question\": {\n \"cloze_format\": \"The effect on equity that exchanges of assets for assets have is that (they (have)) ___.\",\n \"normal_format\": \"Exchanges of assets for assets have what effect on equity?\",\n \"question_choices\": [\n \"increase equity\",\n \"no impact on equity\",\n \"decrease equity\",\n \"There is no relationship between assets and equity.\"\n ],\n \"question_id\": \"fs-idm381340624\",\n \"question_text\": \"Exchanges of assets for assets have what effect on equity?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Acquisitions of assets by incurring liabilities <hl> As you continue to develop your understanding of accounting , you will encounter many types of transactions involving different elements of the financial statements . The previous examples highlighted elements that change the equity of an organization . Not all transactions , however , ultimately impact equity . <hl> For example , the following do not impact the equity or net worth of the organization : 10 10 SFAC No . <hl> 6 , p . 20 .\",\n \"hl_sentences\": \"Acquisitions of assets by incurring liabilities For example , the following do not impact the equity or net worth of the organization : 10 10 SFAC No .\",\n \"question\": {\n \"cloze_format\": \"All of the following increase owner’s equity except ___\",\n \"normal_format\": \"All of the following increase owner’s equity except for which one?\",\n \"question_choices\": [\n \"gains\",\n \"investments by owners\",\n \"revenues\",\n \"acquisitions of assets by incurring liabilities\"\n ],\n \"question_id\": \"fs-idm395691424\",\n \"question_text\": \"All of the following increase owner’s equity except for which one?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"future potential sales price of inventory\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Elements of the Financial Statements <hl> <hl> The statement of owner ’ s equity , which is the second financial statement created by accountants , is a statement that shows how the equity ( or value ) of the organization has changed over time . <hl> Similar to the income statement , the statement of owner ’ s equity is for a specific period of time , typically one year . Recall that another way to think about equity is net worth , or value . So , the statement of owner ’ s equity is a financial statement that shows how the net worth , or value , of the business has changed for a given period of time . In essence , the overall purpose of financial statements is to evaluate the performance of a company , governmental entity , or not-for-profit entity . This chapter illustrates this through a company , which is considered to be in business to generate a profit . <hl> Each financial statement we examine has a unique function , and together they provide information to determine whether a company generated a profit or loss for a given period ( such as a month , quarter , or year ); the assets , which are resources of the company , and accompanying liabilities , which are obligations of the company , that are used to generate the profit or loss ; owner interest in profits or losses ; and the cash position of the company at the end of the period . <hl>\",\n \"hl_sentences\": \"Elements of the Financial Statements The statement of owner ’ s equity , which is the second financial statement created by accountants , is a statement that shows how the equity ( or value ) of the organization has changed over time . Each financial statement we examine has a unique function , and together they provide information to determine whether a company generated a profit or loss for a given period ( such as a month , quarter , or year ); the assets , which are resources of the company , and accompanying liabilities , which are obligations of the company , that are used to generate the profit or loss ; owner interest in profits or losses ; and the cash position of the company at the end of the period .\",\n \"question\": {\n \"cloze_format\": \"___ is not an element of the financial statements.\",\n \"normal_format\": \"Which of the following is not an element of the financial statements?\",\n \"question_choices\": [\n \"future potential sales price of inventory\",\n \"assets\",\n \"liabilities\",\n \"equity\"\n ],\n \"question_id\": \"fs-idm339789968\",\n \"question_text\": \"Which of the following is not an element of the financial statements?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"In this example using a fictitious company , Cheesy Chuck ’ s , we began with the account balances and demonstrated how to prepare the financial statements for the month of June , the first month of operations for the business . <hl> It will be helpful to revisit the process by summarizing the information we started with and how that information was used to create the four financial statements : income statement , statement of owner ’ s equity , balance sheet , and statement of cash flows . <hl>\",\n \"hl_sentences\": \"It will be helpful to revisit the process by summarizing the information we started with and how that information was used to create the four financial statements : income statement , statement of owner ’ s equity , balance sheet , and statement of cash flows .\",\n \"question\": {\n \"cloze_format\": \"___ is the correct order of preparing the financial statements.\",\n \"normal_format\": \"Which of the following is the correct order of preparing the financial statements?\",\n \"question_choices\": [\n \"income statement, statement of cash flows, balance sheet, statement of owner’s equity\",\n \"income statement, statement of owner’s equity, balance sheet, statement of cash flows\",\n \"income statement, balance sheet, statement of owner’s equity, statement of cash flows\",\n \"income statement, balance sheet, statement of cash flows, statement of owner’s equity\"\n ],\n \"question_id\": \"fs-idm383825312\",\n \"question_text\": \"Which of the following is the correct order of preparing the financial statements?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"company, statement title, time period of report\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The last line indicates the time frame of the financial statement . <hl> Do not forget the income statement is for a period of time ( the month of June in our example ) . <hl> The middle line indicates the financial statement that is being presented . <hl> <hl> The first line lists the business name . <hl> <hl> The heading of the income statement includes three lines . <hl>\",\n \"hl_sentences\": \"The last line indicates the time frame of the financial statement . The middle line indicates the financial statement that is being presented . The first line lists the business name . The heading of the income statement includes three lines .\",\n \"question\": {\n \"cloze_format\": \"The three heading lines of financial statements typically include ___ .\",\n \"normal_format\": \"The three heading lines of financial statements typically include which of the following?\",\n \"question_choices\": [\n \"company, statement title, time period of report\",\n \"company headquarters, statement title, name of preparer\",\n \"statement title, time period of report, name of preparer\",\n \"name of auditor, statement title, fiscal year end\"\n ],\n \"question_id\": \"fs-idm374265504\",\n \"question_text\": \"The three heading lines of financial statements typically include which of the following?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Knowing the difference between the cash basis and accrual basis of accounting is necessary to understand the need for the statement of cash flows . <hl> <hl> Stakeholders need to know the financial performance ( as measured by the income statement — that is , net income or net loss ) and financial position ( as measured by the balance sheet — that is , assets , liabilities , and owners ’ equity ) of the business . <hl> This information is provided in the income statement , statement of owner ’ s equity , and balance sheet . However , since these financial statements are prepared using accrual accounting , stakeholders do not have a clear picture of the business ’ s cash activities . The statement of cash flows solves this inadequacy by specifically focusing on the cash inflows and cash outflows . 2.2 Define , Explain , and Provide Examples of Current and Noncurrent Assets , Current and Noncurrent Liabilities , Equity , Revenues , and Expenses <hl> The fourth and final financial statement prepared is the statement of cash flows , which is a statement that lists the cash inflows and cash outflows for the business for a period of time . <hl> At first glance , this may seem like a redundant financial statement . We know the income statement also reports the inflows and outflows for the business for a period of time . In addition , the statement of owner ’ s equity and the balance sheet help to show the other activities , such as investments by and distributions to owners that are not included in the income statement . To understand why the statement of cash flows is necessary , we must first understand the two bases of accounting used to prepare the financial statements . The changes in cash within this statement are often referred to as sources and uses of cash . A source of cash lets one see where cash is coming from . For example , is cash being generated from sales to customers , or is the cash a result of an advance in a large loan . Use of cash looks at what cash is being used for . Is cash being used to make an interest payment on a loan , or is cash being used to purchase a large piece of machinery that will expand business capacity ? The two bases of accounting are the cash basis and the accrual basis , briefly introduced in Describe the Income Statement , Statement of Owner ’ s Equity , Balance Sheet , and Statement of Cash Flows , and How They Interrelate .\",\n \"hl_sentences\": \"Knowing the difference between the cash basis and accrual basis of accounting is necessary to understand the need for the statement of cash flows . Stakeholders need to know the financial performance ( as measured by the income statement — that is , net income or net loss ) and financial position ( as measured by the balance sheet — that is , assets , liabilities , and owners ’ equity ) of the business . The fourth and final financial statement prepared is the statement of cash flows , which is a statement that lists the cash inflows and cash outflows for the business for a period of time .\",\n \"question\": {\n \"cloze_format\": \"The financial statement that shows the financial performance of the company on a cash basis is called the ___.\",\n \"normal_format\": \"Which financial statement shows the financial performance of the company on a cash basis?\",\n \"question_choices\": [\n \"balance sheet\",\n \"statement of owner’s equity\",\n \"statement of cash flows\",\n \"income statement\"\n ],\n \"question_id\": \"fs-idm347423312\",\n \"question_text\": \"Which financial statement shows the financial performance of the company on a cash basis?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"balance sheet\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The third financial statement created is the balance sheet , which shows the company ’ s financial position on a given date . <hl> Cheesy Chuck ’ s balance sheet is shown in Figure 2.13 . <hl> The balance sheet summarizes the financial position of the business on a given date . <hl> Meaning , because of the financial performance over the past twelve months , for example , this is the financial position of the business as of December 31 . Think of the balance sheet as being similar to a team ’ s overall win / loss record — to a certain extent a team ’ s strength can be perceived by its win / loss record .\",\n \"hl_sentences\": \"The third financial statement created is the balance sheet , which shows the company ’ s financial position on a given date . The balance sheet summarizes the financial position of the business on a given date .\",\n \"question\": {\n \"cloze_format\": \"The financial statement that shows the financial position of the company is the ___ .\",\n \"normal_format\": \"Which financial statement shows the financial position of the company?\",\n \"question_choices\": [\n \"balance sheet\",\n \"statement of owner’s equity\",\n \"statement of cash flows\",\n \"income statement\"\n ],\n \"question_id\": \"fs-idm374579344\",\n \"question_text\": \"Which financial statement shows the financial position of the company?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The starting point for understanding liquidity ratios is to define working capital — current assets minus current liabilities . <hl> Recall that current assets and current liabilities are amounts generally settled in one year or less . <hl> Working capital ( current assets minus current liabilities ) is used to assess the dollar amount of assets a business has available to meet its short-term liabilities . <hl> A positive working capital amount is desirable and indicates the business has sufficient current assets to meet short-term obligations ( liabilities ) and still has financial flexibility . A negative amount is undesirable and indicates the business should pay particular attention to the composition of the current assets ( that is , how liquid the current assets are ) and to the timing of the current liabilities . It is unlikely that all of the current liabilities will be due at the same time , but the amount of working capital gives stakeholders of both small and large businesses an indication of the firm ’ s ability to meet its short-term obligations .\",\n \"hl_sentences\": \"The starting point for understanding liquidity ratios is to define working capital — current assets minus current liabilities . Working capital ( current assets minus current liabilities ) is used to assess the dollar amount of assets a business has available to meet its short-term liabilities .\",\n \"question\": {\n \"cloze_format\": \"Working capital is an indication of the firm’s ________.\",\n \"normal_format\": \"Working capital is an indication of the firm’s which of the following?\",\n \"question_choices\": [\n \"asset utilization\",\n \"amount of noncurrent liabilities\",\n \"liquidity\",\n \"amount of noncurrent assets\"\n ],\n \"question_id\": \"fs-idm377566608\",\n \"question_text\": \"Working capital is an indication of the firm’s ________.\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":2,"string":"2"},"chapter_text":{"kind":"string","value":" 2.1 Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate \n\n The study of accounting requires an understanding of precise and sometimes complicated terminology, purposes, principles, concepts, and organizational and legal structures. Typically, your introductory accounting courses will familiarize you with the overall accounting environment, and for those of you who want greater detail, there is an assortment of more advanced accounting courses available. \n\n This chapter concentrates on the four major types of financial statements and their interactions, the major types of business structures, and some of the major terms and concepts used in this course. Coverage here is somewhat basic since these topics are accorded much greater detail in future chapters. \n\n Types of Business Structure \n\n As you learned in Role of Accounting in Society , virtually every activity that occurs in a business has an associated cost or value. Part of an accountant’s role is to quantify these activities, or transactions. \n\n Also, in business—and accounting in particular—it is necessary to distinguish the business entity from the individual owner(s). The personal transactions of the owners, employees, and other parties connected to the business should not be recorded in the organization’s records; this accounting principle is called the business entity concept . Accountants should record only business transactions in business records. \n\n This separation is also reflected in the legal structure of the business. There are several common types of legal business structures. While the accounting concepts for the various types of businesses are essentially the same regardless of the legal structure, the terminology will change slightly depending on the organization’s legal structure, and it is important to understand the differences. \n\n There are three broad categories for the legal structure of an organization: sole proprietorship, partnership, and corporation. A sole proprietorship is a legal business structure consisting of a single individual. Benefits of this type of structure include ease of formation, favorable tax treatment, and a high level of control over the business. The risks involved with sole proprietorships include unlimited personal liability and a limited life for the business. Unless the business is sold, the business ends when the owner retires or passes away. In addition, sole proprietorships have a fairly limited ability to raise capital (funding), and often sole proprietors have limited expertise—they are excellent at what they do but may have limited expertise in other important areas of business, such as accounting or marketing. \n\n A partnership is a legal business structure consisting of an association of two or more people who contribute money, property, or services to operate as co-owners of a business. Benefits of this type of structure include favorable tax treatment, ease of formation of the business, and better access to capital and expertise. The downsides to a partnership include unlimited personal liability (although there are other legal structures—a limited liability partnership, for example—to help mitigate the risk); limited life of the partnership, similar to sole proprietorships; and increased complexity to form the venture (decision-making authority, profit-sharing arrangement, and other important issues need to be formally articulated in a written partnership agreement). \n\n A corporation is a legal business structure involving one or more individuals (owners) who are legally distinct (separate) from the business. A primary benefit of a corporate legal structure is the owners of the organization have limited liability. That is, a corporation is “stand alone,” conducting business as an entity separate from its owners. Under the corporate structure, owners delegate to others (called agents) the responsibility to make day-to-day decisions regarding the operations of the business. Other benefits of the corporate legal structure include relatively easy access to large amounts of capital by obtaining loans or selling ownership (stock), and since the stock is easily sold or transferred to others, the business operates beyond the life of the shareholders. A major disadvantage of a corporate legal structure is double taxation—the business pays income tax and the owners are taxed when distributions (also called dividends) are received. \n\n Types of Business Structures \n\n \n\n Sole Proprietorship \n\n Partnership \n\n Corporation \n\n Number of Owners \n\n Single individual \n\n Two or more individuals \n\n One or more owners \n\n Ease of Formation \n\n Easier to form \n\n Harder to form \n\n Difficult to form \n\n Ability to Raise Capital \n\n Difficult to raise capital \n\n Harder to raise capital \n\n Easier to raise capital \n\n Liability Risk \n\n Unlimited liability \n\n Unlimited liability \n\n Limited liability \n\n Taxation Consideration \n\n Single taxation \n\n Single taxation \n\n Double taxation \n\n Table 2.1 \n\n The Four Financial Statements \n\n Are you a fan of books, movies, or sports? If so, chances are you have heard or said the phrase “spoiler alert.” It is used to forewarn readers, viewers, or fans that the ending of a movie or book or outcome of a game is about to be revealed. Some people prefer knowing the end and skipping all of the details in the middle, while others prefer to fully immerse themselves and then discover the outcome. People often do not know or understand what accountants produce or provide. That is, they are not familiar with the “ending” of the accounting process, but that is the best place to begin the study of accounting. \n\n Accountants create what are known as financial statements. Financial statements are reports that communicate the financial performance and financial position of the organization. \n\n In essence, the overall purpose of financial statements is to evaluate the performance of a company, governmental entity, or not-for-profit entity. This chapter illustrates this through a company, which is considered to be in business to generate a profit. Each financial statement we examine has a unique function, and together they provide information to determine whether a company generated a profit or loss for a given period (such as a month, quarter, or year); the assets, which are resources of the company, and accompanying liabilities, which are obligations of the company, that are used to generate the profit or loss; owner interest in profits or losses; and the cash position of the company at the end of the period. \n\n The four financial statements that perform these functions and the order in which we prepare them are: \n\n Income Statement \n\n Statement of Owner’s Equity \n\n Balance Sheet \n\n Statement of Cash Flows. \n\n The order of preparation is important as it relates to the concept of how financial statements are interrelated. Before explaining each in detail, let’s explore the purpose of each financial statement and its main components. \n\n Continuing Application Introduction to the Gearhead Outfitters Story Gearhead Outfitters , founded by Ted Herget in 1997 in Jonesboro, Arkansas, is a retail chain that sells outdoor gear for men, women, and children. The company’s inventory includes clothing, footwear for hiking and running, camping gear, backpacks, and accessories, by brands such as The North Face , Birkenstock , Wolverine , Yeti , Altra , Mizuno , and Patagonia . Herget fell in love with the outdoor lifestyle while working as a ski instructor in Colorado and wanted to bring that feeling back home to Arkansas. And so, Gearhead was born in a small downtown location in Jonesboro. The company has had great success over the years, expanding to numerous locations in Herget’s home state, as well as Louisiana, Oklahoma, and Missouri. \n\n While Herget knew his industry when starting Gearhead , like many entrepreneurs he faced regulatory and financial issues that were new to him. Several of these issues were related to accounting and the wealth of decision-making information that accounting systems provide. \n\n For example, measuring revenue and expenses, providing information about cash flow to potential lenders, analyzing whether profit and positive cash flow is sustainable to allow for expansion, and managing inventory levels. Accounting, or the preparation of financial statements (balance sheet, income statement, and statement of cash flows), provides the mechanism for business owners such as Herget to make fundamentally sound business decisions. \n\n Purpose of Financial Statements \n\n Before exploring the specific financial statements, it is important to know why these are important documents. To understand this, you must first understand who the users of financial statements are. Users of the information found in financial statements are called stakeholders. A stakeholder is someone affected by decisions made by a company; this can include groups or individuals affected by the actions or policies of an organization, including include investors, creditors, employees, managers, regulators, customers, and suppliers. The stakeholder’s interest sometimes is not directly related to the entity’s financial performance. Examples of stakeholders include lenders, investors/owners, vendors, employees and management, governmental agencies, and the communities in which the businesses operate. Stakeholders are interested in the performance of an organization for various reasons, but the common goal of using the financial statements is to understand the information each contains that is useful for making financial decisions. For example, a banker may be interested in the financial statements to decide whether or not to lend the organization money. \n\n Likewise, small business owners may make decisions based on their familiarity with the business—they know if the business is doing well or not based on their “gut feeling.” By preparing the financial statements, accountants can help owners by providing clarity of the organization’s financial performance. It is important to understand that, in the long term, every activity of the business has a financial impact, and financial statements are a way that accountants report the activities of the business. Stakeholders must make many decisions, and the financial statements provide information that is helpful in the decision-making process. \n\n As described in Role of Accounting in Society , the complete set of financial statements acts as an X-ray of a company’s financial health. By evaluating all of the financial statements together, someone with financial knowledge can determine the overall health of a company. The accountant can use this information to advise outside (and inside) stakeholders on decisions, and management can use this information as one tool to make strategic short- and long-term decisions. \n\n Ethical Considerations Utilitarian View of Accounting Decisions and Stakeholder Well-Being Utilitarianism is a well-known and influential moral theory commonly used as a framework to evaluate business decisions. Utilitarianism suggests that an ethical action is one whose consequence achieves the greatest good for the greatest number of people. So, if we want to make an ethical decision, we should ask ourselves who is helped and who is harmed by it. Focusing on consequences in this way generally does not require us to take into account the means of achieving that particular end, however. Put simply, the utilitarian view is an ethical theory that the best action of a company is the one that maximizes utility of all stakeholders to the decision. This view assumes that all individuals with an interest in the business are considered within the decision. \n\n Financial statements are used to understand the financial performance of companies and to make long- and short-term decisions. A utilitarian approach considers all stakeholders, and both the long- and short-term effects of a business decision. This allows corporate decision makers to choose business actions with the potential to produce the best outcomes for the majority of all stakeholders, not just shareholders, and therefore maximize stakeholder happiness. \n\n Accounting decisions can change the approach a stakeholder has in relation to a business. If a company focuses on modifying operations and financial reporting to maximize short-term shareholder value, this could indicate the prioritization of certain stakeholder interests above others. When a company pursues only short-term profit for shareholders, it neglects the well-being of other stakeholders. Professional accountants should be aware of the interdependent relationship between all stakeholders and consider whether the results of their decisions are good for the majority of stakeholder interests. \n\n Your Turn Business Owners as Decision Makers Think of a business owner in your family or community. Schedule some time to talk with the business owner, and find out how he or she uses financial information to make decisions. \n\n Solution \n\n Business owners will use financial information for many decisions, such as comparing sales from one period to another, determining trends in costs and other expenses, and identifying areas in which to reduce or reallocate expenses. This information will be used to determine, for example, staffing and inventory levels, streamlining of operations, and advertising or other investment decisions. \n\n The Income Statement \n\n The first financial statement prepared is the income statement , a statement that shows the organization’s financial performance for a given period of time . Let’s illustrate the purpose of an income statement using a real-life example. Assume your friend, Chris, who is a sole proprietor, started a summer landscaping business on August 1, 2020. It is categorized as a service entity. To keep this example simple, assume that she is using her family’s tractor, and we are using the cash basis method of accounting to demonstrate Chris’s initial operations for her business. The other available basis method that is commonly used in accounting is the accrual basis method. She is responsible for paying for fuel and any maintenance costs. She named the business Chris’ Landscaping. On August 31, Chris checked the account balance and noticed there is only $250 in the checking account. This balance is lower than expected because she thought she had been paid by some customers. Chris decides to do some research to determine why the balance in the checking account is lower than expected. Her research shows that she earned a total of $1,400 from her customers but had to pay $100 to fix the brakes on her tractor, $50 for fuel, and also made a $1,000 payment to the insurance company for business insurance. The reason for the lower-than-expected balance was due to the fact that she spent ($1,150 for brakes, fuel, and insurance) only slightly less than she earned ($1,400)—a net increase of $250. While she would like the checking balance to grow each month, she realizes most of the August expenses were infrequent (brakes and insurance) and the insurance, in particular, was an unusually large expense. She is convinced the checking account balance will likely grow more in September because she will earn money from some new customers; she also anticipates having fewer expenses. \n\n The Income Statement can also be visualized by the formula: Revenue – Expenses = Net Income/(Loss). \n\n Let’s change this example slightly and assume the $1,000 payment to the insurance company will be paid in September, rather than in August. In this case, the ending balance in Chris’s checking account would be $1,250, a result of earning $1,400 and only spending $100 for the brakes on her car and $50 for fuel. This stream of cash flows is an example of cash basis accounting because it reflects when payments are received and made, not necessarily the time period that they affect. At the end of this section and in The Adjustment Process you will address accrual accounting, which does reflect the time period that they affect. \n\n In accounting, this example illustrates an income statement, a financial statement that is used to measure the financial performance of an organization for a particular period of time. We use the simple landscaping account example to discuss the elements of the income statement, which are revenues, expenses, gains, and losses. Together, these determine whether the organization has net income (where revenues and gains are greater than expenses and losses) or net loss (where expenses and losses are greater than revenues and gains). Revenues, expenses, gains, and losses are further defined here. \n\n Revenue \n\n Revenue 1 is the value of goods and services the organization sold or provided to customers for a given period of time. In our current example, Chris’s landscaping business, the “revenue” earned for the month of August would be $1,400. It is the value Chris received in exchange for the services provided to her clients. Likewise, when a business provides goods or services to customers for cash at the time of the service or in the future, the business classifies the amount(s) as revenue. Just as the $1,400 earned from a business made Chris’s checking account balance increase, revenues increase the value of a business. In accounting, revenues are often also called sales or fees earned. Just as earning wages from a business or summer job reflects the number of hours worked for a given rate of pay or payments from clients for services rendered, revenues (and the other terms) are used to indicate the dollar value of goods and services provided to customers for a given period of time. 1 In a subsequent section of this chapter, you will learn that the accounting profession is governed by the Financial Accounting Standards Board (or FASB), a professional body that issues guidelines/pronouncements for the accounting profession. A set of theoretical pronouncements issued by FASB is called Statement of Financial Accounting Concepts (SFAC). In SFAC No. 6, FASB defines revenues as “inflows or other enhancements of assets of an entity or settlements of its liabilities (or a combination of both) from delivering or producing goods, rendering services, or other activities that constitute the entity’s ongoing major or central operations” (SFAC No. 6, p. 23). \n\n Your Turn Coffee Shop Products Think about the coffee shop in your area. Identify items the coffee shop sells that would be classified as revenues. Remember, revenues for the coffee shop are related to its primary purpose: selling coffee and related items. Or, better yet, make a trip to the local coffee shop and get a first-hand experience. \n\n Solution \n\n Many coffee shops earn revenue through multiple revenue streams, including coffee and other specialty drinks, food items, gift cards, and merchandise. \n\n Expenses \n\n An expense 2 is a cost associated with providing goods or services to customers. In our opening example, the expenses that Chris incurred totaled $1,150 (consisting of $100 for brakes, $50 for fuel, and $1,000 for insurance). You might think of expenses as the opposite of revenue in that expenses reduce Chris’s checking account balance. Likewise, expenses decrease the value of the business and represent the dollar value of costs incurred to provide goods and services to customers for a given period of time. 2 Expenses are formally defined by the FASB as “outflows or other using up of assets or incurrences of liabilities (or a combination of both) from delivering or producing goods, rendering services, or carrying out other activities that constitute the entity’s ongoing major or central operations” (SFAC No. 6, p. 23). \n\n Your Turn Coffee Shop Expenses While thinking about or visiting the coffee shop in your area, look around (or visualize) and identify items or activities that are the expenses of the coffee shop. Remember, expenses for the coffee shop are related to resources consumed while generating revenue from selling coffee and related items. Do not forget about any expenses that might not be so obvious—as a general rule, every activity in a business has an associated cost. \n\n Solution \n\n Costs of the coffee shop that might be readily observed would include rent; wages for the employees; and the cost of the coffee, pastries, and other items/merchandise that may be sold. In addition, costs such as utilities, equipment, and cleaning or other supplies might also be readily observable. More obscure costs of the coffee shop would include insurance, regulatory costs such as health department licensing, point-of-sale/credit card costs, advertising, donations, and payroll costs such as workers’ compensation, unemployment, and so on. \n\n Gains \n\n A gain 3 can result from selling ancillary business items for more than the items are worth. (Ancillary business items are those that are used to support business operations.) To illustrate the concept of a gain, let’s return to our example. However, this example and the accompanying losses example are not going to be part of our income statement, balance sheet, or owner’s equity statement discussions. The gains and losses examples are only to be used in demonstrating the concepts of gains and losses. Assume that Chris paid $1,500 for a small piece of property to use for building a storage facility for her company. Further assume that Chris has an opportunity to sell the land for $2,000. She subsequently found a better storage option and decided to sell the property. After doing so, Chris will have a gain of $500 (a selling price of $2,000 and a cost of $1,500) and will also have $2,000 to deposit into her checking account, which would increase the balance. 3 FASB notes that gains represent an increase in organizational value from activities that are “ incidental or peripheral ” (SFAC No. 6, p. 24) to the primary purpose of the business. \n\n Thinking back to the proceeds ($1,400) Chris received from her landscaping business, we might ask the question: how are gains similar to and different from revenues? The revenue of $1,400 that Chris earned from her business and the $2,000 she received from selling the land are similar in that both increase her checking account balance and make her business more valuable. \n\n A difference, however, is evident if we consider how these funds were earned. Chris earned the $1,400 because she provided services (her labor) to her clients. Chris’s primary objective is to earn revenue by working for her clients. In addition, earning money by selling her land was an infrequent event for Chris, since her primary job was serving as a landscaper. Her primary goal is to earn fees or revenue, not to earn money by selling land. In fact, she cannot consider doing that again because she does not have additional land to sell. \n\n The primary goal of a business is to earn revenue by providing goods and services to customers in exchange for cash at that time or in the future. While selling other items for more than the value of the item does occur in business, these transactions are classified as gains, because these sales are infrequent and not the primary purpose of the business. \n\n Losses \n\n A loss 4 results from selling ancillary business items for less than the items are worth. To illustrate, let’s now assume that Chris sells her land that she purchased for $1,500 at a sales price of $1,200. In this case she would realize (incur) a loss of $300 on the sale of the property ($1,200 sales price minus the $1,500 cost of purchasing the property) and will also have $1,200 to deposit into her checking account, which would increase the balance. 4 FASB notes losses represent a decrease in organizational value from activities that are “ incidental or peripheral ” (SFAC No. 6, p. 24) to the primary purpose of the business. \n\n You should not be confused by the fact that the checking account balance increased even though this transaction resulted in a financial loss. Chris received $1,200 that she can deposit into her checking account and use for future expenses. The $300 loss simply indicates that she received less for the land than she paid for it. These are two aspects of the same transaction that communicate different things, and it is important to understand the differences. \n\n As we saw when comparing gains and revenues, losses are similar to expenses in that both losses and expenses decrease the value of the organization. In addition, just as Chris’s primary goal is to earn money from her job rather than selling land, in business, losses refer to infrequent transactions involving ancillary items of the business. \n\n Net Income (Net Loss) \n\n Net income (net loss) is determined by comparing revenues and expenses. Net income is a result of revenues (inflows) being greater than expenses (outflows). A net loss occurs when expenses (outflows) are greater than revenues (inflows). In accounting it is common to present net income in the following format: \n\n Recall that revenue is the value of goods and services a business provides to its customers and increase the value of the business. Expenses, on the other hand, are the costs of providing the goods and services and decrease the value of the business. When revenues exceed expenses, companies have net income. This means the business has been successful at earning revenues, containing expenses, or a combination of both. If, on the other hand, expenses exceed revenues, companies experience a net loss. This means the business was unsuccessful in earning adequate revenues, sufficiently containing expenses, or a combination of both. While businesses work hard to avoid net loss situations, it is not uncommon for a company to sustain a net loss from time-to-time. It is difficult, however, for businesses to remain viable while experiencing net losses over the long term. \n\n Shown as a formula, the net income (loss) function is: \n\n To be complete, we must also consider the impact of gains and losses. While gains and losses are infrequent in a business, it is not uncommon that a business would present a gain and/or loss in its financial statements. Recall that gains are similar to revenue and losses are similar to expenses. Therefore, the traditional accounting format would be: \n\n Shown as a formula, the net income (loss) function, including gains and losses, is: \n\n When assessing a company’s net income, it is important to understand the source of the net income. Businesses strive to attain “high-quality” net income (earnings). High-quality earnings are based on sustainable earnings—also called permanent earnings—while relying less on infrequent earnings—also called temporary earnings. Recall that revenues represent the ongoing value of goods and services the business provides (sells) to its customers, while gains are infrequent and involve items ancillary to the primary purpose of the business. We should use caution if a business attains a significant portion of its net income as a result of gains, rather than revenues. Likewise, net losses derived as a result of losses should be put into the proper perspective due to the infrequent nature of losses. While net losses are undesirable for any reason, net losses that result from expenses related to ongoing operations, rather than losses that are infrequent, are more concerning for the business. \n\n Statement of Owner’s Equity \n\n Equity is a term that is often confusing but is a concept with which you are probably already familiar. In short, equity is the value of an item that remains after considering what is owed for that item. The following example may help illustrate the concept of equity. \n\n When thinking about the concept of equity, it is often helpful to think about an example many families are familiar with: purchasing a home. Suppose a family purchases a home worth $200,000. After making a down payment of $25,000, they secure a bank loan to pay the remaining $175,000. What is the value of the family’s equity in the home? If you answered $25,000, you are correct. At the time of the purchase, the family owns a home worth $200,000 (an asset), but they owe $175,000 (a liability), so the equity or net worth in the home is $25,000. \n\n The statement of owner’s equity , which is the second financial statement created by accountants, is a statement that shows how the equity (or value) of the organization has changed over time. Similar to the income statement, the statement of owner’s equity is for a specific period of time, typically one year. Recall that another way to think about equity is net worth, or value. So, the statement of owner’s equity is a financial statement that shows how the net worth, or value, of the business has changed for a given period of time. \n\n The elements of the financial statements shown on the statement of owner’s equity include investments by owners as well as distributions to owners . Investments by owners and distributions to owners are two activities that impact the value of the organization (increase and decrease, respectively). In addition, net income or net loss affects the value of the organization (net income increases the value of the organization, and net loss decreases it). Net income (or net loss) is also shown on the statement of owner’s equity; this is an example of how the statements are interrelated. Note that the word owner’s (singular for a sole owner) changes to owners’ (plural, for a group of owners) when preparing this statement for an entity with multiple owners versus a sole proprietorship. \n\n In our example, to make it less complicated, we started with the first month of operations for Chris’s Landscaping. In the first month of operations, the owner’s equity total begins the month of August 2020, at $0, since there have been no transactions. During the month, the business received revenue of $1,400 and incurred expenses of $1,150, for net income of $250. Since Chris did not contribute any investment or make any withdrawals, other than the $1,150 for expenses, the ending balance in the owner’s equity account on August 31, 2020, would be $250, the net income earned. \n\n At this stage, it’s important to point out that we are working with a sole proprietorship to help simplify the examples. We have addressed the owner’s value in the firm as capital or owner’s equity . However, later we switch the structure of the business to a corporation, and instead of owner’s equity we begin using stockholder’s equity, which includes account titles such as common stock and retained earnings to represent the owners’ interests. \n\n The corporate treatment is more complicated because corporations may have a few owners up to potentially thousands of owners (stockholders). More detail on this issue is provided in Define, Explain, and Provide Examples of Current and Noncurrent Assets, Current and Noncurrent Liabilities, Equity, Revenues, and Expenses . \n\n Investments by Owners \n\n Generally, there are two ways by which organizations become more valuable: profitable operations (when revenues exceed expenses) and investments by owners. Organizations often have long-term goals or projects that are very expensive (for example, building a new manufacturing facility or purchasing another company). \n\n While having profitable operations is a viable way to “fund” these goals and projects, organizations often want to undertake these projects in a quicker time frame. Selling ownership is one way to quickly obtain the funding necessary for these goals. Investments by owners represent an exchange of cash or other assets for which the investor is given an ownership interest in the organization. This is a mutually beneficial arrangement: the organization gets the funding it needs on a timely basis, and the investor gets an ownership interest in the organization. \n\n When organizations generate funding by selling ownership, the ownership interest usually takes the form of common stock , which is the corporation’s primary class of stock issued, with each share representing a partial claim to ownership or a share of the company’s business. When the organization issues common stock for the first time, it is called an initial public offering (IPO) . In Corporation Accounting , you learn more about the specifics of this type of accounting. Once a company issues (or sells) common stock after an IPO, we describe the company as a publicly traded company , which simply means the company’s stock can be purchased by the general public on a public exchange like the New York Stock Exchange (NYSE). That is, investors can become owners of the particular company. Companies that issue publicly traded common shares in the United States are regulated by the Securities and Exchange Commission (SEC) , a federal regulatory agency that, among other responsibilities, is charged with oversight of financial investments such as common stock. \n\n Concepts In Practice Roku Goes Public On September 1, 2017, Roku, Inc. filed a Form S-1 with the Securities and Exchange Commission (SEC). 5 In this form, Roku disclosed its intention to become a publicly traded company, meaning its stock will trade (sell) on public stock exchanges, allowing individual and institutional investors an opportunity to own a portion (shares) of the company. The Form S-1 included detailed financial and nonfinancial information about the company. The information from Roku also included the purpose of the offering as well as the intended uses of the funds. Here is a portion of the disclosure: “The principal purposes of this offering are to increase our capitalization and financial flexibility and create a public market for our Class A common stock. We intend to use the net proceeds we receive from this offering primarily for general corporate purposes, including working capital . . . research and development, business development, sales and marketing activities and capital expenditures.” 6 5 Roku, Inc. “Form S-1 Filing with the Securities and Exchange Commission.” September 1, 2017. https://www.sec.gov/Archives/edgar/data/1428439/000119312517275689/d403225ds1.htm 6 Roku, Inc. “Form S-1 Filing with the Securities and Exchange Commission.” September 1, 2017. https://www.sec.gov/Archives/edgar/data/1428439/000119312517275689/d403225ds1.htm \n\n On September 28, 2017, Roku “went public” and exceeded expectations. Prior to the IPO, Roku estimated it would sell between $12 and $14 per share, raising over $117 million for the company. The closing price per share on September 28 was $23.50, nearly doubling initial expectations for the share value. 7 7 Roku, Inc. Data. https://finance.yahoo.com/quote/ROKU/history?p=ROKU \n\n Distributions to Owners \n\n There are basically two ways in which organizations become less valuable in terms of owners’ equity: from unprofitable operations (when expenses or losses exceed revenues or gains) and by distributions to owners. Owners (investors) of an organization want to see their investment appreciate (gain) in value. Over time, owners of common stock can see the value of the stock increase in value—the share price increases—due to the success of the organization. Organizations may also make distributions to owners , which are periodic rewards issued to the owners in the form of cash or other assets. Distributions to owners represent some of the value (equity) of the organization. \n\n For investors who hold common stock in the organization, these periodic payments or distributions to owners are called dividends . For sole proprietorships, distributions to owners are withdrawals or drawings. From the organization’s perspective, dividends represent a portion of the net worth (equity) of the organization that is returned to owners as a reward for their investment. While issuing dividends does, in fact, reduce the organization’s assets, some argue that paying dividends increases the organization’s long-term value by making the stock more desirable. (Note that this topic falls under the category of “dividend policy” and there is a significant stream of research addressing this.) \n\n Balance Sheet \n\n Once the statement of owner’s equity is completed, accountants typically complete the balance sheet , a statement that lists what the organization owns ( assets ), what it owes ( liabilities ), and what it is worth ( equity ) on a specific date . Notice the change in timing of the report. The income statement and statement of owner’s equity report the financial performance and equity change for a period of time. The balance sheet, however, lists the financial position at the close of business on a specific date. (Refer to Figure 2.2 for the balance sheet as of August 31, 2020, for Chris’ Landscaping.) \n\n Assets \n\n If you recall our previous example involving Chris and her newly established landscaping business, you are probably already familiar with the term asset 8 —these are resources used to generate revenue. In Chris’s business, to keep the example relatively simple, the business ended the month with one asset, cash, assuming that the insurance was for one month’s coverage. 8 The FASB defines assets as “probable future economic benefits obtained or controlled by a particular entity as a result of past transactions or events” (SFAC No. 6, p. 12). \n\n However, as organizations become more complex, they often have dozens or more types of assets. An asset can be categorized as a short-term asset or current asset (which is typically used up, sold, or converted to cash in one year or less) or as a long-term asset or noncurrent asset (which is not expected to be converted into cash or used up within one year). Long-term assets are often used in the production of products and services. \n\n Examples of short-term assets that businesses own include cash, accounts receivable, and inventory, while examples of long-term assets include land, machinery, office furniture, buildings, and vehicles. Several of the chapters that you will study are dedicated to an in-depth coverage of the special characteristics of selected assets. Examples include Merchandising Transactions , which are typically short term, and Long-Term Assets , which are typically long term. \n\n An asset can also be categorized as a tangible asset or an intangible asset. Tangible assets have a physical nature, such as trucks or many inventory items, while intangible assets have value but often lack a physical existence or corpus, such as insurance policies or trademarks. \n\n Liabilities \n\n You are also probably already familiar with the term liability 9 —these are amounts owed to others (called creditors). A liability can also be categorized as a short-term liability (or current liability ) or a long-term liability (or noncurrent liability ), similar to the treatment accorded assets. Short-term liabilities are typically expected to be paid within one year or less, while long-term liabilities are typically expected to be due for payment more than one year past the current balance sheet date. 9 The FASB defines liabilities as “probable future sacrifices of economic benefits arising from present obligations of a particular entity to transfer assets or provide services to other entities in the future as a result of past transactions or events” (SFAC No. 6, p. 13). \n\n Common short-term liabilities or amounts owed by businesses include amounts owed for items purchased on credit (also called accounts payable ), taxes, wages, and other business costs that will be paid in the future. Long-term liabilities can include such liabilities as long-term notes payable, mortgages payable, or bonds payable. \n\n Equity \n\n In the Statement of Owner’s Equity discussion, you learned that equity (or net assets ) refers to book value or net worth. In our example, Chris’s Landscaping, we determined that Chris had $250 worth of equity in her company at the end of the first month (see Figure 2.2 ). \n\n At any point in time it is important for stakeholders to know the financial position of a business. Stated differently, it is important for employees, managers, and other interested parties to understand what a business owns, owes, and is worth at any given point. This provides stakeholders with valuable financial information to make decisions related to the business. \n\n Statement of Cash Flows \n\n The fourth and final financial statement prepared is the statement of cash flows , which is a statement that lists the cash inflows and cash outflows for the business for a period of time. At first glance, this may seem like a redundant financial statement. We know the income statement also reports the inflows and outflows for the business for a period of time. In addition, the statement of owner’s equity and the balance sheet help to show the other activities, such as investments by and distributions to owners that are not included in the income statement. To understand why the statement of cash flows is necessary, we must first understand the two bases of accounting used to prepare the financial statements. The changes in cash within this statement are often referred to as sources and uses of cash. A source of cash lets one see where cash is coming from. For example, is cash being generated from sales to customers, or is the cash a result of an advance in a large loan. Use of cash looks at what cash is being used for. Is cash being used to make an interest payment on a loan, or is cash being used to purchase a large piece of machinery that will expand business capacity? The two bases of accounting are the cash basis and the accrual basis, briefly introduced in Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate . \n\n Under cash basis accounting , transactions (i.e., a sale or a purchase) are not recorded in the financial statements until there is an exchange of cash. This type of accounting is permitted for nonprofit entities and small businesses that elect to use this type of accounting. Under accrual basis accounting , transactions are generally recorded in the financial statement when the transactions occur, and not when paid, although in some situations the two events could happen on the same day. \n\n An example of the two methods (cash versus accrual accounting) would probably help clarify their differences. Assume that a mechanic performs a tune-up on a client’s car on May 29, and the customer picks up her car and pays the mechanic $100 on June 2. If the mechanic were using the cash method, the revenue would be recognized on June 2, the date of payment, and any expenses would be recognized when paid. \n\n If the accrual method were used, the mechanic would recognize the revenue and any related expenses on May 29, the day the work was completed. The accrual method will be the basis for your studies here (except for our coverage of the cash flow statement in Statement of Cash Flows ). The accrual method is also discussed in greater detail in Explain the Steps within the Accounting Cycle through the Unadjusted Trial Balance . \n\n While the cash basis of accounting is suited well and is more efficient for small businesses and certain types of businesses, such as farming, and those without inventory, like lawyers and doctors, the accrual basis of accounting is theoretically preferable to the cash basis of accounting. Accrual accounting is advantageous because it distinguishes between the timing of the transactions (when goods and services are provided) and when the cash involved in the transactions is exchanged (which can be a significant amount of time after the initial transaction). This allows accountants to provide, in a timely manner, relevant and complete information to stakeholders. The Adjustment Process explores several common techniques involved in accrual accounting. \n\n Two brief examples may help illustrate the difference between cash accounting and accrual accounting. Assume that a business sells $200 worth of merchandise. In some businesses, there are two ways the customers pay: cash and credit (also referred to as “on account”). Cash sales include checks and credit cards and are paid at the time of the sale. Credit sales (not to be confused with credit card sales) allow the customer to take the merchandise but pay within a specified period of time, usually up to forty-five days. \n\n A cash sale would be recorded in the financial statements under both the cash basis and accrual basis of accounting. It makes sense because the customer received the merchandise and paid the business at the same time. It is considered two events that occur simultaneously (exchange of merchandise for cash). \n\n Similar to the previous example for the mechanic, a credit sale, however, would be treated differently under each of these types of accounting. Under the cash basis of accounting, a credit sale would not be recorded in the financial statements until the cash is received, under terms stipulated by the seller. For example, assume on April 1 a landscaping business provides $500 worth of services to one of its customers. The sale is made on account, with the payment due forty-five days later. Under the cash basis of accounting, the revenue would not be recorded until May 16, when the cash was received. Under the accrual basis of accounting, this sale would be recorded in the financial statements at the time the services were provided, April 1. The reason the sale would be recorded is, under accrual accounting, the business reports that it provided $500 worth of services to its customer. The fact the customers will pay later is viewed as a separate transaction under accrual accounting ( Figure 2.3 ). \n\n Let’s now explore the difference between the cash basis and accrual basis of accounting using an expense. Assume a business purchases $160 worth of printing supplies from a supplier (vendor). Similar to a sale, a purchase of merchandise can be paid for at the time of sale using cash (also a check or credit card) or at a later date (on account). A purchase paid with cash at the time of the sale would be recorded in the financial statements under both cash basis and accrual basis of accounting. It makes sense because the business received the printing supplies from the supplier and paid the supplier at the same time. It is considered two events that occur simultaneously (exchange of merchandise for cash). \n\n If the purchase was made on account (also called a credit purchase ), however, the transaction would be recorded differently under each of these types of accounting. Under the cash basis of accounting, the $160 purchase on account would not be recorded in the financial statements until the cash is paid, as stipulated by the seller’s terms. For example, if the printing supplies were received on July 17 and the payment terms were fifteen days, no transaction would be recorded until August 1, when the goods were paid for. Under the accrual basis of accounting, this purchase would be recorded in the financial statements at the time the business received the printing supplies from the supplier (July 17). The reason the purchase would be recorded is that the business reports that it bought $160 worth of printing supplies from its vendors. The fact the business will pay later is viewed as a separate issue under accrual accounting. Table 2.2 summarizes these examples under the different bases of accounting. \n\n Transactions by Cash Basis versus Accrual Basis of Accounting \n\n Transaction \n\n Under Cash Basis Accounting \n\n Under Accrual Basis Accounting \n\n $200 sale for cash \n\n Recorded in financial statements at time of sale \n\n Recorded in financial statements at time of sale \n\n $200 sale on account \n\n Not recorded in financial statements until cash is received \n\n Recorded in financial statements at time of sale \n\n $160 purchase for cash \n\n Recorded in financial statements at time of purchase \n\n Recorded in financial statements at time of purchase \n\n $160 purchase on account \n\n Not recorded in financial statements until cash is paid \n\n Recorded in financial statements at time of purchase \n\n Table 2.2 Businesses often sell items for cash as well as on account, where payment terms are extended for a period of time (for example, thirty to forty-five days). Likewise, businesses often purchase items from suppliers (also called vendors) for cash or, more likely, on account. Under the cash basis of accounting, these transactions would not be recorded until the cash is exchanged. In contrast, under accrual accounting the transactions are recorded when the transaction occurs, regardless of when the cash is received or paid. \n\n Knowing the difference between the cash basis and accrual basis of accounting is necessary to understand the need for the statement of cash flows. Stakeholders need to know the financial performance (as measured by the income statement—that is, net income or net loss) and financial position (as measured by the balance sheet—that is, assets, liabilities, and owners’ equity) of the business. This information is provided in the income statement, statement of owner’s equity, and balance sheet. However, since these financial statements are prepared using accrual accounting, stakeholders do not have a clear picture of the business’s cash activities. The statement of cash flows solves this inadequacy by specifically focusing on the cash inflows and cash outflows. \n 2.2 Define, Explain, and Provide Examples of Current and Noncurrent Assets, Current and Noncurrent Liabilities, Equity, Revenues, and Expenses \n\n In addition to what you’ve already learned about assets and liabilities, and their potential categories, there are a couple of other points to understand about assets. Plus, given the importance of these concepts, it helps to have an additional review of the material. \n\n To help clarify these points, we return to our coffee shop example and now think of the coffee shop’s assets—items the coffee shop owns or controls. Review the list of assets you created for the local coffee shop. Did you happen to notice many of the items on your list have one thing in common: the items will be used over a long period of time? In accounting, we classify assets based on whether or not the asset will be used or consumed within a certain period of time, generally one year. If the asset will be used or consumed in one year or less, we classify the asset as a current asset . If the asset will be used or consumed over more than one year, we classify the asset as a noncurrent asset . \n\n Another thing you might have recognized when reviewing your list of coffee shop assets is that all of the items were something you could touch or move, each of which is known as a tangible asset. However, as you also learned in Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate , not all assets are tangible. An asset could be an intangible asset, meaning the item lacks physical substance—it cannot be touched or moved. Take a moment to think about your favorite type of shoe or a popular type of farm tractor. Would you be able to recognize the maker of that shoe or the tractor by simply seeing the logo? Chances are you would. These are examples of intangible assets, trademarks to be precise. A trademark has value to the organization that created (or purchased) the trademark, and the trademark is something the organization controls—others cannot use the trademark without permission. \n\n Similar to the accounting for assets, liabilities are classified based on the time frame in which the liabilities are expected to be settled. A liability that will be settled in one year or less (generally) is classified as a current liability , while a liability that is expected to be settled in more than one year is classified as a noncurrent liability . \n\n Examples of current assets include accounts receivable , which is the outstanding customer debt on a credit sale; inventory , which is the value of products to be sold or items to be converted into sellable products; and sometimes a notes receivable , which is the value of amounts loaned that will be received in the future with interest, assuming that it will be paid within a year. \n\n Examples of current liabilities include accounts payable , which is the value of goods or services purchased that will be paid for at a later date, and notes payable , which is the value of amounts borrowed (usually not inventory purchases) that will be paid in the future with interest. \n\n Examples of noncurrent assets include notes receivable (notice notes receivable can be either current or noncurrent), land, buildings, equipment, and vehicles. An example of a noncurrent liability is notes payable (notice notes payable can be either current or noncurrent). \n\n Why Does Current versus Noncurrent Matter? \n\n At this point, let’s take a break and explore why the distinction between current and noncurrent assets and liabilities matters. It is a good question because, on the surface, it does not seem to be important to make such a distinction. After all, assets are things owned or controlled by the organization, and liabilities are amounts owed by the organization; listing those amounts in the financial statements provides valuable information to stakeholders. But we have to dig a little deeper and remind ourselves that stakeholders are using this information to make decisions. Providing the amounts of the assets and liabilities answers the “what” question for stakeholders (that is, it tells stakeholders the value of assets), but it does not answer the “when” question for stakeholders. For example, knowing that an organization has $1,000,000 worth of assets is valuable information, but knowing that $250,000 of those assets are current and will be used or consumed within one year is more valuable to stakeholders. Likewise, it is helpful to know the company owes $750,000 worth of liabilities, but knowing that $125,000 of those liabilities will be paid within one year is even more valuable. In short, the timing of events is of particular interest to stakeholders. \n\n Think It Through Borrowing When money is borrowed by an individual or family from a bank or other lending institution, the loan is considered a personal or consumer loan. Typically, payments on these types of loans begin shortly after the funds are borrowed. Student loans are a special type of consumer borrowing that has a different structure for repayment of the debt. If you are not familiar with the special repayment arrangement for student loans, do a brief internet search to find out when student loan payments are expected to begin. \n\n Now, assume a college student has two loans—one for a car and one for a student loan. Assume the person gets the flu, misses a week of work at his campus job, and does not get paid for the absence. Which loan would the person be most concerned about paying? Why? \n\n Equity and Legal Structure \n\n Recall that equity can also be referred to as net worth—the value of the organization. The concept of equity does not change depending on the legal structure of the business (sole proprietorship, partnership, and corporation). The terminology does, however, change slightly based on the type of entity. For example, investments by owners are considered “capital” transactions for sole proprietorships and partnerships but are considered “common stock” transactions for corporations. Likewise, distributions to owners are considered “drawing” transactions for sole proprietorships and partnerships but are considered “dividend” transactions for corporations. \n\n As another example, in sole proprietorships and partnerships, the final amount of net income or net loss for the business becomes “Owner(s), Capital.” In a corporation, net income or net loss for the business becomes retained earnings , which is the cumulative, undistributed net income or net loss, less dividends paid for the business since its inception. \n\n The essence of these transactions remains the same: organizations become more valuable when owners make investments in the business and the businesses earn a profit (net income), and organizations become less valuable when owners receive distributions (dividends) from the organization and the businesses incur a loss (net loss). Because accountants are providing information to stakeholders, it is important for accountants to fully understand the specific terminology associated with the various legal structures of organizations. \n\n The Accounting Equation \n\n Recall the simple example of a home loan discussed in Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate . In that example, we assumed a family purchased a home valued at $200,000 and made a down payment of $25,000 while financing the remaining balance with a $175,000 bank loan. This example demonstrates one of the most important concepts in the study of accounting: the accounting equation , which is: \n\n In our example, the accounting equation would look like this: \n\n $200,000 = $175,000 + $25,000 $200,000 = $175,000 + $25,000 \n\n As you continue your accounting studies and you consider the different major types of business entities available (sole proprietorships, partnerships, and corporations), there is another important concept for you to remember. This concept is that no matter which of the entity options that you choose, the accounting process for all of them will be predicated on the accounting equation. \n\n It may be helpful to think of the accounting equation from a “sources and claims” perspective. Under this approach, the assets (items owned by the organization) were obtained by incurring liabilities or were provided by owners. Stated differently, every asset has a claim against it—by creditors and/or owners. \n\n Your Turn The Accounting Equation On a sheet of paper, use three columns to create your own accounting equation. In the first column, list all of the things you own (assets). In the second column, list any amounts owed (liabilities). In the third column, using the accounting equation, calculate, you guessed it, the net amount of the asset (equity). When finished, total the columns to determine your net worth. Hint: do not forget to subtract the liability from the value of the asset. \n\n Here is something else to consider: is it possible to have negative equity? It sure is . . . ask any college student who has taken out loans. At first glance there is no asset directly associated with the amount of the loan. But is that, in fact, the case? You might ask yourself why make an investment in a college education—what is the benefit (asset) to going to college? The answer lies in the difference in lifetime earnings with a college degree versus without a college degree. This is influenced by many things, including the supply and demand of jobs and employees. It is also influenced by the earnings for the type of college degree pursued. (Where do you think accounting ranks?) \n\n Solution \n\n Answers will vary but may include vehicles, clothing, electronics (include cell phones and computer/gaming systems, and sports equipment). They may also include money owed on these assets, most likely vehicles and perhaps cell phones. In the case of a student loan, there may be a liability with no corresponding asset (yet). Responses should be able to evaluate the benefit of investing in college is the wage differential between earnings with and without a college degree. \n\n Expanding the Accounting Equation \n\n Let’s continue our exploration of the accounting equation, focusing on the equity component, in particular. Recall that we defined equity as the net worth of an organization. It is helpful to also think of net worth as the value of the organization. Recall, too, that revenues (inflows as a result of providing goods and services) increase the value of the organization. So, every dollar of revenue an organization generates increases the overall value of the organization. \n\n Likewise, expenses (outflows as a result of generating revenue) decrease the value of the organization. So, each dollar of expenses an organization incurs decreases the overall value of the organization. The same approach can be taken with the other elements of the financial statements: \n\n Gains increase the value (equity) of the organization. \n\n Losses decrease the value (equity) of the organization. \n\n Investments by owners increase the value (equity) of the organization. \n\n Distributions to owners decrease the value (equity) of the organization. \n\n Changes in assets and liabilities can either increase or decrease the value (equity) of the organization depending on the net result of the transaction. \n\n A graphical representation of this concept is shown in Figure 2.4 . \n\n The format of this illustration is also intended to introduce you to a concept you will learn more about in your study of accounting. Notice each account subcategory (Current Assets and Noncurrent Assets, for example) has an “increase” side and a “decrease” side. These are called T-accounts and will be used to analyze transactions, which is the beginning of the accounting process. See Analyzing and Recording Transactions for a more comprehensive discussion of analyzing transactions and T-Accounts. \n\n Not All Transactions Affect Equity \n\n As you continue to develop your understanding of accounting, you will encounter many types of transactions involving different elements of the financial statements. The previous examples highlighted elements that change the equity of an organization. Not all transactions, however, ultimately impact equity. For example, the following do not impact the equity or net worth of the organization: 10 10 SFAC No. 6, p. 20. \n\n Exchanges of assets for assets \n\n Exchanges of liabilities for liabilities \n\n Acquisitions of assets by incurring liabilities \n\n Settlements of liabilities by transferring assets \n\n It is important to understand the inseparable connection between the elements of the financial statements and the possible impact on organizational equity (value). We explore this connection in greater detail as we return to the financial statements. \n 2.3 Prepare an Income Statement, Statement of Owner’s Equity, and Balance Sheet \n\n One of the key factors for success for those beginning the study of accounting is to understand how the elements of the financial statements relate to each of the financial statements. That is, once the transactions are categorized into the elements, knowing what to do next is vital. This is the beginning of the process to create the financial statements. It is important to note that financial statements are discussed in the order in which the statements are presented. \n\n Elements of the Financial Statements \n\n When thinking of the relationship between the elements and the financial statements, we might think of a baking analogy: the elements represent the ingredients, and the financial statements represent the finished product. As with baking a cake (see Figure 2.5 ), knowing the ingredients (elements) and how each ingredient relates to the final product (financial statements) is vital to the study of accounting. \n\n To help accountants prepare and users better understand financial statements, the profession has outlined what is referred to as elements of the financial statements , which are those categories or accounts that accountants use to record transactions and prepare financial statements. There are ten elements of the financial statements, and we have already discussed most of them. \n\n Revenue— value of goods and services the organization sold or provided. \n\n Expenses— costs of providing the goods or services for which the organization earns revenue. \n\n Gains— gains are similar to revenue but relate to “incidental or peripheral” activities of the organization. \n\n Losses— losses are similar to expenses but related to “incidental or peripheral” activities of the organization. \n\n Assets— items the organization owns, controls, or has a claim to. \n\n Liabilities— amounts the organization owes to others (also called creditors). \n\n Equity— the net worth (or net assets) of the organization. \n\n Investment by owners— cash or other assets provided to the organization in exchange for an ownership interest. \n\n Distribution to owners— cash, other assets, or ownership interest (equity) provided to owners. \n\n Comprehensive income — defined as the “change in equity of a business enterprise during a period from transactions and other events and circumstances from nonowner sources” (SFAC No. 6, p. 21). While further discussion of comprehensive income is reserved for intermediate and advanced studies in accounting, it is worth noting that comprehensive income has four components, focusing on activities related to foreign currency, derivatives, investments, and pensions. \n\n Financial Statements for a Sample Company \n\n Now it is time to bake the cake (i.e., prepare the financial statements). We have all of the ingredients (elements of the financial statements) ready, so let’s now return to the financial statements themselves. Let’s use as an example a fictitious company named Cheesy Chuck’s Classic Corn. This company is a small retail store that makes and sells a variety of gourmet popcorn treats. It is an exciting time because the store opened in the current month, June. \n\n Assume that as part of your summer job with Cheesy Chuck’s, the owner—you guessed it, Chuck—has asked you to take over for a former employee who graduated college and will be taking an accounting job in New York City. In addition to your duties involving making and selling popcorn at Cheesy Chuck’s, part of your responsibility will be doing the accounting for the business. The owner, Chuck, heard that you are studying accounting and could really use the help, because he spends most of his time developing new popcorn flavors. \n\n The former employee has done a nice job of keeping track of the accounting records, so you can focus on your first task of creating the June financial statements, which Chuck is eager to see. Figure 2.6 shows the financial information (as of June 30) for Cheesy Chuck’s. \n\n We should note that we are oversimplifying some of the things in this example. First, the amounts in the accounting records were given. We did not explain how the amounts would be derived. This process is explained starting in Analyzing and Recording Transactions . Second, we are ignoring the timing of certain cash flows such as hiring, purchases, and other startup costs. In reality, businesses must invest cash to prepare the store, train employees, and obtain the equipment and inventory necessary to open. These costs will precede the selling of goods and services. In the example to follow, for instance, we use Lease payments of $24,000, which represents lease payments for the building ($20,000) and equipment ($4,000). In practice, when companies lease items, the accountants must determine, based on accounting rules, whether or not the business “owns” the item. If it is determined the business “owns” the building or equipment, the item is listed on the balance sheet at the original cost. Accountants also take into account the building or equipment’s value when the item is worn out. The difference in these two values (the original cost and the ending value) will be allocated over a relevant period of time. As an example, assume a business purchased equipment for $18,000 and the equipment will be worth $2,000 after four years, giving an estimated decline in value (due to usage) of $16,000 ($18,000 − $2,000). The business will allocate $4,000 of the equipment cost over each of the four years ($18,000 minus $2,000 over four years). This is called depreciation and is one of the topics that is covered in Long-Term Assets . \n\n Also, the Equipment with a value of $12,500 in the financial information provided was purchased at the end of the first accounting period. It is an asset that will be depreciated in the future, but no depreciation expense is allocated in our example. \n\n Income Statement \n\n Let’s prepare the income statement so we can inform how Cheesy Chuck’s performed for the month of June (remember, an income statement is for a period of time ). Our first step is to determine the value of goods and services that the organization sold or provided for a given period of time. These are the inflows to the business, and because the inflows relate to the primary purpose of the business (making and selling popcorn), we classify those items as Revenues, Sales, or Fees Earned. For this example, we use Revenue. The revenue for Cheesy Chuck’s for the month of June is $85,000. \n\n Next, we need to show the total expenses for Cheesy Chuck’s. Because Cheesy Chuck’s tracks different types of expenses, we need to add the amounts to calculate total expenses. If you added correctly, you get total expenses for the month of June of $79,200. The final step to create the income statement is to determine the amount of net income or net loss for Cheesy Chuck’s. Since revenues ($85,000) are greater than expenses ($79,200), Cheesy Chuck’s has a net income of $5,800 for the month of June. \n\n Figure 2.7 displays the June income statement for Cheesy Chuck’s Classic Corn. \n\n Financial statements are created using numerous standard conventions or practices. The standard conventions provide consistency and help assure financial statement users the information is presented in a similar manner, regardless of the organization issuing the financial statement. Let’s look at the standard conventions shown in the Cheesy Chuck’s income statement: \n\n The heading of the income statement includes three lines.\n\n The first line lists the business name. \n\n The middle line indicates the financial statement that is being presented. \n\n The last line indicates the time frame of the financial statement. Do not forget the income statement is for a period of time (the month of June in our example). \n\n There are three columns.\n\n Going from left to right, the first column is the category heading or account. \n\n The second column is used when there are numerous accounts in a particular category (Expenses, in our example). \n\n The third column is a total column. In this illustration, it is the column where subtotals are listed and net income is determined (subtracting Expenses from Revenues). \n\n Subtotals are indicated by a single underline, while totals are indicated by a double underline. Notice the amount of Miscellaneous Expense ($300) is formatted with a single underline to indicate that a subtotal will follow. Similarly, the amount of “Net Income” ($5,800) is formatted with a double underline to indicate that it is the final value/total of the financial statement. \n\n There are no gains or losses for Cheesy Chuck’s. Gains and losses are not unusual transactions for businesses, but gains and losses may be infrequent for some, especially small, businesses. \n\n Concepts In Practice McDonald’s For the year ended December 31, 2016, McDonald’s had sales of $24.6 billion. 11 The amount of sales is often used by the business as the starting point for planning the next year. No doubt, there are a lot of people involved in the planning for a business the size of McDonald’s . Two key people at McDonald’s are the purchasing manager and the sales manager (although they might have different titles). Let’s look at how McDonald’s 2016 sales amount might be used by each of these individuals. In each case, do not forget that McDonald’s is a global company. 11 McDonald’s Corporation. U.S. Securities and Exchange Commission 10-K Filing. March 1, 2017. http://d18rn0p25nwr6d.cloudfront.net/CIK-0000063908/62200c2b-da82-4364-be92-79ed454e3b88.pdf \n\n A purchasing manager at McDonald’s , for example, is responsible for finding suppliers, negotiating costs, arranging for delivery, and many other functions necessary to have the ingredients ready for the stores to prepare the food for their customers. Expecting that McDonald’s will have over $24 billion of sales during 2017, how many eggs do you think the purchasing manager at McDonald’s would need to purchase for the year? According to the McDonald’s website, the company uses over two billion eggs a year. 12 Take a moment to list the details that would have to be coordinated in order to purchase and deliver over two billion eggs to the many McDonald’s restaurants around the world. 12 McDonald’s. “Our Food. Your Questions. Breakfast.” n.d. https://www.mcdonalds.com/us/en-us/about-our-food/our-food-your-questions/breakfast.html \n\n A sales manager is responsible for establishing and attaining sales goals within the company. Assume that McDonald’s 2017 sales are expected to exceed the amount of sales in 2016. What conclusions would you make based on this information? What do you think might be influencing these amounts? What factors do you think would be important to the sales manager in deciding what action, if any, to take? Now assume that McDonald’s 2017 sales are expected to be below the 2016 sales level. What conclusions would you make based on this information? What do you think might be influencing these amounts? What factors do you think would be important to the sales manager in deciding what action, if any, to take? \n\n Statement of Owner’s Equity \n\n Let’s create the statement of owner’s equity for Cheesy Chuck’s for the month of June. Since Cheesy Chuck’s is a brand-new business, there is no beginning balance of Owner’s Equity. The first items to account for are the increases in value/equity, which are investments by owners and net income. As you look at the accounting information you were provided, you recognize the amount invested by the owner, Chuck, was $12,500. Next, we account for the increase in value as a result of net income, which was determined in the income statement to be $5,800. Next, we determine if there were any activities that decreased the value of the business. More specifically, we are accounting for the value of distributions to the owners and net loss, if any. \n\n It is important to note that an organization will have either net income or net loss for the period, but not both. Also, small businesses in particular may have periods where there are no investments by, or distributions to, the owner(s). For the month of June, Chuck withdrew $1,450 from the business. This is a good time to recall the terminology used by accountants based on the legal structure of the particular business. Since the account was titled “Drawings by Owner” and because Chuck is the only owner, we can assume this is a sole proprietorship. If the business was structured as a corporation, this activity would be called something like “Dividends Paid to Owners.” \n\n At this stage, remember that since we are working with a sole proprietorship to help simplify the examples, we have addressed the owner’s value in the firm as capital or owner’s equity . However, later we switch the structure of the business to a corporation, and instead of owner’s equity, we begin using such account titles as common stock and retained earnings to represent the owner’s interests. The corporate treatment is more complicated, because corporations may have a few owners up to potentially thousands of owners (stockholders). The details of accounting for the interests of corporations are covered in Corporation Accounting . \n\n So how much did the value of Cheesy Chuck’s change during the month of June? You are correct if you answered $16,850. Since this is a brand-new store, the beginning value of the business is zero. During the month, the owner invested $12,500 and the business had profitable operations (net income) of $5,800. Also, during the month the owner withdrew $1,450, resulting in a net change (and ending balance) to owner’s equity of $16,850. Shown in a formula: \n\n Beginning Balance + Investments by Owners ± Net Income (Net Loss) – Distributions, or \n\n $0 + $12,500 + $5,800 – $1,450 = $16,850 $0 + $12,500 + $5,800 – $1,450 = $16,850 \n\n Figure 2.8 shows what the statement of owner’s equity for Cheesy Chuck’s Classic Corn would look like. \n\n Notice the following about the statement of owner’s equity for Cheesy Chuck’s: \n\n The format is similar to the format of the income statement (three lines for the heading, three columns). \n\n The statement follows a chronological order, starting with the first day of the month, accounting for the changes that occurred throughout the month, and ending with the final day of the month. \n\n The statement uses the final number from the financial statement previously completed. In this case, the statement of owner’s equity uses the net income (or net loss) amount from the income statement (Net Income, $5,800). \n\n Balance Sheet \n\n Let’s create a balance sheet for Cheesy Chuck’s for June 30. To begin, we look at the accounting records and determine what assets the business owns and the value of each. Cheesy Chuck’s has two assets: Cash ($6,200) and Equipment ($12,500). Adding the amount of assets gives a total asset value of $18,700. As discussed previously, the equipment that was recently purchased will be depreciated in the future, beginning with the next accounting period. \n\n Next, we determine the amount of money that Cheesy Chuck’s owes (liabilities). There are also two liabilities for Cheesy Chuck’s. The first account listed in the records is Accounts Payable for $650. Accounts Payable is the amount that Cheesy Chuck’s must pay in the future to vendors (also called suppliers) for the ingredients to make the gourmet popcorn. The other liability is Wages Payable for $1,200. This is the amount that Cheesy Chuck’s must pay in the future to employees for work that has been performed. Adding the two amounts gives us total liabilities of $1,850. (Here’s a hint as you develop your understanding of accounting: Liabilities often include the word “payable.” So, when you see “payable” in the account title, know these are amounts owed in the future—liabilities.) \n\n Finally, we determine the amount of equity the owner, Cheesy Chuck, has in the business. The amount of owner’s equity was determined on the statement of owner’s equity in the previous step ($16,850). Can you think of another way to confirm the amount of owner’s equity? Recall that equity is also called net assets (assets minus liabilities). If you take the total assets of Cheesy Chuck’s of $18,700 and subtract the total liabilities of $1,850, you get owner’s equity of $16,850. Using the basic accounting equation, the balance sheet for Cheesy Chuck’s as of June 30 is shown in Figure 2.9 . \n\n Connecting the Income Statement and the Balance Sheet \n\n Another way to think of the connection between the income statement and balance sheet (which is aided by the statement of owner’s equity) is by using a sports analogy. The income statement summarizes the financial performance of the business for a given period of time. The income statement reports how the business performed financially each month—the firm earned either net income or net loss. This is similar to the outcome of a particular game—the team either won or lost. \n\n The balance sheet summarizes the financial position of the business on a given date. Meaning, because of the financial performance over the past twelve months, for example, this is the financial position of the business as of December 31. Think of the balance sheet as being similar to a team’s overall win/loss record—to a certain extent a team’s strength can be perceived by its win/loss record. \n\n However, because different companies have different sizes, you do not necessarily want to compare the balance sheets of two different companies. For example, you would not want to compare a local retail store with Walmart. In most cases you want to compare a company with its past balance sheet information. \n\n Statement of Cash Flows \n\n In Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate , we discussed the function of and the basic characteristics of the statement of cash flows. This fourth and final financial statement lists the cash inflows and cash outflows for the business for a period of time . It was created to fill in some informational gaps that existed in the other three statements (income statement, owner’s equity/retained earnings statement, and the balance sheet). A full demonstration of the creation of the statement of cash flows is presented in Statement of Cash Flows . \n\n Creating Financial Statements: A Summary \n\n In this example using a fictitious company, Cheesy Chuck’s, we began with the account balances and demonstrated how to prepare the financial statements for the month of June, the first month of operations for the business. It will be helpful to revisit the process by summarizing the information we started with and how that information was used to create the four financial statements: income statement, statement of owner’s equity, balance sheet, and statement of cash flows. \n\n We started with the account balances shown in Figure 2.10 . \n\n The next step was to create the income statement, which shows the financial performance of the business. The income statement is shown in Figure 2.11 . \n\n Next, we created the statement of owner’s equity, shown in Figure 2.12 . The statement of owner’s equity demonstrates how the equity (or net worth) of the business changed for the month of June. Do not forget that the Net Income (or Net Loss) is carried forward to the statement of owner’s equity. \n\n The third financial statement created is the balance sheet, which shows the company’s financial position on a given date. Cheesy Chuck’s balance sheet is shown in Figure 2.13 . \n\n Think It Through Financial Statement Analysis In Why It Matters , we pointed out that accounting information from the financial statements can be useful to business owners. The financial statements provide feedback to the owners regarding the financial performance and financial position of the business, helping the owners to make decisions about the business. \n\n Using the June financial statements, analyze Cheesy Chuck’s and prepare a brief presentation. Consider this from the perspective of the owner, Chuck. Describe the financial performance of and financial position of the business. What areas of the business would you want to analyze further to get additional information? What changes would you consider making to the business, if any, and why or why not? \n\n Ethical Considerations Financial Statement Manipulation at Waste Management Inc. Accountants have an ethical duty to accurately report the financial results of their company and to ensure that the company’s annual reports communicate relevant information to stakeholders. If accountants and company management fail to do so, they may incur heavy penalties. \n\n For example, in 2002 the Securities and Exchange Commission (SEC) charged the top management of Waste Management, Inc. with inflating profits by $1.7 billion to meet earnings targets in the period 1992–1997. An SEC press release alleged “that defendants fraudulently manipulated the company’s financial results to meet predetermined earnings targets. . . . They employed a multitude of improper accounting practices to achieve this objective.” 13 The defendants in the case manipulated reports to defer or eliminate expenses, which fraudulently inflated their earnings. Because they failed to accurately report the financial results of their company, the top accountants and management of Waste Management, Inc. face charges. 13 U.S. Securities and Exchange Commission. “Waste Management Founder, Five Other Former Top Officers Sued for Massive Fraud.” March 26, 2002. https://www.sec.gov/news/headlines/wastemgmt6.htm \n\n Thomas C. Newkirk, the associate director of the SEC’s Division of Enforcement, stated, “For years, these defendants cooked the books, enriched themselves, preserved their jobs, and duped unsuspecting shareholders” 14 The defendants, who included members of the company board and executives, benefited personally from their fraud in the millions of dollars through performance-based bonuses, charitable giving, and sale of company stock. The company’s accounting form, Arthur Andersen , abetted the fraud by identifying the improper practices but doing little to stop them. 14 U.S. Securities and Exchange Commission. “Waste Management Founder, Five Other Former Top Officers Sued for Massive Fraud.” March 26, 2002. https://www.sec.gov/news/headlines/wastemgmt6.htm \n\n Liquidity Ratios \n\n In addition to reviewing the financial statements in order to make decisions, owners and other stakeholders may also utilize financial ratios to assess the financial health of the organization. While a more in-depth discussion of financial ratios occurs in Appendix A: Financial Statement Analysis , here we introduce liquidity ratios , a common, easy, and useful way to analyze the financial statements. \n\n Liquidity refers to the business’s ability to convert assets into cash in order to meet short-term cash needs. Examples of the most liquid assets include accounts receivable and inventory for merchandising or manufacturing businesses. The reason these are among the most liquid assets is that these assets will be turned into cash more quickly than land or buildings, for example. Accounts receivable represents goods or services that have already been sold and will typically be paid/collected within thirty to forty-five days. Inventory is less liquid than accounts receivable because the product must first be sold before it generates cash (either through a cash sale or sale on account). Inventory is, however, more liquid than land or buildings because, under most circumstances, it is easier and quicker for a business to find someone to purchase its goods than it is to find a buyer for land or buildings. Working Capital \n\n The starting point for understanding liquidity ratios is to define working capital —current assets minus current liabilities. Recall that current assets and current liabilities are amounts generally settled in one year or less. Working capital (current assets minus current liabilities) is used to assess the dollar amount of assets a business has available to meet its short-term liabilities. A positive working capital amount is desirable and indicates the business has sufficient current assets to meet short-term obligations (liabilities) and still has financial flexibility. A negative amount is undesirable and indicates the business should pay particular attention to the composition of the current assets (that is, how liquid the current assets are) and to the timing of the current liabilities. It is unlikely that all of the current liabilities will be due at the same time, but the amount of working capital gives stakeholders of both small and large businesses an indication of the firm’s ability to meet its short-term obligations. \n\n One limitation of working capital is that it is a dollar amount, which can be misleading because business sizes vary. Recall from the discussion on materiality that $1,000, for example, is more material to a small business (like an independent local movie theater) than it is to a large business (like a movie theater chain). Using percentages or ratios allows financial statement users to more easily compare small and large businesses. \n\n Current Ratio \n\n The current ratio is closely related to working capital; it represents the current assets divided by current liabilities. The current ratio utilizes the same amounts as working capital (current assets and current liabilities) but presents the amount in ratio, rather than dollar, form. That is, the current ratio is defined as current assets/current liabilities. The interpretation of the current ratio is similar to working capital. A ratio of greater than one indicates that the firm has the ability to meet short-term obligations with a buffer, while a ratio of less than one indicates that the firm should pay close attention to the composition of its current assets as well as the timing of the current liabilities. \n\n Sample Working Capital and Current Ratio Calculations \n\n Assume that Chuck, the owner of Cheesy Chuck’s, wants to assess the liquidity of the business. Figure 2.14 shows the June 30, 2018, balance sheet. Assume the Equipment listed on the balance sheet is a noncurrent asset. This is a reasonable assumption as this is the first month of operation and the equipment is expected to last several years. We also assume the Accounts Payable and Wages Payable will be paid within one year and are, therefore, classified as current liabilities. \n\n Working capital is calculated as current assets minus current liabilities. Cheesy Chuck’s has only two assets, and one of the assets, Equipment, is a noncurrent asset, so the value of current assets is the cash amount of $6,200. The working capital of Cheesy Chuck’s is $6,200 – $1,850 or $4,350. Since this amount is over $0 (it is well over $0 in this case), Chuck is confident he has nothing to worry about regarding the liquidity of his business. \n\n Let’s further assume that Chuck, while attending a popcorn conference for store owners, has a conversation with the owner of a much larger popcorn store—Captain Caramel’s. The owner of Captain Caramel’s happens to share the working capital for his store is $52,500. At first Chuck feels his business is not doing so well. But then he realizes that Captain Caramel’s is located in a much bigger city (with more customers) and has been around for many years, which has allowed them to build a solid business, which Chuck aspires to do. How would Chuck compare the liquidity of his new business, opened just one month, with the liquidity of a larger and more-established business in another market? The answer is by calculating the current ratio, which removes the size differences (materiality) of the two businesses. \n\n The current ratio is calculated as current assets/current liabilities. We use the same amounts that we used in the working capital calculation, but this time we divide the amounts rather than subtract the amounts. So Cheesy Chuck’s current ratio is $6,200 (current assets)/$1,850 (current liabilities), or 3.35. This means that for every dollar of current liabilities, Cheesy Chuck’s has $3.35 of current assets. Chuck is pleased with the ratio but does not know how this compares to another popcorn store, so he asked his new friend from Captain Caramel’s. The owner of Captain Caramel’s shares that his store has a current ratio of 4.25. While it is still better than Cheesy Chuck’s, Chuck is encouraged to learn that his store is performing at a more competitive level than he previously thought by comparing the dollar amounts of working capital. \n\n IFRS Connection IFRS and US GAAP in Financial Statements Understanding the elements that make up financial statements, the organization of those elements within the financial statements, and what information each statement relays is important, whether analyzing the financial statements of a US company or one from Honduras. Since most US companies apply generally accepted accounting principles (GAAP) 15 as prescribed by the Financial Accounting Standards Board (FASB), and most international companies apply some version of the International Financial Reporting Standards (IFRS), 16 knowing how these two sets of accounting standards are similar or different regarding the elements of the financial statements will facilitate analysis and decision-making. 15 Publicly traded companies in the United States must file their financial statements with the SEC, and those statements must be compiled using US GAAP. However, in some states, private companies can apply IFRS for SMEs (small and medium entities). 16 The following site identifies which countries require IFRS, which use a modified version of IFRS, and which countries prohibit the use of IFRS. https://www.iasplus.com/en/resources/ifrs-topics/use-of-ifrs \n\n Both IFRS and US GAAP have the same elements as components of financial statements: assets, liabilities, equity, income, and expenses. Equity, income, and expenses have similar subcategorization between the two types of GAAP (US GAAP and IFRS) as described. For example, income can be in the form of earned income (a lawyer providing legal services) or in the form of gains (interest earned on an investment account). The definition of each of these elements is similar between IFRS and US GAAP, but there are some differences that can influence the value of the account or the placement of the account on the financial statements. Many of these differences are discussed in detail later in this course when that element—for example, the nuances of accounting for liabilities—is discussed. Here is an example to illustrate how these minor differences in definition can impact placement within the financial statements when using US GAAP versus IFRS. ACME Car Rental Company typically rents its cars for a time of two years or 60,000 miles. At the end of whichever of these two measures occurs first, the cars are sold. Under both US GAAP and IFRS, the cars are noncurrent assets during the period when they are rented. Once the cars are being “held for sale,” under IFRS rules, the cars become current assets. However, under US GAAP, there is no specific rule as to where to list those “held for sale” cars; thus, they could still list the cars as noncurrent assets. As you learn more about the analysis of companies and financial information, this difference in placement on the financial statements will become more meaningful. At this point, simply know that financial analysis can include ratios, which is the comparison of two numbers, and thus any time you change the denominator or the numerator, the ratio result will change. \n\n There are many similarities and some differences in the actual presentation of the various financial statements, but these are discussed in The Adjustment Process at which point these similarities and differences will be more meaningful and easier to follow. "}}},{"rowIdx":177,"cells":{"bname":{"kind":"string","value":"business_ethics"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":" Summary 9.1 Entrepreneurship and Start-Up Culture \n\n The atmosphere surrounding entrepreneurs and their start-ups can provide a dizzying rush. The opportunities to create a company, be your own boss, make a dramatic impact on business, establish an entrepreneurial culture that will be adopted by others, and possibly become rich in the process certainly all appeal to our human nature. Still, the entrepreneurial lifestyle is challenging, and the success rate for start-ups is exceptionally low. Interpersonal conflicts are prevalent in start-up environments, and entrepreneurs who seek to stay true to their vision and ethical values face a difficult road. At many points, start-up founders have to choose how they most wish to be remembered: for the sake of their business success alone or also for the ethical fashion in which they attained that success and the humane culture they have embedded in their new firm. Sometimes these are mutually exclusive goals, but the most ethical entrepreneurs do their best to ensure that both objectives mesh for themselves and their firms. This lies at the heart of any definition of ethical leadership. \n\n 9.2 The Influence of Advertising \n\n The Internet and social media present new canvasses for marketing that possess great power and for which rules and ethical norms are being developed. Psychological appeals and subliminal messaging present their own ethical issues. Discerning consumers currently must rely on their own sensibility to ferret out factual claims for advertised products and bear the burden of shielding those under their charge from the worst manipulative effects of marketing. \n\n 9.3 The Insurance Industry \n\n Business owners and individuals are willing to pay insurance premiums in the hope that they will never have to be file a claim for reimbursement on their policy. Because the insurance industry profits only when claims are few and small, there may be a bigger role for government to play in managing disaster insurance through a private/public partnership, such as FEMA currently does to provide flood insurance and the California Earthquake Authority does where potentially disastrous earthquakes may occur. Ethical issues such whether to expand the use of public tax revenues to subsidize these partnerships need to be resolved. \n\n 9.4 Ethical Issues in the Provision of Health Care \n\n The United States, unlike countries in Europe, has little tradition of merging the efforts of the state or federal government with that of private employers in the provision of health care. Although the quality of U.S. health care has rarely been challenged, its limited accessibility has posed ethical quandaries for business because many employees necessarily look to their employers for this benefit. The 2010 Affordable Care Act is an ambitious effort to meet the need for health care for all. Individual states have considered, and sometimes enacted, programs of their own to supply universal health care. "},"intro":{"kind":"string","value":" Chapter Outline 9.1 Entrepreneurship and Start-Up Culture 9.2 The Influence of Advertising 9.3 The Insurance Industry 9.4 Ethical Issues in the Provision of Health Care Introduction \n\n As consumers, employees, and community members, we see everywhere the extent to which business can contribute to either social well-being or harm. Some career paths invite special scrutiny because of their influential role in society and the extent to which they serve as magnets for business students. Friends and critics of these professions have studied the unique ethical issues they raise and individuals who pursue careers in these fields should give careful consideration to these findings to decide if the benefits outweigh the potential downsides. \n\n Entrepreneurship, for instance, offers the opportunity to construct your own business in the hope of profit, but at some personal and financial cost. Are the potential gains being overplayed when, in fact, most entrepreneurial businesses fail? Advertising is the driver of sales, but are its claims honest and its delivery platforms, including social media, acting in good faith? Do they exert undue or biased influence on the gullible and the young? Insurance is necessary, but what is the proper and ethical role of property insurers, for example, in the face of increasingly dangerous natural disasters? Health care in the United States is extraordinarily expensive, especially compared with that in other industrialized nations, and access is too often limited to those with means. Should quality health care be a right for all rather than a privilege for the few? "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"<hl> A fairly common characteristic of successful start-ups is charismatic , driven founders with take-no-prisoner competitive mentalities , as was illustrated earlier in this chapter in the example of Kalanick and the leadership values at Uber . <hl> After all , it takes a thick skin and powerful ego to get through the inevitable disappointments that confront a start-up leader . Often , however , even when these self-assured personalities evade the most egregious behavior of a Kalanick , they still remain very difficult for others to abide . Many companies discover that a different leadership ethos is necessary as they grow . Could entrepreneurs still succeed if they also embraced a humanistic leadership style at the outset , or would this invariably undermine the already low initial odds of success ? It is a difficult problem with which many firms wrestle . Dedicated employees may be put off by demanding leaders who are harsh , giving little back to loyal workers even after achieving success . New employees may decide the working climate is less congenial than they anticipated and simply leave . This turnstile effect of workers voting on management with their feet constitutes an ethical judgment of repugnant leadership at the top .","hl_sentences":"A fairly common characteristic of successful start-ups is charismatic , driven founders with take-no-prisoner competitive mentalities , as was illustrated earlier in this chapter in the example of Kalanick and the leadership values at Uber .","question":{"cloze_format":"The characteristic that is common to most entrepreneurs is ___.","normal_format":"What characteristic is common to most entrepreneurs?","question_choices":["an advanced degree","deep management experience","a driven, highly competitive nature","a large network of business contacts"],"question_id":"fs-idm348969840","question_text":"What characteristic is common to most entrepreneurs?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"Newer staff , however , may not share this mindset . They may simply be seeking a secure position with a growing business rather than a chance to get in on the ground floor of a risky start-up . They will not necessarily have the tolerance for the demanding hours , chaos , and abrasive personalities that can characterize the early days of an enterprise . <hl> Can entrepreneurial founders shape a company ’ s culture so it can accommodate talented employees who are looking for a corporate culture that supports some work – life balance ? <hl>","hl_sentences":"Can entrepreneurial founders shape a company ’ s culture so it can accommodate talented employees who are looking for a corporate culture that supports some work – life balance ?","question":{"cloze_format":"Corporate culture comes from ________.","normal_format":"Where does corporate culture come from?","question_choices":["the commitment of the company’s employees","the founder’s idea of what the work environment should be like","government regulations about labor relations","the nature of the company’s product or service"],"question_id":"fs-idm365525264","question_text":"Corporate culture comes from ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"Even if a start-up becomes what its founders wish it to be — astronomically successful — inevitably it will change as it grows , acquires new locations , and hires more employees . <hl> These changes may eventually produce an organization with added layers — essentially , a hardened bureaucracy that slows down and complicates the management process . <hl> The company may no longer make essential decisions with the speed and nimbleness that once were possible . <hl> In short , success for a start-up is often accompanied by the risk of becoming , over time , exactly the traditional business structure its founders once rejected . <hl> So the founders of an entrepreneurial shop , and their successors , must guard against change that radically alters the original spirit of innovation and the free and rapid flow of information , even as the company grows . <hl> No business leader seeks bureaucracy , but it typically accompanies growth within any organization . <hl>","hl_sentences":"These changes may eventually produce an organization with added layers — essentially , a hardened bureaucracy that slows down and complicates the management process . In short , success for a start-up is often accompanied by the risk of becoming , over time , exactly the traditional business structure its founders once rejected . No business leader seeks bureaucracy , but it typically accompanies growth within any organization .","question":{"cloze_format":"One danger a growing start-up can face is ________.","normal_format":"What is one danger a growing start-up can face?","question_choices":["encroaching bureaucracy","lack of good employees","legal issues","venture capitalists"],"question_id":"fs-idm367370736","question_text":"One danger a growing start-up can face is ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"Psychological appeals form the basis of the most successful ads . <hl> Going beyond the standard ad pitch about the product ’ s advantages , psychological appeal s try to reach our self-esteem and persuade us that we will feel better about ourselves if we use certain products . <hl> If advertising frames the purchase of a popular toy as the act of a loving parent rather than an extravagance , for instance , consumers may buy it not because their child needs it but because it makes them feel good about what generous parents they are . This is how psychological appeals become successful , and when they do work , this often constitutes a victory for the power of psychological persuasion at the expense of ethical truthfulness .","hl_sentences":"Going beyond the standard ad pitch about the product ’ s advantages , psychological appeal s try to reach our self-esteem and persuade us that we will feel better about ourselves if we use certain products .","question":{"cloze_format":"Psychological appeals succeed when they ________.","normal_format":"When do sychological appeals succeed?","question_choices":["make consumers feel better about themselves","let consumers compare themselves to their peers","show consumers how to save money","introduce new products"],"question_id":"fs-idm302963728","question_text":"Psychological appeals succeed when they ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"Within the multipayer system , many U . S . workers have traditionally looked to their employers or their unions to subsidize the cost of care and thereby make it available for them and their families . Many reasons explain why this is so . <hl> In contrast to the European and Canadian perspective , for example , in which both the state and employers are presumed to have an interest in and responsibility for underwriting the cost of health care , the traditional U . S . approach is that workers and their employers should be responsible for securing this coverage . <hl> This belief reflects an unease on the part of some about assigning services to the government , because this implies the need for a larger governing entity as well as additional taxes to sustain it . The sentiment also reflects a conviction on the part of some that self-reliance is always to be preferred when securing the necessities of life .","hl_sentences":"In contrast to the European and Canadian perspective , for example , in which both the state and employers are presumed to have an interest in and responsibility for underwriting the cost of health care , the traditional U . S . approach is that workers and their employers should be responsible for securing this coverage .","question":{"cloze_format":"In the European tradition, the main responsibility for supplying workers with health care lies with the group of ___ .","normal_format":"In the European tradition, the main responsibility for supplying workers with health care lies with which of these groups?","question_choices":["the government and labor unions","labor unions","nonprofit agencies and private companies","individual workers"],"question_id":"fs-idm495353568","question_text":"In the European tradition, the main responsibility for supplying workers with health care lies with which of these groups?"},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> A fairly common characteristic of successful start-ups is charismatic , driven founders with take-no-prisoner competitive mentalities , as was illustrated earlier in this chapter in the example of Kalanick and the leadership values at Uber . <hl> After all , it takes a thick skin and powerful ego to get through the inevitable disappointments that confront a start-up leader . Often , however , even when these self-assured personalities evade the most egregious behavior of a Kalanick , they still remain very difficult for others to abide . Many companies discover that a different leadership ethos is necessary as they grow . Could entrepreneurs still succeed if they also embraced a humanistic leadership style at the outset , or would this invariably undermine the already low initial odds of success ? It is a difficult problem with which many firms wrestle . Dedicated employees may be put off by demanding leaders who are harsh , giving little back to loyal workers even after achieving success . New employees may decide the working climate is less congenial than they anticipated and simply leave . This turnstile effect of workers voting on management with their feet constitutes an ethical judgment of repugnant leadership at the top .\",\n \"hl_sentences\": \"A fairly common characteristic of successful start-ups is charismatic , driven founders with take-no-prisoner competitive mentalities , as was illustrated earlier in this chapter in the example of Kalanick and the leadership values at Uber .\",\n \"question\": {\n \"cloze_format\": \"The characteristic that is common to most entrepreneurs is ___.\",\n \"normal_format\": \"What characteristic is common to most entrepreneurs?\",\n \"question_choices\": [\n \"an advanced degree\",\n \"deep management experience\",\n \"a driven, highly competitive nature\",\n \"a large network of business contacts\"\n ],\n \"question_id\": \"fs-idm348969840\",\n \"question_text\": \"What characteristic is common to most entrepreneurs?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"Newer staff , however , may not share this mindset . They may simply be seeking a secure position with a growing business rather than a chance to get in on the ground floor of a risky start-up . They will not necessarily have the tolerance for the demanding hours , chaos , and abrasive personalities that can characterize the early days of an enterprise . <hl> Can entrepreneurial founders shape a company ’ s culture so it can accommodate talented employees who are looking for a corporate culture that supports some work – life balance ? <hl>\",\n \"hl_sentences\": \"Can entrepreneurial founders shape a company ’ s culture so it can accommodate talented employees who are looking for a corporate culture that supports some work – life balance ?\",\n \"question\": {\n \"cloze_format\": \"Corporate culture comes from ________.\",\n \"normal_format\": \"Where does corporate culture come from?\",\n \"question_choices\": [\n \"the commitment of the company’s employees\",\n \"the founder’s idea of what the work environment should be like\",\n \"government regulations about labor relations\",\n \"the nature of the company’s product or service\"\n ],\n \"question_id\": \"fs-idm365525264\",\n \"question_text\": \"Corporate culture comes from ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"Even if a start-up becomes what its founders wish it to be — astronomically successful — inevitably it will change as it grows , acquires new locations , and hires more employees . <hl> These changes may eventually produce an organization with added layers — essentially , a hardened bureaucracy that slows down and complicates the management process . <hl> The company may no longer make essential decisions with the speed and nimbleness that once were possible . <hl> In short , success for a start-up is often accompanied by the risk of becoming , over time , exactly the traditional business structure its founders once rejected . <hl> So the founders of an entrepreneurial shop , and their successors , must guard against change that radically alters the original spirit of innovation and the free and rapid flow of information , even as the company grows . <hl> No business leader seeks bureaucracy , but it typically accompanies growth within any organization . <hl>\",\n \"hl_sentences\": \"These changes may eventually produce an organization with added layers — essentially , a hardened bureaucracy that slows down and complicates the management process . In short , success for a start-up is often accompanied by the risk of becoming , over time , exactly the traditional business structure its founders once rejected . No business leader seeks bureaucracy , but it typically accompanies growth within any organization .\",\n \"question\": {\n \"cloze_format\": \"One danger a growing start-up can face is ________.\",\n \"normal_format\": \"What is one danger a growing start-up can face?\",\n \"question_choices\": [\n \"encroaching bureaucracy\",\n \"lack of good employees\",\n \"legal issues\",\n \"venture capitalists\"\n ],\n \"question_id\": \"fs-idm367370736\",\n \"question_text\": \"One danger a growing start-up can face is ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"Psychological appeals form the basis of the most successful ads . <hl> Going beyond the standard ad pitch about the product ’ s advantages , psychological appeal s try to reach our self-esteem and persuade us that we will feel better about ourselves if we use certain products . <hl> If advertising frames the purchase of a popular toy as the act of a loving parent rather than an extravagance , for instance , consumers may buy it not because their child needs it but because it makes them feel good about what generous parents they are . This is how psychological appeals become successful , and when they do work , this often constitutes a victory for the power of psychological persuasion at the expense of ethical truthfulness .\",\n \"hl_sentences\": \"Going beyond the standard ad pitch about the product ’ s advantages , psychological appeal s try to reach our self-esteem and persuade us that we will feel better about ourselves if we use certain products .\",\n \"question\": {\n \"cloze_format\": \"Psychological appeals succeed when they ________.\",\n \"normal_format\": \"When do sychological appeals succeed?\",\n \"question_choices\": [\n \"make consumers feel better about themselves\",\n \"let consumers compare themselves to their peers\",\n \"show consumers how to save money\",\n \"introduce new products\"\n ],\n \"question_id\": \"fs-idm302963728\",\n \"question_text\": \"Psychological appeals succeed when they ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"Within the multipayer system , many U . S . workers have traditionally looked to their employers or their unions to subsidize the cost of care and thereby make it available for them and their families . Many reasons explain why this is so . <hl> In contrast to the European and Canadian perspective , for example , in which both the state and employers are presumed to have an interest in and responsibility for underwriting the cost of health care , the traditional U . S . approach is that workers and their employers should be responsible for securing this coverage . <hl> This belief reflects an unease on the part of some about assigning services to the government , because this implies the need for a larger governing entity as well as additional taxes to sustain it . The sentiment also reflects a conviction on the part of some that self-reliance is always to be preferred when securing the necessities of life .\",\n \"hl_sentences\": \"In contrast to the European and Canadian perspective , for example , in which both the state and employers are presumed to have an interest in and responsibility for underwriting the cost of health care , the traditional U . S . approach is that workers and their employers should be responsible for securing this coverage .\",\n \"question\": {\n \"cloze_format\": \"In the European tradition, the main responsibility for supplying workers with health care lies with the group of ___ .\",\n \"normal_format\": \"In the European tradition, the main responsibility for supplying workers with health care lies with which of these groups?\",\n \"question_choices\": [\n \"the government and labor unions\",\n \"labor unions\",\n \"nonprofit agencies and private companies\",\n \"individual workers\"\n ],\n \"question_id\": \"fs-idm495353568\",\n \"question_text\": \"In the European tradition, the main responsibility for supplying workers with health care lies with which of these groups?\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":9,"string":"9"},"chapter_text":{"kind":"string","value":" 9.1 Entrepreneurship and Start-Up Culture \n\n Learning Objectives \n\n By the end of this section, you will be able to: \n\n Identify ethical challenges relating to entrepreneurial start-ups \n\n Describe positive and negative effects of growth in a start-up \n\n Discuss the role of the founder in instilling an ethical culture \n\n An entrepreneur is a business leader willing to risk starting a new company and offering a product or service he or she hopes will be sustainable and permit the firm to prosper. The entrepreneur may have to find the money required for this venture and typically draws on business experience gained by working for others first. Entrepreneurship often requires hard work, but the potential for economic payoff and career satisfaction appeals to many. \n\n The Risks of Entrepreneurship \n\n Although the risk of failure associated with starting a business is real and even high, we hear much in the media about success stories and little about those entrepreneurs who crash and burn. Perhaps the allure of entrepreneurship inevitably outshines any mention of the downside. Still, start-ups impose a higher than normal degree of risk, and we turn to the evidence for this now. \n\n What is the specific nature of entrepreneurial risk? Different studies yield different results, but business consultant Patrick Henry reported that “75 percent of venture-backed startups fail.” Henry added that “this statistic is based on a Harvard Business School study by Shikhar Ghosh. In a study by Statistical Brain, ‘Startup Business Failure Rate by Industry,’ the failure rate of all U.S. companies after five years was over 50 percent, and over 70 percent after ten years.” 1 \n\n This figure might be enough to chill the enthusiasm of any would-be entrepreneur who believes an exciting or novel concept is enough to support a successful company with a minimal amount of time and effort and a great deal of other people’s money. Still, the ranks of start-ups expand prodigiously each month in the United States. \n\n Even start-ups that beat the odds financially need to be watchful for a different sort of pitfall, an ethical failure that can be nourished by the very strengths that allow a company to get off the ground. That pitfall is the hubris or excessive pride that may characterize some entrepreneurs, particularly after they have had some initial success. Uber, an application-based, ride-hailing service, was founded in San Francisco by Travis Kalanick and Garrett Camp in 2009. If ever an idea matched the success potential of smartphones, it was this one. Offering a cheaper and more convenient service than hailing a cab on city streets, Uber was valued at $70 billion in 2017 and operated, with varying degrees of success, in seventy countries at that point. However, the corporate culture, especially at headquarters, left many observers aghast in early 2017 after an Uber engineer, Susan Fowler, blogged about her experiences there. Other employees substantiated much of her account, revealing an atmosphere rife with misogyny, homophobia, and sexual harassment. \n\n This culture was permitted—even fostered—by Kalanick, who reigned unchecked for several years over what the New York Times labeled an “aggressive, unrestrained workplace culture.” 2 Muted grumblings from quarters within the company never received much attention outside the firm, allowing Kalanick to become a high-flying role model for would-be entrepreneurs who wished to emulate his success. A reckoning finally arrived when Uber’s board of directors asked him to resign his position as chief executive officer in June 2017. \n\n Yet the workplace culture that prevailed during his years at the company was not unique to Uber. Many firms have experienced it. Holding destructive egos in check is an ethical challenge at many successful businesses, particularly at hard-riding start-ups. Founders and their start-up teams need to be aware of how deeply their attitudes toward others; their visible treatment of employees, customers, and clients; and their display of fairness will come to shape the company they are building. It is not enough for the founders to hypothesize, “we’ll get around to establishing the right protocols after we’re solvent.” Nor is it adequate to insist that standards of courteous business practice will naturally emerge on their own. An initial culture either of ethics or its absence will set a tone from the first day of business. If the founders believe these niceties are not required of them owing to their genius or confidence, such arrogance will displace ethics as a best practice. To believe otherwise is self-deception. \n\n Why Successful Start-Ups Change as They Grow \n\n A legendary example of a start-up that still inspires many today is the Hewlett-Packard Corporation (HP). Its origins lie in the efforts of Bill Hewlett and David Packard, two Stanford University classmates in the 1930s. Much like members of a garage band, they started their company in a real garage, and the firm has outgrown its humble beginnings many times over ( Figure 9.2 ). \n\n Start-ups are exciting. Many of their founders, like the late Steve Jobs of Apple, attain near-rock star status, and the companies can generate enormous profit. They allow many to do what they have always wanted to do and be their own bosses. Yet we often overlook the fact that even some of the most successful entrepreneurs experience many failures before they succeed, and long hours of hard work are typically required even for these failures. Smart entrepreneurs learn from their failures, but each lesson can be painful, frustrating, and time consuming. \n\n A unique personality is required to weather the stresses and strains of a start-up, and it is a personality that tolerates much personal deprivation as it pursues the perceived highest goal of all, success for the firm, no matter what personal or collective costs might be entailed. The culture of entrepreneurialism allows for many business leaders and their staffs to be deprived of a portion of their humanity along the way to success. Thus, a preeminent ethical consideration is whether the result justifies this cost. At the very least, determined entrepreneurs must be advised of these possible sacrifices. They constitute the collateral damage of entrepreneurial dreams that any ambitious start-up founder should contemplate. Will one emerge at the end of the process as the sort of person one most wishes to be? \n\n Even if a start-up becomes what its founders wish it to be—astronomically successful—inevitably it will change as it grows, acquires new locations, and hires more employees. These changes may eventually produce an organization with added layers—essentially, a hardened bureaucracy that slows down and complicates the management process. The company may no longer make essential decisions with the speed and nimbleness that once were possible. In short, success for a start-up is often accompanied by the risk of becoming, over time, exactly the traditional business structure its founders once rejected. So the founders of an entrepreneurial shop, and their successors, must guard against change that radically alters the original spirit of innovation and the free and rapid flow of information, even as the company grows. No business leader seeks bureaucracy, but it typically accompanies growth within any organization. \n\n Particular problems that arise out of bureaucratization are additional layers of management, more codified procedures, and internal obstructions that surface as a business attempts to capitalize on its initial success. As more employees are added to the mix, the original team’s sense of common purpose can become diluted. \n\n Max Weber (1864–1920), the German academic, economist, and sociologist, appreciated the consequences of bureaucracy years ago. In Wirtschaft und Gesellschaft [ Economy and Society ], published posthumously in 1925, he pointed out, “in the private economy, [bureaucracy emerges] only in the most advanced institutions of capitalism.” 3 Weber cemented the link between bureaucracy and capitalism further: “The development of the money economy [emphasis is Weber’s] . . . is a presupposition of bureaucracy. Today it not only prevails but is predominant.” 4 \n\n Because start-ups constitute an “advanced” feature of capitalism, and because bureaucracy presupposes a “money economy,” Weber prophesied that agile start-ups would be ripe for bureaucratization as they grow and age. Finally, he included this acknowledgement of the permanence of bureaucracy: “Once it is firmly established, bureaucracy is among those social structures which are the hardest to destroy.” 5 \n\n More recently, Michael A. Lutzker confirmed Weber’s testimony on the inevitability of bureaucracy: “The administrative function has of course been a pervasive element of all societies, ancient, medieval, and modern, but Weber was among the first to recognize the distinctive character of bureaucracy in the modern era.” 6 \n\n Simply put, the very same success that permits a start-up to flourish often produces bureaucratic structures that chip away at the free-flowing camaraderie that allowed a handful of founders to act instantly and with one mind. As the staff expands, employees’ ranks become more defined, titles and hierarchies appear, and individual achievements become harder to spot. This is what changes within a successful start-up, and it moves the company away from the more congenial atmosphere that characterized it at its outset. An original small partnership often becomes a corporate behemoth, and it takes on many of the attributes of those cubicle workplaces that frequently inspired its founders to strike out on their own in the first place. \n\n All the better, then, if ethical practices that permit coworkers to bond as colleagues with a sense of commitment to each other and to their customers or clients emerge through a company’s trial-and-error experience at the outset. Only if the founders and initial staff emphasize treating all stakeholders with honesty, courtesy, and respect will the new firm stand a chance of indelibly cementing ethics into its operating matrix. \n\n Entrepreneurial Culture \n\n A fairly common characteristic of successful start-ups is charismatic, driven founders with take-no-prisoner competitive mentalities, as was illustrated earlier in this chapter in the example of Kalanick and the leadership values at Uber. After all, it takes a thick skin and powerful ego to get through the inevitable disappointments that confront a start-up leader. Often, however, even when these self-assured personalities evade the most egregious behavior of a Kalanick, they still remain very difficult for others to abide. Many companies discover that a different leadership ethos is necessary as they grow. Could entrepreneurs still succeed if they also embraced a humanistic leadership style at the outset, or would this invariably undermine the already low initial odds of success? It is a difficult problem with which many firms wrestle. Dedicated employees may be put off by demanding leaders who are harsh, giving little back to loyal workers even after achieving success. New employees may decide the working climate is less congenial than they anticipated and simply leave. This turnstile effect of workers voting on management with their feet constitutes an ethical judgment of repugnant leadership at the top. \n\n Link to Learning \n\n Although no single set of traits identifies the ideal start-up leader, a demanding, driven nature is a fairly common characteristic. Consider these brief profiles of entrepreneurs: first, a profile on Walt Disney and then a profile on Steve Jobs as well as this video showing a contrasting view from Kerrie Laird at Vodafone. After watching the videos, consider this thought experiment: Suppose the cult of the charismatic—but dogmatic—entrepreneurial leader such as Walt Disney or Steve Jobs were replaced with one steeped in a commitment to employee empowerment that Kerrie Laird claims for Vodafone? Could this change the culture at start-ups? If it could, do you believe that change would be for the better or worse? \n\n These observations identify what may be unique to entrepreneurial culture . This is a combination of personality and management style often identified with those business leaders who strike out on their own, bring a start-up to life, and shape its initial business practices and culture on the job. If the enterprise is successful, the principles and philosophy of the founder become enshrined in the lore of the company, so that long after his or her departure, succeeding leaders find themselves beholden to the management philosophy exemplified from the early days of the firm. 7 As you seek the right leadership style to implement on the job, begin by asking precisely what kind of leader you would prefer to work for if you were not the boss. The answer you provide may very well be the best model to follow as you develop your own leadership personality, whether it is at a start-up or a more established company. \n\n The first employees of a start-up realize what is at stake as the company tiptoes into new entrepreneurial waters. The founder may be the boss, but those associated with him or her sense a collaborative spirit that directly joins them to the founder as well as each other. There can be a genuine fraternity among those who have been with the firm since day 1 or shortly thereafter. Founding members of an entrepreneurial business are also often willing to undergo the strains and rigors attached to a start-up in return for an ownership stake in the company that allows them to profit handsomely from its later growth and success. \n\n Newer staff, however, may not share this mindset. They may simply be seeking a secure position with a growing business rather than a chance to get in on the ground floor of a risky start-up. They will not necessarily have the tolerance for the demanding hours, chaos, and abrasive personalities that can characterize the early days of an enterprise. Can entrepreneurial founders shape a company’s culture so it can accommodate talented employees who are looking for a corporate culture that supports some work–life balance? \n\n Consider also the ethical practices of an entrepreneur and the ethical expectations of employees. Suppose that one of the distinguishing features woven into the fabric of the start-up is the respect extended to customers or clients. An entrepreneur typically promises always to hold customers in the highest regard, never lie to them, and serve them well. Furthermore, suppose this entrepreneur successfully instills this same ethos among all employees from the outset. Respect for customers is intended to become a distinguishing feature of the business; even if it causes monetary loss to the company, this entrepreneur will not cheat a client or misrepresent the company’s services. Finally, presume that this ethos is embedded into the culture of the company while it is still in start-up mode. \n\n Now, and literally against the odds, suppose the company becomes successful. This may signal the hardest time of all for the entrepreneur. Growth often accompanies success, and growth means, among other things, more employees. Not all these new hires will be as committed to the same degree of responsibility for customers. They will not necessarily set out to cheat clients, but they might lack the founder’s enthusiasm for the most honorable treatment of customers. How can an entrepreneur ensure that the initial commitment carries over to the second generation of leadership? He or she cannot simply order it to happen—human nature usually does not respond so easily. So entrepreneurs must do their best to ensure that their version of customer service, one that prioritizes respect for clients, is passed along to new employees. It may be ingrained in the longest-serving employees, but it must be nurtured to the point where it has the same significance for the newest hires. This is where leadership mettle is tested to the severest degree. \n\n Cases from the Real World Growing Up with a Start-Up In the summer of 1970, a college senior named Paul Orfalea opened a store near the University of California, Santa Barbara, campus. He called it “Kinko’s” after his own nickname and, with his partners, he sold college school supplies and around-the-clock copying services for students. After twenty-five years, Kinko’s had grown to 1,200 stores and 23,000 employees, and Orfalea privately and lucratively sold it to FedEx. \n\n Over the many years that Orfalea ran his start-up, his business became amazingly profitable but also imposed enormous stress on him and his founding partners and coworkers. As he put it, “I don’t hide the fact that I have a problem with anger.” 8 Since selling the company, Orfalea has spent many years mending relationships with those who worked most closely with him while he was building it. \n\n What contributed to the tensions Orfalea felt while managing this burgeoning enterprise? Long hours, of course, but also the need he felt to sustain his initial success, to make each year more profitable than the last. Entrepreneurs often believe they are only as successful as their last quarter’s profit and are driven to exceed it. Orfalea also felt that he alone was equipped to call others to account and veto what he felt were bad business ideas. Anger became a chief enemy he battled. \n\n “In my mid- to late-forties,” he said, “I struggled increasingly to manage my own emotional nature. Sometimes I felt I’d created a monster. The monster wasn’t Kinko’s, it was me.” 9 Orfalea acknowledged the anger and resentment that he often felt toward other longtime staff at the company, which overpowered the respect that he knew he owed them. Consequently, he directed comments and actions at his colleagues that he has spent many subsequent years attempting to redress. All in all, he has labored diligently to repair friendships that he admits were frayed by his behavior alone. \n\n After reflection, Orfalea now offers these recommendations to prospective entrepreneurs: Do not give way to your anger in the midst of the frustrating turns business inevitably takes. Do not take that anger home with you, either. Finally, try to be the person you most genuinely are, both at work and at home. It took Orfalea time to learn these lessons, but they are worthwhile for any would-be entrepreneur to ponder. 10 \n\n Critical Thinking \n\n What price would you be willing to pay to pursue an entrepreneurial career? What price would you demand from your partners in the business? How long could you let work monopolize your life? \n\n In your opinion, was Orfalea right to manage Kinko’s the way he did as it grew? Were the worries, anxieties, and bad moods he experienced inevitable? How would you avoid these? \n 9.2 The Influence of Advertising \n\n Learning Objectives \n\n By the end of this section, you will be able to: \n\n Discuss how social media has altered the advertising landscape \n\n Explain the influence of advertising on consumers \n\n Analyze the potential for subliminal advertising \n\n The advertising industry revolves around creating commercial messages urging the purchase of new or improved products or services in a variety of media: print, online, digital, television, radio, and outdoor. Because as consumers we need and want to be informed, this feature of advertising is to the good. Yet some advertising is intended to lead to the purchase of goods and services we do not need. Some ads may make claims containing only the thinnest slice of truth or exaggerate and distort what the goods and services can actually deliver. All these tactics raise serious ethical concerns that we will consider here. \n\n The Rise of Social Media \n\n Relevant to any discussion of the influence and ethics of advertising is the emergence and dominance of social media , which now serve as the format within which many people most often encounter ads. Kelly Jensen, a digital-marketing consultant, observed that we inhabit a “Digital Era” in which “the internet is arguably the single most influential factor of our culture—transforming the way we view communication, relationships, and even ourselves. Social media platforms have evolved to symbolize the status of both individuals and businesses alike. . . Today, using social media to create brand awareness, drive revenue, engage current customers, and attract new ones isn’t optional anymore. Now it is an absolute ‘must.’” 11 \n\n These are bold claims—as are the claims of some advertising—but Jensen argues convincingly that social media platforms reach many consumers, especially younger ones, who simply cannot be captured by conventional advertising schemes. For those who derive most of the significant information that shapes their lives solely through electronic sources, nothing other than social media–based appeals stands much chance of influencing their purchasing decisions. \n\n This upending of conventional modes of advertising has begun to change the content of ads dramatically. It certainly presents a new stage on which people as young as their teens increasingly rely for help in choosing what to buy. Many marketers have come to appreciate that if they are not spreading the word about their products and services via an electronic source, many millennials will ignore it. 12 \n\n Undeniably, a digital environment for advertising, selling, and delivering products and services functions as a two-edged sword for business. It provides lightning-quick access to potential customers, but it also opens pathways for sensitive corporate and consumer data to be hacked on an alarming scale. It offers astute companies nearly unlimited capacity to brand themselves positively in the minds of purchasers, but it simultaneously offers a platform for disgruntled stakeholders to assail companies for both legitimate and self-serving reasons. \n\n Paul A. Argenti, who has taught business communication for many years at the Tuck School of Business at Dartmouth University, has studied this dilemma. As he put it, “mobile apps have created a new playground for cyber-thieves.” 13 And consumer advocates and purchasers alike “now use technology to rally together and fuel or escalate a crisis—posing additional challenges for the corporation” in the crosshairs of criticism. Finally, “the proliferation of online blogs and social networking sites has greatly increased the visibility and reach of all current events, not excluding large corporate” 14 bungling. \n\n Regardless of the delivery platform, however, any threat that the advertising of unnecessary or harmful products may pose to our autonomy as consumers is complicated by the fact that sometimes we willingly choose to buy goods or services we may not necessarily require. Sometimes we even buy things that have been proven to be harmful to us, such as cigarettes and sugary drinks. Yet we may desire these products even if we do not need them. If we have the disposable income to make these discretionary purchases, why should we not do so, and why should advertisers not advise us of their availability? \n\n Does Advertising Drive Us to Unnecessary Purchases? \n\n By definition, advertising aims to persuade consumers to buy goods and services, many of which are nonessential. Although consumers have long been encouraged to heed the warning caveat emptor (let the buyer beware), it is a valid question whether advertisers have any ethical obligation to rein in the oft-exaggerated claims of their marketing pitches. Most consumers emphatically would agree that they do. \n\n The award-winning Harvard University economist John Kenneth Galbraith directly addressed this issue in The Affluent Society , first published in 1958. In what he depicted as the “the dependence effect,” Galbraith bemoaned the power of corporations to harness wide-ranging advertising strategies, marketing efforts, and sales pitches to influence consumer purchasing decisions. 15 He asked whether it is possible for a sophisticated advertising campaign to create a demand for a product whose benefits are frivolous at best. If so, is there anything inherently wrong with that? Or are informed consumers themselves responsible for resisting tempting—though misleading—advertising claims and exercising their own best judgment about whether to buy a product that might be successful, not because it deserves to be but simply because of the marketing hype behind it? These questions remain fundamental to the manager’s task of creating ethical advertising campaigns in which truthful content is prioritized over inducing wasteful consumption. \n\n Psychological appeals form the basis of the most successful ads. Going beyond the standard ad pitch about the product’s advantages, psychological appeal s try to reach our self-esteem and persuade us that we will feel better about ourselves if we use certain products. If advertising frames the purchase of a popular toy as the act of a loving parent rather than an extravagance, for instance, consumers may buy it not because their child needs it but because it makes them feel good about what generous parents they are. This is how psychological appeals become successful, and when they do work, this often constitutes a victory for the power of psychological persuasion at the expense of ethical truthfulness. \n\n Purchases are also affected by our notion of what constitutes a necessity versus a luxury, and that perception often differs across generations. Older consumers today can probably remember when a cell phone was considered a luxury, for instance, rather than a necessity for every schoolchild. On the other hand, many younger consumers consider the purchase of a landline unnecessary, whereas some older people still use a conventional phone as their main or even preferred means of communication. The cars and suburban homes that were once considered essential purchases for every young family are slowly becoming luxuries, replaced, for many millennials, by travel. Generational differences like these are carefully studied by advertisers who are anxious to make use of psychological appeals in their campaigns. \n\n A consumer craze based on little more than novelty—or, at least, not on necessity or luxury in the conventional sense—is the Pet Rock, a recurring phenomenon that began in 1977. Pet Rocks have been purchased by the millions over the years, despite being nothing more than rocks. During the 2017 holiday shopping season, they retailed at $19.95. 16 Is this a harmless fad, or a rip-off of gullible consumers who are persuaded it can satisfy a real need? In the annals of marketing, the Pet Rock craze denotes one of the most successful campaigns—still unfolding today, though in subdued fashion—in support of so dubious a product. \n\n As long as marketers refrain from breaking the law or engaging in outright lies, are they still acting ethically in undertaking influential advertising campaigns that may drive gullible consumers to purchase products with minimal usefulness? Is this simply the free market in operation? In other words, are manufacturers just supplying a product, promoting it, and then seeing whether customers respond positively to it? Or are savvy marketing campaigns exerting too much influence on consumers ill prepared to resist them? Many people have long asked exactly these questions, and we still have arrived at no clear consensus as to how to answer them. Yet it remains an obligation of each new generation of marketers to reflect on these points and, at the very least, establish their convictions about them. \n\n A second ethical question is how we should expect reasonable people to respond to an avalanche of marketing schemes deliberately intended to separate them from their hard-earned cash. Are consumers obligated to sift through all the messages and ultimately make purchasing decisions in their own best interest? For example, does a perceived “deal” on an unhealthy food option justify the purchase ( Figure 9.3 )? These questions have no consensus answers, but they underlie any discussion of the point at which sophisticated advertising runs headlong into people’s obligation to take responsibility for the wisdom of their purchases. \n\n No one would argue that children are particularly susceptible to the ads commercial television rains over them regularly. Generally, young children have not developed sufficient judgment to know what advertised products are good for them and which ones have little or no benefit or perhaps can even harm. Research has even shown that very young children have difficulty separating what is real on television from what is not. This is especially so as it pertains to advertising for junk food. Savvy marketers take advantage of the fact that young children (those younger than age seven or eight years) view advertising in the same manner they do information from trustworthy adults—that is, as very credible—and so marketers hone pitches for junk food directly to these children. 17 \n\n What restrictions could we reasonably impose on those who gear their ads toward children? We could argue that they should take special care that ads targeting children make absolutely no exaggerated claims, because children are less capable of seeing through the usual puffery that most of us ignore. Children are more literal, and once they gain the ability to understand messages directed toward them, especially when voiced by adult authority figures, they typically accept these as truthful statements. \n\n When adults make poor consumer choices, who is responsible? Is it ourselves? Is it our society and culture, which permit the barrage of marketing to influence us in ways we often come to regret? Is it the persuasive power of marketers, which we should rein in through law? Do adults have the right to some assistance from marketers as they attempt to carry out their responsibility to protect children from manipulative ads? We have no easy answers to these questions, though they have taken on special urgency as technology has expanded the range of advertising even to our smartphones. \n\n Is Subliminal Advertising Real? \n\n It may be possible for marketing to be unfairly persuasive in ways that overwhelm the better judgment of consumers. Whether it is the consumers’ responsibility to resist or marketers’ to tone down their appeals, or both, will continue to be debated. Yet the question of where responsibility lies when consumers are steered to make choices certainly has ethical ramifications. \n\n Some psychologists and educational specialists claim that the very old and the very young are particularly ill prepared to exercise good judgment in the face of subliminal advertising , that is, embedded words or images that allegedly reach us only beneath the level of our consciousness. Other experts, however, disagree and insist that subliminal advertising is an urban myth that no current technology could create or sustain. \n\n A U.S. journalist, Vance Packard, published The Hidden Persuaders in 1957, contending that subliminal messaging had already been introduced into some U.S. cinemas to sell more refreshments at the theaters’ snack bars. Alarms sounded at the prospect, but it turned out that any data on which Packard was relying came from James Vicary, a U.S. market researcher who insisted he had engineered the feat in a cinema in New Jersey. No other substantiation was provided, and Vicary’s claim was eventually dismissed as self-promotion, which he seemed to concede in an interview five years later. Although the immediate threat of subliminal advertising receded, some people remain concerned that such persuasion might indeed be possible, especially with the advent of better technologies, like virtual reality, to implement it. 18 \n\n A 2015 study at the University of South Carolina found that thirsty test subjects placed in the role of shoppers in a simulated grocery store could be subliminally influenced in their choice of beverages if they were primed by images of various beverage brands within fifteen minutes of acknowledging being thirsty. After that window of time passed, however, any impact of subliminal messaging receded. 19 \n\n So the scientific evidence establishing any real phenomenon of subliminal advertising is inconclusive. Put another way, the evidence to this point does not definitively demonstrate the existence of a current technology making subliminal marketing pitches possible. Given this, it cannot be clearly determined whether such a technology, if it did exist, would be effective. Another question is whether virtual reality and augmented reality might eventually make subliminal advertising viable. Real subliminal persuasion might render children, the elderly, and those with developmental disabilities more vulnerable to falling prey. Could even the most skeptical viewer resist a message so powerfully enhanced that the product can be sampled without leaving home? Would you be in favor of federal government regulation to prevent such ads? What sort of ethical imperatives would you be willing to request of or impose on sophisticated marketers? \n\n Link to Learning \n\n Is subliminal messaging real? Watch this video where BBC Earth Lab investigates a bit whimsically what truth might lie in the claim that subliminal advertising is real to learn more. \n\n Advertising plays a useful role in informing consumers of new or modified products and services in the marketplace, and wise purchasers will pay attention to it but with a discerning eye. Even the exaggerated claims that often accompany ads can serve a purpose as long as we do not unquestioningly accept every pitch as true. \n 9.3 The Insurance Industry \n\n Learning Objectives \n\n By the end of this section, you will be able to: \n\n Discuss whether the underlying business model of the insurance industry is an ethical one \n\n Identify the reasons why the government offers certain kinds of insurance \n\n Discuss the ethical issues in insurers’ decisions whether to offer disaster insurance \n\n Explain the concept of redlining \n\n Although the concept of insurance dates back to antiquity, the insurance industry as a profession came of age in the seventeenth century, when maritime trade in valuable commodities like coffee, tea, cocoa, sugar, and silk became an immense industry, but one fraught with uncertainty. Merchants sought a means to limit their financial losses in the event their cargoes were lost at sea. \n\n In England, merchants and shippers gathered together in associations, or syndicates, to distribute the risk of loss as evenly as possible. For a fee, individual merchants and ships’ owners in these syndicates could buy insurance, essentially the right to be financially compensated by the syndicate’s fund for their loss if their shipments or vessels sank. The first such association of traders and shippers began at Samuel Lloyd’s coffee house, on Tower Street near the River Thames, in 1688. This was the origin of the huge insurance market now known as Lloyd’s of London, 20 and from these early forms of group insurance sprang the profession as it exists today. \n\n From the seventeenth century to the present, the profession has faced a fundamental ethical quandary: An insurance company makes money when purchaser fees, called premiums , are numerous and claim s , requests for monetary compensation for covered losses, are few. But the reality is that accidents occur, whether they take the form of shipping losses, vehicular collisions, or home or business fires. So insurance carriers set customer premiums at a high enough rate to compensate themselves with a baseline profit when claims for compensation arise. The ethical question then is what constitutes a reasonable profit. The way the industry defines “reasonable” is directly reflected in the premiums it sets, which also take into account actuarial and statistical calculations of the historic frequency of the occurrence of various claims. \n\n How Insurance Works \n\n The irony of insurance coverage of any sort is that we buy it hoping never to use it. Still, business and consumers alike appreciate that a catastrophic loss can be financially devastating and so they seek to protect against it. Insurance coverage does not prevent illness, accidents, or other unforeseen events from occurring, but it does offer a means to recover, at least partially, from the monetary costs associated with them. \n\n Insurance policies constitute a form of contract between insurers and the insured. To reduce their losses in those situations in which they must pay on a claim, insurers do their best to attach high premiums to the coverage and identify exclusions and limits on it. They worry about being forced to pay out on frivolous and exaggerated claims, while policyholders fear that on the rare occasions when they will have to file a claim, their reimbursement will be minuscule and/or their future premiums will rise. From the perspective of the consumer, the guarantee of a fair payout on a claim is the only inducement to pay insurance premiums in the first place. \n\n What Would You Do? Valuing Your Inventory versus Valuing Your Employees Assume you are the owner of a small apparel manufacturer with approximately fifty employees. Your business is located in a blighted area of town where the jobs you provide are important, but the insurance costs of doing business there are significant, too. Recently, fire and theft coverage has escalated in cost, but it is essential to protect your premises and inventory, and local ordinances require that you purchase it. You have customarily provided health coverage for your employees and their families, which many of them would not be able to afford if they had to bear the cost themselves. You would like to continue providing this coverage—though, due to your small employee base, you are not legally obligated to do so—but these costs have risen too. Finally, you would prefer to stay in this location, because you feel an obligation to your workers, most of whom live nearby, and because you feel welcomed by the community itself, which includes some longtime customers. Still, you may be forced to choose between paying for your employee health care costs and moving to a different area of town where fire and theft coverage would not cost as much. \n\n Critical Thinking \n\n How will you make the decision within an ethical framework? \n\n What will you, your business, and your employees gain and lose based on what you decide? \n\n What, if anything, do you and your business owe the community of which you have been a part for so long? \n\n Insurance protections are, in fact, limited. In August 2017, Hurricane Harvey dumped fifty-two inches of rain on Houston, Texas, accompanied by fierce winds. Tens of thousands of homes, stores, factories, and other industrial sites suffered severe damage and flooding. Although normal homeowners’ and business owners’ insurance provides for loss due to hurricane winds, it does not cover loss due to flooding. As The Economist observed in the immediate aftermath of the hurricane, “whereas wind damage is covered under most standard insurance policies in America, flood insurance is a government-run add-on that far from all homeowners buy. As a result, of over $30 billion in property losses in Texas, only 40 percent may be insured.” 21 \n\n Not only do few homeowners buy flood insurance; few private insurers offer it. After all, most insurance carriers are for-profit, and companies would make little money insuring everyone against flood damage in flood-prone areas. It would be a losing proposition for any carrier to undertake, because insurance companies enjoy their highest returns when claims are few and payouts small. But the federal government is not a commercial broker and does not intend to make a profit from extending any sort of insurance coverage. For that reason, the National Flood Insurance Act of 1968 established a way to dispense flood coverage through a federal agency. Today that supervising agency is the Federal Emergency Management Authority (FEMA), in partnership with the Department of Homeland Security ( Figure 9.4 ). As of August 2017, just before Harvey struck, some five million households had taken out FEMA-sponsored flood coverage. 22 \n\n Link to Learning \n\n Consumers’ criticisms of the insurance industry are not limited to the United States; they pose an international issue for the profession. Read this Sydney Morning Herald article that explores the causes of controversy that haunt insurance carriers in Australia to learn more. Principally, they center on the lengths to which insurers might go to disallow a claim and so dispose of their obligation to pay out on it, at least according to some consumer watchdogs. \n\n The California Earthquake Authority serves a similar function at the state level by managing privately funded insurance against earthquakes in California. The private brokers in the program make no profit from offering this coverage, but they do earn the right to offer (and profit from) other insurance in California. \n\n The Ethical Dilemma of Insuring against Natural Disasters \n\n We do not know with certainty what effect climate change will have on the incidence or severity of natural disasters (i.e., accidents that do not appear to have any direct human cause). We do know, however, that these events can be ruinously expensive, for the carriers that insure against them and for those who suffer them and must put their lives back together afterward. \n\n Business writer Don Jergler said, for example, that “climate change has created a ‘wildfire crisis in California,’ which in turn is ‘causing a fire insurance predicament.’” California insurance commissioner Dave Jones warned in December 2017, after a particularly disastrous fire season in California, that “insurers may start to back off writing insurance in some areas [of the state],” and this would pose a crisis for homeowners who consequently lost insurance protection against losses caused by wildfires. 23 \n\n In Canada, too, “environmental risks linked to climate change are becoming important issues for insurers who need to consider their response to related risks and climate related losses whether arising from weather related events such as flood and storms or liability risks from third party claims.” 24 \n\n When insurance carriers must pay claimholders more often on claims arising from natural disasters, they lose money at a rate that could make them less willing to underwrite similar policies in the future. This unwillingness, in turn, would deny coverage against these disasters to an increasing number of individuals and companies. The high cost of disaster claims and subsequent shrinking of policy offerings are losses first experienced by the insurance industry, but they have rapid and dire consequences for policyholders. \n\n Again, we come to the ethical conundrum as to what we might fairly expect from insurance carriers and from clients who seek to indemnify themselves against natural disasters. In regions where certain kinds of disasters are more likely to occur, is it reasonable to dictate that carriers still must provide coverage? If so, should we consider extending public subsidies to the carriers to protect them against catastrophic payouts? Should premiums be assigned on the basis of the incidence patterns and severity of risk associated with particular disasters in certain regions? With these questions, we return to the ethical consideration of what constitutes a reasonable profit for carriers and what premium policy holders ought to be charged for sufficient coverage. \n\n The United States does not have the strong tradition of private/public ownership of industries, such as petroleum extraction or air travel that some other nations do. 25 Essentially, private/public ownership is an arrangement in which private (industry) and public (government) monies are combined to more safely bear an industry’s risk and also share in its profit. It is often a successful partnership. When we consider the scale of loss that can result from natural disasters, and the extent of the public’s need for protection from such loss, insurance may be a U.S. industry in which private/public ownership of some policies would be appropriate. The National Flood Insurance Program and the California Earthquake Authority are rare examples of public agencies managing insurance coverage that private insurers have declined to provide because the potential for profit is too low. Whether partnerships like this can and should be expanded, and whether they can be funded from federal and state budgets, are ethical questions for federal and state governments and policyholders alike. \n\n Cases from the Real World What Does the Future Hold for the Insurance Industry? Many insurance carriers enjoy a robust business. As an example, UnitedHealth Group Incorporated, headquartered in Minnesota, had about $185 million in sales in 2017 and employed approximately 230,000 people. Still, as an industry report from the business research company Hoovers established, insurers of all stripes, health or auto or property or anything else, face two major hurdles. First, they “are increasingly subject to a large number of regulations and reporting requirements by states. Consequently, some insurers have withdrawn from states that impose burdensome requirements.” Second, large-scale “claims have become more common, creating problematic concentrations of risk for individual insurers. . . . And some risks can be large enough to drive insurers out of business or cause them to curtail services offered, increase rates, or leave states where risk is highest.” 26 Thus, profits can be high within the industry, but so can payouts in the aftermath of major catastrophes. The report goes on to say that “floods, hurricanes, and tornadoes” produce the riskiest economic circumstances for the industry. Consequently, states in which these weather events are more common—Alabama, Florida, and North Carolina—have seen some carriers cease business operations within them. 27 \n\n Critical Thinking \n\n In selecting coverage and setting prices, how does an insurance company choose the ethical balance between making a reasonable profit and risking catastrophic losses of its own? \n\n Should the law require that carriers offer property insurance in states where harsh natural disasters occur? Or should federal and state monies be used to subsidize insurance companies’ resources in these circumstances? In each case, why or why not? \n\n Redlining: Discrimination in Insurance \n\n A specific ethical challenge within the insurance profession is the tendency to engage in redlining . Redlining is the practice of assigning or denying coverage for certain policies, such as auto, homeowners, or business insurance, on the basis of the geographic neighborhoods where applicants for such coverage live, particularly inner-city neighborhoods. A variation on the practice is to charge considerably higher prices for the same coverage in different neighborhoods. Redlining assumes that the propensity for accidents, burglaries, fires, and other catastrophes is higher in some areas than others, so claims and costs will be higher for the insurance carrier. \n\n At first glance, this practice appears to make economic sense from the perspective of both the insurer and the insured. Looking beneath the surface, however, reveals that redlined neighborhoods are often areas where racial and ethnic minorities live. No insurance carrier ever admits to engaging in discriminatory redlining (the term refers to an older practice by which insurance companies marked certain neighborhoods in red on print copies of coverage maps). Nearly every state in the United States forbids the practice. Yet a comprehensive 2017 study by Consumer Reports and ProPublica, a nonprofit research organization, indicated the phenomenon may remain very much a reality. This study focused on rates for auto insurance and found that for “decades, auto insurers have been observed to charge higher average premiums to drivers living in predominantly minority urban neighborhoods than to drivers with similar safety records living in majority White neighborhoods. Insurers have long defended their pricing by saying that the risk of accidents is greater in those neighborhoods, even for motorists who have never had one.” 28 \n\n The authors of the report compared auto insurance premiums and claims paid in four states (California, Illinois, Missouri, and Texas) and found similar results whether the carrier was Allstate, Geico, Liberty Mutual, or another. They contended “that many of the disparities in auto insurance prices between minority and White neighborhoods are wider than differences in risk can explain.” 29 This is significant because laws do typically permit premium rates to be set according to the incidence of claims filed within certain neighborhoods. Yet laws never allow rates to be based solely or predominantly on the race or ethnicity of the residents in different neighborhoods. This is the essence of prohibited redlining. Professionals in the industry do well to steer clear of this practice or even the appearance of it, and that is the overriding theme of this study. \n\n Drawing back, the ethical challenge for any responsible carrier is to ensure that the race, ethnicity, or creed of any policyholder plays absolutely no role in the premiums assigned him or her. There is no defensible reason to base a carrier’s decision to extend or deny insurance coverage or assign the premium amount for it on these factors. \n 9.4 Ethical Issues in the Provision of Health Care \n\n Learning Objectives \n\n By the end of this section, you will be able to: \n\n Identify ethical problems related to the availability and cost of health care in the United States and elsewhere \n\n Discuss recent developments in insuring or otherwise providing for health care in the United States \n\n Private health care in the United States has historically been of high quality and readily available, but only for those who could afford it. This model for rationing health services is rare in the developed world and stands in dramatic contrast to the provision of health care in other industrialized economies. Those who provide health care and administer the health care system find that balancing the quality of, access to, and cost of medical care is an ethical dilemma in which they must continually engage. 30 \n\n Multipayer Health Care in the United States \n\n Typically in the United States, medical services have been dispensed through a multipayer health care system , in which the patient and others, such as an employer and a private health insurance company, all contribute to pay for the patient’s care. Germany, France, and Japan also have multipayer systems. In a single-payer health care system such as those in the United Kingdom and Canada, national tax revenues pay the largest portion of citizens’ medical care, and the government is the sole payer compensating those who provide that care. Contributions provided by employers and employees provide the rest. Both single- and multipayer systems help reduce costs for patients, employers, and insurers; both, especially single-payer, are also heavily dependent on taxes apportioned across employers and the country’s population. In a single-payer system, however, because payment for health care is coordinated and dispensed by the government, almost no one lacks access to medical services, including visitors and nonpermanent residents. \n\n Many reasons exist for the predominance of the multipayer system in the United States. Chief among these is the U.S. tradition that doctors’ services and hospital care are privatized and run for profit. The United States has no federal health care apparatus that organizes physicians, clinics, and medical centers under a single government umbrella. Along with the profit motive, the fact that providers are compensated at a higher average rate than their peers abroad ensures that health care is more expensive in the United States than in most other nations. \n\n The United States also has more health care professionals per citizen than most other countries, and more medical centers and clinics ( Figure 9.5 ). One positive result is that the wait for most elective medical procedures is often shorter than in other countries, and travel time to a nearby medical facility is often less. Still, paying for health care remains one of the most controversial topics in the United States, and many question what it is that Americans gain from the current system to balance the cost. As an exhaustive study from The Commonwealth Fund asserted, “the United States spends far more on health care than other high-income countries, with spending levels that rose continuously over the past three decades. . . . Yet the U.S. population has poorer health than other countries.” 31 \n\n Besides its inefficiencies, the state of U.S. health care raises challenging ethical issues for professionals in the field and for patients as well. What happens if many poorer people cannot afford health care? Should doctors treat them anyway? Who is qualified to receive subsidized (insured) health care? In the absence of universal health care, which is generally ensured elsewhere by a single-payer system that entitles everyone to receive care at very low cost, can the United States truly boast of being the richest nation on Earth? Put another way, when the least materially advantaged in a country do not have access to quality health care, what is the worth such a nation patently is assigning to those human beings residing within it? \n\n Supporters of the status quo for health care in the United States may point to state-of-the-art facilities as evidence of its success. Yet other nations, such as Australia, the United Kingdom, and the Netherlands, have equal levels of medical technologies available for patients and are given much more favorable marks for universal health insurance and accessibility by The Commonwealth Fund. \n\n The High Cost of Prescription Drugs \n\n Discussions of health care accessibility have become politically charged, so for now it is enough to observe that not only is medical care enormously expensive in the United States but so are prescription drugs. According to William B. Schultz, an attorney writing in the Washington Post in 2017, “in the past 35 years, the only significant victory in the battle to control drug prices has been the enactment of legislation that established the generic drug program at the FDA [Federal Drug Administration].” Otherwise, he stated, “prescription drug prices account for 17 percent of the nation’s health-care costs, up from 7 percent in the 1990s,” and “prescription drug spending accounts for nearly 20 percent of total program spending for Medicare, the largest of the governmental health-care programs.” 32 (Schultz is not entirely impartial; he is a partner in a law firm that represents generic drug providers, among other clients.) \n\n Link to Learning \n\n The New York Times asked its readers to relay their experiences as purchasers of prescribed medicines that they thought carried much too high a price tag. This article on some of the reader responses to drug prices was reported by two journalists at the paper, Katie Thomas and Charles Ornstein. \n\n The only way to recoup the enormous cost of developing new drugs, says the pharmaceutical industry, is to pass it along to consumers. Critics, on the other hand, assert that the much of the expense incurred within the industry results from the high cost of marketing new drugs. Wherever the truth lies in this debate, it remains that exorbitant prices for much-needed medicines dramatically reduce their social value when only a few individuals can actually afford to obtain them. What does it say of our priorities if we have the technology to create life-saving medicines but allow astronomic prices effectively to deny them to many patients who require them? \n\n Paying for Health Care and Wellness \n\n Within the multipayer system, many U.S. workers have traditionally looked to their employers or their unions to subsidize the cost of care and thereby make it available for them and their families. Many reasons explain why this is so. In contrast to the European and Canadian perspective, for example, in which both the state and employers are presumed to have an interest in and responsibility for underwriting the cost of health care, the traditional U.S. approach is that workers and their employers should be responsible for securing this coverage. This belief reflects an unease on the part of some about assigning services to the government, because this implies the need for a larger governing entity as well as additional taxes to sustain it. The sentiment also reflects a conviction on the part of some that self-reliance is always to be preferred when securing the necessities of life. \n\n John E. Murray, a professor of economics at the University of Toledo, offered a related explanation. He cited the existence of industrial sickness funds in the United States, which arose in the late nineteenth and early twentieth centuries. These were monies “organized by workers through their employer or union [that] provided the rudiments of health insurance, principally consisting of paid sick leave, to a large minority of the industrial workforce of the late nineteenth and early twentieth centuries.” 33 Murray stated that these funds declined in popularity not because they were ineptly administered or rendered bankrupt by World War I or the Great Depression but rather because they gave way to even more effective instruments in the form of group insurance policies offered by employers or labor unions. \n\n So the U.S. worker’s experience differed from that of European labor in that much significant health care coverage was provided under the auspices of unions and employers rather than the state. Murray noted another source of relief for workers who experienced illness or injury that prevented them from working for any period of time, and that was charity. 34 Specific versions of charity were offered by religious organizations, including Christian churches and Jewish synagogues. Often, these religious bodies banded together to provide monetary benefits for sick or injured members of their own faith who might otherwise have been denied health coverage due to prejudice. 35 The U.S. social experience featured more ethnic and cultural diversity, especially in the nineteenth and early twentieth centuries, than was present in many European nations, and a downside is the racial, ethnic, and religious prejudice it inspired. \n\n A final distinction Murray pointed to is the past opposition of the American Medical Association to any sort of state-sponsored insurance. Early supporters of industrial sickness funds, including some physicians, anticipated that most doctors would support these funds as pathways ultimately directed to state-provided coverage. Instead, in 1920, “the American Medical Association voted officially to state its opposition to government health insurance. A sociologist concluded that from this time to the 1960s, physicians were the loudest opponents of government insurance.” 36 By default, then, many U.S. workers came to rely more on their employers or unions than on any other source for coverage. However, this explanation does not answer the larger ethical question of who should provide health insurance to residents and citizens, a question that continues to roil politics and society in the nation even today. \n\n Physicians and other healthcare professionals in the United States have always been held to high ethical standards in terms of the care they provide their patients. In fact, the American Medical Association first proposed a code of medical ethics in 1847, its founding year. Since then, the AMA has continued to revisit precisely what constitutes medical ethics for its members. In 2008, its code of medical ethics was revised. 37 The revisions imply that education in medical ethics for healthcare professionals is not accomplished once and for all. Rather, retraining and recertification is an ongoing process. More recently, large corporations have moved from providing one-size-fits-all insurance plans to compiling a menu of offerings to accommodate the different needs of their employees. Workers with dependent children may opt for maximum health care coverage for their children. Employees without dependents or a partner may elect a plan without this coverage and thereby pay lower premiums (the initial cost for coverage). Yet others might minimize their health-insurance coverage and convert some of the employer costs that are freed up into added pension or retirement plan value. Employers and workers have become creative in tailoring benefit plans that best suit the needs of employees ( Figure 9.6 ). Some standard features of such plans are the copayment , a set fee per service paid by the patient and typically negotiated between the insurance carrier and the employer; the annual deductible , a preset minimum cost for health care for which the patient is responsible each year before the carrier will assume subsequent costs; and percent totals for certain medical or dental procedures that patients must pay before the carrier picks up the remainder. \n\n Despite the intricacies of this customization, employers have found the group coverage policies they offer to be expensive for them too, more so with each passing year. Full health care coverage is becoming rarer as a standard employment benefit, and it is often available only to those who work full time. California, for example, stipulates that most workers need not be provided with employer health care coverage unless they work at least twenty hours a week. \n\n Rising costs for both employers and employees have combined to leave fewer employees with health care benefits at any given time. Employees with limited or no coverage for themselves and their dependents often cope by cutting back on the medical attention they seek, even when doing so places their health at risk. Whenever workers must skip medical services due to cost considerations, this places both them and their employers in an ethical quandary, because both typically want workers to be in good health. Furthermore, when employees must deny their dependents appropriate health care, this dilemma is all the more intensified. \n\n To try to reduce the costs to themselves of employee health care insurance coverage, some companies have instituted wellness programs to try to ensure that their workforces are as healthy as possible. Some popular wellness program offerings are measures to help smokers quit, workout rooms on work premises or subsidized gym memberships, and revamped vending and cafeteria offerings that provide a range of healthier choices. Some companies even offer employees bonuses or other rewards for quitting smoking or achieving specific fitness goals such as weight loss or miles walked per week. Such employer efforts appear benign at first glance, because these measures truly can produce better health on the part of workers. Still, ethical questions arise as to who the true beneficiaries of such policies are. Is it the employees themselves or the companies for which they work? Furthermore, if such measures were to become compulsory rather than optional, would it still reflect managerial benevolence toward employees? We discuss this in the following paragraphs. \n\n Wellness programs were inspired by safety programs first created by U.S. manufacturers in the 1960s. These companies included Chrysler, DuPont, and Steelcase. Safety programs were intended to reduce workplace accidents resulting in injuries and deaths. Over the years, such programs slowly but steadily grew in scope to encompass the general health of employees on the job. As these policies have expanded, they also have fostered some skepticism and resistance: “Wellness programs have attracted their share of criticism. Some critics argue workplace programs cross the line into employees’ personal lives.” 38 Ann Mirabito, a marketing professor at the Hankamer School of Business at Baylor University agrees there is potential for abuse: “It comes back to the corporate leader. . . . The best companies respect employees’ dignity and offer programs that help employees achieve their personal goals.” 39 \n\n Employees who exercise, eat healthily, maintain their ideal weight, abstain from smoking, and limit their alcoholic consumption have a much better chance of remaining well than do their peers who undertake none of these activities. The participating employees benefit, of course, and so do their employers, because the health insurance they provide grows cheaper as their workers draw on it less. As Michael Hiltzik, a consumer affairs columnist for the Los Angeles Times, noted, “Smoking-cessation, weight-loss and disease-screening programs give workers the impression that their employers really care about their health. Ostensibly they save money too, since a healthy workforce is cheaper to cover and less prone to absenteeism.” 40 \n\n Certainly, employers are also serving their own interests by trying to reduce the cost of insuring their workers. But are there any actual disadvantages for employees of such wellness programs that employers might unethically exploit? Hiltzik suggested one: “The dark downside is that ‘voluntary’ wellness programs also give employers a window into their workers’ health profiles that is otherwise an illegal invasion of their privacy.” 42 Thus the health histories of workers become more transparent to their bosses, and, Hiltzik and others worry, this previously confidential information could allow managers to act with bias (in employee evaluation and promotion decisions, for instance) under cover of concern about employees’ health. \n\n The potential for intrusion into employee privacy through wellness programs is alarming; further, the chance for personal health data to become public as a consequence of enrolling in such programs is concerning. Additionally, what about wellness rules that extend to workers’ behavior off the job? Is it ethical for a company to assert the right to restrict the actions of its employees when they are not on the clock? Some, such as researchers Richard J. Herzog, Katie Counts McClain, and Kymberleigh R. Rigard, argue that workers surrender a degree of privacy simply by going onto payroll: “When employees enter the workplace, they forfeit external privacy. For example, BMI [body mass index] can be visually calculated, smokers can be observed, and food intake monitored.” They acknowledge, however, that “protecting privacy and enhancing productivity can provide a delicate balance.” 41 \n\n Link to Learning \n\n As noted in previous chapters, we can find out a great deal about the ethical intentions of a company by studying its mission statement, although even the noblest statement is irrelevant if the firm fails to live up to it. Here is Anthem, Inc.’s very simple and direct mission statement as an example from a health care insurer. What impression does this statement leave with you? Would you add or delete anything to it? Why or why not? \n\n The Affordable Care Act \n\n Health care reform on a major scale emerged in the United States with the passage of the Patient Protection and Affordable Care Act, more commonly known as the Affordable Care Act (ACA) , in March 2010, during the Obama Administration. The ACA (so-called Obamacare ) represents a controversial plan that strikes its opponents as socialist. For its supporters, however, it is the first effective and comprehensive plan to extend affordable health care to the widest segment of the U.S. population. Furthermore, like most new federal policies, it has undergone tweaks and revision each year since becoming law. The ACA is funded by a combination of payments by enrollees and supplemental federal monies earmarked for this task. \n\n The ACA mandates a certain level of preventive care, a choice of physicians and health care facilities, coverage at no extra cost for individuals with preexisting health conditions, protection against the cancellation of coverage solely on the basis of becoming ill, and mental health and substance abuse treatment, all of which must be met by carriers that participate in the plan. The ACA also permits its holders to select from a number of marketplace plans as opposed to the limited number of plans typically offered by any given employer. 43 All in all, it is a far-reaching and complex plan whose full implications for employers and their employees have yet to be appreciated. Preliminary results seem to indicate that employer-provided coverage on a comprehensive scale remains a cheaper alternative for those workers eligible to receive it. 44 Given the general efficiency of group insurance policies provided by U.S. employers, an ethical issue for all managers is whether these policies offer the best care for the greatest number of employees and so should be the responsibility of management to offer whenever it is possible to do so. Current law requires all companies employing fifty or more workers to make insurance available to that part of their workforce that qualifies for such coverage (e.g., by virtue of hours worked). Is it right, however, to leave the employees of smaller firms to their own devices in securing health care? Even if the law does not require it, we hold that an ethical obligation resides with small businesses to do everything in their power to provide this coverage for their employees. \n\n Evidence of the intense debate the act has engendered is the Trump administration’s attempts, beginning in January 2017, to repeal the ACA entirely, or at least to dilute significantly many of its provisions. Nearly immediately upon his inauguration, President Trump signed Executive Order 13765 in anticipation of ending the ACA. Also that same month, the American Health Care Act was introduced in the House of Representatives, again with an eye to eliminating or seriously weakening the existing act. Much political debate within both the House and Senate ensued in 2017, with proponents of the ACA seeking to ensure its survival and opponents attempting (but, as of this writing, failing) to repeal it. \n\n The ACA represents the first far-reaching health care coverage to take effect since 1965, after many stalled or otherwise frustrated attempts. Since the passage that year of the Medicare and Medicaid Act, which provided health coverage to retired, elderly, and indigent citizens, many presidential administrations, Democrat and Republican alike, have worked to enlarge health care coverage for different segments of the national population. In addition to expanding eligibility for benefits, the Medicare and Medicaid Act had direct implications for business proprietors and their employees. For one, the act set up new automatic earnings deductions and tax schedules for workers and employers, and employers were made responsible for administering these plans, which help fund the programs’ benefits. \n\n The future of the ACA appears to depend on whether a Democrat or Republican sits in the White House and which party controls the Senate and the House in the U.S. Congress. Although legislation does hinge on the political sentiments of the president and the majority party in Congress, what is ethical does not lend itself to a majority vote. So regardless of whether the ACA survives, is revised, or is replaced entirely by new health care legislation, the provision of health care will likely continue to pose ethical implications for U.S. business and the workers who are employed by it. \n\n The ethical debate over universal health care coverage is larger even than business and its employees, of course, but it still carries immense consequences for management and labor irrespective of how the ACA or other legislation fares in the halls of government and the courts. An ethical dilemma for employers is the extent to which they should make health coverage available to their workers at affordable rates, particularly if federal and state government plans provide little or no coverage for residents and the costs of employer-provided coverage continues to climb. \n\n State-Level Experiments with Single-Payer Health Care Plans \n\n Against the backdrop of federal attempts to institute national health care over the past several decades, some individual states in the United States have used their own resources to advance this issue by proposing mandated health care coverage for their citizens. For example, in April 2006, Massachusetts passed An Act Providing Access to Affordable, Quality, Accountable Heath Care, the first significant effort at the state level to ensure near-universal health care coverage. \n\n The Massachusetts act created a state agency, the Commonwealth Health Insurance Connector Authority, to administer the extension of health care coverage to Massachusetts residents. In many ways, it served as the most significant precursor of and guide for the federal ACA, which would follow approximately four years later. By many accounts, the Massachusetts legislation has achieved its purposes with few negative consequences. As Brian C. Mooney, reporting in the Boston Globe , put it about five years after the act’s passage: “A detailed Globe examination [of the implementation of the act] makes it clear that while there have been some stumbles—and some elements of the effort merit a grade of ‘incomplete’—the overhaul, after five years, worked as well as or better than expected.” 45 \n\n The proposed Healthy California Act (SB 562) is another example. SB 562 passed in the California State Senate in June 2017. However, the Speaker of the Assembly, the lower house of the legislature, blocked a hearing of the bill at that time, and a hearing is necessary for the bill to advance to ratification. A new effort was initiated in February 2018 to permit the bill finally to be considered by the lower house. (Two differences between the California bill and the Massachusetts Act include the number of state residents who would be affected. Massachusetts has a population of about seven million compared to California’s nearly forty million. A second distinction is that SB 562 is constitutes a single-payer plan, whereas the Massachusetts Act does not.) \n\n Single-payer health care plans essentially concentrate both the administration of and payment for health care within one entity, such as a state agency. California’s effort is a very simple plan on its face but complex in its implementation. Here is how Michael Hiltzik summarized the intent of California Senate Bill 562: “The program would take over responsibility for almost all medical spending in the state, including federal programs such as Medicare and Medicaid, employer-sponsored health plans, and Affordable Care Act plans. It would relieve employers, their workers and buyers in the individual market of premiums, deductibles and copays, paying the costs out of a state fund.” 46 The bill would create a large, special program apparatus tentatively entitled Healthy California. It is contentious on many fronts, particularly in that it would create the largest single-payer health insurance plan sponsored by a U.S. state and the scope of the plan would necessitate a huge bureaucracy to administer it as well an infusion of state monies to sustain it. Furthermore, it would extend health care coverage to all residents of the state, including undocumented immigrants. \n\n A specific hurdle to passage of Healthy California is that it would cost anywhere from $370 billion to $400 billion and would require federal waivers so California could assume the administration of Medicare and Medicaid in the state as well as the federal funds currently allotted to it. All these conditions would be enormously difficult and time consuming to meet, even if the federal government were sympathetic to California’s attempts to do so. In 2018, that was decidedly not the case. \n\n Is free or inexpensive access to health care a basic human right? If so, which elements within society bear the principal responsibility for providing it: government, business, workers, all these, or other agencies or individuals? This is a foundational ethical question that would invoke different responses on the part of nearly everyone you may ask. \n\n Ethics Across Time and Cultures Free Universal Health Care Except for the United States, the largest advanced economies in the world all provide a heavily subsidized universal health care system , that is, a publicly funded system that provides primary health services to all, usually at a nominal fee only and with no exclusions based on income or wealth. Although these systems are not perfect, their continued existence seems assured, regardless of the cultural or political framework of the various countries. A logical question is why the United States would be an outlier on this issue, and whether that might change in the future. \n\n Some answers, as noted in the text, lie in the United States’ historical reliance on a mostly private system, with approximately 83 percent of health care expenses provided by the private sector through insurers and employers (in contrast, this percentage in the United Kingdom is 17). A solution that has gained traction in recent years is conversion to a single-payer system. How might this work? One article estimates that the cost of instituting a national, single-payer health care insurance program in the United States would be $32 trillion over ten years. If this estimate is accurate, would it be an exorbitant price tag for such a program, or would it be money well spent in terms of making good health care available to all citizens? 47 \n\n Critical Thinking \n\n Do you find it appropriate that health care costs be provided by a mix of private versus public sources? \n\n What advantages might single-payer health care offer over employer-provided coverage, care provided under the ACA, or privately purchased health insurance? \n\n As a nation, the United States has usually preferred a system predicated on private health care providers and insurers to pay for it. This arrangement has worked best in instituting high-quality care with minimal delays even for elective medical procedures. It has systematically failed, however, in establishing any sort of universal dispensation that is affordable for many citizens. \n\n In the early twenty-first century, the United States is moving ever so slowly and with plenty of hiccups toward some degree of national or state management of health care. Precisely where these efforts will take us may not be clear for the next several years. The political, economic, and ethical dimensions of public management of our health care drive considerable controversy and very little agreement. "}}},{"rowIdx":178,"cells":{"bname":{"kind":"string","value":"business_law_i_essentials"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":""},"intro":{"kind":"string","value":" Chapter Outline 14.1 Liability Under the Securities Act 14.2 The Framework of Securities Regulation Introduction \n\n Learning Outcome \n\nDescribe the Securities Exchange Act of 1934 and its impact on business."},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":0,"ans_text":"The New York Stock Exchange."},"bloom":null,"hl_context":"The SEC also oversees self-regulatory organizations ( SROs ) , or private organizations that create and enforce industry standards . These organizations are allowed to “ police ” themselves , but are subject to compliance with SEC regulations . <hl> The various well-known securities exchanges such as the New York Stock Exchange ( NYSE ) , the National Association of Securities Dealers Automated Quotation System ( NASDAQ ) , and the Chicago Board of Options are SROs . <hl> Per Section 12 ( g ) , companies with total assets exceeding $ 10 million and with 500 or more owners of any class of securities must register with the SEC unless they meets exemption requirements .","hl_sentences":"The various well-known securities exchanges such as the New York Stock Exchange ( NYSE ) , the National Association of Securities Dealers Automated Quotation System ( NASDAQ ) , and the Chicago Board of Options are SROs .","question":{"cloze_format":"___ is/are clauses in the U.S. Constitution that are relate to international law.","normal_format":"What are clauses in the U.S. Constitution that relate to international law?","question_choices":["The New York Stock Exchange.","The National Association of Securities Dealers.","The Chicago Board of Options.","All of the above."],"question_id":"fs-2232531356","question_text":"The following are examples of self-regulatory organizations that the SEC oversees:"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"c"},"bloom":null,"hl_context":"<hl> The SEC also oversees self-regulatory organizations ( SROs ) , or private organizations that create and enforce industry standards . <hl> These organizations are allowed to “ police ” themselves , but are subject to compliance with SEC regulations . The various well-known securities exchanges such as the New York Stock Exchange ( NYSE ) , the National Association of Securities Dealers Automated Quotation System ( NASDAQ ) , and the Chicago Board of Options are SROs . <hl> Per Section 12 ( g ) , companies with total assets exceeding $ 10 million and with 500 or more owners of any class of securities must register with the SEC unless they meets exemption requirements . <hl>","hl_sentences":"The SEC also oversees self-regulatory organizations ( SROs ) , or private organizations that create and enforce industry standards . Per Section 12 ( g ) , companies with total assets exceeding $ 10 million and with 500 or more owners of any class of securities must register with the SEC unless they meets exemption requirements .","question":{"cloze_format":"The types of companies that must register with the SEC are ___ .","normal_format":"Which types of companies must register with the SEC?","question_choices":["Companies with over 500 or more owners.","Companies with total assets of $10 million.","Companies with total assets exceeding $10 million and with 500 or more owners.","None of the above."],"question_id":"fs-223531356","question_text":"Which types of companies must register with the SEC?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"d"},"bloom":null,"hl_context":"<hl> The Securities Exchange Act of 1934 created numerous reporting requirements for public companies . <hl> <hl> The purpose of these requirements was transparency , that is , keeping the public up to date and informed of changes that might impact securities prices . <hl> Public companies with securities registered under Section 12 or that are subject to Section 15 ( d ) must file reports with the SEC . Section 12 requires the registration of certain securities and outlines the procedures necessary to do so . Information required by Section 12 includes the nature of the business , its financial structure , the different classes of securities , the names of officers and directors along with their salaries and bonus arrangements , and financial statements . Section 15 requires brokers and dealers to register with the SEC . <hl> Individuals who buy and sell securities are considered traders , and therefore , are not subject to filing under Section 15 . <hl> <hl> Section 15 ( d ) requires registered companies to file periodic reports , such as the the annual Form 10 - K and the quarterly Form 10 - Q . <hl> These reports will be explained in detail in the next section of this chapter . The SEC Commission makes these reports available to all investors through the EDGAR website to help them make informed investment decisions . <hl> Proxy Statements . <hl> Proxy statements are documents that the SEC requires that shareholders of companies with securities registered under Section 12 of the Securities Exchange Act of 1934 receive to allow them to vote on issues that will be decided at a stockholder meeting . This process is commonly applied when voting for directors or deciding corporate actions . Even shareholders who own just one share of a company receive proxy statements ; thus , the process of sending out these statements is a large undertaking for companies . While some companies still use the mail to deliver proxy statements , others send a “ Notice of Internet Availability of Proxy Materials ” to shareholders a minimum of 40 days before the shareholders ’ meeting . <hl> Form 8 - K . <hl> Certain events require the company to file a Form 8 - K , such as a change in the company ’ s officers , mergers , or declarations of bankruptcy . These are required to be filed within four business days with the SEC . <hl> Form 10 - Q . <hl> Form 10 - Qs are quarterly unaudited financial statements that contain financial information . Since they are unaudited , they are less expensive and time-consuming for the company to prepare ; however , investors do not have the additional assurance that they have been analyzed by a neutral CPA . <hl> Form 10 - K . <hl> Form 10 - K , also known as the annual report , contains audited financial statements . Audited financial statements have been reviewed by one or more CPAs who are not affiliated with the company and who provide an objective opinion about whether or not the financial statements , such as the balance sheet , income statement , statement of changes to retained earnings , and cash flow statement , conform with accounting standards known as the Generally Accepted Accounting Principles ( GAAP ) . When the Securities Exchange Act of 1934 was first passed , most companies ’ annual reports contained only the bare minimum amount of information . However , over time , companies came to view their annual reports as a way to not only comply with SEC requirements , but also to attract new investors and impress securities analysts , or financial professionals who study various industries to make recommendations on whether a security should be bought , held , or sold . Today , many annual reports contain not only the required facts , but also compelling narratives that detail the company ’ s mission and strategic goals . The annual reports of certain companies — for example , Berkshire Hathaway , written by Warren Buffett and Charlie Munger — provide not only their opinions on their own operations , known as the management discussion , but also their thoughts on the economy overall . The Form 10 - K is a large responsibility for a company because it must disclose the company ’ s analysis of its financial conditions , potential market risks , internal controls , legal proceedings , defaults , and other information that is deemed important for investors to make sound investment decisions . <hl> Publicly owned companies that meet certain size requirements are called reporting companies , and per Section 13 ( a ) of the Securities Exchange Act of 1934 , they must file periodic disclosures . <hl> The purpose of these disclosures is to help investors make educated decisions regarding how to invest their money . These reports include information about a company ’ s line of business , corporate officers and directors , and financial statements .","hl_sentences":"The Securities Exchange Act of 1934 created numerous reporting requirements for public companies . The purpose of these requirements was transparency , that is , keeping the public up to date and informed of changes that might impact securities prices . Individuals who buy and sell securities are considered traders , and therefore , are not subject to filing under Section 15 . Section 15 ( d ) requires registered companies to file periodic reports , such as the the annual Form 10 - K and the quarterly Form 10 - Q . Proxy Statements . Form 8 - K . Form 10 - Q . Form 10 - K . Publicly owned companies that meet certain size requirements are called reporting companies , and per Section 13 ( a ) of the Securities Exchange Act of 1934 , they must file periodic disclosures .","question":{"cloze_format":"___ is not considered a report required by the Securities Exchange Act of 1934.","normal_format":"All of the following are considered reports required by the Securities Exchange Act of 1934 except which one?","question_choices":["Form 8k.","Form 10 k.","Form 10Q.","All of the above."],"question_id":"fs-22325313560","question_text":"All of the following are considered reports required by the Securities Exchange Act of 1934 except:"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"10."},"bloom":null,"hl_context":"<hl> Corporate insiders are those officers , directors , and beneficial owners who own more than 10 % of a class of securities , registered under Section 12 of the Securities Exchange Act of 1934 . <hl> Corporate insiders must file a statement of ownership with the SEC to be in compliance , and as of August 27 , 2002 , the SEC implemented new rules that shortened the time period to report insider transactions . It is important for a company to have internal controls and a system to ensure their corporate insiders are reporting their trades in a timely fashion . Companies that do not implement and enforce compliance procedures can become liable for the actions of their employees who fail to follow the law .","hl_sentences":"Corporate insiders are those officers , directors , and beneficial owners who own more than 10 % of a class of securities , registered under Section 12 of the Securities Exchange Act of 1934 .","question":{"cloze_format":"Corporate insiders include officers, directors, and beneficial owners who own _____ % of a class of securities registered under Section 12 of the Securities Exchange Act of 1934.","normal_format":"Corporate insiders include officers, directors, and beneficial owners who own how many % of a class of securities registered under Section 12 of the Securities Exchange Act of 1934?","question_choices":["5.","10.","15.","20."],"question_id":"fs-223253356","question_text":"Corporate insiders include officers, directors, and beneficial owners who own _____ % of a class of securities registered under Section 12 of the Securities Exchange Act of 1934."},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"The New York Stock Exchange.\"\n },\n \"bloom\": null,\n \"hl_context\": \"The SEC also oversees self-regulatory organizations ( SROs ) , or private organizations that create and enforce industry standards . These organizations are allowed to “ police ” themselves , but are subject to compliance with SEC regulations . <hl> The various well-known securities exchanges such as the New York Stock Exchange ( NYSE ) , the National Association of Securities Dealers Automated Quotation System ( NASDAQ ) , and the Chicago Board of Options are SROs . <hl> Per Section 12 ( g ) , companies with total assets exceeding $ 10 million and with 500 or more owners of any class of securities must register with the SEC unless they meets exemption requirements .\",\n \"hl_sentences\": \"The various well-known securities exchanges such as the New York Stock Exchange ( NYSE ) , the National Association of Securities Dealers Automated Quotation System ( NASDAQ ) , and the Chicago Board of Options are SROs .\",\n \"question\": {\n \"cloze_format\": \"___ is/are clauses in the U.S. Constitution that are relate to international law.\",\n \"normal_format\": \"What are clauses in the U.S. Constitution that relate to international law?\",\n \"question_choices\": [\n \"The New York Stock Exchange.\",\n \"The National Association of Securities Dealers.\",\n \"The Chicago Board of Options.\",\n \"All of the above.\"\n ],\n \"question_id\": \"fs-2232531356\",\n \"question_text\": \"The following are examples of self-regulatory organizations that the SEC oversees:\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"c\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The SEC also oversees self-regulatory organizations ( SROs ) , or private organizations that create and enforce industry standards . <hl> These organizations are allowed to “ police ” themselves , but are subject to compliance with SEC regulations . The various well-known securities exchanges such as the New York Stock Exchange ( NYSE ) , the National Association of Securities Dealers Automated Quotation System ( NASDAQ ) , and the Chicago Board of Options are SROs . <hl> Per Section 12 ( g ) , companies with total assets exceeding $ 10 million and with 500 or more owners of any class of securities must register with the SEC unless they meets exemption requirements . <hl>\",\n \"hl_sentences\": \"The SEC also oversees self-regulatory organizations ( SROs ) , or private organizations that create and enforce industry standards . Per Section 12 ( g ) , companies with total assets exceeding $ 10 million and with 500 or more owners of any class of securities must register with the SEC unless they meets exemption requirements .\",\n \"question\": {\n \"cloze_format\": \"The types of companies that must register with the SEC are ___ .\",\n \"normal_format\": \"Which types of companies must register with the SEC?\",\n \"question_choices\": [\n \"Companies with over 500 or more owners.\",\n \"Companies with total assets of $10 million.\",\n \"Companies with total assets exceeding $10 million and with 500 or more owners.\",\n \"None of the above.\"\n ],\n \"question_id\": \"fs-223531356\",\n \"question_text\": \"Which types of companies must register with the SEC?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"d\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The Securities Exchange Act of 1934 created numerous reporting requirements for public companies . <hl> <hl> The purpose of these requirements was transparency , that is , keeping the public up to date and informed of changes that might impact securities prices . <hl> Public companies with securities registered under Section 12 or that are subject to Section 15 ( d ) must file reports with the SEC . Section 12 requires the registration of certain securities and outlines the procedures necessary to do so . Information required by Section 12 includes the nature of the business , its financial structure , the different classes of securities , the names of officers and directors along with their salaries and bonus arrangements , and financial statements . Section 15 requires brokers and dealers to register with the SEC . <hl> Individuals who buy and sell securities are considered traders , and therefore , are not subject to filing under Section 15 . <hl> <hl> Section 15 ( d ) requires registered companies to file periodic reports , such as the the annual Form 10 - K and the quarterly Form 10 - Q . <hl> These reports will be explained in detail in the next section of this chapter . The SEC Commission makes these reports available to all investors through the EDGAR website to help them make informed investment decisions . <hl> Proxy Statements . <hl> Proxy statements are documents that the SEC requires that shareholders of companies with securities registered under Section 12 of the Securities Exchange Act of 1934 receive to allow them to vote on issues that will be decided at a stockholder meeting . This process is commonly applied when voting for directors or deciding corporate actions . Even shareholders who own just one share of a company receive proxy statements ; thus , the process of sending out these statements is a large undertaking for companies . While some companies still use the mail to deliver proxy statements , others send a “ Notice of Internet Availability of Proxy Materials ” to shareholders a minimum of 40 days before the shareholders ’ meeting . <hl> Form 8 - K . <hl> Certain events require the company to file a Form 8 - K , such as a change in the company ’ s officers , mergers , or declarations of bankruptcy . These are required to be filed within four business days with the SEC . <hl> Form 10 - Q . <hl> Form 10 - Qs are quarterly unaudited financial statements that contain financial information . Since they are unaudited , they are less expensive and time-consuming for the company to prepare ; however , investors do not have the additional assurance that they have been analyzed by a neutral CPA . <hl> Form 10 - K . <hl> Form 10 - K , also known as the annual report , contains audited financial statements . Audited financial statements have been reviewed by one or more CPAs who are not affiliated with the company and who provide an objective opinion about whether or not the financial statements , such as the balance sheet , income statement , statement of changes to retained earnings , and cash flow statement , conform with accounting standards known as the Generally Accepted Accounting Principles ( GAAP ) . When the Securities Exchange Act of 1934 was first passed , most companies ’ annual reports contained only the bare minimum amount of information . However , over time , companies came to view their annual reports as a way to not only comply with SEC requirements , but also to attract new investors and impress securities analysts , or financial professionals who study various industries to make recommendations on whether a security should be bought , held , or sold . Today , many annual reports contain not only the required facts , but also compelling narratives that detail the company ’ s mission and strategic goals . The annual reports of certain companies — for example , Berkshire Hathaway , written by Warren Buffett and Charlie Munger — provide not only their opinions on their own operations , known as the management discussion , but also their thoughts on the economy overall . The Form 10 - K is a large responsibility for a company because it must disclose the company ’ s analysis of its financial conditions , potential market risks , internal controls , legal proceedings , defaults , and other information that is deemed important for investors to make sound investment decisions . <hl> Publicly owned companies that meet certain size requirements are called reporting companies , and per Section 13 ( a ) of the Securities Exchange Act of 1934 , they must file periodic disclosures . <hl> The purpose of these disclosures is to help investors make educated decisions regarding how to invest their money . These reports include information about a company ’ s line of business , corporate officers and directors , and financial statements .\",\n \"hl_sentences\": \"The Securities Exchange Act of 1934 created numerous reporting requirements for public companies . The purpose of these requirements was transparency , that is , keeping the public up to date and informed of changes that might impact securities prices . Individuals who buy and sell securities are considered traders , and therefore , are not subject to filing under Section 15 . Section 15 ( d ) requires registered companies to file periodic reports , such as the the annual Form 10 - K and the quarterly Form 10 - Q . Proxy Statements . Form 8 - K . Form 10 - Q . Form 10 - K . Publicly owned companies that meet certain size requirements are called reporting companies , and per Section 13 ( a ) of the Securities Exchange Act of 1934 , they must file periodic disclosures .\",\n \"question\": {\n \"cloze_format\": \"___ is not considered a report required by the Securities Exchange Act of 1934.\",\n \"normal_format\": \"All of the following are considered reports required by the Securities Exchange Act of 1934 except which one?\",\n \"question_choices\": [\n \"Form 8k.\",\n \"Form 10 k.\",\n \"Form 10Q.\",\n \"All of the above.\"\n ],\n \"question_id\": \"fs-22325313560\",\n \"question_text\": \"All of the following are considered reports required by the Securities Exchange Act of 1934 except:\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"10.\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Corporate insiders are those officers , directors , and beneficial owners who own more than 10 % of a class of securities , registered under Section 12 of the Securities Exchange Act of 1934 . <hl> Corporate insiders must file a statement of ownership with the SEC to be in compliance , and as of August 27 , 2002 , the SEC implemented new rules that shortened the time period to report insider transactions . It is important for a company to have internal controls and a system to ensure their corporate insiders are reporting their trades in a timely fashion . Companies that do not implement and enforce compliance procedures can become liable for the actions of their employees who fail to follow the law .\",\n \"hl_sentences\": \"Corporate insiders are those officers , directors , and beneficial owners who own more than 10 % of a class of securities , registered under Section 12 of the Securities Exchange Act of 1934 .\",\n \"question\": {\n \"cloze_format\": \"Corporate insiders include officers, directors, and beneficial owners who own _____ % of a class of securities registered under Section 12 of the Securities Exchange Act of 1934.\",\n \"normal_format\": \"Corporate insiders include officers, directors, and beneficial owners who own how many % of a class of securities registered under Section 12 of the Securities Exchange Act of 1934?\",\n \"question_choices\": [\n \"5.\",\n \"10.\",\n \"15.\",\n \"20.\"\n ],\n \"question_id\": \"fs-223253356\",\n \"question_text\": \"Corporate insiders include officers, directors, and beneficial owners who own _____ % of a class of securities registered under Section 12 of the Securities Exchange Act of 1934.\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":14,"string":"14"},"chapter_text":{"kind":"string","value":" 14.1 Liability Under the Securities Act \n\n As explained in the previous section, many companies were initially irritated by the creation of the Securities Exchange Act of 1934, as it created a myriad of legal responsibilities and potential liabilities that impacted their business models. Companies came to recognize that they needed legal counsel and internal systems in place to ensure that they were in compliance. The liabilities for not complying with the Securities and Exchange Act of 1934 include not only monetary fines, but also civil penalties, and in some cases, criminal proceedings. Insider trading is one violation that can result in criminal charges. \n\n Insider Trading \n\n While laws vary from country to country, insider trading can be understood by what the SEC defines as the “buying or selling a security, in breach of a fiduciary duty or other relationship of trust and confidence, on the basis of material, nonpublic information about the security.” The word fiduciary comes from the Latin word for trust and refers to someone who is charged with the responsibility to act in the best interest of the other party. In the case of businesses, fiduciaries are expected to act in the best interests of their investors. However, they are often aware of information that the public is not. This knowledge has important implications as addressed by Section 10(b) and Rule 10b-5 of the Securities Exchange Act of 1934, which prohibits the purchase or sale of securities on the basis of \" material nonpublic information ,\"; meaning information of any kind that would impact the market price of securities that has not been disclosed to the public, i.e., insider information. The directors, large shareholders, and officers of companies frequently have access to nonpublic information that could affect the future value of a security. While an individual, as opposed to an entire company, is often charged as an insider trader, such charges can affect the entire company’s reputation, putting it in a negative light and eroding investor trust. One instance of insider trading that received widespread media attention involved Martha Stewart, who in 2003 became the subject of legal scrutiny after selling her shares in the pharmaceutical company ImClone. Following the advice of her broker, David Bacanovic, Stewart sold all of her shares of ImClone before it lost 16 percent of its value. Bacanovic represented ImClone CEO Sam Waksal, who was selling $5 million of his ImClone shares. While Bacanovic claimed he did not know why, he shared this information with Stewart. As it turned out, the FDA had not approved ImClone’s primary pharmaceutical product, Erbitux, which was a setback that only insiders were privy to. Stewart avoided a $45,673 loss by selling her shares before the public announcement. Even though Stewart may not have known exactly why ImClone would go down in value, the court decided that her decision to act upon her broker’s suggestion constituted a wrongdoing. Stewart’s role as a public figure was also relevant to this decision, as explained by SEC’s Director of Enforcement Stephen M. Cutler, who said, “It is fundamentally unfair for someone to have an edge on the market just because she has a stockbroker who is willing to break the rules and give her an illegal tip. It’s worse still when the individual engaging in the insider trading is the Chairman and CEO of a public company.” \n\n Insider trading is not always illegal. In certain instances, individuals in possession of insider knowledge can disclose their trading activity to the SEC. However, disclosure alone is not enough to make trading on the basis of insider information legally acceptable. Another instance in which the officers of publicly held companies can legally transact securities involves pre-arranged trading plans . For example, SEC Rule 10b5-1 permits executives at public companies to transact securities so long as it is arranged in good faith beforehand to take place on certain predetermined future dates and involves pre-set amounts. So long as these criteria are followed, they are granted safe harbor. Safe harbor , in this context, refers to exemption from insider trading charges for compliant pre-arranged equity trades. \n\n Schedule 13D \n\n In 1968, the Williams Act amended the Securities Exchange Act of 1934 so that investors could have advance warning of possible corporate takeovers. If someone (individual/corporation) becomes the beneficial owner of more than 5% of a company’s stock, that entity must file a Schedule 13D with the SEC within 10 days of purchase. A beneficial owner is anyone with “voting and investment power over their shares.” There are a few exceptions that apply, such as qualified institutional investors —large investors who are deemed to have sophisticated knowledge of securities such that they do not need the same level of protection as general investors. Insurance companies, state employee benefits plans, and investment companies are examples of qualified institutional investors who are allowed to report their holdings at the end of the calendar year. \n\n Insider Transactions \n\n Corporate insiders are those officers, directors, and beneficial owners who own more than 10% of a class of securities, registered under Section 12 of the Securities Exchange Act of 1934. Corporate insiders must file a statement of ownership with the SEC to be in compliance, and as of August 27, 2002, the SEC implemented new rules that shortened the time period to report insider transactions. It is important for a company to have internal controls and a system to ensure their corporate insiders are reporting their trades in a timely fashion. Companies that do not implement and enforce compliance procedures can become liable for the actions of their employees who fail to follow the law. \n\n Reporting Requirements \n\n Publicly owned companies that meet certain size requirements are called reporting companies , and per Section 13(a) of the Securities Exchange Act of 1934, they must file periodic disclosures. The purpose of these disclosures is to help investors make educated decisions regarding how to invest their money. These reports include information about a company’s line of business, corporate officers and directors, and financial statements. \n\n Form 10-K . Form 10-K, also known as the annual report, contains audited financial statements. Audited financial statements have been reviewed by one or more CPAs who are not affiliated with the company and who provide an objective opinion about whether or not the financial statements, such as the balance sheet, income statement, statement of changes to retained earnings, and cash flow statement, conform with accounting standards known as the Generally Accepted Accounting Principles (GAAP). When the Securities Exchange Act of 1934 was first passed, most companies’ annual reports contained only the bare minimum amount of information. However, over time, companies came to view their annual reports as a way to not only comply with SEC requirements, but also to attract new investors and impress securities analysts, or financial professionals who study various industries to make recommendations on whether a security should be bought, held, or sold. Today, many annual reports contain not only the required facts, but also compelling narratives that detail the company’s mission and strategic goals. The annual reports of certain companies—for example, Berkshire Hathaway, written by Warren Buffett and Charlie Munger—provide not only their opinions on their own operations, known as the management discussion , but also their thoughts on the economy overall. The Form 10-K is a large responsibility for a company because it must disclose the company’s analysis of its financial conditions, potential market risks, internal controls, legal proceedings, defaults, and other information that is deemed important for investors to make sound investment decisions. \n\n Form 10-Q . Form 10-Qs are quarterly unaudited financial statements that contain financial information. Since they are unaudited, they are less expensive and time-consuming for the company to prepare; however, investors do not have the additional assurance that they have been analyzed by a neutral CPA. \n\n Form 8-K . Certain events require the company to file a Form 8-K , such as a change in the company’s officers, mergers, or declarations of bankruptcy. These are required to be filed within four business days with the SEC. \n\n Proxy Statements . Proxy statements are documents that the SEC requires that shareholders of companies with securities registered under Section 12 of the Securities Exchange Act of 1934 receive to allow them to vote on issues that will be decided at a stockholder meeting. This process is commonly applied when voting for directors or deciding corporate actions. Even shareholders who own just one share of a company receive proxy statements; thus, the process of sending out these statements is a large undertaking for companies. While some companies still use the mail to deliver proxy statements, others send a “Notice of Internet Availability of Proxy Materials” to shareholders a minimum of 40 days before the shareholders’ meeting. \n\n Ongoing Responsibilities \n\n Businesses must stay current with changes in securities laws that impact their liabilities and responsibilities. The Exchange Act allows the SEC to make new laws, like it did in 2000 with Regulation FD, which stands for “fair disclosure”. In 2013, the SEC started to allow the use of social media channels, in certain circumstances, as a means of distributing information to shareholders. \n\n Summary \n\n These two sections have provided an overview of some of the most important points of the Securities Exchange Act of 1934. Considering the sheer number of exceptions and complexities, coupled with today’s rapidly changing technological and political climates, a successful company needs competent legal counsel to help it navigate the compliance requirements of the SEC. While certain illegal actions can be due to malicious intent, such as insider trading, this situation is not always the case; a corporate insider can fail to comply simply because he or she is not aware of the nuances of the law. \n 14.2 The Framework of Securities Regulation \n\n The Securities Exchange Act of 1934 \n\n In 1929, the United States stock market crashed and lost $25 billion, which would be approximately $319 billion today. The Stock Market crash of 1929 was one cause of the American Great Depression of the 1930s, which caused the failure of nearly half of American banks and created unemployment rates of almost 25 percent by 1933. These dire economic conditions created the need for breadlines , quite literally, hungry people who waited in line at charitable and government organizations for loaves of bread, and shanty towns , or areas where families who had lost their homes lived in cloistered tents on the outskirts of cities. Farmers could not even afford to harvest their crops. \n\n It was amid this social and economic unrest that Congress passed the Securities Exchange Act of 1934. Signed by President Franklin D. Roosevelt, the Securities Exchange Act of 1934 recognized that the stock market crash of 1929 was caused by wild speculation, large and sudden fluctuations, and manipulations involving securities. An article in the 1934 California Law Review described the condition of the market at the time by writing, “Artificial prices of securities were the rule rather than the exception.… The result was vast economic power, with all that implies in a democracy, in the hand of men whose ethical standards were substantially those of gangsters.” \n\n Roosevelt wanted to enact legislature to try to prevent this wild speculation in securities from happening again and to restore the public’s faith. He recognized that stock market crashes would not only destroy wealth in securities markets, but they were also instrumental to the financial security of the nation as a whole. The passing of the Security Exchange Act of 1934 was not only a reaction to the market crash, but it also represented a broad shift in the social and economic paradigms and legal frameworks of the United States. Previously, the United States had largely followed a laissez-faire economic policy. Laissez faire, as popularized by Scottish economist Adam Smith and British philosopher Herbert Spencer, describes an economic philosophy that markets function best when left to their own devices, i.e., without, or with minimal, government involvement or regulations. The rejection of laissez faire was part of a larger social shift that opposed the long hours, unsafe working conditions, and child labor that had become commonplace as a result of the Industrial Revolution. \n\n The SEC \n\n Section 4 of the Securities Exchange Act of 1934 created the Securities and Exchange Commission (SEC) to enforce its ongoing mission. The SEC is an independent agency of the United States federal government. It regulates securities laws and regulations. The first chairperson of the SEC was Joseph P. Kennedy, the father of President John F. Kennedy. The SEC is led by five presidentially appointed commissioners and has five divisions: Division of Corporation Finance, Division of Investment Management, Division of Trading and Markets, Division of Enforcement, and Division of Economic and Risk Analysis. \n\n The SEC also oversees self-regulatory organizations (SROs) , or private organizations that create and enforce industry standards. These organizations are allowed to “police” themselves, but are subject to compliance with SEC regulations. The various well-known securities exchanges such as the New York Stock Exchange (NYSE), the National Association of Securities Dealers Automated Quotation System (NASDAQ), and the Chicago Board of Options are SROs. Per Section 12(g), companies with total assets exceeding $10 million and with 500 or more owners of any class of securities must register with the SEC unless they meets exemption requirements. \n\n The SEC makes new laws in response to emerging technologies. For example, Title III of the Jumpstart Our Business Startups (JOBS) Act of 2012 was added, and in it, Section 4(a)(6) allows crowdfunding , or raising small amounts of money from many people to fund a venture or project, usually over the internet. Crowdfunding transactions are exempt from registration as long as the amount raised does not exceed $1,070,000 in a 12-month period. \n\n Secondary Markets \n\n The Securities Exchange Act of 1934 governs secondary markets , or what is typically referred to as the “stock market.” In contrast to the primary market , which involves the initial sale of a security, such as through an initial public offering (IPO) , secondary markets involve subsequent buyers and sellers of securities. One key difference is that primary market prices are set in advance, while secondary market prices are subject to constantly changing market valuations, as determined by supply and demand and investor expectations. For example, when Facebook initiated its IPO in May of 2012, the price was $38 per share, and technical issues on the NASDAQ complicated the offering. After the IPO, the stock traded sideways , meaning that it stayed within a range that did not indicate strong upward or downward movement. However, Facebook has gone on to trade at values more than four times its initial IPO valuation, due to investor beliefs and expectations. Not all stocks go up in value after their IPO; some vacillate between highs and lows and frustrate investors with their unstable valuation swings. \n\n Reporting Requirements \n\n The Securities Exchange Act of 1934 created numerous reporting requirements for public companies. The purpose of these requirements was transparency , that is, keeping the public up to date and informed of changes that might impact securities prices. Public companies with securities registered under Section 12 or that are subject to Section 15(d) must file reports with the SEC. Section 12 requires the registration of certain securities and outlines the procedures necessary to do so. Information required by Section 12 includes the nature of the business, its financial structure, the different classes of securities, the names of officers and directors along with their salaries and bonus arrangements, and financial statements. Section 15 requires brokers and dealers to register with the SEC. Individuals who buy and sell securities are considered traders, and therefore, are not subject to filing under Section 15. Section 15(d) requires registered companies to file periodic reports, such as the the annual Form 10-K and the quarterly Form 10-Q. These reports will be explained in detail in the next section of this chapter. The SEC Commission makes these reports available to all investors through the EDGAR website to help them make informed investment decisions. \n\n Registration Requirements \n\n The Securities Act of 1933 required companies initiating securities offers and exchanges to register with the SEC, unless they met exemption criteria. Section 5 of the Securities Exchange Act of 1934 built upon this foundation and made it unlawful to transact on unregistered exchanges and specifically extended this regulation to the usage of the mail and interstate commerce. 15 U.S. Code § 78f states that exchanges must not only register with the SEC, but they must also have rules that “prevent fraudulent and manipulative acts and practices, to promote just and equitable principles of trade, to foster cooperation and coordination with persons engaged in regulating, clearing, settling, processing information with respect to, and facilitating transactions in securities, to remove impediments to and perfect the mechanism of a free and open market and a national market system, and, in general, to protect investors and the public interest …” \n\n Blue Sky Laws \n\n When the Securities Exchange Act is discussed, blue sky laws are often mentioned. In 1911, Kansas bank commissioner J.N. Dolley became concerned about what he called “swindles,” in which investors at the time lost money by investing in “fake mines” or “a Central American plantation that was nine parts imagination.” Therefore, he lobbied for the first “comprehensive” securities law in the United States because, as he phrased it, these investments were backed by nothing except the blue skies of Kansas. So, state-level securities laws aimed to combat fraud are called blue sky laws. The SEC does not have jurisdiction over activities within states and does not enforce blue sky laws. "}}},{"rowIdx":179,"cells":{"bname":{"kind":"string","value":"biology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":""},"intro":{"kind":"string","value":" Chapter Outline 43.1 Reproduction Methods 43.2 Fertilization 43.3 Human Reproductive Anatomy and Gametogenesis 43.4 Hormonal Control of Human Reproduction 43.5 Human Pregnancy and Birth 43.6 Fertilization and Early Embryonic Development 43.7 Organogenesis and Vertebrate Formation Introduction Animal reproduction is necessary for the survival of a species. In the animal kingdom, there are innumerable ways that species reproduce. Asexual reproduction produces genetically identical organisms (clones), whereas in sexual reproduction, the genetic material of two individuals combines to produce offspring that are genetically different from their parents. During sexual reproduction the male gamete (sperm) may be placed inside the female’s body for internal fertilization, or the sperm and eggs may be released into the environment for external fertilization. Seahorses, like the one shown in Figure 43.1 , provide an example of the latter. Following a mating dance, the female lays eggs in the male seahorse’s abdominal brood pouch where they are fertilized. The eggs hatch and the offspring develop in the pouch for several weeks. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":0,"ans_text":"asexual"},"bloom":null,"hl_context":"Animals produce offspring through asexual and / or sexual reproduction . Both methods have advantages and disadvantages . Asexual reproduction produces offspring that are genetically identical to the parent because the offspring are all clones of the original parent . A single individual can produce offspring asexually and large numbers of offspring can be produced quickly . <hl> In a stable or predictable environment , asexual reproduction is an effective means of reproduction because all the offspring will be adapted to that environment . <hl> In an unstable or unpredictable environment asexually-reproducing species may be at a disadvantage because all the offspring are genetically identical and may not have the genetic variation to survive in new or different conditions . On the other hand , the rapid rates of asexual reproduction may allow for a speedy response to environmental changes if individuals have mutations . An additional advantage of asexual reproduction is that colonization of new habitats may be easier when an individual does not need to find a mate to reproduce .","hl_sentences":"In a stable or predictable environment , asexual reproduction is an effective means of reproduction because all the offspring will be adapted to that environment .","question":{"cloze_format":"The form of reproduction that is thought to be best in a stable environment is ___.","normal_format":"Which form of reproduction is thought to be best in a stable environment?","question_choices":["asexual","sexual","budding","parthenogenesis"],"question_id":"fs-idm62799008","question_text":"Which form of reproduction is thought to be best in a stable environment?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"fragmentation"},"bloom":null,"hl_context":"<hl> For example , in many sea stars , asexual reproduction is accomplished by fragmentation . <hl> <hl> Figure 43.4 illustrates a sea star for which an arm of the individual is broken off and regenerates a new sea star . <hl> Fisheries workers have been known to try to kill the sea stars eating their clam or oyster beds by cutting them in half and throwing them back into the ocean . Unfortunately for the workers , the two parts can each regenerate a new half , resulting in twice as many sea stars to prey upon the oysters and clams . Fragmentation also occurs in annelid worms , turbellarians , and poriferans . <hl> Fragmentation is the breaking of the body into two parts with subsequent regeneration . <hl> <hl> If the animal is capable of fragmentation , and the part is big enough , a separate individual will regrow . <hl>","hl_sentences":"For example , in many sea stars , asexual reproduction is accomplished by fragmentation . Figure 43.4 illustrates a sea star for which an arm of the individual is broken off and regenerates a new sea star . Fragmentation is the breaking of the body into two parts with subsequent regeneration . If the animal is capable of fragmentation , and the part is big enough , a separate individual will regrow .","question":{"cloze_format":"The form of reproduction that can result from damage to the original animal is ___.","normal_format":"Which form of reproduction can result from damage to the original animal?","question_choices":["asexual","fragmentation","budding","parthenogenesis"],"question_id":"fs-idp65241328","question_text":"Which form of reproduction can result from damage to the original animal?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"hermaphroditism"},"bloom":null,"hl_context":"Hermaphroditism occurs in animals where one individual has both male and female reproductive parts . Invertebrates such as earthworms , slugs , tapeworms and snails , shown in Figure 43.5 , are often hermaphroditic . <hl> Hermaphrodites may self-fertilize or may mate with another of their species , fertilizing each other and both producing offspring . <hl> <hl> Self fertilization is common in animals that have limited mobility or are not motile , such as barnacles and clams . <hl>","hl_sentences":"Hermaphrodites may self-fertilize or may mate with another of their species , fertilizing each other and both producing offspring . Self fertilization is common in animals that have limited mobility or are not motile , such as barnacles and clams .","question":{"cloze_format":"The form of reproduction that is useful to an animal with little mobility that reproduces sexually is ___.","normal_format":"Which form of reproduction is useful to an animal with little mobility that reproduces sexually?","question_choices":["fission","budding","parthenogenesis","hermaphroditism"],"question_id":"fs-idm47940992","question_text":"Which form of reproduction is useful to an animal with little mobility that reproduces sexually?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"sexual reproduction"},"bloom":null,"hl_context":"<hl> Sexual reproduction is the combination of ( usually haploid ) reproductive cells from two individuals to form a third ( usually diploid ) unique offspring . <hl> <hl> Sexual reproduction produces offspring with novel combinations of genes . <hl> This can be an adaptive advantage in unstable or unpredictable environments . As humans , we are used to thinking of animals as having two separate sexes — male and female — determined at conception . However , in the animal kingdom , there are many variations on this theme . <hl> During sexual reproduction the genetic material of two individuals is combined to produce genetically diverse offspring that differ from their parents . <hl> The genetic diversity of sexually produced offspring is thought to give species a better chance of surviving in an unpredictable or changing environment . Species that reproduce sexually must maintain two different types of individuals , males and females , which can limit the ability to colonize new habitats as both sexes must be present .","hl_sentences":"Sexual reproduction is the combination of ( usually haploid ) reproductive cells from two individuals to form a third ( usually diploid ) unique offspring . Sexual reproduction produces offspring with novel combinations of genes . During sexual reproduction the genetic material of two individuals is combined to produce genetically diverse offspring that differ from their parents .","question":{"cloze_format":"Genetically unique individuals are produced through ________.","normal_format":"Through what are genetically unique individuals produced?","question_choices":["sexual reproduction","parthenogenesis","budding","fragmentation"],"question_id":"fs-idm82695104","question_text":"Genetically unique individuals are produced through ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"aquatic"},"bloom":null,"hl_context":"<hl> External fertilization in an aquatic environment protects the eggs from drying out . <hl> Broadcast spawning can result in a greater mixture of the genes within a group , leading to higher genetic diversity and a greater chance of species survival in a hostile environment . For sessile aquatic organisms like sponges , broadcast spawning is the only mechanism for fertilization and colonization of new environments . The presence of the fertilized eggs and developing young in the water provides opportunities for predation resulting in a loss of offspring . Therefore , millions of eggs must be produced by individuals , and the offspring produced through this method must mature rapidly . The survival rate of eggs produced through broadcast spawning is low . <hl> External fertilization usually occurs in aquatic environments where both eggs and sperm are released into the water . <hl> After the sperm reaches the egg , fertilization takes place . Most external fertilization happens during the process of spawning where one or several females release their eggs and the male ( s ) release sperm in the same area , at the same time . The release of the reproductive material may be triggered by water temperature or the length of daylight . Nearly all fish spawn , as do crustaceans ( such as crabs and shrimp ) , mollusks ( such as oysters ) , squid , and echinoderms ( such as sea urchins and sea cucumbers ) . Figure 43.6 shows salmon spawning in a shallow stream . Frogs , like those shown in Figure 43.7 , corals , squid , and octopuses also spawn . Pairs of fish that are not broadcast spawners may exhibit courtship behavior . This allows the female to select a particular male . The trigger for egg and sperm release ( spawning ) causes the egg and sperm to be placed in a small area , enhancing the possibility of fertilization .","hl_sentences":"External fertilization in an aquatic environment protects the eggs from drying out . External fertilization usually occurs in aquatic environments where both eggs and sperm are released into the water .","question":{"cloze_format":"The type of environment that external fertilization occurs in is the ___.","normal_format":"External fertilization occurs in which type of environment?","question_choices":["aquatic","forested","savanna","steppe"],"question_id":"fs-idm65505280","question_text":"External fertilization occurs in which type of environment?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"ovoviparity"},"bloom":null,"hl_context":"<hl> In ovoviparity , fertilized eggs are retained in the female , but the embryo obtains its nourishment from the egg ’ s yolk and the young are fully developed when they are hatched . <hl> This occurs in some bony fish ( like the guppy Lebistes reticulatus ) , some sharks , some lizards , some snakes ( such as the garter snake Thamnophis sirtalis ) , some vipers , and some invertebrate animals ( like the Madagascar hissing cockroach Gromphadorhina portentosa ) .","hl_sentences":"In ovoviparity , fertilized eggs are retained in the female , but the embryo obtains its nourishment from the egg ’ s yolk and the young are fully developed when they are hatched .","question":{"cloze_format":"___ is a term that applies to egg development within the female with nourishment derived from a yolk.","normal_format":"Which term applies to egg development within the female with nourishment derived from a yolk?","question_choices":["oviparity","viviparity","ovoviparity","ovovoparity"],"question_id":"fs-idp176671776","question_text":"Which term applies to egg development within the female with nourishment derived from a yolk?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"oviparity"},"bloom":"1","hl_context":"Internal fertilization occurs most often in land-based animals , although some aquatic animals also use this method . There are three ways that offspring are produced following internal fertilization . <hl> In oviparity , fertilized eggs are laid outside the female ’ s body and develop there , receiving nourishment from the yolk that is a part of the egg . <hl> This occurs in most bony fish , many reptiles , some cartilaginous fish , most amphibians , two mammals , and all birds . Reptiles and insects produce leathery eggs , while birds and turtles produce eggs with high concentrations of calcium carbonate in the shell , making them hard . Chicken eggs are an example of this second type .","hl_sentences":"In oviparity , fertilized eggs are laid outside the female ’ s body and develop there , receiving nourishment from the yolk that is a part of the egg .","question":{"cloze_format":"___ is a term that applies to egg development outside the female with nourishment derived from a yolk.","normal_format":"Which term applies to egg development outside the female with nourishment derived from a yolk?","question_choices":["oviparity","viviparity","ovoviparity","ovovoparity"],"question_id":"fs-idp325930864","question_text":"Which term applies to egg development outside the female with nourishment derived from a yolk?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"seminiferous tubules"},"bloom":null,"hl_context":"<hl> Sperm mature in seminiferous tubules that are coiled inside the testes , as illustrated in Figure 43.8 . <hl> The walls of the seminiferous tubules are made up of the developing sperm cells , with the least developed sperm at the periphery of the tubule and the fully developed sperm in the lumen . The sperm cells are mixed with “ nursemaid ” cells called Sertoli cells which protect the germ cells and promote their development . Other cells mixed in the wall of the tubules are the interstitial cells of Leydig . These cells produce high levels of testosterone once the male reaches adolescence . <hl> Sperm mature in seminiferous tubules in the testes . <hl>","hl_sentences":"Sperm mature in seminiferous tubules that are coiled inside the testes , as illustrated in Figure 43.8 . Sperm mature in seminiferous tubules in the testes .","question":{"cloze_format":"Sperm are produced in the ________.","normal_format":"Where are sperm produced?","question_choices":["scrotum","seminal vesicles","seminiferous tubules","prostate gland"],"question_id":"fs-idp135004256","question_text":"Sperm are produced in the ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"primary spermatocyte"},"bloom":null,"hl_context":"<hl> Spermatogenesis , illustrated in Figure 43.12 , occurs in the wall of the seminiferous tubules ( Figure 43.8 ) , with stem cells at the periphery of the tube and the spermatozoa at the lumen of the tube . <hl> <hl> Immediately under the capsule of the tubule are diploid , undifferentiated cells . <hl> <hl> These stem cells , called spermatogonia ( singular : spermatagonium ) , go through mitosis with one offspring going on to differentiate into a sperm cell and the other giving rise to the next generation of sperm . <hl> <hl> Meiosis starts with a cell called a primary spermatocyte . <hl> At the end of the first meiotic division , a haploid cell is produced called a secondary spermatocyte . This cell is haploid and must go through another meiotic cell division . The cell produced at the end of meiosis is called a spermatid and when it reaches the lumen of the tubule and grows a flagellum , it is called a sperm cell . Four sperm result from each primary spermatocyte that goes through meiosis . Gametogenesis , the production of sperm and eggs , takes place through the process of meiosis . During meiosis , two cell divisions separate the paired chromosomes in the nucleus and then separate the chromatids that were made during an earlier stage of the cell ’ s life cycle . Meiosis produces haploid cells with half of each pair of chromosomes normally found in diploid cells . <hl> The production of sperm is called spermatogenesis and the production of eggs is called oogenesis . <hl>","hl_sentences":"Spermatogenesis , illustrated in Figure 43.12 , occurs in the wall of the seminiferous tubules ( Figure 43.8 ) , with stem cells at the periphery of the tube and the spermatozoa at the lumen of the tube . Immediately under the capsule of the tubule are diploid , undifferentiated cells . These stem cells , called spermatogonia ( singular : spermatagonium ) , go through mitosis with one offspring going on to differentiate into a sperm cell and the other giving rise to the next generation of sperm . Meiosis starts with a cell called a primary spermatocyte . The production of sperm is called spermatogenesis and the production of eggs is called oogenesis .","question":{"cloze_format":"The ___ cell in spermatogenesis is diploid.","normal_format":"Which of the following cells in spermatogenesis is diploid?","question_choices":["primary spermatocyte","secondary spermatocyte","spermatid","sperm"],"question_id":"fs-idm81430816","question_text":"Which of the following cells in spermatogenesis is diploid?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"clitoris"},"bloom":"1","hl_context":"The reproductive tissues of male and female humans develop similarly in utero until a low level of the hormone testosterone is released from male gonads . Testosterone causes the undeveloped tissues to differentiate into male sexual organs . When testosterone is absent , the tissues develop into female sexual tissues . Primitive gonads become testes or ovaries . <hl> Tissues that produce a penis in males produce a clitoris in females . <hl> The tissue that will become the scrotum in a male becomes the labia in a female ; that is , they are homologous structures .","hl_sentences":"Tissues that produce a penis in males produce a clitoris in females .","question":{"cloze_format":"The female organ that has the same embryonic origin as the penis is the ___.","normal_format":"Which female organ has the same embryonic origin as the penis?","question_choices":["clitoris","labia majora","greater vestibular glands","vagina"],"question_id":"fs-idm30849536","question_text":"Which female organ has the same embryonic origin as the penis?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"uterus"},"bloom":null,"hl_context":"<hl> The uterus is a structure about the size of a woman ’ s fist . <hl> <hl> This is lined with an endometrium rich in blood vessels and mucus glands . <hl> <hl> The uterus supports the developing embryo and fetus during gestation . <hl> The thickest portion of the wall of the uterus is made of smooth muscle . Contractions of the smooth muscle in the uterus aid in passing the baby through the vagina during labor . A portion of the lining of the uterus sloughs off during each menstrual period , and then builds up again in preparation for an implantation . Part of the uterus , called the cervix , protrudes into the top of the vagina . The cervix functions as the birth canal .","hl_sentences":"The uterus is a structure about the size of a woman ’ s fist . This is lined with an endometrium rich in blood vessels and mucus glands . The uterus supports the developing embryo and fetus during gestation .","question":{"cloze_format":"The female organ that has an endometrial lining that will support a developing baby is the ___.","normal_format":"Which female organ has an endometrial lining that will support a developing baby?","question_choices":["labia minora","breast","ovaries","uterus"],"question_id":"fs-idp148194704","question_text":"Which female organ has an endometrial lining that will support a developing baby?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"one"},"bloom":"2","hl_context":"Egg production begins before birth , is arrested during meiosis until puberty , and then individual cells continue through at each menstrual cycle . <hl> One egg is produced from each meiotic process , with the extra chromosomes and chromatids going into polar bodies that degenerate and are reabsorbed by the body . <hl> 43.4 Hormonal Control of Human Reproduction Learning Objectives By the end of this chapter , you will be able to :","hl_sentences":"One egg is produced from each meiotic process , with the extra chromosomes and chromatids going into polar bodies that degenerate and are reabsorbed by the body .","question":{"cloze_format":"The amount of eggs that are produced as a result of one meiotic series of cell divisions is ___.","normal_format":"How many eggs are produced as a result of one meiotic series of cell divisions?","question_choices":["one","two","three","four"],"question_id":"fs-idm37013456","question_text":"How many eggs are produced as a result of one meiotic series of cell divisions?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"FSH"},"bloom":null,"hl_context":"At the onset of puberty , the hypothalamus causes the release of FSH and LH into the male system for the first time . <hl> FSH enters the testes and stimulates the Sertoli cells to begin facilitating spermatogenesis using negative feedback , as illustrated in Figure 43.14 . <hl> <hl> LH also enters the testes and stimulates the interstitial cells of Leydig to make and release testosterone into the testes and the blood . <hl> Gametogenesis , the production of sperm and eggs , takes place through the process of meiosis . During meiosis , two cell divisions separate the paired chromosomes in the nucleus and then separate the chromatids that were made during an earlier stage of the cell ’ s life cycle . Meiosis produces haploid cells with half of each pair of chromosomes normally found in diploid cells . <hl> The production of sperm is called spermatogenesis and the production of eggs is called oogenesis . <hl>","hl_sentences":"FSH enters the testes and stimulates the Sertoli cells to begin facilitating spermatogenesis using negative feedback , as illustrated in Figure 43.14 . LH also enters the testes and stimulates the interstitial cells of Leydig to make and release testosterone into the testes and the blood . The production of sperm is called spermatogenesis and the production of eggs is called oogenesis .","question":{"cloze_format":"The ___ hormone causes Leydig cells to make testosterone.","normal_format":"Which hormone causes Leydig cells to make testosterone?","question_choices":["FSH","LH","inhibin","estrogen"],"question_id":"fs-idp21199008","question_text":"Which hormone causes Leydig cells to make testosterone?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"GnRH"},"bloom":null,"hl_context":"The control of reproduction in females is more complex . <hl> As with the male , the anterior pituitary hormones cause the release of the hormones FSH and LH . <hl> In addition , estrogens and progesterone are released from the developing follicles . Estrogen is the reproductive hormone in females that assists in endometrial regrowth , ovulation , and calcium absorption ; it is also responsible for the secondary sexual characteristics of females . These include breast development , flaring of the hips , and a shorter period necessary for bone maturation . Progesterone assists in endometrial re-growth and inhibition of FSH and LH release . The human male and female reproductive cycles are controlled by the interaction of hormones from the hypothalamus and anterior pituitary with hormones from reproductive tissues and organs . In both sexes , the hypothalamus monitors and causes the release of hormones from the pituitary gland . <hl> When the reproductive hormone is required , the hypothalamus sends a gonadotropin-releasing hormone ( GnRH ) to the anterior pituitary . <hl> <hl> This causes the release of follicle stimulating hormone ( FSH ) and luteinizing hormone ( LH ) from the anterior pituitary into the blood . <hl> Note that the body must reach puberty in order for the adrenals to release the hormones that must be present for GnRH to be produced . Although FSH and LH are named after their functions in female reproduction , they are produced in both sexes and play important roles in controlling reproduction . Other hormones have specific functions in the male and female reproductive systems .","hl_sentences":"As with the male , the anterior pituitary hormones cause the release of the hormones FSH and LH . When the reproductive hormone is required , the hypothalamus sends a gonadotropin-releasing hormone ( GnRH ) to the anterior pituitary . This causes the release of follicle stimulating hormone ( FSH ) and luteinizing hormone ( LH ) from the anterior pituitary into the blood .","question":{"cloze_format":"The hormone that causes FSH and LH to be released is ___.","normal_format":"Which hormone causes FSH and LH to be released?","question_choices":["testosterone","estrogen","GnRH","progesterone"],"question_id":"fs-idm55845888","question_text":"Which hormone causes FSH and LH to be released?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"LH"},"bloom":null,"hl_context":"In females , FSH stimulates development of egg cells , called ova , which develop in structures called follicles . Follicle cells produce the hormone inhibin , which inhibits FSH production . <hl> LH also plays a role in the development of ova , induction of ovulation , and stimulation of estradiol and progesterone production by the ovaries . <hl> Estradiol and progesterone are steroid hormones that prepare the body for pregnancy . Estradiol produces secondary sex characteristics in females , while both estradiol and progesterone regulate the menstrual cycle .","hl_sentences":"LH also plays a role in the development of ova , induction of ovulation , and stimulation of estradiol and progesterone production by the ovaries .","question":{"cloze_format":"The hormone that signals ovulation is ___.","normal_format":"Which hormone signals ovulation?","question_choices":["FSH","LH","inhibin","estrogen"],"question_id":"fs-idm171491232","question_text":"Which hormone signals ovulation?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"progesterone"},"bloom":null,"hl_context":"Following ovulation , the ovarian cycle enters its luteal phase , illustrated in Figure 43.15 and the menstrual cycle enters its secretory phase , both of which run from about day 15 to 28 . The luteal and secretory phases refer to changes in the ruptured follicle . The cells in the follicle undergo physical changes and produce a structure called a corpus luteum . The corpus luteum produces estrogen and progesterone . <hl> The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH . <hl> <hl> The uterus is being prepared to accept a fertilized egg , should it occur during this cycle . <hl> The inhibition of FSH and LH prevents any further eggs and follicles from developing , while the progesterone is elevated . The level of estrogen produced by the corpus luteum increases to a steady level for the next few days . The control of reproduction in females is more complex . As with the male , the anterior pituitary hormones cause the release of the hormones FSH and LH . In addition , estrogens and progesterone are released from the developing follicles . Estrogen is the reproductive hormone in females that assists in endometrial regrowth , ovulation , and calcium absorption ; it is also responsible for the secondary sexual characteristics of females . These include breast development , flaring of the hips , and a shorter period necessary for bone maturation . <hl> Progesterone assists in endometrial re-growth and inhibition of FSH and LH release . <hl>","hl_sentences":"The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH . The uterus is being prepared to accept a fertilized egg , should it occur during this cycle . Progesterone assists in endometrial re-growth and inhibition of FSH and LH release .","question":{"cloze_format":"The ___ hormone causes the re-growth of the endometrial lining of the uterus.","normal_format":"Which hormone causes the re-growth of the endometrial lining of the uterus?","question_choices":["testosterone","estrogen","GnRH","progesterone"],"question_id":"fs-idm71478992","question_text":"Which hormone causes the re-growth of the endometrial lining of the uterus?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"diffusion through the endometrium"},"bloom":null,"hl_context":"The gestation period is divided into three equal periods or trimesters . <hl> During the first two to four weeks of the first trimester , nutrition and waste are handled by the endometrial lining through diffusion . <hl> <hl> As the trimester progresses , the outer layer of the embryo begins to merge with the endometrium , and the placenta forms . <hl> <hl> This organ takes over the nutrient and waste requirements of the embryo and fetus , with the mother ’ s blood passing nutrients to the placenta and removing waste from it . <hl> Chemicals from the fetus , such as bilirubin , are processed by the mother ’ s liver for elimination . Some of the mother ’ s immunoglobulins will pass through the placenta , providing passive immunity against some potential infections .","hl_sentences":"During the first two to four weeks of the first trimester , nutrition and waste are handled by the endometrial lining through diffusion . As the trimester progresses , the outer layer of the embryo begins to merge with the endometrium , and the placenta forms . This organ takes over the nutrient and waste requirements of the embryo and fetus , with the mother ’ s blood passing nutrients to the placenta and removing waste from it .","question":{"cloze_format":"Nutrient and waste requirements for the developing fetus are handled during the first few weeks by ___ .","normal_format":"By what, nutrient and waste requirements for the developing fetus are handled during the first few weeks?","question_choices":["the placenta","diffusion through the endometrium","the chorion","the blastocyst"],"question_id":"fs-idp80601616","question_text":"Nutrient and waste requirements for the developing fetus are handled during the first few weeks by:"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"placenta"},"bloom":null,"hl_context":"During the second trimester , the fetus grows to about 30 cm ( 12 inches ) , as shown in Figure 43.20 . It becomes active and the mother usually feels the first movements . All organs and structures continue to develop . <hl> The placenta has taken over the functions of nutrition and waste and the production of estrogen and progesterone from the corpus luteum , which has degenerated . <hl> <hl> The placenta will continue functioning up through the delivery of the baby . <hl> The gestation period is divided into three equal periods or trimesters . During the first two to four weeks of the first trimester , nutrition and waste are handled by the endometrial lining through diffusion . <hl> As the trimester progresses , the outer layer of the embryo begins to merge with the endometrium , and the placenta forms . <hl> <hl> This organ takes over the nutrient and waste requirements of the embryo and fetus , with the mother ’ s blood passing nutrients to the placenta and removing waste from it . <hl> Chemicals from the fetus , such as bilirubin , are processed by the mother ’ s liver for elimination . Some of the mother ’ s immunoglobulins will pass through the placenta , providing passive immunity against some potential infections .","hl_sentences":"The placenta has taken over the functions of nutrition and waste and the production of estrogen and progesterone from the corpus luteum , which has degenerated . The placenta will continue functioning up through the delivery of the baby . As the trimester progresses , the outer layer of the embryo begins to merge with the endometrium , and the placenta forms . This organ takes over the nutrient and waste requirements of the embryo and fetus , with the mother ’ s blood passing nutrients to the placenta and removing waste from it .","question":{"cloze_format":"Progesterone is made during the third trimester by the ___ .","normal_format":"By which, progesterone is made during the third trimester?","question_choices":["placenta","endometrial lining","chorion","corpus luteum"],"question_id":"fs-idp58574848","question_text":"Progesterone is made during the third trimester by the:"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"abstinence"},"bloom":null,"hl_context":"Compliance with the contraceptive method is a strong contributor to the success or failure rate of any particular method . <hl> The only method that is completely effective at preventing conception is abstinence . <hl> The choice of contraceptive method depends on the goals of the woman or couple . Tubal ligation and vasectomy are considered permanent prevention , while other methods are reversible and provide short-term contraception .","hl_sentences":"The only method that is completely effective at preventing conception is abstinence .","question":{"cloze_format":"The contraceptive method that is 100 percent effective at preventing pregnancy is (a) ___ .","normal_format":"Which contraceptive method is 100 percent effective at preventing pregnancy?","question_choices":["condom","oral hormonal methods","sterilization","abstinence"],"question_id":"fs-idm43088464","question_text":"Which contraceptive method is 100 percent effective at preventing pregnancy?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"hormonal"},"bloom":null,"hl_context":"<hl> Hormonal methods use synthetic progesterone ( sometimes in combination with estrogen ) , to inhibit the hypothalamus from releasing FSH or LH , and thus prevent an egg from being available for fertilization . <hl> <hl> The method of administering the hormone affects failure rate . <hl> <hl> The most reliable method , with a failure rate of less than 1 percent , is the implantation of the hormone under the skin . <hl> The same rate can be achieved through the sterilization procedures of vasectomy in the man or of tubal ligation in the woman , or by using an intrauterine device ( IUD ) . IUDs are inserted into the uterus and establish an inflammatory condition that prevents fertilized eggs from implanting into the uterine wall .","hl_sentences":"Hormonal methods use synthetic progesterone ( sometimes in combination with estrogen ) , to inhibit the hypothalamus from releasing FSH or LH , and thus prevent an egg from being available for fertilization . The method of administering the hormone affects failure rate . The most reliable method , with a failure rate of less than 1 percent , is the implantation of the hormone under the skin .","question":{"cloze_format":"The type of short term contraceptive method that is generally more effective than others is ___.","normal_format":"Which type of short term contraceptive method is generally more effective than others?","question_choices":["barrier","hormonal","natural family planning","withdrawal"],"question_id":"fs-idm175851088","question_text":"Which type of short term contraceptive method is generally more effective than others?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"oxytocin"},"bloom":"1","hl_context":"<hl> Labor is the physical efforts of expulsion of the fetus and the placenta from the uterus during birth ( parturition ) . <hl> <hl> Toward the end of the third trimester , estrogen causes receptors on the uterine wall to develop and bind the hormone oxytocin . <hl> At this time , the baby reorients , facing forward and down with the back or crown of the head engaging the cervix ( uterine opening ) . This causes the cervix to stretch and nerve impulses are sent to the hypothalamus , which signals for the release of oxytocin from the posterior pituitary . The oxytocin causes the smooth muscle in the uterine wall to contract . At the same time , the placenta releases prostaglandins into the uterus , increasing the contractions . A positive feedback relay occurs between the uterus , hypothalamus , and the posterior pituitary to assure an adequate supply of oxytocin . As more smooth muscle cells are recruited , the contractions increase in intensity and force .","hl_sentences":"Labor is the physical efforts of expulsion of the fetus and the placenta from the uterus during birth ( parturition ) . Toward the end of the third trimester , estrogen causes receptors on the uterine wall to develop and bind the hormone oxytocin .","question":{"cloze_format":"The ___ hormone is primarily responsible for the contractions during labor.","normal_format":"Which hormone is primarily responsible for the contractions during labor?","question_choices":["oxytocin","estrogen","β-HCG","progesterone"],"question_id":"fs-idp160654912","question_text":"Which hormone is primarily responsible for the contractions during labor?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"first trimester"},"bloom":null,"hl_context":"<hl> Internal organs and body structures begin to develop during the first trimester . <hl> By five weeks , limb buds , eyes , the heart , and liver have been basically formed . By eight weeks , the term fetus applies , and the body is essentially formed , as shown in Figure 43.19 . The individual is about five centimeters ( two inches ) in length and many of the organs , such as the lungs and liver , are not yet functioning . Exposure to any toxins is especially dangerous during the first trimester , as all of the body ’ s organs and structures are going through initial development . Anything that affects that development can have a severe effect on the fetus ’ survival .","hl_sentences":"Internal organs and body structures begin to develop during the first trimester .","question":{"cloze_format":"Major organs begin to develop during the ___ of human gestation.","normal_format":"Major organs begin to develop during which part of human gestation?","question_choices":["fertilization","first trimester","second trimester","third trimester"],"question_id":"fs-idp71215264","question_text":"Major organs begin to develop during which part of human gestation?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"The trophoblast is a germ layer."},"bloom":"4","hl_context":"<hl> The three germs layers , shown in Figure 43.26 , are the endoderm , the ectoderm , and the mesoderm . <hl> The ectoderm gives rise to the nervous system and the epidermis . The mesoderm gives rise to the muscle cells and connective tissue in the body . The endoderm gives rise to columnar cells found in the digestive system and many internal organs . <hl> The typical blastula is a ball of cells . <hl> The next stage in embryonic development is the formation of the body plan . The cells in the blastula rearrange themselves spatially to form three layers of cells . This process is called gastrulation . During gastrulation , the blastula folds upon itself to form the three layers of cells . Each of these layers is called a germ layer and each germ layer differentiates into different organ systems . In mammals , the blastula forms the blastocyst in the next stage of development . <hl> Here the cells in the blastula arrange themselves in two layers : the inner cell mass , and an outer layer called the trophoblast . <hl> <hl> The inner cell mass is also known as the embryoblast and this mass of cells will go on to form the embryo . <hl> At this stage of development , illustrated in Figure 43.25 the inner cell mass consists of embryonic stem cells that will differentiate into the different cell types needed by the organism . The trophoblast will contribute to the placenta and nourish the embryo .","hl_sentences":"The three germs layers , shown in Figure 43.26 , are the endoderm , the ectoderm , and the mesoderm . The typical blastula is a ball of cells . Here the cells in the blastula arrange themselves in two layers : the inner cell mass , and an outer layer called the trophoblast . The inner cell mass is also known as the embryoblast and this mass of cells will go on to form the embryo .","question":{"cloze_format":"It is false that ___.","normal_format":"Which of the following is false?","question_choices":["The endoderm, mesoderm, ectoderm are germ layers.","The trophoblast is a germ layer.","The inner cell mass is a source of embryonic stem cells.","The blastula is often a hollow ball of cells."],"question_id":"fs-idm4742656","question_text":"Which of the following is false?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"does not change significantly"},"bloom":null,"hl_context":"The development of multi-cellular organisms begins from a single-celled zygote , which undergoes rapid cell division to form the blastula . <hl> The rapid , multiple rounds of cell division are termed cleavage . <hl> Cleavage is illustrated in ( Figure 43.24 a ) . After the cleavage has produced over 100 cells , the embryo is called a blastula . The blastula is usually a spherical layer of cells ( the blastoderm ) surrounding a fluid-filled or yolk-filled cavity ( the blastocoel ) . Mammals at this stage form a structure called the blastocyst , characterized by an inner cell mass that is distinct from the surrounding blastula , shown in Figure 43.24 b . <hl> During cleavage , the cells divide without an increase in mass ; that is , one large single-celled zygote divides into multiple smaller cells . <hl> Each cell within the blastula is called a blastomere . Cleavage can take place in two ways : holoblastic ( total ) cleavage or meroblastic ( partial ) cleavage . The type of cleavage depends on the amount of yolk in the eggs . In placental mammals ( including humans ) where nourishment is provided by the mother ’ s body , the eggs have a very small amount of yolk and undergo holoblastic cleavage . Other species , such as birds , with a lot of yolk in the egg to nourish the embryo during development , undergo meroblastic cleavage .","hl_sentences":"The rapid , multiple rounds of cell division are termed cleavage . During cleavage , the cells divide without an increase in mass ; that is , one large single-celled zygote divides into multiple smaller cells .","question":{"cloze_format":"During cleavage, the mass of cells ___.","normal_format":"How the mass of cells changes during cleavage?","question_choices":["increases","decreases","doubles with every cell division","does not change significantly"],"question_id":"fs-idp11431424","question_text":"During cleavage, the mass of cells:"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"ectoderm"},"bloom":null,"hl_context":"Organs form from the germ layers through the process of differentiation . During differentiation , the embryonic stem cells express specific sets of genes which will determine their ultimate cell type . <hl> For example , some cells in the ectoderm will express the genes specific to skin cells . <hl> As a result , these cells will differentiate into epidermal cells . The process of differentiation is regulated by cellular signaling cascades .","hl_sentences":"For example , some cells in the ectoderm will express the genes specific to skin cells .","question":{"cloze_format":"The ___ gives rise to the skin cells.","normal_format":"Which of the following gives rise to the skin cells?","question_choices":["ectoderm","endoderm","mesoderm","none of the above"],"question_id":"fs-idm29405328","question_text":"Which of the following gives rise to the skin cells?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"somites"},"bloom":null,"hl_context":"The mesoderm that lies on either side of the vertebrate neural tube will develop into the various connective tissues of the animal body . <hl> A spatial pattern of gene expression reorganizes the mesoderm into groups of cells called somites with spaces between them . <hl> <hl> The somites , illustrated in Figure 43.29 will further develop into the ribs , lungs , and segmental ( spine ) muscle . <hl> The mesoderm also forms a structure called the notochord , which is rod-shaped and forms the central axis of the animal body .","hl_sentences":"A spatial pattern of gene expression reorganizes the mesoderm into groups of cells called somites with spaces between them . The somites , illustrated in Figure 43.29 will further develop into the ribs , lungs , and segmental ( spine ) muscle .","question":{"cloze_format":"The ribs form from the ________.","normal_format":"From what do the ribs form?","question_choices":["notochord","neural plate","neural tube","somites"],"question_id":"fs-idp40022656","question_text":"The ribs form from the ________."},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"asexual\"\n },\n \"bloom\": null,\n \"hl_context\": \"Animals produce offspring through asexual and / or sexual reproduction . Both methods have advantages and disadvantages . Asexual reproduction produces offspring that are genetically identical to the parent because the offspring are all clones of the original parent . A single individual can produce offspring asexually and large numbers of offspring can be produced quickly . <hl> In a stable or predictable environment , asexual reproduction is an effective means of reproduction because all the offspring will be adapted to that environment . <hl> In an unstable or unpredictable environment asexually-reproducing species may be at a disadvantage because all the offspring are genetically identical and may not have the genetic variation to survive in new or different conditions . On the other hand , the rapid rates of asexual reproduction may allow for a speedy response to environmental changes if individuals have mutations . An additional advantage of asexual reproduction is that colonization of new habitats may be easier when an individual does not need to find a mate to reproduce .\",\n \"hl_sentences\": \"In a stable or predictable environment , asexual reproduction is an effective means of reproduction because all the offspring will be adapted to that environment .\",\n \"question\": {\n \"cloze_format\": \"The form of reproduction that is thought to be best in a stable environment is ___.\",\n \"normal_format\": \"Which form of reproduction is thought to be best in a stable environment?\",\n \"question_choices\": [\n \"asexual\",\n \"sexual\",\n \"budding\",\n \"parthenogenesis\"\n ],\n \"question_id\": \"fs-idm62799008\",\n \"question_text\": \"Which form of reproduction is thought to be best in a stable environment?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"fragmentation\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> For example , in many sea stars , asexual reproduction is accomplished by fragmentation . <hl> <hl> Figure 43.4 illustrates a sea star for which an arm of the individual is broken off and regenerates a new sea star . <hl> Fisheries workers have been known to try to kill the sea stars eating their clam or oyster beds by cutting them in half and throwing them back into the ocean . Unfortunately for the workers , the two parts can each regenerate a new half , resulting in twice as many sea stars to prey upon the oysters and clams . Fragmentation also occurs in annelid worms , turbellarians , and poriferans . <hl> Fragmentation is the breaking of the body into two parts with subsequent regeneration . <hl> <hl> If the animal is capable of fragmentation , and the part is big enough , a separate individual will regrow . <hl>\",\n \"hl_sentences\": \"For example , in many sea stars , asexual reproduction is accomplished by fragmentation . Figure 43.4 illustrates a sea star for which an arm of the individual is broken off and regenerates a new sea star . Fragmentation is the breaking of the body into two parts with subsequent regeneration . If the animal is capable of fragmentation , and the part is big enough , a separate individual will regrow .\",\n \"question\": {\n \"cloze_format\": \"The form of reproduction that can result from damage to the original animal is ___.\",\n \"normal_format\": \"Which form of reproduction can result from damage to the original animal?\",\n \"question_choices\": [\n \"asexual\",\n \"fragmentation\",\n \"budding\",\n \"parthenogenesis\"\n ],\n \"question_id\": \"fs-idp65241328\",\n \"question_text\": \"Which form of reproduction can result from damage to the original animal?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"hermaphroditism\"\n },\n \"bloom\": null,\n \"hl_context\": \"Hermaphroditism occurs in animals where one individual has both male and female reproductive parts . Invertebrates such as earthworms , slugs , tapeworms and snails , shown in Figure 43.5 , are often hermaphroditic . <hl> Hermaphrodites may self-fertilize or may mate with another of their species , fertilizing each other and both producing offspring . <hl> <hl> Self fertilization is common in animals that have limited mobility or are not motile , such as barnacles and clams . <hl>\",\n \"hl_sentences\": \"Hermaphrodites may self-fertilize or may mate with another of their species , fertilizing each other and both producing offspring . Self fertilization is common in animals that have limited mobility or are not motile , such as barnacles and clams .\",\n \"question\": {\n \"cloze_format\": \"The form of reproduction that is useful to an animal with little mobility that reproduces sexually is ___.\",\n \"normal_format\": \"Which form of reproduction is useful to an animal with little mobility that reproduces sexually?\",\n \"question_choices\": [\n \"fission\",\n \"budding\",\n \"parthenogenesis\",\n \"hermaphroditism\"\n ],\n \"question_id\": \"fs-idm47940992\",\n \"question_text\": \"Which form of reproduction is useful to an animal with little mobility that reproduces sexually?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"sexual reproduction\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Sexual reproduction is the combination of ( usually haploid ) reproductive cells from two individuals to form a third ( usually diploid ) unique offspring . <hl> <hl> Sexual reproduction produces offspring with novel combinations of genes . <hl> This can be an adaptive advantage in unstable or unpredictable environments . As humans , we are used to thinking of animals as having two separate sexes — male and female — determined at conception . However , in the animal kingdom , there are many variations on this theme . <hl> During sexual reproduction the genetic material of two individuals is combined to produce genetically diverse offspring that differ from their parents . <hl> The genetic diversity of sexually produced offspring is thought to give species a better chance of surviving in an unpredictable or changing environment . Species that reproduce sexually must maintain two different types of individuals , males and females , which can limit the ability to colonize new habitats as both sexes must be present .\",\n \"hl_sentences\": \"Sexual reproduction is the combination of ( usually haploid ) reproductive cells from two individuals to form a third ( usually diploid ) unique offspring . Sexual reproduction produces offspring with novel combinations of genes . During sexual reproduction the genetic material of two individuals is combined to produce genetically diverse offspring that differ from their parents .\",\n \"question\": {\n \"cloze_format\": \"Genetically unique individuals are produced through ________.\",\n \"normal_format\": \"Through what are genetically unique individuals produced?\",\n \"question_choices\": [\n \"sexual reproduction\",\n \"parthenogenesis\",\n \"budding\",\n \"fragmentation\"\n ],\n \"question_id\": \"fs-idm82695104\",\n \"question_text\": \"Genetically unique individuals are produced through ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"aquatic\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> External fertilization in an aquatic environment protects the eggs from drying out . <hl> Broadcast spawning can result in a greater mixture of the genes within a group , leading to higher genetic diversity and a greater chance of species survival in a hostile environment . For sessile aquatic organisms like sponges , broadcast spawning is the only mechanism for fertilization and colonization of new environments . The presence of the fertilized eggs and developing young in the water provides opportunities for predation resulting in a loss of offspring . Therefore , millions of eggs must be produced by individuals , and the offspring produced through this method must mature rapidly . The survival rate of eggs produced through broadcast spawning is low . <hl> External fertilization usually occurs in aquatic environments where both eggs and sperm are released into the water . <hl> After the sperm reaches the egg , fertilization takes place . Most external fertilization happens during the process of spawning where one or several females release their eggs and the male ( s ) release sperm in the same area , at the same time . The release of the reproductive material may be triggered by water temperature or the length of daylight . Nearly all fish spawn , as do crustaceans ( such as crabs and shrimp ) , mollusks ( such as oysters ) , squid , and echinoderms ( such as sea urchins and sea cucumbers ) . Figure 43.6 shows salmon spawning in a shallow stream . Frogs , like those shown in Figure 43.7 , corals , squid , and octopuses also spawn . Pairs of fish that are not broadcast spawners may exhibit courtship behavior . This allows the female to select a particular male . The trigger for egg and sperm release ( spawning ) causes the egg and sperm to be placed in a small area , enhancing the possibility of fertilization .\",\n \"hl_sentences\": \"External fertilization in an aquatic environment protects the eggs from drying out . External fertilization usually occurs in aquatic environments where both eggs and sperm are released into the water .\",\n \"question\": {\n \"cloze_format\": \"The type of environment that external fertilization occurs in is the ___.\",\n \"normal_format\": \"External fertilization occurs in which type of environment?\",\n \"question_choices\": [\n \"aquatic\",\n \"forested\",\n \"savanna\",\n \"steppe\"\n ],\n \"question_id\": \"fs-idm65505280\",\n \"question_text\": \"External fertilization occurs in which type of environment?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"ovoviparity\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> In ovoviparity , fertilized eggs are retained in the female , but the embryo obtains its nourishment from the egg ’ s yolk and the young are fully developed when they are hatched . <hl> This occurs in some bony fish ( like the guppy Lebistes reticulatus ) , some sharks , some lizards , some snakes ( such as the garter snake Thamnophis sirtalis ) , some vipers , and some invertebrate animals ( like the Madagascar hissing cockroach Gromphadorhina portentosa ) .\",\n \"hl_sentences\": \"In ovoviparity , fertilized eggs are retained in the female , but the embryo obtains its nourishment from the egg ’ s yolk and the young are fully developed when they are hatched .\",\n \"question\": {\n \"cloze_format\": \"___ is a term that applies to egg development within the female with nourishment derived from a yolk.\",\n \"normal_format\": \"Which term applies to egg development within the female with nourishment derived from a yolk?\",\n \"question_choices\": [\n \"oviparity\",\n \"viviparity\",\n \"ovoviparity\",\n \"ovovoparity\"\n ],\n \"question_id\": \"fs-idp176671776\",\n \"question_text\": \"Which term applies to egg development within the female with nourishment derived from a yolk?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"oviparity\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Internal fertilization occurs most often in land-based animals , although some aquatic animals also use this method . There are three ways that offspring are produced following internal fertilization . <hl> In oviparity , fertilized eggs are laid outside the female ’ s body and develop there , receiving nourishment from the yolk that is a part of the egg . <hl> This occurs in most bony fish , many reptiles , some cartilaginous fish , most amphibians , two mammals , and all birds . Reptiles and insects produce leathery eggs , while birds and turtles produce eggs with high concentrations of calcium carbonate in the shell , making them hard . Chicken eggs are an example of this second type .\",\n \"hl_sentences\": \"In oviparity , fertilized eggs are laid outside the female ’ s body and develop there , receiving nourishment from the yolk that is a part of the egg .\",\n \"question\": {\n \"cloze_format\": \"___ is a term that applies to egg development outside the female with nourishment derived from a yolk.\",\n \"normal_format\": \"Which term applies to egg development outside the female with nourishment derived from a yolk?\",\n \"question_choices\": [\n \"oviparity\",\n \"viviparity\",\n \"ovoviparity\",\n \"ovovoparity\"\n ],\n \"question_id\": \"fs-idp325930864\",\n \"question_text\": \"Which term applies to egg development outside the female with nourishment derived from a yolk?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"seminiferous tubules\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Sperm mature in seminiferous tubules that are coiled inside the testes , as illustrated in Figure 43.8 . <hl> The walls of the seminiferous tubules are made up of the developing sperm cells , with the least developed sperm at the periphery of the tubule and the fully developed sperm in the lumen . The sperm cells are mixed with “ nursemaid ” cells called Sertoli cells which protect the germ cells and promote their development . Other cells mixed in the wall of the tubules are the interstitial cells of Leydig . These cells produce high levels of testosterone once the male reaches adolescence . <hl> Sperm mature in seminiferous tubules in the testes . <hl>\",\n \"hl_sentences\": \"Sperm mature in seminiferous tubules that are coiled inside the testes , as illustrated in Figure 43.8 . Sperm mature in seminiferous tubules in the testes .\",\n \"question\": {\n \"cloze_format\": \"Sperm are produced in the ________.\",\n \"normal_format\": \"Where are sperm produced?\",\n \"question_choices\": [\n \"scrotum\",\n \"seminal vesicles\",\n \"seminiferous tubules\",\n \"prostate gland\"\n ],\n \"question_id\": \"fs-idp135004256\",\n \"question_text\": \"Sperm are produced in the ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"primary spermatocyte\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Spermatogenesis , illustrated in Figure 43.12 , occurs in the wall of the seminiferous tubules ( Figure 43.8 ) , with stem cells at the periphery of the tube and the spermatozoa at the lumen of the tube . <hl> <hl> Immediately under the capsule of the tubule are diploid , undifferentiated cells . <hl> <hl> These stem cells , called spermatogonia ( singular : spermatagonium ) , go through mitosis with one offspring going on to differentiate into a sperm cell and the other giving rise to the next generation of sperm . <hl> <hl> Meiosis starts with a cell called a primary spermatocyte . <hl> At the end of the first meiotic division , a haploid cell is produced called a secondary spermatocyte . This cell is haploid and must go through another meiotic cell division . The cell produced at the end of meiosis is called a spermatid and when it reaches the lumen of the tubule and grows a flagellum , it is called a sperm cell . Four sperm result from each primary spermatocyte that goes through meiosis . Gametogenesis , the production of sperm and eggs , takes place through the process of meiosis . During meiosis , two cell divisions separate the paired chromosomes in the nucleus and then separate the chromatids that were made during an earlier stage of the cell ’ s life cycle . Meiosis produces haploid cells with half of each pair of chromosomes normally found in diploid cells . <hl> The production of sperm is called spermatogenesis and the production of eggs is called oogenesis . <hl>\",\n \"hl_sentences\": \"Spermatogenesis , illustrated in Figure 43.12 , occurs in the wall of the seminiferous tubules ( Figure 43.8 ) , with stem cells at the periphery of the tube and the spermatozoa at the lumen of the tube . Immediately under the capsule of the tubule are diploid , undifferentiated cells . These stem cells , called spermatogonia ( singular : spermatagonium ) , go through mitosis with one offspring going on to differentiate into a sperm cell and the other giving rise to the next generation of sperm . Meiosis starts with a cell called a primary spermatocyte . The production of sperm is called spermatogenesis and the production of eggs is called oogenesis .\",\n \"question\": {\n \"cloze_format\": \"The ___ cell in spermatogenesis is diploid.\",\n \"normal_format\": \"Which of the following cells in spermatogenesis is diploid?\",\n \"question_choices\": [\n \"primary spermatocyte\",\n \"secondary spermatocyte\",\n \"spermatid\",\n \"sperm\"\n ],\n \"question_id\": \"fs-idm81430816\",\n \"question_text\": \"Which of the following cells in spermatogenesis is diploid?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"clitoris\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"The reproductive tissues of male and female humans develop similarly in utero until a low level of the hormone testosterone is released from male gonads . Testosterone causes the undeveloped tissues to differentiate into male sexual organs . When testosterone is absent , the tissues develop into female sexual tissues . Primitive gonads become testes or ovaries . <hl> Tissues that produce a penis in males produce a clitoris in females . <hl> The tissue that will become the scrotum in a male becomes the labia in a female ; that is , they are homologous structures .\",\n \"hl_sentences\": \"Tissues that produce a penis in males produce a clitoris in females .\",\n \"question\": {\n \"cloze_format\": \"The female organ that has the same embryonic origin as the penis is the ___.\",\n \"normal_format\": \"Which female organ has the same embryonic origin as the penis?\",\n \"question_choices\": [\n \"clitoris\",\n \"labia majora\",\n \"greater vestibular glands\",\n \"vagina\"\n ],\n \"question_id\": \"fs-idm30849536\",\n \"question_text\": \"Which female organ has the same embryonic origin as the penis?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"uterus\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The uterus is a structure about the size of a woman ’ s fist . <hl> <hl> This is lined with an endometrium rich in blood vessels and mucus glands . <hl> <hl> The uterus supports the developing embryo and fetus during gestation . <hl> The thickest portion of the wall of the uterus is made of smooth muscle . Contractions of the smooth muscle in the uterus aid in passing the baby through the vagina during labor . A portion of the lining of the uterus sloughs off during each menstrual period , and then builds up again in preparation for an implantation . Part of the uterus , called the cervix , protrudes into the top of the vagina . The cervix functions as the birth canal .\",\n \"hl_sentences\": \"The uterus is a structure about the size of a woman ’ s fist . This is lined with an endometrium rich in blood vessels and mucus glands . The uterus supports the developing embryo and fetus during gestation .\",\n \"question\": {\n \"cloze_format\": \"The female organ that has an endometrial lining that will support a developing baby is the ___.\",\n \"normal_format\": \"Which female organ has an endometrial lining that will support a developing baby?\",\n \"question_choices\": [\n \"labia minora\",\n \"breast\",\n \"ovaries\",\n \"uterus\"\n ],\n \"question_id\": \"fs-idp148194704\",\n \"question_text\": \"Which female organ has an endometrial lining that will support a developing baby?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"one\"\n },\n \"bloom\": \"2\",\n \"hl_context\": \"Egg production begins before birth , is arrested during meiosis until puberty , and then individual cells continue through at each menstrual cycle . <hl> One egg is produced from each meiotic process , with the extra chromosomes and chromatids going into polar bodies that degenerate and are reabsorbed by the body . <hl> 43.4 Hormonal Control of Human Reproduction Learning Objectives By the end of this chapter , you will be able to :\",\n \"hl_sentences\": \"One egg is produced from each meiotic process , with the extra chromosomes and chromatids going into polar bodies that degenerate and are reabsorbed by the body .\",\n \"question\": {\n \"cloze_format\": \"The amount of eggs that are produced as a result of one meiotic series of cell divisions is ___.\",\n \"normal_format\": \"How many eggs are produced as a result of one meiotic series of cell divisions?\",\n \"question_choices\": [\n \"one\",\n \"two\",\n \"three\",\n \"four\"\n ],\n \"question_id\": \"fs-idm37013456\",\n \"question_text\": \"How many eggs are produced as a result of one meiotic series of cell divisions?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"FSH\"\n },\n \"bloom\": null,\n \"hl_context\": \"At the onset of puberty , the hypothalamus causes the release of FSH and LH into the male system for the first time . <hl> FSH enters the testes and stimulates the Sertoli cells to begin facilitating spermatogenesis using negative feedback , as illustrated in Figure 43.14 . <hl> <hl> LH also enters the testes and stimulates the interstitial cells of Leydig to make and release testosterone into the testes and the blood . <hl> Gametogenesis , the production of sperm and eggs , takes place through the process of meiosis . During meiosis , two cell divisions separate the paired chromosomes in the nucleus and then separate the chromatids that were made during an earlier stage of the cell ’ s life cycle . Meiosis produces haploid cells with half of each pair of chromosomes normally found in diploid cells . <hl> The production of sperm is called spermatogenesis and the production of eggs is called oogenesis . <hl>\",\n \"hl_sentences\": \"FSH enters the testes and stimulates the Sertoli cells to begin facilitating spermatogenesis using negative feedback , as illustrated in Figure 43.14 . LH also enters the testes and stimulates the interstitial cells of Leydig to make and release testosterone into the testes and the blood . The production of sperm is called spermatogenesis and the production of eggs is called oogenesis .\",\n \"question\": {\n \"cloze_format\": \"The ___ hormone causes Leydig cells to make testosterone.\",\n \"normal_format\": \"Which hormone causes Leydig cells to make testosterone?\",\n \"question_choices\": [\n \"FSH\",\n \"LH\",\n \"inhibin\",\n \"estrogen\"\n ],\n \"question_id\": \"fs-idp21199008\",\n \"question_text\": \"Which hormone causes Leydig cells to make testosterone?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"GnRH\"\n },\n \"bloom\": null,\n \"hl_context\": \"The control of reproduction in females is more complex . <hl> As with the male , the anterior pituitary hormones cause the release of the hormones FSH and LH . <hl> In addition , estrogens and progesterone are released from the developing follicles . Estrogen is the reproductive hormone in females that assists in endometrial regrowth , ovulation , and calcium absorption ; it is also responsible for the secondary sexual characteristics of females . These include breast development , flaring of the hips , and a shorter period necessary for bone maturation . Progesterone assists in endometrial re-growth and inhibition of FSH and LH release . The human male and female reproductive cycles are controlled by the interaction of hormones from the hypothalamus and anterior pituitary with hormones from reproductive tissues and organs . In both sexes , the hypothalamus monitors and causes the release of hormones from the pituitary gland . <hl> When the reproductive hormone is required , the hypothalamus sends a gonadotropin-releasing hormone ( GnRH ) to the anterior pituitary . <hl> <hl> This causes the release of follicle stimulating hormone ( FSH ) and luteinizing hormone ( LH ) from the anterior pituitary into the blood . <hl> Note that the body must reach puberty in order for the adrenals to release the hormones that must be present for GnRH to be produced . Although FSH and LH are named after their functions in female reproduction , they are produced in both sexes and play important roles in controlling reproduction . Other hormones have specific functions in the male and female reproductive systems .\",\n \"hl_sentences\": \"As with the male , the anterior pituitary hormones cause the release of the hormones FSH and LH . When the reproductive hormone is required , the hypothalamus sends a gonadotropin-releasing hormone ( GnRH ) to the anterior pituitary . This causes the release of follicle stimulating hormone ( FSH ) and luteinizing hormone ( LH ) from the anterior pituitary into the blood .\",\n \"question\": {\n \"cloze_format\": \"The hormone that causes FSH and LH to be released is ___.\",\n \"normal_format\": \"Which hormone causes FSH and LH to be released?\",\n \"question_choices\": [\n \"testosterone\",\n \"estrogen\",\n \"GnRH\",\n \"progesterone\"\n ],\n \"question_id\": \"fs-idm55845888\",\n \"question_text\": \"Which hormone causes FSH and LH to be released?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"LH\"\n },\n \"bloom\": null,\n \"hl_context\": \"In females , FSH stimulates development of egg cells , called ova , which develop in structures called follicles . Follicle cells produce the hormone inhibin , which inhibits FSH production . <hl> LH also plays a role in the development of ova , induction of ovulation , and stimulation of estradiol and progesterone production by the ovaries . <hl> Estradiol and progesterone are steroid hormones that prepare the body for pregnancy . Estradiol produces secondary sex characteristics in females , while both estradiol and progesterone regulate the menstrual cycle .\",\n \"hl_sentences\": \"LH also plays a role in the development of ova , induction of ovulation , and stimulation of estradiol and progesterone production by the ovaries .\",\n \"question\": {\n \"cloze_format\": \"The hormone that signals ovulation is ___.\",\n \"normal_format\": \"Which hormone signals ovulation?\",\n \"question_choices\": [\n \"FSH\",\n \"LH\",\n \"inhibin\",\n \"estrogen\"\n ],\n \"question_id\": \"fs-idm171491232\",\n \"question_text\": \"Which hormone signals ovulation?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"progesterone\"\n },\n \"bloom\": null,\n \"hl_context\": \"Following ovulation , the ovarian cycle enters its luteal phase , illustrated in Figure 43.15 and the menstrual cycle enters its secretory phase , both of which run from about day 15 to 28 . The luteal and secretory phases refer to changes in the ruptured follicle . The cells in the follicle undergo physical changes and produce a structure called a corpus luteum . The corpus luteum produces estrogen and progesterone . <hl> The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH . <hl> <hl> The uterus is being prepared to accept a fertilized egg , should it occur during this cycle . <hl> The inhibition of FSH and LH prevents any further eggs and follicles from developing , while the progesterone is elevated . The level of estrogen produced by the corpus luteum increases to a steady level for the next few days . The control of reproduction in females is more complex . As with the male , the anterior pituitary hormones cause the release of the hormones FSH and LH . In addition , estrogens and progesterone are released from the developing follicles . Estrogen is the reproductive hormone in females that assists in endometrial regrowth , ovulation , and calcium absorption ; it is also responsible for the secondary sexual characteristics of females . These include breast development , flaring of the hips , and a shorter period necessary for bone maturation . <hl> Progesterone assists in endometrial re-growth and inhibition of FSH and LH release . <hl>\",\n \"hl_sentences\": \"The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH . The uterus is being prepared to accept a fertilized egg , should it occur during this cycle . Progesterone assists in endometrial re-growth and inhibition of FSH and LH release .\",\n \"question\": {\n \"cloze_format\": \"The ___ hormone causes the re-growth of the endometrial lining of the uterus.\",\n \"normal_format\": \"Which hormone causes the re-growth of the endometrial lining of the uterus?\",\n \"question_choices\": [\n \"testosterone\",\n \"estrogen\",\n \"GnRH\",\n \"progesterone\"\n ],\n \"question_id\": \"fs-idm71478992\",\n \"question_text\": \"Which hormone causes the re-growth of the endometrial lining of the uterus?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"diffusion through the endometrium\"\n },\n \"bloom\": null,\n \"hl_context\": \"The gestation period is divided into three equal periods or trimesters . <hl> During the first two to four weeks of the first trimester , nutrition and waste are handled by the endometrial lining through diffusion . <hl> <hl> As the trimester progresses , the outer layer of the embryo begins to merge with the endometrium , and the placenta forms . <hl> <hl> This organ takes over the nutrient and waste requirements of the embryo and fetus , with the mother ’ s blood passing nutrients to the placenta and removing waste from it . <hl> Chemicals from the fetus , such as bilirubin , are processed by the mother ’ s liver for elimination . Some of the mother ’ s immunoglobulins will pass through the placenta , providing passive immunity against some potential infections .\",\n \"hl_sentences\": \"During the first two to four weeks of the first trimester , nutrition and waste are handled by the endometrial lining through diffusion . As the trimester progresses , the outer layer of the embryo begins to merge with the endometrium , and the placenta forms . This organ takes over the nutrient and waste requirements of the embryo and fetus , with the mother ’ s blood passing nutrients to the placenta and removing waste from it .\",\n \"question\": {\n \"cloze_format\": \"Nutrient and waste requirements for the developing fetus are handled during the first few weeks by ___ .\",\n \"normal_format\": \"By what, nutrient and waste requirements for the developing fetus are handled during the first few weeks?\",\n \"question_choices\": [\n \"the placenta\",\n \"diffusion through the endometrium\",\n \"the chorion\",\n \"the blastocyst\"\n ],\n \"question_id\": \"fs-idp80601616\",\n \"question_text\": \"Nutrient and waste requirements for the developing fetus are handled during the first few weeks by:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"placenta\"\n },\n \"bloom\": null,\n \"hl_context\": \"During the second trimester , the fetus grows to about 30 cm ( 12 inches ) , as shown in Figure 43.20 . It becomes active and the mother usually feels the first movements . All organs and structures continue to develop . <hl> The placenta has taken over the functions of nutrition and waste and the production of estrogen and progesterone from the corpus luteum , which has degenerated . <hl> <hl> The placenta will continue functioning up through the delivery of the baby . <hl> The gestation period is divided into three equal periods or trimesters . During the first two to four weeks of the first trimester , nutrition and waste are handled by the endometrial lining through diffusion . <hl> As the trimester progresses , the outer layer of the embryo begins to merge with the endometrium , and the placenta forms . <hl> <hl> This organ takes over the nutrient and waste requirements of the embryo and fetus , with the mother ’ s blood passing nutrients to the placenta and removing waste from it . <hl> Chemicals from the fetus , such as bilirubin , are processed by the mother ’ s liver for elimination . Some of the mother ’ s immunoglobulins will pass through the placenta , providing passive immunity against some potential infections .\",\n \"hl_sentences\": \"The placenta has taken over the functions of nutrition and waste and the production of estrogen and progesterone from the corpus luteum , which has degenerated . The placenta will continue functioning up through the delivery of the baby . As the trimester progresses , the outer layer of the embryo begins to merge with the endometrium , and the placenta forms . This organ takes over the nutrient and waste requirements of the embryo and fetus , with the mother ’ s blood passing nutrients to the placenta and removing waste from it .\",\n \"question\": {\n \"cloze_format\": \"Progesterone is made during the third trimester by the ___ .\",\n \"normal_format\": \"By which, progesterone is made during the third trimester?\",\n \"question_choices\": [\n \"placenta\",\n \"endometrial lining\",\n \"chorion\",\n \"corpus luteum\"\n ],\n \"question_id\": \"fs-idp58574848\",\n \"question_text\": \"Progesterone is made during the third trimester by the:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"abstinence\"\n },\n \"bloom\": null,\n \"hl_context\": \"Compliance with the contraceptive method is a strong contributor to the success or failure rate of any particular method . <hl> The only method that is completely effective at preventing conception is abstinence . <hl> The choice of contraceptive method depends on the goals of the woman or couple . Tubal ligation and vasectomy are considered permanent prevention , while other methods are reversible and provide short-term contraception .\",\n \"hl_sentences\": \"The only method that is completely effective at preventing conception is abstinence .\",\n \"question\": {\n \"cloze_format\": \"The contraceptive method that is 100 percent effective at preventing pregnancy is (a) ___ .\",\n \"normal_format\": \"Which contraceptive method is 100 percent effective at preventing pregnancy?\",\n \"question_choices\": [\n \"condom\",\n \"oral hormonal methods\",\n \"sterilization\",\n \"abstinence\"\n ],\n \"question_id\": \"fs-idm43088464\",\n \"question_text\": \"Which contraceptive method is 100 percent effective at preventing pregnancy?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"hormonal\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Hormonal methods use synthetic progesterone ( sometimes in combination with estrogen ) , to inhibit the hypothalamus from releasing FSH or LH , and thus prevent an egg from being available for fertilization . <hl> <hl> The method of administering the hormone affects failure rate . <hl> <hl> The most reliable method , with a failure rate of less than 1 percent , is the implantation of the hormone under the skin . <hl> The same rate can be achieved through the sterilization procedures of vasectomy in the man or of tubal ligation in the woman , or by using an intrauterine device ( IUD ) . IUDs are inserted into the uterus and establish an inflammatory condition that prevents fertilized eggs from implanting into the uterine wall .\",\n \"hl_sentences\": \"Hormonal methods use synthetic progesterone ( sometimes in combination with estrogen ) , to inhibit the hypothalamus from releasing FSH or LH , and thus prevent an egg from being available for fertilization . The method of administering the hormone affects failure rate . The most reliable method , with a failure rate of less than 1 percent , is the implantation of the hormone under the skin .\",\n \"question\": {\n \"cloze_format\": \"The type of short term contraceptive method that is generally more effective than others is ___.\",\n \"normal_format\": \"Which type of short term contraceptive method is generally more effective than others?\",\n \"question_choices\": [\n \"barrier\",\n \"hormonal\",\n \"natural family planning\",\n \"withdrawal\"\n ],\n \"question_id\": \"fs-idm175851088\",\n \"question_text\": \"Which type of short term contraceptive method is generally more effective than others?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"oxytocin\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Labor is the physical efforts of expulsion of the fetus and the placenta from the uterus during birth ( parturition ) . <hl> <hl> Toward the end of the third trimester , estrogen causes receptors on the uterine wall to develop and bind the hormone oxytocin . <hl> At this time , the baby reorients , facing forward and down with the back or crown of the head engaging the cervix ( uterine opening ) . This causes the cervix to stretch and nerve impulses are sent to the hypothalamus , which signals for the release of oxytocin from the posterior pituitary . The oxytocin causes the smooth muscle in the uterine wall to contract . At the same time , the placenta releases prostaglandins into the uterus , increasing the contractions . A positive feedback relay occurs between the uterus , hypothalamus , and the posterior pituitary to assure an adequate supply of oxytocin . As more smooth muscle cells are recruited , the contractions increase in intensity and force .\",\n \"hl_sentences\": \"Labor is the physical efforts of expulsion of the fetus and the placenta from the uterus during birth ( parturition ) . Toward the end of the third trimester , estrogen causes receptors on the uterine wall to develop and bind the hormone oxytocin .\",\n \"question\": {\n \"cloze_format\": \"The ___ hormone is primarily responsible for the contractions during labor.\",\n \"normal_format\": \"Which hormone is primarily responsible for the contractions during labor?\",\n \"question_choices\": [\n \"oxytocin\",\n \"estrogen\",\n \"β-HCG\",\n \"progesterone\"\n ],\n \"question_id\": \"fs-idp160654912\",\n \"question_text\": \"Which hormone is primarily responsible for the contractions during labor?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"first trimester\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Internal organs and body structures begin to develop during the first trimester . <hl> By five weeks , limb buds , eyes , the heart , and liver have been basically formed . By eight weeks , the term fetus applies , and the body is essentially formed , as shown in Figure 43.19 . The individual is about five centimeters ( two inches ) in length and many of the organs , such as the lungs and liver , are not yet functioning . Exposure to any toxins is especially dangerous during the first trimester , as all of the body ’ s organs and structures are going through initial development . Anything that affects that development can have a severe effect on the fetus ’ survival .\",\n \"hl_sentences\": \"Internal organs and body structures begin to develop during the first trimester .\",\n \"question\": {\n \"cloze_format\": \"Major organs begin to develop during the ___ of human gestation.\",\n \"normal_format\": \"Major organs begin to develop during which part of human gestation?\",\n \"question_choices\": [\n \"fertilization\",\n \"first trimester\",\n \"second trimester\",\n \"third trimester\"\n ],\n \"question_id\": \"fs-idp71215264\",\n \"question_text\": \"Major organs begin to develop during which part of human gestation?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"The trophoblast is a germ layer.\"\n },\n \"bloom\": \"4\",\n \"hl_context\": \"<hl> The three germs layers , shown in Figure 43.26 , are the endoderm , the ectoderm , and the mesoderm . <hl> The ectoderm gives rise to the nervous system and the epidermis . The mesoderm gives rise to the muscle cells and connective tissue in the body . The endoderm gives rise to columnar cells found in the digestive system and many internal organs . <hl> The typical blastula is a ball of cells . <hl> The next stage in embryonic development is the formation of the body plan . The cells in the blastula rearrange themselves spatially to form three layers of cells . This process is called gastrulation . During gastrulation , the blastula folds upon itself to form the three layers of cells . Each of these layers is called a germ layer and each germ layer differentiates into different organ systems . In mammals , the blastula forms the blastocyst in the next stage of development . <hl> Here the cells in the blastula arrange themselves in two layers : the inner cell mass , and an outer layer called the trophoblast . <hl> <hl> The inner cell mass is also known as the embryoblast and this mass of cells will go on to form the embryo . <hl> At this stage of development , illustrated in Figure 43.25 the inner cell mass consists of embryonic stem cells that will differentiate into the different cell types needed by the organism . The trophoblast will contribute to the placenta and nourish the embryo .\",\n \"hl_sentences\": \"The three germs layers , shown in Figure 43.26 , are the endoderm , the ectoderm , and the mesoderm . The typical blastula is a ball of cells . Here the cells in the blastula arrange themselves in two layers : the inner cell mass , and an outer layer called the trophoblast . The inner cell mass is also known as the embryoblast and this mass of cells will go on to form the embryo .\",\n \"question\": {\n \"cloze_format\": \"It is false that ___.\",\n \"normal_format\": \"Which of the following is false?\",\n \"question_choices\": [\n \"The endoderm, mesoderm, ectoderm are germ layers.\",\n \"The trophoblast is a germ layer.\",\n \"The inner cell mass is a source of embryonic stem cells.\",\n \"The blastula is often a hollow ball of cells.\"\n ],\n \"question_id\": \"fs-idm4742656\",\n \"question_text\": \"Which of the following is false?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"does not change significantly\"\n },\n \"bloom\": null,\n \"hl_context\": \"The development of multi-cellular organisms begins from a single-celled zygote , which undergoes rapid cell division to form the blastula . <hl> The rapid , multiple rounds of cell division are termed cleavage . <hl> Cleavage is illustrated in ( Figure 43.24 a ) . After the cleavage has produced over 100 cells , the embryo is called a blastula . The blastula is usually a spherical layer of cells ( the blastoderm ) surrounding a fluid-filled or yolk-filled cavity ( the blastocoel ) . Mammals at this stage form a structure called the blastocyst , characterized by an inner cell mass that is distinct from the surrounding blastula , shown in Figure 43.24 b . <hl> During cleavage , the cells divide without an increase in mass ; that is , one large single-celled zygote divides into multiple smaller cells . <hl> Each cell within the blastula is called a blastomere . Cleavage can take place in two ways : holoblastic ( total ) cleavage or meroblastic ( partial ) cleavage . The type of cleavage depends on the amount of yolk in the eggs . In placental mammals ( including humans ) where nourishment is provided by the mother ’ s body , the eggs have a very small amount of yolk and undergo holoblastic cleavage . Other species , such as birds , with a lot of yolk in the egg to nourish the embryo during development , undergo meroblastic cleavage .\",\n \"hl_sentences\": \"The rapid , multiple rounds of cell division are termed cleavage . During cleavage , the cells divide without an increase in mass ; that is , one large single-celled zygote divides into multiple smaller cells .\",\n \"question\": {\n \"cloze_format\": \"During cleavage, the mass of cells ___.\",\n \"normal_format\": \"How the mass of cells changes during cleavage?\",\n \"question_choices\": [\n \"increases\",\n \"decreases\",\n \"doubles with every cell division\",\n \"does not change significantly\"\n ],\n \"question_id\": \"fs-idp11431424\",\n \"question_text\": \"During cleavage, the mass of cells:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"ectoderm\"\n },\n \"bloom\": null,\n \"hl_context\": \"Organs form from the germ layers through the process of differentiation . During differentiation , the embryonic stem cells express specific sets of genes which will determine their ultimate cell type . <hl> For example , some cells in the ectoderm will express the genes specific to skin cells . <hl> As a result , these cells will differentiate into epidermal cells . The process of differentiation is regulated by cellular signaling cascades .\",\n \"hl_sentences\": \"For example , some cells in the ectoderm will express the genes specific to skin cells .\",\n \"question\": {\n \"cloze_format\": \"The ___ gives rise to the skin cells.\",\n \"normal_format\": \"Which of the following gives rise to the skin cells?\",\n \"question_choices\": [\n \"ectoderm\",\n \"endoderm\",\n \"mesoderm\",\n \"none of the above\"\n ],\n \"question_id\": \"fs-idm29405328\",\n \"question_text\": \"Which of the following gives rise to the skin cells?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"somites\"\n },\n \"bloom\": null,\n \"hl_context\": \"The mesoderm that lies on either side of the vertebrate neural tube will develop into the various connective tissues of the animal body . <hl> A spatial pattern of gene expression reorganizes the mesoderm into groups of cells called somites with spaces between them . <hl> <hl> The somites , illustrated in Figure 43.29 will further develop into the ribs , lungs , and segmental ( spine ) muscle . <hl> The mesoderm also forms a structure called the notochord , which is rod-shaped and forms the central axis of the animal body .\",\n \"hl_sentences\": \"A spatial pattern of gene expression reorganizes the mesoderm into groups of cells called somites with spaces between them . The somites , illustrated in Figure 43.29 will further develop into the ribs , lungs , and segmental ( spine ) muscle .\",\n \"question\": {\n \"cloze_format\": \"The ribs form from the ________.\",\n \"normal_format\": \"From what do the ribs form?\",\n \"question_choices\": [\n \"notochord\",\n \"neural plate\",\n \"neural tube\",\n \"somites\"\n ],\n \"question_id\": \"fs-idp40022656\",\n \"question_text\": \"The ribs form from the ________.\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":43,"string":"43"},"chapter_text":{"kind":"string","value":"43.1 Reproduction Methods Learning Objectives By the end of this section, you will be able to:\n\n Describe advantages and disadvantages of asexual and sexual reproduction \n\n Discuss asexual reproduction methods \n\n Discuss sexual reproduction methods \n\n Animals produce offspring through asexual and/or sexual reproduction. Both methods have advantages and disadvantages. Asexual reproduction produces offspring that are genetically identical to the parent because the offspring are all clones of the original parent. A single individual can produce offspring asexually and large numbers of offspring can be produced quickly. In a stable or predictable environment, asexual reproduction is an effective means of reproduction because all the offspring will be adapted to that environment. In an unstable or unpredictable environment asexually-reproducing species may be at a disadvantage because all the offspring are genetically identical and may not have the genetic variation to survive in new or different conditions. On the other hand, the rapid rates of asexual reproduction may allow for a speedy response to environmental changes if individuals have mutations. An additional advantage of asexual reproduction is that colonization of new habitats may be easier when an individual does not need to find a mate to reproduce. \n\n During sexual reproduction the genetic material of two individuals is combined to produce genetically diverse offspring that differ from their parents. The genetic diversity of sexually produced offspring is thought to give species a better chance of surviving in an unpredictable or changing environment. Species that reproduce sexually must maintain two different types of individuals, males and females, which can limit the ability to colonize new habitats as both sexes must be present. \n\n Asexual Reproduction \n\n Asexual reproduction occurs in prokaryotic microorganisms (bacteria) and in some eukaryotic single-celled and multi-celled organisms. There are a number of ways that animals reproduce asexually. \n\n Fission \n\n Fission , also called binary fission, occurs in prokaryotic microorganisms and in some invertebrate, multi-celled organisms. After a period of growth, an organism splits into two separate organisms. Some unicellular eukaryotic organisms undergo binary fission by mitosis. In other organisms, part of the individual separates and forms a second individual. This process occurs, for example, in many asteroid echinoderms through splitting of the central disk. Some sea anemones and some coral polyps ( Figure 43.2 ) also reproduce through fission. \n\n Budding Budding is a form of asexual reproduction that results from the outgrowth of a part of a cell or body region leading to a separation from the original organism into two individuals. Budding occurs commonly in some invertebrate animals such as corals and hydras. In hydras, a bud forms that develops into an adult and breaks away from the main body, as illustrated in Figure 43.3 , whereas in coral budding, the bud does not detach and multiplies as part of a new colony. \n\n Link to Learning \n\n Watch a video of a hydra budding.\n\n Click to view content \n\n Fragmentation \n\n Fragmentation is the breaking of the body into two parts with subsequent regeneration. If the animal is capable of fragmentation, and the part is big enough, a separate individual will regrow. \n\n For example, in many sea stars, asexual reproduction is accomplished by fragmentation. Figure 43.4 illustrates a sea star for which an arm of the individual is broken off and regenerates a new sea star. Fisheries workers have been known to try to kill the sea stars eating their clam or oyster beds by cutting them in half and throwing them back into the ocean. Unfortunately for the workers, the two parts can each regenerate a new half, resulting in twice as many sea stars to prey upon the oysters and clams. Fragmentation also occurs in annelid worms, turbellarians, and poriferans. \n\n Note that in fragmentation, there is generally a noticeable difference in the size of the individuals, whereas in fission, two individuals of approximate size are formed. \n\n Parthenogenesis \n\n Parthenogenesis is a form of asexual reproduction where an egg develops into a complete individual without being fertilized. The resulting offspring can be either haploid or diploid, depending on the process and the species. Parthenogenesis occurs in invertebrates such as water flees, rotifers, aphids, stick insects, some ants, wasps, and bees. Bees use parthenogenesis to produce haploid males (drones). If eggs are fertilized, diploid females develop, and if the fertilized eggs are fed special diet (so called royal jelly), a queen is produced. Some vertebrate animals—such as certain reptiles, amphibians, and fish—also reproduce through parthenogenesis. Although more common in plants, parthenogenesis has been observed in animal species that were segregated by sex in terrestrial or marine zoos. Two female Komodo dragons, a hammerhead shark, and a blacktop shark have produced parthenogenic young when the females have been isolated from males. \n\n Sexual Reproduction \n\n Sexual reproduction is the combination of (usually haploid) reproductive cells from two individuals to form a third (usually diploid) unique offspring. Sexual reproduction produces offspring with novel combinations of genes. This can be an adaptive advantage in unstable or unpredictable environments. As humans, we are used to thinking of animals as having two separate sexes—male and female—determined at conception. However, in the animal kingdom, there are many variations on this theme. \n\n Hermaphroditism \n\n Hermaphroditism occurs in animals where one individual has both male and female reproductive parts. Invertebrates such as earthworms, slugs, tapeworms and snails, shown in Figure 43.5 , are often hermaphroditic. Hermaphrodites may self-fertilize or may mate with another of their species, fertilizing each other and both producing offspring. Self fertilization is common in animals that have limited mobility or are not motile, such as barnacles and clams. \n\n Sex Determination \n\n Mammalian sex determination is determined genetically by the presence of X and Y chromosomes. Individuals homozygous for X (XX) are female and heterozygous individuals (XY) are male. The presence of a Y chromosome causes the development of male characteristics and its absence results in female characteristics. The XY system is also found in some insects and plants. \n\n Avian sex determination is dependent on the presence of Z and W chromosomes. Homozygous for Z (ZZ) results in a male and heterozygous (ZW) results in a female. The W appears to be essential in determining the sex of the individual, similar to the Y chromosome in mammals. Some fish, crustaceans, insects (such as butterflies and moths), and reptiles use this system. \n\n The sex of some species is not determined by genetics but by some aspect of the environment. Sex determination in some crocodiles and turtles, for example, is often dependent on the temperature during critical periods of egg development. This is referred to as environmental sex determination, or more specifically as temperature-dependent sex determination. In many turtles, cooler temperatures during egg incubation produce males and warm temperatures produce females. In some crocodiles, moderate temperatures produce males and both warm and cool temperatures produce females. In some species, sex is both genetic- and temperature-dependent. \n\n Individuals of some species change their sex during their lives, alternating between male and female. If the individual is female first, it is termed protogyny or “first female,” if it is male first, its termed protandry or “first male.” Oysters, for example, are born male, grow, and become female and lay eggs; some oyster species change sex multiple times. \n43.2 Fertilization Learning Objectives By the end of this section, you will be able to:\n\n Discuss internal and external methods of fertilization \n\n Describe the methods used by animals for development of offspring during gestation \n\n Describe the anatomical adaptions that occurred in animals to facilitate reproduction \n\n Sexual reproduction starts with the combination of a sperm and an egg in a process called fertilization. This can occur either inside ( internal fertilization ) or outside ( external fertilization ) the body of the female. Humans provide an example of the former whereas seahorse reproduction is an example of the latter. \n\n External Fertilization \n\n External fertilization usually occurs in aquatic environments where both eggs and sperm are released into the water. After the sperm reaches the egg, fertilization takes place. Most external fertilization happens during the process of spawning where one or several females release their eggs and the male(s) release sperm in the same area, at the same time. The release of the reproductive material may be triggered by water temperature or the length of daylight. Nearly all fish spawn, as do crustaceans (such as crabs and shrimp), mollusks (such as oysters), squid, and echinoderms (such as sea urchins and sea cucumbers). Figure 43.6 shows salmon spawning in a shallow stream. Frogs, like those shown in Figure 43.7 , corals, squid, and octopuses also spawn. Pairs of fish that are not broadcast spawners may exhibit courtship behavior. This allows the female to select a particular male. The trigger for egg and sperm release (spawning) causes the egg and sperm to be placed in a small area, enhancing the possibility of fertilization. \n\n External fertilization in an aquatic environment protects the eggs from drying out. Broadcast spawning can result in a greater mixture of the genes within a group, leading to higher genetic diversity and a greater chance of species survival in a hostile environment. For sessile aquatic organisms like sponges, broadcast spawning is the only mechanism for fertilization and colonization of new environments. The presence of the fertilized eggs and developing young in the water provides opportunities for predation resulting in a loss of offspring. Therefore, millions of eggs must be produced by individuals, and the offspring produced through this method must mature rapidly. The survival rate of eggs produced through broadcast spawning is low. \n\n Internal Fertilization \n\n Internal fertilization occurs most often in land-based animals, although some aquatic animals also use this method. There are three ways that offspring are produced following internal fertilization. In oviparity , fertilized eggs are laid outside the female’s body and develop there, receiving nourishment from the yolk that is a part of the egg. This occurs in most bony fish, many reptiles, some cartilaginous fish, most amphibians, two mammals, and all birds. Reptiles and insects produce leathery eggs, while birds and turtles produce eggs with high concentrations of calcium carbonate in the shell, making them hard. Chicken eggs are an example of this second type. \n\n In ovoviparity , fertilized eggs are retained in the female, but the embryo obtains its nourishment from the egg’s yolk and the young are fully developed when they are hatched. This occurs in some bony fish (like the guppy Lebistes reticulatus ), some sharks, some lizards, some snakes (such as the garter snake Thamnophis sirtalis ), some vipers, and some invertebrate animals (like the Madagascar hissing cockroach Gromphadorhina portentosa ). \n\n In viviparity the young develop within the female, receiving nourishment from the mother’s blood through a placenta. The offspring develops in the female and is born alive. This occurs in most mammals, some cartilaginous fish, and a few reptiles. \n\n Internal fertilization has the advantage of protecting the fertilized egg from dehydration on land. The embryo is isolated within the female, which limits predation on the young. Internal fertilization enhances the fertilization of eggs by a specific male. Fewer offspring are produced through this method, but their survival rate is higher than that for external fertilization. \n\n The Evolution of Reproduction \n\n Once multicellular organisms evolved and developed specialized cells, some also developed tissues and organs with specialized functions. An early development in reproduction occurred in the Annelids. These organisms produce sperm and eggs from undifferentiated cells in their coelom and store them in that cavity. When the coelom becomes filled, the cells are released through an excretory opening or by the body splitting open. Reproductive organs evolved with the development of gonads that produce sperm and eggs. These cells went through meiosis, an adaption of mitosis, which reduced the number of chromosomes in each reproductive cell by half, while increasing the number of cells through cell division. \n\n Complete reproductive systems were developed in insects, with separate sexes. Sperm are made in testes and then travel through coiled tubes to the epididymis for storage. Eggs mature in the ovary. When they are released from the ovary, they travel to the uterine tubes for fertilization. Some insects have a specialized sac, called a spermatheca , which stores sperm for later use, sometimes up to a year. Fertilization can be timed with environmental or food conditions that are optimal for offspring survival. \n\n Vertebrates have similar structures, with a few differences. Non-mammals, such as birds and reptiles, have a common body opening, called a cloaca , for the digestive, excretory and reproductive systems. Coupling between birds usually involves positioning the cloaca openings opposite each other for transfer of sperm. Mammals have separate openings for the systems in the female and a uterus for support of developing offspring. The uterus has two chambers in species that produce large numbers of offspring at a time, while species that produce one offspring, such as primates, have a single uterus. \n\n Sperm transfer from the male to the female during reproduction ranges from releasing the sperm into the watery environment for external fertilization, to the joining of cloaca in birds, to the development of a penis for direct delivery into the female’s vagina in mammals. \n43.3 Human Reproductive Anatomy and Gametogenesis Learning Objectives By the end of this section, you will be able to:\n\n Describe human male and female reproductive anatomies \n\n Discuss the human sexual response \n\n Describe spermatogenesis and oogenesis and discuss their differences and similarities \n\n As animals became more complex, specific organs and organ systems developed to support specific functions for the organism. The reproductive structures that evolved in land animals allow males and females to mate, fertilize internally, and support the growth and development of offspring. \n\n Human Reproductive Anatomy \n\n The reproductive tissues of male and female humans develop similarly in utero until a low level of the hormone testosterone is released from male gonads. Testosterone causes the undeveloped tissues to differentiate into male sexual organs. When testosterone is absent, the tissues develop into female sexual tissues. Primitive gonads become testes or ovaries. Tissues that produce a penis in males produce a clitoris in females. The tissue that will become the scrotum in a male becomes the labia in a female; that is, they are homologous structures. \n\n Male Reproductive Anatomy \n\n In the male reproductive system, the scrotum houses the testicles or testes (singular: testis), including providing passage for blood vessels, nerves, and muscles related to testicular function. The testes are a pair of male reproductive organs that produce sperm and some reproductive hormones. Each testis is approximately 2.5 by 3.8 cm (1.5 by 1 in) in size and divided into wedge-shaped lobules by connective tissue called septa. Coiled in each wedge are seminiferous tubules that produce sperm. \n\n Sperm are immobile at body temperature; therefore, the scrotum and penis are external to the body, as illustrated in Figure 43.8 so that a proper temperature is maintained for motility. In land mammals, the pair of testes must be suspended outside the body at about 2 ° C lower than body temperature to produce viable sperm. Infertility can occur in land mammals when the testes do not descend through the abdominal cavity during fetal development. \n\n Visual Connection \n\n Which of the following statements about the male reproductive system is false? \n\n The vas deferens carries sperm from the testes to the penis. \n\n Sperm mature in seminiferous tubules in the testes. \n\n Both the prostate and the bulbourethral glands produce components of the semen. \n\n The prostate gland is located in the testes. \n\n Sperm mature in seminiferous tubules that are coiled inside the testes, as illustrated in Figure 43.8 . The walls of the seminiferous tubules are made up of the developing sperm cells, with the least developed sperm at the periphery of the tubule and the fully developed sperm in the lumen. The sperm cells are mixed with “nursemaid” cells called Sertoli cells which protect the germ cells and promote their development. Other cells mixed in the wall of the tubules are the interstitial cells of Leydig. These cells produce high levels of testosterone once the male reaches adolescence. \n\n When the sperm have developed flagella and are nearly mature, they leave the testicles and enter the epididymis, shown in Figure 43.8 . This structure resembles a comma and lies along the top and posterior portion of the testes; it is the site of sperm maturation. The sperm leave the epididymis and enter the vas deferens (or ductus deferens), which carries the sperm, behind the bladder, and forms the ejaculatory duct with the duct from the seminal vesicles. During a vasectomy, a section of the vas deferens is removed, preventing sperm from being passed out of the body during ejaculation and preventing fertilization. \n\n Semen is a mixture of sperm and spermatic duct secretions (about 10 percent of the total) and fluids from accessory glands that contribute most of the semen’s volume. Sperm are haploid cells, consisting of a flagellum as a tail, a neck that contains the cell’s energy-producing mitochondria, and a head that contains the genetic material. Figure 43.9 shows a micrograph of human sperm as well as a diagram of the parts of the sperm. An acrosome is found at the top of the head of the sperm. This structure contains lysosomal enzymes that can digest the protective coverings that surround the egg to help the sperm penetrate and fertilize the egg. An ejaculate will contain from two to five milliliters of fluid with from 50–120 million sperm per milliliter. \n\n The bulk of the semen comes from the accessory glands associated with the male reproductive system. These are the seminal vesicles, the prostate gland, and the bulbourethral gland, all of which are illustrated in Figure 43.8 . The seminal vesicles are a pair of glands that lie along the posterior border of the urinary bladder. The glands make a solution that is thick, yellowish, and alkaline. As sperm are only motile in an alkaline environment, a basic pH is important to reverse the acidity of the vaginal environment. The solution also contains mucus, fructose (a sperm mitochondrial nutrient), a coagulating enzyme, ascorbic acid, and local-acting hormones called prostaglandins. The seminal vesicle glands account for 60 percent of the bulk of semen. \n\n The penis , illustrated in Figure 43.8 , is an organ that drains urine from the renal bladder and functions as a copulatory organ during intercourse. The penis contains three tubes of erectile tissue running through the length of the organ. These consist of a pair of tubes on the dorsal side, called the corpus cavernosum, and a single tube of tissue on the ventral side, called the corpus spongiosum. This tissue will become engorged with blood, becoming erect and hard, in preparation for intercourse. The organ is inserted into the vagina culminating with an ejaculation. During intercourse, the smooth muscle sphincters at the opening to the renal bladder close and prevent urine from entering the penis. An orgasm is a two-stage process: first, glands and accessory organs connected to the testes contract, then semen (containing sperm) is expelled through the urethra during ejaculation. After intercourse, the blood drains from the erectile tissue and the penis becomes flaccid. \n\n The walnut-shaped prostate gland surrounds the urethra, the connection to the urinary bladder. It has a series of short ducts that directly connect to the urethra. The gland is a mixture of smooth muscle and glandular tissue. The muscle provides much of the force needed for ejaculation to occur. The glandular tissue makes a thin, milky fluid that contains citrate (a nutrient), enzymes, and prostate specific antigen (PSA). PSA is a proteolytic enzyme that helps to liquefy the ejaculate several minutes after release from the male. Prostate gland secretions account for about 30 percent of the bulk of semen. \n\n The bulbourethral gland , or Cowper’s gland, releases its secretion prior to the release of the bulk of the semen. It neutralizes any acid residue in the urethra left over from urine. This usually accounts for a couple of drops of fluid in the total ejaculate and may contain a few sperm. Withdrawal of the penis from the vagina before ejaculation to prevent pregnancy may not work if sperm are present in the bulbourethral gland secretions. The location and functions of the male reproductive organs are summarized in Table 43.1 . \n\n Male Reproductive Anatomy \n\n Organ \n\n Location \n\n Function \n\n Scrotum \n\n External \n\n Carry and support testes \n\n Penis \n\n External \n\n Deliver urine, copulating organ \n\n Testes \n\n Internal \n\n Produce sperm and male hormones \n\n Seminal Vesicles \n\n Internal \n\n Contribute to semen production \n\n Prostate Gland \n\n Internal \n\n Contribute to semen production \n\n Bulbourethral Glands \n\n Internal \n\n Clean urethra at ejaculation \n\n Table 43.1 \n\n Female Reproductive Anatomy \n\n A number of reproductive structures are exterior to the female’s body. These include the breasts and the vulva, which consists of the mons pubis, clitoris, labia majora, labia minora, and the vestibular glands, all illustrated in Figure 43.10 . The location and functions of the female reproductive organs are summarized in Table 43.2 . The vulva is an area associated with the vestibule which includes the structures found in the inguinal (groin) area of women. The mons pubis is a round, fatty area that overlies the pubic symphysis. The clitoris is a structure with erectile tissue that contains a large number of sensory nerves and serves as a source of stimulation during intercourse. The labia majora are a pair of elongated folds of tissue that run posterior from the mons pubis and enclose the other components of the vulva. The labia majora derive from the same tissue that produces the scrotum in a male. The labia minora are thin folds of tissue centrally located within the labia majora. These labia protect the openings to the vagina and urethra. The mons pubis and the anterior portion of the labia majora become covered with hair during adolescence; the labia minora is hairless. The greater vestibular glands are found at the sides of the vaginal opening and provide lubrication during intercourse. \n\n Female Reproductive Anatomy \n\n Organ \n\n Location \n\n Function \n\n Clitoris \n\n External \n\n Sensory organ \n\n Mons pubis \n\n External \n\n Fatty area overlying pubic bone \n\n Labia majora \n\n External \n\n Covers labia minora \n\n Labia minora \n\n External \n\n Covers vestibule \n\n Greater vestibular glands \n\n External \n\n Secrete mucus; lubricate vagina \n\n Breast \n\n External \n\n Produce and deliver milk \n\n Ovaries \n\n Internal \n\n Carry and develop eggs \n\n Oviducts (Fallopian tubes) \n\n Internal \n\n Transport egg to uterus \n\n Uterus \n\n Internal \n\n Support developing embryo \n\n Vagina \n\n Internal \n\n Common tube for intercourse, birth canal, passing menstrual flow \n\n Table 43.2 \n\n The breasts consist of mammary glands and fat. The size of the breast is determined by the amount of fat deposited behind the gland. Each gland consists of 15 to 25 lobes that have ducts that empty at the nipple and that supply the nursing child with nutrient- and antibody-rich milk to aid development and protect the child. \n\n Internal female reproductive structures include ovaries, oviducts, the uterus , and the vagina, shown in Figure 43.10 . The pair of ovaries is held in place in the abdominal cavity by a system of ligaments. Ovaries consist of a medulla and cortex: the medulla contains nerves and blood vessels to supply the cortex with nutrients and remove waste. The outer layers of cells of the cortex are the functional parts of the ovaries. The cortex is made up of follicular cells that surround eggs that develop during fetal development in utero . During the menstrual period, a batch of follicular cells develops and prepares the eggs for release. At ovulation, one follicle ruptures and one egg is released, as illustrated in Figure 43.11 a . \n\n The oviducts , or fallopian tubes, extend from the uterus in the lower abdominal cavity to the ovaries, but they are not in contact with the ovaries. The lateral ends of the oviducts flare out into a trumpet-like structure and have a fringe of finger-like projections called fimbriae, illustrated in Figure 43.10 b . When an egg is released at ovulation, the fimbrae help the non-motile egg enter into the tube and passage to the uterus. The walls of the oviducts are ciliated and are made up mostly of smooth muscle. The cilia beat toward the middle, and the smooth muscle contracts in the same direction, moving the egg toward the uterus. Fertilization usually takes place within the oviducts and the developing embryo is moved toward the uterus for development. It usually takes the egg or embryo a week to travel through the oviduct. Sterilization in women is called a tubal ligation; it is analogous to a vasectomy in males in that the oviducts are severed and sealed. \n\n The uterus is a structure about the size of a woman’s fist. This is lined with an endometrium rich in blood vessels and mucus glands. The uterus supports the developing embryo and fetus during gestation. The thickest portion of the wall of the uterus is made of smooth muscle. Contractions of the smooth muscle in the uterus aid in passing the baby through the vagina during labor. A portion of the lining of the uterus sloughs off during each menstrual period, and then builds up again in preparation for an implantation. Part of the uterus, called the cervix, protrudes into the top of the vagina. The cervix functions as the birth canal. \n\n The vagina is a muscular tube that serves several purposes. It allows menstrual flow to leave the body. It is the receptacle for the penis during intercourse and the vessel for the delivery of offspring. It is lined by stratified squamous epithelial cells to protect the underlying tissue. \n\n Sexual Response during Intercourse \n\n The sexual response in humans is both psychological and physiological. Both sexes experience sexual arousal through psychological and physical stimulation. There are four phases of the sexual response. During phase one, called excitement, vasodilation leads to vasocongestion in erectile tissues in both men and women. The nipples, clitoris, labia, and penis engorge with blood and become enlarged. Vaginal secretions are released to lubricate the vagina to facilitate intercourse. During the second phase, called the plateau, stimulation continues, the outer third of the vaginal wall enlarges with blood, and breathing and heart rate increase. \n\n During phase three, or orgasm, rhythmic, involuntary contractions of muscles occur in both sexes. In the male, the reproductive accessory glands and tubules constrict placing semen in the urethra, then the urethra contracts expelling the semen through the penis. In women, the uterus and vaginal muscles contract in waves that may last slightly less than a second each. During phase four, or resolution, the processes described in the first three phases reverse themselves and return to their normal state. Men experience a refractory period in which they cannot maintain an erection or ejaculate for a period of time ranging from minutes to hours. \n\n Gametogenesis (Spermatogenesis and Oogenesis) \n\n Gametogenesis, the production of sperm and eggs, takes place through the process of meiosis. During meiosis, two cell divisions separate the paired chromosomes in the nucleus and then separate the chromatids that were made during an earlier stage of the cell’s life cycle. Meiosis produces haploid cells with half of each pair of chromosomes normally found in diploid cells. The production of sperm is called spermatogenesis and the production of eggs is called oogenesis . \n\n Spermatogenesis \n\n Spermatogenesis, illustrated in Figure 43.12 , occurs in the wall of the seminiferous tubules ( Figure 43.8 ), with stem cells at the periphery of the tube and the spermatozoa at the lumen of the tube. Immediately under the capsule of the tubule are diploid, undifferentiated cells. These stem cells, called spermatogonia (singular: spermatagonium), go through mitosis with one offspring going on to differentiate into a sperm cell and the other giving rise to the next generation of sperm. Meiosis starts with a cell called a primary spermatocyte. At the end of the first meiotic division, a haploid cell is produced called a secondary spermatocyte. This cell is haploid and must go through another meiotic cell division. The cell produced at the end of meiosis is called a spermatid and when it reaches the lumen of the tubule and grows a flagellum, it is called a sperm cell. Four sperm result from each primary spermatocyte that goes through meiosis. \n\n Stem cells are deposited during gestation and are present at birth through the beginning of adolescence, but in an inactive state. During adolescence, gonadotropic hormones from the anterior pituitary cause the activation of these cells and the production of viable sperm. This continues into old age. \n\n Link to Learning \n\n Visit this site to see the process of spermatogenesis. \n\n Oogenesis \n\n Oogenesis, illustrated in Figure 43.13 , occurs in the outermost layers of the ovaries. As with sperm production, oogenesis starts with a germ cell, called an oogonium (plural: oogonia), but this cell undergoes mitosis to increase in number, eventually resulting in up to about one to two million cells in the embryo. \n\n The cell starting meiosis is called a primary oocyte, as shown in Figure 43.13 . This cell will start the first meiotic division and be arrested in its progress in the first prophase stage. At the time of birth, all future eggs are in the prophase stage. At adolescence, anterior pituitary hormones cause the development of a number of follicles in an ovary. This results in the primary oocyte finishing the first meiotic division. The cell divides unequally, with most of the cellular material and organelles going to one cell, called a secondary oocyte, and only one set of chromosomes and a small amount of cytoplasm going to the other cell. This second cell is called a polar body and usually dies. A secondary meiotic arrest occurs, this time at the metaphase II stage. At ovulation, this secondary oocyte will be released and travel toward the uterus through the oviduct. If the secondary oocyte is fertilized, the cell continues through the meiosis II, producing a second polar body and a fertilized egg containing all 46 chromosomes of a human being, half of them coming from the sperm. \n\n Egg production begins before birth, is arrested during meiosis until puberty, and then individual cells continue through at each menstrual cycle. One egg is produced from each meiotic process, with the extra chromosomes and chromatids going into polar bodies that degenerate and are reabsorbed by the body. \n43.4 Hormonal Control of Human Reproduction Learning Objectives By the end of this chapter, you will be able to:\n\n Describe the roles of male and female reproductive hormones \n\n Discuss the interplay of the ovarian and menstrual cycles \n\n Describe the process of menopause \n\n The human male and female reproductive cycles are controlled by the interaction of hormones from the hypothalamus and anterior pituitary with hormones from reproductive tissues and organs. In both sexes, the hypothalamus monitors and causes the release of hormones from the pituitary gland. When the reproductive hormone is required, the hypothalamus sends a gonadotropin-releasing hormone (GnRH) to the anterior pituitary. This causes the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary into the blood. Note that the body must reach puberty in order for the adrenals to release the hormones that must be present for GnRH to be produced. Although FSH and LH are named after their functions in female reproduction, they are produced in both sexes and play important roles in controlling reproduction. Other hormones have specific functions in the male and female reproductive systems. \n\n Male Hormones \n\n At the onset of puberty, the hypothalamus causes the release of FSH and LH into the male system for the first time. FSH enters the testes and stimulates the Sertoli cells to begin facilitating spermatogenesis using negative feedback, as illustrated in Figure 43.14 . LH also enters the testes and stimulates the interstitial cells of Leydig to make and release testosterone into the testes and the blood. \n\n Testosterone , the hormone responsible for the secondary sexual characteristics that develop in the male during adolescence, stimulates spermatogenesis. These secondary sex characteristics include a deepening of the voice, the growth of facial, axillary, and pubic hair, and the beginnings of the sex drive. \n\n A negative feedback system occurs in the male with rising levels of testosterone acting on the hypothalamus and anterior pituitary to inhibit the release of GnRH, FSH, and LH. The Sertoli cells produce the hormone inhibin , which is released into the blood when the sperm count is too high. This inhibits the release of GnRH and FSH, which will cause spermatogenesis to slow down. If the sperm count reaches 20 million/ml, the Sertoli cells cease the release of inhibin, and the sperm count increases. \n\n Female Hormones \n\n The control of reproduction in females is more complex. As with the male, the anterior pituitary hormones cause the release of the hormones FSH and LH. In addition, estrogens and progesterone are released from the developing follicles. Estrogen is the reproductive hormone in females that assists in endometrial regrowth, ovulation, and calcium absorption; it is also responsible for the secondary sexual characteristics of females. These include breast development, flaring of the hips, and a shorter period necessary for bone maturation. Progesterone assists in endometrial re-growth and inhibition of FSH and LH release. \n\n In females, FSH stimulates development of egg cells, called ova, which develop in structures called follicles. Follicle cells produce the hormone inhibin, which inhibits FSH production. LH also plays a role in the development of ova, induction of ovulation, and stimulation of estradiol and progesterone production by the ovaries. Estradiol and progesterone are steroid hormones that prepare the body for pregnancy. Estradiol produces secondary sex characteristics in females, while both estradiol and progesterone regulate the menstrual cycle. \n\n The Ovarian Cycle and the Menstrual Cycle \n\n The ovarian cycle governs the preparation of endocrine tissues and release of eggs, while the menstrual cycle governs the preparation and maintenance of the uterine lining. These cycles occur concurrently and are coordinated over a 22–32 day cycle, with an average length of 28 days. \n\n The first half of the ovarian cycle is the follicular phase shown in Figure 43.15 . Slowly rising levels of FSH and LH cause the growth of follicles on the surface of the ovary. This process prepares the egg for ovulation. As the follicles grow, they begin releasing estrogens and a low level of progesterone. Progesterone maintains the endometrium to help ensure pregnancy. The trip through the fallopian tube takes about seven days. At this stage of development, called the morula, there are 30-60 cells. If pregnancy implantation does not occur, the lining is sloughed off. After about five days, estrogen levels rise and the menstrual cycle enters the proliferative phase. The endometrium begins to regrow, replacing the blood vessels and glands that deteriorated during the end of the last cycle. \n\n Visual Connection \n\n Which of the following statements about hormone regulation of the female reproductive cycle is false? \n\n LH and FSH are produced in the pituitary, and estradiol and progesterone are produced in the ovaries. \n\n Estradiol and progesterone secreted from the corpus luteum cause the endometrium to thicken. \n\n Both progesterone and estradiol are produced by the follicles. \n\n Secretion of GnRH by the hypothalamus is inhibited by low levels of estradiol but stimulated by high levels of estradiol. \n\n Just prior to the middle of the cycle (approximately day 14), the high level of estrogen causes FSH and especially LH to rise rapidly, then fall. The spike in LH causes ovulation : the most mature follicle, like that shown in Figure 43.16 , ruptures and releases its egg. The follicles that did not rupture degenerate and their eggs are lost. The level of estrogen decreases when the extra follicles degenerate. \n\n Following ovulation, the ovarian cycle enters its luteal phase, illustrated in Figure 43.15 and the menstrual cycle enters its secretory phase, both of which run from about day 15 to 28. The luteal and secretory phases refer to changes in the ruptured follicle. The cells in the follicle undergo physical changes and produce a structure called a corpus luteum. The corpus luteum produces estrogen and progesterone. The progesterone facilitates the regrowth of the uterine lining and inhibits the release of further FSH and LH. The uterus is being prepared to accept a fertilized egg, should it occur during this cycle. The inhibition of FSH and LH prevents any further eggs and follicles from developing, while the progesterone is elevated. The level of estrogen produced by the corpus luteum increases to a steady level for the next few days. \n\n If no fertilized egg is implanted into the uterus, the corpus luteum degenerates and the levels of estrogen and progesterone decrease. The endometrium begins to degenerate as the progesterone levels drop, initiating the next menstrual cycle. The decrease in progesterone also allows the hypothalamus to send GnRH to the anterior pituitary, releasing FSH and LH and starting the cycles again. Figure 43.17 visually compares the ovarian and uterine cycles as well as the commensurate hormone levels. \n\n Visual Connection \n\n Which of the following statements about the menstrual cycle is false? \n\n Progesterone levels rise during the luteal phase of the ovarian cycle and the secretory phase of the uterine cycle. \n\n Menstruation occurs just after LH and FSH levels peak. \n\n Menstruation occurs after progesterone levels drop. \n\n Estrogen levels rise before ovulation, while progesterone levels rise after. \n\n Menopause \n\n As women approach their mid-40s to mid-50s, their ovaries begin to lose their sensitivity to FSH and LH. Menstrual periods become less frequent and finally cease; this is menopause . There are still eggs and potential follicles on the ovaries, but without the stimulation of FSH and LH, they will not produce a viable egg to be released. The outcome of this is the inability to have children. \n\n The side effects of menopause include hot flashes, heavy sweating (especially at night), headaches, some hair loss, muscle pain, vaginal dryness, insomnia, depression, weight gain, and mood swings. Estrogen is involved in calcium metabolism and, without it, blood levels of calcium decrease. To replenish the blood, calcium is lost from bone which may decrease the bone density and lead to osteoporosis. Supplementation of estrogen in the form of hormone replacement therapy (HRT) can prevent bone loss, but the therapy can have negative side effects. While HRT is thought to give some protection from colon cancer, osteoporosis, heart disease, macular degeneration, and possibly depression, its negative side effects include increased risk of: stroke or heart attack, blood clots, breast cancer, ovarian cancer, endometrial cancer, gall bladder disease, and possibly dementia. \n\n Career Connection Reproductive Endocrinologist \n\nA reproductive endocrinologist is a physician who treats a variety of hormonal disorders related to reproduction and infertility in both men and women. The disorders include menstrual problems, infertility, pregnancy loss, sexual dysfunction, and menopause. Doctors may use fertility drugs, surgery, or assisted reproductive techniques (ART) in their therapy. ART involves the use of procedures to manipulate the egg or sperm to facilitate reproduction, such as in vitro fertilization. \n\n Reproductive endocrinologists undergo extensive medical training, first in a four-year residency in obstetrics and gynecology, then in a three-year fellowship in reproductive endocrinology. To be board certified in this area, the physician must pass written and oral exams in both areas. \n43.5 Human Pregnancy and Birth Learning Objectives By the end of this section, you will be able to:\n\n Explain fetal development during the three trimesters of gestation \n\n Describe labor and delivery \n\n Compare the efficacy and duration of various types of contraception \n\n Discuss causes of infertility and the therapeutic options available \n\n Pregnancy begins with the fertilization of an egg and continues through to the birth of the individual. The length of time of gestation varies among animals, but is very similar among the great apes: human gestation is 266 days, while chimpanzee gestation is 237 days, a gorilla’s is 257 days, and orangutan gestation is 260 days long. The fox has a 57-day gestation. Dogs and cats have similar gestations averaging 60 days. The longest gestation for a land mammal is an African elephant at 640 days. The longest gestations among marine mammals are the beluga and sperm whales at 460 days. \n\n Human Gestation \n\n Twenty-four hours before fertilization, the egg has finished meiosis and becomes a mature oocyte. When fertilized (at conception) the egg becomes known as a zygote. The zygote travels through the oviduct to the uterus ( Figure 43.18 ). The developing embryo must implant into the wall of the uterus within seven days, or it will deteriorate and die. The outer layers of the zygote (blastocyst) grow into the endometrium by digesting the endometrial cells, and wound healing of the endometrium closes up the blastocyst into the tissue. Another layer of the blastocyst, the chorion, begins releasing a hormone called human beta chorionic gonadotropin ( β -HCG) which makes its way to the corpus luteum and keeps that structure active. This ensures adequate levels of progesterone that will maintain the endometrium of the uterus for the support of the developing embryo. Pregnancy tests determine the level of β -HCG in urine or serum. If the hormone is present, the test is positive. \n\n The gestation period is divided into three equal periods or trimesters. During the first two to four weeks of the first trimester, nutrition and waste are handled by the endometrial lining through diffusion. As the trimester progresses, the outer layer of the embryo begins to merge with the endometrium, and the placenta forms. This organ takes over the nutrient and waste requirements of the embryo and fetus, with the mother’s blood passing nutrients to the placenta and removing waste from it. Chemicals from the fetus, such as bilirubin, are processed by the mother’s liver for elimination. Some of the mother’s immunoglobulins will pass through the placenta, providing passive immunity against some potential infections. \n\n Internal organs and body structures begin to develop during the first trimester. By five weeks, limb buds, eyes, the heart, and liver have been basically formed. By eight weeks, the term fetus applies, and the body is essentially formed, as shown in Figure 43.19 . The individual is about five centimeters (two inches) in length and many of the organs, such as the lungs and liver, are not yet functioning. Exposure to any toxins is especially dangerous during the first trimester, as all of the body’s organs and structures are going through initial development. Anything that affects that development can have a severe effect on the fetus’ survival. \n\n During the second trimester, the fetus grows to about 30 cm (12 inches), as shown in Figure 43.20 . It becomes active and the mother usually feels the first movements. All organs and structures continue to develop. The placenta has taken over the functions of nutrition and waste and the production of estrogen and progesterone from the corpus luteum, which has degenerated. The placenta will continue functioning up through the delivery of the baby. \n\n During the third trimester, the fetus grows to 3 to 4 kg (6 ½ -8 ½ lbs.) and about 50 cm (19-20 inches) long, as illustrated in Figure 43.21 . This is the period of the most rapid growth during the pregnancy. Organ development continues to birth (and some systems, such as the nervous system and liver, continue to develop after birth). The mother will be at her most uncomfortable during this trimester. She may urinate frequently due to pressure on the bladder from the fetus. There may also be intestinal blockage and circulatory problems, especially in her legs. Clots may form in her legs due to pressure from the fetus on returning veins as they enter the abdominal cavity. \n\n Link to Learning \n\n Visit this site to see the stages of human fetal development. \n\n Labor and Birth \n\n Labor is the physical efforts of expulsion of the fetus and the placenta from the uterus during birth (parturition). Toward the end of the third trimester, estrogen causes receptors on the uterine wall to develop and bind the hormone oxytocin. At this time, the baby reorients, facing forward and down with the back or crown of the head engaging the cervix (uterine opening). This causes the cervix to stretch and nerve impulses are sent to the hypothalamus, which signals for the release of oxytocin from the posterior pituitary. The oxytocin causes the smooth muscle in the uterine wall to contract. At the same time, the placenta releases prostaglandins into the uterus, increasing the contractions. A positive feedback relay occurs between the uterus, hypothalamus, and the posterior pituitary to assure an adequate supply of oxytocin. As more smooth muscle cells are recruited, the contractions increase in intensity and force. \n\n There are three stages to labor. During stage one, the cervix thins and dilates. This is necessary for the baby and placenta to be expelled during birth. The cervix will eventually dilate to about 10 cm. During stage two, the baby is expelled from the uterus. The uterus contracts and the mother pushes as she compresses her abdominal muscles to aid the delivery. The last stage is the passage of the placenta after the baby has been born and the organ has completely disengaged from the uterine wall. If labor should stop before stage two is reached, synthetic oxytocin, known as Pitocin, can be administered to restart and maintain labor. \n\n An alternative to labor and delivery is the surgical delivery of the baby through a procedure called a Caesarian section. This is major abdominal surgery and can lead to post-surgical complications for the mother, but in some cases it may be the only way to safely deliver the baby. \n\n The mother’s mammary glands go through changes during the third trimester to prepare for lactation and breastfeeding. When the baby begins suckling at the breast, signals are sent to the hypothalamus causing the release of prolactin from the anterior pituitary. Prolactin causes the mammary glands to produce milk. Oxytocin is also released, promoting the release of the milk. The milk contains nutrients for the baby’s development and growth as well as immunoglobulins to protect the child from bacterial and viral infections. \n\n Contraception and Birth Control \n\n The prevention of a pregnancy comes under the terms contraception or birth control. Strictly speaking, contraception refers to preventing the sperm and egg from joining. Both terms are, however, frequently used interchangeably. \n\n Contraceptive Methods \n\n Method \n\n Examples \n\n Failure Rate in Typical Use Over 12 Months \n\n Barrier \n\n male condom, female condom, sponge, cervical cap, diaphragm, spermicides \n\n 15 to 24% \n\n Hormonal \n\n oral, patch, vaginal ring \n\n 8% \n\n injection \n\n 3% \n\n implant \n\n less than 1% \n\n Other \n\n natural family planning \n\n 12 to 25% \n\n withdrawal \n\n 27% \n\n sterilization \n\n less than 1% \n\n Table 43.3 \n\n Table 43.3 lists common methods of contraception. The failure rates listed are not the ideal rates that could be realized, but the typical rates that occur. A failure rate is the number of pregnancies resulting from the method’s use over a twelve-month period. Barrier methods, such as condoms, cervical caps, and diaphragms, block sperm from entering the uterus, preventing fertilization. Spermicides are chemicals that are placed in the vagina that kill sperm. Sponges, which are saturated with spermicides, are placed in the vagina at the cervical opening. Combinations of spermicidal chemicals and barrier methods achieve lower failure rates than do the methods when used separately. \n\n Nearly a quarter of the couples using barrier methods, natural family planning, or withdrawal can expect a failure of the method. Natural family planning is based on the monitoring of the menstrual cycle and having intercourse only during times when the egg is not available. A woman’s body temperature may rise a degree Celsius at ovulation and the cervical mucus may increase in volume and become more pliable. These changes give a general indication of when intercourse is more or less likely to result in fertilization. Withdrawal involves the removal of the penis from the vagina during intercourse, before ejaculation occurs. This is a risky method with a high failure rate due to the possible presence of sperm in the bulbourethral gland’s secretion, which may enter the vagina prior to removing the penis. \n\n Hormonal methods use synthetic progesterone (sometimes in combination with estrogen), to inhibit the hypothalamus from releasing FSH or LH, and thus prevent an egg from being available for fertilization. The method of administering the hormone affects failure rate. The most reliable method, with a failure rate of less than 1 percent, is the implantation of the hormone under the skin. The same rate can be achieved through the sterilization procedures of vasectomy in the man or of tubal ligation in the woman, or by using an intrauterine device (IUD). IUDs are inserted into the uterus and establish an inflammatory condition that prevents fertilized eggs from implanting into the uterine wall. \n\n Compliance with the contraceptive method is a strong contributor to the success or failure rate of any particular method. The only method that is completely effective at preventing conception is abstinence. The choice of contraceptive method depends on the goals of the woman or couple. Tubal ligation and vasectomy are considered permanent prevention, while other methods are reversible and provide short-term contraception. \n\n Termination of an existing pregnancy can be spontaneous or voluntary. Spontaneous termination is a miscarriage and usually occurs very early in the pregnancy, usually within the first few weeks. This occurs when the fetus cannot develop properly and the gestation is naturally terminated. Voluntary termination of a pregnancy is an abortion. Laws regulating abortion vary between states and tend to view fetal viability as the criteria for allowing or preventing the procedure. \n\n Infertility \n\n Infertility is the inability to conceive a child or carry a child to birth. About 75 percent of causes of infertility can be identified; these include diseases, such as sexually transmitted diseases that can cause scarring of the reproductive tubes in either men or women, or developmental problems frequently related to abnormal hormone levels in one of the individuals. Inadequate nutrition, especially starvation, can delay menstruation. Stress can also lead to infertility. Short-term stress can affect hormone levels, while long-term stress can delay puberty and cause less frequent menstrual cycles. Other factors that affect fertility include toxins (such as cadmium), tobacco smoking, marijuana use, gonadal injuries, and aging. \n\n If infertility is identified, several assisted reproductive technologies (ART) are available to aid conception. A common type of ART is in vitro fertilization (IVF) where an egg and sperm are combined outside the body and then placed in the uterus. Eggs are obtained from the woman after extensive hormonal treatments that prepare mature eggs for fertilization and prepare the uterus for implantation of the fertilized egg. Sperm are obtained from the man and they are combined with the eggs and supported through several cell divisions to ensure viability of the zygotes. When the embryos have reached the eight-cell stage, one or more is implanted into the woman’s uterus. If fertilization is not accomplished by simple IVF, a procedure that injects the sperm into an egg can be used. This is called intracytoplasmic sperm injection (ICSI) and is shown in Figure 43.22 . IVF procedures produce a surplus of fertilized eggs and embryos that can be frozen and stored for future use. The procedures can also result in multiple births. \n43.6 Fertilization and Early Embryonic Development Learning Objectives By the end of this section, you will be able to:\n\n Discuss how fertilization occurs \n\n Explain how the embryo forms from the zygote \n\n Discuss the role of cleavage and gastrulation in animal development \n\n The process in which an organism develops from a single-celled zygote to a multi-cellular organism is complex and well-regulated. The early stages of embryonic development are also crucial for ensuring the fitness of the organism. \n\n Fertilization \n\n Fertilization, pictured in Figure 43.23 a is the process in which gametes (an egg and sperm) fuse to form a zygote. The egg and sperm each contain one set of chromosomes. To ensure that the offspring has only one complete diploid set of chromosomes, only one sperm must fuse with one egg. In mammals, the egg is protected by a layer of extracellular matrix consisting mainly of glycoproteins called the zona pellucida . When a sperm binds to the zona pellucida, a series of biochemical events, called the acrosomal reactions , take place. In placental mammals, the acrosome contains digestive enzymes that initiate the degradation of the glycoprotein matrix protecting the egg and allowing the sperm plasma membrane to fuse with the egg plasma membrane, as illustrated in Figure 43.23 b . The fusion of these two membranes creates an opening through which the sperm nucleus is transferred into the ovum. The nuclear membranes of the egg and sperm break down and the two haploid genomes condense to form a diploid genome. To ensure that no more than one sperm fertilizes the egg, once the acrosomal reactions take place at one location of the egg membrane, the egg releases proteins in other locations to prevent other sperm from fusing with the egg. If this mechanism fails, multiple sperm can fuse with the egg, resulting in polyspermy . The resulting embryo is not genetically viable and dies within a few days. \n\n Cleavage and Blastula Stage \n\n The development of multi-cellular organisms begins from a single-celled zygote, which undergoes rapid cell division to form the blastula. The rapid, multiple rounds of cell division are termed cleavage. Cleavage is illustrated in ( Figure 43.24 a ). After the cleavage has produced over 100 cells, the embryo is called a blastula. The blastula is usually a spherical layer of cells (the blastoderm) surrounding a fluid-filled or yolk-filled cavity (the blastocoel). Mammals at this stage form a structure called the blastocyst, characterized by an inner cell mass that is distinct from the surrounding blastula, shown in Figure 43.24 b . During cleavage, the cells divide without an increase in mass; that is, one large single-celled zygote divides into multiple smaller cells. Each cell within the blastula is called a blastomere. Cleavage can take place in two ways: holoblastic (total) cleavage or meroblastic (partial) cleavage. The type of cleavage depends on the amount of yolk in the eggs. In placental mammals (including humans) where nourishment is provided by the mother’s body, the eggs have a very small amount of yolk and undergo holoblastic cleavage. Other species, such as birds, with a lot of yolk in the egg to nourish the embryo during development, undergo meroblastic cleavage. \n\n In mammals, the blastula forms the blastocyst in the next stage of development. Here the cells in the blastula arrange themselves in two layers: the inner cell mass , and an outer layer called the trophoblast . The inner cell mass is also known as the embryoblast and this mass of cells will go on to form the embryo. At this stage of development, illustrated in Figure 43.25 the inner cell mass consists of embryonic stem cells that will differentiate into the different cell types needed by the organism. The trophoblast will contribute to the placenta and nourish the embryo. \n\n Link to Learning \n\n Visit the Virtual Human Embryo project at the Endowment for Human Development site to step through an interactive that shows the stages of embryo development, including micrographs and rotating 3-D images. \n\n Gastrulation \n\n The typical blastula is a ball of cells. The next stage in embryonic development is the formation of the body plan. The cells in the blastula rearrange themselves spatially to form three layers of cells. This process is called gastrulation . During gastrulation, the blastula folds upon itself to form the three layers of cells. Each of these layers is called a germ layer and each germ layer differentiates into different organ systems. \n\n The three germs layers, shown in Figure 43.26 , are the endoderm, the ectoderm, and the mesoderm. The ectoderm gives rise to the nervous system and the epidermis. The mesoderm gives rise to the muscle cells and connective tissue in the body. The endoderm gives rise to columnar cells found in the digestive system and many internal organs. \n\n Everyday Connection Are Designer Babies in Our Future? \n\n If you could prevent your child from getting a devastating genetic disease, would you do it? Would you select the sex of your child or select for their attractiveness, strength, or intelligence? How far would you go to maximize the possibility of resistance to disease? The genetic engineering of a human child, the production of \"designer babies\" with desirable phenotypic characteristics, was once a topic restricted to science fiction. This is the case no longer: science fiction is now overlapping into science fact. Many phenotypic choices for offspring are already available, with many more likely to be possible in the not too distant future. Which traits should be selected and how they should be selected are topics of much debate within the worldwide medical community. The ethical and moral line is not always clear or agreed upon, and some fear that modern reproductive technologies could lead to a new form of eugenics. \n\n Eugenics is the use of information and technology from a variety of sources to improve the genetic makeup of the human race. The goal of creating genetically superior humans was quite prevalent (although controversial) in several countries during the early 20 th century, but fell into disrepute when Nazi Germany developed an extensive eugenics program in the 1930's and 40's. As part of their program, the Nazis forcibly sterilized hundreds of thousands of the so-called \"unfit\" and killed tens of thousands of institutionally disabled people as part of a systematic program to develop a genetically superior race of Germans known as Aryans. Ever since, eugenic ideas have not been as publicly expressed, but there are still those who promote them. \n\n Efforts have been made in the past to control traits in human children using donated sperm from men with desired traits. In fact, eugenicist Robert Klark Graham established a sperm bank in 1980 that included samples exclusively from donors with high IQs. The \"genius\" sperm bank failed to capture the public's imagination and the operation closed in 1999. \n\n In more recent times, the procedure known as prenatal genetic diagnosis (PGD) has been developed. PGD involves the screening of human embryos as part of the process of in vitro fertilization, during which embryos are conceived and grown outside the mother's body for some period of time before they are implanted. The term PGD usually refers to both the diagnosis, selection, and the implantation of the selected embryos. \n\n In the least controversial use of PGD, embryos are tested for the presence of alleles which cause genetic diseases such as sickle cell disease, muscular dystrophy, and hemophilia, in which a single disease-causing allele or pair of alleles has been identified. By excluding embryos containing these alleles from implantation into the mother, the disease is prevented, and the unused embryos are either donated to science or discarded. There are relatively few in the worldwide medical community that question the ethics of this type of procedure, which allows individuals scared to have children because of the alleles they carry to do so successfully. The major limitation to this procedure is its expense. Not usually covered by medical insurance and thus out of reach financially for most couples, only a very small percentage of all live births use such complicated methodologies. Yet, even in cases like these where the ethical issues may seem to be clear-cut, not everyone agrees with the morality of these types of procedures. For example, to those who take the position that human life begins at conception, the discarding of unused embryos, a necessary result of PGD, is unacceptable under any circumstances. \n\n A murkier ethical situation is found in the selection of a child's sex, which is easily performed by PGD. Currently, countries such as Great Britain have banned the selection of a child's sex for reasons other than preventing sex-linked diseases. Other countries allow the procedure for \"family balancing\", based on the desire of some parents to have at least one child of each sex. Still others, including the United States, have taken a scattershot approach to regulating these practices, essentially leaving it to the individual practicing physician to decide which practices are acceptable and which are not. \n\n Even murkier are rare instances of disabled parents, such as those with deafness or dwarfism, who select embryos via PGD to ensure that they share their disability. These parents usually cite many positive aspects of their disabilities and associated culture as reasons for their choice, which they see as their moral right. To others, to purposely cause a disability in a child violates the basic medical principle of Primum non nocere, \"first, do no harm.\" This procedure, although not illegal in most countries, demonstrates the complexity of ethical issues associated with choosing genetic traits in offspring. \n\n Where could this process lead? Will this technology become more affordable and how should it be used? With the ability of technology to progress rapidly and unpredictably, a lack of definitive guidelines for the use of reproductive technologies before they arise might make it difficult for legislators to keep pace once they are in fact realized, assuming the process needs any government regulation at all. Other bioethicists argue that we should only deal with technologies that exist now, and not in some uncertain future. They argue that these types of procedures will always be expensive and rare, so the fears of eugenics and \"master\" races are unfounded and overstated. The debate continues. \n43.7 Organogenesis and Vertebrate Formation Learning Objectives By the end of this section, you will be able to:\n\n Describe the process of organogenesis \n\n Identify the anatomical axes formed in vertebrates \n\n Gastrulation leads to the formation of the three germ layers that give rise, during further development, to the different organs in the animal body. This process is called organogenesis . Organogenesis is characterized by rapid and precise movements of the cells within the embryo. \n\n Organogenesis \n\n Organs form from the germ layers through the process of differentiation. During differentiation, the embryonic stem cells express specific sets of genes which will determine their ultimate cell type. For example, some cells in the ectoderm will express the genes specific to skin cells. As a result, these cells will differentiate into epidermal cells. The process of differentiation is regulated by cellular signaling cascades. \n\n Scientists study organogenesis extensively in the lab in fruit flies ( Drosophila ) and the nematode Caenorhabditis elegans . Drosophila have segments along their bodies, and the patterning associated with the segment formation has allowed scientists to study which genes play important roles in organogenesis along the length of the embryo at different time points. The nematode C.elegans has roughly 1000 somatic cells and scientists have studied the fate of each of these cells during their development in the nematode life cycle. There is little variation in patterns of cell lineage between individuals, unlike in mammals where cell development from the embryo is dependent on cellular cues. \n\n In vertebrates, one of the primary steps during organogenesis is the formation of the neural system. The ectoderm forms epithelial cells and tissues, and neuronal tissues. During the formation of the neural system, special signaling molecules called growth factors signal some cells at the edge of the ectoderm to become epidermis cells. The remaining cells in the center form the neural plate. If the signaling by growth factors were disrupted, then the entire ectoderm would differentiate into neural tissue. \n\n The neural plate undergoes a series of cell movements where it rolls up and forms a tube called the neural tube , as illustrated in Figure 43.28 . In further development, the neural tube will give rise to the brain and the spinal cord. \n\n The mesoderm that lies on either side of the vertebrate neural tube will develop into the various connective tissues of the animal body. A spatial pattern of gene expression reorganizes the mesoderm into groups of cells called somites with spaces between them. The somites, illustrated in Figure 43.29 will further develop into the ribs, lungs, and segmental (spine) muscle. The mesoderm also forms a structure called the notochord, which is rod-shaped and forms the central axis of the animal body. \n\n Vertebrate Axis Formation \n\n Even as the germ layers form, the ball of cells still retains its spherical shape. However, animal bodies have lateral-medial (left-right), dorsal-ventral (back-belly), and anterior-posterior (head-feet) axes, illustrated in Figure 43.30 . \n\n How are these established? In one of the most seminal experiments ever to be carried out in developmental biology, Spemann and Mangold took dorsal cells from one embryo and transplanted them into the belly region of another embryo. They found that the transplanted embryo now had two notochords: one at the dorsal site from the original cells and another at the transplanted site. This suggested that the dorsal cells were genetically programmed to form the notochord and define the axis. Since then, researchers have identified many genes that are responsible for axis formation. Mutations in these genes leads to the loss of symmetry required for organism development. \n\n Animal bodies have externally visible symmetry. However, the internal organs are not symmetric. For example, the heart is on the left side and the liver on the right. The formation of the central left-right axis is an important process during development. This internal asymmetry is established very early during development and involves many genes. Research is still ongoing to fully understand the developmental implications of these genes. "}}},{"rowIdx":180,"cells":{"bname":{"kind":"string","value":"introduction_to_sociology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":""},"intro":{"kind":"string","value":"Learning Objectives 11.1 Racial, Ethnic, and Minority Groups \n\n Understand the difference between race and ethnicity \n\n Define a majority group (dominant group) \n\n Define a minority group (subordinate group) \n\n 11.2 Stereotypes, Prejudice, and Discrimination \n\n Explain the difference between stereotypes, prejudice, discrimination, and racism \n\n Identify different types of discrimination \n\n 11.3 Theories of Race and Ethnicity \n\n Describe how major sociological perspectives view race and ethnicity \n\n Identify examples of culture of prejudice \n\n 11.4 Intergroup Relationships \n\n Explain different intergroup relations in terms of their relative levels of tolerance \n\n Give historical and/or contemporary examples of each type of intergroup relation \n\n 11.5 Race and Ethnicity in the United States \n\n Compare and contrast the different experiences of various ethnic groups in the United States \n\n Apply theories of intergroup relations and race and ethnicity to different subordinate groups \n\n Introduction to Race and Ethnicity \n\n In a mixed vocational/academic high school, Ms. Ellis grades papers for her large, diverse, 11 th grade English class. She is currently looking at the papers of three students: Jose, who is Dominican, Kim, who is Vietnamese, and Anthony, who is Italian American. Jose’s grasp of English is weak, and he doesn’t show a high degree of understanding of the themes of Hamlet . However, Ms. Ellis knows that Jose tried hard, and she also believes that, like many of his fellow Hispanic students, he will probably not go to college and continue any studies of English literature. His parents do not speak English and are not overly involved in his schooling. Jose excels in Automotive Shop, which prepares him for a job in that industry, so Ms. Ellis feels that to push him in English will not help him. She gives him a C+ and a few neutral words of encouragement without spending a lot of time pointing out where he could improve. \n\n Ms. Ellis wishes she could have more students like Kim. Kim is unfailingly polite, interested, and hardworking, even though her English still needs work. Her paper on Hamlet is far from perfect, but Ms. Ellis knows that she probably worked harder on it than anyone in the class. As is the case with most of Ms. Ellis’s Asian students, both of Kim’s parents are anxious for Kim to go to college, so even though Kim’s paper does not show much more understanding of Hamlet than Jose’s, Ms. Ellis gives her a B and writes ample comments for areas of improvement. \n\n Anthony is a thorn in Ms. Ellis’s side. In this school where most of the teachers and vocational instructors are Irish American or Italian American, Anthony has always felt at home and overconfident. His uncle is on the staff, and he has several siblings and cousins who have gone through the school. He is aggressive and disruptive in class, distracting other students and causing Ms. Ellis to spend an inordinate amount of time on maintaining discipline. Anthony’s paper is about the same level as Jose’s and Kim’s, but since English is his first language, he really should be able to perform better. Ms. Ellis gives him a C- and a few curt comments. \n\n Ms. Ellis graded three similar papers very differently. She didn’t grade them only on their merits; she relied heavily on her own knowledge of and feelings about the students themselves. Ms. Ellis was guided by her prejudices: her preconceived notions of the students’ work, attitudes, and abilities. To the extent that her prejudices affected her actions, Ms. Ellis also practiced discrimination. But what do these terms mean? Does everyone have prejudices? Is everyone guilty of discrimination? How does our society foster institutional prejudice and discrimination? "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":3,"ans_text":"any of the above"},"bloom":"1","hl_context":"<hl> The next 150 years saw the rise of American slavery , with black Africans being kidnapped from their own lands and shipped to the New World on the trans-Atlantic journey known as the Middle Passage . <hl> Once in the Americas , the black population grew until American-born blacks outnumbered those born in Africa . <hl> But colonial ( and later , American ) slave codes declared that the child of a slave was a slave , so the slave class was created . <hl> By 1869 , the slave trade was internal in the United States , with slaves being bought and sold across state lines like livestock . <hl> If Native Americans are the only minority group whose subordinate status occurred by conquest , African Americans are the exemplar minority group in the United States whose ancestors did not come here by choice . <hl> A Dutch sea captain brought the first Africans to the Virginia colony of Jamestown in 1619 and sold them as indentured servants . This was not an uncommon practice for either blacks or whites , and indentured servants were in high demand . For the next century , black and white indentured servants worked side by side . But the growing agricultural economy demanded greater and cheaper labor , and by 1705 , Virginia passed the slave codes declaring that any foreign-born non-Christian could be a slave , and that slaves were considered property . The social construction of race is also reflected in the way that names for racial categories change with changing times . It ’ s worth noting that race , in this sense , is also a system of labeling that provides a source of identity ; specific labels fall in and out of favor during different social eras . <hl> For example , the category ” negroid , ” popular in the 19th century , evolved into the term “ negro ” by the 1960s , and then this term fell from use and was replaced with “ African American . ” This latter term was intended to celebrate the multiple identities that a black person might hold , but the word choice is a poor one : it lumps together a large variety of ethnic groups under an umbrella term while excluding others who could accurately be described by the label but who do not meet the spirit of the term . <hl> For example , actress Charlize Theron is a blonde-haired , blue-eyed “ African American . ” She was born in South Africa and later became a U . S . citizen . Is her identity that of an “ African American ” as most of us understand the term ?","hl_sentences":"The next 150 years saw the rise of American slavery , with black Africans being kidnapped from their own lands and shipped to the New World on the trans-Atlantic journey known as the Middle Passage . But colonial ( and later , American ) slave codes declared that the child of a slave was a slave , so the slave class was created . If Native Americans are the only minority group whose subordinate status occurred by conquest , African Americans are the exemplar minority group in the United States whose ancestors did not come here by choice . For example , the category ” negroid , ” popular in the 19th century , evolved into the term “ negro ” by the 1960s , and then this term fell from use and was replaced with “ African American . ” This latter term was intended to celebrate the multiple identities that a black person might hold , but the word choice is a poor one : it lumps together a large variety of ethnic groups under an umbrella term while excluding others who could accurately be described by the label but who do not meet the spirit of the term .","question":{"cloze_format":"The racial term “African American” can refer to ___.","normal_format":"What can the racial term “African American” refer to?","question_choices":["a black person living in America","people whose ancestors came to America through the slave trade","a white person who originated in Africa and now lives in the United States","any of the above"],"question_id":"fs-id2103582","question_text":"The racial term “African American” can refer to:"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"Lack of power"},"bloom":"1","hl_context":"<hl> Note that being a numerical minority is not a characteristic of being a minority group ; sometimes larger groups can be considered minority groups due to their lack of power . <hl> It is the lack of power that is the predominant characteristic of a minority , or subordinate group . For example , consider Apartheid in South Africa , in which a numerical majority ( the black inhabitants of the country ) were exploited and oppressed by the white minority . Sociologist Louis Wirth ( 1945 ) defined a minority group as “ any group of people who , because of their physical or cultural characteristics , are singled out from the others in the society in which they live for differential and unequal treatment , and who therefore regard themselves as objects of collective discrimination . ” The term minority connotes discrimination , and in its sociological use , the term subordinate can be used interchangeably with the term minority , while the term dominant is often substituted for the group that ’ s in the majority . <hl> These definitions correlate to the concept that the dominant group is that which holds the most power in a given society , while subordinate groups are those who lack power compared to the dominant group . <hl>","hl_sentences":"Note that being a numerical minority is not a characteristic of being a minority group ; sometimes larger groups can be considered minority groups due to their lack of power . These definitions correlate to the concept that the dominant group is that which holds the most power in a given society , while subordinate groups are those who lack power compared to the dominant group .","question":{"cloze_format":"___ is the one defining feature of a minority group.","normal_format":"What is the one defining feature of a minority group?","question_choices":["Self-definition","Numerical minority","Lack of power","Strong cultural identity"],"question_id":"fs-id1491488","question_text":"What is the one defining feature of a minority group?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"any of the above"},"bloom":"1","hl_context":"<hl> Ethnicity is a term that describes shared culture — the practices , values , and beliefs of a group . <hl> <hl> This might include shared language , religion , and traditions , among other commonalities . <hl> Like race , the term ethnicity is difficult to describe and its meaning has changed over time . And like race , individuals may be identified or self-identify to ethnicities in complex , even contradictory , ways . For example , ethnic groups such as Irish , Italian American , Russian , Jewish , and Serbian might all be groups whose members are predominantly included in the racial category “ white . ” Conversely , the ethnic group British includes citizens from a multiplicity of racial backgrounds : black , white , Asian , and more , plus a variety of race combinations . These examples illustrate the complexity and overlap of these identifying terms . Ethnicity , like race , continues to be an identification method that individuals and institutions use today — whether through the census , affirmative action initiatives , non-discrimination laws , or simply in personal day-to-day relations .","hl_sentences":"Ethnicity is a term that describes shared culture — the practices , values , and beliefs of a group . This might include shared language , religion , and traditions , among other commonalities .","question":{"cloze_format":"Ethnicity describes shared ___ .","normal_format":"What does ethnicity describe as shared?","question_choices":["beliefs","language","religion","any of the above"],"question_id":"fs-id1386692","question_text":"Ethnicity describes shared:"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"Blacks under Apartheid in South Africa"},"bloom":"1","hl_context":"Note that being a numerical minority is not a characteristic of being a minority group ; sometimes larger groups can be considered minority groups due to their lack of power . <hl> It is the lack of power that is the predominant characteristic of a minority , or subordinate group . <hl> <hl> For example , consider Apartheid in South Africa , in which a numerical majority ( the black inhabitants of the country ) were exploited and oppressed by the white minority . <hl>","hl_sentences":"It is the lack of power that is the predominant characteristic of a minority , or subordinate group . For example , consider Apartheid in South Africa , in which a numerical majority ( the black inhabitants of the country ) were exploited and oppressed by the white minority .","question":{"cloze_format":"___ is an example of a numerical majority being treated as a subordinate group.","normal_format":"Which of the following is an example of a numerical majority being treated as a subordinate group?","question_choices":["Jewish people in Germany","Creoles in New Orleans","White people in Brazil","Blacks under Apartheid in South Africa"],"question_id":"fs-id1588910","question_text":"Which of the following is an example of a numerical majority being treated as a subordinate group?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"dominant groups blame subordinate groups for their problems"},"bloom":"1","hl_context":"<hl> Scapegoat theory , developed initially from Dollard ’ s ( 1939 ) Frustration-Aggression theory , suggests that the dominant group will displace their unfocused aggression onto a subordinate group . <hl> History has shown us many examples of the scapegoating of a subordinate group . <hl> An example from the last century is the way that Adolf Hitler was able to use the Jewish people as scapegoats for Germany ’ s social and economic problems . <hl> In the United States , recent immigrants have frequently been the scapegoat for the nation ’ s — or an individual ’ s — woes . Many states have enacted laws to disenfranchise immigrants ; these laws are popular because they let the dominant group scapegoat a subordinate group .","hl_sentences":"Scapegoat theory , developed initially from Dollard ’ s ( 1939 ) Frustration-Aggression theory , suggests that the dominant group will displace their unfocused aggression onto a subordinate group . An example from the last century is the way that Adolf Hitler was able to use the Jewish people as scapegoats for Germany ’ s social and economic problems .","question":{"cloze_format":"Scapegoat theory shows that ___ .","normal_format":"What does scapegoat theory show?","question_choices":["subordinate groups blame dominant groups for their problems","dominant groups blame subordinate groups for their problems","some people are predisposed to prejudice","all of the above"],"question_id":"fs-id1291763","question_text":"Scapegoat theory shows that:"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"all of the above"},"bloom":"1","hl_context":"As stated above , stereotypes are oversimplified ideas about groups of people . <hl> Stereotypes can be based on race , ethnicity , age , gender , sexual orientation — almost any characteristic . <hl> They may be positive ( usually about one ’ s own group , such as when women suggest they are less likely to complain about physical pain ) but are often negative ( usually toward other groups , such as when members of a dominant racial group suggest that a subordinate racial group is stupid or lazy ) . In either case , the stereotype is a generalization that doesn ’ t take individual differences into account .","hl_sentences":"Stereotypes can be based on race , ethnicity , age , gender , sexual orientation — almost any characteristic .","question":{"cloze_format":"Stereotypes can be based on ___.","normal_format":"What can stereotypes be based on?","question_choices":["race","ethnicity","gender","all of the above"],"question_id":"fs-id1363101","question_text":"Stereotypes can be based on:"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"Biased actions against an individual or group"},"bloom":"1","hl_context":"<hl> While prejudice refers to biased thinking , discrimination consists of actions against a group of people . <hl> Discrimination can be based on age , religion , health , and other indicators ; race-based discrimination and antidiscrimination laws strive to address this set of social problems .","hl_sentences":"While prejudice refers to biased thinking , discrimination consists of actions against a group of people .","question":{"cloze_format":"Discrimination is (the) ___.","normal_format":"What is discrimination?","question_choices":["Biased thoughts against an individual or group","Biased actions against an individual or group","Belief that a race different from yours is inferior","Another word for stereotyping"],"question_id":"fs-id2839132","question_text":"What is discrimination?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"It does not need the actions of individuals to continue."},"bloom":null,"hl_context":"However , discrimination cannot be erased from our culture just by enacting laws to abolish it . Even if a magic pill managed to eradicate racism from each individual ’ s psyche , society itself would maintain it . <hl> Sociologist Émile Durkheim calls racism a social fact , meaning that it does not require the action of individuals to continue . <hl> The reasons for this are complex and relate to the educational , criminal , economic , and political systems that exist . For example , when a newspaper prints the race of individuals accused of a crime , it may enhance stereotypes of a certain minority . Another example of racist practices is racial steering , in which real estate agents direct prospective homeowners toward or away from certain neighborhoods based on their race . Racist attitudes and beliefs are often more insidious and hard to pin down than specific racist practices .","hl_sentences":"Sociologist Émile Durkheim calls racism a social fact , meaning that it does not require the action of individuals to continue .","question":{"cloze_format":"The best explanation of racism as a social fact is that ___ .","normal_format":"Which of the following is the best explanation of racism as a social fact?","question_choices":["It needs to be eradicated by laws.","It is like a magic pill.","It does not need the actions of individuals to continue.","None of the above"],"question_id":"fs-id1306686","question_text":"Which of the following is the best explanation of racism as a social fact?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"white privilege"},"bloom":null,"hl_context":"<hl> Institutional discrimination can also involve the promotion of a group ’ s status , such as occurs with white privilege . <hl> While most white people are willing to admit that non-white people live with a set of disadvantages due to the color of their skin , very few white people are willing to acknowledge the benefits they receive simply by being white . <hl> White privilege refers to the fact that dominant groups often accept their experience as the normative ( and hence , superior ) experience . <hl> <hl> Failure to recognize this “ normality ” as race-based is an example of a dominant group institutionalizing racism . <hl> Feminist sociologist Peggy McIntosh ( 1988 ) described several examples of “ white privilege . ” For instance , white women can easily find makeup that matches their skin tone . White people can be assured that , most of the time , they will be dealing with authority figures of their own race . How many other examples of white privilege can you think of ?","hl_sentences":"Institutional discrimination can also involve the promotion of a group ’ s status , such as occurs with white privilege . White privilege refers to the fact that dominant groups often accept their experience as the normative ( and hence , superior ) experience . Failure to recognize this “ normality ” as race-based is an example of a dominant group institutionalizing racism .","question":{"cloze_format":"As a Caucasian in the United States, being reasonably sure that you will be dealing with authority figures of the same race as you is a result of (the) ___ .","normal_format":"As a Caucasian in the United States, being reasonably sure that you will be dealing with authority figures of the same race as you is a result of what?","question_choices":["intersection theory","conflict theory","white privilege","scapegoating theory"],"question_id":"fs-id2274870","question_text":"As a Caucasian in the United States, being reasonably sure that you will be dealing with authority figures of the same race as you is a result of:"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"stereotyping"},"bloom":"1","hl_context":"Culture of prejudice refers to the theory that prejudice is embedded in our culture . We grow up surrounded by images of stereotypes and casual expressions of racism and prejudice . <hl> Consider the casually racist imagery on grocery store shelves or the stereotypes that fill popular movies and advertisements . <hl> <hl> It is easy to see how someone living in the Northeastern United States , who may know no Mexican Americans personally , might gain a stereotyped impression from such sources as Speedy Gonzalez or Taco Bell ’ s talking Chihuahua . <hl> Because we are all exposed to these images and thoughts , it is impossible to know to what extent they have influenced our thought processes . 11.4 Intergroup Relationships","hl_sentences":"Consider the casually racist imagery on grocery store shelves or the stereotypes that fill popular movies and advertisements . It is easy to see how someone living in the Northeastern United States , who may know no Mexican Americans personally , might gain a stereotyped impression from such sources as Speedy Gonzalez or Taco Bell ’ s talking Chihuahua .","question":{"cloze_format":"Speedy Gonzalez is an example of ___.","normal_format":"What is Speedy Gonzalez an example of?","question_choices":["intersection theory","stereotyping","interactionist view","culture of prejudice"],"question_id":"fs-id2368853","question_text":"Speedy Gonzalez is an example of:"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"Genocide"},"bloom":null,"hl_context":"Intergroup relations ( relationships between different groups of people ) range along a spectrum between tolerance and intolerance . The most tolerant form of intergroup relations is pluralism , in which no distinction is made between minority and majority groups , but instead there ’ s equal standing . <hl> At the other end of the continuum are amalgamation , expulsion , and even genocide — stark examples of intolerant intergroup relations . <hl>","hl_sentences":"At the other end of the continuum are amalgamation , expulsion , and even genocide — stark examples of intolerant intergroup relations .","question":{"cloze_format":"The intergroup relation that displays the least tolerance is ___.","normal_format":"Which intergroup relation displays the least tolerance?","question_choices":["Segregation","Assimilation","Genocide","Expulsion"],"question_id":"fs-id1169033060750","question_text":"Which intergroup relation displays the least tolerance?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"Separate but equal"},"bloom":"1","hl_context":"<hl> Segregation refers to the physical separation of two groups , particularly in residence , but also in workplace and social functions . <hl> <hl> It is important to distinguish between de jure segregation ( segregation that is enforced by law ) and de facto segregation ( segregation that occurs without laws but because of other factors ) . <hl> <hl> A stark example of de jure segregation is the apartheid movement of South Africa , which existed from 1948 to 1994 . <hl> Under apartheid , black South Africans were stripped of their civil rights and forcibly relocated to areas that segregated them physically from their white compatriots . Only after decades of degradation , violent uprisings , and international advocacy was apartheid finally abolished .","hl_sentences":"Segregation refers to the physical separation of two groups , particularly in residence , but also in workplace and social functions . It is important to distinguish between de jure segregation ( segregation that is enforced by law ) and de facto segregation ( segregation that occurs without laws but because of other factors ) . A stark example of de jure segregation is the apartheid movement of South Africa , which existed from 1948 to 1994 .","question":{"cloze_format":"The ___ doctrine justified legal segregation in the South.","normal_format":"What doctrine justified legal segregation in the South?","question_choices":["Jim Crow","Plessey v. Ferguson","De jure","Separate but equal"],"question_id":"fs-id1169033068658","question_text":"What doctrine justified legal segregation in the South?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"Pluralism"},"bloom":null,"hl_context":"<hl> Pluralism is represented by the ideal of the United States as a “ salad bowl ” : a great mixture of different cultures where each culture retains its own identity and yet adds to the flavor of the whole . <hl> True pluralism is characterized by mutual respect on the part of all cultures , both dominant and subordinate , creating a multicultural environment of acceptance . In reality , true pluralism is a difficult goal to reach . In the United States , the mutual respect required by pluralism is often missing , and the nation ’ s past pluralist model of a melting pot posits a society where cultural differences aren ’ t embraced as much as erased .","hl_sentences":"Pluralism is represented by the ideal of the United States as a “ salad bowl ” : a great mixture of different cultures where each culture retains its own identity and yet adds to the flavor of the whole .","question":{"cloze_format":"The intergroup relationship that is represented by the “salad bowl” metaphor is called ___.","normal_format":"What intergroup relationship is represented by the “salad bowl” metaphor?","question_choices":["Assimilation","Pluralism","Amalgamation","Segregation"],"question_id":"fs-id1169033058285","question_text":"What intergroup relationship is represented by the “salad bowl” metaphor?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"melting pot"},"bloom":null,"hl_context":"<hl> Amalgamation is the process by which a minority group and a majority group combine to form a new group . <hl> <hl> Amalgamation creates the classic “ melting pot ” analogy ; unlike the “ salad bowl , ” in which each culture retains its individuality , the “ melting pot ” ideal sees the combination of cultures resulting in a new culture entirely . <hl>","hl_sentences":"Amalgamation is the process by which a minority group and a majority group combine to form a new group . Amalgamation creates the classic “ melting pot ” analogy ; unlike the “ salad bowl , ” in which each culture retains its individuality , the “ melting pot ” ideal sees the combination of cultures resulting in a new culture entirely .","question":{"cloze_format":"Amalgamation is represented by the _____________ metaphor.","normal_format":"What metaphor represents Amalgamation?","question_choices":["melting pot","Statue of Liberty","salad bowl","separate but equal"],"question_id":"fs-id1169033063966","question_text":"Amalgamation is represented by the _____________ metaphor."},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"They are the only group that did not come here as immigrants."},"bloom":"1","hl_context":"<hl> However , Native Americans ( some of whom now wished to be called American Indians so as to avoid the “ savage ” connotations of the term “ native ” ) still suffer the effects of centuries of degradation . <hl> Long-term poverty , inadequate education , cultural dislocation , and high rates of unemployment contribute to Native American populations falling to the bottom of the economic spectrum . Native Americans also suffer disproportionately with lower life expectancies than most groups in the United States . <hl> The only nonimmigrant ethnic group in the United States , Native Americans were once a large population but by 2010 made up only 0.9 percent of U . S . populace ( U . S . Census 2010 ) . <hl>","hl_sentences":"However , Native Americans ( some of whom now wished to be called American Indians so as to avoid the “ savage ” connotations of the term “ native ” ) still suffer the effects of centuries of degradation . The only nonimmigrant ethnic group in the United States , Native Americans were once a large population but by 2010 made up only 0.9 percent of U . S . populace ( U . S . Census 2010 ) .","question":{"cloze_format":"The reason that makes Native Americans unique as a subordinate group in the United States is that ___ .","normal_format":"What makes Native Americans unique as a subordinate group in the United States?","question_choices":["They are the only group that experienced expulsion.","They are the only group that was segregated.","They are the only group that was enslaved.","They are the only group that did not come here as immigrants."],"question_id":"fs-id2316262","question_text":"What makes Native Americans unique as a subordinate group in the United States?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"Asian Americans"},"bloom":"1","hl_context":"<hl> Asian Americans certainly have been subject to their share of racial prejudice , despite the seemingly positive stereotype as the model minority . <hl> <hl> The model minority stereotype is applied to a minority group that is seen as reaching significant educational , professional , and socioeconomic levels without challenging the existing establishment . <hl>","hl_sentences":"Asian Americans certainly have been subject to their share of racial prejudice , despite the seemingly positive stereotype as the model minority . The model minority stereotype is applied to a minority group that is seen as reaching significant educational , professional , and socioeconomic levels without challenging the existing establishment .","question":{"cloze_format":"The subordinate group ___ is often referred to as the “model minority\".","normal_format":"Which subordinate group is often referred to as the “model minority?”","question_choices":["African Americans","Asian Americans","White ethnic Americans","Native Americans"],"question_id":"fs-id2401704","question_text":"Which subordinate group is often referred to as the “model minority?”"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"The Bracero Program"},"bloom":"1","hl_context":"<hl> For several decades , Mexican workers crossed the long border into America , both legally and illegally , to work in the fields that provided produce for the developing United States . <hl> <hl> Western growers needed a steady supply of labor , and the 1940s and 1950s saw the official federal Bracero Program ( bracero is Spanish for strong-arm ) that offered protection to Mexican guest workers . <hl> Interestingly , 1954 also saw the enactment of “ Operation Wetback , ” which deported thousands of illegal Mexican workers . <hl> From these examples , we can see that the U . S . treatment of immigration from Mexico has been ambivalent at best . <hl> <hl> Not only are there wide differences among the different origins that make up the Hispanic American population , there are also different names for the group itself . <hl> <hl> The 2010 U . S . Census states that “ Hispanic ” or “ Latino ” refers to a person of Cuban , Mexican , Puerto Rican , South or Central American , or other Spanish culture or origin regardless of race . ” There have been some disagreements over whether Hispanic or Latino is the correct term for a group this diverse , and whether it would be better for people to refer to themselves as being of their origin specifically , for example , Mexican American or Dominican American . <hl> This section will compare the experiences of Mexican Americans and Cuban Americans .","hl_sentences":"For several decades , Mexican workers crossed the long border into America , both legally and illegally , to work in the fields that provided produce for the developing United States . Western growers needed a steady supply of labor , and the 1940s and 1950s saw the official federal Bracero Program ( bracero is Spanish for strong-arm ) that offered protection to Mexican guest workers . From these examples , we can see that the U . S . treatment of immigration from Mexico has been ambivalent at best . Not only are there wide differences among the different origins that make up the Hispanic American population , there are also different names for the group itself . The 2010 U . S . Census states that “ Hispanic ” or “ Latino ” refers to a person of Cuban , Mexican , Puerto Rican , South or Central American , or other Spanish culture or origin regardless of race . ” There have been some disagreements over whether Hispanic or Latino is the correct term for a group this diverse , and whether it would be better for people to refer to themselves as being of their origin specifically , for example , Mexican American or Dominican American .","question":{"cloze_format":"___ is the federal act or program that was designed to allow more Hispanic American immigration, not block it.","normal_format":"Which federal act or program was designed to allow more Hispanic American immigration, not block it?","question_choices":["The Bracero Program","Immigration Reform and Control Act","Operation Wetback","SB 1070"],"question_id":"fs-id1364602","question_text":"Which federal act or program was designed to allow more Hispanic American immigration, not block it?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"Islamophobia"},"bloom":"1","hl_context":"<hl> Although the rate of hate crimes against Arab Americans has slowed , Arab Americans are still victims of racism and prejudice . <hl> <hl> Racial profiling has proceeded against Arab Americans as a matter of course since 9/11 . <hl> Particularly when engaged in air travel , being young and Arab-looking is enough to warrant a special search or detainment . <hl> This Islamophobia ( irrational fear of or hatred against Muslims ) does not show signs of abating . <hl> Scholars noted that white domestic terrorists like Timothy McVeigh , who detonated a bomb at an Oklahoma courthouse in 1995 , have not inspired similar racial profiling or hate crimes against whites .","hl_sentences":"Although the rate of hate crimes against Arab Americans has slowed , Arab Americans are still victims of racism and prejudice . Racial profiling has proceeded against Arab Americans as a matter of course since 9/11 . This Islamophobia ( irrational fear of or hatred against Muslims ) does not show signs of abating .","question":{"cloze_format":"Many Arab Americans face _______________, especially after 9/11.","normal_format":"What do many Arab Americans face, especially after 9/11?","question_choices":["racism","segregation","Islamophobia","prejudice"],"question_id":"fs-id2620520","question_text":"Many Arab Americans face _______________, especially after 9/11."},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"Because they were forced out of their own countries"},"bloom":"3","hl_context":"The Irish immigrants of the same time period were not always as well off financially , especially after the Irish Potato Famine of 1845 . Irish immigrants settled mainly in the cities of the East Coast , where they were employed as laborers and where they faced significant discrimination . German and Irish immigration continued into the late 19th century and earlier 20th century , at which point the numbers for Southern and Eastern European immigrants started growing as well . Italians , mainly from the Southern part of the country , began arriving in large numbers in the 1890s . Eastern European immigrants — people from Russia , Poland , Bulgaria , and Austria-Hungary — started arriving around the same time . <hl> Many of these Eastern Europeans were peasants forced into a hardscrabble existence in their native lands ; political unrest , land shortages , and crop failures drove them to seek better opportunities in the United States . <hl> The Eastern European immigration wave also included Jewish people escaping pogroms ( anti-Jewish uprisings ) of Eastern Europe and the Pale of Settlement in what was then Poland and Russia . <hl> White Ethnic Americans <hl>","hl_sentences":"Many of these Eastern Europeans were peasants forced into a hardscrabble existence in their native lands ; political unrest , land shortages , and crop failures drove them to seek better opportunities in the United States . White Ethnic Americans","question":{"cloze_format":"Most white ethnic Americans came to the United States ___.","normal_format":"Why did most white ethnic Americans come to the United States?","question_choices":["For a better life","To escape oppression","Because they were forced out of their own countries","a and b only"],"question_id":"fs-id1381364","question_text":"Why did most white ethnic Americans come to the United States?"},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"any of the above\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> The next 150 years saw the rise of American slavery , with black Africans being kidnapped from their own lands and shipped to the New World on the trans-Atlantic journey known as the Middle Passage . <hl> Once in the Americas , the black population grew until American-born blacks outnumbered those born in Africa . <hl> But colonial ( and later , American ) slave codes declared that the child of a slave was a slave , so the slave class was created . <hl> By 1869 , the slave trade was internal in the United States , with slaves being bought and sold across state lines like livestock . <hl> If Native Americans are the only minority group whose subordinate status occurred by conquest , African Americans are the exemplar minority group in the United States whose ancestors did not come here by choice . <hl> A Dutch sea captain brought the first Africans to the Virginia colony of Jamestown in 1619 and sold them as indentured servants . This was not an uncommon practice for either blacks or whites , and indentured servants were in high demand . For the next century , black and white indentured servants worked side by side . But the growing agricultural economy demanded greater and cheaper labor , and by 1705 , Virginia passed the slave codes declaring that any foreign-born non-Christian could be a slave , and that slaves were considered property . The social construction of race is also reflected in the way that names for racial categories change with changing times . It ’ s worth noting that race , in this sense , is also a system of labeling that provides a source of identity ; specific labels fall in and out of favor during different social eras . <hl> For example , the category ” negroid , ” popular in the 19th century , evolved into the term “ negro ” by the 1960s , and then this term fell from use and was replaced with “ African American . ” This latter term was intended to celebrate the multiple identities that a black person might hold , but the word choice is a poor one : it lumps together a large variety of ethnic groups under an umbrella term while excluding others who could accurately be described by the label but who do not meet the spirit of the term . <hl> For example , actress Charlize Theron is a blonde-haired , blue-eyed “ African American . ” She was born in South Africa and later became a U . S . citizen . Is her identity that of an “ African American ” as most of us understand the term ?\",\n \"hl_sentences\": \"The next 150 years saw the rise of American slavery , with black Africans being kidnapped from their own lands and shipped to the New World on the trans-Atlantic journey known as the Middle Passage . But colonial ( and later , American ) slave codes declared that the child of a slave was a slave , so the slave class was created . If Native Americans are the only minority group whose subordinate status occurred by conquest , African Americans are the exemplar minority group in the United States whose ancestors did not come here by choice . For example , the category ” negroid , ” popular in the 19th century , evolved into the term “ negro ” by the 1960s , and then this term fell from use and was replaced with “ African American . ” This latter term was intended to celebrate the multiple identities that a black person might hold , but the word choice is a poor one : it lumps together a large variety of ethnic groups under an umbrella term while excluding others who could accurately be described by the label but who do not meet the spirit of the term .\",\n \"question\": {\n \"cloze_format\": \"The racial term “African American” can refer to ___.\",\n \"normal_format\": \"What can the racial term “African American” refer to?\",\n \"question_choices\": [\n \"a black person living in America\",\n \"people whose ancestors came to America through the slave trade\",\n \"a white person who originated in Africa and now lives in the United States\",\n \"any of the above\"\n ],\n \"question_id\": \"fs-id2103582\",\n \"question_text\": \"The racial term “African American” can refer to:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"Lack of power\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Note that being a numerical minority is not a characteristic of being a minority group ; sometimes larger groups can be considered minority groups due to their lack of power . <hl> It is the lack of power that is the predominant characteristic of a minority , or subordinate group . For example , consider Apartheid in South Africa , in which a numerical majority ( the black inhabitants of the country ) were exploited and oppressed by the white minority . Sociologist Louis Wirth ( 1945 ) defined a minority group as “ any group of people who , because of their physical or cultural characteristics , are singled out from the others in the society in which they live for differential and unequal treatment , and who therefore regard themselves as objects of collective discrimination . ” The term minority connotes discrimination , and in its sociological use , the term subordinate can be used interchangeably with the term minority , while the term dominant is often substituted for the group that ’ s in the majority . <hl> These definitions correlate to the concept that the dominant group is that which holds the most power in a given society , while subordinate groups are those who lack power compared to the dominant group . <hl>\",\n \"hl_sentences\": \"Note that being a numerical minority is not a characteristic of being a minority group ; sometimes larger groups can be considered minority groups due to their lack of power . These definitions correlate to the concept that the dominant group is that which holds the most power in a given society , while subordinate groups are those who lack power compared to the dominant group .\",\n \"question\": {\n \"cloze_format\": \"___ is the one defining feature of a minority group.\",\n \"normal_format\": \"What is the one defining feature of a minority group?\",\n \"question_choices\": [\n \"Self-definition\",\n \"Numerical minority\",\n \"Lack of power\",\n \"Strong cultural identity\"\n ],\n \"question_id\": \"fs-id1491488\",\n \"question_text\": \"What is the one defining feature of a minority group?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"any of the above\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Ethnicity is a term that describes shared culture — the practices , values , and beliefs of a group . <hl> <hl> This might include shared language , religion , and traditions , among other commonalities . <hl> Like race , the term ethnicity is difficult to describe and its meaning has changed over time . And like race , individuals may be identified or self-identify to ethnicities in complex , even contradictory , ways . For example , ethnic groups such as Irish , Italian American , Russian , Jewish , and Serbian might all be groups whose members are predominantly included in the racial category “ white . ” Conversely , the ethnic group British includes citizens from a multiplicity of racial backgrounds : black , white , Asian , and more , plus a variety of race combinations . These examples illustrate the complexity and overlap of these identifying terms . Ethnicity , like race , continues to be an identification method that individuals and institutions use today — whether through the census , affirmative action initiatives , non-discrimination laws , or simply in personal day-to-day relations .\",\n \"hl_sentences\": \"Ethnicity is a term that describes shared culture — the practices , values , and beliefs of a group . This might include shared language , religion , and traditions , among other commonalities .\",\n \"question\": {\n \"cloze_format\": \"Ethnicity describes shared ___ .\",\n \"normal_format\": \"What does ethnicity describe as shared?\",\n \"question_choices\": [\n \"beliefs\",\n \"language\",\n \"religion\",\n \"any of the above\"\n ],\n \"question_id\": \"fs-id1386692\",\n \"question_text\": \"Ethnicity describes shared:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"Blacks under Apartheid in South Africa\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Note that being a numerical minority is not a characteristic of being a minority group ; sometimes larger groups can be considered minority groups due to their lack of power . <hl> It is the lack of power that is the predominant characteristic of a minority , or subordinate group . <hl> <hl> For example , consider Apartheid in South Africa , in which a numerical majority ( the black inhabitants of the country ) were exploited and oppressed by the white minority . <hl>\",\n \"hl_sentences\": \"It is the lack of power that is the predominant characteristic of a minority , or subordinate group . For example , consider Apartheid in South Africa , in which a numerical majority ( the black inhabitants of the country ) were exploited and oppressed by the white minority .\",\n \"question\": {\n \"cloze_format\": \"___ is an example of a numerical majority being treated as a subordinate group.\",\n \"normal_format\": \"Which of the following is an example of a numerical majority being treated as a subordinate group?\",\n \"question_choices\": [\n \"Jewish people in Germany\",\n \"Creoles in New Orleans\",\n \"White people in Brazil\",\n \"Blacks under Apartheid in South Africa\"\n ],\n \"question_id\": \"fs-id1588910\",\n \"question_text\": \"Which of the following is an example of a numerical majority being treated as a subordinate group?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"dominant groups blame subordinate groups for their problems\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Scapegoat theory , developed initially from Dollard ’ s ( 1939 ) Frustration-Aggression theory , suggests that the dominant group will displace their unfocused aggression onto a subordinate group . <hl> History has shown us many examples of the scapegoating of a subordinate group . <hl> An example from the last century is the way that Adolf Hitler was able to use the Jewish people as scapegoats for Germany ’ s social and economic problems . <hl> In the United States , recent immigrants have frequently been the scapegoat for the nation ’ s — or an individual ’ s — woes . Many states have enacted laws to disenfranchise immigrants ; these laws are popular because they let the dominant group scapegoat a subordinate group .\",\n \"hl_sentences\": \"Scapegoat theory , developed initially from Dollard ’ s ( 1939 ) Frustration-Aggression theory , suggests that the dominant group will displace their unfocused aggression onto a subordinate group . An example from the last century is the way that Adolf Hitler was able to use the Jewish people as scapegoats for Germany ’ s social and economic problems .\",\n \"question\": {\n \"cloze_format\": \"Scapegoat theory shows that ___ .\",\n \"normal_format\": \"What does scapegoat theory show?\",\n \"question_choices\": [\n \"subordinate groups blame dominant groups for their problems\",\n \"dominant groups blame subordinate groups for their problems\",\n \"some people are predisposed to prejudice\",\n \"all of the above\"\n ],\n \"question_id\": \"fs-id1291763\",\n \"question_text\": \"Scapegoat theory shows that:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"all of the above\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"As stated above , stereotypes are oversimplified ideas about groups of people . <hl> Stereotypes can be based on race , ethnicity , age , gender , sexual orientation — almost any characteristic . <hl> They may be positive ( usually about one ’ s own group , such as when women suggest they are less likely to complain about physical pain ) but are often negative ( usually toward other groups , such as when members of a dominant racial group suggest that a subordinate racial group is stupid or lazy ) . In either case , the stereotype is a generalization that doesn ’ t take individual differences into account .\",\n \"hl_sentences\": \"Stereotypes can be based on race , ethnicity , age , gender , sexual orientation — almost any characteristic .\",\n \"question\": {\n \"cloze_format\": \"Stereotypes can be based on ___.\",\n \"normal_format\": \"What can stereotypes be based on?\",\n \"question_choices\": [\n \"race\",\n \"ethnicity\",\n \"gender\",\n \"all of the above\"\n ],\n \"question_id\": \"fs-id1363101\",\n \"question_text\": \"Stereotypes can be based on:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"Biased actions against an individual or group\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> While prejudice refers to biased thinking , discrimination consists of actions against a group of people . <hl> Discrimination can be based on age , religion , health , and other indicators ; race-based discrimination and antidiscrimination laws strive to address this set of social problems .\",\n \"hl_sentences\": \"While prejudice refers to biased thinking , discrimination consists of actions against a group of people .\",\n \"question\": {\n \"cloze_format\": \"Discrimination is (the) ___.\",\n \"normal_format\": \"What is discrimination?\",\n \"question_choices\": [\n \"Biased thoughts against an individual or group\",\n \"Biased actions against an individual or group\",\n \"Belief that a race different from yours is inferior\",\n \"Another word for stereotyping\"\n ],\n \"question_id\": \"fs-id2839132\",\n \"question_text\": \"What is discrimination?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"It does not need the actions of individuals to continue.\"\n },\n \"bloom\": null,\n \"hl_context\": \"However , discrimination cannot be erased from our culture just by enacting laws to abolish it . Even if a magic pill managed to eradicate racism from each individual ’ s psyche , society itself would maintain it . <hl> Sociologist Émile Durkheim calls racism a social fact , meaning that it does not require the action of individuals to continue . <hl> The reasons for this are complex and relate to the educational , criminal , economic , and political systems that exist . For example , when a newspaper prints the race of individuals accused of a crime , it may enhance stereotypes of a certain minority . Another example of racist practices is racial steering , in which real estate agents direct prospective homeowners toward or away from certain neighborhoods based on their race . Racist attitudes and beliefs are often more insidious and hard to pin down than specific racist practices .\",\n \"hl_sentences\": \"Sociologist Émile Durkheim calls racism a social fact , meaning that it does not require the action of individuals to continue .\",\n \"question\": {\n \"cloze_format\": \"The best explanation of racism as a social fact is that ___ .\",\n \"normal_format\": \"Which of the following is the best explanation of racism as a social fact?\",\n \"question_choices\": [\n \"It needs to be eradicated by laws.\",\n \"It is like a magic pill.\",\n \"It does not need the actions of individuals to continue.\",\n \"None of the above\"\n ],\n \"question_id\": \"fs-id1306686\",\n \"question_text\": \"Which of the following is the best explanation of racism as a social fact?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"white privilege\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Institutional discrimination can also involve the promotion of a group ’ s status , such as occurs with white privilege . <hl> While most white people are willing to admit that non-white people live with a set of disadvantages due to the color of their skin , very few white people are willing to acknowledge the benefits they receive simply by being white . <hl> White privilege refers to the fact that dominant groups often accept their experience as the normative ( and hence , superior ) experience . <hl> <hl> Failure to recognize this “ normality ” as race-based is an example of a dominant group institutionalizing racism . <hl> Feminist sociologist Peggy McIntosh ( 1988 ) described several examples of “ white privilege . ” For instance , white women can easily find makeup that matches their skin tone . White people can be assured that , most of the time , they will be dealing with authority figures of their own race . How many other examples of white privilege can you think of ?\",\n \"hl_sentences\": \"Institutional discrimination can also involve the promotion of a group ’ s status , such as occurs with white privilege . White privilege refers to the fact that dominant groups often accept their experience as the normative ( and hence , superior ) experience . Failure to recognize this “ normality ” as race-based is an example of a dominant group institutionalizing racism .\",\n \"question\": {\n \"cloze_format\": \"As a Caucasian in the United States, being reasonably sure that you will be dealing with authority figures of the same race as you is a result of (the) ___ .\",\n \"normal_format\": \"As a Caucasian in the United States, being reasonably sure that you will be dealing with authority figures of the same race as you is a result of what?\",\n \"question_choices\": [\n \"intersection theory\",\n \"conflict theory\",\n \"white privilege\",\n \"scapegoating theory\"\n ],\n \"question_id\": \"fs-id2274870\",\n \"question_text\": \"As a Caucasian in the United States, being reasonably sure that you will be dealing with authority figures of the same race as you is a result of:\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"stereotyping\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Culture of prejudice refers to the theory that prejudice is embedded in our culture . We grow up surrounded by images of stereotypes and casual expressions of racism and prejudice . <hl> Consider the casually racist imagery on grocery store shelves or the stereotypes that fill popular movies and advertisements . <hl> <hl> It is easy to see how someone living in the Northeastern United States , who may know no Mexican Americans personally , might gain a stereotyped impression from such sources as Speedy Gonzalez or Taco Bell ’ s talking Chihuahua . <hl> Because we are all exposed to these images and thoughts , it is impossible to know to what extent they have influenced our thought processes . 11.4 Intergroup Relationships\",\n \"hl_sentences\": \"Consider the casually racist imagery on grocery store shelves or the stereotypes that fill popular movies and advertisements . It is easy to see how someone living in the Northeastern United States , who may know no Mexican Americans personally , might gain a stereotyped impression from such sources as Speedy Gonzalez or Taco Bell ’ s talking Chihuahua .\",\n \"question\": {\n \"cloze_format\": \"Speedy Gonzalez is an example of ___.\",\n \"normal_format\": \"What is Speedy Gonzalez an example of?\",\n \"question_choices\": [\n \"intersection theory\",\n \"stereotyping\",\n \"interactionist view\",\n \"culture of prejudice\"\n ],\n \"question_id\": \"fs-id2368853\",\n \"question_text\": \"Speedy Gonzalez is an example of:\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"Genocide\"\n },\n \"bloom\": null,\n \"hl_context\": \"Intergroup relations ( relationships between different groups of people ) range along a spectrum between tolerance and intolerance . The most tolerant form of intergroup relations is pluralism , in which no distinction is made between minority and majority groups , but instead there ’ s equal standing . <hl> At the other end of the continuum are amalgamation , expulsion , and even genocide — stark examples of intolerant intergroup relations . <hl>\",\n \"hl_sentences\": \"At the other end of the continuum are amalgamation , expulsion , and even genocide — stark examples of intolerant intergroup relations .\",\n \"question\": {\n \"cloze_format\": \"The intergroup relation that displays the least tolerance is ___.\",\n \"normal_format\": \"Which intergroup relation displays the least tolerance?\",\n \"question_choices\": [\n \"Segregation\",\n \"Assimilation\",\n \"Genocide\",\n \"Expulsion\"\n ],\n \"question_id\": \"fs-id1169033060750\",\n \"question_text\": \"Which intergroup relation displays the least tolerance?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"Separate but equal\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Segregation refers to the physical separation of two groups , particularly in residence , but also in workplace and social functions . <hl> <hl> It is important to distinguish between de jure segregation ( segregation that is enforced by law ) and de facto segregation ( segregation that occurs without laws but because of other factors ) . <hl> <hl> A stark example of de jure segregation is the apartheid movement of South Africa , which existed from 1948 to 1994 . <hl> Under apartheid , black South Africans were stripped of their civil rights and forcibly relocated to areas that segregated them physically from their white compatriots . Only after decades of degradation , violent uprisings , and international advocacy was apartheid finally abolished .\",\n \"hl_sentences\": \"Segregation refers to the physical separation of two groups , particularly in residence , but also in workplace and social functions . It is important to distinguish between de jure segregation ( segregation that is enforced by law ) and de facto segregation ( segregation that occurs without laws but because of other factors ) . A stark example of de jure segregation is the apartheid movement of South Africa , which existed from 1948 to 1994 .\",\n \"question\": {\n \"cloze_format\": \"The ___ doctrine justified legal segregation in the South.\",\n \"normal_format\": \"What doctrine justified legal segregation in the South?\",\n \"question_choices\": [\n \"Jim Crow\",\n \"Plessey v. Ferguson\",\n \"De jure\",\n \"Separate but equal\"\n ],\n \"question_id\": \"fs-id1169033068658\",\n \"question_text\": \"What doctrine justified legal segregation in the South?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"Pluralism\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Pluralism is represented by the ideal of the United States as a “ salad bowl ” : a great mixture of different cultures where each culture retains its own identity and yet adds to the flavor of the whole . <hl> True pluralism is characterized by mutual respect on the part of all cultures , both dominant and subordinate , creating a multicultural environment of acceptance . In reality , true pluralism is a difficult goal to reach . In the United States , the mutual respect required by pluralism is often missing , and the nation ’ s past pluralist model of a melting pot posits a society where cultural differences aren ’ t embraced as much as erased .\",\n \"hl_sentences\": \"Pluralism is represented by the ideal of the United States as a “ salad bowl ” : a great mixture of different cultures where each culture retains its own identity and yet adds to the flavor of the whole .\",\n \"question\": {\n \"cloze_format\": \"The intergroup relationship that is represented by the “salad bowl” metaphor is called ___.\",\n \"normal_format\": \"What intergroup relationship is represented by the “salad bowl” metaphor?\",\n \"question_choices\": [\n \"Assimilation\",\n \"Pluralism\",\n \"Amalgamation\",\n \"Segregation\"\n ],\n \"question_id\": \"fs-id1169033058285\",\n \"question_text\": \"What intergroup relationship is represented by the “salad bowl” metaphor?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"melting pot\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Amalgamation is the process by which a minority group and a majority group combine to form a new group . <hl> <hl> Amalgamation creates the classic “ melting pot ” analogy ; unlike the “ salad bowl , ” in which each culture retains its individuality , the “ melting pot ” ideal sees the combination of cultures resulting in a new culture entirely . <hl>\",\n \"hl_sentences\": \"Amalgamation is the process by which a minority group and a majority group combine to form a new group . Amalgamation creates the classic “ melting pot ” analogy ; unlike the “ salad bowl , ” in which each culture retains its individuality , the “ melting pot ” ideal sees the combination of cultures resulting in a new culture entirely .\",\n \"question\": {\n \"cloze_format\": \"Amalgamation is represented by the _____________ metaphor.\",\n \"normal_format\": \"What metaphor represents Amalgamation?\",\n \"question_choices\": [\n \"melting pot\",\n \"Statue of Liberty\",\n \"salad bowl\",\n \"separate but equal\"\n ],\n \"question_id\": \"fs-id1169033063966\",\n \"question_text\": \"Amalgamation is represented by the _____________ metaphor.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"They are the only group that did not come here as immigrants.\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> However , Native Americans ( some of whom now wished to be called American Indians so as to avoid the “ savage ” connotations of the term “ native ” ) still suffer the effects of centuries of degradation . <hl> Long-term poverty , inadequate education , cultural dislocation , and high rates of unemployment contribute to Native American populations falling to the bottom of the economic spectrum . Native Americans also suffer disproportionately with lower life expectancies than most groups in the United States . <hl> The only nonimmigrant ethnic group in the United States , Native Americans were once a large population but by 2010 made up only 0.9 percent of U . S . populace ( U . S . Census 2010 ) . <hl>\",\n \"hl_sentences\": \"However , Native Americans ( some of whom now wished to be called American Indians so as to avoid the “ savage ” connotations of the term “ native ” ) still suffer the effects of centuries of degradation . The only nonimmigrant ethnic group in the United States , Native Americans were once a large population but by 2010 made up only 0.9 percent of U . S . populace ( U . S . Census 2010 ) .\",\n \"question\": {\n \"cloze_format\": \"The reason that makes Native Americans unique as a subordinate group in the United States is that ___ .\",\n \"normal_format\": \"What makes Native Americans unique as a subordinate group in the United States?\",\n \"question_choices\": [\n \"They are the only group that experienced expulsion.\",\n \"They are the only group that was segregated.\",\n \"They are the only group that was enslaved.\",\n \"They are the only group that did not come here as immigrants.\"\n ],\n \"question_id\": \"fs-id2316262\",\n \"question_text\": \"What makes Native Americans unique as a subordinate group in the United States?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"Asian Americans\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Asian Americans certainly have been subject to their share of racial prejudice , despite the seemingly positive stereotype as the model minority . <hl> <hl> The model minority stereotype is applied to a minority group that is seen as reaching significant educational , professional , and socioeconomic levels without challenging the existing establishment . <hl>\",\n \"hl_sentences\": \"Asian Americans certainly have been subject to their share of racial prejudice , despite the seemingly positive stereotype as the model minority . The model minority stereotype is applied to a minority group that is seen as reaching significant educational , professional , and socioeconomic levels without challenging the existing establishment .\",\n \"question\": {\n \"cloze_format\": \"The subordinate group ___ is often referred to as the “model minority\\\".\",\n \"normal_format\": \"Which subordinate group is often referred to as the “model minority?”\",\n \"question_choices\": [\n \"African Americans\",\n \"Asian Americans\",\n \"White ethnic Americans\",\n \"Native Americans\"\n ],\n \"question_id\": \"fs-id2401704\",\n \"question_text\": \"Which subordinate group is often referred to as the “model minority?”\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"The Bracero Program\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> For several decades , Mexican workers crossed the long border into America , both legally and illegally , to work in the fields that provided produce for the developing United States . <hl> <hl> Western growers needed a steady supply of labor , and the 1940s and 1950s saw the official federal Bracero Program ( bracero is Spanish for strong-arm ) that offered protection to Mexican guest workers . <hl> Interestingly , 1954 also saw the enactment of “ Operation Wetback , ” which deported thousands of illegal Mexican workers . <hl> From these examples , we can see that the U . S . treatment of immigration from Mexico has been ambivalent at best . <hl> <hl> Not only are there wide differences among the different origins that make up the Hispanic American population , there are also different names for the group itself . <hl> <hl> The 2010 U . S . Census states that “ Hispanic ” or “ Latino ” refers to a person of Cuban , Mexican , Puerto Rican , South or Central American , or other Spanish culture or origin regardless of race . ” There have been some disagreements over whether Hispanic or Latino is the correct term for a group this diverse , and whether it would be better for people to refer to themselves as being of their origin specifically , for example , Mexican American or Dominican American . <hl> This section will compare the experiences of Mexican Americans and Cuban Americans .\",\n \"hl_sentences\": \"For several decades , Mexican workers crossed the long border into America , both legally and illegally , to work in the fields that provided produce for the developing United States . Western growers needed a steady supply of labor , and the 1940s and 1950s saw the official federal Bracero Program ( bracero is Spanish for strong-arm ) that offered protection to Mexican guest workers . From these examples , we can see that the U . S . treatment of immigration from Mexico has been ambivalent at best . Not only are there wide differences among the different origins that make up the Hispanic American population , there are also different names for the group itself . The 2010 U . S . Census states that “ Hispanic ” or “ Latino ” refers to a person of Cuban , Mexican , Puerto Rican , South or Central American , or other Spanish culture or origin regardless of race . ” There have been some disagreements over whether Hispanic or Latino is the correct term for a group this diverse , and whether it would be better for people to refer to themselves as being of their origin specifically , for example , Mexican American or Dominican American .\",\n \"question\": {\n \"cloze_format\": \"___ is the federal act or program that was designed to allow more Hispanic American immigration, not block it.\",\n \"normal_format\": \"Which federal act or program was designed to allow more Hispanic American immigration, not block it?\",\n \"question_choices\": [\n \"The Bracero Program\",\n \"Immigration Reform and Control Act\",\n \"Operation Wetback\",\n \"SB 1070\"\n ],\n \"question_id\": \"fs-id1364602\",\n \"question_text\": \"Which federal act or program was designed to allow more Hispanic American immigration, not block it?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"Islamophobia\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Although the rate of hate crimes against Arab Americans has slowed , Arab Americans are still victims of racism and prejudice . <hl> <hl> Racial profiling has proceeded against Arab Americans as a matter of course since 9/11 . <hl> Particularly when engaged in air travel , being young and Arab-looking is enough to warrant a special search or detainment . <hl> This Islamophobia ( irrational fear of or hatred against Muslims ) does not show signs of abating . <hl> Scholars noted that white domestic terrorists like Timothy McVeigh , who detonated a bomb at an Oklahoma courthouse in 1995 , have not inspired similar racial profiling or hate crimes against whites .\",\n \"hl_sentences\": \"Although the rate of hate crimes against Arab Americans has slowed , Arab Americans are still victims of racism and prejudice . Racial profiling has proceeded against Arab Americans as a matter of course since 9/11 . This Islamophobia ( irrational fear of or hatred against Muslims ) does not show signs of abating .\",\n \"question\": {\n \"cloze_format\": \"Many Arab Americans face _______________, especially after 9/11.\",\n \"normal_format\": \"What do many Arab Americans face, especially after 9/11?\",\n \"question_choices\": [\n \"racism\",\n \"segregation\",\n \"Islamophobia\",\n \"prejudice\"\n ],\n \"question_id\": \"fs-id2620520\",\n \"question_text\": \"Many Arab Americans face _______________, especially after 9/11.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"Because they were forced out of their own countries\"\n },\n \"bloom\": \"3\",\n \"hl_context\": \"The Irish immigrants of the same time period were not always as well off financially , especially after the Irish Potato Famine of 1845 . Irish immigrants settled mainly in the cities of the East Coast , where they were employed as laborers and where they faced significant discrimination . German and Irish immigration continued into the late 19th century and earlier 20th century , at which point the numbers for Southern and Eastern European immigrants started growing as well . Italians , mainly from the Southern part of the country , began arriving in large numbers in the 1890s . Eastern European immigrants — people from Russia , Poland , Bulgaria , and Austria-Hungary — started arriving around the same time . <hl> Many of these Eastern Europeans were peasants forced into a hardscrabble existence in their native lands ; political unrest , land shortages , and crop failures drove them to seek better opportunities in the United States . <hl> The Eastern European immigration wave also included Jewish people escaping pogroms ( anti-Jewish uprisings ) of Eastern Europe and the Pale of Settlement in what was then Poland and Russia . <hl> White Ethnic Americans <hl>\",\n \"hl_sentences\": \"Many of these Eastern Europeans were peasants forced into a hardscrabble existence in their native lands ; political unrest , land shortages , and crop failures drove them to seek better opportunities in the United States . White Ethnic Americans\",\n \"question\": {\n \"cloze_format\": \"Most white ethnic Americans came to the United States ___.\",\n \"normal_format\": \"Why did most white ethnic Americans come to the United States?\",\n \"question_choices\": [\n \"For a better life\",\n \"To escape oppression\",\n \"Because they were forced out of their own countries\",\n \"a and b only\"\n ],\n \"question_id\": \"fs-id1381364\",\n \"question_text\": \"Why did most white ethnic Americans come to the United States?\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":11,"string":"11"},"chapter_text":{"kind":"string","value":"11.1 Racial, Ethnic, and Minority Groups \n\n While many students first entering a sociology classroom are accustomed to conflating the terms “race,” “ethnicity,” and “minority group,” these three terms have distinct meanings for sociologists. The idea of race refers to superficial physical differences that a particular society considers significant, while ethnicity is a term that describes shared culture. And minority groups describe groups that are subordinate, or lacking power in society regardless of skin color or country of origin. For example, in modern U.S. history, the elderly might be considered a minority group due to a diminished status resulting from popular prejudice and discrimination against them. The World Health Organization’s research on elderly maltreatment shows that 10 percent of nursing home staff admit to physically abusing an elderly person in the past year, and 40 percent admit to psychological abuse (2011). As a minority group, the elderly are also subject to economic, social, and workplace discrimination. \n\n What Is Race? \n\n Historically, the concept of race has changed across cultures and eras, eventually becoming less connected with ancestral and familial ties, and more concerned with superficial physical characteristics. In the past, theorists have posited categories of race based on various geographic regions, ethnicities, skin colors, and more. Their labels for racial groups have connoted regions (Mongolia and the Caucus Mountains, for instance) or denoted skin tones (black, white, yellow, and red, for example). \n\n However, this typology of race developed during early racial science has fallen into disuse, and the social construction of race is a far more common way of understanding racial categories. According to this school of thought, race is not biologically identifiable. When considering skin color, for example, the social construction of race perspective recognizes that the relative darkness or fairness of skin is an evolutionary adaptation to the available sunlight in different regions of the world. Contemporary conceptions of race, therefore, which tend to be based on socioeconomic assumptions, illuminate how far removed modern race understanding is from biological qualities. In modern society, some people who consider themselves “white” actually have more melanin (a pigment that determines skin color) in their skin than other people who identify as ”black.” Consider the case of the actress Rashida Jones. She is the daughter of a black man (Quincy Jones) but she does not play a black woman in her television or film roles. In some countries, such as Brazil, class is more important than skin color in determining racial categorization. People with high levels of melanin in their skin may consider themselves \"white\" if they enjoy a middle-class lifestyle. On the other hand, someone with low levels of melanin in their skin might be assigned the identity of \"black\" if they have little education or money. \n\n The social construction of race is also reflected in the way that names for racial categories change with changing times. It’s worth noting that race, in this sense, is also a system of labeling that provides a source of identity; specific labels fall in and out of favor during different social eras. For example, the category ”negroid,” popular in the 19th century, evolved into the term “negro” by the 1960s, and then this term fell from use and was replaced with “African American.” This latter term was intended to celebrate the multiple identities that a black person might hold, but the word choice is a poor one: it lumps together a large variety of ethnic groups under an umbrella term while excluding others who could accurately be described by the label but who do not meet the spirit of the term. For example, actress Charlize Theron is a blonde-haired, blue-eyed “African American.” She was born in South Africa and later became a U.S. citizen. Is her identity that of an “African American” as most of us understand the term? \n\n What Is Ethnicity? \n\n Ethnicity is a term that describes shared culture—the practices, values, and beliefs of a group. This might include shared language, religion, and traditions, among other commonalities. Like race, the term ethnicity is difficult to describe and its meaning has changed over time. And like race, individuals may be identified or self-identify to ethnicities in complex, even contradictory, ways. For example, ethnic groups such as Irish, Italian American, Russian, Jewish, and Serbian might all be groups whose members are predominantly included in the racial category “white.” Conversely, the ethnic group British includes citizens from a multiplicity of racial backgrounds: black, white, Asian, and more, plus a variety of race combinations. These examples illustrate the complexity and overlap of these identifying terms. Ethnicity, like race, continues to be an identification method that individuals and institutions use today—whether through the census, affirmative action initiatives, non-discrimination laws, or simply in personal day-to-day relations. \n\n What Are Minority Groups? \n\n Sociologist Louis Wirth (1945) defined a minority group as “any group of people who, because of their physical or cultural characteristics, are singled out from the others in the society in which they live for differential and unequal treatment, and who therefore regard themselves as objects of collective discrimination.” The term minority connotes discrimination, and in its sociological use, the term subordinate can be used interchangeably with the term minority, while the term dominant is often substituted for the group that’s in the majority. These definitions correlate to the concept that the dominant group is that which holds the most power in a given society, while subordinate groups are those who lack power compared to the dominant group. \n\n Note that being a numerical minority is not a characteristic of being a minority group; sometimes larger groups can be considered minority groups due to their lack of power. It is the lack of power that is the predominant characteristic of a minority, or subordinate group. For example, consider Apartheid in South Africa, in which a numerical majority (the black inhabitants of the country) were exploited and oppressed by the white minority. \n\n According to Charles Wagley and Marvin Harris (1958), a minority group is distinguished by five characteristics: (1) unequal treatment and less power over their lives, (2) distinguishing physical or cultural traits like skin color or language, (3) involuntary membership in the group, (4) awareness of subordination, and (5) high rate of in-group marriage. Additional examples of minority groups might include the LBGT community, religious practitioners whose faith is not widely practiced where they live, and people with disabilities. \n\n Scapegoat theory , developed initially from Dollard’s (1939) Frustration-Aggression theory, suggests that the dominant group will displace their unfocused aggression onto a subordinate group. History has shown us many examples of the scapegoating of a subordinate group. An example from the last century is the way that Adolf Hitler was able to use the Jewish people as scapegoats for Germany’s social and economic problems. In the United States, recent immigrants have frequently been the scapegoat for the nation’s—or an individual’s—woes. Many states have enacted laws to disenfranchise immigrants; these laws are popular because they let the dominant group scapegoat a subordinate group. \n\n Multiple Identities \n\n Prior to the 20th century, racial intermarriage (referred to as miscegenation) was extremely rare, and in many places, illegal. While the sexual subordination of slaves did result in children of mixed race, these children were usually considered black, and therefore, property. There was no question of multiple racial identities with the possible exception of the Creole. Creole society developed in the port city of New Orleans, where a mixed-race culture grew from French and African inhabitants. Unlike in other parts of the country, “Creoles of color” had greater social, economic, and educational opportunities than most African Americans. \n\n Increasingly during the modern era, the removal of miscegenation laws and a trend toward equal rights and legal protection against racism have steadily reduced the social stigma attached to racial exogamy (exogamy refers to marriage outside of one’s core social unit). It is now common for the children of racially mixed parents to acknowledge and celebrate their various ethnic identities. Golfer Tiger Woods, for instance, has Chinese, Thai, African American, Native American, and Dutch heritage; he jokingly refers to his ethnicity as “Cablinasian,” a term he coined to combine several of his ethnic backgrounds. While this is the trend, it is not yet evident in all aspects of our society. For example, the U.S. Census only recently added additional categories for people to identify themselves, such as non-white Hispanic. A growing number of people chose multiple races to describe themselves on the 2010 Census, paving the way for the 2020 Census to provide yet more choices. \n11.2 Stereotypes, Prejudice, and Discrimination \n\n Stereotypes \n\n The terms stereotype, prejudice, discrimination, and racism are often used interchangeably in everyday conversation. But when discussing these terms from a sociological perspective, it is important to define them: stereotypes are oversimplified ideas about groups of people, prejudice refers to thoughts and feelings about those groups, while discrimination refers to actions toward them. Racism is a type of prejudice that involves set beliefs about a specific racial group. \n\n As stated above, stereotypes are oversimplified ideas about groups of people. Stereotypes can be based on race, ethnicity, age, gender, sexual orientation—almost any characteristic. They may be positive (usually about one’s own group, such as when women suggest they are less likely to complain about physical pain) but are often negative (usually toward other groups, such as when members of a dominant racial group suggest that a subordinate racial group is stupid or lazy). In either case, the stereotype is a generalization that doesn’t take individual differences into account. \n\n Where do stereotypes come from? In fact new stereotypes are rarely created; rather, they are recycled from subordinate groups that have assimilated into society and are reused to describe newly subordinate groups. For example, many stereotypes that are currently used to characterize black people were used earlier in American history to characterize Irish and Eastern European immigrants. \n\n Prejudice and Racism \n\n Prejudice refers to beliefs, thoughts, feelings, and attitudes that someone holds about a group. A prejudice is not based on experience; instead, it is a prejudgment, originating outside of actual experience. Racism is a type of prejudice that is used to justify the belief that one racial category is somehow superior or inferior to others. The Ku Klux Klan is an example of a racist organization; its members’ belief in white supremacy has encouraged over a century of hate crime and hate speech. \n\n Discrimination \n\n While prejudice refers to biased thinking , discrimination consists of actions against a group of people. Discrimination can be based on age, religion, health, and other indicators; race-based discrimination and antidiscrimination laws strive to address this set of social problems. \n\n Discrimination based on race or ethnicity can take many forms, from unfair housing practices to biased hiring systems. Overt discrimination has long been part of U.S. history. In the late 19th century, it was not uncommon for business owners to hang signs that read, “Help Wanted: No Irish Need Apply.” And of course, southern Jim Crow laws, with their “Whites Only” signs, exemplified overt discrimination that is not tolerated today. \n\n However, discrimination cannot be erased from our culture just by enacting laws to abolish it. Even if a magic pill managed to eradicate racism from each individual’s psyche, society itself would maintain it. Sociologist Émile Durkheim calls racism a social fact, meaning that it does not require the action of individuals to continue. The reasons for this are complex and relate to the educational, criminal, economic, and political systems that exist. For example, when a newspaper prints the race of individuals accused of a crime, it may enhance stereotypes of a certain minority. Another example of racist practices is racial steering , in which real estate agents direct prospective homeowners toward or away from certain neighborhoods based on their race. Racist attitudes and beliefs are often more insidious and hard to pin down than specific racist practices. \n\n Prejudice and discrimination can overlap and intersect in many ways. To illustrate, here are four examples of how prejudice and discrimination can occur. Unprejudiced nondiscriminators are open-minded, tolerant, and accepting individuals. Unprejudiced discriminators might be those who, unthinkingly, practice sexism in their workplace by not considering females for certain positions that have traditionally been held by men. Prejudiced nondiscriminators are those who hold racist beliefs but don’t act on them, such as a racist store owner who serves minority customers. Prejudiced discriminators include those who actively make disparaging remarks about others or who perpetuate hate crimes. \n\n Discrimination also manifests in different ways. The illustrations above are examples of individual discrimination, but other types exist. Institutional discrimination is when a societal system has developed with an embedded disenfranchisement of a group, such as the U.S. military’s historical nonacceptance of minority sexualities as recently experienced surrounding the “don’t ask, don’t tell” policy. \n\n Institutional discrimination can also involve the promotion of a group’s status, such as occurs with white privilege. While most white people are willing to admit that non-white people live with a set of disadvantages due to the color of their skin, very few white people are willing to acknowledge the benefits they receive simply by being white. White privilege refers to the fact that dominant groups often accept their experience as the normative (and hence, superior) experience. Failure to recognize this “normality” as race-based is an example of a dominant group institutionalizing racism. Feminist sociologist Peggy McIntosh (1988) described several examples of “white privilege.” For instance, white women can easily find makeup that matches their skin tone. White people can be assured that, most of the time, they will be dealing with authority figures of their own race. How many other examples of white privilege can you think of? \n\n The Confederate Flag vs. the First Amendment \n\n In January 2006, two girls walked into Burleson High School in Texas carrying purses that displayed large images of Confederate flags. School administrators told the girls that they were in violation of the dress code, which prohibited apparel with inappropriate symbolism or clothing that discriminated based on race. To stay in school, they’d have to have someone pick up their purses or leave them in the office. The girls chose to go home for the day, but proceeded on a path of challenging the action, appealing first to the principal, then to the district superintendent, then to the U.S. District Court, and finally to the Fifth Circuit Court of Appeals. \n\n Why did the school ban the purses, and why did they stand behind that ban, even when being sued? Why did the girls, identified anonymously in court documents as A.M. and A.T., pursue such strong legal measures for their right to carry the purses? The issue, of course, is not the purses: it is the Confederate flag that adorns them. This case, A.M. and A.T. v Burleson Independent School District et al. (2009), joins a long line of people and institutions that have fought for their right to display the Confederate flag. In the end, the court sided with the district and noted that the Confederate flag carried symbolism significant enough to disrupt normal school activities. \n\n While many young Americans like to believe that racism is mostly in the country’s past, this case illustrates how racism and discrimination are quite alive today. If the Confederate flag is synonymous with slavery, is there any place for its display in modern society? Those who fight for their right to display the flag say that such a display should be covered by the First Amendment: the right to free speech. But others say that the flag is equivalent to hate speech, which is not covered by the First Amendment. Do you think that displaying the Confederate flag should considered free speech or hate speech? \n11.3 Theories of Race and Ethnicity \n\n Theoretical Perspectives \n\n Issues of race and ethnicity can be observed through three major sociological perspectives: functionalism, conflict theory, and symbolic interactionism. As you read through these theories, ask yourself which one makes the most sense, and why. Is more than one theory needed to explain racism, prejudice, stereotypes, and discrimination? \n\n Functionalism \n\n In the view of functionalism, racial and ethnic inequalities must have served an important function in order to exist as long as they have. This concept, of course, is problematic. How can racism and discrimination contribute positively to society? Sociologists who adhere to the functionalist view argue that racism and discrimination do contribute positively, but only to the dominant group. Historically, it has indeed served dominant groups well to discriminate against subordinate groups. Slavery, of course, was beneficial to slaveholders. Holding racist views can benefit those who want to deny rights and privileges to people they view as inferior to them, but over time, racism harms society. Outcomes of race-based disenfranchisement—such as poverty levels, crime rates, and discrepancies in employment and education opportunities—illustrate the long-term (and clearly negative) results of slavery and racism in American society. \n\n Conflict Theory \n\n Conflict theories are often applied to inequalities of gender, social class, education, race, and ethnicity. A conflict theory perspective of U.S. history would examine the numerous past and current struggles between the white ruling class and racial and ethnic minorities, noting specific conflicts that have arisen when the dominant group perceived a threat from the minority group. In the late 19th century, the rising power of black Americans after the Civil War resulted in draconian Jim Crow laws that severely limited black political and social power. The years since then have showed a pattern of attempted disenfranchisement, with gerrymandering and voter suppression efforts aimed at predominantly minority neighborhoods. \n\n Feminist sociologist Patricia Hill Collins (1990) developed intersection theory , which suggests we cannot separate the effects of race, class, gender, sexual orientation, and other attributes. When we examine race and how it can bring us both advantages and disadvantages, it is important to acknowledge that the way we experience race is shaped, for example, by our gender and class. Multiple layers of disadvantage intersect to create the way we experience race. For example, if we want to understand prejudice, we must understand that the prejudice focused on a white woman because of her gender is very different from the layered prejudice focused on a poor Asian woman, who is affected by stereotypes related to being poor, being a woman, and her ethnic status. \n\n Interactionism \n\n For symbolic interactionists, race and ethnicity provide strong symbols as sources of identity. In fact, some interactionists propose that the symbols of race, not race itself, are what lead to racism. Famed Interactionist Herbert Blumer (1958) suggested that racial prejudice is formed through interactions between members of the dominant group: Without these interactions, individuals in the dominant group would not hold racist views. These interactions contribute to an abstract picture of the subordinate group that allows the dominant group to support its view of the subordinate group, thus maintaining the status quo. An example of this might be an individual whose beliefs about a particular group are based on images conveyed in popular media, and those are unquestionably believed because the individual has never personally met a member of that group. \n\n Culture of Prejudice \n\n Culture of prejudice refers to the theory that prejudice is embedded in our culture. We grow up surrounded by images of stereotypes and casual expressions of racism and prejudice. Consider the casually racist imagery on grocery store shelves or the stereotypes that fill popular movies and advertisements. It is easy to see how someone living in the Northeastern United States, who may know no Mexican Americans personally, might gain a stereotyped impression from such sources as Speedy Gonzalez or Taco Bell’s talking Chihuahua. Because we are all exposed to these images and thoughts, it is impossible to know to what extent they have influenced our thought processes. \n11.4 Intergroup Relationships \n\n Intergroup relations (relationships between different groups of people) range along a spectrum between tolerance and intolerance. The most tolerant form of intergroup relations is pluralism, in which no distinction is made between minority and majority groups, but instead there’s equal standing. At the other end of the continuum are amalgamation, expulsion, and even genocide—stark examples of intolerant intergroup relations. \n\n Genocide \n\n Genocide , the deliberate annihilation of a targeted (usually subordinate) group, is the most toxic intergroup relationship. Historically, we can see that genocide has included both the intent to exterminate a group and the function of exterminating of a group, intentional or not. \n\n Possibly the most well-known case of genocide is Hitler’s attempt to exterminate the Jewish people in the first part of the 20th century. Also known as the Holocaust, the explicit goal of Hitler’s “Final Solution” was the eradication of European Jewry, as well as the decimation of other minority groups such as Catholics, people with disabilities, and homosexuals. With forced emigration, concentration camps, and mass executions in gas chambers, Hitler’s Nazi regime was responsible for the deaths of 12 million people, six million of whom were Jewish. Hitler’s intent was clear, and the high Jewish death toll certainly indicates that Hitler and his regime committed genocide. But how do we understand genocide that is not so overt and deliberate? \n\n During the European colonization of the United States, some historians estimate that Native American populations dwindled from approximately 12 million people in the year 1500 to barely 237,000 Native Americans by the year 1900 (Lewy 2004). European settlers coerced American Indians off their own lands, often causing thousands of deaths in forced removals, such as occurred in the Cherokee or Potawatomi Trail of Tears. Settlers also enslaved Native Americans and forced them to give up their religious and cultural practices. But the major cause of Native American death was neither slavery nor war nor forced removal: it was the introduction of European diseases and Indians’ lack of immunity to them. Smallpox, diphtheria, and measles flourished among indigenous American tribes who had no exposure to the diseases and no ability to fight them. Quite simply, these diseases decimated the tribes. How planned this genocide was remains a topic of contention. Some argue that the spread of disease was an unintended effect of conquest, while others believe it was intentional with rumors of smallpox-infected blankets being distributed as “gifts” to tribes. \n\n Importantly, genocide is not a just a historical concept, but one practiced today. Recently, ethnic and geographic conflicts in the Darfur region of Sudan have led to hundreds of thousands of deaths. As part of an ongoing land conflict, the Sudanese government and their state-sponsored Janjaweed militia have led a campaign of killing, forced displacement, and systematic rape of Darfuri people. Although a treaty was signed in 2011, the peace is fragile and may break under pressure. \n\n Expulsion \n\n Expulsion refers to a subordinate group being forced, by a dominant group, to leave a certain area or country. As seen in the examples of the Trail of Tears and the Holocaust, expulsion can be a factor in genocide. However, it can also stand on its own as a destructive group interaction. Expulsion has often occurred historically with an ethnic or racial basis. In the United States, President Franklin D. Roosevelt issued Executive Order 9066 in 1942, after the Japanese government’s attack on Pearl Harbor. The Order authorized the establishment of internment camps for anyone with as little as one-eighth Japanese ancestry (i.e., one great-grandparent who was Japanese). Over 120,000 legal Japanese residents and Japanese American citizens, many of them children, were held in these camps for up to four years, despite the fact that there was never any evidence of collusion or espionage. (In fact, many Japanese Americans continued to demonstrate their loyalty to the United States by serving in the American military during the War.) In the 1990s, the U.S. executive branch issued a formal apology for this expulsion; reparation efforts continue today. \n\n Segregation \n\n Segregation refers to the physical separation of two groups, particularly in residence, but also in workplace and social functions. It is important to distinguish between de jure segregation (segregation that is enforced by law) and de facto segregation (segregation that occurs without laws but because of other factors). A stark example of de jure segregation is the apartheid movement of South Africa, which existed from 1948 to 1994. Under apartheid, black South Africans were stripped of their civil rights and forcibly relocated to areas that segregated them physically from their white compatriots. Only after decades of degradation, violent uprisings, and international advocacy was apartheid finally abolished. \n\n De jure segregation occurred in the United States for many years after the Civil War. During this time, many former Confederate states passed “Jim Crow” laws that required segregated facilities for blacks and whites. These laws were codified in 1896’s landmark Supreme Court case Plessey v. Ferguson , which stated that “separate but equal” facilities were constitutional. For the next five decades, blacks were subjected to legalized discrimination, forced to live, work, and go to school in separate—but unequal —facilities. It wasn’t until 1954 and the Brown v. Board of Education case that the Supreme Court declared that “separate educational facilities are inherently unequal,” thus ending de jure segregation in the United States. \n\n De facto segregation, however, cannot be abolished by any court mandate. Segregation is still alive and well in the United States, with different racial or ethnic groups often segregated by neighborhood, borough, or parish. Sociologists use segregation indices to measure racial segregation of different races in different areas. The indices employ a scale from zero to 100, where zero is the most integrated and 100 is the least. In the New York metropolitan area, for instance, the black-white segregation index was 79 for the years 2005–2009. This means that 79 percent of either blacks or whites would have to move in order for each neighborhood to have the same racial balance as the whole metro region (Population Studies Center 2010). \n\n Pluralism \n\n Pluralism is represented by the ideal of the United States as a “salad bowl”: a great mixture of different cultures where each culture retains its own identity and yet adds to the flavor of the whole. True pluralism is characterized by mutual respect on the part of all cultures, both dominant and subordinate, creating a multicultural environment of acceptance. In reality, true pluralism is a difficult goal to reach. In the United States, the mutual respect required by pluralism is often missing, and the nation’s past pluralist model of a melting pot posits a society where cultural differences aren’t embraced as much as erased. \n\n Assimilation \n\n Assimilation describes the process by which a minority individual or group gives up its own identity by taking on the characteristics of the dominant culture. In the United States, which has a history of welcoming and absorbing immigrants from different lands, assimilation has been a function of immigration. \n\n Most Americans have immigrant ancestors. In relatively recent history, between 1890 and 1920, the United States became home to around 24 million immigrants. In the decades since then, further waves of immigrants have come to these shores and have eventually been absorbed into American culture, sometimes after facing extended periods of prejudice and discrimination. Assimilation may lead to the loss of the minority group’s cultural identity as they become absorbed into the dominant culture, but assimilation has minimal to no impact on the majority group’s cultural identity. Some groups may keep only symbolic gestures of their original ethnicity. For instance, many Irish Americans may celebrate Saint Patrick’s Day, many Hindu Americans enjoy a Diwali festival, and many Mexican Americans may celebrate Cinco de Mayo (a May 5th commemoration of Mexican independence and heritage). However, for the rest of the year, other aspects of their originating culture may be forgotten. \n\n Assimilation is antithetical to the “salad bowl” created by pluralism; rather than maintaining their own cultural flavor, subordinate cultures give up their own traditions in order to conform to their new environment. Sociologists measure the degree to which immigrants have assimilated to a new culture with four benchmarks: socioeconomic status, spatial concentration, language assimilation, and intermarriage. When faced with racial and ethnic discrimination, it can be difficult for new immigrants to fully assimilate. Language assimilation, in particular, can be a formidable barrier, limiting employment and educational options and therefore constraining growth in socioeconomic status. \n\n Amalgamation \n\n Amalgamation is the process by which a minority group and a majority group combine to form a new group. Amalgamation creates the classic “melting pot” analogy; unlike the “salad bowl,” in which each culture retains its individuality, the “melting pot” ideal sees the combination of cultures resulting in a new culture entirely. \n\n Amalgamation, also known as miscegenation, is achieved through intermarriage between races. In the United States, anti-miscegenation laws flourished in the South during the Jim Crow era. It wasn’t until 1967’s Loving v. Virginia that the last antimiscegenation law was struck from the books, making these laws unconstitutional. \n11.5 Race and Ethnicity in the United States \n\n When colonists came to the New World, they found a land that did not need “discovering” since it was already occupied. While the first wave of immigrants came from Western Europe, eventually the bulk of people entering North America were from Northern Europe, then Eastern Europe, then Latin America and Asia. And let us not forget the forced immigration of African slaves. Most of these groups underwent a period of disenfranchisement in which they were relegated to the bottom of the social hierarchy before they managed (for those who could) to achieve social mobility. Today, our society is multicultural, although the extent to which this multiculturality is embraced varies, and the many manifestations of multiculturalism carry significant political repercussions. The sections below will describe how several groups became part of American society, discuss the history of intergroup relations for each faction, and assess each group’s status today. \n\n Native Americans \n\n The only nonimmigrant ethnic group in the United States, Native Americans were once a large population but by 2010 made up only 0.9 percent of U.S. populace (U.S. Census 2010). \n\n Sociology in the Real World Sports Teams with Native American Names The sports world abounds with team names like the Indians, the Warriors, the Braves, and even the Savages and Redskins. These names arise from historically prejudiced views of Native Americans as fierce, brave, and strong savages: attributes that would be beneficial to a sports team, but are not necessarily beneficial to Americans who should be seen as more than just fierce savages. \n\n Since the civil rights movement of the 1960s, the National Congress of American Indians (NCAI) has been campaigning against the use of such mascots, asserting that the “warrior savage myth . . . reinforces the racist view that Indians are uncivilized and uneducated and it has been used to justify policies of forced assimilation and destruction of Indian culture” (NCAI Resolution #TUL-05-087 2005). The campaign has met with only limited success. While some teams have changed their names, hundreds of professional, college, and K–12 school teams still have names derived from this stereotype. Another group, American Indian Cultural Support (AICS), is especially concerned with such names at K-12 schools, grades where children should be gaining a fuller and more realistic understanding of Native Americans than such stereotypes supply. \n\n What do you think about such names? Should they be allowed or banned? What argument would a symbolic interactionist make on this topic? \n\n How and Why They Came \n\n The earliest immigrants to America arrived millennia before European immigrants. Dates of the migration are debated with estimates ranging from between 45,000 and 12,000 BCE. It is thought that early Indians migrated to this new land in search of big game to hunt, which they found in huge herds of grazing herbivores in the Americas. Over the centuries and then the millennia, Native American culture blossomed into an intricate web of hundreds of interconnected tribes, each with its own customs, traditions, languages, and religions. \n\n History of Intergroup Relations \n\n Native American culture prior to European settlement is referred to as Pre-Columbian: that is, prior to the coming of Christopher Columbus in 1492. Mistakenly believing that he had landed in the East Indies, Columbus named the indigenous people “Indians:” a name that has persisted for centuries despite it being a geographical misnomer used to homogenously label over 500 distinct people groups who have their own languages and traditions. \n\n The history of intergroup relations between European colonists and Native Americans is a brutal one that most Americans are familiar with. As discussed in the section on genocide, the effect of European settlement of the Americans was to nearly destroy the indigenous population. And although Native Americans’ lack of immunity to European diseases caused the most deaths, overt mistreatment of Native Americans by Europeans was equally devastating. \n\n From the first Spanish colonists to the French, English, and Dutch who followed, European settlers took what land they wanted, expanding across the continent at will. If indigenous people tried to retain their stewardship of the land, Europeans fought them off with superior weapons. A key element of this issue is the indigenous view of land and land ownership. Most tribes considered the earth a living entity whose resources they were stewards of, the concepts of land ownership and conquest didn’t exist in Native American society. Europeans’ domination of the Americas was indeed a conquest; one scholar points out that Native Americans are the only minority group in the United States whose subordination occurred purely through conquest by the dominant group (Marger 1993). \n\n After the establishment of the United States government, discrimination against Native Americans was codified and formalized in a series of laws intended to subjugate them and keep them from gaining any power. Some of the most impactful laws are as follows: \n\n The Indian Removal Act of 1930 forced the relocation of any native tribes east of the Mississippi River to lands west of the river. \n\n The Indian Appropriation Acts funded further removals and declared that no Indian tribe could be recognized as an independent nation, tribe, or power with which the American government would have to make treaties. This made it even easier for the U.S. government to take land it wanted. \n\n The Dawes Act of 1887 reversed the policy of isolating Native Americans on reservations, instead forcing them onto individual properties that were intermingled with white settlers, thereby reducing their capacity for power as a group. \n\n Native American culture was further eroded by the establishment of Indian boarding schools in the late 19th century. These schools, run by both Christian missionaries and the United States government, had the express purpose of “civilizing” Native American children and assimilating them into white society. The boarding schools were located off-reservation to ensure that children were separated from their families and culture. Schools forced children to cut their hair, speak English, and practice Christianity. Physical and sexual abuses were rampant for decades; only in 1987 did the Bureau of Indian Affairs issue a policy on sexual abuse in boarding schools. Some scholars argue that many of the problems that Native Americans face today result from almost a century of mistreatment at these boarding schools. \n\n Current Status \n\n The eradication of Native American culture continued until the 1960s, when Native Americans were able to participate in and benefit from the civil rights movement. The Indian Civil Rights Act of 1968 guaranteed Indian tribes most of the rights of the United States Bill of Rights. New laws like the Indian Self-Determination Act of 1975 and the Education Assistance Act of the same year recognized tribal governments and gave them more power. Indian boarding schools have dwindled to only a few, and Native American cultural groups are striving to preserve and maintain old traditions to keep them from being lost forever. \n\n However, Native Americans (some of whom now wished to be called American Indians so as to avoid the “savage” connotations of the term “native”) still suffer the effects of centuries of degradation. Long-term poverty, inadequate education, cultural dislocation, and high rates of unemployment contribute to Native American populations falling to the bottom of the economic spectrum. Native Americans also suffer disproportionately with lower life expectancies than most groups in the United States. \n\n African Americans \n\n As discussed in the section on race, the term African American can be a misnomer for many individuals. Many people with dark skin may have their more recent roots in Europe or the Caribbean, seeing themselves as Dominican American or Dutch American. Further, actual immigrants from Africa may feel that they have more of a claim to the term African American than those who are many generations removed from ancestors who originally came to this country. This section will focus on the experience of the slaves who were transported from Africa to the United States, and their progeny. \n\n How and Why They Came \n\n If Native Americans are the only minority group whose subordinate status occurred by conquest, African Americans are the exemplar minority group in the United States whose ancestors did not come here by choice. A Dutch sea captain brought the first Africans to the Virginia colony of Jamestown in 1619 and sold them as indentured servants. This was not an uncommon practice for either blacks or whites, and indentured servants were in high demand. For the next century, black and white indentured servants worked side by side. But the growing agricultural economy demanded greater and cheaper labor, and by 1705, Virginia passed the slave codes declaring that any foreign-born non-Christian could be a slave, and that slaves were considered property. \n\n The next 150 years saw the rise of American slavery, with black Africans being kidnapped from their own lands and shipped to the New World on the trans-Atlantic journey known as the Middle Passage. Once in the Americas, the black population grew until American-born blacks outnumbered those born in Africa. But colonial (and later, American) slave codes declared that the child of a slave was a slave, so the slave class was created. By 1869, the slave trade was internal in the United States, with slaves being bought and sold across state lines like livestock. \n\n History of Intergroup Relations \n\n There is no starker illustration of the dominant-subordinate group relationship than that of slavery. In order to justify their severely discriminatory behavior, slaveholders and their supporters had to view blacks as innately inferior. Slaves were denied even the most basic rights of citizenship, a crucial factor for slaveholders and their supporters. Slavery poses an excellent example of conflict theory’s perspective on race relations; the dominant group needed complete control over the subordinate group in order to maintain its power. Whippings, executions, rapes, denial of schooling and health care were all permissible and widely practiced. \n\n Slavery eventually became an issue over which the nation divided into geographically and ideologically distinct factions, leading to the Civil War. And while the abolition of slavery on moral grounds was certainly a catalyst to war, it was not the only driving force. Students of American history will know that the institution of slavery was crucial to the Southern economy, whose production of crops like rice, cotton, and tobacco relied on the virtually limitless and cheap labor that slavery provided. In contrast, the North didn’t benefit economically from slavery, resulting in an economic disparity tied to racial/political issues. \n\n A century later, the civil rights movement was characterized by boycotts, marches, sit-ins, and freedom rides: demonstrations by a subordinate group that would no longer willingly submit to domination. The major blow to America’s formally institutionalized racism was the Civil Rights Act of 1964. This Act, which is still followed today, banned discrimination based on race, color, religion, sex, or national origin. Some sociologists, however, would argue that institutionalized racism persists. \n\n Current Status \n\n Although government-sponsored, formalized discrimination against African Americans has been outlawed, true equality does not yet exist. The National Urban League’s 2011 Equality Index reports that blacks’ overall equality level with whites has dropped in the past year, from 71.5 percent to 71.1 percent in 2010. The Index , which has been published since 2005, notes a growing trend of increased inequality with whites, especially in the areas of unemployment, insurance coverage, and incarceration. Blacks also trail whites considerably in the areas of economics, health, and education. \n\n To what degree do racism and prejudice contribute to this continued inequality? The answer is complex. 2008 saw the election of this country’s first African American president: Barack Hussein Obama. Despite being popularly identified as black, we should note that President Obama is of a mixed background that is equally white, and although all presidents have been publicly mocked at times (Gerald Ford was depicted as a klutz, Bill Clinton as someone who could not control his libido), a startling percentage of the critiques of Obama have been based on his race. The most blatant of these was the controversy over his birth certificate, where the “birther” movement questioned his citizenship and right to hold office. Although blacks have come a long way from slavery, the echoes of centuries of disempowerment are still evident. \n\n Asian Americans \n\n Like many groups this section discusses, Asian Americans represent a great diversity of cultures and backgrounds. The experience of a Japanese American whose family has been in the United States for three generations will be drastically different from a Laotian American who has only been in the U.S. for a few years. This section primarily discusses Chinese, Japanese, and Vietnamese immigrants and shows the differences between their experiences. \n\n How and Why They Came \n\n The national and ethnic diversity of Asian American immigration history is reflected in the variety of their experiences in joining American society. Asian immigrants have come to the United States in waves, at different times, and for different reasons. \n\n The first Asian immigrants to come to the United States in the mid-19th century were Chinese. These immigrants were primarily men whose intention was to work for several years in order to earn incomes to support their families in China. Their main destination was the American West, where the Gold Rush was drawing people with its lure of abundant money. The construction of the Transcontinental Railroad was underway at this time, and the Central Pacific section hired thousands of migrant Chinese men to complete the laying of rails across the rugged Sierra Nevada mountain range. Chinese men also engaged in other manual labor like mining and agricultural work. The work was grueling and underpaid, but like many immigrants, they persevered. \n\n Japanese immigration began in the 1880s, on the heels of the Chinese Exclusion Act of 1882. Many Japanese immigrants came to Hawaii to participate in the sugar industry; others came to the mainland, especially to California. Unlike the Chinese, however, the Japanese had a strong government that negotiated with the United States government to ensure the well-being of their immigrants. Japanese men were able to bring their wives and families to the United States, and were thus able to produce second- and third-generation Japanese Americans more quickly than their Chinese counterparts. \n\n The most recent large-scale Asian immigration came from Korea and Vietnam and largely took place during the second half of the 20th century. While Korean immigration has been fairly gradual, Vietnamese immigration occurred primarily post-1975, after the fall of Saigon and the establishment of restrictive communist policies in Vietnam. Whereas many Asian immigrants came to the United States to seek better economic opportunities, Vietnamese immigrants came as political refugees, seeking asylum from harsh conditions in their homeland. The Refugee Act of 1980 helped them to find a place to settle in the United States. \n\n History of Intergroup Relations \n\n Chinese immigration came to an abrupt end with the Chinese Exclusion Act of 1882. This act was a result of anti-Chinese sentiment burgeoned by a depressed economy and loss of jobs. White workers blamed Chinese migrants for taking jobs, and the passage of the Act meant the number of Chinese workers decreased. Chinese men did not have the funds to return to China or to bring their families to America, so they remained physically and culturally segregated in the Chinatowns of large cities. Later legislation, the Immigration Act of 1924, further curtailed Chinese immigration. The Act included the race-based National Origins Act, which was aimed at keeping American ethnic stock as undiluted as possible by reducing “undesirable” immigrants. It was not until after the Immigration and Nationality Act of 1965 that Chinese immigration again increased and many Chinese families were reunited. \n\n Although Japanese Americans have deep, long-reaching roots in the U.S., their history here has not always been smooth. The California Alien Land Law of 1913 was aimed at them and other Asian immigrants, and it prohibited aliens from owning land. An even uglier action was the Japanese internment camps of World War II, discussed earlier as an illustration of expulsion. \n\n Current Status \n\n Asian Americans certainly have been subject to their share of racial prejudice, despite the seemingly positive stereotype as the model minority. The model minority stereotype is applied to a minority group that is seen as reaching significant educational, professional, and socioeconomic levels without challenging the existing establishment. \n\n This stereotype is typically applied to Asian groups in the United States, and it can result in unrealistic expectations, putting a stigma on members of this group that do not meet the expectations. Stereotyping all Asians as smart and capable can also lead to a lack of much-needed government assistance and to educational and professional discrimination. \n\n Hispanic Americans \n\n Like the individuals comprising many “groups,” Hispanic Americans have a wide range of backgrounds and nationalities. According to the 2010 U.S. Census, about 75 percent of the respondents who identify as Hispanic report being of Mexican, Puerto Rican, or Cuban origin. Of the total Hispanic group, 60 percent reported as Mexican, 44 percent reported as Cuban, and nine percent reported as Puerto Rican. Remember that the U.S. Census allows people to report as being more than one ethnicity. \n\n Not only are there wide differences among the different origins that make up the Hispanic American population, there are also different names for the group itself. The 2010 U.S. Census states that “Hispanic” or “Latino” refers to a person of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin regardless of race.” There have been some disagreements over whether Hispanic or Latino is the correct term for a group this diverse, and whether it would be better for people to refer to themselves as being of their origin specifically, for example, Mexican American or Dominican American. This section will compare the experiences of Mexican Americans and Cuban Americans. \n\n How and Why They Came \n\n Mexican Americans form the largest Hispanic subgroup and also the oldest. Mexican migration to the United States started in the early 1900s in response to the need for cheap agricultural labor. Mexican migration was often circular; workers would stay for a few years, and then go back to Mexico with more money than they could have made in their country of origin. The length of Mexico’s shared border with the United States has made immigration easier than for many other immigrant groups. \n\n Cuban Americans are the second-largest Hispanic subgroup, and their history is quite different from that of Mexican Americans. The main wave of Cuban immigration to the United States started after Fidel Castro came to power in 1959 and reached its crest with the Mariel boatlift in 1980. Castro’s Cuban Revolution ushered in an era of communism that continues to this day. To avoid having their assets seized by the government, many wealthy and educated Cubans migrated north, generally to the Miami area. \n\n History of Intergroup Relations \n\n For several decades, Mexican workers crossed the long border into America, both legally and illegally, to work in the fields that provided produce for the developing United States. Western growers needed a steady supply of labor, and the 1940s and 1950s saw the official federal Bracero Program ( bracero is Spanish for strong-arm ) that offered protection to Mexican guest workers. Interestingly, 1954 also saw the enactment of “Operation Wetback,” which deported thousands of illegal Mexican workers. From these examples, we can see that the U.S. treatment of immigration from Mexico has been ambivalent at best. \n\n Sociologist Douglas Massey (2006) suggests that although the average standard of living in Mexico may be lower in the United States, it is not so low as to make permanent migration the goal of most Mexicans. However, the strengthening of the border that began with 1986’s Immigration Reform and Control Act has made one-way migration the rule for most Mexicans. Massey argues that the rise of illegal one-way immigration of Mexicans is a direct outcome of the law that was intended to reduce it. \n\n Cuban Americans, perhaps because of their relative wealth and education level at the time of immigration, have fared better than many immigrants. Further, because they were fleeing a Communist country, they were given refugee status and offered protection and social services. The Cuban Migration Agreement of 1995 has curtailed legal immigration from Cuba, leading many Cubans to try to immigrate illegally by boat. According to a 2009 report from the Congressional Research Service, the U.S. government applies a “wet foot/dry foot” policy toward Cuban immigrants; Cubans who are intercepted while still at sea will be returned to Cuba, while those who reach the shore will be permitted to stay in the United States. \n\n Current Status \n\n Mexican Americans, especially those who are here illegally, are at the center of a national debate about immigration. Myers (2007) observes that no other minority group (except the Chinese) has immigrated to the United States in such an environment of illegality. He notes that in some years, three times as many Mexican immigrants may have entered the United States illegally as those who arrived legally. It should be noted that this is due to enormous disparity of economic opportunity on two sides of an open border, not because of any inherent inclination to break laws. In his report, “Measuring Immigrant Assimilation in the United States,” Jacob Vigdor (2008) states that Mexican immigrants experience relatively low rates of economic and civil assimilation. He further suggests that “the slow rates of economic and civic assimilation set Mexicans apart from other immigrants, and may reflect the fact that the large numbers of Mexican immigrants residing in the United States illegally have few opportunities to advance themselves along these dimensions.” \n\n By contrast, Cuban Americans are often seen as a model minority group within the larger Hispanic group. Many Cubans had higher socioeconomic status when they arrived in this country, and their anti-Communist agenda has made them welcome refugees to this country. In south Florida, especially, Cuban Americans are active in local politics and professional life. As with Asian Americans, however, being a model minority can mask the issue of powerlessness that these minority groups face in U.S. society. \n\n Social Policy and Debate Arizona’s Senate Bill 1070 As both legal and illegal immigrants, and with high population numbers, Mexican Americans are often the target of stereotyping, racism, and discrimination. A harsh example of this is in Arizona, where a new stringent immigration law—known as SB 1070 (for Senate Bill 1070)—has caused a nationwide controversy. The law requires that during a lawful stop, detention, or arrest, Arizona police officers must establish the immigration status of anyone they suspect may be here illegally. The law makes it a crime for individuals to fail to have documents confirming their legal status, and it gives police officers the right to detain people they suspect may be in the country illegally. \n\n To many, the most troublesome aspect of this law is the latitude it affords police officers in terms of whose citizenship they may question. Having “reasonable suspicion that the person is an alien who is unlawfully present in the United States” is reason enough to demand immigration papers (Senate Bill 1070 2010). Critics say this law will encourage racial profiling (the illegal practice of law enforcement using race as a basis for suspecting someone of a crime), making it hazardous to be caught “Driving While Brown,” a takeoff on the legal term Driving While Intoxicated (DWI) or the slang reference of “Driving While Black.” Driving While Brown refers to the likelihood of getting pulled over just for being nonwhite. \n\n SB 1070 has been the subject of many lawsuits, from parties as diverse as Arizona police officers, the American Civil Liberties Union, and even the federal government, which is suing on the basis of Arizona contradicting federal immigration laws (ACLU 2011). The future of SB 1070 is uncertain, but many other states have tried or are trying to pass similar measures. Do you think such measures are appropriate? \n\n Arab Americans \n\n If ever a category was hard to define, the various groups lumped under the name “Arab American” is it. After all, Hispanic Americans or Asian Americans are so designated because of their counties of origin. But for Arab Americans, their country of origin—Arabia—has not existed for centuries. In addition, Arab Americans represent all religious practices, despite there being a stereotype of them as Islamic. As Myers (2007) asserts, not all Arabs are Muslim, and not all Muslims are Arab, complicating the stereotype of what it means to be an Arab American. Geographically, the Arab region comprises the Middle East and parts of northern Africa. People whose ancestry lies in that area or who speak primarily Arabic may consider themselves Arabs. \n\n The U.S. Census has struggled with the issue of Arab identity. The 2010 Census, as in previous years, did not offer an “Arab” box to check under the question of race. Individuals who want to be counted as Arabs had to check the box for “Some other race” and then write in their race. However, when the Census data is tallied, they will be marked as white. This is problematic, however, denying Arab Americans opportunities for federal assistance. \n\n Why They Came \n\n The first Arab immigrants came to this country in the late 19th and early 20th century. They were predominantly Syrian, Lebanese, and Jordanian Christians, and they came to escape persecution and to make a better life. These early immigrants and their descendants, who were more likely to think of themselves as Syrian or Lebanese than Arab, represent almost half of the Arab American population today (Myers 2007). Restrictive immigration policies from the 1920s until 1965 curtailed all immigration, but Arab immigration since 1965 has been steady. Immigrants from this time period have been more likely to be Muslim and more highly educated, escaping political unrest and looking for better opportunities. \n\n History of Intergroup Relations Relations between Arab Americans and the dominant majority have been marked by mistrust, misinformation, and deeply entrenched beliefs. Helen Samhan of the Arab American Institute suggests that Arab-Israeli conflicts in the 1970s contributed significantly to cultural and political anti-Arab sentiment in the United States (2001). The United States has historically supported the State of Israel, while some Middle Eastern countries deny the existence of the Israeli state. Disputes over these issues have involved Egypt, Syria, Iraq, Jordan, Lebanon, and Palestine. \n\n As is often the case with stereotyping and prejudice, the actions of extremists come to define the entire group, regardless of the fact that most U.S. citizens with ties to the Middle Eastern community condemn terrorist actions, as do most inhabitants of the Middle East. Would it be fair to judge all Catholics by the events of the Inquisition? Of course, the United States was deeply affected by the events of September 11, 2001. This event has left a deep scar on the American psyche, and it has fortified anti-Arab sentiment for a large percentage of Americans. In the first month after 9/11, hundreds of hate crimes were perpetrated against people who looked like they might be of Arab descent. \n\n Current Status \n\n Although the rate of hate crimes against Arab Americans has slowed, Arab Americans are still victims of racism and prejudice. Racial profiling has proceeded against Arab Americans as a matter of course since 9/11. Particularly when engaged in air travel, being young and Arab-looking is enough to warrant a special search or detainment. This Islamophobia (irrational fear of or hatred against Muslims) does not show signs of abating. Scholars noted that white domestic terrorists like Timothy McVeigh, who detonated a bomb at an Oklahoma courthouse in 1995, have not inspired similar racial profiling or hate crimes against whites. \n\n White Ethnic Americans \n\n As we have seen, there is no minority group that fits easily in a category or that can be described simply. While sociologists believe that individual experiences can often be understood in light of their social characteristics (such as race, class, or gender), we must balance this perspective with awareness that no two individuals’ experiences are alike. Making generalizations can lead to stereotypes and prejudice. The same is true for white ethnic Americans, who come from diverse backgrounds and have had a great variety of experiences. In this section, we will focus on German, Irish, Italian, and Eastern European immigrants. \n\n Why They Came \n\n White ethnic Europeans formed the second and third great waves of immigration, from the early 19th century to the mid-20th century. They joined a newly minted United States that was primarily made up of white Protestants from England. While most immigrants came searching for a better life, their experiences were not all the same. \n\n The first major influx of European immigrants came from Germany and Ireland, starting in the 1820s. Germans came both for economic opportunity and to escape political unrest and military conscription, especially after the Revolutions of 1848. Many German immigrants of this period were political refugees: liberals who wanted to escape from an oppressive government. They were well-off enough to make their way inland, and they formed heavily German enclaves in the Midwest that exist to this day. \n\n The Irish immigrants of the same time period were not always as well off financially, especially after the Irish Potato Famine of 1845. Irish immigrants settled mainly in the cities of the East Coast, where they were employed as laborers and where they faced significant discrimination. German and Irish immigration continued into the late 19th century and earlier 20th century, at which point the numbers for Southern and Eastern European immigrants started growing as well. Italians, mainly from the Southern part of the country, began arriving in large numbers in the 1890s. Eastern European immigrants—people from Russia, Poland, Bulgaria, and Austria-Hungary—started arriving around the same time. Many of these Eastern Europeans were peasants forced into a hardscrabble existence in their native lands; political unrest, land shortages, and crop failures drove them to seek better opportunities in the United States. The Eastern European immigration wave also included Jewish people escaping pogroms (anti-Jewish uprisings) of Eastern Europe and the Pale of Settlement in what was then Poland and Russia. \n\n History of Intergroup Relations \n\n In a broad sense, German immigrants were not victimized to the same degree as many of the other subordinate groups this section discusses. While they may not have been welcomed with open arms, they were able to settle in enclaves and establish roots. A notable exception to this was during the lead up to World War I and through World War II, when anti-German sentiment was virulent. \n\n Irish immigrants, many of whom were very poor, were more of an underclass than the Germans. In Ireland, the English had oppressed the Irish for centuries, eradicating their language and culture and discriminating against their religion (Catholicism). Although the Irish had a larger population than the English, they were a subordinate group. This dynamic reached into the new world, where Anglo Americans saw Irish immigrants as a race apart: dirty, lacking ambition, and suitable for only the most menial jobs. In fact, Irish immigrants were subject to criticism identical to that with which the dominant group characterized African Americans. By necessity, Irish immigrants formed tight communities segregated from their Anglo neighbors. \n\n The later wave of immigrants from Southern and Eastern Europe was also subject to intense discrimination and prejudice. In particular, the dominant group—which now included second- and third-generation Germans and Irish—saw Italian immigrants as the dregs of Europe and worried about the purity of the American race (Myers 2007). Italian immigrants lived in segregated slums in Northeastern cities, and in some cases were even victims of violence and lynchings similar to what African Americans endured. They worked harder and were paid less than other workers, often doing the dangerous work that other laborers were reluctant to take on. \n\n Current Status \n\n The U.S. Census from 2008 shows that 16.5 percent of respondents reported being of German descent: the largest group in the country. For many years, German Americans endeavored to maintain a strong cultural identity, but they are now culturally assimilated into the dominant culture. \n\n There are now more Irish Americans in the United States than there are Irish in Ireland. One of the country’s largest cultural groups, Irish Americans have slowly achieved acceptance and assimilation into the dominant group. \n\n Myers (2007) states that Italian Americans’ cultural assimilation is “almost complete, but with remnants of ethnicity.” The presence of “Little Italy” neighborhoods—originally segregated slums where Italians congregated in the 19th century—exist today. While tourists flock to the saints’ festivals in Little Italies, most Italian Americans have moved to the suburbs at the same rate as other white groups. "}}},{"rowIdx":181,"cells":{"bname":{"kind":"string","value":"introduction_to_sociology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":""},"intro":{"kind":"string","value":"Learning Objectives 7.1 Deviance and Control \n\n Define deviance and explain the nature of deviant behavior \n\n Differentiate between methods of social control \n\n 7.2 Theoretical Perspectives on Deviance \n\n Describe the functionalist view of deviance in society through four sociologist’s theories \n\n Explain how conflict theory understands deviance and crime in society \n\n Describe the symbolic interactionist approach to deviance, including labeling and other theories \n\n 7.3 Crime and the Law \n\n Identify and differentiate between different types of crimes \n\n Evaluate U.S. crime statistics \n\n Understand the three branches of the U.S. criminal justice system \n\n Introduction to Deviance, Crime, and Social Control \n\n Philip Hudson entered Morehouse College at age 19 wearing men’s jeans and long hair tied back in dreadlocks. “The first day I got to campus, I was a boy,” Philip recalled a few years later. He said he was “trying to be this masculine boy, real cool and real quiet.” By the end of his sophomore year, Philip had swapped his jeans for skirts and found himself the target of a strong backlash (King 2010). Morehouse College made national news for its response to the teen’s lifestyle, establishing a schoolwide ban on the wearing of women’s clothing by men (Chen 2010). \n\n Morehouse College, an all-male college in Atlanta, Georgia, has a prestigious history. Established in 1867 as a place of higher learning for former slaves, Morehouse is the alma mater of great leaders such as “Dr. Martin Luther King, Jr. and Howard Thurman, and celebrities such as Samuel L. Jackson and Spike Lee” (Mungin 2009). The sense of revolution is what brought Philip to Morehouse, a place where he hoped he could be himself. \n\n After a difficult upbringing where his gendered-ness resulted in abuse and rape, he realized that he identified as a female and wanted to express that aspect of his person. He began taking female hormones to start his biological transition to the female sex. Although Philip initially halted his treatment once he began college, he soon found others like himself. At Morehouse, he met Diamond Poulin, a student who defined himself as a man who felt comfortable in women’s clothes. Joined by a handful of others, Philip and Diamond donned skirts, high heels, and other traditionally female attire on campus in an attempt to be themselves. They were jeered at and ridiculed—even attacked. \n\n Then came the school’s shocking decision in late 2009. The new rules, titled the “Appropriate Attire Policy,” banned cross-dressing anywhere on the campus grounds. Those who broke the rules were not allowed to attend class unless they changed their clothing, and multiple transgressions led to disciplinary action and suspension. \n\n Diamond left Morehouse that fall, but returned once in the spring to visit his friends. He found himself escorted off campus by school security for violating the dress code. Philip remained at Morehouse for another year before leaving because of stress. He now plans to resume his studies at a larger university in Florida. What he’s most looking forward to is walking around in public without being verbally attacked. “They’ll stare,” Philip says with resignation, “but I’m used to that” (King 2010). "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":3,"ans_text":"Deviance is socially defined."},"bloom":"1","hl_context":"What , exactly , is deviance ? And what is the relationship between deviance and crime ? <hl> As Philip Hudson found out , some behaviors , such as wearing clothes of the opposite sex , can be deviant in certain places , criminal in some places , and perfectly acceptable elsewhere . <hl> <hl> According to sociologist William Graham Sumner , deviance is a violation of established contextual , cultural , or social norms , whether folkways , mores , or codified law ( 1906 ) . <hl> <hl> It can be as minor as picking one ’ s nose in public or as major as committing murder . <hl> Although the word “ deviance ” has a negative connotation in everyday language , sociologists recognize that deviance is not necessarily bad ( Schoepflin 2011 ) . In fact , from a structural functionalist perspective , one of the positive contributions of deviance is that it fosters social change . For example , during the U . S . civil rights movement , Rosa Parks violated social norms when she refused to move to the “ black section ” of the bus , and the Little Rock Nine broke customs of segregation to attend an Arkansas public school .","hl_sentences":"As Philip Hudson found out , some behaviors , such as wearing clothes of the opposite sex , can be deviant in certain places , criminal in some places , and perfectly acceptable elsewhere . According to sociologist William Graham Sumner , deviance is a violation of established contextual , cultural , or social norms , whether folkways , mores , or codified law ( 1906 ) . It can be as minor as picking one ’ s nose in public or as major as committing murder .","question":{"cloze_format":"Deviance is best described as ___ .","normal_format":"Which of the following best describes how deviance is defined?","question_choices":["Deviance is defined by federal, state, and local laws.","Deviance’s definition is determined by one’s religion.","Deviance occurs whenever someone else is harmed by an action.","Deviance is socially defined."],"question_id":"fs-id1370636","question_text":"Which of the following best describes how deviance is defined?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"An act of deviance"},"bloom":null,"hl_context":"Although deviance is a violation of social norms , it ’ s not always punishable , and it ’ s not necessarily bad . Crime , on the other hand , is a behavior that violates official law and is punishable through formal sanctions . Walking to class backwards is a deviant behavior . Driving with a blood alcohol percentage over the state ’ s limit is a crime . <hl> Like other forms of deviance , however , ambiguity exists concerning what constitutes a crime and whether all crimes are , in fact , “ bad ” and deserve punishment . <hl> <hl> For example , during the 1960s , civil rights activists often violated laws intentionally as part of their effort to bring about racial equality . <hl> <hl> In hindsight , we recognize that the laws that deemed many of their actions crimes — for instance , Rosa Parks taking a seat in the “ whites only ” section of the bus — were inconsistent with social equality . <hl> What , exactly , is deviance ? And what is the relationship between deviance and crime ? As Philip Hudson found out , some behaviors , such as wearing clothes of the opposite sex , can be deviant in certain places , criminal in some places , and perfectly acceptable elsewhere . According to sociologist William Graham Sumner , deviance is a violation of established contextual , cultural , or social norms , whether folkways , mores , or codified law ( 1906 ) . It can be as minor as picking one ’ s nose in public or as major as committing murder . Although the word “ deviance ” has a negative connotation in everyday language , sociologists recognize that deviance is not necessarily bad ( Schoepflin 2011 ) . <hl> In fact , from a structural functionalist perspective , one of the positive contributions of deviance is that it fosters social change . <hl> <hl> For example , during the U . S . civil rights movement , Rosa Parks violated social norms when she refused to move to the “ black section ” of the bus , and the Little Rock Nine broke customs of segregation to attend an Arkansas public school . <hl>","hl_sentences":"Like other forms of deviance , however , ambiguity exists concerning what constitutes a crime and whether all crimes are , in fact , “ bad ” and deserve punishment . For example , during the 1960s , civil rights activists often violated laws intentionally as part of their effort to bring about racial equality . In hindsight , we recognize that the laws that deemed many of their actions crimes — for instance , Rosa Parks taking a seat in the “ whites only ” section of the bus — were inconsistent with social equality . In fact , from a structural functionalist perspective , one of the positive contributions of deviance is that it fosters social change . For example , during the U . S . civil rights movement , Rosa Parks violated social norms when she refused to move to the “ black section ” of the bus , and the Little Rock Nine broke customs of segregation to attend an Arkansas public school .","question":{"cloze_format":"During the civil rights movement, Rosa Parks and other black protestors spoke out against segregation by refusing to sit at the back of the bus. This is an example of ________.","normal_format":"During the civil rights movement, Rosa Parks and other black protestors spoke out against segregation by refusing to sit at the back of the bus. Which is this an example of?","question_choices":["An act of social control","An act of deviance","A social norm","Criminal mores"],"question_id":"fs-id1303155","question_text":"During the civil rights movement, Rosa Parks and other black protestors spoke out against segregation by refusing to sit at the back of the bus. This is an example of ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"formal sanctions"},"bloom":null,"hl_context":"As you learned previously , all societies have informal and formal ways of maintaining social control . <hl> Within these systems of norms , societies have legal codes that maintain formal social control through laws , which are rules adopted and enforced by a political authority . <hl> Those who violate these rules incur negative formal sanctions . Normally , punishments are relative to the degree of the crime and the importance to society of the value underlying the law . As we will see , however , there are other factors that influence criminal sentencing .","hl_sentences":"Within these systems of norms , societies have legal codes that maintain formal social control through laws , which are rules adopted and enforced by a political authority .","question":{"cloze_format":"Societies practice social control to maintain ________.","normal_format":"Societies practice social control to maintain what?","question_choices":["formal sanctions","social order","cultural deviance","sanction labeling"],"question_id":"fs-id3135713","question_text":"Societies practice social control to maintain ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"A senator"},"bloom":"1","hl_context":"<hl> In his book The Power Elite ( 1956 ) , sociologist C . Wright Mills described the existence of what he dubbed the power elite , a small group of wealthy and influential people at the top of society who hold the power and resources . <hl> <hl> Wealthy executives , politicians , celebrities , and military leaders often have access to national and international power , and in some cases , their decisions affect everyone in society . <hl> Because of this , the rules of society are stacked in favor of a privileged few who manipulate them to stay on top . It is these people who decide what is criminal and what is not , and the effects are often felt most by those who have little power . Mills ’ theories explain why celebrities such as Chris Brown and Paris Hilton , or once-powerful politicians such as Eliot Spitzer and Tom DeLay , can commit crimes with little or no legal retribution .","hl_sentences":"In his book The Power Elite ( 1956 ) , sociologist C . Wright Mills described the existence of what he dubbed the power elite , a small group of wealthy and influential people at the top of society who hold the power and resources . Wealthy executives , politicians , celebrities , and military leaders often have access to national and international power , and in some cases , their decisions affect everyone in society .","question":{"cloze_format":"According to C. Wright Mills, the person that is most likely to be a member of the power elite is ___.","normal_format":"According to C. Wright Mills, which of the following people is most likely to be a member of the power elite?","question_choices":["A war veteran","A senator","A professor","A mechanic"],"question_id":"fs-id1366105","question_text":"According to C. Wright Mills, which of the following people is most likely to be a member of the power elite?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A community where neighbors don’t know each other very well"},"bloom":null,"hl_context":"<hl> Developed by researchers at the University of Chicago in the 1920s and 1930s , social disorganization theory asserts that crime is most likely to occur in communities with weak social ties and the absence of social control . <hl> An individual who grows up in a poor neighborhood with high rates of drug use , violence , teenage delinquency , and deprived parenting is more likely to become a criminal than an individual from a wealthy neighborhood with a good school system and families who are involved positively in the community .","hl_sentences":"Developed by researchers at the University of Chicago in the 1920s and 1930s , social disorganization theory asserts that crime is most likely to occur in communities with weak social ties and the absence of social control .","question":{"cloze_format":"According to social disorganization theory, crime is most likely to occur in ___.","normal_format":"According to social disorganization theory, crime is most likely to occur where?","question_choices":["A community where neighbors don’t know each other very well","A neighborhood with mostly elderly citizens","A city with a large minority population ","A college campus with students who are very competitive"],"question_id":"fs-id909380","question_text":"According to social disorganization theory, crime is most likely to occur where?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"wealth"},"bloom":"1","hl_context":"<hl> The theory of Shaw and McKay has been further tested and expounded upon by Robert Sampson and Byron Groves ( 1989 ) . <hl> <hl> They found that poverty , ethnic diversity , and family disruption in given localities had a strong positive correlation with social disorganization . <hl> They also determined that social disorganization was , in turn , associated with high rates of crime and delinquency — or deviance . Recent studies Sampson conducted with Lydia Bean ( 2006 ) revealed similar findings . High rates of poverty and single-parent homes correlated with high rates of juvenile violence . Cultural deviance theory suggests that conformity to the prevailing cultural norms of lower-class society causes crime . <hl> Researchers Clifford Shaw and Henry McKay ( 1942 ) studied crime patterns in Chicago in the early 1900s . <hl> <hl> They found that violence and crime were at their worst in the middle of the city and gradually decreased the farther one traveled from the urban center toward the suburbs . <hl> Shaw and McKay noticed that this pattern matched the migration patterns of Chicago citizens . New immigrants , many of them poor and lacking knowledge of English , lived in neighborhoods inside the city . As the urban population expanded , wealthier people moved to the suburbs , leaving behind the less privileged .","hl_sentences":"The theory of Shaw and McKay has been further tested and expounded upon by Robert Sampson and Byron Groves ( 1989 ) . They found that poverty , ethnic diversity , and family disruption in given localities had a strong positive correlation with social disorganization . Researchers Clifford Shaw and Henry McKay ( 1942 ) studied crime patterns in Chicago in the early 1900s . They found that violence and crime were at their worst in the middle of the city and gradually decreased the farther one traveled from the urban center toward the suburbs .","question":{"cloze_format":"Shaw and McKay found that crime is linked primarily to ________.","normal_format":"Shaw and McKay found that crime is linked primarily to which of the following?","question_choices":["power","master status","family values","wealth"],"question_id":"fs-id1824438","question_text":"Shaw and McKay found that crime is linked primarily to ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"Because his fame protects him from retribution"},"bloom":"4","hl_context":"<hl> In his book The Power Elite ( 1956 ) , sociologist C . Wright Mills described the existence of what he dubbed the power elite , a small group of wealthy and influential people at the top of society who hold the power and resources . <hl> <hl> Wealthy executives , politicians , celebrities , and military leaders often have access to national and international power , and in some cases , their decisions affect everyone in society . <hl> Because of this , the rules of society are stacked in favor of a privileged few who manipulate them to stay on top . It is these people who decide what is criminal and what is not , and the effects are often felt most by those who have little power . <hl> Mills ’ theories explain why celebrities such as Chris Brown and Paris Hilton , or once-powerful politicians such as Eliot Spitzer and Tom DeLay , can commit crimes with little or no legal retribution . <hl>","hl_sentences":"In his book The Power Elite ( 1956 ) , sociologist C . Wright Mills described the existence of what he dubbed the power elite , a small group of wealthy and influential people at the top of society who hold the power and resources . Wealthy executives , politicians , celebrities , and military leaders often have access to national and international power , and in some cases , their decisions affect everyone in society . Mills ’ theories explain why celebrities such as Chris Brown and Paris Hilton , or once-powerful politicians such as Eliot Spitzer and Tom DeLay , can commit crimes with little or no legal retribution .","question":{"cloze_format":"According to the concept of the power elite, the reason a celebrity such as Charlie Sheen would commit a crime is ___ .","normal_format":"According to the concept of the power elite, why would a celebrity such as Charlie Sheen commit a crime?","question_choices":["Because his parents committed similar crimes","Because his fame protects him from retribution","Because his fame disconnects him from society","Because he is challenging socially accepted norms"],"question_id":"fs-id1674578","question_text":"According to the concept of the power elite, why would a celebrity such as Charlie Sheen commit a crime?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"The offender has been labeled deviant by society and has accepted a new master status."},"bloom":"3","hl_context":"Sometimes , in more extreme cases , primary deviance can morph into secondary deviance . <hl> Secondary deviance occurs when a person ’ s self-concept and behavior begin to change after his or her actions are labeled as deviant by members of society . <hl> <hl> The person may begin to take on and fulfill the role of a “ deviant ” as an act of rebellion against the society that has labeled that individual as such . <hl> For example , consider a high school student who often cuts class and gets into fights . The student is reprimanded frequently by teachers and school staff , and soon enough , he develops a reputation as a “ troublemaker . ” As a result , the student starts acting out even more and breaking more rules ; he has adopted the “ troublemaker ” label and embraced this deviant identity . <hl> Secondary deviance can be so strong that it bestows a master status on an individual . <hl> A master status is a label that describes the chief characteristic of an individual . Some people see themselves primarily as doctors , artists , or grandfathers . Others see themselves as beggars , convicts , or addicts .","hl_sentences":"Secondary deviance occurs when a person ’ s self-concept and behavior begin to change after his or her actions are labeled as deviant by members of society . The person may begin to take on and fulfill the role of a “ deviant ” as an act of rebellion against the society that has labeled that individual as such . Secondary deviance can be so strong that it bestows a master status on an individual .","question":{"cloze_format":"A convicted sexual offender is released on parole and arrested two weeks later for repeated sexual crimes. Labeling theory would explain that ___ .","normal_format":"A convicted sexual offender is released on parole and arrested two weeks later for repeated sexual crimes. How would labeling theory explain this?","question_choices":["The offender has been labeled deviant by society and has accepted a new master status.","The offender has returned to his old neighborhood and so reestablished his former habits.","The offender has lost the social bonds he made in prison and feels disconnected from society.","The offender is poor and responding to the different cultural values that exist in his community."],"question_id":"fs-id2916966","question_text":"A convicted sexual offender is released on parole and arrested two weeks later for repeated sexual crimes. How would labeling theory explain this?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"Primary; does not"},"bloom":"1","hl_context":"Sociologist Edwin Lemert expanded on the concepts of labeling theory , identifying two types of deviance that affect identity formation . <hl> Primary deviance is a violation of norms that does not result in any long-term effects on the individual ’ s self-image or interactions with others . <hl> Speeding is a deviant act , but receiving a speeding ticket generally does not make others view you as a bad person , nor does it alter your own self-concept . Individuals who engage in primary deviance still maintain a feeling of belonging in society and are likely to continue to conform to norms in the future .","hl_sentences":"Primary deviance is a violation of norms that does not result in any long-term effects on the individual ’ s self-image or interactions with others .","question":{"cloze_format":"______ deviance is a violation of norms that ______result in a person being labeled a deviant.","normal_format":"What deviance is a violation of norms? And does it result in a person being labeled a deviant? ","question_choices":["Secondary; does not","Negative; does","Primary; does not","Primary; may or may not"],"question_id":"fs-id2732159","question_text":"______ deviance is a violation of norms that ______result in a person being labeled a deviant."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"Embezzlement"},"bloom":null,"hl_context":"When we think of crime , we often picture street crime , or offenses committed by ordinary people against other people or organizations , usually in public spaces . An often overlooked category is corporate crime , or crime committed by white-collar workers in a business environment . <hl> Embezzlement , insider trading , and identity theft are all types of corporate crime . <hl> Although these types of offenses rarely receive the same amount of media coverage as street crimes , they can be far more damaging . The current economic recession in the United States is the ultimate result of a financial collapse triggered by corporate crime .","hl_sentences":"Embezzlement , insider trading , and identity theft are all types of corporate crime .","question":{"cloze_format":"___ is an example of corporate crime.","normal_format":"Which of the following is an example of corporate crime?","question_choices":["Embezzlement","Larceny","Assault","Burglary"],"question_id":"fs-id2885117","question_text":"Which of the following is an example of corporate crime?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"violent crime"},"bloom":null,"hl_context":"Not all crimes are given equal weight . Society generally socializes its members to view certain crimes as more severe than others . For example , most people would consider murdering someone to be far worse than stealing a wallet and would expect a murderer to be punished more severely than a thief . In modern American society , crimes are classified as one of two types based on their severity . <hl> Violent crimes ( also known as “ crimes against a person ” ) are based on the use of force or the threat of force . <hl> <hl> Rape , murder , and armed robbery fall under this category . <hl> Nonviolent crimes involve the destruction or theft of property , but do not use force or the threat of force . Because of this , they are also sometimes called “ property crimes . ” Larceny , car theft , and vandalism are all types of nonviolent crimes . If you use a crowbar to break into a car , you are committing a nonviolent crime ; if you mug someone with the crowbar , you are committing a violent crime .","hl_sentences":"Violent crimes ( also known as “ crimes against a person ” ) are based on the use of force or the threat of force . Rape , murder , and armed robbery fall under this category .","question":{"cloze_format":"Spousal abuse is an example of a ________.","normal_format":"What is spousal abuse an example of?","question_choices":["street crime","corporate crime","violent crime","nonviolent crime"],"question_id":"fs-id1003194","question_text":"Spousal abuse is an example of a ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"Rates of violent and nonviolent crimes are decreasing."},"bloom":"1","hl_context":"While neither of these publications can take into account all of the crimes committed in the country , some general trends may be noted . <hl> Crime rates were on the rise after 1960 , but following an all-time high in the 1980s and 1990s , rates of violent and non-violent crimes once again started to decline . <hl>","hl_sentences":"Crime rates were on the rise after 1960 , but following an all-time high in the 1980s and 1990s , rates of violent and non-violent crimes once again started to decline .","question":{"cloze_format":"The situation that best describes crime trends in the United States is that ___.","normal_format":"Which of the following situations best describes crime trends in the United States?","question_choices":["Rates of violent and nonviolent crimes are decreasing.","Rates of violent crimes are decreasing, but there are more nonviolent crimes now than ever before.","Crime rates have skyrocketed since the 1970s due to lax corrections laws.","Rates of street crime have gone up, but corporate crime has gone down."],"question_id":"fs-id2071330","question_text":"Which of the following situations best describes crime trends in the United States?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"The NCVS may be unable to reach important groups, such as those without phones."},"bloom":"1","hl_context":"<hl> Though the NCVS is a critical source of statistical information , disadvantages exist . <hl> <hl> “ Non-response , ” or a victim ’ s failure to participate in the survey or a particular question , is among them . <hl> <hl> Inability to contact important demographics , such as those who don ’ t have access to phones or frequently relocate , also skews the data . <hl> For those who participate , memory issues can be problematic for the data sets . Some victims ’ recollection of the crimes can be inaccurate or simply forgotten over time ( Cantor and Lynch 2000 ) .","hl_sentences":"Though the NCVS is a critical source of statistical information , disadvantages exist . “ Non-response , ” or a victim ’ s failure to participate in the survey or a particular question , is among them . Inability to contact important demographics , such as those who don ’ t have access to phones or frequently relocate , also skews the data .","question":{"cloze_format":"A disadvantage of the National Crime Victimization Survey (NCVS) is that ___.","normal_format":"What is a disadvantage of the National Crime Victimization Survey (NCVS)?","question_choices":["The NCVS doesn’t include demographic data, such as age or gender.","The NCVS may be unable to reach important groups, such as those without phones.","The NCVS doesn’t address the relationship between the criminal and the victim.","The NCVS only includes information collected by police officers."],"question_id":"fs-id2913595","question_text":"What is a disadvantage of the National Crime Victimization Survey (NCVS)?"},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"Deviance is socially defined.\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"What , exactly , is deviance ? And what is the relationship between deviance and crime ? <hl> As Philip Hudson found out , some behaviors , such as wearing clothes of the opposite sex , can be deviant in certain places , criminal in some places , and perfectly acceptable elsewhere . <hl> <hl> According to sociologist William Graham Sumner , deviance is a violation of established contextual , cultural , or social norms , whether folkways , mores , or codified law ( 1906 ) . <hl> <hl> It can be as minor as picking one ’ s nose in public or as major as committing murder . <hl> Although the word “ deviance ” has a negative connotation in everyday language , sociologists recognize that deviance is not necessarily bad ( Schoepflin 2011 ) . In fact , from a structural functionalist perspective , one of the positive contributions of deviance is that it fosters social change . For example , during the U . S . civil rights movement , Rosa Parks violated social norms when she refused to move to the “ black section ” of the bus , and the Little Rock Nine broke customs of segregation to attend an Arkansas public school .\",\n \"hl_sentences\": \"As Philip Hudson found out , some behaviors , such as wearing clothes of the opposite sex , can be deviant in certain places , criminal in some places , and perfectly acceptable elsewhere . According to sociologist William Graham Sumner , deviance is a violation of established contextual , cultural , or social norms , whether folkways , mores , or codified law ( 1906 ) . It can be as minor as picking one ’ s nose in public or as major as committing murder .\",\n \"question\": {\n \"cloze_format\": \"Deviance is best described as ___ .\",\n \"normal_format\": \"Which of the following best describes how deviance is defined?\",\n \"question_choices\": [\n \"Deviance is defined by federal, state, and local laws.\",\n \"Deviance’s definition is determined by one’s religion.\",\n \"Deviance occurs whenever someone else is harmed by an action.\",\n \"Deviance is socially defined.\"\n ],\n \"question_id\": \"fs-id1370636\",\n \"question_text\": \"Which of the following best describes how deviance is defined?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"An act of deviance\"\n },\n \"bloom\": null,\n \"hl_context\": \"Although deviance is a violation of social norms , it ’ s not always punishable , and it ’ s not necessarily bad . Crime , on the other hand , is a behavior that violates official law and is punishable through formal sanctions . Walking to class backwards is a deviant behavior . Driving with a blood alcohol percentage over the state ’ s limit is a crime . <hl> Like other forms of deviance , however , ambiguity exists concerning what constitutes a crime and whether all crimes are , in fact , “ bad ” and deserve punishment . <hl> <hl> For example , during the 1960s , civil rights activists often violated laws intentionally as part of their effort to bring about racial equality . <hl> <hl> In hindsight , we recognize that the laws that deemed many of their actions crimes — for instance , Rosa Parks taking a seat in the “ whites only ” section of the bus — were inconsistent with social equality . <hl> What , exactly , is deviance ? And what is the relationship between deviance and crime ? As Philip Hudson found out , some behaviors , such as wearing clothes of the opposite sex , can be deviant in certain places , criminal in some places , and perfectly acceptable elsewhere . According to sociologist William Graham Sumner , deviance is a violation of established contextual , cultural , or social norms , whether folkways , mores , or codified law ( 1906 ) . It can be as minor as picking one ’ s nose in public or as major as committing murder . Although the word “ deviance ” has a negative connotation in everyday language , sociologists recognize that deviance is not necessarily bad ( Schoepflin 2011 ) . <hl> In fact , from a structural functionalist perspective , one of the positive contributions of deviance is that it fosters social change . <hl> <hl> For example , during the U . S . civil rights movement , Rosa Parks violated social norms when she refused to move to the “ black section ” of the bus , and the Little Rock Nine broke customs of segregation to attend an Arkansas public school . <hl>\",\n \"hl_sentences\": \"Like other forms of deviance , however , ambiguity exists concerning what constitutes a crime and whether all crimes are , in fact , “ bad ” and deserve punishment . For example , during the 1960s , civil rights activists often violated laws intentionally as part of their effort to bring about racial equality . In hindsight , we recognize that the laws that deemed many of their actions crimes — for instance , Rosa Parks taking a seat in the “ whites only ” section of the bus — were inconsistent with social equality . In fact , from a structural functionalist perspective , one of the positive contributions of deviance is that it fosters social change . For example , during the U . S . civil rights movement , Rosa Parks violated social norms when she refused to move to the “ black section ” of the bus , and the Little Rock Nine broke customs of segregation to attend an Arkansas public school .\",\n \"question\": {\n \"cloze_format\": \"During the civil rights movement, Rosa Parks and other black protestors spoke out against segregation by refusing to sit at the back of the bus. This is an example of ________.\",\n \"normal_format\": \"During the civil rights movement, Rosa Parks and other black protestors spoke out against segregation by refusing to sit at the back of the bus. Which is this an example of?\",\n \"question_choices\": [\n \"An act of social control\",\n \"An act of deviance\",\n \"A social norm\",\n \"Criminal mores\"\n ],\n \"question_id\": \"fs-id1303155\",\n \"question_text\": \"During the civil rights movement, Rosa Parks and other black protestors spoke out against segregation by refusing to sit at the back of the bus. This is an example of ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"formal sanctions\"\n },\n \"bloom\": null,\n \"hl_context\": \"As you learned previously , all societies have informal and formal ways of maintaining social control . <hl> Within these systems of norms , societies have legal codes that maintain formal social control through laws , which are rules adopted and enforced by a political authority . <hl> Those who violate these rules incur negative formal sanctions . Normally , punishments are relative to the degree of the crime and the importance to society of the value underlying the law . As we will see , however , there are other factors that influence criminal sentencing .\",\n \"hl_sentences\": \"Within these systems of norms , societies have legal codes that maintain formal social control through laws , which are rules adopted and enforced by a political authority .\",\n \"question\": {\n \"cloze_format\": \"Societies practice social control to maintain ________.\",\n \"normal_format\": \"Societies practice social control to maintain what?\",\n \"question_choices\": [\n \"formal sanctions\",\n \"social order\",\n \"cultural deviance\",\n \"sanction labeling\"\n ],\n \"question_id\": \"fs-id3135713\",\n \"question_text\": \"Societies practice social control to maintain ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"A senator\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> In his book The Power Elite ( 1956 ) , sociologist C . Wright Mills described the existence of what he dubbed the power elite , a small group of wealthy and influential people at the top of society who hold the power and resources . <hl> <hl> Wealthy executives , politicians , celebrities , and military leaders often have access to national and international power , and in some cases , their decisions affect everyone in society . <hl> Because of this , the rules of society are stacked in favor of a privileged few who manipulate them to stay on top . It is these people who decide what is criminal and what is not , and the effects are often felt most by those who have little power . Mills ’ theories explain why celebrities such as Chris Brown and Paris Hilton , or once-powerful politicians such as Eliot Spitzer and Tom DeLay , can commit crimes with little or no legal retribution .\",\n \"hl_sentences\": \"In his book The Power Elite ( 1956 ) , sociologist C . Wright Mills described the existence of what he dubbed the power elite , a small group of wealthy and influential people at the top of society who hold the power and resources . Wealthy executives , politicians , celebrities , and military leaders often have access to national and international power , and in some cases , their decisions affect everyone in society .\",\n \"question\": {\n \"cloze_format\": \"According to C. Wright Mills, the person that is most likely to be a member of the power elite is ___.\",\n \"normal_format\": \"According to C. Wright Mills, which of the following people is most likely to be a member of the power elite?\",\n \"question_choices\": [\n \"A war veteran\",\n \"A senator\",\n \"A professor\",\n \"A mechanic\"\n ],\n \"question_id\": \"fs-id1366105\",\n \"question_text\": \"According to C. Wright Mills, which of the following people is most likely to be a member of the power elite?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A community where neighbors don’t know each other very well\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Developed by researchers at the University of Chicago in the 1920s and 1930s , social disorganization theory asserts that crime is most likely to occur in communities with weak social ties and the absence of social control . <hl> An individual who grows up in a poor neighborhood with high rates of drug use , violence , teenage delinquency , and deprived parenting is more likely to become a criminal than an individual from a wealthy neighborhood with a good school system and families who are involved positively in the community .\",\n \"hl_sentences\": \"Developed by researchers at the University of Chicago in the 1920s and 1930s , social disorganization theory asserts that crime is most likely to occur in communities with weak social ties and the absence of social control .\",\n \"question\": {\n \"cloze_format\": \"According to social disorganization theory, crime is most likely to occur in ___.\",\n \"normal_format\": \"According to social disorganization theory, crime is most likely to occur where?\",\n \"question_choices\": [\n \"A community where neighbors don’t know each other very well\",\n \"A neighborhood with mostly elderly citizens\",\n \"A city with a large minority population \",\n \"A college campus with students who are very competitive\"\n ],\n \"question_id\": \"fs-id909380\",\n \"question_text\": \"According to social disorganization theory, crime is most likely to occur where?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"wealth\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> The theory of Shaw and McKay has been further tested and expounded upon by Robert Sampson and Byron Groves ( 1989 ) . <hl> <hl> They found that poverty , ethnic diversity , and family disruption in given localities had a strong positive correlation with social disorganization . <hl> They also determined that social disorganization was , in turn , associated with high rates of crime and delinquency — or deviance . Recent studies Sampson conducted with Lydia Bean ( 2006 ) revealed similar findings . High rates of poverty and single-parent homes correlated with high rates of juvenile violence . Cultural deviance theory suggests that conformity to the prevailing cultural norms of lower-class society causes crime . <hl> Researchers Clifford Shaw and Henry McKay ( 1942 ) studied crime patterns in Chicago in the early 1900s . <hl> <hl> They found that violence and crime were at their worst in the middle of the city and gradually decreased the farther one traveled from the urban center toward the suburbs . <hl> Shaw and McKay noticed that this pattern matched the migration patterns of Chicago citizens . New immigrants , many of them poor and lacking knowledge of English , lived in neighborhoods inside the city . As the urban population expanded , wealthier people moved to the suburbs , leaving behind the less privileged .\",\n \"hl_sentences\": \"The theory of Shaw and McKay has been further tested and expounded upon by Robert Sampson and Byron Groves ( 1989 ) . They found that poverty , ethnic diversity , and family disruption in given localities had a strong positive correlation with social disorganization . Researchers Clifford Shaw and Henry McKay ( 1942 ) studied crime patterns in Chicago in the early 1900s . They found that violence and crime were at their worst in the middle of the city and gradually decreased the farther one traveled from the urban center toward the suburbs .\",\n \"question\": {\n \"cloze_format\": \"Shaw and McKay found that crime is linked primarily to ________.\",\n \"normal_format\": \"Shaw and McKay found that crime is linked primarily to which of the following?\",\n \"question_choices\": [\n \"power\",\n \"master status\",\n \"family values\",\n \"wealth\"\n ],\n \"question_id\": \"fs-id1824438\",\n \"question_text\": \"Shaw and McKay found that crime is linked primarily to ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"Because his fame protects him from retribution\"\n },\n \"bloom\": \"4\",\n \"hl_context\": \"<hl> In his book The Power Elite ( 1956 ) , sociologist C . Wright Mills described the existence of what he dubbed the power elite , a small group of wealthy and influential people at the top of society who hold the power and resources . <hl> <hl> Wealthy executives , politicians , celebrities , and military leaders often have access to national and international power , and in some cases , their decisions affect everyone in society . <hl> Because of this , the rules of society are stacked in favor of a privileged few who manipulate them to stay on top . It is these people who decide what is criminal and what is not , and the effects are often felt most by those who have little power . <hl> Mills ’ theories explain why celebrities such as Chris Brown and Paris Hilton , or once-powerful politicians such as Eliot Spitzer and Tom DeLay , can commit crimes with little or no legal retribution . <hl>\",\n \"hl_sentences\": \"In his book The Power Elite ( 1956 ) , sociologist C . Wright Mills described the existence of what he dubbed the power elite , a small group of wealthy and influential people at the top of society who hold the power and resources . Wealthy executives , politicians , celebrities , and military leaders often have access to national and international power , and in some cases , their decisions affect everyone in society . Mills ’ theories explain why celebrities such as Chris Brown and Paris Hilton , or once-powerful politicians such as Eliot Spitzer and Tom DeLay , can commit crimes with little or no legal retribution .\",\n \"question\": {\n \"cloze_format\": \"According to the concept of the power elite, the reason a celebrity such as Charlie Sheen would commit a crime is ___ .\",\n \"normal_format\": \"According to the concept of the power elite, why would a celebrity such as Charlie Sheen commit a crime?\",\n \"question_choices\": [\n \"Because his parents committed similar crimes\",\n \"Because his fame protects him from retribution\",\n \"Because his fame disconnects him from society\",\n \"Because he is challenging socially accepted norms\"\n ],\n \"question_id\": \"fs-id1674578\",\n \"question_text\": \"According to the concept of the power elite, why would a celebrity such as Charlie Sheen commit a crime?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"The offender has been labeled deviant by society and has accepted a new master status.\"\n },\n \"bloom\": \"3\",\n \"hl_context\": \"Sometimes , in more extreme cases , primary deviance can morph into secondary deviance . <hl> Secondary deviance occurs when a person ’ s self-concept and behavior begin to change after his or her actions are labeled as deviant by members of society . <hl> <hl> The person may begin to take on and fulfill the role of a “ deviant ” as an act of rebellion against the society that has labeled that individual as such . <hl> For example , consider a high school student who often cuts class and gets into fights . The student is reprimanded frequently by teachers and school staff , and soon enough , he develops a reputation as a “ troublemaker . ” As a result , the student starts acting out even more and breaking more rules ; he has adopted the “ troublemaker ” label and embraced this deviant identity . <hl> Secondary deviance can be so strong that it bestows a master status on an individual . <hl> A master status is a label that describes the chief characteristic of an individual . Some people see themselves primarily as doctors , artists , or grandfathers . Others see themselves as beggars , convicts , or addicts .\",\n \"hl_sentences\": \"Secondary deviance occurs when a person ’ s self-concept and behavior begin to change after his or her actions are labeled as deviant by members of society . The person may begin to take on and fulfill the role of a “ deviant ” as an act of rebellion against the society that has labeled that individual as such . Secondary deviance can be so strong that it bestows a master status on an individual .\",\n \"question\": {\n \"cloze_format\": \"A convicted sexual offender is released on parole and arrested two weeks later for repeated sexual crimes. Labeling theory would explain that ___ .\",\n \"normal_format\": \"A convicted sexual offender is released on parole and arrested two weeks later for repeated sexual crimes. How would labeling theory explain this?\",\n \"question_choices\": [\n \"The offender has been labeled deviant by society and has accepted a new master status.\",\n \"The offender has returned to his old neighborhood and so reestablished his former habits.\",\n \"The offender has lost the social bonds he made in prison and feels disconnected from society.\",\n \"The offender is poor and responding to the different cultural values that exist in his community.\"\n ],\n \"question_id\": \"fs-id2916966\",\n \"question_text\": \"A convicted sexual offender is released on parole and arrested two weeks later for repeated sexual crimes. How would labeling theory explain this?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"Primary; does not\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Sociologist Edwin Lemert expanded on the concepts of labeling theory , identifying two types of deviance that affect identity formation . <hl> Primary deviance is a violation of norms that does not result in any long-term effects on the individual ’ s self-image or interactions with others . <hl> Speeding is a deviant act , but receiving a speeding ticket generally does not make others view you as a bad person , nor does it alter your own self-concept . Individuals who engage in primary deviance still maintain a feeling of belonging in society and are likely to continue to conform to norms in the future .\",\n \"hl_sentences\": \"Primary deviance is a violation of norms that does not result in any long-term effects on the individual ’ s self-image or interactions with others .\",\n \"question\": {\n \"cloze_format\": \"______ deviance is a violation of norms that ______result in a person being labeled a deviant.\",\n \"normal_format\": \"What deviance is a violation of norms? And does it result in a person being labeled a deviant? \",\n \"question_choices\": [\n \"Secondary; does not\",\n \"Negative; does\",\n \"Primary; does not\",\n \"Primary; may or may not\"\n ],\n \"question_id\": \"fs-id2732159\",\n \"question_text\": \"______ deviance is a violation of norms that ______result in a person being labeled a deviant.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"Embezzlement\"\n },\n \"bloom\": null,\n \"hl_context\": \"When we think of crime , we often picture street crime , or offenses committed by ordinary people against other people or organizations , usually in public spaces . An often overlooked category is corporate crime , or crime committed by white-collar workers in a business environment . <hl> Embezzlement , insider trading , and identity theft are all types of corporate crime . <hl> Although these types of offenses rarely receive the same amount of media coverage as street crimes , they can be far more damaging . The current economic recession in the United States is the ultimate result of a financial collapse triggered by corporate crime .\",\n \"hl_sentences\": \"Embezzlement , insider trading , and identity theft are all types of corporate crime .\",\n \"question\": {\n \"cloze_format\": \"___ is an example of corporate crime.\",\n \"normal_format\": \"Which of the following is an example of corporate crime?\",\n \"question_choices\": [\n \"Embezzlement\",\n \"Larceny\",\n \"Assault\",\n \"Burglary\"\n ],\n \"question_id\": \"fs-id2885117\",\n \"question_text\": \"Which of the following is an example of corporate crime?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"violent crime\"\n },\n \"bloom\": null,\n \"hl_context\": \"Not all crimes are given equal weight . Society generally socializes its members to view certain crimes as more severe than others . For example , most people would consider murdering someone to be far worse than stealing a wallet and would expect a murderer to be punished more severely than a thief . In modern American society , crimes are classified as one of two types based on their severity . <hl> Violent crimes ( also known as “ crimes against a person ” ) are based on the use of force or the threat of force . <hl> <hl> Rape , murder , and armed robbery fall under this category . <hl> Nonviolent crimes involve the destruction or theft of property , but do not use force or the threat of force . Because of this , they are also sometimes called “ property crimes . ” Larceny , car theft , and vandalism are all types of nonviolent crimes . If you use a crowbar to break into a car , you are committing a nonviolent crime ; if you mug someone with the crowbar , you are committing a violent crime .\",\n \"hl_sentences\": \"Violent crimes ( also known as “ crimes against a person ” ) are based on the use of force or the threat of force . Rape , murder , and armed robbery fall under this category .\",\n \"question\": {\n \"cloze_format\": \"Spousal abuse is an example of a ________.\",\n \"normal_format\": \"What is spousal abuse an example of?\",\n \"question_choices\": [\n \"street crime\",\n \"corporate crime\",\n \"violent crime\",\n \"nonviolent crime\"\n ],\n \"question_id\": \"fs-id1003194\",\n \"question_text\": \"Spousal abuse is an example of a ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"Rates of violent and nonviolent crimes are decreasing.\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"While neither of these publications can take into account all of the crimes committed in the country , some general trends may be noted . <hl> Crime rates were on the rise after 1960 , but following an all-time high in the 1980s and 1990s , rates of violent and non-violent crimes once again started to decline . <hl>\",\n \"hl_sentences\": \"Crime rates were on the rise after 1960 , but following an all-time high in the 1980s and 1990s , rates of violent and non-violent crimes once again started to decline .\",\n \"question\": {\n \"cloze_format\": \"The situation that best describes crime trends in the United States is that ___.\",\n \"normal_format\": \"Which of the following situations best describes crime trends in the United States?\",\n \"question_choices\": [\n \"Rates of violent and nonviolent crimes are decreasing.\",\n \"Rates of violent crimes are decreasing, but there are more nonviolent crimes now than ever before.\",\n \"Crime rates have skyrocketed since the 1970s due to lax corrections laws.\",\n \"Rates of street crime have gone up, but corporate crime has gone down.\"\n ],\n \"question_id\": \"fs-id2071330\",\n \"question_text\": \"Which of the following situations best describes crime trends in the United States?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"The NCVS may be unable to reach important groups, such as those without phones.\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Though the NCVS is a critical source of statistical information , disadvantages exist . <hl> <hl> “ Non-response , ” or a victim ’ s failure to participate in the survey or a particular question , is among them . <hl> <hl> Inability to contact important demographics , such as those who don ’ t have access to phones or frequently relocate , also skews the data . <hl> For those who participate , memory issues can be problematic for the data sets . Some victims ’ recollection of the crimes can be inaccurate or simply forgotten over time ( Cantor and Lynch 2000 ) .\",\n \"hl_sentences\": \"Though the NCVS is a critical source of statistical information , disadvantages exist . “ Non-response , ” or a victim ’ s failure to participate in the survey or a particular question , is among them . Inability to contact important demographics , such as those who don ’ t have access to phones or frequently relocate , also skews the data .\",\n \"question\": {\n \"cloze_format\": \"A disadvantage of the National Crime Victimization Survey (NCVS) is that ___.\",\n \"normal_format\": \"What is a disadvantage of the National Crime Victimization Survey (NCVS)?\",\n \"question_choices\": [\n \"The NCVS doesn’t include demographic data, such as age or gender.\",\n \"The NCVS may be unable to reach important groups, such as those without phones.\",\n \"The NCVS doesn’t address the relationship between the criminal and the victim.\",\n \"The NCVS only includes information collected by police officers.\"\n ],\n \"question_id\": \"fs-id2913595\",\n \"question_text\": \"What is a disadvantage of the National Crime Victimization Survey (NCVS)?\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":7,"string":"7"},"chapter_text":{"kind":"string","value":"7.1 Deviance and Control \n\n What, exactly, is deviance? And what is the relationship between deviance and crime? As Philip Hudson found out, some behaviors, such as wearing clothes of the opposite sex, can be deviant in certain places, criminal in some places, and perfectly acceptable elsewhere. According to sociologist William Graham Sumner, deviance is a violation of established contextual, cultural, or social norms, whether folkways, mores, or codified law (1906). It can be as minor as picking one’s nose in public or as major as committing murder. Although the word “deviance” has a negative connotation in everyday language, sociologists recognize that deviance is not necessarily bad (Schoepflin 2011). In fact, from a structural functionalist perspective, one of the positive contributions of deviance is that it fosters social change. For example, during the U.S. civil rights movement, Rosa Parks violated social norms when she refused to move to the “black section” of the bus, and the Little Rock Nine broke customs of segregation to attend an Arkansas public school. \n\n “What is deviant behavior?” cannot be answered in a straightforward manner. Whether an act is labeled deviant or not depends on many factors, including location, audience, and the individual committing the act (Becker 1963). Listening to your iPod on the way to class is considered acceptable behavior. Listening to your iPod during your 2 o’clock sociology lecture is considered rude. Listening to your iPod when on the witness stand before a judge may cause you to be held in contempt of court, and consequently fined or jailed. \n\n As norms vary across culture and time, it makes sense that notions of deviance change also. Fifty years ago, public schools in the United States had strict dress codes that, among other stipulations, often banned women from wearing pants to class. Today, it’s socially acceptable for women to wear pants, but less so for men to wear skirts. In a time of war, acts usually considered morally reprehensible, such as taking the life of another, may actually be rewarded. Whether an act is deviant or not depends on society’s response to that act. \n\n Why I Drive a Hearse \n\n When sociologist Todd Schoepflin ran into his childhood friend Bill, he was shocked to see him driving a hearse. A professionally trained researcher, Schoepflin wondered what effect driving a hearse had on his friend and what effect it might have on others on the road. Would using such a vehicle for everyday errands be considered deviant by most people? \n\n Schoepflin interviewed Bill, curious first to know why he drove such an unconventional car. Bill had simply been on the lookout for a reliable winter car; on a tight budget, he searched used car ads and stumbled upon one for the hearse. The car ran well and the price was right, so he bought it. \n\n Bill admitted that others’ reactions to the car had been mixed. His parents were appalled and he received odd stares from his coworkers. A mechanic once refused to work on it, stating that it was “a dead person machine.” On the whole, however, Bill received mostly positive reactions. Strangers gave him a thumbs-up on the highway and stopped him in parking lots to chat about his car. His girlfriend loved it, his friends wanted to take it tailgating, and people offered to buy it. Could it be that driving a hearse isn’t really so deviant after all? \n\n Schoepflin theorized that, although viewed as outside conventional norms, driving a hearse is such a mild form of deviance that it actually becomes a mark of distinction. Conformists find the choice of vehicle intriguing or appealing, while nonconformists see a fellow oddball to whom they can relate. As one of Bill’s friends remarked, “Every guy wants to own a unique car like this and you can certainly pull it off.” Such anecdotes remind us that although deviance is often viewed as a violation of norms, it’s not always viewed in a negative light (Schoepflin 2011). \n\n Social Control \n\n When a person violates a social norm, what happens? A driver caught speeding can receive a speeding ticket. A student who wears a bathrobe to class gets a warning from a professor. An adult belching loudly is avoided. All societies practice social control , the regulation and enforcement of norms. The underlying goal of social control is to maintain social order , an arrangement of practices and behaviors on which society’s members base their daily lives. Think of social order as an employee handbook and social control as a manager. When a worker violates a workplace guideline, the manager steps in to enforce the rules. \n\n The means of enforcing rules are known as sanctions . Sanctions can be positive as well as negative. Positive sanctions are rewards given for conforming to norms. A promotion at work is a positive sanction for working hard. Negative sanctions are punishments for violating norms. Being arrested is a punishment for shoplifting. Both types of sanctions play a role in social control. \n\n Sociologists also classify sanctions as formal or informal. Although shoplifting, a form of social deviance, may be illegal, there are no laws dictating the proper way to scratch one’s nose. That doesn’t mean picking your nose in public won’t be punished; instead, you will encounter informal sanctions . Informal sanctions emerge in face-to-face social interactions. For example, wearing flip-flops to an opera or swearing loudly in church may draw disapproving looks or even verbal reprimands, whereas behavior that is seen as positive—such as helping an old man carry grocery bags across the street—may receive positive informal reactions, such as a smile or pat on the back. \n\n Formal sanctions , on the other hand, are ways to officially recognize and enforce norm violations. If a student violates her college’s code of conduct, for example, she might be expelled. Someone who speaks inappropriately to the boss could be fired. Someone who commits a crime may be arrested or imprisoned. On the positive side, a soldier who saves a life may receive an official commendation. \n\n The table below shows the relationship between different types of sanctions. \n\n Informal \n\n Formal \n\n Positive \n\n An expression of thanks \n\n A promotion at work \n\n Negative \n\n An angry comment \n\n A parking fine \n\n Table 7.1 Informal/Formal Sanctions Formal and informal sanctions may be positive or negative. Informal sanctions arise in social interactions, whereas formal sanctions officially enforce norms. \n7.2 Theoretical Perspectives on Deviance \n\n Why does deviance occur? How does it affect a society? Since the early days of sociology, scholars have developed theories attempting to explain what deviance and crime mean to society. These theories can be grouped according to the three major sociological paradigms: functionalism, symbolic interactionism, and conflict theory. \n\n Functionalism \n\n Sociologists who follow the functionalist approach are concerned with how the different elements of a society contribute to the whole. They view deviance as a key component of a functioning society. Strain theory, social disorganization theory, and cultural deviance theory represent three functionalist perspectives on deviance in society. \n\n Émile Durkheim: The Essential Nature of Deviance \n\n Émile Durkheim believed that deviance is a necessary part of a successful society. One way deviance is functional, he argued, is that it challenges people’s present views (1893). For instance, when black students across the United States participated in “sit-ins” during the civil rights movement, they challenged society’s notions of segregation. Moreover, Durkheim noted, when deviance is punished, it reaffirms currently held social norms, which also contributes to society (1893). Seeing a student given detention for skipping class reminds other high schoolers that playing hooky isn’t allowed and that they, too, could get detention. \n\n Robert Merton: Strain Theory \n\n Sociologist Robert Merton agreed that deviance is an inherent part of a functioning society, but he expanded on Durkheim’s ideas by developing strain theory , which notes that access to socially acceptable goals plays a part in determining whether a person conforms or deviates. From birth, we’re encouraged to achieve the “American Dream” of financial success. A woman who attends business school, receives her MBA, and goes on to make a million-dollar income as CEO of a company is said to be a success. However, not everyone in our society stands on equal footing. A person may have the socially acceptable goal of financial success but lack a socially acceptable way to reach that goal. According to Merton’s theory, an entrepreneur who can’t afford to launch his own company may be tempted to embezzle from his employer for start-up funds. \n\n Merton defined five ways that people respond to this gap between having a socially accepted goal but no socially accepted way to pursue it. \n\n Conformity : Those who conform choose not to deviate. They pursue their goals to the extent that they can through socially accepted means. \n\n Innovation : Those who innovate pursue goals they cannot reach through legitimate means by instead using criminal or deviant means. \n\n Ritualism : People who ritualize lower their goals until they can reach them through socially acceptable ways. These members of society focus on conformity rather than attaining a distant dream. \n\n Retreatism : Others retreat and reject society’s goals and means. Some beggars and street people have withdrawn from society’s goal of financial success. \n\n Rebellion : A handful of people rebel, replacing a society’s goals and means with their own. Terrorists or freedom fighters look to overthrow a society’s goals through socially unacceptable means. \n\n Social Disorganization Theory \n\n Developed by researchers at the University of Chicago in the 1920s and 1930s, social disorganization theory asserts that crime is most likely to occur in communities with weak social ties and the absence of social control. An individual who grows up in a poor neighborhood with high rates of drug use, violence, teenage delinquency, and deprived parenting is more likely to become a criminal than an individual from a wealthy neighborhood with a good school system and families who are involved positively in the community. \n\n Social disorganization theory points to broad social factors as the cause of deviance. A person isn’t born a criminal, but becomes one over time, often based on factors in his or her social environment. Research into social disorganization theory can greatly influence public policy. For instance, studies have found that children from disadvantaged communities who attend preschool programs that teach basic social skills are significantly less likely to engage in criminal activity. \n\n Clifford Shaw and Henry McKay: Cultural Deviance Theory \n\n Cultural deviance theory suggests that conformity to the prevailing cultural norms of lower-class society causes crime. Researchers Clifford Shaw and Henry McKay (1942) studied crime patterns in Chicago in the early 1900s. They found that violence and crime were at their worst in the middle of the city and gradually decreased the farther one traveled from the urban center toward the suburbs. Shaw and McKay noticed that this pattern matched the migration patterns of Chicago citizens. New immigrants, many of them poor and lacking knowledge of English, lived in neighborhoods inside the city. As the urban population expanded, wealthier people moved to the suburbs, leaving behind the less privileged. \n\n Shaw and McKay concluded that socioeconomic status correlated to race and ethnicity resulted in a higher crime rate. The mix of cultures and values created a smaller society with different ideas of deviance, and those values and ideas were transferred from generation to generation. \n\n The theory of Shaw and McKay has been further tested and expounded upon by Robert Sampson and Byron Groves (1989). They found that poverty, ethnic diversity, and family disruption in given localities had a strong positive correlation with social disorganization. They also determined that social disorganization was, in turn, associated with high rates of crime and delinquency—or deviance. Recent studies Sampson conducted with Lydia Bean (2006) revealed similar findings. High rates of poverty and single-parent homes correlated with high rates of juvenile violence. \n\n Conflict Theory \n\n Conflict theory looks to social and economic factors as the causes of crime and deviance. Unlike functionalists, conflict theorists don’t see these factors as positive functions of society, but as evidence of inequality in the system. They also challenge social disorganization theory and control theory, arguing that both ignore racial and socioeconomic issues and oversimplify social trends (Akers 1991). Conflict theorists also look for answers to the correlation of gender and race with wealth and crime. \n\n Karl Marx: An Unequal System \n\n Conflict theory is derived greatly from the work of sociologist, philosopher, and revolutionary Karl Marx. Marx divided the general population into two rigid social groups: the proletariat and the bourgeois. The bourgeois are a small and wealthy segment of society who controls the means of production, while the proletariat is composed of the workers who rely on those means of production for employment and survival. By centralizing these vital resources into few hands, the bourgeois also has the means to control the way society is regulated—from laws, to government, to other authority agencies—which gives the bourgeois the opportunity to maintain and expand their power in society. Though Marx spoke little of deviance, his ideas created the foundation for conflict theorists who study the intersection of deviance and crime with wealth and power. \n\n C. Wright Mills: The Power Elite \n\n In his book The Power Elite (1956), sociologist C. Wright Mills described the existence of what he dubbed the power elite , a small group of wealthy and influential people at the top of society who hold the power and resources. Wealthy executives, politicians, celebrities, and military leaders often have access to national and international power, and in some cases, their decisions affect everyone in society. Because of this, the rules of society are stacked in favor of a privileged few who manipulate them to stay on top. It is these people who decide what is criminal and what is not, and the effects are often felt most by those who have little power. Mills’ theories explain why celebrities such as Chris Brown and Paris Hilton, or once-powerful politicians such as Eliot Spitzer and Tom DeLay, can commit crimes with little or no legal retribution. \n\n Crime and Social Class \n\n While crime is often associated with the underprivileged, crimes committed by the wealthy and powerful remain an under-punished and costly problem within society. The FBI reported that victims of burglary, larceny, and motor vehicle theft lost a total of $15.3 billion dollars in 2009 (FB1 2010). In comparison, when Bernie Madoff was arrested in 2008, the US Securities and Exchange Commission reported that the estimated losses of his financial Ponzi scheme fraud were close to $50 billion (SEC 2009). \n\n This imbalance based on class power is also found within US criminal law. In the 1980s, the use of crack cocaine (cocaine in its purest form) quickly became an epidemic sweeping the country’s poorest urban communities. Its pricier counterpart, cocaine, was associated with upscale users and was a drug of choice for the wealthy. The legal implications of being caught by authorities with crack versus cocaine were starkly different. In 1986, federal law mandated that being caught in possession of 50 grams of crack was punishable by a 10-year prison sentence. An equivalent prison sentence for cocaine possession, however, required possession of 5,000 grams. In other words, the sentencing disparity was 1 to 100 (New York Times Editorial Staff 2011). This inequality in the severity of punishment for crack versus cocaine paralleled the unequal social class of respective users. A conflict theorist would note that those in society who hold the power are also the ones who make the laws concerning crime. In doing so, they make laws that will benefit them, while the powerless classes who lack the resources to make such decisions suffer the consequences. The crack-cocaine punishment disparity remained until 2010, when President Obama signed the Fair Sentencing Act, which decreased the disparity to 1 to 18 (The Sentencing Project 2010). \n\n Symbolic Interactionism \n\n Symbolic interactionism is a theoretical approach that can be used to explain how societies and/or social groups come to view behaviors as deviant or conventional. Labeling theory, differential association, social disorganization theory, and control theory fall within the realm of symbolic interactionism. \n\n Labeling Theory \n\n Although all of us violate norms from time to time, few people would consider themselves deviant. Those who do, however, have often been labeled “deviant” by society and have gradually come to believe it themselves. Labeling theory examines the ascribing of a deviant behavior to another person by members of society. Thus, what is considered deviant is determined not so much by the behaviors themselves or the people who commit them, but by the reactions of others to these behaviors. As a result, what is considered deviant changes over time and can vary significantly across cultures. \n\n Sociologist Edwin Lemert expanded on the concepts of labeling theory, identifying two types of deviance that affect identity formation. Primary deviance is a violation of norms that does not result in any long-term effects on the individual’s self-image or interactions with others. Speeding is a deviant act, but receiving a speeding ticket generally does not make others view you as a bad person, nor does it alter your own self-concept. Individuals who engage in primary deviance still maintain a feeling of belonging in society and are likely to continue to conform to norms in the future. \n\n Sometimes, in more extreme cases, primary deviance can morph into secondary deviance. Secondary deviance occurs when a person’s self-concept and behavior begin to change after his or her actions are labeled as deviant by members of society. The person may begin to take on and fulfill the role of a “deviant” as an act of rebellion against the society that has labeled that individual as such. For example, consider a high school student who often cuts class and gets into fights. The student is reprimanded frequently by teachers and school staff, and soon enough, he develops a reputation as a “troublemaker.” As a result, the student starts acting out even more and breaking more rules; he has adopted the “troublemaker” label and embraced this deviant identity. Secondary deviance can be so strong that it bestows a master status on an individual. A master status is a label that describes the chief characteristic of an individual. Some people see themselves primarily as doctors, artists, or grandfathers. Others see themselves as beggars, convicts, or addicts. \n\n Social Policy and Debate The Right to Vote Before she lost her job as an administrative assistant, Leola Strickland postdated and mailed a handful of checks for amounts ranging from $90 to $500. By the time she was able to find a new job, the checks had bounced, and she was convicted of fraud under Mississippi law. Strickland pleaded guilty to a felony charge and repaid her debts; in return, she was spared from serving prison time. \n\n Strickland appeared in court in 2001. More than ten years later, she is still feeling the sting of her sentencing. Why? Because Mississippi is one of 12 states in the United States that bans convicted felons from voting (ProCon 2011). \n\n To Strickland, who said she had always voted, the news came as a great shock. She isn’t alone. Some 5.3 million people in the United States are currently barred from voting because of felony convictions (ProCon 2009). These individuals include inmates, parolees, probationers, and even people who have never been jailed, such as Leola Strickland. \n\n Under the Fourteenth Amendment, states are allowed to deny voting privileges to individuals who have participated in “rebellion or other crime” (Krajick 2004). Although there are no federally mandated laws on the matter, most states practice at least one form of felony disenfranchisement . At present, it’s estimated that approximately 2.4 percent of the possible voting population is disfranchised, that is, lacking the right to vote (ProCon 2011). \n\n Is it fair to prevent citizens from participating in such an important process? Proponents of disfranchisement laws argue that felons have a debt to pay to society. Being stripped of their right to vote is part of the punishment for criminal deeds. Such proponents point out that voting isn’t the only instance in which ex-felons are denied rights; state laws also ban released criminals from holding public office, obtaining professional licenses, and sometimes even inheriting property (Lott and Jones 2008). \n\n Opponents of felony disfranchisement in the United States argue that voting is a basic human right and should be available to all citizens regardless of past deeds. Many point out that felony disfranchisement has its roots in the 1800s, when it was used primarily to block black citizens from voting. Even nowadays, these laws disproportionately target poor minority members, denying them a chance to participate in a system that, as a social conflict theorist would point out, is already constructed to their disadvantage (Holding 2006). Those who cite labeling theory worry that denying deviants the right to vote will only further encourage deviant behavior. If ex-criminals are disenfranchised from voting, are they being disenfranchised from society? \n\n Edwin Sutherland: Differential Association \n\n In the early 1900s, sociologist Edwin Sutherland sought to understand how deviant behavior developed among people. Since criminology was a young field, he drew on other aspects of sociology including social interactions and group learning (Laub 2006). His conclusions established differential association theory , stating that individuals learn deviant behavior from those close to them who provide models of and opportunities for deviance. According to Sutherland, deviance is less a personal choice and more a result of differential socialization processes. A tween whose friends are sexually active is more likely to view sexual activity as acceptable. \n\n Sutherland’s theory may account for why crime is multigenerational. A longitudinal study beginning in the 1960s found that the best predictor of antisocial and criminal behavior in children was whether their parents had been convicted of a crime (Todd and Jury 1996). Children who were younger than 10 when their parents were convicted were more likely than other children to engage in spousal abuse and criminal behavior by their early thirties. Even when taking socioeconomic factors such as dangerous neighborhoods, poor school systems, and overcrowded housing into consideration, researchers found that parents were the main influence on the behavior of their offspring (Todd and Jury 1996). \n\n Travis Hirschi: Control Theory \n\n Continuing with an examination of large social factors, control theory states that social control is directly affected by the strength of social bonds and that deviance results from a feeling of disconnection from society. Individuals who believe they are a part of society are less likely to commit crimes against it. Travis Hirschi (1969) identified four types of social bonds that connect people to society: \n\n Attachment measures our connections to others. When we are closely attached to people, we worry about their opinions of us. People conform to society’s norms in order to gain approval (and prevent disapproval) from family, friends, and romantic partners. \n\n Commitment refers to the investments we make in the community. A well-respected local businesswoman who volunteers at her synagogue and is a member of the neighborhood block organization has more to lose from committing a crime than a woman who doesn’t have a career or ties to the community. \n\n Similarly, levels of involvement , or participation in socially legitimate activities, lessen a person’s likelihood of deviance. Children who are members of little league baseball teams have fewer family crises. \n\n The final bond, belief , is an agreement on common values in society. If a person views social values as beliefs, he or she will conform to them. An environmentalist is more likely to pick up trash in a park because a clean environment is a social value to him (Hirschi 1969). \n7.3 Crime and the Law \n\n On December 16, 2011, 20-year-old Colton Harris-Moore was sentenced to seven years in prison by an Island County judge after pleading guilty to dozens of charges including burglary, fraud, and identity theft. Harris-Moore, dubbed the “Barefoot Bandit,” spent two years evading the police by means of transportation theft and squatting, frequently leaving a trail of bare footprints in his wake (Johnson 2011). \n\n \"Colton's very pleased (with the sentence),\" his attorney John Henry Browne told the New York Times . \"He was expecting the worst.\" \n\n The son of an alcoholic mother, Harris-Moore’s life was filled with physical and verbal abuse, and a series of convict boyfriends frequently inhabited the Harris-Moore home. After dropping out of school in the ninth grade, Harris Moore’s crimes increased in severity. His antics gained worldwide media attention after he began stealing and successfully piloting planes, though he’d had no aviation training. When authorities caught him, he was driving a stolen boat off the coast of the Bahamas (Yardley 2010). \n\n \"This case is a tragedy in many ways,” said Judge Churchill, “but it's a triumph of the human spirit in other ways. I could have been reading about the history of a mass murderer. I could have been reading about a drug abusive, alcoholic young man. That is the triumph of Colton Harris-Moore: He has survived\" (Johnson 2011). \n\n Though the judge’s ruling was largely sympathetic, Harris-Moore had immediate regrets. \"Let me put it this way,” said his attorney. “He wishes he had done things a little differently in his life\" (CNN News Wire Staff 2010). \n\n Although deviance is a violation of social norms, it’s not always punishable, and it’s not necessarily bad. Crime , on the other hand, is a behavior that violates official law and is punishable through formal sanctions. Walking to class backwards is a deviant behavior. Driving with a blood alcohol percentage over the state’s limit is a crime. Like other forms of deviance, however, ambiguity exists concerning what constitutes a crime and whether all crimes are, in fact, “bad” and deserve punishment. For example, during the 1960s, civil rights activists often violated laws intentionally as part of their effort to bring about racial equality. In hindsight, we recognize that the laws that deemed many of their actions crimes—for instance, Rosa Parks taking a seat in the “whites only” section of the bus—were inconsistent with social equality. \n\n As you learned previously, all societies have informal and formal ways of maintaining social control. Within these systems of norms, societies have legal codes that maintain formal social control through laws, which are rules adopted and enforced by a political authority. Those who violate these rules incur negative formal sanctions. Normally, punishments are relative to the degree of the crime and the importance to society of the value underlying the law. As we will see, however, there are other factors that influence criminal sentencing. \n\n Types of Crimes \n\n Not all crimes are given equal weight. Society generally socializes its members to view certain crimes as more severe than others. For example, most people would consider murdering someone to be far worse than stealing a wallet and would expect a murderer to be punished more severely than a thief. In modern American society, crimes are classified as one of two types based on their severity. Violent crimes (also known as “crimes against a person”) are based on the use of force or the threat of force. Rape, murder, and armed robbery fall under this category. Nonviolent crimes involve the destruction or theft of property, but do not use force or the threat of force. Because of this, they are also sometimes called “property crimes.” Larceny, car theft, and vandalism are all types of nonviolent crimes. If you use a crowbar to break into a car, you are committing a nonviolent crime; if you mug someone with the crowbar, you are committing a violent crime. \n\n When we think of crime, we often picture street crime , or offenses committed by ordinary people against other people or organizations, usually in public spaces. An often overlooked category is corporate crime , or crime committed by white-collar workers in a business environment. Embezzlement, insider trading, and identity theft are all types of corporate crime. Although these types of offenses rarely receive the same amount of media coverage as street crimes, they can be far more damaging. The current economic recession in the United States is the ultimate result of a financial collapse triggered by corporate crime. \n\n An often-debated third type of crime is victimless crime . These are called victimless because the perpetrator is not explicitly harming another person. As opposed to battery or theft, which clearly have a victim, a crime like drinking a beer at age 20 or selling a sexual act do not result in injury to anyone other than the individual who engages in them, although they are illegal. While some claim acts like these are victimless, others argue that they actually do harm society. Prostitution may foster abuse toward women by clients or pimps. Drug use may increase the likelihood of employee absences. Such debates highlight how the deviant and criminal nature of actions develops through ongoing public discussion. \n\n Big Picture Hate Crimes On the evening of October 3, 2010, a 17-year-old boy from the Bronx was abducted by a group of young men from his neighborhood and taken to an abandoned row house. After being beaten, the boy admitted he was gay. His attackers seized his partner and beat him as well. Both victims were drugged, sodomized, and forced to burn one another with cigarettes. When questioned by police, the ringleader of the crime explained that the victims were gay and “looked like [they] liked it” (Wilson and Baker 2010). \n\n Attacks based on a person’s race, religion, or other characteristics are known as hate crimes . Hate crimes in the United States evolved from the time of early European settlers and their violence toward Native Americans. Such crimes weren’t investigated until the early 1900s, when the Ku Klux Klan began to draw national attention for its activities against blacks and other groups. The term “hate crime,” however, didn’t become official until the1980s (Federal Bureau of Investigations 2011). \n\n An average of 195,000 Americans fall victim to hate crimes each year, but fewer than five percent ever report the crime (FBI 2010). The majority of hate crimes are racially motivated, but many are based on religious (especially anti-Semitic) prejudice (FBI 2010). After incidents like the murder of Matthew Shepard in Wyoming in 1998 and the tragic suicide of Rutgers University student Tyler Clementi in 2010, there has been a growing awareness of hate crimes based on sexual orientation. \n\n Crime Statistics \n\n What crimes are people in the United States most likely to commit, and who is most likely to commit them? To understand criminal statistics, you must first understand how these statistics are collected. \n\n Since 1930, the Federal Bureau of Investigation has been collecting and publishing an archive of crime statistics. Known as Uniform Crime Reports (UCR), these annual publications contain data from approximately 17,000 law enforcement agencies (FBI 2011). Although the UCR contains comprehensive data on police reports, it fails to take into account the fact that many crimes go unreported due to the victim’s unwillingness to report them, largely based on fear, shame, or distrust of the police. The quality of the data collected by the UCR also varies greatly. Because officers’ approaches to gathering victims’ accounts frequently differed, important details were not always asked for or reported (Cantor and Lynch 2000). \n\n To offset this publication, in 1973 the U.S. Bureau of Justice Statistics began to publish a separate report known as the National Crime Victimization Survey (NCVS). The NCVS is a self-report study . A self-report study is a collection of data acquired using voluntary response methods, such as questionnaires or telephone interviews. Each year, survey data are gathered from approximately 135,000 people in the United States on the frequency and type of crime they experience in their daily lives (BJS 2011). The surveys are thorough, providing a wider scope of information than was previously available. This allows researchers to examine crime from more detailed perspectives and to analyze the data based on factors such as the relationship between victims and offenders, the consequences of the crimes, and substance abuse involved in the crimes. Demographics are also analyzed, such as age, race, gender, location, and income level (National Archive of Criminal Justice Data 2010). The NCVS reports a higher rate of crime than the UCR. \n\n Though the NCVS is a critical source of statistical information, disadvantages exist. “Non-response,” or a victim’s failure to participate in the survey or a particular question, is among them. Inability to contact important demographics, such as those who don’t have access to phones or frequently relocate, also skews the data. For those who participate, memory issues can be problematic for the data sets. Some victims’ recollection of the crimes can be inaccurate or simply forgotten over time (Cantor and Lynch 2000). \n\n While neither of these publications can take into account all of the crimes committed in the country, some general trends may be noted. Crime rates were on the rise after 1960, but following an all-time high in the 1980s and 1990s, rates of violent and non-violent crimes once again started to decline. \n\n In 2009, approximately 4.3 million violent crimes occurred in the United States, the majority being assault and robbery. An estimated 15.6 million nonviolent crimes took place, the most common being larceny. Less than half of all violent and nonviolent crimes were reported to the police (BJS 2010). \n\n In general, demographic patterns tend to correlate with crime: factors such as sex and socioeconomic status may relate to a person’s chances of being a crime victim or a perpetrator. Women are much more likely than men to be victimized by someone they know, such as a family member or friend, and one-fourth of all nonfatal attacks on women are carried out by a romantic partner (BJS 2011b). \n\n The United States Criminal Justice System A criminal justice system is an organization that exists to enforce a legal code. There are three branches of the United States criminal justice system: the police, the courts, and the corrections system. \n\n Police \n\n Police are a civil force in charge of enforcing laws and public order at a federal, state, or community level. No unified national police force exists in the United States, although there are federal law enforcement officers. Federal officers operate under specific government agencies such as the Federal Bureau of Investigations (FBI); the Bureau of Alcohol, Tobacco, Firearms, and Explosives (ATF); and the Department of Homeland Security (DHS). Federal officers can only deal with matters that are explicitly within the power of the federal government, and their field of expertise is usually narrow. A county police officer may spend time responding to emergency calls, working at the local jail, or patrolling areas as needed, whereas a federal officer would be more likely to investigate suspects in firearms trafficking or provide security for government officials. \n\n State police have the authority to enforce statewide laws, including regulating traffic on highways. Local or county police, on the other hand, have a limited jurisdiction with authority only in the town or county in which they serve. \n\n Courts Once a crime has been committed and a violator is identified by the police, the case goes to the court. A court is a system that has the authority to make decisions based on law. Similar to the police, the U.S. judicial system is divided into federal courts and state courts. As the name implies, federal courts (including the U.S. Supreme Court) deal with federal matters, including trade disputes, military justice, and government lawsuits. Judges who preside over federal courts are selected by the president with the consent of Congress. \n\n State courts vary in their structure, but generally include three levels: trial courts, appellate courts, and state supreme courts. Unlike the large courtroom trials in TV shows, most noncriminal cases are decided by a judge without a jury present. Traffic court and small claims court are both types of trial courts that handle specific civil matters. \n\n Criminal cases are heard by trial courts that handle general jurisdictions. Usually, a judge and jury are both present. It is the jury’s responsibility to determine guilt, and the judge’s responsibility to determine the penalty, though in some states, the jury may also decide the penalty. Unless a defendant is found “not guilty,” any member of the prosecution or defense can appeal the case to a higher court. In some states, the case then goes to a special appellate court; in others, it goes to the highest state court, often known as the state supreme court. \n\n Corrections \n\n The corrections system , more commonly known as the prison system, is tasked with supervising individuals who have been arrested, convicted, and sentenced for a criminal offense. At the end of 2010, approximately seven million Americans were behind bars (BJS 2011d). \n\n The United States incarceration rate has grown considerably in the last hundred years. In 2008, more than 1 in 100 U.S. adults were in jail or prison, the highest benchmark in our nation’s history. And while Americans account for 5 percent of the global population, we have 25 percent of the world’s inmates, the largest number of prisoners in the world (Liptak 2008b). \n\n Prison is different from jail. A jail provides temporary confinement, usually while an individual awaits trial or parole. Prisons are facilities built for individuals serving sentences of more than a year. Whereas jails are small and local, prisons are large and run by either the state or the federal government. \n\n Parole refers to a temporary release from prison or jail that requires supervision and the consent of officials. Parole is different from probation, which is supervised time used as an alternative to prison. Probation and parole can both follow a period of incarceration in prison, especially if the prison sentence is shortened. "}}},{"rowIdx":182,"cells":{"bname":{"kind":"string","value":"principles_of_accounting,_volume_1:_financial_accounting"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":" Summary 7.1 Define and Describe the Components of an Accounting Information System \n\n An accounting information system is a set of business processes that record transactions using journals and ledgers (a paper-based system) or computer files (using a computerized system) to keep track of a company’s money and other assets. \n\n The key steps in an accounting information system are input, processing, and output.\n\n Input: This is any way to record the transaction. \n\n Processing: This is a method of combining similar kinds of information (like adding all cash sales together to get a total that is separate from all credit sales; and then adding everything to find total sales). \n\n Output: Any way used to display the results of the processing is output. \n\n Source document: This is a record that a transaction has taken place; it is often used at the input stage. \n\n Storage: This is any method used to save the results generated by the system. Data that is stored is retrieved and used in the input, processing, or output stage. Additional data and information are also stored during these processes. \n\n 7.2 Describe and Explain the Purpose of Special Journals and Their Importance to Stakeholders \n\n We use special journals to keep track of similar types of transactions. \n\n We use special journals to save time because the same types of transactions occur over and over. \n\n To decide which special journal to use, first ask, “Is cash involved?” If the answer is “Yes,” then use either the cash receipts or cash disbursements journal. \n\n The cash receipts journal always debits cash but can credit almost anything (primarily sales, Accounts Receivable, or a new loan from the bank). \n\n The cash disbursements journal always credits cash but can debit almost anything (Accounts Payable, Notes Payable, sales returns and allowances, telephone expense, etc.). \n\n The sales journal always debits Accounts Receivable and always credits Sales. If the company uses a perpetual inventory method, it also debits cost of goods sold and credits inventory. \n\n The purchases journal always debits Purchases (if using the periodic inventory method) or Inventory (if using the perpetual inventory method) and credits Accounts Payable. \n\n We post the monthly balance from each of the special journals to the general ledger at the end of the month. \n\n We post from all journals to the subsidiary ledgers daily. \n\n We use the general journal for transactions that do not fit anywhere else—generally, for adjusting and closing entries, and can be for sales returns and/or purchase returns. \n\n The accounts receivable subsidiary ledger contains all of the details about individual accounts. \n\n The total of the accounts receivable subsidiary ledger must equal the total in the Accounts Receivable general ledger account. \n\n The accounts payable subsidiary ledger contains all of the details about individual accounts payable accounts. \n\n The total of the accounts payable subsidiary ledger must equal the total in the Accounts Payable general ledger account. \n\n 7.3 Analyze and Journalize Transactions Using Special Journals \n\n Rules of cash receipts journals: Use any time you receive cash. Always debit Cash and credit Accounts Receivable or some other account. \n\n Rules of cash disbursements journals: Any time a check is issued, there should be a credit to cash and a debit to AP or typically an expense. Always credit Cash and debit Accounts Payable or some other account. \n\n Rules of sales journals: Use only for sales of goods on credit (when customers charge the amount). Always debit Accounts Receivable and credit Sales and debit Cost of Goods Sold and credit Merchandise Inventory when using a perpetual inventory system. \n\n Rules of purchases journals: Use only for purchase of goods (inventory) on credit (when you charge the amount). Always debit Merchandise Inventory when using a perpetual inventory system (or Purchases when using a periodic inventory system) and credit Accounts Payable. \n\n Post daily to the subsidiary ledgers. \n\n Monthly, at the end of each month, after totaling all of the columns in each journal, post to the general ledger accounts which include the Accounts Receivable and Accounts Payable (general ledger) controlling accounts. Note that the only column that you do not post the total to the general ledger account is the Other Accounts column. There is no general ledger account called Other accounts. As mentioned, each entry in that column is posted individually to its respective account. \n\n 7.4 Prepare a Subsidiary Ledger \n\n A schedule of accounts receivable is a list of all individual accounts and balances that make up accounts receivable. \n\n A schedule of accounts payable is a list of all individual accounts and balances that make up accounts payable. \n\n 7.5 Describe Career Paths Open to Individuals with a Joint Education in Accounting and Information Systems \n\n Data analytics, artificial intelligence systems, data security credentials, blockchain applications, and forensic accounting are some of the areas that provide newer career avenues for accounting professionals. \n\n Taxes will continue to be prepared using software that pulls information from the accounting information system. \n\n Integrating accounting software with inventory management and electronic payment as used by Walmart and Amazon will set new standards of business process automation. \n\n Forensic accounting, data security, artificial intelligence, and data analytics, are all areas for which companies and government agencies will be seeking accounting graduates who are also knowledgeable about information systems. "},"intro":{"kind":"string","value":" Chapter Outline 7.1 Define and Describe the Components of an Accounting Information System 7.2 Describe and Explain the Purpose of Special Journals and Their Importance to Stakeholders 7.3 Analyze and Journalize Transactions Using Special Journals 7.4 Prepare a Subsidiary Ledger 7.5 Describe Career Paths Open to Individuals with a Joint Education in Accounting and Information Systems Why It Matters \n\n Shane was a talented tennis player at his university. He had a hard time finding a job in his field upon graduation. While he worked toward finding employment, he spent time on a tennis court playing, and parents began asking if he would give lessons to their kids. Excited for the opportunity and income, he started giving lessons and kept track of sessions and payments by printing out notes and piling them on his desk. When it came time to file a tax return, though, he realized that he should have been keeping up with his bookkeeping all along, either manually in some sort of ledger or electronically on his computer. \n\n Rather quickly, his student pool grew. Some clients paid up front for lessons, others paid after a few lessons were complete, and still others were not sure if they had paid yet. These various payment methods created a record-keeping challenge for Shane. With winter coming, Shane was exploring the idea of securing court time at an indoor facility to continue teaching and knew he would need to consider court time rental costs in his lesson expenses. Additionally, Shane planned to offer group lessons as well as camps and would need to hire another coach. As Shane’s impromptu business blossomed, it came with additional sources and types of revenues as well as new expenses. He needed a better system to keep track of the financial aspects of his business. \n\n A friend told him he needed an accounting information system to organize the financial aspects of his business and to allow him to measure the financial performance of his growing business. But what did Shane’s friend mean? What is an accounting information system? In this chapter, we explain accounting information systems, their evolution from paper-based to digital formats, and how a company—whether small like Shane’s tennis lesson venture or large like a major corporation—uses these systems to stay on top of its finances and to inform important business decisions. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"Firms are also developing and using artificial intelligence ( AI ) systems to perform tasks previously performed by accounting professionals , but now are freeing up the professionals to perform higher-level tasks requiring analysis and judgment . Finally , security of all of this available data is a very important issue , and there are a number of career paths and certifications that information technology professionals can attain . The Information Systems Audit and Control Association ( ISACA ) offers several certifications including Certified Information Systems Auditor ( CISA ) , Certified in Risk and Information System Controls ( CRISC ) , Certified Information Security Manager ( CISM ) , and others . There is so much technology that we are inundated with more information than we can use . <hl> Because the information is being generated by a machine , we generally trust the computation ( although there are cases where a bug in the program can even cause problems with simple math ) , but we also know the old saying , “ garbage in , garbage out . ” The computer does not always know that your typo is garbage . <hl> <hl> If you enter the wrong number , the system processes it as if it were the right number . <hl> That means we have to build some way into the program to control what is input into the system . For example , if you fill out a form online and it asks for your zip code , does it let you enter just four digits ? No — the computer knows that it should only go to the next step if you enter five digits . However , you can enter the wrong digits and it might not catch it . It is critical that we build as many internal controls into our computerized systems as possible so that we can find errors at the input stage before they get into our system . In other words , by using these “ preventive ” controls , we do not allow “ garbage ” data to get into our system .","hl_sentences":"Because the information is being generated by a machine , we generally trust the computation ( although there are cases where a bug in the program can even cause problems with simple math ) , but we also know the old saying , “ garbage in , garbage out . ” The computer does not always know that your typo is garbage . If you enter the wrong number , the system processes it as if it were the right number .","question":{"cloze_format":"So far, computer systems cannot yet ________.","normal_format":"So far, what can computer systems not yet?","question_choices":["receive data and instructions from input devices such as a scanner.","decide how to record a business transaction.","communicate with other computers electronically.","recognize that you made a mistake entering $100 when you meant to enter $101."],"question_id":"fs-idm458596784","question_text":"So far, computer systems cannot yet ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"output"},"bloom":null,"hl_context":"AISs , whether computerized or manual , generally involve three stages : input , processing , and output . <hl> We enter raw data into our system at the input stage and try to correct any errors prior to going on to the next stage of processing the data . <hl> <hl> We ultimately produce “ output , ” which is in the form of useful information . <hl>","hl_sentences":"We enter raw data into our system at the input stage and try to correct any errors prior to going on to the next stage of processing the data . We ultimately produce “ output , ” which is in the form of useful information .","question":{"cloze_format":"Any device used to provide the results of processing data is a(n) ________ device.","normal_format":"What is a(n) device used to provide the results of processing data?","question_choices":["sources","input","output","storage"],"question_id":"fs-idm209030288","question_text":"Any device used to provide the results of processing data is a(n) ________ device."},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"<hl> Businesses need a way to input data from the source document such as a sales invoice or purchase order . <hl> <hl> This was previously done with pen and paper and is currently done by keying it in on a computer keyboard ; scanning , with a scanner such as one that reads MICR ( magnetic ink character recognition ) symbols ( found on bank checks ) or POS system scanners at cash registers that scan product bar codes / UPC symbols ; or receiving it by e-transmission ( or electronic funds transfer [ EFT ] ) . <hl> Input often involves the use of hardware such as scanners , keypads , keyboards , touch screens , or fingerprint readers called biometric devices . Once data has been input , it must be processed in order to be useful .","hl_sentences":"Businesses need a way to input data from the source document such as a sales invoice or purchase order . This was previously done with pen and paper and is currently done by keying it in on a computer keyboard ; scanning , with a scanner such as one that reads MICR ( magnetic ink character recognition ) symbols ( found on bank checks ) or POS system scanners at cash registers that scan product bar codes / UPC symbols ; or receiving it by e-transmission ( or electronic funds transfer [ EFT ] ) .","question":{"cloze_format":"Source documents ________.","normal_format":"What are source documents?","question_choices":["are input devices","are output devices","do not have to be on paper","cannot be electronic files"],"question_id":"fs-idm176579696","question_text":"Source documents ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"software to process the source data"},"bloom":null,"hl_context":"<hl> Input : This includes entering the data from the source document on the computer keyboard , electronically scanning the bar code of each product purchased at the grocery store ( at checkout counter and to receive goods from vendor off the truck ) , maybe fingerprinting at the time clock , or keying in a price on the register . <hl> <hl> Businesses need a way to input data from the source document such as a sales invoice or purchase order . <hl> <hl> This was previously done with pen and paper and is currently done by keying it in on a computer keyboard ; scanning , with a scanner such as one that reads MICR ( magnetic ink character recognition ) symbols ( found on bank checks ) or POS system scanners at cash registers that scan product bar codes / UPC symbols ; or receiving it by e-transmission ( or electronic funds transfer [ EFT ] ) . <hl> <hl> Input often involves the use of hardware such as scanners , keypads , keyboards , touch screens , or fingerprint readers called biometric devices . <hl> Once data has been input , it must be processed in order to be useful .","hl_sentences":"Input : This includes entering the data from the source document on the computer keyboard , electronically scanning the bar code of each product purchased at the grocery store ( at checkout counter and to receive goods from vendor off the truck ) , maybe fingerprinting at the time clock , or keying in a price on the register . Businesses need a way to input data from the source document such as a sales invoice or purchase order . This was previously done with pen and paper and is currently done by keying it in on a computer keyboard ; scanning , with a scanner such as one that reads MICR ( magnetic ink character recognition ) symbols ( found on bank checks ) or POS system scanners at cash registers that scan product bar codes / UPC symbols ; or receiving it by e-transmission ( or electronic funds transfer [ EFT ] ) . Input often involves the use of hardware such as scanners , keypads , keyboards , touch screens , or fingerprint readers called biometric devices .","question":{"cloze_format":"All of the following can provide source data except ________.","normal_format":"Which of the following cannot provide source data?","question_choices":["a scanning device at the grocery store","a utility bill received in the mail","a bar code reader","software to process the source data"],"question_id":"fs-idm465768128","question_text":"All of the following can provide source data except ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> Some companies send paper bills in the mail , often asking the recipient to tear off part of the bill and return it with the payment . <hl> <hl> This tear-off portion is a turn-around document and helps ensure that the payment is applied to the correct customer account and invoice . <hl> Generally , this document began as printed output , an invoice , from the billing part of the AIS . When the customer tears off a part of it and returns it in the envelope with a check to the company , it has now been “ turned around ” and will be used as an input source document , called a remittance advice . A remittance advice is a document that customers send along with checks and informs the recipient as to which invoice the customer is paying for . Figure 7.4 is an example of a turn-around document .","hl_sentences":"Some companies send paper bills in the mail , often asking the recipient to tear off part of the bill and return it with the payment . This tear-off portion is a turn-around document and helps ensure that the payment is applied to the correct customer account and invoice .","question":{"cloze_format":"A document that asks you to return an identifying part of it with your payment is a(n) ________.","normal_format":"What document asks you to return an identifying part of it with your payment?","question_choices":["source document","cloud document","point-of-sale document","turn-around document"],"question_id":"fs-idm196998080","question_text":"A document that asks you to return an identifying part of it with your payment is a(n) ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"They prevent errors and stop employees from stealing inventory."},"bloom":null,"hl_context":"<hl> Interestingly , the term accounting information system predates computers . <hl> <hl> Technically , an AIS is a system or set of processes for collecting data about accounting transactions ; recording , organizing , and summarizing the data ; and culminating with the preparation of financial statements and other reports for internal and external users . <hl> These systems or processes can exist as a series of paper ledgers , computer databases , or some combination of the two . Examples of external users include banks that might lend the company money , investors , and the Securities and Exchange Commission ( SEC ) , which requires that publicly traded companies submit audited financial statements . Since business enterprises needed to produce financial statements long before computers existed , they used manual accounting systems to gather the data needed . Data is the term for parts of accounting transactions that constitute the input to an AIS . You have examined many forms of data in this course , for example , the cash received upon the sale of an item is one data point , the reduction of the inventory account related to that specific sold item is another data point , and both the revenue and the cost of goods sold would be additional data points associated with that single transaction of a sale . These data points are summarized and aggregated ( in other words “ processed ” ) into more meaningful and useful numbers that appear in the financial statements , and all this data is typically referred to as financial information . A company that may have used a manual AIS years ago likely uses a computerized AIS today . It is important to remember that a computerized accounting system does not change what we do with accounting transactions , it only changes how we do it , and how we can present the information to different users .","hl_sentences":"Interestingly , the term accounting information system predates computers . Technically , an AIS is a system or set of processes for collecting data about accounting transactions ; recording , organizing , and summarizing the data ; and culminating with the preparation of financial statements and other reports for internal and external users .","question":{"cloze_format":"It is false about accounting information systems that ___.","normal_format":"Which of the following is false about accounting information systems?","question_choices":["They provide reports that people analyze.","They prevent errors and stop employees from stealing inventory.","They are designed to gather data about the company’s transactions.","They consist of processes that involve input of data from source documents, processing, output, and storage."],"question_id":"fs-idm236075968","question_text":"Which of the following is false about accounting information systems?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"<hl> All of the amounts owed to the company in the accounts receivable subsidiary ledger must equal the amounts in the accounts receivable general ledger account . <hl>","hl_sentences":"All of the amounts owed to the company in the accounts receivable subsidiary ledger must equal the amounts in the accounts receivable general ledger account .","question":{"cloze_format":"The sum of all the accounts in the accounts receivable subsidiary ledger should ________.","normal_format":"The sum of all the accounts in the accounts receivable subsidiary ledger should what?","question_choices":["equal the accounts receivable account balance in the general ledger before posting any amounts","equal the accounts payable account balance in the general ledger before posting any amounts","equal the accounts receivable account balance in the general ledger after posting all amounts","equal the cash account balance in the general ledger after posting all amounts"],"question_id":"fs-idm364136464","question_text":"The sum of all the accounts in the accounts receivable subsidiary ledger should ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> The use of a reference code in any of the special journals is very important . <hl> <hl> Remember , after a sale is recorded in the sales journal , it is posted to the accounts receivable subsidiary ledger , and the use of a reference code helps link the transactions between the journals and ledgers . <hl> Recall that the accounts receivable subsidiary ledger is a record of each customer ’ s account . It looked like Figure 7.16 for Baker Co .","hl_sentences":"The use of a reference code in any of the special journals is very important . Remember , after a sale is recorded in the sales journal , it is posted to the accounts receivable subsidiary ledger , and the use of a reference code helps link the transactions between the journals and ledgers .","question":{"cloze_format":"You just posted a debit to ABC Co. in the accounts receivable subsidiary ledger. The journal from which it came from is the ___ .","normal_format":"You just posted a debit to ABC Co. in the accounts receivable subsidiary ledger. Which special journal did it come from?","question_choices":["sales journal","cash receipts journal","purchases journal","cash disbursements journal","general journal"],"question_id":"fs-idm319013520","question_text":"You just posted a debit to ABC Co. in the accounts receivable subsidiary ledger. Which special journal did it come from?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"sales journal"},"bloom":null,"hl_context":"In addition to the four special journals , there are two special ledgers , the accounts receivable subsidiary ledger and the accounts payable subsidiary ledger . The accounts receivable subsidiary ledger gives details about each person who owes the company money , as shown in Figure 7.13 . Each colored block represents an individual ’ s account and shows only the amount that person owes the company . <hl> Notice that the subsidiary ledger provides the date of the transaction and a reference column to link the transaction to the same information posted in one of the special journals ( or general journal if special journals are not used ) — this reference is usually a code that references the special journal such as SJ for the sales special journal , as well as the amounts owed in the debit column and the payments made in the credit column . <hl> The amounts owed by all of the individuals , as indicated in the subsidiary ledger , are added together to form the accounts receivable control total , and this should equal the Accounts Receivable balance reported in the general ledger as shown in Figure 7.14 . Key points about the accounts receivable subsidiary ledger are :","hl_sentences":"Notice that the subsidiary ledger provides the date of the transaction and a reference column to link the transaction to the same information posted in one of the special journals ( or general journal if special journals are not used ) — this reference is usually a code that references the special journal such as SJ for the sales special journal , as well as the amounts owed in the debit column and the payments made in the credit column .","question":{"cloze_format":"You just posted a credit to Stars Inc. in the accounts receivable subsidiary ledger. The special journal which it came from is the ___ .","normal_format":"You just posted a credit to Stars Inc. in the accounts receivable subsidiary ledger. Which special journal did it come from?","question_choices":["sales journal","cash receipts journal","purchases journal","cash disbursements journal","general journal"],"question_id":"fs-idm362017728","question_text":"You just posted a credit to Stars Inc. in the accounts receivable subsidiary ledger. Which special journal did it come from?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"When the customer pays the amount owed , ( generally using a check ) , bookkeepers use another shortcut to record its receipt . <hl> They use a second special journal , the cash receipts journal . <hl> <hl> The cash receipts journal is used to record all receipts of cash ( recorded by a debit to Cash ) . <hl> In the preceding example , if Baker Co . paid the $ 1,450 owed , there would be a debit to Cash for $ 1,450 and a credit to Accounts Receivable . A notation would be made in the reference column to indicate the payment had been posted to Baker Co . ’ s accounts receivable subsidiary ledger . After Baker Co . ’ s payment , the cash receipts journal would appear as in Figure 7.21 .","hl_sentences":"They use a second special journal , the cash receipts journal . The cash receipts journal is used to record all receipts of cash ( recorded by a debit to Cash ) .","question":{"cloze_format":"You just posted a debit to Cash in the general ledger. The special journal which it came from is the ___ .","normal_format":"You just posted a debit to Cash in the general ledger. Which special journal did it come from?","question_choices":["sales journal","cash receipts journal","purchases journal","cash disbursements journal","general journal"],"question_id":"fs-idm631941488","question_text":"You just posted a debit to Cash in the general ledger. Which special journal did it come from?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"cash receipts journal"},"bloom":null,"hl_context":"<hl> In the cash receipts journal , the credit can be to Accounts Receivable when a customer pays on an account , or Sales , in the case of a cash sale , or to some other account when cash is received for other reasons . <hl> For example , if we overpaid our electric bill , we could get a refund check in the mail . We would use the cash receipts journal because we are receiving cash , but the credit would be to our Utility Expense account . If you look at the example in Figure 7.23 , you see that there is no column for Utility Expense , so how would it be recorded ? We would use some generic column title such as “ other ” to represent those cash transactions in the subsidiary ledger though the specific accounts would actually be identified by account number in the special journal . We would look up the account number for Utility Expense and credit the account for the amount of the check . If we received a refund from the electric company on January 28 in the amount of $ 100 , we would find the account number for utility expense ( say it is 615 ) and record it . At the end of the month , we total the Cash column in the cash receipts journal and debit the Cash account in the general ledger for the total . In this case there were two entries in the cash receipts journal , the cash received from Baker and the refund check for an overpayment on utilities for a total cash received and recorded in the cash receipts journal of $ 1,550 , as shown in Figure 7.24 .","hl_sentences":"In the cash receipts journal , the credit can be to Accounts Receivable when a customer pays on an account , or Sales , in the case of a cash sale , or to some other account when cash is received for other reasons .","question":{"cloze_format":"You just posted a credit to Accounts Receivable. The special journal which it came from is the ___ .","normal_format":"You just posted a credit to Accounts Receivable. Which special journal did it come from?","question_choices":["sales journal","cash receipts journal","purchases journal","cash disbursements journal","general journal"],"question_id":"fs-idm628978928","question_text":"You just posted a credit to Accounts Receivable. Which special journal did it come from?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"Most companies have four special journals , but there can be more depending on the business needs . The four main special journals are the sales journal , purchases journal , cash disbursements journal , and cash receipts journal . These special journals were designed because some journal entries occur repeatedly . <hl> For example , selling goods for cash is always a debit to Cash and a credit to Sales recorded in the cash receipts journal . <hl> Likewise , we would record a sale of goods on credit in the sales journal , as a debit to accounts receivable and a credit to sales . Companies using a perpetual inventory system also record a second entry for a sale with a debit to cost of goods sold and a credit to inventory . You can see sample entries in Figure 7.9 .","hl_sentences":"For example , selling goods for cash is always a debit to Cash and a credit to Sales recorded in the cash receipts journal .","question":{"cloze_format":"You just posted a credit to Sales and a debit to Cash. The special journal from which it came from is the ___ .","normal_format":"You just posted a credit to Sales and a debit to Cash. Which special journal did it come from?","question_choices":["sales journal","cash receipts journal","purchases journal","cash disbursements journal","general journal"],"question_id":"fs-idm631601440","question_text":"You just posted a credit to Sales and a debit to Cash. Which special journal did it come from?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"is a large, company-wide integrated accounting information system that connects all of a company’s applications"},"bloom":null,"hl_context":"Later in the section on how to Prepare a Subsidiary Ledger , you will be provided with a series of transactions for a small business and you will be asked to first enter the transactions manually into the appropriate journal , post the information from the journals to the general ledger , prepare trial balances , adjusting and closing entries , and manually produce financial statements just as Macy ’ s or any other business would have done prior to the use of various computer technologies . You will then perform the same tasks using QuickBooks , a popular accounting software program used by many small and medium-sized businesses . A company as large as Macy ’ s has stores in locations all over the country and a large volume of transactions , so it is more likely to use a software package designed to meet the needs of a very large business . <hl> This is often referred to as an enterprise resource planning ( ERP ) system which stands for enterprise resource planning ( ERP ) system . <hl> <hl> An ERP system integrates all of the company ’ s computerized systems including accounting systems and nonaccounting systems . <hl> That is , large companies have various accounting subsystems such as the revenue system ( sales / accounts receivable / cash receipts ) , the expenditure system ( purchasing / accounts payable / cash disbursements ) , the production system , the payroll system , and the general ledger system . Nonaccounting systems might include research and development , marketing , and human resources , which , while not an integral part of the accounting system , in a large companywide ERP system are integrated with the accounting modules . Examples of popular ERP software systems are PeopleSoft and SAP .","hl_sentences":"This is often referred to as an enterprise resource planning ( ERP ) system which stands for enterprise resource planning ( ERP ) system . An ERP system integrates all of the company ’ s computerized systems including accounting systems and nonaccounting systems .","question":{"cloze_format":"An enterprise resource planning (ERP) system ________.","normal_format":"What is an enterprise resource planning (ERP) system?","question_choices":["is software to help you prepare your tax return","requires that you pay ransom before you can operate it","is a large, company-wide integrated accounting information system that connects all of a company’s applications","is part of the darknet"],"question_id":"fs-idm757178432","question_text":"An enterprise resource planning (ERP) system ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"to find business trends"},"bloom":null,"hl_context":"We use accounting information to make decisions about the business . Computer applications now provide so much data that data analytics is one of the newest career areas in business . Universities are beginning to offer degrees in data analysis . Software companies have created different applications to analyze data including SAS , Apache Hadoop , Apache Spark , SPSS , RapidMiner , Power BI , ACL , IDEA , and many more to help companies discover useful information from the transactions that occur . <hl> Big data refers to the availability of large amounts of data from various sources , including the internet . <hl> <hl> For example , social media sites contain tremendous amounts of data that marketing companies analyze to determine how popular a product is , and how best to market it . <hl> <hl> There is so much data to analyze that new ways of mining it for predictive value have evolved . <hl>","hl_sentences":"Big data refers to the availability of large amounts of data from various sources , including the internet . For example , social media sites contain tremendous amounts of data that marketing companies analyze to determine how popular a product is , and how best to market it . There is so much data to analyze that new ways of mining it for predictive value have evolved .","question":{"cloze_format":"Big data is mined ________.","normal_format":"Why is big data mined?","question_choices":["to find business trends","to record transactions","as an alternative to creating an accounting information system","as an alternative to the darknet"],"question_id":"fs-idm204034528","question_text":"Big data is mined ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"<hl> Firms are also developing and using artificial intelligence ( AI ) systems to perform tasks previously performed by accounting professionals , but now are freeing up the professionals to perform higher-level tasks requiring analysis and judgment . <hl> Finally , security of all of this available data is a very important issue , and there are a number of career paths and certifications that information technology professionals can attain . The Information Systems Audit and Control Association ( ISACA ) offers several certifications including Certified Information Systems Auditor ( CISA ) , Certified in Risk and Information System Controls ( CRISC ) , Certified Information Security Manager ( CISM ) , and others . There is so much technology that we are inundated with more information than we can use . Because the information is being generated by a machine , we generally trust the computation ( although there are cases where a bug in the program can even cause problems with simple math ) , but we also know the old saying , “ garbage in , garbage out . ” The computer does not always know that your typo is garbage . If you enter the wrong number , the system processes it as if it were the right number . That means we have to build some way into the program to control what is input into the system . For example , if you fill out a form online and it asks for your zip code , does it let you enter just four digits ? No — the computer knows that it should only go to the next step if you enter five digits . However , you can enter the wrong digits and it might not catch it . It is critical that we build as many internal controls into our computerized systems as possible so that we can find errors at the input stage before they get into our system . In other words , by using these “ preventive ” controls , we do not allow “ garbage ” data to get into our system .","hl_sentences":"Firms are also developing and using artificial intelligence ( AI ) systems to perform tasks previously performed by accounting professionals , but now are freeing up the professionals to perform higher-level tasks requiring analysis and judgment .","question":{"cloze_format":"Artificial intelligence refers to ________.","normal_format":"What does artificial intelligence refer to?","question_choices":["tutorials that can make humans smarter than they naturally are","programming computers to mimic human reasoning and perform tasks previously performed by humans","humans that do not possess reasonably high IQs","a concept that exists only in science fiction but has not yet been achieved today"],"question_id":"fs-idm215563008","question_text":"Artificial intelligence refers to ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"involves the use of a single shared ledger between the many parties that may be involved in a transaction."},"bloom":null,"hl_context":"Another emerging area involves cryptocurrency , or the use of a digital currency that uses encryption technologies that make these cryptocurrencies impossible to counterfeit . The use of cryptocurrency does not require a bank to transfer or clear funds as is the case with other currencies . Bitcoin is the most well-known cryptocurrency . Blockchain is the platform on which Bitcoin is built . <hl> Blockchain serves as a shared ledger for Bitcoin but is also the foundation of many other applications . <hl> <hl> Simply put , blockchain offers different parties to a transaction ( e . g . , a buyer and a seller ) the opportunity to use a shared ledger rather than each having their own separate ledgers as is the case with traditional systems . <hl> Bitcoin is currently accepted by some large , well-known companies including PwC and EY ( the two largest of the “ big 4 ” accounting firms ) , and Overstock.com .","hl_sentences":"Blockchain serves as a shared ledger for Bitcoin but is also the foundation of many other applications . Simply put , blockchain offers different parties to a transaction ( e . g . , a buyer and a seller ) the opportunity to use a shared ledger rather than each having their own separate ledgers as is the case with traditional systems .","question":{"cloze_format":"Blockchain is a technology that ________.","normal_format":"Which of the following is correct about blockchain?","question_choices":["is in the early stages of being developed","was a failed attempt to change the way we do business","refers to an application developed strictly for the real estate business","involves the use of a single shared ledger between the many parties that may be involved in a transaction."],"question_id":"fs-idm216256096","question_text":"Blockchain is a technology that ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"Another emerging area involves cryptocurrency , or the use of a digital currency that uses encryption technologies that make these cryptocurrencies impossible to counterfeit . <hl> The use of cryptocurrency does not require a bank to transfer or clear funds as is the case with other currencies . <hl> <hl> Bitcoin is the most well-known cryptocurrency . <hl> Blockchain is the platform on which Bitcoin is built . Blockchain serves as a shared ledger for Bitcoin but is also the foundation of many other applications . Simply put , blockchain offers different parties to a transaction ( e . g . , a buyer and a seller ) the opportunity to use a shared ledger rather than each having their own separate ledgers as is the case with traditional systems . <hl> Bitcoin is currently accepted by some large , well-known companies including PwC and EY ( the two largest of the “ big 4 ” accounting firms ) , and Overstock.com . <hl>","hl_sentences":"The use of cryptocurrency does not require a bank to transfer or clear funds as is the case with other currencies . Bitcoin is the most well-known cryptocurrency . Bitcoin is currently accepted by some large , well-known companies including PwC and EY ( the two largest of the “ big 4 ” accounting firms ) , and Overstock.com .","question":{"cloze_format":"It is not true about cybercurrency that ___.","normal_format":"Which of the following is not true about cybercurrency?","question_choices":["Bitcoin is one of several cybercurrencies.","It is an alternate currency that does not go through the banking system.","It does not involve the actual exchange of physical currency.","It is not accepted by any legitimate businesses."],"question_id":"fs-idm203836800","question_text":"Which of the following is not true about cybercurrency?"},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"Firms are also developing and using artificial intelligence ( AI ) systems to perform tasks previously performed by accounting professionals , but now are freeing up the professionals to perform higher-level tasks requiring analysis and judgment . Finally , security of all of this available data is a very important issue , and there are a number of career paths and certifications that information technology professionals can attain . The Information Systems Audit and Control Association ( ISACA ) offers several certifications including Certified Information Systems Auditor ( CISA ) , Certified in Risk and Information System Controls ( CRISC ) , Certified Information Security Manager ( CISM ) , and others . There is so much technology that we are inundated with more information than we can use . <hl> Because the information is being generated by a machine , we generally trust the computation ( although there are cases where a bug in the program can even cause problems with simple math ) , but we also know the old saying , “ garbage in , garbage out . ” The computer does not always know that your typo is garbage . <hl> <hl> If you enter the wrong number , the system processes it as if it were the right number . <hl> That means we have to build some way into the program to control what is input into the system . For example , if you fill out a form online and it asks for your zip code , does it let you enter just four digits ? No — the computer knows that it should only go to the next step if you enter five digits . However , you can enter the wrong digits and it might not catch it . It is critical that we build as many internal controls into our computerized systems as possible so that we can find errors at the input stage before they get into our system . In other words , by using these “ preventive ” controls , we do not allow “ garbage ” data to get into our system .\",\n \"hl_sentences\": \"Because the information is being generated by a machine , we generally trust the computation ( although there are cases where a bug in the program can even cause problems with simple math ) , but we also know the old saying , “ garbage in , garbage out . ” The computer does not always know that your typo is garbage . If you enter the wrong number , the system processes it as if it were the right number .\",\n \"question\": {\n \"cloze_format\": \"So far, computer systems cannot yet ________.\",\n \"normal_format\": \"So far, what can computer systems not yet?\",\n \"question_choices\": [\n \"receive data and instructions from input devices such as a scanner.\",\n \"decide how to record a business transaction.\",\n \"communicate with other computers electronically.\",\n \"recognize that you made a mistake entering $100 when you meant to enter $101.\"\n ],\n \"question_id\": \"fs-idm458596784\",\n \"question_text\": \"So far, computer systems cannot yet ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"output\"\n },\n \"bloom\": null,\n \"hl_context\": \"AISs , whether computerized or manual , generally involve three stages : input , processing , and output . <hl> We enter raw data into our system at the input stage and try to correct any errors prior to going on to the next stage of processing the data . <hl> <hl> We ultimately produce “ output , ” which is in the form of useful information . <hl>\",\n \"hl_sentences\": \"We enter raw data into our system at the input stage and try to correct any errors prior to going on to the next stage of processing the data . We ultimately produce “ output , ” which is in the form of useful information .\",\n \"question\": {\n \"cloze_format\": \"Any device used to provide the results of processing data is a(n) ________ device.\",\n \"normal_format\": \"What is a(n) device used to provide the results of processing data?\",\n \"question_choices\": [\n \"sources\",\n \"input\",\n \"output\",\n \"storage\"\n ],\n \"question_id\": \"fs-idm209030288\",\n \"question_text\": \"Any device used to provide the results of processing data is a(n) ________ device.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Businesses need a way to input data from the source document such as a sales invoice or purchase order . <hl> <hl> This was previously done with pen and paper and is currently done by keying it in on a computer keyboard ; scanning , with a scanner such as one that reads MICR ( magnetic ink character recognition ) symbols ( found on bank checks ) or POS system scanners at cash registers that scan product bar codes / UPC symbols ; or receiving it by e-transmission ( or electronic funds transfer [ EFT ] ) . <hl> Input often involves the use of hardware such as scanners , keypads , keyboards , touch screens , or fingerprint readers called biometric devices . Once data has been input , it must be processed in order to be useful .\",\n \"hl_sentences\": \"Businesses need a way to input data from the source document such as a sales invoice or purchase order . This was previously done with pen and paper and is currently done by keying it in on a computer keyboard ; scanning , with a scanner such as one that reads MICR ( magnetic ink character recognition ) symbols ( found on bank checks ) or POS system scanners at cash registers that scan product bar codes / UPC symbols ; or receiving it by e-transmission ( or electronic funds transfer [ EFT ] ) .\",\n \"question\": {\n \"cloze_format\": \"Source documents ________.\",\n \"normal_format\": \"What are source documents?\",\n \"question_choices\": [\n \"are input devices\",\n \"are output devices\",\n \"do not have to be on paper\",\n \"cannot be electronic files\"\n ],\n \"question_id\": \"fs-idm176579696\",\n \"question_text\": \"Source documents ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"software to process the source data\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Input : This includes entering the data from the source document on the computer keyboard , electronically scanning the bar code of each product purchased at the grocery store ( at checkout counter and to receive goods from vendor off the truck ) , maybe fingerprinting at the time clock , or keying in a price on the register . <hl> <hl> Businesses need a way to input data from the source document such as a sales invoice or purchase order . <hl> <hl> This was previously done with pen and paper and is currently done by keying it in on a computer keyboard ; scanning , with a scanner such as one that reads MICR ( magnetic ink character recognition ) symbols ( found on bank checks ) or POS system scanners at cash registers that scan product bar codes / UPC symbols ; or receiving it by e-transmission ( or electronic funds transfer [ EFT ] ) . <hl> <hl> Input often involves the use of hardware such as scanners , keypads , keyboards , touch screens , or fingerprint readers called biometric devices . <hl> Once data has been input , it must be processed in order to be useful .\",\n \"hl_sentences\": \"Input : This includes entering the data from the source document on the computer keyboard , electronically scanning the bar code of each product purchased at the grocery store ( at checkout counter and to receive goods from vendor off the truck ) , maybe fingerprinting at the time clock , or keying in a price on the register . Businesses need a way to input data from the source document such as a sales invoice or purchase order . This was previously done with pen and paper and is currently done by keying it in on a computer keyboard ; scanning , with a scanner such as one that reads MICR ( magnetic ink character recognition ) symbols ( found on bank checks ) or POS system scanners at cash registers that scan product bar codes / UPC symbols ; or receiving it by e-transmission ( or electronic funds transfer [ EFT ] ) . Input often involves the use of hardware such as scanners , keypads , keyboards , touch screens , or fingerprint readers called biometric devices .\",\n \"question\": {\n \"cloze_format\": \"All of the following can provide source data except ________.\",\n \"normal_format\": \"Which of the following cannot provide source data?\",\n \"question_choices\": [\n \"a scanning device at the grocery store\",\n \"a utility bill received in the mail\",\n \"a bar code reader\",\n \"software to process the source data\"\n ],\n \"question_id\": \"fs-idm465768128\",\n \"question_text\": \"All of the following can provide source data except ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Some companies send paper bills in the mail , often asking the recipient to tear off part of the bill and return it with the payment . <hl> <hl> This tear-off portion is a turn-around document and helps ensure that the payment is applied to the correct customer account and invoice . <hl> Generally , this document began as printed output , an invoice , from the billing part of the AIS . When the customer tears off a part of it and returns it in the envelope with a check to the company , it has now been “ turned around ” and will be used as an input source document , called a remittance advice . A remittance advice is a document that customers send along with checks and informs the recipient as to which invoice the customer is paying for . Figure 7.4 is an example of a turn-around document .\",\n \"hl_sentences\": \"Some companies send paper bills in the mail , often asking the recipient to tear off part of the bill and return it with the payment . This tear-off portion is a turn-around document and helps ensure that the payment is applied to the correct customer account and invoice .\",\n \"question\": {\n \"cloze_format\": \"A document that asks you to return an identifying part of it with your payment is a(n) ________.\",\n \"normal_format\": \"What document asks you to return an identifying part of it with your payment?\",\n \"question_choices\": [\n \"source document\",\n \"cloud document\",\n \"point-of-sale document\",\n \"turn-around document\"\n ],\n \"question_id\": \"fs-idm196998080\",\n \"question_text\": \"A document that asks you to return an identifying part of it with your payment is a(n) ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"They prevent errors and stop employees from stealing inventory.\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Interestingly , the term accounting information system predates computers . <hl> <hl> Technically , an AIS is a system or set of processes for collecting data about accounting transactions ; recording , organizing , and summarizing the data ; and culminating with the preparation of financial statements and other reports for internal and external users . <hl> These systems or processes can exist as a series of paper ledgers , computer databases , or some combination of the two . Examples of external users include banks that might lend the company money , investors , and the Securities and Exchange Commission ( SEC ) , which requires that publicly traded companies submit audited financial statements . Since business enterprises needed to produce financial statements long before computers existed , they used manual accounting systems to gather the data needed . Data is the term for parts of accounting transactions that constitute the input to an AIS . You have examined many forms of data in this course , for example , the cash received upon the sale of an item is one data point , the reduction of the inventory account related to that specific sold item is another data point , and both the revenue and the cost of goods sold would be additional data points associated with that single transaction of a sale . These data points are summarized and aggregated ( in other words “ processed ” ) into more meaningful and useful numbers that appear in the financial statements , and all this data is typically referred to as financial information . A company that may have used a manual AIS years ago likely uses a computerized AIS today . It is important to remember that a computerized accounting system does not change what we do with accounting transactions , it only changes how we do it , and how we can present the information to different users .\",\n \"hl_sentences\": \"Interestingly , the term accounting information system predates computers . Technically , an AIS is a system or set of processes for collecting data about accounting transactions ; recording , organizing , and summarizing the data ; and culminating with the preparation of financial statements and other reports for internal and external users .\",\n \"question\": {\n \"cloze_format\": \"It is false about accounting information systems that ___.\",\n \"normal_format\": \"Which of the following is false about accounting information systems?\",\n \"question_choices\": [\n \"They provide reports that people analyze.\",\n \"They prevent errors and stop employees from stealing inventory.\",\n \"They are designed to gather data about the company’s transactions.\",\n \"They consist of processes that involve input of data from source documents, processing, output, and storage.\"\n ],\n \"question_id\": \"fs-idm236075968\",\n \"question_text\": \"Which of the following is false about accounting information systems?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> All of the amounts owed to the company in the accounts receivable subsidiary ledger must equal the amounts in the accounts receivable general ledger account . <hl>\",\n \"hl_sentences\": \"All of the amounts owed to the company in the accounts receivable subsidiary ledger must equal the amounts in the accounts receivable general ledger account .\",\n \"question\": {\n \"cloze_format\": \"The sum of all the accounts in the accounts receivable subsidiary ledger should ________.\",\n \"normal_format\": \"The sum of all the accounts in the accounts receivable subsidiary ledger should what?\",\n \"question_choices\": [\n \"equal the accounts receivable account balance in the general ledger before posting any amounts\",\n \"equal the accounts payable account balance in the general ledger before posting any amounts\",\n \"equal the accounts receivable account balance in the general ledger after posting all amounts\",\n \"equal the cash account balance in the general ledger after posting all amounts\"\n ],\n \"question_id\": \"fs-idm364136464\",\n \"question_text\": \"The sum of all the accounts in the accounts receivable subsidiary ledger should ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The use of a reference code in any of the special journals is very important . <hl> <hl> Remember , after a sale is recorded in the sales journal , it is posted to the accounts receivable subsidiary ledger , and the use of a reference code helps link the transactions between the journals and ledgers . <hl> Recall that the accounts receivable subsidiary ledger is a record of each customer ’ s account . It looked like Figure 7.16 for Baker Co .\",\n \"hl_sentences\": \"The use of a reference code in any of the special journals is very important . Remember , after a sale is recorded in the sales journal , it is posted to the accounts receivable subsidiary ledger , and the use of a reference code helps link the transactions between the journals and ledgers .\",\n \"question\": {\n \"cloze_format\": \"You just posted a debit to ABC Co. in the accounts receivable subsidiary ledger. The journal from which it came from is the ___ .\",\n \"normal_format\": \"You just posted a debit to ABC Co. in the accounts receivable subsidiary ledger. Which special journal did it come from?\",\n \"question_choices\": [\n \"sales journal\",\n \"cash receipts journal\",\n \"purchases journal\",\n \"cash disbursements journal\",\n \"general journal\"\n ],\n \"question_id\": \"fs-idm319013520\",\n \"question_text\": \"You just posted a debit to ABC Co. in the accounts receivable subsidiary ledger. Which special journal did it come from?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"sales journal\"\n },\n \"bloom\": null,\n \"hl_context\": \"In addition to the four special journals , there are two special ledgers , the accounts receivable subsidiary ledger and the accounts payable subsidiary ledger . The accounts receivable subsidiary ledger gives details about each person who owes the company money , as shown in Figure 7.13 . Each colored block represents an individual ’ s account and shows only the amount that person owes the company . <hl> Notice that the subsidiary ledger provides the date of the transaction and a reference column to link the transaction to the same information posted in one of the special journals ( or general journal if special journals are not used ) — this reference is usually a code that references the special journal such as SJ for the sales special journal , as well as the amounts owed in the debit column and the payments made in the credit column . <hl> The amounts owed by all of the individuals , as indicated in the subsidiary ledger , are added together to form the accounts receivable control total , and this should equal the Accounts Receivable balance reported in the general ledger as shown in Figure 7.14 . Key points about the accounts receivable subsidiary ledger are :\",\n \"hl_sentences\": \"Notice that the subsidiary ledger provides the date of the transaction and a reference column to link the transaction to the same information posted in one of the special journals ( or general journal if special journals are not used ) — this reference is usually a code that references the special journal such as SJ for the sales special journal , as well as the amounts owed in the debit column and the payments made in the credit column .\",\n \"question\": {\n \"cloze_format\": \"You just posted a credit to Stars Inc. in the accounts receivable subsidiary ledger. The special journal which it came from is the ___ .\",\n \"normal_format\": \"You just posted a credit to Stars Inc. in the accounts receivable subsidiary ledger. Which special journal did it come from?\",\n \"question_choices\": [\n \"sales journal\",\n \"cash receipts journal\",\n \"purchases journal\",\n \"cash disbursements journal\",\n \"general journal\"\n ],\n \"question_id\": \"fs-idm362017728\",\n \"question_text\": \"You just posted a credit to Stars Inc. in the accounts receivable subsidiary ledger. Which special journal did it come from?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"When the customer pays the amount owed , ( generally using a check ) , bookkeepers use another shortcut to record its receipt . <hl> They use a second special journal , the cash receipts journal . <hl> <hl> The cash receipts journal is used to record all receipts of cash ( recorded by a debit to Cash ) . <hl> In the preceding example , if Baker Co . paid the $ 1,450 owed , there would be a debit to Cash for $ 1,450 and a credit to Accounts Receivable . A notation would be made in the reference column to indicate the payment had been posted to Baker Co . ’ s accounts receivable subsidiary ledger . After Baker Co . ’ s payment , the cash receipts journal would appear as in Figure 7.21 .\",\n \"hl_sentences\": \"They use a second special journal , the cash receipts journal . The cash receipts journal is used to record all receipts of cash ( recorded by a debit to Cash ) .\",\n \"question\": {\n \"cloze_format\": \"You just posted a debit to Cash in the general ledger. The special journal which it came from is the ___ .\",\n \"normal_format\": \"You just posted a debit to Cash in the general ledger. Which special journal did it come from?\",\n \"question_choices\": [\n \"sales journal\",\n \"cash receipts journal\",\n \"purchases journal\",\n \"cash disbursements journal\",\n \"general journal\"\n ],\n \"question_id\": \"fs-idm631941488\",\n \"question_text\": \"You just posted a debit to Cash in the general ledger. Which special journal did it come from?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"cash receipts journal\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> In the cash receipts journal , the credit can be to Accounts Receivable when a customer pays on an account , or Sales , in the case of a cash sale , or to some other account when cash is received for other reasons . <hl> For example , if we overpaid our electric bill , we could get a refund check in the mail . We would use the cash receipts journal because we are receiving cash , but the credit would be to our Utility Expense account . If you look at the example in Figure 7.23 , you see that there is no column for Utility Expense , so how would it be recorded ? We would use some generic column title such as “ other ” to represent those cash transactions in the subsidiary ledger though the specific accounts would actually be identified by account number in the special journal . We would look up the account number for Utility Expense and credit the account for the amount of the check . If we received a refund from the electric company on January 28 in the amount of $ 100 , we would find the account number for utility expense ( say it is 615 ) and record it . At the end of the month , we total the Cash column in the cash receipts journal and debit the Cash account in the general ledger for the total . In this case there were two entries in the cash receipts journal , the cash received from Baker and the refund check for an overpayment on utilities for a total cash received and recorded in the cash receipts journal of $ 1,550 , as shown in Figure 7.24 .\",\n \"hl_sentences\": \"In the cash receipts journal , the credit can be to Accounts Receivable when a customer pays on an account , or Sales , in the case of a cash sale , or to some other account when cash is received for other reasons .\",\n \"question\": {\n \"cloze_format\": \"You just posted a credit to Accounts Receivable. The special journal which it came from is the ___ .\",\n \"normal_format\": \"You just posted a credit to Accounts Receivable. Which special journal did it come from?\",\n \"question_choices\": [\n \"sales journal\",\n \"cash receipts journal\",\n \"purchases journal\",\n \"cash disbursements journal\",\n \"general journal\"\n ],\n \"question_id\": \"fs-idm628978928\",\n \"question_text\": \"You just posted a credit to Accounts Receivable. Which special journal did it come from?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"Most companies have four special journals , but there can be more depending on the business needs . The four main special journals are the sales journal , purchases journal , cash disbursements journal , and cash receipts journal . These special journals were designed because some journal entries occur repeatedly . <hl> For example , selling goods for cash is always a debit to Cash and a credit to Sales recorded in the cash receipts journal . <hl> Likewise , we would record a sale of goods on credit in the sales journal , as a debit to accounts receivable and a credit to sales . Companies using a perpetual inventory system also record a second entry for a sale with a debit to cost of goods sold and a credit to inventory . You can see sample entries in Figure 7.9 .\",\n \"hl_sentences\": \"For example , selling goods for cash is always a debit to Cash and a credit to Sales recorded in the cash receipts journal .\",\n \"question\": {\n \"cloze_format\": \"You just posted a credit to Sales and a debit to Cash. The special journal from which it came from is the ___ .\",\n \"normal_format\": \"You just posted a credit to Sales and a debit to Cash. Which special journal did it come from?\",\n \"question_choices\": [\n \"sales journal\",\n \"cash receipts journal\",\n \"purchases journal\",\n \"cash disbursements journal\",\n \"general journal\"\n ],\n \"question_id\": \"fs-idm631601440\",\n \"question_text\": \"You just posted a credit to Sales and a debit to Cash. Which special journal did it come from?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"is a large, company-wide integrated accounting information system that connects all of a company’s applications\"\n },\n \"bloom\": null,\n \"hl_context\": \"Later in the section on how to Prepare a Subsidiary Ledger , you will be provided with a series of transactions for a small business and you will be asked to first enter the transactions manually into the appropriate journal , post the information from the journals to the general ledger , prepare trial balances , adjusting and closing entries , and manually produce financial statements just as Macy ’ s or any other business would have done prior to the use of various computer technologies . You will then perform the same tasks using QuickBooks , a popular accounting software program used by many small and medium-sized businesses . A company as large as Macy ’ s has stores in locations all over the country and a large volume of transactions , so it is more likely to use a software package designed to meet the needs of a very large business . <hl> This is often referred to as an enterprise resource planning ( ERP ) system which stands for enterprise resource planning ( ERP ) system . <hl> <hl> An ERP system integrates all of the company ’ s computerized systems including accounting systems and nonaccounting systems . <hl> That is , large companies have various accounting subsystems such as the revenue system ( sales / accounts receivable / cash receipts ) , the expenditure system ( purchasing / accounts payable / cash disbursements ) , the production system , the payroll system , and the general ledger system . Nonaccounting systems might include research and development , marketing , and human resources , which , while not an integral part of the accounting system , in a large companywide ERP system are integrated with the accounting modules . Examples of popular ERP software systems are PeopleSoft and SAP .\",\n \"hl_sentences\": \"This is often referred to as an enterprise resource planning ( ERP ) system which stands for enterprise resource planning ( ERP ) system . An ERP system integrates all of the company ’ s computerized systems including accounting systems and nonaccounting systems .\",\n \"question\": {\n \"cloze_format\": \"An enterprise resource planning (ERP) system ________.\",\n \"normal_format\": \"What is an enterprise resource planning (ERP) system?\",\n \"question_choices\": [\n \"is software to help you prepare your tax return\",\n \"requires that you pay ransom before you can operate it\",\n \"is a large, company-wide integrated accounting information system that connects all of a company’s applications\",\n \"is part of the darknet\"\n ],\n \"question_id\": \"fs-idm757178432\",\n \"question_text\": \"An enterprise resource planning (ERP) system ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"to find business trends\"\n },\n \"bloom\": null,\n \"hl_context\": \"We use accounting information to make decisions about the business . Computer applications now provide so much data that data analytics is one of the newest career areas in business . Universities are beginning to offer degrees in data analysis . Software companies have created different applications to analyze data including SAS , Apache Hadoop , Apache Spark , SPSS , RapidMiner , Power BI , ACL , IDEA , and many more to help companies discover useful information from the transactions that occur . <hl> Big data refers to the availability of large amounts of data from various sources , including the internet . <hl> <hl> For example , social media sites contain tremendous amounts of data that marketing companies analyze to determine how popular a product is , and how best to market it . <hl> <hl> There is so much data to analyze that new ways of mining it for predictive value have evolved . <hl>\",\n \"hl_sentences\": \"Big data refers to the availability of large amounts of data from various sources , including the internet . For example , social media sites contain tremendous amounts of data that marketing companies analyze to determine how popular a product is , and how best to market it . There is so much data to analyze that new ways of mining it for predictive value have evolved .\",\n \"question\": {\n \"cloze_format\": \"Big data is mined ________.\",\n \"normal_format\": \"Why is big data mined?\",\n \"question_choices\": [\n \"to find business trends\",\n \"to record transactions\",\n \"as an alternative to creating an accounting information system\",\n \"as an alternative to the darknet\"\n ],\n \"question_id\": \"fs-idm204034528\",\n \"question_text\": \"Big data is mined ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Firms are also developing and using artificial intelligence ( AI ) systems to perform tasks previously performed by accounting professionals , but now are freeing up the professionals to perform higher-level tasks requiring analysis and judgment . <hl> Finally , security of all of this available data is a very important issue , and there are a number of career paths and certifications that information technology professionals can attain . The Information Systems Audit and Control Association ( ISACA ) offers several certifications including Certified Information Systems Auditor ( CISA ) , Certified in Risk and Information System Controls ( CRISC ) , Certified Information Security Manager ( CISM ) , and others . There is so much technology that we are inundated with more information than we can use . Because the information is being generated by a machine , we generally trust the computation ( although there are cases where a bug in the program can even cause problems with simple math ) , but we also know the old saying , “ garbage in , garbage out . ” The computer does not always know that your typo is garbage . If you enter the wrong number , the system processes it as if it were the right number . That means we have to build some way into the program to control what is input into the system . For example , if you fill out a form online and it asks for your zip code , does it let you enter just four digits ? No — the computer knows that it should only go to the next step if you enter five digits . However , you can enter the wrong digits and it might not catch it . It is critical that we build as many internal controls into our computerized systems as possible so that we can find errors at the input stage before they get into our system . In other words , by using these “ preventive ” controls , we do not allow “ garbage ” data to get into our system .\",\n \"hl_sentences\": \"Firms are also developing and using artificial intelligence ( AI ) systems to perform tasks previously performed by accounting professionals , but now are freeing up the professionals to perform higher-level tasks requiring analysis and judgment .\",\n \"question\": {\n \"cloze_format\": \"Artificial intelligence refers to ________.\",\n \"normal_format\": \"What does artificial intelligence refer to?\",\n \"question_choices\": [\n \"tutorials that can make humans smarter than they naturally are\",\n \"programming computers to mimic human reasoning and perform tasks previously performed by humans\",\n \"humans that do not possess reasonably high IQs\",\n \"a concept that exists only in science fiction but has not yet been achieved today\"\n ],\n \"question_id\": \"fs-idm215563008\",\n \"question_text\": \"Artificial intelligence refers to ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"involves the use of a single shared ledger between the many parties that may be involved in a transaction.\"\n },\n \"bloom\": null,\n \"hl_context\": \"Another emerging area involves cryptocurrency , or the use of a digital currency that uses encryption technologies that make these cryptocurrencies impossible to counterfeit . The use of cryptocurrency does not require a bank to transfer or clear funds as is the case with other currencies . Bitcoin is the most well-known cryptocurrency . Blockchain is the platform on which Bitcoin is built . <hl> Blockchain serves as a shared ledger for Bitcoin but is also the foundation of many other applications . <hl> <hl> Simply put , blockchain offers different parties to a transaction ( e . g . , a buyer and a seller ) the opportunity to use a shared ledger rather than each having their own separate ledgers as is the case with traditional systems . <hl> Bitcoin is currently accepted by some large , well-known companies including PwC and EY ( the two largest of the “ big 4 ” accounting firms ) , and Overstock.com .\",\n \"hl_sentences\": \"Blockchain serves as a shared ledger for Bitcoin but is also the foundation of many other applications . Simply put , blockchain offers different parties to a transaction ( e . g . , a buyer and a seller ) the opportunity to use a shared ledger rather than each having their own separate ledgers as is the case with traditional systems .\",\n \"question\": {\n \"cloze_format\": \"Blockchain is a technology that ________.\",\n \"normal_format\": \"Which of the following is correct about blockchain?\",\n \"question_choices\": [\n \"is in the early stages of being developed\",\n \"was a failed attempt to change the way we do business\",\n \"refers to an application developed strictly for the real estate business\",\n \"involves the use of a single shared ledger between the many parties that may be involved in a transaction.\"\n ],\n \"question_id\": \"fs-idm216256096\",\n \"question_text\": \"Blockchain is a technology that ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"Another emerging area involves cryptocurrency , or the use of a digital currency that uses encryption technologies that make these cryptocurrencies impossible to counterfeit . <hl> The use of cryptocurrency does not require a bank to transfer or clear funds as is the case with other currencies . <hl> <hl> Bitcoin is the most well-known cryptocurrency . <hl> Blockchain is the platform on which Bitcoin is built . Blockchain serves as a shared ledger for Bitcoin but is also the foundation of many other applications . Simply put , blockchain offers different parties to a transaction ( e . g . , a buyer and a seller ) the opportunity to use a shared ledger rather than each having their own separate ledgers as is the case with traditional systems . <hl> Bitcoin is currently accepted by some large , well-known companies including PwC and EY ( the two largest of the “ big 4 ” accounting firms ) , and Overstock.com . <hl>\",\n \"hl_sentences\": \"The use of cryptocurrency does not require a bank to transfer or clear funds as is the case with other currencies . Bitcoin is the most well-known cryptocurrency . Bitcoin is currently accepted by some large , well-known companies including PwC and EY ( the two largest of the “ big 4 ” accounting firms ) , and Overstock.com .\",\n \"question\": {\n \"cloze_format\": \"It is not true about cybercurrency that ___.\",\n \"normal_format\": \"Which of the following is not true about cybercurrency?\",\n \"question_choices\": [\n \"Bitcoin is one of several cybercurrencies.\",\n \"It is an alternate currency that does not go through the banking system.\",\n \"It does not involve the actual exchange of physical currency.\",\n \"It is not accepted by any legitimate businesses.\"\n ],\n \"question_id\": \"fs-idm203836800\",\n \"question_text\": \"Which of the following is not true about cybercurrency?\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":7,"string":"7"},"chapter_text":{"kind":"string","value":" 7.1 Define and Describe the Components of an Accounting Information System \n\n Today, when we refer to an accounting information system (AIS) , we usually mean a computerized accounting system, because computers and computer software that help us process accounting transactions have become relatively inexpensive. The benefits of using a computerized accounting system outweigh the costs of purchasing one, and almost all companies, even very small ones, can afford to and do use a computerized accounting system. That is not to say that paper-based or manual accounting systems and processes have disappeared. Most businesses have some form of both noncomputerized and computerized systems. QuickBooks is an example of a relatively inexpensive accounting software application that is popular with small and medium-sized businesses. \n\n Manual and Computerized Accounting Information Systems \n\n Interestingly, the term accounting information system predates computers. Technically, an AIS is a system or set of processes for collecting data about accounting transactions; recording, organizing, and summarizing the data; and culminating with the preparation of financial statements and other reports for internal and external users. These systems or processes can exist as a series of paper ledgers, computer databases, or some combination of the two. Examples of external users include banks that might lend the company money, investors, and the Securities and Exchange Commission (SEC), which requires that publicly traded companies submit audited financial statements. Since business enterprises needed to produce financial statements long before computers existed, they used manual accounting systems to gather the data needed. Data is the term for parts of accounting transactions that constitute the input to an AIS. You have examined many forms of data in this course, for example, the cash received upon the sale of an item is one data point, the reduction of the inventory account related to that specific sold item is another data point, and both the revenue and the cost of goods sold would be additional data points associated with that single transaction of a sale. These data points are summarized and aggregated (in other words “processed”) into more meaningful and useful numbers that appear in the financial statements, and all this data is typically referred to as financial information. A company that may have used a manual AIS years ago likely uses a computerized AIS today. It is important to remember that a computerized accounting system does not change what we do with accounting transactions, it only changes how we do it, and how we can present the information to different users. \n\n Let’s consider the example of a company that came into existence before we had computers, the department store Macy’s , which currently operates stores in nearly all fifty US states. Macy’s began as a small, fancy dry goods store that opened in New York City in 1858, became a department store, R.H. Macy & Co., in 1877 using the same red star logo it still uses today. We can assume that even one hundred years ago, Macy’s needed to perform the same tasks it does today: \n\n purchase merchandise inventory to sell to customers; \n\n record returns of some of the inventory; \n\n record sales made to customers at the sales price; \n\n record the cost of the goods sold at the amount Macy’s paid to purchase them; \n\n record payments from customers; \n\n record returns from customers; \n\n purchase other kinds of items needed for operations, like office supplies and fixed assets; \n\n pay for prior purchases; \n\n pay for rent, utilities, and other services; \n\n pay employees; \n\n enter all of these transactions; \n\n post all transactions; \n\n record adjusting journal entries; \n\n record closing journal entries; \n\n keep track of its receivables, payables, and inventory; and \n\n produce financial statements for internal and external users as well as other reports useful to managers in assessing various performance measures needed to evaluate the success of the company. \n\n As you might imagine, doing all this without computers is quite different than performing these tasks with the aid of computers. In a manual system, each business transaction is recorded, in the form of a journal entry in the general journal or one of the four common other special journals described in Describe and Explain the Purpose of Special Journals and Their Importance to Stakeholders , using pen and paper. Journal entries are then posted to a general ledger; balances would be computed by hand or with an adding machine/calculator for each general ledger account; a trial balance is prepared; adjusting journal entries are prepared; and finally financial statements prepared, all manually. \n\n Concepts In Practice Modernization of Accounting Systems In 1955, in one of the earliest uses of a true computer to facilitate accounting tasks, General Electric Company used a UNIVAC computer to process its payroll. Initially it took the computer forty hours just to process payroll for one pay period. The first modern era spreadsheet software for personal computers, VisiCalc, became available in 1978. Thus, between these time periods there were minor improvements to the use of computerized accounting tools, but it was not until the mid-1980s that comprehensive computerized accounting programs became widely used. Thus, prior to the mid-1980s, much accounting was done manually or using a variety of less-advanced computer systems in conjunction with manual systems. Imagine the number of bookkeepers it would take to record the transactions of many companies. For example, on the first day of business at Macy’s in 1858, the store had revenues of $11.06. 1 The actual accounting ledger used to record those sales is shown in Figure 7.2 , which seems quite simple. Today Macy’s has over $24 billion in sales revenue—can you imagine accounting for all of those transactions (along with all expenses) by hand? 1 Fraser Sherman. “The History of Computerized Accounting.” Career Trend. January 14, 2019. https://careertrend.com/about-6328213-history-computerized-accounting.html \n\n Today, Macy’s and other large and small companies perform the same accounting tasks using computer hardware (computers, printers, and keyboards), and software. For example, cashiers can enter transactions into a computer using a keyboard, scanner, or touch screen. The screen displays the data entered or fields available for data entry. As an example, most retail stores have a point-of-sale system (POS) that enters the sale by scanning the item at the point of sale , meaning at the time the transaction is made. This system records the sale and at the same time updates inventory by reducing it based on the number of items purchased. \n\n Later in the section on how to Prepare a Subsidiary Ledger , you will be provided with a series of transactions for a small business and you will be asked to first enter the transactions manually into the appropriate journal, post the information from the journals to the general ledger, prepare trial balances, adjusting and closing entries, and manually produce financial statements just as Macy’s or any other business would have done prior to the use of various computer technologies. You will then perform the same tasks using QuickBooks, a popular accounting software program used by many small and medium-sized businesses. A company as large as Macy’s has stores in locations all over the country and a large volume of transactions, so it is more likely to use a software package designed to meet the needs of a very large business. This is often referred to as an enterprise resource planning (ERP) system which stands for enterprise resource planning (ERP) system. An ERP system integrates all of the company’s computerized systems including accounting systems and nonaccounting systems. That is, large companies have various accounting subsystems such as the revenue system (sales/accounts receivable/cash receipts), the expenditure system (purchasing/accounts payable/cash disbursements), the production system, the payroll system, and the general ledger system. Nonaccounting systems might include research and development, marketing, and human resources, which, while not an integral part of the accounting system, in a large companywide ERP system are integrated with the accounting modules. Examples of popular ERP software systems are PeopleSoft and SAP. \n\n Like many businesses today, Macy’s also maintains a company website and engages in e-commerce by offering the sale of many company products online. Accounting software companies like QuickBooks and larger software vendors have upgraded the ways in which they can provide AIS software to meet these needs. For example, a small local retail shoe store can purchase QuickBooks software provided on an electronic storage device such as a CD and upload it to be stored on the hard drive of the company’s computers, or the store can purchase a “cloud” version. The cloud version provides the shoe store purchasing the software with access to the QuickBooks software online via a user ID and password with no need to load the software on the store’s computers. QuickBooks updates the software when new versions are released and stores the company’s accounting data in the cloud. Cloud computing refers to using the internet to access software and information storage facilities provided by companies rather than, or in addition to, storing this data on the company’s computer hard drive or in paper form. An advantage of cloud computing is that company employees can access the software and enter transactions from any device with an internet connection at any location. The company pays a monthly fee for access to updated software, which can be less costly than buying software stored on individual computers. Potential disadvantages include security concerns because an outside company is storing company programs and data, and if the hosting company experiences technical difficulties, companies paying for these services may temporarily be unable to access their own data or conduct business. Nevertheless, cloud services are increasingly popular. \n\n Here, we illustrate the concepts and practices of an AIS using Intuit QuickBooks, a popular and widely used AIS. \n\n While a company typically selects an AIS to suit its specific needs, all systems should have components capable of: \n\n inputting/entering data (e.g., entering a sale to a customer); \n\n storing data; \n\n processing data and computing additional amounts related to transactions (e.g., computing sales tax on the sale, as well as shipping costs and insurance fees; computing an employee’s pay by multiplying hours worked by hourly pay rate; processing inventory changes from both inventory purchases and inventory sales and data from any other transaction that occurs in the business); \n\n aggregating/summarizing data (e.g., computing total sales for the year); \n\n presenting data (e.g., producing a balance sheet and other financial statements and reports for the year); and \n\n storing data (such as the customer’s name, address, shipping address, and credit limit). \n\n AISs, whether computerized or manual, generally involve three stages: input, processing, and output. We enter raw data into our system at the input stage and try to correct any errors prior to going on to the next stage of processing the data. We ultimately produce “output,” which is in the form of useful information. \n\n Inputting/Entering Data \n\n A source document is the original document that provides evidence that a transaction occurred. If you hire a company to paint your house, it will most likely provide a document showing how much you owe. That is the company’s sales document and your invoice. When you pay, your check or digital transaction record is also a source document for the company that provided the service, in this case, the home painter. \n\n Assume you go into the university bookstore to purchase a school sweatshirt, and it is sold out. You then fill out a document ordering a size medium sweatshirt in blue. The form you fill out is a purchase order to you, and it is a sales order to the university bookstore. It is also a source document that provides evidence that you have ordered the sweatshirt. Assume the bookstore does not ask you to pay in advance because it is not sure it will be able to obtain the sweatshirt for you. At that point, no sale has been made, and you owe no money to the bookstore. A few days later, the bookstore manages to acquire the sweatshirt you ordered and sends you an email notifying you of this. When you return to the bookstore, you are presented with the sweatshirt and an invoice (also known as a bill) that you must pay in order to take your sweatshirt home. This invoice/bill is also a source document. It provides evidence of the sale and your obligation to pay that amount. Let’s look at an example. \n\n Figure 7.3 is a source document—an invoice (bill) from Symmetry Mold Design for mold design services. Note the terms (agreements about payments) are listed at the top and how the company calculates those outcomes at the bottom. \n\n Some companies send paper bills in the mail, often asking the recipient to tear off part of the bill and return it with the payment. This tear-off portion is a turn-around document and helps ensure that the payment is applied to the correct customer account and invoice. Generally, this document began as printed output, an invoice, from the billing part of the AIS. When the customer tears off a part of it and returns it in the envelope with a check to the company, it has now been “turned around” and will be used as an input source document, called a remittance advice. A remittance advice is a document that customers send along with checks and informs the recipient as to which invoice the customer is paying for. Figure 7.4 is an example of a turn-around document. \n\n Both manual and computerized accounting systems utilized source documents. E-commerce systems have some additional source documents related to online transactions. Source documents help to establish an audit trail , which is a trail of evidence documenting the history of a specific transaction starting from its inception/source document and showing all the steps it went through until its final disposition. The trail of source documents and other records (the audit trail) makes it easier to investigate errors or questions by customers, vendors, employees, and others. For example, when a customer places an order by phone, by mail, or online, the sales order becomes the source document. If the customer does not receive the product ordered, the company can locate the original order, see if a picking ticket was generated (a picking ticket tells warehouse employees what inventory items the customer ordered, that now need to be picked off the shelf), locate the shipping documents, which provide evidence that the product was given to the shipper, and check for customer signature confirming receipt of goods. The trail of documents and entries in journals and ledgers and their electronic equivalent generated by this transaction provides evidence of all the steps that took place along the way. This makes it easy for anyone to verify or investigate, and perhaps find the weak links, where the process may have broken down. It allows the company to identify the reason why the customer never received the goods ordered. Maybe the order was never shipped because the company was out of stock of this specific product, maybe it was shipped and left at the customer’s doorstep with no signature requested, or maybe the order was shipped to the wrong customer or to an incorrect address. An audit trail will help company personnel investigate any of these common issues. It should also help them identify weaknesses in their processes and precipitate improvements. \n\n Businesses need a way to input data from the source document such as a sales invoice or purchase order. This was previously done with pen and paper and is currently done by keying it in on a computer keyboard; scanning, with a scanner such as one that reads MICR (magnetic ink character recognition) symbols (found on bank checks) or POS system scanners at cash registers that scan product bar codes/UPC symbols; or receiving it by e-transmission (or electronic funds transfer [EFT]). Input often involves the use of hardware such as scanners, keypads, keyboards, touch screens, or fingerprint readers called biometric devices. Once data has been input, it must be processed in order to be useful. \n\n Processing Data \n\n Companies need the accounting system to process the data that has been entered and transform it into useful information. In manual accounting systems, employees process all transaction data by journalizing, posting, and creating financial reports using paper. However, as technology has advanced, it became easier to keep records by using computers with software programs specifically developed for accounting transactions. Computers are good at repetition and calculations, both of which are involved in accounting, and computers can perform these calculations and analyses more quickly, and with fewer errors, thus making them a very effective tool for accounting from both an input and an output standpoint. \n\n Link to Learning \n\n See a list of popular bookkeeping software packages. With this information, potential options for sample accounting software options can be evaluated. \n\n Output: Presenting Information \n\n An AIS should provide a way to present system output (printed page, screen image, e-transmission). Any accounting software application such as that used by large companies (an ERP system) or one used by smaller businesses (QuickBooks) can easily print financial statements and other documents as well as display them on the screen. \n\n Some financial information must be provided to other sources such as banks or government agencies, and though in past decades everything was presented and submitted on paper, today, most of this information is submitted electronically, and AISs help facilitate having the information in the necessary electronic format. Many banks require electronic data, and the Internal Revenue System (IRS) accepts your information as a digital transmission instead of a paper form. In 2017, 92 percent of all taxpayers who filed their own taxes did so electronically. 2 Most corporations choose to file their taxes electronically, and those with assets over $10 million are required to file electronically with the IRS. 3 Since May 5, 1996, all publicly traded companies are required to submit their filings, such as financial statements and stock offerings, to the SEC electronically. 4 The SEC places all the data into an electronic database known as the Electronic Data Gathering, Analysis, and Retrieval System (EDGAR) . This database allows anyone to search the database for financial and other information about any publicly traded company. Thus, AISs facilitate not only internal access to financial information, but the sharing of that information externally as needed or required. Just as the EDGAR system used by the SEC stores data for retrieval, an AIS must provide a way to store and retrieve data. 2 Income Tax Return Statistics. eFile. May 2018. https://www.efile.com/efile-tax-return-direct-deposit-statistics/ 3 Income Tax Return Statistics. eFile. May 2018. https://www.efile.com/efile-tax-return-direct-deposit-statistics/ 4 There is a hardship exemption for companies that cannot file their documents electronically. See U.S. Securities and Exchange Commission. Important Information about EDGAR. February 16, 2010. https://www.sec.gov/edgar/aboutedgar.htm \n\n Storing Data \n\n Data can be stored by an AIS in paper, digital, or cloud formats. Before computers were widely used, financial data was stored on paper, like the journal and ledger shown in Figure 7.5 . \n\n As technology has evolved, so have storage systems—from floppy disks to CDs, thumb drives, and the cloud. The hard drive on your computer is a data storage device, as is an external hard drive you can purchase. Data that is stored must have the ability to be retrieved when needed. As you can see from Figure 7.6 , stored data comes from and/or flows through the three main functions of an AIS (input, processes, and output) with the end result being the use of the data in forms needed for decision-making, such as financial statements. Access to the ability to input data, manage processes, or retrieve data requires adequate controls to prevent fraud or unauthorized access and requires the implementation of data security measures. Figure 7.6 illustrates the key functions performed by an AIS. \n\n Your Turn The Steps in an Accounting Information System The three steps of an accounting information system are input, processing, and output. Data is the raw ingredient used in these processes. Some of the data may be obtained from a source document, and other data is obtained from the database where it had previously been stored. When the data has been processed, the final result is usually information. Information is more useful than data. Take, for example, another process that a bakery might use to bake chocolate chip cookies. While computers might not necessarily need to be involved, we begin the process by assembling a bunch of raw ingredients such as eggs, sugar, flour, chocolate chips, and oil, in a large bowl. Taking a spoonful of what is in the bowl at the time is not very pleasing to the taste buds or “useful” to someone craving a chocolate chip cookie. We process the raw ingredients by mixing them well and turning them into dough, cutting them into shapes, baking them, and glazing them. Similarly, raw data about a single sale contained on the sales invoice, such as customer name, date of sale, and amount of sale, is individually not very useful to a financial statement user such as an investor. However, by processing the data related to the sale, making sure it is correct by checking that the number of items ordered were in stock and actually shipped, aggregating it with other sales for the period, and producing an income statement containing the sales for the period is substantially more useful than the individual pieces of data relating to a single sale. \n\n Can you give an example of each of the three steps, as well as a source document that might be used in the input stage and stored data that might be used in the input and processing stages, first for a grocery store, and then a medical office? \n\n Solution \n\n Grocery store: \n\n Source Document: This would include a check to be deposited; totals from each cash register, including total cash; an invoice for produce; an application for employment by a potential new employee; time card information; a W-4 form (employment information); and so on. \n\n Input: This includes entering the data from the source document on the computer keyboard, electronically scanning the bar code of each product purchased at the grocery store (at checkout counter and to receive goods from vendor off the truck), maybe fingerprinting at the time clock, or keying in a price on the register. \n\n Processing: A cash register processes (accumulates and totals) different categories of items (coupons, checks, and charges) by the user; inventory can be tracked by RFID (radio-frequency identification); and software programs can process information gathered by individual cash registers as well as employee information. \n\n Output: Data that has been processed can be viewed on a computer screen, printed as a hard copy (paper output), or sent as electronic output from the cash register to the computer (can be done wirelessly or with a cable). \n\n Storage: Data can be stored in the company database on its computer hard drive or as cloud storage. Hopefully the store is also paying for safe backup storage offsite (in case of fire at the store or hackers attempting to obtain information), generally accessed through the internet and stored in “the cloud.” Otherwise, storage can be on paper printouts, the computer hard drive, disks, or external drives. The data that is stored may be retrieved and used at the input, processing, and output stages. \n\n Doctor’s office: \n\n Source Document: This includes a check to be deposited from the patient; the patient’s insurance information on file; a doctor’s record of the diagnosis and procedures performed on the patient, to be submitted to the insurance company; and an invoice for medical supplies. \n\n Input: Data from the source document, for example, containing the diagnosis and a treatment plan, would be entered on the computer keyboard. \n\n Processing: The system might retrieve the treatment codes corresponding to every procedure the doctor performed, so it contains the appropriate information for the insurance company. \n\n Output: The treatment form is printed and then mailed to the insurance company for payment. \n\n Storage: The diagnosis and treatment plan are stored on the computer database for retrieval on the next visit for this patient. The form to be sent to the insurance company is also stored electronically so there can be follow-up until the payment from the insurance company is received. Also note that during processing, the system had to retrieve the treatment codes from a file of all of the codes that was stored in the database. \n\n Your Turn The Accounting Information System (AIS) What are some of the types of information the accounting information system should be able to provide to the owners, managers, and employees of business, at the end of the day, or week, or month, which they in turn may need to provide to other external users? \n\n Solution \n\n Information for internal purposes will include total sales and how much it cost to generate the sales. Also considered is how much inventory is on hand so a decision can be made as to whether or not to order more inventory. \n\n The company will need to record all of the economic events of the business in order to find total sales, cost of goods sold, expenses, and net income, as well as the number of hours employees worked, the employee’s social security number, and how much the company promised to pay the employee per hour. \n\n Information for external users, such as the IRS or state and local government agencies, would include income tax returns and sales and payroll tax forms. The business owners and managers will need all sales and expenses, sales tax collected, and employees’ earnings. \n\n In other words, the company needs an AIS. \n\n While an AIS has the primary functions of input, processing, output, and storage, each company or system will decide on the exact steps and processes under each of these broad functions. We know that data is used to create the types of information needed by users to make decisions. One way in which a retail organization may obtain, input, process, and store data related to a sales transaction is through a point-of-sale system (POS) . When a customer is ready to buy an item, the cashier scans the product being purchased, the price is retrieved from the price file, the sale is recorded, and inventory is updated. Most POS systems include a scanner, a computer screen, or a tablet with a touch screen. Customer payments are stored in the cash drawer. For noncash sales, credit card readers allow customers to insert, swipe, or tap their cards to pay (which also helps prevent keyboard input errors and keeps the information safer). \n\n Ethical Considerations Ethical Standards in Retail Stores Professional sales employees operate the POS systems. There is an ethical code for sales professionals created by the Association of Professional Sales to help sales professionals maintain good judgment. 5 The organization sets forth standards such as the following: 5 Association of Professional Sales. “APS Sales Code of Conduct.” n.d. https://www.associationofprofessionalsales.com/professional-development/sales-code-conduct-aps-ethical-professional/aps-sales-code-conduct/ \n\n Maintain the highest standards of integrity in all business relationships. \n\n Provide our customers with a buying experience in which we “do the right thing and thereby help get the right results.” \n\n Promote and protect good sales practices. \n\n Always act in line with my organization’s codes and within the law. \n\n Accountants can assist sales professionals in creating an ethical environment. The ethical environment will permit the users of accounting data to make solid business decisions and to better operate a company. \n\n However, the POS is just part of the AIS. As each sale is entered into the register, other data is collected, recorded, and processed by the AIS and becomes information. Data about each sale is recorded in the information system: what was sold, how much it cost, the sales price, and any sales tax. It also records the time of day, the clerk, and anything else the company programmed the cash register to record. When all the sales for the day are totaled, it provides information in the form of organized and processed data with meaning to the company. A business might want to see which hour of the day resulted in the most sales, or to know which product was the best seller. An AIS can provide this information. \n\n A system is created when processes work together to generate information for the business. The sales process accesses customers, accounts receivable, and inventory data and updates the appropriate files. The purchases process also accesses inventory and accounts payable and updates them, because most companies buy goods on credit. Since no two companies operate exactly the same way, you would expect each company to have a slightly different AIS. Some businesses do not have a cash register, but they will still have a Sales account. Some companies only have cash sales, so they would not have an Accounts Receivable account. Regardless of the type of business—retail, manufacturing, or service—an AIS is an important component of the business as it is this system that provides the information needed by internal and external decision-makers. \n\n Concepts In Practice Is This an Accounting Information System? Do you think your average food truck proprietor has an accounting information system? \n\n Food trucks will have some type of accounting information system whether paper based or electronic. One common method of creating an accounting information system in this type of business environment is to use an app, such as Square Point of Sale ( Square Inc. ). The Square Point of Sale (POS) software system keeps track of the sales. With this type of system, a food truck will likely have a Square Stand (a tablet-based POS), a cash drawer, and printers. The information input into the Square Stand is stored on Square servers using the cloud (online storage space offered by different companies and products) and is accessible by the company via an online dashboard. This system allows the handling of both cash sales and credit card sales. These components—the Square Point of Sale software, the Square Stand, cash drawer, and the printers—make up part of the accounting information system for a food truck. \n\n IFRS Connection Accounting Information Systems in an International Business Environment All companies, regardless of whether they are domestic or international, will have an accounting information system with the features described in this chapter. It would be easy to assume that the accounting information systems created by public companies in the United States are created based on US generally accepted accounting principles (GAAP). This implies that these companies design their processes and controls so that in addition to meeting the reporting and monitoring goals of the company, the system also collects, measures, and reports the information that is required under US GAAP. But is this true? What about companies that have subsidiaries or a portion of their operations in another country? Do purely international companies use accounting information systems similar to their US counterparts? \n\n As previously indicated, all companies will create some sort of accounting information system. General Electric (GE) , as a US-based manufacturer, uses an accounting information system that allows it to record, collect, produce, and analyze the operations of its various businesses. Since GE is a US corporation, headquartered in Boston, Massachusetts, its accounting information system is designed around the rules set out by US GAAP. Fiat Chrysler Automobiles (FCA) is headquartered in the United Kingdom, and it designs its accounting information system to produce financials under International Financial Reporting Standards (IFRS). On the surface, it looks as though each company will create an information system based on the accounting rules in its own home country. However, it is not quite that simple. Today, companies take advantage of the ability to borrow money across borders. The lenders often require the financial statements of the borrower to be presented using the accounting rules required by the lender’s country. For example, if GE wanted to borrow money from the Royal Bank of Scotland , it would likely have to present its financial statements based on IFRS rules. Similarly, if FCA wanted to borrow from Citibank , it would need its financial statements in US GAAP form. \n\n Borrowing is not the only reason a company may need to present financial statements based on a different set of accounting principles. As of 2017, GE had over 130 subsidiaries, and these businesses were located across 130 countries. A subsidiary is a business over which the parent company has decision-making control, usually indicated by an ownership interest of more than 50 percent. Many of these GE subsidiaries established their accounting information systems based on the accepted accounting principles in the countries in which they were located, as required in order to be in compliance with local regulations such as for local taxes. Thus, GE must convert the financial information obtained from the subsidiary’s accounting information system, often based on IFRS, to US GAAP in order to consolidate the transactions and operations of all of the subsidiaries with those of the parent company to create one set of financial statements. \n\n We have basically become a two GAAP world—IFRS and US GAAP—and many companies will find it necessary to have accounting information systems that can handle both sets of rules due to the global nature of business and the global nature of raising money through borrowing and issuing stock. This may seem crazy, to have two systems, but a little over ten years ago there were more than seventy different GAAP. Today, since many countries now use IFRS, the quality and consistency of financial reporting have improved. As a result, the cost associated with having accounting information systems that can combine many different sets of accounting rules has decreased. \n 7.2 Describe and Explain the Purpose of Special Journals and Their Importance to Stakeholders \n\n The larger the business, the greater the likelihood that that business will have a large volume of transactions that need to be recorded in and processed by the company’s accounting information system. You’ve learned that each transaction is recorded in the general journal, which is a chronological listing of transactions. In other words, transactions are recorded into the general journal as they occur. While this is correct accounting methodology, it also can create a cumbersome general journal with which to work and may make finding specific pieces of information very challenging. For example, assume customer John Smith charged an item for $100 on June 1. In the general journal, the company would record the following. \n\n This journal entry would be followed by a journal entry for every other transaction the company had for the remainder of the period. Suppose, on June 27, Mr. Smith asked, “How much do I owe?” To answer this question, the company would need to review all of the pages of the general journal for nearly an entire month to find all of the sales transactions relating to Mr. Smith. And if Mr. Smith said, “I thought I paid part of that two weeks ago,” the company would have to go through the general journal to find all payment entries for Mr. Smith. Imagine if there were 1,000 similar credit sales transactions for the month, each one would be written in the general journal in a similar fashion, and all other transactions, such as the paying of bills, or the buying of inventory, would also be recorded, in chronological order, in the general journal. Thus, recording all transactions to the general journal makes it difficult to find the particular tidbits of information that are needed for one of our customers, Mr. Smith. The use of special journal and subsidiary ledgers can make the accounting information system more effective and allow for certain types of information to be obtained more easily. \n\n Your Turn Using General Ledger (Control) Accounts Here is the information from the accounts payable subsidiary ledger: \n\n What should the total be in the Accounts Payable Control Total? \n\n Here is the information from the accounts receivable subsidiary ledger. \n\n What should the total be in the Accounts Receivable Control Total? \n\n Solution \n\n Accounts Payable Control Total is: 1,362 + 4,468 + 8,167 = 13,997 \n\n Accounts Receivable Control Total is: 2,250 + 0 + 1,500 + 8,160 = 11,910 \n\n Special Journals \n\n Instead of having just one general journal, companies group transactions of the same kind together and record them in special journals rather than in the general journal. This makes it easier and more efficient to find a specific type of transaction and speeds up the process of posting these transactions. In each special journal, all transactions are totaled at the end of the month, and these totals are posted to the general ledger. In addition, instead of one person entering all of the transactions in all of the journals, companies often assign a given special journal’s entries to one person. The relationship between the special journals, the general journal, and the general ledger can be seen in Figure 7.8 . \n\n Most companies have four special journals, but there can be more depending on the business needs. The four main special journals are the sales journal , purchases journal , cash disbursements journal , and cash receipts journal . These special journals were designed because some journal entries occur repeatedly. For example, selling goods for cash is always a debit to Cash and a credit to Sales recorded in the cash receipts journal. Likewise, we would record a sale of goods on credit in the sales journal, as a debit to accounts receivable and a credit to sales. Companies using a perpetual inventory system also record a second entry for a sale with a debit to cost of goods sold and a credit to inventory. You can see sample entries in Figure 7.9 . \n\n Note there is a column to enter the date the transaction took place; a column to indicate the customer to whom the transaction pertains; an invoice number that should match the number on the invoice given (in paper or electronically) to the customer; a reference box that indicates the transaction has been posted to the customer’s account and can include something as simple as a check mark or a code that links the transaction to other journals and ledgers; and the last two columns that indicate the accounts and amounts debited and credited. \n\n Purchases of inventory on credit would be recorded in the purchases journal ( Figure 7.10 ) with a debit to Merchandise Inventory and a credit to Accounts Payable. \n\n Paying bills is recorded in the cash disbursements journal ( Figure 7.11 ) and is always a debit to Accounts Payable (or another payable or expense) and a credit to Cash. \n\n The receipt of cash from the sale of goods, as payment on accounts receivable or from other transactions, is recorded in a cash receipts journal ( Figure 7.12 ) with a debit to cash and a credit to the source of the cash, whether that is from sales revenue, payment on an account receivable, or some other account. \n\n Table 7.1 summarizes the typical transactions in the special journals previously illustrated. \n\n Types and Purposes of Special Journals \n\n Journal Name \n\n Journal Purpose \n\n Account(s) Debited \n\n Account(s) Credited \n\n Sales Journal \n\n Sales on credit \n\n Accounts Receivable, Cost of Goods Sold \n\n Sales, Inventory \n\n Purchases Journal \n\n Purchases on credit \n\n Inventory \n\n Accounts Payable \n\n Cash Disbursements Journal \n\n Paying cash \n\n Could be: Accounts Payable, or other accounts \n\n Cash \n\n Cash Receipts Journal \n\n Receiving cash \n\n Cash \n\n Could be: Sales, Accounts Receivable, or other accounts \n\n General Journal \n\n Any transaction not covered previously; adjusting and closing entries \n\n Could be: Depreciation Expense \n\n Could be: Accumulated Depreciation \n\n Table 7.1 \n\n How will you remember all of this? Remember, “Cash Is King,” so we consider cash transactions first. If you receive cash, regardless of the source of the transaction, and even if it is only a part of the transaction, it goes in the cash receipts journal . For example, if the company made a sale for $1,000 and the customer gave $300 in cash and promised to pay the remaining balance in the future, the entire transaction would go into the cash receipts journal, because some cash was received, even if it was only part of a transaction. You could not split this journal entry between two journals, because each transaction’s debits must equal the credits or else your journal totals will not balance at the end of the month. You might consider splitting this transaction into two separate transactions and considering it a cash sale for $300 and a sale on account for $700, but that would also be inappropriate. Although the balances in the general ledger accounts would technically be correct if you did that, this is not the right approach. Good internal control dictates that this is a single transaction, associated with one invoice number on a given date, and should be recorded in its entirety in a single journal, which in this case is the cash receipts journal. If any cash is received, even if it is only a part of the transaction, the entire transaction is entered in the cash receipts journal. For this example, the transaction entered in the cash receipts journal would have a debit to cash for $300, a debit to Accounts Receivable for $700, and a credit to Sales for $1,000. \n\n If you pay cash (usually by writing a check), for any reason, even if it is only a part of the transaction, the entire transaction is recorded in the cash disbursements journal . For example, if the company purchased a building for $500,000 and gave a check for $100,000 as a down payment, the entire transaction would be recorded in the cash disbursements journal as a credit to cash for $100,000, a credit to mortgage payable for $400,000, and a debit to buildings for $500,000. \n\n If the transaction does not involve cash, it will be recorded in one of the other special journals. If it is a credit sale (also known as a sale on account), it is recorded in the sales journal. If it is a credit purchase (also known as a purchase on account), it is recorded in the purchases journal. If it is none of the above, it is recorded in the general journal. \n\n Continuing Application Accounting Information Systems Let’s consider what Gearhead Outfitters ’ accounting information system might look like. What information will company management find important? Likewise, what information might external users of Gearhead’s financial reports need? Do regulatory requirements dictate what Gearhead needs to track in its accounting system? \n\n Gearhead will want to know its financial position, results of operations, and cash flows. Such data will help management make decisions about the company. Likewise, external users want this data (balance sheet, income statement, and statement of cash flows) to make decisions such as whether or not to extend credit to Gearhead . \n\n To keep accurate records, company operations must be considered. For example, inventory is purchased, sales are made, customers are billed, cash is collected, employees work and need to be paid, and other expenses are incurred. All of these operations involve different recording processes. Inventory will require a purchases journal. Sales will require a sales journal, cash receipts journal, and accounts receivable subsidiary ledger (discussed later) journal. Payroll and other disbursements will require their own journals to accurately track transactions. \n\n Such journals allow a company to record accounting information and generate financial statements. The data also provides management with the information needed to make sound business decisions. For example, subsidiary ledgers, such as the accounts receivable ledger, provide data about the aging and collectability of receivables. Thus, the proper design, implementation, and maintenance of the accounting information system are vital to a company’s sustainability. \n\n What other questions can be answered through the analysis of information gathered by the accounting information system? Think in terms of the timing of inventory orders and cash flow needs. Is there nonfinancial information to extract from the accounting system? An accounting information system should provide the information needed for a business to meet its goals. \n\n Subsidiary Ledgers \n\n In addition to the four special journals, there are two special ledgers, the accounts receivable subsidiary ledger and the accounts payable subsidiary ledger. The accounts receivable subsidiary ledger gives details about each person who owes the company money, as shown in Figure 7.13 . Each colored block represents an individual’s account and shows only the amount that person owes the company. Notice that the subsidiary ledger provides the date of the transaction and a reference column to link the transaction to the same information posted in one of the special journals (or general journal if special journals are not used)—this reference is usually a code that references the special journal such as SJ for the sales special journal, as well as the amounts owed in the debit column and the payments made in the credit column. The amounts owed by all of the individuals, as indicated in the subsidiary ledger, are added together to form the accounts receivable control total, and this should equal the Accounts Receivable balance reported in the general ledger as shown in Figure 7.14 . Key points about the accounts receivable subsidiary ledger are: \n\n Accounts Receivable in the general ledger is the total of all of the individual account totals that are listed in the accounts receivable subsidiary ledger. \n\n All of the amounts owed to the company in the accounts receivable subsidiary ledger must equal the amounts in the accounts receivable general ledger account. \n\n Ethical Considerations Subsidiary Ledger Fraud 6 Subsidiary ledgers have to balance and agree with the general ledger. Accountants using QuickBooks and other accounting systems may not have to perform this step, because in these systems the subsidiary ledger updates the general ledger automatically. However, a dishonest person might manipulate accounting records by recording a smaller amount of cash receipts in the control account than is recorded on the subsidiary ledger cards. The ethical accountant must be vigilant to ensure that the ledgers remain balanced and that proper internal controls are in place to ensure the soundness of the accounting system. \n\n 6 Joseph R. Dervaes. “Accounts Receivable Fraud, Part Five: Other Accounting Manipulations.” Fraud Magazine . July/August, 2004. http://www.fraud-magazine.com/article.aspx?id=4294967822 \n\n The accounts payable subsidiary ledger holds the details about all of the amounts a company owes to people and/or companies. In the accounts payable subsidiary ledger, each vendor (the person or company from whom you purchased inventory or other items) has an account that shows the details of all transactions. Similar to the accounts receivable subsidiary ledger, the purchases subsidiary journal indicates the date on which a transaction took place; a reference column used in the same manner as previously described for accounts receivable subsidiary ledgers; and finally, the subsidiary ledger shows the amount charged or the amount paid. Following are the transactions for ABC Inc. and XYZ Inc. The final balance indicated on each subsidiary purchases journal shows the amount the company owes ABC and XYZ. \n\n If the two amounts are added together, the company owes $305 in total to the two companies. The $305 is the amount that will show in the Accounts Payable general ledger account. \n\n Your Turn Using the Accounts Payable Subsidiary Ledger Find the balance in each account in the accounts payable subsidiary ledger that follows. Note that each vendor account has a unique account number or AP No. \n\n Solution \n 7.3 Analyze and Journalize Transactions Using Special Journals \n\n Accounting information systems were paper based until the introduction of the computer, so special journals were widely used. When accountants used a paper system, they had to write the same number in multiple places and thus could make a mistake. Now that most businesses use digital technology, the step of posting to journals is performed by the accounting software. The transactions themselves end up on transaction files rather than in paper journals, but companies still print or make available on the screen something that closely resembles the journals. Years ago, all accounting record keeping was manual. If a company had many transactions, that meant many journal entries to be recorded in the general journal. People soon realized that certain types of transactions occurred more frequently than any other types of transaction, so to save time, they designed a special journal for each type that occurs frequently (e.g., credit sales, credit purchases, receipts of cash, and disbursements of cash). We would enter these four types of transactions into their own journals, respectively, rather than in the general journal. Thus, in addition to the general journal, we also have the sales journal, cash receipts journal, purchases journal, and cash disbursements journals. \n\n The main difference between special journals using the perpetual inventory method and the periodic inventory method is that the sales journal in the perpetual method, as you have seen in the prior examples in the chapter, will have a column to record a debit to Cost of Goods Sold and a credit to Inventory. In the purchases journal, using the perpetual method will require we debit Inventory instead of Purchases. Another difference is that the perpetual method will include freight charges in the Inventory account, while the periodic method will have a special Freight-in account that will be added when Cost of Goods Sold will be computed. For a refresher on perpetual versus periodic and related accounts such as freight-in, please refer to Merchandising Transactions . \n\n Think It Through Which Journal? If you received a check from Mr. Jones for $500 for work you performed last week, which journal would you use to record receipt of the amount they owed you? What would be recorded? \n\n The Sales Journal \n\n The sales journal is used to record sales on account (meaning sales on credit or credit sale). Selling on credit always requires a debit to Accounts Receivable and a credit to Sales. Because every credit sales transaction is recorded in the same way, recording all of those transactions in one place simplifies the accounting process. Figure 7.15 shows an example of a sales journal. Note there is a single column for both the debit to Accounts Receivable and the credit to Sales, although we need to post to both Accounts Receivable and Sales at the end of each month. There is also a single column for the debit to Cost of Goods Sold and the credit to Merchandise Inventory, though again, we need to post to both of those. In addition, for companies using the perpetual inventory method, there is another column representing a debit to Cost of Goods Sold and a credit to Merchandise Inventory, since two entries are made to record a sale on account under the perpetual inventory method. \n\n The information in the sales journal was taken from a copy of the sales invoice, which is the source document representing the sale. The sales invoice number is entered so the bookkeeper could look up the sales invoice and assist the customer. One benefit of using special journals is that one person can work with this journal while someone else works with a different special journal. \n\n At the end of the month, the bookkeeper, or computer program, would total the A/R Dr and Sales Cr column and post the amount to the Accounts Receivable control account in the general ledger and the Sales account in the general ledger. The Accounts Receivable control account in the general ledger is the total of all of the amounts customers owed the company. Also at the end of the month, the total debit in the cost of goods sold column and the total credit to the merchandise inventory column would be posted to their respective general ledger accounts. \n\n The company could have made these entries in the general journal instead of the special journal, but if it had, this would have likely caused the sales transactions to be separated from each other and spread throughout the journal, making it harder to find and keep track of them. When a sales journal is used, if the company is one where sales tax is collected from the customer, then the journal entry would be a debit to Accounts Receivable and a credit to Sales and Sales Tax Payable, and this would require an additional column in the sales journal to record the sales tax. For example, a $100 sale with $10 additional sales tax collected would be recorded as a debit to Accounts Receivable for $110, a credit to Sales for $100 and a credit to Sales Tax Payable for $10. \n\n The use of a reference code in any of the special journals is very important. Remember, after a sale is recorded in the sales journal, it is posted to the accounts receivable subsidiary ledger, and the use of a reference code helps link the transactions between the journals and ledgers. Recall that the accounts receivable subsidiary ledger is a record of each customer’s account. It looked like Figure 7.16 for Baker Co. \n\n Using the reference information, if anyone had a question about this entry, he or she would go to the sales journal, page 26, transactions #45321 and #45324. This helps to create an audit trail, or a way to go back and find the original documents supporting a transaction. \n\n Your Turn Which Journal Do You Use? Match each of the transactions in the right column with the appropriate journal from the left column. \n\n A. Purchases journal \n\n i. Sales on account \n\n B. Cash receipts journal \n\n ii. Adjusting entries \n\n C. Cash disbursements journal \n\n iii. Receiving cash from a charge customer \n\n D. Sales journal \n\n iv. Buying inventory on credit \n\n E. General journal \n\n v. Paying the electric bill \n\n Solution \n\n A. iv; B. iii; C. v; D. i; E. ii. \n\n Comprehensive Example \n\n Let us return to the sales journal, shown in Figure 7.17 that includes information about Baker Co. as well as other companies with whom the company does business. \n\n At the end of the month, the total Sales on credit were $2,775. The transactions would be posted in chronological order in the sales journal. As you can see, the first transaction is posted to Baker Co., the second one to Alpha Co., then Tau Inc., and then another to Baker Co. On the date each transaction is posted in the sales journal, the appropriate information would be posted in the subsidiary ledger for each of the customers. As an example, on January 3, amounts related to invoices 45321 and 45322 are posted to Baker’s and Alpha’s accounts, respectively, in the appropriate subsidiary ledger. At the end of the month, the total of $2,775 would be posted to the Accounts Receivable control account in the general ledger. Baker Co.’s account in the subsidiary ledger would show that they owe $1,450; Alpha Co. owes $625; and Tau Inc. owes $700 ( Figure 7.18 ). \n\n At the end of the month, we would post the totals from the sales journal to the general ledger ( Figure 7.19 ). \n\n Altogether, the three individual accounts owe the company $2,775, which is the amount shown in the Accounts Receivable control account. It is called a control total because it helps keep accurate records, and the total in the accounts receivable must equal the balance in Accounts Receivable in the general ledger. If the amount of all the individual accounts receivable accounts did not add up to the total in the Accounts Receivable general ledger/control account, it would indicate that we made a mistake. Figure 7.20 shows how the accounts and amounts are posted. \n\n The Cash Receipts Journal \n\n When the customer pays the amount owed, (generally using a check), bookkeepers use another shortcut to record its receipt. They use a second special journal, the cash receipts journal . The cash receipts journal is used to record all receipts of cash (recorded by a debit to Cash). In the preceding example, if Baker Co. paid the $1,450 owed, there would be a debit to Cash for $1,450 and a credit to Accounts Receivable. A notation would be made in the reference column to indicate the payment had been posted to Baker Co.’s accounts receivable subsidiary ledger. After Baker Co.’s payment, the cash receipts journal would appear as in Figure 7.21 . \n\n And the accounts receivable subsidiary ledger for Baker Co. would also show the payment had been posted ( Figure 7.22 ). \n\n In the cash receipts journal, the credit can be to Accounts Receivable when a customer pays on an account, or Sales, in the case of a cash sale, or to some other account when cash is received for other reasons. For example, if we overpaid our electric bill, we could get a refund check in the mail. We would use the cash receipts journal because we are receiving cash, but the credit would be to our Utility Expense account. If you look at the example in Figure 7.23 , you see that there is no column for Utility Expense, so how would it be recorded? We would use some generic column title such as “other” to represent those cash transactions in the subsidiary ledger though the specific accounts would actually be identified by account number in the special journal. We would look up the account number for Utility Expense and credit the account for the amount of the check. If we received a refund from the electric company on January 28 in the amount of $100, we would find the account number for utility expense (say it is 615) and record it. At the end of the month, we total the Cash column in the cash receipts journal and debit the Cash account in the general ledger for the total. In this case there were two entries in the cash receipts journal, the cash received from Baker and the refund check for an overpayment on utilities for a total cash received and recorded in the cash receipts journal of $1,550, as shown in Figure 7.24 . \n\n Any accounts used in the Other Accounts column must be entered separately in the general ledger to the appropriate account. Figure 7.25 shows how the refund would be posted to the utilities expense account in the general ledger. \n\n The Cash Disbursements Journal \n\n Many transactions involve cash. We enter all cash received into the cash receipts journal, and we enter all cash payments into the cash disbursements journal , sometimes also known as the cash payments journal . Good internal control dictates the best rule is that all cash received by a business should be deposited, and all cash paid out for monies owed by the business should be made by check. Money paid out is recorded in the cash disbursements journal, which is generally kept in numerical order by check number and includes all of the checks recorded in the checkbook register. If we paid this month’s phone bill of $135 with check #4011, we would enter it as shown in Figure 7.26 in the cash disbursements journal. \n\n The total of all of the cash disbursements for the month would be recorded in the general ledger Cash account ( Figure 7.27 ) as follows. Note that the information for both the cash receipts journal and the cash disbursements journal are recorded in the general ledger Cash account. \n\n The Purchases Journal \n\n Many companies enter only purchases of inventory on account in the purchases journal . Some companies also use it to record purchases of other supplies on account. However, in this chapter we use the purchases journal for purchases of inventory on account, only. It will always have a debit to Merchandise Inventory if you are using the perpetual inventory method and a credit to Accounts Payable, or a debit to Purchases and a credit to Accounts Payable if using the periodic inventory method. It is similar to the sales journal because it has a corresponding subsidiary ledger, the accounts payable subsidiary ledger. Since the purchases journal is only for purchases of inventory on account, it means the company owes money. To keep track of whom the company owes money to and when payment is due, the entries are posted daily to the accounts payable subsidiary ledger. Accounts Payable in the general ledger becomes a control account just like Accounts Receivable. If we ordered inventory from Jones Mfg. (account number 789) using purchase order #123 and received the bill for $250, this would be recorded in the purchases journal as shown in Figure 7.28 . \n\n The posting reference would be to indicate that we had entered the amount in the accounts payable subsidiary ledger ( Figure 7.29 ). \n\n The total of all accounts payable subsidiary ledgers would be posted at the end of the month to the general ledger Accounts Payable control account. The sum of all the subsidiary ledgers must equal the amount reported in the general ledger. \n\n General Journal \n\n Why use a general journal if we have all the special journals? The reason is that some transactions do not fit in any special journal. In addition to the four special journals presented previously (sales, cash receipts, cash disbursements, and purchases), some companies also use a special journal for Sales returns and allowances and another special journal for Purchase returns and allowances if they have many sales returns and purchase returns transactions. However, most firms enter those transactions in the general journal, along with other transactions that do not fit the description of the specific types of transactions contained in the four special journals. The general journal is also necessary for adjusting entries (such as to recognize depreciation, prepaid rent, and supplies that we have consumed) and closing entries. \n\n Your Turn Using the Sales and Cash Receipts Journals You own and operate a business that sells goods to other businesses. You allow established customers to buy goods from you on account, meaning you let them charge purchases and offer terms of 2/10, n/30. Record the following transactions in the sales journal and cash receipts journal: \n\n Jan. 3 \n\n Sales on credit to VJ Armitraj, Ltd., amount of $7,200, Invoice # 317745 \n\n Jan. 9 \n\n Sales on credit to M. Baghdatis Inc., amount of $5,200, Invoice # 317746 \n\n Jan. 16 \n\n Receive $7,200 from VJ Armitraj, Ltd. (did not receive during the discount period) \n\n Jan. 17 \n\n Sales on credit to A. Ashe Inc., amount of $3,780, Invoice #317747 \n\n Jan. 18 \n\n Receive the full amount owed from M. Baghdatis Inc. within the discount period \n\n Solution \n\n Ensure that the total of all individual accounts receivable equals the total of accounts receivable, or: \n\n 0 + $3,780 + 0 = $3,780. \n 7.4 Prepare a Subsidiary Ledger \n\n Now that you have seen four special journals and two special ledgers, it is time to put all the pieces together. \n\n Record the following transactions for Store Inc. in the special journals and post to the general ledger provided. Also post to the subsidiary ledgers provided. Beginning account balances are shown below. Use the perpetual inventory method and the gross method of dealing with sales terms. \n\n First, enter these transactions manually by creating the relevant journals and subsidiary ledgers. Then enter them using QuickBooks. \n\n Transactions for Store Inc. \n\n Jan. 2 \n\n Issued check #629 for January store rent: $350.00 \n\n Jan. 3 \n\n Received check from PB&J in payment for December sale on credit, $915.00 \n\n Jan. 4 \n\n Issued check #630 to D & D in payment for December purchase on credit of $736.00 \n\n Jan. 5 \n\n Sold goods for $328.00 to Jones Co. on credit, Invoice #234 (Note: COGS is $164) \n\n Jan. 6 \n\n Bought goods from BSA for $4,300.00, Purchase Order #71, terms: 2/10, net/30 \n\n Jan. 8 \n\n Sold goods on credit to Black & White Inc. for $2,100, Invoice #235, terms: 1/10, net/30 (Note: COGS is $1,050) \n\n Jan. 9 \n\n Issued check #63 for telephone bill received today, $72.00 \n\n Jan. 10 \n\n Issued check #632 to pay BSA in full, PO 71. \n\n Jan. 15 \n\n Received full payment from Black & White, Inc., Invoice #235 \n\n Jan. 20 \n\n Bought merchandise from Dow John, $525.00 payable in 30 days, Purchase Order #72 \n\n Jan. 26 \n\n Returned $100 of merchandise to Dow John, relating to Purchase Order #72 \n\n Jan. 31 \n\n Recorded cash sales for the month of $3,408 (Note: COGS is $1,704) \n\n Jan. 31 \n\n Recognized that half of the Prepaid Insurance has been consumed \n\n Table 7.2 Record all transactions using the sales journal, purchases journal, cash receipts journal, cash disbursements journal, and the general journal and post to the accounts receivable and accounts payable subsidiary ledgers. Then prepare a schedule of accounts receivable and a schedule of accounts payable. \n\n Explanation: \n\n Jan. 3 \n\n The company received payment from PB&J; thus, a cash receipt is recorded. \n\n Jan. 15 \n\n The company received payment on goods that were sold on Jan. 8 with credit terms if paid within the discount period. The payment was received within the discount period. \n\n Jan. 31 \n\n Cash sales are recorded. \n\n Explanation: \n\n Jan. 26 \n\n The company returns merchandise (inventory) previously purchased. Since the company is using the perpetual method, a credit is made to Inventory. \n\n Jan. 31 \n\n An adjusting entry is made to recognize insurance expense for the current month that had previously been prepaid. \n\n Explanation: \n\n Jan. 8 \n\n Sales on credit are recorded \n\n Explanation: \n\n Jan. 2 \n\n Rent for the month is paid. \n\n Jan. 4 \n\n Payment is made for inventory purchased on account in a prior month. \n\n Jan. 9 \n\n Paid the telephone bill. \n\n Jan. 10 \n\n Paid for inventory purchased earlier on account. The payment arrangement had credit terms; the invoice was paid within the time allowed, and the discount was taken. \n\n Explanation: \n\n Jan. 6 \n\n Inventory is purchased on account. \n\n Jan. 20 \n\n Inventory is purchased on account. \n\n At the end of the month, each of the previous journal totals are posted to the appropriate account in the general ledger, and any individual account postings, such as to Rent Expense (Jan. 2 transaction) would also be posted to the general ledger. Note that each account used by the company has its own account section in the general ledger. \n\n If you check Accounts Receivable in the general ledger, you see the balance is $2,989, and the balance in Accounts Payable is $6,071. If the numbers did not match, we would have to find out where the error was and then fix it. \n\n The purpose of keeping subsidiary ledger s is for accuracy and efficiency. They aid us in keeping accurate records. Since the total of the accounts receivable subsidiary ledger must agree with the balance shown in the accounts receivable general ledger account, the system helps us find mistakes. Since bookkeeping using ledgers is older than the United States, it was an ingenious way to double-check without having to actually do everything twice. It provided an internal control over record keeping. Today, computerized accounting information systems use the same method to store and total amounts, but it takes a lot less time. \n 7.5 Describe Career Paths Open to Individuals with a Joint Education in Accounting and Information Systems \n\n We use accounting information to make decisions about the business. Computer applications now provide so much data that data analytics is one of the newest career areas in business. Universities are beginning to offer degrees in data analysis. Software companies have created different applications to analyze data including SAS, Apache Hadoop, Apache Spark, SPSS, RapidMiner, Power BI, ACL, IDEA, and many more to help companies discover useful information from the transactions that occur. Big data refers to the availability of large amounts of data from various sources, including the internet. For example, social media sites contain tremendous amounts of data that marketing companies analyze to determine how popular a product is, and how best to market it. There is so much data to analyze that new ways of mining it for predictive value have evolved. \n\n Another emerging area involves cryptocurrency , or the use of a digital currency that uses encryption technologies that make these cryptocurrencies impossible to counterfeit. The use of cryptocurrency does not require a bank to transfer or clear funds as is the case with other currencies. Bitcoin is the most well-known cryptocurrency. Blockchain is the platform on which Bitcoin is built. Blockchain serves as a shared ledger for Bitcoin but is also the foundation of many other applications. Simply put, blockchain offers different parties to a transaction (e.g., a buyer and a seller) the opportunity to use a shared ledger rather than each having their own separate ledgers as is the case with traditional systems. Bitcoin is currently accepted by some large, well-known companies including PwC and EY (the two largest of the “big 4” accounting firms), and Overstock.com . \n\n Enterprise resource planning (ERP) software is a collection of integrated programs that track all operations in a company, from payroll to accounts payable, manufacturing, and maintaining electronic connections with suppliers. For example, companies that sell goods to Walmart , have access to Walmart’s electronic inventory records so the vendors can make sure Walmart has the right amount of goods on hand. Having such a close relationship brings rewards. They will probably receive payment sooner, using EFT (electronic funds transfer). \n\n The use of accounting information system s (AISs) has drastically changed the way we prepare tax returns. Software is now written to walk anyone through preparing his or her own tax return using an expert system . An expert system asks questions like: are you married? If the answer is yes, the software knows to use the married tax tables, and if the answer is no, it uses the single tables. Based on this answer, it will know what kind of question to ask next. Accountants who understand expert systems and tax will be writing and auditing tax software programs. \n\n Firms are also developing and using artificial intelligence (AI) systems to perform tasks previously performed by accounting professionals, but now are freeing up the professionals to perform higher-level tasks requiring analysis and judgment. Finally, security of all of this available data is a very important issue, and there are a number of career paths and certifications that information technology professionals can attain. The Information Systems Audit and Control Association (ISACA) offers several certifications including Certified Information Systems Auditor (CISA) , Certified in Risk and Information System Controls (CRISC) , Certified Information Security Manager (CISM) , and others. There is so much technology that we are inundated with more information than we can use. Because the information is being generated by a machine, we generally trust the computation (although there are cases where a bug in the program can even cause problems with simple math), but we also know the old saying, “garbage in, garbage out.” The computer does not always know that your typo is garbage. If you enter the wrong number, the system processes it as if it were the right number. That means we have to build some way into the program to control what is input into the system. For example, if you fill out a form online and it asks for your zip code, does it let you enter just four digits? No—the computer knows that it should only go to the next step if you enter five digits. However, you can enter the wrong digits and it might not catch it. It is critical that we build as many internal controls into our computerized systems as possible so that we can find errors at the input stage before they get into our system. In other words, by using these “preventive” controls, we do not allow “garbage” data to get into our system. \n\n Computerized AISs have also brought changes to the audit trail. In the past, accountants had a set of books that were paper based. You could see where a transaction was recorded and posted (and see if it had been erased). Once you enter it into a computer, it becomes part of an electronic audit trail, but the trail is only as good as the program that runs it. The screen could show you one number, but the system could be working with a different number all together. In fact, there have been criminal cases in which people wrote programs to cover up fraud. One such program functioned so that when an item was scanned, the correct amount displayed to the customer, but it was recorded in the books as a smaller amount, so the company paid less in sales tax and much less in income tax. \n\n AISs have become more important because information and technology are more important. \n\n Concepts In Practice Is Technology Always Better? Technology allows one person to do a job that once took a dozen people to do. However, that can also lead to problems. For example, years ago, one person working in the accounts receivable department at Burlington Industries would have been in charge of a few customers. If those customers were not paying their bills on time, a person would be aware of it. Today, one person might be in charge of all accounts receivable. That person may not have time to call individual customers, so everything is preprogrammed. If the customer wanted to place a large order that caused them to go over their limit, the software would deny it instead of having a person weigh the risk of extending more credit. \n\n A risk inherent in an AIS is that one person has access to a lot of information, and sometimes the information crosses department lines. Companies have to figure out ways to mitigate the risk, because AISs are truly essential to businesses today, especially with the growth of e-business and e-commerce. Think of the different business processes when a purchase is made through Amazon.com . Their AIS must be able to access inventory records, access customer information and records, process credit cards, calculate delivery dates, handle coupons or discounts, and remember where to ship the goods. Amazon would not be what it is today without all of its systems working together. Seeing what Amazon has accomplished opens the door for other companies to follow, and they will need people who understand the system. \n\n Forensic accounting involves the use of accounting skills to inspect the accounting records in order to determine if fraud or embezzlement have occurred. Many universities are offering forensic accounting degrees to prepare students who can testify to criminal activity present in the accounting records. \n\n Concepts In Practice The Founding of the Securities and Exchange Commission In 1933 and 1934, the US Congress passed two acts that established the Securities and Exchange Commission (SEC) , giving it the right to regulate and enforce the regulations concerning commerce in the United States. The website of the SEC (https://www.SEC.gov/) allows you to view all public company financial reporting and provides a link to all current litigation against individuals and companies that have been accused of breaking an SEC regulation. If you go to the site and look for the Litigation Releases section, you can click on individual cases and find that some cases of fraud involve the use of an accounting information system. \n\n The Patriot Act also came out of the 9/11 attacks (signed October 26, 2001). The letters in Patriot stand for the following: providing appropriate tools required to intercept and obstruct terrorism. The goal of the act was to prevent any other attacks on the United States by allowing enhanced surveillance procedures. \n\n The act gave law enforcement officials the right to access computers to track IP addresses, websites visited, credit card information provided electronically, and so on, in an effort to uncover terrorism before an attack was made. Several parts of the act call for banks to report suspected money laundering activities. Money laundering is an attempt to hide the facts of the original transaction and would involve an accountant. If you were selling drugs for cash and then tried to deposit that much cash in a bank, the bank would report it, so you would try to cover up where the cash came from and run it through a legitimate company. That is money laundering. \n\n The Patriot Act also includes a section requiring auditors to verify that a company has controls in place to prevent an attack on its accounting information system and that the company has a disaster plan including backup records in case of a disaster. \n\n The AIS enables a company to record all of its business transactions. Systems are different depending on the company’s needs. The AIS holds a lot of the information used to run a business. One system can provide everything needed for external reporting to government agencies involving payroll and income taxation. The same system can provide the data needed for managerial analysis used for pricing, budgeting, decision-making, and efficiency studies. Every company is required to keep records of their financial activity, and this means job security for people who are knowledgeable about AISs. "}}},{"rowIdx":183,"cells":{"bname":{"kind":"string","value":"psychology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":" Summary 16.1 Mental Health Treatment: Past and Present \n\n It was once believed that people with psychological disorders, or those exhibiting strange behavior, were possessed by demons. These people were forced to take part in exorcisms, were imprisoned, or executed. Later, asylums were built to house the mentally ill, but the patients received little to no treatment, and many of the methods used were cruel. Philippe Pinel and Dorothea Dix argued for more humane treatment of people with psychological disorders. In the mid-1960s, the deinstitutionalization movement gained support and asylums were closed, enabling people with mental illness to return home and receive treatment in their own communities. Some did go to their family homes, but many became homeless due to a lack of resources and support mechanisms. \n\n Today, instead of asylums, there are psychiatric hospitals run by state governments and local community hospitals, with the emphasis on short-term stays. However, most people suffering from mental illness are not hospitalized. A person suffering symptoms could speak with a primary care physician, who most likely would refer him to someone who specializes in therapy. The person can receive outpatient mental health services from a variety of sources, including psychologists, psychiatrists, marriage and family therapists, school counselors, clinical social workers, and religious personnel. These therapy sessions would be covered through insurance, government funds, or private (self) pay. \n\n 16.2 Types of Treatment \n\n Psychoanalysis was developed by Sigmund Freud. Freud’s theory is that a person’s psychological problems are the result of repressed impulses or childhood trauma. The goal of the therapist is to help a person uncover buried feelings by using techniques such as free association and dream analysis. \n\n Play therapy is a psychodynamic therapy technique often used with children. The idea is that children play out their hopes, fantasies, and traumas, using dolls, stuffed animals, and sandbox figurines. \n\n In behavior therapy, a therapist employs principles of learning from classical and operant conditioning to help clients change undesirable behaviors. Counterconditioning is a commonly used therapeutic technique in which a client learns a new response to a stimulus that has previously elicited an undesirable behavior via classical conditioning. Principles of operant conditioning can be applied to help people deal with a wide range of psychological problems. Token economy is an example of a popular operant conditioning technique. \n\n Cognitive therapy is a technique that focuses on how thoughts lead to feelings of distress. The idea behind cognitive therapy is that how you think determines how you feel and act. Cognitive therapists help clients change dysfunctional thoughts in order to relieve distress. Cognitive-behavioral therapy explores how our thoughts affect our behavior. Cognitive-behavioral therapy aims to change cognitive distortions and self-defeating behaviors. Humanistic therapy focuses on helping people achieve their potential. One form of humanistic therapy developed by Carl Rogers is known as client-centered or Rogerian therapy. Client-centered therapists use the techniques of active listening, unconditional positive regard, genuineness, and empathy to help clients become more accepting of themselves. \n\n Often in combination with psychotherapy, people can be prescribed biologically based treatments such as psychotropic medications and/or other medical procedures such as electro-convulsive therapy. \n\n 16.3 Treatment Modalities \n\n There are several modalities of treatment: individual therapy, group therapy, couples therapy, and family therapy are the most common. In an individual therapy session, a client works one-on-one with a trained therapist. In group therapy, usually 5–10 people meet with a trained group therapist to discuss a common issue (e.g., divorce, grief, eating disorders, substance abuse, or anger management). Couples therapy involves two people in an intimate relationship who are having difficulties and are trying to resolve them. The couple may be dating, partnered, engaged, or married. The therapist helps them resolve their problems as well as implement strategies that will lead to a healthier and happier relationship. Family therapy is a special form of group therapy. The therapy group is made up of one or more families. The goal of this approach is to enhance the growth of each individual family member and the family as a whole. \n\n 16.4 Substance-Related and Addictive Disorders: A Special Case \n\n Addiction is often viewed as a chronic disease that rewires the brain. This helps explain why relapse rates tend to be high, around 40%–60% (McLellan, Lewis, & O’Brien, & Kleber, 2000). The goal of treatment is to help an addict stop compulsive drug-seeking behaviors. Treatment usually includes behavioral therapy, which can take place individually or in a group setting. Treatment may also include medication. Sometimes a person has comorbid disorders, which usually means that they have a substance-related disorder diagnosis and another psychiatric diagnosis, such as depression, bipolar disorder, or schizophrenia. The best treatment would address both problems simultaneously. \n\n 16.5 The Sociocultural Model and Therapy Utilization \n\n The sociocultural perspective looks at you, your behaviors, and your symptoms in the context of your culture and background. Clinicians using this approach integrate cultural and religious beliefs into the therapeutic process. Research has shown that ethnic minorities are less likely to access mental health services than their White middle-class American counterparts. Barriers to treatment include lack of insurance, transportation, and time; cultural views that mental illness is a stigma; fears about treatment; and language barriers. "},"intro":{"kind":"string","value":" Chapter Outline 16.1 Mental Health Treatment: Past and Present 16.2 Types of Treatment 16.3 Treatment Modalities 16.4 Substance-Related and Addictive Disorders: A Special Case 16.5 The Sociocultural Model and Therapy Utilization Introduction \n\n What comes to mind when you think about therapy for psychological problems? You might picture someone lying on a couch talking about his childhood while the therapist sits and takes notes, à la Sigmund Freud. But can you envision a therapy session in which someone is wearing virtual reality headgear to conquer a fear of snakes? \n\n In this chapter, you will see that approaches to therapy include both psychological and biological interventions, all with the goal of alleviating distress. Because psychological problems can originate from various sources—biology, genetics, childhood experiences, conditioning, and sociocultural influences—psychologists have developed many different therapeutic techniques and approaches. The Ocean Therapy program shown in Figure 16.1 uses multiple approaches to support the mental health of veterans in the group. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":1,"ans_text":"medieval priests"},"bloom":null,"hl_context":"<hl> In the 19th century , Dorothea Dix led reform efforts for mental health care in the United States ( Figure 16.6 ) . <hl> She investigated how those who are mentally ill and poor were cared for , and she discovered an underfunded and unregulated system that perpetuated abuse of this population ( Tiffany , 1891 ) . Horrified by her findings , Dix began lobbying various state legislatures and the U . S . Congress for change ( Tiffany , 1891 ) . Her efforts led to the creation of the first mental asylums in the United States . <hl> In the late 1700s , a French physician , Philippe Pinel , argued for more humane treatment of the mentally ill . <hl> He suggested that they be unchained and talked to , and that ’ s just what he did for patients at La Salpêtrière in Paris in 1795 ( Figure 16.5 ) . Patients benefited from this more humane treatment , and many were able to leave the hospital . For much of history , the mentally ill have been treated very poorly . It was believed that mental illness was caused by demonic possession , witchcraft , or an angry god ( Szasz , 1960 ) . <hl> For example , in medieval times , abnormal behaviors were viewed as a sign that a person was possessed by demons . <hl> <hl> If someone was considered to be possessed , there were several forms of treatment to release spirits from the individual . <hl> The most common treatment was exorcism , often conducted by priests or other religious figures : Incantations and prayers were said over the person ’ s body , and she may have been given some medicinal drinks . Another form of treatment for extreme cases of mental illness was trephining : A small hole was made in the afflicted individual ’ s skull to release spirits from the body . Most people treated in this manner died . In addition to exorcism and trephining , other practices involved execution or imprisonment of people with psychological disorders . Still others were left to be homeless beggars . Generally speaking , most people who exhibited strange behaviors were greatly misunderstood and treated cruelly . The prevailing theory of psychopathology in earlier history was the idea that mental illness was the result of demonic possession by either an evil spirit or an evil god because early beliefs incorrectly attributed all unexplainable phenomena to deities deemed either good or evil .","hl_sentences":"In the 19th century , Dorothea Dix led reform efforts for mental health care in the United States ( Figure 16.6 ) . In the late 1700s , a French physician , Philippe Pinel , argued for more humane treatment of the mentally ill . For example , in medieval times , abnormal behaviors were viewed as a sign that a person was possessed by demons . If someone was considered to be possessed , there were several forms of treatment to release spirits from the individual .","question":{"cloze_format":"____ does not support the humane and improved treatment of mentally ill persons.","normal_format":"Who of the following does not support the humane and improved treatment of mentally ill persons?","question_choices":["Philippe Pinel","medieval priests","Dorothea Dix","All of the above"],"question_id":"fs-idm9640640","question_text":"Who of the following does not support the humane and improved treatment of mentally ill persons?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"deinstitutionalization"},"bloom":"1","hl_context":"Starting in 1954 and gaining popularity in the 1960s , antipsychotic medications were introduced . These proved a tremendous help in controlling the symptoms of certain psychological disorders , such as psychosis . Psychosis was a common diagnosis of individuals in mental hospitals , and it was often evidenced by symptoms like hallucinations and delusions , indicating a loss of contact with reality . Then in 1963 , Congress passed and John F . Kennedy signed the Mental Retardation Facilities and Community Mental Health Centers Construction Act , which provided federal support and funding for community mental health centers ( National Institutes of Health , 2013 ) . This legislation changed how mental health services were delivered in the United States . <hl> It started the process of deinstitutionalization , the closing of large asylums , by providing for people to stay in their communities and be treated locally . <hl> In 1955 , there were 558,239 severely mentally ill patients institutionalized at public hospitals ( Torrey , 1997 ) . By 1994 , by percentage of the population , there were 92 % fewer hospitalized individuals ( Torrey , 1997 ) .","hl_sentences":"It started the process of deinstitutionalization , the closing of large asylums , by providing for people to stay in their communities and be treated locally .","question":{"cloze_format":"The process of closing large asylums and providing for people to stay in the community to be treated locally is known as ________.","normal_format":"What is the process of closing large asylums and providing for people to stay in the community to be treated locally known as?","question_choices":["deinstitutionalization","exorcism","deactivation","decentralization"],"question_id":"fs-idm83080272","question_text":"The process of closing large asylums and providing for people to stay in the community to be treated locally is known as ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"involuntary"},"bloom":"1","hl_context":"Some people seek therapy because the criminal justice system referred them or required them to go . For some individuals , for example , attending weekly counseling sessions might be a condition of parole . If an individual is mandated to attend therapy , she is seeking services involuntarily . <hl> Involuntary treatment refers to therapy that is not the individual ’ s choice . <hl> Other individuals might voluntarily seek treatment . Voluntary treatment means the person chooses to attend therapy to obtain relief from symptoms .","hl_sentences":"Involuntary treatment refers to therapy that is not the individual ’ s choice .","question":{"cloze_format":"Joey was convicted of domestic violence. As part of his sentence, the judge has ordered that he attend therapy for anger management. This is considered ________ treatment.","normal_format":"Joey was convicted of domestic violence. As part of his sentence, the judge has ordered that he attend therapy for anger management. What treatment is this considered to be?","question_choices":["involuntary","voluntary","forced","mandatory"],"question_id":"fs-idm100302928","question_text":"Joey was convicted of domestic violence. As part of his sentence, the judge has ordered that he attend therapy for anger management. This is considered ________ treatment."},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"are an imminent threat to themselves or others"},"bloom":null,"hl_context":"Today , instead of asylums , there are psychiatric hospitals run by state governments and local community hospitals focused on short-term care . In all types of hospitals , the emphasis is on short-term stays , with the average length of stay being less than two weeks and often only several days . This is partly due to the very high cost of psychiatric hospitalization , which can be about $ 800 to $ 1000 per night ( Stensland , Watson , & Grazier , 2012 ) . Therefore , insurance coverage often limits the length of time a person can be hospitalized for treatment . <hl> Usually individuals are hospitalized only if they are an imminent threat to themselves or others . <hl>","hl_sentences":"Usually individuals are hospitalized only if they are an imminent threat to themselves or others .","question":{"cloze_format":"Today, most people with psychological problems are not hospitalized. Typically they are only hospitalized if they ________.","normal_format":"Today, most people with psychological problems are not hospitalized. When are they only typically hospitalized?","question_choices":["have schizophrenia","have insurance","are an imminent threat to themselves or others","require therapy"],"question_id":"fs-idm9089504","question_text":"Today, most people with psychological problems are not hospitalized. Typically they are only hospitalized if they ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"cognitive therapy"},"bloom":null,"hl_context":"<hl> Cognitive therapy is a form of psychotherapy that focuses on how a person ’ s thoughts lead to feelings of distress . <hl> <hl> The idea behind cognitive therapy is that how you think determines how you feel and act . <hl> Cognitive therapists help their clients change dysfunctional thoughts in order to relieve distress . They help a client see how they misinterpret a situation ( cognitive distortion ) . For example , a client may overgeneralize . Because Ray failed one test in his Psychology 101 course , he feels he is stupid and worthless . These thoughts then cause his mood to worsen . Therapists also help clients recognize when they blow things out of proportion . Because Ray failed his Psychology 101 test , he has concluded that he ’ s going to fail the entire course and probably flunk out of college altogether . These errors in thinking have contributed to Ray ’ s feelings of distress . His therapist will help him challenge these irrational beliefs , focus on their illogical basis , and correct them with more logical and rational thoughts and beliefs .","hl_sentences":"Cognitive therapy is a form of psychotherapy that focuses on how a person ’ s thoughts lead to feelings of distress . The idea behind cognitive therapy is that how you think determines how you feel and act .","question":{"cloze_format":"The idea behind ________ is that how you think determines how you feel and act.","normal_format":"How you think determines how you feel and act. Is the idea behind what?","question_choices":["cognitive therapy","cognitive-behavioral therapy","behavior therapy","client-centered therapy"],"question_id":"fs-idm128445200","question_text":"The idea behind ________ is that how you think determines how you feel and act."},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"bipolar disorder"},"bloom":null,"hl_context":"<hl> Lithium , Depakote , Lamictal , Tegretol <hl> Different types and classes of medications are prescribed for different disorders . <hl> A depressed person might be given an antidepressant , a bipolar individual might be given a mood stabilizer , and a schizophrenic individual might be given an antipsychotic . <hl> <hl> These medications treat the symptoms of a psychological disorder . <hl> They can help people feel better so that they can function on a daily basis , but they do not cure the disorder . Some people may only need to take a psychotropic medication for a short period of time . Others with severe disorders like bipolar disorder or schizophrenia may need to take psychotropic medication for a long time . Table 16.2 shows the types of medication and how they are used .","hl_sentences":"Lithium , Depakote , Lamictal , Tegretol A depressed person might be given an antidepressant , a bipolar individual might be given a mood stabilizer , and a schizophrenic individual might be given an antipsychotic . These medications treat the symptoms of a psychological disorder .","question":{"cloze_format":"Mood stabilizers, such as lithium, are used to treat ________.","normal_format":"What are mood stabilizers, such as lithium, used to treat?","question_choices":["anxiety disorders","depression","bipolar disorder","ADHD"],"question_id":"fs-idm113610720","question_text":"Mood stabilizers, such as lithium, are used to treat ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"group therapy"},"bloom":null,"hl_context":"<hl> In group therapy , a clinician meets together with several clients with similar problems ( Figure 16.16 ) . <hl> When children are placed in group therapy , it is particularly important to match clients for age and problems . One benefit of group therapy is that it can help decrease a client ’ s shame and isolation about a problem while offering needed support , both from the therapist and other members of the group ( American Psychological Association , 2014 ) . A nine-year-old sexual abuse victim , for example , may feel very embarrassed and ashamed . If he is placed in a group with other sexually abused boys , he will realize that he is not alone . A child struggling with poor social skills would likely benefit from a group with a specific curriculum to foster special skills . A woman suffering from post-partum depression could feel less guilty and more supported by being in a group with similar women .","hl_sentences":"In group therapy , a clinician meets together with several clients with similar problems ( Figure 16.16 ) .","question":{"cloze_format":"A treatment modality in which 5–10 people with the same issue or concern meet together with a trained clinician is known as ________.","normal_format":"What is a treatment modality in which 5–10 people with the same issue or concern meet together with a trained clinician known as?","question_choices":["family therapy","couples therapy","group therapy","self-help group"],"question_id":"fs-idm161631280","question_text":"A treatment modality in which 5–10 people with the same issue or concern meet together with a trained clinician is known as ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"The therapist gathers specific information to address the client’s immediate needs such as the presenting problem, the client’s support system, and insurance status. The therapist informs the client about confidentiality, fees, and what to expect in a therapy session."},"bloom":"2","hl_context":"Once a person seeks treatment , whether voluntarily or involuntarily , he has an intake done to assess his clinical needs . <hl> An intake is the therapist ’ s first meeting with the client . <hl> <hl> The therapist gathers specific information to address the client ’ s immediate needs , such as the presenting problem , the client ’ s support system , and insurance status . <hl> <hl> The therapist informs the client about confidentiality , fees , and what to expect in treatment . <hl> Confidentiality means the therapist cannot disclose confidential communications to any third party unless mandated or permitted by law to do so . During the intake , the therapist and client will work together to discuss treatment goals . Then a treatment plan will be formulated , usually with specific measurable objectives . Also , the therapist and client will discuss how treatment success will be measured and the estimated length of treatment . There are several different modalities of treatment ( Figure 16.14 ): Individual therapy , family therapy , couples therapy , and group therapy are the most common .","hl_sentences":"An intake is the therapist ’ s first meeting with the client . The therapist gathers specific information to address the client ’ s immediate needs , such as the presenting problem , the client ’ s support system , and insurance status . The therapist informs the client about confidentiality , fees , and what to expect in treatment .","question":{"cloze_format":"The following happens during an intake: ____.","normal_format":"What happens during an intake?","question_choices":["The therapist gathers specific information to address the client’s immediate needs such as the presenting problem, the client’s support system, and insurance status. The therapist informs the client about confidentiality, fees, and what to expect in a therapy session.","The therapist guides what happens in the therapy session and designs a detailed approach to resolving each member’s presenting problem.","The therapist meets with a couple to help them see how their individual backgrounds, beliefs, and actions are affecting their relationship.","The therapist examines and discusses with the family the boundaries and structure of the family: For example, who makes the rules, who sleeps in the bed with whom, and how decisions are made."],"question_id":"fs-idm109208208","question_text":"What happens during an intake?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"3 months"},"bloom":null,"hl_context":"Specific factors make substance-related treatment much more effective . One factor is duration of treatment . <hl> Generally , a person with addict needs to be in treatment for at least three months to achieve a positive outcome ( Simpson , 1981 ; Simpson , Joe , & Bracy , 1982 ; NIDA , 2012 ) . <hl> This is due to the psychological , physiological , behavioral , and social aspects of abuse ( Simpson , 1981 ; Simpson et al . , 1982 ; NIDA , 2012 ) . While in treatment , a person with addiction might receive behavior therapy , which can help motivate the person with addiction to participate in the treatment program and teach strategies for dealing with cravings and how to prevent relapse . Also , treatment needs to be holistic and address multiple needs , not just the drug addiction . This means that treatment will address factors such as communication , stress management , relationship issues , parenting , vocational concerns , and legal concerns ( McGovern & Carroll , 2003 ; NIDA , 2012 ) . While individual therapy is used in the treatment of substance-related disorders , group therapy is the most widespread treatment modality ( Weiss , Jaffee , de Menil , & Cogley , 2004 ) . The rationale behind using group therapy for addiction treatment is that people with addiction are much more likely to maintain sobriety in a group format . It has been suggested that this is due to the rewarding and therapeutic benefits of the group , such as support , affiliation , identification , and even confrontation ( Center for Substance Abuse Treatment , 2005 ) . For teenagers , the whole family often needs to participate in treatment to address issues such as family dynamics , communication , and relapse prevention . Family involvement in teen drug addiction is vital . Research suggests that greater parental involvement is correlated with a greater reduction in use by teen substance abusers . Also , mothers who participated in treatment displayed better mental health and greater warmth toward their children ( Bertrand et al . , 2013 ) . However , neither individual nor group therapy has been found to be more effective ( Weiss et al . , 2004 ) . Regardless of the type of treatment service , the primary focus is on abstinence or at the very least a significant reduction in use ( McGovern & Carroll , 2003 ) . Treatment also usually involves medications to detox a person with addiction safely after an overdose , to prevent seizures and agitation that often occur in detox , to prevent reuse of the drug , and to manage withdrawal symptoms . Getting off drugs often involves the use of drugs — some of which can be just as addictive . Detox can be difficult and dangerous . Link to Learning","hl_sentences":"Generally , a person with addict needs to be in treatment for at least three months to achieve a positive outcome ( Simpson , 1981 ; Simpson , Joe , & Bracy , 1982 ; NIDA , 2012 ) .","question":{"cloze_format":"The minimum amount of time addicts should receive treatment is ___ if they are to achieve a desired outcome.","normal_format":"What is the minimum amount of time addicts should receive treatment if they are to achieve a desired outcome?","question_choices":["3 months","6 months","9 months","12 months"],"question_id":"fs-idm135992096","question_text":"What is the minimum amount of time addicts should receive treatment if they are to achieve a desired outcome?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"comorbid disorder"},"bloom":null,"hl_context":"Frequently , a person with an addiction to drugs and / or alcohol has an additional psychological disorder . <hl> Saying a person has comorbid disorders means the individual has two or more diagnoses . <hl> <hl> This can often be a substance-related diagnosis and another psychiatric diagnosis , such as depression , bipolar disorder , or schizophrenia . <hl> These individuals fall into the category of mentally ill and chemically addicted ( MICA ) — their problems are often chronic and expensive to treat , with limited success . Compared with the overall population , substance abusers are twice as likely to have a mood or anxiety disorder . Drug abuse can cause symptoms of mood and anxiety disorders and the reverse is also true — people with debilitating symptoms of a psychiatric disorder may self-medicate and abuse substances . In cases of comorbidity , the best treatment is thought to address both ( or multiple ) disorders simultaneously ( NIDA , 2012 ) . Behavior therapies are used to treat comorbid conditions , and in many cases , psychotropic medications are used along with psychotherapy . For example , evidence suggests that bupropion ( trade names : Wellbutrin and Zyban ) , approved for treating depression and nicotine dependence , might also help reduce craving and use of the drug methamphetamine ( NIDA , 2011 ) . However , more research is needed to better understand how these medications work — particularly when combined in patients with comorbidities . 16.5 The Sociocultural Model and Therapy Utilization Learning Objectives By the end of this section , you will be able to :","hl_sentences":"Saying a person has comorbid disorders means the individual has two or more diagnoses . This can often be a substance-related diagnosis and another psychiatric diagnosis , such as depression , bipolar disorder , or schizophrenia .","question":{"cloze_format":"When an individual has two or more diagnoses, which often includes a substance-related diagnosis and another psychiatric diagnosis, this is known as ________.","normal_format":"When an individual has two or more diagnoses, which often includes a substance-related diagnosis and another psychiatric diagnosis, this is known as which of the following?","question_choices":["bipolar disorder","comorbid disorder","codependency","bi-morbid disorder"],"question_id":"fs-idm132593184","question_text":"When an individual has two or more diagnoses, which often includes a substance-related diagnosis and another psychiatric diagnosis, this is known as ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"relapse"},"bloom":null,"hl_context":"Specific factors make substance-related treatment much more effective . One factor is duration of treatment . Generally , a person with addict needs to be in treatment for at least three months to achieve a positive outcome ( Simpson , 1981 ; Simpson , Joe , & Bracy , 1982 ; NIDA , 2012 ) . This is due to the psychological , physiological , behavioral , and social aspects of abuse ( Simpson , 1981 ; Simpson et al . , 1982 ; NIDA , 2012 ) . While in treatment , a person with addiction might receive behavior therapy , which can help motivate the person with addiction to participate in the treatment program and teach strategies for dealing with cravings and how to prevent relapse . Also , treatment needs to be holistic and address multiple needs , not just the drug addiction . This means that treatment will address factors such as communication , stress management , relationship issues , parenting , vocational concerns , and legal concerns ( McGovern & Carroll , 2003 ; NIDA , 2012 ) . While individual therapy is used in the treatment of substance-related disorders , group therapy is the most widespread treatment modality ( Weiss , Jaffee , de Menil , & Cogley , 2004 ) . The rationale behind using group therapy for addiction treatment is that people with addiction are much more likely to maintain sobriety in a group format . It has been suggested that this is due to the rewarding and therapeutic benefits of the group , such as support , affiliation , identification , and even confrontation ( Center for Substance Abuse Treatment , 2005 ) . <hl> For teenagers , the whole family often needs to participate in treatment to address issues such as family dynamics , communication , and relapse prevention . <hl> Family involvement in teen drug addiction is vital . Research suggests that greater parental involvement is correlated with a greater reduction in use by teen substance abusers . Also , mothers who participated in treatment displayed better mental health and greater warmth toward their children ( Bertrand et al . , 2013 ) . However , neither individual nor group therapy has been found to be more effective ( Weiss et al . , 2004 ) . Regardless of the type of treatment service , the primary focus is on abstinence or at the very least a significant reduction in use ( McGovern & Carroll , 2003 ) . <hl> Treatment also usually involves medications to detox a person with addiction safely after an overdose , to prevent seizures and agitation that often occur in detox , to prevent reuse of the drug , and to manage withdrawal symptoms . <hl> <hl> Getting off drugs often involves the use of drugs — some of which can be just as addictive . <hl> <hl> Detox can be difficult and dangerous . <hl> Link to Learning","hl_sentences":"For teenagers , the whole family often needs to participate in treatment to address issues such as family dynamics , communication , and relapse prevention . Treatment also usually involves medications to detox a person with addiction safely after an overdose , to prevent seizures and agitation that often occur in detox , to prevent reuse of the drug , and to manage withdrawal symptoms . Getting off drugs often involves the use of drugs — some of which can be just as addictive . Detox can be difficult and dangerous .","question":{"cloze_format":"John was drug-free for almost six months. Then he started hanging out with his addict friends, and he has now started abusing drugs again. This is an example of ________.","normal_format":"John was drug-free for almost six months. Then he started hanging out with his addict friends, and he has now started abusing drugs again. What is this an example of?","question_choices":["release","reversion","re-addiction","relapse"],"question_id":"fs-idm44869248","question_text":"John was drug-free for almost six months. Then he started hanging out with his addict friends, and he has now started abusing drugs again. This is an example of ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"culture and background"},"bloom":null,"hl_context":"<hl> The sociocultural perspective looks at you , your behaviors , and your symptoms in the context of your culture and background . <hl> For example , José is an 18 - year-old Hispanic male from a traditional family . José comes to treatment because of depression . During the intake session , he reveals that he is gay and is nervous about telling his family . He also discloses that he is concerned because his religious background has taught him that homosexuality is wrong . How does his religious and cultural background affect him ? How might his cultural background affect how his family reacts if José were to tell them he is gay ?","hl_sentences":"The sociocultural perspective looks at you , your behaviors , and your symptoms in the context of your culture and background .","question":{"cloze_format":"The sociocultural perspective looks at you, your behaviors, and your symptoms in the context of your ________.","normal_format":"In which context, the sociocultural perspective looks at you, your behaviors, and your symptoms?","question_choices":["education","socioeconomic status","culture and background","age"],"question_id":"fs-idp27071728","question_text":"The sociocultural perspective looks at you, your behaviors, and your symptoms in the context of your ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"being a member of the ethnic majority"},"bloom":"1","hl_context":"Statistically , ethnic minorities tend to utilize mental health services less frequently than White , middle-class Americans ( Alegría et al . , 2008 ; Richman , Kohn-Wood , & Williams , 2007 ) . Why is this so ? Perhaps the reason has to do with access and availability of mental health services . Ethnic minorities and individuals of low socioeconomic status ( SES ) report that barriers to services include lack of insurance , transportation , and time ( Thomas & Snowden , 2002 ) . However , researchers have found that even when income levels and insurance variables are taken into account , ethnic minorities are far less likely to seek out and utilize mental health services . <hl> And when access to mental health services is comparable across ethnic and racial groups , differences in service utilization remain ( Richman et al . , 2007 ) . <hl>","hl_sentences":"And when access to mental health services is comparable across ethnic and racial groups , differences in service utilization remain ( Richman et al . , 2007 ) .","question":{"cloze_format":"___ is not listed as a barrier to mental health treatment.","normal_format":"Which of the following was not listed as a barrier to mental health treatment?","question_choices":["fears about treatment","language","transportation","being a member of the ethnic majority"],"question_id":"fs-idm127432976","question_text":"Which of the following was not listed as a barrier to mental health treatment?"},"references_are_paraphrase":0}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"medieval priests\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> In the 19th century , Dorothea Dix led reform efforts for mental health care in the United States ( Figure 16.6 ) . <hl> She investigated how those who are mentally ill and poor were cared for , and she discovered an underfunded and unregulated system that perpetuated abuse of this population ( Tiffany , 1891 ) . Horrified by her findings , Dix began lobbying various state legislatures and the U . S . Congress for change ( Tiffany , 1891 ) . Her efforts led to the creation of the first mental asylums in the United States . <hl> In the late 1700s , a French physician , Philippe Pinel , argued for more humane treatment of the mentally ill . <hl> He suggested that they be unchained and talked to , and that ’ s just what he did for patients at La Salpêtrière in Paris in 1795 ( Figure 16.5 ) . Patients benefited from this more humane treatment , and many were able to leave the hospital . For much of history , the mentally ill have been treated very poorly . It was believed that mental illness was caused by demonic possession , witchcraft , or an angry god ( Szasz , 1960 ) . <hl> For example , in medieval times , abnormal behaviors were viewed as a sign that a person was possessed by demons . <hl> <hl> If someone was considered to be possessed , there were several forms of treatment to release spirits from the individual . <hl> The most common treatment was exorcism , often conducted by priests or other religious figures : Incantations and prayers were said over the person ’ s body , and she may have been given some medicinal drinks . Another form of treatment for extreme cases of mental illness was trephining : A small hole was made in the afflicted individual ’ s skull to release spirits from the body . Most people treated in this manner died . In addition to exorcism and trephining , other practices involved execution or imprisonment of people with psychological disorders . Still others were left to be homeless beggars . Generally speaking , most people who exhibited strange behaviors were greatly misunderstood and treated cruelly . The prevailing theory of psychopathology in earlier history was the idea that mental illness was the result of demonic possession by either an evil spirit or an evil god because early beliefs incorrectly attributed all unexplainable phenomena to deities deemed either good or evil .\",\n \"hl_sentences\": \"In the 19th century , Dorothea Dix led reform efforts for mental health care in the United States ( Figure 16.6 ) . In the late 1700s , a French physician , Philippe Pinel , argued for more humane treatment of the mentally ill . For example , in medieval times , abnormal behaviors were viewed as a sign that a person was possessed by demons . If someone was considered to be possessed , there were several forms of treatment to release spirits from the individual .\",\n \"question\": {\n \"cloze_format\": \"____ does not support the humane and improved treatment of mentally ill persons.\",\n \"normal_format\": \"Who of the following does not support the humane and improved treatment of mentally ill persons?\",\n \"question_choices\": [\n \"Philippe Pinel\",\n \"medieval priests\",\n \"Dorothea Dix\",\n \"All of the above\"\n ],\n \"question_id\": \"fs-idm9640640\",\n \"question_text\": \"Who of the following does not support the humane and improved treatment of mentally ill persons?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"deinstitutionalization\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Starting in 1954 and gaining popularity in the 1960s , antipsychotic medications were introduced . These proved a tremendous help in controlling the symptoms of certain psychological disorders , such as psychosis . Psychosis was a common diagnosis of individuals in mental hospitals , and it was often evidenced by symptoms like hallucinations and delusions , indicating a loss of contact with reality . Then in 1963 , Congress passed and John F . Kennedy signed the Mental Retardation Facilities and Community Mental Health Centers Construction Act , which provided federal support and funding for community mental health centers ( National Institutes of Health , 2013 ) . This legislation changed how mental health services were delivered in the United States . <hl> It started the process of deinstitutionalization , the closing of large asylums , by providing for people to stay in their communities and be treated locally . <hl> In 1955 , there were 558,239 severely mentally ill patients institutionalized at public hospitals ( Torrey , 1997 ) . By 1994 , by percentage of the population , there were 92 % fewer hospitalized individuals ( Torrey , 1997 ) .\",\n \"hl_sentences\": \"It started the process of deinstitutionalization , the closing of large asylums , by providing for people to stay in their communities and be treated locally .\",\n \"question\": {\n \"cloze_format\": \"The process of closing large asylums and providing for people to stay in the community to be treated locally is known as ________.\",\n \"normal_format\": \"What is the process of closing large asylums and providing for people to stay in the community to be treated locally known as?\",\n \"question_choices\": [\n \"deinstitutionalization\",\n \"exorcism\",\n \"deactivation\",\n \"decentralization\"\n ],\n \"question_id\": \"fs-idm83080272\",\n \"question_text\": \"The process of closing large asylums and providing for people to stay in the community to be treated locally is known as ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"involuntary\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Some people seek therapy because the criminal justice system referred them or required them to go . For some individuals , for example , attending weekly counseling sessions might be a condition of parole . If an individual is mandated to attend therapy , she is seeking services involuntarily . <hl> Involuntary treatment refers to therapy that is not the individual ’ s choice . <hl> Other individuals might voluntarily seek treatment . Voluntary treatment means the person chooses to attend therapy to obtain relief from symptoms .\",\n \"hl_sentences\": \"Involuntary treatment refers to therapy that is not the individual ’ s choice .\",\n \"question\": {\n \"cloze_format\": \"Joey was convicted of domestic violence. As part of his sentence, the judge has ordered that he attend therapy for anger management. This is considered ________ treatment.\",\n \"normal_format\": \"Joey was convicted of domestic violence. As part of his sentence, the judge has ordered that he attend therapy for anger management. What treatment is this considered to be?\",\n \"question_choices\": [\n \"involuntary\",\n \"voluntary\",\n \"forced\",\n \"mandatory\"\n ],\n \"question_id\": \"fs-idm100302928\",\n \"question_text\": \"Joey was convicted of domestic violence. As part of his sentence, the judge has ordered that he attend therapy for anger management. This is considered ________ treatment.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"are an imminent threat to themselves or others\"\n },\n \"bloom\": null,\n \"hl_context\": \"Today , instead of asylums , there are psychiatric hospitals run by state governments and local community hospitals focused on short-term care . In all types of hospitals , the emphasis is on short-term stays , with the average length of stay being less than two weeks and often only several days . This is partly due to the very high cost of psychiatric hospitalization , which can be about $ 800 to $ 1000 per night ( Stensland , Watson , & Grazier , 2012 ) . Therefore , insurance coverage often limits the length of time a person can be hospitalized for treatment . <hl> Usually individuals are hospitalized only if they are an imminent threat to themselves or others . <hl>\",\n \"hl_sentences\": \"Usually individuals are hospitalized only if they are an imminent threat to themselves or others .\",\n \"question\": {\n \"cloze_format\": \"Today, most people with psychological problems are not hospitalized. Typically they are only hospitalized if they ________.\",\n \"normal_format\": \"Today, most people with psychological problems are not hospitalized. When are they only typically hospitalized?\",\n \"question_choices\": [\n \"have schizophrenia\",\n \"have insurance\",\n \"are an imminent threat to themselves or others\",\n \"require therapy\"\n ],\n \"question_id\": \"fs-idm9089504\",\n \"question_text\": \"Today, most people with psychological problems are not hospitalized. Typically they are only hospitalized if they ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"cognitive therapy\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Cognitive therapy is a form of psychotherapy that focuses on how a person ’ s thoughts lead to feelings of distress . <hl> <hl> The idea behind cognitive therapy is that how you think determines how you feel and act . <hl> Cognitive therapists help their clients change dysfunctional thoughts in order to relieve distress . They help a client see how they misinterpret a situation ( cognitive distortion ) . For example , a client may overgeneralize . Because Ray failed one test in his Psychology 101 course , he feels he is stupid and worthless . These thoughts then cause his mood to worsen . Therapists also help clients recognize when they blow things out of proportion . Because Ray failed his Psychology 101 test , he has concluded that he ’ s going to fail the entire course and probably flunk out of college altogether . These errors in thinking have contributed to Ray ’ s feelings of distress . His therapist will help him challenge these irrational beliefs , focus on their illogical basis , and correct them with more logical and rational thoughts and beliefs .\",\n \"hl_sentences\": \"Cognitive therapy is a form of psychotherapy that focuses on how a person ’ s thoughts lead to feelings of distress . The idea behind cognitive therapy is that how you think determines how you feel and act .\",\n \"question\": {\n \"cloze_format\": \"The idea behind ________ is that how you think determines how you feel and act.\",\n \"normal_format\": \"How you think determines how you feel and act. Is the idea behind what?\",\n \"question_choices\": [\n \"cognitive therapy\",\n \"cognitive-behavioral therapy\",\n \"behavior therapy\",\n \"client-centered therapy\"\n ],\n \"question_id\": \"fs-idm128445200\",\n \"question_text\": \"The idea behind ________ is that how you think determines how you feel and act.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"bipolar disorder\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Lithium , Depakote , Lamictal , Tegretol <hl> Different types and classes of medications are prescribed for different disorders . <hl> A depressed person might be given an antidepressant , a bipolar individual might be given a mood stabilizer , and a schizophrenic individual might be given an antipsychotic . <hl> <hl> These medications treat the symptoms of a psychological disorder . <hl> They can help people feel better so that they can function on a daily basis , but they do not cure the disorder . Some people may only need to take a psychotropic medication for a short period of time . Others with severe disorders like bipolar disorder or schizophrenia may need to take psychotropic medication for a long time . Table 16.2 shows the types of medication and how they are used .\",\n \"hl_sentences\": \"Lithium , Depakote , Lamictal , Tegretol A depressed person might be given an antidepressant , a bipolar individual might be given a mood stabilizer , and a schizophrenic individual might be given an antipsychotic . These medications treat the symptoms of a psychological disorder .\",\n \"question\": {\n \"cloze_format\": \"Mood stabilizers, such as lithium, are used to treat ________.\",\n \"normal_format\": \"What are mood stabilizers, such as lithium, used to treat?\",\n \"question_choices\": [\n \"anxiety disorders\",\n \"depression\",\n \"bipolar disorder\",\n \"ADHD\"\n ],\n \"question_id\": \"fs-idm113610720\",\n \"question_text\": \"Mood stabilizers, such as lithium, are used to treat ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"group therapy\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> In group therapy , a clinician meets together with several clients with similar problems ( Figure 16.16 ) . <hl> When children are placed in group therapy , it is particularly important to match clients for age and problems . One benefit of group therapy is that it can help decrease a client ’ s shame and isolation about a problem while offering needed support , both from the therapist and other members of the group ( American Psychological Association , 2014 ) . A nine-year-old sexual abuse victim , for example , may feel very embarrassed and ashamed . If he is placed in a group with other sexually abused boys , he will realize that he is not alone . A child struggling with poor social skills would likely benefit from a group with a specific curriculum to foster special skills . A woman suffering from post-partum depression could feel less guilty and more supported by being in a group with similar women .\",\n \"hl_sentences\": \"In group therapy , a clinician meets together with several clients with similar problems ( Figure 16.16 ) .\",\n \"question\": {\n \"cloze_format\": \"A treatment modality in which 5–10 people with the same issue or concern meet together with a trained clinician is known as ________.\",\n \"normal_format\": \"What is a treatment modality in which 5–10 people with the same issue or concern meet together with a trained clinician known as?\",\n \"question_choices\": [\n \"family therapy\",\n \"couples therapy\",\n \"group therapy\",\n \"self-help group\"\n ],\n \"question_id\": \"fs-idm161631280\",\n \"question_text\": \"A treatment modality in which 5–10 people with the same issue or concern meet together with a trained clinician is known as ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"The therapist gathers specific information to address the client’s immediate needs such as the presenting problem, the client’s support system, and insurance status. The therapist informs the client about confidentiality, fees, and what to expect in a therapy session.\"\n },\n \"bloom\": \"2\",\n \"hl_context\": \"Once a person seeks treatment , whether voluntarily or involuntarily , he has an intake done to assess his clinical needs . <hl> An intake is the therapist ’ s first meeting with the client . <hl> <hl> The therapist gathers specific information to address the client ’ s immediate needs , such as the presenting problem , the client ’ s support system , and insurance status . <hl> <hl> The therapist informs the client about confidentiality , fees , and what to expect in treatment . <hl> Confidentiality means the therapist cannot disclose confidential communications to any third party unless mandated or permitted by law to do so . During the intake , the therapist and client will work together to discuss treatment goals . Then a treatment plan will be formulated , usually with specific measurable objectives . Also , the therapist and client will discuss how treatment success will be measured and the estimated length of treatment . There are several different modalities of treatment ( Figure 16.14 ): Individual therapy , family therapy , couples therapy , and group therapy are the most common .\",\n \"hl_sentences\": \"An intake is the therapist ’ s first meeting with the client . The therapist gathers specific information to address the client ’ s immediate needs , such as the presenting problem , the client ’ s support system , and insurance status . The therapist informs the client about confidentiality , fees , and what to expect in treatment .\",\n \"question\": {\n \"cloze_format\": \"The following happens during an intake: ____.\",\n \"normal_format\": \"What happens during an intake?\",\n \"question_choices\": [\n \"The therapist gathers specific information to address the client’s immediate needs such as the presenting problem, the client’s support system, and insurance status. The therapist informs the client about confidentiality, fees, and what to expect in a therapy session.\",\n \"The therapist guides what happens in the therapy session and designs a detailed approach to resolving each member’s presenting problem.\",\n \"The therapist meets with a couple to help them see how their individual backgrounds, beliefs, and actions are affecting their relationship.\",\n \"The therapist examines and discusses with the family the boundaries and structure of the family: For example, who makes the rules, who sleeps in the bed with whom, and how decisions are made.\"\n ],\n \"question_id\": \"fs-idm109208208\",\n \"question_text\": \"What happens during an intake?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"3 months\"\n },\n \"bloom\": null,\n \"hl_context\": \"Specific factors make substance-related treatment much more effective . One factor is duration of treatment . <hl> Generally , a person with addict needs to be in treatment for at least three months to achieve a positive outcome ( Simpson , 1981 ; Simpson , Joe , & Bracy , 1982 ; NIDA , 2012 ) . <hl> This is due to the psychological , physiological , behavioral , and social aspects of abuse ( Simpson , 1981 ; Simpson et al . , 1982 ; NIDA , 2012 ) . While in treatment , a person with addiction might receive behavior therapy , which can help motivate the person with addiction to participate in the treatment program and teach strategies for dealing with cravings and how to prevent relapse . Also , treatment needs to be holistic and address multiple needs , not just the drug addiction . This means that treatment will address factors such as communication , stress management , relationship issues , parenting , vocational concerns , and legal concerns ( McGovern & Carroll , 2003 ; NIDA , 2012 ) . While individual therapy is used in the treatment of substance-related disorders , group therapy is the most widespread treatment modality ( Weiss , Jaffee , de Menil , & Cogley , 2004 ) . The rationale behind using group therapy for addiction treatment is that people with addiction are much more likely to maintain sobriety in a group format . It has been suggested that this is due to the rewarding and therapeutic benefits of the group , such as support , affiliation , identification , and even confrontation ( Center for Substance Abuse Treatment , 2005 ) . For teenagers , the whole family often needs to participate in treatment to address issues such as family dynamics , communication , and relapse prevention . Family involvement in teen drug addiction is vital . Research suggests that greater parental involvement is correlated with a greater reduction in use by teen substance abusers . Also , mothers who participated in treatment displayed better mental health and greater warmth toward their children ( Bertrand et al . , 2013 ) . However , neither individual nor group therapy has been found to be more effective ( Weiss et al . , 2004 ) . Regardless of the type of treatment service , the primary focus is on abstinence or at the very least a significant reduction in use ( McGovern & Carroll , 2003 ) . Treatment also usually involves medications to detox a person with addiction safely after an overdose , to prevent seizures and agitation that often occur in detox , to prevent reuse of the drug , and to manage withdrawal symptoms . Getting off drugs often involves the use of drugs — some of which can be just as addictive . Detox can be difficult and dangerous . Link to Learning\",\n \"hl_sentences\": \"Generally , a person with addict needs to be in treatment for at least three months to achieve a positive outcome ( Simpson , 1981 ; Simpson , Joe , & Bracy , 1982 ; NIDA , 2012 ) .\",\n \"question\": {\n \"cloze_format\": \"The minimum amount of time addicts should receive treatment is ___ if they are to achieve a desired outcome.\",\n \"normal_format\": \"What is the minimum amount of time addicts should receive treatment if they are to achieve a desired outcome?\",\n \"question_choices\": [\n \"3 months\",\n \"6 months\",\n \"9 months\",\n \"12 months\"\n ],\n \"question_id\": \"fs-idm135992096\",\n \"question_text\": \"What is the minimum amount of time addicts should receive treatment if they are to achieve a desired outcome?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"comorbid disorder\"\n },\n \"bloom\": null,\n \"hl_context\": \"Frequently , a person with an addiction to drugs and / or alcohol has an additional psychological disorder . <hl> Saying a person has comorbid disorders means the individual has two or more diagnoses . <hl> <hl> This can often be a substance-related diagnosis and another psychiatric diagnosis , such as depression , bipolar disorder , or schizophrenia . <hl> These individuals fall into the category of mentally ill and chemically addicted ( MICA ) — their problems are often chronic and expensive to treat , with limited success . Compared with the overall population , substance abusers are twice as likely to have a mood or anxiety disorder . Drug abuse can cause symptoms of mood and anxiety disorders and the reverse is also true — people with debilitating symptoms of a psychiatric disorder may self-medicate and abuse substances . In cases of comorbidity , the best treatment is thought to address both ( or multiple ) disorders simultaneously ( NIDA , 2012 ) . Behavior therapies are used to treat comorbid conditions , and in many cases , psychotropic medications are used along with psychotherapy . For example , evidence suggests that bupropion ( trade names : Wellbutrin and Zyban ) , approved for treating depression and nicotine dependence , might also help reduce craving and use of the drug methamphetamine ( NIDA , 2011 ) . However , more research is needed to better understand how these medications work — particularly when combined in patients with comorbidities . 16.5 The Sociocultural Model and Therapy Utilization Learning Objectives By the end of this section , you will be able to :\",\n \"hl_sentences\": \"Saying a person has comorbid disorders means the individual has two or more diagnoses . This can often be a substance-related diagnosis and another psychiatric diagnosis , such as depression , bipolar disorder , or schizophrenia .\",\n \"question\": {\n \"cloze_format\": \"When an individual has two or more diagnoses, which often includes a substance-related diagnosis and another psychiatric diagnosis, this is known as ________.\",\n \"normal_format\": \"When an individual has two or more diagnoses, which often includes a substance-related diagnosis and another psychiatric diagnosis, this is known as which of the following?\",\n \"question_choices\": [\n \"bipolar disorder\",\n \"comorbid disorder\",\n \"codependency\",\n \"bi-morbid disorder\"\n ],\n \"question_id\": \"fs-idm132593184\",\n \"question_text\": \"When an individual has two or more diagnoses, which often includes a substance-related diagnosis and another psychiatric diagnosis, this is known as ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"relapse\"\n },\n \"bloom\": null,\n \"hl_context\": \"Specific factors make substance-related treatment much more effective . One factor is duration of treatment . Generally , a person with addict needs to be in treatment for at least three months to achieve a positive outcome ( Simpson , 1981 ; Simpson , Joe , & Bracy , 1982 ; NIDA , 2012 ) . This is due to the psychological , physiological , behavioral , and social aspects of abuse ( Simpson , 1981 ; Simpson et al . , 1982 ; NIDA , 2012 ) . While in treatment , a person with addiction might receive behavior therapy , which can help motivate the person with addiction to participate in the treatment program and teach strategies for dealing with cravings and how to prevent relapse . Also , treatment needs to be holistic and address multiple needs , not just the drug addiction . This means that treatment will address factors such as communication , stress management , relationship issues , parenting , vocational concerns , and legal concerns ( McGovern & Carroll , 2003 ; NIDA , 2012 ) . While individual therapy is used in the treatment of substance-related disorders , group therapy is the most widespread treatment modality ( Weiss , Jaffee , de Menil , & Cogley , 2004 ) . The rationale behind using group therapy for addiction treatment is that people with addiction are much more likely to maintain sobriety in a group format . It has been suggested that this is due to the rewarding and therapeutic benefits of the group , such as support , affiliation , identification , and even confrontation ( Center for Substance Abuse Treatment , 2005 ) . <hl> For teenagers , the whole family often needs to participate in treatment to address issues such as family dynamics , communication , and relapse prevention . <hl> Family involvement in teen drug addiction is vital . Research suggests that greater parental involvement is correlated with a greater reduction in use by teen substance abusers . Also , mothers who participated in treatment displayed better mental health and greater warmth toward their children ( Bertrand et al . , 2013 ) . However , neither individual nor group therapy has been found to be more effective ( Weiss et al . , 2004 ) . Regardless of the type of treatment service , the primary focus is on abstinence or at the very least a significant reduction in use ( McGovern & Carroll , 2003 ) . <hl> Treatment also usually involves medications to detox a person with addiction safely after an overdose , to prevent seizures and agitation that often occur in detox , to prevent reuse of the drug , and to manage withdrawal symptoms . <hl> <hl> Getting off drugs often involves the use of drugs — some of which can be just as addictive . <hl> <hl> Detox can be difficult and dangerous . <hl> Link to Learning\",\n \"hl_sentences\": \"For teenagers , the whole family often needs to participate in treatment to address issues such as family dynamics , communication , and relapse prevention . Treatment also usually involves medications to detox a person with addiction safely after an overdose , to prevent seizures and agitation that often occur in detox , to prevent reuse of the drug , and to manage withdrawal symptoms . Getting off drugs often involves the use of drugs — some of which can be just as addictive . Detox can be difficult and dangerous .\",\n \"question\": {\n \"cloze_format\": \"John was drug-free for almost six months. Then he started hanging out with his addict friends, and he has now started abusing drugs again. This is an example of ________.\",\n \"normal_format\": \"John was drug-free for almost six months. Then he started hanging out with his addict friends, and he has now started abusing drugs again. What is this an example of?\",\n \"question_choices\": [\n \"release\",\n \"reversion\",\n \"re-addiction\",\n \"relapse\"\n ],\n \"question_id\": \"fs-idm44869248\",\n \"question_text\": \"John was drug-free for almost six months. Then he started hanging out with his addict friends, and he has now started abusing drugs again. This is an example of ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"culture and background\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The sociocultural perspective looks at you , your behaviors , and your symptoms in the context of your culture and background . <hl> For example , José is an 18 - year-old Hispanic male from a traditional family . José comes to treatment because of depression . During the intake session , he reveals that he is gay and is nervous about telling his family . He also discloses that he is concerned because his religious background has taught him that homosexuality is wrong . How does his religious and cultural background affect him ? How might his cultural background affect how his family reacts if José were to tell them he is gay ?\",\n \"hl_sentences\": \"The sociocultural perspective looks at you , your behaviors , and your symptoms in the context of your culture and background .\",\n \"question\": {\n \"cloze_format\": \"The sociocultural perspective looks at you, your behaviors, and your symptoms in the context of your ________.\",\n \"normal_format\": \"In which context, the sociocultural perspective looks at you, your behaviors, and your symptoms?\",\n \"question_choices\": [\n \"education\",\n \"socioeconomic status\",\n \"culture and background\",\n \"age\"\n ],\n \"question_id\": \"fs-idp27071728\",\n \"question_text\": \"The sociocultural perspective looks at you, your behaviors, and your symptoms in the context of your ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"being a member of the ethnic majority\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Statistically , ethnic minorities tend to utilize mental health services less frequently than White , middle-class Americans ( Alegría et al . , 2008 ; Richman , Kohn-Wood , & Williams , 2007 ) . Why is this so ? Perhaps the reason has to do with access and availability of mental health services . Ethnic minorities and individuals of low socioeconomic status ( SES ) report that barriers to services include lack of insurance , transportation , and time ( Thomas & Snowden , 2002 ) . However , researchers have found that even when income levels and insurance variables are taken into account , ethnic minorities are far less likely to seek out and utilize mental health services . <hl> And when access to mental health services is comparable across ethnic and racial groups , differences in service utilization remain ( Richman et al . , 2007 ) . <hl>\",\n \"hl_sentences\": \"And when access to mental health services is comparable across ethnic and racial groups , differences in service utilization remain ( Richman et al . , 2007 ) .\",\n \"question\": {\n \"cloze_format\": \"___ is not listed as a barrier to mental health treatment.\",\n \"normal_format\": \"Which of the following was not listed as a barrier to mental health treatment?\",\n \"question_choices\": [\n \"fears about treatment\",\n \"language\",\n \"transportation\",\n \"being a member of the ethnic majority\"\n ],\n \"question_id\": \"fs-idm127432976\",\n \"question_text\": \"Which of the following was not listed as a barrier to mental health treatment?\"\n },\n \"references_are_paraphrase\": 0\n }\n]","isConversational":false},"chapter":{"kind":"number","value":16,"string":"16"},"chapter_text":{"kind":"string","value":" 16.1 Mental Health Treatment: Past and Present Learning Objectives By the end of this section, you will be able to:\n\n Explain how people with psychological disorders have been treated throughout the ages \n\n Discuss deinstitutionalization \n\n Discuss the ways in which mental health services are delivered today \n\n Distinguish between voluntary and involuntary treatment \n\n Before we explore the various approaches to therapy used today, let’s begin our study of therapy by looking at how many people experience mental illness and how many receive treatment. According to the U.S. Department of Health and Human Services (2013), 19% of U.S. adults experienced mental illness in 2012. For teens (ages 13–18), the rate is similar to that of adults, and for children ages 8–15, current estimates suggest that 13% experience mental illness in a given year (National Institute of Mental Health [NIMH], n.d.-a) \n\n With many different treatment options available, approximately how many people receive mental health treatment per year? According to the Substance Abuse and Mental Health Services Administration (SAMHSA), in 2008, 13.4% of adults received treatment for a mental health issue (NIMH, n.d.-b). These percentages, shown in Figure 16.2 , reflect the number of adults who received care in inpatient and outpatient settings and/or used prescription medication for psychological disorders. \n\n Children and adolescents also receive mental health services. The Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) found that approximately half (50.6%) of children with mental disorders had received treatment for their disorder within the past year (NIMH, n.d.-c). However, there were some differences between treatment rates by category of disorder ( Figure 16.3 ). For example, children with anxiety disorders were least likely to have received treatment in the past year, while children with ADHD or a conduct disorder were more likely to receive treatment. Can you think of some possible reasons for these differences in receiving treatment? \n\n Considering the many forms of treatment for mental health disorders available today, how did these forms of treatment emerge? Let’s take a look at the history of mental health treatment from the past (with some questionable approaches in light of modern understanding of mental illness) to where we are today. \n\n Treatment in the Past \n\n For much of history, the mentally ill have been treated very poorly. It was believed that mental illness was caused by demonic possession, witchcraft, or an angry god (Szasz, 1960). For example, in medieval times, abnormal behaviors were viewed as a sign that a person was possessed by demons. If someone was considered to be possessed, there were several forms of treatment to release spirits from the individual. The most common treatment was exorcism, often conducted by priests or other religious figures: Incantations and prayers were said over the person’s body, and she may have been given some medicinal drinks. Another form of treatment for extreme cases of mental illness was trephining: A small hole was made in the afflicted individual’s skull to release spirits from the body. Most people treated in this manner died. In addition to exorcism and trephining, other practices involved execution or imprisonment of people with psychological disorders. Still others were left to be homeless beggars. Generally speaking, most people who exhibited strange behaviors were greatly misunderstood and treated cruelly. The prevailing theory of psychopathology in earlier history was the idea that mental illness was the result of demonic possession by either an evil spirit or an evil god because early beliefs incorrectly attributed all unexplainable phenomena to deities deemed either good or evil. \n\n From the late 1400s to the late 1600s, a common belief perpetuated by some religious organizations was that some people made pacts with the devil and committed horrible acts, such as eating babies (Blumberg, 2007). These people were considered to be witches and were tried and condemned by courts—they were often burned at the stake. Worldwide, it is estimated that tens of thousands of mentally ill people were killed after being accused of being witches or under the influence of witchcraft (Hemphill, 1966) \n\n By the 18th century, people who were considered odd and unusual were placed in asylums ( Figure 16.4 ). Asylums were the first institutions created for the specific purpose of housing people with psychological disorders, but the focus was ostracizing them from society rather than treating their disorders. Often these people were kept in windowless dungeons, beaten, chained to their beds, and had little to no contact with caregivers. \n\n In the late 1700s, a French physician, Philippe Pinel , argued for more humane treatment of the mentally ill. He suggested that they be unchained and talked to, and that’s just what he did for patients at La Salpêtrière in Paris in 1795 ( Figure 16.5 ). Patients benefited from this more humane treatment, and many were able to leave the hospital. \n\n In the 19th century, Dorothea Dix led reform efforts for mental health care in the United States ( Figure 16.6 ). She investigated how those who are mentally ill and poor were cared for, and she discovered an underfunded and unregulated system that perpetuated abuse of this population (Tiffany, 1891). Horrified by her findings, Dix began lobbying various state legislatures and the U.S. Congress for change (Tiffany, 1891). Her efforts led to the creation of the first mental asylums in the United States. \n\n Despite reformers’ efforts, however, a typical asylum was filthy, offered very little treatment, and often kept people for decades. At Willard Psychiatric Center in upstate New York, for example, one treatment was to submerge patients in cold baths for long periods of time. Electroshock treatment was also used, and the way the treatment was administered often broke patients’ backs; in 1943, doctors at Willard administered 1,443 shock treatments (Willard Psychiatric Center, 2009). (Electroshock is now called electroconvulsive treatment, and the therapy is still used, but with safeguards and under anesthesia. A brief application of electric stimulus is used to produce a generalized seizure. Controversy continues over its effectiveness versus the side effects.) Many of the wards and rooms were so cold that a glass of water would be frozen by morning (Willard Psychiatric Center, 2009). Willard’s doors were not closed until 1995. Conditions like these remained commonplace until well into the 20th century. \n\n Starting in 1954 and gaining popularity in the 1960s, antipsychotic medications were introduced. These proved a tremendous help in controlling the symptoms of certain psychological disorders, such as psychosis. Psychosis was a common diagnosis of individuals in mental hospitals, and it was often evidenced by symptoms like hallucinations and delusions, indicating a loss of contact with reality. Then in 1963, Congress passed and John F. Kennedy signed the Mental Retardation Facilities and Community Mental Health Centers Construction Act, which provided federal support and funding for community mental health centers (National Institutes of Health, 2013). This legislation changed how mental health services were delivered in the United States. It started the process of deinstitutionalization , the closing of large asylums, by providing for people to stay in their communities and be treated locally. In 1955, there were 558,239 severely mentally ill patients institutionalized at public hospitals (Torrey, 1997). By 1994, by percentage of the population, there were 92% fewer hospitalized individuals (Torrey, 1997). \n\n Mental Health Treatment Today \n\n Today, there are community mental health centers across the nation. They are located in neighborhoods near the homes of clients, and they provide large numbers of people with mental health services of various kinds and for many kinds of problems. Unfortunately, part of what occurred with deinstitutionalization was that those released from institutions were supposed to go to newly created centers, but the system was not set up effectively. Centers were underfunded, staff was not trained to handle severe illnesses such as schizophrenia, there was high staff burnout, and no provision was made for the other services people needed, such as housing, food, and job training. Without these supports, those people released under deinstitutionalization often ended up homeless. Even today, a large portion of the homeless population is considered to be mentally ill ( Figure 16.7 ). Statistics show that 26% of homeless adults living in shelters experience mental illness (U.S. Department of Housing and Urban Development [HUD], 2011). \n\n Another group of the mentally ill population is involved in the corrections system. According to a 2006 special report by the Bureau of Justice Statistics (BJS), approximately 705,600 mentally ill adults were incarcerated in the state prison system, and another 78,800 were incarcerated in the federal prison system. A further 479,000 were in local jails. According to the study, “people with mental illnesses are overrepresented in probation and parole populations at estimated rates ranging from two to four times the general population” (Prins & Draper, 2009, p. 23). The Treatment Advocacy Center reported that the growing number of mentally ill inmates has placed a burden on the correctional system (Torrey et al., 2014). \n\n Today, instead of asylums, there are psychiatric hospitals run by state governments and local community hospitals focused on short-term care. In all types of hospitals, the emphasis is on short-term stays, with the average length of stay being less than two weeks and often only several days. This is partly due to the very high cost of psychiatric hospitalization, which can be about $800 to $1000 per night (Stensland, Watson, & Grazier, 2012). Therefore, insurance coverage often limits the length of time a person can be hospitalized for treatment. Usually individuals are hospitalized only if they are an imminent threat to themselves or others. \n\n Link to Learning \n\n View this timeline showing the history of mental institutions in the United States. \n\n Most people suffering from mental illnesses are not hospitalized. If someone is feeling very depressed, complains of hearing voices, or feels anxious all the time, he or she might seek psychological treatment. A friend, spouse, or parent might refer someone for treatment. The individual might go see his primary care physician first and then be referred to a mental health practitioner. \n\n Some people seek treatment because they are involved with the state’s child protective services—that is, their children have been removed from their care due to abuse or neglect. The parents might be referred to psychiatric or substance abuse facilities and the children would likely receive treatment for trauma. If the parents are interested in and capable of becoming better parents, the goal of treatment might be family reunification. For other children whose parents are unable to change—for example, the parent or parents who are heavily addicted to drugs and refuse to enter treatment—the goal of therapy might be to help the children adjust to foster care and/or adoption ( Figure 16.8 ). \n\n Some people seek therapy because the criminal justice system referred them or required them to go. For some individuals, for example, attending weekly counseling sessions might be a condition of parole. If an individual is mandated to attend therapy, she is seeking services involuntarily. Involuntary treatment refers to therapy that is not the individual’s choice. Other individuals might voluntarily seek treatment. Voluntary treatment means the person chooses to attend therapy to obtain relief from symptoms. \n\n Psychological treatment can occur in a variety of places. An individual might go to a community mental health center or a practitioner in private or community practice. A child might see a school counselor, school psychologist, or school social worker. An incarcerated person might receive group therapy in prison. There are many different types of treatment providers, and licensing requirements vary from state to state. Besides psychologists and psychiatrists, there are clinical social workers, marriage and family therapists, and trained religious personnel who also perform counseling and therapy. \n\n A range of funding sources pay for mental health treatment: health insurance, government, and private pay. In the past, even when people had health insurance, the coverage would not always pay for mental health services. This changed with the Mental Health Parity and Addiction Equity Act of 2008, which requires group health plans and insurers to make sure there is parity of mental health services (U.S. Department of Labor, n.d.). This means that co-pays, total number of visits, and deductibles for mental health and substance abuse treatment need to be equal to and cannot be more restrictive or harsher than those for physical illnesses and medical/surgical problems. \n\n Finding treatment sources is also not always easy: there may be limited options, especially in rural areas and low-income urban areas; waiting lists; poor quality of care available for indigent patients; and financial obstacles such as co-pays, deductibles, and time off from work. Over 85% of the l,669 federally designated mental health professional shortage areas are rural; often primary care physicians and law enforcement are the first-line mental health providers (Ivey, Scheffler, & Zazzali, 1998), although they do not have the specialized training of a mental health professional, who often would be better equipped to provide care. Availability, accessibility, and acceptability (the stigma attached to mental illness) are all problems in rural areas. Approximately two-thirds of those with symptoms receive no care at all (U.S. Department of Health and Human Services, 2005; Wagenfeld, Murray, Mohatt, & DeBruiynb, 1994). At the end of 2013, the U.S. Department of Agriculture announced an investment of $50 million to help improve access and treatment for mental health problems as part of the Obama administration’s effort to strengthen rural communities. \n 16.2 Types of Treatment Learning Objectives By the end of this section, you will be able to:\n\n Distinguish between psychotherapy and biomedical therapy \n\n Recognize various orientations to psychotherapy \n\n Discuss psychotropic medications and recognize which medications are used to treat specific psychological disorders \n\n One of the goals of therapy is to help a person stop repeating and reenacting destructive patterns and to start looking for better solutions to difficult situations. This goal is reflected in the following poem: \n\n Autobiography in Five Short Chapters by Portia Nelson (1993) \n\n Chapter One\n\n I walk down the street.\n\n There is a deep hole in the sidewalk.\n\n I fall in.\n\n I am lost. . . . I am helpless.\n\n It isn't my fault.\n\n It takes forever to find a way out. \n\n Chapter Two\n\n I walk down the same street.\n\n There is a deep hole in the sidewalk.\n\n I pretend I don't see it.\n\n I fall in again.\n\n I can't believe I am in this same place.\n\n But, it isn't my fault.\n\n It still takes a long time to get out. \n\n Chapter Three\n\n I walk down the same street.\n\n There is a deep hole in the sidewalk.\n\n I see it is there.\n\n I still fall in . . . it's a habit . . . but,\n\n my eyes are open.\n\n I know where I am.\n\n It is my fault.\n\n I get out immediately. \n\n Chapter Four\n\n I walk down the same street.\n\n There is a deep hole in the sidewalk.\n\n I walk around it. \n\n Chapter Five\n\n I walk down another street. \n\n Two types of therapy are psychotherapy and biomedical therapy. Both types of treatment help people with psychological disorders, such as depression, anxiety, and schizophrenia. Psychotherapy is a psychological treatment that employs various methods to help someone overcome personal problems, or to attain personal growth. In modern practice, it has evolved ino what is known as psychodynamic therapy, which will be discussed later. Biomedical therapy involves medication and/or medical procedures to treat psychological disorders. First, we will explore the various psychotherapeutic orientations outlined in Table 16.1 (many of these orientations were discussed in the Introduction chapter). \n\n Type \n\n Description \n\n Example \n\n Psychodynamic psychotherapy \n\n Talk therapy based on belief that the unconscious and childhood conflicts impact behavior \n\n Patient talks about his past \n\n Play therapy \n\n Psychoanalytical therapy wherein interaction with toys is used instead of talk; used in child therapy \n\n Patient (child) acts out family scenes with dolls \n\n Behavior therapy \n\n Principles of learning applied to change undesirable behaviors \n\n Patient learns to overcome fear of elevators through several stages of relaxation techniques \n\n Cognitive therapy \n\n Awareness of cognitive process helps patients eliminate thought patterns that lead to distress \n\n Patient learns not to overgeneralize failure based on single failure \n\n Cognitive-behavioral therapy \n\n Work to change cognitive distortions and self-defeating behaviors \n\n Patient learns to identify self-defeating behaviors to overcome an eating disorder \n\n Humanistic therapy \n\n Increase self-awareness and acceptance through focus on conscious thoughts \n\n Patient learns to articulate thoughts that keep her from achieving her goals \n\n Table 16.1 Various Psychotherapy Techniques Psychotherapy Techniques: Psychoanalysis \n\n Psychoanalysis was developed by Sigmund Freud and was the first form of psychotherapy. It was the dominant therapeutic technique in the early 20th century, but it has since waned significantly in popularity. Freud believed most of our psychological problems are the result of repressed impulses and trauma experienced in childhood, and he believed psychoanalysis would help uncover long-buried feelings. In a psychoanalyst’s office, you might see a patient lying on a couch speaking of dreams or childhood memories, and the therapist using various Freudian methods such as free association and dream analysis ( Figure 16.9 ). In free association , the patient relaxes and then says whatever comes to mind at the moment. However, Freud felt that the ego would at times try to block, or repress, unacceptable urges or painful conflicts during free association. Consequently, a patient would demonstrate resistance to recalling these thoughts or situations. In dream analysis , a therapist interprets the underlying meaning of dreams. \n\n Psychoanalysis is a therapy approach that typically takes years. Over the course of time, the patient reveals a great deal about himself to the therapist. Freud suggested that during this patient-therapist relationship, the patient comes to develop strong feelings for the therapist—maybe positive feelings, maybe negative feelings. Freud called this transference : the patient transfers all the positive or negative emotions associated with the patient’s other relationships to the psychoanalyst. For example, Crystal is seeing a psychoanalyst. During the years of therapy, she comes to see her therapist as a father figure. She transfers her feelings about her father onto her therapist, perhaps in an effort to gain the love and attention she did not receive from her own father. \n\n Today, Freud’s psychoanalytical perspective has been expanded upon by the developments of subsequent theories and methodologies: the psychodynamic perspective. This approach to therapy remains centered on the role of people’s internal drives and forces, but treatment is less intensive than Freud’s original model. \n\n Link to Learning \n\n View a brief video that presents an overview of psychoanalysis theory, research, and practice. \n\n Psychotherapy: Play Therapy \n\n Play therapy is often used with children since they are not likely to sit on a couch and recall their dreams or engage in traditional talk therapy. This technique uses a therapeutic process of play to “help clients prevent or resolve psychosocial difficulties and achieve optimal growth” (O’Connor, 2000, p. 7). The idea is that children play out their hopes, fantasies, and traumas while using dolls, stuffed animals, and sandbox figurines ( Figure 16.10 ). Play therapy can also be used to help a therapist make a diagnosis. The therapist observes how the child interacts with toys (e.g., dolls, animals, and home settings) in an effort to understand the roots of the child’s disturbed behavior. Play therapy can be nondirective or directive. In nondirective play therapy, children are encouraged to work through their problems by playing freely while the therapist observes (LeBlanc & Ritchie, 2001). In directive play therapy, the therapist provides more structure and guidance in the play session by suggesting topics, asking questions, and even playing with the child (Harter, 1977). \n\n Psychotherapy: Behavior Therapy \n\n In psychoanalysis , therapists help their patients look into their past to uncover repressed feelings. In behavior therapy , a therapist employs principles of learning to help clients change undesirable behaviors—rather than digging deeply into one’s unconscious. Therapists with this orientation believe that dysfunctional behaviors, like phobias and bedwetting, can be changed by teaching clients new, more constructive behaviors. Behavior therapy employs both classical and operant conditioning techniques to change behavior. \n\n One type of behavior therapy utilizes classical conditioning techniques. Therapists using these techniques believe that dysfunctional behaviors are conditioned responses. Applying the conditioning principles developed by Ivan Pavlov, these therapists seek to recondition their clients and thus change their behavior. Emmie is eight years old, and frequently wets her bed at night. She’s been invited to several sleepovers, but she won’t go because of her problem. Using a type of conditioning therapy, Emmie begins to sleep on a liquid-sensitive bed pad that is hooked to an alarm. When moisture touches the pad, it sets off the alarm, waking up Emmie. When this process is repeated enough times, Emmie develops an association between urinary relaxation and waking up, and this stops the bedwetting. Emmie has now gone three weeks without wetting her bed and is looking forward to her first sleepover this weekend. \n\n One commonly used classical conditioning therapeutic technique is counterconditioning : a client learns a new response to a stimulus that has previously elicited an undesirable behavior. Two counterconditioning techniques are aversive conditioning and exposure therapy. Aversive conditioning uses an unpleasant stimulus to stop an undesirable behavior. Therapists apply this technique to eliminate addictive behaviors, such as smoking, nail biting, and drinking. In aversion therapy, clients will typically engage in a specific behavior (such as nail biting) and at the same time are exposed to something unpleasant, such as a mild electric shock or a bad taste. After repeated associations between the unpleasant stimulus and the behavior, the client can learn to stop the unwanted behavior. \n\n Aversion therapy has been used effectively for years in the treatment of alcoholism (Davidson, 1974; Elkins, 1991; Streeton & Whelan, 2001). One common way this occurs is through a chemically based substance known as Antabuse. When a person takes Antabuse and then consumes alcohol, uncomfortable side effects result including nausea, vomiting, increased heart rate, heart palpitations, severe headache, and shortness of breath. Antabuse is repeatedly paired with alcohol until the client associates alcohol with unpleasant feelings, which decreases the client’s desire to consume alcohol. Antabuse creates a conditioned aversion to alcohol because it replaces the original pleasure response with an unpleasant one. \n\n In exposure therapy , a therapist seeks to treat clients’ fears or anxiety by presenting them with the object or situation that causes their problem, with the idea that they will eventually get used to it. This can be done via reality, imagination, or virtual reality. Exposure therapy was first reported in 1924 by Mary Cover Jones, who is considered the mother of behavior therapy. Jones worked with a boy named Peter who was afraid of rabbits. Her goal was to replace Peter’s fear of rabbits with a conditioned response of relaxation, which is a response that is incompatible with fear ( Figure 16.11 ). How did she do it? Jones began by placing a caged rabbit on the other side of a room with Peter while he ate his afternoon snack. Over the course of several days, Jones moved the rabbit closer and closer to where Peter was seated with his snack. After two months of being exposed to the rabbit while relaxing with his snack, Peter was able to hold the rabbit and pet it while eating (Jones, 1924). \n\n Thirty years later, Joseph Wolpe (1958) refined Jones’s techniques, giving us the behavior therapy technique of exposure therapy that is used today. A popular form of exposure therapy is systematic desensitization , wherein a calm and pleasant state is gradually associated with increasing levels of anxiety-inducing stimuli. The idea is that you can’t be nervous and relaxed at the same time. Therefore, if you can learn to relax when you are facing environmental stimuli that make you nervous or fearful, you can eventually eliminate your unwanted fear response (Wolpe, 1958) ( Figure 16.12 ). \n\n How does exposure therapy work? Jayden is terrified of elevators. Nothing bad has ever happened to him on an elevator, but he’s so afraid of elevators that he will always take the stairs. That wasn’t a problem when Jayden worked on the second floor of an office building, but now he has a new job—on the 29th floor of a skyscraper in downtown Los Angeles. Jayden knows he can’t climb 29 flights of stairs in order to get to work each day, so he decided to see a behavior therapist for help. The therapist asks Jayden to first construct a hierarchy of elevator-related situations that elicit fear and anxiety. They range from situations of mild anxiety such as being nervous around the other people in the elevator, to the fear of getting an arm caught in the door, to panic-provoking situations such as getting trapped or the cable snapping. Next, the therapist uses progressive relaxation. She teaches Jayden how to relax each of his muscle groups so that he achieves a drowsy, relaxed, and comfortable state of mind. Once he’s in this state, she asks Jayden to imagine a mildly anxiety-provoking situation. Jayden is standing in front of the elevator thinking about pressing the call button. \n\n If this scenario causes Jayden anxiety, he lifts his finger. The therapist would then tell Jayden to forget the scene and return to his relaxed state. She repeats this scenario over and over until Jayden can imagine himself pressing the call button without anxiety. Over time the therapist and Jayden use progressive relaxation and imagination to proceed through all of the situations on Jayden’s hierarchy until he becomes desensitized to each one. After this, Jayden and the therapist begin to practice what he only previously envisioned in therapy, gradually going from pressing the button to actually riding an elevator. The goal is that Jayden will soon be able to take the elevator all the way up to the 29th floor of his office without feeling any anxiety. \n\n Sometimes, it’s too impractical, expensive, or embarrassing to re-create anxiety- producing situations, so a therapist might employ virtual reality exposure therapy by using a simulation to help conquer fears. Virtual reality exposure therapy has been used effectively to treat numerous anxiety disorders such as the fear of public speaking, claustrophobia (fear of enclosed spaces), aviophobia (fear of flying), and post-traumatic stress disorder (PTSD), a trauma and stressor-related disorder (Gerardi, Cukor, Difede, Rizzo, & Rothbaum, 2010). \n\n Link to Learning \n\n A new virtual reality exposure therapy is being used to treat PTSD in soldiers. Virtual Iraq is a simulation that mimics Middle Eastern cities and desert roads with situations similar to those soldiers experienced while deployed in Iraq. This method of virtual reality exposure therapy has been effective in treating PTSD for combat veterans. Approximately 80% of participants who completed treatment saw clinically significant reduction in their symptoms of PTSD, anxiety, and depression (Rizzo et al., 2010). Watch this Virtual Iraq video showing soldiers being treated via simulation. Some behavior therapies employ operant conditioning. Recall what you learned about operant conditioning: We have a tendency to repeat behaviors that are reinforced. What happens to behaviors that are not reinforced? They become extinguished. These principles can be applied to help people with a wide range of psychological problems. For instance, operant conditioning techniques designed to reinforce positive behaviors and punish unwanted behaviors have been an effective tool to help children with autism (Lovaas, 1987, 2003; Sallows & Graupner, 2005; Wolf & Risley, 1967). This technique is called Applied Behavior Analysis (ABA). In this treatment, child-specific reinforcers (e.g., stickers, praise, candy, bubbles, and extra play time) are used to reward and motivate autistic children when they demonstrate desired behaviors such as sitting on a chair when requested, verbalizing a greeting, or making eye contact. Punishment such as a timeout or a sharp “No!” from the therapist or parent might be used to discourage undesirable behaviors such as pinching, scratching, and pulling hair. \n\n One popular operant conditioning intervention is called the token economy . This involves a controlled setting where individuals are reinforced for desirable behaviors with tokens, such as a poker chip, that can be exchanged for items or privileges. Token economies are often used in psychiatric hospitals to increase patient cooperation and activity levels. Patients are rewarded with tokens when they engage in positive behaviors (e.g., making their beds, brushing their teeth, coming to the cafeteria on time, and socializing with other patients). They can later exchange the tokens for extra TV time, private rooms, visits to the canteen, and so on (Dickerson, Tenhula, & Green-Paden, 2005). \n\n Psychotherapy: Cognitive Therapy \n\n Cognitive therapy is a form of psychotherapy that focuses on how a person’s thoughts lead to feelings of distress. The idea behind cognitive therapy is that how you think determines how you feel and act. Cognitive therapists help their clients change dysfunctional thoughts in order to relieve distress. They help a client see how they misinterpret a situation (cognitive distortion). For example, a client may overgeneralize. Because Ray failed one test in his Psychology 101 course, he feels he is stupid and worthless. These thoughts then cause his mood to worsen. Therapists also help clients recognize when they blow things out of proportion. Because Ray failed his Psychology 101 test, he has concluded that he’s going to fail the entire course and probably flunk out of college altogether. These errors in thinking have contributed to Ray’s feelings of distress. His therapist will help him challenge these irrational beliefs, focus on their illogical basis, and correct them with more logical and rational thoughts and beliefs. \n\n Cognitive therapy was developed by psychiatrist Aaron Beck in the 1960s. His initial focus was on depression and how a client’s self-defeating attitude served to maintain a depression despite positive factors in her life (Beck, Rush, Shaw, & Emery, 1979) ( Figure 16.13 ). Through questioning, a cognitive therapist can help a client recognize dysfunctional ideas, challenge catastrophizing thoughts about themselves and their situations, and find a more positive way to view things (Beck, 2011). \n\n Link to Learning \n\n View a brief video in which Judith Beck talks about cognitive therapy and conducts a session with a client. \n\n Psychotherapy: Cognitive-Behavioral Therapy Cognitive-behavioral therapists focus much more on present issues than on a patient’s childhood or past, as in other forms of psychotherapy. One of the first forms of cognitive-behavioral therapy was rational emotive therapy (RET) , which was founded by Albert Ellis and grew out of his dislike of Freudian psychoanalysis (Daniel, n.d.). Behaviorists such as Joseph Wolpe also influenced Ellis’s therapeutic approach (National Association of Cognitive-Behavioral Therapists, 2009). Cognitive-behavioral therapy (CBT) helps clients examine how their thoughts affect their behavior. It aims to change cognitive distortions and self-defeating behaviors. In essence, this approach is designed to change the way people think as well as how they act. It is similar to cognitive therapy in that CBT attempts to make individuals aware of their irrational and negative thoughts and helps people replace them with new, more positive ways of thinking. It is also similar to behavior therapies in that CBT teaches people how to practice and engage in more positive and healthy approaches to daily situations. In total, hundreds of studies have shown the effectiveness of cognitive-behavioral therapy in the treatment of numerous psychological disorders such as depression, PTSD, anxiety disorders, eating disorders, bipolar disorder, and substance abuse (Beck Institute for Cognitive Behavior Therapy, n.d.). For example, CBT has been found to be effective in decreasing levels of hopelessness and suicidal thoughts in previously suicidal teenagers (Alavi, Sharifi, Ghanizadeh, & Dehbozorgi, 2013). Cognitive-behavioral therapy has also been effective in reducing PTSD in specific populations, such as transit workers (Lowinger & Rombom, 2012). Cognitive-behavioral therapy aims to change cognitive distortions and self-defeating behaviors using techniques like the ABC model. With this model, there is an A ction (sometimes called an activating event), the B elief about the event, and the C onsequences of this belief. Let’s say, Jon and Joe both go to a party. Jon and Joe each have met a young woman at the party: Jon is talking with Megan most of the party, and Joe is talking with Amanda. At the end of the party, Jon asks Megan for her phone number and Joe asks Amanda. Megan tells Jon she would rather not give him her number, and Amanda tells Joe the same thing. Both Jon and Joe are surprised, as they thought things were going well. What can Jon and Joe tell themselves about why the women were not interested? Let’s say Jon tells himself he is a loser, or is ugly, or “has no game.” Jon then gets depressed and decides not to go to another party, which starts a cycle that keeps him depressed. Joe tells himself that he had bad breath, goes out and buys a new toothbrush, goes to another party, and meets someone new. Jon’s belief about what happened results in a consequence of further depression, whereas Joe’s belief does not. Jon is internalizing the attribution or reason for the rebuffs, which triggers his depression. On the other hand, Joe is externalizing the cause, so his thinking does not contribute to feelings of depression. Cognitive-behavioral therapy examines specific maladaptive and automatic thoughts and cognitive distortions. Some examples of cognitive distortions are all-or-nothing thinking, overgeneralization, and jumping to conclusions. In overgeneralization, someone takes a small situation and makes it huge—for example, instead of saying, “This particular woman was not interested in me,” the man says, “I am ugly, a loser, and no one is ever going to be interested in me.” All or nothing thinking, which is a common type of cognitive distortion for people suffering from depression, reflects extremes. In other words, everything is black or white. After being turned down for a date, Jon begins to think, “No woman will ever go out with me. I’m going to be alone forever.” He begins to feel anxious and sad as he contemplates his future. \n\n The third kind of distortion involves jumping to conclusions—assuming that people are thinking negatively about you or reacting negatively to you, even though there is no evidence. Consider the example of Savannah and Hillaire, who recently met at a party. They have a lot in common, and Savannah thinks they could become friends. She calls Hillaire to invite her for coffee. Since Hillaire doesn’t answer, Savannah leaves her a message. Several days go by and Savannah never hears back from her potential new friend. Maybe Hillaire never received the message because she lost her phone or she is too busy to return the phone call. But if Savannah believes that Hillaire didn’t like Savannah or didn’t want to be her friend, she is demonstrating the cognitive distortion of jumping to conclusions. \n\n How effective is CBT? One client said this about his cognitive-behavioral therapy: \n\n I have had many painful episodes of depression in my life, and this has had a negative effect on my career and has put considerable strain on my friends and family. The treatments I have received, such as taking antidepressants and psychodynamic counseling, have helped [me] to cope with the symptoms and to get some insights into the roots of my problems. CBT has been by far the most useful approach I have found in tackling these mood problems. It has raised my awareness of how my thoughts impact on my moods. How the way I think about myself, about others and about the world can lead me into depression. It is a practical approach, which does not dwell so much on childhood experiences, whilst acknowledging that it was then that these patterns were learned. It looks at what is happening now, and gives tools to manage these moods on a daily basis. (Martin, 2007, n.p.) Psychotherapy: Humanistic Therapy \n\n Humanistic psychology focuses on helping people achieve their potential. So it makes sense that the goal of humanistic therapy is to help people become more self-aware and accepting of themselves. In contrast to psychoanalysis, humanistic therapists focus on conscious rather than unconscious thoughts. They also emphasize the patient’s present and future, as opposed to exploring the patient’s past. \n\n Psychologist Carl Rogers developed a therapeutic orientation known as Rogerian , or client-centered therapy . Note the change from patients to clients . Rogers (1951) felt that the term patient suggested the person seeking help was sick and looking for a cure. Since this is a form of nondirective therapy , a therapeutic approach in which the therapist does not give advice or provide interpretations but helps the person to identify conflicts and understand feelings, Rogers (1951) emphasized the importance of the person taking control of his own life to overcome life’s challenges. \n\n In client-centered therapy, the therapist uses the technique of active listening. In active listening, the therapist acknowledges, restates, and clarifies what the client expresses. Therapists also practice what Rogers called unconditional positive regard , which involves not judging clients and simply accepting them for who they are. Rogers (1951) also felt that therapists should demonstrate genuineness, empathy, and acceptance toward their clients because this helps people become more accepting of themselves, which results in personal growth. \n\n Evaluating Various Forms of Psychotherapy \n\n How can we assess the effectiveness of psychotherapy? Is one technique more effective than another? For anyone considering therapy, these are important questions. According to the American Psychological Association, three factors work together to produce successful treatment. The first is the use of evidence-based treatment that is deemed appropriate for your particular issue. The second important factor is the clinical expertise of the psychologist or therapist. The third factor is your own characteristics, values, preferences, and culture. Many people begin psychotherapy feeling like their problem will never be resolved; however, psychotherapy helps people see that they can do things to make their situation better. Psychotherapy can help reduce a person’s anxiety, depression, and maladaptive behaviors. Through psychotherapy, individuals can learn to engage in healthy behaviors designed to help them better express emotions, improve relationships, think more positively, and perform more effectively at work or school. \n\n Many studies have explored the effectiveness of psychotherapy. For example, one large-scale study that examined 16 meta-analyses of CBT reported that it was equally effective or more effective than other therapies in treating PTSD, generalized anxiety disorder, depression, and social phobia (Butlera, Chapmanb, Formanc, & Becka, 2006). Another study found that CBT was as effective at treating depression (43% success rate) as prescription medication (50% success rate) compared to the placebo rate of 25% (DeRubeis et al., 2005). Another meta-analysis found that psychodynamic therapy was also as effective at treating these types of psychological issues as CBT (Shedler, 2010). However, no studies have found one psychotherapeutic approach more effective than another (Abbass, Kisely, & Kroenke, 2006; Chorpita et al., 2011), nor have they shown any relationship between a client’s treatment outcome and the level of the clinician’s training or experience (Wampold, 2007). Regardless of which type of psychotherapy an individual chooses, one critical factor that determines the success of treatment is the person’s relationship with the psychologist or therapist. \n\n Biomedical Therapies Individuals can be prescribed biologically based treatments or psychotropic medications that are used to treat mental disorders. While these are often used in combination with psychotherapy, they also are taken by individuals not in therapy. This is known as biomedical therapy . Medications used to treat psychological disorders are called psychotropic medications and are prescribed by medical doctors, including psychiatrists. In Louisiana and New Mexico, psychologists are able to prescribe some types of these medications (American Psychological Association, 2014). \n\n Different types and classes of medications are prescribed for different disorders. A depressed person might be given an antidepressant, a bipolar individual might be given a mood stabilizer, and a schizophrenic individual might be given an antipsychotic. These medications treat the symptoms of a psychological disorder. They can help people feel better so that they can function on a daily basis, but they do not cure the disorder. Some people may only need to take a psychotropic medication for a short period of time. Others with severe disorders like bipolar disorder or schizophrenia may need to take psychotropic medication for a long time. Table 16.2 shows the types of medication and how they are used. \n\n Type of Medication \n\n Used to Treat \n\n Brand Names of Commonly Prescribed Medications \n\n How They Work \n\n Side Effects \n\n Antipsychotics (developed in the 1950s) \n\n Schizophrenia and other types of severe thought disorders \n\n Haldol, Mellaril, Prolixin, Thorazine \n\n Treat positive psychotic symptoms such as auditory and visual hallucinations, delusions, and paranoia by blocking the neurotransmitter dopamine \n\n Long-term use can lead to tardive dyskinesia, involuntary movements of the arms, legs, tongue and facial muscles, resulting in Parkinson’s-like tremors \n\n Atypical Antipsychotics (developed in the late 1980s) \n\n Schizophrenia and other types of severe thought disorders \n\n Abilify, Risperdal, Clozaril \n\n Treat the negative symptoms of schizophrenia, such as withdrawal and apathy, by targeting both dopamine and serotonin receptors; newer medications may treat both positive and negative symptoms \n\n Can increase the risk of obesity and diabetes as well as elevate cholesterol levels; constipation, dry mouth, blurred vision, drowsiness, and dizziness \n\n Anti-depressants \n\n Depression and increasingly for anxiety \n\n Paxil, Prozac, Zoloft (selective serotonin reuptake inhibitors, [SSRIs]); Tofranil and Elavil (tricyclics) \n\n Alter levels of neurotransmitters such as serotonin and norepinephrine \n\n SSRIs: headache, nausea, weight gain, drowsiness, reduced sex drive Tricyclics: dry mouth, constipation, blurred vision, drowsiness, reduced sex drive, increased risk of suicide \n\n Anti-anxiety agents \n\n Anxiety and agitation that occur in OCD, PTSD, panic disorder, and social phobia \n\n Xanax, Valium, Ativan \n\n Depress central nervous system activity \n\n Drowsiness, dizziness, headache, fatigue, lightheadedness \n\n Mood Stabilizers \n\n Bipolar disorder \n\n Lithium, Depakote, Lamictal, Tegretol \n\n Treat episodes of mania as well as depression \n\n Excessive thirst, irregular heartbeat, itching/rash, swelling (face, mouth, and extremities), nausea, loss of appetite \n\n Stimulants \n\n ADHD \n\n Adderall, Ritalin \n\n Improve ability to focus on a task and maintain attention \n\n Decreased appetite, difficulty sleeping, stomachache, headache \n\n Table 16.2 Commonly Prescribed Psychotropic Medications Another biologically based treatment that continues to be used, although infrequently, is electroconvulsive therapy (ECT) (formerly known by its unscientific name as electroshock therapy). It involves using an electrical current to induce seizures to help alleviate the effects of severe depression. The exact mechanism is unknown, although it does help alleviate symptoms for people with severe depression who have not responded to traditional drug therapy (Pagnin, de Queiroz, Pini, & Cassano, 2004). About 85% of people treated with ECT improve (Reti, n.d.). However, the memory loss associated with repeated administrations has led to it being implemented as a last resort (Donahue, 2000; Prudic, Peyser, & Sackeim, 2000). A more recent alternative is transcranial magnetic stimulation (TMS), a procedure approved by the FDA in 2008 that uses magnetic fields to stimulate nerve cells in the brain to improve depression symptoms; it is used when other treatments have not worked (Mayo Clinic, 2012). \n\n Dig Deeper Evidence-based Practice A buzzword in therapy today is evidence-based practice. However, it’s not a novel concept but one that has been used in medicine for at least two decades. Evidence-based practice is used to reduce errors in treatment selection by making clinical decisions based on research (Sackett & Rosenberg, 1995). In any case, evidence-based treatment is on the rise in the field of psychology. So what is it, and why does it matter? In an effort to determine which treatment methodologies are evidenced-based, professional organizations such as the American Psychological Association (APA) have recommended that specific psychological treatments be used to treat certain psychological disorders (Chambless & Ollendick, 2001). According to the APA (2005), “Evidence-based practice in psychology (EBPP) is the integration of the best available research with clinical expertise in the context of patient characteristics, culture, and preferences” (p. 1). \n\n The foundational idea behind evidence based treatment is that best practices are determined by research evidence that has been compiled by comparing various forms of treatment (Charman & Barkham, 2005). These treatments are then operationalized and placed in treatment manuals—trained therapists follow these manuals. The benefits are that evidence-based treatment can reduce variability between therapists to ensure that a specific approach is delivered with integrity (Charman & Barkham, 2005). Therefore, clients have a higher chance of receiving therapeutic interventions that are effective at treating their specific disorder. While EBPP is based on randomized control trials, critics of EBPP reject it stating that the results of trials cannot be applied to individuals and instead determinations regarding treatment should be based on a therapist’s judgment (Mullen & Streiner, 2004). \n 16.3 Treatment Modalities Learning Objectives By the end of this section, you will be able to:\n\n Distinguish between the various modalities of treatment \n\n Discuss benefits of group therapy \n\n Once a person seeks treatment, whether voluntarily or involuntarily, he has an intake done to assess his clinical needs. An intake is the therapist’s first meeting with the client. The therapist gathers specific information to address the client’s immediate needs, such as the presenting problem, the client’s support system, and insurance status. The therapist informs the client about confidentiality, fees, and what to expect in treatment. Confidentiality means the therapist cannot disclose confidential communications to any third party unless mandated or permitted by law to do so. During the intake, the therapist and client will work together to discuss treatment goals. Then a treatment plan will be formulated, usually with specific measurable objectives. Also, the therapist and client will discuss how treatment success will be measured and the estimated length of treatment. There are several different modalities of treatment ( Figure 16.14 ): Individual therapy, family therapy, couples therapy, and group therapy are the most common. \n\n Individual Therapy \n\n In individual therapy , also known as individual psychotherapy or individual counseling, the client and clinician meet one-on-one (usually from 45 minutes to 1 hour). These meetings typically occur weekly or every other week, and sessions are conducted in a confidential and caring environment ( Figure 16.15 ). The clinician will work with clients to help them explore their feelings, work through life challenges, identify aspects of themselves and their lives that they wish to change, and set goals to help them work towards these changes. A client might see a clinician for only a few sessions, or the client may attend individual therapy sessions for a year or longer. The amount of time spent in therapy depends on the needs of the client as well as her personal goals. \n\n Group Therapy \n\n In group therapy , a clinician meets together with several clients with similar problems ( Figure 16.16 ). When children are placed in group therapy, it is particularly important to match clients for age and problems. One benefit of group therapy is that it can help decrease a client’s shame and isolation about a problem while offering needed support, both from the therapist and other members of the group (American Psychological Association, 2014). A nine-year-old sexual abuse victim, for example, may feel very embarrassed and ashamed. If he is placed in a group with other sexually abused boys, he will realize that he is not alone. A child struggling with poor social skills would likely benefit from a group with a specific curriculum to foster special skills. A woman suffering from post-partum depression could feel less guilty and more supported by being in a group with similar women. \n\n Group therapy also has some specific limitations. Members of the group may be afraid to speak in front of other people because sharing secrets and problems with complete strangers can be stressful and overwhelming. There may be personality clashes and arguments among group members. There could also be concerns about confidentiality: Someone from the group might share what another participant said to people outside of the group. \n\n Another benefit of group therapy is that members can confront each other about their patterns. For those with some types of problems, such as sexual abusers, group therapy is the recommended treatment. Group treatment for this population is considered to have several benefits: \n\n Group treatment is more economical than individual, couples, or family therapy. Sexual abusers often feel more comfortable admitting and discussing their offenses in a treatment group where others are modeling openness. Clients often accept feedback about their behavior more willingly from other group members than from therapists. Finally, clients can practice social skills in group treatment settings. (McGrath, Cumming, Burchard, Zeoli, & Ellerby, 2009) Groups that have a strong educational component are called psycho-educational groups. For example, a group for children whose parents have cancer might discuss in depth what cancer is, types of treatment for cancer, and the side effects of treatments, such as hair loss. Often, group therapy sessions with children take place in school. They are led by a school counselor, a school psychologist, or a school social worker. Groups might focus on test anxiety, social isolation, self-esteem, bullying, or school failure (Shechtman, 2002). Whether the group is held in school or in a clinician’s office, group therapy has been found to be effective with children facing numerous kinds of challenges (Shechtman, 2002). \n\n During a group session, the entire group could reflect on an individual’s problem or difficulties, and others might disclose what they have done in that situation. When a clinician is facilitating a group, the focus is always on making sure that everyone benefits and participates in the group and that no one person is the focus of the entire session. Groups can be organized in various ways: some have an overarching theme or purpose, some are time-limited, some have open membership that allows people to come and go, and some are closed. Some groups are structured with planned activities and goals, while others are unstructured: There is no specific plan, and group members themselves decide how the group will spend its time and on what goals it will focus. This can become a complex and emotionally charged process, but it is also an opportunity for personal growth (Page & Berkow, 1994). \n\n Couples Therapy \n\n Couples therapy involves two people in an intimate relationship who are having difficulties and are trying to resolve them ( Figure 16.17 ). The couple may be dating, partnered, engaged, or married. The primary therapeutic orientation used in couples counseling is cognitive-behavioral therapy (Rathus & Sanderson, 1999). Couples meet with a therapist to discuss conflicts and/or aspects of their relationship that they want to change. The therapist helps them see how their individual backgrounds, beliefs, and actions are affecting their relationship. Often, a therapist tries to help the couple resolve these problems, as well as implement strategies that will lead to a healthier and happier relationship, such as how to listen, how to argue, and how to express feelings. However, sometimes, after working with a therapist, a couple will realize that they are too incompatible and will decide to separate. Some couples seek therapy to work out their problems, while others attend therapy to determine whether staying together is the best solution. Counseling couples in a high-conflict and volatile relationship can be difficult. In fact, psychologists Peter Pearson and Ellyn Bader, who founded the Couples Institute in Palo Alto, California, have compared the experience of the clinician in couples’ therapy to be like “piloting a helicopter in a hurricane” (Weil, 2012, para. 7). \n\n Family Therapy \n\n Family therapy is a special form of group therapy, consisting of one or more families. Although there are many theoretical orientations in family therapy, one of the most predominant is the systems approach. The family is viewed as an organized system, and each individual within the family is a contributing member who creates and maintains processes within the system that shape behavior (Minuchin, 1985). Each member of the family influences and is influenced by the others. The goal of this approach is to enhance the growth of each family member as well as that of the family as a whole. \n\n Often, dysfunctional patterns of communication that develop between family members can lead to conflict. A family with this dynamic might wish to attend therapy together rather than individually. In many cases, one member of the family has problems that detrimentally affect everyone. For example, a mother’s depression, teen daughter’s eating disorder, or father’s alcohol dependence could affect all members of the family. The therapist would work with all members of the family to help them cope with the issue, and to encourage resolution and growth in the case of the individual family member with the problem. \n\n With family therapy, the nuclear family (i.e., parents and children) or the nuclear family plus whoever lives in the household (e.g., grandparent) come into treatment. Family therapists work with the whole family unit to heal the family. There are several different types of family therapy. In structural family therapy , the therapist examines and discusses the boundaries and structure of the family: who makes the rules, who sleeps in the bed with whom, how decisions are made, and what are the boundaries within the family. In some families, the parents do not work together to make rules, or one parent may undermine the other, leading the children to act out. The therapist helps them resolve these issues and learn to communicate more effectively. \n\n Link to Learning \n\n Watch this video to view a structural family session. \n\n In strategic family therapy , the goal is to address specific problems within the family that can be dealt with in a relatively short amount of time. Typically, the therapist would guide what happens in the therapy session and design a detailed approach to resolving each member’s problem (Madanes, 1991). \n 16.4 Substance-Related and Addictive Disorders: A Special Case Learning Objectives By the end of this section, you will be able to:\n\n Recognize the goal of substance-related and addictive disorders treatment \n\n Discuss what makes for effective treatment \n\n Describe how comorbid disorders are treated \n\n Addiction is often viewed as a chronic disease ( Figure 16.18 ). The choice to use a substance is initially voluntary; however, because chronic substance use can permanently alter the neural structure in the prefrontal cortex, an area of the brain associated with decision-making and judgment, a person becomes driven to use drugs and/or alcohol (Muñoz-Cuevas, Athilingam, Piscopo, & Wilbrecht, 2013). This helps explain why relapse rates tend to be high. About 40%–60% of individuals relapse , which means they return to abusing drugs and/or alcohol after a period of improvement (National Institute on Drug Abuse [NIDA], 2008). \n\n The goal of substance-related treatment is to help a person with an addiction stop compulsive drug-seeking behaviors (NIDA, 2012). This means a person with addction will need long-term treatment, similar to a person battling a chronic physical disease such as hypertension or diabetes. Treatment usually includes behavioral therapy and/or medication, depending on the individual (NIDA, 2012). Specialized therapies have also been developed for specific types of substance-related disorders, including alcohol, cocaine, and opioids (McGovern & Carroll, 2003). Substance-related treatment is considered much more cost-effective than incarceration or not treating those with addictions (NIDA, 2012) ( Figure 16.19 ). What Makes Treatment Effective? \n\n Specific factors make substance-related treatment much more effective. One factor is duration of treatment. Generally, a person with addict needs to be in treatment for at least three months to achieve a positive outcome (Simpson, 1981; Simpson, Joe, & Bracy, 1982; NIDA, 2012). This is due to the psychological, physiological, behavioral, and social aspects of abuse (Simpson, 1981; Simpson et al., 1982; NIDA, 2012). While in treatment, a person with addiction might receive behavior therapy, which can help motivate the person with addiction to participate in the treatment program and teach strategies for dealing with cravings and how to prevent relapse. Also, treatment needs to be holistic and address multiple needs, not just the drug addiction. This means that treatment will address factors such as communication, stress management, relationship issues, parenting, vocational concerns, and legal concerns (McGovern & Carroll, 2003; NIDA, 2012). While individual therapy is used in the treatment of substance-related disorders, group therapy is the most widespread treatment modality (Weiss, Jaffee, de Menil, & Cogley, 2004). The rationale behind using group therapy for addiction treatment is that people with addiction are much more likely to maintain sobriety in a group format. It has been suggested that this is due to the rewarding and therapeutic benefits of the group, such as support, affiliation, identification, and even confrontation (Center for Substance Abuse Treatment, 2005). For teenagers, the whole family often needs to participate in treatment to address issues such as family dynamics, communication, and relapse prevention. Family involvement in teen drug addiction is vital. Research suggests that greater parental involvement is correlated with a greater reduction in use by teen substance abusers. Also, mothers who participated in treatment displayed better mental health and greater warmth toward their children (Bertrand et al., 2013). However, neither individual nor group therapy has been found to be more effective (Weiss et al., 2004). Regardless of the type of treatment service, the primary focus is on abstinence or at the very least a significant reduction in use (McGovern & Carroll, 2003). Treatment also usually involves medications to detox a person with addiction safely after an overdose, to prevent seizures and agitation that often occur in detox, to prevent reuse of the drug, and to manage withdrawal symptoms. Getting off drugs often involves the use of drugs—some of which can be just as addictive. Detox can be difficult and dangerous. Link to Learning \n\n Watch this video to find out more about treating substance-related disorders using the biological, behavioral, and psychodynamic approaches. \n\n Comorbid Disorders \n\n Frequently, a person with an addiction to drugs and/or alcohol has an additional psychological disorder. Saying a person has comorbid disorders means the individual has two or more diagnoses. This can often be a substance-related diagnosis and another psychiatric diagnosis, such as depression, bipolar disorder, or schizophrenia. These individuals fall into the category of mentally ill and chemically addicted (MICA)—their problems are often chronic and expensive to treat, with limited success. Compared with the overall population, substance abusers are twice as likely to have a mood or anxiety disorder. Drug abuse can cause symptoms of mood and anxiety disorders and the reverse is also true—people with debilitating symptoms of a psychiatric disorder may self-medicate and abuse substances. In cases of comorbidity , the best treatment is thought to address both (or multiple) disorders simultaneously (NIDA, 2012). Behavior therapies are used to treat comorbid conditions, and in many cases, psychotropic medications are used along with psychotherapy. For example, evidence suggests that bupropion (trade names: Wellbutrin and Zyban), approved for treating depression and nicotine dependence, might also help reduce craving and use of the drug methamphetamine (NIDA, 2011). However, more research is needed to better understand how these medications work—particularly when combined in patients with comorbidities. \n 16.5 The Sociocultural Model and Therapy Utilization Learning Objectives By the end of this section, you will be able to:\n\n Explain how the sociocultural model is used in therapy \n\n Discuss barriers to mental health services among ethnic minorities \n\n The sociocultural perspective looks at you, your behaviors, and your symptoms in the context of your culture and background. For example, José is an 18-year-old Hispanic male from a traditional family. José comes to treatment because of depression. During the intake session, he reveals that he is gay and is nervous about telling his family. He also discloses that he is concerned because his religious background has taught him that homosexuality is wrong. How does his religious and cultural background affect him? How might his cultural background affect how his family reacts if José were to tell them he is gay? \n\n As our society becomes increasingly multiethnic and multiracial, mental health professionals must develop cultural competence ( Figure 16.20 ), which means they must understand and address issues of race, culture, and ethnicity. They must also develop strategies to effectively address the needs of various populations for which Eurocentric therapies have limited application (Sue, 2004). For example, a counselor whose treatment focuses on individual decision making may be ineffective at helping a Chinese client with a collectivist approach to problem solving (Sue, 2004). Multicultural counseling and therapy aims to offer both a helping role and process that uses modalities and defines goals consistent with the life experiences and cultural values of clients. It strives to recognize client identities to include individual, group, and universal dimensions, advocate the use of universal and culture-specific strategies and roles in the healing process, and balancs the importance of individualism and collectivism in the assessment, diagnosis, and treatment of client and client systems (Sue, 2001). \n\n This therapeutic perspective integrates the impact of cultural and social norms, starting at the beginning of treatment. Therapists who use this perspective work with clients to obtain and integrate information about their cultural patterns into a unique treatment approach based on their particular situation (Stewart, Simmons, & Habibpour, 2012). Sociocultural therapy can include individual, group, family, and couples treatment modalities. \n\n Link to Learning \n\n Watch this short video to learn more about cultural competence and sociocultural treatments. \n\n Barriers to Treatment \n\n Statistically, ethnic minorities tend to utilize mental health services less frequently than White, middle-class Americans (Alegría et al., 2008; Richman, Kohn-Wood, & Williams, 2007). Why is this so? Perhaps the reason has to do with access and availability of mental health services. Ethnic minorities and individuals of low socioeconomic status (SES) report that barriers to services include lack of insurance, transportation, and time (Thomas & Snowden, 2002). However, researchers have found that even when income levels and insurance variables are taken into account, ethnic minorities are far less likely to seek out and utilize mental health services. And when access to mental health services is comparable across ethnic and racial groups, differences in service utilization remain (Richman et al., 2007). \n\n In a study involving thousands of women, it was found that the prevalence rate of anorexia was similar across different races, but that bulimia nervosa was more prevalent among Hispanic and African American women when compared with non-Hispanic whites (Marques et al., 2011). Although they have similar or higher rates of eating disorders, Hispanic and African American women with these disorders tend to seek and engage in treatment far less than Caucasian women. These findings suggest ethnic disparities in access to care, as well as clinical and referral practices that may prevent Hispanic and African American women from receiving care, which could include lack of bilingual treatment, stigma, fear of not being understood, family privacy, and lack of education about eating disorders. \n\n Perceptions and attitudes toward mental health services may also contribute to this imbalance. A recent study at King’s College, London, found many complex reasons why people do not seek treatment: self-sufficiency and not seeing the need for help, not seeing therapy as effective, concerns about confidentiality, and the many effects of stigma and shame (Clement et al., 2014). And in another study, African Americans exhibiting depression were less willing to seek treatment due to fear of possible psychiatric hospitalization as well as fear of the treatment itself (Sussman, Robins, & Earls, 1987). Instead of mental health treatment, many African Americans prefer to be self-reliant or use spiritual practices (Snowden, 2001; Belgrave & Allison, 2010). For example, it has been found that the Black church plays a significant role as an alternative to mental health services by providing prevention and treatment-type programs designed to enhance the psychological and physical well-being of its members (Blank, Mahmood, Fox, & Guterbock, 2002). \n\n Additionally, people belonging to ethnic groups that already report concerns about prejudice and discrimination are less likely to seek services for a mental illness because they view it as an additional stigma (Gary, 2005; Townes, Cunningham, & Chavez-Korell, 2009; Scott, McCoy, Munson, Snowden, & McMillen, 2011). For example, in one recent study of 462 older Korean Americans (over the age of 60) many participants reported suffering from depressive symptoms. However, 71% indicated they thought depression was a sign of personal weakness, and 14% reported that having a mentally ill family member would bring shame to the family (Jang, Chiriboga, & Okazaki, 2009). \n\n Language differences are a further barrier to treatment. In the previous study on Korean Americans’ attitudes toward mental health services, it was found that there were no Korean-speaking mental health professionals where the study was conducted (Orlando and Tampa, Florida) (Jang et al., 2009). Because of the growing number of people from ethnically diverse backgrounds, there is a need for therapists and psychologists to develop knowledge and skills to become culturally competent (Ahmed, Wilson, Henriksen, & Jones, 2011). Those providing therapy must approach the process from the context of the unique culture of each client (Sue & Sue, 2007). \n\n Dig Deeper Treatment Perceptions By the time a child is a senior in high school, 20% of his classmates—that is 1 in 5—will have experienced a mental health problem (U.S. Department of Health and Human Services, 1999), and 8%—about 1 in 12—will have attempted suicide (Centers for Disease Control and Prevention, 2014). Of those classmates experiencing mental disorders, only 20% will receive professional help (U.S. Public Health Service, 2000). Why? It seems that the public has a negative perception of children and teens with mental health disorders. According to researchers from Indiana University, the University of Virginia, and Columbia University, interviews with over 1,300 U.S. adults show that they believe children with depression are prone to violence and that if a child receives treatment for a psychological disorder, then that child is more likely to be rejected by peers at school. \n\n Bernice Pescosolido, author of the study, asserts that this is a misconception. However, stigmatization of psychological disorders is one of the main reasons why young people do not get the help they need when they are having difficulties. Pescosolido and her colleagues caution that this stigma surrounding mental illness, based on misconceptions rather than facts, can be devastating to the emotional and social well-being of our nation’s children. \n\n This warning played out as a national tragedy in the 2012 shootings at Sandy Hook Elementary. In her blog, Suzy DeYoung (2013), co-founder of Sandy Hook Promise (the organization parents and concerned others set up in the wake of the school massacre) speaks to treatment perceptions and what happens when children do not receive the mental health treatment they desperately need. \n\n I've become accustomed to the reaction when I tell people where I'm from. \n\n Eleven months later, it's as consistent as it was back in January. \n\n Just yesterday, inquiring as to the availability of a rental house this holiday season, the gentleman taking my information paused to ask, “Newtown, CT? Isn't that where that...that thing happened? \n\n A recent encounter in the Massachusetts Berkshires, however, took me by surprise. \n\n It was in a small, charming art gallery. The proprietor, a woman who looked to be in her 60s, asked where we were from. My response usually depends on my present mood and readiness for the inevitable dialogue. Sometimes it's simply, Connecticut. This time, I replied, Newtown, CT. \n\n The woman's demeanor abruptly shifted from one of amiable graciousness to one of visible agitation. \n\n “Oh my god,” she said wide eyed and open mouthed. “Did you know her?” \n\n . . . . \n\n “Her?” I inquired \n\n That woman,” she replied with disdain, “that woman that raised that monster.” \n\n “That woman's” name was Nancy Lanza. Her son, Adam, killed her with a rifle blast to the head before heading out to kill 20 children and six educators at Sandy Hook Elementary School in Newtown, CT last December 14th. \n\n When Nelba Marquez Greene, whose beautiful 6-year-old daughter, Ana, was killed by Adam Lanza, was recently asked how she felt about “that woman,” this was her reply: \n\n “She's a victim herself. And it's time in America that we start looking at mental illness with compassion, and helping people who need it. \n\n “This was a family that needed help, an individual that needed help and didn't get it. And what better can come of this, of this time in America, than if we can get help to people who really need it?” (pars. 1–7, 10–15) \n\n Fortunately, we are starting to see campaigns related to the destigmatization of mental illness and an increase in public education and awareness. Join the effort by encouraging and supporting those around you to seek help if they need it. To learn more, visit the National Alliance on Mental Illness (NAMI) website (http://www.nami.org/). The nation’s largest nonprofit mental health advocacy and support organization is NAMI. "}}},{"rowIdx":184,"cells":{"bname":{"kind":"string","value":"u.s._history"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":" Summary 21.1 The Origins of the Progressive Spirit in America \n\n In its first decade, the Progressive Era was a grassroots effort that ushered in reforms at state and local levels. At the beginning of the twentieth century, however, Progressive endeavors captured the attention of the federal government. The challenges of the late nineteenth century were manifold: fast-growing cities that were ill-equipped to house the working poor, hands-off politicians shackled into impotence by their system of political favors, and rural Americans struggling to keep their farms afloat. The muckraking journalists of the era published books and articles highlighting the social inequities of the day and extolling everyday Americans to help find solutions. Educated, middle-class, Anglo-Saxon Protestants dominated the movement, but Progressives were not a homogenous group: The movement counted African Americans, both women and men, and urban as well as rural dwellers among its ranks. Progressive causes ranged from anti-liquor campaigns to fair pay. Together, Progressives sought to advance the spread of democracy, improve efficiency in government and industry, and promote social justice. \n\n 21.2 Progressivism at the Grassroots Level \n\n Progressive campaigns stretched from the hurricane-ruined townships of Texas to the slums of New York, from the factory floor to the saloon door. But what tied together these disparate causes and groups was the belief that the country was in dire need of reform, and that answers were to be found within the activism and expertise of predominantly middle-class Americans on behalf of troubled communities. Some efforts, such as the National Child Labor Committee, pushed for federal legislation; however, most Progressive initiatives took place at the state and local levels, as Progressives sought to harness public support to place pressure on politicians. \n\n At the beginning of the twentieth century, a more radical, revolutionary breed of Progressivism began to evolve. While these radical Progressives generally shared the goals of their more mainstream counterparts, their strategies differed significantly. Mainstream Progressives and many middle-class Americans feared groups such as the Socialist Party of America and the Industrial Workers of the World, which emphasized workers’ empowerment and direct action. \n\n 21.3 New Voices for Women and African Americans \n\n The Progressive commitment to promoting democracy and social justice created an environment within which the movements for women’s and African American rights grew and flourished. Emergent leaders such as Elizabeth Cady Stanton, Susan B. Anthony, Carrie Chapman Catt, and Alice Paul spread the cause of woman suffrage, drawing in other activists and making the case for a constitutional amendment ensuring a woman’s right to vote. African Americans—guided by leaders such as Booker T. Washington and W. E. B. Du Bois—strove for civil rights and economic opportunity, although their philosophies and strategies differed significantly. In the women’s and civil rights movements alike, activists both advanced their own causes and paved the way for later efforts aimed at expanding equal opportunity and citizenship. 21.4 Progressivism in the White House \n\n Theodore Roosevelt became president only by historical accident, but his activism in the executive branch spoke to the Progressive spirit in the nation and transformed the president’s office for the twentieth century. The courage he displayed in his confrontation of big business and willingness to side with workers in capital-labor disputes, as well as his commitment to the preservation of federal lands, set an agenda his successors had to match. Like Roosevelt, William Howard Taft pushed antitrust rulings and expanded federal oversight of interstate commerce. But estrangement from his predecessor and mentor left Taft in a difficult position for reelection. Roosevelt’s third-party challenge as a Progressive split the Republican vote and handed Woodrow Wilson the presidency in 1912. A Progressive like his predecessors, Wilson was also a political creature who understood the need to do more in order to ensure his reelection. He, too, sought to limit the power of big businesses and stabilize the economy, and he ushered in a wave of Progressive legislation that grassroots Progressives had long called for. The nation’s entanglement in World War I, however, soon shunted the Progressive goals of democracy, efficiency, regulation, and social justice to the back burner. The nation’s new priorities included national security and making the world “safe for democracy.” "},"intro":{"kind":"string","value":" Chapter Outline 21.1 The Origins of the Progressive Spirit in America 21.2 Progressivism at the Grassroots Level 21.3 New Voices for Women and African Americans 21.4 Progressivism in the White House Introduction \n\n Women’s suffrage was one of many causes that emerged in the Progressive Era, as Americans confronted the numerous challenges of the late nineteenth century. Starting in the late 1800s, women increasingly were working outside the home—a task almost always done for money, not empowerment—as well as pursuing higher education, both at universities that were beginning to allow women to enroll and at female-only schools. Often, it was educated middle-class women with more time and resources that took up causes such as child labor and family health. As more women led new organizations or institutions, such as the settlement houses, they grew to have a greater voice on issues of social change. By the turn of the century, a strong movement had formed to advocate for a woman’s right to vote. For three decades, suffragist groups pushed for legislation to give women the right to vote in every state. As the illustration above shows ( Figure 21.1 ), the western states were the first to grant women the right to vote; it would not be until 1920 that the nation would extend that right to all women."},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"Beginning in the second half of the nineteenth century , these Progressive journalists sought to expose critical social problems and exhort the public to take action . In his book , How the Other Half Lives ( 1890 ) , journalist and photographer Jacob Riis used photojournalism to capture the dismal and dangerous living conditions in working-class tenements in New York City ( Figure 21.3 ) . <hl> Ida Tarbell , perhaps the most well-known female muckraker , wrote a series of articles on the dangers of John D . Rockefeller ’ s powerful monopoly , Standard Oil . <hl> Her articles followed Henry Demarest Lloyd ’ s book , Wealth Against Commonwealth , published in 1894 , which examined the excesses of Standard Oil . Other writers , like Lincoln Steffens , explored corruption in city politics , or , like Ray Stannard Baker , researched unsafe working conditions and low pay in the coal mines .","hl_sentences":"Ida Tarbell , perhaps the most well-known female muckraker , wrote a series of articles on the dangers of John D . Rockefeller ’ s powerful monopoly , Standard Oil .","question":{"cloze_format":"Ida Tarbell wrote publicly about ___.","normal_format":"What did Ida Tarbell publicly write about?","question_choices":["the need for better housing in rural America","the sinister business practices of Standard Oil","the need for a national temperance movement","the women’s suffrage cause in the American West"],"question_id":"fs-idm6317264","question_text":"Ida Tarbell wrote publicly about"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"land reform"},"bloom":null,"hl_context":"<hl> Progressive groups made tremendous strides on issues involving democracy , efficiency , and social justice . <hl> <hl> But they found that their grassroots approach was ill-equipped to push back against the most powerful beneficiaries of growing inequality , economic concentration , and corruption — big business . <hl> In their fight against the trusts , Progressives needed the leadership of the federal government , and they found it in Theodore Roosevelt in 1901 , through an accident of history . Muckrakers drew public attention to some of the most glaring inequities and scandals that grew out of the social ills of the Gilded Age and the hands-off approach of the federal government since the end of Reconstruction . These writers by and large addressed a White , middle-class and elite , native-born audience , even though Progressive movements and organizations involved a diverse range of Americans . What united these Progressives beyond their different backgrounds and causes was a set of uniting principles , however . Most strove for a perfection of democracy , which required the expansion of suffrage to worthy citizens and the restriction of political participation for those considered “ unfit ” on account of health , education , or race . <hl> Progressives also agreed that democracy had to be balanced with an emphasis on efficiency , a reliance on science and technology , and deference to the expertise of professionals . <hl> <hl> They repudiated party politics but looked to government to regulate the modern market economy . <hl> <hl> And they saw themselves as the agents of social justice and reform , as well as the stewards and guides of workers and the urban poor . <hl> Often , reformers ’ convictions and faith in their own expertise led them to dismiss the voices of the very people they sought to help .","hl_sentences":"Progressive groups made tremendous strides on issues involving democracy , efficiency , and social justice . But they found that their grassroots approach was ill-equipped to push back against the most powerful beneficiaries of growing inequality , economic concentration , and corruption — big business . Progressives also agreed that democracy had to be balanced with an emphasis on efficiency , a reliance on science and technology , and deference to the expertise of professionals . They repudiated party politics but looked to government to regulate the modern market economy . And they saw themselves as the agents of social justice and reform , as well as the stewards and guides of workers and the urban poor .","question":{"cloze_format":"____ was not a key area of focus for the Progressives.","normal_format":"Which of the following was not a key area of focus for the Progressives?","question_choices":["land reform","democracy","business regulation","social justice"],"question_id":"fs-idm22827856","question_text":"Which of the following was not a key area of focus for the Progressives?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"candidate selection by convention delegates"},"bloom":null,"hl_context":"<hl> The first law involved the creation of the direct primary . <hl> <hl> Prior to this time , the only people who had a hand in selecting candidates for elections were delegates at conventions . <hl> <hl> Direct primaries allowed party members to vote directly for a candidate , with the nomination going to the one with the most votes . <hl> This was the beginning of the current system of holding a primary election before a general election . South Carolina adopted this system for statewide elections in 1896 ; in 1901 , Florida became the first state to use the direct primary in nominations for the presidency . It is the method currently used in three-quarters of U . S . states .","hl_sentences":"The first law involved the creation of the direct primary . Prior to this time , the only people who had a hand in selecting candidates for elections were delegates at conventions . Direct primaries allowed party members to vote directly for a candidate , with the nomination going to the one with the most votes .","question":{"cloze_format":"The direct primary replaced ____.","normal_format":"What system did the direct primary replace?","question_choices":["candidate selection by secret ballots","candidate selection by machine bosses","candidate selection by convention delegates","an indirect primary"],"question_id":"fs-idm62784336","question_text":"What system did the direct primary replace?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"What do you think about William Shepherd ’ s description ? What effect do you think it had on newspaper readers in the Midwest ? <hl> Another cause that garnered support from a key group of Progressives was the prohibition of liquor . <hl> <hl> This crusade , which gained followers through the Woman ’ s Christian Temperance Union ( WCTU ) and the Anti-Saloon League , directly linked Progressivism with morality and Christian reform initiatives , and saw in alcohol both a moral vice and a practical concern , as workingmen spent their wages on liquor and saloons , often turning violent towards each other or their families at home . <hl> The WCTU and Anti-Saloon League moved the efforts to eliminate the sale of alcohol from a bar-to-bar public opinion campaign to one of city-to-city and state-by-state votes ( Figure 21.9 ) . Through local option votes and subsequent statewide initiatives and referendums , the Anti-Saloon League succeeded in urging 40 percent of the nation ’ s counties to “ go dry ” by 1906 , and a full dozen states to do the same by 1909 . Their political pressure culminated in the passage of the Eighteenth Amendment to the U . S . Constitution , ratified in 1919 , which prohibited the manufacture , sale , and transportation of alcoholic beverages nationwide . <hl> Florence Kelley , a Progressive supporter of the NCLC , championed other social justice causes as well . <hl> <hl> As the first general secretary of the National Consumers League , which was founded in 1899 by Jane Addams and others , Kelley led one of the original battles to try and secure safety in factory working conditions . <hl> She particularly opposed sweatshop labor and urged the passage of an eight-hour-workday law in order to specifically protect women in the workplace . Kelley ’ s efforts were initially met with strong resistance from factory owners who exploited women ’ s labor and were unwilling to give up the long hours and low wages they paid in order to offer the cheapest possible product to consumers . But in 1911 , a tragedy turned the tide of public opinion in favor of Kelley ’ s cause . On March 25 of that year , a fire broke out at the Triangle Shirtwaist Company on the eighth floor of the Asch building in New York City , resulting in the deaths of 146 garment workers , most of them young , immigrant women ( Figure 21.8 ) . Management had previously blockaded doors and fire escapes in an effort to control workers and keep out union organizers ; in the blaze , many died due to the crush of bodies trying to evacuate the building . Others died when they fell off the flimsy fire escape or jumped to their deaths to escape the flames . This tragedy provided the National Consumers League with the moral argument to convince politicians of the need to pass workplace safety laws and codes . <hl> The Progressives ’ work towards social justice took many forms . <hl> <hl> In some cases , it was focused on those who suffered due to pervasive inequality , such as African Americans , other ethnic groups , and women . <hl> In others , the goal was to help those who were in desperate need due to circumstance , such as poor immigrants from southern and eastern Europe who often suffered severe discrimination , the working poor , and those with ill health . Women were in the vanguard of social justice reform . Jane Addams , Lillian Wald , and Ellen Gates Starr , for example , led the settlement house movement of the 1880s ( discussed in a previous chapter ) . <hl> Their work to provide social services , education , and health care to working-class women and their children was among the earliest Progressive grassroots efforts in the country . <hl>","hl_sentences":"Another cause that garnered support from a key group of Progressives was the prohibition of liquor . This crusade , which gained followers through the Woman ’ s Christian Temperance Union ( WCTU ) and the Anti-Saloon League , directly linked Progressivism with morality and Christian reform initiatives , and saw in alcohol both a moral vice and a practical concern , as workingmen spent their wages on liquor and saloons , often turning violent towards each other or their families at home . Florence Kelley , a Progressive supporter of the NCLC , championed other social justice causes as well . As the first general secretary of the National Consumers League , which was founded in 1899 by Jane Addams and others , Kelley led one of the original battles to try and secure safety in factory working conditions . The Progressives ’ work towards social justice took many forms . In some cases , it was focused on those who suffered due to pervasive inequality , such as African Americans , other ethnic groups , and women . Their work to provide social services , education , and health care to working-class women and their children was among the earliest Progressive grassroots efforts in the country .","question":{"cloze_format":"___ is not an example of social justice Progressivism.","normal_format":"Which of the following is not an example of social justice Progressivism?","question_choices":["anti-liquor campaigns","referendums","workplace safety initiatives","improvements in education"],"question_id":"fs-idp1462368","question_text":"Which of the following is not an example of social justice Progressivism?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"immediate protests for equal rights"},"bloom":null,"hl_context":"Yet , many African Americans disagreed with Washington ’ s approach . Much in the same manner that Alice Paul felt the pace of the struggle for women ’ s rights was moving too slowly under the NAWSA , some within the African American community felt that immediate agitation for the rights guaranteed under the Thirteenth , Fourteenth , and Fifteenth Amendments , established during the immediate aftermath of the Civil War , was necessary . In 1905 , a group of prominent civil rights leaders , led by W . E . B . Du Bois , met in a small hotel on the Canadian side of Niagara Falls — where segregation laws did not bar them from hotel accommodations — to discuss what immediate steps were needed for equal rights ( Figure 21.15 ) . Du Bois , a professor at the all-Black Atlanta University and the first African American with a doctorate from Harvard , emerged as the prominent spokesperson for what would later be dubbed the Niagara Movement . <hl> By 1905 , he had grown wary of Booker T . Washington ’ s calls for African Americans to accommodate White racism and focus solely on self-improvement . <hl> <hl> Du Bois , and others alongside him , wished to carve a more direct path towards equality that drew on the political leadership and litigation skills of the Black , educated elite , which he termed the “ talented tenth . ” At the meeting , Du Bois led the others in drafting the “ Declaration of Principles , ” which called for immediate political , economic , and social equality for African Americans . <hl> These rights included universal suffrage , compulsory education , and the elimination of the convict lease system in which tens of thousands of Blacks had endured slavery-like conditions in southern road construction , mines , prisons , and penal farms since the end of Reconstruction . Within a year , Niagara chapters had sprung up in twenty-one states across the country . By 1908 , internal fights over the role of women in the fight for African American equal rights lessened the interest in the Niagara Movement . But the movement laid the groundwork for the creation of the National Association for the Advancement of Colored People ( NAACP ) , founded in 1909 . Du Bois served as the influential director of publications for the NAACP from its inception until 1933 . As the editor of the journal The Crisis , Du Bois had a platform to express his views on a variety of issues facing African Americans in the later Progressive Era , as well as during World War I and its aftermath . In both Washington and Du Bois , African Americans found leaders to push forward the fight for their place in the new century , each with a very different strategy . Both men cultivated ground for a new generation of African American spokespeople and leaders who would then pave the road to the modern civil rights movement after World War II . 21.4 Progressivism in the White House Learning Objectives By the end of this section , you will be able to : In a speech delivered at the Cotton States and International Exposition in Atlanta in 1895 , which was meant to promote the economy of a “ New South , ” Washington proposed what came to be known as the Atlanta Compromise ( Figure 21.14 ) . <hl> Speaking to a racially mixed audience , Washington called upon African Americans to work diligently for their own uplift and prosperity rather than preoccupy themselves with political and civil rights . <hl> <hl> Their success and hard work , he implied , would eventually convince southern Whites to grant these rights . <hl> Not surprisingly , most Whites liked Washington ’ s model of race relations , since it placed the burden of change on Blacks and required nothing of them . Wealthy industrialists such as Andrew Carnegie and John D . Rockefeller provided funding for many of Washington ’ s self-help programs , as did Sears , Roebuck & Co . co-founder Julius Rosenwald , and Washington was the first African American invited to the White House by President Roosevelt in 1901 . At the same time , his message also appealed to many in the Black community , and some attribute this widespread popularity to his consistent message that social and economic growth , even within a segregated society , would do more for African Americans than an all-out agitation for equal rights on all fronts . <hl> Born into slavery in Virginia in 1856 , Booker T . Washington became an influential African American leader at the outset of the Progressive Era . <hl> In 1881 , he became the first principal for the Tuskegee Normal and Industrial Institute in Alabama , a position he held until he died in 1915 . Tuskegee was an all-Black “ normal school ” — an old term for a teachers ’ college — teaching African Americans a curriculum geared towards practical skills such as cooking , farming , and housekeeping . Graduates would often then travel through the South , teaching new farming and industrial techniques to rural communities . Washington extolled the school ’ s graduates to focus on the Black community ’ s self-improvement and prove that they were productive members of society even in freedom — something White Americans throughout the nation had always doubted .","hl_sentences":"By 1905 , he had grown wary of Booker T . Washington ’ s calls for African Americans to accommodate White racism and focus solely on self-improvement . Du Bois , and others alongside him , wished to carve a more direct path towards equality that drew on the political leadership and litigation skills of the Black , educated elite , which he termed the “ talented tenth . ” At the meeting , Du Bois led the others in drafting the “ Declaration of Principles , ” which called for immediate political , economic , and social equality for African Americans . Speaking to a racially mixed audience , Washington called upon African Americans to work diligently for their own uplift and prosperity rather than preoccupy themselves with political and civil rights . Their success and hard work , he implied , would eventually convince southern Whites to grant these rights . Born into slavery in Virginia in 1856 , Booker T . Washington became an influential African American leader at the outset of the Progressive Era .","question":{"cloze_format":"____ was not a feature of Booker T. Washington's strategy to improve the lives of African Americans.","normal_format":"Which of the following was not a feature of Booker T. Washington’s strategy to improve the lives of African Americans?","question_choices":["self-help","accommodating/tolerating White racism","immediate protests for equal rights","learning new trades/skills"],"question_id":"fs-idm4273328","question_text":"Which of the following was not a feature of Booker T. Washington’s strategy to improve the lives of African Americans?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"For some in the NAWSA , however , the pace of change was too slow . Frustrated with the lack of response by state and national legislators , Alice Paul , who joined the organization in 1912 , sought to expand the scope of the organization as well as to adopt more direct protest tactics to draw greater media attention . When others in the group were unwilling to move in her direction , Paul split from the NAWSA to create the Congressional Union for Woman Suffrage , later renamed the National Woman ’ s Party , in 1913 . <hl> Known as the Silent Sentinels ( Figure 21.12 ) , Paul and her group picketed outside the White House for nearly two years , starting in 1917 . <hl> In the latter stages of their protests , many women , including Paul , were arrested and thrown in jail , where they staged a hunger strike as self-proclaimed political prisoners . Prison guards ultimately force-fed Paul to keep her alive . At a time — during World War I — when women volunteered as army nurses , worked in vital defense industries , and supported Wilson ’ s campaign to “ make the world safe for democracy , ” the scandalous mistreatment of Paul embarrassed President Woodrow Wilson . Enlightened to the injustice toward all American women , he changed his position in support of a woman ’ s constitutional right to vote . While Catt and Paul used different strategies , their combined efforts brought enough pressure to bear for Congress to pass the Nineteenth Amendment , which prohibited voter discrimination on the basis of sex , during a special session in the summer of 1919 . Subsequently , the required thirty-six states approved its adoption , with Tennessee doing so in August of 1920 , in time for that year ’ s presidential election .","hl_sentences":"Known as the Silent Sentinels ( Figure 21.12 ) , Paul and her group picketed outside the White House for nearly two years , starting in 1917 .","question":{"cloze_format":"The \"Silent Sentinels\" were ___.","normal_format":"Who were the “Silent Sentinels”?","question_choices":["a group of progressive African Americans who drafted the Declaration of Principles","anti-suffrage women","an offshoot of the Industrial Workers of the World","suffragists who protested outside the White House"],"question_id":"fs-idm55137504","question_text":"Who were the “Silent Sentinels”?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"In 1902 , Roosevelt launched his administration ’ s first antitrust suit against the Northern Securities Trust Company , which included powerful businessmen , like John D . Rockefeller and J . P . Morgan , and controlled many of the large midwestern railroads . The suit wound through the judicial system , all the way to the U . S . Supreme Court . In 1904 , the highest court in the land ultimately affirmed the ruling to break up the trust in a narrow five-to-four vote . For Roosevelt , that was enough of a mandate ; he immediately moved against other corporations as well , including the American Tobacco Company and — most significantly — Rockefeller ’ s Standard Oil Company . Although Roosevelt enjoyed the nickname “ the Trustbuster , ” he did not consider all trusts dangerous to the public welfare . The “ good trusts , ” Roosevelt reasoned , used their power in the marketplace and economies of scale to deliver goods and services to customers more cheaply . For example , he allowed Morgan ’ s U . S . Steel Corporation to continue its operations and let it take over smaller steel companies . At the same time , Roosevelt used the presidency as a “ bully pulpit ” to publicly denounce “ bad trusts ” — those corporations that exploited their market positions for short-term gains — before he ordered prosecutions by the Justice Department . In total , Roosevelt initiated over two dozen successful anti-trust suits , more than any president before him . Roosevelt also showed in other contexts that he dared to face the power of corporations . <hl> When an anthracite coal strike gripped the nation for much of the year in 1902 , Roosevelt directly intervened in the dispute and invited both sides to the White House to negotiate a deal that included minor wage increases and a slight improvement in working hours . <hl> For Roosevelt , his intervention in the matter symbolized his belief that the federal government should adopt a more proactive role and serve as a steward of all Americans ( Figure 21.17 ) . This stood in contrast to his predecessors , who had time and again bolstered industrialists in their fight against workers ’ rights with the deployment of federal troops .","hl_sentences":"When an anthracite coal strike gripped the nation for much of the year in 1902 , Roosevelt directly intervened in the dispute and invited both sides to the White House to negotiate a deal that included minor wage increases and a slight improvement in working hours .","question":{"cloze_format":"Roosevelt interceded in the Anthracite Coal Strike of 1902 ___.","normal_format":"How did Roosevelt intercede in the Anthracite Coal Strike of 1902?","question_choices":["He invited strikers and workers to the White House.","He urged the owners to negotiate a deal.","He threatened to send in the army to work the mines.","He ordered the National Guard to protect the strikers."],"question_id":"fs-idp6155392","question_text":"How did Roosevelt intercede in the Anthracite Coal Strike of 1902?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"the Payne-Aldrich Act"},"bloom":null,"hl_context":"Political infighting within his own party exposed the limitations of Taft ’ s presidential authority , especially on the issue of protective tariffs . <hl> When House Republicans passed a measure to significantly reduce tariffs on several imported goods , Taft endorsed the Senate version , later known as the Payne-Aldrich Act of 1909 , which raised tariff rates on over eight hundred products in the original bill . <hl> <hl> Taft also angered Progressives in his own party when he created the U . S . Chamber of Commerce in 1912 , viewed by many as an attempt to offset the growing influence of the labor union movement at the time . <hl> The rift between Taft and his party ’ s Progressives widened when the president supported conservative party candidates for the 1910 House and Senate elections . Taft ’ s biggest political blunder came in the area of land conservation . In 1909 , Taft ’ s Secretary of the Interior , Richard Ballinger , approved the sale of millions of acres of federal land to a company for which he had previously worked over Gifford Pinchot ’ s objections . Pinchot publicly criticized the secretary for violating the principle of conservation and for his conflict of interest — a charge that in the public debate also reflected on the president . Taft fired Pinchot , a move that widened the gap between him and the former president . Upon his return from Africa , Roosevelt appeared primed to attack . He referred to the sitting president as a “ fathead ” and a “ puzzlewit , ” and announced his intention to “ throw my hat in the ring for the 1912 presidential election . ”","hl_sentences":"When House Republicans passed a measure to significantly reduce tariffs on several imported goods , Taft endorsed the Senate version , later known as the Payne-Aldrich Act of 1909 , which raised tariff rates on over eight hundred products in the original bill . Taft also angered Progressives in his own party when he created the U . S . Chamber of Commerce in 1912 , viewed by many as an attempt to offset the growing influence of the labor union movement at the time .","question":{"cloze_format":"___ was a key Progressive item passed by Taft.","normal_format":"Which of the following was a key Progressive item passed by Taft?","question_choices":["the Pure Food and Drug Act","the U.S. Forestry Service","the Mann-Elkins Act","the Payne-Aldrich Act"],"question_id":"fs-idm81830848","question_text":"Which of the following was a key Progressive item passed by Taft?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"When Wilson took office in March 1913 , he immediately met with Congress to outline his New Freedom agenda for how progressive interests could be best preserved . His plan was simple : regulate the banks and big businesses , and lower tariff rates to increase international trade , increasing competition in the interest of consumers . <hl> Wilson took the unusual step of calling a special session of Congress in April 1913 to tackle the tariff question , which resulted in the Revenue Act of 1913 , also known as the Underwood Tariff Act . <hl> <hl> This legislation lowered tariff rates across the board by approximately 15 percent and completely eliminated tariffs on several imports , including steel , iron ore , woolen products , and farm tools . <hl> To offset the potential loss of federal revenue , this new law reinstituted the federal income tax , which followed the ratification of the Sixteenth Amendment . This first income tax required married couples who earned $ 4000 or more , and single people who earned $ 3000 or more , to pay a 1 - percent , graduated income tax , with the tax rate getting progressively higher for those who earned more .","hl_sentences":"Wilson took the unusual step of calling a special session of Congress in April 1913 to tackle the tariff question , which resulted in the Revenue Act of 1913 , also known as the Underwood Tariff Act . This legislation lowered tariff rates across the board by approximately 15 percent and completely eliminated tariffs on several imports , including steel , iron ore , woolen products , and farm tools .","question":{"cloze_format":"___ was not an outcome of the Underwood Tariff Act.","normal_format":"Which of the following was not an outcome of the Underwood Tariff Act?","question_choices":["It reduced tariffs 15 percent across all imports.","It eliminated tariffs for steel.","It eliminated tariffs for iron ore.","It established a federal banking system to oversee tariffs."],"question_id":"fs-idp96060096","question_text":"Which of the following was not an outcome of the Underwood Tariff Act?"},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"Beginning in the second half of the nineteenth century , these Progressive journalists sought to expose critical social problems and exhort the public to take action . In his book , How the Other Half Lives ( 1890 ) , journalist and photographer Jacob Riis used photojournalism to capture the dismal and dangerous living conditions in working-class tenements in New York City ( Figure 21.3 ) . <hl> Ida Tarbell , perhaps the most well-known female muckraker , wrote a series of articles on the dangers of John D . Rockefeller ’ s powerful monopoly , Standard Oil . <hl> Her articles followed Henry Demarest Lloyd ’ s book , Wealth Against Commonwealth , published in 1894 , which examined the excesses of Standard Oil . Other writers , like Lincoln Steffens , explored corruption in city politics , or , like Ray Stannard Baker , researched unsafe working conditions and low pay in the coal mines .\",\n \"hl_sentences\": \"Ida Tarbell , perhaps the most well-known female muckraker , wrote a series of articles on the dangers of John D . Rockefeller ’ s powerful monopoly , Standard Oil .\",\n \"question\": {\n \"cloze_format\": \"Ida Tarbell wrote publicly about ___.\",\n \"normal_format\": \"What did Ida Tarbell publicly write about?\",\n \"question_choices\": [\n \"the need for better housing in rural America\",\n \"the sinister business practices of Standard Oil\",\n \"the need for a national temperance movement\",\n \"the women’s suffrage cause in the American West\"\n ],\n \"question_id\": \"fs-idm6317264\",\n \"question_text\": \"Ida Tarbell wrote publicly about\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"land reform\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Progressive groups made tremendous strides on issues involving democracy , efficiency , and social justice . <hl> <hl> But they found that their grassroots approach was ill-equipped to push back against the most powerful beneficiaries of growing inequality , economic concentration , and corruption — big business . <hl> In their fight against the trusts , Progressives needed the leadership of the federal government , and they found it in Theodore Roosevelt in 1901 , through an accident of history . Muckrakers drew public attention to some of the most glaring inequities and scandals that grew out of the social ills of the Gilded Age and the hands-off approach of the federal government since the end of Reconstruction . These writers by and large addressed a White , middle-class and elite , native-born audience , even though Progressive movements and organizations involved a diverse range of Americans . What united these Progressives beyond their different backgrounds and causes was a set of uniting principles , however . Most strove for a perfection of democracy , which required the expansion of suffrage to worthy citizens and the restriction of political participation for those considered “ unfit ” on account of health , education , or race . <hl> Progressives also agreed that democracy had to be balanced with an emphasis on efficiency , a reliance on science and technology , and deference to the expertise of professionals . <hl> <hl> They repudiated party politics but looked to government to regulate the modern market economy . <hl> <hl> And they saw themselves as the agents of social justice and reform , as well as the stewards and guides of workers and the urban poor . <hl> Often , reformers ’ convictions and faith in their own expertise led them to dismiss the voices of the very people they sought to help .\",\n \"hl_sentences\": \"Progressive groups made tremendous strides on issues involving democracy , efficiency , and social justice . But they found that their grassroots approach was ill-equipped to push back against the most powerful beneficiaries of growing inequality , economic concentration , and corruption — big business . Progressives also agreed that democracy had to be balanced with an emphasis on efficiency , a reliance on science and technology , and deference to the expertise of professionals . They repudiated party politics but looked to government to regulate the modern market economy . And they saw themselves as the agents of social justice and reform , as well as the stewards and guides of workers and the urban poor .\",\n \"question\": {\n \"cloze_format\": \"____ was not a key area of focus for the Progressives.\",\n \"normal_format\": \"Which of the following was not a key area of focus for the Progressives?\",\n \"question_choices\": [\n \"land reform\",\n \"democracy\",\n \"business regulation\",\n \"social justice\"\n ],\n \"question_id\": \"fs-idm22827856\",\n \"question_text\": \"Which of the following was not a key area of focus for the Progressives?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"candidate selection by convention delegates\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The first law involved the creation of the direct primary . <hl> <hl> Prior to this time , the only people who had a hand in selecting candidates for elections were delegates at conventions . <hl> <hl> Direct primaries allowed party members to vote directly for a candidate , with the nomination going to the one with the most votes . <hl> This was the beginning of the current system of holding a primary election before a general election . South Carolina adopted this system for statewide elections in 1896 ; in 1901 , Florida became the first state to use the direct primary in nominations for the presidency . It is the method currently used in three-quarters of U . S . states .\",\n \"hl_sentences\": \"The first law involved the creation of the direct primary . Prior to this time , the only people who had a hand in selecting candidates for elections were delegates at conventions . Direct primaries allowed party members to vote directly for a candidate , with the nomination going to the one with the most votes .\",\n \"question\": {\n \"cloze_format\": \"The direct primary replaced ____.\",\n \"normal_format\": \"What system did the direct primary replace?\",\n \"question_choices\": [\n \"candidate selection by secret ballots\",\n \"candidate selection by machine bosses\",\n \"candidate selection by convention delegates\",\n \"an indirect primary\"\n ],\n \"question_id\": \"fs-idm62784336\",\n \"question_text\": \"What system did the direct primary replace?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"What do you think about William Shepherd ’ s description ? What effect do you think it had on newspaper readers in the Midwest ? <hl> Another cause that garnered support from a key group of Progressives was the prohibition of liquor . <hl> <hl> This crusade , which gained followers through the Woman ’ s Christian Temperance Union ( WCTU ) and the Anti-Saloon League , directly linked Progressivism with morality and Christian reform initiatives , and saw in alcohol both a moral vice and a practical concern , as workingmen spent their wages on liquor and saloons , often turning violent towards each other or their families at home . <hl> The WCTU and Anti-Saloon League moved the efforts to eliminate the sale of alcohol from a bar-to-bar public opinion campaign to one of city-to-city and state-by-state votes ( Figure 21.9 ) . Through local option votes and subsequent statewide initiatives and referendums , the Anti-Saloon League succeeded in urging 40 percent of the nation ’ s counties to “ go dry ” by 1906 , and a full dozen states to do the same by 1909 . Their political pressure culminated in the passage of the Eighteenth Amendment to the U . S . Constitution , ratified in 1919 , which prohibited the manufacture , sale , and transportation of alcoholic beverages nationwide . <hl> Florence Kelley , a Progressive supporter of the NCLC , championed other social justice causes as well . <hl> <hl> As the first general secretary of the National Consumers League , which was founded in 1899 by Jane Addams and others , Kelley led one of the original battles to try and secure safety in factory working conditions . <hl> She particularly opposed sweatshop labor and urged the passage of an eight-hour-workday law in order to specifically protect women in the workplace . Kelley ’ s efforts were initially met with strong resistance from factory owners who exploited women ’ s labor and were unwilling to give up the long hours and low wages they paid in order to offer the cheapest possible product to consumers . But in 1911 , a tragedy turned the tide of public opinion in favor of Kelley ’ s cause . On March 25 of that year , a fire broke out at the Triangle Shirtwaist Company on the eighth floor of the Asch building in New York City , resulting in the deaths of 146 garment workers , most of them young , immigrant women ( Figure 21.8 ) . Management had previously blockaded doors and fire escapes in an effort to control workers and keep out union organizers ; in the blaze , many died due to the crush of bodies trying to evacuate the building . Others died when they fell off the flimsy fire escape or jumped to their deaths to escape the flames . This tragedy provided the National Consumers League with the moral argument to convince politicians of the need to pass workplace safety laws and codes . <hl> The Progressives ’ work towards social justice took many forms . <hl> <hl> In some cases , it was focused on those who suffered due to pervasive inequality , such as African Americans , other ethnic groups , and women . <hl> In others , the goal was to help those who were in desperate need due to circumstance , such as poor immigrants from southern and eastern Europe who often suffered severe discrimination , the working poor , and those with ill health . Women were in the vanguard of social justice reform . Jane Addams , Lillian Wald , and Ellen Gates Starr , for example , led the settlement house movement of the 1880s ( discussed in a previous chapter ) . <hl> Their work to provide social services , education , and health care to working-class women and their children was among the earliest Progressive grassroots efforts in the country . <hl>\",\n \"hl_sentences\": \"Another cause that garnered support from a key group of Progressives was the prohibition of liquor . This crusade , which gained followers through the Woman ’ s Christian Temperance Union ( WCTU ) and the Anti-Saloon League , directly linked Progressivism with morality and Christian reform initiatives , and saw in alcohol both a moral vice and a practical concern , as workingmen spent their wages on liquor and saloons , often turning violent towards each other or their families at home . Florence Kelley , a Progressive supporter of the NCLC , championed other social justice causes as well . As the first general secretary of the National Consumers League , which was founded in 1899 by Jane Addams and others , Kelley led one of the original battles to try and secure safety in factory working conditions . The Progressives ’ work towards social justice took many forms . In some cases , it was focused on those who suffered due to pervasive inequality , such as African Americans , other ethnic groups , and women . Their work to provide social services , education , and health care to working-class women and their children was among the earliest Progressive grassroots efforts in the country .\",\n \"question\": {\n \"cloze_format\": \"___ is not an example of social justice Progressivism.\",\n \"normal_format\": \"Which of the following is not an example of social justice Progressivism?\",\n \"question_choices\": [\n \"anti-liquor campaigns\",\n \"referendums\",\n \"workplace safety initiatives\",\n \"improvements in education\"\n ],\n \"question_id\": \"fs-idp1462368\",\n \"question_text\": \"Which of the following is not an example of social justice Progressivism?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"immediate protests for equal rights\"\n },\n \"bloom\": null,\n \"hl_context\": \"Yet , many African Americans disagreed with Washington ’ s approach . Much in the same manner that Alice Paul felt the pace of the struggle for women ’ s rights was moving too slowly under the NAWSA , some within the African American community felt that immediate agitation for the rights guaranteed under the Thirteenth , Fourteenth , and Fifteenth Amendments , established during the immediate aftermath of the Civil War , was necessary . In 1905 , a group of prominent civil rights leaders , led by W . E . B . Du Bois , met in a small hotel on the Canadian side of Niagara Falls — where segregation laws did not bar them from hotel accommodations — to discuss what immediate steps were needed for equal rights ( Figure 21.15 ) . Du Bois , a professor at the all-Black Atlanta University and the first African American with a doctorate from Harvard , emerged as the prominent spokesperson for what would later be dubbed the Niagara Movement . <hl> By 1905 , he had grown wary of Booker T . Washington ’ s calls for African Americans to accommodate White racism and focus solely on self-improvement . <hl> <hl> Du Bois , and others alongside him , wished to carve a more direct path towards equality that drew on the political leadership and litigation skills of the Black , educated elite , which he termed the “ talented tenth . ” At the meeting , Du Bois led the others in drafting the “ Declaration of Principles , ” which called for immediate political , economic , and social equality for African Americans . <hl> These rights included universal suffrage , compulsory education , and the elimination of the convict lease system in which tens of thousands of Blacks had endured slavery-like conditions in southern road construction , mines , prisons , and penal farms since the end of Reconstruction . Within a year , Niagara chapters had sprung up in twenty-one states across the country . By 1908 , internal fights over the role of women in the fight for African American equal rights lessened the interest in the Niagara Movement . But the movement laid the groundwork for the creation of the National Association for the Advancement of Colored People ( NAACP ) , founded in 1909 . Du Bois served as the influential director of publications for the NAACP from its inception until 1933 . As the editor of the journal The Crisis , Du Bois had a platform to express his views on a variety of issues facing African Americans in the later Progressive Era , as well as during World War I and its aftermath . In both Washington and Du Bois , African Americans found leaders to push forward the fight for their place in the new century , each with a very different strategy . Both men cultivated ground for a new generation of African American spokespeople and leaders who would then pave the road to the modern civil rights movement after World War II . 21.4 Progressivism in the White House Learning Objectives By the end of this section , you will be able to : In a speech delivered at the Cotton States and International Exposition in Atlanta in 1895 , which was meant to promote the economy of a “ New South , ” Washington proposed what came to be known as the Atlanta Compromise ( Figure 21.14 ) . <hl> Speaking to a racially mixed audience , Washington called upon African Americans to work diligently for their own uplift and prosperity rather than preoccupy themselves with political and civil rights . <hl> <hl> Their success and hard work , he implied , would eventually convince southern Whites to grant these rights . <hl> Not surprisingly , most Whites liked Washington ’ s model of race relations , since it placed the burden of change on Blacks and required nothing of them . Wealthy industrialists such as Andrew Carnegie and John D . Rockefeller provided funding for many of Washington ’ s self-help programs , as did Sears , Roebuck & Co . co-founder Julius Rosenwald , and Washington was the first African American invited to the White House by President Roosevelt in 1901 . At the same time , his message also appealed to many in the Black community , and some attribute this widespread popularity to his consistent message that social and economic growth , even within a segregated society , would do more for African Americans than an all-out agitation for equal rights on all fronts . <hl> Born into slavery in Virginia in 1856 , Booker T . Washington became an influential African American leader at the outset of the Progressive Era . <hl> In 1881 , he became the first principal for the Tuskegee Normal and Industrial Institute in Alabama , a position he held until he died in 1915 . Tuskegee was an all-Black “ normal school ” — an old term for a teachers ’ college — teaching African Americans a curriculum geared towards practical skills such as cooking , farming , and housekeeping . Graduates would often then travel through the South , teaching new farming and industrial techniques to rural communities . Washington extolled the school ’ s graduates to focus on the Black community ’ s self-improvement and prove that they were productive members of society even in freedom — something White Americans throughout the nation had always doubted .\",\n \"hl_sentences\": \"By 1905 , he had grown wary of Booker T . Washington ’ s calls for African Americans to accommodate White racism and focus solely on self-improvement . Du Bois , and others alongside him , wished to carve a more direct path towards equality that drew on the political leadership and litigation skills of the Black , educated elite , which he termed the “ talented tenth . ” At the meeting , Du Bois led the others in drafting the “ Declaration of Principles , ” which called for immediate political , economic , and social equality for African Americans . Speaking to a racially mixed audience , Washington called upon African Americans to work diligently for their own uplift and prosperity rather than preoccupy themselves with political and civil rights . Their success and hard work , he implied , would eventually convince southern Whites to grant these rights . Born into slavery in Virginia in 1856 , Booker T . Washington became an influential African American leader at the outset of the Progressive Era .\",\n \"question\": {\n \"cloze_format\": \"____ was not a feature of Booker T. Washington's strategy to improve the lives of African Americans.\",\n \"normal_format\": \"Which of the following was not a feature of Booker T. Washington’s strategy to improve the lives of African Americans?\",\n \"question_choices\": [\n \"self-help\",\n \"accommodating/tolerating White racism\",\n \"immediate protests for equal rights\",\n \"learning new trades/skills\"\n ],\n \"question_id\": \"fs-idm4273328\",\n \"question_text\": \"Which of the following was not a feature of Booker T. Washington’s strategy to improve the lives of African Americans?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"For some in the NAWSA , however , the pace of change was too slow . Frustrated with the lack of response by state and national legislators , Alice Paul , who joined the organization in 1912 , sought to expand the scope of the organization as well as to adopt more direct protest tactics to draw greater media attention . When others in the group were unwilling to move in her direction , Paul split from the NAWSA to create the Congressional Union for Woman Suffrage , later renamed the National Woman ’ s Party , in 1913 . <hl> Known as the Silent Sentinels ( Figure 21.12 ) , Paul and her group picketed outside the White House for nearly two years , starting in 1917 . <hl> In the latter stages of their protests , many women , including Paul , were arrested and thrown in jail , where they staged a hunger strike as self-proclaimed political prisoners . Prison guards ultimately force-fed Paul to keep her alive . At a time — during World War I — when women volunteered as army nurses , worked in vital defense industries , and supported Wilson ’ s campaign to “ make the world safe for democracy , ” the scandalous mistreatment of Paul embarrassed President Woodrow Wilson . Enlightened to the injustice toward all American women , he changed his position in support of a woman ’ s constitutional right to vote . While Catt and Paul used different strategies , their combined efforts brought enough pressure to bear for Congress to pass the Nineteenth Amendment , which prohibited voter discrimination on the basis of sex , during a special session in the summer of 1919 . Subsequently , the required thirty-six states approved its adoption , with Tennessee doing so in August of 1920 , in time for that year ’ s presidential election .\",\n \"hl_sentences\": \"Known as the Silent Sentinels ( Figure 21.12 ) , Paul and her group picketed outside the White House for nearly two years , starting in 1917 .\",\n \"question\": {\n \"cloze_format\": \"The \\\"Silent Sentinels\\\" were ___.\",\n \"normal_format\": \"Who were the “Silent Sentinels”?\",\n \"question_choices\": [\n \"a group of progressive African Americans who drafted the Declaration of Principles\",\n \"anti-suffrage women\",\n \"an offshoot of the Industrial Workers of the World\",\n \"suffragists who protested outside the White House\"\n ],\n \"question_id\": \"fs-idm55137504\",\n \"question_text\": \"Who were the “Silent Sentinels”?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"In 1902 , Roosevelt launched his administration ’ s first antitrust suit against the Northern Securities Trust Company , which included powerful businessmen , like John D . Rockefeller and J . P . Morgan , and controlled many of the large midwestern railroads . The suit wound through the judicial system , all the way to the U . S . Supreme Court . In 1904 , the highest court in the land ultimately affirmed the ruling to break up the trust in a narrow five-to-four vote . For Roosevelt , that was enough of a mandate ; he immediately moved against other corporations as well , including the American Tobacco Company and — most significantly — Rockefeller ’ s Standard Oil Company . Although Roosevelt enjoyed the nickname “ the Trustbuster , ” he did not consider all trusts dangerous to the public welfare . The “ good trusts , ” Roosevelt reasoned , used their power in the marketplace and economies of scale to deliver goods and services to customers more cheaply . For example , he allowed Morgan ’ s U . S . Steel Corporation to continue its operations and let it take over smaller steel companies . At the same time , Roosevelt used the presidency as a “ bully pulpit ” to publicly denounce “ bad trusts ” — those corporations that exploited their market positions for short-term gains — before he ordered prosecutions by the Justice Department . In total , Roosevelt initiated over two dozen successful anti-trust suits , more than any president before him . Roosevelt also showed in other contexts that he dared to face the power of corporations . <hl> When an anthracite coal strike gripped the nation for much of the year in 1902 , Roosevelt directly intervened in the dispute and invited both sides to the White House to negotiate a deal that included minor wage increases and a slight improvement in working hours . <hl> For Roosevelt , his intervention in the matter symbolized his belief that the federal government should adopt a more proactive role and serve as a steward of all Americans ( Figure 21.17 ) . This stood in contrast to his predecessors , who had time and again bolstered industrialists in their fight against workers ’ rights with the deployment of federal troops .\",\n \"hl_sentences\": \"When an anthracite coal strike gripped the nation for much of the year in 1902 , Roosevelt directly intervened in the dispute and invited both sides to the White House to negotiate a deal that included minor wage increases and a slight improvement in working hours .\",\n \"question\": {\n \"cloze_format\": \"Roosevelt interceded in the Anthracite Coal Strike of 1902 ___.\",\n \"normal_format\": \"How did Roosevelt intercede in the Anthracite Coal Strike of 1902?\",\n \"question_choices\": [\n \"He invited strikers and workers to the White House.\",\n \"He urged the owners to negotiate a deal.\",\n \"He threatened to send in the army to work the mines.\",\n \"He ordered the National Guard to protect the strikers.\"\n ],\n \"question_id\": \"fs-idp6155392\",\n \"question_text\": \"How did Roosevelt intercede in the Anthracite Coal Strike of 1902?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"the Payne-Aldrich Act\"\n },\n \"bloom\": null,\n \"hl_context\": \"Political infighting within his own party exposed the limitations of Taft ’ s presidential authority , especially on the issue of protective tariffs . <hl> When House Republicans passed a measure to significantly reduce tariffs on several imported goods , Taft endorsed the Senate version , later known as the Payne-Aldrich Act of 1909 , which raised tariff rates on over eight hundred products in the original bill . <hl> <hl> Taft also angered Progressives in his own party when he created the U . S . Chamber of Commerce in 1912 , viewed by many as an attempt to offset the growing influence of the labor union movement at the time . <hl> The rift between Taft and his party ’ s Progressives widened when the president supported conservative party candidates for the 1910 House and Senate elections . Taft ’ s biggest political blunder came in the area of land conservation . In 1909 , Taft ’ s Secretary of the Interior , Richard Ballinger , approved the sale of millions of acres of federal land to a company for which he had previously worked over Gifford Pinchot ’ s objections . Pinchot publicly criticized the secretary for violating the principle of conservation and for his conflict of interest — a charge that in the public debate also reflected on the president . Taft fired Pinchot , a move that widened the gap between him and the former president . Upon his return from Africa , Roosevelt appeared primed to attack . He referred to the sitting president as a “ fathead ” and a “ puzzlewit , ” and announced his intention to “ throw my hat in the ring for the 1912 presidential election . ”\",\n \"hl_sentences\": \"When House Republicans passed a measure to significantly reduce tariffs on several imported goods , Taft endorsed the Senate version , later known as the Payne-Aldrich Act of 1909 , which raised tariff rates on over eight hundred products in the original bill . Taft also angered Progressives in his own party when he created the U . S . Chamber of Commerce in 1912 , viewed by many as an attempt to offset the growing influence of the labor union movement at the time .\",\n \"question\": {\n \"cloze_format\": \"___ was a key Progressive item passed by Taft.\",\n \"normal_format\": \"Which of the following was a key Progressive item passed by Taft?\",\n \"question_choices\": [\n \"the Pure Food and Drug Act\",\n \"the U.S. Forestry Service\",\n \"the Mann-Elkins Act\",\n \"the Payne-Aldrich Act\"\n ],\n \"question_id\": \"fs-idm81830848\",\n \"question_text\": \"Which of the following was a key Progressive item passed by Taft?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"When Wilson took office in March 1913 , he immediately met with Congress to outline his New Freedom agenda for how progressive interests could be best preserved . His plan was simple : regulate the banks and big businesses , and lower tariff rates to increase international trade , increasing competition in the interest of consumers . <hl> Wilson took the unusual step of calling a special session of Congress in April 1913 to tackle the tariff question , which resulted in the Revenue Act of 1913 , also known as the Underwood Tariff Act . <hl> <hl> This legislation lowered tariff rates across the board by approximately 15 percent and completely eliminated tariffs on several imports , including steel , iron ore , woolen products , and farm tools . <hl> To offset the potential loss of federal revenue , this new law reinstituted the federal income tax , which followed the ratification of the Sixteenth Amendment . This first income tax required married couples who earned $ 4000 or more , and single people who earned $ 3000 or more , to pay a 1 - percent , graduated income tax , with the tax rate getting progressively higher for those who earned more .\",\n \"hl_sentences\": \"Wilson took the unusual step of calling a special session of Congress in April 1913 to tackle the tariff question , which resulted in the Revenue Act of 1913 , also known as the Underwood Tariff Act . This legislation lowered tariff rates across the board by approximately 15 percent and completely eliminated tariffs on several imports , including steel , iron ore , woolen products , and farm tools .\",\n \"question\": {\n \"cloze_format\": \"___ was not an outcome of the Underwood Tariff Act.\",\n \"normal_format\": \"Which of the following was not an outcome of the Underwood Tariff Act?\",\n \"question_choices\": [\n \"It reduced tariffs 15 percent across all imports.\",\n \"It eliminated tariffs for steel.\",\n \"It eliminated tariffs for iron ore.\",\n \"It established a federal banking system to oversee tariffs.\"\n ],\n \"question_id\": \"fs-idp96060096\",\n \"question_text\": \"Which of the following was not an outcome of the Underwood Tariff Act?\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":21,"string":"21"},"chapter_text":{"kind":"string","value":" 21.1 The Origins of the Progressive Spirit in America Learning Objectives By the end of this section, you will be able to: \n\n Describe the role that muckrakers played in catalyzing the Progressive Era \n\n Explain the main features of Progressivism \n\n The Progressive Era was a time of wide-ranging causes and varied movements, where activists and reformers from diverse backgrounds and with very different agendas pursued their goals of a better America. These reformers were reacting to the challenges that faced the country at the end of the nineteenth century: rapid urban sprawl, immigration, corruption, industrial working conditions, the growth of large corporations, women’s rights, and surging anti-Black violence and White supremacy in the South. Investigative journalists of the day uncovered social inequality and encouraged Americans to take action. The campaigns of the Progressives were often grassroots in their origin. While different causes shared some underlying elements, each movement largely focused on its own goals, be it the right of women to vote, the removal of alcohol from communities, or the desire for a more democratic voting process.\n\n THE MUCKRAKERS \n\n A group of journalists and writers collectively known as muckrakers provided an important spark that ignited the Progressive movement. Unlike the “yellow journalists” who were interested only in sensationalized articles designed to sell newspapers, muckrakers exposed problems in American society and urged the public to identify solutions. Whether those problems were associated with corrupt machine politics, poor working conditions in factories, or the questionable living conditions of the working class (among others), muckrakers shined a light on the problem and provoked outraged responses from Americans. President Theodore Roosevelt knew many of these investigative journalists well and considered himself a Progressive. Yet, unhappy with the way they forced agendas into national politics, he was the one who first gave them the disparaging nickname “muckrakers,” invoking an ill-spirited character obsessed with filth from The Pilgrim’s Progress , a 1678 Christian allegory written by John Bunyan.\n\n Beginning in the second half of the nineteenth century, these Progressive journalists sought to expose critical social problems and exhort the public to take action. In his book, How the Other Half Lives (1890), journalist and photographer Jacob Riis used photojournalism to capture the dismal and dangerous living conditions in working-class tenements in New York City ( Figure 21.3 ). Ida Tarbell, perhaps the most well-known female muckraker, wrote a series of articles on the dangers of John D. Rockefeller’s powerful monopoly, Standard Oil. Her articles followed Henry Demarest Lloyd’s book, Wealth Against Commonwealth , published in 1894, which examined the excesses of Standard Oil. Other writers, like Lincoln Steffens, explored corruption in city politics, or, like Ray Stannard Baker, researched unsafe working conditions and low pay in the coal mines.\n\n The work of the muckrakers not only revealed serious problems in American society, but also agitated, often successfully, for change. Their articles, in magazines such as McClure’s , as well as books garnered attention for issues such as child labor, anti-trust, big business break-ups, and health and safety. Progressive activists took up these causes and lobbied for legislation to address some of the ills troubling industrial America. \n\n THE FEATURES OF PROGRESSIVISM \n\nMuckrakers drew public attention to some of the most glaring inequities and scandals that grew out of the social ills of the Gilded Age and the hands-off approach of the federal government since the end of Reconstruction. These writers by and large addressed a White, middle-class and elite, native-born audience, even though Progressive movements and organizations involved a diverse range of Americans. What united these Progressives beyond their different backgrounds and causes was a set of uniting principles, however. Most strove for a perfection of democracy, which required the expansion of suffrage to worthy citizens and the restriction of political participation for those considered “unfit” on account of health, education, or race. Progressives also agreed that democracy had to be balanced with an emphasis on efficiency, a reliance on science and technology, and deference to the expertise of professionals. They repudiated party politics but looked to government to regulate the modern market economy. And they saw themselves as the agents of social justice and reform, as well as the stewards and guides of workers and the urban poor. Often, reformers’ convictions and faith in their own expertise led them to dismiss the voices of the very people they sought to help.\n\nThe expressions of these Progressive principles developed at the grassroots level. It was not until Theodore Roosevelt unexpectedly became president in 1901 that the federal government would engage in Progressive reforms. Before then, Progressivism was work done by the people, for the people. What knit Progressives together was the feeling that the country was moving at a dangerous pace in a dangerous direction and required the efforts of everyday Americans to help put it back on track.\n 21.2 Progressivism at the Grassroots Level Learning Objectives By the end of this section, you will be able to: \n\n Identify specific examples of grassroots Progressivism relating to the spread of democracy, efficiency in government, and social justice \n\n Describe the more radical movements associated with the Progressive Era \n\n A wide variety of causes fell under the Progressive label. For example, Wisconsin’s Robert M. (“Fighting Bob”) La Follette, one of the most Progressive politicians of his day, fought hard to curb the power of special interests in politics and reform the democratic process at state and local levels. Others sought out safer working conditions for factory workers. Different groups prioritized banning the sale of alcohol, which, they believed, was the root of much of the trouble for the working poor. No matter what the cause, Progressive campaigns often started with issues brought to the public’s attention by muckraking journalists. EXPANDING DEMOCRACY \n\nOne of the key ideals that Progressives considered vital to the growth and health of the country was the concept of a perfected democracy. They felt, quite simply, that Americans needed to exert more control over their government. This shift, they believed, would ultimately lead to a system of government that was better able to address the needs of its citizens. Grassroots Progressives pushed forward their agenda of direct democracy through the passage of three state-level reforms .\n\nThe first law involved the creation of the direct primary . Prior to this time, the only people who had a hand in selecting candidates for elections were delegates at conventions. Direct primaries allowed party members to vote directly for a candidate, with the nomination going to the one with the most votes. This was the beginning of the current system of holding a primary election before a general election. South Carolina adopted this system for statewide elections in 1896; in 1901, Florida became the first state to use the direct primary in nominations for the presidency. It is the method currently used in three-quarters of U.S. states.\n\nAnother series of reforms pushed forward by Progressives that sought to sidestep the power of special interests in state legislatures and restore the democratic political process were three election innovations—the initiative , referendum , and recall . The first permitted voters to enact legislation by petitioning to place an idea, or initiative, on the ballot. In 1898, South Dakota became the first state to allow initiatives to appear on a ballot. By 1920, twenty states had adopted the procedure. The second innovation allowed voters to counteract legislation by holding a referendum—that is, putting an existing law on the ballot for voters to either affirm or reject. Currently twenty-four states allow some form of initiative and referendum. The third element of this direct democracy agenda was the recall. The recall permitted citizens to remove a public official from office through a process of petition and vote, similar to the initiative and referendum. While this measure was not as widely adopted as the others, Oregon, in 1910, became the first state to allow recalls. By 1920, twelve states had adopted this tool. It has only been used successfully a handful of times on the statewide level, for example, to remove the governor of North Dakota in 1921, and, more recently, the governor of California in 2003.\n\nProgressives also pushed for democratic reform that affected the federal government. In an effort to achieve a fairer representation of state constituencies in the U.S. Congress, they lobbied for approval of the Seventeenth Amendment to the U.S. Constitution, which mandated the direct election of U.S. senators. The Seventeenth Amendment replaced the previous system of having state legislatures choose senators. William Jennings Bryan, the 1896 Democratic presidential candidate who received significant support from the Populist Party, was among the leading Progressives who championed this cause.\n\n EXPERTISE AND EFFICIENCY \n\n In addition to making government more directly accountable to the voters, Progressives also fought to rid politics of inefficiency, waste, and corruption. Progressives in large cities were particularly frustrated with the corruption and favoritism of machine politics, which wasted enormous sums of taxpayer money and ultimately stalled the progress of cities for the sake of entrenched politicians, like the notorious Democratic Party Boss William Tweed in New York’s Tammany Hall. Progressives sought to change this corrupt system and had success in places like Galveston, Texas, where, in 1901, they pushed the city to adopt a commission system. A hurricane the previous year ( Figure 21.4 ) had led to the collapse of the old city government, which had proved incapable of leading the city through the natural disaster. The storm claimed over eight thousand lives—the highest death toll from a natural disaster in the history of the country—and afterwards, the community had no faith that the existing government could rebuild. The commission system involved the election of a number of commissioners, each responsible for one specific operation of the city, with titles like water commissioner, fire commissioner, police commissioner, and so on. With no single political “boss” in charge, the prevalence of graft and corruption greatly decreased. The commissioner system is widely used in modern cities throughout the United States.\n\nAnother model of municipal government reform took shape in Staunton, Virginia, in 1908, where the citizens switched to the city manager form of government. Designed to avoid the corruption inherent in political machines, the city manager system separated the daily operations of the city from both the electoral process and political parties. In this system, citizens elected city councilors who would pass laws and handle all legislative issues. However, their first job was to hire a city manager to deal with the daily management operation of the city. This person, unlike the politicians, was an engineer or businessman who understood the practical elements of city operations and oversaw city workers. Currently, over thirty-seven hundred cities have adopted the city manager system, including some of the largest cities in the country, such as Austin, Dallas, and Phoenix.\n\n At the state level, perhaps the greatest advocate of Progressive government was Robert La Follette ( Figure 21.5 ). During his time as governor, from 1901 through 1906, La Follette introduced the Wisconsin Idea , wherein he hired experts to research and advise him in drafting legislation to improve conditions in his state. “Fighting Bob” supported numerous Progressive ideas while governor: He signed into law the first workman’s compensation system, approved a minimum wage law, developed a progressive tax law, adopted the direct election of U.S. senators before the subsequent constitutional amendment made it mandatory, and advocated for women’s suffrage. La Follette subsequently served as a popular U.S. senator from Wisconsin from 1906 through 1925, and ran for president on the Progressive Party ticket in 1924. \n\n Many Progressive reformers were also committed to the principle of efficiency in business as well as in government. The growth of large corporations at the time fostered the emergence of a class of professional managers. Fredrick Winslow Taylor, arguably the first American management consultant, laid out his argument of increased industrial efficiency through improvements in human productivity in his book The Principles of Scientific Management (1911). Through time-motion studies and the principles of standardization, Taylor sought to place workers in the most efficient positions of the industrial process. Management, he argued, should determine the work routine, leaving workers to simply execute the task at hand. The image below ( Figure 21.6 ) shows a machinist in a factory where Taylor had consulted; he is alone and focused solely on his job. Progressive in its emphasis on efficiency, the use of science, and the reliance on experts, Taylorism , as scientific management became known, was not widely popular among workers who resented managerial authority and the loss of autonomy over their work. Many workers went on strikes in response, although some favored Taylor’s methods, since their pay was directly linked to the productivity increases that his methods achieved and since increased efficiency allowed companies to charge consumers lower prices.\n\n SOCIAL JUSTICE \n\n The Progressives’ work towards social justice took many forms. In some cases, it was focused on those who suffered due to pervasive inequality, such as African Americans, other ethnic groups, and women. In others, the goal was to help those who were in desperate need due to circumstance, such as poor immigrants from southern and eastern Europe who often suffered severe discrimination, the working poor, and those with ill health. Women were in the vanguard of social justice reform. Jane Addams, Lillian Wald, and Ellen Gates Starr, for example, led the settlement house movement of the 1880s (discussed in a previous chapter). Their work to provide social services, education, and health care to working-class women and their children was among the earliest Progressive grassroots efforts in the country.\n\n Building on the successes of the settlement houses, social justice reformers took on other, related challenges. The National Child Labor Committee (NCLC), formed in 1904, urged the passage of labor legislation to ban child labor in the industrial sector. In 1900, U.S. census records indicated that one out of every six children between the ages of five and ten were working, a 50-percent increase over the previous decade. If the sheer numbers alone were not enough to spur action, the fact that managers paid child workers noticeably less for their labor gave additional fuel to the NCLC’s efforts to radically curtail child labor. The committee employed photographer Lewis Hine to engage in a decade-long pictorial campaign to educate Americans on the plight of children working in factories ( Figure 21.7 ).\n\n Although low-wage industries fiercely opposed any federal restriction on child labor, the NCLC did succeed in 1912, urging President William Howard Taft to sign into law the creation of the U.S. Children’s Bureau. As a branch of the Department of Labor, the bureau worked closely with the NCLC to bring greater awareness to the issue of child labor. In 1916, the pressure from the NCLC and the general public resulted in the passage of the Keating-Owen Act, which prohibited the interstate trade of any goods produced with child labor. Although the U.S. Supreme Court later declared the law unconstitutional, Keating-Owen reflected a significant shift in the public perception of child labor. Finally, in 1938, the passage of the Fair Labor Standards Act signaled the victory of supporters of Keating-Owen. This new law outlawed the interstate trade of any products produced by children under the age of sixteen. \n\n Florence Kelley, a Progressive supporter of the NCLC, championed other social justice causes as well. As the first general secretary of the National Consumers League, which was founded in 1899 by Jane Addams and others, Kelley led one of the original battles to try and secure safety in factory working conditions. She particularly opposed sweatshop labor and urged the passage of an eight-hour-workday law in order to specifically protect women in the workplace. Kelley’s efforts were initially met with strong resistance from factory owners who exploited women’s labor and were unwilling to give up the long hours and low wages they paid in order to offer the cheapest possible product to consumers. But in 1911, a tragedy turned the tide of public opinion in favor of Kelley’s cause. On March 25 of that year, a fire broke out at the Triangle Shirtwaist Company on the eighth floor of the Asch building in New York City, resulting in the deaths of 146 garment workers, most of them young, immigrant women ( Figure 21.8 ). Management had previously blockaded doors and fire escapes in an effort to control workers and keep out union organizers; in the blaze, many died due to the crush of bodies trying to evacuate the building. Others died when they fell off the flimsy fire escape or jumped to their deaths to escape the flames. This tragedy provided the National Consumers League with the moral argument to convince politicians of the need to pass workplace safety laws and codes. \n\n My Story William Shepherd on the Triangle Shirtwaist Factory Fire The tragedy of the Triangle Shirtwaist Factory fire was a painful wake-up call to a country that was largely ignoring issues of poor working conditions and worker health and safety. While this fire was far from the only instance of worker death, the sheer number of people killed—almost one hundred fifty—and the fact they were all young women, made a strong impression. Furthering the power of this tragedy was the first-hand account shared by William Shepherd, a United Press reporter who was on the scene, giving his eyewitness account over a telephone. His account appeared, just two days later, in the Milwaukee Journal , and word of the tragedy spread from there. Public outrage over their deaths was enough to give the National Consumers League the power it needed to push politicians to get involved.\n\n \n\nI saw every feature of the tragedy visible from outside the building. I learned a new sound—a more horrible sound than description can picture. It was the thud of a speeding, living body on a stone sidewalk.\n\nThud-dead, thud-dead, thud-dead, thud-dead.Sixty-two thud-deads. I call them that, because the sound and the thought of death came to me each time, at the same instant. There was plenty of chance to watch them as they came down. The height was eighty feet.\n\nThe first ten thud-deads shocked me. I looked up—saw that there were scores of girls at the windows. The flames from the floor below were beating in their faces. Somehow I knew that they, too, must come down. . . .\n\nA policeman later went about with tags, which he fastened with wires to the wrists of the dead girls, numbering each with a lead pencil, and I saw him fasten tag no. 54 to the wrist of a girl who wore an engagement ring. A fireman who came downstairs from the building told me that there were at least fifty bodies in the big room on the seventh floor. Another fireman told me that more girls had jumped down an air shaft in the rear of the building. I went back there, into the narrow court, and saw a heap of dead girls. . . .\n\nThe floods of water from the firemen’s hose that ran into the gutter were actually stained red with blood. I looked upon the heap of dead bodies and I remembered these girls were the shirtwaist makers. I remembered their great strike of last year in which these same girls had demanded more sanitary conditions and more safety precautions in the shops. These dead bodies were the answer.\n\n \n\n What do you think about William Shepherd’s description? What effect do you think it had on newspaper readers in the Midwest? Another cause that garnered support from a key group of Progressives was the prohibition of liquor. This crusade, which gained followers through the Woman’s Christian Temperance Union (WCTU) and the Anti-Saloon League, directly linked Progressivism with morality and Christian reform initiatives, and saw in alcohol both a moral vice and a practical concern, as workingmen spent their wages on liquor and saloons, often turning violent towards each other or their families at home. The WCTU and Anti-Saloon League moved the efforts to eliminate the sale of alcohol from a bar-to-bar public opinion campaign to one of city-to-city and state-by-state votes ( Figure 21.9 ). Through local option votes and subsequent statewide initiatives and referendums, the Anti-Saloon League succeeded in urging 40 percent of the nation’s counties to “go dry” by 1906, and a full dozen states to do the same by 1909. Their political pressure culminated in the passage of the Eighteenth Amendment to the U.S. Constitution, ratified in 1919, which prohibited the manufacture, sale, and transportation of alcoholic beverages nationwide. \n\n RADICAL PROGRESSIVES \n\n The Progressive Era also witnessed a wave of radicalism, with leaders who believed that America was beyond reform and that only a complete revolution of sorts would bring about the necessary changes. The radicals had early roots in the labor and political movements of the mid-nineteenth century but soon grew to feel that the more moderate Progressive ideals were inadequate. Conversely, one reason why mainstream Progressives felt the need to succeed on issues of social inequity was because radicals offered remedies that middle-class Americans considered far more dangerous. The two most prominent radical movements to emerge at the beginning of the century were the Socialist Party of America (SPA), founded in 1901, and the Industrial Workers of the World (IWW), founded in 1905, whose emphasis on worker empowerment deviated from the more paternalistic approach of Progressive reformers.\n\nLabor leader Eugene Debs, disenchanted with the failures of the labor movement, was a founding member and prominent leader of the SPA ( Figure 21.10 ). Advocating for change via the ballot box, the SPA sought to elect Socialists to positions at the local, state, and federal levels in order to initiate change from within. Between 1901 and 1918, the SPA enjoyed tremendous success, electing over seventy Socialist mayors, over thirty state legislators, and two U.S. congressmen, Victor Berger from Wisconsin and Meyer London from New York. Debs himself ran for president as the SPA candidate in five elections between 1900 and 1920, twice earning nearly one million votes.\n\n As had been true for the Populist and Progressive movements, the radical movement suffered numerous fissures. Although Debs established a tenuous relationship with Samuel Gompers and the American Federation of Labor, some within the Socialist Party favored a more radical political stance than Debs’s craft union structure. As a result, William “Big Bill” Haywood formed the more radical IWW, or Wobblies , in 1905. Although he remained an active member of the Socialist Party until 1919, Haywood appreciated the outcry of the more radical arm of the party that desired an industrial union approach to labor organization. The IWW advocated for direct action and, in particular, the general strike, as the most effective revolutionary method to overthrow the capitalist system. By 1912, the Wobblies had played a significant role in a number of major strikes, including the Paterson Silk Strike, the Lawrence Textile Strike, and the Mesabi Range Iron Strike. The government viewed the Wobblies as a significant threat, and in a response far greater than their actions warranted, targeted them with arrests, tar-and-featherings, shootings, and lynchings. Both the Socialist Party and the IWW reflected elements of the Progressive desire for democracy and social justice. The difference was simply that for this small but vocal minority in the United States, the corruption of government at all levels meant that the desire for a better life required a different approach. What they sought mirrored the work of all grassroots Progressives, differing only in degree and strategy. \n 21.3 New Voices for Women and African Americans Learning Objectives By the end of this section, you will be able to: \n\n Understand the origins and growth of the women’s rights movement \n\n Identify the different strands of the early African American civil rights movement \n\n The Progressive drive for a more perfect democracy and social justice also fostered the growth of two new movements that attacked the oldest and most long-standing betrayals of the American promise of equal opportunity and citizenship—the disfranchisement of women and civil rights for African Americans. African Americans across the nation identified an agenda for civil rights and economic opportunity during the Progressive Era, but they disagreed strongly on how to meet these goals in the face of universal discrimination and disfranchisement, segregation, and racial violence in the South. And beginning in the late nineteenth century, the women’s movement cultivated a cadre of new leaders, national organizations, and competing rationales for women’s rights—especially the right to vote. LEADERS EMERGE IN THE WOMEN’S MOVEMENT \n\nWomen like Jane Addams and Florence Kelley were instrumental in the early Progressive settlement house movement, and female leaders dominated organizations such as the WCTU and the Anti-Saloon League. From these earlier efforts came new leaders who, in their turn, focused their efforts on the key goal of the Progressive Era as it pertained to women: the right to vote.\n\n Women had first formulated their demand for the right to vote in the Declaration of Sentiments at a convention in Seneca Falls, New York, in 1848, and saw their first opportunity of securing suffrage during Reconstruction when legislators—driven by racial animosity—sought to enfranchise women to counter the votes of Black men following the ratification of the Fifteenth Amendment. By 1900, the western frontier states of Colorado, Idaho, Utah, and Wyoming had already responded to women’s movements with the right to vote in state and local elections, regardless of gender. They conceded to the suffragists’ demands, partly in order to attract more women to these male-dominated regions. But women’s lives in the West also rarely fit with the nineteenth-century ideology of “separate spheres” that had legitimized the exclusion of women from the rough-and-tumble party competitions of public politics. In 1890, the National American Women’s Suffrage Association (NAWSA) organized several hundred state and local chapters to urge the passage of a federal amendment to guarantee a woman’s right to vote. Its leaders, Elizabeth Cady Stanton and Susan B. Anthony, were veterans of the women’s suffrage movement and had formulated the first demand for the right to vote at Seneca Falls in 1848 ( Figure 21.11 ). Under the subsequent leadership of Carrie Chapman Catt, beginning in 1900, the group decided to make suffrage its first priority. Soon, its membership began to grow. Using modern marketing efforts like celebrity endorsements to attract a younger audience, the NAWSA became a significant political pressure group for the passage of an amendment to the U.S. Constitution.\n\n For some in the NAWSA, however, the pace of change was too slow. Frustrated with the lack of response by state and national legislators, Alice Paul, who joined the organization in 1912, sought to expand the scope of the organization as well as to adopt more direct protest tactics to draw greater media attention. When others in the group were unwilling to move in her direction, Paul split from the NAWSA to create the Congressional Union for Woman Suffrage, later renamed the National Woman’s Party, in 1913. Known as the Silent Sentinels ( Figure 21.12 ), Paul and her group picketed outside the White House for nearly two years, starting in 1917. In the latter stages of their protests, many women, including Paul, were arrested and thrown in jail, where they staged a hunger strike as self-proclaimed political prisoners. Prison guards ultimately force-fed Paul to keep her alive. At a time—during World War I—when women volunteered as army nurses, worked in vital defense industries, and supported Wilson’s campaign to “make the world safe for democracy,” the scandalous mistreatment of Paul embarrassed President Woodrow Wilson. Enlightened to the injustice toward all American women, he changed his position in support of a woman’s constitutional right to vote. While Catt and Paul used different strategies, their combined efforts brought enough pressure to bear for Congress to pass the Nineteenth Amendment, which prohibited voter discrimination on the basis of sex, during a special session in the summer of 1919. Subsequently, the required thirty-six states approved its adoption, with Tennessee doing so in August of 1920, in time for that year’s presidential election. \n\n Defining American The Anti-Suffragist Movement The early suffragists may have believed that the right to vote was a universal one, but they faced waves of discrimination and ridicule from both men and women. The image below ( Figure 21.13 ) shows one of the organizations pushing back against the suffragist movement, but much of the anti-suffrage campaign was carried out through ridiculing postcards and signs that showed suffragists as sexually wanton, grasping, irresponsible, or impossibly ugly. Men in anti-suffragist posters were depicted as henpecked, crouching to clean the floor, while their suffragist wives marched out the door to campaign for the vote. They also showed cartoons of women gambling, drinking, and smoking cigars, that is, taking on men’s vices, once they gained voting rights. \n\n Other anti-suffragists believed that women could better influence the country from outside the realm of party politics, through their clubs, petitions, and churches. Many women also opposed women’s suffrage because they thought the dirty world of politics was a morass to which ladies should not be exposed. The National Association Opposed to Woman Suffrage formed in 1911; around the country, state representatives used the organization’s speakers, funds, and literature to promote the anti-suffragist cause. As the link below illustrates, the suffragists endured much prejudice and backlash in their push for equal rights. \n\n LEADERS EMERGE IN THE EARLY CIVIL RIGHTS MOVEMENT \n\n Racial mob violence against African Americans permeated much of the “New South”—and, to a lesser extent, the West, where Mexican Americans and other immigrant groups also suffered severe discrimination and violence—by the late nineteenth century. The Ku Klux Klan and a system of Jim Crow laws governed much of the South (discussed in a previous chapter). White middle-class reformers were appalled at the violence of race relations in the nation but typically shared the belief in racial characteristics and the superiority of Anglo-Saxon Whites over African Americans, Asians, “ethnic” Europeans, Native Americans, and Latin American populations. Southern reformers considered segregation a Progressive solution to racial violence; across the nation, educated middle-class Americans enthusiastically followed the work of eugenicists who identified virtually all human behavior as inheritable traits and issued awards at county fairs to families and individuals for their “racial fitness.” It was against this tide that African American leaders developed their own voice in the Progressive Era, working along diverse paths to improve the lives and conditions of African Americans throughout the country.\n\n Born into slavery in Virginia in 1856, Booker T. Washington became an influential African American leader at the outset of the Progressive Era. In 1881, he became the first principal for the Tuskegee Normal and Industrial Institute in Alabama, a position he held until he died in 1915. Tuskegee was an all-Black “normal school”—an old term for a teachers’ college—teaching African Americans a curriculum geared towards practical skills such as cooking, farming, and housekeeping. Graduates would often then travel through the South, teaching new farming and industrial techniques to rural communities. Washington extolled the school’s graduates to focus on the Black community’s self-improvement and prove that they were productive members of society even in freedom—something White Americans throughout the nation had always doubted.\n\n In a speech delivered at the Cotton States and International Exposition in Atlanta in 1895, which was meant to promote the economy of a “New South,” Washington proposed what came to be known as the Atlanta Compromise ( Figure 21.14 ). Speaking to a racially mixed audience, Washington called upon African Americans to work diligently for their own uplift and prosperity rather than preoccupy themselves with political and civil rights. Their success and hard work, he implied, would eventually convince southern Whites to grant these rights. Not surprisingly, most Whites liked Washington’s model of race relations, since it placed the burden of change on Blacks and required nothing of them. Wealthy industrialists such as Andrew Carnegie and John D. Rockefeller provided funding for many of Washington’s self-help programs, as did Sears, Roebuck & Co. co-founder Julius Rosenwald, and Washington was the first African American invited to the White House by President Roosevelt in 1901. At the same time, his message also appealed to many in the Black community, and some attribute this widespread popularity to his consistent message that social and economic growth, even within a segregated society, would do more for African Americans than an all-out agitation for equal rights on all fronts. \n\n Yet, many African Americans disagreed with Washington’s approach. Much in the same manner that Alice Paul felt the pace of the struggle for women’s rights was moving too slowly under the NAWSA, some within the African American community felt that immediate agitation for the rights guaranteed under the Thirteenth, Fourteenth, and Fifteenth Amendments, established during the immediate aftermath of the Civil War, was necessary. In 1905, a group of prominent civil rights leaders, led by W. E. B. Du Bois, met in a small hotel on the Canadian side of Niagara Falls—where segregation laws did not bar them from hotel accommodations—to discuss what immediate steps were needed for equal rights ( Figure 21.15 ). Du Bois, a professor at the all-Black Atlanta University and the first African American with a doctorate from Harvard, emerged as the prominent spokesperson for what would later be dubbed the Niagara Movement . By 1905, he had grown wary of Booker T. Washington’s calls for African Americans to accommodate White racism and focus solely on self-improvement. Du Bois, and others alongside him, wished to carve a more direct path towards equality that drew on the political leadership and litigation skills of the Black, educated elite, which he termed the “talented tenth.” At the meeting, Du Bois led the others in drafting the “Declaration of Principles,” which called for immediate political, economic, and social equality for African Americans. These rights included universal suffrage, compulsory education, and the elimination of the convict lease system in which tens of thousands of Blacks had endured slavery-like conditions in southern road construction, mines, prisons, and penal farms since the end of Reconstruction. Within a year, Niagara chapters had sprung up in twenty-one states across the country. By 1908, internal fights over the role of women in the fight for African American equal rights lessened the interest in the Niagara Movement. But the movement laid the groundwork for the creation of the National Association for the Advancement of Colored People ( NAACP ), founded in 1909. Du Bois served as the influential director of publications for the NAACP from its inception until 1933. As the editor of the journal The Crisis , Du Bois had a platform to express his views on a variety of issues facing African Americans in the later Progressive Era, as well as during World War I and its aftermath. In both Washington and Du Bois, African Americans found leaders to push forward the fight for their place in the new century, each with a very different strategy. Both men cultivated ground for a new generation of African American spokespeople and leaders who would then pave the road to the modern civil rights movement after World War II. \n 21.4 Progressivism in the White House Learning Objectives By the end of this section, you will be able to: \n\n Explain the key features of Theodore Roosevelt’s “Square Deal” \n\n Explain the key features of William Howard Taft’s Progressive agenda \n\n Identify the main pieces of legislation that Woodrow Wilson’s “New Freedom” agenda comprised \n\nProgressive groups made tremendous strides on issues involving democracy, efficiency, and social justice. But they found that their grassroots approach was ill-equipped to push back against the most powerful beneficiaries of growing inequality, economic concentration, and corruption—big business. In their fight against the trusts, Progressives needed the leadership of the federal government, and they found it in Theodore Roosevelt in 1901, through an accident of history.\n\nIn 1900, a sound economic recovery, a unifying victory in the Spanish-American War, and the annexation of the Philippines had helped President William McKinley secure his reelection with the first solid popular majority since 1872. His new vice president was former New York Governor and Assistant Secretary of the Navy, Theodore Roosevelt. But when an assassin shot and killed President McKinley in 1901 ( Figure 21.16 ) at the Pan-American Exposition in Buffalo, New York, Theodore Roosevelt unexpectedly became the youngest president in the nation’s history. More importantly, it ushered in a new era of progressive national politics and changed the role of the presidency for the twentieth century.\n\n BUSTING THE TRUSTS \n\n Roosevelt’s early career showed him to be a dynamic leader with a Progressive agenda. Many Republican Party leaders disliked Roosevelt’s Progressive ideas and popular appeal and hoped to end his career with a nomination to the vice presidency—long considered a dead end in politics. When an assassin’s bullet toppled this scheme, Mark Hanna, a prominent Republican senator and party leader, lamented, “Now look! That damned cowboy is now president!”\n\n As the new president, however, Roosevelt moved cautiously with his agenda while he finished out McKinley’s term. Roosevelt kept much of McKinley’s cabinet intact, and his initial message to Congress gave only one overriding Progressive goal for his presidency: to eliminate business trusts. In the three years prior to Roosevelt’s presidency, the nation had witnessed a wave of mergers and the creation of mega-corporations. To counter this trend, Roosevelt created the Department of Commerce and Labor in 1903, which included the Bureau of Corporations, whose job it was to investigate trusts. He also asked the Department of Justice to resume prosecutions under the Sherman Antitrust Act of 1890. Intended to empower federal prosecutors to ban monopolies as conspiracies against interstate trade, the law had run afoul of a conservative Supreme Court.\n\n In 1902, Roosevelt launched his administration’s first antitrust suit against the Northern Securities Trust Company, which included powerful businessmen, like John D. Rockefeller and J. P. Morgan, and controlled many of the large midwestern railroads. The suit wound through the judicial system, all the way to the U.S. Supreme Court. In 1904, the highest court in the land ultimately affirmed the ruling to break up the trust in a narrow five-to-four vote. For Roosevelt, that was enough of a mandate; he immediately moved against other corporations as well, including the American Tobacco Company and—most significantly—Rockefeller’s Standard Oil Company. Although Roosevelt enjoyed the nickname “the Trustbuster,” he did not consider all trusts dangerous to the public welfare. The “good trusts,” Roosevelt reasoned, used their power in the marketplace and economies of scale to deliver goods and services to customers more cheaply. For example, he allowed Morgan’s U.S. Steel Corporation to continue its operations and let it take over smaller steel companies. At the same time, Roosevelt used the presidency as a “bully pulpit” to publicly denounce “bad trusts”—those corporations that exploited their market positions for short-term gains—before he ordered prosecutions by the Justice Department. In total, Roosevelt initiated over two dozen successful anti-trust suits, more than any president before him. Roosevelt also showed in other contexts that he dared to face the power of corporations. When an anthracite coal strike gripped the nation for much of the year in 1902, Roosevelt directly intervened in the dispute and invited both sides to the White House to negotiate a deal that included minor wage increases and a slight improvement in working hours. For Roosevelt, his intervention in the matter symbolized his belief that the federal government should adopt a more proactive role and serve as a steward of all Americans ( Figure 21.17 ). This stood in contrast to his predecessors, who had time and again bolstered industrialists in their fight against workers’ rights with the deployment of federal troops. \n\n THE SQUARE DEAL \n\n Roosevelt won his second term in 1904 with an overwhelming 57 percent of the popular vote. After the election, he moved quickly to enact his own brand of Progressivism, which he called a Square Deal for the American people. Early in his second term, Roosevelt read muckraker Upton Sinclair’s 1905 novel and exposé on the meatpacking industry, The Jungle . Although Roosevelt initially questioned the book due to Sinclair’s professed Socialist leanings, a subsequent presidential commission investigated the industry and corroborated the deplorable conditions under which Chicago’s meatpackers processed meats for American consumers. Alarmed by the results and under pressure from an outraged public disgusted with the revelations, Roosevelt moved quickly to protect public health. He urged the passage of two laws to do so. The first, the Meat Inspection Act of 1906, established a system of government inspection for meat products, including grading the meat based on its quality. This standard was also used for imported meats. The second was the Pure Food and Drug Act of 1906, which required labels on all food and drug products that clearly stated the materials in the product. The law also prohibited any “adulterated” products, a measure aimed at some specific, unhealthy food preservatives. For Sinclair, this outcome was a disappointment nonetheless, since he had sought to draw attention to the plight of workers in the slaughterhouses, not the poor quality of the meat products. “I aimed at the public’s heart, and by accident I hit it in the stomach,” he concluded with frustration.\n\n Another key element of Roosevelt’s Progressivism was the protection of public land ( Figure 21.18 ). Roosevelt was a longtime outdoorsman, with an interest that went back to his childhood and college days, as well as his time cattle ranching in the West, and he chose to appoint his good friend Gifford Pinchot as the country’s first chief of the newly created U.S. Forestry Service. Under Pinchot’s supervision, the department carved out several nature habitats on federal land in order to preserve the nation’s environmental beauty and protect it from development or commercial use. Apart from national parks like Oregon’s Crater Lake or Colorado’s Mesa Verde, and monuments designed for preservation, Roosevelt conserved public land for regulated use for future generations. To this day, the 150 national forests created under Roosevelt’s stewardship carry the slogan “land of many uses.” In all, Roosevelt established eighteen national monuments, fifty-one federal bird preserves, five national parks, and over one hundred fifty national forests, which amounted to about 230 million acres of public land.\n\n In his second term in office, Roosevelt signed legislation on Progressive issues such as factory inspections, child labor, and business regulation. He urged the passage of the Elkins Act of 1903 and the Hepburn Act of 1906, both of which strengthened the position of the Interstate Commerce Commission to regulate railroad prices. These laws also extended the Commission’s authority to regulate interstate transportation on bridges, ferries, and even oil pipelines. As the 1908 election approached, Roosevelt was at the height of popularity among the American public, if not among the big businesses and conservative leaders of his own Republican Party. Nonetheless, he promised on the night of his reelection in 1904 that he would not seek a third term. Roosevelt stepped aside as the election approached, but he did hand-pick a successor—Secretary of War and former Governor General of the Philippines William Howard Taft of Ohio—a personal friend who, he assured the American public, would continue the path of the “Square Deal” ( Figure 21.19 ). With such a ringing endorsement, Taft easily won the 1908 presidential election, defeating three-time Democratic presidential nominee William Jennings Bryan, whose ideas on taxes and corporate regulations reminded voters of the more far-reaching Populist platforms of Bryan’s past candidacies. \n\n THE TAFT PRESIDENCY \n\n Although six feet tall and nearly 340 pounds, as Roosevelt’s successor, Taft had big shoes to fill. The public expected much from Roosevelt’s hand-picked replacement, as did Roosevelt himself, who kept a watchful eye over Taft’s presidency.\n\n The new president’s background suggested he would be a strong administrator. He had previously served as the governor of the Philippines following the Spanish-American War , had a distinguished judicial career, and served as Roosevelt’s Secretary of War from 1904 to 1908. Republican leaders, however, were anxious to reestablish tighter control over the party after Roosevelt’s departure, and they left Taft little room to maneuver. He stayed the course of his predecessor by signing the Mann-Elkins Act of 1910, which extended the authority of the Interstate Commerce Commission over telephones and telegraphs. Additionally, during his tenure, Congress proposed constitutional amendments to authorize a federal income tax and mandate the direct election of U.S. senators. But even though Taft initiated twice as many antitrust suits against big business as Roosevelt, he lacked the political negotiating skills and focus on the public good of his predecessor, who felt betrayed when Taft took J.P. Morgan’s U.S. Steel Corporation to court over an acquisition that Roosevelt had promised Morgan would not result in a prosecution.\n\n Political infighting within his own party exposed the limitations of Taft’s presidential authority, especially on the issue of protective tariffs. When House Republicans passed a measure to significantly reduce tariffs on several imported goods, Taft endorsed the Senate version, later known as the Payne-Aldrich Act of 1909, which raised tariff rates on over eight hundred products in the original bill. Taft also angered Progressives in his own party when he created the U.S. Chamber of Commerce in 1912, viewed by many as an attempt to offset the growing influence of the labor union movement at the time. The rift between Taft and his party’s Progressives widened when the president supported conservative party candidates for the 1910 House and Senate elections. Taft’s biggest political blunder came in the area of land conservation. In 1909, Taft’s Secretary of the Interior, Richard Ballinger, approved the sale of millions of acres of federal land to a company for which he had previously worked over Gifford Pinchot’s objections. Pinchot publicly criticized the secretary for violating the principle of conservation and for his conflict of interest—a charge that in the public debate also reflected on the president. Taft fired Pinchot, a move that widened the gap between him and the former president. Upon his return from Africa, Roosevelt appeared primed to attack. He referred to the sitting president as a “fathead” and a “puzzlewit,” and announced his intention to “throw my hat in the ring for the 1912 presidential election.” \n\n THE 1912 PRESIDENTIAL ELECTION \n\n Although not as flamboyant or outwardly progressive as Roosevelt, Taft’s organizational skills and generally solid performance as president aligned with the party leadership’s concerns over another Roosevelt presidency and secured for him the Republican Party’s nomination. Angry over this snub, in 1912, Roosevelt and the other Progressive Republicans bolted from the Republican Party and formed the Progressive Party . His popularity had him hoping to win the presidential race as a third-party candidate. When he survived an assassination attempt in Milwaukee, Wisconsin, in October 1912—the assassin’s bullet hit his eyeglass case and only injured him superficially—he turned the near-death experience into a political opportunity. Insisting upon delivering the speech before seeking medical attention, he told the crowd, “It takes more than a bullet to kill a bull moose!” The moniker stuck, and Roosevelt’s Progressive Party would be known as the Bull Moose Party for the remainder of the campaign ( Figure 21.20 ).\n\nThe Democrats realized that a split Republican Party gave them a good chance of regaining the White House for the first time since 1896. They found their candidate in the Progressive governor of New Jersey, Woodrow Wilson. A former history professor and president at Princeton University, Wilson had an academic demeanor that appealed to many Progressive reformers. Many Democrats also viewed Wilson as a Washington outsider who had made far fewer political enemies than Roosevelt and Taft.\n\n Taft never truly campaigned for the post, did not deliver a single speech, and did not seem like a serious contender. In their campaigns, Roosevelt and Wilson formulated competing Progressive platforms. Wilson described his more moderate approach as one of New Freedom , which stood for a smaller federal government to protect public interests from the evils associated with big businesses and banks. Roosevelt campaigned on the promise of New Nationalism , a charge that he said required a vigorous and powerful federal government to protect public interests. He sought to capitalize on the stewardship approach that he had made famous during his previous administration. \n\n Wilson won the 1912 election with over six million votes, with four million votes going to Roosevelt and three and one-half million for Taft. The internal split among Republicans not only cost them the White House but control of the Senate as well—and Democrats had already won a House majority in 1910. Wilson won the presidency with just 42 percent of the popular vote, which meant that he would have to sway a large number of voters should he have any aspirations for a second term. \n\n Defining American The Unprecedented Election of 1912 In his 2002 article on the 1912 election, historian Sidney M. Milkis writes, \n\n The Progressive Party’s “compromise” with public opinion in the United States points to its legacy for American politics and government. Arguably, the failure of the 1912 experiment and the Progressive Party’s demise underscore the incoherence of the Progressive movement. Nevertheless, it was neither the Democrats, nor the Republicans, nor the Socialists who set the tone of the 1912 campaign. It was the Progressives. Beyond the 1912 election, their program of political and social reform has been an enduring feature of American political discourse and electoral struggle. The Progressive Party forged a path of reform that left both social democracy and conservatism—Taft’s constitutional sobriety—behind. Similarly, T.R.’s celebrity, and the popularity of the Progressive doctrine of the people’s right to rule, tended to subordinate the more populist to the more plebiscitary schemes in the platform, such as the initiative, the referendum, and the direct primary, which exalted not the “grass roots” but mass opinion. Indeed, in the wake of the excitement aroused by the Progressive Party, Wilson, whose New Freedom campaign was far more sympathetic to the decentralized state of courts and parties than T.R.’s, felt compelled, as president, to govern as a New Nationalist Progressive. \n\n It is interesting to think of how this most unusual election—one with three major candidates that pitted a former president against an incumbent and a major party contender—related to the larger Progressive movement. The cartoon below is only one of many cartoons of that era that sought to point out the differences between the candidates ( Figure 21.21 ). While Roosevelt and the Progressive Party ultimately lost the election, they required the dialogue of the campaign to remain on the goals of Progressivism, particularly around more direct democracy and business regulation. The American public responded with fervor to Roosevelt’s campaign, partly because of his immense popularity, but partly also because he espoused a kind of direct democracy that gave people a voice in federal politics. Although Wilson and his New Freedom platform won the election, his presidency undertook a more activist role than his campaign suggested. The American public had made clear that, no matter who sat in the White House, they were seeking a more progressive America.\n\n WILSON’S NEW FREEDOM \n\nWhen Wilson took office in March 1913, he immediately met with Congress to outline his New Freedom agenda for how progressive interests could be best preserved. His plan was simple: regulate the banks and big businesses, and lower tariff rates to increase international trade, increasing competition in the interest of consumers. Wilson took the unusual step of calling a special session of Congress in April 1913 to tackle the tariff question, which resulted in the Revenue Act of 1913, also known as the Underwood Tariff Act. This legislation lowered tariff rates across the board by approximately 15 percent and completely eliminated tariffs on several imports, including steel, iron ore, woolen products, and farm tools. To offset the potential loss of federal revenue, this new law reinstituted the federal income tax, which followed the ratification of the Sixteenth Amendment. This first income tax required married couples who earned $4000 or more, and single people who earned $3000 or more, to pay a 1-percent, graduated income tax, with the tax rate getting progressively higher for those who earned more.\n\n Late in 1913, Wilson signed the Federal Reserve Act to regulate the banking industry and establish a federal banking system ( Figure 21.22 ). Designed to remove power over interest rates from the hands of private bankers, the new system created twelve privately owned regional reserve banks regulated by a presidentially appointed Federal Reserve Board. The Board, known informally as the Fed, regulated the interest rate at which reserve banks loaned or distributed money to other banks around the country. Thus, when economic times were challenging, such as during a recession, the Fed could lower this “discount rate” and encourage more borrowing, which put more currency in circulation for people to spend or invest. Conversely, the Fed could curb inflationary trends with interest hikes that discouraged borrowing. This system is still the basis for the country’s modern banking model. \n\n In early 1914, Wilson completed his New Freedom agenda with the passage of the Clayton Antitrust Act. This law expanded the power of the original Sherman Antitrust Act in order to allow the investigation and dismantling of more monopolies. The new act also took on the “interlocking directorates”—competing companies that still operated together in a form of oligopoly or conspiracy to restrain trade. His New Freedom agenda complete, Wilson turned his attention to foreign affairs, as war was quickly encompassing Europe.\n\n THE FINAL VESTIGES OF PROGRESSIVISM \n\n As the 1916 election approached, Wilson’s focus on foreign affairs, as well as the natural effect of his small government agenda, left the 60 percent of the American public who had not voted for him the first time disinclined to change their minds and keep him in office. Realizing this, Wilson began a flurry of new Progressive reforms that impressed the voting public and ultimately proved to be the last wave of the Progressive Era. Some of the important measures that Wilson undertook to pass included the Federal Farm Act, which provided oversight of low-interest loans to millions of farmers in need of debt relief; the Keating-Owen Child Labor Act, which, although later deemed unconstitutional by the U.S. Supreme Court, prohibited the interstate distribution of products by child workers under the age of fourteen; and the Adamson Act, which put in place the first federally mandated eight-hour workday for railroad workers.\n\n Wilson also gained significant support from Jewish voters with his 1916 appointment of the first Jewish U.S. Supreme Court justice, Louis D. Brandeis. Popular among social justice Progressives, Brandeis went on to become one of the most renowned justices on the court for his defense of freedom of speech and right to privacy issues. Finally, Wilson gained the support of many working-class voters with his defense of labor and union rights during a violent coal strike in Ludlow, Colorado, as well as his actions to forestall a potential railroad strike with the passage of the aforementioned Adamson Act. \n\n Wilson’s actions in 1916 proved enough, but barely. In a close presidential election, he secured a second term by defeating former New York governor Charles Evans Hughes by a scant twenty-three electoral votes, and less than 600,000 popular votes. Influential states like Minnesota and New Hampshire were decided by less than four hundred votes. Despite the fact that he ran for reelection with the slogan, “He Kept Us Out of the War,” Wilson could not avoid the reach of World War I much longer. For Wilson and the American public, the Progressive Era was rapidly winding down. Although a few Progressive achievements were still to come in the areas of women’s suffrage and prohibition, the country would soon be gripped by the war that Wilson had tried to avoid during his first term in office. When he took the oath for his second term, on March 4, 1917, Wilson was barely five weeks away from leading the United States in declaring war on Germany, a move that would put an end to the Progressive Era. "}}},{"rowIdx":185,"cells":{"bname":{"kind":"string","value":"anatomy_and_physiology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":""},"intro":{"kind":"string","value":" Chapter Objectives \n\n After studying this chapter, you will be able to:\n\n List and explain the steps involved in fertilization \n\n Describe the major events in embryonic development \n\n Describe the major events in fetal development \n\n Discuss the adaptations of a woman’s body to pregnancy \n\n Describe the physiologic adjustments that the newborn must make in the first hours of extrauterine life \n\n Summarize the physiology of lactation \n\n Classify and describe the different patterns of inheritance \n\n Introduction In approximately nine months, a single cell—a fertilized egg—develops into a fully formed infant consisting of trillions of cells with myriad specialized functions. The dramatic changes of fertilization, embryonic development, and fetal development are followed by remarkable adaptations of the newborn to life outside the womb. An offspring’s normal development depends upon the appropriate synthesis of structural and functional proteins. This, in turn, is governed by the genetic material inherited from the parental egg and sperm, as well as environmental factors. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":0,"ans_text":"most do not reach the oocyte"},"bloom":"1","hl_context":"Fertilization is a numbers game . <hl> During ejaculation , hundreds of millions of sperm ( spermatozoa ) are released into the vagina . <hl> <hl> Almost immediately , millions of these sperm are overcome by the acidity of the vagina ( approximately pH 3.8 ) , and millions more may be blocked from entering the uterus by thick cervical mucus . <hl> <hl> Of those that do enter , thousands are destroyed by phagocytic uterine leukocytes . <hl> <hl> Thus , the race into the uterine tubes , which is the most typical site for sperm to encounter the oocyte , is reduced to a few thousand contenders . <hl> Their journey — thought to be facilitated by uterine contractions — usually takes from 30 minutes to 2 hours . If the sperm do not encounter an oocyte immediately , they can survive in the uterine tubes for another 3 – 5 days . Thus , fertilization can still occur if intercourse takes place a few days before ovulation . In comparison , an oocyte can survive independently for only approximately 24 hours following ovulation . Intercourse more than a day after ovulation will therefore usually not result in fertilization .","hl_sentences":"During ejaculation , hundreds of millions of sperm ( spermatozoa ) are released into the vagina . Almost immediately , millions of these sperm are overcome by the acidity of the vagina ( approximately pH 3.8 ) , and millions more may be blocked from entering the uterus by thick cervical mucus . Of those that do enter , thousands are destroyed by phagocytic uterine leukocytes . Thus , the race into the uterine tubes , which is the most typical site for sperm to encounter the oocyte , is reduced to a few thousand contenders .","question":{"cloze_format":"Although the male ejaculate contains hundreds of millions of sperm, ________.","normal_format":"Which of the following is true, although the male ejaculate contains hundreds of millions of sperm?","question_choices":["most do not reach the oocyte","most are destroyed by the alkaline environment of the uterus","it takes millions to penetrate the outer layers of the oocyte","most are destroyed by capacitation"],"question_id":"fs-id1407729","question_text":"Although the male ejaculate contains hundreds of millions of sperm, ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"corona radiata"},"bloom":"1","hl_context":"As it is swept along the distal uterine tube , the oocyte encounters the surviving capacitated sperm , which stream toward it in response to chemical attractants released by the cells of the corona radiata . <hl> To reach the oocyte itself , the sperm must penetrate the two protective layers . <hl> <hl> The sperm first burrow through the cells of the corona radiata . <hl> Then , upon contact with the zona pellucida , the sperm bind to receptors in the zona pellucida . This initiates a process called the acrosomal reaction in which the enzyme-filled “ cap ” of the sperm , called the acrosome , releases its stored digestive enzymes . These enzymes clear a path through the zona pellucida that allows sperm to reach the oocyte . Finally , a single sperm makes contact with sperm-binding receptors on the oocyte ’ s plasma membrane ( Figure 28.2 ) . The plasma membrane of that sperm then fuses with the oocyte ’ s plasma membrane , and the head and mid-piece of the “ winning ” sperm enter the oocyte interior .","hl_sentences":"To reach the oocyte itself , the sperm must penetrate the two protective layers . The sperm first burrow through the cells of the corona radiata .","question":{"cloze_format":"As sperm first reach the oocyte, they will contact the ________.","normal_format":"As sperm first reach the oocyte, which will they contact?","question_choices":["acrosome","corona radiata","sperm-binding receptors","zona pellucida"],"question_id":"fs-id2346687","question_text":"As sperm first reach the oocyte, they will contact the ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"fertilization"},"bloom":"1","hl_context":"Recall that at the point of fertilization , the oocyte has not yet completed meiosis ; all secondary oocytes remain arrested in metaphase of meiosis II until fertilization . Only upon fertilization does the oocyte complete meiosis . The unneeded complement of genetic material that results is stored in a second polar body that is eventually ejected . At this moment , the oocyte has become an ovum , the female haploid gamete . The two haploid nuclei derived from the sperm and oocyte and contained within the egg are referred to as pronuclei . They decondense , expand , and replicate their DNA in preparation for mitosis . <hl> The pronuclei then migrate toward each other , their nuclear envelopes disintegrate , and the male - and female-derived genetic material intermingles . <hl> <hl> This step completes the process of fertilization and results in a single-celled diploid zygote with all the genetic instructions it needs to develop into a human . <hl>","hl_sentences":"The pronuclei then migrate toward each other , their nuclear envelopes disintegrate , and the male - and female-derived genetic material intermingles . This step completes the process of fertilization and results in a single-celled diploid zygote with all the genetic instructions it needs to develop into a human .","question":{"cloze_format":"Fusion of pronuclei occurs during ________.","normal_format":"During which of the following fusion of pronuclei occurs?","question_choices":["spermatogenesis","ovulation","fertilization","capacitation"],"question_id":"fs-id1288730","question_text":"Fusion of pronuclei occurs during ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"capacitation"},"bloom":"1","hl_context":"During the journey , fluids in the female reproductive tract prepare the sperm for fertilization through a process called capacitation , or priming . The fluids improve the motility of the spermatozoa . They also deplete cholesterol molecules embedded in the membrane of the head of the sperm , thinning the membrane in such a way that will help facilitate the release of the lysosomal ( digestive ) enzymes needed for the sperm to penetrate the oocyte ’ s exterior once contact is made . <hl> Sperm must undergo the process of capacitation in order to have the “ capacity ” to fertilize an oocyte . <hl> If they reach the oocyte before capacitation is complete , they will be unable to penetrate the oocyte ’ s thick outer layer of cells .","hl_sentences":"Sperm must undergo the process of capacitation in order to have the “ capacity ” to fertilize an oocyte .","question":{"cloze_format":"Sperm must first complete ________ to enable the fertilization of an oocyte.","normal_format":"What must sperm first complete to enable the fertilization of an oocyte?","question_choices":["capacitation","the acrosomal reaction","the cortical reaction","the fast block"],"question_id":"fs-id2111179","question_text":"Sperm must first complete ________ to enable the fertilization of an oocyte."},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"blastomeres"},"bloom":"1","hl_context":"Following fertilization , the zygote and its associated membranes , together referred to as the conceptus , continue to be projected toward the uterus by peristalsis and beating cilia of the epithelial cells of the Fallopian tube . During its journey to the uterus , the zygote undergoes five or six rapid mitotic cell divisions . Although each cleavage results in more cells , it does not increase the total volume of the conceptus ( Figure 28.4 ) . <hl> Each daughter cell produced by cleavage is called a blastomere ( blastos = “ germ , ” in the sense of a seed or sprout ) . <hl>","hl_sentences":"Each daughter cell produced by cleavage is called a blastomere ( blastos = “ germ , ” in the sense of a seed or sprout ) .","question":{"cloze_format":"Cleavage produces daughter cells called ________.","normal_format":"What are cleavage produces daughter cells?","question_choices":["trophoblasts","blastocysts","morulae","blastomeres"],"question_id":"fs-id2282515","question_text":"Cleavage produces daughter cells called ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"divides"},"bloom":null,"hl_context":"Approximately 3 days after fertilization , a 16 - cell conceptus reaches the uterus . The cells that had been loosely grouped are now compacted and look more like a solid mass . The name given to this structure is the morula ( morula = “ little mulberry ” ) . <hl> Once inside the uterus , the conceptus floats freely for several more days . <hl> <hl> It continues to divide , creating a ball of approximately 100 cells , and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens . <hl> The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity , the blastocoel . At this developmental stage , the conceptus is referred to as a blastocyst . Within this structure , a group of cells forms into an inner cell mass , which is fated to become the embryo . The cells that form the outer shell are called trophoblasts ( trophe = “ to feed ” or “ to nourish ” ) . These cells will develop into the chorionic sac and the fetal portion of the placenta ( the organ of nutrient , waste , and gas exchange between mother and the developing offspring ) .","hl_sentences":"Once inside the uterus , the conceptus floats freely for several more days . It continues to divide , creating a ball of approximately 100 cells , and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens .","question":{"cloze_format":"The conceptus, upon reaching the uterus, first ________.","normal_format":"What does the conceptus, upon reaching the uterus, do first?","question_choices":["implants","divides","disintegrates","hatches"],"question_id":"fs-id2483344","question_text":"The conceptus, upon reaching the uterus, first ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"embryo"},"bloom":null,"hl_context":"Approximately 3 days after fertilization , a 16 - cell conceptus reaches the uterus . The cells that had been loosely grouped are now compacted and look more like a solid mass . The name given to this structure is the morula ( morula = “ little mulberry ” ) . Once inside the uterus , the conceptus floats freely for several more days . It continues to divide , creating a ball of approximately 100 cells , and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens . The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity , the blastocoel . <hl> At this developmental stage , the conceptus is referred to as a blastocyst . <hl> <hl> Within this structure , a group of cells forms into an inner cell mass , which is fated to become the embryo . <hl> The cells that form the outer shell are called trophoblasts ( trophe = “ to feed ” or “ to nourish ” ) . These cells will develop into the chorionic sac and the fetal portion of the placenta ( the organ of nutrient , waste , and gas exchange between mother and the developing offspring ) .","hl_sentences":"At this developmental stage , the conceptus is referred to as a blastocyst . Within this structure , a group of cells forms into an inner cell mass , which is fated to become the embryo .","question":{"cloze_format":"The inner cell mass of the blastocyst is destined to become the ________.","normal_format":"What is the inner cell mass of the blastocyst destined to become?","question_choices":["embryo","trophoblast","chorionic villi","placenta"],"question_id":"fs-id2521627","question_text":"The inner cell mass of the blastocyst is destined to become the ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"ectoderm"},"bloom":"1","hl_context":"Each of these germ layers will develop into specific structures in the embryo . Whereas the ectoderm and endoderm form tightly connected epithelial sheets , the mesodermal cells are less organized and exist as a loosely connected cell community . <hl> The ectoderm gives rise to cell lineages that differentiate to become the central and peripheral nervous systems , sensory organs , epidermis , hair , and nails . <hl> Mesodermal cells ultimately become the skeleton , muscles , connective tissue , heart , blood vessels , and kidneys . The endoderm goes on to form the epithelial lining of the gastrointestinal tract , liver , and pancreas , as well as the lungs ( Figure 28.10 ) .","hl_sentences":"The ectoderm gives rise to cell lineages that differentiate to become the central and peripheral nervous systems , sensory organs , epidermis , hair , and nails .","question":{"cloze_format":"The primary germ layer that gave rise to the cells that eventually became the central nervous system is the ___.","normal_format":"Which primary germ layer gave rise to the cells that eventually became the central nervous system?","question_choices":["endoderm","ectoderm","acrosome","mesoderm"],"question_id":"fs-id2569816","question_text":"Which primary germ layer gave rise to the cells that eventually became the central nervous system?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"Menses would flush the blastocyst out of the uterus."},"bloom":"3","hl_context":"When implantation succeeds and the blastocyst adheres to the endometrium , the superficial cells of the trophoblast fuse with each other , forming the syncytiotrophoblast , a multinucleated body that digests endometrial cells to firmly secure the blastocyst to the uterine wall . In response , the uterine mucosa rebuilds itself and envelops the blastocyst ( Figure 28.6 ) . <hl> The trophoblast secretes human chorionic gonadotropin ( hCG ) , a hormone that directs the corpus luteum to survive , enlarge , and continue producing progesterone and estrogen to suppress menses . <hl> These functions of hCG are necessary for creating an environment suitable for the developing embryo . As a result of this increased production , hCG accumulates in the maternal bloodstream and is excreted in the urine . Implantation is complete by the middle of the second week . Just a few days after implantation , the trophoblast has secreted enough hCG for an at-home urine pregnancy test to give a positive result . At the end of the first week , the blastocyst comes in contact with the uterine wall and adheres to it , embedding itself in the uterine lining via the trophoblast cells . Thus begins the process of implantation , which signals the end of the pre-embryonic stage of development ( Figure 28.5 ) . Implantation can be accompanied by minor bleeding . The blastocyst typically implants in the fundus of the uterus or on the posterior wall . However , if the endometrium is not fully developed and ready to receive the blastocyst , the blastocyst will detach and find a better spot . <hl> A significant percentage ( 50 – 75 percent ) of blastocysts fail to implant ; when this occurs , the blastocyst is shed with the endometrium during menses . <hl> The high rate of implantation failure is one reason why pregnancy typically requires several ovulation cycles to achieve .","hl_sentences":"The trophoblast secretes human chorionic gonadotropin ( hCG ) , a hormone that directs the corpus luteum to survive , enlarge , and continue producing progesterone and estrogen to suppress menses . A significant percentage ( 50 – 75 percent ) of blastocysts fail to implant ; when this occurs , the blastocyst is shed with the endometrium during menses .","question":{"cloze_format":"If the trophoblast did not secrete hCG upon implantation of the blastocyst ___.","normal_format":"What would happen if the trophoblast did not secrete hCG upon implantation of the blastocyst?","question_choices":["The cells would not continue to divide.","The corpus luteum would continue to produce progesterone and estrogen.","Menses would flush the blastocyst out of the uterus.","The uterine mucosa would not envelop the blastocyst."],"question_id":"fs-id2325889","question_text":"What would happen if the trophoblast did not secrete hCG upon implantation of the blastocyst?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"embryonic folding"},"bloom":"1","hl_context":"<hl> The embryo , which begins as a flat sheet of cells , begins to acquire a cylindrical shape through the process of embryonic folding ( Figure 28.14 ) . <hl> The embryo folds laterally and again at either end , forming a C-shape with distinct head and tail ends . The embryo envelops a portion of the yolk sac , which protrudes with the umbilical cord from what will become the abdomen . The folding essentially creates a tube , called the primitive gut , that is lined by the endoderm . <hl> The amniotic sac , which was sitting on top of the flat embryo , envelops the embryo as it folds . <hl>","hl_sentences":"The embryo , which begins as a flat sheet of cells , begins to acquire a cylindrical shape through the process of embryonic folding ( Figure 28.14 ) . The amniotic sac , which was sitting on top of the flat embryo , envelops the embryo as it folds .","question":{"cloze_format":"The amnion envelops the embryo during the ___ process.","normal_format":"During what process does the amnion envelop the embryo?","question_choices":["embryonic folding","gastrulation","implantation","organogenesis"],"question_id":"fs-id2583932","question_text":"During what process does the amnion envelop the embryo?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"the mother’s endometrium and the embryo’s chorionic membrane"},"bloom":"1","hl_context":"<hl> The maternal portion of the placenta develops from the deepest layer of the endometrium , the decidua basalis . <hl> <hl> To form the embryonic portion of the placenta , the syncytiotrophoblast and the underlying cells of the trophoblast ( cytotrophoblast cells ) begin to proliferate along with a layer of extraembryonic mesoderm cells . <hl> <hl> These form the chorionic membrane , which envelops the entire conceptus as the chorion . <hl> <hl> The chorionic membrane forms finger-like structures called chorionic villi that burrow into the endometrium like tree roots , making up the fetal portion of the placenta . <hl> The cytotrophoblast cells perforate the chorionic villi , burrow farther into the endometrium , and remodel maternal blood vessels to augment maternal blood flow surrounding the villi . Meanwhile , fetal mesenchymal cells derived from the mesoderm fill the villi and differentiate into blood vessels , including the three umbilical blood vessels that connect the embryo to the developing placenta ( Figure 28.11 ) . During the first several weeks of development , the cells of the endometrium — referred to as decidual cells — nourish the nascent embryo . During prenatal weeks 4 – 12 , the developing placenta gradually takes over the role of feeding the embryo , and the decidual cells are no longer needed . <hl> The mature placenta is composed of tissues derived from the embryo , as well as maternal tissues of the endometrium . <hl> The placenta connects to the conceptus via the umbilical cord , which carries deoxygenated blood and wastes from the fetus through two umbilical arteries ; nutrients and oxygen are carried from the mother to the fetus through the single umbilical vein . The umbilical cord is surrounded by the amnion , and the spaces within the cord around the blood vessels are filled with Wharton ’ s jelly , a mucous connective tissue .","hl_sentences":"The maternal portion of the placenta develops from the deepest layer of the endometrium , the decidua basalis . To form the embryonic portion of the placenta , the syncytiotrophoblast and the underlying cells of the trophoblast ( cytotrophoblast cells ) begin to proliferate along with a layer of extraembryonic mesoderm cells . These form the chorionic membrane , which envelops the entire conceptus as the chorion . The chorionic membrane forms finger-like structures called chorionic villi that burrow into the endometrium like tree roots , making up the fetal portion of the placenta . The mature placenta is composed of tissues derived from the embryo , as well as maternal tissues of the endometrium .","question":{"cloze_format":"The placenta is formed from ________.","normal_format":"From what is the placenta formed?","question_choices":["the embryo’s mesenchymal cells","the mother’s endometrium only","the mother’s endometrium and the embryo’s chorionic membrane","the mother’s endometrium and the embryo’s umbilical cord"],"question_id":"fs-id2036445","question_text":"The placenta is formed from ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"lungs"},"bloom":"1","hl_context":"Although the fetal liver is semifunctional , the fetal lungs are nonfunctional . <hl> The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale , a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether . <hl> Most of the rest of the blood is pumped to the right ventricle , and from there , into the pulmonary trunk , which splits into pulmonary arteries . However , a shunt within the pulmonary artery , the ductus arteriosus , diverts a portion of this blood into the aorta . This ensures that only a small volume of oxygenated blood passes through the immature pulmonary circuit , which has only minor metabolic requirements . Blood vessels of uninflated lungs have high resistance to flow , a condition that encourages blood to flow to the aorta , which presents much lower resistance . The oxygenated blood moves through the foramen ovale into the left atrium , where it mixes with the now deoxygenated blood returning from the pulmonary circuit . This blood then moves into the left ventricle , where it is pumped into the aorta . Some of this blood moves through the coronary arteries into the myocardium , and some moves through the carotid arteries to the brain .","hl_sentences":"The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale , a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether .","question":{"cloze_format":"The foramen ovale causes the fetal circulatory system to bypass the ________.","normal_format":"The foramen ovale causes the fetal circulatory system to bypass what?","question_choices":["liver","lungs","kidneys","gonads"],"question_id":"fs-id2294217","question_text":"The foramen ovale causes the fetal circulatory system to bypass the ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"It adds to the amniotic fluid."},"bloom":"1","hl_context":"At the beginning of the second week , the cells of the inner cell mass form into a two-layered disc of embryonic cells , and a space — the amniotic cavity — opens up between it and the trophoblast ( Figure 28.8 ) . Cells from the upper layer of the disc ( the epiblast ) extend around the amniotic cavity , creating a membranous sac that forms into the amnion by the end of the second week . The amnion fills with amniotic fluid and eventually grows to surround the embryo . <hl> Early in development , amniotic fluid consists almost entirely of a filtrate of maternal plasma , but as the kidneys of the fetus begin to function at approximately the eighth week , they add urine to the volume of amniotic fluid . <hl> Floating within the amniotic fluid , the embryo — and later , the fetus — is protected from trauma and rapid temperature changes . It can move freely within the fluid and can prepare for swallowing and breathing out of the uterus .","hl_sentences":"Early in development , amniotic fluid consists almost entirely of a filtrate of maternal plasma , but as the kidneys of the fetus begin to function at approximately the eighth week , they add urine to the volume of amniotic fluid .","question":{"cloze_format":"When the kidneys begin to function, it happens to the urine excreted by the fetus that ___.","normal_format":"What happens to the urine excreted by the fetus when the kidneys begin to function?","question_choices":["The umbilical cord carries it to the placenta for removal.","The endometrium absorbs it.","It adds to the amniotic fluid.","It is turned into meconium."],"question_id":"fs-id2311187","question_text":"What happens to the urine excreted by the fetus when the kidneys begin to function?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"bone marrow begins to assume erythrocyte production"},"bloom":"1","hl_context":"<hl> Other Organ Systems During weeks 9 – 12 of fetal development , the brain continues to expand , the body elongates , and ossification continues . <hl> <hl> Fetal movements are frequent during this period , but are jerky and not well-controlled . <hl> <hl> The bone marrow begins to take over the process of erythrocyte production — a task that the liver performed during the embryonic period . <hl> The liver now secretes bile . The fetus circulates amniotic fluid by swallowing it and producing urine . The eyes are well-developed by this stage , but the eyelids are fused shut . The fingers and toes begin to develop nails . By the end of week 12 , the fetus measures approximately 9 cm ( 3.5 in ) from crown to rump . Weeks 13 – 16 are marked by sensory organ development . The eyes move closer together ; blinking motions begin , although the eyes remain sealed shut . The lips exhibit sucking motions . The ears move upward and lie flatter against the head . The scalp begins to grow hair . The excretory system is also developing : the kidneys are well-formed , and meconium , or fetal feces , begins to accumulate in the intestines . Meconium consists of ingested amniotic fluid , cellular debris , mucus , and bile .","hl_sentences":"Other Organ Systems During weeks 9 – 12 of fetal development , the brain continues to expand , the body elongates , and ossification continues . Fetal movements are frequent during this period , but are jerky and not well-controlled . The bone marrow begins to take over the process of erythrocyte production — a task that the liver performed during the embryonic period .","question":{"cloze_format":"During weeks 9–12 of fetal development, ________.","normal_format":"What happens during weeks 9–12 of fetal development?","question_choices":["bone marrow begins to assume erythrocyte production","meconium begins to accumulate in the intestines","surfactant production begins in the fetal lungs","the spinal cord begins to be myelinated"],"question_id":"fs-id1893042","question_text":"During weeks 9–12 of fetal development, ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"FSH and LH"},"bloom":"1","hl_context":"<hl> The placenta takes over the synthesis and secretion of progesterone throughout pregnancy as the corpus luteum degenerates . <hl> <hl> Like estrogen , progesterone suppresses FSH and LH . <hl> It also inhibits uterine contractions , protecting the fetus from preterm birth . This hormone decreases in late gestation , allowing uterine contractions to intensify and eventually progress to true labor . The placenta also produces hCG . In addition to promoting survival of the corpus luteum , hCG stimulates the male fetal gonads to secrete testosterone , which is essential for the development of the male reproductive system .","hl_sentences":"The placenta takes over the synthesis and secretion of progesterone throughout pregnancy as the corpus luteum degenerates . Like estrogen , progesterone suppresses FSH and LH .","question":{"cloze_format":"Progesterone secreted by the placenta suppresses ________ to prevent maturation of ovarian follicles.","normal_format":"What does Progesterone secreted by the placenta suppress to prevent maturation of ovarian follicles?","question_choices":["LH and estrogen","hCG and FSH","FSH and LH","estrogen and hCG"],"question_id":"fs-id2102462","question_text":"Progesterone secreted by the placenta suppresses ________ to prevent maturation of ovarian follicles."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"decreased intestinal peristalsis"},"bloom":"1","hl_context":"<hl> Nausea and vomiting , sometimes triggered by an increased sensitivity to odors , are common during the first few weeks to months of pregnancy . <hl> <hl> This phenomenon is often referred to as “ morning sickness , ” although the nausea may persist all day . <hl> The source of pregnancy nausea is thought to be the increased circulation of pregnancy-related hormones , specifically circulating estrogen , progesterone , and hCG . <hl> Decreased intestinal peristalsis may also contribute to nausea . <hl> By about week 12 of pregnancy , nausea typically subsides .","hl_sentences":"Nausea and vomiting , sometimes triggered by an increased sensitivity to odors , are common during the first few weeks to months of pregnancy . This phenomenon is often referred to as “ morning sickness , ” although the nausea may persist all day . Decreased intestinal peristalsis may also contribute to nausea .","question":{"cloze_format":"___ is a possible culprit of “morning sickness”.","normal_format":"Which of the following is a possible culprit of “morning sickness”?","question_choices":["increased minute respiration","decreased intestinal peristalsis","decreased aldosterone secretion","increased blood volume"],"question_id":"fs-id805292","question_text":"Which of the following is a possible culprit of “morning sickness”?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"decreasing the inhibition of uterine contractility"},"bloom":"2","hl_context":"<hl> First , recall that progesterone inhibits uterine contractions throughout the first several months of pregnancy . <hl> As the pregnancy enters its seventh month , progesterone levels plateau and then drop . Estrogen levels , however , continue to rise in the maternal circulation ( Figure 28.20 ) . The increasing ratio of estrogen to progesterone makes the myometrium ( the uterine smooth muscle ) more sensitive to stimuli that promote contractions ( because progesterone no longer inhibits them ) . Moreover , in the eighth month of pregnancy , fetal cortisol rises , which boosts estrogen secretion by the placenta and further overpowers the uterine-calming effects of progesterone . Some women may feel the result of the decreasing levels of progesterone in late pregnancy as weak and irregular peristaltic Braxton Hicks contractions , also called false labor . These contractions can often be relieved with rest or hydration . The placenta takes over the synthesis and secretion of progesterone throughout pregnancy as the corpus luteum degenerates . <hl> Like estrogen , progesterone suppresses FSH and LH . <hl> <hl> It also inhibits uterine contractions , protecting the fetus from preterm birth . <hl> <hl> This hormone decreases in late gestation , allowing uterine contractions to intensify and eventually progress to true labor . <hl> The placenta also produces hCG . In addition to promoting survival of the corpus luteum , hCG stimulates the male fetal gonads to secrete testosterone , which is essential for the development of the male reproductive system .","hl_sentences":"First , recall that progesterone inhibits uterine contractions throughout the first several months of pregnancy . Like estrogen , progesterone suppresses FSH and LH . It also inhibits uterine contractions , protecting the fetus from preterm birth . This hormone decreases in late gestation , allowing uterine contractions to intensify and eventually progress to true labor .","question":{"cloze_format":"The decrease in progesterone at the last weeks of pregnancy help to bring on labor by ___.","normal_format":"How does the decrease in progesterone at the last weeks of pregnancy help to bring on labor?","question_choices":["stimulating FSH production","decreasing the levels of estrogens","dilating the cervix","decreasing the inhibition of uterine contractility"],"question_id":"fs-id1978449","question_text":"How does the decrease in progesterone at the last weeks of pregnancy help to bring on labor?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"vertex occiput posterior"},"bloom":null,"hl_context":"The expulsion stage begins when the fetal head enters the birth canal and ends with birth of the newborn . It typically takes up to 2 hours , but it can last longer or be completed in minutes , depending in part on the orientation of the fetus . <hl> The vertex presentation known as the occiput anterior vertex is the most common presentation and is associated with the greatest ease of vaginal birth . <hl> <hl> The fetus faces the maternal spinal cord and the smallest part of the head ( the posterior aspect called the occiput ) exits the birth canal first . <hl>","hl_sentences":"The vertex presentation known as the occiput anterior vertex is the most common presentation and is associated with the greatest ease of vaginal birth . The fetus faces the maternal spinal cord and the smallest part of the head ( the posterior aspect called the occiput ) exits the birth canal first .","question":{"cloze_format":"The fetal presentation that is the easiest for vaginal birth is a ___.","normal_format":"Which of these fetal presentations is the easiest for vaginal birth?","question_choices":["complete breech","vertex occiput anterior","frank breech","vertex occiput posterior"],"question_id":"fs-id1474295","question_text":"Which of these fetal presentations is the easiest for vaginal birth?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"foramen ovale"},"bloom":"3","hl_context":"Although the fetal liver is semifunctional , the fetal lungs are nonfunctional . <hl> The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale , a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether . <hl> Most of the rest of the blood is pumped to the right ventricle , and from there , into the pulmonary trunk , which splits into pulmonary arteries . However , a shunt within the pulmonary artery , the ductus arteriosus , diverts a portion of this blood into the aorta . This ensures that only a small volume of oxygenated blood passes through the immature pulmonary circuit , which has only minor metabolic requirements . Blood vessels of uninflated lungs have high resistance to flow , a condition that encourages blood to flow to the aorta , which presents much lower resistance . The oxygenated blood moves through the foramen ovale into the left atrium , where it mixes with the now deoxygenated blood returning from the pulmonary circuit . This blood then moves into the left ventricle , where it is pumped into the aorta . Some of this blood moves through the coronary arteries into the myocardium , and some moves through the carotid arteries to the brain .","hl_sentences":"The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale , a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether .","question":{"cloze_format":"The ___ shunt exists between the right and left atria.","normal_format":"Which of these shunts exists between the right and left atria?","question_choices":["foramen ovale","ductus venosus","ductus arteriosis","foramen venosus"],"question_id":"fs-id810682","question_text":"Which of these shunts exists between the right and left atria?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"It can be broken down to generate heat for thermoregulation."},"bloom":"1","hl_context":"<hl> The breakdown of brown fat occurs automatically upon exposure to cold , so it is an important heat regulator in newborns . <hl> During fetal development , the placenta secretes inhibitors that prevent metabolism of brown adipose fat and promote its accumulation in preparation for birth . <hl> Newborns , however , do have a special method for generating heat : nonshivering thermogenesis , which involves the breakdown of brown adipose tissue , or brown fat , which is distributed over the back , chest , and shoulders . <hl> Brown fat differs from the more familiar white fat in two ways :","hl_sentences":"The breakdown of brown fat occurs automatically upon exposure to cold , so it is an important heat regulator in newborns . Newborns , however , do have a special method for generating heat : nonshivering thermogenesis , which involves the breakdown of brown adipose tissue , or brown fat , which is distributed over the back , chest , and shoulders .","question":{"cloze_format":"Brown fat is important because ___ .","normal_format":"Why is brown fat important?","question_choices":["It is the newborn’s primary source of insulation.","It can be broken down to generate heat for thermoregulation.","It can be broken down for energy between feedings.","It can be converted to white fat."],"question_id":"fs-id1390282","question_text":"Why is brown fat important?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"elevates carbon dioxide levels in the blood"},"bloom":"1","hl_context":"Although the fetus “ practices ” breathing by inhaling amniotic fluid in utero , there is no air in the uterus and thus no true opportunity to breathe . ( There is also no need to breathe because the placenta supplies the fetus with all the oxygenated blood it needs . ) During gestation , the partially collapsed lungs are filled with amniotic fluid and exhibit very little metabolic activity . Several factors stimulate newborns to take their first breath at birth . <hl> First , labor contractions temporarily constrict umbilical blood vessels , reducing oxygenated blood flow to the fetus and elevating carbon dioxide levels in the blood . <hl> High carbon dioxide levels cause acidosis and stimulate the respiratory center in the brain , triggering the newborn to take a breath .","hl_sentences":"First , labor contractions temporarily constrict umbilical blood vessels , reducing oxygenated blood flow to the fetus and elevating carbon dioxide levels in the blood .","question":{"cloze_format":"Constriction of umbilical blood vessels during vaginal birth ________.","normal_format":"Which of the following causes are true about constriction of umbilical blood vessels during vaginal birth?","question_choices":["causes respiratory alkalosis","inhibits the respiratory center in the brain","elevates carbon dioxide levels in the blood","both a and b"],"question_id":"fs-id23202320","question_text":"Constriction of umbilical blood vessels during vaginal birth ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"lactiferous ducts"},"bloom":null,"hl_context":"Mammary glands are modified sweat glands . The non-pregnant and non-lactating female breast is composed primarily of adipose and collagenous tissue , with mammary glands making up a very minor proportion of breast volume . The mammary gland is composed of milk-transporting lactiferous ducts , which expand and branch extensively during pregnancy in response to estrogen , growth hormone , cortisol , and prolactin . Moreover , in response to progesterone , clusters of breast alveoli bud from the ducts and expand outward toward the chest wall . <hl> Breast alveoli are balloon-like structures lined with milk-secreting cuboidal cells , or lactocytes , that are surrounded by a net of contractile myoepithelial cells . <hl> Milk is secreted from the lactocytes , fills the alveoli , and is squeezed into the ducts . <hl> Clusters of alveoli that drain to a common duct are called lobules ; the lactating female has 12 – 20 lobules organized radially around the nipple . <hl> <hl> Milk drains from lactiferous ducts into lactiferous sinuses that meet at 4 to 18 perforations in the nipple , called nipple pores . <hl> The small bumps of the areola ( the darkened skin around the nipple ) are called Montgomery glands . They secrete oil to cleanse the nipple opening and prevent chapping and cracking of the nipple during breastfeeding .","hl_sentences":"Breast alveoli are balloon-like structures lined with milk-secreting cuboidal cells , or lactocytes , that are surrounded by a net of contractile myoepithelial cells . Clusters of alveoli that drain to a common duct are called lobules ; the lactating female has 12 – 20 lobules organized radially around the nipple . Milk drains from lactiferous ducts into lactiferous sinuses that meet at 4 to 18 perforations in the nipple , called nipple pores .","question":{"cloze_format":"Alveoli are connected to the lactiferous sinuses by ________.","normal_format":"By what are alveol connected to the lactiferous sinuses?","question_choices":["lactocytes","lactiferous ducts","nipple pores","lobules"],"question_id":"fs-id14839790","question_text":"Alveoli are connected to the lactiferous sinuses by ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"It helps boost the newborn’s immune system."},"bloom":"3","hl_context":"Colostrum is secreted during the first 48 – 72 hours postpartum . Only a small volume of colostrum is produced — approximately 3 ounces in a 24 - hour period — but it is sufficient for the newborn in the first few days of life . <hl> Colostrum is rich with immunoglobulins , which confer gastrointestinal , and also likely systemic , immunity as the newborn adjusts to a nonsterile environment . <hl>","hl_sentences":"Colostrum is rich with immunoglobulins , which confer gastrointestinal , and also likely systemic , immunity as the newborn adjusts to a nonsterile environment .","question":{"cloze_format":"Colostrum is most important to a newborn because ___ .","normal_format":"How is colostrum most important to a newborn?","question_choices":["It helps boost the newborn’s immune system.","It provides much needed fat.","It satisfies the newborn’s thirst.","It satisfies the infant’s appetite."],"question_id":"fs-id2348104","question_text":"How is colostrum most important to a newborn?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"has more fat than cow’s milk"},"bloom":"1","hl_context":"<hl> After about the third postpartum day , the mother secretes transitional milk that represents an intermediate between mature milk and colostrum . <hl> This is followed by mature milk from approximately postpartum day 10 ( see Table 28.3 ) . <hl> As you can see in the accompanying table , cow ’ s milk is not a substitute for breast milk . <hl> <hl> It contains less lactose , less fat , and more protein and minerals . <hl> <hl> Moreover , the proteins in cow ’ s milk are difficult for an infant ’ s immature digestive system to metabolize and absorb . <hl>","hl_sentences":"After about the third postpartum day , the mother secretes transitional milk that represents an intermediate between mature milk and colostrum . As you can see in the accompanying table , cow ’ s milk is not a substitute for breast milk . It contains less lactose , less fat , and more protein and minerals . Moreover , the proteins in cow ’ s milk are difficult for an infant ’ s immature digestive system to metabolize and absorb .","question":{"cloze_format":"Mature breast milk ________.","normal_format":"Which of the following is correct about mature breast milk?","question_choices":["has more sodium than cow’s milk","has more calcium than cow’s milk","has more protein than cow’s milk","has more fat than cow’s milk"],"question_id":"fs-id2242284","question_text":"Mature breast milk ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"multiple alleles"},"bloom":"1","hl_context":"In the simplest scenario , a single pair of genes will determine a single heritable characteristic . However , it is quite common for multiple genes to interact to confer a feature . For instance , eight or more genes — each with their own alleles — determine eye color in humans . <hl> Moreover , although any one person can only have two alleles corresponding to a given gene , more than two alleles commonly exist in a population . <hl> <hl> This phenomenon is called multiple alleles . <hl> <hl> For example , there are three different alleles that encode ABO blood type ; these are designated I A , I B , and i . <hl>","hl_sentences":"Moreover , although any one person can only have two alleles corresponding to a given gene , more than two alleles commonly exist in a population . This phenomenon is called multiple alleles . For example , there are three different alleles that encode ABO blood type ; these are designated I A , I B , and i .","question":{"cloze_format":"In addition to codominance, the ABO blood group antigens are also an example of ________.","normal_format":"In addition to codominance, what are the ABO blood group antigens also an example of?","question_choices":["incomplete dominance","X-linked recessive inheritance","multiple alleles","recessive lethal inheritance"],"question_id":"fs-id1340094","question_text":"In addition to codominance, the ABO blood group antigens are also an example of ________."},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"most do not reach the oocyte\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Fertilization is a numbers game . <hl> During ejaculation , hundreds of millions of sperm ( spermatozoa ) are released into the vagina . <hl> <hl> Almost immediately , millions of these sperm are overcome by the acidity of the vagina ( approximately pH 3.8 ) , and millions more may be blocked from entering the uterus by thick cervical mucus . <hl> <hl> Of those that do enter , thousands are destroyed by phagocytic uterine leukocytes . <hl> <hl> Thus , the race into the uterine tubes , which is the most typical site for sperm to encounter the oocyte , is reduced to a few thousand contenders . <hl> Their journey — thought to be facilitated by uterine contractions — usually takes from 30 minutes to 2 hours . If the sperm do not encounter an oocyte immediately , they can survive in the uterine tubes for another 3 – 5 days . Thus , fertilization can still occur if intercourse takes place a few days before ovulation . In comparison , an oocyte can survive independently for only approximately 24 hours following ovulation . Intercourse more than a day after ovulation will therefore usually not result in fertilization .\",\n \"hl_sentences\": \"During ejaculation , hundreds of millions of sperm ( spermatozoa ) are released into the vagina . Almost immediately , millions of these sperm are overcome by the acidity of the vagina ( approximately pH 3.8 ) , and millions more may be blocked from entering the uterus by thick cervical mucus . Of those that do enter , thousands are destroyed by phagocytic uterine leukocytes . Thus , the race into the uterine tubes , which is the most typical site for sperm to encounter the oocyte , is reduced to a few thousand contenders .\",\n \"question\": {\n \"cloze_format\": \"Although the male ejaculate contains hundreds of millions of sperm, ________.\",\n \"normal_format\": \"Which of the following is true, although the male ejaculate contains hundreds of millions of sperm?\",\n \"question_choices\": [\n \"most do not reach the oocyte\",\n \"most are destroyed by the alkaline environment of the uterus\",\n \"it takes millions to penetrate the outer layers of the oocyte\",\n \"most are destroyed by capacitation\"\n ],\n \"question_id\": \"fs-id1407729\",\n \"question_text\": \"Although the male ejaculate contains hundreds of millions of sperm, ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"corona radiata\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"As it is swept along the distal uterine tube , the oocyte encounters the surviving capacitated sperm , which stream toward it in response to chemical attractants released by the cells of the corona radiata . <hl> To reach the oocyte itself , the sperm must penetrate the two protective layers . <hl> <hl> The sperm first burrow through the cells of the corona radiata . <hl> Then , upon contact with the zona pellucida , the sperm bind to receptors in the zona pellucida . This initiates a process called the acrosomal reaction in which the enzyme-filled “ cap ” of the sperm , called the acrosome , releases its stored digestive enzymes . These enzymes clear a path through the zona pellucida that allows sperm to reach the oocyte . Finally , a single sperm makes contact with sperm-binding receptors on the oocyte ’ s plasma membrane ( Figure 28.2 ) . The plasma membrane of that sperm then fuses with the oocyte ’ s plasma membrane , and the head and mid-piece of the “ winning ” sperm enter the oocyte interior .\",\n \"hl_sentences\": \"To reach the oocyte itself , the sperm must penetrate the two protective layers . The sperm first burrow through the cells of the corona radiata .\",\n \"question\": {\n \"cloze_format\": \"As sperm first reach the oocyte, they will contact the ________.\",\n \"normal_format\": \"As sperm first reach the oocyte, which will they contact?\",\n \"question_choices\": [\n \"acrosome\",\n \"corona radiata\",\n \"sperm-binding receptors\",\n \"zona pellucida\"\n ],\n \"question_id\": \"fs-id2346687\",\n \"question_text\": \"As sperm first reach the oocyte, they will contact the ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"fertilization\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Recall that at the point of fertilization , the oocyte has not yet completed meiosis ; all secondary oocytes remain arrested in metaphase of meiosis II until fertilization . Only upon fertilization does the oocyte complete meiosis . The unneeded complement of genetic material that results is stored in a second polar body that is eventually ejected . At this moment , the oocyte has become an ovum , the female haploid gamete . The two haploid nuclei derived from the sperm and oocyte and contained within the egg are referred to as pronuclei . They decondense , expand , and replicate their DNA in preparation for mitosis . <hl> The pronuclei then migrate toward each other , their nuclear envelopes disintegrate , and the male - and female-derived genetic material intermingles . <hl> <hl> This step completes the process of fertilization and results in a single-celled diploid zygote with all the genetic instructions it needs to develop into a human . <hl>\",\n \"hl_sentences\": \"The pronuclei then migrate toward each other , their nuclear envelopes disintegrate , and the male - and female-derived genetic material intermingles . This step completes the process of fertilization and results in a single-celled diploid zygote with all the genetic instructions it needs to develop into a human .\",\n \"question\": {\n \"cloze_format\": \"Fusion of pronuclei occurs during ________.\",\n \"normal_format\": \"During which of the following fusion of pronuclei occurs?\",\n \"question_choices\": [\n \"spermatogenesis\",\n \"ovulation\",\n \"fertilization\",\n \"capacitation\"\n ],\n \"question_id\": \"fs-id1288730\",\n \"question_text\": \"Fusion of pronuclei occurs during ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"capacitation\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"During the journey , fluids in the female reproductive tract prepare the sperm for fertilization through a process called capacitation , or priming . The fluids improve the motility of the spermatozoa . They also deplete cholesterol molecules embedded in the membrane of the head of the sperm , thinning the membrane in such a way that will help facilitate the release of the lysosomal ( digestive ) enzymes needed for the sperm to penetrate the oocyte ’ s exterior once contact is made . <hl> Sperm must undergo the process of capacitation in order to have the “ capacity ” to fertilize an oocyte . <hl> If they reach the oocyte before capacitation is complete , they will be unable to penetrate the oocyte ’ s thick outer layer of cells .\",\n \"hl_sentences\": \"Sperm must undergo the process of capacitation in order to have the “ capacity ” to fertilize an oocyte .\",\n \"question\": {\n \"cloze_format\": \"Sperm must first complete ________ to enable the fertilization of an oocyte.\",\n \"normal_format\": \"What must sperm first complete to enable the fertilization of an oocyte?\",\n \"question_choices\": [\n \"capacitation\",\n \"the acrosomal reaction\",\n \"the cortical reaction\",\n \"the fast block\"\n ],\n \"question_id\": \"fs-id2111179\",\n \"question_text\": \"Sperm must first complete ________ to enable the fertilization of an oocyte.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"blastomeres\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Following fertilization , the zygote and its associated membranes , together referred to as the conceptus , continue to be projected toward the uterus by peristalsis and beating cilia of the epithelial cells of the Fallopian tube . During its journey to the uterus , the zygote undergoes five or six rapid mitotic cell divisions . Although each cleavage results in more cells , it does not increase the total volume of the conceptus ( Figure 28.4 ) . <hl> Each daughter cell produced by cleavage is called a blastomere ( blastos = “ germ , ” in the sense of a seed or sprout ) . <hl>\",\n \"hl_sentences\": \"Each daughter cell produced by cleavage is called a blastomere ( blastos = “ germ , ” in the sense of a seed or sprout ) .\",\n \"question\": {\n \"cloze_format\": \"Cleavage produces daughter cells called ________.\",\n \"normal_format\": \"What are cleavage produces daughter cells?\",\n \"question_choices\": [\n \"trophoblasts\",\n \"blastocysts\",\n \"morulae\",\n \"blastomeres\"\n ],\n \"question_id\": \"fs-id2282515\",\n \"question_text\": \"Cleavage produces daughter cells called ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"divides\"\n },\n \"bloom\": null,\n \"hl_context\": \"Approximately 3 days after fertilization , a 16 - cell conceptus reaches the uterus . The cells that had been loosely grouped are now compacted and look more like a solid mass . The name given to this structure is the morula ( morula = “ little mulberry ” ) . <hl> Once inside the uterus , the conceptus floats freely for several more days . <hl> <hl> It continues to divide , creating a ball of approximately 100 cells , and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens . <hl> The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity , the blastocoel . At this developmental stage , the conceptus is referred to as a blastocyst . Within this structure , a group of cells forms into an inner cell mass , which is fated to become the embryo . The cells that form the outer shell are called trophoblasts ( trophe = “ to feed ” or “ to nourish ” ) . These cells will develop into the chorionic sac and the fetal portion of the placenta ( the organ of nutrient , waste , and gas exchange between mother and the developing offspring ) .\",\n \"hl_sentences\": \"Once inside the uterus , the conceptus floats freely for several more days . It continues to divide , creating a ball of approximately 100 cells , and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens .\",\n \"question\": {\n \"cloze_format\": \"The conceptus, upon reaching the uterus, first ________.\",\n \"normal_format\": \"What does the conceptus, upon reaching the uterus, do first?\",\n \"question_choices\": [\n \"implants\",\n \"divides\",\n \"disintegrates\",\n \"hatches\"\n ],\n \"question_id\": \"fs-id2483344\",\n \"question_text\": \"The conceptus, upon reaching the uterus, first ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"embryo\"\n },\n \"bloom\": null,\n \"hl_context\": \"Approximately 3 days after fertilization , a 16 - cell conceptus reaches the uterus . The cells that had been loosely grouped are now compacted and look more like a solid mass . The name given to this structure is the morula ( morula = “ little mulberry ” ) . Once inside the uterus , the conceptus floats freely for several more days . It continues to divide , creating a ball of approximately 100 cells , and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens . The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity , the blastocoel . <hl> At this developmental stage , the conceptus is referred to as a blastocyst . <hl> <hl> Within this structure , a group of cells forms into an inner cell mass , which is fated to become the embryo . <hl> The cells that form the outer shell are called trophoblasts ( trophe = “ to feed ” or “ to nourish ” ) . These cells will develop into the chorionic sac and the fetal portion of the placenta ( the organ of nutrient , waste , and gas exchange between mother and the developing offspring ) .\",\n \"hl_sentences\": \"At this developmental stage , the conceptus is referred to as a blastocyst . Within this structure , a group of cells forms into an inner cell mass , which is fated to become the embryo .\",\n \"question\": {\n \"cloze_format\": \"The inner cell mass of the blastocyst is destined to become the ________.\",\n \"normal_format\": \"What is the inner cell mass of the blastocyst destined to become?\",\n \"question_choices\": [\n \"embryo\",\n \"trophoblast\",\n \"chorionic villi\",\n \"placenta\"\n ],\n \"question_id\": \"fs-id2521627\",\n \"question_text\": \"The inner cell mass of the blastocyst is destined to become the ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"ectoderm\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Each of these germ layers will develop into specific structures in the embryo . Whereas the ectoderm and endoderm form tightly connected epithelial sheets , the mesodermal cells are less organized and exist as a loosely connected cell community . <hl> The ectoderm gives rise to cell lineages that differentiate to become the central and peripheral nervous systems , sensory organs , epidermis , hair , and nails . <hl> Mesodermal cells ultimately become the skeleton , muscles , connective tissue , heart , blood vessels , and kidneys . The endoderm goes on to form the epithelial lining of the gastrointestinal tract , liver , and pancreas , as well as the lungs ( Figure 28.10 ) .\",\n \"hl_sentences\": \"The ectoderm gives rise to cell lineages that differentiate to become the central and peripheral nervous systems , sensory organs , epidermis , hair , and nails .\",\n \"question\": {\n \"cloze_format\": \"The primary germ layer that gave rise to the cells that eventually became the central nervous system is the ___.\",\n \"normal_format\": \"Which primary germ layer gave rise to the cells that eventually became the central nervous system?\",\n \"question_choices\": [\n \"endoderm\",\n \"ectoderm\",\n \"acrosome\",\n \"mesoderm\"\n ],\n \"question_id\": \"fs-id2569816\",\n \"question_text\": \"Which primary germ layer gave rise to the cells that eventually became the central nervous system?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"Menses would flush the blastocyst out of the uterus.\"\n },\n \"bloom\": \"3\",\n \"hl_context\": \"When implantation succeeds and the blastocyst adheres to the endometrium , the superficial cells of the trophoblast fuse with each other , forming the syncytiotrophoblast , a multinucleated body that digests endometrial cells to firmly secure the blastocyst to the uterine wall . In response , the uterine mucosa rebuilds itself and envelops the blastocyst ( Figure 28.6 ) . <hl> The trophoblast secretes human chorionic gonadotropin ( hCG ) , a hormone that directs the corpus luteum to survive , enlarge , and continue producing progesterone and estrogen to suppress menses . <hl> These functions of hCG are necessary for creating an environment suitable for the developing embryo . As a result of this increased production , hCG accumulates in the maternal bloodstream and is excreted in the urine . Implantation is complete by the middle of the second week . Just a few days after implantation , the trophoblast has secreted enough hCG for an at-home urine pregnancy test to give a positive result . At the end of the first week , the blastocyst comes in contact with the uterine wall and adheres to it , embedding itself in the uterine lining via the trophoblast cells . Thus begins the process of implantation , which signals the end of the pre-embryonic stage of development ( Figure 28.5 ) . Implantation can be accompanied by minor bleeding . The blastocyst typically implants in the fundus of the uterus or on the posterior wall . However , if the endometrium is not fully developed and ready to receive the blastocyst , the blastocyst will detach and find a better spot . <hl> A significant percentage ( 50 – 75 percent ) of blastocysts fail to implant ; when this occurs , the blastocyst is shed with the endometrium during menses . <hl> The high rate of implantation failure is one reason why pregnancy typically requires several ovulation cycles to achieve .\",\n \"hl_sentences\": \"The trophoblast secretes human chorionic gonadotropin ( hCG ) , a hormone that directs the corpus luteum to survive , enlarge , and continue producing progesterone and estrogen to suppress menses . A significant percentage ( 50 – 75 percent ) of blastocysts fail to implant ; when this occurs , the blastocyst is shed with the endometrium during menses .\",\n \"question\": {\n \"cloze_format\": \"If the trophoblast did not secrete hCG upon implantation of the blastocyst ___.\",\n \"normal_format\": \"What would happen if the trophoblast did not secrete hCG upon implantation of the blastocyst?\",\n \"question_choices\": [\n \"The cells would not continue to divide.\",\n \"The corpus luteum would continue to produce progesterone and estrogen.\",\n \"Menses would flush the blastocyst out of the uterus.\",\n \"The uterine mucosa would not envelop the blastocyst.\"\n ],\n \"question_id\": \"fs-id2325889\",\n \"question_text\": \"What would happen if the trophoblast did not secrete hCG upon implantation of the blastocyst?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"embryonic folding\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> The embryo , which begins as a flat sheet of cells , begins to acquire a cylindrical shape through the process of embryonic folding ( Figure 28.14 ) . <hl> The embryo folds laterally and again at either end , forming a C-shape with distinct head and tail ends . The embryo envelops a portion of the yolk sac , which protrudes with the umbilical cord from what will become the abdomen . The folding essentially creates a tube , called the primitive gut , that is lined by the endoderm . <hl> The amniotic sac , which was sitting on top of the flat embryo , envelops the embryo as it folds . <hl>\",\n \"hl_sentences\": \"The embryo , which begins as a flat sheet of cells , begins to acquire a cylindrical shape through the process of embryonic folding ( Figure 28.14 ) . The amniotic sac , which was sitting on top of the flat embryo , envelops the embryo as it folds .\",\n \"question\": {\n \"cloze_format\": \"The amnion envelops the embryo during the ___ process.\",\n \"normal_format\": \"During what process does the amnion envelop the embryo?\",\n \"question_choices\": [\n \"embryonic folding\",\n \"gastrulation\",\n \"implantation\",\n \"organogenesis\"\n ],\n \"question_id\": \"fs-id2583932\",\n \"question_text\": \"During what process does the amnion envelop the embryo?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"the mother’s endometrium and the embryo’s chorionic membrane\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> The maternal portion of the placenta develops from the deepest layer of the endometrium , the decidua basalis . <hl> <hl> To form the embryonic portion of the placenta , the syncytiotrophoblast and the underlying cells of the trophoblast ( cytotrophoblast cells ) begin to proliferate along with a layer of extraembryonic mesoderm cells . <hl> <hl> These form the chorionic membrane , which envelops the entire conceptus as the chorion . <hl> <hl> The chorionic membrane forms finger-like structures called chorionic villi that burrow into the endometrium like tree roots , making up the fetal portion of the placenta . <hl> The cytotrophoblast cells perforate the chorionic villi , burrow farther into the endometrium , and remodel maternal blood vessels to augment maternal blood flow surrounding the villi . Meanwhile , fetal mesenchymal cells derived from the mesoderm fill the villi and differentiate into blood vessels , including the three umbilical blood vessels that connect the embryo to the developing placenta ( Figure 28.11 ) . During the first several weeks of development , the cells of the endometrium — referred to as decidual cells — nourish the nascent embryo . During prenatal weeks 4 – 12 , the developing placenta gradually takes over the role of feeding the embryo , and the decidual cells are no longer needed . <hl> The mature placenta is composed of tissues derived from the embryo , as well as maternal tissues of the endometrium . <hl> The placenta connects to the conceptus via the umbilical cord , which carries deoxygenated blood and wastes from the fetus through two umbilical arteries ; nutrients and oxygen are carried from the mother to the fetus through the single umbilical vein . The umbilical cord is surrounded by the amnion , and the spaces within the cord around the blood vessels are filled with Wharton ’ s jelly , a mucous connective tissue .\",\n \"hl_sentences\": \"The maternal portion of the placenta develops from the deepest layer of the endometrium , the decidua basalis . To form the embryonic portion of the placenta , the syncytiotrophoblast and the underlying cells of the trophoblast ( cytotrophoblast cells ) begin to proliferate along with a layer of extraembryonic mesoderm cells . These form the chorionic membrane , which envelops the entire conceptus as the chorion . The chorionic membrane forms finger-like structures called chorionic villi that burrow into the endometrium like tree roots , making up the fetal portion of the placenta . The mature placenta is composed of tissues derived from the embryo , as well as maternal tissues of the endometrium .\",\n \"question\": {\n \"cloze_format\": \"The placenta is formed from ________.\",\n \"normal_format\": \"From what is the placenta formed?\",\n \"question_choices\": [\n \"the embryo’s mesenchymal cells\",\n \"the mother’s endometrium only\",\n \"the mother’s endometrium and the embryo’s chorionic membrane\",\n \"the mother’s endometrium and the embryo’s umbilical cord\"\n ],\n \"question_id\": \"fs-id2036445\",\n \"question_text\": \"The placenta is formed from ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"lungs\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Although the fetal liver is semifunctional , the fetal lungs are nonfunctional . <hl> The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale , a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether . <hl> Most of the rest of the blood is pumped to the right ventricle , and from there , into the pulmonary trunk , which splits into pulmonary arteries . However , a shunt within the pulmonary artery , the ductus arteriosus , diverts a portion of this blood into the aorta . This ensures that only a small volume of oxygenated blood passes through the immature pulmonary circuit , which has only minor metabolic requirements . Blood vessels of uninflated lungs have high resistance to flow , a condition that encourages blood to flow to the aorta , which presents much lower resistance . The oxygenated blood moves through the foramen ovale into the left atrium , where it mixes with the now deoxygenated blood returning from the pulmonary circuit . This blood then moves into the left ventricle , where it is pumped into the aorta . Some of this blood moves through the coronary arteries into the myocardium , and some moves through the carotid arteries to the brain .\",\n \"hl_sentences\": \"The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale , a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether .\",\n \"question\": {\n \"cloze_format\": \"The foramen ovale causes the fetal circulatory system to bypass the ________.\",\n \"normal_format\": \"The foramen ovale causes the fetal circulatory system to bypass what?\",\n \"question_choices\": [\n \"liver\",\n \"lungs\",\n \"kidneys\",\n \"gonads\"\n ],\n \"question_id\": \"fs-id2294217\",\n \"question_text\": \"The foramen ovale causes the fetal circulatory system to bypass the ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"It adds to the amniotic fluid.\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"At the beginning of the second week , the cells of the inner cell mass form into a two-layered disc of embryonic cells , and a space — the amniotic cavity — opens up between it and the trophoblast ( Figure 28.8 ) . Cells from the upper layer of the disc ( the epiblast ) extend around the amniotic cavity , creating a membranous sac that forms into the amnion by the end of the second week . The amnion fills with amniotic fluid and eventually grows to surround the embryo . <hl> Early in development , amniotic fluid consists almost entirely of a filtrate of maternal plasma , but as the kidneys of the fetus begin to function at approximately the eighth week , they add urine to the volume of amniotic fluid . <hl> Floating within the amniotic fluid , the embryo — and later , the fetus — is protected from trauma and rapid temperature changes . It can move freely within the fluid and can prepare for swallowing and breathing out of the uterus .\",\n \"hl_sentences\": \"Early in development , amniotic fluid consists almost entirely of a filtrate of maternal plasma , but as the kidneys of the fetus begin to function at approximately the eighth week , they add urine to the volume of amniotic fluid .\",\n \"question\": {\n \"cloze_format\": \"When the kidneys begin to function, it happens to the urine excreted by the fetus that ___.\",\n \"normal_format\": \"What happens to the urine excreted by the fetus when the kidneys begin to function?\",\n \"question_choices\": [\n \"The umbilical cord carries it to the placenta for removal.\",\n \"The endometrium absorbs it.\",\n \"It adds to the amniotic fluid.\",\n \"It is turned into meconium.\"\n ],\n \"question_id\": \"fs-id2311187\",\n \"question_text\": \"What happens to the urine excreted by the fetus when the kidneys begin to function?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"bone marrow begins to assume erythrocyte production\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Other Organ Systems During weeks 9 – 12 of fetal development , the brain continues to expand , the body elongates , and ossification continues . <hl> <hl> Fetal movements are frequent during this period , but are jerky and not well-controlled . <hl> <hl> The bone marrow begins to take over the process of erythrocyte production — a task that the liver performed during the embryonic period . <hl> The liver now secretes bile . The fetus circulates amniotic fluid by swallowing it and producing urine . The eyes are well-developed by this stage , but the eyelids are fused shut . The fingers and toes begin to develop nails . By the end of week 12 , the fetus measures approximately 9 cm ( 3.5 in ) from crown to rump . Weeks 13 – 16 are marked by sensory organ development . The eyes move closer together ; blinking motions begin , although the eyes remain sealed shut . The lips exhibit sucking motions . The ears move upward and lie flatter against the head . The scalp begins to grow hair . The excretory system is also developing : the kidneys are well-formed , and meconium , or fetal feces , begins to accumulate in the intestines . Meconium consists of ingested amniotic fluid , cellular debris , mucus , and bile .\",\n \"hl_sentences\": \"Other Organ Systems During weeks 9 – 12 of fetal development , the brain continues to expand , the body elongates , and ossification continues . Fetal movements are frequent during this period , but are jerky and not well-controlled . The bone marrow begins to take over the process of erythrocyte production — a task that the liver performed during the embryonic period .\",\n \"question\": {\n \"cloze_format\": \"During weeks 9–12 of fetal development, ________.\",\n \"normal_format\": \"What happens during weeks 9–12 of fetal development?\",\n \"question_choices\": [\n \"bone marrow begins to assume erythrocyte production\",\n \"meconium begins to accumulate in the intestines\",\n \"surfactant production begins in the fetal lungs\",\n \"the spinal cord begins to be myelinated\"\n ],\n \"question_id\": \"fs-id1893042\",\n \"question_text\": \"During weeks 9–12 of fetal development, ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"FSH and LH\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> The placenta takes over the synthesis and secretion of progesterone throughout pregnancy as the corpus luteum degenerates . <hl> <hl> Like estrogen , progesterone suppresses FSH and LH . <hl> It also inhibits uterine contractions , protecting the fetus from preterm birth . This hormone decreases in late gestation , allowing uterine contractions to intensify and eventually progress to true labor . The placenta also produces hCG . In addition to promoting survival of the corpus luteum , hCG stimulates the male fetal gonads to secrete testosterone , which is essential for the development of the male reproductive system .\",\n \"hl_sentences\": \"The placenta takes over the synthesis and secretion of progesterone throughout pregnancy as the corpus luteum degenerates . Like estrogen , progesterone suppresses FSH and LH .\",\n \"question\": {\n \"cloze_format\": \"Progesterone secreted by the placenta suppresses ________ to prevent maturation of ovarian follicles.\",\n \"normal_format\": \"What does Progesterone secreted by the placenta suppress to prevent maturation of ovarian follicles?\",\n \"question_choices\": [\n \"LH and estrogen\",\n \"hCG and FSH\",\n \"FSH and LH\",\n \"estrogen and hCG\"\n ],\n \"question_id\": \"fs-id2102462\",\n \"question_text\": \"Progesterone secreted by the placenta suppresses ________ to prevent maturation of ovarian follicles.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"decreased intestinal peristalsis\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Nausea and vomiting , sometimes triggered by an increased sensitivity to odors , are common during the first few weeks to months of pregnancy . <hl> <hl> This phenomenon is often referred to as “ morning sickness , ” although the nausea may persist all day . <hl> The source of pregnancy nausea is thought to be the increased circulation of pregnancy-related hormones , specifically circulating estrogen , progesterone , and hCG . <hl> Decreased intestinal peristalsis may also contribute to nausea . <hl> By about week 12 of pregnancy , nausea typically subsides .\",\n \"hl_sentences\": \"Nausea and vomiting , sometimes triggered by an increased sensitivity to odors , are common during the first few weeks to months of pregnancy . This phenomenon is often referred to as “ morning sickness , ” although the nausea may persist all day . Decreased intestinal peristalsis may also contribute to nausea .\",\n \"question\": {\n \"cloze_format\": \"___ is a possible culprit of “morning sickness”.\",\n \"normal_format\": \"Which of the following is a possible culprit of “morning sickness”?\",\n \"question_choices\": [\n \"increased minute respiration\",\n \"decreased intestinal peristalsis\",\n \"decreased aldosterone secretion\",\n \"increased blood volume\"\n ],\n \"question_id\": \"fs-id805292\",\n \"question_text\": \"Which of the following is a possible culprit of “morning sickness”?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"decreasing the inhibition of uterine contractility\"\n },\n \"bloom\": \"2\",\n \"hl_context\": \"<hl> First , recall that progesterone inhibits uterine contractions throughout the first several months of pregnancy . <hl> As the pregnancy enters its seventh month , progesterone levels plateau and then drop . Estrogen levels , however , continue to rise in the maternal circulation ( Figure 28.20 ) . The increasing ratio of estrogen to progesterone makes the myometrium ( the uterine smooth muscle ) more sensitive to stimuli that promote contractions ( because progesterone no longer inhibits them ) . Moreover , in the eighth month of pregnancy , fetal cortisol rises , which boosts estrogen secretion by the placenta and further overpowers the uterine-calming effects of progesterone . Some women may feel the result of the decreasing levels of progesterone in late pregnancy as weak and irregular peristaltic Braxton Hicks contractions , also called false labor . These contractions can often be relieved with rest or hydration . The placenta takes over the synthesis and secretion of progesterone throughout pregnancy as the corpus luteum degenerates . <hl> Like estrogen , progesterone suppresses FSH and LH . <hl> <hl> It also inhibits uterine contractions , protecting the fetus from preterm birth . <hl> <hl> This hormone decreases in late gestation , allowing uterine contractions to intensify and eventually progress to true labor . <hl> The placenta also produces hCG . In addition to promoting survival of the corpus luteum , hCG stimulates the male fetal gonads to secrete testosterone , which is essential for the development of the male reproductive system .\",\n \"hl_sentences\": \"First , recall that progesterone inhibits uterine contractions throughout the first several months of pregnancy . Like estrogen , progesterone suppresses FSH and LH . It also inhibits uterine contractions , protecting the fetus from preterm birth . This hormone decreases in late gestation , allowing uterine contractions to intensify and eventually progress to true labor .\",\n \"question\": {\n \"cloze_format\": \"The decrease in progesterone at the last weeks of pregnancy help to bring on labor by ___.\",\n \"normal_format\": \"How does the decrease in progesterone at the last weeks of pregnancy help to bring on labor?\",\n \"question_choices\": [\n \"stimulating FSH production\",\n \"decreasing the levels of estrogens\",\n \"dilating the cervix\",\n \"decreasing the inhibition of uterine contractility\"\n ],\n \"question_id\": \"fs-id1978449\",\n \"question_text\": \"How does the decrease in progesterone at the last weeks of pregnancy help to bring on labor?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"vertex occiput posterior\"\n },\n \"bloom\": null,\n \"hl_context\": \"The expulsion stage begins when the fetal head enters the birth canal and ends with birth of the newborn . It typically takes up to 2 hours , but it can last longer or be completed in minutes , depending in part on the orientation of the fetus . <hl> The vertex presentation known as the occiput anterior vertex is the most common presentation and is associated with the greatest ease of vaginal birth . <hl> <hl> The fetus faces the maternal spinal cord and the smallest part of the head ( the posterior aspect called the occiput ) exits the birth canal first . <hl>\",\n \"hl_sentences\": \"The vertex presentation known as the occiput anterior vertex is the most common presentation and is associated with the greatest ease of vaginal birth . The fetus faces the maternal spinal cord and the smallest part of the head ( the posterior aspect called the occiput ) exits the birth canal first .\",\n \"question\": {\n \"cloze_format\": \"The fetal presentation that is the easiest for vaginal birth is a ___.\",\n \"normal_format\": \"Which of these fetal presentations is the easiest for vaginal birth?\",\n \"question_choices\": [\n \"complete breech\",\n \"vertex occiput anterior\",\n \"frank breech\",\n \"vertex occiput posterior\"\n ],\n \"question_id\": \"fs-id1474295\",\n \"question_text\": \"Which of these fetal presentations is the easiest for vaginal birth?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"foramen ovale\"\n },\n \"bloom\": \"3\",\n \"hl_context\": \"Although the fetal liver is semifunctional , the fetal lungs are nonfunctional . <hl> The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale , a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether . <hl> Most of the rest of the blood is pumped to the right ventricle , and from there , into the pulmonary trunk , which splits into pulmonary arteries . However , a shunt within the pulmonary artery , the ductus arteriosus , diverts a portion of this blood into the aorta . This ensures that only a small volume of oxygenated blood passes through the immature pulmonary circuit , which has only minor metabolic requirements . Blood vessels of uninflated lungs have high resistance to flow , a condition that encourages blood to flow to the aorta , which presents much lower resistance . The oxygenated blood moves through the foramen ovale into the left atrium , where it mixes with the now deoxygenated blood returning from the pulmonary circuit . This blood then moves into the left ventricle , where it is pumped into the aorta . Some of this blood moves through the coronary arteries into the myocardium , and some moves through the carotid arteries to the brain .\",\n \"hl_sentences\": \"The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale , a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether .\",\n \"question\": {\n \"cloze_format\": \"The ___ shunt exists between the right and left atria.\",\n \"normal_format\": \"Which of these shunts exists between the right and left atria?\",\n \"question_choices\": [\n \"foramen ovale\",\n \"ductus venosus\",\n \"ductus arteriosis\",\n \"foramen venosus\"\n ],\n \"question_id\": \"fs-id810682\",\n \"question_text\": \"Which of these shunts exists between the right and left atria?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"It can be broken down to generate heat for thermoregulation.\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> The breakdown of brown fat occurs automatically upon exposure to cold , so it is an important heat regulator in newborns . <hl> During fetal development , the placenta secretes inhibitors that prevent metabolism of brown adipose fat and promote its accumulation in preparation for birth . <hl> Newborns , however , do have a special method for generating heat : nonshivering thermogenesis , which involves the breakdown of brown adipose tissue , or brown fat , which is distributed over the back , chest , and shoulders . <hl> Brown fat differs from the more familiar white fat in two ways :\",\n \"hl_sentences\": \"The breakdown of brown fat occurs automatically upon exposure to cold , so it is an important heat regulator in newborns . Newborns , however , do have a special method for generating heat : nonshivering thermogenesis , which involves the breakdown of brown adipose tissue , or brown fat , which is distributed over the back , chest , and shoulders .\",\n \"question\": {\n \"cloze_format\": \"Brown fat is important because ___ .\",\n \"normal_format\": \"Why is brown fat important?\",\n \"question_choices\": [\n \"It is the newborn’s primary source of insulation.\",\n \"It can be broken down to generate heat for thermoregulation.\",\n \"It can be broken down for energy between feedings.\",\n \"It can be converted to white fat.\"\n ],\n \"question_id\": \"fs-id1390282\",\n \"question_text\": \"Why is brown fat important?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"elevates carbon dioxide levels in the blood\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Although the fetus “ practices ” breathing by inhaling amniotic fluid in utero , there is no air in the uterus and thus no true opportunity to breathe . ( There is also no need to breathe because the placenta supplies the fetus with all the oxygenated blood it needs . ) During gestation , the partially collapsed lungs are filled with amniotic fluid and exhibit very little metabolic activity . Several factors stimulate newborns to take their first breath at birth . <hl> First , labor contractions temporarily constrict umbilical blood vessels , reducing oxygenated blood flow to the fetus and elevating carbon dioxide levels in the blood . <hl> High carbon dioxide levels cause acidosis and stimulate the respiratory center in the brain , triggering the newborn to take a breath .\",\n \"hl_sentences\": \"First , labor contractions temporarily constrict umbilical blood vessels , reducing oxygenated blood flow to the fetus and elevating carbon dioxide levels in the blood .\",\n \"question\": {\n \"cloze_format\": \"Constriction of umbilical blood vessels during vaginal birth ________.\",\n \"normal_format\": \"Which of the following causes are true about constriction of umbilical blood vessels during vaginal birth?\",\n \"question_choices\": [\n \"causes respiratory alkalosis\",\n \"inhibits the respiratory center in the brain\",\n \"elevates carbon dioxide levels in the blood\",\n \"both a and b\"\n ],\n \"question_id\": \"fs-id23202320\",\n \"question_text\": \"Constriction of umbilical blood vessels during vaginal birth ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"lactiferous ducts\"\n },\n \"bloom\": null,\n \"hl_context\": \"Mammary glands are modified sweat glands . The non-pregnant and non-lactating female breast is composed primarily of adipose and collagenous tissue , with mammary glands making up a very minor proportion of breast volume . The mammary gland is composed of milk-transporting lactiferous ducts , which expand and branch extensively during pregnancy in response to estrogen , growth hormone , cortisol , and prolactin . Moreover , in response to progesterone , clusters of breast alveoli bud from the ducts and expand outward toward the chest wall . <hl> Breast alveoli are balloon-like structures lined with milk-secreting cuboidal cells , or lactocytes , that are surrounded by a net of contractile myoepithelial cells . <hl> Milk is secreted from the lactocytes , fills the alveoli , and is squeezed into the ducts . <hl> Clusters of alveoli that drain to a common duct are called lobules ; the lactating female has 12 – 20 lobules organized radially around the nipple . <hl> <hl> Milk drains from lactiferous ducts into lactiferous sinuses that meet at 4 to 18 perforations in the nipple , called nipple pores . <hl> The small bumps of the areola ( the darkened skin around the nipple ) are called Montgomery glands . They secrete oil to cleanse the nipple opening and prevent chapping and cracking of the nipple during breastfeeding .\",\n \"hl_sentences\": \"Breast alveoli are balloon-like structures lined with milk-secreting cuboidal cells , or lactocytes , that are surrounded by a net of contractile myoepithelial cells . Clusters of alveoli that drain to a common duct are called lobules ; the lactating female has 12 – 20 lobules organized radially around the nipple . Milk drains from lactiferous ducts into lactiferous sinuses that meet at 4 to 18 perforations in the nipple , called nipple pores .\",\n \"question\": {\n \"cloze_format\": \"Alveoli are connected to the lactiferous sinuses by ________.\",\n \"normal_format\": \"By what are alveol connected to the lactiferous sinuses?\",\n \"question_choices\": [\n \"lactocytes\",\n \"lactiferous ducts\",\n \"nipple pores\",\n \"lobules\"\n ],\n \"question_id\": \"fs-id14839790\",\n \"question_text\": \"Alveoli are connected to the lactiferous sinuses by ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"It helps boost the newborn’s immune system.\"\n },\n \"bloom\": \"3\",\n \"hl_context\": \"Colostrum is secreted during the first 48 – 72 hours postpartum . Only a small volume of colostrum is produced — approximately 3 ounces in a 24 - hour period — but it is sufficient for the newborn in the first few days of life . <hl> Colostrum is rich with immunoglobulins , which confer gastrointestinal , and also likely systemic , immunity as the newborn adjusts to a nonsterile environment . <hl>\",\n \"hl_sentences\": \"Colostrum is rich with immunoglobulins , which confer gastrointestinal , and also likely systemic , immunity as the newborn adjusts to a nonsterile environment .\",\n \"question\": {\n \"cloze_format\": \"Colostrum is most important to a newborn because ___ .\",\n \"normal_format\": \"How is colostrum most important to a newborn?\",\n \"question_choices\": [\n \"It helps boost the newborn’s immune system.\",\n \"It provides much needed fat.\",\n \"It satisfies the newborn’s thirst.\",\n \"It satisfies the infant’s appetite.\"\n ],\n \"question_id\": \"fs-id2348104\",\n \"question_text\": \"How is colostrum most important to a newborn?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"has more fat than cow’s milk\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> After about the third postpartum day , the mother secretes transitional milk that represents an intermediate between mature milk and colostrum . <hl> This is followed by mature milk from approximately postpartum day 10 ( see Table 28.3 ) . <hl> As you can see in the accompanying table , cow ’ s milk is not a substitute for breast milk . <hl> <hl> It contains less lactose , less fat , and more protein and minerals . <hl> <hl> Moreover , the proteins in cow ’ s milk are difficult for an infant ’ s immature digestive system to metabolize and absorb . <hl>\",\n \"hl_sentences\": \"After about the third postpartum day , the mother secretes transitional milk that represents an intermediate between mature milk and colostrum . As you can see in the accompanying table , cow ’ s milk is not a substitute for breast milk . It contains less lactose , less fat , and more protein and minerals . Moreover , the proteins in cow ’ s milk are difficult for an infant ’ s immature digestive system to metabolize and absorb .\",\n \"question\": {\n \"cloze_format\": \"Mature breast milk ________.\",\n \"normal_format\": \"Which of the following is correct about mature breast milk?\",\n \"question_choices\": [\n \"has more sodium than cow’s milk\",\n \"has more calcium than cow’s milk\",\n \"has more protein than cow’s milk\",\n \"has more fat than cow’s milk\"\n ],\n \"question_id\": \"fs-id2242284\",\n \"question_text\": \"Mature breast milk ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"multiple alleles\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"In the simplest scenario , a single pair of genes will determine a single heritable characteristic . However , it is quite common for multiple genes to interact to confer a feature . For instance , eight or more genes — each with their own alleles — determine eye color in humans . <hl> Moreover , although any one person can only have two alleles corresponding to a given gene , more than two alleles commonly exist in a population . <hl> <hl> This phenomenon is called multiple alleles . <hl> <hl> For example , there are three different alleles that encode ABO blood type ; these are designated I A , I B , and i . <hl>\",\n \"hl_sentences\": \"Moreover , although any one person can only have two alleles corresponding to a given gene , more than two alleles commonly exist in a population . This phenomenon is called multiple alleles . For example , there are three different alleles that encode ABO blood type ; these are designated I A , I B , and i .\",\n \"question\": {\n \"cloze_format\": \"In addition to codominance, the ABO blood group antigens are also an example of ________.\",\n \"normal_format\": \"In addition to codominance, what are the ABO blood group antigens also an example of?\",\n \"question_choices\": [\n \"incomplete dominance\",\n \"X-linked recessive inheritance\",\n \"multiple alleles\",\n \"recessive lethal inheritance\"\n ],\n \"question_id\": \"fs-id1340094\",\n \"question_text\": \"In addition to codominance, the ABO blood group antigens are also an example of ________.\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":28,"string":"28"},"chapter_text":{"kind":"string","value":" 28.1 Fertilization Learning Objectives By the end of this section, you will be able to: \n\n Describe the obstacles that sperm must overcome to reach an oocyte \n\n Explain capacitation and its importance in fertilization \n\n Summarize the events that occur as a sperm fertilizes an oocyte \n\n Fertilization occurs when a sperm and an oocyte (egg) combine and their nuclei fuse. Because each of these reproductive cells is a haploid cell containing half of the genetic material needed to form a human being, their combination forms a diploid cell. This new single cell, called a zygote , contains all of the genetic material needed to form a human—half from the mother and half from the father. \n\n Transit of Sperm \n\n Fertilization is a numbers game. During ejaculation, hundreds of millions of sperm (spermatozoa) are released into the vagina. Almost immediately, millions of these sperm are overcome by the acidity of the vagina (approximately pH 3.8), and millions more may be blocked from entering the uterus by thick cervical mucus. Of those that do enter, thousands are destroyed by phagocytic uterine leukocytes. Thus, the race into the uterine tubes, which is the most typical site for sperm to encounter the oocyte, is reduced to a few thousand contenders. Their journey—thought to be facilitated by uterine contractions—usually takes from 30 minutes to 2 hours. If the sperm do not encounter an oocyte immediately, they can survive in the uterine tubes for another 3–5 days. Thus, fertilization can still occur if intercourse takes place a few days before ovulation. In comparison, an oocyte can survive independently for only approximately 24 hours following ovulation. Intercourse more than a day after ovulation will therefore usually not result in fertilization. \n\n During the journey, fluids in the female reproductive tract prepare the sperm for fertilization through a process called capacitation , or priming. The fluids improve the motility of the spermatozoa. They also deplete cholesterol molecules embedded in the membrane of the head of the sperm, thinning the membrane in such a way that will help facilitate the release of the lysosomal (digestive) enzymes needed for the sperm to penetrate the oocyte’s exterior once contact is made. Sperm must undergo the process of capacitation in order to have the “capacity” to fertilize an oocyte. If they reach the oocyte before capacitation is complete, they will be unable to penetrate the oocyte’s thick outer layer of cells. \n\n Contact Between Sperm and Oocyte \n\n Upon ovulation, the oocyte released by the ovary is swept into—and along—the uterine tube. Fertilization must occur in the distal uterine tube because an unfertilized oocyte cannot survive the 72-hour journey to the uterus. As you will recall from your study of the oogenesis, this oocyte (specifically a secondary oocyte) is surrounded by two protective layers. The corona radiata is an outer layer of follicular (granulosa) cells that form around a developing oocyte in the ovary and remain with it upon ovulation. The underlying zona pellucida (pellucid = “transparent”) is a transparent, but thick, glycoprotein membrane that surrounds the cell’s plasma membrane. \n\n As it is swept along the distal uterine tube, the oocyte encounters the surviving capacitated sperm, which stream toward it in response to chemical attractants released by the cells of the corona radiata. To reach the oocyte itself, the sperm must penetrate the two protective layers. The sperm first burrow through the cells of the corona radiata. Then, upon contact with the zona pellucida, the sperm bind to receptors in the zona pellucida. This initiates a process called the acrosomal reaction in which the enzyme-filled “cap” of the sperm, called the acrosome , releases its stored digestive enzymes. These enzymes clear a path through the zona pellucida that allows sperm to reach the oocyte. Finally, a single sperm makes contact with sperm-binding receptors on the oocyte’s plasma membrane ( Figure 28.2 ). The plasma membrane of that sperm then fuses with the oocyte’s plasma membrane, and the head and mid-piece of the “winning” sperm enter the oocyte interior. \n\n How do sperm penetrate the corona radiata? Some sperm undergo a spontaneous acrosomal reaction, which is an acrosomal reaction not triggered by contact with the zona pellucida. The digestive enzymes released by this reaction digest the extracellular matrix of the corona radiata. As you can see, the first sperm to reach the oocyte is never the one to fertilize it. Rather, hundreds of sperm cells must undergo the acrosomal reaction, each helping to degrade the corona radiata and zona pellucida until a path is created to allow one sperm to contact and fuse with the plasma membrane of the oocyte. If you consider the loss of millions of sperm between entry into the vagina and degradation of the zona pellucida, you can understand why a low sperm count can cause male infertility. \n\n When the first sperm fuses with the oocyte, the oocyte deploys two mechanisms to prevent polyspermy , which is penetration by more than one sperm. This is critical because if more than one sperm were to fertilize the oocyte, the resulting zygote would be a triploid organism with three sets of chromosomes. This is incompatible with life. \n\n The first mechanism is the fast block, which involves a near instantaneous change in sodium ion permeability upon binding of the first sperm, depolarizing the oocyte plasma membrane and preventing the fusion of additional sperm cells. The fast block sets in almost immediately and lasts for about a minute, during which time an influx of calcium ions following sperm penetration triggers the second mechanism, the slow block. In this process, referred to as the cortical reaction , cortical granules sitting immediately below the oocyte plasma membrane fuse with the membrane and release zonal inhibiting proteins and mucopolysaccharides into the space between the plasma membrane and the zona pellucida. Zonal inhibiting proteins cause the release of any other attached sperm and destroy the oocyte’s sperm receptors, thus preventing any more sperm from binding. The mucopolysaccharides then coat the nascent zygote in an impenetrable barrier that, together with hardened zona pellucida, is called a fertilization membrane . \n\n The Zygote \n\n Recall that at the point of fertilization, the oocyte has not yet completed meiosis; all secondary oocytes remain arrested in metaphase of meiosis II until fertilization. Only upon fertilization does the oocyte complete meiosis. The unneeded complement of genetic material that results is stored in a second polar body that is eventually ejected. At this moment, the oocyte has become an ovum, the female haploid gamete. The two haploid nuclei derived from the sperm and oocyte and contained within the egg are referred to as pronuclei. They decondense, expand, and replicate their DNA in preparation for mitosis. The pronuclei then migrate toward each other, their nuclear envelopes disintegrate, and the male- and female-derived genetic material intermingles. This step completes the process of fertilization and results in a single-celled diploid zygote with all the genetic instructions it needs to develop into a human. \n\n Most of the time, a woman releases a single egg during an ovulation cycle. However, in approximately 1 percent of ovulation cycles, two eggs are released and both are fertilized. Two zygotes form, implant, and develop, resulting in the birth of dizygotic (or fraternal) twins. Because dizygotic twins develop from two eggs fertilized by two sperm, they are no more identical than siblings born at different times. \n\n Much less commonly, a zygote can divide into two separate offspring during early development. This results in the birth of monozygotic (or identical) twins. Although the zygote can split as early as the two-cell stage, splitting occurs most commonly during the early blastocyst stage, with roughly 70–100 cells present. These two scenarios are distinct from each other, in that the twin embryos that separated at the two-cell stage will have individual placentas, whereas twin embryos that form from separation at the blastocyst stage will share a placenta and a chorionic cavity. \n\n Everyday Connection In Vitro Fertilization \n\nIVF, which stands for in vitro fertilization, is an assisted reproductive technology. In vitro, which in Latin translates to “in glass,” refers to a procedure that takes place outside of the body. There are many different indications for IVF. For example, a woman may produce normal eggs, but the eggs cannot reach the uterus because the uterine tubes are blocked or otherwise compromised. A man may have a low sperm count, low sperm motility, sperm with an unusually high percentage of morphological abnormalities, or sperm that are incapable of penetrating the zona pellucida of an egg. \n\n A typical IVF procedure begins with egg collection. A normal ovulation cycle produces only one oocyte, but the number can be boosted significantly (to 10–20 oocytes) by administering a short course of gonadotropins. The course begins with follicle-stimulating hormone (FSH) analogs, which support the development of multiple follicles, and ends with a luteinizing hormone (LH) analog that triggers ovulation. Right before the ova would be released from the ovary, they are harvested using ultrasound-guided oocyte retrieval. In this procedure, ultrasound allows a physician to visualize mature follicles. The ova are aspirated (sucked out) using a syringe. \n\n In parallel, sperm are obtained from the male partner or from a sperm bank. The sperm are prepared by washing to remove seminal fluid because seminal fluid contains a peptide, FPP (or, fertilization promoting peptide), that—in high concentrations—prevents capacitation of the sperm. The sperm sample is also concentrated, to increase the sperm count per milliliter. \n\n Next, the eggs and sperm are mixed in a petri dish. The ideal ratio is 75,000 sperm to one egg. If there are severe problems with the sperm—for example, the count is exceedingly low, or the sperm are completely nonmotile, or incapable of binding to or penetrating the zona pellucida—a sperm can be injected into an egg. This is called intracytoplasmic sperm injection (ICSI). \n\n The embryos are then incubated until they either reach the eight-cell stage or the blastocyst stage. In the United States, fertilized eggs are typically cultured to the blastocyst stage because this results in a higher pregnancy rate. Finally, the embryos are transferred to a woman’s uterus using a plastic catheter (tube). Figure 28.3 illustrates the steps involved in IVF. \n\n IVF is a relatively new and still evolving technology, and until recently it was necessary to transfer multiple embryos to achieve a good chance of a pregnancy. Today, however, transferred embryos are much more likely to implant successfully, so countries that regulate the IVF industry cap the number of embryos that can be transferred per cycle at two. This reduces the risk of multiple-birth pregnancies. \n\n The rate of success for IVF is correlated with a woman’s age. More than 40 percent of women under 35 succeed in giving birth following IVF, but the rate drops to a little over 10 percent in women over 40. \n\n Interactive Link \n\n Go to this site to view resources covering various aspects of fertilization, including movies and animations showing sperm structure and motility, ovulation, and fertilization. \n 28.2 Embryonic Development Learning Objectives By the end of this section, you will be able to: \n\n Distinguish the stages of embryonic development that occur before implantation \n\n Describe the process of implantation \n\n List and describe four embryonic membranes \n\n Explain gastrulation \n\n Describe how the placenta is formed and identify its functions \n\n Explain how an embryo transforms from a flat disc of cells into a three-dimensional shape resembling a human \n\n Summarize the process of organogenesis \n\n Throughout this chapter, we will express embryonic and fetal ages in terms of weeks from fertilization, commonly called conception. The period of time required for full development of a fetus in utero is referred to as gestation (gestare = “to carry” or “to bear”). It can be subdivided into distinct gestational periods. The first 2 weeks of prenatal development are referred to as the pre-embryonic stage. A developing human is referred to as an embryo during weeks 3–8, and a fetus from the ninth week of gestation until birth. In this section, we’ll cover the pre-embryonic and embryonic stages of development, which are characterized by cell division, migration, and differentiation. By the end of the embryonic period, all of the organ systems are structured in rudimentary form, although the organs themselves are either nonfunctional or only semi-functional. \n\n Pre-implantation Embryonic Development \n\n Following fertilization, the zygote and its associated membranes, together referred to as the conceptus , continue to be projected toward the uterus by peristalsis and beating cilia of the epithelial cells of the Fallopian tube. During its journey to the uterus, the zygote undergoes five or six rapid mitotic cell divisions. Although each cleavage results in more cells, it does not increase the total volume of the conceptus ( Figure 28.4 ). Each daughter cell produced by cleavage is called a blastomere (blastos = “germ,” in the sense of a seed or sprout). \n\n Approximately 3 days after fertilization, a 16-cell conceptus reaches the uterus. The cells that had been loosely grouped are now compacted and look more like a solid mass. The name given to this structure is the morula (morula = “little mulberry”). Once inside the uterus, the conceptus floats freely for several more days. It continues to divide, creating a ball of approximately 100 cells, and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens. The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity, the blastocoel . At this developmental stage, the conceptus is referred to as a blastocyst . Within this structure, a group of cells forms into an inner cell mass , which is fated to become the embryo. The cells that form the outer shell are called trophoblasts (trophe = “to feed” or “to nourish”). These cells will develop into the chorionic sac and the fetal portion of the placenta (the organ of nutrient, waste, and gas exchange between mother and the developing offspring). \n\n The inner mass of embryonic cells is totipotent during this stage, meaning that each cell has the potential to differentiate into any cell type in the human body. Totipotency lasts for only a few days before the cells’ fates are set as being the precursors to a specific lineage of cells. \n\n As the blastocyst forms, the trophoblast excretes enzymes that begin to degrade the zona pellucida. In a process called “hatching,” the conceptus breaks free of the zona pellucida in preparation for implantation. \n\n Interactive Link \n\n View this time-lapse movie of a conceptus starting at day 3. What is the first structure you see? At what point in the movie does the blastocoel first appear? What event occurs at the end of the movie? \n\n Implantation \n\n At the end of the first week, the blastocyst comes in contact with the uterine wall and adheres to it, embedding itself in the uterine lining via the trophoblast cells. Thus begins the process of implantation , which signals the end of the pre-embryonic stage of development ( Figure 28.5 ). Implantation can be accompanied by minor bleeding. The blastocyst typically implants in the fundus of the uterus or on the posterior wall. However, if the endometrium is not fully developed and ready to receive the blastocyst, the blastocyst will detach and find a better spot. A significant percentage (50–75 percent) of blastocysts fail to implant; when this occurs, the blastocyst is shed with the endometrium during menses. The high rate of implantation failure is one reason why pregnancy typically requires several ovulation cycles to achieve. \n\n When implantation succeeds and the blastocyst adheres to the endometrium, the superficial cells of the trophoblast fuse with each other, forming the syncytiotrophoblast , a multinucleated body that digests endometrial cells to firmly secure the blastocyst to the uterine wall. In response, the uterine mucosa rebuilds itself and envelops the blastocyst ( Figure 28.6 ). The trophoblast secretes human chorionic gonadotropin (hCG) , a hormone that directs the corpus luteum to survive, enlarge, and continue producing progesterone and estrogen to suppress menses. These functions of hCG are necessary for creating an environment suitable for the developing embryo. As a result of this increased production, hCG accumulates in the maternal bloodstream and is excreted in the urine. Implantation is complete by the middle of the second week. Just a few days after implantation, the trophoblast has secreted enough hCG for an at-home urine pregnancy test to give a positive result. \n\n Most of the time an embryo implants within the body of the uterus in a location that can support growth and development. However, in one to two percent of cases, the embryo implants either outside the uterus (an ectopic pregnancy ) or in a region of uterus that can create complications for the pregnancy. If the embryo implants in the inferior portion of the uterus, the placenta can potentially grow over the opening of the cervix, a condition call placenta previa . \n\n Disorders of the... Development of the Embryo \n\nIn the vast majority of ectopic pregnancies, the embryo does not complete its journey to the uterus and implants in the uterine tube, referred to as a tubal pregnancy. However, there are also ovarian ectopic pregnancies (in which the egg never left the ovary) and abdominal ectopic pregnancies (in which an egg was “lost” to the abdominal cavity during the transfer from ovary to uterine tube, or in which an embryo from a tubal pregnancy re-implanted in the abdomen). Once in the abdominal cavity, an embryo can implant into any well-vascularized structure—the rectouterine cavity (Douglas’ pouch), the mesentery of the intestines, and the greater omentum are some common sites. \n\n Tubal pregnancies can be caused by scar tissue within the tube following a sexually transmitted bacterial infection. The scar tissue impedes the progress of the embryo into the uterus—in some cases “snagging” the embryo and, in other cases, blocking the tube completely. Approximately one half of tubal pregnancies resolve spontaneously. Implantation in a uterine tube causes bleeding, which appears to stimulate smooth muscle contractions and expulsion of the embryo. In the remaining cases, medical or surgical intervention is necessary. If an ectopic pregnancy is detected early, the embryo’s development can be arrested by the administration of the cytotoxic drug methotrexate, which inhibits the metabolism of folic acid. If diagnosis is late and the uterine tube is already ruptured, surgical repair is essential. \n\n Even if the embryo has successfully found its way to the uterus, it does not always implant in an optimal location (the fundus or the posterior wall of the uterus). Placenta previa can result if an embryo implants close to the internal os of the uterus (the internal opening of the cervix). As the fetus grows, the placenta can partially or completely cover the opening of the cervix ( Figure 28.7 ). Although it occurs in only 0.5 percent of pregnancies, placenta previa is the leading cause of antepartum hemorrhage (profuse vaginal bleeding after week 24 of pregnancy but prior to childbirth). \n\n Embryonic Membranes \n\n During the second week of development, with the embryo implanted in the uterus, cells within the blastocyst start to organize into layers. Some grow to form the extra-embryonic membranes needed to support and protect the growing embryo: the amnion, the yolk sac, the allantois, and the chorion. \n\n At the beginning of the second week, the cells of the inner cell mass form into a two-layered disc of embryonic cells, and a space—the amniotic cavity —opens up between it and the trophoblast ( Figure 28.8 ). Cells from the upper layer of the disc (the epiblast ) extend around the amniotic cavity, creating a membranous sac that forms into the amnion by the end of the second week. The amnion fills with amniotic fluid and eventually grows to surround the embryo. Early in development, amniotic fluid consists almost entirely of a filtrate of maternal plasma, but as the kidneys of the fetus begin to function at approximately the eighth week, they add urine to the volume of amniotic fluid. Floating within the amniotic fluid, the embryo—and later, the fetus—is protected from trauma and rapid temperature changes. It can move freely within the fluid and can prepare for swallowing and breathing out of the uterus. \n\n On the ventral side of the embryonic disc, opposite the amnion, cells in the lower layer of the embryonic disk (the hypoblast ) extend into the blastocyst cavity and form a yolk sac . The yolk sac supplies some nutrients absorbed from the trophoblast and also provides primitive blood circulation to the developing embryo for the second and third week of development. When the placenta takes over nourishing the embryo at approximately week 4, the yolk sac has been greatly reduced in size and its main function is to serve as the source of blood cells and germ cells (cells that will give rise to gametes). During week 3, a finger-like outpocketing of the yolk sac develops into the allantois , a primitive excretory duct of the embryo that will become part of the urinary bladder. Together, the stalks of the yolk sac and allantois establish the outer structure of the umbilical cord. \n\n The last of the extra-embryonic membranes is the chorion , which is the one membrane that surrounds all others. The development of the chorion will be discussed in more detail shortly, as it relates to the growth and development of the placenta. \n\n Embryogenesis \n\n As the third week of development begins, the two-layered disc of cells becomes a three-layered disc through the process of gastrulation , during which the cells transition from totipotency to multipotency. The embryo, which takes the shape of an oval-shaped disc, forms an indentation called the primitive streak along the dorsal surface of the epiblast. A node at the caudal or “tail” end of the primitive streak emits growth factors that direct cells to multiply and migrate. Cells migrate toward and through the primitive streak and then move laterally to create two new layers of cells. The first layer is the endoderm , a sheet of cells that displaces the hypoblast and lies adjacent to the yolk sac. The second layer of cells fills in as the middle layer, or mesoderm . The cells of the epiblast that remain (not having migrated through the primitive streak) become the ectoderm ( Figure 28.9 ). \n\n Each of these germ layers will develop into specific structures in the embryo. Whereas the ectoderm and endoderm form tightly connected epithelial sheets, the mesodermal cells are less organized and exist as a loosely connected cell community. The ectoderm gives rise to cell lineages that differentiate to become the central and peripheral nervous systems, sensory organs, epidermis, hair, and nails. Mesodermal cells ultimately become the skeleton, muscles, connective tissue, heart, blood vessels, and kidneys. The endoderm goes on to form the epithelial lining of the gastrointestinal tract, liver, and pancreas, as well as the lungs ( Figure 28.10 ). \n\n Development of the Placenta \n\n During the first several weeks of development, the cells of the endometrium—referred to as decidual cells—nourish the nascent embryo. During prenatal weeks 4–12, the developing placenta gradually takes over the role of feeding the embryo, and the decidual cells are no longer needed. The mature placenta is composed of tissues derived from the embryo, as well as maternal tissues of the endometrium. The placenta connects to the conceptus via the umbilical cord , which carries deoxygenated blood and wastes from the fetus through two umbilical arteries; nutrients and oxygen are carried from the mother to the fetus through the single umbilical vein. The umbilical cord is surrounded by the amnion, and the spaces within the cord around the blood vessels are filled with Wharton’s jelly, a mucous connective tissue. \n\n The maternal portion of the placenta develops from the deepest layer of the endometrium, the decidua basalis. To form the embryonic portion of the placenta, the syncytiotrophoblast and the underlying cells of the trophoblast (cytotrophoblast cells) begin to proliferate along with a layer of extraembryonic mesoderm cells. These form the chorionic membrane , which envelops the entire conceptus as the chorion. The chorionic membrane forms finger-like structures called chorionic villi that burrow into the endometrium like tree roots, making up the fetal portion of the placenta. The cytotrophoblast cells perforate the chorionic villi, burrow farther into the endometrium, and remodel maternal blood vessels to augment maternal blood flow surrounding the villi. Meanwhile, fetal mesenchymal cells derived from the mesoderm fill the villi and differentiate into blood vessels, including the three umbilical blood vessels that connect the embryo to the developing placenta ( Figure 28.11 ). \n\n The placenta develops throughout the embryonic period and during the first several weeks of the fetal period; placentation is complete by weeks 14–16. As a fully developed organ, the placenta provides nutrition and excretion, respiration, and endocrine function ( Table 28.1 and Figure 28.12 ). It receives blood from the fetus through the umbilical arteries. Capillaries in the chorionic villi filter fetal wastes out of the blood and return clean, oxygenated blood to the fetus through the umbilical vein. Nutrients and oxygen are transferred from maternal blood surrounding the villi through the capillaries and into the fetal bloodstream. Some substances move across the placenta by simple diffusion. Oxygen, carbon dioxide, and any other lipid-soluble substances take this route. Other substances move across by facilitated diffusion. This includes water-soluble glucose. The fetus has a high demand for amino acids and iron, and those substances are moved across the placenta by active transport. \n\n Maternal and fetal blood does not commingle because blood cells cannot move across the placenta. This separation prevents the mother’s cytotoxic T cells from reaching and subsequently destroying the fetus, which bears “non-self” antigens. Further, it ensures the fetal red blood cells do not enter the mother’s circulation and trigger antibody development (if they carry “non-self” antigens)—at least until the final stages of pregnancy or birth. This is the reason that, even in the absence of preventive treatment, an Rh − mother doesn’t develop antibodies that could cause hemolytic disease in her first Rh + fetus. \n\n Although blood cells are not exchanged, the chorionic villi provide ample surface area for the two-way exchange of substances between maternal and fetal blood. The rate of exchange increases throughout gestation as the villi become thinner and increasingly branched. The placenta is permeable to lipid-soluble fetotoxic substances: alcohol, nicotine, barbiturates, antibiotics, certain pathogens, and many other substances that can be dangerous or fatal to the developing embryo or fetus. For these reasons, pregnant women should avoid fetotoxic substances. Alcohol consumption by pregnant women, for example, can result in a range of abnormalities referred to as fetal alcohol spectrum disorders (FASD). These include organ and facial malformations, as well as cognitive and behavioral disorders. \n\n Functions of the Placenta \n\n Nutrition and digestion \n\n Respiration \n\n Endocrine function \n\n Mediates diffusion of maternal glucose, amino acids, fatty acids, vitamins, and minerals \n\n Stores nutrients during early pregnancy to accommodate increased fetal demand later in pregnancy \n\n Excretes and filters fetal nitrogenous wastes into maternal blood \n\n Mediates maternal-to-fetal oxygen transport and fetal-to-maternal carbon dioxide transport \n\n Secretes several hormones, including hCG, estrogens, and progesterone, to maintain the pregnancy and stimulate maternal and fetal development \n\n Mediates the transmission of maternal hormones into fetal blood and vice versa \n\n Table 28.1 \n\n Organogenesis Following gastrulation, rudiments of the central nervous system develop from the ectoderm in the process of neurulation ( Figure 28.13 ). Specialized neuroectodermal tissues along the length of the embryo thicken into the neural plate . During the fourth week, tissues on either side of the plate fold upward into a neural fold . The two folds converge to form the neural tube . The tube lies atop a rod-shaped, mesoderm-derived notochord , which eventually becomes the nucleus pulposus of intervertebral discs. Block-like structures called somites form on either side of the tube, eventually differentiating into the axial skeleton, skeletal muscle, and dermis. During the fourth and fifth weeks, the anterior neural tube dilates and subdivides to form vesicles that will become the brain structures. \n\n Folate, one of the B vitamins, is important to the healthy development of the neural tube. A deficiency of maternal folate in the first weeks of pregnancy can result in neural tube defects, including spina bifida—a birth defect in which spinal tissue protrudes through the newborn’s vertebral column, which has failed to completely close. A more severe neural tube defect is anencephaly, a partial or complete absence of brain tissue. \n\n The embryo, which begins as a flat sheet of cells, begins to acquire a cylindrical shape through the process of embryonic folding ( Figure 28.14 ). The embryo folds laterally and again at either end, forming a C-shape with distinct head and tail ends. The embryo envelops a portion of the yolk sac, which protrudes with the umbilical cord from what will become the abdomen. The folding essentially creates a tube, called the primitive gut, that is lined by the endoderm. The amniotic sac, which was sitting on top of the flat embryo, envelops the embryo as it folds. \n\n Within the first 8 weeks of gestation, a developing embryo establishes the rudimentary structures of all of its organs and tissues from the ectoderm, mesoderm, and endoderm. This process is called organogenesis . \n\n Like the central nervous system, the heart also begins its development in the embryo as a tube-like structure, connected via capillaries to the chorionic villi. Cells of the primitive tube-shaped heart are capable of electrical conduction and contraction. The heart begins beating in the beginning of the fourth week, although it does not actually pump embryonic blood until a week later, when the oversized liver has begun producing red blood cells. (This is a temporary responsibility of the embryonic liver that the bone marrow will assume during fetal development.) During weeks 4–5, the eye pits form, limb buds become apparent, and the rudiments of the pulmonary system are formed. \n\n During the sixth week, uncontrolled fetal limb movements begin to occur. The gastrointestinal system develops too rapidly for the embryonic abdomen to accommodate it, and the intestines temporarily loop into the umbilical cord. Paddle-shaped hands and feet develop fingers and toes by the process of apoptosis (programmed cell death), which causes the tissues between the fingers to disintegrate. By week 7, the facial structure is more complex and includes nostrils, outer ears, and lenses ( Figure 28.15 ). By the eighth week, the head is nearly as large as the rest of the embryo’s body, and all major brain structures are in place. The external genitalia are apparent, but at this point, male and female embryos are indistinguishable. Bone begins to replace cartilage in the embryonic skeleton through the process of ossification. By the end of the embryonic period, the embryo is approximately 3 cm (1.2 in) from crown to rump and weighs approximately 8 g (0.25 oz). \n\n Interactive Link Use this interactive tool to view the process of embryogenesis from fertilization through pregnancy to birth. Can you identify when neurulation occurs in the embryo? \n 28.3 Fetal Development Learning Objectives By the end of this section, you will be able to: \n\n Differentiate between the embryonic period and the fetal period \n\n Briefly describe the process of sexual differentiation \n\n Describe the fetal circulatory system and explain the role of the shunts \n\n Trace the development of a fetus from the end of the embryonic period to birth \n\n As you will recall, a developing human is called a fetus from the ninth week of gestation until birth. This 30-week period of development is marked by continued cell growth and differentiation, which fully develop the structures and functions of the immature organ systems formed during the embryonic period. The completion of fetal development results in a newborn who, although still immature in many ways, is capable of survival outside the womb. \n\n Sexual Differentiation \n\n Sexual differentiation does not begin until the fetal period, during weeks 9–12. Embryonic males and females, though genetically distinguishable, are morphologically identical ( Figure 28.16 ). Bipotential gonads, or gonads that can develop into male or female sexual organs, are connected to a central cavity called the cloaca via Müllerian ducts and Wolffian ducts. (The cloaca is an extension of the primitive gut.) Several events lead to sexual differentiation during this period. \n\n During male fetal development, the bipotential gonads become the testes and associated epididymis. The Müllerian ducts degenerate. The Wolffian ducts become the vas deferens, and the cloaca becomes the urethra and rectum. \n\n During female fetal development, the bipotential gonads develop into ovaries. The Wolffian ducts degenerate. The Müllerian ducts become the uterine tubes and uterus, and the cloaca divides and develops into a vagina, a urethra, and a rectum. \n\n The Fetal Circulatory System \n\n During prenatal development, the fetal circulatory system is integrated with the placenta via the umbilical cord so that the fetus receives both oxygen and nutrients from the placenta. However, after childbirth, the umbilical cord is severed, and the newborn’s circulatory system must be reconfigured. When the heart first forms in the embryo, it exists as two parallel tubes derived from mesoderm and lined with endothelium, which then fuse together. As the embryo develops into a fetus, the tube-shaped heart folds and further differentiates into the four chambers present in a mature heart. Unlike a mature cardiovascular system, however, the fetal cardiovascular system also includes circulatory shortcuts, or shunts. A shunt is an anatomical (or sometimes surgical) diversion that allows blood flow to bypass immature organs such as the lungs and liver until childbirth. \n\n The placenta provides the fetus with necessary oxygen and nutrients via the umbilical vein. (Remember that veins carry blood toward the heart. In this case, the blood flowing to the fetal heart is oxygenated because it comes from the placenta. The respiratory system is immature and cannot yet oxygenate blood on its own.) From the umbilical vein, the oxygenated blood flows toward the inferior vena cava, all but bypassing the immature liver, via the ductus venosus shunt ( Figure 28.17 ). The liver receives just a trickle of blood, which is all that it needs in its immature, semifunctional state. Blood flows from the inferior vena cava to the right atrium, mixing with fetal venous blood along the way. \n\n Although the fetal liver is semifunctional, the fetal lungs are nonfunctional. The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale , a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether. Most of the rest of the blood is pumped to the right ventricle, and from there, into the pulmonary trunk, which splits into pulmonary arteries. However, a shunt within the pulmonary artery, the ductus arteriosus , diverts a portion of this blood into the aorta. This ensures that only a small volume of oxygenated blood passes through the immature pulmonary circuit, which has only minor metabolic requirements. Blood vessels of uninflated lungs have high resistance to flow, a condition that encourages blood to flow to the aorta, which presents much lower resistance. The oxygenated blood moves through the foramen ovale into the left atrium, where it mixes with the now deoxygenated blood returning from the pulmonary circuit. This blood then moves into the left ventricle, where it is pumped into the aorta. Some of this blood moves through the coronary arteries into the myocardium, and some moves through the carotid arteries to the brain. \n\n The descending aorta carries partially oxygenated and partially deoxygenated blood into the lower regions of the body. It eventually passes into the umbilical arteries through branches of the internal iliac arteries. The deoxygenated blood collects waste as it circulates through the fetal body and returns to the umbilical cord. Thus, the two umbilical arteries carry blood low in oxygen and high in carbon dioxide and fetal wastes. This blood is filtered through the placenta, where wastes diffuse into the maternal circulation. Oxygen and nutrients from the mother diffuse into the placenta and from there into the fetal blood, and the process repeats. \n\n Other Organ Systems During weeks 9–12 of fetal development, the brain continues to expand, the body elongates, and ossification continues. Fetal movements are frequent during this period, but are jerky and not well-controlled. The bone marrow begins to take over the process of erythrocyte production—a task that the liver performed during the embryonic period. The liver now secretes bile. The fetus circulates amniotic fluid by swallowing it and producing urine. The eyes are well-developed by this stage, but the eyelids are fused shut. The fingers and toes begin to develop nails. By the end of week 12, the fetus measures approximately 9 cm (3.5 in) from crown to rump. Weeks 13–16 are marked by sensory organ development. The eyes move closer together; blinking motions begin, although the eyes remain sealed shut. The lips exhibit sucking motions. The ears move upward and lie flatter against the head. The scalp begins to grow hair. The excretory system is also developing: the kidneys are well-formed, and meconium , or fetal feces, begins to accumulate in the intestines. Meconium consists of ingested amniotic fluid, cellular debris, mucus, and bile. \n\n During approximately weeks 16–20, as the fetus grows and limb movements become more powerful, the mother may begin to feel quickening , or fetal movements. However, space restrictions limit these movements and typically force the growing fetus into the “fetal position,” with the arms crossed and the legs bent at the knees. Sebaceous glands coat the skin with a waxy, protective substance called vernix caseosa that protects and moisturizes the skin and may provide lubrication during childbirth. A silky hair called lanugo also covers the skin during weeks 17–20, but it is shed as the fetus continues to grow. Extremely premature infants sometimes exhibit residual lanugo. \n\n Developmental weeks 21–30 are characterized by rapid weight gain, which is important for maintaining a stable body temperature after birth. The bone marrow completely takes over erythrocyte synthesis, and the axons of the spinal cord begin to be myelinated, or coated in the electrically insulating glial cell sheaths that are necessary for efficient nervous system functioning. (The process of myelination is not completed until adolescence.) During this period, the fetus grows eyelashes. The eyelids are no longer fused and can be opened and closed. The lungs begin producing surfactant, a substance that reduces surface tension in the lungs and assists proper lung expansion after birth. Inadequate surfactant production in premature newborns may result in respiratory distress syndrome, and as a result, the newborn may require surfactant replacement therapy, supplemental oxygen, or maintenance in a continuous positive airway pressure (CPAP) chamber during their first days or weeks of life. In male fetuses, the testes descend into the scrotum near the end of this period. The fetus at 30 weeks measures 28 cm (11 in) from crown to rump and exhibits the approximate body proportions of a full-term newborn, but still is much leaner. \n\n Interactive Link \n\n Visit this site for a summary of the stages of pregnancy, as experienced by the mother, and view the stages of development of the fetus throughout gestation. At what point in fetal development can a regular heartbeat be detected? \n\n The fetus continues to lay down subcutaneous fat from week 31 until birth. The added fat fills out the hypodermis, and the skin transitions from red and wrinkled to soft and pink. Lanugo is shed, and the nails grow to the tips of the fingers and toes. Immediately before birth, the average crown-to-rump length is 35.5–40.5 cm (14–16 in), and the fetus weighs approximately 2.5–4 kg (5.5–8.8 lbs). Once born, the newborn is no longer confined to the fetal position, so subsequent measurements are made from head-to-toe instead of from crown-to-rump. At birth, the average length is approximately 51 cm (20 in). \n\n Disorders of the... Developing Fetus \n\nThroughout the second half of gestation, the fetal intestines accumulate a tarry, greenish black meconium. The newborn’s first stools consist almost entirely of meconium; they later transition to seedy yellow stools or slightly formed tan stools as meconium is cleared and replaced with digested breast milk or formula, respectively. Unlike these later stools, meconium is sterile; it is devoid of bacteria because the fetus is in a sterile environment and has not consumed any breast milk or formula. Typically, an infant does not pass meconium until after birth. However, in 5–20 percent of births, the fetus has a bowel movement in utero, which can cause major complications in the newborn. \n\n The passage of meconium in the uterus signals fetal distress, particularly fetal hypoxia (i.e., oxygen deprivation). This may be caused by maternal drug abuse (especially tobacco or cocaine), maternal hypertension, depletion of amniotic fluid, long labor or difficult birth, or a defect in the placenta that prevents it from delivering adequate oxygen to the fetus. Meconium passage is typically a complication of full-term or post-term newborns because it is rarely passed before 34 weeks of gestation, when the gastrointestinal system has matured and is appropriately controlled by nervous system stimuli. Fetal distress can stimulate the vagus nerve to trigger gastrointestinal peristalsis and relaxation of the anal sphincter. Notably, fetal hypoxic stress also induces a gasping reflex, increasing the likelihood that meconium will be inhaled into the fetal lungs. \n\n Although meconium is a sterile substance, it interferes with the antibiotic properties of the amniotic fluid and makes the newborn and mother more vulnerable to bacterial infections at birth and during the perinatal period. Specifically, inflammation of the fetal membranes, inflammation of the uterine lining, or neonatal sepsis (infection in the newborn) may occur. Meconium also irritates delicate fetal skin and can cause a rash. \n\n The first sign that a fetus has passed meconium usually does not come until childbirth, when the amniotic sac ruptures. Normal amniotic fluid is clear and watery, but amniotic fluid in which meconium has been passed is stained greenish or yellowish. Antibiotics given to the mother may reduce the incidence of maternal bacterial infections, but it is critical that meconium is aspirated from the newborn before the first breath. Under these conditions, an obstetrician will extensively aspirate the infant’s airways as soon as the head is delivered, while the rest of the infant’s body is still inside the birth canal. \n\n Aspiration of meconium with the first breath can result in labored breathing, a barrel-shaped chest, or a low Apgar score. An obstetrician can identify meconium aspiration by listening to the lungs with a stethoscope for a coarse rattling sound. Blood gas tests and chest X-rays of the infant can confirm meconium aspiration. Inhaled meconium after birth could obstruct a newborn’s airways leading to alveolar collapse, interfere with surfactant function by stripping it from the lungs, or cause pulmonary inflammation or hypertension. Any of these complications will make the newborn much more vulnerable to pulmonary infection, including pneumonia. \n 28.4 Maternal Changes During Pregnancy, Labor, and Birth Learning Objectives By the end of this section, you will be able to: \n\n Explain how estrogen, progesterone, and hCG are involved in maintaining pregnancy \n\n List the contributors to weight gain during pregnancy \n\n Describe the major changes to the maternal digestive, circulatory, and integumentary systems during pregnancy \n\n Summarize the events leading to labor \n\n Identify and describe each of the three stages of childbirth \n\n A full-term pregnancy lasts approximately 270 days (approximately 38.5 weeks) from conception to birth. Because it is easier to remember the first day of the last menstrual period (LMP) than to estimate the date of conception, obstetricians set the due date as 284 days (approximately 40.5 weeks) from the LMP. This assumes that conception occurred on day 14 of the woman’s cycle, which is usually a good approximation. The 40 weeks of an average pregnancy are usually discussed in terms of three trimesters , each approximately 13 weeks. During the second and third trimesters, the pre-pregnancy uterus—about the size of a fist—grows dramatically to contain the fetus, causing a number of anatomical changes in the mother ( Figure 28.18 ). \n\n Effects of Hormones \n\n Virtually all of the effects of pregnancy can be attributed in some way to the influence of hormones—particularly estrogens, progesterone, and hCG. During weeks 7–12 from the LMP, the pregnancy hormones are primarily generated by the corpus luteum. Progesterone secreted by the corpus luteum stimulates the production of decidual cells of the endometrium that nourish the blastocyst before placentation. As the placenta develops and the corpus luteum degenerates during weeks 12–17, the placenta gradually takes over as the endocrine organ of pregnancy. \n\n The placenta converts weak androgens secreted by the maternal and fetal adrenal glands to estrogens, which are necessary for pregnancy to progress. Estrogen levels climb throughout the pregnancy, increasing 30-fold by childbirth. Estrogens have the following actions: \n\n They suppress FSH and LH production, effectively preventing ovulation. (This function is the biological basis of hormonal birth control pills.) \n\n They induce the growth of fetal tissues and are necessary for the maturation of the fetal lungs and liver. \n\n They promote fetal viability by regulating progesterone production and triggering fetal synthesis of cortisol, which helps with the maturation of the lungs, liver, and endocrine organs such as the thyroid gland and adrenal gland. \n\n They stimulate maternal tissue growth, leading to uterine enlargement and mammary duct expansion and branching. \n\n Relaxin, another hormone secreted by the corpus luteum and then by the placenta, helps prepare the mother’s body for childbirth. It increases the elasticity of the symphysis pubis joint and pelvic ligaments, making room for the growing fetus and allowing expansion of the pelvic outlet for childbirth. Relaxin also helps dilate the cervix during labor. \n\n The placenta takes over the synthesis and secretion of progesterone throughout pregnancy as the corpus luteum degenerates. Like estrogen, progesterone suppresses FSH and LH. It also inhibits uterine contractions, protecting the fetus from preterm birth. This hormone decreases in late gestation, allowing uterine contractions to intensify and eventually progress to true labor. The placenta also produces hCG. In addition to promoting survival of the corpus luteum, hCG stimulates the male fetal gonads to secrete testosterone, which is essential for the development of the male reproductive system. \n\n The anterior pituitary enlarges and ramps up its hormone production during pregnancy, raising the levels of thyrotropin, prolactin, and adrenocorticotropic hormone (ACTH). Thyrotropin, in conjunction with placental hormones, increases the production of thyroid hormone, which raises the maternal metabolic rate. This can markedly augment a pregnant woman’s appetite and cause hot flashes. Prolactin stimulates enlargement of the mammary glands in preparation for milk production. ACTH stimulates maternal cortisol secretion, which contributes to fetal protein synthesis. In addition to the pituitary hormones, increased parathyroid levels mobilize calcium from maternal bones for fetal use. \n\n Weight Gain \n\n The second and third trimesters of pregnancy are associated with dramatic changes in maternal anatomy and physiology. The most obvious anatomical sign of pregnancy is the dramatic enlargement of the abdominal region, coupled with maternal weight gain. This weight results from the growing fetus as well as the enlarged uterus, amniotic fluid, and placenta. Additional breast tissue and dramatically increased blood volume also contribute to weight gain ( Table 28.2 ). Surprisingly, fat storage accounts for only approximately 2.3 kg (5 lbs) in a normal pregnancy and serves as a reserve for the increased metabolic demand of breastfeeding. \n\n During the first trimester, the mother does not need to consume additional calories to maintain a healthy pregnancy. However, a weight gain of approximately 0.45 kg (1 lb) per month is common. During the second and third trimesters, the mother’s appetite increases, but it is only necessary for her to consume an additional 300 calories per day to support the growing fetus. Most women gain approximately 0.45 kg (1 lb) per week. \n\n Contributors to Weight Gain During Pregnancy \n\n Component \n\n Weight (kg) \n\n Weight (lb) \n\n Fetus \n\n 3.2–3.6 \n\n 7–8 \n\n Placenta and fetal membranes \n\n 0.9–1.8 \n\n 2–4 \n\n Amniotic fluid \n\n 0.9–1.4 \n\n 2–3 \n\n Breast tissue \n\n 0.9–1.4 \n\n 2–3 \n\n Blood \n\n 1.4 \n\n 4 \n\n Fat \n\n 0.9–4.1 \n\n 3–9 \n\n Uterus \n\n 0.9–2.3 \n\n 2–5 \n\n Total \n\n 10–16.3 \n\n 22–36 \n\n Table 28.2 \n\n Changes in Organ Systems During Pregnancy \n\n As the woman’s body adapts to pregnancy, characteristic physiologic changes occur. These changes can sometimes prompt symptoms often referred to collectively as the common discomforts of pregnancy. \n\n Digestive and Urinary System Changes \n\n Nausea and vomiting, sometimes triggered by an increased sensitivity to odors, are common during the first few weeks to months of pregnancy. This phenomenon is often referred to as “morning sickness,” although the nausea may persist all day. The source of pregnancy nausea is thought to be the increased circulation of pregnancy-related hormones, specifically circulating estrogen, progesterone, and hCG. Decreased intestinal peristalsis may also contribute to nausea. By about week 12 of pregnancy, nausea typically subsides. \n\n A common gastrointestinal complaint during the later stages of pregnancy is gastric reflux, or heartburn, which results from the upward, constrictive pressure of the growing uterus on the stomach. The same decreased peristalsis that may contribute to nausea in early pregnancy is also thought to be responsible for pregnancy-related constipation as pregnancy progresses. \n\n The downward pressure of the uterus also compresses the urinary bladder, leading to frequent urination. The problem is exacerbated by increased urine production. In addition, the maternal urinary system processes both maternal and fetal wastes, further increasing the total volume of urine. \n\n Circulatory System Changes \n\n Blood volume increases substantially during pregnancy, so that by childbirth, it exceeds its preconception volume by 30 percent, or approximately 1–2 liters. The greater blood volume helps to manage the demands of fetal nourishment and fetal waste removal. In conjunction with increased blood volume, the pulse and blood pressure also rise moderately during pregnancy. As the fetus grows, the uterus compresses underlying pelvic blood vessels, hampering venous return from the legs and pelvic region. As a result, many pregnant women develop varicose veins or hemorrhoids. \n\n Respiratory System Changes \n\n During the second half of pregnancy, the respiratory minute volume (volume of gas inhaled or exhaled by the lungs per minute) increases by 50 percent to compensate for the oxygen demands of the fetus and the increased maternal metabolic rate. The growing uterus exerts upward pressure on the diaphragm, decreasing the volume of each inspiration and potentially causing shortness of breath, or dyspnea. During the last several weeks of pregnancy, the pelvis becomes more elastic, and the fetus descends lower in a process called lightening . This typically ameliorates dyspnea. \n\n The respiratory mucosa swell in response to increased blood flow during pregnancy, leading to nasal congestion and nose bleeds, particularly when the weather is cold and dry. Humidifier use and increased fluid intake are often recommended to counteract congestion. \n\n Integumentary System Changes The dermis stretches extensively to accommodate the growing uterus, breast tissue, and fat deposits on the thighs and hips. Torn connective tissue beneath the dermis can cause striae (stretch marks) on the abdomen, which appear as red or purple marks during pregnancy that fade to a silvery white color in the months after childbirth. \n\n An increase in melanocyte-stimulating hormone, in conjunction with estrogens, darkens the areolae and creates a line of pigment from the umbilicus to the pubis called the linea nigra ( Figure 28.19 ). Melanin production during pregnancy may also darken or discolor skin on the face to create a chloasma, or “mask of pregnancy.” \n\n Physiology of Labor \n\n Childbirth, or parturition , typically occurs within a week of a woman’s due date, unless the woman is pregnant with more than one fetus, which usually causes her to go into labor early. As a pregnancy progresses into its final weeks, several physiological changes occur in response to hormones that trigger labor. \n\n First, recall that progesterone inhibits uterine contractions throughout the first several months of pregnancy. As the pregnancy enters its seventh month, progesterone levels plateau and then drop. Estrogen levels, however, continue to rise in the maternal circulation ( Figure 28.20 ). The increasing ratio of estrogen to progesterone makes the myometrium (the uterine smooth muscle) more sensitive to stimuli that promote contractions (because progesterone no longer inhibits them). Moreover, in the eighth month of pregnancy, fetal cortisol rises, which boosts estrogen secretion by the placenta and further overpowers the uterine-calming effects of progesterone. Some women may feel the result of the decreasing levels of progesterone in late pregnancy as weak and irregular peristaltic Braxton Hicks contractions , also called false labor. These contractions can often be relieved with rest or hydration. \n\n A common sign that labor will be short is the so-called “bloody show.” During pregnancy, a plug of mucus accumulates in the cervical canal, blocking the entrance to the uterus. Approximately 1–2 days prior to the onset of true labor, this plug loosens and is expelled, along with a small amount of blood. \n\n Meanwhile, the posterior pituitary has been boosting its secretion of oxytocin, a hormone that stimulates the contractions of labor. At the same time, the myometrium increases its sensitivity to oxytocin by expressing more receptors for this hormone. As labor nears, oxytocin begins to stimulate stronger, more painful uterine contractions, which—in a positive feedback loop—stimulate the secretion of prostaglandins from fetal membranes. Like oxytocin, prostaglandins also enhance uterine contractile strength. The fetal pituitary also secretes oxytocin, which increases prostaglandins even further. Given the importance of oxytocin and prostaglandins to the initiation and maintenance of labor, it is not surprising that, when a pregnancy is not progressing to labor and needs to be induced, a pharmaceutical version of these compounds (called pitocin) is administered by intravenous drip. \n\n Finally, stretching of the myometrium and cervix by a full-term fetus in the vertex (head-down) position is regarded as a stimulant to uterine contractions. The sum of these changes initiates the regular contractions known as true labor , which become more powerful and more frequent with time. The pain of labor is attributed to myometrial hypoxia during uterine contractions. \n\n Stages of Childbirth \n\n The process of childbirth can be divided into three stages: cervical dilation, expulsion of the newborn, and afterbirth ( Figure 28.21 ). \n\n Cervical Dilation \n\n For vaginal birth to occur, the cervix must dilate fully to 10 cm in diameter—wide enough to deliver the newborn’s head. The dilation stage is the longest stage of labor and typically takes 6–12 hours. However, it varies widely and may take minutes, hours, or days, depending in part on whether the mother has given birth before; in each subsequent labor, this stage tends to be shorter. True labor progresses in a positive feedback loop in which uterine contractions stretch the cervix, causing it to dilate and efface, or become thinner. Cervical stretching induces reflexive uterine contractions that dilate and efface the cervix further. In addition, cervical dilation boosts oxytocin secretion from the pituitary, which in turn triggers more powerful uterine contractions. When labor begins, uterine contractions may occur only every 3–30 minutes and last only 20–40 seconds; however, by the end of this stage, contractions may occur as frequently as every 1.5–2 minutes and last for a full minute. \n\n Each contraction sharply reduces oxygenated blood flow to the fetus. For this reason, it is critical that a period of relaxation occur after each contraction. Fetal distress, measured as a sustained decrease or increase in the fetal heart rate, can result from severe contractions that are too powerful or lengthy for oxygenated blood to be restored to the fetus. Such a situation can be cause for an emergency birth with vacuum, forceps, or surgically by Caesarian section. \n\n The amniotic membranes rupture before the onset of labor in about 12 percent of women; they typically rupture at the end of the dilation stage in response to excessive pressure from the fetal head entering the birth canal. \n\n Expulsion Stage \n\n The expulsion stage begins when the fetal head enters the birth canal and ends with birth of the newborn. It typically takes up to 2 hours, but it can last longer or be completed in minutes, depending in part on the orientation of the fetus. The vertex presentation known as the occiput anterior vertex is the most common presentation and is associated with the greatest ease of vaginal birth. The fetus faces the maternal spinal cord and the smallest part of the head (the posterior aspect called the occiput) exits the birth canal first. \n\n In fewer than 5 percent of births, the infant is oriented in the breech presentation, or buttocks down. In a complete breech, both legs are crossed and oriented downward. In a frank breech presentation, the legs are oriented upward. Before the 1960s, it was common for breech presentations to be delivered vaginally. Today, most breech births are accomplished by Caesarian section. \n\n Vaginal birth is associated with significant stretching of the vaginal canal, the cervix, and the perineum. Until recent decades, it was routine procedure for an obstetrician to numb the perineum and perform an episiotomy , an incision in the posterior vaginal wall and perineum. The perineum is now more commonly allowed to tear on its own during birth. Both an episiotomy and a perineal tear need to be sutured shortly after birth to ensure optimal healing. Although suturing the jagged edges of a perineal tear may be more difficult than suturing an episiotomy, tears heal more quickly, are less painful, and are associated with less damage to the muscles around the vagina and rectum. \n\n Upon birth of the newborn’s head, an obstetrician will aspirate mucus from the mouth and nose before the newborn’s first breath. Once the head is birthed, the rest of the body usually follows quickly. The umbilical cord is then double-clamped, and a cut is made between the clamps. This completes the second stage of childbirth. \n\n Afterbirth \n\n The delivery of the placenta and associated membranes, commonly referred to as the afterbirth , marks the final stage of childbirth. After expulsion of the newborn, the myometrium continues to contract. This movement shears the placenta from the back of the uterine wall. It is then easily delivered through the vagina. Continued uterine contractions then reduce blood loss from the site of the placenta. Delivery of the placenta marks the beginning of the postpartum period—the period of approximately 6 weeks immediately following childbirth during which the mother’s body gradually returns to a non-pregnant state. If the placenta does not birth spontaneously within approximately 30 minutes, it is considered retained, and the obstetrician may attempt manual removal. If this is not successful, surgery may be required. \n\n It is important that the obstetrician examines the expelled placenta and fetal membranes to ensure that they are intact. If fragments of the placenta remain in the uterus, they can cause postpartum hemorrhage. Uterine contractions continue for several hours after birth to return the uterus to its pre-pregnancy size in a process called involution , which also allows the mother’s abdominal organs to return to their pre-pregnancy locations. Breastfeeding facilitates this process. \n\n Although postpartum uterine contractions limit blood loss from the detachment of the placenta, the mother does experience a postpartum vaginal discharge called lochia . This is made up of uterine lining cells, erythrocytes, leukocytes, and other debris. Thick, dark, lochia rubra (red lochia) typically continues for 2–3 days, and is replaced by lochia serosa, a thinner, pinkish form that continues until about the tenth postpartum day. After this period, a scant, creamy, or watery discharge called lochia alba (white lochia) may continue for another 1–2 weeks. \n 28.5 Adjustments of the Infant at Birth and Postnatal Stages Learning Objectives By the end of this section, you will be able to: \n\n Discuss the importance of an infant’s first breath \n\n Explain the closing of the cardiac shunts \n\n Describe thermoregulation in the newborn \n\n Summarize the importance of intestinal flora in the newborn \n\n From a fetal perspective, the process of birth is a crisis. In the womb, the fetus was snuggled in a soft, warm, dark, and quiet world. The placenta provided nutrition and oxygen continuously. Suddenly, the contractions of labor and vaginal childbirth forcibly squeeze the fetus through the birth canal, limiting oxygenated blood flow during contractions and shifting the skull bones to accommodate the small space. After birth, the newborn’s system must make drastic adjustments to a world that is colder, brighter, and louder, and where he or she will experience hunger and thirst. The neonatal period (neo- = “new”; -natal = “birth”) spans the first to the thirtieth day of life outside of the uterus. \n\n Respiratory Adjustments \n\n Although the fetus “practices” breathing by inhaling amniotic fluid in utero, there is no air in the uterus and thus no true opportunity to breathe. (There is also no need to breathe because the placenta supplies the fetus with all the oxygenated blood it needs.) During gestation, the partially collapsed lungs are filled with amniotic fluid and exhibit very little metabolic activity. Several factors stimulate newborns to take their first breath at birth. First, labor contractions temporarily constrict umbilical blood vessels, reducing oxygenated blood flow to the fetus and elevating carbon dioxide levels in the blood. High carbon dioxide levels cause acidosis and stimulate the respiratory center in the brain, triggering the newborn to take a breath. \n\n The first breath typically is taken within 10 seconds of birth, after mucus is aspirated from the infant’s mouth and nose. The first breaths inflate the lungs to nearly full capacity and dramatically decrease lung pressure and resistance to blood flow, causing a major circulatory reconfiguration. Pulmonary alveoli open, and alveolar capillaries fill with blood. Amniotic fluid in the lungs drains or is absorbed, and the lungs immediately take over the task of the placenta, exchanging carbon dioxide for oxygen by the process of respiration. \n\n Circulatory Adjustments \n\n The process of clamping and cutting the umbilical cord collapses the umbilical blood vessels. In the absence of medical assistance, this occlusion would occur naturally within 20 minutes of birth because the Wharton’s jelly within the umbilical cord would swell in response to the lower temperature outside of the mother’s body, and the blood vessels would constrict. Natural occlusion has occurred when the umbilical cord is no longer pulsating. For the most part, the collapsed vessels atrophy and become fibrotic remnants, existing in the mature circulatory system as ligaments of the abdominal wall and liver. The ductus venosus degenerates to become the ligamentum venosum beneath the liver. Only the proximal sections of the two umbilical arteries remain functional, taking on the role of supplying blood to the upper part of the bladder ( Figure 28.22 ). \n\n The newborn’s first breath is vital to initiate the transition from the fetal to the neonatal circulatory pattern. Inflation of the lungs decreases blood pressure throughout the pulmonary system, as well as in the right atrium and ventricle. In response to this pressure change, the flow of blood temporarily reverses direction through the foramen ovale, moving from the left to the right atrium, and blocking the shunt with two flaps of tissue. Within 1 year, the tissue flaps usually fuse over the shunt, turning the foramen ovale into the fossa ovalis. The ductus arteriosus constricts as a result of increased oxygen concentration, and becomes the ligamentum arteriosum. Closing of the ductus arteriosus ensures that all blood pumped to the pulmonary circuit will be oxygenated by the newly functional neonatal lungs. \n\n Thermoregulatory Adjustments \n\n The fetus floats in warm amniotic fluid that is maintained at a temperature of approximately 98.6°F with very little fluctuation. Birth exposes newborns to a cooler environment in which they have to regulate their own body temperature. Newborns have a higher ratio of surface area to volume than adults. This means that their body has less volume throughout which to produce heat, and more surface area from which to lose heat. As a result, newborns produce heat more slowly and lose it more quickly. Newborns also have immature musculature that limits their ability to generate heat by shivering. Moreover, their nervous systems are underdeveloped, so they cannot quickly constrict superficial blood vessels in response to cold. They also have little subcutaneous fat for insulation. All these factors make it harder for newborns to maintain their body temperature. \n\n Newborns, however, do have a special method for generating heat: nonshivering thermogenesis , which involves the breakdown of brown adipose tissue , or brown fat, which is distributed over the back, chest, and shoulders. Brown fat differs from the more familiar white fat in two ways: \n\n It is highly vascularized. This allows for faster delivery of oxygen, which leads to faster cellular respiration. \n\n It is packed with a special type of mitochondria that are able to engage in cellular respiration reactions that produce less ATP and more heat than standard cellular respiration reactions. \n\n The breakdown of brown fat occurs automatically upon exposure to cold, so it is an important heat regulator in newborns. During fetal development, the placenta secretes inhibitors that prevent metabolism of brown adipose fat and promote its accumulation in preparation for birth. \n\n Gastrointestinal and Urinary Adjustments \n\n In adults, the gastrointestinal tract harbors bacterial flora—trillions of bacteria that aid in digestion, produce vitamins, and protect from the invasion or replication of pathogens. In stark contrast, the fetal intestine is sterile. The first consumption of breast milk or formula floods the neonatal gastrointestinal tract with beneficial bacteria that begin to establish the bacterial flora. \n\n The fetal kidneys filter blood and produce urine, but the neonatal kidneys are still immature and inefficient at concentrating urine. Therefore, newborns produce very dilute urine, making it particularly important for infants to obtain sufficient fluids from breast milk or formula. \n\n Homeostatic Imbalances Homeostasis in the Newborn: Apgar Score \n\nIn the minutes following birth, a newborn must undergo dramatic systemic changes to be able to survive outside the womb. An obstetrician, midwife, or nurse can estimate how well a newborn is doing by obtaining an Apgar score. The Apgar score was introduced in 1952 by the anesthesiologist Dr. Virginia Apgar as a method to assess the effects on the newborn of anesthesia given to the laboring mother. Healthcare providers now use it to assess the general wellbeing of the newborn, whether or not analgesics or anesthetics were used. \n\n Five criteria—skin color, heart rate, reflex, muscle tone, and respiration—are assessed, and each criterion is assigned a score of 0, 1, or 2. Scores are taken at 1 minute after birth and again at 5 minutes after birth. Each time that scores are taken, the five scores are added together. High scores (out of a possible 10) indicate the baby has made the transition from the womb well, whereas lower scores indicate that the baby may be in distress. \n\n The technique for determining an Apgar score is quick and easy, painless for the newborn, and does not require any instruments except for a stethoscope. A convenient way to remember the five scoring criteria is to apply the mnemonic APGAR, for “appearance” (skin color), “pulse” (heart rate), “grimace” (reflex), “activity” (muscle tone), and “respiration.” \n\n Of the five Apgar criteria, heart rate and respiration are the most critical. Poor scores for either of these measurements may indicate the need for immediate medical attention to resuscitate or stabilize the newborn. In general, any score lower than 7 at the 5-minute mark indicates that medical assistance may be needed. A total score below 5 indicates an emergency situation. Normally, a newborn will get an intermediate score of 1 for some of the Apgar criteria and will progress to a 2 by the 5-minute assessment. Scores of 8 or above are normal. \n 28.6 Lactation Learning Objectives By the end of this section, you will be able to: \n\n Describe the structure of the lactating breast \n\n Summarize the process of lactation \n\n Explain how the composition of breast milk changes during the first days of lactation and in the course of a single feeding \n\n Lactation is the process by which milk is synthesized and secreted from the mammary glands of the postpartum female breast in response to an infant sucking at the nipple. Breast milk provides ideal nutrition and passive immunity for the infant, encourages mild uterine contractions to return the uterus to its pre-pregnancy size (i.e., involution), and induces a substantial metabolic increase in the mother, consuming the fat reserves stored during pregnancy. \n\n Structure of the Lactating Breast \n\n Mammary glands are modified sweat glands. The non-pregnant and non-lactating female breast is composed primarily of adipose and collagenous tissue, with mammary glands making up a very minor proportion of breast volume. The mammary gland is composed of milk-transporting lactiferous ducts, which expand and branch extensively during pregnancy in response to estrogen, growth hormone, cortisol, and prolactin. Moreover, in response to progesterone, clusters of breast alveoli bud from the ducts and expand outward toward the chest wall. Breast alveoli are balloon-like structures lined with milk-secreting cuboidal cells, or lactocytes, that are surrounded by a net of contractile myoepithelial cells. Milk is secreted from the lactocytes, fills the alveoli, and is squeezed into the ducts. Clusters of alveoli that drain to a common duct are called lobules; the lactating female has 12–20 lobules organized radially around the nipple. Milk drains from lactiferous ducts into lactiferous sinuses that meet at 4 to 18 perforations in the nipple, called nipple pores. The small bumps of the areola (the darkened skin around the nipple) are called Montgomery glands. They secrete oil to cleanse the nipple opening and prevent chapping and cracking of the nipple during breastfeeding. \n\n The Process of Lactation \n\n The pituitary hormone prolactin is instrumental in the establishment and maintenance of breast milk supply. It also is important for the mobilization of maternal micronutrients for breast milk. \n\n Near the fifth week of pregnancy, the level of circulating prolactin begins to increase, eventually rising to approximately 10–20 times the pre-pregnancy concentration. We noted earlier that, during pregnancy, prolactin and other hormones prepare the breasts anatomically for the secretion of milk. The level of prolactin plateaus in late pregnancy, at a level high enough to initiate milk production. However, estrogen, progesterone, and other placental hormones inhibit prolactin-mediated milk synthesis during pregnancy. It is not until the placenta is expelled that this inhibition is lifted and milk production commences. \n\n After childbirth, the baseline prolactin level drops sharply, but it is restored for a 1-hour spike during each feeding to stimulate the production of milk for the next feeding. With each prolactin spike, estrogen and progesterone also increase slightly. \n\n When the infant suckles, sensory nerve fibers in the areola trigger a neuroendocrine reflex that results in milk secretion from lactocytes into the alveoli. The posterior pituitary releases oxytocin, which stimulates myoepithelial cells to squeeze milk from the alveoli so it can drain into the lactiferous ducts, collect in the lactiferous sinuses, and discharge through the nipple pores. It takes less than 1 minute from the time when an infant begins suckling (the latent period) until milk is secreted (the let-down). Figure 28.23 summarizes the positive feedback loop of the let-down reflex . \n\n The prolactin-mediated synthesis of milk changes with time. Frequent milk removal by breastfeeding (or pumping) will maintain high circulating prolactin levels for several months. However, even with continued breastfeeding, baseline prolactin will decrease over time to its pre-pregnancy level. In addition to prolactin and oxytocin, growth hormone, cortisol, parathyroid hormone, and insulin contribute to lactation, in part by facilitating the transport of maternal amino acids, fatty acids, glucose, and calcium to breast milk. \n\n Changes in the Composition of Breast Milk \n\n In the final weeks of pregnancy, the alveoli swell with colostrum , a thick, yellowish substance that is high in protein but contains less fat and glucose than mature breast milk ( Table 28.3 ). Before childbirth, some women experience leakage of colostrum from the nipples. In contrast, mature breast milk does not leak during pregnancy and is not secreted until several days after childbirth. \n\n Compositions of Human Colostrum, Mature Breast Milk, and Cow’s Milk (g/L) \n\n Human colostrum \n\n Human breast milk \n\n Cow’s milk* \n\n Total protein \n\n 23 \n\n 11 \n\n 31 \n\n Immunoglobulins \n\n 19 \n\n 0.1 \n\n 1 \n\n Fat \n\n 30 \n\n 45 \n\n 38 \n\n Lactose \n\n 57 \n\n 71 \n\n 47 \n\n Calcium \n\n 0.5 \n\n 0.3 \n\n 1.4 \n\n Phosphorus \n\n 0.16 \n\n 0.14 \n\n 0.90 \n\n Sodium \n\n 0.50 \n\n 0.15 \n\n 0.41 \n\n Table 28.3 *Cow’s milk should never be given to an infant. Its composition is not suitable and its proteins are difficult for the infant to digest. \n\n Colostrum is secreted during the first 48–72 hours postpartum. Only a small volume of colostrum is produced—approximately 3 ounces in a 24-hour period—but it is sufficient for the newborn in the first few days of life. Colostrum is rich with immunoglobulins, which confer gastrointestinal, and also likely systemic, immunity as the newborn adjusts to a nonsterile environment. \n\n After about the third postpartum day, the mother secretes transitional milk that represents an intermediate between mature milk and colostrum. This is followed by mature milk from approximately postpartum day 10 (see Table 28.3 ). As you can see in the accompanying table, cow’s milk is not a substitute for breast milk. It contains less lactose, less fat, and more protein and minerals. Moreover, the proteins in cow’s milk are difficult for an infant’s immature digestive system to metabolize and absorb. \n\n The first few weeks of breastfeeding may involve leakage, soreness, and periods of milk engorgement as the relationship between milk supply and infant demand becomes established. Once this period is complete, the mother will produce approximately 1.5 liters of milk per day for a single infant, and more if she has twins or triplets. As the infant goes through growth spurts, the milk supply constantly adjusts to accommodate changes in demand. A woman can continue to lactate for years, but once breastfeeding is stopped for approximately 1 week, any remaining milk will be reabsorbed; in most cases, no more will be produced, even if suckling or pumping is resumed. \n\n Mature milk changes from the beginning to the end of a feeding. The early milk, called foremilk , is watery, translucent, and rich in lactose and protein. Its purpose is to quench the infant’s thirst. Hindmilk is delivered toward the end of a feeding. It is opaque, creamy, and rich in fat, and serves to satisfy the infant’s appetite. \n\n During the first days of a newborn’s life, it is important for meconium to be cleared from the intestines and for bilirubin to be kept low in the circulation. Recall that bilirubin, a product of erythrocyte breakdown, is processed by the liver and secreted in bile. It enters the gastrointestinal tract and exits the body in the stool. Breast milk has laxative properties that help expel meconium from the intestines and clear bilirubin through the excretion of bile. A high concentration of bilirubin in the blood causes jaundice. Some degree of jaundice is normal in newborns, but a high level of bilirubin—which is neurotoxic—can cause brain damage. Newborns, who do not yet have a fully functional blood–brain barrier, are highly vulnerable to the bilirubin circulating in the blood. Indeed, hyperbilirubinemia, a high level of circulating bilirubin, is the most common condition requiring medical attention in newborns. Newborns with hyperbilirubinemia are treated with phototherapy because UV light helps to break down the bilirubin quickly. \n 28.7 Patterns of Inheritance Learning Objectives By the end of this section, you will be able to: \n\n Differentiate between genotype and phenotype \n\n Describe how alleles determine a person’s traits \n\n Summarize Mendel’s experiments and relate them to human genetics \n\n Explain the inheritance of autosomal dominant and recessive and sex-linked genetic disorders \n\n We have discussed the events that lead to the development of a newborn. But what makes each newborn unique? The answer lies, of course, in the DNA in the sperm and oocyte that combined to produce that first diploid cell, the human zygote. \n\n From Genotype to Phenotype \n\n Each human body cell has a full complement of DNA stored in 23 pairs of chromosomes. Figure 28.24 shows the pairs in a systematic arrangement called a karyotype . Among these is one pair of chromosomes, called the sex chromosomes , that determines the sex of the individual (XX in females, XY in males). The remaining 22 chromosome pairs are called autosomal chromosomes . Each of these chromosomes carries hundreds or even thousands of genes, each of which codes for the assembly of a particular protein—that is, genes are “expressed” as proteins. An individual’s complete genetic makeup is referred to as his or her genotype . The characteristics that the genes express, whether they are physical, behavioral, or biochemical, are a person’s phenotype . \n\n You inherit one chromosome in each pair—a full complement of 23—from each parent. This occurs when the sperm and oocyte combine at the moment of your conception. Homologous chromosomes—those that make up a complementary pair—have genes for the same characteristics in the same location on the chromosome. Because one copy of a gene, an allele , is inherited from each parent, the alleles in these complementary pairs may vary. Take for example an allele that encodes for dimples. A child may inherit the allele encoding for dimples on the chromosome from the father and the allele that encodes for smooth skin (no dimples) on the chromosome from the mother. \n\n Although a person can have two identical alleles for a single gene (a homozygous state), it is also possible for a person to have two different alleles (a heterozygous state). The two alleles can interact in several different ways. The expression of an allele can be dominant, for which the activity of this gene will mask the expression of a nondominant, or recessive, allele. Sometimes dominance is complete; at other times, it is incomplete. In some cases, both alleles are expressed at the same time in a form of expression known as codominance. \n\n In the simplest scenario, a single pair of genes will determine a single heritable characteristic. However, it is quite common for multiple genes to interact to confer a feature. For instance, eight or more genes—each with their own alleles—determine eye color in humans. Moreover, although any one person can only have two alleles corresponding to a given gene, more than two alleles commonly exist in a population. This phenomenon is called multiple alleles. For example, there are three different alleles that encode ABO blood type; these are designated I A , I B , and i. \n\n Over 100 years of theoretical and experimental genetics studies, and the more recent sequencing and annotation of the human genome, have helped scientists to develop a better understanding of how an individual’s genotype is expressed as their phenotype. This body of knowledge can help scientists and medical professionals to predict, or at least estimate, some of the features that an offspring will inherit by examining the genotypes or phenotypes of the parents. One important application of this knowledge is to identify an individual’s risk for certain heritable genetic disorders. However, most diseases have a multigenic pattern of inheritance and can also be affected by the environment, so examining the genotypes or phenotypes of a person’s parents will provide only limited information about the risk of inheriting a disease. Only for a handful of single-gene disorders can genetic testing allow clinicians to calculate the probability with which a child born to the two parents tested may inherit a specific disease. \n\n Mendel’s Theory of Inheritance \n\n Our contemporary understanding of genetics rests on the work of a nineteenth-century monk. Working in the mid-1800s, long before anyone knew about genes or chromosomes, Gregor Mendel discovered that garden peas transmit their physical characteristics to subsequent generations in a discrete and predictable fashion. When he mated, or crossed, two pure-breeding pea plants that differed by a certain characteristic, the first-generation offspring all looked like one of the parents. For instance, when he crossed tall and dwarf pure-breeding pea plants, all of the offspring were tall. Mendel called tallness dominant because it was expressed in offspring when it was present in a purebred parent. He called dwarfism recessive because it was masked in the offspring if one of the purebred parents possessed the dominant characteristic. Note that tallness and dwarfism are variations on the characteristic of height. Mendel called such a variation a trait . We now know that these traits are the expression of different alleles of the gene encoding height. \n\n Mendel performed thousands of crosses in pea plants with differing traits for a variety of characteristics. And he repeatedly came up with the same results—among the traits he studied, one was always dominant, and the other was always recessive. (Remember, however, that this dominant–recessive relationship between alleles is not always the case; some alleles are codominant, and sometimes dominance is incomplete.) \n\n Using his understanding of dominant and recessive traits, Mendel tested whether a recessive trait could be lost altogether in a pea lineage or whether it would resurface in a later generation. By crossing the second-generation offspring of purebred parents with each other, he showed that the latter was true: recessive traits reappeared in third-generation plants in a ratio of 3:1 (three offspring having the dominant trait and one having the recessive trait). Mendel then proposed that characteristics such as height were determined by heritable “factors” that were transmitted, one from each parent, and inherited in pairs by offspring. \n\n In the language of genetics, Mendel’s theory applied to humans says that if an individual receives two dominant alleles, one from each parent, the individual’s phenotype will express the dominant trait. If an individual receives two recessive alleles, then the recessive trait will be expressed in the phenotype. Individuals who have two identical alleles for a given gene, whether dominant or recessive, are said to be homozygous for that gene (homo- = “same”). Conversely, an individual who has one dominant allele and one recessive allele is said to be heterozygous for that gene (hetero- = “different” or “other”). In this case, the dominant trait will be expressed, and the individual will be phenotypically identical to an individual who possesses two dominant alleles for the trait. \n\n It is common practice in genetics to use capital and lowercase letters to represent dominant and recessive alleles. Using Mendel’s pea plants as an example, if a tall pea plant is homozygous, it will possess two tall alleles ( TT ). A dwarf pea plant must be homozygous because its dwarfism can only be expressed when two recessive alleles are present ( tt ). A heterozygous pea plant ( Tt ) would be tall and phenotypically indistinguishable from a tall homozygous pea plant because of the dominant tall allele. Mendel deduced that a 3:1 ratio of dominant to recessive would be produced by the random segregation of heritable factors (genes) when crossing two heterozygous pea plants. In other words, for any given gene, parents are equally likely to pass down either one of their alleles to their offspring in a haploid gamete, and the result will be expressed in a dominant–recessive pattern if both parents are heterozygous for the trait. \n\n Because of the random segregation of gametes, the laws of chance and probability come into play when predicting the likelihood of a given phenotype. Consider a cross between an individual with two dominant alleles for a trait ( AA ) and an individual with two recessive alleles for the same trait ( aa ). All of the parental gametes from the dominant individual would be A , and all of the parental gametes from the recessive individual would be a ( Figure 28.25 ). All of the offspring of that second generation, inheriting one allele from each parent, would have the genotype Aa , and the probability of expressing the phenotype of the dominant allele would be 4 out of 4, or 100 percent. \n\n This seems simple enough, but the inheritance pattern gets interesting when the second-generation Aa individuals are crossed. In this generation, 50 percent of each parent’s gametes are A and the other 50 percent are a . By Mendel’s principle of random segregation, the possible combinations of gametes that the offspring can receive are AA , Aa , aA (which is the same as Aa ), and aa . Because segregation and fertilization are random, each offspring has a 25 percent chance of receiving any of these combinations. Therefore, if an Aa × Aa cross were performed 1000 times, approximately 250 (25 percent) of the offspring would be AA ; 500 (50 percent) would be Aa (that is, Aa plus aA ); and 250 (25 percent) would be aa . The genotypic ratio for this inheritance pattern is 1:2:1. However, we have already established that AA and Aa (and aA ) individuals all express the dominant trait (i.e., share the same phenotype), and can therefore be combined into one group. The result is Mendel’s third-generation phenotype ratio of 3:1. \n\n Mendel’s observation of pea plants also included many crosses that involved multiple traits, which prompted him to formulate the principle of independent assortment. The law states that the members of one pair of genes (alleles) from a parent will sort independently from other pairs of genes during the formation of gametes. Applied to pea plants, that means that the alleles associated with the different traits of the plant, such as color, height, or seed type, will sort independently of one another. This holds true except when two alleles happen to be located close to one other on the same chromosome. Independent assortment provides for a great degree of diversity in offspring. \n\n Mendelian genetics represent the fundamentals of inheritance, but there are two important qualifiers to consider when applying Mendel’s findings to inheritance studies in humans. First, as we’ve already noted, not all genes are inherited in a dominant–recessive pattern. Although all diploid individuals have two alleles for every gene, allele pairs may interact to create several types of inheritance patterns, including incomplete dominance and codominance. \n\n Secondly, Mendel performed his studies using thousands of pea plants. He was able to identify a 3:1 phenotypic ratio in second-generation offspring because his large sample size overcame the influence of variability resulting from chance. In contrast, no human couple has ever had thousands of children. If we know that a man and woman are both heterozygous for a recessive genetic disorder, we would predict that one in every four of their children would be affected by the disease. In real life, however, the influence of chance could change that ratio significantly. For example, if a man and a woman are both heterozygous for cystic fibrosis, a recessive genetic disorder that is expressed only when the individual has two defective alleles, we would expect one in four of their children to have cystic fibrosis. However, it is entirely possible for them to have seven children, none of whom is affected, or for them to have two children, both of whom are affected. For each individual child, the presence or absence of a single gene disorder depends on which alleles that child inherits from his or her parents. \n\n Autosomal Dominant Inheritance \n\n In the case of cystic fibrosis, the disorder is recessive to the normal phenotype. However, a genetic abnormality may be dominant to the normal phenotype. When the dominant allele is located on one of the 22 pairs of autosomes (non-sex chromosomes), we refer to its inheritance pattern as autosomal dominant . An example of an autosomal dominant disorder is neurofibromatosis type I, a disease that induces tumor formation within the nervous system that leads to skin and skeletal deformities. Consider a couple in which one parent is heterozygous for this disorder (and who therefore has neurofibromatosis), Nn , and one parent is homozygous for the normal gene, nn . The heterozygous parent would have a 50 percent chance of passing the dominant allele for this disorder to his or her offspring, and the homozygous parent would always pass the normal allele. Therefore, four possible offspring genotypes are equally likely to occur: Nn , Nn , nn , and nn . That is, every child of this couple would have a 50 percent chance of inheriting neurofibromatosis. This inheritance pattern is shown in Figure 28.26 , in a form called a Punnett square , named after its creator, the British geneticist Reginald Punnett. \n\n Other genetic diseases that are inherited in this pattern are achondroplastic dwarfism, Marfan syndrome, and Huntington’s disease. Because autosomal dominant disorders are expressed by the presence of just one gene, an individual with the disorder will know that he or she has at least one faulty gene. The expression of the disease may manifest later in life, after the childbearing years, which is the case in Huntington’s disease (discussed in more detail later in this section). \n\n Autosomal Recessive Inheritance \n\n When a genetic disorder is inherited in an autosomal recessive pattern, the disorder corresponds to the recessive phenotype. Heterozygous individuals will not display symptoms of this disorder, because their unaffected gene will compensate. Such an individual is called a carrier . Carriers for an autosomal recessive disorder may never know their genotype unless they have a child with the disorder. \n\n An example of an autosomal recessive disorder is cystic fibrosis (CF), which we introduced earlier. CF is characterized by the chronic accumulation of a thick, tenacious mucus in the lungs and digestive tract. Decades ago, children with CF rarely lived to adulthood. With advances in medical technology, the average lifespan in developed countries has increased into middle adulthood. CF is a relatively common disorder that occurs in approximately 1 in 2000 Caucasians. A child born to two CF carriers would have a 25 percent chance of inheriting the disease. This is the same 3:1 dominant:recessive ratio that Mendel observed in his pea plants would apply here. The pattern is shown in Figure 28.27 , using a diagram that tracks the likely incidence of an autosomal recessive disorder on the basis of parental genotypes. \n\n On the other hand, a child born to a CF carrier and someone with two unaffected alleles would have a 0 percent probability of inheriting CF, but would have a 50 percent chance of being a carrier. Other examples of autosome recessive genetic illnesses include the blood disorder sickle-cell anemia, the fatal neurological disorder Tay–Sachs disease, and the metabolic disorder phenylketonuria. \n\n X-linked Dominant or Recessive Inheritance \n\n An X-linked transmission pattern involves genes located on the X chromosome of the 23rd pair ( Figure 28.28 ). Recall that a male has one X and one Y chromosome. When a father transmits a Y chromosome, the child is male, and when he transmits an X chromosome, the child is female. A mother can transmit only an X chromosome, as both her sex chromosomes are X chromosomes. \n\n When an abnormal allele for a gene that occurs on the X chromosome is dominant over the normal allele, the pattern is described as X-linked dominant . This is the case with vitamin D–resistant rickets: an affected father would pass the disease gene to all of his daughters, but none of his sons, because he donates only the Y chromosome to his sons (see Figure 28.28 a ). If it is the mother who is affected, all of her children—male or female—would have a 50 percent chance of inheriting the disorder because she can only pass an X chromosome on to her children (see Figure 28.28 b ). For an affected female, the inheritance pattern would be identical to that of an autosomal dominant inheritance pattern in which one parent is heterozygous and the other is homozygous for the normal gene. \n\n X-linked recessive inheritance is much more common because females can be carriers of the disease yet still have a normal phenotype. Diseases transmitted by X-linked recessive inheritance include color blindness, the blood-clotting disorder hemophilia, and some forms of muscular dystrophy. For an example of X-linked recessive inheritance, consider parents in which the mother is an unaffected carrier and the father is normal. None of the daughters would have the disease because they receive a normal gene from their father. However, they have a 50 percent chance of receiving the disease gene from their mother and becoming a carrier. In contrast, 50 percent of the sons would be affected ( Figure 28.29 ). \n\n With X-linked recessive diseases, males either have the disease or are genotypically normal—they cannot be carriers. Females, however, can be genotypically normal, a carrier who is phenotypically normal, or affected with the disease. A daughter can inherit the gene for an X-linked recessive illness when her mother is a carrier or affected, or her father is affected. The daughter will be affected by the disease only if she inherits an X-linked recessive gene from both parents. As you can imagine, X-linked recessive disorders affect many more males than females. For example, color blindness affects at least 1 in 20 males, but only about 1 in 400 females. \n\n Other Inheritance Patterns: Incomplete Dominance, Codominance, and Lethal Alleles \n\n Not all genetic disorders are inherited in a dominant–recessive pattern. In incomplete dominance , the offspring express a heterozygous phenotype that is intermediate between one parent’s homozygous dominant trait and the other parent’s homozygous recessive trait. An example of this can be seen in snapdragons when red-flowered plants and white-flowered plants are crossed to produce pink-flowered plants. In humans, incomplete dominance occurs with one of the genes for hair texture. When one parent passes a curly hair allele (the incompletely dominant allele) and the other parent passes a straight-hair allele, the effect on the offspring will be intermediate, resulting in hair that is wavy. \n\n Codominance is characterized by the equal, distinct, and simultaneous expression of both parents’ different alleles. This pattern differs from the intermediate, blended features seen in incomplete dominance. A classic example of codominance in humans is ABO blood type. People are blood type A if they have an allele for an enzyme that facilitates the production of surface antigen A on their erythrocytes. This allele is designated I A . In the same manner, people are blood type B if they express an enzyme for the production of surface antigen B. People who have alleles for both enzymes ( I A and I B ) produce both surface antigens A and B. As a result, they are blood type AB. Because the effect of both alleles (or enzymes) is observed, we say that the I A and I B alleles are codominant. There is also a third allele that determines blood type. This allele ( i ) produces a nonfunctional enzyme. People who have two i alleles do not produce either A or B surface antigens: they have type O blood. If a person has I A and i alleles, the person will have blood type A. Notice that it does not make any difference whether a person has two I A alleles or one I A and one i allele. In both cases, the person is blood type A. Because I A masks i , we say that I A is dominant to i . Table 28.4 summarizes the expression of blood type. \n\n Expression of Blood Types \n\n Blood type \n\n Genotype \n\n Pattern of inheritance \n\n A \n\n I A I A or I A i \n\n I A is dominant to i \n\n B \n\n I B I B or I B i \n\n I B is dominant to i \n\n AB \n\n I A I B \n\n I A is co-dominant to I B \n\n O \n\n ii \n\n Two recessive alleles \n\n Table 28.4 \n\n Certain combinations of alleles can be lethal, meaning they prevent the individual from developing in utero, or cause a shortened life span. In recessive lethal inheritance patterns, a child who is born to two heterozygous (carrier) parents and who inherited the faulty allele from both would not survive. An example of this is Tay–Sachs, a fatal disorder of the nervous system. In this disorder, parents with one copy of the allele for the disorder are carriers. If they both transmit their abnormal allele, their offspring will develop the disease and will die in childhood, usually before age 5. \n\n Dominant lethal inheritance patterns are much more rare because neither heterozygotes nor homozygotes survive. Of course, dominant lethal alleles that arise naturally through mutation and cause miscarriages or stillbirths are never transmitted to subsequent generations. However, some dominant lethal alleles, such as the allele for Huntington’s disease, cause a shortened life span but may not be identified until after the person reaches reproductive age and has children. Huntington’s disease causes irreversible nerve cell degeneration and death in 100 percent of affected individuals, but it may not be expressed until the individual reaches middle age. In this way, dominant lethal alleles can be maintained in the human population. Individuals with a family history of Huntington’s disease are typically offered genetic counseling, which can help them decide whether or not they wish to be tested for the faulty gene. \n\n Mutations \n\n A mutation is a change in the sequence of DNA nucleotides that may or may not affect a person’s phenotype. Mutations can arise spontaneously from errors during DNA replication, or they can result from environmental insults such as radiation, certain viruses, or exposure to tobacco smoke or other toxic chemicals. Because genes encode for the assembly of proteins, a mutation in the nucleotide sequence of a gene can change amino acid sequence and, consequently, a protein’s structure and function. Spontaneous mutations occurring during meiosis are thought to account for many spontaneous abortions (miscarriages). \n\n Chromosomal Disorders \n\n Sometimes a genetic disease is not caused by a mutation in a gene, but by the presence of an incorrect number of chromosomes. For example, Down syndrome is caused by having three copies of chromosome 21. This is known as trisomy 21. The most common cause of trisomy 21 is chromosomal nondisjunction during meiosis. The frequency of nondisjunction events appears to increase with age, so the frequency of bearing a child with Down syndrome increases in women over 36. The age of the father matters less because nondisjunction is much less likely to occur in a sperm than in an egg. \n\n Whereas Down syndrome is caused by having three copies of a chromosome, Turner syndrome is caused by having just one copy of the X chromosome. This is known as monosomy. The affected child is always female. Women with Turner syndrome are sterile because their sexual organs do not mature. \n\n Career Connection Genetic Counselor \n\nGiven the intricate orchestration of gene expression, cell migration, and cell differentiation during prenatal development, it is amazing that the vast majority of newborns are healthy and free of major birth defects. When a woman over 35 is pregnant or intends to become pregnant, or her partner is over 55, or if there is a family history of a genetic disorder, she and her partner may want to speak to a genetic counselor to discuss the likelihood that their child may be affected by a genetic or chromosomal disorder. A genetic counselor can interpret a couple’s family history and estimate the risks to their future offspring. \n\n For many genetic diseases, a DNA test can determine whether a person is a carrier. For instance, carrier status for Fragile X, an X-linked disorder associated with mental retardation, or for cystic fibrosis can be determined with a simple blood draw to obtain DNA for testing. A genetic counselor can educate a couple about the implications of such a test and help them decide whether to undergo testing. For chromosomal disorders, the available testing options include a blood test, amniocentesis (in which amniotic fluid is tested), and chorionic villus sampling (in which tissue from the placenta is tested). Each of these has advantages and drawbacks. A genetic counselor can also help a couple cope with the news that either one or both partners is a carrier of a genetic illness, or that their unborn child has been diagnosed with a chromosomal disorder or other birth defect. \n\n To become a genetic counselor, one needs to complete a 4-year undergraduate program and then obtain a Master of Science in Genetic Counseling from an accredited university. Board certification is attained after passing examinations by the American Board of Genetic Counseling. Genetic counselors are essential professionals in many branches of medicine, but there is a particular demand for preconception and prenatal genetic counselors. \n\n Interactive Link \n\n Visit the National Society of Genetic Counselors website for more information about genetic counselors. \n\n Interactive Link \n\n Visit the American Board of Genetic Counselors, Inc., website for more information about genetic counselors. "}}},{"rowIdx":186,"cells":{"bname":{"kind":"string","value":"biology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":""},"intro":{"kind":"string","value":" Chapter Outline 40.1 Overview of the Circulatory System 40.2 Components of the Blood 40.3 Mammalian Heart and Blood Vessels 40.4 Blood Flow and Blood Pressure Regulation Introduction Most animals are complex multicellular organisms that require a mechanism for transporting nutrients throughout their bodies and removing waste products. The circulatory system has evolved over time from simple diffusion through cells in the early evolution of animals to a complex network of blood vessels that reach all parts of the human body. This extensive network supplies the cells, tissues, and organs with oxygen and nutrients, and removes carbon dioxide and waste, which are byproducts of respiration. At the core of the human circulatory system is the heart. The size of a clenched fist, the human heart is protected beneath the rib cage. Made of specialized and unique cardiac muscle, it pumps blood throughout the body and to the heart itself. Heart contractions are driven by intrinsic electrical impulses that the brain and endocrine hormones help to regulate. Understanding the heart’s basic anatomy and function is important to understanding the body’s circulatory and respiratory systems. Gas exchange is one essential function of the circulatory system. A circulatory system is not needed in organisms with no specialized respiratory organs because oxygen and carbon dioxide diffuse directly between their body tissues and the external environment. However, in organisms that possess lungs and gills, oxygen must be transported from these specialized respiratory organs to the body tissues via a circulatory system. Therefore, circulatory systems have had to evolve to accommodate the great diversity of body sizes and body types present among animals. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":0,"ans_text":"They use less metabolic energy."},"bloom":null,"hl_context":"The circulatory system is effectively a network of cylindrical vessels : the arteries , veins , and capillaries that emanate from a pump , the heart . In all vertebrate organisms , as well as some invertebrates , this is a closed-loop system , in which the blood is not free in a cavity . In a closed circulatory system , blood is contained inside blood vessels and circulates unidirectionally from the heart around the systemic circulatory route , then returns to the heart again , as illustrated in Figure 40.2 a . As opposed to a closed system , arthropods — including insects , crustaceans , and most mollusks — have an open circulatory system , as illustrated in Figure 40.2 b . In an open circulatory system , the blood is not enclosed in the blood vessels but is pumped into a cavity called a hemocoel and is called hemolymph because the blood mixes with the interstitial fluid . As the heart beats and the animal moves , the hemolymph circulates around the organs within the body cavity and then reenters the hearts through openings called ostia . This movement allows for gas and nutrient exchange . <hl> An open circulatory system does not use as much energy as a closed system to operate or to maintain ; however , there is a trade-off with the amount of blood that can be moved to metabolically active organs and tissues that require high levels of oxygen . <hl> In fact , one reason that insects with wing spans of up to two feet wide ( 70 cm ) are not around today is probably because they were outcompeted by the arrival of birds 150 million years ago . Birds , having a closed circulatory system , are thought to have moved more agilely , allowing them to get food faster and possibly to prey on the insects .","hl_sentences":"An open circulatory system does not use as much energy as a closed system to operate or to maintain ; however , there is a trade-off with the amount of blood that can be moved to metabolically active organs and tissues that require high levels of oxygen .","question":{"cloze_format":"The reason open circulatory systems are advantageous to some animals is that ___ .","normal_format":"Why are open circulatory systems advantageous to some animals?","question_choices":["They use less metabolic energy.","They help the animal move faster.","They do not need a heart.","They help large insects develop."],"question_id":"fs-idm300553744","question_text":"Why are open circulatory systems advantageous to some animals?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"None of the above"},"bloom":null,"hl_context":"The circulatory system varies from simple systems in invertebrates to more complex systems in vertebrates . <hl> The simplest animals , such as the sponges ( Porifera ) and rotifers ( Rotifera ) , do not need a circulatory system because diffusion allows adequate exchange of water , nutrients , and waste , as well as dissolved gases , as shown in Figure 40.3 a . <hl> Organisms that are more complex but still only have two layers of cells in their body plan , such as jellies ( Cnidaria ) and comb jellies ( Ctenophora ) also use diffusion through their epidermis and internally through the gastrovascular compartment . Both their internal and external tissues are bathed in an aqueous environment and exchange fluids by diffusion on both sides , as illustrated in Figure 40.3 b . Exchange of fluids is assisted by the pulsing of the jellyfish body . For more complex organisms , diffusion is not efficient for cycling gases , nutrients , and waste effectively through the body ; therefore , more complex circulatory systems evolved . Most arthropods and many mollusks have open circulatory systems . In an open system , an elongated beating heart pushes the hemolymph through the body and muscle contractions help to move fluids . The larger more complex crustaceans , including lobsters , have developed arterial-like vessels to push blood through their bodies , and the most active mollusks , such as squids , have evolved a closed circulatory system and are able to move rapidly to catch prey . Closed circulatory systems are a characteristic of vertebrates ; however , there are significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due to adaptation during evolution and associated differences in anatomy . Figure 40.4 illustrates the basic circulatory systems of some vertebrates : fish , amphibians , reptiles , and mammals . As illustrated in Figure 40.4 a Fish have a single circuit for blood flow and a two-chambered heart that has only a single atrium and a single ventricle . The atrium collects blood that has returned from the body and the ventricle pumps the blood to the gills where gas exchange occurs and the blood is re-oxygenated ; this is called gill circulation . The blood then continues through the rest of the body before arriving back at the atrium ; this is called systemic circulation . This unidirectional flow of blood produces a gradient of oxygenated to deoxygenated blood around the fish ’ s systemic circuit . The result is a limit in the amount of oxygen that can reach some of the organs and tissues of the body , reducing the overall metabolic capacity of fish . In amphibians , reptiles , birds , and mammals , blood flow is directed in two circuits : one through the lungs and back to the heart , which is called pulmonary circulation , and the other throughout the rest of the body and its organs including the brain ( systemic circulation ) . In amphibians , gas exchange also occurs through the skin during pulmonary circulation and is referred to as pulmocutaneous circulation . Chapter Outline 40.1 Overview of the Circulatory System 40.2 Components of the Blood 40.3 Mammalian Heart and Blood Vessels 40.4 Blood Flow and Blood Pressure Regulation Introduction Most animals are complex multicellular organisms that require a mechanism for transporting nutrients throughout their bodies and removing waste products . <hl> The circulatory system has evolved over time from simple diffusion through cells in the early evolution of animals to a complex network of blood vessels that reach all parts of the human body . <hl> This extensive network supplies the cells , tissues , and organs with oxygen and nutrients , and removes carbon dioxide and waste , which are byproducts of respiration . At the core of the human circulatory system is the heart . The size of a clenched fist , the human heart is protected beneath the rib cage . Made of specialized and unique cardiac muscle , it pumps blood throughout the body and to the heart itself . Heart contractions are driven by intrinsic electrical impulses that the brain and endocrine hormones help to regulate . Understanding the heart ’ s basic anatomy and function is important to understanding the body ’ s circulatory and respiratory systems . Gas exchange is one essential function of the circulatory system . A circulatory system is not needed in organisms with no specialized respiratory organs because oxygen and carbon dioxide diffuse directly between their body tissues and the external environment . However , in organisms that possess lungs and gills , oxygen must be transported from these specialized respiratory organs to the body tissues via a circulatory system . Therefore , circulatory systems have had to evolve to accommodate the great diversity of body sizes and body types present among animals .","hl_sentences":"The simplest animals , such as the sponges ( Porifera ) and rotifers ( Rotifera ) , do not need a circulatory system because diffusion allows adequate exchange of water , nutrients , and waste , as well as dissolved gases , as shown in Figure 40.3 a . The circulatory system has evolved over time from simple diffusion through cells in the early evolution of animals to a complex network of blood vessels that reach all parts of the human body .","question":{"cloze_format":"Some animals use diffusion instead of a circulatory system. Examples include ___.","normal_format":"What is an example of an animal that uses diffusion instead of a circulatory system?","question_choices":["birds and jellyfish","flatworms and arthropods","mollusks and jellyfish","None of the above"],"question_id":"fs-idm216101712","question_text":"Some animals use diffusion instead of a circulatory system. Examples include:"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"pulmonary circulation"},"bloom":null,"hl_context":"The circulatory system varies from simple systems in invertebrates to more complex systems in vertebrates . The simplest animals , such as the sponges ( Porifera ) and rotifers ( Rotifera ) , do not need a circulatory system because diffusion allows adequate exchange of water , nutrients , and waste , as well as dissolved gases , as shown in Figure 40.3 a . Organisms that are more complex but still only have two layers of cells in their body plan , such as jellies ( Cnidaria ) and comb jellies ( Ctenophora ) also use diffusion through their epidermis and internally through the gastrovascular compartment . Both their internal and external tissues are bathed in an aqueous environment and exchange fluids by diffusion on both sides , as illustrated in Figure 40.3 b . Exchange of fluids is assisted by the pulsing of the jellyfish body . For more complex organisms , diffusion is not efficient for cycling gases , nutrients , and waste effectively through the body ; therefore , more complex circulatory systems evolved . Most arthropods and many mollusks have open circulatory systems . In an open system , an elongated beating heart pushes the hemolymph through the body and muscle contractions help to move fluids . The larger more complex crustaceans , including lobsters , have developed arterial-like vessels to push blood through their bodies , and the most active mollusks , such as squids , have evolved a closed circulatory system and are able to move rapidly to catch prey . Closed circulatory systems are a characteristic of vertebrates ; however , there are significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due to adaptation during evolution and associated differences in anatomy . Figure 40.4 illustrates the basic circulatory systems of some vertebrates : fish , amphibians , reptiles , and mammals . As illustrated in Figure 40.4 a Fish have a single circuit for blood flow and a two-chambered heart that has only a single atrium and a single ventricle . The atrium collects blood that has returned from the body and the ventricle pumps the blood to the gills where gas exchange occurs and the blood is re-oxygenated ; this is called gill circulation . The blood then continues through the rest of the body before arriving back at the atrium ; this is called systemic circulation . This unidirectional flow of blood produces a gradient of oxygenated to deoxygenated blood around the fish ’ s systemic circuit . The result is a limit in the amount of oxygen that can reach some of the organs and tissues of the body , reducing the overall metabolic capacity of fish . <hl> In amphibians , reptiles , birds , and mammals , blood flow is directed in two circuits : one through the lungs and back to the heart , which is called pulmonary circulation , and the other throughout the rest of the body and its organs including the brain ( systemic circulation ) . <hl> In amphibians , gas exchange also occurs through the skin during pulmonary circulation and is referred to as pulmocutaneous circulation .","hl_sentences":"In amphibians , reptiles , birds , and mammals , blood flow is directed in two circuits : one through the lungs and back to the heart , which is called pulmonary circulation , and the other throughout the rest of the body and its organs including the brain ( systemic circulation ) .","question":{"cloze_format":"Blood flow that is directed through the lungs and back to the heart is called ________.","normal_format":"What is blood flow called that is directed through the lungs and back to the heart?","question_choices":["unidirectional circulation","gill circulation","pulmonary circulation","pulmocutaneous circulation"],"question_id":"fs-idm225583056","question_text":"Blood flow that is directed through the lungs and back to the heart is called ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"All of the above"},"bloom":null,"hl_context":"The morphology of white blood cells differs significantly from red blood cells . They have nuclei and do not contain hemoglobin . The different types of white blood cells are identified by their microscopic appearance after histologic staining , and each has a different specialized function . <hl> The two main groups , both illustrated in Figure 40.7 are the granulocytes , which include the neutrophils , eosinophils , and basophils , and the agranulocytes , which include the monocytes and lymphocytes . <hl> <hl> White blood cells , also called leukocytes ( leuko = white ) , make up approximately one percent by volume of the cells in blood . <hl> <hl> The role of white blood cells is very different than that of red blood cells : they are primarily involved in the immune response to identify and target pathogens , such as invading bacteria , viruses , and other foreign organisms . <hl> White blood cells are formed continually ; some only live for hours or days , but some live for years .","hl_sentences":"The two main groups , both illustrated in Figure 40.7 are the granulocytes , which include the neutrophils , eosinophils , and basophils , and the agranulocytes , which include the monocytes and lymphocytes . White blood cells , also called leukocytes ( leuko = white ) , make up approximately one percent by volume of the cells in blood . The role of white blood cells is very different than that of red blood cells : they are primarily involved in the immune response to identify and target pathogens , such as invading bacteria , viruses , and other foreign organisms .","question":{"cloze_format":"White blood cells ___ .","normal_format":"White blood cells are what?","question_choices":["can be classified as granulocytes or agranulocytes","defend the body against bacteria and viruses","are also called leucocytes","All of the above"],"question_id":"fs-idm6200624","question_text":"White blood cells:"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"when platelets are attracted to a site of blood vessel damage"},"bloom":null,"hl_context":"Blood must clot to heal wounds and prevent excess blood loss . <hl> Small cell fragments called platelets ( thrombocytes ) are attracted to the wound site where they adhere by extending many projections and releasing their contents . <hl> These contents activate other platelets and also interact with other coagulation factors , which convert fibrinogen , a water-soluble protein present in blood serum into fibrin ( a non-water soluble protein ) , causing the blood to clot . Many of the clotting factors require vitamin K to work , and vitamin K deficiency can lead to problems with blood clotting . <hl> Many platelets converge and stick together at the wound site forming a platelet plug ( also called a fibrin clot ) , as illustrated in Figure 40.8 b . <hl> The plug or clot lasts for a number of days and stops the loss of blood . Platelets are formed from the disintegration of larger cells called megakaryocytes , like that shown in Figure 40.8 a . For each megakaryocyte , 2000 – 3000 platelets are formed with 150,000 to 400,000 platelets present in each cubic millimeter of blood . Each platelet is disc shaped and 2 – 4 μm in diameter . They contain many small vesicles but do not contain a nucleus .","hl_sentences":"Small cell fragments called platelets ( thrombocytes ) are attracted to the wound site where they adhere by extending many projections and releasing their contents . Many platelets converge and stick together at the wound site forming a platelet plug ( also called a fibrin clot ) , as illustrated in Figure 40.8 b .","question":{"cloze_format":"The point at which platelet plug formation occurs is ___ .","normal_format":"Platelet plug formation occurs at which point?","question_choices":["when large megakaryocytes break up into thousands of smaller fragments","when platelets are dispersed through the blood stream","when platelets are attracted to a site of blood vessel damage","none of the above"],"question_id":"fs-idm26244160","question_text":"Platelet plug formation occurs at which point?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"25 percent"},"bloom":null,"hl_context":"Hemoglobin is responsible for distributing oxygen , and to a lesser extent , carbon dioxide , throughout the circulatory systems of humans , vertebrates , and many invertebrates . The blood is more than the proteins , though . Blood is actually a term used to describe the liquid that moves through the vessels and includes plasma ( the liquid portion , which contains water , proteins , salts , lipids , and glucose ) and the cells ( red and white cells ) and cell fragments called platelets . Blood plasma is actually the dominant component of blood and contains the water , proteins , electrolytes , lipids , and glucose . The cells are responsible for carrying the gases ( red cells ) and immune the response ( white ) . The platelets are responsible for blood clotting . Interstitial fluid that surrounds cells is separate from the blood , but in hemolymph , they are combined . <hl> In humans , cellular components make up approximately 45 percent of the blood and the liquid plasma 55 percent . <hl> Blood is 20 percent of a person ’ s extracellular fluid and eight percent of weight . The Role of Blood in the Body","hl_sentences":"In humans , cellular components make up approximately 45 percent of the blood and the liquid plasma 55 percent .","question":{"cloze_format":"In humans, the plasma comprises a percentage of ___ of the blood.","normal_format":"In humans, the plasma comprises what percentage of the blood?","question_choices":["45 percent","55 percent","25 percent","90 percent"],"question_id":"fs-idm67048352","question_text":"In humans, the plasma comprises what percentage of the blood?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"they have nuclei"},"bloom":null,"hl_context":"Red blood cells , or erythrocytes ( erythro - = “ red ” ; - cyte = “ cell ” ) , are specialized cells that circulate through the body delivering oxygen to cells ; they are formed from stem cells in the bone marrow . In mammals , red blood cells are small biconcave cells that at maturity do not contain a nucleus or mitochondria and are only 7 – 8 µm in size . <hl> In birds and non-avian reptiles , a nucleus is still maintained in red blood cells . <hl> The red coloring of blood comes from the iron-containing protein hemoglobin , illustrated in Figure 40.6 a . The principal job of this protein is to carry oxygen , but it also transports carbon dioxide as well . Hemoglobin is packed into red blood cells at a rate of about 250 million molecules of hemoglobin per cell . Each hemoglobin molecule binds four oxygen molecules so that each red blood cell carries one billion molecules of oxygen . There are approximately 25 trillion red blood cells in the five liters of blood in the human body , which could carry up to 25 sextillion ( 25 × 10 21 ) molecules of oxygen in the body at any time . In mammals , the lack of organelles in erythrocytes leaves more room for the hemoglobin molecules , and the lack of mitochondria also prevents use of the oxygen for metabolic respiration . Only mammals have anucleated red blood cells , and some mammals ( camels , for instance ) even have nucleated red blood cells . The advantage of nucleated red blood cells is that these cells can undergo mitosis . Anucleated red blood cells metabolize anaerobically ( without oxygen ) , making use of a primitive metabolic pathway to produce ATP and increase the efficiency of oxygen transport .","hl_sentences":"In birds and non-avian reptiles , a nucleus is still maintained in red blood cells .","question":{"cloze_format":"The red blood cells of birds differ from mammalian red blood cells because ___ .","normal_format":"Why do the red blood cells of birds differ from mammalian red blood cells?","question_choices":["they are white and have nuclei","they do not have nuclei","they have nuclei","they fight disease"],"question_id":"fs-idm93132096","question_text":"The red blood cells of birds differ from mammalian red blood cells because:"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"the excitation of cardiac muscle cells at the sinoatrial node followed by the atrioventricular node"},"bloom":null,"hl_context":"<hl> The autonomous beating of cardiac muscle cells is regulated by the heart ’ s internal pacemaker that uses electrical signals to time the beating of the heart . <hl> The electrical signals and mechanical actions , illustrated in Figure 40.14 , are intimately intertwined . The internal pacemaker starts at the sinoatrial ( SA ) node , which is located near the wall of the right atrium . Electrical charges spontaneously pulse from the SA node causing the two atria to contract in unison . The pulse reaches a second node , called the atrioventricular ( AV ) node , between the right atrium and right ventricle where it pauses for approximately 0.1 second before spreading to the walls of the ventricles . From the AV node , the electrical impulse enters the bundle of His , then to the left and right bundle branches extending through the interventricular septum . Finally , the Purkinje fibers conduct the impulse from the apex of the heart up the ventricular myocardium , and then the ventricles contract . This pause allows the atria to empty completely into the ventricles before the ventricles pump out the blood . The electrical impulses in the heart produce electrical currents that flow through the body and can be measured on the skin using electrodes . This information can be observed as an electrocardiogram ( ECG ) — a recording of the electrical impulses of the cardiac muscle . <hl> The pumping of the heart is a function of the cardiac muscle cells , or cardiomyocytes , that make up the heart muscle . <hl> Cardiomyocytes , shown in Figure 40.13 , are distinctive muscle cells that are striated like skeletal muscle but pump rhythmically and involuntarily like smooth muscle ; they are connected by intercalated disks exclusive to cardiac muscle . They are self-stimulated for a period of time and isolated cardiomyocytes will beat if given the correct balance of nutrients and electrolytes .","hl_sentences":"The autonomous beating of cardiac muscle cells is regulated by the heart ’ s internal pacemaker that uses electrical signals to time the beating of the heart . The pumping of the heart is a function of the cardiac muscle cells , or cardiomyocytes , that make up the heart muscle .","question":{"cloze_format":"The heart’s internal pacemaker beats by ___.","normal_format":"How does the heart’s internal pacemaker beat by?","question_choices":["an internal implant that sends an electrical impulse through the heart","the excitation of cardiac muscle cells at the sinoatrial node followed by the atrioventricular node","the excitation of cardiac muscle cells at the atrioventricular node followed by the sinoatrial node","the action of the sinus"],"question_id":"fs-idp26179632","question_text":"The heart’s internal pacemaker beats by:"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"contracting"},"bloom":null,"hl_context":"The main purpose of the heart is to pump blood through the body ; it does so in a repeating sequence called the cardiac cycle . The cardiac cycle is the coordination of the filling and emptying of the heart of blood by electrical signals that cause the heart muscles to contract and relax . The human heart beats over 100,000 times per day . <hl> In each cardiac cycle , the heart contracts ( systole ) , pushing out the blood and pumping it through the body ; this is followed by a relaxation phase ( diastole ) , where the heart fills with blood , as illustrated in Figure 40.12 . <hl> The atria contract at the same time , forcing blood through the atrioventricular valves into the ventricles . Closing of the atrioventricular valves produces a monosyllabic “ lup ” sound . Following a brief delay , the ventricles contract at the same time forcing blood through the semilunar valves into the aorta and the artery transporting blood to the lungs ( via the pulmonary artery ) . Closing of the semilunar valves produces a monosyllabic “ dup ” sound .","hl_sentences":"In each cardiac cycle , the heart contracts ( systole ) , pushing out the blood and pumping it through the body ; this is followed by a relaxation phase ( diastole ) , where the heart fills with blood , as illustrated in Figure 40.12 .","question":{"cloze_format":"During the systolic phase of the cardiac cycle, the heart is ________.","normal_format":"During the systolic phase of the cardiac cycle, what is the heart doing?","question_choices":["contracting","relaxing","contracting and relaxing","filling with blood"],"question_id":"fs-idm153328976","question_text":"During the systolic phase of the cardiac cycle, the heart is ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"they are striated"},"bloom":null,"hl_context":"The pumping of the heart is a function of the cardiac muscle cells , or cardiomyocytes , that make up the heart muscle . <hl> Cardiomyocytes , shown in Figure 40.13 , are distinctive muscle cells that are striated like skeletal muscle but pump rhythmically and involuntarily like smooth muscle ; they are connected by intercalated disks exclusive to cardiac muscle . <hl> They are self-stimulated for a period of time and isolated cardiomyocytes will beat if given the correct balance of nutrients and electrolytes .","hl_sentences":"Cardiomyocytes , shown in Figure 40.13 , are distinctive muscle cells that are striated like skeletal muscle but pump rhythmically and involuntarily like smooth muscle ; they are connected by intercalated disks exclusive to cardiac muscle .","question":{"cloze_format":"Cardiomyocytes are similar to skeletal muscle because ___ .","normal_format":"Why are cardiomyocytes similar to skeletal muscle?","question_choices":["they beat involuntarily","they are used for weight lifting","they pulse rhythmically","they are striated"],"question_id":"fs-idm232681600","question_text":"Cardiomyocytes are similar to skeletal muscle because:"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"Arteries have thicker smooth muscle layers to accommodate the changes in pressure from the heart."},"bloom":"2","hl_context":"Veins and arteries both have two further tunics that surround the endothelium : the middle tunic is composed of smooth muscle and the outermost layer is connective tissue ( collagen and elastic fibers ) . The elastic connective tissue stretches and supports the blood vessels , and the smooth muscle layer helps regulate blood flow by altering vascular resistance through vasoconstriction and vasodilation . <hl> The arteries have thicker smooth muscle and connective tissue than the veins to accommodate the higher pressure and speed of freshly pumped blood . <hl> The veins are thinner walled as the pressure and rate of flow are much lower . In addition , veins are structurally different than arteries in that veins have valves to prevent the backflow of blood . Because veins have to work against gravity to get blood back to the heart , contraction of skeletal muscle assists with the flow of blood back to the heart . 40.4 Blood Flow and Blood Pressure Regulation Learning Objectives By the end of this section , you will be able to :","hl_sentences":"The arteries have thicker smooth muscle and connective tissue than the veins to accommodate the higher pressure and speed of freshly pumped blood .","question":{"cloze_format":"Arteries differ from veins because ___.","normal_format":"How do arteries differ from veins?","question_choices":["Arteries have thicker smooth muscle layers to accommodate the changes in pressure from the heart.","Arteries carry blood.","Arteries have thinner smooth muscle layers and valves and move blood by the action of skeletal muscle.","Arteries are thin walled and are used for gas exchange."],"question_id":"fs-idm25699712","question_text":"How do arteries differ from veins?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"a high cardiac output and high peripheral resistance"},"bloom":null,"hl_context":"Cardiac output is the volume of blood pumped by the heart in one minute . It is calculated by multiplying the number of heart contractions that occur per minute ( heart rate ) times the stroke volume ( the volume of blood pumped into the aorta per contraction of the left ventricle ) . Therefore , cardiac output can be increased by increasing heart rate , as when exercising . However , cardiac output can also be increased by increasing stroke volume , such as if the heart contracts with greater strength . Stroke volume can also be increased by speeding blood circulation through the body so that more blood enters the heart between contractions . During heavy exertion , the blood vessels relax and increase in diameter , offsetting the increased heart rate and ensuring adequate oxygenated blood gets to the muscles . <hl> Stress triggers a decrease in the diameter of the blood vessels , consequently increasing blood pressure . <hl> <hl> These changes can also be caused by nerve signals or hormones , and even standing up or lying down can have a great effect on blood pressure . <hl> The pressure of the blood flow in the body is produced by the hydrostatic pressure of the fluid ( blood ) against the walls of the blood vessels . Fluid will move from areas of high to low hydrostatic pressures . In the arteries , the hydrostatic pressure near the heart is very high and blood flows to the arterioles where the rate of flow is slowed by the narrow openings of the arterioles . During systole , when new blood is entering the arteries , the artery walls stretch to accommodate the increase of pressure of the extra blood ; during diastole , the walls return to normal because of their elastic properties . The blood pressure of the systole phase and the diastole phase , graphed in Figure 40.19 , gives the two pressure readings for blood pressure . For example , 120/80 indicates a reading of 120 mm Hg during the systole and 80 mm Hg during diastole . Throughout the cardiac cycle , the blood continues to empty into the arterioles at a relatively even rate . <hl> This resistance to blood flow is called peripheral resistance . <hl> Long necked animals , such as giraffes , need to pump blood upward from the heart against gravity . The blood pressure required from the pumping of the left ventricle would be equivalent to 250 mm Hg ( mm Hg = millimeters of mercury , a unit of pressure ) to reach the height of a giraffe ’ s head , which is 2.5 meters higher than the heart . However , if checks and balances were not in place , this blood pressure would damage the giraffe ’ s brain , particularly if it was bending down to drink . <hl> These checks and balances include valves and feedback mechanisms that reduce the rate of cardiac output . <hl> Long-necked dinosaurs such as the sauropods had to pump blood even higher , up to ten meters above the heart . This would have required a blood pressure of more than 600 mm Hg , which could only have been achieved by an enormous heart . Evidence for such an enormous heart does not exist and mechanisms to reduce the blood pressure required include the slowing of metabolism as these animals grew larger . It is likely that they did not routinely feed on tree tops but grazed on the ground .","hl_sentences":"Stress triggers a decrease in the diameter of the blood vessels , consequently increasing blood pressure . These changes can also be caused by nerve signals or hormones , and even standing up or lying down can have a great effect on blood pressure . This resistance to blood flow is called peripheral resistance . These checks and balances include valves and feedback mechanisms that reduce the rate of cardiac output .","question":{"cloze_format":"High blood pressure would be a result of ________.","normal_format":"What would high blood pressure be a result of?","question_choices":["a high cardiac output and high peripheral resistance","a high cardiac output and low peripheral resistance","a low cardiac output and high peripheral resistance","a low cardiac output and low peripheral resistance"],"question_id":"fs-idm95376912","question_text":"High blood pressure would be a result of ________."},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"They use less metabolic energy.\"\n },\n \"bloom\": null,\n \"hl_context\": \"The circulatory system is effectively a network of cylindrical vessels : the arteries , veins , and capillaries that emanate from a pump , the heart . In all vertebrate organisms , as well as some invertebrates , this is a closed-loop system , in which the blood is not free in a cavity . In a closed circulatory system , blood is contained inside blood vessels and circulates unidirectionally from the heart around the systemic circulatory route , then returns to the heart again , as illustrated in Figure 40.2 a . As opposed to a closed system , arthropods — including insects , crustaceans , and most mollusks — have an open circulatory system , as illustrated in Figure 40.2 b . In an open circulatory system , the blood is not enclosed in the blood vessels but is pumped into a cavity called a hemocoel and is called hemolymph because the blood mixes with the interstitial fluid . As the heart beats and the animal moves , the hemolymph circulates around the organs within the body cavity and then reenters the hearts through openings called ostia . This movement allows for gas and nutrient exchange . <hl> An open circulatory system does not use as much energy as a closed system to operate or to maintain ; however , there is a trade-off with the amount of blood that can be moved to metabolically active organs and tissues that require high levels of oxygen . <hl> In fact , one reason that insects with wing spans of up to two feet wide ( 70 cm ) are not around today is probably because they were outcompeted by the arrival of birds 150 million years ago . Birds , having a closed circulatory system , are thought to have moved more agilely , allowing them to get food faster and possibly to prey on the insects .\",\n \"hl_sentences\": \"An open circulatory system does not use as much energy as a closed system to operate or to maintain ; however , there is a trade-off with the amount of blood that can be moved to metabolically active organs and tissues that require high levels of oxygen .\",\n \"question\": {\n \"cloze_format\": \"The reason open circulatory systems are advantageous to some animals is that ___ .\",\n \"normal_format\": \"Why are open circulatory systems advantageous to some animals?\",\n \"question_choices\": [\n \"They use less metabolic energy.\",\n \"They help the animal move faster.\",\n \"They do not need a heart.\",\n \"They help large insects develop.\"\n ],\n \"question_id\": \"fs-idm300553744\",\n \"question_text\": \"Why are open circulatory systems advantageous to some animals?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"None of the above\"\n },\n \"bloom\": null,\n \"hl_context\": \"The circulatory system varies from simple systems in invertebrates to more complex systems in vertebrates . <hl> The simplest animals , such as the sponges ( Porifera ) and rotifers ( Rotifera ) , do not need a circulatory system because diffusion allows adequate exchange of water , nutrients , and waste , as well as dissolved gases , as shown in Figure 40.3 a . <hl> Organisms that are more complex but still only have two layers of cells in their body plan , such as jellies ( Cnidaria ) and comb jellies ( Ctenophora ) also use diffusion through their epidermis and internally through the gastrovascular compartment . Both their internal and external tissues are bathed in an aqueous environment and exchange fluids by diffusion on both sides , as illustrated in Figure 40.3 b . Exchange of fluids is assisted by the pulsing of the jellyfish body . For more complex organisms , diffusion is not efficient for cycling gases , nutrients , and waste effectively through the body ; therefore , more complex circulatory systems evolved . Most arthropods and many mollusks have open circulatory systems . In an open system , an elongated beating heart pushes the hemolymph through the body and muscle contractions help to move fluids . The larger more complex crustaceans , including lobsters , have developed arterial-like vessels to push blood through their bodies , and the most active mollusks , such as squids , have evolved a closed circulatory system and are able to move rapidly to catch prey . Closed circulatory systems are a characteristic of vertebrates ; however , there are significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due to adaptation during evolution and associated differences in anatomy . Figure 40.4 illustrates the basic circulatory systems of some vertebrates : fish , amphibians , reptiles , and mammals . As illustrated in Figure 40.4 a Fish have a single circuit for blood flow and a two-chambered heart that has only a single atrium and a single ventricle . The atrium collects blood that has returned from the body and the ventricle pumps the blood to the gills where gas exchange occurs and the blood is re-oxygenated ; this is called gill circulation . The blood then continues through the rest of the body before arriving back at the atrium ; this is called systemic circulation . This unidirectional flow of blood produces a gradient of oxygenated to deoxygenated blood around the fish ’ s systemic circuit . The result is a limit in the amount of oxygen that can reach some of the organs and tissues of the body , reducing the overall metabolic capacity of fish . In amphibians , reptiles , birds , and mammals , blood flow is directed in two circuits : one through the lungs and back to the heart , which is called pulmonary circulation , and the other throughout the rest of the body and its organs including the brain ( systemic circulation ) . In amphibians , gas exchange also occurs through the skin during pulmonary circulation and is referred to as pulmocutaneous circulation . Chapter Outline 40.1 Overview of the Circulatory System 40.2 Components of the Blood 40.3 Mammalian Heart and Blood Vessels 40.4 Blood Flow and Blood Pressure Regulation Introduction Most animals are complex multicellular organisms that require a mechanism for transporting nutrients throughout their bodies and removing waste products . <hl> The circulatory system has evolved over time from simple diffusion through cells in the early evolution of animals to a complex network of blood vessels that reach all parts of the human body . <hl> This extensive network supplies the cells , tissues , and organs with oxygen and nutrients , and removes carbon dioxide and waste , which are byproducts of respiration . At the core of the human circulatory system is the heart . The size of a clenched fist , the human heart is protected beneath the rib cage . Made of specialized and unique cardiac muscle , it pumps blood throughout the body and to the heart itself . Heart contractions are driven by intrinsic electrical impulses that the brain and endocrine hormones help to regulate . Understanding the heart ’ s basic anatomy and function is important to understanding the body ’ s circulatory and respiratory systems . Gas exchange is one essential function of the circulatory system . A circulatory system is not needed in organisms with no specialized respiratory organs because oxygen and carbon dioxide diffuse directly between their body tissues and the external environment . However , in organisms that possess lungs and gills , oxygen must be transported from these specialized respiratory organs to the body tissues via a circulatory system . Therefore , circulatory systems have had to evolve to accommodate the great diversity of body sizes and body types present among animals .\",\n \"hl_sentences\": \"The simplest animals , such as the sponges ( Porifera ) and rotifers ( Rotifera ) , do not need a circulatory system because diffusion allows adequate exchange of water , nutrients , and waste , as well as dissolved gases , as shown in Figure 40.3 a . The circulatory system has evolved over time from simple diffusion through cells in the early evolution of animals to a complex network of blood vessels that reach all parts of the human body .\",\n \"question\": {\n \"cloze_format\": \"Some animals use diffusion instead of a circulatory system. Examples include ___.\",\n \"normal_format\": \"What is an example of an animal that uses diffusion instead of a circulatory system?\",\n \"question_choices\": [\n \"birds and jellyfish\",\n \"flatworms and arthropods\",\n \"mollusks and jellyfish\",\n \"None of the above\"\n ],\n \"question_id\": \"fs-idm216101712\",\n \"question_text\": \"Some animals use diffusion instead of a circulatory system. Examples include:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"pulmonary circulation\"\n },\n \"bloom\": null,\n \"hl_context\": \"The circulatory system varies from simple systems in invertebrates to more complex systems in vertebrates . The simplest animals , such as the sponges ( Porifera ) and rotifers ( Rotifera ) , do not need a circulatory system because diffusion allows adequate exchange of water , nutrients , and waste , as well as dissolved gases , as shown in Figure 40.3 a . Organisms that are more complex but still only have two layers of cells in their body plan , such as jellies ( Cnidaria ) and comb jellies ( Ctenophora ) also use diffusion through their epidermis and internally through the gastrovascular compartment . Both their internal and external tissues are bathed in an aqueous environment and exchange fluids by diffusion on both sides , as illustrated in Figure 40.3 b . Exchange of fluids is assisted by the pulsing of the jellyfish body . For more complex organisms , diffusion is not efficient for cycling gases , nutrients , and waste effectively through the body ; therefore , more complex circulatory systems evolved . Most arthropods and many mollusks have open circulatory systems . In an open system , an elongated beating heart pushes the hemolymph through the body and muscle contractions help to move fluids . The larger more complex crustaceans , including lobsters , have developed arterial-like vessels to push blood through their bodies , and the most active mollusks , such as squids , have evolved a closed circulatory system and are able to move rapidly to catch prey . Closed circulatory systems are a characteristic of vertebrates ; however , there are significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due to adaptation during evolution and associated differences in anatomy . Figure 40.4 illustrates the basic circulatory systems of some vertebrates : fish , amphibians , reptiles , and mammals . As illustrated in Figure 40.4 a Fish have a single circuit for blood flow and a two-chambered heart that has only a single atrium and a single ventricle . The atrium collects blood that has returned from the body and the ventricle pumps the blood to the gills where gas exchange occurs and the blood is re-oxygenated ; this is called gill circulation . The blood then continues through the rest of the body before arriving back at the atrium ; this is called systemic circulation . This unidirectional flow of blood produces a gradient of oxygenated to deoxygenated blood around the fish ’ s systemic circuit . The result is a limit in the amount of oxygen that can reach some of the organs and tissues of the body , reducing the overall metabolic capacity of fish . <hl> In amphibians , reptiles , birds , and mammals , blood flow is directed in two circuits : one through the lungs and back to the heart , which is called pulmonary circulation , and the other throughout the rest of the body and its organs including the brain ( systemic circulation ) . <hl> In amphibians , gas exchange also occurs through the skin during pulmonary circulation and is referred to as pulmocutaneous circulation .\",\n \"hl_sentences\": \"In amphibians , reptiles , birds , and mammals , blood flow is directed in two circuits : one through the lungs and back to the heart , which is called pulmonary circulation , and the other throughout the rest of the body and its organs including the brain ( systemic circulation ) .\",\n \"question\": {\n \"cloze_format\": \"Blood flow that is directed through the lungs and back to the heart is called ________.\",\n \"normal_format\": \"What is blood flow called that is directed through the lungs and back to the heart?\",\n \"question_choices\": [\n \"unidirectional circulation\",\n \"gill circulation\",\n \"pulmonary circulation\",\n \"pulmocutaneous circulation\"\n ],\n \"question_id\": \"fs-idm225583056\",\n \"question_text\": \"Blood flow that is directed through the lungs and back to the heart is called ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"All of the above\"\n },\n \"bloom\": null,\n \"hl_context\": \"The morphology of white blood cells differs significantly from red blood cells . They have nuclei and do not contain hemoglobin . The different types of white blood cells are identified by their microscopic appearance after histologic staining , and each has a different specialized function . <hl> The two main groups , both illustrated in Figure 40.7 are the granulocytes , which include the neutrophils , eosinophils , and basophils , and the agranulocytes , which include the monocytes and lymphocytes . <hl> <hl> White blood cells , also called leukocytes ( leuko = white ) , make up approximately one percent by volume of the cells in blood . <hl> <hl> The role of white blood cells is very different than that of red blood cells : they are primarily involved in the immune response to identify and target pathogens , such as invading bacteria , viruses , and other foreign organisms . <hl> White blood cells are formed continually ; some only live for hours or days , but some live for years .\",\n \"hl_sentences\": \"The two main groups , both illustrated in Figure 40.7 are the granulocytes , which include the neutrophils , eosinophils , and basophils , and the agranulocytes , which include the monocytes and lymphocytes . White blood cells , also called leukocytes ( leuko = white ) , make up approximately one percent by volume of the cells in blood . The role of white blood cells is very different than that of red blood cells : they are primarily involved in the immune response to identify and target pathogens , such as invading bacteria , viruses , and other foreign organisms .\",\n \"question\": {\n \"cloze_format\": \"White blood cells ___ .\",\n \"normal_format\": \"White blood cells are what?\",\n \"question_choices\": [\n \"can be classified as granulocytes or agranulocytes\",\n \"defend the body against bacteria and viruses\",\n \"are also called leucocytes\",\n \"All of the above\"\n ],\n \"question_id\": \"fs-idm6200624\",\n \"question_text\": \"White blood cells:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"when platelets are attracted to a site of blood vessel damage\"\n },\n \"bloom\": null,\n \"hl_context\": \"Blood must clot to heal wounds and prevent excess blood loss . <hl> Small cell fragments called platelets ( thrombocytes ) are attracted to the wound site where they adhere by extending many projections and releasing their contents . <hl> These contents activate other platelets and also interact with other coagulation factors , which convert fibrinogen , a water-soluble protein present in blood serum into fibrin ( a non-water soluble protein ) , causing the blood to clot . Many of the clotting factors require vitamin K to work , and vitamin K deficiency can lead to problems with blood clotting . <hl> Many platelets converge and stick together at the wound site forming a platelet plug ( also called a fibrin clot ) , as illustrated in Figure 40.8 b . <hl> The plug or clot lasts for a number of days and stops the loss of blood . Platelets are formed from the disintegration of larger cells called megakaryocytes , like that shown in Figure 40.8 a . For each megakaryocyte , 2000 – 3000 platelets are formed with 150,000 to 400,000 platelets present in each cubic millimeter of blood . Each platelet is disc shaped and 2 – 4 μm in diameter . They contain many small vesicles but do not contain a nucleus .\",\n \"hl_sentences\": \"Small cell fragments called platelets ( thrombocytes ) are attracted to the wound site where they adhere by extending many projections and releasing their contents . Many platelets converge and stick together at the wound site forming a platelet plug ( also called a fibrin clot ) , as illustrated in Figure 40.8 b .\",\n \"question\": {\n \"cloze_format\": \"The point at which platelet plug formation occurs is ___ .\",\n \"normal_format\": \"Platelet plug formation occurs at which point?\",\n \"question_choices\": [\n \"when large megakaryocytes break up into thousands of smaller fragments\",\n \"when platelets are dispersed through the blood stream\",\n \"when platelets are attracted to a site of blood vessel damage\",\n \"none of the above\"\n ],\n \"question_id\": \"fs-idm26244160\",\n \"question_text\": \"Platelet plug formation occurs at which point?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"25 percent\"\n },\n \"bloom\": null,\n \"hl_context\": \"Hemoglobin is responsible for distributing oxygen , and to a lesser extent , carbon dioxide , throughout the circulatory systems of humans , vertebrates , and many invertebrates . The blood is more than the proteins , though . Blood is actually a term used to describe the liquid that moves through the vessels and includes plasma ( the liquid portion , which contains water , proteins , salts , lipids , and glucose ) and the cells ( red and white cells ) and cell fragments called platelets . Blood plasma is actually the dominant component of blood and contains the water , proteins , electrolytes , lipids , and glucose . The cells are responsible for carrying the gases ( red cells ) and immune the response ( white ) . The platelets are responsible for blood clotting . Interstitial fluid that surrounds cells is separate from the blood , but in hemolymph , they are combined . <hl> In humans , cellular components make up approximately 45 percent of the blood and the liquid plasma 55 percent . <hl> Blood is 20 percent of a person ’ s extracellular fluid and eight percent of weight . The Role of Blood in the Body\",\n \"hl_sentences\": \"In humans , cellular components make up approximately 45 percent of the blood and the liquid plasma 55 percent .\",\n \"question\": {\n \"cloze_format\": \"In humans, the plasma comprises a percentage of ___ of the blood.\",\n \"normal_format\": \"In humans, the plasma comprises what percentage of the blood?\",\n \"question_choices\": [\n \"45 percent\",\n \"55 percent\",\n \"25 percent\",\n \"90 percent\"\n ],\n \"question_id\": \"fs-idm67048352\",\n \"question_text\": \"In humans, the plasma comprises what percentage of the blood?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"they have nuclei\"\n },\n \"bloom\": null,\n \"hl_context\": \"Red blood cells , or erythrocytes ( erythro - = “ red ” ; - cyte = “ cell ” ) , are specialized cells that circulate through the body delivering oxygen to cells ; they are formed from stem cells in the bone marrow . In mammals , red blood cells are small biconcave cells that at maturity do not contain a nucleus or mitochondria and are only 7 – 8 µm in size . <hl> In birds and non-avian reptiles , a nucleus is still maintained in red blood cells . <hl> The red coloring of blood comes from the iron-containing protein hemoglobin , illustrated in Figure 40.6 a . The principal job of this protein is to carry oxygen , but it also transports carbon dioxide as well . Hemoglobin is packed into red blood cells at a rate of about 250 million molecules of hemoglobin per cell . Each hemoglobin molecule binds four oxygen molecules so that each red blood cell carries one billion molecules of oxygen . There are approximately 25 trillion red blood cells in the five liters of blood in the human body , which could carry up to 25 sextillion ( 25 × 10 21 ) molecules of oxygen in the body at any time . In mammals , the lack of organelles in erythrocytes leaves more room for the hemoglobin molecules , and the lack of mitochondria also prevents use of the oxygen for metabolic respiration . Only mammals have anucleated red blood cells , and some mammals ( camels , for instance ) even have nucleated red blood cells . The advantage of nucleated red blood cells is that these cells can undergo mitosis . Anucleated red blood cells metabolize anaerobically ( without oxygen ) , making use of a primitive metabolic pathway to produce ATP and increase the efficiency of oxygen transport .\",\n \"hl_sentences\": \"In birds and non-avian reptiles , a nucleus is still maintained in red blood cells .\",\n \"question\": {\n \"cloze_format\": \"The red blood cells of birds differ from mammalian red blood cells because ___ .\",\n \"normal_format\": \"Why do the red blood cells of birds differ from mammalian red blood cells?\",\n \"question_choices\": [\n \"they are white and have nuclei\",\n \"they do not have nuclei\",\n \"they have nuclei\",\n \"they fight disease\"\n ],\n \"question_id\": \"fs-idm93132096\",\n \"question_text\": \"The red blood cells of birds differ from mammalian red blood cells because:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"the excitation of cardiac muscle cells at the sinoatrial node followed by the atrioventricular node\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The autonomous beating of cardiac muscle cells is regulated by the heart ’ s internal pacemaker that uses electrical signals to time the beating of the heart . <hl> The electrical signals and mechanical actions , illustrated in Figure 40.14 , are intimately intertwined . The internal pacemaker starts at the sinoatrial ( SA ) node , which is located near the wall of the right atrium . Electrical charges spontaneously pulse from the SA node causing the two atria to contract in unison . The pulse reaches a second node , called the atrioventricular ( AV ) node , between the right atrium and right ventricle where it pauses for approximately 0.1 second before spreading to the walls of the ventricles . From the AV node , the electrical impulse enters the bundle of His , then to the left and right bundle branches extending through the interventricular septum . Finally , the Purkinje fibers conduct the impulse from the apex of the heart up the ventricular myocardium , and then the ventricles contract . This pause allows the atria to empty completely into the ventricles before the ventricles pump out the blood . The electrical impulses in the heart produce electrical currents that flow through the body and can be measured on the skin using electrodes . This information can be observed as an electrocardiogram ( ECG ) — a recording of the electrical impulses of the cardiac muscle . <hl> The pumping of the heart is a function of the cardiac muscle cells , or cardiomyocytes , that make up the heart muscle . <hl> Cardiomyocytes , shown in Figure 40.13 , are distinctive muscle cells that are striated like skeletal muscle but pump rhythmically and involuntarily like smooth muscle ; they are connected by intercalated disks exclusive to cardiac muscle . They are self-stimulated for a period of time and isolated cardiomyocytes will beat if given the correct balance of nutrients and electrolytes .\",\n \"hl_sentences\": \"The autonomous beating of cardiac muscle cells is regulated by the heart ’ s internal pacemaker that uses electrical signals to time the beating of the heart . The pumping of the heart is a function of the cardiac muscle cells , or cardiomyocytes , that make up the heart muscle .\",\n \"question\": {\n \"cloze_format\": \"The heart’s internal pacemaker beats by ___.\",\n \"normal_format\": \"How does the heart’s internal pacemaker beat by?\",\n \"question_choices\": [\n \"an internal implant that sends an electrical impulse through the heart\",\n \"the excitation of cardiac muscle cells at the sinoatrial node followed by the atrioventricular node\",\n \"the excitation of cardiac muscle cells at the atrioventricular node followed by the sinoatrial node\",\n \"the action of the sinus\"\n ],\n \"question_id\": \"fs-idp26179632\",\n \"question_text\": \"The heart’s internal pacemaker beats by:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"contracting\"\n },\n \"bloom\": null,\n \"hl_context\": \"The main purpose of the heart is to pump blood through the body ; it does so in a repeating sequence called the cardiac cycle . The cardiac cycle is the coordination of the filling and emptying of the heart of blood by electrical signals that cause the heart muscles to contract and relax . The human heart beats over 100,000 times per day . <hl> In each cardiac cycle , the heart contracts ( systole ) , pushing out the blood and pumping it through the body ; this is followed by a relaxation phase ( diastole ) , where the heart fills with blood , as illustrated in Figure 40.12 . <hl> The atria contract at the same time , forcing blood through the atrioventricular valves into the ventricles . Closing of the atrioventricular valves produces a monosyllabic “ lup ” sound . Following a brief delay , the ventricles contract at the same time forcing blood through the semilunar valves into the aorta and the artery transporting blood to the lungs ( via the pulmonary artery ) . Closing of the semilunar valves produces a monosyllabic “ dup ” sound .\",\n \"hl_sentences\": \"In each cardiac cycle , the heart contracts ( systole ) , pushing out the blood and pumping it through the body ; this is followed by a relaxation phase ( diastole ) , where the heart fills with blood , as illustrated in Figure 40.12 .\",\n \"question\": {\n \"cloze_format\": \"During the systolic phase of the cardiac cycle, the heart is ________.\",\n \"normal_format\": \"During the systolic phase of the cardiac cycle, what is the heart doing?\",\n \"question_choices\": [\n \"contracting\",\n \"relaxing\",\n \"contracting and relaxing\",\n \"filling with blood\"\n ],\n \"question_id\": \"fs-idm153328976\",\n \"question_text\": \"During the systolic phase of the cardiac cycle, the heart is ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"they are striated\"\n },\n \"bloom\": null,\n \"hl_context\": \"The pumping of the heart is a function of the cardiac muscle cells , or cardiomyocytes , that make up the heart muscle . <hl> Cardiomyocytes , shown in Figure 40.13 , are distinctive muscle cells that are striated like skeletal muscle but pump rhythmically and involuntarily like smooth muscle ; they are connected by intercalated disks exclusive to cardiac muscle . <hl> They are self-stimulated for a period of time and isolated cardiomyocytes will beat if given the correct balance of nutrients and electrolytes .\",\n \"hl_sentences\": \"Cardiomyocytes , shown in Figure 40.13 , are distinctive muscle cells that are striated like skeletal muscle but pump rhythmically and involuntarily like smooth muscle ; they are connected by intercalated disks exclusive to cardiac muscle .\",\n \"question\": {\n \"cloze_format\": \"Cardiomyocytes are similar to skeletal muscle because ___ .\",\n \"normal_format\": \"Why are cardiomyocytes similar to skeletal muscle?\",\n \"question_choices\": [\n \"they beat involuntarily\",\n \"they are used for weight lifting\",\n \"they pulse rhythmically\",\n \"they are striated\"\n ],\n \"question_id\": \"fs-idm232681600\",\n \"question_text\": \"Cardiomyocytes are similar to skeletal muscle because:\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"Arteries have thicker smooth muscle layers to accommodate the changes in pressure from the heart.\"\n },\n \"bloom\": \"2\",\n \"hl_context\": \"Veins and arteries both have two further tunics that surround the endothelium : the middle tunic is composed of smooth muscle and the outermost layer is connective tissue ( collagen and elastic fibers ) . The elastic connective tissue stretches and supports the blood vessels , and the smooth muscle layer helps regulate blood flow by altering vascular resistance through vasoconstriction and vasodilation . <hl> The arteries have thicker smooth muscle and connective tissue than the veins to accommodate the higher pressure and speed of freshly pumped blood . <hl> The veins are thinner walled as the pressure and rate of flow are much lower . In addition , veins are structurally different than arteries in that veins have valves to prevent the backflow of blood . Because veins have to work against gravity to get blood back to the heart , contraction of skeletal muscle assists with the flow of blood back to the heart . 40.4 Blood Flow and Blood Pressure Regulation Learning Objectives By the end of this section , you will be able to :\",\n \"hl_sentences\": \"The arteries have thicker smooth muscle and connective tissue than the veins to accommodate the higher pressure and speed of freshly pumped blood .\",\n \"question\": {\n \"cloze_format\": \"Arteries differ from veins because ___.\",\n \"normal_format\": \"How do arteries differ from veins?\",\n \"question_choices\": [\n \"Arteries have thicker smooth muscle layers to accommodate the changes in pressure from the heart.\",\n \"Arteries carry blood.\",\n \"Arteries have thinner smooth muscle layers and valves and move blood by the action of skeletal muscle.\",\n \"Arteries are thin walled and are used for gas exchange.\"\n ],\n \"question_id\": \"fs-idm25699712\",\n \"question_text\": \"How do arteries differ from veins?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"a high cardiac output and high peripheral resistance\"\n },\n \"bloom\": null,\n \"hl_context\": \"Cardiac output is the volume of blood pumped by the heart in one minute . It is calculated by multiplying the number of heart contractions that occur per minute ( heart rate ) times the stroke volume ( the volume of blood pumped into the aorta per contraction of the left ventricle ) . Therefore , cardiac output can be increased by increasing heart rate , as when exercising . However , cardiac output can also be increased by increasing stroke volume , such as if the heart contracts with greater strength . Stroke volume can also be increased by speeding blood circulation through the body so that more blood enters the heart between contractions . During heavy exertion , the blood vessels relax and increase in diameter , offsetting the increased heart rate and ensuring adequate oxygenated blood gets to the muscles . <hl> Stress triggers a decrease in the diameter of the blood vessels , consequently increasing blood pressure . <hl> <hl> These changes can also be caused by nerve signals or hormones , and even standing up or lying down can have a great effect on blood pressure . <hl> The pressure of the blood flow in the body is produced by the hydrostatic pressure of the fluid ( blood ) against the walls of the blood vessels . Fluid will move from areas of high to low hydrostatic pressures . In the arteries , the hydrostatic pressure near the heart is very high and blood flows to the arterioles where the rate of flow is slowed by the narrow openings of the arterioles . During systole , when new blood is entering the arteries , the artery walls stretch to accommodate the increase of pressure of the extra blood ; during diastole , the walls return to normal because of their elastic properties . The blood pressure of the systole phase and the diastole phase , graphed in Figure 40.19 , gives the two pressure readings for blood pressure . For example , 120/80 indicates a reading of 120 mm Hg during the systole and 80 mm Hg during diastole . Throughout the cardiac cycle , the blood continues to empty into the arterioles at a relatively even rate . <hl> This resistance to blood flow is called peripheral resistance . <hl> Long necked animals , such as giraffes , need to pump blood upward from the heart against gravity . The blood pressure required from the pumping of the left ventricle would be equivalent to 250 mm Hg ( mm Hg = millimeters of mercury , a unit of pressure ) to reach the height of a giraffe ’ s head , which is 2.5 meters higher than the heart . However , if checks and balances were not in place , this blood pressure would damage the giraffe ’ s brain , particularly if it was bending down to drink . <hl> These checks and balances include valves and feedback mechanisms that reduce the rate of cardiac output . <hl> Long-necked dinosaurs such as the sauropods had to pump blood even higher , up to ten meters above the heart . This would have required a blood pressure of more than 600 mm Hg , which could only have been achieved by an enormous heart . Evidence for such an enormous heart does not exist and mechanisms to reduce the blood pressure required include the slowing of metabolism as these animals grew larger . It is likely that they did not routinely feed on tree tops but grazed on the ground .\",\n \"hl_sentences\": \"Stress triggers a decrease in the diameter of the blood vessels , consequently increasing blood pressure . These changes can also be caused by nerve signals or hormones , and even standing up or lying down can have a great effect on blood pressure . This resistance to blood flow is called peripheral resistance . These checks and balances include valves and feedback mechanisms that reduce the rate of cardiac output .\",\n \"question\": {\n \"cloze_format\": \"High blood pressure would be a result of ________.\",\n \"normal_format\": \"What would high blood pressure be a result of?\",\n \"question_choices\": [\n \"a high cardiac output and high peripheral resistance\",\n \"a high cardiac output and low peripheral resistance\",\n \"a low cardiac output and high peripheral resistance\",\n \"a low cardiac output and low peripheral resistance\"\n ],\n \"question_id\": \"fs-idm95376912\",\n \"question_text\": \"High blood pressure would be a result of ________.\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":40,"string":"40"},"chapter_text":{"kind":"string","value":"40.1 Overview of the Circulatory System Learning Objectives By the end of this section, you will be able to:\n\n Describe an open and closed circulatory system \n\n Describe interstitial fluid and hemolymph \n\n Compare and contrast the organization and evolution of the vertebrate circulatory system. \n\n In all animals, except a few simple types, the circulatory system is used to transport nutrients and gases through the body. Simple diffusion allows some water, nutrient, waste, and gas exchange into primitive animals that are only a few cell layers thick; however, bulk flow is the only method by which the entire body of larger more complex organisms is accessed. \n\n Circulatory System Architecture \n\n The circulatory system is effectively a network of cylindrical vessels: the arteries, veins, and capillaries that emanate from a pump, the heart. In all vertebrate organisms, as well as some invertebrates, this is a closed-loop system, in which the blood is not free in a cavity. In a closed circulatory system , blood is contained inside blood vessels and circulates unidirectionally from the heart around the systemic circulatory route, then returns to the heart again, as illustrated in Figure 40.2 a . As opposed to a closed system, arthropods—including insects, crustaceans, and most mollusks—have an open circulatory system, as illustrated in Figure 40.2 b . In an open circulatory system , the blood is not enclosed in the blood vessels but is pumped into a cavity called a hemocoel and is called hemolymph because the blood mixes with the interstitial fluid . As the heart beats and the animal moves, the hemolymph circulates around the organs within the body cavity and then reenters the hearts through openings called ostia . This movement allows for gas and nutrient exchange. An open circulatory system does not use as much energy as a closed system to operate or to maintain; however, there is a trade-off with the amount of blood that can be moved to metabolically active organs and tissues that require high levels of oxygen. In fact, one reason that insects with wing spans of up to two feet wide (70 cm) are not around today is probably because they were outcompeted by the arrival of birds 150 million years ago. Birds, having a closed circulatory system, are thought to have moved more agilely, allowing them to get food faster and possibly to prey on the insects. \n\n Circulatory System Variation in Animals \n\n The circulatory system varies from simple systems in invertebrates to more complex systems in vertebrates. The simplest animals, such as the sponges (Porifera) and rotifers (Rotifera), do not need a circulatory system because diffusion allows adequate exchange of water, nutrients, and waste, as well as dissolved gases, as shown in Figure 40.3 a . Organisms that are more complex but still only have two layers of cells in their body plan, such as jellies (Cnidaria) and comb jellies (Ctenophora) also use diffusion through their epidermis and internally through the gastrovascular compartment. Both their internal and external tissues are bathed in an aqueous environment and exchange fluids by diffusion on both sides, as illustrated in Figure 40.3 b . Exchange of fluids is assisted by the pulsing of the jellyfish body. For more complex organisms, diffusion is not efficient for cycling gases, nutrients, and waste effectively through the body; therefore, more complex circulatory systems evolved. Most arthropods and many mollusks have open circulatory systems. In an open system, an elongated beating heart pushes the hemolymph through the body and muscle contractions help to move fluids. The larger more complex crustaceans, including lobsters, have developed arterial-like vessels to push blood through their bodies, and the most active mollusks, such as squids, have evolved a closed circulatory system and are able to move rapidly to catch prey. Closed circulatory systems are a characteristic of vertebrates; however, there are significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due to adaptation during evolution and associated differences in anatomy. Figure 40.4 illustrates the basic circulatory systems of some vertebrates: fish, amphibians, reptiles, and mammals. As illustrated in Figure 40.4 a Fish have a single circuit for blood flow and a two-chambered heart that has only a single atrium and a single ventricle. The atrium collects blood that has returned from the body and the ventricle pumps the blood to the gills where gas exchange occurs and the blood is re-oxygenated; this is called gill circulation . The blood then continues through the rest of the body before arriving back at the atrium; this is called systemic circulation . This unidirectional flow of blood produces a gradient of oxygenated to deoxygenated blood around the fish’s systemic circuit. The result is a limit in the amount of oxygen that can reach some of the organs and tissues of the body, reducing the overall metabolic capacity of fish. In amphibians, reptiles, birds, and mammals, blood flow is directed in two circuits: one through the lungs and back to the heart, which is called pulmonary circulation , and the other throughout the rest of the body and its organs including the brain (systemic circulation). In amphibians, gas exchange also occurs through the skin during pulmonary circulation and is referred to as pulmocutaneous circulation . \n\n As shown in Figure 40.4 b , amphibians have a three-chambered heart that has two atria and one ventricle rather than the two-chambered heart of fish. The two atria (superior heart chambers) receive blood from the two different circuits (the lungs and the systems), and then there is some mixing of the blood in the heart’s ventricle (inferior heart chamber), which reduces the efficiency of oxygenation. The advantage to this arrangement is that high pressure in the vessels pushes blood to the lungs and body. The mixing is mitigated by a ridge within the ventricle that diverts oxygen-rich blood through the systemic circulatory system and deoxygenated blood to the pulmocutaneous circuit. For this reason, amphibians are often described as having double circulation . Most reptiles also have a three-chambered heart similar to the amphibian heart that directs blood to the pulmonary and systemic circuits, as shown in Figure 40.4 c . The ventricle is divided more effectively by a partial septum, which results in less mixing of oxygenated and deoxygenated blood. Some reptiles (alligators and crocodiles) are the most primitive animals to exhibit a four-chambered heart. Crocodilians have a unique circulatory mechanism where the heart shunts blood from the lungs toward the stomach and other organs during long periods of submergence, for instance, while the animal waits for prey or stays underwater waiting for prey to rot. One adaptation includes two main arteries that leave the same part of the heart: one takes blood to the lungs and the other provides an alternate route to the stomach and other parts of the body. Two other adaptations include a hole in the heart between the two ventricles, called the foramen of Panizza, which allows blood to move from one side of the heart to the other, and specialized connective tissue that slows the blood flow to the lungs. Together these adaptations have made crocodiles and alligators one of the most evolutionarily successful animal groups on earth. In mammals and birds, the heart is also divided into four chambers: two atria and two ventricles, as illustrated in Figure 40.4 d . The oxygenated blood is separated from the deoxygenated blood, which improves the efficiency of double circulation and is probably required for the warm-blooded lifestyle of mammals and birds. The four-chambered heart of birds and mammals evolved independently from a three-chambered heart. The independent evolution of the same or a similar biological trait is referred to as convergent evolution. \n40.2 Components of the Blood Learning Objectives By the end of this section, you will be able to:\n\n List the basic components of the blood \n\n Compare red and white blood cells \n\n Describe blood plasma and serum \n\n Hemoglobin is responsible for distributing oxygen, and to a lesser extent, carbon dioxide, throughout the circulatory systems of humans, vertebrates, and many invertebrates. The blood is more than the proteins, though. Blood is actually a term used to describe the liquid that moves through the vessels and includes plasma (the liquid portion, which contains water, proteins, salts, lipids, and glucose) and the cells (red and white cells) and cell fragments called platelets . Blood plasma is actually the dominant component of blood and contains the water, proteins, electrolytes, lipids, and glucose. The cells are responsible for carrying the gases (red cells) and immune the response (white). The platelets are responsible for blood clotting. Interstitial fluid that surrounds cells is separate from the blood, but in hemolymph, they are combined. In humans, cellular components make up approximately 45 percent of the blood and the liquid plasma 55 percent. Blood is 20 percent of a person’s extracellular fluid and eight percent of weight. The Role of Blood in the Body \n\n Blood, like the human blood illustrated in Figure 40.5 is important for regulation of the body’s systems and homeostasis. Blood helps maintain homeostasis by stabilizing pH, temperature, osmotic pressure, and by eliminating excess heat. Blood supports growth by distributing nutrients and hormones, and by removing waste. Blood plays a protective role by transporting clotting factors and platelets to prevent blood loss and transporting the disease-fighting agents or white blood cells to sites of infection. \n\n Red Blood Cells \n\n Red blood cells , or erythrocytes (erythro- = “red”; -cyte = “cell”), are specialized cells that circulate through the body delivering oxygen to cells; they are formed from stem cells in the bone marrow. In mammals, red blood cells are small biconcave cells that at maturity do not contain a nucleus or mitochondria and are only 7–8 µm in size. In birds and non-avian reptiles, a nucleus is still maintained in red blood cells. The red coloring of blood comes from the iron-containing protein hemoglobin, illustrated in Figure 40.6 a . The principal job of this protein is to carry oxygen, but it also transports carbon dioxide as well. Hemoglobin is packed into red blood cells at a rate of about 250 million molecules of hemoglobin per cell. Each hemoglobin molecule binds four oxygen molecules so that each red blood cell carries one billion molecules of oxygen. There are approximately 25 trillion red blood cells in the five liters of blood in the human body, which could carry up to 25 sextillion (25 × 10 21 ) molecules of oxygen in the body at any time. In mammals, the lack of organelles in erythrocytes leaves more room for the hemoglobin molecules, and the lack of mitochondria also prevents use of the oxygen for metabolic respiration. Only mammals have anucleated red blood cells, and some mammals (camels, for instance) even have nucleated red blood cells. The advantage of nucleated red blood cells is that these cells can undergo mitosis. Anucleated red blood cells metabolize anaerobically (without oxygen), making use of a primitive metabolic pathway to produce ATP and increase the efficiency of oxygen transport. \n\n Not all organisms use hemoglobin as the method of oxygen transport. Invertebrates that utilize hemolymph rather than blood use different pigments to bind to the oxygen. These pigments use copper or iron to the oxygen. Invertebrates have a variety of other respiratory pigments. Hemocyanin, a blue-green, copper-containing protein, illustrated in Figure 40.6 b is found in mollusks, crustaceans, and some of the arthropods. Chlorocruorin, a green-colored, iron-containing pigment is found in four families of polychaete tubeworms. Hemerythrin, a red, iron-containing protein is found in some polychaete worms and annelids and is illustrated in Figure 40.6 c . Despite the name, hemerythrin does not contain a heme group and its oxygen-carrying capacity is poor compared to hemoglobin. \n\n The small size and large surface area of red blood cells allows for rapid diffusion of oxygen and carbon dioxide across the plasma membrane. In the lungs, carbon dioxide is released and oxygen is taken in by the blood. In the tissues, oxygen is released from the blood and carbon dioxide is bound for transport back to the lungs. Studies have found that hemoglobin also binds nitrous oxide (NO). NO is a vasodilator that relaxes the blood vessels and capillaries and may help with gas exchange and the passage of red blood cells through narrow vessels. Nitroglycerin, a heart medication for angina and heart attacks, is converted to NO to help relax the blood vessels and increase oxygen flow through the body. \n\n A characteristic of red blood cells is their glycolipid and glycoprotein coating; these are lipids and proteins that have carbohydrate molecules attached. In humans, the surface glycoproteins and glycolipids on red blood cells vary between individuals, producing the different blood types, such as A, B, and O. Red blood cells have an average life span of 120 days, at which time they are broken down and recycled in the liver and spleen by phagocytic macrophages, a type of white blood cell. \n\n White Blood Cells \n\n White blood cells, also called leukocytes (leuko = white), make up approximately one percent by volume of the cells in blood. The role of white blood cells is very different than that of red blood cells: they are primarily involved in the immune response to identify and target pathogens, such as invading bacteria, viruses, and other foreign organisms. White blood cells are formed continually; some only live for hours or days, but some live for years. \n\n The morphology of white blood cells differs significantly from red blood cells. They have nuclei and do not contain hemoglobin. The different types of white blood cells are identified by their microscopic appearance after histologic staining, and each has a different specialized function. The two main groups, both illustrated in Figure 40.7 are the granulocytes, which include the neutrophils, eosinophils, and basophils, and the agranulocytes, which include the monocytes and lymphocytes. \n\n Granulocytes contain granules in their cytoplasm; the agranulocytes are so named because of the lack of granules in their cytoplasm. Some leukocytes become macrophages that either stay at the same site or move through the blood stream and gather at sites of infection or inflammation where they are attracted by chemical signals from foreign particles and damaged cells. Lymphocytes are the primary cells of the immune system and include B cells, T cells, and natural killer cells. B cells destroy bacteria and inactivate their toxins. They also produce antibodies. T cells attack viruses, fungi, some bacteria, transplanted cells, and cancer cells. T cells attack viruses by releasing toxins that kill the viruses. Natural killer cells attack a variety of infectious microbes and certain tumor cells. \n\n One reason that HIV poses significant management challenges is because the virus directly targets T cells by gaining entry through a receptor. Once inside the cell, HIV then multiplies using the T cell’s own genetic machinery. After the HIV virus replicates, it is transmitted directly from the infected T cell to macrophages. The presence of HIV can remain unrecognized for an extensive period of time before full disease symptoms develop. \n\n Platelets and Coagulation Factors \n\n Blood must clot to heal wounds and prevent excess blood loss. Small cell fragments called platelets (thrombocytes) are attracted to the wound site where they adhere by extending many projections and releasing their contents. These contents activate other platelets and also interact with other coagulation factors, which convert fibrinogen, a water-soluble protein present in blood serum into fibrin (a non-water soluble protein), causing the blood to clot. Many of the clotting factors require vitamin K to work, and vitamin K deficiency can lead to problems with blood clotting. Many platelets converge and stick together at the wound site forming a platelet plug (also called a fibrin clot), as illustrated in Figure 40.8 b . The plug or clot lasts for a number of days and stops the loss of blood. Platelets are formed from the disintegration of larger cells called megakaryocytes, like that shown in Figure 40.8 a . For each megakaryocyte, 2000–3000 platelets are formed with 150,000 to 400,000 platelets present in each cubic millimeter of blood. Each platelet is disc shaped and 2–4 μm in diameter. They contain many small vesicles but do not contain a nucleus. \n\n Plasma and Serum The liquid component of blood is called plasma, and it is separated by spinning or centrifuging the blood at high rotations (3000 rpm or higher). The blood cells and platelets are separated by centrifugal forces to the bottom of a specimen tube. The upper liquid layer, the plasma, consists of 90 percent water along with various substances required for maintaining the body’s pH, osmotic load, and for protecting the body. The plasma also contains the coagulation factors and antibodies. \n\n The plasma component of blood without the coagulation factors is called the serum . Serum is similar to interstitial fluid in which the correct composition of key ions acting as electrolytes is essential for normal functioning of muscles and nerves. Other components in the serum include proteins that assist with maintaining pH and osmotic balance while giving viscosity to the blood. The serum also contains antibodies, specialized proteins that are important for defense against viruses and bacteria. Lipids, including cholesterol, are also transported in the serum, along with various other substances including nutrients, hormones, metabolic waste, plus external substances, such as, drugs, viruses, and bacteria. \n\n Human serum albumin is the most abundant protein in human blood plasma and is synthesized in the liver. Albumin, which constitutes about half of the blood serum protein, transports hormones and fatty acids, buffers pH, and maintains osmotic pressures. Immunoglobin is a protein antibody produced in the mucosal lining and plays an important role in antibody mediated immunity. \n\n Evolution Connection Blood Types Related to Proteins on the Surface of the Red Blood Cells \n\nRed blood cells are coated in antigens made of glycolipids and glycoproteins. The composition of these molecules is determined by genetics, which have evolved over time. In humans, the different surface antigens are grouped into 24 different blood groups with more than 100 different antigens on each red blood cell. The two most well known blood groups are the ABO, shown in Figure 40.9 , and Rh systems. The surface antigens in the ABO blood group are glycolipids, called antigen A and antigen B. People with blood type A have antigen A, those with blood type B have antigen B, those with blood type AB have both antigens, and people with blood type O have neither antigen. Antibodies called agglutinougens are found in the blood plasma and react with the A or B antigens, if the two are mixed. When type A and type B blood are combined, agglutination (clumping) of the blood occurs because of antibodies in the plasma that bind with the opposing antigen; this causes clots that coagulate in the kidney causing kidney failure. Type O blood has neither A or B antigens, and therefore, type O blood can be given to all blood types. Type O negative blood is the universal donor. Type AB positive blood is the universal acceptor because it has both A and B antigen. The ABO blood groups were discovered in 1900 and 1901 by Karl Landsteiner at the University of Vienna. \n\n The Rh blood group was first discovered in Rhesus monkeys. Most people have the Rh antigen (Rh+) and do not have anti-Rh antibodies in their blood. The few people who do not have the Rh antigen and are Rh– can develop anti-Rh antibodies if exposed to Rh+ blood. This can happen after a blood transfusion or after an Rh– woman has an Rh+ baby. The first exposure does not usually cause a reaction; however, at the second exposure, enough antibodies have built up in the blood to produce a reaction that causes agglutination and breakdown of red blood cells. An injection can prevent this reaction. \n\n Link to Learning \n\n Play a blood typing game on the Nobel Prize website to solidify your understanding of blood types. \n40.3 Mammalian Heart and Blood Vessels Learning Objectives By the end of this section, you will be able to:\n\n Describe the structure of the heart and explain how cardiac muscle is different from other muscles \n\n Describe the cardiac cycle \n\n Explain the structure of arteries, veins, and capillaries, and how blood flows through the body \n\n The heart is a complex muscle that pumps blood through the three divisions of the circulatory system: the coronary (vessels that serve the heart), pulmonary (heart and lungs), and systemic (systems of the body), as shown in Figure 40.10 . Coronary circulation intrinsic to the heart takes blood directly from the main artery (aorta) coming from the heart. For pulmonary and systemic circulation, the heart has to pump blood to the lungs or the rest of the body, respectively. In vertebrates, the lungs are relatively close to the heart in the thoracic cavity. The shorter distance to pump means that the muscle wall on the right side of the heart is not as thick as the left side which must have enough pressure to pump blood all the way to your big toe. Visual Connection \n\n Which of the following statements about the circulatory system is false? \n\n Blood in the pulmonary vein is deoxygenated. \n\n Blood in the inferior vena cava is deoxygenated. \n\n Blood in the pulmonary artery is deoxygenated. \n\n Blood in the aorta is oxygenated. \n\n Structure of the Heart \n\n The heart muscle is asymmetrical as a result of the distance blood must travel in the pulmonary and systemic circuits. Since the right side of the heart sends blood to the pulmonary circuit it is smaller than the left side which must send blood out to the whole body in the systemic circuit, as shown in Figure 40.11 . In humans, the heart is about the size of a clenched fist; it is divided into four chambers: two atria and two ventricles. There is one atrium and one ventricle on the right side and one atrium and one ventricle on the left side. The atria are the chambers that receive blood, and the ventricles are the chambers that pump blood. The right atrium receives deoxygenated blood from the superior vena cava , which drains blood from the jugular vein that comes from the brain and from the veins that come from the arms, as well as from the inferior vena cava which drains blood from the veins that come from the lower organs and the legs. In addition, the right atrium receives blood from the coronary sinus which drains deoxygenated blood from the heart itself. This deoxygenated blood then passes to the right ventricle through the atrioventricular valve or the tricuspid valve , a flap of connective tissue that opens in only one direction to prevent the backflow of blood. The valve separating the chambers on the left side of the heart valve is called the biscuspid or mitral valve. After it is filled, the right ventricle pumps the blood through the pulmonary arteries, by-passing the semilunar valve (or pulmonic valve) to the lungs for re-oxygenation. After blood passes through the pulmonary arteries, the right semilunar valves close preventing the blood from flowing backwards into the right ventricle. The left atrium then receives the oxygen-rich blood from the lungs via the pulmonary veins. This blood passes through the bicuspid valve or mitral valve (the atrioventricular valve on the left side of the heart) to the left ventricle where the blood is pumped out through aorta , the major artery of the body, taking oxygenated blood to the organs and muscles of the body. Once blood is pumped out of the left ventricle and into the aorta, the aortic semilunar valve (or aortic valve) closes preventing blood from flowing backward into the left ventricle. This pattern of pumping is referred to as double circulation and is found in all mammals. \n\n Visual Connection \n\n Which of the following statements about the heart is false? \n\n The mitral valve separates the left ventricle from the left atrium. \n\n Blood travels through the bicuspid valve to the left atrium. \n\n Both the aortic and the pulmonary valves are semilunar valves. \n\n The mitral valve is an atrioventricular valve. \n\n The heart is composed of three layers; the epicardium, the myocardium, and the endocardium, illustrated in Figure 40.11 . The inner wall of the heart has a lining called the endocardium . The myocardium consists of the heart muscle cells that make up the middle layer and the bulk of the heart wall. The outer layer of cells is called the epicardium , of which the second layer is a membranous layered structure called the pericardium that surrounds and protects the heart; it allows enough room for vigorous pumping but also keeps the heart in place to reduce friction between the heart and other structures. \n\n The heart has its own blood vessels that supply the heart muscle with blood. The coronary arteries branch from the aorta and surround the outer surface of the heart like a crown. They diverge into capillaries where the heart muscle is supplied with oxygen before converging again into the coronary veins to take the deoxygenated blood back to the right atrium where the blood will be re-oxygenated through the pulmonary circuit. The heart muscle will die without a steady supply of blood. Atherosclerosis is the blockage of an artery by the buildup of fatty plaques. Because of the size (narrow) of the coronary arteries and their function in serving the heart itself, atherosclerosis can be deadly in these arteries. The slowdown of blood flow and subsequent oxygen deprivation that results from atherosclerosis causes severe pain, known as angina , and complete blockage of the arteries will cause myocardial infarction : the death of cardiac muscle tissue, commonly known as a heart attack. \n\n The Cardiac Cycle \n\n The main purpose of the heart is to pump blood through the body; it does so in a repeating sequence called the cardiac cycle. The cardiac cycle is the coordination of the filling and emptying of the heart of blood by electrical signals that cause the heart muscles to contract and relax. The human heart beats over 100,000 times per day. In each cardiac cycle, the heart contracts ( systole ), pushing out the blood and pumping it through the body; this is followed by a relaxation phase ( diastole ), where the heart fills with blood, as illustrated in Figure 40.12 . The atria contract at the same time, forcing blood through the atrioventricular valves into the ventricles. Closing of the atrioventricular valves produces a monosyllabic “lup” sound. Following a brief delay, the ventricles contract at the same time forcing blood through the semilunar valves into the aorta and the artery transporting blood to the lungs (via the pulmonary artery). Closing of the semilunar valves produces a monosyllabic “dup” sound. \n\n The pumping of the heart is a function of the cardiac muscle cells, or cardiomyocytes, that make up the heart muscle. Cardiomyocytes , shown in Figure 40.13 , are distinctive muscle cells that are striated like skeletal muscle but pump rhythmically and involuntarily like smooth muscle; they are connected by intercalated disks exclusive to cardiac muscle. They are self-stimulated for a period of time and isolated cardiomyocytes will beat if given the correct balance of nutrients and electrolytes. \n\n The autonomous beating of cardiac muscle cells is regulated by the heart’s internal pacemaker that uses electrical signals to time the beating of the heart. The electrical signals and mechanical actions, illustrated in Figure 40.14 , are intimately intertwined. The internal pacemaker starts at the sinoatrial (SA) node , which is located near the wall of the right atrium. Electrical charges spontaneously pulse from the SA node causing the two atria to contract in unison. The pulse reaches a second node, called the atrioventricular (AV) node, between the right atrium and right ventricle where it pauses for approximately 0.1 second before spreading to the walls of the ventricles. From the AV node, the electrical impulse enters the bundle of His, then to the left and right bundle branches extending through the interventricular septum. Finally, the Purkinje fibers conduct the impulse from the apex of the heart up the ventricular myocardium, and then the ventricles contract. This pause allows the atria to empty completely into the ventricles before the ventricles pump out the blood. The electrical impulses in the heart produce electrical currents that flow through the body and can be measured on the skin using electrodes. This information can be observed as an electrocardiogram (ECG) —a recording of the electrical impulses of the cardiac muscle. \n\n Link to Learning \n\n Visit this site and select the dropdown “Your Heart’s Electrical System” to see the heart’s “pacemaker” in action. \n\n Arteries, Veins, and Capillaries \n\n The blood from the heart is carried through the body by a complex network of blood vessels ( Figure 40.15 ). Arteries take blood away from the heart. The main artery is the aorta that branches into major arteries that take blood to different limbs and organs. These major arteries include the carotid artery that takes blood to the brain, the brachial arteries that take blood to the arms, and the thoracic artery that takes blood to the thorax and then into the hepatic, renal, and gastric arteries for the liver, kidney, and stomach, respectively. The iliac artery takes blood to the lower limbs. The major arteries diverge into minor arteries, and then smaller vessels called arterioles , to reach more deeply into the muscles and organs of the body. \n\n Arterioles diverge into capillary beds. Capillary beds contain a large number (10 to 100) of capillaries that branch among the cells and tissues of the body. Capillaries are narrow-diameter tubes that can fit red blood cells through in single file and are the sites for the exchange of nutrients, waste, and oxygen with tissues at the cellular level. Fluid also crosses into the interstitial space from the capillaries. The capillaries converge again into venules that connect to minor veins that finally connect to major veins that take blood high in carbon dioxide back to the heart. Veins are blood vessels that bring blood back to the heart. The major veins drain blood from the same organs and limbs that the major arteries supply. Fluid is also brought back to the heart via the lymphatic system. \n\n The structure of the different types of blood vessels reflects their function or layers. There are three distinct layers, or tunics, that form the walls of blood vessels ( Figure 40.16 ). The first tunic is a smooth, inner lining of endothelial cells that are in contact with the red blood cells. The endothelial tunic is continuous with the endocardium of the heart. In capillaries, this single layer of cells is the location of diffusion of oxygen and carbon dioxide between the endothelial cells and red blood cells, as well as the exchange site via endocytosis and exocytosis. The movement of materials at the site of capillaries is regulated by vasoconstriction , narrowing of the blood vessels, and vasodilation , widening of the blood vessels; this is important in the overall regulation of blood pressure. \n\n Veins and arteries both have two further tunics that surround the endothelium: the middle tunic is composed of smooth muscle and the outermost layer is connective tissue (collagen and elastic fibers). The elastic connective tissue stretches and supports the blood vessels, and the smooth muscle layer helps regulate blood flow by altering vascular resistance through vasoconstriction and vasodilation. The arteries have thicker smooth muscle and connective tissue than the veins to accommodate the higher pressure and speed of freshly pumped blood. The veins are thinner walled as the pressure and rate of flow are much lower. In addition, veins are structurally different than arteries in that veins have valves to prevent the backflow of blood. Because veins have to work against gravity to get blood back to the heart, contraction of skeletal muscle assists with the flow of blood back to the heart. \n40.4 Blood Flow and Blood Pressure Regulation Learning Objectives By the end of this section, you will be able to:\n\n Describe the system of blood flow through the body \n\n Describe how blood pressure is regulated \n\n Blood pressure (BP) is the pressure exerted by blood on the walls of a blood vessel that helps to push blood through the body. Systolic blood pressure measures the amount of pressure that blood exerts on vessels while the heart is beating. The optimal systolic blood pressure is 120 mmHg. Diastolic blood pressure measures the pressure in the vessels between heartbeats. The optimal diastolic blood pressure is 80 mmHg. Many factors can affect blood pressure, such as hormones, stress, exercise, eating, sitting, and standing. Blood flow through the body is regulated by the size of blood vessels, by the action of smooth muscle, by one-way valves, and by the fluid pressure of the blood itself. \n\n How Blood Flows Through the Body Blood is pushed through the body by the action of the pumping heart. With each rhythmic pump, blood is pushed under high pressure and velocity away from the heart, initially along the main artery, the aorta. In the aorta, the blood travels at 30 cm/sec. As blood moves into the arteries, arterioles, and ultimately to the capillary beds, the rate of movement slows dramatically to about 0.026 cm/sec, one-thousand times slower than the rate of movement in the aorta. While the diameter of each individual arteriole and capillary is far narrower than the diameter of the aorta, and according to the law of continuity, fluid should travel faster through a narrower diameter tube, the rate is actually slower due to the overall diameter of all the combined capillaries being far greater than the diameter of the individual aorta. \n\n The slow rate of travel through the capillary beds, which reach almost every cell in the body, assists with gas and nutrient exchange and also promotes the diffusion of fluid into the interstitial space. After the blood has passed through the capillary beds to the venules, veins, and finally to the main venae cavae, the rate of flow increases again but is still much slower than the initial rate in the aorta. Blood primarily moves in the veins by the rhythmic movement of smooth muscle in the vessel wall and by the action of the skeletal muscle as the body moves. Because most veins must move blood against the pull of gravity, blood is prevented from flowing backward in the veins by one-way valves. Because skeletal muscle contraction aids in venous blood flow, it is important to get up and move frequently after long periods of sitting so that blood will not pool in the extremities. \n\n Blood flow through the capillary beds is regulated depending on the body’s needs and is directed by nerve and hormone signals. For example, after a large meal, most of the blood is diverted to the stomach by vasodilation of vessels of the digestive system and vasoconstriction of other vessels. During exercise, blood is diverted to the skeletal muscles through vasodilation while blood to the digestive system would be lessened through vasoconstriction. The blood entering some capillary beds is controlled by small muscles, called precapillary sphincters, illustrated in Figure 40.17 . If the sphincters are open, the blood will flow into the associated branches of the capillary blood. If all of the sphincters are closed, then the blood will flow directly from the arteriole to the venule through the thoroughfare channel (see Figure 40.17 ). These muscles allow the body to precisely control when capillary beds receive blood flow. At any given moment only about 5-10% of our capillary beds actually have blood flowing through them. Visual Connection \n\n Varicose veins are veins that become enlarged because the valves no longer close properly, allowing blood to flow backward. Varicose veins are often most prominent on the legs. Why do you think this is the case? \n\n Link to Learning \n\n See the circulatory system’s blood flow.\n\n Click to view content \n\n Proteins and other large solutes cannot leave the capillaries. The loss of the watery plasma creates a hyperosmotic solution within the capillaries, especially near the venules. This causes about 85% of the plasma that leaves the capillaries to eventually diffuses back into the capillaries near the venules. The remaining 15% of blood plasma drains out from the interstitial fluid into nearby lymphatic vessels ( Figure 40.18 ). The fluid in the lymph is similar in composition to the interstitial fluid. The lymph fluid passes through lymph nodes before it returns to the heart via the vena cava. Lymph nodes are specialized organs that filter the lymph by percolation through a maze of connective tissue filled with white blood cells. The white blood cells remove infectious agents, such as bacteria and viruses, to clean the lymph before it returns to the bloodstream. After it is cleaned, the lymph returns to the heart by the action of smooth muscle pumping, skeletal muscle action, and one-way valves joining the returning blood near the junction of the venae cavae entering the right atrium of the heart. Evolution Connection Vertebrate Diversity in Blood Circulation \n\nBlood circulation has evolved differently in vertebrates and may show variation in different animals for the required amount of pressure, organ and vessel location, and organ size. Animals with longs necks and those that live in cold environments have distinct blood pressure adaptations. \n\n Long necked animals, such as giraffes, need to pump blood upward from the heart against gravity. The blood pressure required from the pumping of the left ventricle would be equivalent to 250 mm Hg (mm Hg = millimeters of mercury, a unit of pressure) to reach the height of a giraffe’s head, which is 2.5 meters higher than the heart. However, if checks and balances were not in place, this blood pressure would damage the giraffe’s brain, particularly if it was bending down to drink. These checks and balances include valves and feedback mechanisms that reduce the rate of cardiac output. Long-necked dinosaurs such as the sauropods had to pump blood even higher, up to ten meters above the heart. This would have required a blood pressure of more than 600 mm Hg, which could only have been achieved by an enormous heart. Evidence for such an enormous heart does not exist and mechanisms to reduce the blood pressure required include the slowing of metabolism as these animals grew larger. It is likely that they did not routinely feed on tree tops but grazed on the ground. \n\n Living in cold water, whales need to maintain the temperature in their blood. This is achieved by the veins and arteries being close together so that heat exchange can occur. This mechanism is called a countercurrent heat exchanger. The blood vessels and the whole body are also protected by thick layers of blubber to prevent heat loss. In land animals that live in cold environments, thick fur and hibernation are used to retain heat and slow metabolism. \n\n Blood Pressure \n\n The pressure of the blood flow in the body is produced by the hydrostatic pressure of the fluid (blood) against the walls of the blood vessels. Fluid will move from areas of high to low hydrostatic pressures. In the arteries, the hydrostatic pressure near the heart is very high and blood flows to the arterioles where the rate of flow is slowed by the narrow openings of the arterioles. During systole, when new blood is entering the arteries, the artery walls stretch to accommodate the increase of pressure of the extra blood; during diastole, the walls return to normal because of their elastic properties. The blood pressure of the systole phase and the diastole phase, graphed in Figure 40.19 , gives the two pressure readings for blood pressure. For example, 120/80 indicates a reading of 120 mm Hg during the systole and 80 mm Hg during diastole. Throughout the cardiac cycle, the blood continues to empty into the arterioles at a relatively even rate. This resistance to blood flow is called peripheral resistance . \n\n Blood Pressure Regulation \n\n Cardiac output is the volume of blood pumped by the heart in one minute. It is calculated by multiplying the number of heart contractions that occur per minute (heart rate) times the stroke volume (the volume of blood pumped into the aorta per contraction of the left ventricle). Therefore, cardiac output can be increased by increasing heart rate, as when exercising. However, cardiac output can also be increased by increasing stroke volume, such as if the heart contracts with greater strength. Stroke volume can also be increased by speeding blood circulation through the body so that more blood enters the heart between contractions. During heavy exertion, the blood vessels relax and increase in diameter, offsetting the increased heart rate and ensuring adequate oxygenated blood gets to the muscles. Stress triggers a decrease in the diameter of the blood vessels, consequently increasing blood pressure. These changes can also be caused by nerve signals or hormones, and even standing up or lying down can have a great effect on blood pressure. "}}},{"rowIdx":187,"cells":{"bname":{"kind":"string","value":"microbiology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":" Summary 18.1 Overview of Specific Adaptive Immunity \n\n Adaptive immunity is an acquired defense against foreign pathogens that is characterized by specificity and memory. The first exposure to an antigen stimulates a primary response , and subsequent exposures stimulate a faster and strong secondary response. \n\n Adaptive immunity is a dual system involving humoral immunity (antibodies produced by B cells) and cellular immunity (T cells directed against intracellular pathogens). \n\n Antigens , also called immunogens , are molecules that activate adaptive immunity. A single antigen possesses smaller epitopes , each capable of inducing a specific adaptive immune response. \n\n An antigen’s ability to stimulate an immune response depends on several factors, including its molecular class, molecular complexity, and size. \n\n Antibodies ( immunoglobulins ) are Y-shaped glycoproteins with two Fab sites for binding antigens and an Fc portion involved in complement activation and opsonization. \n\n The five classes of antibody are IgM , IgG , IgA , IgE , and IgD , each differing in size, arrangement, location within the body, and function. The five primary functions of antibodies are neutralization, opsonization, agglutination, complement activation, and antibody-dependent cell-mediated cytotoxicity (ADCC). \n\n 18.2 Major Histocompatibility Complexes and Antigen-Presenting Cells \n\n Major histocompatibility complex (MHC) is a collection of genes coding for glycoprotein molecules expressed on the surface of all nucleated cells. \n\n MHC I molecules are expressed on all nucleated cells and are essential for presentation of normal “self” antigens. Cells that become infected by intracellular pathogens can present foreign antigens on MHC I as well, marking the infected cell for destruction. \n\n MHC II molecules are expressed only on the surface of antigen-presenting cells (macrophages, dendritic cells, and B cells). Antigen presentation with MHC II is essential for the activation of T cells. \n\n Antigen-presenting cells (APCs) primarily ingest pathogens by phagocytosis, destroy them in the phagolysosomes, process the protein antigens, and select the most antigenic/immunodominant epitopes with MHC II for presentation to T cells. \n\n Cross-presentation is a mechanism of antigen presentation and T-cell activation used by dendritic cells not directly infected by the pathogen; it involves phagocytosis of the pathogen but presentation on MHC I rather than MHC II. \n\n 18.3 T Lymphocytes and Cellular Immunity \n\n Immature T lymphocytes are produced in the red bone marrow and travel to the thymus for maturation. \n\n Thymic selection is a three-step process of negative and positive selection that determines which T cells will mature and exit the thymus into the peripheral bloodstream. \n\n Central tolerance involves negative selection of self-reactive T cells in the thymus, and peripheral tolerance involves anergy and regulatory T cells that prevent self-reactive immune responses and autoimmunity. \n\n The TCR is similar in structure to immunoglobulins, but less complex. Millions of unique epitope-binding TCRs are encoded through a process of genetic rearrangement of V, D, and J gene segments. \n\n T cells can be divided into three classes— helper T cells, cytotoxic T cells, and regulatory T cells— based on their expression of CD4 or CD8, the MHC molecules with which they interact for activation, and their respective functions. \n\n Activated helper T cells differentiate into T H 1, T H 2, T H 17 , or memory T cell subtypes . Differentiation is directed by the specific cytokines to which they are exposed. T H 1, T H 2, and T H 17 perform different functions related to stimulation of adaptive and innate immune defenses. Memory T cells are long-lived cells that can respond quickly to secondary exposures. \n\n Once activated, cytotoxic T cells target and kill cells infected with intracellular pathogens. Killing requires recognition of specific pathogen epitopes presented on the cell surface using MHC I molecules. Killing is mediated by perforin and granzymes that induce apoptosis. \n\n Superantigens are bacterial or viral proteins that cause a nonspecific activation of helper T cells, leading to an excessive release of cytokines ( cytokine storm ) and a systemic, potentially fatal inflammatory response. \n\n 18.4 B Lymphocytes and Humoral Immunity \n\n B lymphocytes or B cells produce antibodies involved in humoral immunity. B cells are produced in the bone marrow, where the initial stages of maturation occur, and travel to the spleen for final steps of maturation into naïve mature B cells. \n\n B-cell receptors (BCRs) are membrane-bound monomeric forms of IgD and IgM that bind specific antigen epitopes with their Fab antigen-binding regions. Diversity of antigen binding specificity is created by genetic rearrangement of V, D, and J segments similar to the mechanism used for TCR diversity. \n\n Protein antigens are called T-dependent antigens because they can only activate B cells with the cooperation of helper T cells. Other molecule classes do not require T cell cooperation and are called T-independent antigens . \n\n T cell-independent activation of B cells involves cross-linkage of BCRs by repetitive nonprotein antigen epitopes. It is characterized by the production of IgM by plasma cells and does not produce memory B cells. \n\n T cell-dependent activation of B cells involves processing and presentation of protein antigens to helper T cells, activation of the B cells by cytokines secreted from activated T H 2 cells, and plasma cells that produce different classes of antibodies as a result of class switching . Memory B cells are also produced. \n\n Secondary exposures to T-dependent antigens result in a secondary antibody response initiated by memory B cells. The secondary response develops more quickly and produces higher and more sustained levels of antibody with higher affinity for the specific antigen. \n\n 18.5 Vaccines \n\n Adaptive immunity can be divided into four distinct classifications: natural active immunity, natural passive immunity, artificial passive immunity, and artificial active immunity. \n\n Artificial active immunity is the foundation for vaccination and vaccine development. Vaccination programs not only confer artificial immunity on individuals, but also foster herd immunity in populations. \n\n Variolation against smallpox originated in the 10 th century in China, but the procedure was risky because it could cause the disease it was intended to prevent. Modern vaccination was developed by Edward Jenner, who developed the practice of inoculating patients with infectious materials from cowpox lesions to prevent smallpox. \n\n Live attenuated vaccines and inactivated vaccines contain whole pathogens that are weak, killed, or inactivated. Subunit vaccines, toxoid vaccines, and conjugate vaccines contain acellular components with antigens that stimulate an immune response. "},"intro":{"kind":"string","value":" Chapter Outline 18.1 Overview of Specific Adaptive Immunity 18.2 Major Histocompatibility Complexes and Antigen-Presenting Cells 18.3 T Lymphocytes and Cellular Immunity 18.4 B Lymphocytes and Humoral Immunity 18.5 Vaccines Introduction People living in developed nations and born in the 1960s or later may have difficulty understanding the once heavy burden of devastating infectious diseases. For example, smallpox , a deadly viral disease, once destroyed entire civilizations but has since been eradicated. Thanks to the vaccination efforts by multiple groups, including the World Health Organization, Rotary International, and the United Nations Children’s Fund (UNICEF), smallpox has not been diagnosed in a patient since 1977. Polio is another excellent example. This crippling viral disease paralyzed patients, who were often kept alive in “iron lung wards” as recently as the 1950s ( Figure 18.1 ). Today, vaccination against polio has nearly eradicated the disease. Vaccines have also reduced the prevalence of once-common infectious diseases such as chickenpox , German measles , measles , mumps , and whooping cough . The success of these and other vaccines is due to the very specific and adaptive host defenses that are the focus of this chapter. Innate Nonspecific Host Defenses described innate immunity against microbial pathogens. Higher animals, such as humans, also possess an adaptive immune defense, which is highly specific for individual microbial pathogens. This specific adaptive immunity is acquired through active infection or vaccination and serves as an important defense against pathogens that evade the defenses of innate immunity. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"Once a B cell is activated , it undergoes clonal proliferation and daughter cells differentiate into plasma cells . <hl> Plasma cells are antibody factories that secrete large quantities of antibodies . <hl> After differentiation , the surface BCRs disappear and the plasma cell secretes pentameric IgM molecules that have the same antigen specificity as the BCRs ( Figure 18.21 ) .","hl_sentences":"Plasma cells are antibody factories that secrete large quantities of antibodies .","question":{"cloze_format":"Antibodies are produced by ________.","normal_format":"What produced Antibodies? ","question_choices":["plasma cells","T cells","bone marrow","Macrophages"],"question_id":"fs-id1167660323124","question_text":"Antibodies are produced by ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"As explained in Overview of Specific Adaptive Immunity , the antibodies involved in humoral immunity often bind pathogens and toxins before they can attach to and invade host cells . Thus , humoral immunity is primarily concerned with fighting pathogens in extracellular spaces . However , pathogens that have already gained entry to host cells are largely protected from the humoral antibody-mediated defenses . <hl> Cellular immunity , on the other hand , targets and eliminates intracellular pathogens through the actions of T lymphocytes , or T cells ( Figure 18.13 ) . <hl> T cells also play a more central role in orchestrating the overall adaptive immune response ( humoral as well as cellular ) along with the cellular defenses of innate immunity .","hl_sentences":"Cellular immunity , on the other hand , targets and eliminates intracellular pathogens through the actions of T lymphocytes , or T cells ( Figure 18.13 ) .","question":{"cloze_format":"Cellular adaptive immunity is carried out by ________.","normal_format":"What is cellular adaptive immunity carried out by?","question_choices":["B cells","T cells","bone marrow","neutrophils"],"question_id":"fs-id1167662771044","question_text":"Cellular adaptive immunity is carried out by ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"One reason the three-dimensional complexity of antigens is so important is that antibodies and T cells do not recognize and interact with an entire antigen but with smaller exposed regions on the surface of antigens called epitopes . <hl> A single antigen may possess several different epitopes ( Figure 18.3 ) , and different antibodies may bind to different epitopes on the same antigen ( Figure 18.4 ) . <hl> For example , the bacterial flagellum is a large , complex protein structure that can possess hundreds or even thousands of epitopes with unique three-dimensional structures . Moreover , flagella from different bacterial species ( or even strains of the same species ) contain unique epitopes that can only be bound by specific antibodies .","hl_sentences":"A single antigen may possess several different epitopes ( Figure 18.3 ) , and different antibodies may bind to different epitopes on the same antigen ( Figure 18.4 ) .","question":{"cloze_format":"A single antigen molecule may be composed of many individual ________.","normal_format":"An single antigen molecule may be dcomposed into what?","question_choices":["T-cell receptors","B-cell receptors","MHC II","epitopes"],"question_id":"fs-id1167662665461","question_text":"A single antigen molecule may be composed of many individual ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"Antigens may belong to any number of molecular classes , including carbohydrates , lipids , nucleic acids , proteins , and combinations of these molecules . Antigens of different classes vary in their ability to stimulate adaptive immune defenses as well as in the type of response they stimulate ( humoral or cellular ) . <hl> The structural complexity of an antigenic molecule is an important factor in its antigenic potential . <hl> <hl> In general , more complex molecules are more effective as antigens . <hl> <hl> For example , the three-dimensional complex structure of proteins make them the most effective and potent antigens , capable of stimulating both humoral and cellular immunity . <hl> In comparison , carbohydrates are less complex in structure and therefore less effective as antigens ; they can only stimulate humoral immune defenses . Lipids and nucleic acids are the least antigenic molecules , and in some cases may only become antigenic when combined with proteins or carbohydrates to form glycolipids , lipoproteins , or nucleoproteins .","hl_sentences":"The structural complexity of an antigenic molecule is an important factor in its antigenic potential . In general , more complex molecules are more effective as antigens . For example , the three-dimensional complex structure of proteins make them the most effective and potent antigens , capable of stimulating both humoral and cellular immunity .","question":{"cloze_format":"The class of molecules that is the most antigenic are ___.","normal_format":"Which class of molecules is the most antigenic?","question_choices":["polysaccharides","lipids","proteins","carbohydrates"],"question_id":"fs-id1167660276851","question_text":"Which class of molecules is the most antigenic?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> MHC I molecules , found on all normal , healthy , nucleated cells , signal to the immune system that the cell is a normal “ self ” cell . <hl> In a healthy cell , proteins normally found in the cytoplasm are degraded by proteasomes ( enzyme complexes responsible for degradation and processing of proteins ) and processed into self-antigen epitopes ; these self-antigen epitopes bind within the MHC I antigen-binding cleft and are then presented on the cell surface . Immune cells , such as NK cells , recognize these self-antigens and do not target the cell for destruction . <hl> However , if a cell becomes infected with an intracellular pathogen ( e . g . , a virus ) , protein antigens specific to the pathogen are processed in the proteasomes and bind with MHC I molecules for presentation on the cell surface . <hl> <hl> This presentation of pathogen-specific antigens with MHC I signals that the infected cell must be targeted for destruction along with the pathogen . <hl>","hl_sentences":"MHC I molecules , found on all normal , healthy , nucleated cells , signal to the immune system that the cell is a normal “ self ” cell . However , if a cell becomes infected with an intracellular pathogen ( e . g . , a virus ) , protein antigens specific to the pathogen are processed in the proteasomes and bind with MHC I molecules for presentation on the cell surface . This presentation of pathogen-specific antigens with MHC I signals that the infected cell must be targeted for destruction along with the pathogen .","question":{"cloze_format":"MHC I molecules present ___.","normal_format":"What do MHC I molecules present?","question_choices":["processed foreign antigens from proteasomes.","processed self-antigens from phagolysosome.","antibodies.","T cell antigens."],"question_id":"fs-id1167662450417","question_text":"MHC I molecules present"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"After a dendritic cell recognizes and attaches to a pathogen cell , the pathogen is internalized by phagocytosis and is initially contained within a phagosome . <hl> Lysosomes containing antimicrobial enzymes and chemicals fuse with the phagosome to create a phagolysosome , where degradation of the pathogen for antigen processing begins . <hl> <hl> Proteases ( protein-degrading ) are especially important in antigen processing because only protein antigen epitopes are presented to T cells by MHC II ( Figure 18.12 ) . <hl>","hl_sentences":"Lysosomes containing antimicrobial enzymes and chemicals fuse with the phagosome to create a phagolysosome , where degradation of the pathogen for antigen processing begins . Proteases ( protein-degrading ) are especially important in antigen processing because only protein antigen epitopes are presented to T cells by MHC II ( Figure 18.12 ) .","question":{"cloze_format":"MHC II molecules present ___.","normal_format":"What do MHC II molecules present?","question_choices":["processed self-antigens from proteasomes.","processed foreign antigens from phagolysosomes.","antibodies.","T cell receptors."],"question_id":"fs-id1167660364789","question_text":"MHC II molecules present"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"There are two classes of MHC molecules involved in adaptive immunity , MHC I and MHC II ( Figure 18.11 ) . <hl> MHC I molecules are found on all nucleated cells ; they present normal self-antigens as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity . <hl> In contrast , MHC II molecules are only found on macrophages , dendritic cells , and B cells ; they present abnormal or nonself pathogen antigens for the initial activation of T cells .","hl_sentences":"MHC I molecules are found on all nucleated cells ; they present normal self-antigens as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity .","question":{"cloze_format":"___ is/are a type of antigen-presenting molecule that is found on all nucleated cells.","normal_format":"Which type of antigen-presenting molecule is found on all nucleated cells?","question_choices":["MHC II","MHC I","antibodies","B-cell receptors"],"question_id":"fs-id1167660619092","question_text":"Which type of antigen-presenting molecule is found on all nucleated cells?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"There are two classes of MHC molecules involved in adaptive immunity , MHC I and MHC II ( Figure 18.11 ) . MHC I molecules are found on all nucleated cells ; they present normal self-antigens as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity . <hl> In contrast , MHC II molecules are only found on macrophages , dendritic cells , and B cells ; they present abnormal or nonself pathogen antigens for the initial activation of T cells . <hl>","hl_sentences":"In contrast , MHC II molecules are only found on macrophages , dendritic cells , and B cells ; they present abnormal or nonself pathogen antigens for the initial activation of T cells .","question":{"cloze_format":"The antigen-presenting molecule ___ is found only on macrophages, dendritic cells, and B cells.","normal_format":"Which type of antigen-presenting molecule is found only on macrophages, dendritic cells, and B cells?","question_choices":["MHC I","MHC II","T-cell receptors","B-cell receptors"],"question_id":"fs-id1167662747086","question_text":"Which type of antigen-presenting molecule is found only on macrophages, dendritic cells, and B cells?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> The mechanism of T cell activation by superantigens involves their simultaneous binding to MHC II molecules of APCs and the variable region of the TCR β chain . <hl> This binding occurs outside of the antigen-binding cleft of MHC II , so the superantigen will bridge together and activate MHC II and TCR without specific foreign epitope recognition ( Figure 18.19 ) . <hl> The result is an excessive , uncontrolled release of cytokines , often called a cytokine storm , which stimulates an excessive inflammatory response . <hl> This can lead to a dangerous decrease in blood pressure , shock , multi-organ failure , and potentially , death .","hl_sentences":"The mechanism of T cell activation by superantigens involves their simultaneous binding to MHC II molecules of APCs and the variable region of the TCR β chain . The result is an excessive , uncontrolled release of cytokines , often called a cytokine storm , which stimulates an excessive inflammatory response .","question":{"cloze_format":"A superantigen is ___.","normal_format":"What is a superantigen?","question_choices":["a protein that is highly efficient at stimulating a single type of productive and specific T cell response","a protein produced by antigen-presenting cells to enhance their presentation capabilities","a protein produced by T cells as a way of increasing the antigen activation they receive from antigen-presenting cells","a protein that activates T cells in a nonspecific and uncontrolled manner"],"question_id":"fs-id11676603890420","question_text":"What is a superantigen?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"<hl> Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II . <hl> <hl> The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft . <hl> <hl> The second step involves the interaction of CD4 on the helper T cell with a region of the MHC II molecule separate from the antigen-binding cleft . <hl> This second interaction anchors the MHC II-TCR complex and ensures that the helper T cell is recognizing both the foreign ( “ nonself ” ) epitope and “ self ” antigen of the APC ; both recognitions are required for activation of the cell . In the third step , the APC and T cell secrete cytokines that activate the helper T cell . The activated helper T cell then proliferates , dividing by mitosis to produce clonal naïve helper T cells that differentiate into subtypes with different functions ( Figure 18.17 ) .","hl_sentences":"Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II . The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft . The second step involves the interaction of CD4 on the helper T cell with a region of the MHC II molecule separate from the antigen-binding cleft .","question":{"cloze_format":"The TCR of a helper T cell binds ___ .","normal_format":"To what does the TCR of a helper T cell bind?","question_choices":["antigens presented with MHC I molecules","antigens presented with MHC II molecules","free antigen in a soluble form","haptens only"],"question_id":"fs-id1167662849721","question_text":"To what does the TCR of a helper T cell bind?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II . <hl> <hl> The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft . <hl> <hl> The second step involves the interaction of CD4 on the helper T cell with a region of the MHC II molecule separate from the antigen-binding cleft . <hl> This second interaction anchors the MHC II-TCR complex and ensures that the helper T cell is recognizing both the foreign ( “ nonself ” ) epitope and “ self ” antigen of the APC ; both recognitions are required for activation of the cell . In the third step , the APC and T cell secrete cytokines that activate the helper T cell . The activated helper T cell then proliferates , dividing by mitosis to produce clonal naïve helper T cells that differentiate into subtypes with different functions ( Figure 18.17 ) .","hl_sentences":"Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II . The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft . The second step involves the interaction of CD4 on the helper T cell with a region of the MHC II molecule separate from the antigen-binding cleft .","question":{"cloze_format":"Cytotoxic T cells will bind with their TCR to ___ .","normal_format":"Cytotoxic T cells will bind with their TCR to which of the following?","question_choices":["antigens presented with MHC I molecules","antigens presented with MHC II molecules","free antigen in a soluble form","haptens only"],"question_id":"fs-id1167662684321","question_text":"Cytotoxic T cells will bind with their TCR to which of the following?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> All T cells produce cluster of differentiation ( CD ) molecules , cell surface glycoproteins that can be used to identify and distinguish between the various types of white blood cells . <hl> Although T cells can produce a variety of CD molecules , CD4 and CD8 are the two most important used for differentiation of the classes . Helper T cells and regulatory T cells are characterized by the expression of CD4 on their surface , whereas cytotoxic T cells are characterized by the expression of CD8 .","hl_sentences":"All T cells produce cluster of differentiation ( CD ) molecules , cell surface glycoproteins that can be used to identify and distinguish between the various types of white blood cells .","question":{"cloze_format":"A ________ molecule is a glycoprotein used to identify and distinguish white blood cells.","normal_format":"Which molecule is a glycoprotein used to identify and distinguish white blood cells?\n","question_choices":["T-cell receptor","B-cell receptor","MHC I","cluster of differentiation"],"question_id":"fs-id1167660257688","question_text":"A ________ molecule is a glycoprotein used to identify and distinguish white blood cells."},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"<hl> T H 2 cells play an important role in orchestrating the humoral immune response through their secretion of cytokines that activate B cells and direct B cell differentiation and antibody production . <hl> Various cytokines produced by T H 2 cells orchestrate antibody class switching , which allows B cells to switch between the production of IgM , IgG , IgA , and IgE as needed to carry out specific antibody functions and to provide pathogen-specific humoral immune responses .","hl_sentences":"T H 2 cells play an important role in orchestrating the humoral immune response through their secretion of cytokines that activate B cells and direct B cell differentiation and antibody production .","question":{"cloze_format":"The T helper cell subset involved in antibody production is ___.","normal_format":"Name the T helper cell subset involved in antibody production.","question_choices":["TH1","TH2","TH17","CTL"],"question_id":"fs-id1167662795181","question_text":"Name the T helper cell subset involved in antibody production."},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"Activation of B cells occurs through different mechanisms depending on the molecular class of the antigen . Activation of a B cell by a protein antigen requires the B cell to function as an APC , presenting the protein epitopes with MHC II to helper T cells . <hl> Because of their dependence on T cells for activation of B cells , protein antigens are classified as T-dependent antigens . <hl> In contrast , polysaccharides , lipopolysaccharides , and other nonprotein antigens are considered T-independent antigens because they can activate B cells without antigen processing and presentation to T cells .","hl_sentences":"Because of their dependence on T cells for activation of B cells , protein antigens are classified as T-dependent antigens .","question":{"cloze_format":"___ would be a T-dependent antigen.","normal_format":"Which of the following would be a T-dependent antigen?","question_choices":["lipopolysaccharide","glycolipid","protein","carbohydrate"],"question_id":"fs-id1167663529755","question_text":"Which of the following would be a T-dependent antigen?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"Like T cells , B cells possess antigen-specific receptors with diverse specificities . Although they rely on T cells for optimum function , B cells can be activated without help from T cells . <hl> B-cell receptors ( BCRs ) for naïve mature B cells are membrane-bound monomeric forms of IgD and IgM . <hl> They have two identical heavy chains and two identical light chains connected by disulfide bonds into a basic “ Y ” shape ( Figure 18.20 ) . The trunk of the Y-shaped molecule , the constant region of the two heavy chains , spans the B cell membrane . The two antigen-binding sites exposed to the exterior of the B cell are involved in the binding of specific pathogen epitopes to initiate the activation process . It is estimated that each naïve mature B cell has upwards of 100,000 BCRs on its membrane , and each of these BCRs has an identical epitope-binding specificity .","hl_sentences":"B-cell receptors ( BCRs ) for naïve mature B cells are membrane-bound monomeric forms of IgD and IgM .","question":{"cloze_format":"___ would be a BCR.","normal_format":"Which of the following would be a BCR?","question_choices":["CD4","MHC II","MHC I","IgD"],"question_id":"fs-id1167661419638","question_text":"Which of the following would be a BCR?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"T cell-dependent activation of B cells plays an important role in both the primary and secondary responses associated with adaptive immunity . With the first exposure to a protein antigen , a T cell-dependent primary antibody response occurs . The initial stage of the primary response is a lag period , or latent period , of approximately 10 days , during which no antibody can be detected in serum . <hl> This lag period is the time required for all of the steps of the primary response , including naïve mature B cell binding of antigen with BCRs , antigen processing and presentation , helper T cell activation , B cell activation , and clonal proliferation . <hl> The end of the lag period is characterized by a rise in IgM levels in the serum , as T H 2 cells stimulate B cell differentiation into plasma cells . IgM levels reach their peak around 14 days after primary antigen exposure ; at about this same time , T H 2 stimulates antibody class switching , and IgM levels in serum begin to decline . Meanwhile , levels of IgG increase until they reach a peak about three weeks into the primary response ( Figure 18.23 ) .","hl_sentences":"This lag period is the time required for all of the steps of the primary response , including naïve mature B cell binding of antigen with BCRs , antigen processing and presentation , helper T cell activation , B cell activation , and clonal proliferation .","question":{"cloze_format":"(The) ___ does not occur during the lag period of the primary antibody response.","normal_format":"Which of the following does not occur during the lag period of the primary antibody response?","question_choices":["activation of helper T cells","class switching to IgG","presentation of antigen with MHC II","binding of antigen to BCRs"],"question_id":"fs-id1167661409386","question_text":"Which of the following does not occur during the lag period of the primary antibody response?"},"references_are_paraphrase":0}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"Once a B cell is activated , it undergoes clonal proliferation and daughter cells differentiate into plasma cells . <hl> Plasma cells are antibody factories that secrete large quantities of antibodies . <hl> After differentiation , the surface BCRs disappear and the plasma cell secretes pentameric IgM molecules that have the same antigen specificity as the BCRs ( Figure 18.21 ) .\",\n \"hl_sentences\": \"Plasma cells are antibody factories that secrete large quantities of antibodies .\",\n \"question\": {\n \"cloze_format\": \"Antibodies are produced by ________.\",\n \"normal_format\": \"What produced Antibodies? \",\n \"question_choices\": [\n \"plasma cells\",\n \"T cells\",\n \"bone marrow\",\n \"Macrophages\"\n ],\n \"question_id\": \"fs-id1167660323124\",\n \"question_text\": \"Antibodies are produced by ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"As explained in Overview of Specific Adaptive Immunity , the antibodies involved in humoral immunity often bind pathogens and toxins before they can attach to and invade host cells . Thus , humoral immunity is primarily concerned with fighting pathogens in extracellular spaces . However , pathogens that have already gained entry to host cells are largely protected from the humoral antibody-mediated defenses . <hl> Cellular immunity , on the other hand , targets and eliminates intracellular pathogens through the actions of T lymphocytes , or T cells ( Figure 18.13 ) . <hl> T cells also play a more central role in orchestrating the overall adaptive immune response ( humoral as well as cellular ) along with the cellular defenses of innate immunity .\",\n \"hl_sentences\": \"Cellular immunity , on the other hand , targets and eliminates intracellular pathogens through the actions of T lymphocytes , or T cells ( Figure 18.13 ) .\",\n \"question\": {\n \"cloze_format\": \"Cellular adaptive immunity is carried out by ________.\",\n \"normal_format\": \"What is cellular adaptive immunity carried out by?\",\n \"question_choices\": [\n \"B cells\",\n \"T cells\",\n \"bone marrow\",\n \"neutrophils\"\n ],\n \"question_id\": \"fs-id1167662771044\",\n \"question_text\": \"Cellular adaptive immunity is carried out by ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"One reason the three-dimensional complexity of antigens is so important is that antibodies and T cells do not recognize and interact with an entire antigen but with smaller exposed regions on the surface of antigens called epitopes . <hl> A single antigen may possess several different epitopes ( Figure 18.3 ) , and different antibodies may bind to different epitopes on the same antigen ( Figure 18.4 ) . <hl> For example , the bacterial flagellum is a large , complex protein structure that can possess hundreds or even thousands of epitopes with unique three-dimensional structures . Moreover , flagella from different bacterial species ( or even strains of the same species ) contain unique epitopes that can only be bound by specific antibodies .\",\n \"hl_sentences\": \"A single antigen may possess several different epitopes ( Figure 18.3 ) , and different antibodies may bind to different epitopes on the same antigen ( Figure 18.4 ) .\",\n \"question\": {\n \"cloze_format\": \"A single antigen molecule may be composed of many individual ________.\",\n \"normal_format\": \"An single antigen molecule may be dcomposed into what?\",\n \"question_choices\": [\n \"T-cell receptors\",\n \"B-cell receptors\",\n \"MHC II\",\n \"epitopes\"\n ],\n \"question_id\": \"fs-id1167662665461\",\n \"question_text\": \"A single antigen molecule may be composed of many individual ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"Antigens may belong to any number of molecular classes , including carbohydrates , lipids , nucleic acids , proteins , and combinations of these molecules . Antigens of different classes vary in their ability to stimulate adaptive immune defenses as well as in the type of response they stimulate ( humoral or cellular ) . <hl> The structural complexity of an antigenic molecule is an important factor in its antigenic potential . <hl> <hl> In general , more complex molecules are more effective as antigens . <hl> <hl> For example , the three-dimensional complex structure of proteins make them the most effective and potent antigens , capable of stimulating both humoral and cellular immunity . <hl> In comparison , carbohydrates are less complex in structure and therefore less effective as antigens ; they can only stimulate humoral immune defenses . Lipids and nucleic acids are the least antigenic molecules , and in some cases may only become antigenic when combined with proteins or carbohydrates to form glycolipids , lipoproteins , or nucleoproteins .\",\n \"hl_sentences\": \"The structural complexity of an antigenic molecule is an important factor in its antigenic potential . In general , more complex molecules are more effective as antigens . For example , the three-dimensional complex structure of proteins make them the most effective and potent antigens , capable of stimulating both humoral and cellular immunity .\",\n \"question\": {\n \"cloze_format\": \"The class of molecules that is the most antigenic are ___.\",\n \"normal_format\": \"Which class of molecules is the most antigenic?\",\n \"question_choices\": [\n \"polysaccharides\",\n \"lipids\",\n \"proteins\",\n \"carbohydrates\"\n ],\n \"question_id\": \"fs-id1167660276851\",\n \"question_text\": \"Which class of molecules is the most antigenic?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> MHC I molecules , found on all normal , healthy , nucleated cells , signal to the immune system that the cell is a normal “ self ” cell . <hl> In a healthy cell , proteins normally found in the cytoplasm are degraded by proteasomes ( enzyme complexes responsible for degradation and processing of proteins ) and processed into self-antigen epitopes ; these self-antigen epitopes bind within the MHC I antigen-binding cleft and are then presented on the cell surface . Immune cells , such as NK cells , recognize these self-antigens and do not target the cell for destruction . <hl> However , if a cell becomes infected with an intracellular pathogen ( e . g . , a virus ) , protein antigens specific to the pathogen are processed in the proteasomes and bind with MHC I molecules for presentation on the cell surface . <hl> <hl> This presentation of pathogen-specific antigens with MHC I signals that the infected cell must be targeted for destruction along with the pathogen . <hl>\",\n \"hl_sentences\": \"MHC I molecules , found on all normal , healthy , nucleated cells , signal to the immune system that the cell is a normal “ self ” cell . However , if a cell becomes infected with an intracellular pathogen ( e . g . , a virus ) , protein antigens specific to the pathogen are processed in the proteasomes and bind with MHC I molecules for presentation on the cell surface . This presentation of pathogen-specific antigens with MHC I signals that the infected cell must be targeted for destruction along with the pathogen .\",\n \"question\": {\n \"cloze_format\": \"MHC I molecules present ___.\",\n \"normal_format\": \"What do MHC I molecules present?\",\n \"question_choices\": [\n \"processed foreign antigens from proteasomes.\",\n \"processed self-antigens from phagolysosome.\",\n \"antibodies.\",\n \"T cell antigens.\"\n ],\n \"question_id\": \"fs-id1167662450417\",\n \"question_text\": \"MHC I molecules present\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"After a dendritic cell recognizes and attaches to a pathogen cell , the pathogen is internalized by phagocytosis and is initially contained within a phagosome . <hl> Lysosomes containing antimicrobial enzymes and chemicals fuse with the phagosome to create a phagolysosome , where degradation of the pathogen for antigen processing begins . <hl> <hl> Proteases ( protein-degrading ) are especially important in antigen processing because only protein antigen epitopes are presented to T cells by MHC II ( Figure 18.12 ) . <hl>\",\n \"hl_sentences\": \"Lysosomes containing antimicrobial enzymes and chemicals fuse with the phagosome to create a phagolysosome , where degradation of the pathogen for antigen processing begins . Proteases ( protein-degrading ) are especially important in antigen processing because only protein antigen epitopes are presented to T cells by MHC II ( Figure 18.12 ) .\",\n \"question\": {\n \"cloze_format\": \"MHC II molecules present ___.\",\n \"normal_format\": \"What do MHC II molecules present?\",\n \"question_choices\": [\n \"processed self-antigens from proteasomes.\",\n \"processed foreign antigens from phagolysosomes.\",\n \"antibodies.\",\n \"T cell receptors.\"\n ],\n \"question_id\": \"fs-id1167660364789\",\n \"question_text\": \"MHC II molecules present\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"There are two classes of MHC molecules involved in adaptive immunity , MHC I and MHC II ( Figure 18.11 ) . <hl> MHC I molecules are found on all nucleated cells ; they present normal self-antigens as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity . <hl> In contrast , MHC II molecules are only found on macrophages , dendritic cells , and B cells ; they present abnormal or nonself pathogen antigens for the initial activation of T cells .\",\n \"hl_sentences\": \"MHC I molecules are found on all nucleated cells ; they present normal self-antigens as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity .\",\n \"question\": {\n \"cloze_format\": \"___ is/are a type of antigen-presenting molecule that is found on all nucleated cells.\",\n \"normal_format\": \"Which type of antigen-presenting molecule is found on all nucleated cells?\",\n \"question_choices\": [\n \"MHC II\",\n \"MHC I\",\n \"antibodies\",\n \"B-cell receptors\"\n ],\n \"question_id\": \"fs-id1167660619092\",\n \"question_text\": \"Which type of antigen-presenting molecule is found on all nucleated cells?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"There are two classes of MHC molecules involved in adaptive immunity , MHC I and MHC II ( Figure 18.11 ) . MHC I molecules are found on all nucleated cells ; they present normal self-antigens as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity . <hl> In contrast , MHC II molecules are only found on macrophages , dendritic cells , and B cells ; they present abnormal or nonself pathogen antigens for the initial activation of T cells . <hl>\",\n \"hl_sentences\": \"In contrast , MHC II molecules are only found on macrophages , dendritic cells , and B cells ; they present abnormal or nonself pathogen antigens for the initial activation of T cells .\",\n \"question\": {\n \"cloze_format\": \"The antigen-presenting molecule ___ is found only on macrophages, dendritic cells, and B cells.\",\n \"normal_format\": \"Which type of antigen-presenting molecule is found only on macrophages, dendritic cells, and B cells?\",\n \"question_choices\": [\n \"MHC I\",\n \"MHC II\",\n \"T-cell receptors\",\n \"B-cell receptors\"\n ],\n \"question_id\": \"fs-id1167662747086\",\n \"question_text\": \"Which type of antigen-presenting molecule is found only on macrophages, dendritic cells, and B cells?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The mechanism of T cell activation by superantigens involves their simultaneous binding to MHC II molecules of APCs and the variable region of the TCR β chain . <hl> This binding occurs outside of the antigen-binding cleft of MHC II , so the superantigen will bridge together and activate MHC II and TCR without specific foreign epitope recognition ( Figure 18.19 ) . <hl> The result is an excessive , uncontrolled release of cytokines , often called a cytokine storm , which stimulates an excessive inflammatory response . <hl> This can lead to a dangerous decrease in blood pressure , shock , multi-organ failure , and potentially , death .\",\n \"hl_sentences\": \"The mechanism of T cell activation by superantigens involves their simultaneous binding to MHC II molecules of APCs and the variable region of the TCR β chain . The result is an excessive , uncontrolled release of cytokines , often called a cytokine storm , which stimulates an excessive inflammatory response .\",\n \"question\": {\n \"cloze_format\": \"A superantigen is ___.\",\n \"normal_format\": \"What is a superantigen?\",\n \"question_choices\": [\n \"a protein that is highly efficient at stimulating a single type of productive and specific T cell response\",\n \"a protein produced by antigen-presenting cells to enhance their presentation capabilities\",\n \"a protein produced by T cells as a way of increasing the antigen activation they receive from antigen-presenting cells\",\n \"a protein that activates T cells in a nonspecific and uncontrolled manner\"\n ],\n \"question_id\": \"fs-id11676603890420\",\n \"question_text\": \"What is a superantigen?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II . <hl> <hl> The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft . <hl> <hl> The second step involves the interaction of CD4 on the helper T cell with a region of the MHC II molecule separate from the antigen-binding cleft . <hl> This second interaction anchors the MHC II-TCR complex and ensures that the helper T cell is recognizing both the foreign ( “ nonself ” ) epitope and “ self ” antigen of the APC ; both recognitions are required for activation of the cell . In the third step , the APC and T cell secrete cytokines that activate the helper T cell . The activated helper T cell then proliferates , dividing by mitosis to produce clonal naïve helper T cells that differentiate into subtypes with different functions ( Figure 18.17 ) .\",\n \"hl_sentences\": \"Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II . The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft . The second step involves the interaction of CD4 on the helper T cell with a region of the MHC II molecule separate from the antigen-binding cleft .\",\n \"question\": {\n \"cloze_format\": \"The TCR of a helper T cell binds ___ .\",\n \"normal_format\": \"To what does the TCR of a helper T cell bind?\",\n \"question_choices\": [\n \"antigens presented with MHC I molecules\",\n \"antigens presented with MHC II molecules\",\n \"free antigen in a soluble form\",\n \"haptens only\"\n ],\n \"question_id\": \"fs-id1167662849721\",\n \"question_text\": \"To what does the TCR of a helper T cell bind?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II . <hl> <hl> The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft . <hl> <hl> The second step involves the interaction of CD4 on the helper T cell with a region of the MHC II molecule separate from the antigen-binding cleft . <hl> This second interaction anchors the MHC II-TCR complex and ensures that the helper T cell is recognizing both the foreign ( “ nonself ” ) epitope and “ self ” antigen of the APC ; both recognitions are required for activation of the cell . In the third step , the APC and T cell secrete cytokines that activate the helper T cell . The activated helper T cell then proliferates , dividing by mitosis to produce clonal naïve helper T cells that differentiate into subtypes with different functions ( Figure 18.17 ) .\",\n \"hl_sentences\": \"Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II . The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft . The second step involves the interaction of CD4 on the helper T cell with a region of the MHC II molecule separate from the antigen-binding cleft .\",\n \"question\": {\n \"cloze_format\": \"Cytotoxic T cells will bind with their TCR to ___ .\",\n \"normal_format\": \"Cytotoxic T cells will bind with their TCR to which of the following?\",\n \"question_choices\": [\n \"antigens presented with MHC I molecules\",\n \"antigens presented with MHC II molecules\",\n \"free antigen in a soluble form\",\n \"haptens only\"\n ],\n \"question_id\": \"fs-id1167662684321\",\n \"question_text\": \"Cytotoxic T cells will bind with their TCR to which of the following?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> All T cells produce cluster of differentiation ( CD ) molecules , cell surface glycoproteins that can be used to identify and distinguish between the various types of white blood cells . <hl> Although T cells can produce a variety of CD molecules , CD4 and CD8 are the two most important used for differentiation of the classes . Helper T cells and regulatory T cells are characterized by the expression of CD4 on their surface , whereas cytotoxic T cells are characterized by the expression of CD8 .\",\n \"hl_sentences\": \"All T cells produce cluster of differentiation ( CD ) molecules , cell surface glycoproteins that can be used to identify and distinguish between the various types of white blood cells .\",\n \"question\": {\n \"cloze_format\": \"A ________ molecule is a glycoprotein used to identify and distinguish white blood cells.\",\n \"normal_format\": \"Which molecule is a glycoprotein used to identify and distinguish white blood cells?\\n\",\n \"question_choices\": [\n \"T-cell receptor\",\n \"B-cell receptor\",\n \"MHC I\",\n \"cluster of differentiation\"\n ],\n \"question_id\": \"fs-id1167660257688\",\n \"question_text\": \"A ________ molecule is a glycoprotein used to identify and distinguish white blood cells.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> T H 2 cells play an important role in orchestrating the humoral immune response through their secretion of cytokines that activate B cells and direct B cell differentiation and antibody production . <hl> Various cytokines produced by T H 2 cells orchestrate antibody class switching , which allows B cells to switch between the production of IgM , IgG , IgA , and IgE as needed to carry out specific antibody functions and to provide pathogen-specific humoral immune responses .\",\n \"hl_sentences\": \"T H 2 cells play an important role in orchestrating the humoral immune response through their secretion of cytokines that activate B cells and direct B cell differentiation and antibody production .\",\n \"question\": {\n \"cloze_format\": \"The T helper cell subset involved in antibody production is ___.\",\n \"normal_format\": \"Name the T helper cell subset involved in antibody production.\",\n \"question_choices\": [\n \"TH1\",\n \"TH2\",\n \"TH17\",\n \"CTL\"\n ],\n \"question_id\": \"fs-id1167662795181\",\n \"question_text\": \"Name the T helper cell subset involved in antibody production.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"Activation of B cells occurs through different mechanisms depending on the molecular class of the antigen . Activation of a B cell by a protein antigen requires the B cell to function as an APC , presenting the protein epitopes with MHC II to helper T cells . <hl> Because of their dependence on T cells for activation of B cells , protein antigens are classified as T-dependent antigens . <hl> In contrast , polysaccharides , lipopolysaccharides , and other nonprotein antigens are considered T-independent antigens because they can activate B cells without antigen processing and presentation to T cells .\",\n \"hl_sentences\": \"Because of their dependence on T cells for activation of B cells , protein antigens are classified as T-dependent antigens .\",\n \"question\": {\n \"cloze_format\": \"___ would be a T-dependent antigen.\",\n \"normal_format\": \"Which of the following would be a T-dependent antigen?\",\n \"question_choices\": [\n \"lipopolysaccharide\",\n \"glycolipid\",\n \"protein\",\n \"carbohydrate\"\n ],\n \"question_id\": \"fs-id1167663529755\",\n \"question_text\": \"Which of the following would be a T-dependent antigen?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"Like T cells , B cells possess antigen-specific receptors with diverse specificities . Although they rely on T cells for optimum function , B cells can be activated without help from T cells . <hl> B-cell receptors ( BCRs ) for naïve mature B cells are membrane-bound monomeric forms of IgD and IgM . <hl> They have two identical heavy chains and two identical light chains connected by disulfide bonds into a basic “ Y ” shape ( Figure 18.20 ) . The trunk of the Y-shaped molecule , the constant region of the two heavy chains , spans the B cell membrane . The two antigen-binding sites exposed to the exterior of the B cell are involved in the binding of specific pathogen epitopes to initiate the activation process . It is estimated that each naïve mature B cell has upwards of 100,000 BCRs on its membrane , and each of these BCRs has an identical epitope-binding specificity .\",\n \"hl_sentences\": \"B-cell receptors ( BCRs ) for naïve mature B cells are membrane-bound monomeric forms of IgD and IgM .\",\n \"question\": {\n \"cloze_format\": \"___ would be a BCR.\",\n \"normal_format\": \"Which of the following would be a BCR?\",\n \"question_choices\": [\n \"CD4\",\n \"MHC II\",\n \"MHC I\",\n \"IgD\"\n ],\n \"question_id\": \"fs-id1167661419638\",\n \"question_text\": \"Which of the following would be a BCR?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"T cell-dependent activation of B cells plays an important role in both the primary and secondary responses associated with adaptive immunity . With the first exposure to a protein antigen , a T cell-dependent primary antibody response occurs . The initial stage of the primary response is a lag period , or latent period , of approximately 10 days , during which no antibody can be detected in serum . <hl> This lag period is the time required for all of the steps of the primary response , including naïve mature B cell binding of antigen with BCRs , antigen processing and presentation , helper T cell activation , B cell activation , and clonal proliferation . <hl> The end of the lag period is characterized by a rise in IgM levels in the serum , as T H 2 cells stimulate B cell differentiation into plasma cells . IgM levels reach their peak around 14 days after primary antigen exposure ; at about this same time , T H 2 stimulates antibody class switching , and IgM levels in serum begin to decline . Meanwhile , levels of IgG increase until they reach a peak about three weeks into the primary response ( Figure 18.23 ) .\",\n \"hl_sentences\": \"This lag period is the time required for all of the steps of the primary response , including naïve mature B cell binding of antigen with BCRs , antigen processing and presentation , helper T cell activation , B cell activation , and clonal proliferation .\",\n \"question\": {\n \"cloze_format\": \"(The) ___ does not occur during the lag period of the primary antibody response.\",\n \"normal_format\": \"Which of the following does not occur during the lag period of the primary antibody response?\",\n \"question_choices\": [\n \"activation of helper T cells\",\n \"class switching to IgG\",\n \"presentation of antigen with MHC II\",\n \"binding of antigen to BCRs\"\n ],\n \"question_id\": \"fs-id1167661409386\",\n \"question_text\": \"Which of the following does not occur during the lag period of the primary antibody response?\"\n },\n \"references_are_paraphrase\": 0\n }\n]","isConversational":false},"chapter":{"kind":"number","value":18,"string":"18"},"chapter_text":{"kind":"string","value":" 18.1 Overview of Specific Adaptive Immunity \n\n Learning Objectives \n\n Define memory, primary response, secondary response, and specificity \n\n Distinguish between humoral and cellular immunity \n\n Differentiate between antigens, epitopes, and haptens \n\n Describe the structure and function of antibodies and distinguish between the different classes of antibodies \n\n Clinical Focus Part 1 Olivia, a one-year old infant, is brought to the emergency room by her parents, who report her symptoms: excessive crying, irritability, sensitivity to light, unusual lethargy, and vomiting. A physician feels swollen lymph nodes in Olivia’s throat and armpits. In addition, the area of the abdomen over the spleen is swollen and tender. \n\n What do these symptoms suggest? \n\n What tests might be ordered to try to diagnose the problem? \n\n Jump to the next Clinical Focus box. \n\n Adaptive immunity is defined by two important characteristics: specificity and memory . Specificity refers to the adaptive immune system’s ability to target specific pathogens, and memory refers to its ability to quickly respond to pathogens to which it has previously been exposed. For example, when an individual recovers from chickenpox, the body develops a memory of the infection that will specifically protect it from the causative agent, the varicella-zoster virus, if it is exposed to the virus again later. \n\n Specificity and memory are achieved by essentially programming certain cells involved in the immune response to respond rapidly to subsequent exposures of the pathogen. This programming occurs as a result of the first exposure to a pathogen or vaccine, which triggers a primary response . Subsequent exposures result in a secondary response that is faster and stronger as a result of the body’s memory of the first exposure ( Figure 18.2 ). This secondary response, however, is specific to the pathogen in question. For example, exposure to one virus (e.g., varicella-zoster virus) will not provide protection against other viral diseases (e.g., measles, mumps, or polio). \n\n Adaptive specific immunity involves the actions of two distinct cell types: B lymphocytes ( B cells ) and T lymphocytes ( T cells ). Although B cells and T cells arise from a common hematopoietic stem cell differentiation pathway (see Figure 17.12 ), their sites of maturation and their roles in adaptive immunity are very different. \n\n B cells mature in the bone marrow and are responsible for the production of glycoproteins called antibodies , or immunoglobulins . Antibodies are involved in the body’s defense against pathogens and toxins in the extracellular environment. Mechanisms of adaptive specific immunity that involve B cells and antibody production are referred to as humoral immunity . The maturation of T cells occurs in the thymus . T cells function as the central orchestrator of both innate and adaptive immune responses. They are also responsible for destruction of cells infected with intracellular pathogens. The targeting and destruction of intracellular pathogens by T cells is called cell-mediated immunity, or cellular immunity . \n\n Check Your Understanding \n\n List the two defining characteristics of adaptive immunity. \n\n Explain the difference between a primary and secondary immune response. \n\n How do humoral and cellular immunity differ? \n\n Antigens \n\n Activation of the adaptive immune defenses is triggered by pathogen-specific molecular structures called antigens . Antigens are similar to the pathogen-associated molecular patterns (PAMPs) discussed in Pathogen Recognition and Phagocytosis ; however, whereas PAMPs are molecular structures found on numerous pathogens, antigens are unique to a specific pathogen. The antigens that stimulate adaptive immunity to chickenpox, for example, are unique to the varicella-zoster virus but significantly different from the antigens associated with other viral pathogens. \n\n The term antigen was initially used to describe molecules that stimulate the production of antibodies; in fact, the term comes from a combination of the words anti body and gen erator, and a molecule that stimulates antibody production is said to be antigenic . However, the role of antigens is not limited to humoral immunity and the production of antibodies; antigens also play an essential role in stimulating cellular immunity, and for this reason antigens are sometimes more accurately referred to as immunogens . In this text, however, we will typically refer to them as antigens. \n\n Pathogens possess a variety of structures that may contain antigens. For example, antigens from bacterial cells may be associated with their capsules, cell walls, fimbriae, flagella, or pili. Bacterial antigens may also be associated with extracellular toxins and enzymes that they secrete. Viruses possess a variety of antigens associated with their capsids, envelopes, and the spike structures they use for attachment to cells. \n\n Antigens may belong to any number of molecular classes, including carbohydrates, lipids, nucleic acids, proteins, and combinations of these molecules. Antigens of different classes vary in their ability to stimulate adaptive immune defenses as well as in the type of response they stimulate (humoral or cellular). The structural complexity of an antigenic molecule is an important factor in its antigenic potential. In general, more complex molecules are more effective as antigens. For example, the three-dimensional complex structure of proteins make them the most effective and potent antigens, capable of stimulating both humoral and cellular immunity. In comparison, carbohydrates are less complex in structure and therefore less effective as antigens; they can only stimulate humoral immune defenses. Lipids and nucleic acids are the least antigenic molecules, and in some cases may only become antigenic when combined with proteins or carbohydrates to form glycolipids, lipoproteins, or nucleoproteins. \n\n One reason the three-dimensional complexity of antigens is so important is that antibodies and T cells do not recognize and interact with an entire antigen but with smaller exposed regions on the surface of antigens called epitopes . A single antigen may possess several different epitopes ( Figure 18.3 ), and different antibodies may bind to different epitopes on the same antigen ( Figure 18.4 ). For example, the bacterial flagellum is a large, complex protein structure that can possess hundreds or even thousands of epitopes with unique three-dimensional structures. Moreover, flagella from different bacterial species (or even strains of the same species) contain unique epitopes that can only be bound by specific antibodies. \n\n An antigen’s size is another important factor in its antigenic potential. Whereas large antigenic structures like flagella possess multiple epitopes, some molecules are too small to be antigenic by themselves. Such molecules, called haptens , are essentially free epitopes that are not part of the complex three-dimensional structure of a larger antigen. For a hapten to become antigenic, it must first attach to a larger carrier molecule (usually a protein) to produce a conjugate antigen. The hapten-specific antibodies produced in response to the conjugate antigen are then able to interact with unconjugated free hapten molecules. Haptens are not known to be associated with any specific pathogens, but they are responsible for some allergic responses. For example, the hapten urushiol , a molecule found in the oil of plants that cause poison ivy , causes an immune response that can result in a severe rash (called contact dermatitis). Similarly, the hapten penicillin can cause allergic reactions to drugs in the penicillin class. \n\n Check Your Understanding \n\n What is the difference between an antigen and an epitope? \n\n What factors affect an antigen’s antigenic potential? \n\n Why are haptens typically not antigenic, and how do they become antigenic? \n\n Antibodies \n\n Antibodies (also called immunoglobulins) are glycoproteins that are present in both the blood and tissue fluids. The basic structure of an antibody monomer consists of four protein chains held together by disulfide bonds ( Figure 18.5 ). A disulfide bond is a covalent bond between the sulfhydryl R groups found on two cysteine amino acids. The two largest chains are identical to each other and are called the heavy chains . The two smaller chains are also identical to each other and are called the light chains . Joined together, the heavy and light chains form a basic Y-shaped structure. \n\n The two ‘arms’ of the Y-shaped antibody molecule are known as the Fab region , for “fragment of antigen binding.” The far end of the Fab region is the variable region, which serves as the site of antigen binding . The amino acid sequence in the variable region dictates the three-dimensional structure, and thus the specific three-dimensional epitope to which the Fab region is capable of binding. Although the epitope specificity of the Fab regions is identical for each arm of a single antibody molecule, this region displays a high degree of variability between antibodies with different epitope specificities. Binding to the Fab region is necessary for neutralization of pathogens, agglutination or aggregation of pathogens, and antibody-dependent cell-mediated cytotoxicity. \n\n The constant region of the antibody molecule includes the trunk of the Y and lower portion of each arm of the Y. The trunk of the Y is also called the Fc region , for “fragment of crystallization,” and is the site of complement factor binding and binding to phagocytic cells during antibody-mediated opsonization . \n\n Check Your Understanding \n\n Describe the different functions of the Fab region and the Fc region. \n\n Antibody Classes \n\n The constant region of an antibody molecule determines its class, or isotype . The five classes of antibodies are IgG, IgM, IgA, IgD, and IgE. Each class possesses unique heavy chains designated by Greek letters γ, μ, α, δ, and ε, respectively. Antibody classes also exhibit important differences in abundance in serum, arrangement, body sites of action, functional roles, and size ( Figure 18.6 ). \n\n IgG is a monomer that is by far the most abundant antibody in human blood, accounting for about 80% of total serum antibody. IgG penetrates efficiently into tissue spaces, and is the only antibody class with the ability to cross the placental barrier , providing passive immunity to the developing fetus during pregnancy. IgG is also the most versatile antibody class in terms of its role in the body’s defense against pathogens. \n\n IgM is initially produced in a monomeric membrane-bound form that serves as an antigen-binding receptor on B cells. The secreted form of IgM assembles into a pentamer with five monomers of IgM bound together by a protein structure called the J chain . Although the location of the J chain relative to the Fc regions of the five monomers prevents IgM from performing some of the functions of IgG, the ten available Fab sites associated with a pentameric IgM make it an important antibody in the body’s arsenal of defenses. IgM is the first antibody produced and secreted by B cells during the primary and secondary immune responses, making pathogen-specific IgM a valuable diagnostic marker during active or recent infections. \n\n IgA accounts for about 13% of total serum antibody, and secretory IgA is the most common and abundant antibody class found in the mucus secretions that protect the mucous membranes. IgA can also be found in other secretions such as breast milk , tears , and saliva . Secretory IgA is assembled into a dimeric form with two monomers joined by a protein structure called the secretory component. One of the important functions of secretory IgA is to trap pathogens in mucus so that they can later be eliminated from the body. \n\n Similar to IgM, IgD is a membrane-bound monomer found on the surface of B cells, where it serves as an antigen-binding receptor. However, IgD is not secreted by B cells, and only trace amounts are detected in serum. These trace amounts most likely come from the degradation of old B cells and the release of IgD molecules from their cytoplasmic membranes. \n\n IgE is the least abundant antibody class in serum. Like IgG, it is secreted as a monomer, but its role in adaptive immunity is restricted to anti-parasitic defenses . The Fc region of IgE binds to basophils and mast cells . The Fab region of the bound IgE then interacts with specific antigen epitopes, causing the cells to release potent pro-inflammatory mediators. The inflammatory reaction resulting from the activation of mast cells and basophils aids in the defense against parasites, but this reaction is also central to allergic reactions (see Diseases of the Immune System . \n\n Check Your Understanding \n\n What part of an antibody molecule determines its class? \n\n What class of antibody is involved in protection against parasites? \n\n Describe the difference in structure between IgM and IgG. \n\n Antigen-Antibody Interactions \n\n Different classes of antibody play important roles in the body’s defense against pathogens. These functions include neutralization of pathogens, opsonization for phagocytosis, agglutination, complement activation, and antibody-dependent cell-mediated cytotoxicity. For most of these functions, antibodies also provide an important link between adaptive specific immunity and innate nonspecific immunity. \n\n Neutralization involves the binding of certain antibodies (IgG, IgM, or IgA) to epitopes on the surface of pathogens or toxins, preventing their attachment to cells. For example, Secretory IgA can bind to specific pathogens and block initial attachment to intestinal mucosal cells. Similarly, specific antibodies can bind to certain toxins, blocking them from attaching to target cells and thus neutralizing their toxic effects. Viruses can be neutralized and prevented from infecting a cell by the same mechanism ( Figure 18.7 ). \n\n As described in Chemical Defenses , opsonization is the coating of a pathogen with molecules, such as complement factors, C-reactive protein , and serum amyloid A , to assist in phagocyte binding to facilitate phagocytosis . IgG antibodies also serve as excellent opsonins, binding their Fab sites to specific epitopes on the surface of pathogens. Phagocytic cells such as macrophages , dendritic cells , and neutrophils have receptors on their surfaces that recognize and bind to the Fc portion of the IgG molecules; thus, IgG helps such phagocytes attach to and engulf the pathogens they have bound ( Figure 18.8 ). \n\n Agglutination or aggregation involves the cross-linking of pathogens by antibodies to create large aggregates ( Figure 18.9 ). IgG has two Fab antigen-binding sites , which can bind to two separate pathogen cells, clumping them together. When multiple IgG antibodies are involved, large aggregates can develop; these aggregates are easier for the kidneys and spleen to filter from the blood and easier for phagocytes to ingest for destruction. The pentameric structure of IgM provides ten Fab binding sites per molecule, making it the most efficient antibody for agglutination. \n\n Another important function of antibodies is activation of the complement cascade . As discussed in the previous chapter, the complement system is an important component of the innate defenses, promoting the inflammatory response, recruiting phagocytes to site of infection, enhancing phagocytosis by opsonization, and killing gram-negative bacterial pathogens with the membrane attack complex (MAC) . Complement activation can occur through three different pathways (see Figure 17.9 ), but the most efficient is the classical pathway , which requires the initial binding of IgG or IgM antibodies to the surface of a pathogen cell, allowing for recruitment and activation of the C1 complex . \n\n Yet another important function of antibodies is antibody-dependent cell-mediated cytotoxicity (ADCC) , which enhances killing of pathogens that are too large to be phagocytosed. This process is best characterized for natural killer cells ( NK cells ), as shown in Figure 18.10 , but it can also involve macrophages and eosinophils . ADCC occurs when the Fab region of an IgG antibody binds to a large pathogen; Fc receptors on effector cells (e.g., NK cells) then bind to the Fc region of the antibody, bringing them into close proximity with the target pathogen. The effector cell then secretes powerful cytotoxins (e.g., perforin and granzymes ) that kill the pathogen. \n\n Check Your Understanding \n\n Where is IgA normally found? \n\n Which class of antibody crosses the placenta, providing protection to the fetus? \n\n Compare the mechanisms of opsonization and antibody-dependent cell-mediated cytotoxicity. \n 18.2 Major Histocompatibility Complexes and Antigen-Presenting Cells \n\n Learning Objectives \n\n Identify cells that express MHC I and/or MHC II molecules and describe the structures and cellular location of MHC I and MHC II molecules \n\n Identify the cells that are antigen-presenting cells \n\n Describe the process of antigen processing and presentation with MHC I and MHC II \n\n As discussed in Cellular Defenses , major histocompatibility complex (MHC) molecules are expressed on the surface of healthy cells, identifying them as normal and “self” to natural killer (NK) cells . MHC molecules also play an important role in the presentation of foreign antigens, which is a critical step in the activation of T cells and thus an important mechanism of the adaptive immune system. \n\n Major Histocompatibility Complex Molecules \n\n The major histocompatibility complex ( MHC ) is a collection of genes coding for MHC molecules found on the surface of all nucleated cells of the body. In humans, the MHC genes are also referred to as human leukocyte antigen (HLA) genes . Mature red blood cells , which lack a nucleus, are the only cells that do not express MHC molecules on their surface. \n\n There are two classes of MHC molecules involved in adaptive immunity, MHC I and MHC II ( Figure 18.11 ). MHC I molecules are found on all nucleated cells; they present normal self-antigens as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity. In contrast, MHC II molecules are only found on macrophages , dendritic cells , and B cells ; they present abnormal or nonself pathogen antigens for the initial activation of T cells. \n\n Both types of MHC molecules are transmembrane glycoproteins that assemble as dimers in the cytoplasmic membrane of cells, but their structures are quite different. MHC I molecules are composed of a longer α protein chain coupled with a smaller β 2 microglobulin protein, and only the α chain spans the cytoplasmic membrane. The α chain of the MHC I molecule folds into three separate domains: α 1 , α 2 and α 3 . MHC II molecules are composed of two protein chains (an α and a β chain) that are approximately similar in length. Both chains of the MHC II molecule possess portions that span the plasma membrane, and each chain folds into two separate domains: α 1 and α 2 , and β 1 , and β 2 . In order to present abnormal or non-self-antigens to T cells, MHC molecules have a cleft that serves as the antigen-binding site near the “top” (or outermost) portion of the MHC-I or MHC-II dimer. For MHC I, the antigen-binding cleft is formed by the α 1 and α 2 domains, whereas for MHC II, the cleft is formed by the α 1 and β 1 domains ( Figure 18.11 ). \n\n Check Your Understanding \n\n Compare the structures of the MHC I and MHC II molecules. \n\n Antigen-Presenting Cells (APCs) \n\n All nucleated cells in the body have mechanisms for processing and presenting antigens in association with MHC molecules. This signals the immune system, indicating whether the cell is normal and healthy or infected with an intracellular pathogen. However, only macrophages, dendritic cells, and B cells have the ability to present antigens specifically for the purpose of activating T cells; for this reason, these types of cells are sometimes referred to as antigen-presenting cells (APCs) . \n\n While all APCs play a similar role in adaptive immunity, there are some important differences to consider. Macrophages and dendritic cells are phagocytes that ingest and kill pathogens that penetrate the first-line barriers (i.e., skin and mucous membranes). B cells, on the other hand, do not function as phagocytes but play a primary role in the production and secretion of antibodies. In addition, whereas macrophages and dendritic cells recognize pathogens through nonspecific receptor interactions (e.g., PAMPs , toll-like receptors , and receptors for opsonizing complement or antibody), B cells interact with foreign pathogens or their free antigens using antigen-specific immunoglobulin as receptors (monomeric IgD and IgM ). When the immunoglobulin receptors bind to an antigen, the B cell internalizes the antigen by endocytosis before processing and presentting the antigen to T cells. \n\n Antigen Presentation with MHC II Molecules \n\n MHC II molecules are only found on the surface of APCs. Macrophages and dendritic cells use similar mechanisms for processing and presentation of antigens and their epitopes in association with MHC II; B cells use somewhat different mechanisms that will be described further in B Lymphocytes and Humoral Immunity . For now, we will focus on the steps of the process as they pertain to dendritic cells. \n\n After a dendritic cell recognizes and attaches to a pathogen cell, the pathogen is internalized by phagocytosis and is initially contained within a phagosome . Lysosomes containing antimicrobial enzymes and chemicals fuse with the phagosome to create a phagolysosome, where degradation of the pathogen for antigen processing begins. Proteases (protein-degrading) are especially important in antigen processing because only protein antigen epitopes are presented to T cells by MHC II ( Figure 18.12 ). \n\n APCs do not present all possible epitopes to T cells; only a selection of the most antigenic or immunodominant epitopes are presented. The mechanism by which epitopes are selected for processing and presentation by an APC is complicated and not well understood; however, once the most antigenic, immunodominant epitopes have been processed, they associate within the antigen-binding cleft of MHC II molecules and are translocated to the cell surface of the dendritic cell for presentation to T cells. \n\n Check Your Understanding \n\n What are the three kinds of APCs? \n\n What role to MHC II molecules play in antigen presentation? \n\n What is the role of antigen presentation in adaptive immunity? \n\n Antigen Presentation with MHC I Molecules \n\n MHC I molecules, found on all normal, healthy, nucleated cells , signal to the immune system that the cell is a normal “self” cell. In a healthy cell, proteins normally found in the cytoplasm are degraded by proteasomes (enzyme complexes responsible for degradation and processing of proteins) and processed into self-antigen epitopes ; these self-antigen epitopes bind within the MHC I antigen-binding cleft and are then presented on the cell surface. Immune cells, such as NK cells, recognize these self-antigens and do not target the cell for destruction. However, if a cell becomes infected with an intracellular pathogen (e.g., a virus), protein antigens specific to the pathogen are processed in the proteasomes and bind with MHC I molecules for presentation on the cell surface. This presentation of pathogen-specific antigens with MHC I signals that the infected cell must be targeted for destruction along with the pathogen. \n\n Before elimination of infected cells can begin, APCs must first activate the T cells involved in cellular immunity. If an intracellular pathogen directly infects the cytoplasm of an APC, then the processing and presentation of antigens can occur as described (in proteasomes and on the cell surface with MHC I). However, if the intracellular pathogen does not directly infect APCs, an alternative strategy called cross-presentation is utilized. In cross-presentation, antigens are brought into the APC by mechanisms normally leading to presentation with MHC II (i.e., through phagocytosis), but the antigen is presented on an MHC I molecule for CD8 T cells. The exact mechanisms by which cross-presentation occur are not yet well understood, but it appears that cross-presentation is primarily a function of dendritic cells and not macrophages or B cells. \n\n Check Your Understanding \n\n Compare and contrast antigen processing and presentation associated with MHC I and MHC II molecules. \n\n What is cross-presentation, and when is it likely to occur? \n 18.3 T Lymphocytes and Cellular Immunity \n\n Learning Objectives \n\n Describe the process of T-cell maturation and thymic selection \n\n Explain the genetic events that lead to diversity of T-cell receptors \n\n Compare and contrast the various classes and subtypes of T cells in terms of activation and function \n\n Explain the mechanism by which superantigens effect unregulated T-cell activation \n\n As explained in Overview of Specific Adaptive Immunity , the antibodies involved in humoral immunity often bind pathogens and toxins before they can attach to and invade host cells. Thus, humoral immunity is primarily concerned with fighting pathogens in extracellular spaces. However, pathogens that have already gained entry to host cells are largely protected from the humoral antibody-mediated defenses. Cellular immunity, on the other hand, targets and eliminates intracellular pathogens through the actions of T lymphocytes, or T cells ( Figure 18.13 ). T cells also play a more central role in orchestrating the overall adaptive immune response (humoral as well as cellular) along with the cellular defenses of innate immunity. \n\n T Cell Production and Maturation \n\n T cells, like all other white blood cells involved in innate and adaptive immunity, are formed from multipotent hematopoietic stem cells (HSCs) in the bone marrow (see Figure 17.12 ). However, unlike the white blood cells of innate immunity, eventual T cells differentiate first into lymphoid stem cells that then become small, immature lymphocytes, sometimes called lymphoblasts . The first steps of differentiation occur in the red marrow of bones ( Figure 18.14 ), after which immature T lymphocytes enter the bloodstream and travel to the thymus for the final steps of maturation ( Figure 18.15 ). Once in the thymus, the immature T lymphocytes are referred to as thymocytes . \n\n The maturation of thymocytes within the thymus can be divided into three critical steps of positive and negative selection, collectively referred to as thymic selection . The first step of thymic selection occurs in the cortex of the thymus and involves the development of a functional T-cell receptor (TCR) that is required for activation by APCs. Thymocytes with defective TCRs are removed by negative selection through the induction of apoptosis (programmed controlled cell death). The second step of thymic selection also occurs in the cortex and involves the positive selection of thymocytes that will interact appropriately with MHC molecules. Thymocytes that can interact appropriately with MHC molecules receive a positive stimulation that moves them further through the process of maturation, whereas thymocytes that do not interact appropriately are not stimulated and are eliminated by apoptosis . The third and final step of thymic selection occurs in both the cortex and medulla and involves negative selection to remove self-reacting thymocytes , those that react to self-antigens, by apoptosis. This final step is sometimes referred to as central tolerance because it prevents self-reacting T cells from reaching the bloodstream and potentially causing autoimmune disease , which occurs when the immune system attacks healthy “self” cells. \n\n Despite central tolerance, some self-reactive T cells generally escape the thymus and enter the peripheral bloodstream. Therefore, a second line of defense called peripheral tolerance is needed to protect against autoimmune disease. Peripheral tolerance involves mechanisms of anergy and inhibition of self-reactive T cells by regulatory T cells . Anergy refers to a state of nonresponsiveness to antigen stimulation. In the case of self-reactive T cells that escape the thymus, lack of an essential co-stimulatory signal required for activation causes anergy and prevents autoimmune activation. Regulatory T cells participate in peripheral tolerance by inhibiting the activation and function of self-reactive T cells and by secreting anti-inflammatory cytokines. \n\n It is not completely understood what events specifically direct maturation of thymocytes into regulatory T cells. Current theories suggest the critical events may occur during the third step of thymic selection, when most self-reactive T cells are eliminated. Regulatory T cells may receive a unique signal that is below the threshold required to target them for negative selection and apoptosis. Consequently, these cells continue to mature and then exit the thymus, armed to inhibit the activation of self-reactive T cells. \n\n It has been estimated that the three steps of thymic selection eliminate 98% of thymocytes. The remaining 2% that exit the thymus migrate through the bloodstream and lymphatic system to sites of secondary lymphoid organs/tissues, such as the lymph nodes , spleen , and tonsils ( Figure 18.15 ), where they await activation through the presentation of specific antigens by APCs. Until they are activated, they are known as mature naïve T cells . \n\n Check Your Understanding \n\n What anatomical sites are involved in T cell production and maturation? \n\n What are the three steps involved in thymic selection? \n\n Why are central tolerance and peripheral tolerance important? What do they prevent? \n\n Classes of T Cells \n\n T cells can be categorized into three distinct classes: helper T cells , regulatory T cells, and cytotoxic T cells . These classes are differentiated based on their expression of certain surface molecules, their mode of activation, and their functional roles in adaptive immunity ( Table 18.1 ). \n\n All T cells produce cluster of differentiation (CD) molecules , cell surface glycoproteins that can be used to identify and distinguish between the various types of white blood cells. Although T cells can produce a variety of CD molecules, CD4 and CD8 are the two most important used for differentiation of the classes. Helper T cells and regulatory T cells are characterized by the expression of CD4 on their surface, whereas cytotoxic T cells are characterized by the expression of CD8. \n\n Classes of T cells can also be distinguished by the specific MHC molecules and APCs with which they interact for activation. Helper T cells and regulatory T cells can only be activated by APCs presenting antigens associated with MHC II . In contrast, cytotoxic T cells recognize antigens presented in association with MHC I , either by APCs or by nucleated cells infected with an intracellular pathogen. \n\n The different classes of T cells also play different functional roles in the immune system. Helper T cells serve as the central orchestrators that help activate and direct functions of humoral and cellular immunity. In addition, helper T cells enhance the pathogen-killing functions of macrophages and NK cells of innate immunity. In contrast, the primary role of regulatory T cells is to prevent undesirable and potentially damaging immune responses. Their role in peripheral tolerance , for example, protects against autoimmune disorders , as discussed earlier. Finally, cytotoxic T cells are the primary effector cells for cellular immunity. They recognize and target cells that have been infected by intracellular pathogens , destroying infected cells along with the pathogens inside. \n\n Classes of T Cells \n\n Class \n\n Surface CD Molecules \n\n Activation \n\n Functions \n\n Helper T cells \n\n CD4 \n\n APCs presenting antigens associated with MHC II \n\n Orchestrate humoral and cellular immunity \n\n Involved in the activation of macrophages and NK cells \n\n Regulatory T cells \n\n CD4 \n\n APCs presenting antigens associated with MHC II \n\n Involved in peripheral tolerance and prevention of autoimmune responses \n\n Cytotoxic T cells \n\n CD8 \n\n APCs or infected nucleated cells presenting antigens associated with MHC I \n\n Destroy cells infected with intracellular pathogens \n\n Table 18.1 \n\n Check Your Understanding \n\n What are the unique functions of the three classes of T cells? \n\n Which T cells can be activated by antigens presented by cells other than APCs? \n\n T-Cell Receptors \n\n For both helper T cells and cytotoxic T cells, activation is a complex process that requires the interactions of multiple molecules and exposure to cytokines. The T-cell receptor (TCR) is involved in the first step of pathogen epitope recognition during the activation process. \n\n The TCR comes from the same receptor family as the antibodies IgD and IgM, the antigen receptors on the B cell membrane surface, and thus shares common structural elements. Similar to antibodies, the TCR has a variable region and a constant region , and the variable region provides the antigen-binding site ( Figure 18.16 ). However, the structure of TCR is smaller and less complex than the immunoglobulin molecules ( Figure 18.5 ). Whereas immunoglobulins have four peptide chains and Y-shaped structures, the TCR consists of just two peptide chains (α and β chains), both of which span the cytoplasmic membrane of the T cell. \n\n TCRs are epitope-specific, and it has been estimated that 25 million T cells with unique epitope-binding TCRs are required to protect an individual against a wide range of microbial pathogens. Because the human genome only contains about 25,000 genes, we know that each specific TCR cannot be encoded by its own set of genes. This raises the question of how such a vast population of T cells with millions of specific TCRs can be achieved. The answer is a process called genetic rearrangement , which occurs in the thymus during the first step of thymic selection . \n\n The genes that code for the variable regions of the TCR are divided into distinct gene segments called variable (V), diversity (D), and joining (J) segments . The genes segments associated with the α chain of the TCR consist 70 or more different V α segments and 61 different J α segments. The gene segments associated with the β chain of the TCR consist of 52 different V β segments, two different D β segments, and 13 different J β segments. During the development of the functional TCR in the thymus, genetic rearrangement in a T cell brings together one V α segment and one J α segment to code for the variable region of the α chain. Similarly, genetic rearrangement brings one of the V β segments together with one of the D β segments and one of thetJ β segments to code for the variable region of the β chain. All the possible combinations of rearrangements between different segments of V, D, and J provide the genetic diversity required to produce millions of TCRs with unique epitope-specific variable regions. \n\n Check Your Understanding \n\n What are the similarities and differences between TCRs and immunoglobulins? \n\n What process is used to provide millions of unique TCR binding sites? \n\n Activation and Differentiation of Helper T Cells \n\n Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II . The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft . The second step involves the interaction of CD4 on the helper T cell with a region of the MHC II molecule separate from the antigen-binding cleft. This second interaction anchors the MHC II-TCR complex and ensures that the helper T cell is recognizing both the foreign (“nonself”) epitope and “self” antigen of the APC; both recognitions are required for activation of the cell. In the third step, the APC and T cell secrete cytokines that activate the helper T cell. The activated helper T cell then proliferates, dividing by mitosis to produce clonal naïve helper T cells that differentiate into subtypes with different functions ( Figure 18.17 ). \n\n Activated helper T cells can differentiate into one of four distinct subtypes, summarized in Table 18.2 . The differentiation process is directed by APC-secreted cytokines . Depending on which APC-secreted cytokines interact with an activated helper T cell, the cell may differentiate into a T helper 1 (T H 1) cell, a T helper 2 (T H 2) cell, or a memory helper T cell. The two types of helper T cells are relatively short-lived effector cells , meaning that they perform various functions of the immediate immune response. In contrast, memory helper T cells are relatively long lived; they are programmed to “remember” a specific antigen or epitope in order to mount a rapid, strong, secondary response to subsequent exposures. \n\n T H 1 cells secrete their own cytokines that are involved in stimulating and orchestrating other cells involved in adaptive and innate immunity. For example, they stimulate cytotoxic T cells, enhancing their killing of infected cells and promoting differentiation into memory cytotoxic T cells . T H 1 cells also stimulate macrophages and neutrophils to become more effective in their killing of intracellular bacteria. They can also stimulate NK cells to become more effective at killing target cells. \n\n T H 2 cells play an important role in orchestrating the humoral immune response through their secretion of cytokines that activate B cells and direct B cell differentiation and antibody production . Various cytokines produced by T H 2 cells orchestrate antibody class switching , which allows B cells to switch between the production of IgM, IgG, IgA, and IgE as needed to carry out specific antibody functions and to provide pathogen-specific humoral immune responses. \n\n A third subtype of helper T cells called T H 17 cells was discovered through observations that immunity to some infections is not associated with T H 1 or T H 2 cells. T H 17 cells and the cytokines they produce appear to be specifically responsible for the body’s defense against chronic mucocutaneous infections. Patients who lack sufficient T H 17 cells in the mucosa (e.g., HIV patients) may be more susceptible to bacteremia and gastrointestinal infections. 1 1 Blaschitz C., Raffatellu M. “Th17 cytokines and the gut mucosal barrier.” J Clin Immunol. 2010 Mar; 30(2):196-203. doi: 10.1007/s10875-010-9368-7. \n\n Subtypes of Helper T Cells \n\n Subtype \n\n Functions \n\n T H 1 cells \n\n Stimulate cytotoxic T cells and produce memory cytotoxic T cells \n\n Stimulate macrophages and neutrophils (PMNs) for more effective intracellular killing of pathogens \n\n Stimulate NK cells to kill more effectively \n\n T H 2 cells \n\n Stimulate B cell activation and differentiation into plasma cells and memory B cells \n\n Direct antibody class switching in B cells \n\n T H 17 cells \n\n Stimulate immunity to specific infections such as chronic mucocutaneous infections \n\n Memory helper T cells \n\n “Remember” a specific pathogen and mount a strong, rapid secondary response upon re-exposure \n\n Table 18.2 \n\n Activation and Differentiation of Cytotoxic T Cells \n\n Cytotoxic T cells (also referred to as cytotoxic T lymphocytes , or CTLs) are activated by APCs in a three-step process similar to that of helper T cells. The key difference is that the activation of cytotoxic T cells involves recognition of an antigen presented with MHC I (as opposed to MHC II) and interaction of CD8 (as opposed to CD4) with the receptor complex. After the successful co-recognition of foreign epitope and self-antigen, the production of cytokines by the APC and the cytotoxic T cell activate clonal proliferation and differentiation. Activated cytotoxic T cells can differentiate into effector cytotoxic T cells that target pathogens for destruction or memory cells that are ready to respond to subsequent exposures. \n\n As noted, proliferation and differentiation of cytotoxic T cells is also stimulated by cytokines secreted from T H 1 cells activated by the same foreign epitope. The co-stimulation that comes from these T H 1 cells is provided by secreted cytokines. Although it is possible for activation of cytotoxic T cells to occur without stimulation from T H 1 cells, the activation is not as effective or long-lasting. \n\n Once activated, cytotoxic T cells serve as the effector cells of cellular immunity, recognizing and kill cells infected with intracellular pathogens through a mechanism very similar to that of NK cells . However, whereas NK cells recognize nonspecific signals of cell stress or abnormality, cytotoxic T cells recognize infected cells through antigen presentation of pathogen-specific epitopes associated with MHC I . Once an infected cell is recognized, the TCR of the cytotoxic T cell binds to the epitope and releases perforin and granzymes that destroy the infected cell ( Figure 18.18 ). Perforin is a protein that creates pores in the target cell, and granzymes are proteases that enter the pores and induce apoptosis . This mechanism of programmed cell death is a controlled and efficient means of destroying and removing infected cells without releasing the pathogens inside to infect neighboring cells, as might occur if the infected cells were simply lysed. \n\n Link to Learning \n\n In this video , you can see a cytotoxic T cell inducing apoptosis in a target cell. \n\n Check Your Understanding \n\n Compare and contrast the activation of helper T cells and cytotoxic T cells. \n\n What are the different functions of helper T cell subtypes? \n\n What is the mechanism of CTL-mediated destruction of infected cells? \n\n Superantigens and Unregulated Activation of T Cells \n\n When T cell activation is controlled and regulated, the result is a protective response that is effective in combating infections. However, if T cell activation is unregulated and excessive, the result can be life-threatening. Certain bacterial and viral pathogens produce toxins known as superantigens (see Virulence Factors of Bacterial and Viral Pathogens ) that can trigger such an unregulated response. Known bacterial superantigens include toxic shock syndrome toxin (TSST) , staphylococcal enterotoxins , streptococcal pyrogenic toxins , streptococcal superantigen , and the streptococcal mitogenic exotoxin . Viruses known to produce superantigens include Epstein-Barr virus (human herpesvirus 4), cytomegalovirus (human herpesvirus 5), and others. \n\n The mechanism of T cell activation by superantigens involves their simultaneous binding to MHC II molecules of APCs and the variable region of the TCR β chain. This binding occurs outside of the antigen-binding cleft of MHC II, so the superantigen will bridge together and activate MHC II and TCR without specific foreign epitope recognition ( Figure 18.19 ). The result is an excessive, uncontrolled release of cytokines, often called a cytokine storm , which stimulates an excessive inflammatory response. This can lead to a dangerous decrease in blood pressure, shock, multi-organ failure, and potentially, death. \n\n Check Your Understanding \n\n What are examples of superantigens? \n\n How does a superantigen activate a helper T cell? \n\n What effect does a superantigen have on a T cell? \n\n Case in Point Superantigens Melissa, an otherwise healthy 22-year-old woman, is brought to the emergency room by her concerned boyfriend. She complains of a sudden onset of high fever, vomiting, diarrhea, and muscle aches. In her initial interview, she tells the attending physician that she is on hormonal birth control and also is two days into the menstruation portion of her cycle. She is on no other medications and is not abusing any drugs or alcohol. She is not a smoker. She is not diabetic and does not currently have an infection of any kind to her knowledge. \n\n While waiting in the emergency room, Melissa’s blood pressure begins to drop dramatically and her mental state deteriorates to general confusion. The physician believes she is likely suffering from toxic shock syndrome (TSS) . TSS is caused by the toxin TSST-1, a superantigen associated with Staphylococcus aureus , and improper tampon use is a common cause of infections leading to TSS. The superantigen inappropriately stimulates widespread T cell activation and excessive cytokine release, resulting in a massive and systemic inflammatory response that can be fatal. \n\n Vaginal or cervical swabs may be taken to confirm the presence of the microbe, but these tests are not critical to perform based on Melissa’s symptoms and medical history. The physician prescribes rehydration, supportive therapy, and antibiotics to stem the bacterial infection. She also prescribes drugs to increase Melissa’s blood pressure. Melissa spends three days in the hospital undergoing treatment; in addition, her kidney function is monitored because of the high risk of kidney failure associated with TSS. After 72 hours, Melissa is well enough to be discharged to continue her recovery at home. \n\n In what way would antibiotic therapy help to combat a superantigen? \n\n Clinical Focus Part 2 Olivia’s swollen lymph nodes, abdomen, and spleen suggest a strong immune response to a systemic infection in progress. In addition, little Olivia is reluctant to turn her head and appears to be experiencing severe neck pain. The physician orders a complete blood count, blood culture, and lumbar puncture. The cerebrospinal fluid (CSF) obtained appears cloudy and is further evaluated by Gram stain assessment and culturing for potential bacterial pathogens. The complete blood count indicates elevated numbers of white blood cells in Olivia’s bloodstream. The white blood cell increases are recorded at 28.5 K/µL (normal range: 6.0–17.5 K/µL). The neutrophil percentage was recorded as 60% (normal range: 23–45%). Glucose levels in the CSF were registered at 30 mg/100 mL (normal range: 50–80 mg/100 mL). The WBC count in the CSF was 1,163/mm 3 (normal range: 5–20/mm 3 ). \n\n Based on these results, do you have a preliminary diagnosis? \n\n What is a recommended treatment based on this preliminary diagnosis? \n\n Jump to the next Clinical Focus box. Go back to the previous Clinical Focus box. \n 18.4 B Lymphocytes and Humoral Immunity \n\n Learning Objectives \n\n Describe the production and maturation of B cells \n\n Compare the structure of B-cell receptors and T-cell receptors \n\n Compare T-dependent and T-independent activation of B cells \n\n Compare the primary and secondary antibody responses \n\n Humoral immunity refers to mechanisms of the adaptive immune defenses that are mediated by antibodies secreted by B lymphocytes, or B cells. This section will focus on B cells and discuss their production and maturation, receptors, and mechanisms of activation. \n\n B Cell Production and Maturation \n\n Like T cells, B cells are formed from multipotent hematopoietic stem cells (HSCs) in the bone marrow and follow a pathway through lymphoid stem cell and lymphoblast (see Figure 17.12 ). Unlike T cells, however, lymphoblasts destined to become B cells do not leave the bone marrow and travel to the thymus for maturation. Rather, eventual B cells continue to mature in the bone marrow. \n\n The first step of B cell maturation is an assessment of the functionality of their antigen-binding receptors. This occurs through positive selection for B cells with normal functional receptors. A mechanism of negative selection is then used to eliminate self-reacting B cells and minimize the risk of autoimmunity . Negative selection of self-reacting B cells can involve elimination by apoptosis , editing or modification of the receptors so they are no longer self-reactive, or induction of anergy in the B cell. Immature B cells that pass the selection in the bone marrow then travel to the spleen for their final stages of maturation. There they become naïve mature B cells , i.e., mature B cells that have not yet been activated. \n\n Check Your Understanding \n\n Compare the maturation of B cells with the maturation of T cells. \n\n B-Cell Receptors \n\n Like T cells, B cells possess antigen-specific receptors with diverse specificities. Although they rely on T cells for optimum function, B cells can be activated without help from T cells. B-cell receptors (BCRs) for naïve mature B cells are membrane-bound monomeric forms of IgD and IgM . They have two identical heavy chains and two identical light chains connected by disulfide bonds into a basic “Y” shape ( Figure 18.20 ). The trunk of the Y-shaped molecule, the constant region of the two heavy chains, spans the B cell membrane. The two antigen-binding sites exposed to the exterior of the B cell are involved in the binding of specific pathogen epitopes to initiate the activation process. It is estimated that each naïve mature B cell has upwards of 100,000 BCRs on its membrane, and each of these BCRs has an identical epitope-binding specificity. \n\n In order to be prepared to react to a wide range of microbial epitopes, B cells, like T cells, use genetic rearrangement of hundreds of gene segments to provide the necessary diversity of receptor specificities. The variable region of the BCR heavy chain is made up of V, D, and J segments , similar to the β chain of the TCR. The variable region of the BCR light chain is made up of V and J segments, similar to the α chain of the TCR. Genetic rearrangement of all possible combinations of V-J-D (heavy chain) and V-J (light chain) provides for millions of unique antigen-binding sites for the BCR and for the antibodies secreted after activation. \n\n One important difference between BCRs and TCRs is the way they can interact with antigenic epitopes. Whereas TCRs can only interact with antigenic epitopes that are presented within the antigen-binding cleft of MHC I or MHC II , BCRs do not require antigen presentation with MHC; they can interact with epitopes on free antigens or with epitopes displayed on the surface of intact pathogens. Another important difference is that TCRs only recognize protein epitopes, whereas BCRs can recognize epitopes associated with different molecular classes (e.g., proteins, polysaccharides, lipopolysaccharides). \n\n Activation of B cells occurs through different mechanisms depending on the molecular class of the antigen. Activation of a B cell by a protein antigen requires the B cell to function as an APC, presenting the protein epitopes with MHC II to helper T cells. Because of their dependence on T cells for activation of B cells , protein antigens are classified as T-dependent antigens . In contrast, polysaccharides, lipopolysaccharides, and other nonprotein antigens are considered T-independent antigens because they can activate B cells without antigen processing and presentation to T cells. \n\n Check Your Understanding \n\n What types of molecules serve as the BCR? \n\n What are the differences between TCRs and BCRs with respect to antigen recognition? \n\n Which molecule classes are T-dependent antigens and which are T-independent antigens? \n\n T Cell-Independent Activation of B cells \n\n Activation of B cells without the cooperation of helper T cells is referred to as T cell-independent activation and occurs when BCRs interact with T-independent antigens. T-independent antigens (e.g., polysaccharide capsules, lipopolysaccharide) have repetitive epitope units within their structure, and this repetition allows for the cross-linkage of multiple BCRs, providing the first signal for activation ( Figure 18.21 ). Because T cells are not involved, the second signal has to come from other sources, such as interactions of toll-like receptors with PAMPs or interactions with factors from the complement system . \n\n Once a B cell is activated, it undergoes clonal proliferation and daughter cells differentiate into plasma cells. Plasma cells are antibody factories that secrete large quantities of antibodies. After differentiation, the surface BCRs disappear and the plasma cell secretes pentameric IgM molecules that have the same antigen specificity as the BCRs ( Figure 18.21 ). \n\n The T cell-independent response is short-lived and does not result in the production of memory B cells . Thus it will not result in a secondary response to subsequent exposures to T-independent antigens. \n\n Check Your Understanding \n\n What are the two signals required for T cell-independent activation of B cells? \n\n What is the function of a plasma cell? \n\n T Cell-Dependent Activation of B cells \n\n T cell-dependent activation of B cells is more complex than T cell-independent activation, but the resulting immune response is stronger and develops memory. T cell-dependent activation can occur either in response to free protein antigens or to protein antigens associated with an intact pathogen. Interaction between the BCRs on a naïve mature B cell and a free protein antigen stimulate internalization of the antigen, whereas interaction with antigens associated with an intact pathogen initiates the extraction of the antigen from the pathogen before internalization. Once internalized inside the B cell, the protein antigen is processed and presented with MHC II . The presented antigen is then recognized by helper T cells specific to the same antigen. The TCR of the helper T cell recognizes the foreign antigen, and the T cell’s CD4 molecule interacts with MHC II on the B cell. The coordination between B cells and helper T cells that are specific to the same antigen is referred to as linked recognition . \n\n Once activated by linked recognition, T H 2 cells produce and secrete cytokines that activate the B cell and cause proliferation into clonal daughter cells. After several rounds of proliferation, additional cytokines provided by the T H 2 cells stimulate the differentiation of activated B cell clones into memory B cells , which will quickly respond to subsequent exposures to the same protein epitope, and plasma cells that lose their membrane BCRs and initially secrete pentameric IgM ( Figure 18.22 ). \n\n After initial secretion of IgM, cytokines secreted by T H 2 cells stimulate the plasma cells to switch from IgM production to production of IgG , IgA , or IgE . This process, called class switching or isotype switching , allows plasma cells cloned from the same activated B cell to produce a variety of antibody classes with the same epitope specificity. Class switching is accomplished by genetic rearrangement of gene segments encoding the constant region , which determines an antibody’s class. The variable region is not changed, so the new class of antibody retains the original epitope specificity. \n\n Check Your Understanding \n\n What steps are required for T cell-dependent activation of B cells? \n\n What is antibody class switching and why is it important? \n\n Primary and Secondary Responses \n\n T cell-dependent activation of B cells plays an important role in both the primary and secondary responses associated with adaptive immunity. With the first exposure to a protein antigen, a T cell-dependent primary antibody response occurs. The initial stage of the primary response is a lag period , or latent period , of approximately 10 days, during which no antibody can be detected in serum. This lag period is the time required for all of the steps of the primary response, including naïve mature B cell binding of antigen with BCRs, antigen processing and presentation, helper T cell activation, B cell activation, and clonal proliferation. The end of the lag period is characterized by a rise in IgM levels in the serum, as T H 2 cells stimulate B cell differentiation into plasma cells . IgM levels reach their peak around 14 days after primary antigen exposure; at about this same time, T H 2 stimulates antibody class switching, and IgM levels in serum begin to decline. Meanwhile, levels of IgG increase until they reach a peak about three weeks into the primary response ( Figure 18.23 ). \n\n During the primary response, some of the cloned B cells are differentiated into memory B cells programmed to respond to subsequent exposures. This secondary response occurs more quickly and forcefully than the primary response. The lag period is decreased to only a few days and the production of IgG is significantly higher than observed for the primary response ( Figure 18.23 ). In addition, the antibodies produced during the secondary response are more effective and bind with higher affinity to the targeted epitopes. Plasma cells produced during secondary responses live longer than those produced during the primary response, so levels of specific antibody remain elevated for a longer period of time. \n\n Check Your Understanding \n\n What events occur during the lag period of the primary antibody response? \n\n Why do antibody levels remain elevated longer during the secondary antibody response? \n 18.5 Vaccines \n\n Learning Objectives \n\n Compare the various kinds of artificial immunity \n\n Differentiate between variolation and vaccination \n\n Describe different types of vaccines and explain their respective advantages and disadvantages \n\n For many diseases, prevention is the best form of treatment, and few strategies for disease prevention are as effective as vaccination. Vaccination is a form of artificial immunity. By artificially stimulating the adaptive immune defenses, a vaccine triggers memory cell production similar to that which would occur during a primary response . In so doing, the patient is able to mount a strong secondary response upon exposure to the pathogen—but without having to first suffer through an initial infection. In this section, we will explore several different kinds of artificial immunity along with various types of vaccines and the mechanisms by which they induce artificial immunity. \n\n Classifications of Adaptive Immunity \n\n All forms of adaptive immunity can be described as either active or passive. Active immunity refers to the activation of an individual’s own adaptive immune defenses, whereas passive immunity refers to the transfer of adaptive immune defenses from another individual or animal. Active and passive immunity can be further subdivided based on whether the protection is acquired naturally or artificially. \n\n Natural active immunity is adaptive immunity that develops after natural exposure to a pathogen ( Figure 18.24 ). Examples would include the lifelong immunity that develops after recovery from a chickenpox or measles infection (although an acute infection is not always necessary to activate adaptive immunity). The length of time that an individual is protected can vary substantially depending upon the pathogen and antigens involved. For example, activation of adaptive immunity by protein spike structures during an intracellular viral infection can activate lifelong immunity, whereas activation by carbohydrate capsule antigens during an extracellular bacterial infection may activate shorter-term immunity. \n\n Natural passive immunity involves the natural passage of antibodies from a mother to her child before and after birth. IgG is the only antibody class that can cross the placenta from mother’s blood to the fetal blood supply. Placental transfer of IgG is an important passive immune defense for the infant, lasting up to six months after birth. Secretory IgA can also be transferred from mother to infant through breast milk . \n\n Artificial passive immunity refers to the transfer of antibodies produced by a donor (human or animal) to another individual. This transfer of antibodies may be done as a prophylactic measure (i.e., to prevent disease after exposure to a pathogen) or as a strategy for treating an active infection. For example, artificial passive immunity is commonly used for post-exposure prophylaxis against rabies , hepatitis A, hepatitis B , and chickenpox (in high risk individuals). Active infections treated by artificial passive immunity include cytomegalovirus infections in immunocompromised patients and Ebola virus infections. In 1995, eight patients in the Democratic Republic of the Congo with active Ebola infections were treated with blood transfusions from patients who were recovering from Ebola. Only one of the eight patients died (a 12.5% mortality rate), which was much lower than the expected 80% mortality rate for Ebola in untreated patients. 2 Artificial passive immunity is also used for the treatment of diseases caused by bacterial toxins, including tetanus , botulism , and diphtheria . 2 K. Mupapa, M. Massamba, K. Kibadi, K. Kivula, A. Bwaka, M. Kipasa, R. Colebunders, J. J. Muyembe-Tamfum. “Treatment of Ebola Hemorrhagic Fever with Blood Transfusions from Convalescent Patients.” Journal of Infectious Diseases 179 Suppl. (1999): S18–S23. \n\n Artificial active immunity is the foundation for vaccination . It involves the activation of adaptive immunity through the deliberate exposure of an individual to weakened or inactivated pathogens, or preparations consisting of key pathogen antigens. \n\n Check Your Understanding \n\n What is the difference between active and passive immunity? \n\n What kind of immunity is conferred by a vaccine? \n\n Herd Immunity \n\n The four kinds of immunity just described result from an individual’s adaptive immune system. For any given disease, an individual may be considered immune or susceptible depending on his or her ability to mount an effective immune response upon exposure. Thus, any given population is likely to have some individuals who are immune and other individuals who are susceptible. If a population has very few susceptible individuals, even those susceptible individuals will be protected by a phenomenon called herd immunity . Herd immunity has nothing to do with an individual’s ability to mount an effective immune response; rather, it occurs because there are too few susceptible individuals in a population for the disease to spread effectively. \n\n Vaccination programs create herd immunity by greatly reducing the number of susceptible individuals in a population. Even if some individuals in the population are not vaccinated, as long as a certain percentage is immune (either naturally or artificially), the few susceptible individuals are unlikely to be exposed to the pathogen. However, because new individuals are constantly entering populations (for example, through birth or relocation), vaccination programs are necessary to maintain herd immunity. \n\n Eye on Ethics Vaccination: Obligation or Choice A growing number of parents are choosing not to vaccinate their children. They are dubbed “ antivaxxers ,” and the majority of them believe that vaccines are a cause of autism (or other disease conditions), a link that has now been thoroughly disproven. Others object to vaccines on religious or moral grounds (e.g., the argument that Gardasil vaccination against HPV may promote sexual promiscuity), on personal ethical grounds (e.g., a conscientious objection to any medical intervention), or on political grounds (e.g., the notion that mandatory vaccinations are a violation of individual liberties). 3 3 Elizabeth Yale. “Why Anti-Vaccination Movements Can Never Be Tamed.” Religion & Politics , July 22, 2014. http://religionandpolitics.org/2014/07/22/why-anti-vaccination-movements-can-never-be-tamed. \n\n It is believed that this growing number of unvaccinated individuals has led to new outbreaks of whooping cough and measles . We would expect that herd immunity would protect those unvaccinated in our population, but herd immunity can only be maintained if enough individuals are being vaccinated. \n\n Vaccination is clearly beneficial for public health. But from the individual parent’s perspective the view can be murkier. Vaccines, like all medical interventions, have associated risks, and while the risks of vaccination may be extremely low compared to the risks of infection, parents may not always understand or accept the consensus of the medical community. Do such parents have a right to withhold vaccination from their children? Should they be allowed to put their children—and society at large—at risk? \n\n Many governments insist on childhood vaccinations as a condition for entering public school, but it has become easy in most states to opt out of the requirement or to keep children out of the public system. Since the 1970s, West Virginia and Mississippi have had in place a stringent requirement for childhood vaccination, without exceptions, and neither state has had a case of measles since the early 1990s. California lawmakers recently passed a similar law in response to a measles outbreak in 2015, making it much more difficult for parents to opt out of vaccines if their children are attending public schools. Given this track record and renewed legislative efforts, should other states adopt similarly strict requirements? \n\n What role should health-care providers play in promoting or enforcing universal vaccination? Studies have shown that many parents’ minds can be changed in response to information delivered by health-care workers, but is it the place of health-care workers to try to persuade parents to have their children vaccinated? Some health-care providers are understandably reluctant to treat unvaccinated patients. Do they have the right to refuse service to patients who decline vaccines? Do insurance companies have the right to deny coverage to antivaxxers? These are all ethical questions that policymakers may be forced to address as more parents skirt vaccination norms. \n\n Variolation and Vaccination \n\n Thousands of years ago, it was first recognized that individuals who survived a smallpox infection were immune to subsequent infections. The practice of inoculating individuals to actively protect them from smallpox appears to have originated in the 10 th century in China, when the practice of variolation was described ( Figure 18.25 ). Variolation refers to the deliberate inoculation of individuals with infectious material from scabs or pustules of smallpox victims. Infectious materials were either injected into the skin or introduced through the nasal route. The infection that developed was usually milder than naturally acquired smallpox, and recovery from the milder infection provided protection against the more serious disease. \n\n Although the majority of individuals treated by variolation developed only mild infections, the practice was not without risks. More serious and sometimes fatal infections did occur, and because smallpox was contagious, infections resulting from variolation could lead to epidemics. Even so, the practice of variolation for smallpox prevention spread to other regions, including India, Africa, and Europe. \n\n Although variolation had been practiced for centuries, the English physician Edward Jenner (1749–1823) is generally credited with developing the modern process of vaccination. Jenner observed that milkmaids who developed cowpox , a disease similar to smallpox but milder, were immune to the more serious smallpox. This led Jenner to hypothesize that exposure to a less virulent pathogen could provide immune protection against a more virulent pathogen, providing a safer alternative to variolation. In 1796, Jenner tested his hypothesis by obtaining infectious samples from a milkmaid’s active cowpox lesion and injecting the materials into a young boy ( Figure 18.26 ). The boy developed a mild infection that included a low-grade fever, discomfort in his axillae (armpit) and loss of appetite. When the boy was later infected with infectious samples from smallpox lesions, he did not contract smallpox. 4 This new approach was termed vaccination , a name deriving from the use of cowpox (Latin vacca meaning “cow”) to protect against smallpox. Today, we know that Jenner’s vaccine worked because the cowpox virus is genetically and antigenically related to the Variola viruses that caused smallpox. Exposure to cowpox antigens resulted in a primary response and the production of memory cells that identical or related epitopes of Variola virus upon a later exposure to smallpox. 4 N. J. Willis. “Edward Jenner and the Eradication of Smallpox.” Scottish Medical Journal 42 (1997): 118–121. \n\n The success of Jenner’s smallpox vaccination led other scientists to develop vaccines for other diseases. Perhaps the most notable was Louis Pasteur , who developed vaccines for rabies , cholera , and anthrax . During the 20 th and 21 st centuries, effective vaccines were developed to prevent a wide range of diseases caused by viruses (e.g., chickenpox and shingles, hepatitis, measles, mumps, polio, and yellow fever) and bacteria (e.g., diphtheria, pneumococcal pneumonia, tetanus, and whooping cough,) . \n\n Check Your Understanding \n\n What is the difference between variolation and vaccination for smallpox? \n\n Explain why vaccination is less risky than variolation. \n\n Classes of Vaccines \n\n For a vaccine to provide protection against a disease, it must expose an individual to pathogen-specific antigens that will stimulate a protective adaptive immune response. By its very nature, this entails some risk. As with any pharmaceutical drug, vaccines have the potential to cause adverse effects. However, the ideal vaccine causes no severe adverse effects and poses no risk of contracting the disease that it is intended to prevent. Various types of vaccines have been developed with these goals in mind. These different classes of vaccines are described in the next section and summarized in Table 18.3 . \n\n Live Attenuated Vaccines \n\n Live attenuated vaccines expose an individual to a weakened strain of a pathogen with the goal of establishing a subclinical infection that will activate the adaptive immune defenses. Pathogens are attenuated to decrease their virulence using methods such as genetic manipulation (to eliminate key virulence factors) or long-term culturing in an unnatural host or environment (to promote mutations and decrease virulence). \n\n By establishing an active infection, live attenuated vaccines stimulate a more comprehensive immune response than some other types of vaccines. Live attenuated vaccines activate both cellular and humoral immunity and stimulate the development of memory for long-lasting immunity. In some cases, vaccination of one individual with a live attenuated pathogen can even lead to natural transmission of the attenuated pathogen to other individuals. This can cause the other individuals to also develop an active, subclinical infection that activates their adaptive immune defenses. \n\n Disadvantages associated with live attenuated vaccines include the challenges associated with long-term storage and transport as well as the potential for a patient to develop signs and symptoms of disease during the active infection (particularly in immunocompromised patients). There is also a risk of the attenuated pathogen reverting back to full virulence. Table 18.3 lists examples live attenuated vaccines. \n\n Inactivated Vaccines \n\n Inactivated vaccines contain whole pathogens that have been killed or inactivated with heat, chemicals, or radiation. For inactivated vaccines to be effective, the inactivation process must not affect the structure of key antigens on the pathogen. \n\n Because the pathogen is killed or inactive, inactivated vaccines do not produce an active infection, and the resulting immune response is weaker and less comprehensive than that provoked by a live attenuated vaccine. Typically the response involves only humoral immunity, and the pathogen cannot be transmitted to other individuals. In addition, inactivated vaccines usually require higher doses and multiple boosters, possibly causing inflammatory reactions at the site of injection. \n\n Despite these disadvantages, inactivated vaccines do have the advantages of long-term storage stability and ease of transport. Also, there is no risk of causing severe active infections. However, inactivated vaccines are not without their side effects. Table 18.3 lists examples of inactivated vaccines. \n\n Subunit Vaccines \n\n Whereas live attenuated and inactive vaccines expose an individual to a weakened or dead pathogen, subunit vaccines only expose the patient to the key antigens of a pathogen—not whole cells or viruses. Subunit vaccines can be produced either by chemically degrading a pathogen and isolating its key antigens or by producing the antigens through genetic engineering. Because these vaccines contain only the essential antigens of a pathogen, the risk of side effects is relatively low. Table 18.3 lists examples of subunit vaccines. \n\n Toxoid Vaccines \n\n Like subunit vaccines, toxoid vaccines do not introduce a whole pathogen to the patient; they contain inactivated bacterial toxins , called toxoids. Toxoid vaccines are used to prevent diseases in which bacterial toxins play an important role in pathogenesis. These vaccines activate humoral immunity that neutralizes the toxins. Table 18.3 lists examples of toxoid vaccines. \n\n Conjugate Vaccines \n\n A conjugate vaccine is a type of subunit vaccine that consists of a protein conjugated to a capsule polysaccharide. Conjugate vaccines have been developed to enhance the efficacy of subunit vaccines against pathogens that have protective polysaccharide capsules that help them evade phagocytosis , causing invasive infections that can lead to meningitis and other serious conditions. The subunit vaccines against these pathogens introduce T-independent capsular polysaccharide antigens that result in the production of antibodies that can opsonize the capsule and thus combat the infection; however, children under the age of two years do not respond effectively to these vaccines. Children do respond effectively when vaccinated with the conjugate vaccine, in which a protein with T-dependent antigens is conjugated to the capsule polysaccharide. The conjugated protein-polysaccharide antigen stimulates production of antibodies against both the protein and the capsule polysaccharide. Table 18.3 lists examples of conjugate vaccines. \n\n Classes of Vaccines \n\n Class \n\n Description \n\n Advantages \n\n Disadvantages \n\n Examples \n\n Live attenuated \n\n Weakened strain of whole pathogen \n\n Cellular and humoral immunity \n\n Difficult to store and transport \n\n Chickenpox, German measles, measles, mumps, tuberculosis, typhoid fever, yellow fever \n\n Long-lasting immunity \n\n Risk of infection in immunocompromised patients \n\n Transmission to contacts \n\n Risk of reversion \n\n Inactivated \n\n Whole pathogen killed or inactivated with heat, chemicals, or radiation \n\n Ease of storage and transport \n\n Weaker immunity (humoral only) \n\n Cholera, hepatitis A, influenza, plague, rabies \n\n No risk of severe active infection \n\n Higher doses and more boosters required \n\n Subunit \n\n Immunogenic antigens \n\n Lower risk of side effects \n\n Limited longevity \n\n Anthrax, hepatitis B, influenza, meningitis, papillomavirus, pneumococcal pneumonia, whooping cough \n\n Multiple doses required \n\n No protection against antigenic variation \n\n Toxoid \n\n Inactivated bacterial toxin \n\n Humoral immunity to neutralize toxin \n\n Does not prevent infection \n\n Botulism, diphtheria, pertussis, tetanus \n\n Conjugate \n\n Capsule polysaccharide conjugated to protein \n\n T-dependent response to capsule \n\n Costly to produce \n\n Meningitis ( Haemophilus influenzae , Streptococcus pneumoniae , Neisseria meningitides ) \n\n No protection against antigenic variation \n\n Better response in young children \n\n May interfere with other vaccines \n\n Table 18.3 \n\n Check Your Understanding \n\n What is the risk associated with a live attenuated vaccine? \n\n Why is a conjugated vaccine necessary in some cases? \n\n Micro Connections DNA Vaccines DNA vaccines represent a relatively new and promising approach to vaccination. A DNA vaccine is produced by incorporating genes for antigens into a recombinant plasmid vaccine. Introduction of the DNA vaccine into a patient leads to uptake of the recombinant plasmid by some of the patient’s cells, followed by transcription and translation of antigens and presentation of these antigens with MHC I to activate adaptive immunity. This results in the stimulation of both humoral and cellular immunity without the risk of active disease associated with live attenuated vaccines. \n\n Although most DNA vaccines for humans are still in development, it is likely that they will become more prevalent in the near future as researchers are working on engineering DNA vaccines that will activate adaptive immunity against several different pathogens at once. First-generation DNA vaccines tested in the 1990s looked promising in animal models but were disappointing when tested in human subjects. Poor cellular uptake of the DNA plasmids was one of the major problems impacting their efficacy. Trials of second-generation DNA vaccines have been more promising thanks to new techniques for enhancing cellular uptake and optimizing antigens. DNA vaccines for various cancers and viral pathogens such as HIV, HPV, and hepatitis B and C are currently in development. \n\n Some DNA vaccines are already in use. In 2005, a DNA vaccine against West Nile virus was approved for use in horses in the United States. Canada has also approved a DNA vaccine to protect fish from infectious hematopoietic necrosis virus. 5 A DNA vaccine against Japanese encephalitis virus was approved for use in humans in 2010 in Australia. 6 5 M. Alonso and J. C. Leong. “Licensed DNA Vaccines Against Infectious Hematopoietic Necrosis Virus (IHNV).” Recent Patents on DNA & Gene Sequences (Discontinued) 7 no. 1 (2013): 62–65, issn 1872-2156/2212-3431. doi 10.2174/1872215611307010009. 6 S.B. Halstead and S. J. Thomas. “New Japanese Encephalitis Vaccines: Alternatives to Production in Mouse Brain.” Expert Review of Vaccines 10 no. 3 (2011): 355–64. \n\n Clinical Focus Resolution Based on Olivia’s symptoms, her physician made a preliminary diagnosis of bacterial meningitis without waiting for positive identification from the blood and CSF samples sent to the lab. Olivia was admitted to the hospital and treated with intravenous broad-spectrum antibiotics and rehydration therapy. Over the next several days, her condition began to improve, and new blood samples and lumbar puncture samples showed an absence of microbes in the blood and CSF with levels of white blood cells returning to normal. During this time, the lab produced a positive identification of Neisseria meningitidis , the causative agent of meningococcal meningitis , in her original CSF sample. \n\n N. meningitidis produces a polysaccharide capsule that serves as a virulence factor. N. meningitidis tends to affect infants after they begin to lose the natural passive immunity provided by maternal antibodies. At one year of age, Olivia’s maternal IgG antibodies would have disappeared, and she would not have developed memory cells capable of recognizing antigens associated with the polysaccharide capsule of the N. meningitidis. As a result, her adaptive immune system was unable to produce protective antibodies to combat the infection, and without antibiotics she may not have survived. Olivia’s infection likely would have been avoided altogether had she been vaccinated. A conjugate vaccine to prevent meningococcal meningitis is available and approved for infants as young as two months of age. However, current vaccination schedules in the United States recommend that the vaccine be administered at age 11–12 with a booster at age 16. \n\n Go back to the previous Clinical Focus box. \n\n Link to Learning \n\n In countries with developed public health systems, many vaccines are routinely administered to children and adults. Vaccine schedules are changed periodically, based on new information and research results gathered by public health agencies. In the United States, the CDC publishes schedules and other updated information about vaccines. "}}},{"rowIdx":188,"cells":{"bname":{"kind":"string","value":"u.s._history"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":" Summary 15.1 The Origins and Outbreak of the Civil War \n\n The election of Abraham Lincoln to the presidency in 1860 proved to be a watershed event. While it did not cause the Civil War, it was the culmination of increasing tensions between the proslavery South and the antislavery North. Before Lincoln had even taken office, seven Deep South states had seceded from the Union to form the CSA, dedicated to maintaining racial slavery and White supremacy. Last-minute efforts to reach a compromise, such as the proposal by Senator Crittenden and the Corwin amendment, went nowhere. The time for compromise had come to an end. With the Confederate attack on Fort Sumter, the Civil War began. \n\n 15.2 Early Mobilization and War \n\n Many in both the North and the South believed that a short, decisive confrontation in 1861 would settle the question of the Confederacy. These expectations did not match reality, however, and the war dragged on into a second year. Both sides mobilized, with advantages and disadvantages on each side that led to a rough equilibrium. The losses of battles at Manassas and Fredericksburg, Virginia, kept the North from achieving the speedy victory its generals had hoped for, but the Union did make gains and continued to press forward. While they could not capture the Southern capital of Richmond, they were victorious in the Battle of Shiloh and captured New Orleans and Memphis. Thus, the Confederates lost major ground on the western front. \n\n 15.3 1863: The Changing Nature of the War \n\n The year 1863 proved decisive in the Civil War for two major reasons. First, the Union transformed the purpose of the struggle from restoring the Union to ending slavery. While Lincoln’s Emancipation Proclamation actually succeeded in freeing few of the enslaved, it made freedom for African Americans a cause of the Union. Second, the tide increasingly turned against the Confederacy. The success of the Vicksburg Campaign had given the Union control of the Mississippi River, and Lee’s defeat at Gettysburg had ended the attempted Confederate invasion of the North. \n\n 15.4 The Union Triumphant \n\n Having failed to win the support it expected from either Great Britain or France, the Confederacy faced a long war with limited resources and no allies. Lincoln won reelection in 1864, and continued to pursue the Union campaign, not only in the east and west, but also with a drive into the South under the leadership of General Sherman, whose March to the Sea through Georgia destroyed everything in its path. Cut off and outnumbered, Confederate general Lee surrendered to Union general Grant on April 9 at Appomattox Court House in Virginia. Within days of Lee’s surrender, Confederate troops had lay down their arms, and the devastating war came to a close. "},"intro":{"kind":"string","value":" Chapter Outline 15.1 The Origins and Outbreak of the Civil War 15.2 Early Mobilization and War 15.3 1863: The Changing Nature of the War 15.4 The Union Triumphant Introduction \n\n In May 1864, General Ulysses S. Grant ordered the Union’s Army of the Potomac to cross the Rapidan River in Virginia. Grant knew that Confederate general Robert E. Lee would defend the Confederate capital at Richmond at all costs, committing troops that might otherwise be sent to the Shenandoah or the Deep South to stop Union general William Tecumseh Sherman from capturing Atlanta, a key Confederate city. For two days, the Army of the Potomac fought Lee’s troops in the Wilderness, a wooded area along the Rapidan River. Nearly ten thousand Confederate soldiers were killed or wounded, as were more than seventeen thousand Union troops. A few weeks later, the armies would meet again at the Battle of Cold Harbor, where another fifteen thousand men would be wounded or killed. As in many battles, the bodies of those who died were left on the field where they fell. A year later, African Americans, who were often called upon to perform menial labor for the Union army ( Figure 15.1 ), collected the skeletal remains of the dead for a proper burial. The state of the graves of many Civil War soldiers partly inspired the creation of Memorial Day, a day set aside for visiting and decorating the graves of the dead. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":0,"ans_text":"that the Five Civilized Tribes would be admitted into the Confederacy"},"bloom":null,"hl_context":"<hl> The Confederacy also gained the backing of the Five Civilized Tribes , as they were called , in the Indian Territory . <hl> The Five Civilized Tribes comprised the Choctaws , Chickasaws , Creeks , Seminoles , and Cherokees . The tribes supported slavery and many members were enslavers . These Native American slaveholders , who had been forced from their lands in Georgia and elsewhere in the Deep South during the presidency of Andrew Jackson , now found unprecedented common cause with White slaveholders . The CSA even allowed them to send delegates to the Confederate Congress . Despite the ruptures and tensions , by the 1860s , some hope of healing the nation still existed . Before Lincoln took office , John Crittenden , a senator from Kentucky who had helped form the Constitutional Union Party during the 1860 presidential election , attempted to defuse the explosive situation by offering six constitutional amendments and a series of resolutions , known as the Crittenden Compromise . Crittenden ’ s goal was to keep the South from seceding , and his strategy was to transform the Constitution to explicitly protect slavery forever . <hl> Specifically , Crittenden proposed an amendment that would restore the 36 ° 30 ′ line from the Missouri Compromise and extend it all the way to the Pacific Ocean , protecting and ensuring slavery south of the line while prohibiting it north of the line ( Figure 15.3 ) . <hl> <hl> He further proposed an amendment that would prohibit Congress from abolishing slavery anywhere it already existed or from interfering with the interstate slave trade . <hl>","hl_sentences":"The Confederacy also gained the backing of the Five Civilized Tribes , as they were called , in the Indian Territory . Specifically , Crittenden proposed an amendment that would restore the 36 ° 30 ′ line from the Missouri Compromise and extend it all the way to the Pacific Ocean , protecting and ensuring slavery south of the line while prohibiting it north of the line ( Figure 15.3 ) . He further proposed an amendment that would prohibit Congress from abolishing slavery anywhere it already existed or from interfering with the interstate slave trade .","question":{"cloze_format":"It was not a provision of the Crittenden Compromise ___.","normal_format":"Which was not a provision of the Crittenden Compromise?","question_choices":["that the Five Civilized Tribes would be admitted into the Confederacy","that the 36°30′ line from the Missouri Compromise would be restored and extended","that Congress would be prohibited from abolishing slavery where it already existed","that the interstate slave trade would be allowed to continue"],"question_id":"fs-idp27020016","question_text":"Which was not a provision of the Crittenden Compromise?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"the ability to fight defensively, rather than offensively"},"bloom":null,"hl_context":"<hl> The Union side held many advantages as well . <hl> <hl> Its larger population , bolstered by continued immigration from Europe throughout the 1860s , gave it greater manpower reserves to draw upon . <hl> <hl> The North ’ s greater industrial capabilities and extensive railroad grid made it far better able to mobilize men and supplies for the war effort . <hl> <hl> The Industrial Revolution and the transportation revolution , beginning in the 1820s and continuing over the next several decades , had transformed the North . <hl> Throughout the war , the North was able to produce more war materials and move goods more quickly than the South . Furthermore , the farms of New England , the Mid-Atlantic , the Old Northwest , and the prairie states supplied Northern civilians and Union troops with abundant food throughout the war . Food shortages and hungry civilians were common in the South , where the best land was devoted to raising cotton , but not in the North .","hl_sentences":"The Union side held many advantages as well . Its larger population , bolstered by continued immigration from Europe throughout the 1860s , gave it greater manpower reserves to draw upon . The North ’ s greater industrial capabilities and extensive railroad grid made it far better able to mobilize men and supplies for the war effort . The Industrial Revolution and the transportation revolution , beginning in the 1820s and continuing over the next several decades , had transformed the North .","question":{"cloze_format":"All the following were strengths of the Union except ________.","normal_format":"Which of the following was not a strength of the Union?","question_choices":["a large population","substantial industry","an extensive railroad","the ability to fight defensively, rather than offensively"],"question_id":"fs-idp121046624","question_text":"All the following were strengths of the Union except ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> Unlike the South , however , which could hunker down to defend itself and needed to maintain relatively short supply lines , the North had to go forth and conquer . <hl> Union armies had to establish long supply lines , and Union soldiers had to fight on unfamiliar ground and contend with a hostile civilian population off the battlefield . Furthermore , to restore the Union — Lincoln ’ s overriding goal , in 1861 — the United States , after defeating the Southern forces , would then need to pacify a conquered Confederacy , an area of over half a million square miles with nearly nine million residents . In short , although it had better resources and a larger population , the Union faced a daunting task against the well-positioned Confederacy . <hl> The Confederates had the advantage of being able to wage a defensive war , rather than an offensive one . <hl> They had to protect and preserve their new boundaries , but they did not have to be the aggressors against the Union . <hl> The war would be fought primarily in the South , which gave the Confederates the advantages of the knowledge of the terrain and the support of the civilian population . <hl> Further , the vast coastline from Texas to Virginia offered ample opportunities to evade the Union blockade . <hl> And with the addition of the Upper South states , especially Virginia , North Carolina , Tennessee , and Arkansas , the Confederacy gained a much larger share of natural resources and industrial might than the Deep South states could muster . <hl>","hl_sentences":"Unlike the South , however , which could hunker down to defend itself and needed to maintain relatively short supply lines , the North had to go forth and conquer . The Confederates had the advantage of being able to wage a defensive war , rather than an offensive one . The war would be fought primarily in the South , which gave the Confederates the advantages of the knowledge of the terrain and the support of the civilian population . And with the addition of the Upper South states , especially Virginia , North Carolina , Tennessee , and Arkansas , the Confederacy gained a much larger share of natural resources and industrial might than the Deep South states could muster .","question":{"cloze_format":"All the following were strengths of the Confederacy except ________.","normal_format":"Which of the following was not a strength of the Confederacy?","question_choices":["the ability to wage a defensive war","shorter supply lines","the resources of the Upper South states","a strong navy"],"question_id":"fs-idm80927376","question_text":"All the following were strengths of the Confederacy except ________."},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"In keeping with their longstanding objective of keeping slavery out of the newly settled western territories , the Republicans in Congress ( the dominant party ) passed several measures in 1862 . <hl> First , the Homestead Act provided generous inducements for Northerners to relocate and farm in the West . <hl> Settlers could lay claim to 160 acres of federal land by residing on the property for five years and improving it . The act not only motivated free-labor farmers to move west , but it also aimed to increase agricultural output for the war effort . The federal government also turned its attention to creating a transcontinental railroad to facilitate the movement of people and goods across the country . Congress chartered two companies , the Union Pacific and the Central Pacific , and provided generous funds for these two businesses to connect the country by rail . One of the reasons that the Confederacy was so economically devastated was its ill-advised gamble that cotton sales would continue during the war . The government had high hopes that Great Britain and France , which both used cotton as the raw material in their textile mills , would ensure the South ’ s economic strength — and therefore victory in the war — by continuing to buy . Furthermore , the Confederate government hoped that Great Britain and France would make loans to their new nation in order to ensure the continued flow of raw materials . <hl> These hopes were never realized . <hl> <hl> Great Britain in particular did not wish to risk war with the United States , which would have meant the invasion of Canada . <hl> The United States was also a major source of grain for Britain and an important purchaser of British goods . Furthermore , the blockade made Southern trade with Europe difficult . <hl> Instead , Great Britain , the major consumer of American cotton , found alternate sources in India and Egypt , leaving the South without the income or alliance it had anticipated . <hl> The war efforts were costing the new nation dearly . Nevertheless , the Confederate Congress heeded the pleas of wealthy plantation owners and refused to place a tax on enslaved people or cotton , despite the Confederacy ’ s desperate need for the revenue that such a tax would have raised . Instead , the Confederacy drafted a taxation plan that kept the Southern elite happy but in no way met the needs of the war . <hl> The government also resorted to printing immense amounts of paper money , which quickly led to runaway inflation . <hl> Food prices soared , and poor , White Southerners faced starvation . In April 1863 , thousands of hungry people rioted in Richmond , Virginia ( Figure 15.10 ) . Many of the rioters were mothers who could not feed their children . The riot ended when President Davis threatened to have Confederate forces open fire on the crowds . The Confederate government in Richmond , Virginia , exercised sweeping powers to ensure victory , in stark contradiction to the states ’ rights sentiments held by many Southern leaders . <hl> The initial emotional outburst of enthusiasm for war in the Confederacy waned , and the Confederate government instituted a military draft in April 1862 . <hl> Under the terms of the draft , all men between the ages of eighteen and thirty-five would serve three years . The draft had a different effect on men of different socioeconomic classes . One loophole permitted men to hire substitutes instead of serving in the Confederate army . This provision favored the wealthy over the poor , and led to much resentment and resistance . Exercising its power over the states , the Confederate Congress denied state efforts to circumvent the draft .","hl_sentences":"First , the Homestead Act provided generous inducements for Northerners to relocate and farm in the West . These hopes were never realized . Great Britain in particular did not wish to risk war with the United States , which would have meant the invasion of Canada . Instead , Great Britain , the major consumer of American cotton , found alternate sources in India and Egypt , leaving the South without the income or alliance it had anticipated . The government also resorted to printing immense amounts of paper money , which quickly led to runaway inflation . The initial emotional outburst of enthusiasm for war in the Confederacy waned , and the Confederate government instituted a military draft in April 1862 .","question":{"cloze_format":"The North did not ___ to mobilize for war.","normal_format":"Which of the following did the North not do to mobilize for war?","question_choices":["institute a military draft","form a military alliance with Great Britain","print paper money","pass the Homestead Act"],"question_id":"fs-idp25495200","question_text":"Which of the following did the North not do to mobilize for war?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"Northern Democrats railed against Lincoln and the war . Republicans labeled these vocal opponents of the President Copperheads , a term that many antiwar Democrats accepted . As the anti-Lincoln poster below illustrates , his enemies tried to paint him as an untrustworthy and suspect leader ( Figure 15.18 ) . <hl> It seemed to most in the North that the Democratic candidate , General George B . McClellan , who did not support abolition and was replaced with another commander by Lincoln , would win the election . <hl> <hl> Despite the military successes for the Union army in 1863 , in 1864 , Lincoln ’ s status among many Northern voters plummeted . <hl> <hl> Citing the suspension of the writ of habeas corpus , many saw him as a dictator , bent on grabbing power while senselessly and uncaringly drafting more young men into combat . <hl> <hl> Arguably , his greatest liability , however , was the Emancipation Proclamation and the enlistment of African American soldiers . <hl> Many Whites in the North found this deeply offensive , since they still believed in racial inequality . The 1863 New York City Draft Riots illustrated the depth of White anger .","hl_sentences":"It seemed to most in the North that the Democratic candidate , General George B . McClellan , who did not support abolition and was replaced with another commander by Lincoln , would win the election . Despite the military successes for the Union army in 1863 , in 1864 , Lincoln ’ s status among many Northern voters plummeted . Citing the suspension of the writ of habeas corpus , many saw him as a dictator , bent on grabbing power while senselessly and uncaringly drafting more young men into combat . Arguably , his greatest liability , however , was the Emancipation Proclamation and the enlistment of African American soldiers .","question":{"cloze_format":"Many peaple did not oppose Lincoln's reelection in 1864 because ___.","normal_format":"Which of the following is not a reason why many people opposed Lincoln’s reelection in 1864?","question_choices":["He appeared to have overstepped his authority by suspending the writ of habeas corpus.","He issued the Emancipation Proclamation.","He had replaced General George B. McClellan.","He was seen as a power-hungry dictator."],"question_id":"fs-idp210630432","question_text":"Which of the following is not a reason why many people opposed Lincoln’s reelection in 1864?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"to destroy military and civilian resources wherever possible"},"bloom":null,"hl_context":"The other major Union campaigns of 1864 were more successful and gave President Lincoln the advantage that he needed to win reelection in November . In August 1864 , the Union navy captured Mobile Bay . <hl> General Sherman invaded the Deep South , advancing slowly from Tennessee into Georgia , confronted at every turn by the Confederates , who were commanded by Johnston . <hl> When President Davis replaced Johnston with General John B . Hood , the Confederates made a daring but ultimately costly direct attack on the Union army that failed to drive out the invaders . Atlanta fell to Union forces on September 2 , 1864 . The fall of Atlanta held tremendous significance for the war-weary Union and helped to reverse the North ’ s sinking morale . In keeping with the logic of total war , Sherman ’ s forces cut a swath of destruction to Savannah . <hl> On Sherman ’ s March to the Sea , the Union army , seeking to demoralize the South , destroyed everything in its path , despite strict instructions regarding the preservation of civilian property . <hl> Although towns were left standing , houses and barns were burned . Homes were looted , food was stolen , crops were destroyed , orchards were burned , and livestock was killed or confiscated . Savannah fell on December 21 , 1864 — a Christmas gift for Lincoln , Sherman proclaimed . In 1865 , Sherman ’ s forces invaded South Carolina , capturing Charleston and Columbia . In Columbia , the state capital , the Union army burned slaveholders ’ homes and destroyed much of the city . From South Carolina , Sherman ’ s force moved north in an effort to join Grant and destroy Lee ’ s army .","hl_sentences":"General Sherman invaded the Deep South , advancing slowly from Tennessee into Georgia , confronted at every turn by the Confederates , who were commanded by Johnston . On Sherman ’ s March to the Sea , the Union army , seeking to demoralize the South , destroyed everything in its path , despite strict instructions regarding the preservation of civilian property .","question":{"cloze_format":"General Sherman's objective on his March to the Sea was ____.","normal_format":"What was General Sherman’s objective on his March to the Sea?","question_choices":["to destroy military and civilian resources wherever possible","to free Black prisoners of war","to join his army to that of General Grant","to capture General Robert E. Lee"],"question_id":"fs-idp151921552","question_text":"What was General Sherman’s objective on his March to the Sea?"},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"that the Five Civilized Tribes would be admitted into the Confederacy\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The Confederacy also gained the backing of the Five Civilized Tribes , as they were called , in the Indian Territory . <hl> The Five Civilized Tribes comprised the Choctaws , Chickasaws , Creeks , Seminoles , and Cherokees . The tribes supported slavery and many members were enslavers . These Native American slaveholders , who had been forced from their lands in Georgia and elsewhere in the Deep South during the presidency of Andrew Jackson , now found unprecedented common cause with White slaveholders . The CSA even allowed them to send delegates to the Confederate Congress . Despite the ruptures and tensions , by the 1860s , some hope of healing the nation still existed . Before Lincoln took office , John Crittenden , a senator from Kentucky who had helped form the Constitutional Union Party during the 1860 presidential election , attempted to defuse the explosive situation by offering six constitutional amendments and a series of resolutions , known as the Crittenden Compromise . Crittenden ’ s goal was to keep the South from seceding , and his strategy was to transform the Constitution to explicitly protect slavery forever . <hl> Specifically , Crittenden proposed an amendment that would restore the 36 ° 30 ′ line from the Missouri Compromise and extend it all the way to the Pacific Ocean , protecting and ensuring slavery south of the line while prohibiting it north of the line ( Figure 15.3 ) . <hl> <hl> He further proposed an amendment that would prohibit Congress from abolishing slavery anywhere it already existed or from interfering with the interstate slave trade . <hl>\",\n \"hl_sentences\": \"The Confederacy also gained the backing of the Five Civilized Tribes , as they were called , in the Indian Territory . Specifically , Crittenden proposed an amendment that would restore the 36 ° 30 ′ line from the Missouri Compromise and extend it all the way to the Pacific Ocean , protecting and ensuring slavery south of the line while prohibiting it north of the line ( Figure 15.3 ) . He further proposed an amendment that would prohibit Congress from abolishing slavery anywhere it already existed or from interfering with the interstate slave trade .\",\n \"question\": {\n \"cloze_format\": \"It was not a provision of the Crittenden Compromise ___.\",\n \"normal_format\": \"Which was not a provision of the Crittenden Compromise?\",\n \"question_choices\": [\n \"that the Five Civilized Tribes would be admitted into the Confederacy\",\n \"that the 36°30′ line from the Missouri Compromise would be restored and extended\",\n \"that Congress would be prohibited from abolishing slavery where it already existed\",\n \"that the interstate slave trade would be allowed to continue\"\n ],\n \"question_id\": \"fs-idp27020016\",\n \"question_text\": \"Which was not a provision of the Crittenden Compromise?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"the ability to fight defensively, rather than offensively\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The Union side held many advantages as well . <hl> <hl> Its larger population , bolstered by continued immigration from Europe throughout the 1860s , gave it greater manpower reserves to draw upon . <hl> <hl> The North ’ s greater industrial capabilities and extensive railroad grid made it far better able to mobilize men and supplies for the war effort . <hl> <hl> The Industrial Revolution and the transportation revolution , beginning in the 1820s and continuing over the next several decades , had transformed the North . <hl> Throughout the war , the North was able to produce more war materials and move goods more quickly than the South . Furthermore , the farms of New England , the Mid-Atlantic , the Old Northwest , and the prairie states supplied Northern civilians and Union troops with abundant food throughout the war . Food shortages and hungry civilians were common in the South , where the best land was devoted to raising cotton , but not in the North .\",\n \"hl_sentences\": \"The Union side held many advantages as well . Its larger population , bolstered by continued immigration from Europe throughout the 1860s , gave it greater manpower reserves to draw upon . The North ’ s greater industrial capabilities and extensive railroad grid made it far better able to mobilize men and supplies for the war effort . The Industrial Revolution and the transportation revolution , beginning in the 1820s and continuing over the next several decades , had transformed the North .\",\n \"question\": {\n \"cloze_format\": \"All the following were strengths of the Union except ________.\",\n \"normal_format\": \"Which of the following was not a strength of the Union?\",\n \"question_choices\": [\n \"a large population\",\n \"substantial industry\",\n \"an extensive railroad\",\n \"the ability to fight defensively, rather than offensively\"\n ],\n \"question_id\": \"fs-idp121046624\",\n \"question_text\": \"All the following were strengths of the Union except ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Unlike the South , however , which could hunker down to defend itself and needed to maintain relatively short supply lines , the North had to go forth and conquer . <hl> Union armies had to establish long supply lines , and Union soldiers had to fight on unfamiliar ground and contend with a hostile civilian population off the battlefield . Furthermore , to restore the Union — Lincoln ’ s overriding goal , in 1861 — the United States , after defeating the Southern forces , would then need to pacify a conquered Confederacy , an area of over half a million square miles with nearly nine million residents . In short , although it had better resources and a larger population , the Union faced a daunting task against the well-positioned Confederacy . <hl> The Confederates had the advantage of being able to wage a defensive war , rather than an offensive one . <hl> They had to protect and preserve their new boundaries , but they did not have to be the aggressors against the Union . <hl> The war would be fought primarily in the South , which gave the Confederates the advantages of the knowledge of the terrain and the support of the civilian population . <hl> Further , the vast coastline from Texas to Virginia offered ample opportunities to evade the Union blockade . <hl> And with the addition of the Upper South states , especially Virginia , North Carolina , Tennessee , and Arkansas , the Confederacy gained a much larger share of natural resources and industrial might than the Deep South states could muster . <hl>\",\n \"hl_sentences\": \"Unlike the South , however , which could hunker down to defend itself and needed to maintain relatively short supply lines , the North had to go forth and conquer . The Confederates had the advantage of being able to wage a defensive war , rather than an offensive one . The war would be fought primarily in the South , which gave the Confederates the advantages of the knowledge of the terrain and the support of the civilian population . And with the addition of the Upper South states , especially Virginia , North Carolina , Tennessee , and Arkansas , the Confederacy gained a much larger share of natural resources and industrial might than the Deep South states could muster .\",\n \"question\": {\n \"cloze_format\": \"All the following were strengths of the Confederacy except ________.\",\n \"normal_format\": \"Which of the following was not a strength of the Confederacy?\",\n \"question_choices\": [\n \"the ability to wage a defensive war\",\n \"shorter supply lines\",\n \"the resources of the Upper South states\",\n \"a strong navy\"\n ],\n \"question_id\": \"fs-idm80927376\",\n \"question_text\": \"All the following were strengths of the Confederacy except ________.\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"In keeping with their longstanding objective of keeping slavery out of the newly settled western territories , the Republicans in Congress ( the dominant party ) passed several measures in 1862 . <hl> First , the Homestead Act provided generous inducements for Northerners to relocate and farm in the West . <hl> Settlers could lay claim to 160 acres of federal land by residing on the property for five years and improving it . The act not only motivated free-labor farmers to move west , but it also aimed to increase agricultural output for the war effort . The federal government also turned its attention to creating a transcontinental railroad to facilitate the movement of people and goods across the country . Congress chartered two companies , the Union Pacific and the Central Pacific , and provided generous funds for these two businesses to connect the country by rail . One of the reasons that the Confederacy was so economically devastated was its ill-advised gamble that cotton sales would continue during the war . The government had high hopes that Great Britain and France , which both used cotton as the raw material in their textile mills , would ensure the South ’ s economic strength — and therefore victory in the war — by continuing to buy . Furthermore , the Confederate government hoped that Great Britain and France would make loans to their new nation in order to ensure the continued flow of raw materials . <hl> These hopes were never realized . <hl> <hl> Great Britain in particular did not wish to risk war with the United States , which would have meant the invasion of Canada . <hl> The United States was also a major source of grain for Britain and an important purchaser of British goods . Furthermore , the blockade made Southern trade with Europe difficult . <hl> Instead , Great Britain , the major consumer of American cotton , found alternate sources in India and Egypt , leaving the South without the income or alliance it had anticipated . <hl> The war efforts were costing the new nation dearly . Nevertheless , the Confederate Congress heeded the pleas of wealthy plantation owners and refused to place a tax on enslaved people or cotton , despite the Confederacy ’ s desperate need for the revenue that such a tax would have raised . Instead , the Confederacy drafted a taxation plan that kept the Southern elite happy but in no way met the needs of the war . <hl> The government also resorted to printing immense amounts of paper money , which quickly led to runaway inflation . <hl> Food prices soared , and poor , White Southerners faced starvation . In April 1863 , thousands of hungry people rioted in Richmond , Virginia ( Figure 15.10 ) . Many of the rioters were mothers who could not feed their children . The riot ended when President Davis threatened to have Confederate forces open fire on the crowds . The Confederate government in Richmond , Virginia , exercised sweeping powers to ensure victory , in stark contradiction to the states ’ rights sentiments held by many Southern leaders . <hl> The initial emotional outburst of enthusiasm for war in the Confederacy waned , and the Confederate government instituted a military draft in April 1862 . <hl> Under the terms of the draft , all men between the ages of eighteen and thirty-five would serve three years . The draft had a different effect on men of different socioeconomic classes . One loophole permitted men to hire substitutes instead of serving in the Confederate army . This provision favored the wealthy over the poor , and led to much resentment and resistance . Exercising its power over the states , the Confederate Congress denied state efforts to circumvent the draft .\",\n \"hl_sentences\": \"First , the Homestead Act provided generous inducements for Northerners to relocate and farm in the West . These hopes were never realized . Great Britain in particular did not wish to risk war with the United States , which would have meant the invasion of Canada . Instead , Great Britain , the major consumer of American cotton , found alternate sources in India and Egypt , leaving the South without the income or alliance it had anticipated . The government also resorted to printing immense amounts of paper money , which quickly led to runaway inflation . The initial emotional outburst of enthusiasm for war in the Confederacy waned , and the Confederate government instituted a military draft in April 1862 .\",\n \"question\": {\n \"cloze_format\": \"The North did not ___ to mobilize for war.\",\n \"normal_format\": \"Which of the following did the North not do to mobilize for war?\",\n \"question_choices\": [\n \"institute a military draft\",\n \"form a military alliance with Great Britain\",\n \"print paper money\",\n \"pass the Homestead Act\"\n ],\n \"question_id\": \"fs-idp25495200\",\n \"question_text\": \"Which of the following did the North not do to mobilize for war?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"Northern Democrats railed against Lincoln and the war . Republicans labeled these vocal opponents of the President Copperheads , a term that many antiwar Democrats accepted . As the anti-Lincoln poster below illustrates , his enemies tried to paint him as an untrustworthy and suspect leader ( Figure 15.18 ) . <hl> It seemed to most in the North that the Democratic candidate , General George B . McClellan , who did not support abolition and was replaced with another commander by Lincoln , would win the election . <hl> <hl> Despite the military successes for the Union army in 1863 , in 1864 , Lincoln ’ s status among many Northern voters plummeted . <hl> <hl> Citing the suspension of the writ of habeas corpus , many saw him as a dictator , bent on grabbing power while senselessly and uncaringly drafting more young men into combat . <hl> <hl> Arguably , his greatest liability , however , was the Emancipation Proclamation and the enlistment of African American soldiers . <hl> Many Whites in the North found this deeply offensive , since they still believed in racial inequality . The 1863 New York City Draft Riots illustrated the depth of White anger .\",\n \"hl_sentences\": \"It seemed to most in the North that the Democratic candidate , General George B . McClellan , who did not support abolition and was replaced with another commander by Lincoln , would win the election . Despite the military successes for the Union army in 1863 , in 1864 , Lincoln ’ s status among many Northern voters plummeted . Citing the suspension of the writ of habeas corpus , many saw him as a dictator , bent on grabbing power while senselessly and uncaringly drafting more young men into combat . Arguably , his greatest liability , however , was the Emancipation Proclamation and the enlistment of African American soldiers .\",\n \"question\": {\n \"cloze_format\": \"Many peaple did not oppose Lincoln's reelection in 1864 because ___.\",\n \"normal_format\": \"Which of the following is not a reason why many people opposed Lincoln’s reelection in 1864?\",\n \"question_choices\": [\n \"He appeared to have overstepped his authority by suspending the writ of habeas corpus.\",\n \"He issued the Emancipation Proclamation.\",\n \"He had replaced General George B. McClellan.\",\n \"He was seen as a power-hungry dictator.\"\n ],\n \"question_id\": \"fs-idp210630432\",\n \"question_text\": \"Which of the following is not a reason why many people opposed Lincoln’s reelection in 1864?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"to destroy military and civilian resources wherever possible\"\n },\n \"bloom\": null,\n \"hl_context\": \"The other major Union campaigns of 1864 were more successful and gave President Lincoln the advantage that he needed to win reelection in November . In August 1864 , the Union navy captured Mobile Bay . <hl> General Sherman invaded the Deep South , advancing slowly from Tennessee into Georgia , confronted at every turn by the Confederates , who were commanded by Johnston . <hl> When President Davis replaced Johnston with General John B . Hood , the Confederates made a daring but ultimately costly direct attack on the Union army that failed to drive out the invaders . Atlanta fell to Union forces on September 2 , 1864 . The fall of Atlanta held tremendous significance for the war-weary Union and helped to reverse the North ’ s sinking morale . In keeping with the logic of total war , Sherman ’ s forces cut a swath of destruction to Savannah . <hl> On Sherman ’ s March to the Sea , the Union army , seeking to demoralize the South , destroyed everything in its path , despite strict instructions regarding the preservation of civilian property . <hl> Although towns were left standing , houses and barns were burned . Homes were looted , food was stolen , crops were destroyed , orchards were burned , and livestock was killed or confiscated . Savannah fell on December 21 , 1864 — a Christmas gift for Lincoln , Sherman proclaimed . In 1865 , Sherman ’ s forces invaded South Carolina , capturing Charleston and Columbia . In Columbia , the state capital , the Union army burned slaveholders ’ homes and destroyed much of the city . From South Carolina , Sherman ’ s force moved north in an effort to join Grant and destroy Lee ’ s army .\",\n \"hl_sentences\": \"General Sherman invaded the Deep South , advancing slowly from Tennessee into Georgia , confronted at every turn by the Confederates , who were commanded by Johnston . On Sherman ’ s March to the Sea , the Union army , seeking to demoralize the South , destroyed everything in its path , despite strict instructions regarding the preservation of civilian property .\",\n \"question\": {\n \"cloze_format\": \"General Sherman's objective on his March to the Sea was ____.\",\n \"normal_format\": \"What was General Sherman’s objective on his March to the Sea?\",\n \"question_choices\": [\n \"to destroy military and civilian resources wherever possible\",\n \"to free Black prisoners of war\",\n \"to join his army to that of General Grant\",\n \"to capture General Robert E. Lee\"\n ],\n \"question_id\": \"fs-idp151921552\",\n \"question_text\": \"What was General Sherman’s objective on his March to the Sea?\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":15,"string":"15"},"chapter_text":{"kind":"string","value":" 15.1 The Origins and Outbreak of the Civil War Learning Objectives By the end of this section, you will be able to: \n\n Explain the major events that occurred during the Secession Crisis \n\n Describe the creation and founding principles of the Confederate States of America \n\n The 1860 election of Abraham Lincoln was a turning point for the United States. Throughout the tumultuous 1850s, the Fire-Eaters of the southern states had been threatening to leave the Union. With Lincoln’s election, they prepared to make good on their threats. Indeed, the Republican president-elect appeared to be their worst nightmare. The Republican Party committed itself to keeping slavery out of the territories as the country expanded westward, a position that shocked southern sensibilities. Meanwhile, southern leaders suspected that Republican abolitionists would employ the violent tactics of John Brown to deprive southerners of their enslaved property. The threat posed by the Republican victory in the election of 1860 spurred eleven southern states to leave the Union to form the Confederate States of America, a new republic dedicated to maintaining and expanding slavery. The Union, led by President Lincoln, was unwilling to accept the departure of these states and committed itself to restoring the country. Beginning in 1861 and continuing until 1865, the United States engaged in a brutal Civil War that claimed the lives of over 600,000 soldiers. By 1863, the conflict had become not only a war to save the Union, but also a war to end slavery in the United States. Only after four years of fighting did the North prevail. The Union was preserved, and the institution of slavery had been destroyed in the nation. \n\n THE CAUSES OF THE CIVIL WAR \n\n Lincoln’s election sparked the southern secession fever into flame, but it did not cause the Civil War. For decades before Lincoln took office, the sectional divisions in the country had been widening. Both the Northern and southern states engaged in inflammatory rhetoric and agitation, and violent emotions ran strong on both sides. Several factors played into the ultimate split between the North and the South. \n\n One key irritant was the question of slavery’s expansion westward. The debate over whether new states would be slave or free reached back to the controversy over statehood for Missouri beginning in 1819 and Texas in the 1830s and early 1840s. This question arose again after the Mexican-American War (1846–1848), when the government debated whether slavery would be permitted in the territories taken from Mexico. Efforts in Congress to reach a compromise in 1850 fell back on the principle of popular sovereignty—letting the people in the new territories south of the 1820 Missouri Compromise line decide whether to allow slavery. This same principle came to be applied to the Kansas-Nebraska territories in 1854, a move that added fuel to the fire of sectional conflict by destroying the Missouri Compromise boundary and leading to the birth of the Republican Party. In the end, popular sovereignty proved to be no solution at all. This was especially true in “Bleeding Kansas” in the mid-1850s, as pro- and antislavery forces battled each another in an effort to gain the upper hand. \n\n The small but very vocal abolitionist movement further contributed to the escalating tensions between the North and the South. Since the 1830s, abolitionists, led by journalist and reformer William Lloyd Garrison, had cast slavery as a national sin and called for its immediate end. For three decades, the abolitionists—a minority even within the antislavery movement—had had a significant effect on American society by bringing the evils of slavery into the public consciousness. By the 1850s, some of the most radical abolitionists, such as John Brown, had resorted to violence in their efforts to destroy the institution of slavery. \n\n The formation of the Liberty Party (1840), the Free-Soil Party (1848), and the Republican Party (1854), all of which strongly opposed the spread of slavery to the West, brought the question solidly into the political arena. Although not all those who opposed the westward expansion of slavery had a strong abolitionist bent, the attempt to limit slaveholders’ control of their human property stiffened the resolve of southern leaders to defend their society at all costs. Prohibiting slavery’s expansion, they argued, ran counter to fundamental American property rights. Across the country, people of all political stripes worried that the nation’s arguments would cause irreparable rifts in the country. \n\n Despite the ruptures and tensions, by the 1860s, some hope of healing the nation still existed. Before Lincoln took office, John Crittenden, a senator from Kentucky who had helped form the Constitutional Union Party during the 1860 presidential election, attempted to defuse the explosive situation by offering six constitutional amendments and a series of resolutions, known as the Crittenden Compromise . Crittenden’s goal was to keep the South from seceding, and his strategy was to transform the Constitution to explicitly protect slavery forever. Specifically, Crittenden proposed an amendment that would restore the 36°30′ line from the Missouri Compromise and extend it all the way to the Pacific Ocean, protecting and ensuring slavery south of the line while prohibiting it north of the line ( Figure 15.3 ). He further proposed an amendment that would prohibit Congress from abolishing slavery anywhere it already existed or from interfering with the interstate slave trade. \n\n Republicans, including President-elect Lincoln, rejected Crittenden’s proposals because they ran counter to the party’s goal of keeping slavery out of the territories. The southern states also rejected Crittenden’s attempts at compromise, because it would prevent slaveholders from taking their human chattel north of the 36°30′ line. On December 20, 1860, only a few days after Crittenden’s proposal was introduced in Congress, South Carolina began the march towards war when it seceded from the United States. Three more states of the Deep South—Mississippi, Florida, and Alabama—seceded before the U.S. Senate rejected Crittenden’s proposal on January 16, 1861. Georgia, Louisiana, and Texas joined them in rapid succession on January 19, January 26, and February 1, respectively ( Figure 15.4 ). In many cases, these secessions occurred after extremely divided conventions and popular votes. A lack of unanimity prevailed in much of the South. \n\n THE CREATION OF THE CONFEDERATE STATES OF AMERICA \n\n The seven Deep South states that seceded quickly formed a new government. In the opinion of many Southern politicians, the federal Constitution that united the states as one nation was a contract by which individual states had agreed to be bound. However, they maintained, the states had not sacrificed their autonomy and could withdraw their consent to be controlled by the federal government. In their eyes, their actions were in keeping with the nature of the Constitution and the social contract theory of government that had influenced the founders of the American Republic. \n\n The new nation formed by these men would not be a federal union, but a confederation. In a confederation, individual member states agree to unite under a central government for some purposes, such as defense, but to retain autonomy in other areas of government. In this way, states could protect themselves, and slavery, from interference by what they perceived to be an overbearing central government. The constitution of the Confederate States of America (CSA), or the Confederacy , drafted at a convention in Montgomery, Alabama, in February 1861, closely followed the 1787 Constitution. The only real difference between the two documents centered on slavery. The Confederate Constitution declared that the new nation existed to defend and perpetuate racial slavery, and the leadership of the slaveholding class. Specifically, the constitution protected the interstate slave trade, guaranteed that slavery would exist in any new territory gained by the Confederacy, and, perhaps most importantly, in Article One, Section Nine, declared that “No . . . law impairing or denying the right of property in negro slaves shall be passed.” Beyond its focus on slavery, the Confederate Constitution resembled the 1787 U.S. Constitution. It allowed for a Congress composed of two chambers, a judicial branch, and an executive branch with a president to serve for six years. \n\n The convention delegates chose Jefferson Davis of Mississippi to lead the new provisional government as president and Alexander Stephens of Georgia to serve as vice president until elections could be held in the spring and fall of 1861. By that time, four new states—Virginia, Arkansas, Tennessee, and North Carolina—had joined the CSA. As 1861 progressed, the Confederacy claimed Missouri and Kentucky, even though no ordinance of secession had been approved in those states. Southern nationalism ran high, and the Confederacy, buoyed by its sense of purpose, hoped that their new nation would achieve eminence in the world. \n\n By the time Lincoln reached Washington, DC, in February 1861, the CSA had already been established. The new president confronted an unprecedented crisis. A conference held that month with delegates from the Southern states failed to secure a promise of peace or to restore the Union. On inauguration day, March 4, 1861, the new president repeated his views on slavery: “I have no purpose, directly or indirectly, to interfere with the institution of slavery in the States where it exists. I believe I have no lawful right to do so, and I have no inclination to do so.” His recognition of slavery in the South did nothing to mollify slaveholders, however, because Lincoln also pledged to keep slavery from expanding into the new western territories. Furthermore, in his inaugural address, Lincoln made clear his commitment to maintaining federal power against the secessionists working to destroy it. Lincoln declared that the Union could not be dissolved by individual state actions, and, therefore, secession was unconstitutional. \n\n FORT SUMTER \n\n President Lincoln made it clear to Southern secessionists that he would fight to maintain federal property and to keep the Union intact. Other politicians, however, still hoped to avoid the use of force to resolve the crisis. In February 1861, in an effort to entice the rebellious states to return to the Union without resorting to force, Thomas Corwin, a representative from Ohio, introduced a proposal to amend the Constitution in the House of Representatives. His was but one of several measures proposed in January and February 1861, to head off the impending conflict and save the United States. The proposed amendment would have made it impossible for Congress to pass any law abolishing slavery. The proposal passed the House on February 28, 1861, and the Senate passed the proposal on March 2, 1861. It was then sent to the states to be ratified. Once ratified by three-quarters of state legislatures, it would become law. In his inaugural address, Lincoln stated that he had no objection to the amendment, and his predecessor James Buchanan had supported it. By the time of Lincoln’s inauguration, however, seven states had already left the Union. Of the remaining states, Ohio ratified the amendment in 1861, and Maryland and Illinois did so in 1862. Despite this effort at reconciliation, the Confederate states did not return to the Union. \n\n Indeed, by the time of the Corwin amendment’s passage through Congress, Confederate forces in the Deep South had already begun to take over federal forts. The loss of Fort Sumter , in the harbor of Charleston, South Carolina, proved to be the flashpoint in the contest between the new Confederacy and the federal government. A small Union garrison of fewer than one hundred soldiers and officers held the fort, making it a vulnerable target for the Confederacy. Fire-Eaters pressured Jefferson Davis to take Fort Sumter and thereby demonstrate the Confederate government’s resolve. Some also hoped that the Confederacy would gain foreign recognition, especially from Great Britain, by taking the fort in the South’s most important Atlantic port. The situation grew dire as local merchants refused to sell food to the fort’s Union soldiers, and by mid-April, the garrison’s supplies began to run out. President Lincoln let it be known to Confederate leaders that he planned to resupply the Union forces. His strategy was clear: The decision to start the war would rest squarely on the Confederates, not on the Union. On April 12, 1861, Confederate forces in Charleston began a bombardment of Fort Sumter ( Figure 15.5 ). Two days later, the Union soldiers there surrendered. \n\n The attack on Fort Sumter meant war had come, and on April 15, 1861, Lincoln called upon loyal states to supply armed forces to defeat the rebellion and regain Fort Sumter. Faced with the need to choose between the Confederacy and the Union, border states and those of the Upper South, which earlier had been reluctant to dissolve their ties with the United States, were inspired to take action. They quickly voted for secession. A convention in Virginia that had been assembled earlier to consider the question of secession voted to join the Confederacy on April 17, two days after Lincoln called for troops. Arkansas left the Union on May 6 along with Tennessee one day later. North Carolina followed on May 20. \n\n Not all residents of the border states and the Upper South wished to join the Confederacy, however. Pro-Union feelings remained strong in Tennessee, especially in the eastern part of the state where the enslaved population was small and consisted largely of house servants owned by the wealthy. The state of Virginia—home of revolutionary leaders and presidents such as George Washington, Thomas Jefferson, James Madison, and James Monroe—literally was split on the issue of secession. Residents in the north and west of the state, where few slaveholders resided, rejected secession. These counties subsequently united to form “West Virginia,” which entered the Union as a free state in 1863. The rest of Virginia, including the historic lands along the Chesapeake Bay that were home to such early American settlements as Jamestown and Williamsburg, joined the Confederacy. The addition of this area gave the Confederacy even greater hope and brought General Robert E. Lee, arguably the best military commander of the day, to their side. In addition, the secession of Virginia brought Washington, DC, perilously close to the Confederacy, and fears that the border state of Maryland would also join the CSA, thus trapping the U.S. capital within Confederate territories, plagued Lincoln. \n\n The Confederacy also gained the backing of the Five Civilized Tribes, as they were called, in the Indian Territory. The Five Civilized Tribes comprised the Choctaws, Chickasaws, Creeks, Seminoles, and Cherokees. The tribes supported slavery and many members were enslavers. These Native American slaveholders, who had been forced from their lands in Georgia and elsewhere in the Deep South during the presidency of Andrew Jackson, now found unprecedented common cause with White slaveholders. The CSA even allowed them to send delegates to the Confederate Congress. \n\n While most slaveholding states joined the Confederacy, four crucial slave states remained in the Union ( Figure 15.6 ). Delaware, which was technically a slave state despite its tiny enslaved population, never voted to secede. Maryland, despite deep divisions, remained in the Union as well. Missouri became the site of vicious fighting and the home of pro-Confederate guerillas but never joined the Confederacy. Kentucky declared itself neutral, although that did little to stop the fighting that occurred within the state. In all, these four states deprived the Confederacy of key resources and soldiers. \n 15.2 Early Mobilization and War Learning Objectives By the end of this section, you will be able to: \n\n Assess the strengths and weaknesses of the Confederacy and the Union \n\n Explain the strategic importance of the Battle of Bull Run and the Battle of Shiloh \n\n In 1861, enthusiasm for war ran high on both sides. The North fought to restore the Union, which Lincoln declared could never be broken. The Confederacy, which by the summer of 1861 consisted of eleven states, fought for its independence from the United States. The continuation of slavery was a central issue in the war, of course, although abolitionism and western expansion also played roles, and Northerners and Southerners alike flocked eagerly to the conflict. Both sides thought it would be over quickly. Militarily, however, the North and South were more equally matched than Lincoln had realized, and it soon became clear that the war effort would be neither brief nor painless. In 1861, Americans in both the North and South romanticized war as noble and positive. Soon the carnage and slaughter would awaken them to the horrors of war. \n\n THE FIRST BATTLE OF BULL RUN \n\n After the fall of Fort Sumter on April 15, 1861, Lincoln called for seventy-five thousand volunteers from state militias to join federal forces. His goal was a ninety-day campaign to put down the Southern rebellion. The response from state militias was overwhelming, and the number of Northern troops exceeded the requisition. Also in April, Lincoln put in place a naval blockade of the South, a move that gave tacit recognition of the Confederacy while providing a legal excuse for the British and the French to trade with Southerners. The Confederacy responded to the blockade by declaring that a state of war existed with the United States. This official pronouncement confirmed the beginning of the Civil War. Men rushed to enlist, and the Confederacy turned away tens of thousands who hoped to defend the new nation. \n\n Many believed that a single, heroic battle would decide the contest. Some questioned how committed Southerners really were to their cause. Northerners hoped that most Southerners would not actually fire on the American flag. Meanwhile, Lincoln and military leaders in the North hoped a quick blow to the South, especially if they could capture the Confederacy’s new capital of Richmond, Virginia, would end the rebellion before it went any further. On July 21, 1861, the two armies met near Manassas, Virginia, along Bull Run Creek , only thirty miles from Washington, DC. So great was the belief that this would be a climactic Union victory that many Washington socialites and politicians brought picnic lunches to a nearby area, hoping to witness history unfolding before them. At the First Battle of Bull Run, also known as First Manassas, some sixty thousand troops assembled, most of whom had never seen combat, and each side sent eighteen thousand into the fray. The Union forces attacked first, only to be pushed back. The Confederate forces then carried the day, sending the Union soldiers and Washington, DC, onlookers scrambling back from Virginia and destroying Union hopes of a quick, decisive victory. Instead, the war would drag on for four long, deadly years ( Figure 15.7 ). \n\n BALANCE SHEET: THE UNION AND THE CONFEDERACY \n\n As it became clearer that the Union would not be dealing with an easily quashed rebellion, the two sides assessed their strengths and weaknesses. At the onset on the war, in 1861 and 1862, they stood as relatively equal combatants. \n\n The Confederates had the advantage of being able to wage a defensive war, rather than an offensive one. They had to protect and preserve their new boundaries, but they did not have to be the aggressors against the Union. The war would be fought primarily in the South, which gave the Confederates the advantages of the knowledge of the terrain and the support of the civilian population. Further, the vast coastline from Texas to Virginia offered ample opportunities to evade the Union blockade. And with the addition of the Upper South states, especially Virginia, North Carolina, Tennessee, and Arkansas, the Confederacy gained a much larger share of natural resources and industrial might than the Deep South states could muster. \n\n Still, the Confederacy had disadvantages. The South’s economy depended heavily on the export of cotton, but with the naval blockade, the flow of cotton to England, the region’s primary importer, came to an end. The blockade also made it difficult to import manufactured goods. Although the secession of the Upper South added some industrial assets to the Confederacy, overall, the South lacked substantive industry or an extensive railroad infrastructure to move men and supplies. To deal with the lack of commerce and the resulting lack of funds, the Confederate government began printing paper money, leading to runaway inflation ( Figure 15.8 ). The advantage that came from fighting on home territory quickly turned to a disadvantage when Confederate armies were defeated and Union forces destroyed Southern farms and towns, and forced Southern civilians to take to the road as refugees. Finally, the population of the South stood at fewer than nine million people, of whom nearly four million were enslaved Black people, compared to over twenty million residents in the North. These limited numbers became a major factor as the war dragged on and the death toll rose. \n\n The Union side held many advantages as well. Its larger population, bolstered by continued immigration from Europe throughout the 1860s, gave it greater manpower reserves to draw upon. The North’s greater industrial capabilities and extensive railroad grid made it far better able to mobilize men and supplies for the war effort. The Industrial Revolution and the transportation revolution, beginning in the 1820s and continuing over the next several decades, had transformed the North. Throughout the war, the North was able to produce more war materials and move goods more quickly than the South. Furthermore, the farms of New England, the Mid-Atlantic, the Old Northwest, and the prairie states supplied Northern civilians and Union troops with abundant food throughout the war. Food shortages and hungry civilians were common in the South, where the best land was devoted to raising cotton, but not in the North. \n\n Unlike the South, however, which could hunker down to defend itself and needed to maintain relatively short supply lines, the North had to go forth and conquer. Union armies had to establish long supply lines, and Union soldiers had to fight on unfamiliar ground and contend with a hostile civilian population off the battlefield. Furthermore, to restore the Union—Lincoln’s overriding goal, in 1861—the United States, after defeating the Southern forces, would then need to pacify a conquered Confederacy, an area of over half a million square miles with nearly nine million residents. In short, although it had better resources and a larger population, the Union faced a daunting task against the well-positioned Confederacy. \n\n MILITARY STALEMATE \n\n The military forces of the Confederacy and the Union battled in 1861 and early 1862 without either side gaining the upper hand. The majority of military leaders on both sides had received the same military education and often knew one another personally, either from their time as students at West Point or as commanding officers in the Mexican-American War. This familiarity allowed them to anticipate each other’s strategies. Both sides believed in the use of concentrated armies charged with taking the capital city of the enemy. For the Union, this meant the capture of the Confederate capital in Richmond, Virginia, whereas Washington, DC, stood as the prize for Confederate forces. After hopes of a quick victory faded at Bull Run, the months dragged on without any major movement on either side ( Figure 15.9 ). \n\n General George B. McClellan, the general in chief of the army, responsible for overall control of Union land forces, proved especially reluctant to engage in battle with the Confederates. In direct command of the Army of the Potomac , the Union fighting force operating outside Washington, DC, McClellan believed, incorrectly, that Confederate forces were too strong to defeat and was reluctant to risk his troops in battle. His cautious nature made him popular with his men but not with the president or Congress. By 1862, however, both President Lincoln and the new Secretary of War Edwin Stanton had tired of waiting. The Union put forward a new effort to bolster troop strength, enlisting one million men to serve for three-year stints in the Army of the Potomac. In January 1862, Lincoln and Stanton ordered McClellan to invade the Confederacy with the goal of capturing Richmond. \n\n To that end, General McClellan slowly moved 100,000 soldiers of the Army of the Potomac toward Richmond but stopped a few miles outside the city. As he did so, a Confederate force led by Thomas “Stonewall” Jackson moved north to take Washington, DC. To fend off Jackson’s attack, somewhere between one-quarter and one-third of McClellan’s soldiers, led by Major General Irvin McDowell, returned to defend the nation’s capital, a move that Jackson hoped would leave the remaining troops near Richmond more vulnerable. Having succeeding in drawing off a sizable portion of the Union force, he joined General Lee to launch an attack on McClellan’s remaining soldiers near Richmond. From June 25 to July 1, 1862, the two sides engaged in the brutal Seven Days Battles that killed or wounded almost twenty thousand Confederate and ten thousand Union soldiers. McClellan’s army finally returned north, having failed to take Richmond. \n\n General Lee, flush from his success at keeping McClellan out of Richmond, tried to capitalize on the Union’s failure by taking the fighting northward. He moved his forces into northern Virginia, where, at the Second Battle of Bull Run, the Confederates again defeated the Union forces. Lee then pressed into Maryland, where his troops met the much larger Union forces near Sharpsburg, at Antietam Creek. The ensuing one-day battle on September 17, 1862, led to a tremendous loss of life. Although there are varying opinions about the total number of deaths, eight thousand soldiers were killed or wounded, more than on any other single day of combat. Once again, McClellan, mistakenly believing that the Confederate troops outnumbered his own, held back a significant portion of his forces. Lee withdrew from the field first, but McClellan, fearing he was outnumbered, refused to pursue him. \n\n The Union army’s inability to destroy Lee’s army at Antietam made it clear to Lincoln that McClellan would never win the war, and the president was forced to seek a replacement. Lincoln wanted someone who could deliver a decisive Union victory. He also personally disliked McClellan, who referred to the president as a “baboon” and a “gorilla,” and constantly criticized his decisions. Lincoln chose General Ambrose E. Burnside to replace McClellan as commander of the Army of the Potomac, but Burnside’s efforts to push into Virginia failed in December 1862, as Confederates held their position at Fredericksburg and devastated Burnside’s forces with heavy artillery fire. The Union’s defeat at Fredericksburg harmed morale in the North but bolstered Confederate spirits. By the end of 1862, the Confederates were still holding their ground in Virginia. Burnside’s failure led Lincoln to make another change in leadership, and Joseph “Fighting Joe” Hooker took over command of the Army of the Potomac in January 1863. \n\n General Ulysses S. Grant’s Army of the West , operating in Kentucky, Tennessee, and the Mississippi River Valley, had been more successful. In the western campaign, the goal of both the Union and the Confederacy was to gain control of the major rivers in the west, especially the Mississippi. If the Union could control the Mississippi, the Confederacy would be split in two. The fighting in this campaign initially centered in Tennessee, where Union forces commanded by Grant pushed Confederate troops back and gained control of the state. The major battle in the western theater took place at Pittsburgh Landing, Tennessee, on April 6 and 7, 1862. Grant’s army was camped on the west side of the Tennessee River near a small log church called Shiloh, which gave the battle its name. On Sunday morning, April 6, Confederate forces under General Albert Sidney Johnston attacked Grant’s encampment with the goal of separating them from their supply line on the Tennessee River and driving them into the swamps on the river’s western side, where they could be destroyed. Union general William Tecumseh Sherman tried to rally the Union forces as Grant, who had been convalescing from an injured leg when the attack began and was unable to walk without crutches, called for reinforcements and tried to mount a defense. Many of Union troops fled in terror. \n\n Unfortunately for the Confederates, Johnston was killed on the afternoon of the first day. Leadership of the Southern forces fell to General P. G. T. Beauregard, who ordered an assault at the end of that day. This assault was so desperate that one of the two attacking columns did not even have ammunition. Heavily reinforced Union forces counterattacked the next day, and the Confederate forces were routed. Grant had maintained the Union foothold in the western part of the Confederacy. The North could now concentrate on its efforts to gain control of the Mississippi River, splitting the Confederacy in two and depriving it of its most important water route. \n\n In the spring and summer of 1862, the Union was successful in gaining control of part of the Mississippi River. In April 1862, the Union navy under Admiral David Farragut fought its way past the forts that guarded New Orleans and fired naval guns upon the below-sea-level city. When it became obvious that New Orleans could no longer be defended, Confederate major general Marshall Lovell sent his artillery upriver to Vicksburg, Mississippi. Armed civilians in New Orleans fought the Union forces that entered the city. They also destroyed ships and military supplies that might be used by the Union. Upriver, Union naval forces also bombarded Fort Pillow, forty miles from Memphis, Tennessee, a Southern industrial center and one of the largest cities in the Confederacy. On June 4, 1862, the Confederate defenders abandoned the fort. On June 6, Memphis fell to the Union after the ships defending it were destroyed. \n 15.3 1863: The Changing Nature of the War Learning Objectives By the end of this section, you will be able to: \n\n Explain what is meant by the term “total war” and provide examples \n\n Describe mobilization efforts in the North and the South \n\n Explain why 1863 was a pivotal year in the war \n\n Wars have their own logic; they last far longer than anyone anticipates at the beginning of hostilities. As they drag on, the energy and zeal that marked the entry into warfare often wane, as losses increase and people on both sides suffer the tolls of war. The American Civil War is a case study of this characteristic of modern war. \n\n Although Northerners and Southerners both anticipated that the battle between the Confederacy and the Union would be settled quickly, it soon became clear to all that there was no resolution in sight. The longer the war continued, the more it began to affect life in both the North and the South. Increased need for manpower, the issue of slavery, and the ongoing challenges of keeping the war effort going changed the way life on both sides as the conflict progressed. \n\n MASS MOBILIZATION \n\n By late 1862, the course of the war had changed to take on the characteristics of total war , in which armies attempt to demoralize the enemy by both striking military targets and disrupting their opponent’s ability to wage war through destruction of their resources. In this type of war, armies often make no distinction between civilian and military targets. Both the Union and Confederate forces moved toward total war, although neither side ever entirely abolished the distinction between military and civilian. Total war also requires governments to mobilize all resources, extending their reach into their citizens’ lives as never before. Another reality of war that became apparent in 1862 and beyond was the influence of combat on the size and scope of government. Both the Confederacy and the Union governments had to continue to grow in order to manage the logistics of recruiting men and maintaining, feeding, and equipping an army. \n\n Confederate Mobilization \n\n The Confederate government in Richmond, Virginia, exercised sweeping powers to ensure victory, in stark contradiction to the states’ rights sentiments held by many Southern leaders. The initial emotional outburst of enthusiasm for war in the Confederacy waned, and the Confederate government instituted a military draft in April 1862. Under the terms of the draft, all men between the ages of eighteen and thirty-five would serve three years. The draft had a different effect on men of different socioeconomic classes. One loophole permitted men to hire substitutes instead of serving in the Confederate army. This provision favored the wealthy over the poor, and led to much resentment and resistance. Exercising its power over the states, the Confederate Congress denied state efforts to circumvent the draft. \n\n In order to fund the war, the Confederate government also took over the South’s economy. The government ran Southern industry and built substantial transportation and industrial infrastructure to make the weapons of war. Over the objections of slaveholders, it impressed enslaved people, seizing these enslaved workers from their owners and forcing them to work on fortifications and rail lines. Concerned about the resistance to and unhappiness with the government measures, in 1862, the Confederate Congress gave President Davis the power to suspend the writ of habeas corpus , the right of those arrested to be brought before a judge or court to determine whether there is cause to hold the prisoner. With a stated goal of bolstering national security in the fledgling republic, this change meant that the Confederacy could arrest and detain indefinitely any suspected enemy without giving a reason. This growth of the Confederate central government stood as a glaring contradiction to the earlier states’ rights argument of pro-Confederate advocates. \n\n The war efforts were costing the new nation dearly. Nevertheless, the Confederate Congress heeded the pleas of wealthy plantation owners and refused to place a tax on enslaved people or cotton, despite the Confederacy’s desperate need for the revenue that such a tax would have raised. Instead, the Confederacy drafted a taxation plan that kept the Southern elite happy but in no way met the needs of the war. The government also resorted to printing immense amounts of paper money, which quickly led to runaway inflation. Food prices soared, and poor, White Southerners faced starvation. In April 1863, thousands of hungry people rioted in Richmond, Virginia ( Figure 15.10 ). Many of the rioters were mothers who could not feed their children. The riot ended when President Davis threatened to have Confederate forces open fire on the crowds. \n\n One of the reasons that the Confederacy was so economically devastated was its ill-advised gamble that cotton sales would continue during the war. The government had high hopes that Great Britain and France, which both used cotton as the raw material in their textile mills, would ensure the South’s economic strength—and therefore victory in the war—by continuing to buy. Furthermore, the Confederate government hoped that Great Britain and France would make loans to their new nation in order to ensure the continued flow of raw materials. These hopes were never realized. Great Britain in particular did not wish to risk war with the United States, which would have meant the invasion of Canada. The United States was also a major source of grain for Britain and an important purchaser of British goods. Furthermore, the blockade made Southern trade with Europe difficult. Instead, Great Britain, the major consumer of American cotton, found alternate sources in India and Egypt, leaving the South without the income or alliance it had anticipated. \n\n Dissent within the Confederacy also affected the South’s ability to fight the war. Confederate politicians disagreed over the amount of power that the central government should be allowed to exercise. Many states’ rights advocates, who favored a weak central government and supported the sovereignty of individual states, resented President Davis’s efforts to conscript troops, impose taxation to pay for the war, and requisition necessary resources. Governors in the Confederate states often proved reluctant to provide supplies or troops for the use of the Confederate government. Even Jefferson Davis’s vice president Alexander Stephens opposed conscription, the seizure of enslaved property to work for the Confederacy, and suspension of habeas corpus. Class divisions also divided Confederates. Poor White people resented the ability of wealthy slaveholders to excuse themselves from military service. Racial tensions plagued the South as well. On those occasions when free Black people volunteered to serve in the Confederate army, they were turned away, and enslaved African Americans were regarded with fear and suspicion, as White people whispered among themselves about the possibility of insurrections by enslaved people. \n\n Union Mobilization \n\n Mobilization for war proved to be easier in the North than it was in the South. During the war, the federal government in Washington, DC, like its Southern counterpart, undertook a wide range of efforts to ensure its victory over the Confederacy. To fund the war effort and finance the expansion of Union infrastructure, Republicans in Congress drastically expanded government activism, impacting citizens’ everyday lives through measures such as new types of taxation. The government also contracted with major suppliers of food, weapons, and other needed materials. Virtually every sector of the Northern economy became linked to the war effort. \n\n In keeping with their longstanding objective of keeping slavery out of the newly settled western territories, the Republicans in Congress (the dominant party) passed several measures in 1862. First, the Homestead Act provided generous inducements for Northerners to relocate and farm in the West. Settlers could lay claim to 160 acres of federal land by residing on the property for five years and improving it. The act not only motivated free-labor farmers to move west, but it also aimed to increase agricultural output for the war effort. The federal government also turned its attention to creating a transcontinental railroad to facilitate the movement of people and goods across the country. Congress chartered two companies, the Union Pacific and the Central Pacific, and provided generous funds for these two businesses to connect the country by rail. \n\n The Republican emphasis on free labor, rather than enslaved labor, also influenced the 1862 Land Grant College Act, commonly known as the Morrill Act after its author, Vermont Republican senator Justin Smith Morrill. The measure provided for the creation of agricultural colleges, funded through federal grants, to teach the latest agricultural techniques. Each state in the Union would be granted thirty thousand acres of federal land for the use of these institutions of higher education. \n\n Congress paid for the war using several strategies. They levied a tax on the income of the wealthy, as well as a tax on all inheritances. They also put high tariffs in place. Finally, they passed two National Bank Acts, one in 1863 and one in 1864, calling on the U.S. Treasury to issue war bonds and on Union banks to buy the bonds. A Union campaign to convince individuals to buy the bonds helped increase sales. The Republicans also passed the Legal Tender Act of 1862, calling for paper money—known as greenbacks —to be printed Figure 15.11 ). Some $150 million worth of greenbacks became legal tender, and the Northern economy boomed, although high inflation also resulted. \n\n Like the Confederacy, the Union turned to conscription to provide the troops needed for the war. In March 1863, Congress passed the Enrollment Act, requiring all unmarried men between the ages of twenty and twenty-five, and all married men between the ages of thirty-five and forty-five—including immigrants who had filed for citizenship—to register with the Union to fight in the Civil War. All who registered were subject to military service, and draftees were selected by a lottery system ( Figure 15.12 ). As in the South, a loophole in the law allowed individuals to hire substitutes if they could afford it. Others could avoid enlistment by paying $300 to the federal government. In keeping with the Supreme Court decision in Dred Scott v. Sandford , African Americans were not citizens and were therefore exempt from the draft. \n\n Like the Confederacy, the Union also took the step of suspending habeas corpus rights, so those suspected of pro-Confederate sympathies could be arrested and held without being given the reason. Lincoln had selectively suspended the writ of habeas corpus in the slave state of Maryland, home to many Confederate sympathizers, in 1861 and 1862, in an effort to ensure that the Union capital would be safe. In March 1863, he signed into law the Habeas Corpus Suspension Act, giving him the power to detain suspected Confederate operatives throughout the Union. The Lincoln administration also closed down three hundred newspapers as a national security measure during the war. \n\n In both the North and the South, the Civil War dramatically increased the power of the belligerent governments. Breaking all past precedents in American history, both the Confederacy and the Union employed the power of their central governments to mobilize resources and citizens. \n\n Women’s Mobilization \n\n As men on both sides mobilized for the war, so did women. In both the North and the South, women were forced to take over farms and businesses abandoned by their husbands as they left for war. Women organized themselves into ladies’ aid societies to sew uniforms, knit socks, and raise money to purchase necessities for the troops. In the South, women took wounded soldiers into their homes to nurse. In the North, women volunteered for the United States Sanitary Commission, which formed in June 1861. They inspected military camps with the goal of improving cleanliness and reducing the number of soldiers who died from disease, the most common cause of death in the war. They also raised money to buy medical supplies and helped with the injured. Other women found jobs in the Union army as cooks and laundresses. Thousands volunteered to care for the sick and wounded in response to a call by reformer Dorothea Dix, who was placed in charge of the Union army’s nurses. According to rumor, Dix sought respectable women over the age of thirty who were “plain almost to repulsion in dress” and thus could be trusted not to form romantic liaisons with soldiers. Women on both sides also acted as spies and, disguised as men, engaged in combat. \n\n EMANCIPATION \n\n Early in the war, President Lincoln approached the issue of slavery cautiously. While he disapproved of slavery personally, he did not believe that he had the authority to abolish it. Furthermore, he feared that making the abolition of slavery an objective of the war would cause the border slave states to join the Confederacy. His one objective in 1861 and 1862 was to restore the Union. \n\n Defining American Lincoln’s Evolving Thoughts on Slavery President Lincoln wrote the following letter to newspaper editor Horace Greeley on August 22, 1862. In it, Lincoln states his position on slavery, which is notable for being a middle-of-the-road stance. Lincoln’s later public speeches on the issue take the more strident antislavery tone for which he is remembered. \n\n I would save the Union. I would save it the shortest way under the Constitution. The sooner the national authority can be restored the nearer the Union will be “the Union as it was.” If there be those who would not save the Union unless they could at the same time save Slavery, I do not agree with them. If there be those who would not save the Union unless they could at the same time destroy Slavery, I do not agree with them. My paramount object in this struggle is to save the Union, and is not either to save or destroy Slavery. If I could save the Union without freeing any slave, I would do it, and if I could save it by freeing all the slaves, I would do it, and if I could save it by freeing some and leaving others alone, I would also do that. What I do about Slavery and the colored race, I do because I believe it helps to save this Union, and what I forbear, I forbear because I do not believe it would help to save the Union. I shall do less whenever I shall believe what I am doing hurts the cause, and I shall do more whenever I shall believe doing more will help the cause. I shall try to correct errors when shown to be errors; and I shall adopt new views so fast as they shall appear to be true views. I have here stated my purpose according to my view of official duty, and I intend no modification of my oft-expressed personal wish that all men, everywhere, could be free. Yours, A. LINCOLN. \n\n How would you characterize Lincoln’s public position in August 1862? What was he prepared to do for enslaved people, and under what conditions? \n\n Since the beginning of the war, thousands of enslaved people had fled to the safety of Union lines. In May 1861, Union general Benjamin Butler and others labeled these refugees from slavery contrabands . Butler reasoned that since Southern states had left the United States, he was not obliged to follow federal fugitive slave laws. Escaped enslaved people who made it through the Union lines were shielded by the U.S. military and not returned to slavery. The intent was not only to assist them but also to deprive the South of a valuable source of manpower. \n\n Congress began to define the status of formerly enslaved people in 1861 and 1862. In August 1861, legislators approved the Confiscation Act of 1861, empowering the Union to seize property, including the enslaved, used by the Confederacy. The Republican-dominated Congress took additional steps, abolishing slavery in Washington, DC, in April 1862. Congress passed a second Confiscation Act in July 1862, which extended freedom to escaped enslaved people and those captured by Union armies. In that month, Congress also addressed the issue of slavery in the West, banning the practice in the territories. This federal law made the 1846 Wilmot Proviso and the dreams of the Free-Soil Party a reality. However, even as the Union government took steps to aid enslaved individuals and to limit the practice of slavery, it passed no measure to address the institution of slavery as a whole. \n\n Lincoln moved slowly and cautiously on the issue of abolition. His primary concern was the cohesion of the Union and the bringing of the Southern states back into the fold. However, as the war dragged on and many thousands of contrabands made their way north, Republicans in Congress continued to call for the end of slavery. Throughout his political career, Lincoln’s plans for formerly enslaved people had been to send them to Liberia. As late as August 1862, he had hoped to interest African Americans in building a colony for formerly enslaved people in Central America, an idea that found favor neither with Black leaders nor with abolitionists, and thus was abandoned by Lincoln. Responding to Congressional demands for an end to slavery, Lincoln presented an ultimatum to the Confederates on September 22, 1862, shortly after the Confederate retreat at Antietam. He gave the Confederate states until January 1, 1863, to rejoin the Union. If they did, slavery would continue in the slave states. If they refused to rejoin, however, the war would continue and all of the enslaved would be freed at its conclusion. The Confederacy took no action. It had committed itself to maintaining its independence and had no interest in the president’s ultimatum. \n\n On January 1, 1863, Lincoln made good on his promise and signed the Emancipation Proclamation . It stated “That on the first day of January, in the year of our Lord one thousand eight hundred and sixty-three, all persons held as slaves within any State or designated part of a State, the people whereof shall then be in rebellion against the United States, shall be then, thenceforward, and forever free.” The proclamation did not immediately free the those enslaved in the Confederate states. Although they were in rebellion against the United States, the lack of the Union army’s presence in such areas meant that the president’s directive could not be enforced. The proclamation also did not free those enslaved in the border states, because these states were not, by definition, in rebellion. Lincoln relied on his powers as commander-in-chief in issuing the Emancipation Proclamation. He knew the proclamation could be easily challenged in court, but by excluding the territories still outside his control, slaveholders and slave governments could not sue him. Moreover, slave states in the Union, such as Kentucky, could not sue because the proclamation did not apply to them. Slaveholders in Kentucky knew full well that if the institution were abolished throughout the South, it would not survive in a handful of border territories. Despite the limits of the proclamation, Lincoln dramatically shifted the objective of the war increasingly toward ending slavery. The Emancipation Proclamation became a monumental step forward on the road to changing the character of the United States. \n\n The proclamation generated quick and dramatic reactions. The news created euphoria among enslaved people, as it signaled the eventual end of their bondage. Predictably, Confederate leaders raged against the proclamation, reinforcing their commitment to fight to maintain slavery, the foundation of the Confederacy. In the North, opinions split widely on the issue. Abolitionists praised Lincoln’s actions, which they saw as the fulfillment of their long campaign to strike down an immoral institution. But other Northerners, especially Irish, working-class, urban dwellers loyal to the Democratic Party and others with racist beliefs, hated the new goal of emancipation and found the idea of freed slaves repugnant. At its core, much of this racism had an economic foundation: Many Northerners feared competing with emancipated people for scarce jobs. \n\n In New York City, the Emancipation Proclamation, combined with unhappiness over the Union draft, which began in March 1863, fanned the flames of White racism. Many New Yorkers supported the Confederacy for business reasons, and, in 1861, the city’s mayor actually suggested that New York City leave the Union. On July 13, 1863, two days after the first draft lottery took place, this racial hatred erupted into violence. A volunteer fire company whose commander had been drafted initiated a riot, and the violence spread quickly across the city. The rioters chose targets associated either with the Union army or with African Americans. An armory was destroyed, as was a Brooks Brothers’ store, which supplied uniforms to the army. White mobs attacked and killed Black New Yorkers and destroyed an African American orphanage ( Figure 15.13 ). On the fourth day of the riots, federal troops dispatched by Lincoln arrived in the city and ended the violence. Millions of dollars in property had been destroyed. More than one hundred people died, approximately one thousand were left injured, and about one-fifth of the city’s African American population fled New York in fear. \n\n UNION ADVANCES \n\n The war in the west continued in favor of the North in 1863. At the start of the year, Union forces controlled much of the Mississippi River. In the spring and summer of 1862, they had captured New Orleans—the most important port in the Confederacy, through which cotton harvested from all the Southern states was exported—and Memphis. Grant had then attempted to capture Vicksburg, Mississippi, a commercial center on the bluffs above the Mississippi River. Once Vicksburg fell, the Union would have won complete control over the river. A military bombardment that summer failed to force a Confederate surrender. An assault by land forces also failed in December 1862. \n\n In April 1863, the Union began a final attempt to capture Vicksburg. On July 3, after more than a month of a Union siege, during which Vicksburg’s residents hid in caves to protect themselves from the bombardment and ate their pets to stay alive, Grant finally achieved his objective. The trapped Confederate forces surrendered. The Union had succeeded in capturing Vicksburg and splitting the Confederacy ( Figure 15.14 ). This victory inflicted a serious blow to the Southern war effort. \n\n As Grant and his forces pounded Vicksburg, Confederate strategists, at the urging of General Lee, who had defeated a larger Union army at Chancellorsville, Virginia, in May 1863, decided on a bold plan to invade the North. Leaders hoped this invasion would force the Union to send troops engaged in the Vicksburg campaign east, thus weakening their power over the Mississippi. Further, they hoped the aggressive action of pushing north would weaken the Union’s resolve to fight. Lee also hoped that a significant Confederate victory in the North would convince Great Britain and France to extend support to Jefferson Davis’s government and encourage the North to negotiate peace. \n\n Beginning in June 1863, General Lee began to move the Army of Northern Virginia north through Maryland. The Union army—the Army of the Potomac—traveled east to end up alongside the Confederate forces. The two armies met at Gettysburg, Pennsylvania, where Confederate forces had gone to secure supplies. The resulting battle lasted three days, July 1–3 ( Figure 15.15 ) and remains the biggest and costliest battle ever fought in North America. The climax of the Battle of Gettysburg occurred on the third day. In the morning, after a fight lasting several hours, Union forces fought back a Confederate attack on Culp’s Hill, one of the Union’s defensive positions. To regain a perceived advantage and secure victory, Lee ordered a frontal assault, known as Pickett’s Charge (for Confederate general George Pickett), against the center of the Union lines on Cemetery Ridge. Approximately fifteen thousand Confederate soldiers took part, and more than half lost their lives, as they advanced nearly a mile across an open field to attack the entrenched Union forces. In all, more than a third of the Army of Northern Virginia had been lost, and on the evening of July 4, Lee and his men slipped away in the rain. General George Meade did not pursue them. Both sides suffered staggering losses. Total casualties numbered around twenty-three thousand for the Union and some twenty-eight thousand among the Confederates. With its defeats at Gettysburg and Vicksburg, both on the same day, the Confederacy lost its momentum. The tide had turned in favor of the Union in both the east and the west. \n\n Following the Battle of Gettysburg, the bodies of those who had fallen were hastily buried. Attorney David Wills, a resident of Gettysburg, campaigned for the creation of a national cemetery on the site of the battlefield, and the governor of Pennsylvania tasked him with creating it. President Lincoln was invited to attend the cemetery’s dedication. After the featured orator had delivered a two-hour speech, Lincoln addressed the crowd for several minutes. In his speech, known as the Gettysburg Address , which he had finished writing while a guest in David Wills’ home the day before the dedication, Lincoln invoked the Founding Fathers and the spirit of the American Revolution. The Union soldiers who had died at Gettysburg, he proclaimed, had died not only to preserve the Union, but also to guarantee freedom and equality for all. \n\n Defining American Lincoln’s Gettysburg Address Several months after the battle at Gettysburg, Lincoln traveled to Pennsylvania and, speaking to an audience at the dedication of the new Soldiers’ National Ceremony near the site of the battle, he delivered his now-famous Gettysburg Address to commemorate the turning point of the war and the soldiers whose sacrifices had made it possible. The two-minute speech was politely received at the time, although press reactions split along party lines. Upon receiving a letter of congratulations from Massachusetts politician and orator William Everett, whose speech at the ceremony had lasted for two hours, Lincoln said he was glad to know that his brief address, now virtually immortal, was not “a total failure.” \n\n Four score and seven years ago our fathers brought forth on this continent, a new nation, conceived in Liberty, and dedicated to the proposition that all men are created equal. \n\n Now we are engaged in a great civil war, testing whether that nation, or any nation so conceived and so dedicated, can long endure. We are met on a great battle-field of that war. We have come to dedicate a portion of that field, as a final resting place for those who here gave their lives that that nation might live. It is altogether fitting and proper that we should do this. \n\n It is for us the living . . . to be here dedicated to the great task remaining before us—that from these honored dead we take increased devotion to that cause for which they gave the last full measure of devotion—that we here highly resolve that these dead shall not have died in vain—that this nation, under God, shall have a new birth of freedom—and that government of the people, by the people, for the people, shall not perish from the earth.\n\n —Abraham Lincoln, Gettysburg Address, November 19, 1863 \n\n What did Lincoln mean by “a new birth of freedom”? What did he mean when he said “a government of the people, by the people, for the people, shall not perish from the earth”? \n 15.4 The Union Triumphant Learning Objectives By the end of this section, you will be able to: \n\n Describe the reasons why many Americans doubted that Abraham Lincoln would be reelected \n\n Explain how the Union forces overpowered the Confederacy \n\n By the outset of 1864, after three years of war, the Union had mobilized its resources for the ongoing struggle on a massive scale. The government had overseen the construction of new railroad lines and for the first time used standardized rail tracks that allowed the North to move men and materials with greater ease. The North’s economy had shifted to a wartime model. The Confederacy also mobilized, perhaps to a greater degree than the Union, its efforts to secure independence and maintain slavery. Yet the Confederacy experienced ever-greater hardships after years of war. Without the population of the North, it faced a shortage of manpower. The lack of industry, compared to the North, undercut the ability to sustain and wage war. Rampant inflation as well as food shortages in the South lowered morale. \n\n THE RELATIONSHIP WITH EUROPE \n\n From the beginning of the war, the Confederacy placed great hope in being recognized and supported by Great Britain and France. European intervention in the conflict remained a strong possibility, but when it did occur, it was not in a way anticipated by either the Confederacy or the Union. \n\n Napoleon III of France believed the Civil War presented an opportunity for him to restore a French empire in the Americas. With the United States preoccupied, the time seemed ripe for action. Napoleon’s target was Mexico, and in 1861, a large French fleet took Veracruz. The French then moved to capture Mexico City, but the advance came to an end when Mexican forces defeated the French in 1862. Despite this setback, France eventually did conquer Mexico, establishing a regime that lasted until 1867. Rather than coming to the aid of the Confederacy, France used the Civil War to provide a pretext for efforts to reestablish its former eighteenth-century colonial holdings. \n\n Still, the Confederacy had great confidence that it would find an ally in Great Britain despite the antislavery sentiment there. Southerners hoped Britain’s dependence on cotton for its textile mills would keep the country on their side. The fact that the British proved willing to build and sell ironclad ships intended to smash through the Union naval blockade further raised Southern hopes. The Confederacy purchased two of these armored blockade runners, the CSS Florida and the CSS Alabama . Both were destroyed during the war. \n\n The Confederacy’s staunch commitment to slavery eventually worked against British recognition and support, since Great Britain had abolished slavery in 1833. The 1863 Emancipation Proclamation ended any doubts the British had about the goals of the Union cause. In the aftermath of the proclamation, many in Great Britain cheered for a Union victory. Ultimately, Great Britain, like France, disappointed the Confederacy’s hope of an alliance, leaving the outnumbered and out-resourced states that had left the Union to fend for themselves. \n\n AFRICAN AMERICAN SOLDIERS \n\n At the beginning of the war, in 1861 and 1862, Union forces had used contrabands, or escaped enslaved people, for manual labor. The Emancipation Proclamation, however, led to the enrollment of African American men as Union soldiers. Huge numbers of formerly enslaved as well as free Black people from the North enlisted, and by the end of the war in 1865, their numbers had swelled to over 190,000. Racism among White people in the Union army ran deep, however, fueling the belief that Black soldiers could never be effective or trustworthy. The Union also feared for the fate of captured Black soldiers. Although many Black soldiers saw combat duty, these factors affected the types of tasks assigned to them. Many Black regiments were limited to hauling supplies, serving as cooks, digging trenches, and doing other types of labor, rather than serving on the battlefield ( Figure 15.16 ). \n\n African American soldiers also received lower wages than their White counterparts: ten dollars per month, with three dollars deducted for clothing. White soldiers, in contrast, received thirteen dollars monthly, with no deductions. Abolitionists and their Republican supporters in Congress worked to correct this discriminatory practice, and in 1864, Black soldiers began to receive the same pay as White soldiers plus retroactive pay to 1863 ( Figure 15.17 ). \n\n For their part, African American soldiers welcomed the opportunity to prove themselves. Some 85 percent were formerly enslaved people who were fighting for the liberation of all of the enslaved and the end of slavery. When given the opportunity to serve, many Black regiments did so heroically. One such regiment, the Fifty-Fourth Regiment of Massachusetts Volunteers, distinguished itself at Fort Wagner in South Carolina by fighting valiantly against an entrenched Confederate position. They willingly gave their lives for the cause. \n\n The Confederacy, not surprisingly, showed no mercy to African American troops. In April 1864, Southern forces attempted to take Fort Pillow in Tennessee from the Union forces that had captured it in 1862. Confederate troops under Major General Nathan Bedford Forrest, the future founder of the Ku Klux Klan, quickly overran the fort, and the Union defenders surrendered. Instead of taking the African American soldiers prisoner, as they did the White soldiers, the Confederates executed them. The massacre outraged the North, and the Union refused to engage in any future exchanges of prisoners with the Confederacy. \n\n THE CAMPAIGNS OF 1864 AND 1865 \n\n In the final years of the war, the Union continued its efforts on both the eastern and western fronts while bringing the war into the Deep South. Union forces increasingly engaged in total war, not distinguishing between military and civilian targets. They destroyed everything that lay in their path, committed to breaking the will of the Confederacy and forcing an end to the war. General Grant, mastermind of the Vicksburg campaign, took charge of the war effort. He understood the advantage of having large numbers of soldiers at his disposal and recognized that Union soldiers could be replaced, whereas the Confederates, whose smaller population was feeling the strain of the years of war, could not. Grant thus pushed forward relentlessly, despite huge losses of men. In 1864, Grant committed his forces to destroying Lee’s army in Virginia. \n\n In the Virginia campaign, Grant hoped to use his larger army to his advantage. But at the Battle of the Wilderness, fought from May 5 to May 7, Confederate forces stopped Grant’s advance. Rather than retreating, he pushed forward. At the Battle of Spotsylvania on May 8 through 12, Grant again faced determined Confederate resistance, and again his advance was halted. As before, he renewed the Union campaign. At the Battle of Cold Harbor in early June, Grant had between 100,000 and 110,000 soldiers, whereas the Confederates had slightly more than half that number. Again, the Union advance was halted, if only momentarily, as Grant awaited reinforcements. An attack on the Confederate position on June 3 resulted in heavy casualties for the Union, and nine days later, Grant led his army away from Cold Harbor to Petersburg, Virginia, a rail center that supplied Richmond. The immense losses that Grant’s forces suffered severely hurt Union morale. The war seemed unending, and with the tremendous loss of life, many in the North began to question the war and desire peace. Undaunted by the changing opinion in the North and hoping to destroy the Confederate rail network in the Upper South, however, Grant laid siege to Petersburg for nine months. As the months wore on, both sides dug in, creating miles of trenches and gun emplacements. \n\n The other major Union campaigns of 1864 were more successful and gave President Lincoln the advantage that he needed to win reelection in November. In August 1864, the Union navy captured Mobile Bay. General Sherman invaded the Deep South, advancing slowly from Tennessee into Georgia, confronted at every turn by the Confederates, who were commanded by Johnston. When President Davis replaced Johnston with General John B. Hood, the Confederates made a daring but ultimately costly direct attack on the Union army that failed to drive out the invaders. Atlanta fell to Union forces on September 2, 1864. The fall of Atlanta held tremendous significance for the war-weary Union and helped to reverse the North’s sinking morale. In keeping with the logic of total war, Sherman’s forces cut a swath of destruction to Savannah. On Sherman’s March to the Sea , the Union army, seeking to demoralize the South, destroyed everything in its path, despite strict instructions regarding the preservation of civilian property. Although towns were left standing, houses and barns were burned. Homes were looted, food was stolen, crops were destroyed, orchards were burned, and livestock was killed or confiscated. Savannah fell on December 21, 1864—a Christmas gift for Lincoln, Sherman proclaimed. In 1865, Sherman’s forces invaded South Carolina, capturing Charleston and Columbia. In Columbia, the state capital, the Union army burned slaveholders’ homes and destroyed much of the city. From South Carolina, Sherman’s force moved north in an effort to join Grant and destroy Lee’s army. \n\n My Story Dolly Sumner Lunt on Sherman’s March to the Sea The following account is by Dolly Sumner Lunt, a widow who ran her Georgia cotton plantation after the death of her husband. She describes General Sherman’s march to Savannah, where he enacted the policy of total war by burning and plundering the landscape to inhibit the Confederates’ ability to keep fighting. \n\n Alas! little did I think while trying to save my house from plunder and fire that they were forcing my boys [slaves] from home at the point of the bayonet. One, Newton, jumped into bed in his cabin, and declared himself sick. Another crawled under the floor,—a lame boy he was,—but they pulled him out, placed him on a horse, and drove him off. Mid, poor Mid! The last I saw of him, a man had him going around the garden, looking, as I thought, for my sheep, as he was my shepherd. Jack came crying to me, the big tears coursing down his cheeks, saying they were making him go. I said: ‘Stay in my room.’ \n\n But a man followed in, cursing him and threatening to shoot him if he did not go; so poor Jack had to yield. . . . \n\n Sherman himself and a greater portion of his army passed my house that day. All day, as the sad moments rolled on, were they passing not only in front of my house, but from behind; they tore down my garden palings, made a road through my back-yard and lot field, driving their stock and riding through, tearing down my fences and desolating my home—wantonly doing it when there was no necessity for it. . . . \n\n About ten o’clock they had all passed save one, who came in and wanted coffee made, which was done, and he, too, went on. A few minutes elapsed, and two couriers riding rapidly passed back. Then, presently, more soldiers came by, and this ended the passing of Sherman’s army by my place, leaving me poorer by thirty thousand dollars than I was yesterday morning. And a much stronger Rebel! \n\n According to this account, what was the reaction of enslaved people to the arrival of the Union forces? What did the Union forces do with the enslaved? For Lunt, did the strategy of total war work as planned? \n\n THE ELECTION OF 1864 \n\n Despite the military successes for the Union army in 1863, in 1864, Lincoln’s status among many Northern voters plummeted. Citing the suspension of the writ of habeas corpus, many saw him as a dictator, bent on grabbing power while senselessly and uncaringly drafting more young men into combat. Arguably, his greatest liability, however, was the Emancipation Proclamation and the enlistment of African American soldiers. Many Whites in the North found this deeply offensive, since they still believed in racial inequality. The 1863 New York City Draft Riots illustrated the depth of White anger. \n\n Northern Democrats railed against Lincoln and the war. Republicans labeled these vocal opponents of the President Copperheads , a term that many antiwar Democrats accepted. As the anti-Lincoln poster below illustrates, his enemies tried to paint him as an untrustworthy and suspect leader ( Figure 15.18 ). It seemed to most in the North that the Democratic candidate, General George B. McClellan, who did not support abolition and was replaced with another commander by Lincoln, would win the election. \n\n The Republican Party also split over the issue of reelecting Lincoln. Those who found him timid and indecisive, and favored extending full rights to African Americans, as well as completely refashioning the South after its defeat, earned the name Radicals. A moderate faction of Republicans opposed the Radicals. For his part, Lincoln did not align himself with either group. \n\n The tide of the election campaign turned in favor of Lincoln, however, in the fall of 1864. Above all else, Union victories, including the fall of Atlanta in September and General Philip Sheridan’s successes in the Shenandoah Valley of Virginia, bolstered Lincoln’s popularity and his reelection bid. In November 1864, despite earlier forecasts to the contrary, Lincoln was reelected. Lincoln won all but three states—New Jersey and the border states of Delaware and Kentucky. To the chagrin of his opponent, McClellan, even Union army troops voted overwhelmingly for the incumbent President. \n\n THE WAR ENDS \n\n By the spring of 1865, it had become clear to both sides that the Confederacy could not last much longer. Most of its major cities, ports, and industrial centers—Atlanta, Savannah, Charleston, Columbia, Mobile, New Orleans, and Memphis—had been captured. In April 1865, Lee had abandoned both Petersburg and Richmond. His goal in doing so was to unite his depleted army with Confederate forces commanded by General Johnston. Grant effectively cut him off. On April 9, 1865, Lee surrendered to Grant at Appomattox Court House in Virginia ( Figure 15.19 ). By that time, he had fewer than 35,000 soldiers, while Grant had some 100,000. Meanwhile, Sherman’s army proceeded to North Carolina, where General Johnston surrendered on April 19, 1865. The Civil War had come to an end. The war had cost the lives of more than 600,000 soldiers. Many more had been wounded. Thousands of women were left widowed. Children were left without fathers, and many parents were deprived of a source of support in their old age. In some areas, where local volunteer units had marched off to battle, never to return, an entire generation of young women was left without marriage partners. Millions of dollars’ worth of property had been destroyed, and towns and cities were laid to waste. With the conflict finally over, the very difficult work of reconciling North and South and reestablishing the United States lay ahead. "}}},{"rowIdx":189,"cells":{"bname":{"kind":"string","value":"microbiology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":" Summary 4.1 Prokaryote Habitats, Relationships, and Microbiomes \n\n Prokaryotes are unicellular microorganisms whose cells have no nucleus. \n\n Prokaryotes can be found everywhere on our planet, even in the most extreme environments. \n\n Prokaryotes are very flexible metabolically, so they are able to adjust their feeding to the available natural resources. \n\n Prokaryotes live in communities that interact among themselves and with large organisms that they use as hosts (including humans). \n\n The totality of forms of prokaryotes (particularly bacteria) living on the human body is called the human microbiome, which varies between regions of the body and individuals, and changes over time. \n\n The totality of forms of prokaryotes (particularly bacteria) living in a certain region of the human body (e.g., mouth, throat, gut, eye, vagina) is called the microbiota of this region. \n\n Prokaryotes are classified into domains Archaea and Bacteria. \n\n In recent years, the traditional approaches to classification of prokaryotes have been supplemented by approaches based on molecular genetics. \n\n 4.2 Proteobacteria \n\n Proteobacteria is a phylum of gram-negative bacteria discovered by Carl Woese in the 1980s based on nucleotide sequence homology. \n\n Proteobacteria are further classified into the classes alpha-, beta-, gamma-, delta- and epsilonproteobacteria, each class having separate orders, families, genera, and species. \n\n Alphaproteobacteria include several obligate and facultative intracellular pathogens, including the rickettsias. Some Alphaproteobacteria can convert atmospheric nitrogen to nitrites, making nitrogen usable for other forms of life. \n\n Betaproteobacteria are a diverse group of bacteria that include human pathogens of the genus Neisseria and the species Bordetella pertussis . \n\n Gammaproteobacteria are the largest and the most diverse group of Proteobacteria. Many are human pathogens that are aerobes or facultative anaerobes. Some Gammaproteobacteria are enteric bacteria that may be coliform or noncoliform. Escherichia coli , a member of Gammaproteobacteria, is perhaps the most studied bacterium. \n\n Deltaproteobacteria make up a small group able to reduce sulfate or elemental sulfur. Some are scavengers and form myxospores, with multicellular fruiting bodies. \n\n Epsilonproteobacteria make up the smallest group of Proteobacteria. The genera Campylobacter and Helicobacter are human pathogens. \n\n 4.3 Nonproteobacteria Gram-Negative Bacteria and Phototrophic Bacteria \n\n Gram-negative nonproteobacteria include the taxa spirochetes ; the Chlamydia , Cytophaga , Fusobacterium , Bacteroides group; Planctomycetes; and many representatives of phototrophic bacteria. \n\n Spirochetes are motile, spiral bacteria with a long, narrow body; they are difficult or impossible to culture. \n\n Several genera of spirochetes contain human pathogens that cause such diseases as syphilis and Lyme disease. \n\n Cytophaga , Fusobacterium , and Bacteroides are classified together as a phylum called the CFB group . They are rod-shaped anaerobic organoheterotrophs and avid fermenters. Cytophaga are aquatic bacteria with the gliding motility. Fusobacteria inhabit the human mouth and may cause severe infectious diseases. Bacteroides are present in vast numbers in the human gut, most of them being mutualistic but some are pathogenic. \n\n Planctomycetes are aquatic bacteria that reproduce by budding; they may form large colonies, and develop a holdfast. \n\n Phototrophic bacteria are not a taxon but, rather, a group categorized by their ability to use the energy of sunlight. They include Proteobacteria and nonproteobacteria, as well as sulfur and nonsulfur bacteria colored purple or green. \n\n Sulfur bacteria perform anoxygenic photosynthesis, using sulfur compounds as donors of electrons, whereas nonsulfur bacteria use organic compounds (succinate, malate) as donors of electrons. \n\n Some phototrophic bacteria are able to fix nitrogen, providing the usable forms of nitrogen to other organisms. \n\n Cyanobacteria are oxygen-producing bacteria thought to have played a critical role in the forming of the earth’s atmosphere. \n\n 4.4 Gram-Positive Bacteria \n\n Gram-positive bacteria are a very large and diverse group of microorganisms. Understanding their taxonomy and knowing their unique features is important for diagnostics and treatment of infectious diseases. \n\n Gram-positive bacteria are classified into high G+C gram-positive and low G+C gram-positive bacteria, based on the prevalence of guanine and cytosine nucleotides in their genome \n\n Actinobacteria is the taxonomic name of the class of high G+C gram-positive bacteria. This class includes the genera Actinomyces, Arthrobacter, Corynebacterium, Frankia, Gardnerella, Micrococcus, Mycobacterium, Nocardia , Propionibacterium, Rhodococcus, and Streptomyces . Some representatives of these genera are used in industry; others are human or animal pathogens. \n\n Examples of high G+C gram-positive bacteria that are human pathogens include Mycobacterium tuberculosis , which causes tuberculosis; M. leprae , which causes leprosy (Hansen’s disease); and Corynebacterium diphtheriae , which causes diphtheria. \n\n Clostridia spp. are low G+C gram-positive bacteria that are generally obligate anaerobes and can form endospores. Pathogens in this genus include C. perfringens (gas gangrene), C. tetani (tetanus), and C. botulinum (botulism). \n\n Lactobacillales include the genera Enterococcus , Lactobacillus , Leuconostoc , and Streptococcus. Streptococcus is responsible for many human diseases, including pharyngitis (strep throat), scarlet fever, rheumatic fever, glomerulonephritis, pneumonia, and other respiratory infections. \n\n Bacilli is a taxonomic class of low G+C gram-positive bacteria that include rod-shaped and coccus-shaped species, including the genera Bacillus and Staphylococcus . B. anthracis causes anthrax, B. cereus may cause opportunistic infections of the gastrointestinal tract, and S. aureus strains can cause a wide range of infections and diseases, many of which are highly resistant to antibiotics. \n\n Mycoplasma spp. are very small, pleomorphic low G+C gram-positive bacteria that lack cell walls. M. pneumoniae causes atypical pneumonia. \n\n 4.5 Deeply Branching Bacteria \n\n Deeply branching bacteria are phylogenetically the most ancient forms of life, being the closest to the last universal common ancestor. \n\n Deeply branching bacteria include many species that thrive in extreme environments that are thought to resemble conditions on earth billions of years ago \n\n Deeply branching bacteria are important for our understanding of evolution; some of them are used in industry \n\n 4.6 Archaea \n\n Archaea are unicellular, prokaryotic microorganisms that differ from bacteria in their genetics, biochemistry, and ecology. \n\n Some archaea are extremophiles, living in environments with extremely high or low temperatures, or extreme salinity. \n\n Only archaea are known to produce methane. Methane-producing archaea are called methanogens . \n\n Halophilic archaea prefer a concentration of salt close to saturation and perform photosynthesis using bacteriorhodopsin. \n\n Some archaea, based on fossil evidence, are among the oldest organisms on earth. \n\n Archaea do not live in great numbers in human microbiomes and are not known to cause disease. "},"intro":{"kind":"string","value":" Chapter Outline 4.1 Prokaryote Habitats, Relationships, and Microbiomes 4.2 Proteobacteria 4.3 Nonproteobacteria Gram-Negative Bacteria and Phototrophic Bacteria 4.4 Gram-Positive Bacteria 4.5 Deeply Branching Bacteria 4.6 Archaea Introduction Scientists have studied prokaryotes for centuries, but it wasn’t until 1966 that scientist Thomas Brock (1926–) discovered that certain bacteria can live in boiling water. This led many to wonder whether prokaryotes may also live in other extreme environments, such as at the bottom of the ocean, at high altitudes, or inside volcanoes, or even on other planets. Prokaryotes have an important role in changing, shaping, and sustaining the entire biosphere. They can produce proteins and other substances used by molecular biologists in basic research and in medicine and industry. For example, the bacterium Shewanella lives in the deep sea, where oxygen is scarce. It grows long appendages, which have special sensors used to seek the limited oxygen in its environment. It can also digest toxic waste and generate electricity. Other species of prokaryotes can produce more oxygen than the entire Amazon rainforest, while still others supply plants, animals, and humans with usable forms of nitrogen; and inhabit our body, protecting us from harmful microorganisms and producing some vitally important substances. This chapter will examine the diversity, structure, and function of prokaryotes. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"All living organisms are classified into three domains of life : Archaea , Bacteria , and Eukarya . In this chapter , we will focus on the domains Archaea and Bacteria . <hl> Archaea and bacteria are unicellular prokaryotic organisms . <hl> <hl> Unlike eukaryotes , they have no nuclei or any other membrane-bound organelles . <hl>","hl_sentences":"Archaea and bacteria are unicellular prokaryotic organisms . Unlike eukaryotes , they have no nuclei or any other membrane-bound organelles .","question":{"cloze_format":"The term prokaryotes refers to ___.","normal_format":"The term prokaryotes refers to which of the following?","question_choices":["very small organisms","unicellular organisms that have no nucleus","multicellular organisms","cells that resemble animal cells more than plant cells"],"question_id":"fs-id1172100562431","question_text":"The term prokaryotes refers to which of the following?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"<hl> One important achievement of the Human Microbiome Project is establishing the first reference database on microorganisms living in and on the human body . <hl> Many of the microbes in the microbiome are beneficial , but some are not . It was found , somewhat unexpectedly , that all of us have some serious microbial pathogens in our microbiota . For example , the conjunctiva of the human eye contains 24 genera of bacteria and numerous pathogenic species . 7 A healthy human mouth contains a number of species of the genus Streptococcus , including pathogenic species S . pyogenes and S . pneumoniae . 8 This raises the question of why certain prokaryotic organisms exist commensally in certain individuals but act as deadly pathogens in others . Also unexpected was the number of organisms that had never been cultured . For example , in one metagenomic study of the human gut microbiota , 174 new species of bacteria were identified . 9 7 Q . Dong et al . “ Diversity of Bacteria at Healthy Human Conjunctiva . ” Investigative Ophthalmology & Visual Science 52 no . 8 ( 2011 ): 5408 – 5413 . 8 F . E . Dewhirst et al . “ The Human Oral Microbiome . ” Journal of Bacteriology 192 no . 19 ( 2010 ): 5002 – 5017 . 9 J . C . Lagier et al . “ Microbial Culturomics : Paradigm Shift in the Human Gut Microbiome Study . ” Clinical Microbiology and Infection 18 no . 12 ( 2012 ): 1185 – 1193 . Scientists have coined the term microbiome to refer to all prokaryotic and eukaryotic microorganisms and their genetic material that are associated with a certain organism or environment . <hl> Within the human microbiome , there are resident microbiota and transient microbiota . <hl> <hl> The resident microbiota consists of microorganisms that constantly live in or on our bodies . <hl> <hl> The term transient microbiota refers to microorganisms that are only temporarily found in the human body , and these may include pathogenic microorganisms . <hl> Hygiene and diet can alter both the resident and transient microbiota . The resident microbiota is amazingly diverse , not only in terms of the variety of species but also in terms of the preference of different microorganisms for different areas of the human body . For example , in the human mouth , there are thousands of commensal or mutualistic species of bacteria . Some of these bacteria prefer to inhabit the surface of the tongue , whereas others prefer the internal surface of the cheeks , and yet others prefer the front or back teeth or gums . The inner surface of the cheek has the least diverse microbiota because of its exposure to oxygen . By contrast , the crypts of the tongue and the spaces between teeth are two sites with limited oxygen exposure , so these sites have more diverse microbiota , including bacteria living in the absence of oxygen ( e . g . , Bacteroides , Fusobacterium ) . Differences in the oral microbiota between randomly chosen human individuals are also significant . Studies have shown , for example , that the prevalence of such bacteria as Streptococcus , Haemophilus , Neisseria , and others was dramatically different when compared between individuals . 4 4 E . M . Bik et al . “ Bacterial Diversity in the Oral Cavity of 10 Healthy Individuals . ” The ISME Journal 4 no . 8 ( 2010 ): 962 – 974 .","hl_sentences":"One important achievement of the Human Microbiome Project is establishing the first reference database on microorganisms living in and on the human body . Within the human microbiome , there are resident microbiota and transient microbiota . The resident microbiota consists of microorganisms that constantly live in or on our bodies . The term transient microbiota refers to microorganisms that are only temporarily found in the human body , and these may include pathogenic microorganisms .","question":{"cloze_format":"The term microbiota refers to ___ .","normal_format":"The term microbiota refers to which of the following?","question_choices":["all microorganisms of the same species","all of the microorganisms involved in a symbiotic relationship","all microorganisms in a certain region of the human body","all microorganisms in a certain geographic region"],"question_id":"fs-id1172100771337","question_text":"The term microbiota refers to which of the following?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"When two species benefit from each other , the symbiosis is called mutualism ( or syntropy , or crossfeeding ) . For example , humans have a mutualistic relationship with the bacterium Bacteroides thetaiotaomicron , which lives in the intestinal tract . Bacteroides thetaiotaomicron digests complex polysaccharide plant materials that human digestive enzymes cannot break down , converting them into monosaccharides that can be absorbed by human cells . Humans also have a mutualistic relationship with certain strains of Escherichia coli , another bacterium found in the gut . E . coli relies on intestinal contents for nutrients , and humans derive certain vitamins from E . coli , particularly vitamin K , which is required for the formation of blood clotting factors . ( This is only true for some strains of E . coli , however . Other strains are pathogenic and do not have a mutualistic relationship with humans . ) A type of symbiosis in which one population harms another but remains unaffected itself is called amensalism . In the case of bacteria , some amensalist species produce bactericidal substances that kill other species of bacteria . The microbiota of the skin is composed of a variety of bacterial species , including Staphylococcus epidermidis and Propionibacterium acnes . Although both species have the potential to cause infectious diseases when protective barriers are breached , they both produce a variety of antibacterial bacteriocins and bacteriocin-like compounds . S . epidermidis and P . acnes are unaffected by the bacteriocins and bacteriocin-like compounds they produce , but these compounds can target and kill other potential pathogens . <hl> In another type of symbiosis , called commensalism , one organism benefits while the other is unaffected . <hl> This occurs when the bacterium Staphylococcus epidermidis uses the dead cells of the human skin as nutrients . Billions of these bacteria live on our skin , but in most cases ( especially when our immune system is healthy ) , we do not react to them in any way . S . epidermidis provides an excellent example of how the classifications of symbiotic relationships are not always distinct . One could also consider the symbiotic relationship of S . epidermidis with humans as mutualism . Humans provide a food source of dead skin cells to the bacterium , and in turn the production of bacteriocin can provide an defense against potential pathogens . If neither of the symbiotic organisms is affected in any way , we call this type of symbiosis neutralism . An example of neutralism is the coexistence of metabolically active ( vegetating ) bacteria and endospores ( dormant , metabolically passive bacteria ) . For example , the bacterium Bacillus anthracis typically forms endospores in soil when conditions are unfavorable . If the soil is warmed and enriched with nutrients , some B . anthracis endospores germinate and remain in symbiosis with other species of endospores that have not germinated . A type of symbiosis in which one organism benefits while harming the other is called parasitism . The relationship between humans and many pathogenic prokaryotes can be characterized as parasitic because these organisms invade the body , producing toxic substances or infectious diseases that cause harm . Diseases such as tetanus , diphtheria , pertussis , tuberculosis , and leprosy all arise from interactions between bacteria and humans . <hl> Prokaryotes live in a community , or a group of interacting populations of organisms . <hl> A population is a group of individual organisms belonging to the same biological species and limited to a certain geographic area . Populations can have cooperative interactions , which benefit the populations , or competitive interactions , in which one population competes with another for resources . The study of these interactions between microbial populations and their environment is called microbial ecology . <hl> Any interaction between different species that are associated with each other within a community is called symbiosis . <hl> Such interactions fall along a continuum between opposition and cooperation . Interactions in a symbiotic relationship may be beneficial or harmful , or have no effect on one or both of the species involved . Table 4.1 summarizes the main types of symbiotic interactions among prokaryotes .","hl_sentences":"In another type of symbiosis , called commensalism , one organism benefits while the other is unaffected . Prokaryotes live in a community , or a group of interacting populations of organisms . Any interaction between different species that are associated with each other within a community is called symbiosis .","question":{"cloze_format":"___ refers to the type of interaction between two prokaryotic populations in which one population benefits and the other is not affected.","normal_format":"Which of the following refers to the type of interaction between two prokaryotic populations in which one population benefits and the other is not affected?","question_choices":["mutualism","commensalism","parasitism","neutralism"],"question_id":"fs-id1172098549514","question_text":"Which of the following refers to the type of interaction between two prokaryotic populations in which one population benefits and the other is not affected?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"In 1987 , the American microbiologist Carl Woese ( 1928 – 2012 ) suggested that a large and diverse group of bacteria that he called “ purple bacteria and their relatives ” should be defined as a separate phylum within the domain Bacteria based on the similarity of the nucleotide sequences in their genome . <hl> 10 This phylum of gram-negative bacteria subsequently received the name Proteobacteria . <hl> It includes many bacteria that are part of the normal human microbiota as well as many pathogens . The Proteobacteria are further divided into five classes : Alphaproteobacteria , Betaproteobacteria , Gammaproteobacteria , Deltaproteobacteria , and Epsilonproteobacteria ( Appendix D ) . 10 C . R . Woese . “ Bacterial Evolution . ” Microbiological Review 51 no . 2 ( 1987 ): 221 – 271 .","hl_sentences":"10 This phylum of gram-negative bacteria subsequently received the name Proteobacteria .","question":{"cloze_format":"___ describes Proteobacteria in domain Bacteria.","normal_format":"Which of the following describes Proteobacteria in domain Bacteria?","question_choices":["phylum","class","species","genus"],"question_id":"fs-id1172098559637","question_text":"Which of the following describes Proteobacteria in domain Bacteria?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> Obligate intracellular bacteria ; transmitted by ticks ; may cause Rocky Mountain spotted fever and typhus <hl> <hl> Gram-negative , pleomorphic , flagellated coccobacillus <hl> <hl> Bartonella <hl>","hl_sentences":"Obligate intracellular bacteria ; transmitted by ticks ; may cause Rocky Mountain spotted fever and typhus Gram-negative , pleomorphic , flagellated coccobacillus Bartonella","question":{"cloze_format":"The Alphaproteobacteria that is the cause of Rocky Mountain spotted fever and typhus is ___ .","normal_format":"Which of the following Alphaproteobacteria is the cause of Rocky Mountain spotted fever and typhus?","question_choices":["Bartonella","Coxiella","Rickettsia","Ehrlichia","Brucella"],"question_id":"fs-id1172098544345","question_text":"Which of the following Alphaproteobacteria is the cause of Rocky Mountain spotted fever and typhus?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> Neisseria <hl> <hl> Leptothrix <hl> <hl> Bordetella <hl> <hl> Class Betaproteobacteria <hl>","hl_sentences":"Neisseria Leptothrix Bordetella Class Betaproteobacteria","question":{"cloze_format":"Class Betaproteobacteria includes all but the genera of ___.","normal_format":"Class Betaproteobacteria includes all but which of the following genera?","question_choices":["Neisseria.","Bordetella.","Leptothrix.","Campylobacter."],"question_id":"fs-id1172098564103","question_text":"Class Betaproteobacteria includes all but which of the following genera?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"The Pasteurellaceae also includes several clinically relevant genera and species . This family includes several bacteria that are human and / or animal pathogens . For example , Pasteurella haemolytica causes severe pneumonia in sheep and goats . P . multocida is a species that can be transmitted from animals to humans through bites , causing infections of the skin and deeper tissues . <hl> The genus Haemophilus contains two human pathogens , H . influenzae and H . ducreyi . <hl> Despite its name , H . influenzae does not cause influenza ( which is a viral disease ) . <hl> H . influenzae can cause both upper and lower respiratory tract infections , including sinusitis , bronchitis , ear infections , and pneumonia . <hl> Before the development of effective vaccination , strains of H . influenzae were a leading cause of more invasive diseases , like meningitis in children . H . ducreyi causes the STI known as chancroid .","hl_sentences":"The genus Haemophilus contains two human pathogens , H . influenzae and H . ducreyi . H . influenzae can cause both upper and lower respiratory tract infections , including sinusitis , bronchitis , ear infections , and pneumonia .","question":{"cloze_format":"Haemophilus influenzae is a common cause of ___ .","normal_format":"Haemophilus influenzae is a common cause of which of the following?","question_choices":["influenza","dysentery","upper respiratory tract infections","hemophilia"],"question_id":"fs-id1172100577825","question_text":"Haemophilus influenzae is a common cause of which of the following?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"Spirochetes are characterized by their long ( up to 250 μm ) , spiral-shaped bodies . Most spirochetes are also very thin , which makes it difficult to examine gram-stained preparations under a conventional brightfield microscope . Darkfield fluorescent microscopy is typically used instead . <hl> Spirochetes are also difficult or even impossible to culture . <hl> <hl> They are highly motile , using their axial filament to propel themselves . <hl> The axial filament is similar to a flagellum , but it wraps around the cell and runs inside the cell body of a spirochete in the periplasmic space between the outer membrane and the plasma membrane ( Figure 4.13 ) .","hl_sentences":"Spirochetes are also difficult or even impossible to culture . They are highly motile , using their axial filament to propel themselves .","question":{"cloze_format":"The ___ is the organelle that spirochetes use to propel themselves.","normal_format":"Which of the following is the organelle that spirochetes use to propel themselves?","question_choices":["plasma membrane","axial filament","pilum","fimbria"],"question_id":"fs-id1172100831616","question_text":"Which of the following is the organelle that spirochetes use to propel themselves?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"Cytophaga are motile aquatic bacteria that glide . Fusobacteria inhabit the human mouth and may cause severe infectious diseases . <hl> The largest genus of the CFB group is Bacteroides , which includes dozens of species that are prevalent inhabitants of the human large intestine , making up about 30 % of the entire gut microbiome ( Figure 4.14 ) . <hl> One gram of human feces contains up to 100 billion Bacteroides cells . Most Bacteroides are mutualistic . They benefit from nutrients they find in the gut , and humans benefit from their ability to prevent pathogens from colonizing the large intestine . Indeed , when populations of Bacteroides are reduced in the gut — as often occurs when a patient takes antibiotics — the gut becomes a more favorable environment for pathogenic bacteria and fungi , which can cause secondary infections .","hl_sentences":"The largest genus of the CFB group is Bacteroides , which includes dozens of species that are prevalent inhabitants of the human large intestine , making up about 30 % of the entire gut microbiome ( Figure 4.14 ) .","question":{"cloze_format":"The bacteria that are the most prevalent in the human gut are ___.","normal_format":"Which of the following bacteria are the most prevalent in the human gut?","question_choices":["cyanobacteria","staphylococci","Borrelia","Bacteroides"],"question_id":"fs-id1172100770659","question_text":"Which of the following bacteria are the most prevalent in the human gut?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"The green nonsulfur bacteria are similar to green sulfur bacteria but they use substrates other than sulfides for oxidation . Chloroflexus is an example of a green nonsulfur bacterium . It often has an orange color when it grows in the dark , but it becomes green when it grows in sunlight . <hl> It stores bacteriochlorophyll in chlorosomes , similar to Chlorobium , and performs anoxygenic photosynthesis , using organic sulfites ( low concentrations ) or molecular hydrogen as electron donors , so it can survive in the dark if oxygen is available . <hl> Chloroflexus does not have flagella but can glide , like Cytophaga . It grows at a wide range of temperatures , from 35 ° C to 70 ° C , thus can be thermophilic .","hl_sentences":"It stores bacteriochlorophyll in chlorosomes , similar to Chlorobium , and performs anoxygenic photosynthesis , using organic sulfites ( low concentrations ) or molecular hydrogen as electron donors , so it can survive in the dark if oxygen is available .","question":{"cloze_format":"___ refers to photosynthesis performed by bacteria with the use of water as the donor of electrons.","normal_format":"Which of the following refers to photosynthesis performed by bacteria with the use of water as the donor of electrons?","question_choices":["oxygenic","anoxygenic","heterotrophic","phototrophic"],"question_id":"fs-id1172100936469","question_text":"Which of the following refers to photosynthesis performed by bacteria with the use of water as the donor of electrons?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> Based on their prevalence of guanine and cytosine nucleotides , gram-positive bacteria are also classified into low G + C and high G + C gram-positive bacteria . <hl> The low G + C gram-positive bacteria have less than 50 % of guanine and cytosine nucleotides in their DNA . They include human pathogens , such as those that cause anthrax ( Bacillus anthracis ) , tetanus ( Clostridium tetani ) , and listeriosis ( Listeria monocytogenes ) . <hl> High G + C gram-positive bacteria , which have more than 50 % guanine and cytosine nucleotides in their DNA , include the bacteria that cause diphtheria ( Corynebacterium diphtheriae ) , tuberculosis ( Mycobacterium tuberculosis ) , and other diseases . <hl>","hl_sentences":"Based on their prevalence of guanine and cytosine nucleotides , gram-positive bacteria are also classified into low G + C and high G + C gram-positive bacteria . High G + C gram-positive bacteria , which have more than 50 % guanine and cytosine nucleotides in their DNA , include the bacteria that cause diphtheria ( Corynebacterium diphtheriae ) , tuberculosis ( Mycobacterium tuberculosis ) , and other diseases .","question":{"cloze_format":"___ is/are a bacterial specie that is classified as high G+C gram-positive.","normal_format":"Which of the following bacterial species is classified as high G+C gram-positive?","question_choices":["Corynebacterium diphtheriae","Staphylococcus aureus","Bacillus anthracis","Streptococcus pneumonia"],"question_id":"fs-id1172100813972","question_text":"Which of the following bacterial species is classified as high G+C gram-positive?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"<hl> On a phylogenetic tree ( see A Systematic Approach ) , the trunk or root of the tree represents a common ancient evolutionary ancestor , often called the last universal common ancestor ( LUCA ) , and the branches are its evolutionary descendants . <hl> <hl> Scientists consider the deeply branching bacteria , such as the genus Acetothermus , to be the first of these non-LUCA forms of life produced by evolution some 3.5 billion years ago . <hl> When placed on the phylogenetic tree , they stem from the common root of life , deep and close to the LUCA root — hence the name “ deeply branching ” ( Figure 4.24 ) .","hl_sentences":"On a phylogenetic tree ( see A Systematic Approach ) , the trunk or root of the tree represents a common ancient evolutionary ancestor , often called the last universal common ancestor ( LUCA ) , and the branches are its evolutionary descendants . Scientists consider the deeply branching bacteria , such as the genus Acetothermus , to be the first of these non-LUCA forms of life produced by evolution some 3.5 billion years ago .","question":{"cloze_format":"The term “deeply branching” refers to ___ .","normal_format":"The term “deeply branching” refers to which of the following?","question_choices":["the cellular shape of deeply branching bacteria","the position in the evolutionary tree of deeply branching bacteria","the ability of deeply branching bacteria to live in deep ocean waters","the pattern of growth in culture of deeply branching bacteria"],"question_id":"fs-id1172100906155","question_text":"The term “deeply branching” refers to which of the following?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"<hl> Finally , the deeply branching bacterium Deinococcus radiodurans belongs to a genus whose name is derived from a Greek word meaning terrible berry . <hl> <hl> Nicknamed “ Conan the Bacterium , ” D . radiodurans is considered a polyextremophile because of its ability to survive under the many different kinds of extreme conditions — extreme heat , drought , vacuum , acidity , and radiation . <hl> It owes its name to its ability to withstand doses of ionizing radiation that kill all other known bacteria ; this special ability is attributed to some unique mechanisms of DNA repair . 4.6 Archaea","hl_sentences":"Finally , the deeply branching bacterium Deinococcus radiodurans belongs to a genus whose name is derived from a Greek word meaning terrible berry . Nicknamed “ Conan the Bacterium , ” D . radiodurans is considered a polyextremophile because of its ability to survive under the many different kinds of extreme conditions — extreme heat , drought , vacuum , acidity , and radiation .","question":{"cloze_format":"The deeply branching bacteria that is considered a polyextremophile is the ___.","normal_format":"Which of these deeply branching bacteria is considered a polyextremophile?","question_choices":["Aquifex pyrophilus","Deinococcus radiodurans","Staphylococcus aureus","Mycobacterium tuberculosis"],"question_id":"fs-id1172100937701","question_text":"Which of these deeply branching bacteria is considered a polyextremophile?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> Like organisms in the domain Bacteria , organisms of the domain Archaea are all unicellular organisms . <hl> However , archaea differ structurally from bacteria in several significant ways , as discussed in Unique Characteristics of Prokaryotic Cells . To summarize : All living organisms are classified into three domains of life : Archaea , Bacteria , and Eukarya . In this chapter , we will focus on the domains Archaea and Bacteria . <hl> Archaea and bacteria are unicellular prokaryotic organisms . <hl> Unlike eukaryotes , they have no nuclei or any other membrane-bound organelles .","hl_sentences":"Like organisms in the domain Bacteria , organisms of the domain Archaea are all unicellular organisms . Archaea and bacteria are unicellular prokaryotic organisms .","question":{"cloze_format":"Archaea and Bacteria are most similar in terms of their ________.","normal_format":"Archaea and Bacteria are most similar in terms of what?","question_choices":["genetics","cell wall structure","ecology","unicellular structure"],"question_id":"fs-id1172102014650","question_text":"Archaea and Bacteria are most similar in terms of their ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"The phylum Euryarchaeota includes several distinct classes . Species in the classes Methanobacteria , Methanococci , and Methanomicrobia represent Archaea that can be generally described as methanogens . <hl> Methanogens are unique in that they can reduce carbon dioxide in the presence of hydrogen , producing methane . <hl> <hl> They can live in the most extreme environments and can reproduce at temperatures varying from below freezing to boiling . <hl> Methanogens have been found in hot springs as well as deep under ice in Greenland . Methanogens also produce gases in ruminants and humans . Some scientists have even hypothesized that methanogen s may inhabit the planet Mars because the mixture of gases produced by methanogens resembles the makeup of the Martian atmosphere . 26 26 R . R . Britt “ Crater Critters : Where Mars Microbes Might Lurk . ” http://www.space.com/1880-crater-critters-mars-microbes-lurk.html . Accessed April 7 , 2015 .","hl_sentences":"Methanogens are unique in that they can reduce carbon dioxide in the presence of hydrogen , producing methane . They can live in the most extreme environments and can reproduce at temperatures varying from below freezing to boiling .","question":{"cloze_format":"Of archaea that produce methane, the true statement is that ___ .","normal_format":"Which of the following is true of archaea that produce methane?","question_choices":["They reduce carbon dioxide in the presence of nitrogen.","They live in the most extreme environments.","They are always anaerobes.","They have been discovered on Mars."],"question_id":"fs-id1172097276615","question_text":"Which of the following is true of archaea that produce methane?"},"references_are_paraphrase":0}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"All living organisms are classified into three domains of life : Archaea , Bacteria , and Eukarya . In this chapter , we will focus on the domains Archaea and Bacteria . <hl> Archaea and bacteria are unicellular prokaryotic organisms . <hl> <hl> Unlike eukaryotes , they have no nuclei or any other membrane-bound organelles . <hl>\",\n \"hl_sentences\": \"Archaea and bacteria are unicellular prokaryotic organisms . Unlike eukaryotes , they have no nuclei or any other membrane-bound organelles .\",\n \"question\": {\n \"cloze_format\": \"The term prokaryotes refers to ___.\",\n \"normal_format\": \"The term prokaryotes refers to which of the following?\",\n \"question_choices\": [\n \"very small organisms\",\n \"unicellular organisms that have no nucleus\",\n \"multicellular organisms\",\n \"cells that resemble animal cells more than plant cells\"\n ],\n \"question_id\": \"fs-id1172100562431\",\n \"question_text\": \"The term prokaryotes refers to which of the following?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> One important achievement of the Human Microbiome Project is establishing the first reference database on microorganisms living in and on the human body . <hl> Many of the microbes in the microbiome are beneficial , but some are not . It was found , somewhat unexpectedly , that all of us have some serious microbial pathogens in our microbiota . For example , the conjunctiva of the human eye contains 24 genera of bacteria and numerous pathogenic species . 7 A healthy human mouth contains a number of species of the genus Streptococcus , including pathogenic species S . pyogenes and S . pneumoniae . 8 This raises the question of why certain prokaryotic organisms exist commensally in certain individuals but act as deadly pathogens in others . Also unexpected was the number of organisms that had never been cultured . For example , in one metagenomic study of the human gut microbiota , 174 new species of bacteria were identified . 9 7 Q . Dong et al . “ Diversity of Bacteria at Healthy Human Conjunctiva . ” Investigative Ophthalmology & Visual Science 52 no . 8 ( 2011 ): 5408 – 5413 . 8 F . E . Dewhirst et al . “ The Human Oral Microbiome . ” Journal of Bacteriology 192 no . 19 ( 2010 ): 5002 – 5017 . 9 J . C . Lagier et al . “ Microbial Culturomics : Paradigm Shift in the Human Gut Microbiome Study . ” Clinical Microbiology and Infection 18 no . 12 ( 2012 ): 1185 – 1193 . Scientists have coined the term microbiome to refer to all prokaryotic and eukaryotic microorganisms and their genetic material that are associated with a certain organism or environment . <hl> Within the human microbiome , there are resident microbiota and transient microbiota . <hl> <hl> The resident microbiota consists of microorganisms that constantly live in or on our bodies . <hl> <hl> The term transient microbiota refers to microorganisms that are only temporarily found in the human body , and these may include pathogenic microorganisms . <hl> Hygiene and diet can alter both the resident and transient microbiota . The resident microbiota is amazingly diverse , not only in terms of the variety of species but also in terms of the preference of different microorganisms for different areas of the human body . For example , in the human mouth , there are thousands of commensal or mutualistic species of bacteria . Some of these bacteria prefer to inhabit the surface of the tongue , whereas others prefer the internal surface of the cheeks , and yet others prefer the front or back teeth or gums . The inner surface of the cheek has the least diverse microbiota because of its exposure to oxygen . By contrast , the crypts of the tongue and the spaces between teeth are two sites with limited oxygen exposure , so these sites have more diverse microbiota , including bacteria living in the absence of oxygen ( e . g . , Bacteroides , Fusobacterium ) . Differences in the oral microbiota between randomly chosen human individuals are also significant . Studies have shown , for example , that the prevalence of such bacteria as Streptococcus , Haemophilus , Neisseria , and others was dramatically different when compared between individuals . 4 4 E . M . Bik et al . “ Bacterial Diversity in the Oral Cavity of 10 Healthy Individuals . ” The ISME Journal 4 no . 8 ( 2010 ): 962 – 974 .\",\n \"hl_sentences\": \"One important achievement of the Human Microbiome Project is establishing the first reference database on microorganisms living in and on the human body . Within the human microbiome , there are resident microbiota and transient microbiota . The resident microbiota consists of microorganisms that constantly live in or on our bodies . The term transient microbiota refers to microorganisms that are only temporarily found in the human body , and these may include pathogenic microorganisms .\",\n \"question\": {\n \"cloze_format\": \"The term microbiota refers to ___ .\",\n \"normal_format\": \"The term microbiota refers to which of the following?\",\n \"question_choices\": [\n \"all microorganisms of the same species\",\n \"all of the microorganisms involved in a symbiotic relationship\",\n \"all microorganisms in a certain region of the human body\",\n \"all microorganisms in a certain geographic region\"\n ],\n \"question_id\": \"fs-id1172100771337\",\n \"question_text\": \"The term microbiota refers to which of the following?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"When two species benefit from each other , the symbiosis is called mutualism ( or syntropy , or crossfeeding ) . For example , humans have a mutualistic relationship with the bacterium Bacteroides thetaiotaomicron , which lives in the intestinal tract . Bacteroides thetaiotaomicron digests complex polysaccharide plant materials that human digestive enzymes cannot break down , converting them into monosaccharides that can be absorbed by human cells . Humans also have a mutualistic relationship with certain strains of Escherichia coli , another bacterium found in the gut . E . coli relies on intestinal contents for nutrients , and humans derive certain vitamins from E . coli , particularly vitamin K , which is required for the formation of blood clotting factors . ( This is only true for some strains of E . coli , however . Other strains are pathogenic and do not have a mutualistic relationship with humans . ) A type of symbiosis in which one population harms another but remains unaffected itself is called amensalism . In the case of bacteria , some amensalist species produce bactericidal substances that kill other species of bacteria . The microbiota of the skin is composed of a variety of bacterial species , including Staphylococcus epidermidis and Propionibacterium acnes . Although both species have the potential to cause infectious diseases when protective barriers are breached , they both produce a variety of antibacterial bacteriocins and bacteriocin-like compounds . S . epidermidis and P . acnes are unaffected by the bacteriocins and bacteriocin-like compounds they produce , but these compounds can target and kill other potential pathogens . <hl> In another type of symbiosis , called commensalism , one organism benefits while the other is unaffected . <hl> This occurs when the bacterium Staphylococcus epidermidis uses the dead cells of the human skin as nutrients . Billions of these bacteria live on our skin , but in most cases ( especially when our immune system is healthy ) , we do not react to them in any way . S . epidermidis provides an excellent example of how the classifications of symbiotic relationships are not always distinct . One could also consider the symbiotic relationship of S . epidermidis with humans as mutualism . Humans provide a food source of dead skin cells to the bacterium , and in turn the production of bacteriocin can provide an defense against potential pathogens . If neither of the symbiotic organisms is affected in any way , we call this type of symbiosis neutralism . An example of neutralism is the coexistence of metabolically active ( vegetating ) bacteria and endospores ( dormant , metabolically passive bacteria ) . For example , the bacterium Bacillus anthracis typically forms endospores in soil when conditions are unfavorable . If the soil is warmed and enriched with nutrients , some B . anthracis endospores germinate and remain in symbiosis with other species of endospores that have not germinated . A type of symbiosis in which one organism benefits while harming the other is called parasitism . The relationship between humans and many pathogenic prokaryotes can be characterized as parasitic because these organisms invade the body , producing toxic substances or infectious diseases that cause harm . Diseases such as tetanus , diphtheria , pertussis , tuberculosis , and leprosy all arise from interactions between bacteria and humans . <hl> Prokaryotes live in a community , or a group of interacting populations of organisms . <hl> A population is a group of individual organisms belonging to the same biological species and limited to a certain geographic area . Populations can have cooperative interactions , which benefit the populations , or competitive interactions , in which one population competes with another for resources . The study of these interactions between microbial populations and their environment is called microbial ecology . <hl> Any interaction between different species that are associated with each other within a community is called symbiosis . <hl> Such interactions fall along a continuum between opposition and cooperation . Interactions in a symbiotic relationship may be beneficial or harmful , or have no effect on one or both of the species involved . Table 4.1 summarizes the main types of symbiotic interactions among prokaryotes .\",\n \"hl_sentences\": \"In another type of symbiosis , called commensalism , one organism benefits while the other is unaffected . Prokaryotes live in a community , or a group of interacting populations of organisms . Any interaction between different species that are associated with each other within a community is called symbiosis .\",\n \"question\": {\n \"cloze_format\": \"___ refers to the type of interaction between two prokaryotic populations in which one population benefits and the other is not affected.\",\n \"normal_format\": \"Which of the following refers to the type of interaction between two prokaryotic populations in which one population benefits and the other is not affected?\",\n \"question_choices\": [\n \"mutualism\",\n \"commensalism\",\n \"parasitism\",\n \"neutralism\"\n ],\n \"question_id\": \"fs-id1172098549514\",\n \"question_text\": \"Which of the following refers to the type of interaction between two prokaryotic populations in which one population benefits and the other is not affected?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"In 1987 , the American microbiologist Carl Woese ( 1928 – 2012 ) suggested that a large and diverse group of bacteria that he called “ purple bacteria and their relatives ” should be defined as a separate phylum within the domain Bacteria based on the similarity of the nucleotide sequences in their genome . <hl> 10 This phylum of gram-negative bacteria subsequently received the name Proteobacteria . <hl> It includes many bacteria that are part of the normal human microbiota as well as many pathogens . The Proteobacteria are further divided into five classes : Alphaproteobacteria , Betaproteobacteria , Gammaproteobacteria , Deltaproteobacteria , and Epsilonproteobacteria ( Appendix D ) . 10 C . R . Woese . “ Bacterial Evolution . ” Microbiological Review 51 no . 2 ( 1987 ): 221 – 271 .\",\n \"hl_sentences\": \"10 This phylum of gram-negative bacteria subsequently received the name Proteobacteria .\",\n \"question\": {\n \"cloze_format\": \"___ describes Proteobacteria in domain Bacteria.\",\n \"normal_format\": \"Which of the following describes Proteobacteria in domain Bacteria?\",\n \"question_choices\": [\n \"phylum\",\n \"class\",\n \"species\",\n \"genus\"\n ],\n \"question_id\": \"fs-id1172098559637\",\n \"question_text\": \"Which of the following describes Proteobacteria in domain Bacteria?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Obligate intracellular bacteria ; transmitted by ticks ; may cause Rocky Mountain spotted fever and typhus <hl> <hl> Gram-negative , pleomorphic , flagellated coccobacillus <hl> <hl> Bartonella <hl>\",\n \"hl_sentences\": \"Obligate intracellular bacteria ; transmitted by ticks ; may cause Rocky Mountain spotted fever and typhus Gram-negative , pleomorphic , flagellated coccobacillus Bartonella\",\n \"question\": {\n \"cloze_format\": \"The Alphaproteobacteria that is the cause of Rocky Mountain spotted fever and typhus is ___ .\",\n \"normal_format\": \"Which of the following Alphaproteobacteria is the cause of Rocky Mountain spotted fever and typhus?\",\n \"question_choices\": [\n \"Bartonella\",\n \"Coxiella\",\n \"Rickettsia\",\n \"Ehrlichia\",\n \"Brucella\"\n ],\n \"question_id\": \"fs-id1172098544345\",\n \"question_text\": \"Which of the following Alphaproteobacteria is the cause of Rocky Mountain spotted fever and typhus?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Neisseria <hl> <hl> Leptothrix <hl> <hl> Bordetella <hl> <hl> Class Betaproteobacteria <hl>\",\n \"hl_sentences\": \"Neisseria Leptothrix Bordetella Class Betaproteobacteria\",\n \"question\": {\n \"cloze_format\": \"Class Betaproteobacteria includes all but the genera of ___.\",\n \"normal_format\": \"Class Betaproteobacteria includes all but which of the following genera?\",\n \"question_choices\": [\n \"Neisseria.\",\n \"Bordetella.\",\n \"Leptothrix.\",\n \"Campylobacter.\"\n ],\n \"question_id\": \"fs-id1172098564103\",\n \"question_text\": \"Class Betaproteobacteria includes all but which of the following genera?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"The Pasteurellaceae also includes several clinically relevant genera and species . This family includes several bacteria that are human and / or animal pathogens . For example , Pasteurella haemolytica causes severe pneumonia in sheep and goats . P . multocida is a species that can be transmitted from animals to humans through bites , causing infections of the skin and deeper tissues . <hl> The genus Haemophilus contains two human pathogens , H . influenzae and H . ducreyi . <hl> Despite its name , H . influenzae does not cause influenza ( which is a viral disease ) . <hl> H . influenzae can cause both upper and lower respiratory tract infections , including sinusitis , bronchitis , ear infections , and pneumonia . <hl> Before the development of effective vaccination , strains of H . influenzae were a leading cause of more invasive diseases , like meningitis in children . H . ducreyi causes the STI known as chancroid .\",\n \"hl_sentences\": \"The genus Haemophilus contains two human pathogens , H . influenzae and H . ducreyi . H . influenzae can cause both upper and lower respiratory tract infections , including sinusitis , bronchitis , ear infections , and pneumonia .\",\n \"question\": {\n \"cloze_format\": \"Haemophilus influenzae is a common cause of ___ .\",\n \"normal_format\": \"Haemophilus influenzae is a common cause of which of the following?\",\n \"question_choices\": [\n \"influenza\",\n \"dysentery\",\n \"upper respiratory tract infections\",\n \"hemophilia\"\n ],\n \"question_id\": \"fs-id1172100577825\",\n \"question_text\": \"Haemophilus influenzae is a common cause of which of the following?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"Spirochetes are characterized by their long ( up to 250 μm ) , spiral-shaped bodies . Most spirochetes are also very thin , which makes it difficult to examine gram-stained preparations under a conventional brightfield microscope . Darkfield fluorescent microscopy is typically used instead . <hl> Spirochetes are also difficult or even impossible to culture . <hl> <hl> They are highly motile , using their axial filament to propel themselves . <hl> The axial filament is similar to a flagellum , but it wraps around the cell and runs inside the cell body of a spirochete in the periplasmic space between the outer membrane and the plasma membrane ( Figure 4.13 ) .\",\n \"hl_sentences\": \"Spirochetes are also difficult or even impossible to culture . They are highly motile , using their axial filament to propel themselves .\",\n \"question\": {\n \"cloze_format\": \"The ___ is the organelle that spirochetes use to propel themselves.\",\n \"normal_format\": \"Which of the following is the organelle that spirochetes use to propel themselves?\",\n \"question_choices\": [\n \"plasma membrane\",\n \"axial filament\",\n \"pilum\",\n \"fimbria\"\n ],\n \"question_id\": \"fs-id1172100831616\",\n \"question_text\": \"Which of the following is the organelle that spirochetes use to propel themselves?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"Cytophaga are motile aquatic bacteria that glide . Fusobacteria inhabit the human mouth and may cause severe infectious diseases . <hl> The largest genus of the CFB group is Bacteroides , which includes dozens of species that are prevalent inhabitants of the human large intestine , making up about 30 % of the entire gut microbiome ( Figure 4.14 ) . <hl> One gram of human feces contains up to 100 billion Bacteroides cells . Most Bacteroides are mutualistic . They benefit from nutrients they find in the gut , and humans benefit from their ability to prevent pathogens from colonizing the large intestine . Indeed , when populations of Bacteroides are reduced in the gut — as often occurs when a patient takes antibiotics — the gut becomes a more favorable environment for pathogenic bacteria and fungi , which can cause secondary infections .\",\n \"hl_sentences\": \"The largest genus of the CFB group is Bacteroides , which includes dozens of species that are prevalent inhabitants of the human large intestine , making up about 30 % of the entire gut microbiome ( Figure 4.14 ) .\",\n \"question\": {\n \"cloze_format\": \"The bacteria that are the most prevalent in the human gut are ___.\",\n \"normal_format\": \"Which of the following bacteria are the most prevalent in the human gut?\",\n \"question_choices\": [\n \"cyanobacteria\",\n \"staphylococci\",\n \"Borrelia\",\n \"Bacteroides\"\n ],\n \"question_id\": \"fs-id1172100770659\",\n \"question_text\": \"Which of the following bacteria are the most prevalent in the human gut?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"The green nonsulfur bacteria are similar to green sulfur bacteria but they use substrates other than sulfides for oxidation . Chloroflexus is an example of a green nonsulfur bacterium . It often has an orange color when it grows in the dark , but it becomes green when it grows in sunlight . <hl> It stores bacteriochlorophyll in chlorosomes , similar to Chlorobium , and performs anoxygenic photosynthesis , using organic sulfites ( low concentrations ) or molecular hydrogen as electron donors , so it can survive in the dark if oxygen is available . <hl> Chloroflexus does not have flagella but can glide , like Cytophaga . It grows at a wide range of temperatures , from 35 ° C to 70 ° C , thus can be thermophilic .\",\n \"hl_sentences\": \"It stores bacteriochlorophyll in chlorosomes , similar to Chlorobium , and performs anoxygenic photosynthesis , using organic sulfites ( low concentrations ) or molecular hydrogen as electron donors , so it can survive in the dark if oxygen is available .\",\n \"question\": {\n \"cloze_format\": \"___ refers to photosynthesis performed by bacteria with the use of water as the donor of electrons.\",\n \"normal_format\": \"Which of the following refers to photosynthesis performed by bacteria with the use of water as the donor of electrons?\",\n \"question_choices\": [\n \"oxygenic\",\n \"anoxygenic\",\n \"heterotrophic\",\n \"phototrophic\"\n ],\n \"question_id\": \"fs-id1172100936469\",\n \"question_text\": \"Which of the following refers to photosynthesis performed by bacteria with the use of water as the donor of electrons?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Based on their prevalence of guanine and cytosine nucleotides , gram-positive bacteria are also classified into low G + C and high G + C gram-positive bacteria . <hl> The low G + C gram-positive bacteria have less than 50 % of guanine and cytosine nucleotides in their DNA . They include human pathogens , such as those that cause anthrax ( Bacillus anthracis ) , tetanus ( Clostridium tetani ) , and listeriosis ( Listeria monocytogenes ) . <hl> High G + C gram-positive bacteria , which have more than 50 % guanine and cytosine nucleotides in their DNA , include the bacteria that cause diphtheria ( Corynebacterium diphtheriae ) , tuberculosis ( Mycobacterium tuberculosis ) , and other diseases . <hl>\",\n \"hl_sentences\": \"Based on their prevalence of guanine and cytosine nucleotides , gram-positive bacteria are also classified into low G + C and high G + C gram-positive bacteria . High G + C gram-positive bacteria , which have more than 50 % guanine and cytosine nucleotides in their DNA , include the bacteria that cause diphtheria ( Corynebacterium diphtheriae ) , tuberculosis ( Mycobacterium tuberculosis ) , and other diseases .\",\n \"question\": {\n \"cloze_format\": \"___ is/are a bacterial specie that is classified as high G+C gram-positive.\",\n \"normal_format\": \"Which of the following bacterial species is classified as high G+C gram-positive?\",\n \"question_choices\": [\n \"Corynebacterium diphtheriae\",\n \"Staphylococcus aureus\",\n \"Bacillus anthracis\",\n \"Streptococcus pneumonia\"\n ],\n \"question_id\": \"fs-id1172100813972\",\n \"question_text\": \"Which of the following bacterial species is classified as high G+C gram-positive?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> On a phylogenetic tree ( see A Systematic Approach ) , the trunk or root of the tree represents a common ancient evolutionary ancestor , often called the last universal common ancestor ( LUCA ) , and the branches are its evolutionary descendants . <hl> <hl> Scientists consider the deeply branching bacteria , such as the genus Acetothermus , to be the first of these non-LUCA forms of life produced by evolution some 3.5 billion years ago . <hl> When placed on the phylogenetic tree , they stem from the common root of life , deep and close to the LUCA root — hence the name “ deeply branching ” ( Figure 4.24 ) .\",\n \"hl_sentences\": \"On a phylogenetic tree ( see A Systematic Approach ) , the trunk or root of the tree represents a common ancient evolutionary ancestor , often called the last universal common ancestor ( LUCA ) , and the branches are its evolutionary descendants . Scientists consider the deeply branching bacteria , such as the genus Acetothermus , to be the first of these non-LUCA forms of life produced by evolution some 3.5 billion years ago .\",\n \"question\": {\n \"cloze_format\": \"The term “deeply branching” refers to ___ .\",\n \"normal_format\": \"The term “deeply branching” refers to which of the following?\",\n \"question_choices\": [\n \"the cellular shape of deeply branching bacteria\",\n \"the position in the evolutionary tree of deeply branching bacteria\",\n \"the ability of deeply branching bacteria to live in deep ocean waters\",\n \"the pattern of growth in culture of deeply branching bacteria\"\n ],\n \"question_id\": \"fs-id1172100906155\",\n \"question_text\": \"The term “deeply branching” refers to which of the following?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Finally , the deeply branching bacterium Deinococcus radiodurans belongs to a genus whose name is derived from a Greek word meaning terrible berry . <hl> <hl> Nicknamed “ Conan the Bacterium , ” D . radiodurans is considered a polyextremophile because of its ability to survive under the many different kinds of extreme conditions — extreme heat , drought , vacuum , acidity , and radiation . <hl> It owes its name to its ability to withstand doses of ionizing radiation that kill all other known bacteria ; this special ability is attributed to some unique mechanisms of DNA repair . 4.6 Archaea\",\n \"hl_sentences\": \"Finally , the deeply branching bacterium Deinococcus radiodurans belongs to a genus whose name is derived from a Greek word meaning terrible berry . Nicknamed “ Conan the Bacterium , ” D . radiodurans is considered a polyextremophile because of its ability to survive under the many different kinds of extreme conditions — extreme heat , drought , vacuum , acidity , and radiation .\",\n \"question\": {\n \"cloze_format\": \"The deeply branching bacteria that is considered a polyextremophile is the ___.\",\n \"normal_format\": \"Which of these deeply branching bacteria is considered a polyextremophile?\",\n \"question_choices\": [\n \"Aquifex pyrophilus\",\n \"Deinococcus radiodurans\",\n \"Staphylococcus aureus\",\n \"Mycobacterium tuberculosis\"\n ],\n \"question_id\": \"fs-id1172100937701\",\n \"question_text\": \"Which of these deeply branching bacteria is considered a polyextremophile?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Like organisms in the domain Bacteria , organisms of the domain Archaea are all unicellular organisms . <hl> However , archaea differ structurally from bacteria in several significant ways , as discussed in Unique Characteristics of Prokaryotic Cells . To summarize : All living organisms are classified into three domains of life : Archaea , Bacteria , and Eukarya . In this chapter , we will focus on the domains Archaea and Bacteria . <hl> Archaea and bacteria are unicellular prokaryotic organisms . <hl> Unlike eukaryotes , they have no nuclei or any other membrane-bound organelles .\",\n \"hl_sentences\": \"Like organisms in the domain Bacteria , organisms of the domain Archaea are all unicellular organisms . Archaea and bacteria are unicellular prokaryotic organisms .\",\n \"question\": {\n \"cloze_format\": \"Archaea and Bacteria are most similar in terms of their ________.\",\n \"normal_format\": \"Archaea and Bacteria are most similar in terms of what?\",\n \"question_choices\": [\n \"genetics\",\n \"cell wall structure\",\n \"ecology\",\n \"unicellular structure\"\n ],\n \"question_id\": \"fs-id1172102014650\",\n \"question_text\": \"Archaea and Bacteria are most similar in terms of their ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"The phylum Euryarchaeota includes several distinct classes . Species in the classes Methanobacteria , Methanococci , and Methanomicrobia represent Archaea that can be generally described as methanogens . <hl> Methanogens are unique in that they can reduce carbon dioxide in the presence of hydrogen , producing methane . <hl> <hl> They can live in the most extreme environments and can reproduce at temperatures varying from below freezing to boiling . <hl> Methanogens have been found in hot springs as well as deep under ice in Greenland . Methanogens also produce gases in ruminants and humans . Some scientists have even hypothesized that methanogen s may inhabit the planet Mars because the mixture of gases produced by methanogens resembles the makeup of the Martian atmosphere . 26 26 R . R . Britt “ Crater Critters : Where Mars Microbes Might Lurk . ” http://www.space.com/1880-crater-critters-mars-microbes-lurk.html . Accessed April 7 , 2015 .\",\n \"hl_sentences\": \"Methanogens are unique in that they can reduce carbon dioxide in the presence of hydrogen , producing methane . They can live in the most extreme environments and can reproduce at temperatures varying from below freezing to boiling .\",\n \"question\": {\n \"cloze_format\": \"Of archaea that produce methane, the true statement is that ___ .\",\n \"normal_format\": \"Which of the following is true of archaea that produce methane?\",\n \"question_choices\": [\n \"They reduce carbon dioxide in the presence of nitrogen.\",\n \"They live in the most extreme environments.\",\n \"They are always anaerobes.\",\n \"They have been discovered on Mars.\"\n ],\n \"question_id\": \"fs-id1172097276615\",\n \"question_text\": \"Which of the following is true of archaea that produce methane?\"\n },\n \"references_are_paraphrase\": 0\n }\n]","isConversational":false},"chapter":{"kind":"number","value":4,"string":"4"},"chapter_text":{"kind":"string","value":" 4.1 Prokaryote Habitats, Relationships, and Microbiomes \n\n Learning Objectives \n\n Identify and describe unique examples of prokaryotes in various habitats on earth \n\n Identify and describe symbiotic relationships \n\n Compare normal/commensal/resident microbiota to transient microbiota \n\n Explain how prokaryotes are classified \n\n Clinical Focus Part 1 Marsha, a 20-year-old university student, recently returned to the United States from a trip to Nigeria, where she had interned as a medical assistant for an organization working to improve access to laboratory services for tuberculosis testing. When she returned, Marsha began to feel fatigue, which she initially attributed to jet lag. However, the fatigue persisted, and Marsha soon began to experience other bothersome symptoms, such as occasional coughing, night sweats, loss of appetite, and a low-grade fever of 37.4 °C (99.3 °F). \n\n Marsha expected her symptoms would subside in a few days, but instead, they gradually became more severe. About two weeks after returning home, she coughed up some sputum and noticed that it contained blood and small whitish clumps resembling cottage cheese. Her fever spiked to 38.2 °C (100.8 °F), and she began feeling sharp pains in her chest when breathing deeply. Concerned that she seemed to be getting worse, Marsha scheduled an appointment with her physician. \n\n Could Marsha’s symptoms be related to her overseas travel, even several weeks after returning home? \n\n Jump to the next Clinical Focus box. \n\n All living organisms are classified into three domains of life: Archaea , Bacteria , and Eukarya . In this chapter, we will focus on the domains Archaea and Bacteria. Archaea and bacteria are unicellular prokaryotic organisms. Unlike eukaryotes, they have no nuclei or any other membrane-bound organelles. \n\n Prokaryote Habitats and Functions \n\n Prokaryotes are ubiquitous. They can be found everywhere on our planet, even in hot springs, in the Antarctic ice shield, and under extreme pressure two miles under water. One bacterium, Paracoccus denitrificans , has even been shown to survive when scientists removed it from its native environment (soil) and used a centrifuge to subject it to forces of gravity as strong as those found on the surface of Jupiter. \n\n Prokaryotes also are abundant on and within the human body. According to a report by National Institutes of Health, prokaryotes , especially bacteria, outnumber human cells 10:1. 1 More recent studies suggest the ratio could be closer to 1:1, but even that ratio means that there are a great number of bacteria within the human body. 2 Bacteria thrive in the human mouth, nasal cavity, throat, ears, gastrointestinal tract, and vagina. Large colonies of bacteria can be found on healthy human skin, especially in moist areas (armpits, navel, and areas behind ears). However, even drier areas of the skin are not free from bacteria. 1 Medical Press. “Mouth Bacteria Can Change Their Diet, Supercomputers Reveal.” August 12, 2014. http://medicalxpress.com/news/2014-08-mouth-bacteria-diet-supercomputers-reveal.html. Accessed February 24, 2015. 2 A. Abbott. “Scientists Bust Myth That Our Bodies Have More Bacteria Than Human Cells: Decades-Old Assumption about Microbiota Revisited.” Nature. http://www.nature.com/news/scientists-bust-myth-that-our-bodies-have-more-bacteria-than-human-cells-1.19136. Accessed June 3, 2016. \n\n The existence of prokaryotes is very important for the stability and thriving of ecosystems. For example, they are a necessary part of soil formation and stabilization processes through the breakdown of organic matter and development of biofilms. One gram of soil contains up to 10 billion microorganisms (most of them prokaryotic) belonging to about 1,000 species. Many species of bacteria use substances released from plant roots, such as acids and carbohydrates, as nutrients. The bacteria metabolize these plant substances and release the products of bacterial metabolism back to the soil, forming humus and thus increasing the soil’s fertility. In salty lakes such as the Dead Sea ( Figure 4.2 ), salt-loving halobacteria decompose dead brine shrimp and nourish young brine shrimp and flies with the products of bacterial metabolism. \n\n In addition to living in the ground and the water, prokaryotic microorganisms are abundant in the air, even high in the atmosphere. There may be up to 2,000 different kinds of bacteria in the air, similar to their diversity in the soil. \n\n Prokaryotes can be found everywhere on earth because they are extremely resilient and adaptable. They are often metabolically flexible, which means that they might easily switch from one energy source to another, depending on the availability of the sources, or from one metabolic pathway to another. For example, certain prokaryotic cyanobacteria can switch from a conventional type of lipid metabolism, which includes production of fatty aldehydes, to a different type of lipid metabolism that generates biofuel, such as fatty acids and wax esters. Groundwater bacteria store complex high-energy carbohydrates when grown in pure groundwater, but they metabolize these molecules when the groundwater is enriched with phosphates. Some bacteria get their energy by reducing sulfates into sulfides, but can switch to a different metabolic pathway when necessary, producing acids and free hydrogen ions. \n\n Prokaryotes perform functions vital to life on earth by capturing (or “fixing”) and recycling elements like carbon and nitrogen. Organisms such as animals require organic carbon to grow, but, unlike prokaryotes, they are unable to use inorganic carbon sources like carbon dioxide. Thus, animals rely on prokaryotes to convert carbon dioxide into organic carbon products that they can use. This process of converting carbon dioxide to organic carbon products is called carbon fixation . \n\n Plants and animals also rely heavily on prokaryotes for nitrogen fixation , the conversion of atmospheric nitrogen into ammonia, a compound that some plants can use to form many different biomolecules necessary to their survival. Bacteria in the genus Rhizobium , for example, are nitrogen-fixing bacteria; they live in the roots of legume plants such as clover, alfalfa, and peas ( Figure 4.3 ). Ammonia produced by Rhizobium helps these plants to survive by enabling them to make building blocks of nucleic acids. In turn, these plants may be eaten by animals—sustaining their growth and survival—or they may die, in which case the products of nitrogen fixation will enrich the soil and be used by other plants. \n\n Another positive function of prokaryotes is in cleaning up the environment. Recently, some researchers focused on the diversity and functions of prokaryotes in manmade environments. They found that some bacteria play a unique role in degrading toxic chemicals that pollute water and soil. 3 3 A.M. Kravetz “Unique Bacteria Fights Man-Made Chemical Waste.” 2012. http://www.livescience.com/25181-bacteria-strain-cleans-up-toxins-nsf-bts.html. Accessed March 9, 2015. \n\n Despite all of the positive and helpful roles prokaryotes play, some are human pathogens that may cause illness or infection when they enter the body. In addition, some bacteria can contaminate food, causing spoilage or foodborne illness, which makes them subjects of concern in food preparation and safety. Less than 1% of prokaryotes (all of them bacteria) are thought to be human pathogens, but collectively these species are responsible for a large number of the diseases that afflict humans. \n\n Besides pathogens, which have a direct impact on human health, prokaryotes also affect humans in many indirect ways. For example, prokaryotes are now thought to be key players in the processes of climate change . In recent years, as temperatures in the earth’s polar regions have risen, soil that was formerly frozen year-round (permafrost) has begun to thaw. Carbon trapped in the permafrost is gradually released and metabolized by prokaryotes. This produces massive amounts of carbon dioxide and methane, greenhouse gases that escape into the atmosphere and contribute to the greenhouse effect. \n\n Check Your Understanding \n\n In what types of environments can prokaryotes be found? \n\n Name some ways that plants and animals rely on prokaryotes. \n\n Symbiotic Relationships \n\n As we have learned, prokaryotic microorganisms can associate with plants and animals. Often, this association results in unique relationships between organisms. For example, bacteria living on the roots or leaves of a plant get nutrients from the plant and, in return, produce substances that protect the plant from pathogens. On the other hand, some bacteria are plant pathogens that use mechanisms of infection similar to bacterial pathogens of animals and humans. \n\n Prokaryotes live in a community , or a group of interacting populations of organisms. A population is a group of individual organisms belonging to the same biological species and limited to a certain geographic area. Populations can have cooperative interactions , which benefit the populations, or competitive interactions , in which one population competes with another for resources. The study of these interactions between microbial populations and their environment is called microbial ecology . Any interaction between different species that are associated with each other within a community is called symbiosis . Such interactions fall along a continuum between opposition and cooperation. Interactions in a symbiotic relationship may be beneficial or harmful, or have no effect on one or both of the species involved. Table 4.1 summarizes the main types of symbiotic interactions among prokaryotes. \n\n Types of Symbiotic Relationships \n\n Type \n\n Population A \n\n Population B \n\n Mutualism \n\n Benefitted \n\n Benefitted \n\n Amensalism \n\n Harmed \n\n Unaffected \n\n Commensalism \n\n Benefitted \n\n Unaffected \n\n Neutralism \n\n Unaffected \n\n Unaffected \n\n Parasitism \n\n Benefitted \n\n Harmed \n\n Table 4.1 \n\n When two species benefit from each other, the symbiosis is called mutualism (or syntropy, or crossfeeding). For example, humans have a mutualistic relationship with the bacterium Bacteroides thetaiotaomicron , which lives in the intestinal tract. Bacteroides thetaiotaomicron digests complex polysaccharide plant materials that human digestive enzymes cannot break down, converting them into monosaccharides that can be absorbed by human cells. Humans also have a mutualistic relationship with certain strains of Escherichia coli , another bacterium found in the gut. E. coli relies on intestinal contents for nutrients, and humans derive certain vitamins from E. coli, particularly vitamin K, which is required for the formation of blood clotting factors. (This is only true for some strains of E. coli , however. Other strains are pathogenic and do not have a mutualistic relationship with humans.) A type of symbiosis in which one population harms another but remains unaffected itself is called amensalism . In the case of bacteria, some amensalist species produce bactericidal substances that kill other species of bacteria. The microbiota of the skin is composed of a variety of bacterial species, including Staphylococcus epidermidis and Propionibacterium acnes . Although both species have the potential to cause infectious diseases when protective barriers are breached, they both produce a variety of antibacterial bacteriocins and bacteriocin-like compounds. S. epidermidis and P. acnes are unaffected by the bacteriocins and bacteriocin-like compounds they produce, but these compounds can target and kill other potential pathogens. In another type of symbiosis, called commensalism , one organism benefits while the other is unaffected. This occurs when the bacterium Staphylococcus epidermidis uses the dead cells of the human skin as nutrients. Billions of these bacteria live on our skin, but in most cases (especially when our immune system is healthy), we do not react to them in any way. S. epidermidis provides an excellent example of how the classifications of symbiotic relationships are not always distinct. One could also consider the symbiotic relationship of S. epidermidis with humans as mutualism. Humans provide a food source of dead skin cells to the bacterium, and in turn the production of bacteriocin can provide an defense against potential pathogens. If neither of the symbiotic organisms is affected in any way, we call this type of symbiosis neutralism . An example of neutralism is the coexistence of metabolically active (vegetating) bacteria and endospores (dormant, metabolically passive bacteria). For example, the bacterium Bacillus anthracis typically forms endospores in soil when conditions are unfavorable. If the soil is warmed and enriched with nutrients, some B. anthracis endospores germinate and remain in symbiosis with other species of endospores that have not germinated. A type of symbiosis in which one organism benefits while harming the other is called parasitism . The relationship between humans and many pathogenic prokaryotes can be characterized as parasitic because these organisms invade the body, producing toxic substances or infectious diseases that cause harm. Diseases such as tetanus, diphtheria, pertussis, tuberculosis, and leprosy all arise from interactions between bacteria and humans. \n\n Scientists have coined the term microbiome to refer to all prokaryotic and eukaryotic microorganisms and their genetic material that are associated with a certain organism or environment. Within the human microbiome , there are resident microbiota and transient microbiota . The resident microbiota consists of microorganisms that constantly live in or on our bodies. The term transient microbiota refers to microorganisms that are only temporarily found in the human body, and these may include pathogenic microorganisms. Hygiene and diet can alter both the resident and transient microbiota. The resident microbiota is amazingly diverse, not only in terms of the variety of species but also in terms of the preference of different microorganisms for different areas of the human body. For example, in the human mouth, there are thousands of commensal or mutualistic species of bacteria. Some of these bacteria prefer to inhabit the surface of the tongue, whereas others prefer the internal surface of the cheeks, and yet others prefer the front or back teeth or gums. The inner surface of the cheek has the least diverse microbiota because of its exposure to oxygen. By contrast, the crypts of the tongue and the spaces between teeth are two sites with limited oxygen exposure, so these sites have more diverse microbiota, including bacteria living in the absence of oxygen (e.g., Bacteroides , Fusobacterium ). Differences in the oral microbiota between randomly chosen human individuals are also significant. Studies have shown, for example, that the prevalence of such bacteria as Streptococcus , Haemophilus , Neisseria , and others was dramatically different when compared between individuals. 4 4 E.M. Bik et al. “Bacterial Diversity in the Oral Cavity of 10 Healthy Individuals.” The ISME Journal 4 no. 8 (2010):962–974. \n\n There are also significant differences between the microbiota of different sites of the same human body. The inner surface of the cheek has a predominance of Streptococcus , whereas in the throat, the palatine tonsil, and saliva, there are two to three times fewer Streptococcus , and several times more Fusobacterium . In the plaque removed from gums, the predominant bacteria belong to the genus Fusobacterium. However, in the intestine, both Streptococcus and Fusobacterium disappear, and the genus Bacteroides becomes predominant. \n\n Not only can the microbiota vary from one body site to another, the microbiome can also change over time within the same individual. Humans acquire their first inoculations of normal flora during natural birth and shortly after birth. Before birth, there is a rapid increase in the population of Lactobacillus spp. in the vagina, and this population serves as the first colonization of microbiota during natural birth. After birth, additional microbes are acquired from health-care providers, parents, other relatives, and individuals who come in contact with the baby. This process establishes a microbiome that will continue to evolve over the course of the individual’s life as new microbes colonize and are eliminated from the body. For example, it is estimated that within a 9-hour period, the microbiota of the small intestine can change so that half of the microbial inhabitants will be different. 5 The importance of the initial Lactobacillus colonization during vaginal child birth is highlighted by studies demonstrating a higher incidence of diseases in individuals born by cesarean section , compared to those born vaginally. Studies have shown that babies born vaginally are predominantly colonized by vaginal lactobacillus, whereas babies born by cesarean section are more frequently colonized by microbes of the normal skin microbiota, including common hospital-acquired pathogens. 5 C.C. Booijink et al. “High Temporal and Intra-Individual Variation Detected in the Human Ileal Microbiota.” Environmental Microbiology 12 no. 12 (2010):3213–3227. \n\n Throughout the body, resident microbiotas are important for human health because they occupy niches that might be otherwise taken by pathogenic microorganisms. For instance, Lactobacillus spp. are the dominant bacterial species of the normal vaginal microbiota for most women. lactobacillus produce lactic acid, contributing to the acidity of the vagina and inhibiting the growth of pathogenic yeasts. However, when the population of the resident microbiota is decreased for some reason (e.g., because of taking antibiotics), the pH of the vagina increases, making it a more favorable environment for the growth of yeasts such as Candida albicans . Antibiotic therapy can also disrupt the microbiota of the intestinal tract and respiratory tract, increasing the risk for secondary infections and/or promoting the long-term carriage and shedding of pathogens. \n\n Check Your Understanding \n\n Explain the difference between cooperative and competitive interactions in microbial communities. \n\n List the types of symbiosis and explain how each population is affected. \n\n Taxonomy and Systematics \n\n Assigning prokaryotes to a certain species is challenging. They do not reproduce sexually, so it is not possible to classify them according to the presence or absence of interbreeding. Also, they do not have many morphological features. Traditionally, the classification of prokaryotes was based on their shape, staining patterns, and biochemical or physiological differences. More recently, as technology has improved, the nucleotide sequences in genes have become an important criterion of microbial classification. \n\n In 1923, American microbiologist David Hendricks Bergey (1860–1937) published A Manual in Determinative Bacteriology. With this manual, he attempted to summarize the information about the kinds of bacteria known at that time, using Latin binomial classification. Bergey also included the morphological, physiological, and biochemical properties of these organisms. His manual has been updated multiple times to include newer bacteria and their properties. It is a great aid in bacterial taxonomy and methods of characterization of bacteria. A more recent sister publication, the five-volume Bergey’s Manual of Systematic Bacteriology , expands on Bergey’s original manual. It includes a large number of additional species, along with up-to-date descriptions of the taxonomy and biological properties of all named prokaryotic taxa. This publication incorporates the approved names of bacteria as determined by the List of Prokaryotic Names with Standing in Nomenclature (LPSN). \n\n Link to Learning \n\n The 7th edition (published in 1957) of Bergey’s Manual of Determinative Bacteriology is now available . More recent, updated editions are available in print. You can also access a searchable database of microbial reference strains, published by the American Type Culture Collection (ATCC). \n\n Classification by Staining Patterns \n\n According to their staining patterns , which depend on the properties of their cell walls, bacteria have traditionally been classified into gram-positive, gram-negative, and “atypical,” meaning neither gram-positive nor gram-negative. As explained in Staining Microscopic Specimens , gram-positive bacteria possess a thick peptidoglycan cell wall that retains the primary stain (crystal violet) during the decolorizing step; they remain purple after the gram-stain procedure because the crystal violet dominates the light red/pink color of the secondary counterstain, safranin. In contrast, gram-negative bacteria possess a thin peptidoglycan cell wall that does not prevent the crystal violet from washing away during the decolorizing step; therefore, they appear light red/pink after staining with the safranin. Bacteria that cannot be stained by the standard Gram stain procedure are called atypical bacteria . Included in the atypical category are species of Mycoplasma and Chlamydia . Rickettsia are also considered atypical because they are too small to be evaluated by the Gram stain. More recently, scientists have begun to further classify gram-negative and gram-positive bacteria. They have added a special group of deeply branching bacteria based on a combination of physiological, biochemical, and genetic features. They also now further classify gram-negative bacteria into Proteobacteria , Cytophaga-Flavobacterium-Bacteroides (CFB) , and spirochetes . \n\n The deeply branching bacteria are thought to be a very early evolutionary form of bacteria (see Deeply Branching Bacteria ). They live in hot, acidic, ultraviolet-light-exposed, and anaerobic (deprived of oxygen) conditions. Proteobacteria is a phylum of very diverse groups of gram-negative bacteria; it includes some important human pathogens (e.g., E. coli and Bordetella pertussis ). The CFB group of bacteria includes components of the normal human gut microbiota, like Bacteroides . The spirochetes are spiral-shaped bacteria and include the pathogen Treponema pallidum , which causes syphilis. We will characterize these groups of bacteria in more detail later in the chapter. \n\n Based on their prevalence of guanine and cytosine nucleotides, gram-positive bacteria are also classified into low G+C and high G+C gram-positive bacteria . The low G+C gram-positive bacteria have less than 50% of guanine and cytosine nucleotides in their DNA. They include human pathogens, such as those that cause anthrax ( Bacillus anthracis ), tetanus ( Clostridium tetani ), and listeriosis ( Listeria monocytogenes ). High G+C gram-positive bacteria, which have more than 50% guanine and cytosine nucleotides in their DNA, include the bacteria that cause diphtheria ( Corynebacterium diphtheriae ), tuberculosis ( Mycobacterium tuberculosis ), and other diseases. \n\n The classifications of prokaryotes are constantly changing as new species are being discovered. We will describe them in more detail, along with the diseases they cause, in later sections and chapters. \n\n Check Your Understanding \n\n How do scientists classify prokaryotes? \n\n Micro Connections Human Microbiome Project The Human Microbiome Project was launched by the National Institutes of Health (NIH) in 2008. One main goal of the project is to create a large repository of the gene sequences of important microbes found in humans, helping biologists and clinicians understand the dynamics of the human microbiome and the relationship between the human microbiota and diseases. A network of labs working together has been compiling the data from swabs of several areas of the skin, gut, and mouth from hundreds of individuals. \n\n One of the challenges in understanding the human microbiome has been the difficulty of culturing many of the microbes that inhabit the human body. It has been estimated that we are only able to culture 1% of the bacteria in nature and that we are unable to grow the remaining 99%. To address this challenge, researchers have used metagenomic analysis , which studies genetic material harvested directly from microbial communities, as opposed to that of individual species grown in a culture. This allows researchers to study the genetic material of all microbes in the microbiome, rather than just those that can be cultured. 6 6 National Institutes of Health. “Human Microbiome Project. Overview.” http://commonfund.nih.gov/hmp/overview. Accessed June 7, 2016. \n\n One important achievement of the Human Microbiome Project is establishing the first reference database on microorganisms living in and on the human body. Many of the microbes in the microbiome are beneficial, but some are not. It was found, somewhat unexpectedly, that all of us have some serious microbial pathogens in our microbiota. For example, the conjunctiva of the human eye contains 24 genera of bacteria and numerous pathogenic species. 7 A healthy human mouth contains a number of species of the genus Streptococcus , including pathogenic species S. pyogenes and S. pneumoniae . 8 This raises the question of why certain prokaryotic organisms exist commensally in certain individuals but act as deadly pathogens in others. Also unexpected was the number of organisms that had never been cultured. For example, in one metagenomic study of the human gut microbiota, 174 new species of bacteria were identified. 9 7 Q. Dong et al. “Diversity of Bacteria at Healthy Human Conjunctiva.” Investigative Ophthalmology & Visual Science 52 no. 8 (2011):5408–5413. 8 F.E. Dewhirst et al. “The Human Oral Microbiome.” Journal of Bacteriology 192 no. 19 (2010):5002–5017. 9 J.C. Lagier et al. “Microbial Culturomics: Paradigm Shift in the Human Gut Microbiome Study.” Clinical Microbiology and Infection 18 no. 12 (2012):1185–1193. \n\n Another goal for the near future is to characterize the human microbiota in patients with different diseases and to find out whether there are any relationships between the contents of an individual’s microbiota and risk for or susceptibility to specific diseases. Analyzing the microbiome in a person with a specific disease may reveal new ways to fight diseases. \n 4.2 Proteobacteria \n\n Learning Objectives \n\n Describe the unique features of each class within the phylum Proteobacteria: Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Deltaproteobacteria, and Epsilonproteobacteria \n\n Give an example of a bacterium in each class of Proteobacteria \n\n In 1987, the American microbiologist Carl Woese (1928–2012) suggested that a large and diverse group of bacteria that he called “purple bacteria and their relatives” should be defined as a separate phylum within the domain Bacteria based on the similarity of the nucleotide sequences in their genome. 10 This phylum of gram-negative bacteria subsequently received the name Proteobacteria . It includes many bacteria that are part of the normal human microbiota as well as many pathogens. The Proteobacteria are further divided into five classes: Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Deltaproteobacteria, and Epsilonproteobacteria ( Appendix D ). 10 C.R. Woese. “Bacterial Evolution.” Microbiological Review 51 no. 2 (1987):221–271. \n\n Alphaproteobacteria \n\n The first class of Proteobacteria is the Alphaproteobacteria , many of which are obligate or facultative intracellular bacteria. Some species are characterized as oligotroph s, organisms capable of living in low-nutrient environments such as deep oceanic sediments, glacial ice, or deep undersurface soil. \n\n Among the Alphaproteobacteria are rickettsias, obligate intracellular pathogen s, that require part of their life cycle to occur inside other cells called host cells. When not growing inside a host cell, Rickettsia are metabolically inactive outside the host cell. They cannot synthesize their own adenosine triphosphate (ATP), and, therefore, rely on cells for their energy needs. Rickettsia spp. include a number of serious human pathogens. For example, R. rickettsii causes Rocky Mountain spotted fever , a life-threatening form of meningoencephalitis (inflammation of the membranes that wrap the brain). R. rickettsii infects ticks and can be transmitted to humans via a bite from an infected tick ( Figure 4.4 ). \n\n Another species of Rickettsia , R. prowazekii , is spread by lice. It causes epidemic typhus , a severe infectious disease common during warfare and mass migrations of people. R. prowazekii infects human endothelium cells, causing inflammation of the inner lining of blood vessels, high fever, abdominal pain, and sometimes delirium. A relative, R. typhi , causes a less severe disease known as murine or endemic typhus, which is still observed in the southwestern United States during warm seasons. \n\n Table 4.2 summarizes the characteristics of important genera of Alphaproteobacteria. \n\n C. trachomatis is a human pathogen that causes trachoma , a disease of the eyes, often leading to blindness. C. trachomatis also causes the sexually transmitted disease lymphogranuloma venereum (LGV). This disease is often mildly symptomatic, manifesting as regional lymph node swelling, or it may be asymptomatic, but it is extremely contagious and is common on college campuses. \n\n Class Alphaproteobacteria \n\n Genus \n\n Microscopic Morphology \n\n Unique Characteristics \n\n Agrobacterium \n\n Gram-negative bacillus \n\n Plant pathogen; one species, A. tumefaciens , causes tumors in plants \n\n Bartonella \n\n Gram-negative, pleomorphic, flagellated coccobacillus \n\n Facultative intracellular bacteria, transmitted by lice and fleas, cause trench fever and cat scratch disease in humans \n\n Brucella \n\n Gram-negative, small, flagellated coccobacillus \n\n Facultative intracellular bacteria, transmitted by contaminated milk from infected cows, cause brucellosis in cattle and humans \n\n Caulobacter \n\n Gram-negative bacillus \n\n Used in studies on cellular adaptation and differentiation because of its peculiar life cycle (during cell division, forms “swarm” cells and “stalked” cells) \n\n Coxiella \n\n Small, gram-negative bacillus \n\n Obligatory intracellular bacteria; cause Q fever; potential for use as biological weapon \n\n Ehrlichia \n\n Very small, gram-negative, coccoid or ovoid bacteria \n\n Obligatory intracellular bacteria; can be transported from cell to cell; transmitted by ticks; cause ehrlichiosis (destruction of white blood cells and inflammation) in humans and dogs \n\n Hyphomicrobium \n\n Gram-negative bacilli; grows from a stalk \n\n Similar to Caulobacter \n\n Methylocystis \n\n Gram-negative, coccoid or short bacilli \n\n Nitrogen-fixing aerobic bacteria \n\n Rhizobium \n\n Gram-negative, rectangular bacilli with rounded ends forming clusters \n\n Nitrogen-fixing bacteria that live in soil and form symbiotic relationship with roots of legumes (e.g., clover, alfalfa, and beans) \n\n Rickettsia \n\n Gram-negative, highly pleomorphic bacteria (may be cocci, rods, or threads) \n\n Obligate intracellular bacteria; transmitted by ticks; may cause Rocky Mountain spotted fever and typhus \n\n Table 4.2 Check Your Understanding \n\n What is a common characteristic among the human pathogenic Alphaproteobacteria? \n\n Betaproteobacteria \n\n Betaproteobacteria are a diverse group of bacteria. The different bacterial species within this group utilize a wide range of metabolic strategies and can survive in a range of environments. Some genera include species that are human pathogens, able to cause severe, sometimes life-threatening disease. The genus Neisseria , for example, includes the bacteria N. gonorrhoeae, the causative agent of the STI gonorrhea , and N. meningitides , the causative agent of bacterial meningitis . \n\n Neisseria are cocci that live on mucosal surfaces of the human body. They are fastidious, or difficult to culture, and they require high levels of moisture, nutrient supplements, and carbon dioxide. Also, Neisseria are microaerophilic, meaning that they require low levels of oxygen. For optimal growth and for the purposes of identification, Neisseria spp. are grown on chocolate agar (i.e., agar supplemented by partially hemolyzed red blood cells). Their characteristic pattern of growth in culture is diplococcal: pairs of cells resembling coffee beans ( Figure 4.5 ). \n\n The pathogen responsible for pertussis ( whooping cough ) is also a member of Betaproteobacteria. The bacterium Bordetella pertussis , from the order Burkholderiales , produces several toxins that paralyze the movement of cilia in the human respiratory tract and directly damage cells of the respiratory tract, causing a severe cough. \n\n Table 4.3 summarizes the characteristics of important genera of Betaproteobacteria. \n\n Class Betaproteobacteria \n\n Example Genus \n\n Microscopic Morphology \n\n Unique Characteristics \n\n Bordetella \n\n A small, gram-negative coccobacillus \n\n Aerobic, very fastidious; B. pertussis causes pertussis (whooping cough) \n\n Burkholderia \n\n Gram-negative bacillus \n\n Aerobic, aquatic, cause diseases in horses and humans (especially patients with cystic fibrosis); agents of nosocomial infections \n\n Leptothrix \n\n Gram-negative, sheathed, filamentous bacillus \n\n Aquatic; oxidize iron and manganese; can live in wastewater treatment plants and clog pipes \n\n Neisseria \n\n Gram-negative, coffee bean-shaped coccus forming pairs \n\n Require moisture and high concentration of carbon dioxide; oxidase positive, grow on chocolate agar; pathogenic species cause gonorrhea and meningitis \n\n Thiobacillus \n\n Gram-negative bacillus \n\n Thermophilic, acidophilic, strictly aerobic bacteria; oxidize iron and sulfur \n\n Table 4.3 \n\n Check Your Understanding \n\n Why are Neisseria classified as microaerophilic? \n\n Clinical Focus Part 2 When Marsha finally went to the doctor’s office, the physician listened to her breathing through a stethoscope. He heard some crepitation (a crackling sound) in her lungs, so he ordered a chest radiograph and asked the nurse to collect a sputum sample for microbiological evaluation and cytology. The radiologic evaluation found cavities, opacities, and a particular pattern of distribution of abnormal material ( Figure 4.6 ). \n\n What are some possible diseases that could be responsible for Marsha’s radiograph results? \n\n Jump to the next Clinical Focus box. Go back to the previous Clinical Focus box. \n\n Gammaproteobacteria \n\n The most diverse class of gram-negative bacteria is Gammaproteobacteria , and it includes a number of human pathogens. For example, a large and diverse family, Pseudomonaceae , includes the genus Pseudomonas . Within this genus is the species P. aeruginosa , a pathogen responsible for diverse infections in various regions of the body. P. aeruginosa is a strictly aerobic, nonfermenting, highly motile bacterium. It often infects wounds and burns, can be the cause of chronic urinary tract infections, and can be an important cause of respiratory infections in patients with cystic fibrosis or patients on mechanical ventilators. Infections by P. aeruginosa are often difficult to treat because the bacterium is resistant to many antibiotics and has a remarkable ability to form biofilms. Other representatives of Pseudomonas include the fluorescent (glowing) bacterium P. fluorescens and the soil bacteria P. putida , which is known for its ability to degrade xenobiotics (substances not naturally produced or found in living organisms). \n\n The Pasteurellaceae also includes several clinically relevant genera and species. This family includes several bacteria that are human and/or animal pathogens. For example, Pasteurella haemolytica causes severe pneumonia in sheep and goats. P. multocida is a species that can be transmitted from animals to humans through bites, causing infections of the skin and deeper tissues. The genus Haemophilus contains two human pathogens, H. influenzae and H. ducreyi . Despite its name, H. influenzae does not cause influenza (which is a viral disease). H. influenzae can cause both upper and lower respiratory tract infections, including sinusitis, bronchitis, ear infections, and pneumonia. Before the development of effective vaccination, strains of H. influenzae were a leading cause of more invasive diseases, like meningitis in children. H. ducreyi causes the STI known as chancroid . \n\n The order Vibrionales includes the human pathogen Vibrio cholerae . This comma-shaped aquatic bacterium thrives in highly alkaline environments like shallow lagoons and sea ports. A toxin produced by V. cholerae causes hypersecretion of electrolytes and water in the large intestine, leading to profuse watery diarrhea and dehydration. V. parahaemolyticus is also a cause of gastrointestinal disease in humans, whereas V. vulnificus causes serious and potentially life-threatening cellulitis (infection of the skin and deeper tissues) and blood-borne infections. Another representative of Vibrionales, Aliivibrio fischeri , engages in a symbiotic relationship with squid. The squid provides nutrients for the bacteria to grow and the bacteria produce bioluminescence that protects the squid from predators ( Figure 4.7 ). \n\n The genus Legionella also belongs to the Gammaproteobacteria. L. pneumophila, the pathogen responsible for Legionnaires disease , is an aquatic bacterium that tends to inhabit pools of warm water, such as those found in the tanks of air conditioning units in large buildings ( Figure 4.8 ). Because the bacteria can spread in aerosols, outbreaks of Legionnaires disease often affect residents of a building in which the water has become contaminated with Legionella. In fact, these bacteria derive their name from the first known outbreak of Legionnaires disease, which occurred in a hotel hosting an American Legion veterans’ association convention in Philadelphia in 1976. \n\n Enterobacteriaceae is a large family of enteric (intestinal) bacteria belonging to the Gammaproteobacteria . They are facultative anaerobes and are able to ferment carbohydrates. Within this family, microbiologists recognize two distinct categories. The first category is called the coliforms, after its prototypical bacterium species, Escherichia coli . Coliforms are able to ferment lactose completely (i.e., with the production of acid and gas). The second category, noncoliforms , either cannot ferment lactose or can only ferment it incompletely (producing either acid or gas, but not both). The noncoliforms include some notable human pathogens, such as Salmonella spp ., Shigella spp ., and Yersinia pestis . \n\n E. coli has been perhaps the most studied bacterium since it was first described in 1886 by Theodor Escherich (1857–1911). Many strains of E. coli are in mutualistic relationships with humans. However, some strains produce a potentially deadly toxin called Shiga toxin. Shiga toxin is one of the most potent bacterial toxins identified. Upon entering target cells, Shiga toxin interacts with ribosomes, stopping protein synthesis. Lack of protein synthesis leads to cellular death and hemorrhagic colitis, characterized by inflammation of intestinal tract and bloody diarrhea. In the most severe cases, patients can develop a deadly hemolytic uremic syndrome. Other E. coli strains may cause traveler’s diarrhea, a less severe but very widespread disease. The genus Salmonella , which belongs to the noncoliform group of Enterobacteriaceae , is interesting in that there is still no consensus about how many species it includes. Scientists have reclassified many of the groups they once thought to be species as serotypes (also called serovars ), which are strains or variations of the same species of bacteria. Their classification is based on patterns of reactivity by animal antisera against molecules on the surface of the bacterial cells. A number of serotypes of Salmonella can cause salmonellosis , characterized by inflammation of the small and the large intestine, accompanied by fever, vomiting, and diarrhea. The species S. enterobacterica (serovar typhi ) causes typhoid fever , with symptoms including fever, abdominal pain, and skin rashes ( Figure 4.9 ). \n\n Table 4.4 summarizes the characteristics of important genera of Gammaproteobacteria. \n\n Class Gammaproteobacteria \n\n Example Genus \n\n Microscopic Morphology \n\n Unique Characteristics \n\n Beggiatoa \n\n Gram-negative bacteria; disc-shaped or cylindrical \n\n Aquatic, live in water with high content of hydrogen disulfide; can cause problems for sewage treatment \n\n Enterobacter \n\n Gram-negative bacillus \n\n Facultative anaerobe; cause urinary and respiratory tract infections in hospitalized patients; implicated in the pathogenesis of obesity \n\n Erwinia \n\n Gram-negative bacillus \n\n Plant pathogen causing leaf spots and discoloration; may digest cellulose; prefer relatively low temperatures (25–30 °C) \n\n Escherichia \n\n Gram-negative bacillus \n\n Facultative anaerobe; inhabit the gastrointestinal tract of warm-blooded animals; some strains are mutualists, producing vitamin K; others, like serotype E. coli O157:H7, are pathogens; E. coli has been a model organism for many studies in genetics and molecular biology \n\n Hemophilus \n\n Gram-negative bacillus \n\n Pleomorphic, may appear as coccobacillus, aerobe, or facultative anaerobe; grow on blood agar; pathogenic species can cause respiratory infections, chancroid, and other diseases \n\n Klebsiella \n\n Gram-negative bacillus; appears rounder and thicker than other members of Enterobacteriaceae \n\n Facultative anaerobe, encapsulated, nonmotile; pathogenic species may cause pneumonia, especially in people with alcoholism \n\n Legionella \n\n Gram-negative bacillus \n\n Fastidious, grow on charcoal-buffered yeast extract; L. pneumophila causes Legionnaires disease \n\n Methylomonas \n\n Gram-negative bacillus \n\n Use methane as source of carbon and energy \n\n Proteus \n\n Gram-negative bacillus (pleomorphic) \n\n Common inhabitants of the human gastrointestinal tract; motile; produce urease; opportunistic pathogens; may cause urinary tract infections and sepsis \n\n Pseudomonas \n\n Gram-negative bacillus \n\n Aerobic; versatile; produce yellow and blue pigments, making them appear green in culture; opportunistic, antibiotic-resistant pathogens may cause wound infections, hospital-acquired infections, and secondary infections in patients with cystic fibrosis \n\n Serratia \n\n Gram-negative bacillus \n\n Motile; may produce red pigment; opportunistic pathogens responsible for a large number of hospital-acquired infections \n\n Shigella \n\n Gram-negative bacillus \n\n Nonmotile; dangerously pathogenic; produce Shiga toxin, which can destroy cells of the gastrointestinal tract; can cause dysentery \n\n Vibrio \n\n Gram-negative, comma- or curved rod-shaped bacteria \n\n Inhabit seawater; flagellated, motile; may produce toxin that causes hypersecretion of water and electrolytes in the gastrointestinal tract; some species may cause serious wound infections \n\n Yersinia \n\n Gram-negative bacillus \n\n Carried by rodents; human pathogens; Y. pestis causes bubonic plague and pneumonic plague; Y. enterocolitica can be a pathogen causing diarrhea in humans \n\n Table 4.4 \n\n Check Your Understanding \n\n List two families of Gammaproteobacteria. \n\n Deltaproteobacteria \n\n The Deltaproteobacteria is a small class of gram-negative Proteobacteria that includes sulfate-reducing bacteria (SRBs), so named because they use sulfate as the final electron acceptor in the electron transport chain. Few SRBs are pathogenic. However, the SRB Desulfovibrio orale is associated with periodontal disease (disease of the gums). \n\n Deltaproteobacteria also includes the genus Bdellovibrio , species of which are parasites of other gram-negative bacteria. Bdellovibrio invades the cells of the host bacterium, positioning itself in the periplasm, the space between the plasma membrane and the cell wall, feeding on the host’s proteins and polysaccharides. The infection is lethal for the host cells. \n\n Another type of Deltaproteobacteria, myxobacteria , lives in the soil, scavenging inorganic compounds. Motile and highly social, they interact with other bacteria within and outside their own group. They can form multicellular, macroscopic “ fruiting bodies ” ( Figure 4.10 ), structures that are still being studied by biologists and bacterial ecologists. 11 These bacteria can also form metabolically inactive myxospores . 11 H. Reichenbach. “Myxobacteria, Producers of Novel Bioactive Substances.” Journal of Industrial Microbiology & Biotechnology 27 no. 3 (2001):149–156. \n\n Table 4.5 summarizes the characteristics of several important genera of Deltaproteobacteria. \n\n Class Deltaproteobacteria \n\n Genus \n\n Microscopic Morphology \n\n Unique characteristics \n\n Bdellovibrio \n\n Gram-negative, comma-shaped rod \n\n Obligate aerobes; motile; parasitic (infecting other bacteria) \n\n Desulfovibrio (formerly Desufuromonas ) \n\n Gram-negative, comma-shaped rod \n\n Reduce sulfur; can be used for removal of toxic and radioactive waste \n\n Myxobacterium \n\n Gram-negative, coccoid bacteria forming colonies (swarms) \n\n Live in soil; can move by gliding; used as a model organism for studies of intercellular communication (signaling) \n\n Table 4.5 \n\n Check Your Understanding \n\n What type of Deltaproteobacteria forms fruiting bodies? \n\n Epsilonproteobacteria \n\n The smallest class of Proteobacteria is Epsilonproteobacteria , which are gram-negative microaerophilic bacteria (meaning they only require small amounts of oxygen in their environment). Two clinically relevant genera of Epsilonproteobacteria are Campylobacter and Helicobacter , both of which include human pathogens. Campylobacter can cause food poisoning that manifests as severe enteritis (inflammation in the small intestine). This condition, caused by the species C. jejuni , is rather common in developed countries, usually because of eating contaminated poultry products. Chickens often harbor C. jejuni in their gastrointestinal tract and feces, and their meat can become contaminated during processing. \n\n Within the genus Helicobacter, the helical, flagellated bacterium H. pylori has been identified as a beneficial member of the stomach microbiota, but it is also the most common cause of chronic gastritis and ulcers of the stomach and duodenum ( Figure 4.11 ). Studies have also shown that H. pylori is linked to stomach cancer. 12 H. pylori is somewhat unusual in its ability to survive in the highly acidic environment of the stomach. It produces urease and other enzymes that modify its environment to make it less acidic. 12 S. Suerbaum, P. Michetti. “ Helicobacter pylori infection.” New England Journal of Medicine 347 no. 15 (2002):1175–1186. \n\n Table 4.6 summarizes the characteristics of the most clinically relevant genera of Epsilonproteobacteria. \n\n Class Epsilonproteobacteria \n\n Example Genus \n\n Microscopic Morphology \n\n Unique Characteristics \n\n Campylobacter \n\n Gram-negative, spiral-shaped rod \n\n Aerobic (microaerophilic); often infects chickens; may infect humans via undercooked meat, causing severe enteritis \n\n Helicobacter \n\n Gram-negative, spiral-shaped rod \n\n Aerobic (microaerophilic) bacterium; can damage the inner lining of the stomach, causing chronic gastritis, peptic ulcers, and stomach cancer \n\n Table 4.6 \n\n Check Your Understanding \n\n Name two Epsilonproteobacteria that cause gastrointestinal disorders. \n 4.3 Nonproteobacteria Gram-Negative Bacteria and Phototrophic Bacteria \n\n Learning Objectives \n\n Describe the unique features of nonproteobacteria gram-negative bacteria \n\n Give an example of a nonproteobacteria bacterium in each category \n\n Describe the unique features of phototrophic bacteria \n\n Identify phototrophic bacteria \n\n The majority of the gram-negative bacteria belong to the phylum Proteobacteria, discussed in the previous section. Those that do not are called the nonproteobacteria . In this section, we will describe four classes of gram-negative nonproteobacteria: Chlamydia , the spirochetes, the CFB group, and the Planctomycetes. A diverse group of phototrophic bacteria that includes Proteobacteria and nonproteobacteria will be discussed at the end of this section. Chlamydia \n\n Chlamydia is another taxon of the Alphaproteobacteria. Members of this genus are gram-negative, obligate intracellular pathogens that are extremely resistant to the cellular defenses, giving them the ability to spread from host to host rapidly via elementary bodies. The metabolically and reproductively inactive elementary bodies are the endospore-like form of intracellular bacteria that enter an epithelial cell, where they become active. Figure 4.12 illustrates the life cycle of Chlamydia .\n\n Spirochetes \n\n Spirochetes are characterized by their long (up to 250 μm), spiral-shaped bodies. Most spirochetes are also very thin, which makes it difficult to examine gram-stained preparations under a conventional brightfield microscope. Darkfield fluorescent microscopy is typically used instead. Spirochetes are also difficult or even impossible to culture. They are highly motile, using their axial filament to propel themselves. The axial filament is similar to a flagellum, but it wraps around the cell and runs inside the cell body of a spirochete in the periplasmic space between the outer membrane and the plasma membrane ( Figure 4.13 ). \n\n Several genera of spirochetes include human pathogens. For example, the genus Treponema includes a species T. pallidum , which is further classified into four subspecies: T. pallidum pallidum , T. pallidum pertenue, T. pallidum carateum, and T. pallidum endemicum . The subspecies T. pallidum pallidum causes the sexually transmitted infection known as syphilis , the third most prevalent sexually transmitted bacterial infection in the United States, after chlamydia and gonorrhea. The other subspecies of T. pallidum cause tropical infectious diseases of the skin, bones, and joints. \n\n Another genus of spirochete, Borrelia , contains a number of pathogenic species. B. burgdorferi causes Lyme disease , which is transmitted by several genera of ticks (notably Ixodes and Amblyomma ) and often produces a “bull’s eye” rash, fever, fatigue, and, sometimes, debilitating arthritis. B. recurrens causes a condition known as relapsing fever. Appendix D lists the genera, species, and related diseases for spirochetes. \n\n Check Your Understanding \n\n Why do scientists typically use darkfield fluorescent microscopy to visualize spirochetes? \n\n Cytophaga , Fusobacterium , and Bacteroides \n\n The gram-negative nonproteobacteria of the genera Cytophaga , Fusobacterium , and Bacteroides are classified together as a phylum and called the CFB group . Although they are phylogenetically diverse, bacteria of the CFB group share some similarities in the sequence of nucleotides in their DNA. They are rod-shaped bacteria adapted to anaerobic environments, such as the tissue of the gums, gut, and rumen of ruminating animals. CFB bacteria are avid fermenters, able to process cellulose in rumen, thus enabling ruminant animals to obtain carbon and energy from grazing. \n\n Cytophaga are motile aquatic bacteria that glide. Fusobacteria inhabit the human mouth and may cause severe infectious diseases. The largest genus of the CFB group is Bacteroides , which includes dozens of species that are prevalent inhabitants of the human large intestine, making up about 30% of the entire gut microbiome ( Figure 4.14 ). One gram of human feces contains up to 100 billion Bacteroides cells. Most Bacteroides are mutualistic. They benefit from nutrients they find in the gut, and humans benefit from their ability to prevent pathogens from colonizing the large intestine. Indeed, when populations of Bacteroides are reduced in the gut—as often occurs when a patient takes antibiotics—the gut becomes a more favorable environment for pathogenic bacteria and fungi, which can cause secondary infections. \n\n Only a few species of Bacteroides are pathogenic. B. melaninogenicus , for example, can cause wound infections in patients with weakened immune systems. \n\n Check Your Understanding \n\n Why are Cytophaga , Fusobacterium , and Bacteroides classified together as the CFB group? \n\n Planctomycetes \n\n The Planctomycetes are found in aquatic environments, inhabiting freshwater, saltwater, and brackish water. Planctomycetes are unusual in that they reproduce by budding, meaning that instead of one maternal cell splitting into two equal daughter cells in the process of binary fission, the mother cell forms a bud that detaches from the mother cell and lives as an independent cell. These so-called swarmer cells are motile and not attached to a surface. However, they will soon differentiate into sessile (immobile) cells with an appendage called a holdfast that allows them to attach to surfaces in the water ( Figure 4.15 ). Only the sessile cells are able to reproduce. \n\n Table 4.7 summarizes the characteristics of some of the most clinically relevant genera of nonproteobacteria. \n\n Nonproteobacteria \n\n Example Genus \n\n Microscopic Morphology \n\n Unique Characteristics \n\n Chlamydia \n\n Gram-negative, coccoid or ovoid bacterium \n\n Obligatory intracellular bacteria; some cause chlamydia, trachoma, and pneumonia \n\n Bacteroides \n\n Gram-negative bacillus \n\n Obligate anaerobic bacteria; abundant in the human gastrointestinal tract; usually mutualistic, although some species are opportunistic pathogens \n\n Cytophaga \n\n Gram-negative bacillus \n\n Motile by gliding; live in soil or water; decompose cellulose; may cause disease in fish \n\n Fusobacterium \n\n Gram-negative bacillus with pointed ends \n\n Anaerobic; form; biofilms; some species cause disease in humans (periodontitis, ulcers) \n\n Leptospira \n\n Spiral-shaped bacterium (spirochetes); gram negative-like (better viewed by darkfield microscopy); very thin \n\n Aerobic, abundant in shallow water reservoirs; infect rodents and domestic animals; can be transmitted to humans by infected animals’ urine; may cause severe disease \n\n Borrelia \n\n Gram-negative-like spirochete; very thin; better viewed by darkfield microscopy \n\n B. burgdorferi causes Lyme disease and B. recurrens causes relapsing fever \n\n Treponema \n\n Gram-negative-like spirochete; very thin; better viewed by darkfield microscopy \n\n Motile; do not grow in culture; T. pallidum (subspecies T. pallidum pallidum ) causes syphilis \n\n Table 4.7 Check Your Understanding \n\n How do Planctomycetes reproduce? \n\n Phototrophic Bacteria \n\n The phototrophic bacteria are a large and diverse category of bacteria that do not represent a taxon but, rather, a group of bacteria that use sunlight as their primary source of energy. This group contains both Proteobacteria and nonproteobacteria . They use solar energy to synthesize ATP through photosynthesis . When they produce oxygen, they perform oxygenic photosynthesis. When they do not produce oxygen, they perform anoxygenic photosynthesis. With the exception of some cyanobacteria, the majority of phototrophic bacteria perform anoxygenic photosynthesis. \n\n One large group of phototrophic bacteria includes the purple or green bacteria that perform photosynthesis with the help of bacteriochlorophylls , which are green, purple, or blue pigments similar to chlorophyll in plants. Some of these bacteria have a varying amount of red or orange pigments called carotenoids . Their color varies from orange to red to purple to green ( Figure 4.16 ), and they are able to absorb light of various wavelengths. Traditionally, these bacteria are classified into sulfur and nonsulfur bacteria ; they are further differentiated by color. \n\n The sulfur bacteria perform anoxygenic photosynthesis, using sulfites as electron donors and releasing free elemental sulfur. Nonsulfur bacteria use organic substrates, such as succinate and malate, as donors of electrons. \n\n The purple sulfur bacteria oxidize hydrogen sulfide into elemental sulfur and sulfuric acid and get their purple color from the pigments bacteriochlorophylls and carotenoids. Bacteria of the genus Chromatium are purple sulfur Gammaproteobacteria . These microorganisms are strict anaerobes and live in water. They use carbon dioxide as their only source of carbon, but their survival and growth are possible only in the presence of sulfites, which they use as electron donors. Chromatium has been used as a model for studies of bacterial photosynthesis since the 1950s. 13 13 R.C. Fuller et al. “Carbon Metabolism in Chromatium .” Journal of Biological Chemistry 236 (1961):2140–2149. \n\n The green sulfur bacteria use sulfide for oxidation and produce large amounts of green bacteriochlorophyll. The genus Chlorobium is a green sulfur bacterium that is implicated in climate change because it produces methane, a greenhouse gas. These bacteria use at least four types of chlorophyll for photosynthesis . The most prevalent of these, bacteriochlorophyll, is stored in special vesicle-like organelles called chlorosomes . \n\n Purple nonsulfur bacteria are similar to purple sulfur bacteria, except that they use hydrogen rather than hydrogen sulfide for oxidation. Among the purple nonsulfur bacteria is the genus Rhodospirillum . These microorganisms are facultative anaerobes, which are actually pink rather than purple, and can metabolize (“fix”) nitrogen. They may be valuable in the field of biotechnology because of their potential ability to produce biological plastic and hydrogen fuel. 14 14 T.T. Selao et al. “Comparative Proteomic Studies in Rhodospirillum rubrum Grown Under Different Nitrogen Conditions.” Journal of Proteome Research 7 no. 8 (2008):3267–3275. \n\n The green nonsulfur bacteria are similar to green sulfur bacteria but they use substrates other than sulfides for oxidation. Chloroflexus is an example of a green nonsulfur bacterium. It often has an orange color when it grows in the dark, but it becomes green when it grows in sunlight. It stores bacteriochlorophyll in chlorosomes, similar to Chlorobium , and performs anoxygenic photosynthesis , using organic sulfites (low concentrations) or molecular hydrogen as electron donors, so it can survive in the dark if oxygen is available. Chloroflexus does not have flagella but can glide, like Cytophaga . It grows at a wide range of temperatures, from 35 °C to 70 °C, thus can be thermophilic. \n\n Another large, diverse group of phototrophic bacteria compose the phylum Cyanobacteria ; they get their blue-green color from the chlorophyll contained in their cells ( Figure 4.17 ). Species of this group perform oxygenic photosynthesis, producing megatons of gaseous oxygen. Scientists hypothesize that cyanobacteria played a critical role in the change of our planet’s anoxic atmosphere 1–2 billion years ago to the oxygen-rich environment we have today. 15 15 A. De los Rios et al. “Ultrastructural and Genetic Characteristics of Endolithic Cyanobacterial Biofilms Colonizing Antarctic Granite Rocks.” FEMS Microbiology Ecology 59 no. 2 (2007):386–395. \n\n Cyanobacteria have other remarkable properties. Amazingly adaptable, they thrive in many habitats, including marine and freshwater environments, soil, and even rocks. They can live at a wide range of temperatures, even in the extreme temperatures of the Antarctic. They can live as unicellular organisms or in colonies, and they can be filamentous, forming sheaths or biofilms. Many of them fix nitrogen, converting molecular nitrogen into nitrites and nitrates that other bacteria, plants, and animals can use. The reactions of nitrogen fixation occur in specialized cells called heterocysts . \n\n Photosynthesis in Cyanobacteria is oxygenic, using the same type of chlorophyll a found in plants and algae as the primary photosynthetic pigment. Cyanobacteria also use phycocyanin and cyanophycin , two secondary photosynthetic pigments that give them their characteristic blue color. They are located in special organelles called phycobilisomes and in folds of the cellular membrane called thylakoids , which are remarkably similar to the photosynthetic apparatus of plants. Scientists hypothesize that plants originated from endosymbiosis of ancestral eukaryotic cells and ancestral photosynthetic bacteria. 16 Cyanobacteria are also an interesting object of research in biochemistry, 17 with studies investigating their potential as biosorbents 18 and products of human nutrition. 19 16 T. Cavalier-Smith. “Membrane Heredity and Early Chloroplast Evolution.” Trends in Plant Science 5 no. 4 (2000):174–182. 17 S. Zhang, D.A. Bryant. “The Tricarboxylic Acid Cycle in Cyanobacteria.” Science 334 no. 6062 (2011):1551–1553. 18 A. Cain et al. “Cyanobacteria as a Biosorbent for Mercuric Ion.” Bioresource Technology 99 no. 14 (2008):6578–6586. 19 C.S. Ku et al. “Edible Blue-Green Algae Reduce the Production of Pro-Inflammatory Cytokines by Inhibiting NF-κB Pathway in Macrophages and Splenocytes.” Biochimica et Biophysica Acta 1830 no. 4 (2013):2981–2988. \n\n Unfortunately, cyanobacteria can sometimes have a negative impact on human health. Genera such as Microcystis can form harmful cyanobacterial blooms , forming dense mats on bodies of water and producing large quantities of toxins that can harm wildlife and humans. These toxins have been implicated in tumors of the liver and diseases of the nervous system in animals and humans. 20 20 I. Stewart et al. Cyanobacterial Poisoning in Livestock, Wild Mammals and Birds – an Overview. Advances in Experimental Medicine and Biology 619 (2008):613–637. \n\n Table 4.8 summarizes the characteristics of important phototrophic bacteria. \n\n Phototrophic Bacteria \n\n Phylum \n\n Class \n\n Example Genus or Species \n\n Common Name \n\n Oxygenic or Anoxygenic \n\n Sulfur Deposition \n\n Cyanobacteria \n\n Cyanophyceae \n\n Microcystis aeruginosa \n\n Blue-green bacteria \n\n Oxygenic \n\n None \n\n Chlorobi \n\n Chlorobia \n\n Chlorobium \n\n Green sulfur bacteria \n\n Anoxygenic \n\n Outside the cell \n\n Chloroflexi (Division) \n\n Chloroflexi \n\n Chloroflexus \n\n Green nonsulfur bacteria \n\n Anoxygenic \n\n None \n\n Proteobacteria \n\n Alphaproteobacteria \n\n Rhodospirillum \n\n Purple nonsulfur bacteria \n\n Anoxygenic \n\n None \n\n Betaproteobacteria \n\n Rhodocyclus \n\n Purple nonsulfur bacteria \n\n Anoxygenic \n\n None \n\n Gammaproteobacteria \n\n Chromatium \n\n Purple sulfur bacteria \n\n Anoxygenic \n\n Inside the cell \n\n Table 4.8 \n\n Check Your Understanding \n\n What characteristic makes phototrophic bacteria different from other prokaryotes? \n 4.4 Gram-Positive Bacteria \n\n Learning Objectives \n\n Describe the unique features of each category of high G+C and low G+C gram-positive bacteria \n\n Identify similarities and differences between high G+C and low G+C bacterial groups \n\n Give an example of a bacterium of high G+C and low G+C group commonly associated with each category \n\n Prokaryotes are identified as gram-positive if they have a multiple layer matrix of peptidoglycan forming the cell wall. Crystal violet, the primary stain of the Gram stain procedure, is readily retained and stabilized within this matrix, causing gram-positive prokaryotes to appear purple under a brightfield microscope after Gram staining. For many years, the retention of Gram stain was one of the main criteria used to classify prokaryotes, even though some prokaryotes did not readily stain with either the primary or secondary stains used in the Gram stain procedure. \n\n Advances in nucleic acid biochemistry have revealed additional characteristics that can be used to classify gram-positive prokaryotes, namely the guanine to cytosine ratios (G+C) in DNA and the composition of 16S rRNA subunits. Microbiologists currently recognize two distinct groups of gram-positive, or weakly staining gram-positive, prokaryotes. The class Actinobacteria comprises the high G+C gram-positive bacteria , which have more than 50% guanine and cytosine nucleotides in their DNA. The class Bacilli comprises low G+C gram-positive bacteria , which have less than 50% of guanine and cytosine nucleotides in their DNA. \n\n Actinobacteria: High G+C Gram-Positive Bacteria \n\n The name Actinobacteria comes from the Greek words for rays and small rod , but Actinobacteria are very diverse. Their microscopic appearance can range from thin filamentous branching rods to coccobacilli. Some Actinobacteria are very large and complex, whereas others are among the smallest independently living organisms. Most Actinobacteria live in the soil, but some are aquatic. The vast majority are aerobic. One distinctive feature of this group is the presence of several different peptidoglycans in the cell wall. \n\n The genus Actinomyces is a much studied representative of Actinobacteria. Actinomyces spp. play an important role in soil ecology, and some species are human pathogens. A number of Actinomyces spp. inhabit the human mouth and are opportunistic pathogens, causing infectious diseases like periodontitis (inflammation of the gums) and oral abscesses. The species A. israelii is an anaerobe notorious for causing endocarditis (inflammation of the inner lining of the heart) ( Figure 4.18 ). \n\n The genus Mycobacterium is represented by bacilli covered with a mycolic acid coat. This waxy coat protects the bacteria from some antibiotics, prevents them from drying out, and blocks penetration by Gram stain reagents (see Staining Microscopic Specimens ). Because of this, a special acid-fast staining procedure is used to visualize these bacteria. The genus Mycobacterium is an important cause of a diverse group of infectious diseases. M. tuberculosis is the causative agent of tuberculosis , a disease that primarily impacts the lungs but can infect other parts of the body as well. It has been estimated that one-third of the world’s population has been infected with M. tuberculosis and millions of new infections occur each year. Treatment of M. tuberculosis is challenging and requires patients to take a combination of drugs for an extended time. Complicating treatment even further is the development and spread of multidrug-resistant strains of this pathogen. \n\n Another pathogenic species, M. leprae , is the cause of Hansen’s disease ( leprosy ), a chronic disease that impacts peripheral nerves and the integrity of the skin and mucosal surface of the respiratory tract. Loss of pain sensation and the presence of skin lesions increase susceptibility to secondary injuries and infections with other pathogens. \n\n Bacteria in the genus Corynebacterium contain diaminopimelic acid in their cell walls, and microscopically often form palisades , or pairs of rod-shaped cells resembling the letter V. Cells may contain metachromatic granules , intracellular storage of inorganic phosphates that are useful for identification of Corynebacterium . The vast majority of Corynebacterium spp. are nonpathogenic; however, C. diphtheria is the causative agent of diphtheria , a disease that can be fatal, especially in children ( Figure 4.18 ). C. diphtheria produces a toxin that forms a pseudomembrane in the patient’s throat, causing swelling, difficulty breathing, and other symptoms that can become serious if untreated. \n\n The genus Bifidobacterium consists of filamentous anaerobes, many of which are commonly found in the gastrointestinal tract, vagina, and mouth. In fact, Bifidobacterium spp. constitute a substantial part of the human gut microbiota and are frequently used as probiotics and in yogurt production. \n\n The genus Gardnerella , contains only one species, G. vaginalis . This species is defined as “gram-variable” because its small coccobacilli do not show consistent results when Gram stained ( Figure 4.18 ). Based on its genome, it is placed into the high G+C gram-positive group. G. vaginalis can cause bacterial vaginosis in women; symptoms are typically mild or even undetectable, but can lead to complications during pregnancy. \n\n Table 4.9 summarizes the characteristics of some important genera of Actinobacteria. Additional information on Actinobacteria appears in Appendix D . \n\n Actinobacteria: High G+C Gram-Positive \n\n Example Genus \n\n Microscopic Morphology \n\n Unique Characteristics \n\n Actinomyces \n\n Gram-positive bacillus; in colonies, shows fungus-like threads (hyphae) \n\n Facultative anaerobes; in soil, decompose organic matter; in the human mouth, may cause gum disease \n\n Arthrobacter \n\n Gram-positive bacillus (at the exponential stage of growth) or coccus (in stationary phase) \n\n Obligate aerobes; divide by “snapping,” forming V-like pairs of daughter cells; degrade phenol, can be used in bioremediation \n\n Bifidobacterium \n\n Gram-positive, filamentous actinobacterium \n\n Anaerobes commonly found in human gut microbiota \n\n Corynebacterium \n\n Gram-positive bacillus \n\n Aerobes or facultative anaerobes; form palisades; grow slowly; require enriched media in culture; C. diphtheriae causes diphtheria \n\n Frankia \n\n Gram-positive, fungus-like (filamentous) bacillus \n\n Nitrogen-fixing bacteria; live in symbiosis with legumes \n\n Gardnerella \n\n Gram-variable coccobacillus \n\n Colonize the human vagina, may alter the microbial ecology, thus leading to vaginosis \n\n Micrococcus \n\n Gram-positive coccus, form microscopic clusters \n\n Ubiquitous in the environment and on the human skin; oxidase-positive (as opposed to morphologically similar S. aureus ); some are opportunistic pathogens \n\n Mycobacterium \n\n Gram-positive, acid-fast bacillus \n\n Slow growing, aerobic, resistant to drying and phagocytosis; covered with a waxy coat made of mycolic acid; M. tuberculosis causes tuberculosis; M. leprae causes leprosy \n\n Nocardia \n\n Weakly gram-positive bacillus; forms acid-fast branches \n\n May colonize the human gingiva; may cause severe pneumonia and inflammation of the skin \n\n Propionibacterium \n\n Gram-positive bacillus \n\n Aerotolerant anaerobe; slow-growing; P. acnes reproduces in the human sebaceous glands and may cause or contribute to acne \n\n Rhodococcus \n\n Gram-positive bacillus \n\n Strict aerobe; used in industry for biodegradation of pollutants; R. fascians is a plant pathogen, and R. equi causes pneumonia in foals \n\n Streptomyces \n\n Gram-positive, fungus-like (filamentous) bacillus \n\n Very diverse genus (>500 species); aerobic, spore-forming bacteria; scavengers, decomposers found in soil (give the soil its “earthy” odor); used in pharmaceutical industry as antibiotic producers (more than two-thirds of clinically useful antibiotics) \n\n Table 4.9 \n\n Check Your Understanding \n\n What is one distinctive feature of Actinobacteria? \n\n Low G+C Gram-positive Bacteria \n\n The low G+C gram-positive bacteria have less than 50% guanine and cytosine in their DNA, and this group of bacteria includes a number of genera of bacteria that are pathogenic. \n\n Clinical Focus Part 3 Based on her symptoms, Marsha’s doctor suspected that she had a case of tuberculosis. Although less common in the United States, tuberculosis is still extremely common in many parts of the world, including Nigeria. Marsha’s work there in a medical lab likely exposed her to Mycobacterium tuberculosis , the bacterium that causes tuberculosis. \n\n Marsha’s doctor ordered her to stay at home, wear a respiratory mask, and confine herself to one room as much as possible. He also said that Marsha had to take one semester off school. He prescribed isoniazid and rifampin, antibiotics used in a drug cocktail to treat tuberculosis, which Marsha was to take three times a day for at least three months. \n\n Why did the doctor order Marsha to stay home for three months? \n\n Jump to the next Clinical Focus box. Go back to the previous Clinical Focus box. \n\n Clostridia \n\n One large and diverse class of low G+C gram-positive bacteria is Clostridia. The best studied genus of this class is Clostridium . These rod-shaped bacteria are generally obligate anaerobes that produce endospores and can be found in anaerobic habitats like soil and aquatic sediments rich in organic nutrients. The endospores may survive for many years. \n\n Clostridium spp. produce more kinds of protein toxins than any other bacterial genus, and several species are human pathogens. C. perfringens is the third most common cause of food poisoning in the United States and is the causative agent of an even more serious disease called gas gangrene . Gas gangrene occurs when C. perfringens endospores enter a wound and germinate, becoming viable bacterial cells and producing a toxin that can cause the necrosis (death) of tissue. C. tetani , which causes tetanus , produces a neurotoxin that is able to enter neurons, travel to regions of the central nervous system where it blocks the inhibition of nerve impulses involved in muscle contractions, and cause a life-threatening spastic paralysis. C. botulinum produces botulinum neurotoxin , the most lethal biological toxin known. Botulinum toxin is responsible for rare but frequently fatal cases of botulism . The toxin blocks the release of acetylcholine in neuromuscular junctions, causing flaccid paralysis. In very small concentrations, botulinum toxin has been used to treat muscle pathologies in humans and in a cosmetic procedure to eliminate wrinkles. C. difficile is a common source of hospital-acquired infections ( Figure 4.19 ) that can result in serious and even fatal cases of colitis (inflammation of the large intestine). Infections often occur in patients who are immunosuppressed or undergoing antibiotic therapy that alters the normal microbiota of the gastrointestinal tract. Appendix D lists the genera, species, and related diseases for Clostridia. \n\n Lactobacillales \n\n The order Lactobacillales comprises low G+C gram-positive bacteria that include both bacilli and cocci in the genera Lactobacillus , Leuconostoc , Enterococcus , and Streptococcus . Bacteria of the latter three genera typically are spherical or ovoid and often form chains. \n\n Streptococcus , the name of which comes from the Greek word for twisted chain , is responsible for many types of infectious diseases in humans. Species from this genus, often referred to as streptococci , are usually classified by serotypes called Lancefield groups, and by their ability to lyse red blood cells when grown on blood agar. \n\n S. pyogenes belongs to the Lancefield group A, β-hemolytic Streptococcus . This species is considered a pyogenic pathogen because of the associated pus production observed with infections it causes ( Figure 4.20 ). S. pyogenes is the most common cause of bacterial pharyngitis ( strep throat ); it is also an important cause of various skin infections that can be relatively mild (e.g., impetigo ) or life threatening (e.g., necrotizing fasciitis , also known as flesh eating disease), life threatening. \n\n The nonpyogenic (i.e., not associated with pus production) streptococci are a group of streptococcal species that are not a taxon but are grouped together because they inhabit the human mouth. The nonpyogenic streptococci do not belong to any of the Lancefield groups. Most are commensals, but a few, such as S. mutans , are implicated in the development of dental caries. \n\n S. pneumoniae (commonly referred to as pneumococcus), is a Streptococcus species that also does not belong to any Lancefield group . S. pneumoniae cells appear microscopically as diplococci, pairs of cells, rather than the long chains typical of most streptococci. Scientists have known since the 19th century that S. pneumoniae causes pneumonia and other respiratory infections. However, this bacterium can also cause a wide range of other diseases, including meningitis, septicemia, osteomyelitis, and endocarditis, especially in newborns, the elderly, and patients with immunodeficiency. \n\n Bacilli \n\n The name of the class Bacilli suggests that it is made up of bacteria that are bacillus in shape, but it is a morphologically diverse class that includes bacillus-shaped and cocccus-shaped genera. Among the many genera in this class are two that are very important clinically: Bacillus and Staphylococcus . \n\n Bacteria in the genus Bacillus are bacillus in shape and can produce endospores . They include aerobes or facultative anaerobes. A number of Bacillus spp. are used in various industries, including the production of antibiotics (e.g., barnase), enzymes (e.g., alpha-amylase, BamH1 restriction endonuclease), and detergents (e.g., subtilisin). \n\n Two notable pathogens belong to the genus Bacillus. B. anthracis is the pathogen that causes anthrax , a severe disease that affects wild and domesticated animals and can spread from infected animals to humans. Anthrax manifests in humans as charcoal-black ulcers on the skin, severe enterocolitis, pneumonia, and brain damage due to swelling. If untreated, anthrax is lethal. B. cereus , a closely related species, is a pathogen that may cause food poisoning. It is a rod-shaped species that forms chains. Colonies appear milky white with irregular shapes when cultured on blood agar ( Figure 4.21 ). One other important species is B. thuringiensis . This bacterium produces a number of substances used as insecticides because they are toxic for insects. \n\n The genus Staphylococcus also belongs to the class Bacilli, even though its shape is coccus rather than a bacillus. The name Staphylococcus comes from a Greek word for bunches of grapes , which describes their microscopic appearance in culture ( Figure 4.22 ). Staphylococcus spp. are facultative anaerobic, halophilic, and nonmotile. The two best-studied species of this genus are S. epidermidis and S. aureus . \n\n S. epidermidis , whose main habitat is the human skin, is thought to be nonpathogenic for humans with healthy immune systems, but in patients with immunodeficiency, it may cause infections in skin wounds and prostheses (e.g., artificial joints, heart valves) . S. epidermidis is also an important cause of infections associated with intravenous catheters. This makes it a dangerous pathogen in hospital settings, where many patients may be immunocompromised. \n\n Strains of S. aureus cause a wide variety of infections in humans, including skin infections that produce boils, carbuncles, cellulitis, or impetigo. Certain strains of S. aureus produce a substance called enterotoxin , which can cause severe enteritis, often called staph food poisoning. Some strains of S. aureus produce the toxin responsible for toxic shock syndrome , which can result in cardiovascular collapse and death. \n\n Many strains of S. aureus have developed resistance to antibiotics. Some antibiotic-resistant strains are designated as methicillin-resistant S. aureus ( MRSA ) and vancomycin-resistant S. aureus (VRSA) . These strains are some of the most difficult to treat because they exhibit resistance to nearly all available antibiotics, not just methicillin and vancomycin. Because they are difficult to treat with antibiotics, infections can be lethal. MRSA and VRSA are also contagious, posing a serious threat in hospitals, nursing homes, dialysis facilities, and other places where there are large populations of elderly, bedridden, and/or immunocompromised patients. Appendix D lists the genera, species, and related diseases for bacilli. \n\n Mycoplasmas \n\n Although Mycoplasma spp. do not possess a cell wall and, therefore, are not stained by Gram-stain reagents, this genus is still included with the low G+C gram-positive bacteria. The genus Mycoplasma includes more than 100 species, which share several unique characteristics. They are very small cells, some with a diameter of about 0.2 μm, which is smaller than some large viruses. They have no cell walls and, therefore, are pleomorphic , meaning that they may take on a variety of shapes and can even resemble very small animal cells. Because they lack a characteristic shape, they can be difficult to identify. One species, M. pneumoniae , causes the mild form of pneumonia known as “ walking pneumonia ” or “ atypical pneumonia .” This form of pneumonia is typically less severe than forms caused by other bacteria or viruses. \n\n Table 4.10 summarizes the characteristics of notable genera low G+C Gram-positive bacteria. \n\n Bacilli: Low G+C Gram-Positive Bacteria \n\n Example Genus \n\n Microscopic Morphology \n\n Unique Characteristics \n\n Bacillus \n\n Large, gram-positive bacillus \n\n Aerobes or facultative anaerobes; form endospores; B. anthracis causes anthrax in cattle and humans, B. cereus may cause food poisoning \n\n Clostridium \n\n Gram-positive bacillus \n\n Strict anaerobes; form endospores; all known species are pathogenic, causing tetanus, gas gangrene, botulism, and colitis \n\n Enterococcus \n\n Gram-positive coccus; forms microscopic pairs in culture (resembling Streptococcus pneumoniae ) \n\n Anaerobic aerotolerant bacteria, abundant in the human gut, may cause urinary tract and other infections in the nosocomial environment \n\n Lactobacillus \n\n Gram-positive bacillus \n\n Facultative anaerobes; ferment sugars into lactic acid; part of the vaginal microbiota; used as probiotics \n\n Leuconostoc \n\n Gram-positive coccus; may form microscopic chains in culture \n\n Fermenter, used in food industry to produce sauerkraut and kefir \n\n Mycoplasma \n\n The smallest bacteria; appear pleomorphic under electron microscope \n\n Have no cell wall; classified as low G+C Gram-positive bacteria because of their genome; M. pneumoniae causes “walking” pneumonia \n\n Staphylococcus \n\n Gram-positive coccus; forms microscopic clusters in culture that resemble bunches of grapes \n\n Tolerate high salt concentration; facultative anaerobes; produce catalase; S. aureus can also produce coagulase and toxins responsible for local (skin) and generalized infections \n\n Streptococcus \n\n Gram-positive coccus; forms chains or pairs in culture \n\n Diverse genus; classified into groups based on sharing certain antigens; some species cause hemolysis and may produce toxins responsible for human local (throat) and generalized disease \n\n Ureaplasma \n\n Similar to Mycoplasma \n\n Part of the human vaginal and lower urinary tract microbiota; may cause inflammation, sometimes leading to internal scarring and infertility \n\n Table 4.10 \n\n Check Your Understanding \n\n Name some ways in which streptococci are classified. \n\n Name one pathogenic low G+C gram-positive bacterium and a disease it causes. \n\n Clinical Focus Resolution Marsha’s sputum sample was sent to the microbiology lab to confirm the identity of the microorganism causing her infection. The lab also performed antimicrobial susceptibility testing (AST) on the sample to confirm that the physician has prescribed the correct antimicrobial drugs. \n\n Direct microscopic examination of the sputum revealed acid-fast bacteria (AFB) present in Marsha’s sputum. When placed in culture, there were no signs of growth for the first 8 days, suggesting that microorganism was either dead or growing very slowly. Slow growth is a distinctive characteristic of M. tuberculosis . \n\n After four weeks, the lab microbiologist observed distinctive colorless granulated colonies ( Figure 4.23 ). The colonies contained AFB showing the same microscopic characteristics as those revealed during the direct microscopic examination of Marsha’s sputum. To confirm the identification of the AFB, samples of the colonies were analyzed using nucleic acid hybridization, or direct nucleic acid amplification (NAA) testing. When a bacterium is acid-fast, it is classified in the family Mycobacteriaceae . DNA sequencing of variable genomic regions of the DNA extracted from these bacteria revealed that it was high G+C. This fact served to finalize Marsha’s diagnosis as infection with M. tuberculosis . After nine months of treatment with the drugs prescribed by her doctor, Marsha made a full recovery. \n\n Go back to the previous Clinical Focus box. \n\n Eye on Ethics Biopiracy and Bioprospecting In 1969, an employee of a Swiss pharmaceutical company was vacationing in Norway and decided to collect some soil samples. He took them back to his lab, and the Swiss company subsequently used the fungus Tolypocladium inflatum in those samples to develop cyclosporine A, a drug widely used in patients who undergo tissue or organ transplantation. The Swiss company earns more than $1 billion a year for production of cyclosporine A, yet Norway receives nothing in return—no payment to the government or benefit for the Norwegian people. Despite the fact the cyclosporine A saves numerous lives, many consider the means by which the soil samples were obtained to be an act of “biopiracy,” essentially a form of theft. Do the ends justify the means in a case like this? \n\n Nature is full of as-yet-undiscovered bacteria and other microorganisms that could one day be used to develop new life-saving drugs or treatments. 21 Pharmaceutical and biotechnology companies stand to reap huge profits from such discoveries, but ethical questions remain. To whom do biological resources belong? Should companies who invest (and risk) millions of dollars in research and development be required to share revenue or royalties for the right to access biological resources? 21 J. Andre. Bioethics as Practice . Chapel Hill, NC: University of North Carolina Press, 2002. \n\n Compensation is not the only issue when it comes to bioprospecting. Some communities and cultures are philosophically opposed to bioprospecting, fearing unforeseen consequences of collecting genetic or biological material. Native Hawaiians, for example, are very protective of their unique biological resources. \n\n For many years, it was unclear what rights government agencies, private corporations, and citizens had when it came to collecting samples of microorganisms from public land. Then, in 1993, the Convention on Biological Diversity granted each nation the rights to any genetic and biological material found on their own land. Scientists can no longer collect samples without a prior arrangement with the land owner for compensation. This convention now ensures that companies act ethically in obtaining the samples they use to create their products. \n 4.5 Deeply Branching Bacteria \n\n Learning Objectives \n\n Describe the unique features of deeply branching bacteria \n\n Give examples of significant deeply branching bacteria \n\n On a phylogenetic tree (see A Systematic Approach ), the trunk or root of the tree represents a common ancient evolutionary ancestor, often called the last universal common ancestor (LUCA) , and the branches are its evolutionary descendants. Scientists consider the deeply branching bacteria , such as the genus Acetothermus , to be the first of these non-LUCA forms of life produced by evolution some 3.5 billion years ago. When placed on the phylogenetic tree, they stem from the common root of life, deep and close to the LUCA root—hence the name “deeply branching” ( Figure 4.24 ). \n\n The deeply branching bacteria may provide clues regarding the structure and function of ancient and now extinct forms of life. We can hypothesize that ancient bacteria, like the deeply branching bacteria that still exist, were thermophiles or hyperthermophiles , meaning that they thrived at very high temperatures. Acetothermus paucivorans , a gram-negative anaerobic bacterium discovered in 1988 in sewage sludge, is a thermophile growing at an optimal temperature of 58 °C. 22 Scientists have determined it to be the deepest branching bacterium, or the closest evolutionary relative of the LUCA ( Figure 4.24 ). 22 G. Dietrich et al. “ Acetothermus paucivorans , gen. nov., sp. Nov., a Strictly Anaerobic, Thermophilic Bacterium From Sewage Sludge, Fermenting Hexoses to Acetate, CO 2 , and H 2 .” Systematic and Applied Microbiology 10 no. 2 (1988):174–179. \n\n The class Aquificae includes deeply branching bacteria that are adapted to the harshest conditions on our planet, resembling the conditions thought to dominate the earth when life first appeared. Bacteria from the genus Aquifex are hyperthermophiles, living in hot springs at a temperature higher than 90 °C. The species A. pyrophilus thrives near underwater volcanoes and thermal ocean vents, where the temperature of water (under high pressure) can reach 138 °C. Aquifex bacteria use inorganic substances as nutrients. For example, A. pyrophilus can reduce oxygen, and it is able to reduce nitrogen in anaerobic conditions. They also show a remarkable resistance to ultraviolet light and ionizing radiation. Taken together, these observations support the hypothesis that the ancient ancestors of deeply branching bacteria began evolving more than 3 billion years ago, when the earth was hot and lacked an atmosphere, exposing the bacteria to nonionizing and ionizing radiation. \n\n The class Thermotogae is represented mostly by hyperthermophilic, as well as some mesophilic (preferring moderate temperatures), anaerobic gram-negative bacteria whose cells are wrapped in a peculiar sheath-like outer membrane called a toga . The thin layer of peptidoglycan in their cell wall has an unusual structure; it contains diaminopimelic acid and D-lysine. These bacteria are able to use a variety of organic substrates and produce molecular hydrogen, which can be used in industry. The class contains several genera, of which the best known is the genus Thermotoga . One species of this genus, T. maritima , lives near the thermal ocean vents and thrives in temperatures of 90 °C; another species, T. subterranea , lives in underground oil reservoirs. \n\n Finally, the deeply branching bacterium Deinococcus radiodurans belongs to a genus whose name is derived from a Greek word meaning terrible berry . Nicknamed “ Conan the Bacterium ,” D. radiodurans is considered a polyextremophile because of its ability to survive under the many different kinds of extreme conditions—extreme heat, drought, vacuum, acidity, and radiation. It owes its name to its ability to withstand doses of ionizing radiation that kill all other known bacteria; this special ability is attributed to some unique mechanisms of DNA repair. \n 4.6 Archaea \n\n Learning Objectives \n\n Describe the unique features of each category of Archaea \n\n Explain why archaea might not be associated with human microbiomes or pathology \n\n Give common examples of archaea commonly associated with unique environmental habitats \n\n Like organisms in the domain Bacteria, organisms of the domain Archaea are all unicellular organisms. However, archaea differ structurally from bacteria in several significant ways, as discussed in Unique Characteristics of Prokaryotic Cells . To summarize: \n\n The archaeal cell membrane is composed of ether linkages with branched isoprene chains (as opposed to the bacterial cell membrane, which has ester linkages with unbranched fatty acids). \n\n Archaeal cell walls lack peptidoglycan, but some contain a structurally similar substance called pseudopeptidoglycan or pseudomurein . \n\n The genomes of Archaea are larger and more complex than those of bacteria. \n\n Domain Archaea is as diverse as domain Bacteria, and its representatives can be found in any habitat. Some archaea are mesophiles , and many are extremophiles , preferring extreme hot or cold, extreme salinity, or other conditions that are hostile to most other forms of life on earth. Their metabolism is adapted to the harsh environments, and they can perform methanogenesis , for example, which bacteria and eukaryotes cannot. \n\n The size and complexity of the archaeal genome makes it difficult to classify. Most taxonomists agree that within the Archaea, there are currently five major phyla: Crenarchaeota , Euryarchaeota , Korarchaeota , Nanoarchaeota , and Thaumarchaeota . There are likely many other archaeal groups that have not yet been systematically studied and classified. \n\n With few exceptions, archaea are not present in the human microbiota, and none are currently known to be associated with infectious diseases in humans, animals, plants, or microorganisms. However, many play important roles in the environment and may thus have an indirect impact on human health. \n\n Crenarchaeota \n\n Crenarchaeota is a class of Archaea that is extremely diverse, containing genera and species that differ vastly in their morphology and requirements for growth. All Crenarchaeota are aquatic organisms, and they are thought to be the most abundant microorganisms in the oceans. Most, but not all, Crenarchaeota are hyperthermophiles; some of them (notably, the genus Pyrolobus ) are able to grow at temperatures up to 113 °C. 23 23 E. Blochl et al.“ Pyrolobus fumani , gen. and sp. nov., represents a novel group of Archaea, extending the upper temperature limit for life to 113 ° C.” Extremophiles 1 (1997):14–21. \n\n Archaea of the genus Sulfolobus ( Figure 4.26 ) are thermophiles that prefer temperatures around 70–80°C and acidophiles that prefer a pH of 2–3. 24 Sulfolobus can live in aerobic or anaerobic environments. In the presence of oxygen, Sulfolobus spp. use metabolic processes similar to those of heterotrophs. In anaerobic environments, they oxidize sulfur to produce sulfuric acid, which is stored in granules. Sulfolobus spp. are used in biotechnology for the production of thermostable and acid-resistant proteins called affitins . 25 Affitins can bind and neutralize various antigens (molecules found in toxins or infectious agents that provoke an immune response from the body). 24 T.D. Brock et al. “ Sulfolobus : A New Genus of Sulfur-Oxidizing Bacteria Living at Low pH and High Temperature.” Archiv für Mikrobiologie 84 no. 1 (1972):54–68. 25 S. Pacheco et al. “Affinity Transfer to the Archaeal Extremophilic Sac7d Protein by Insertion of a CDR.” Protein Engineering Design and Selection 27 no. 10 (2014):431-438. \n\n Another genus, Thermoproteus , is represented by strictly anaerobic organisms with an optimal growth temperature of 85 °C. They have flagella and, therefore, are motile. Thermoproteus has a cellular membrane in which lipids form a monolayer rather than a bilayer, which is typical for archaea. Its metabolism is autotrophic. To synthesize ATP, Thermoproteus spp. reduce sulfur or molecular hydrogen and use carbon dioxide or carbon monoxide as a source of carbon. Thermoproteus is thought to be the deepest-branching genus of Archaea, and thus is a living example of some of our planet’s earliest forms of life. \n\n Check Your Understanding \n\n What types of environments do Crenarchaeota prefer? \n\n Euryarchaeota \n\n The phylum Euryarchaeota includes several distinct classes. Species in the classes Methanobacteria, Methanococci, and Methanomicrobia represent Archaea that can be generally described as methanogens. Methanogens are unique in that they can reduce carbon dioxide in the presence of hydrogen, producing methane. They can live in the most extreme environments and can reproduce at temperatures varying from below freezing to boiling. Methanogens have been found in hot springs as well as deep under ice in Greenland. Methanogens also produce gases in ruminants and humans. Some scientists have even hypothesized that methanogen s may inhabit the planet Mars because the mixture of gases produced by methanogens resembles the makeup of the Martian atmosphere. 26 26 R.R. Britt “Crater Critters: Where Mars Microbes Might Lurk.” http://www.space.com/1880-crater-critters-mars-microbes-lurk.html. Accessed April 7, 2015. \n\n The class Halobacteria (which was named before scientists recognized the distinction between Archaea and Bacteria) includes halophilic (“salt-loving”) archaea. Halobacteria require a very high concentrations of sodium chloride in their aquatic environment. The required concentration is close to saturation, at 36%; such environments include the Dead Sea as well as some salty lakes in Antarctica and south-central Asia. One remarkable feature of these organisms is that they perform photosynthesis using the protein bacteriorhodopsin , which gives them, and the bodies of water they inhabit, a beautiful purple color ( Figure 4.27 ). \n\n Notable species of Halobacteria include Halobacterium salinarum , which may be the oldest living organism on earth; scientists have isolated its DNA from fossils that are 250 million years old. 27 Another species, Haloferax volcanii , shows a very sophisticated system of ion exchange, which enables it to balance the concentration of salts at high temperatures. 27 H. Vreeland et al. “Fatty acid and DA Analyses of Permian Bacterium Isolated From Ancient Salt Crystals Reveal Differences With Their Modern Relatives.” Extremophiles 10 (2006):71–78. \n\n Check Your Understanding \n\n Where do Halobacteria live? \n\n Micro Connections Finding a Link Between Archaea and Disease Archaea are not known to cause any disease in humans, animals, plants, bacteria, or in other archaea. Although this makes sense for the extremophiles, not all archaea live in extreme environments. Many genera and species of Archaea are mesophiles, so they can live in human and animal microbiomes, although they rarely do. As we have learned, some methanogens exist in the human gastrointestinal tract. Yet we have no reliable evidence pointing to any archaean as the causative agent of any human disease. \n\n Still, scientists have attempted to find links between human disease and archaea. For example, in 2004, Lepp et al. presented evidence that an archaean called Methanobrevibacter oralis inhabits the gums of patients with periodontal disease. The authors suggested that the activity of these methanogens causes the disease. 28 However, it was subsequently shown that there was no causal relationship between M. oralis and periodontitis. It seems more likely that periodontal disease causes an enlargement of anaerobic regions in the mouth that are subsequently populated by M. oralis . 29 28 P.W. Lepp et al. “Methanogenic Archaea and Human Gum Disease.” Proceedings of the National Academies of Science of the United States of America 101 no. 16 (2004):6176–6181. 29 R.I. Aminov. “Role of Archaea in Human Disease.” Frontiers in Cellular and Infection Microbiology 3 (2013):42. \n\n There remains no good answer as to why archaea do not seem to be pathogenic, but scientists continue to speculate and hope to find the answer. "}}},{"rowIdx":190,"cells":{"bname":{"kind":"string","value":"anatomy_and_physiology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":""},"intro":{"kind":"string","value":" Chapter Objectives \n\n After studying this chapter, you will be able to:\n\n Identify and describe the interior and exterior parts of the human heart \n\n Describe the path of blood through the cardiac circuits \n\n Describe the size, shape, and location of the heart \n\n Compare cardiac muscle to skeletal and smooth muscle \n\n Explain the cardiac conduction system \n\n Describe the process and purpose of an electrocardiogram \n\n Explain the cardiac cycle \n\n Calculate cardiac output \n\n Describe the effects of exercise on cardiac output and heart rate \n\n Name the centers of the brain that control heart rate and describe their function \n\n Identify other factors affecting heart rate \n\n Describe fetal heart development \n\n Introduction In this chapter, you will explore the remarkable pump that propels the blood into the vessels. There is no single better word to describe the function of the heart other than “pump,” since its contraction develops the pressure that ejects blood into the major vessels: the aorta and pulmonary trunk. From these vessels, the blood is distributed to the remainder of the body. Although the connotation of the term “pump” suggests a mechanical device made of steel and plastic, the anatomical structure is a living, sophisticated muscle. As you read this chapter, try to keep these twin concepts in mind: pump and muscle. Although the term “heart” is an English word, cardiac (heart-related) terminology can be traced back to the Latin term, “kardia.” Cardiology is the study of the heart, and cardiologists are the physicians who deal primarily with the heart. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":3,"ans_text":"endocardium"},"bloom":"1","hl_context":"When the myocardium of the ventricle contracts , pressure within the ventricular chamber rises . Blood , like any fluid , flows from higher pressure to lower pressure areas , in this case , toward the pulmonary trunk and the atrium . <hl> To prevent any potential backflow , the papillary muscles also contract , generating tension on the chordae tendineae . <hl> <hl> This prevents the flaps of the valves from being forced into the atria and regurgitation of the blood back into the atria during ventricular contraction . <hl> Figure 19.11 shows papillary muscles and chordae tendineae attached to the tricuspid valve .","hl_sentences":"To prevent any potential backflow , the papillary muscles also contract , generating tension on the chordae tendineae . This prevents the flaps of the valves from being forced into the atria and regurgitation of the blood back into the atria during ventricular contraction .","question":{"cloze_format":"___ is/are not important in preventing backflow of blood.","normal_format":"Which of the following is not important in preventing backflow of blood?","question_choices":["chordae tendineae","papillary muscles","AV valves","endocardium"],"question_id":"fs-id2627639","question_text":"Which of the following is not important in preventing backflow of blood?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"mitral"},"bloom":"1","hl_context":"<hl> Located at the opening between the left atrium and left ventricle is the mitral valve , also called the bicuspid valve or the left atrioventricular valve . <hl> Structurally , this valve consists of two cusps , compared to the three cusps of the tricuspid valve . In a clinical setting , the valve is referred to as the mitral valve , rather than the bicuspid valve . The two cusps of the mitral valve are attached by chordae tendineae to two papillary muscles that project from the wall of the ventricle . After exchange of gases in the pulmonary capillaries , blood returns to the left atrium high in oxygen via one of the four pulmonary veins . While the left atrium does not contain pectinate muscles , it does have an auricle that includes these pectinate ridges . Blood flows nearly continuously from the pulmonary veins back into the atrium , which acts as the receiving chamber , and from here through an opening into the left ventricle . Most blood flows passively into the heart while both the atria and ventricles are relaxed , but toward the end of the ventricular relaxation period , the left atrium will contract , pumping blood into the ventricle . This atrial contraction accounts for approximately 20 percent of ventricular filling . <hl> The opening between the left atrium and ventricle is guarded by the mitral valve . <hl>","hl_sentences":"Located at the opening between the left atrium and left ventricle is the mitral valve , also called the bicuspid valve or the left atrioventricular valve . The opening between the left atrium and ventricle is guarded by the mitral valve .","question":{"cloze_format":"The valve that separates the left atrium from the left ventricle is the ___.","normal_format":"Which valve separates the left atrium from the left ventricle?","question_choices":["mitral","tricuspid","pulmonary","aortic"],"question_id":"fs-id2367256","question_text":"Which valve separates the left atrium from the left ventricle?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"tricuspid, pulmonary semilunar, bicuspid, aortic semilunar"},"bloom":"1","hl_context":"<hl> At the base of the aorta is the aortic semilunar valve , or the aortic valve , which prevents backflow from the aorta . <hl> It normally is composed of three flaps . When the ventricle relaxes and blood attempts to flow back into the ventricle from the aorta , blood will fill the cusps of the valve , causing it to close and producing an audible sound . <hl> Located at the opening between the left atrium and left ventricle is the mitral valve , also called the bicuspid valve or the left atrioventricular valve . <hl> Structurally , this valve consists of two cusps , compared to the three cusps of the tricuspid valve . In a clinical setting , the valve is referred to as the mitral valve , rather than the bicuspid valve . The two cusps of the mitral valve are attached by chordae tendineae to two papillary muscles that project from the wall of the ventricle . <hl> A transverse section through the heart slightly above the level of the atrioventricular septum reveals all four heart valves along the same plane ( Figure 19.12 ) . <hl> <hl> The valves ensure unidirectional blood flow through the heart . <hl> <hl> Between the right atrium and the right ventricle is the right atrioventricular valve , or tricuspid valve . <hl> It typically consists of three flaps , or leaflets , made of endocardium reinforced with additional connective tissue . The flaps are connected by chordae tendineae to the papillary muscles , which control the opening and closing of the valves . <hl> Emerging from the right ventricle at the base of the pulmonary trunk is the pulmonary semilunar valve , or the pulmonary valve ; it is also known as the pulmonic valve or the right semilunar valve . <hl> The pulmonary valve is comprised of three small flaps of endothelium reinforced with connective tissue . When the ventricle relaxes , the pressure differential causes blood to flow back into the ventricle from the pulmonary trunk . This flow of blood fills the pocket-like flaps of the pulmonary valve , causing the valve to close and producing an audible sound . Unlike the atrioventricular valves , there are no papillary muscles or chordae tendineae associated with the pulmonary valve .","hl_sentences":"At the base of the aorta is the aortic semilunar valve , or the aortic valve , which prevents backflow from the aorta . Located at the opening between the left atrium and left ventricle is the mitral valve , also called the bicuspid valve or the left atrioventricular valve . A transverse section through the heart slightly above the level of the atrioventricular septum reveals all four heart valves along the same plane ( Figure 19.12 ) . The valves ensure unidirectional blood flow through the heart . Between the right atrium and the right ventricle is the right atrioventricular valve , or tricuspid valve . Emerging from the right ventricle at the base of the pulmonary trunk is the pulmonary semilunar valve , or the pulmonary valve ; it is also known as the pulmonic valve or the right semilunar valve .","question":{"cloze_format":"____ lists the valves in the order through which the blood flows from the vena cava through the heart.","normal_format":"Which of the following lists the valves in the order through which the blood flows from the vena cava through the heart?","question_choices":["tricuspid, pulmonary semilunar, bicuspid, aortic semilunar","mitral, pulmonary semilunar, bicuspid, aortic semilunar","aortic semilunar, pulmonary semilunar, tricuspid, bicuspid","bicuspid, aortic semilunar, tricuspid, pulmonary semilunar"],"question_id":"fs-id1228297","question_text":"Which of the following lists the valves in the order through which the blood flows from the vena cava through the heart?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"right atrium"},"bloom":"1","hl_context":"<hl> The right atrium serves as the receiving chamber for blood returning to the heart from the systemic circulation . <hl> The two major systemic veins , the superior and inferior venae cavae , and the large coronary vein called the coronary sinus that drains the heart myocardium empty into the right atrium . The superior vena cava drains blood from regions superior to the diaphragm : the head , neck , upper limbs , and the thoracic region . It empties into the superior and posterior portions of the right atrium . The inferior vena cava drains blood from areas inferior to the diaphragm : the lower limbs and abdominopelvic region of the body . It , too , empties into the posterior portion of the atria , but inferior to the opening of the superior vena cava . Immediately superior and slightly medial to the opening of the inferior vena cava on the posterior surface of the atrium is the opening of the coronary sinus . This thin-walled vessel drains most of the coronary veins that return systemic blood from the heart . The majority of the internal heart structures discussed in this and subsequent sections are illustrated in Figure 19.9 . The human heart consists of four chambers : The left side and the right side each have one atrium and one ventricle . <hl> Each of the upper chambers , the right atrium ( plural = atria ) and the left atrium , acts as a receiving chamber and contracts to push blood into the lower chambers , the right ventricle and the left ventricle . <hl> The ventricles serve as the primary pumping chambers of the heart , propelling blood to the lungs or to the rest of the body .","hl_sentences":"The right atrium serves as the receiving chamber for blood returning to the heart from the systemic circulation . Each of the upper chambers , the right atrium ( plural = atria ) and the left atrium , acts as a receiving chamber and contracts to push blood into the lower chambers , the right ventricle and the left ventricle .","question":{"cloze_format":"The chamber that initially receives blood from the systemic circuit is the ___ .","normal_format":"Which chamber initially receives blood from the systemic circuit?","question_choices":["left atrium","left ventricle","right atrium","right ventricle"],"question_id":"fs-id2002743","question_text":"Which chamber initially receives blood from the systemic circuit?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"endocardium"},"bloom":"1","hl_context":"<hl> Once regarded as a simple lining layer , recent evidence indicates that the endothelium of the endocardium and the coronary capillaries may play active roles in regulating the contraction of the muscle within the myocardium . <hl> <hl> The endothelium may also regulate the growth patterns of the cardiac muscle cells throughout life , and the endothelins it secretes create an environment in the surrounding tissue fluids that regulates ionic concentrations and states of contractility . <hl> <hl> Endothelins are potent vasoconstrictors and , in a normal individual , establish a homeostatic balance with other vasoconstrictors and vasodilators . <hl> <hl> The innermost layer of the heart wall , the endocardium , is joined to the myocardium with a thin layer of connective tissue . <hl> The endocardium lines the chambers where the blood circulates and covers the heart valves . It is made of simple squamous epithelium called endothelium , which is continuous with the endothelial lining of the blood vessels ( see Figure 19.5 ) .","hl_sentences":"Once regarded as a simple lining layer , recent evidence indicates that the endothelium of the endocardium and the coronary capillaries may play active roles in regulating the contraction of the muscle within the myocardium . The endothelium may also regulate the growth patterns of the cardiac muscle cells throughout life , and the endothelins it secretes create an environment in the surrounding tissue fluids that regulates ionic concentrations and states of contractility . Endothelins are potent vasoconstrictors and , in a normal individual , establish a homeostatic balance with other vasoconstrictors and vasodilators . The innermost layer of the heart wall , the endocardium , is joined to the myocardium with a thin layer of connective tissue .","question":{"cloze_format":"The ________ layer secretes chemicals that help to regulate ionic environments and strength of contraction and serve as powerful vasoconstrictors.","normal_format":"Which layer secretes chemicals that help to regulate ionic environments and strength of contraction and serve as powerful vasoconstrictors?","question_choices":["pericardial sac","endocardium","myocardium","epicardium"],"question_id":"fs-id2515169","question_text":"The ________ layer secretes chemicals that help to regulate ionic environments and strength of contraction and serve as powerful vasoconstrictors."},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"left ventricle"},"bloom":"1","hl_context":"<hl> Recall that , although both sides of the heart will pump the same amount of blood , the muscular layer is much thicker in the left ventricle compared to the right ( see Figure 19.8 ) . <hl> Like the right ventricle , the left also has trabeculae carneae , but there is no moderator band . The mitral valve is connected to papillary muscles via chordae tendineae . There are two papillary muscles on the left — the anterior and posterior — as opposed to three on the right . <hl> Although the ventricles on the right and left sides pump the same amount of blood per contraction , the muscle of the left ventricle is much thicker and better developed than that of the right ventricle . <hl> In order to overcome the high resistance required to pump blood into the long systemic circuit , the left ventricle must generate a great amount of pressure . The right ventricle does not need to generate as much pressure , since the pulmonary circuit is shorter and provides less resistance . Figure 19.8 illustrates the differences in muscular thickness needed for each of the ventricles . <hl> The middle and thickest layer is the myocardium , made largely of cardiac muscle cells . <hl> It is built upon a framework of collagenous fibers , plus the blood vessels that supply the myocardium and the nerve fibers that help regulate the heart . It is the contraction of the myocardium that pumps blood through the heart and into the major arteries . The muscle pattern is elegant and complex , as the muscle cells swirl and spiral around the chambers of the heart . They form a figure 8 pattern around the atria and around the bases of the great vessels . Deeper ventricular muscles also form a figure 8 around the two ventricles and proceed toward the apex . More superficial layers of ventricular muscle wrap around both ventricles . This complex swirling pattern allows the heart to pump blood more effectively than a simple linear pattern would . Figure 19.7 illustrates the arrangement of muscle cells . <hl> The wall of the heart is composed of three layers of unequal thickness . <hl> <hl> From superficial to deep , these are the epicardium , the myocardium , and the endocardium ( see Figure 19.5 ) . <hl> The outermost layer of the wall of the heart is also the innermost layer of the pericardium , the epicardium , or the visceral pericardium discussed earlier .","hl_sentences":"Recall that , although both sides of the heart will pump the same amount of blood , the muscular layer is much thicker in the left ventricle compared to the right ( see Figure 19.8 ) . Although the ventricles on the right and left sides pump the same amount of blood per contraction , the muscle of the left ventricle is much thicker and better developed than that of the right ventricle . The middle and thickest layer is the myocardium , made largely of cardiac muscle cells . The wall of the heart is composed of three layers of unequal thickness . From superficial to deep , these are the epicardium , the myocardium , and the endocardium ( see Figure 19.5 ) .","question":{"cloze_format":"The myocardium would be the thickest in the ________.","normal_format":"In what would the myocardium be the thickest?","question_choices":["left atrium","left ventricle","right atrium","right ventricle"],"question_id":"fs-id2300602","question_text":"The myocardium would be the thickest in the ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"atrioventricular septum"},"bloom":null,"hl_context":"<hl> The septum between the atria and ventricles is known as the atrioventricular septum . <hl> <hl> It is marked by the presence of four openings that allow blood to move from the atria into the ventricles and from the ventricles into the pulmonary trunk and aorta . <hl> Located in each of these openings between the atria and ventricles is a valve , a specialized structure that ensures one-way flow of blood . The valves between the atria and ventricles are known generically as atrioventricular valves . The valves at the openings that lead to the pulmonary trunk and aorta are known generically as semilunar valves . The interventricular septum is visible in Figure 19.9 . In this figure , the atrioventricular septum has been removed to better show the bicuspid and tricuspid valves ; the interatrial septum is not visible , since its location is covered by the aorta and pulmonary trunk . Since these openings and valves structurally weaken the atrioventricular septum , the remaining tissue is heavily reinforced with dense connective tissue called the cardiac skeleton , or skeleton of the heart . It includes four rings that surround the openings between the atria and ventricles , and the openings to the pulmonary trunk and aorta , and serve as the point of attachment for the heart valves . The cardiac skeleton also provides an important boundary in the heart electrical conduction system .","hl_sentences":"The septum between the atria and ventricles is known as the atrioventricular septum . It is marked by the presence of four openings that allow blood to move from the atria into the ventricles and from the ventricles into the pulmonary trunk and aorta .","question":{"cloze_format":"The septum in which it is normal to find openings in the adult is the ___.","normal_format":"In which septum is it normal to find openings in the adult?","question_choices":["interatrial septum","interventricular septum","atrioventricular septum","all of the above"],"question_id":"fs-id1795973","question_text":"In which septum is it normal to find openings in the adult?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"Only cardiac muscle is capable of autorhythmicity"},"bloom":"1","hl_context":"<hl> Recall that cardiac muscle shares a few characteristics with both skeletal muscle and smooth muscle , but it has some unique properties of its own . <hl> Not the least of these exceptional properties is its ability to initiate an electrical potential at a fixed rate that spreads rapidly from cell to cell to trigger the contractile mechanism . <hl> This property is known as autorhythmicity . <hl> Neither smooth nor skeletal muscle can do this . Even though cardiac muscle has autorhythmicity , heart rate is modulated by the endocrine and nervous systems .","hl_sentences":"Recall that cardiac muscle shares a few characteristics with both skeletal muscle and smooth muscle , but it has some unique properties of its own . This property is known as autorhythmicity .","question":{"cloze_format":"It is unique to cardiac muscle cells that ___.","normal_format":"Which of the following is unique to cardiac muscle cells?","question_choices":["Only cardiac muscle contains a sarcoplasmic reticulum.","Only cardiac muscle has gap junctions.","Only cardiac muscle is capable of autorhythmicity","Only cardiac muscle has a high concentration of mitochondria."],"question_id":"fs-id2481331","question_text":"Which of the following is unique to cardiac muscle cells?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"calcium"},"bloom":"1","hl_context":"<hl> Calcium ions play two critical roles in the physiology of cardiac muscle . <hl> <hl> Their influx through slow calcium channels accounts for the prolonged plateau phase and absolute refractory period that enable cardiac muscle to function properly . <hl> Calcium ions also combine with the regulatory protein troponin in the troponin-tropomyosin complex ; this complex removes the inhibition that prevents the heads of the myosin molecules from forming cross bridges with the active sites on actin that provide the power stroke of contraction . This mechanism is virtually identical to that of skeletal muscle . Approximately 20 percent of the calcium required for contraction is supplied by the influx of Ca 2 + during the plateau phase . The remaining Ca 2 + for contraction is released from storage in the sarcoplasmic reticulum .","hl_sentences":"Calcium ions play two critical roles in the physiology of cardiac muscle . Their influx through slow calcium channels accounts for the prolonged plateau phase and absolute refractory period that enable cardiac muscle to function properly .","question":{"cloze_format":"The ion of which the influx accounts for the plateau phase is ___.","normal_format":"The influx of which ion accounts for the plateau phase?","question_choices":["sodium","potassium","chloride","calcium"],"question_id":"fs-id2050334","question_text":"The influx of which ion accounts for the plateau phase?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"none of the above: atrial repolarization is masked by ventricular depolarization"},"bloom":"1","hl_context":"<hl> Contraction of the atria follows depolarization , represented by the P wave of the ECG . <hl> As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum , pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular ( tricuspid , and mitral or bicuspid ) valves . At the start of atrial systole , the ventricles are normally filled with approximately 70 – 80 percent of their capacity due to inflow during diastole . Atrial contraction , also referred to as the “ atrial kick , ” contributes the remaining 20 – 30 percent of filling ( see Figure 19.27 ) . Atrial systole lasts approximately 100 ms and ends prior to ventricular systole , as the atrial muscle returns to diastole . There are five prominent points on the ECG : the P wave , the QRS complex , and the T wave . <hl> The small P wave represents the depolarization of the atria . <hl> The atria begin contracting approximately 25 ms after the start of the P wave . The large QRS complex represents the depolarization of the ventricles , which requires a much stronger electrical signal because of the larger size of the ventricular cardiac muscle . The ventricles begin to contract as the QRS reaches the peak of the R wave . Lastly , the T wave represents the repolarization of the ventricles . The repolarization of the atria occurs during the QRS complex , which masks it on an ECG .","hl_sentences":"Contraction of the atria follows depolarization , represented by the P wave of the ECG . The small P wave represents the depolarization of the atria .","question":{"cloze_format":"The portion of the ECG that corresponds to repolarization of the atria is the ___ .","normal_format":"Which portion of the ECG corresponds to repolarization of the atria?","question_choices":["P wave","QRS complex","T wave","none of the above: atrial repolarization is masked by ventricular depolarization"],"question_id":"fs-id2042928","question_text":"Which portion of the ECG corresponds to repolarization of the atria?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"Purkinje fibers"},"bloom":"1","hl_context":"The pattern of prepotential or spontaneous depolarization , followed by rapid depolarization and repolarization just described , are seen in the SA node and a few other conductive cells in the heart . Since the SA node is the pacemaker , it reaches threshold faster than any other component of the conduction system . It will initiate the impulses spreading to the other conducting cells . The SA node , without nervous or endocrine control , would initiate a heart impulse approximately 80 – 100 times per minute . Although each component of the conduction system is capable of generating its own impulse , the rate progressively slows as you proceed from the SA node to the Purkinje fibers . <hl> Without the SA node , the AV node would generate a heart rate of 40 – 60 beats per minute . <hl> <hl> If the AV node were blocked , the atrioventricular bundle would fire at a rate of approximately 30 – 40 impulses per minute . <hl> <hl> The bundle branches would have an inherent rate of 20 – 30 impulses per minute , and the Purkinje fibers would fire at 15 – 20 impulses per minute . <hl> While a few exceptionally trained aerobic athletes demonstrate resting heart rates in the range of 30 – 40 beats per minute ( the lowest recorded figure is 28 beats per minute for Miguel Indurain , a cyclist ) , for most individuals , rates lower than 50 beats per minute would indicate a condition called bradycardia . Depending upon the specific individual , as rates fall much below this level , the heart would be unable to maintain adequate flow of blood to vital tissues , initially resulting in decreasing loss of function across the systems , unconsciousness , and ultimately death .","hl_sentences":"Without the SA node , the AV node would generate a heart rate of 40 – 60 beats per minute . If the AV node were blocked , the atrioventricular bundle would fire at a rate of approximately 30 – 40 impulses per minute . The bundle branches would have an inherent rate of 20 – 30 impulses per minute , and the Purkinje fibers would fire at 15 – 20 impulses per minute .","question":{"cloze_format":"The component of the heart conduction system that would have the slowest rate of firing is the ___.","normal_format":"Which component of the heart conduction system would have the slowest rate of firing?","question_choices":["atrioventricular node","atrioventricular bundle","bundle branches","Purkinje fibers"],"question_id":"fs-id2060782","question_text":"Which component of the heart conduction system would have the slowest rate of firing?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"isovolumic contraction"},"bloom":"1","hl_context":"<hl> Initially , as the muscles in the ventricle contract , the pressure of the blood within the chamber rises , but it is not yet high enough to open the semilunar ( pulmonary and aortic ) valves and be ejected from the heart . <hl> <hl> However , blood pressure quickly rises above that of the atria that are now relaxed and in diastole . <hl> <hl> This increase in pressure causes blood to flow back toward the atria , closing the tricuspid and mitral valves . <hl> <hl> Since blood is not being ejected from the ventricles at this early stage , the volume of blood within the chamber remains constant . <hl> <hl> Consequently , this initial phase of ventricular systole is known as isovolumic contraction , also called isovolumetric contraction ( see Figure 19.27 ) . <hl>","hl_sentences":"Initially , as the muscles in the ventricle contract , the pressure of the blood within the chamber rises , but it is not yet high enough to open the semilunar ( pulmonary and aortic ) valves and be ejected from the heart . However , blood pressure quickly rises above that of the atria that are now relaxed and in diastole . This increase in pressure causes blood to flow back toward the atria , closing the tricuspid and mitral valves . Since blood is not being ejected from the ventricles at this early stage , the volume of blood within the chamber remains constant . Consequently , this initial phase of ventricular systole is known as isovolumic contraction , also called isovolumetric contraction ( see Figure 19.27 ) .","question":{"cloze_format":"The cardiac cycle consists of a distinct relaxation and contraction phase. The term that is typically used to refer ventricular contraction while no blood is being ejected is ___.","normal_format":"The cardiac cycle consists of a distinct relaxation and contraction phase. Which term is typically used to refer ventricular contraction while no blood is being ejected?","question_choices":["systole","diastole","quiescent","isovolumic contraction"],"question_id":"fs-id2001918","question_text":"The cardiac cycle consists of a distinct relaxation and contraction phase. Which term is typically used to refer ventricular contraction while no blood is being ejected?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"atrial diastole"},"bloom":"1","hl_context":"Contraction of the atria follows depolarization , represented by the P wave of the ECG . <hl> As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum , pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular ( tricuspid , and mitral or bicuspid ) valves . <hl> <hl> At the start of atrial systole , the ventricles are normally filled with approximately 70 – 80 percent of their capacity due to inflow during diastole . <hl> Atrial contraction , also referred to as the “ atrial kick , ” contributes the remaining 20 – 30 percent of filling ( see Figure 19.27 ) . Atrial systole lasts approximately 100 ms and ends prior to ventricular systole , as the atrial muscle returns to diastole .","hl_sentences":"As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum , pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular ( tricuspid , and mitral or bicuspid ) valves . At the start of atrial systole , the ventricles are normally filled with approximately 70 – 80 percent of their capacity due to inflow during diastole .","question":{"cloze_format":"Most blood enters the ventricle during ________.","normal_format":"During what do most blood enter the ventricle?","question_choices":["atrial systole","atrial diastole","ventricular systole","isovolumic contraction"],"question_id":"fs-id2321229","question_text":"Most blood enters the ventricle during ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"closing of the atrioventricular valves"},"bloom":null,"hl_context":"<hl> In a normal , healthy heart , there are only two audible heart sounds : S 1 and S 2 . <hl> <hl> S 1 is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as a “ lub , ” or first heart sound . <hl> The second heart sound , S 2 , is the sound of the closing of the semilunar valves during ventricular diastole and is described as a “ dub ” ( Figure 19.29 ) . In both cases , as the valves close , the openings within the atrioventricular septum guarded by the valves will become reduced , and blood flow through the opening will become more turbulent until the valves are fully closed . There is a third heart sound , S 3 , but it is rarely heard in healthy individuals . It may be the sound of blood flowing into the atria , or blood sloshing back and forth in the ventricle , or even tensing of the chordae tendineae . S 3 may be heard in youth , some athletes , and pregnant women . If the sound is heard later in life , it may indicate congestive heart failure , warranting further tests . Some cardiologists refer to the collective S 1 , S 2 , and S 3 sounds as the “ Kentucky gallop , ” because they mimic those produced by a galloping horse . The fourth heart sound , S 4 , results from the contraction of the atria pushing blood into a stiff or hypertrophic ventricle , indicating failure of the left ventricle . S 4 occurs prior to S 1 and the collective sounds S 4 , S 1 , and S 2 are referred to by some cardiologists as the “ Tennessee gallop , ” because of their similarity to the sound produced by a galloping horse with a different gait . A few individuals may have both S 3 and S 4 , and this combined sound is referred to as S 7 .","hl_sentences":"In a normal , healthy heart , there are only two audible heart sounds : S 1 and S 2 . S 1 is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as a “ lub , ” or first heart sound .","question":{"cloze_format":"The ___ is the portion of the cardiac cycle that the first heart sound represents.","normal_format":"The first heart sound represents which portion of the cardiac cycle?","question_choices":["atrial systole","ventricular systole","closing of the atrioventricular valves","closing of the semilunar valves"],"question_id":"fs-id2672256","question_text":"The first heart sound represents which portion of the cardiac cycle?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"ventricular repolarization"},"bloom":"1","hl_context":"<hl> Ventricular relaxation , or diastole , follows repolarization of the ventricles and is represented by the T wave of the ECG . <hl> It too is divided into two distinct phases and lasts approximately 430 ms .","hl_sentences":"Ventricular relaxation , or diastole , follows repolarization of the ventricles and is represented by the T wave of the ECG .","question":{"cloze_format":"Ventricular relaxation immediately follows ________.","normal_format":"What does ventricular relaxation immediately follow?","question_choices":["atrial depolarization","ventricular repolarization","ventricular depolarization","atrial repolarization"],"question_id":"fs-id2060926","question_text":"Ventricular relaxation immediately follows ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"afterload"},"bloom":"1","hl_context":"<hl> Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system . <hl> <hl> Any condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood . <hl> Damage to the valves , such as stenosis , which makes them harder to open will also increase afterload . Any decrease in resistance decreases the afterload . Figure 19.34 summarizes the major factors influencing SV , Figure 19.35 summarizes the major factors influencing CO , and Table 19.3 and Table 19.4 summarize cardiac responses to increased and decreased blood flow and pressure in order to restore homeostasis . Many of the same factors that regulate HR also impact cardiac function by altering SV . While a number of variables are involved , SV is ultimately dependent upon the difference between EDV and ESV . <hl> The three primary factors to consider are preload , or the stretch on the ventricles prior to contraction ; the contractility , or the force or strength of the contraction itself ; and afterload , the force the ventricles must generate to pump blood against the resistance in the vessels . <hl> These factors are summarized in Table 19.1 and Table 19.2 .","hl_sentences":"Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system . Any condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood . The three primary factors to consider are preload , or the stretch on the ventricles prior to contraction ; the contractility , or the force or strength of the contraction itself ; and afterload , the force the ventricles must generate to pump blood against the resistance in the vessels .","question":{"cloze_format":"The force the heart must overcome to pump blood is known as ________.","normal_format":"What is the force the heart must overcome to pump blood?","question_choices":["preload","afterload","cardiac output","stroke volume"],"question_id":"fs-id2187635","question_text":"The force the heart must overcome to pump blood is known as ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"medulla oblongata"},"bloom":"1","hl_context":"<hl> Nervous control over HR is centralized within the two paired cardiovascular centers of the medulla oblongata ( Figure 19.32 ) . <hl> The cardioaccelerator regions stimulate activity via sympathetic stimulation of the cardioaccelerator nerves , and the cardioinhibitory centers decrease heart activity via parasympathetic stimulation as one component of the vagus nerve , cranial nerve X . During rest , both centers provide slight stimulation to the heart , contributing to autonomic tone . This is a similar concept to tone in skeletal muscles . Normally , vagal stimulation predominates as , left unregulated , the SA node would initiate a sinus rhythm of approximately 100 bpm .","hl_sentences":"Nervous control over HR is centralized within the two paired cardiovascular centers of the medulla oblongata ( Figure 19.32 ) .","question":{"cloze_format":"The area of the brain in which the cardiovascular centers are located is the ___.","normal_format":"The cardiovascular centers are located in which area of the brain?","question_choices":["medulla oblongata","pons","mesencephalon (midbrain)","cerebrum"],"question_id":"fs-id2161526","question_text":"The cardiovascular centers are located in which area of the brain?"},"references_are_paraphrase":0},{"answer":{"ans_choice":1,"ans_text":"It decreases."},"bloom":"3","hl_context":"Initially , physiological conditions that cause HR to increase also trigger an increase in SV . During exercise , the rate of blood returning to the heart increases . However as the HR rises , there is less time spent in diastole and consequently less time for the ventricles to fill with blood . Even though there is less filling time , SV will initially remain high . However , as HR continues to increase , SV gradually decreases due to decreased filling time . CO will initially stabilize as the increasing HR compensates for the decreasing SV , but at very high rates , CO will eventually decrease as increasing rates are no longer able to compensate for the decreasing SV . Consider this phenomenon in a healthy young individual . Initially , as HR increases from resting to approximately 120 bpm , CO will rise . As HR increases from 120 to 160 bpm , CO remains stable , since the increase in rate is offset by decreasing ventricular filling time and , consequently , SV . <hl> As HR continues to rise above 160 bpm , CO actually decreases as SV falls faster than HR increases . <hl> So although aerobic exercises are critical to maintain the health of the heart , individuals are cautioned to monitor their HR to ensure they stay within the target heart rate range of between 120 and 160 bpm , so CO is maintained . The target HR is loosely defined as the range in which both the heart and lungs receive the maximum benefit from the aerobic workout and is dependent upon age . <hl> Cardiac output ( CO ) is a measurement of the amount of blood pumped by each ventricle in one minute . <hl> <hl> To calculate this value , multiply stroke volume ( SV ) , the amount of blood pumped by each ventricle , by heart rate ( HR ) , in contractions per minute ( or beats per minute , bpm ) . <hl> It can be represented mathematically by the following equation :","hl_sentences":"As HR continues to rise above 160 bpm , CO actually decreases as SV falls faster than HR increases . Cardiac output ( CO ) is a measurement of the amount of blood pumped by each ventricle in one minute . To calculate this value , multiply stroke volume ( SV ) , the amount of blood pumped by each ventricle , by heart rate ( HR ) , in contractions per minute ( or beats per minute , bpm ) .","question":{"cloze_format":"In a healthy young adult, when heart rate increases above 160 bpm, the effect on the cardiac output is that ___.","normal_format":"In a healthy young adult, what happens to cardiac output when heart rate increases above 160 bpm?","question_choices":["It increases.","It decreases.","It remains constant.","There is no way to predict."],"question_id":"fs-id2049139","question_text":"In a healthy young adult, what happens to cardiac output when heart rate increases above 160 bpm?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"heart"},"bloom":"1","hl_context":"<hl> The human heart is the first functional organ to develop . <hl> It begins beating and pumping blood around day 21 or 22 , a mere three weeks after fertilization . This emphasizes the critical nature of the heart in distributing blood through the vessels and the vital exchange of nutrients , oxygen , and wastes both to and from the developing baby . The critical early development of the heart is reflected by the prominent heart bulge that appears on the anterior surface of the embryo .","hl_sentences":"The human heart is the first functional organ to develop .","question":{"cloze_format":"The earliest organ to form and begin function within the developing human is the ________.","normal_format":"What is the earliest organ to form and begin function within the developing human?","question_choices":["brain","stomach","lungs","heart"],"question_id":"fs-id1532146","question_text":"The earliest organ to form and begin function within the developing human is the ________."},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"mesoderm"},"bloom":"1","hl_context":"The heart forms from an embryonic tissue called mesoderm around 18 to 19 days after fertilization . <hl> Mesoderm is one of the three primary germ layers that differentiates early in development that collectively gives rise to all subsequent tissues and organs . <hl> The heart begins to develop near the head of the embryo in a region known as the cardiogenic area . Following chemical signals called factors from the underlying endoderm ( another of the three primary germ layers ) , the cardiogenic area begins to form two strands called the cardiogenic cords ( Figure 19.36 ) . As the cardiogenic cords develop , a lumen rapidly develops within them . At this point , they are referred to as endocardial tubes . The two tubes migrate together and fuse to form a single primitive heart tube . The primitive heart tube quickly forms five distinct regions . From head to tail , these include the truncus arteriosus , bulbus cordis , primitive ventricle , primitive atrium , and the sinus venosus . Initially , all venous blood flows into the sinus venosus , and contractions propel the blood from tail to head , or from the sinus venosus to the truncus arteriosus . This is a very different pattern from that of an adult .","hl_sentences":"Mesoderm is one of the three primary germ layers that differentiates early in development that collectively gives rise to all subsequent tissues and organs .","question":{"cloze_format":"Of the three germ layers that give rise to all adult tissues and organs, the ___ gives rise to the heart.","normal_format":"Of the three germ layers that give rise to all adult tissues and organs, which gives rise to the heart?","question_choices":["ectoderm","endoderm","mesoderm","placenta"],"question_id":"fs-id1883900","question_text":"Of the three germ layers that give rise to all adult tissues and organs, which gives rise to the heart?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"bulbus cordis"},"bloom":"1","hl_context":"<hl> The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart . <hl> The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk . <hl> The bulbus cordis develops into the right ventricle . <hl> The primitive ventricle forms the left ventricle . The primitive atrium becomes the anterior portions of both the right and left atria , and the two auricles . The sinus venosus develops into the posterior portion of the right atrium , the SA node , and the coronary sinus .","hl_sentences":"The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart . The bulbus cordis develops into the right ventricle .","question":{"cloze_format":"The primitive area of the heart that will give rise to the right ventricle is the ___.","normal_format":"Which primitive area of the heart will give rise to the right ventricle?","question_choices":["bulbus cordis","primitive ventricle","sinus venosus","truncus arteriosus"],"question_id":"fs-id2189685","question_text":"Which primitive area of the heart will give rise to the right ventricle?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"truncus arteriosus"},"bloom":"1","hl_context":"The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart . <hl> The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk . <hl> The bulbus cordis develops into the right ventricle . The primitive ventricle forms the left ventricle . The primitive atrium becomes the anterior portions of both the right and left atria , and the two auricles . The sinus venosus develops into the posterior portion of the right atrium , the SA node , and the coronary sinus .","hl_sentences":"The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk .","question":{"cloze_format":"The primitive heart structure the pulmonary trunk and aorta are derived from is the ___.","normal_format":"The pulmonary trunk and aorta are derived from which primitive heart structure?","question_choices":["bulbus cordis","primitive ventricle","sinus venosus","truncus arteriosus"],"question_id":"fs-id1846332","question_text":"The pulmonary trunk and aorta are derived from which primitive heart structure?"},"references_are_paraphrase":0}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"endocardium\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"When the myocardium of the ventricle contracts , pressure within the ventricular chamber rises . Blood , like any fluid , flows from higher pressure to lower pressure areas , in this case , toward the pulmonary trunk and the atrium . <hl> To prevent any potential backflow , the papillary muscles also contract , generating tension on the chordae tendineae . <hl> <hl> This prevents the flaps of the valves from being forced into the atria and regurgitation of the blood back into the atria during ventricular contraction . <hl> Figure 19.11 shows papillary muscles and chordae tendineae attached to the tricuspid valve .\",\n \"hl_sentences\": \"To prevent any potential backflow , the papillary muscles also contract , generating tension on the chordae tendineae . This prevents the flaps of the valves from being forced into the atria and regurgitation of the blood back into the atria during ventricular contraction .\",\n \"question\": {\n \"cloze_format\": \"___ is/are not important in preventing backflow of blood.\",\n \"normal_format\": \"Which of the following is not important in preventing backflow of blood?\",\n \"question_choices\": [\n \"chordae tendineae\",\n \"papillary muscles\",\n \"AV valves\",\n \"endocardium\"\n ],\n \"question_id\": \"fs-id2627639\",\n \"question_text\": \"Which of the following is not important in preventing backflow of blood?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"mitral\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Located at the opening between the left atrium and left ventricle is the mitral valve , also called the bicuspid valve or the left atrioventricular valve . <hl> Structurally , this valve consists of two cusps , compared to the three cusps of the tricuspid valve . In a clinical setting , the valve is referred to as the mitral valve , rather than the bicuspid valve . The two cusps of the mitral valve are attached by chordae tendineae to two papillary muscles that project from the wall of the ventricle . After exchange of gases in the pulmonary capillaries , blood returns to the left atrium high in oxygen via one of the four pulmonary veins . While the left atrium does not contain pectinate muscles , it does have an auricle that includes these pectinate ridges . Blood flows nearly continuously from the pulmonary veins back into the atrium , which acts as the receiving chamber , and from here through an opening into the left ventricle . Most blood flows passively into the heart while both the atria and ventricles are relaxed , but toward the end of the ventricular relaxation period , the left atrium will contract , pumping blood into the ventricle . This atrial contraction accounts for approximately 20 percent of ventricular filling . <hl> The opening between the left atrium and ventricle is guarded by the mitral valve . <hl>\",\n \"hl_sentences\": \"Located at the opening between the left atrium and left ventricle is the mitral valve , also called the bicuspid valve or the left atrioventricular valve . The opening between the left atrium and ventricle is guarded by the mitral valve .\",\n \"question\": {\n \"cloze_format\": \"The valve that separates the left atrium from the left ventricle is the ___.\",\n \"normal_format\": \"Which valve separates the left atrium from the left ventricle?\",\n \"question_choices\": [\n \"mitral\",\n \"tricuspid\",\n \"pulmonary\",\n \"aortic\"\n ],\n \"question_id\": \"fs-id2367256\",\n \"question_text\": \"Which valve separates the left atrium from the left ventricle?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"tricuspid, pulmonary semilunar, bicuspid, aortic semilunar\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> At the base of the aorta is the aortic semilunar valve , or the aortic valve , which prevents backflow from the aorta . <hl> It normally is composed of three flaps . When the ventricle relaxes and blood attempts to flow back into the ventricle from the aorta , blood will fill the cusps of the valve , causing it to close and producing an audible sound . <hl> Located at the opening between the left atrium and left ventricle is the mitral valve , also called the bicuspid valve or the left atrioventricular valve . <hl> Structurally , this valve consists of two cusps , compared to the three cusps of the tricuspid valve . In a clinical setting , the valve is referred to as the mitral valve , rather than the bicuspid valve . The two cusps of the mitral valve are attached by chordae tendineae to two papillary muscles that project from the wall of the ventricle . <hl> A transverse section through the heart slightly above the level of the atrioventricular septum reveals all four heart valves along the same plane ( Figure 19.12 ) . <hl> <hl> The valves ensure unidirectional blood flow through the heart . <hl> <hl> Between the right atrium and the right ventricle is the right atrioventricular valve , or tricuspid valve . <hl> It typically consists of three flaps , or leaflets , made of endocardium reinforced with additional connective tissue . The flaps are connected by chordae tendineae to the papillary muscles , which control the opening and closing of the valves . <hl> Emerging from the right ventricle at the base of the pulmonary trunk is the pulmonary semilunar valve , or the pulmonary valve ; it is also known as the pulmonic valve or the right semilunar valve . <hl> The pulmonary valve is comprised of three small flaps of endothelium reinforced with connective tissue . When the ventricle relaxes , the pressure differential causes blood to flow back into the ventricle from the pulmonary trunk . This flow of blood fills the pocket-like flaps of the pulmonary valve , causing the valve to close and producing an audible sound . Unlike the atrioventricular valves , there are no papillary muscles or chordae tendineae associated with the pulmonary valve .\",\n \"hl_sentences\": \"At the base of the aorta is the aortic semilunar valve , or the aortic valve , which prevents backflow from the aorta . Located at the opening between the left atrium and left ventricle is the mitral valve , also called the bicuspid valve or the left atrioventricular valve . A transverse section through the heart slightly above the level of the atrioventricular septum reveals all four heart valves along the same plane ( Figure 19.12 ) . The valves ensure unidirectional blood flow through the heart . Between the right atrium and the right ventricle is the right atrioventricular valve , or tricuspid valve . Emerging from the right ventricle at the base of the pulmonary trunk is the pulmonary semilunar valve , or the pulmonary valve ; it is also known as the pulmonic valve or the right semilunar valve .\",\n \"question\": {\n \"cloze_format\": \"____ lists the valves in the order through which the blood flows from the vena cava through the heart.\",\n \"normal_format\": \"Which of the following lists the valves in the order through which the blood flows from the vena cava through the heart?\",\n \"question_choices\": [\n \"tricuspid, pulmonary semilunar, bicuspid, aortic semilunar\",\n \"mitral, pulmonary semilunar, bicuspid, aortic semilunar\",\n \"aortic semilunar, pulmonary semilunar, tricuspid, bicuspid\",\n \"bicuspid, aortic semilunar, tricuspid, pulmonary semilunar\"\n ],\n \"question_id\": \"fs-id1228297\",\n \"question_text\": \"Which of the following lists the valves in the order through which the blood flows from the vena cava through the heart?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"right atrium\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> The right atrium serves as the receiving chamber for blood returning to the heart from the systemic circulation . <hl> The two major systemic veins , the superior and inferior venae cavae , and the large coronary vein called the coronary sinus that drains the heart myocardium empty into the right atrium . The superior vena cava drains blood from regions superior to the diaphragm : the head , neck , upper limbs , and the thoracic region . It empties into the superior and posterior portions of the right atrium . The inferior vena cava drains blood from areas inferior to the diaphragm : the lower limbs and abdominopelvic region of the body . It , too , empties into the posterior portion of the atria , but inferior to the opening of the superior vena cava . Immediately superior and slightly medial to the opening of the inferior vena cava on the posterior surface of the atrium is the opening of the coronary sinus . This thin-walled vessel drains most of the coronary veins that return systemic blood from the heart . The majority of the internal heart structures discussed in this and subsequent sections are illustrated in Figure 19.9 . The human heart consists of four chambers : The left side and the right side each have one atrium and one ventricle . <hl> Each of the upper chambers , the right atrium ( plural = atria ) and the left atrium , acts as a receiving chamber and contracts to push blood into the lower chambers , the right ventricle and the left ventricle . <hl> The ventricles serve as the primary pumping chambers of the heart , propelling blood to the lungs or to the rest of the body .\",\n \"hl_sentences\": \"The right atrium serves as the receiving chamber for blood returning to the heart from the systemic circulation . Each of the upper chambers , the right atrium ( plural = atria ) and the left atrium , acts as a receiving chamber and contracts to push blood into the lower chambers , the right ventricle and the left ventricle .\",\n \"question\": {\n \"cloze_format\": \"The chamber that initially receives blood from the systemic circuit is the ___ .\",\n \"normal_format\": \"Which chamber initially receives blood from the systemic circuit?\",\n \"question_choices\": [\n \"left atrium\",\n \"left ventricle\",\n \"right atrium\",\n \"right ventricle\"\n ],\n \"question_id\": \"fs-id2002743\",\n \"question_text\": \"Which chamber initially receives blood from the systemic circuit?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"endocardium\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Once regarded as a simple lining layer , recent evidence indicates that the endothelium of the endocardium and the coronary capillaries may play active roles in regulating the contraction of the muscle within the myocardium . <hl> <hl> The endothelium may also regulate the growth patterns of the cardiac muscle cells throughout life , and the endothelins it secretes create an environment in the surrounding tissue fluids that regulates ionic concentrations and states of contractility . <hl> <hl> Endothelins are potent vasoconstrictors and , in a normal individual , establish a homeostatic balance with other vasoconstrictors and vasodilators . <hl> <hl> The innermost layer of the heart wall , the endocardium , is joined to the myocardium with a thin layer of connective tissue . <hl> The endocardium lines the chambers where the blood circulates and covers the heart valves . It is made of simple squamous epithelium called endothelium , which is continuous with the endothelial lining of the blood vessels ( see Figure 19.5 ) .\",\n \"hl_sentences\": \"Once regarded as a simple lining layer , recent evidence indicates that the endothelium of the endocardium and the coronary capillaries may play active roles in regulating the contraction of the muscle within the myocardium . The endothelium may also regulate the growth patterns of the cardiac muscle cells throughout life , and the endothelins it secretes create an environment in the surrounding tissue fluids that regulates ionic concentrations and states of contractility . Endothelins are potent vasoconstrictors and , in a normal individual , establish a homeostatic balance with other vasoconstrictors and vasodilators . The innermost layer of the heart wall , the endocardium , is joined to the myocardium with a thin layer of connective tissue .\",\n \"question\": {\n \"cloze_format\": \"The ________ layer secretes chemicals that help to regulate ionic environments and strength of contraction and serve as powerful vasoconstrictors.\",\n \"normal_format\": \"Which layer secretes chemicals that help to regulate ionic environments and strength of contraction and serve as powerful vasoconstrictors?\",\n \"question_choices\": [\n \"pericardial sac\",\n \"endocardium\",\n \"myocardium\",\n \"epicardium\"\n ],\n \"question_id\": \"fs-id2515169\",\n \"question_text\": \"The ________ layer secretes chemicals that help to regulate ionic environments and strength of contraction and serve as powerful vasoconstrictors.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"left ventricle\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Recall that , although both sides of the heart will pump the same amount of blood , the muscular layer is much thicker in the left ventricle compared to the right ( see Figure 19.8 ) . <hl> Like the right ventricle , the left also has trabeculae carneae , but there is no moderator band . The mitral valve is connected to papillary muscles via chordae tendineae . There are two papillary muscles on the left — the anterior and posterior — as opposed to three on the right . <hl> Although the ventricles on the right and left sides pump the same amount of blood per contraction , the muscle of the left ventricle is much thicker and better developed than that of the right ventricle . <hl> In order to overcome the high resistance required to pump blood into the long systemic circuit , the left ventricle must generate a great amount of pressure . The right ventricle does not need to generate as much pressure , since the pulmonary circuit is shorter and provides less resistance . Figure 19.8 illustrates the differences in muscular thickness needed for each of the ventricles . <hl> The middle and thickest layer is the myocardium , made largely of cardiac muscle cells . <hl> It is built upon a framework of collagenous fibers , plus the blood vessels that supply the myocardium and the nerve fibers that help regulate the heart . It is the contraction of the myocardium that pumps blood through the heart and into the major arteries . The muscle pattern is elegant and complex , as the muscle cells swirl and spiral around the chambers of the heart . They form a figure 8 pattern around the atria and around the bases of the great vessels . Deeper ventricular muscles also form a figure 8 around the two ventricles and proceed toward the apex . More superficial layers of ventricular muscle wrap around both ventricles . This complex swirling pattern allows the heart to pump blood more effectively than a simple linear pattern would . Figure 19.7 illustrates the arrangement of muscle cells . <hl> The wall of the heart is composed of three layers of unequal thickness . <hl> <hl> From superficial to deep , these are the epicardium , the myocardium , and the endocardium ( see Figure 19.5 ) . <hl> The outermost layer of the wall of the heart is also the innermost layer of the pericardium , the epicardium , or the visceral pericardium discussed earlier .\",\n \"hl_sentences\": \"Recall that , although both sides of the heart will pump the same amount of blood , the muscular layer is much thicker in the left ventricle compared to the right ( see Figure 19.8 ) . Although the ventricles on the right and left sides pump the same amount of blood per contraction , the muscle of the left ventricle is much thicker and better developed than that of the right ventricle . The middle and thickest layer is the myocardium , made largely of cardiac muscle cells . The wall of the heart is composed of three layers of unequal thickness . From superficial to deep , these are the epicardium , the myocardium , and the endocardium ( see Figure 19.5 ) .\",\n \"question\": {\n \"cloze_format\": \"The myocardium would be the thickest in the ________.\",\n \"normal_format\": \"In what would the myocardium be the thickest?\",\n \"question_choices\": [\n \"left atrium\",\n \"left ventricle\",\n \"right atrium\",\n \"right ventricle\"\n ],\n \"question_id\": \"fs-id2300602\",\n \"question_text\": \"The myocardium would be the thickest in the ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"atrioventricular septum\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The septum between the atria and ventricles is known as the atrioventricular septum . <hl> <hl> It is marked by the presence of four openings that allow blood to move from the atria into the ventricles and from the ventricles into the pulmonary trunk and aorta . <hl> Located in each of these openings between the atria and ventricles is a valve , a specialized structure that ensures one-way flow of blood . The valves between the atria and ventricles are known generically as atrioventricular valves . The valves at the openings that lead to the pulmonary trunk and aorta are known generically as semilunar valves . The interventricular septum is visible in Figure 19.9 . In this figure , the atrioventricular septum has been removed to better show the bicuspid and tricuspid valves ; the interatrial septum is not visible , since its location is covered by the aorta and pulmonary trunk . Since these openings and valves structurally weaken the atrioventricular septum , the remaining tissue is heavily reinforced with dense connective tissue called the cardiac skeleton , or skeleton of the heart . It includes four rings that surround the openings between the atria and ventricles , and the openings to the pulmonary trunk and aorta , and serve as the point of attachment for the heart valves . The cardiac skeleton also provides an important boundary in the heart electrical conduction system .\",\n \"hl_sentences\": \"The septum between the atria and ventricles is known as the atrioventricular septum . It is marked by the presence of four openings that allow blood to move from the atria into the ventricles and from the ventricles into the pulmonary trunk and aorta .\",\n \"question\": {\n \"cloze_format\": \"The septum in which it is normal to find openings in the adult is the ___.\",\n \"normal_format\": \"In which septum is it normal to find openings in the adult?\",\n \"question_choices\": [\n \"interatrial septum\",\n \"interventricular septum\",\n \"atrioventricular septum\",\n \"all of the above\"\n ],\n \"question_id\": \"fs-id1795973\",\n \"question_text\": \"In which septum is it normal to find openings in the adult?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"Only cardiac muscle is capable of autorhythmicity\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Recall that cardiac muscle shares a few characteristics with both skeletal muscle and smooth muscle , but it has some unique properties of its own . <hl> Not the least of these exceptional properties is its ability to initiate an electrical potential at a fixed rate that spreads rapidly from cell to cell to trigger the contractile mechanism . <hl> This property is known as autorhythmicity . <hl> Neither smooth nor skeletal muscle can do this . Even though cardiac muscle has autorhythmicity , heart rate is modulated by the endocrine and nervous systems .\",\n \"hl_sentences\": \"Recall that cardiac muscle shares a few characteristics with both skeletal muscle and smooth muscle , but it has some unique properties of its own . This property is known as autorhythmicity .\",\n \"question\": {\n \"cloze_format\": \"It is unique to cardiac muscle cells that ___.\",\n \"normal_format\": \"Which of the following is unique to cardiac muscle cells?\",\n \"question_choices\": [\n \"Only cardiac muscle contains a sarcoplasmic reticulum.\",\n \"Only cardiac muscle has gap junctions.\",\n \"Only cardiac muscle is capable of autorhythmicity\",\n \"Only cardiac muscle has a high concentration of mitochondria.\"\n ],\n \"question_id\": \"fs-id2481331\",\n \"question_text\": \"Which of the following is unique to cardiac muscle cells?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"calcium\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Calcium ions play two critical roles in the physiology of cardiac muscle . <hl> <hl> Their influx through slow calcium channels accounts for the prolonged plateau phase and absolute refractory period that enable cardiac muscle to function properly . <hl> Calcium ions also combine with the regulatory protein troponin in the troponin-tropomyosin complex ; this complex removes the inhibition that prevents the heads of the myosin molecules from forming cross bridges with the active sites on actin that provide the power stroke of contraction . This mechanism is virtually identical to that of skeletal muscle . Approximately 20 percent of the calcium required for contraction is supplied by the influx of Ca 2 + during the plateau phase . The remaining Ca 2 + for contraction is released from storage in the sarcoplasmic reticulum .\",\n \"hl_sentences\": \"Calcium ions play two critical roles in the physiology of cardiac muscle . Their influx through slow calcium channels accounts for the prolonged plateau phase and absolute refractory period that enable cardiac muscle to function properly .\",\n \"question\": {\n \"cloze_format\": \"The ion of which the influx accounts for the plateau phase is ___.\",\n \"normal_format\": \"The influx of which ion accounts for the plateau phase?\",\n \"question_choices\": [\n \"sodium\",\n \"potassium\",\n \"chloride\",\n \"calcium\"\n ],\n \"question_id\": \"fs-id2050334\",\n \"question_text\": \"The influx of which ion accounts for the plateau phase?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"none of the above: atrial repolarization is masked by ventricular depolarization\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Contraction of the atria follows depolarization , represented by the P wave of the ECG . <hl> As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum , pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular ( tricuspid , and mitral or bicuspid ) valves . At the start of atrial systole , the ventricles are normally filled with approximately 70 – 80 percent of their capacity due to inflow during diastole . Atrial contraction , also referred to as the “ atrial kick , ” contributes the remaining 20 – 30 percent of filling ( see Figure 19.27 ) . Atrial systole lasts approximately 100 ms and ends prior to ventricular systole , as the atrial muscle returns to diastole . There are five prominent points on the ECG : the P wave , the QRS complex , and the T wave . <hl> The small P wave represents the depolarization of the atria . <hl> The atria begin contracting approximately 25 ms after the start of the P wave . The large QRS complex represents the depolarization of the ventricles , which requires a much stronger electrical signal because of the larger size of the ventricular cardiac muscle . The ventricles begin to contract as the QRS reaches the peak of the R wave . Lastly , the T wave represents the repolarization of the ventricles . The repolarization of the atria occurs during the QRS complex , which masks it on an ECG .\",\n \"hl_sentences\": \"Contraction of the atria follows depolarization , represented by the P wave of the ECG . The small P wave represents the depolarization of the atria .\",\n \"question\": {\n \"cloze_format\": \"The portion of the ECG that corresponds to repolarization of the atria is the ___ .\",\n \"normal_format\": \"Which portion of the ECG corresponds to repolarization of the atria?\",\n \"question_choices\": [\n \"P wave\",\n \"QRS complex\",\n \"T wave\",\n \"none of the above: atrial repolarization is masked by ventricular depolarization\"\n ],\n \"question_id\": \"fs-id2042928\",\n \"question_text\": \"Which portion of the ECG corresponds to repolarization of the atria?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"Purkinje fibers\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"The pattern of prepotential or spontaneous depolarization , followed by rapid depolarization and repolarization just described , are seen in the SA node and a few other conductive cells in the heart . Since the SA node is the pacemaker , it reaches threshold faster than any other component of the conduction system . It will initiate the impulses spreading to the other conducting cells . The SA node , without nervous or endocrine control , would initiate a heart impulse approximately 80 – 100 times per minute . Although each component of the conduction system is capable of generating its own impulse , the rate progressively slows as you proceed from the SA node to the Purkinje fibers . <hl> Without the SA node , the AV node would generate a heart rate of 40 – 60 beats per minute . <hl> <hl> If the AV node were blocked , the atrioventricular bundle would fire at a rate of approximately 30 – 40 impulses per minute . <hl> <hl> The bundle branches would have an inherent rate of 20 – 30 impulses per minute , and the Purkinje fibers would fire at 15 – 20 impulses per minute . <hl> While a few exceptionally trained aerobic athletes demonstrate resting heart rates in the range of 30 – 40 beats per minute ( the lowest recorded figure is 28 beats per minute for Miguel Indurain , a cyclist ) , for most individuals , rates lower than 50 beats per minute would indicate a condition called bradycardia . Depending upon the specific individual , as rates fall much below this level , the heart would be unable to maintain adequate flow of blood to vital tissues , initially resulting in decreasing loss of function across the systems , unconsciousness , and ultimately death .\",\n \"hl_sentences\": \"Without the SA node , the AV node would generate a heart rate of 40 – 60 beats per minute . If the AV node were blocked , the atrioventricular bundle would fire at a rate of approximately 30 – 40 impulses per minute . The bundle branches would have an inherent rate of 20 – 30 impulses per minute , and the Purkinje fibers would fire at 15 – 20 impulses per minute .\",\n \"question\": {\n \"cloze_format\": \"The component of the heart conduction system that would have the slowest rate of firing is the ___.\",\n \"normal_format\": \"Which component of the heart conduction system would have the slowest rate of firing?\",\n \"question_choices\": [\n \"atrioventricular node\",\n \"atrioventricular bundle\",\n \"bundle branches\",\n \"Purkinje fibers\"\n ],\n \"question_id\": \"fs-id2060782\",\n \"question_text\": \"Which component of the heart conduction system would have the slowest rate of firing?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"isovolumic contraction\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Initially , as the muscles in the ventricle contract , the pressure of the blood within the chamber rises , but it is not yet high enough to open the semilunar ( pulmonary and aortic ) valves and be ejected from the heart . <hl> <hl> However , blood pressure quickly rises above that of the atria that are now relaxed and in diastole . <hl> <hl> This increase in pressure causes blood to flow back toward the atria , closing the tricuspid and mitral valves . <hl> <hl> Since blood is not being ejected from the ventricles at this early stage , the volume of blood within the chamber remains constant . <hl> <hl> Consequently , this initial phase of ventricular systole is known as isovolumic contraction , also called isovolumetric contraction ( see Figure 19.27 ) . <hl>\",\n \"hl_sentences\": \"Initially , as the muscles in the ventricle contract , the pressure of the blood within the chamber rises , but it is not yet high enough to open the semilunar ( pulmonary and aortic ) valves and be ejected from the heart . However , blood pressure quickly rises above that of the atria that are now relaxed and in diastole . This increase in pressure causes blood to flow back toward the atria , closing the tricuspid and mitral valves . Since blood is not being ejected from the ventricles at this early stage , the volume of blood within the chamber remains constant . Consequently , this initial phase of ventricular systole is known as isovolumic contraction , also called isovolumetric contraction ( see Figure 19.27 ) .\",\n \"question\": {\n \"cloze_format\": \"The cardiac cycle consists of a distinct relaxation and contraction phase. The term that is typically used to refer ventricular contraction while no blood is being ejected is ___.\",\n \"normal_format\": \"The cardiac cycle consists of a distinct relaxation and contraction phase. Which term is typically used to refer ventricular contraction while no blood is being ejected?\",\n \"question_choices\": [\n \"systole\",\n \"diastole\",\n \"quiescent\",\n \"isovolumic contraction\"\n ],\n \"question_id\": \"fs-id2001918\",\n \"question_text\": \"The cardiac cycle consists of a distinct relaxation and contraction phase. Which term is typically used to refer ventricular contraction while no blood is being ejected?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"atrial diastole\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"Contraction of the atria follows depolarization , represented by the P wave of the ECG . <hl> As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum , pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular ( tricuspid , and mitral or bicuspid ) valves . <hl> <hl> At the start of atrial systole , the ventricles are normally filled with approximately 70 – 80 percent of their capacity due to inflow during diastole . <hl> Atrial contraction , also referred to as the “ atrial kick , ” contributes the remaining 20 – 30 percent of filling ( see Figure 19.27 ) . Atrial systole lasts approximately 100 ms and ends prior to ventricular systole , as the atrial muscle returns to diastole .\",\n \"hl_sentences\": \"As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum , pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular ( tricuspid , and mitral or bicuspid ) valves . At the start of atrial systole , the ventricles are normally filled with approximately 70 – 80 percent of their capacity due to inflow during diastole .\",\n \"question\": {\n \"cloze_format\": \"Most blood enters the ventricle during ________.\",\n \"normal_format\": \"During what do most blood enter the ventricle?\",\n \"question_choices\": [\n \"atrial systole\",\n \"atrial diastole\",\n \"ventricular systole\",\n \"isovolumic contraction\"\n ],\n \"question_id\": \"fs-id2321229\",\n \"question_text\": \"Most blood enters the ventricle during ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"closing of the atrioventricular valves\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> In a normal , healthy heart , there are only two audible heart sounds : S 1 and S 2 . <hl> <hl> S 1 is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as a “ lub , ” or first heart sound . <hl> The second heart sound , S 2 , is the sound of the closing of the semilunar valves during ventricular diastole and is described as a “ dub ” ( Figure 19.29 ) . In both cases , as the valves close , the openings within the atrioventricular septum guarded by the valves will become reduced , and blood flow through the opening will become more turbulent until the valves are fully closed . There is a third heart sound , S 3 , but it is rarely heard in healthy individuals . It may be the sound of blood flowing into the atria , or blood sloshing back and forth in the ventricle , or even tensing of the chordae tendineae . S 3 may be heard in youth , some athletes , and pregnant women . If the sound is heard later in life , it may indicate congestive heart failure , warranting further tests . Some cardiologists refer to the collective S 1 , S 2 , and S 3 sounds as the “ Kentucky gallop , ” because they mimic those produced by a galloping horse . The fourth heart sound , S 4 , results from the contraction of the atria pushing blood into a stiff or hypertrophic ventricle , indicating failure of the left ventricle . S 4 occurs prior to S 1 and the collective sounds S 4 , S 1 , and S 2 are referred to by some cardiologists as the “ Tennessee gallop , ” because of their similarity to the sound produced by a galloping horse with a different gait . A few individuals may have both S 3 and S 4 , and this combined sound is referred to as S 7 .\",\n \"hl_sentences\": \"In a normal , healthy heart , there are only two audible heart sounds : S 1 and S 2 . S 1 is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as a “ lub , ” or first heart sound .\",\n \"question\": {\n \"cloze_format\": \"The ___ is the portion of the cardiac cycle that the first heart sound represents.\",\n \"normal_format\": \"The first heart sound represents which portion of the cardiac cycle?\",\n \"question_choices\": [\n \"atrial systole\",\n \"ventricular systole\",\n \"closing of the atrioventricular valves\",\n \"closing of the semilunar valves\"\n ],\n \"question_id\": \"fs-id2672256\",\n \"question_text\": \"The first heart sound represents which portion of the cardiac cycle?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"ventricular repolarization\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Ventricular relaxation , or diastole , follows repolarization of the ventricles and is represented by the T wave of the ECG . <hl> It too is divided into two distinct phases and lasts approximately 430 ms .\",\n \"hl_sentences\": \"Ventricular relaxation , or diastole , follows repolarization of the ventricles and is represented by the T wave of the ECG .\",\n \"question\": {\n \"cloze_format\": \"Ventricular relaxation immediately follows ________.\",\n \"normal_format\": \"What does ventricular relaxation immediately follow?\",\n \"question_choices\": [\n \"atrial depolarization\",\n \"ventricular repolarization\",\n \"ventricular depolarization\",\n \"atrial repolarization\"\n ],\n \"question_id\": \"fs-id2060926\",\n \"question_text\": \"Ventricular relaxation immediately follows ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"afterload\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system . <hl> <hl> Any condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood . <hl> Damage to the valves , such as stenosis , which makes them harder to open will also increase afterload . Any decrease in resistance decreases the afterload . Figure 19.34 summarizes the major factors influencing SV , Figure 19.35 summarizes the major factors influencing CO , and Table 19.3 and Table 19.4 summarize cardiac responses to increased and decreased blood flow and pressure in order to restore homeostasis . Many of the same factors that regulate HR also impact cardiac function by altering SV . While a number of variables are involved , SV is ultimately dependent upon the difference between EDV and ESV . <hl> The three primary factors to consider are preload , or the stretch on the ventricles prior to contraction ; the contractility , or the force or strength of the contraction itself ; and afterload , the force the ventricles must generate to pump blood against the resistance in the vessels . <hl> These factors are summarized in Table 19.1 and Table 19.2 .\",\n \"hl_sentences\": \"Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system . Any condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood . The three primary factors to consider are preload , or the stretch on the ventricles prior to contraction ; the contractility , or the force or strength of the contraction itself ; and afterload , the force the ventricles must generate to pump blood against the resistance in the vessels .\",\n \"question\": {\n \"cloze_format\": \"The force the heart must overcome to pump blood is known as ________.\",\n \"normal_format\": \"What is the force the heart must overcome to pump blood?\",\n \"question_choices\": [\n \"preload\",\n \"afterload\",\n \"cardiac output\",\n \"stroke volume\"\n ],\n \"question_id\": \"fs-id2187635\",\n \"question_text\": \"The force the heart must overcome to pump blood is known as ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"medulla oblongata\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> Nervous control over HR is centralized within the two paired cardiovascular centers of the medulla oblongata ( Figure 19.32 ) . <hl> The cardioaccelerator regions stimulate activity via sympathetic stimulation of the cardioaccelerator nerves , and the cardioinhibitory centers decrease heart activity via parasympathetic stimulation as one component of the vagus nerve , cranial nerve X . During rest , both centers provide slight stimulation to the heart , contributing to autonomic tone . This is a similar concept to tone in skeletal muscles . Normally , vagal stimulation predominates as , left unregulated , the SA node would initiate a sinus rhythm of approximately 100 bpm .\",\n \"hl_sentences\": \"Nervous control over HR is centralized within the two paired cardiovascular centers of the medulla oblongata ( Figure 19.32 ) .\",\n \"question\": {\n \"cloze_format\": \"The area of the brain in which the cardiovascular centers are located is the ___.\",\n \"normal_format\": \"The cardiovascular centers are located in which area of the brain?\",\n \"question_choices\": [\n \"medulla oblongata\",\n \"pons\",\n \"mesencephalon (midbrain)\",\n \"cerebrum\"\n ],\n \"question_id\": \"fs-id2161526\",\n \"question_text\": \"The cardiovascular centers are located in which area of the brain?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"It decreases.\"\n },\n \"bloom\": \"3\",\n \"hl_context\": \"Initially , physiological conditions that cause HR to increase also trigger an increase in SV . During exercise , the rate of blood returning to the heart increases . However as the HR rises , there is less time spent in diastole and consequently less time for the ventricles to fill with blood . Even though there is less filling time , SV will initially remain high . However , as HR continues to increase , SV gradually decreases due to decreased filling time . CO will initially stabilize as the increasing HR compensates for the decreasing SV , but at very high rates , CO will eventually decrease as increasing rates are no longer able to compensate for the decreasing SV . Consider this phenomenon in a healthy young individual . Initially , as HR increases from resting to approximately 120 bpm , CO will rise . As HR increases from 120 to 160 bpm , CO remains stable , since the increase in rate is offset by decreasing ventricular filling time and , consequently , SV . <hl> As HR continues to rise above 160 bpm , CO actually decreases as SV falls faster than HR increases . <hl> So although aerobic exercises are critical to maintain the health of the heart , individuals are cautioned to monitor their HR to ensure they stay within the target heart rate range of between 120 and 160 bpm , so CO is maintained . The target HR is loosely defined as the range in which both the heart and lungs receive the maximum benefit from the aerobic workout and is dependent upon age . <hl> Cardiac output ( CO ) is a measurement of the amount of blood pumped by each ventricle in one minute . <hl> <hl> To calculate this value , multiply stroke volume ( SV ) , the amount of blood pumped by each ventricle , by heart rate ( HR ) , in contractions per minute ( or beats per minute , bpm ) . <hl> It can be represented mathematically by the following equation :\",\n \"hl_sentences\": \"As HR continues to rise above 160 bpm , CO actually decreases as SV falls faster than HR increases . Cardiac output ( CO ) is a measurement of the amount of blood pumped by each ventricle in one minute . To calculate this value , multiply stroke volume ( SV ) , the amount of blood pumped by each ventricle , by heart rate ( HR ) , in contractions per minute ( or beats per minute , bpm ) .\",\n \"question\": {\n \"cloze_format\": \"In a healthy young adult, when heart rate increases above 160 bpm, the effect on the cardiac output is that ___.\",\n \"normal_format\": \"In a healthy young adult, what happens to cardiac output when heart rate increases above 160 bpm?\",\n \"question_choices\": [\n \"It increases.\",\n \"It decreases.\",\n \"It remains constant.\",\n \"There is no way to predict.\"\n ],\n \"question_id\": \"fs-id2049139\",\n \"question_text\": \"In a healthy young adult, what happens to cardiac output when heart rate increases above 160 bpm?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"heart\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> The human heart is the first functional organ to develop . <hl> It begins beating and pumping blood around day 21 or 22 , a mere three weeks after fertilization . This emphasizes the critical nature of the heart in distributing blood through the vessels and the vital exchange of nutrients , oxygen , and wastes both to and from the developing baby . The critical early development of the heart is reflected by the prominent heart bulge that appears on the anterior surface of the embryo .\",\n \"hl_sentences\": \"The human heart is the first functional organ to develop .\",\n \"question\": {\n \"cloze_format\": \"The earliest organ to form and begin function within the developing human is the ________.\",\n \"normal_format\": \"What is the earliest organ to form and begin function within the developing human?\",\n \"question_choices\": [\n \"brain\",\n \"stomach\",\n \"lungs\",\n \"heart\"\n ],\n \"question_id\": \"fs-id1532146\",\n \"question_text\": \"The earliest organ to form and begin function within the developing human is the ________.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"mesoderm\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"The heart forms from an embryonic tissue called mesoderm around 18 to 19 days after fertilization . <hl> Mesoderm is one of the three primary germ layers that differentiates early in development that collectively gives rise to all subsequent tissues and organs . <hl> The heart begins to develop near the head of the embryo in a region known as the cardiogenic area . Following chemical signals called factors from the underlying endoderm ( another of the three primary germ layers ) , the cardiogenic area begins to form two strands called the cardiogenic cords ( Figure 19.36 ) . As the cardiogenic cords develop , a lumen rapidly develops within them . At this point , they are referred to as endocardial tubes . The two tubes migrate together and fuse to form a single primitive heart tube . The primitive heart tube quickly forms five distinct regions . From head to tail , these include the truncus arteriosus , bulbus cordis , primitive ventricle , primitive atrium , and the sinus venosus . Initially , all venous blood flows into the sinus venosus , and contractions propel the blood from tail to head , or from the sinus venosus to the truncus arteriosus . This is a very different pattern from that of an adult .\",\n \"hl_sentences\": \"Mesoderm is one of the three primary germ layers that differentiates early in development that collectively gives rise to all subsequent tissues and organs .\",\n \"question\": {\n \"cloze_format\": \"Of the three germ layers that give rise to all adult tissues and organs, the ___ gives rise to the heart.\",\n \"normal_format\": \"Of the three germ layers that give rise to all adult tissues and organs, which gives rise to the heart?\",\n \"question_choices\": [\n \"ectoderm\",\n \"endoderm\",\n \"mesoderm\",\n \"placenta\"\n ],\n \"question_id\": \"fs-id1883900\",\n \"question_text\": \"Of the three germ layers that give rise to all adult tissues and organs, which gives rise to the heart?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"bulbus cordis\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"<hl> The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart . <hl> The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk . <hl> The bulbus cordis develops into the right ventricle . <hl> The primitive ventricle forms the left ventricle . The primitive atrium becomes the anterior portions of both the right and left atria , and the two auricles . The sinus venosus develops into the posterior portion of the right atrium , the SA node , and the coronary sinus .\",\n \"hl_sentences\": \"The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart . The bulbus cordis develops into the right ventricle .\",\n \"question\": {\n \"cloze_format\": \"The primitive area of the heart that will give rise to the right ventricle is the ___.\",\n \"normal_format\": \"Which primitive area of the heart will give rise to the right ventricle?\",\n \"question_choices\": [\n \"bulbus cordis\",\n \"primitive ventricle\",\n \"sinus venosus\",\n \"truncus arteriosus\"\n ],\n \"question_id\": \"fs-id2189685\",\n \"question_text\": \"Which primitive area of the heart will give rise to the right ventricle?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"truncus arteriosus\"\n },\n \"bloom\": \"1\",\n \"hl_context\": \"The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart . <hl> The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk . <hl> The bulbus cordis develops into the right ventricle . The primitive ventricle forms the left ventricle . The primitive atrium becomes the anterior portions of both the right and left atria , and the two auricles . The sinus venosus develops into the posterior portion of the right atrium , the SA node , and the coronary sinus .\",\n \"hl_sentences\": \"The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk .\",\n \"question\": {\n \"cloze_format\": \"The primitive heart structure the pulmonary trunk and aorta are derived from is the ___.\",\n \"normal_format\": \"The pulmonary trunk and aorta are derived from which primitive heart structure?\",\n \"question_choices\": [\n \"bulbus cordis\",\n \"primitive ventricle\",\n \"sinus venosus\",\n \"truncus arteriosus\"\n ],\n \"question_id\": \"fs-id1846332\",\n \"question_text\": \"The pulmonary trunk and aorta are derived from which primitive heart structure?\"\n },\n \"references_are_paraphrase\": 0\n }\n]","isConversational":false},"chapter":{"kind":"number","value":19,"string":"19"},"chapter_text":{"kind":"string","value":" 19.1 Heart Anatomy Learning Objectives By the end of this section, you will be able to: \n\n Describe the location and position of the heart within the body cavity \n\n Describe the internal and external anatomy of the heart \n\n Identify the tissue layers of the heart \n\n Relate the structure of the heart to its function as a pump \n\n Compare systemic circulation to pulmonary circulation \n\n Identify the veins and arteries of the coronary circulation system \n\n Trace the pathway of oxygenated and deoxygenated blood thorough the chambers of the heart \n\n The vital importance of the heart is obvious. If one assumes an average rate of contraction of 75 contractions per minute, a human heart would contract approximately 108,000 times in one day, more than 39 million times in one year, and nearly 3 billion times during a 75-year lifespan. Each of the major pumping chambers of the heart ejects approximately 70 mL blood per contraction in a resting adult. This would be equal to 5.25 liters of fluid per minute and approximately 14,000 liters per day. Over one year, that would equal 10,000,000 liters or 2.6 million gallons of blood sent through roughly 60,000 miles of vessels. In order to understand how that happens, it is necessary to understand the anatomy and physiology of the heart. \n\n Location of the Heart \n\n The human heart is located within the thoracic cavity, medially between the lungs in the space known as the mediastinum. Figure 19.2 shows the position of the heart within the thoracic cavity. Within the mediastinum, the heart is separated from the other mediastinal structures by a tough membrane known as the pericardium, or pericardial sac, and sits in its own space called the pericardial cavity . The dorsal surface of the heart lies near the bodies of the vertebrae, and its anterior surface sits deep to the sternum and costal cartilages. The great veins, the superior and inferior venae cavae, and the great arteries, the aorta and pulmonary trunk, are attached to the superior surface of the heart, called the base. The base of the heart is located at the level of the third costal cartilage, as seen in Figure 19.2 . The inferior tip of the heart, the apex, lies just to the left of the sternum between the junction of the fourth and fifth ribs near their articulation with the costal cartilages. The right side of the heart is deflected anteriorly, and the left side is deflected posteriorly. It is important to remember the position and orientation of the heart when placing a stethoscope on the chest of a patient and listening for heart sounds, and also when looking at images taken from a midsagittal perspective. The slight deviation of the apex to the left is reflected in a depression in the medial surface of the inferior lobe of the left lung, called the cardiac notch . \n\n Everyday Connection CPR \n\nThe position of the heart in the torso between the vertebrae and sternum (see Figure 19.2 for the position of the heart within the thorax) allows for individuals to apply an emergency technique known as cardiopulmonary resuscitation (CPR) if the heart of a patient should stop. By applying pressure with the flat portion of one hand on the sternum in the area between the line at T4 and T9 ( Figure 19.3 ), it is possible to manually compress the blood within the heart enough to push some of the blood within it into the pulmonary and systemic circuits. This is particularly critical for the brain, as irreversible damage and death of neurons occur within minutes of loss of blood flow. Current standards call for compression of the chest at least 5 cm deep and at a rate of 100 compressions per minute, a rate equal to the beat in “Staying Alive,” recorded in 1977 by the Bee Gees. If you are unfamiliar with this song, a version is available on www.youtube.com. At this stage, the emphasis is on performing high-quality chest compressions, rather than providing artificial respiration. CPR is generally performed until the patient regains spontaneous contraction or is declared dead by an experienced healthcare professional. \n\n When performed by untrained or overzealous individuals, CPR can result in broken ribs or a broken sternum, and can inflict additional severe damage on the patient. It is also possible, if the hands are placed too low on the sternum, to manually drive the xiphoid process into the liver, a consequence that may prove fatal for the patient. Proper training is essential. This proven life-sustaining technique is so valuable that virtually all medical personnel as well as concerned members of the public should be certified and routinely recertified in its application. CPR courses are offered at a variety of locations, including colleges, hospitals, the American Red Cross, and some commercial companies. They normally include practice of the compression technique on a mannequin. \n\n Interactive Link \n\n Visit the American Heart Association website to help locate a course near your home in the United States. There are also many other national and regional heart associations that offer the same service, depending upon the location. \n\n Shape and Size of the Heart \n\n The shape of the heart is similar to a pinecone, rather broad at the superior surface and tapering to the apex (see Figure 19.2 ). A typical heart is approximately the size of your fist: 12 cm (5 in) in length, 8 cm (3.5 in) wide, and 6 cm (2.5 in) in thickness. Given the size difference between most members of the sexes, the weight of a female heart is approximately 250–300 grams (9 to 11 ounces), and the weight of a male heart is approximately 300–350 grams (11 to 12 ounces). The heart of a well-trained athlete, especially one specializing in aerobic sports, can be considerably larger than this. Cardiac muscle responds to exercise in a manner similar to that of skeletal muscle. That is, exercise results in the addition of protein myofilaments that increase the size of the individual cells without increasing their numbers, a concept called hypertrophy. Hearts of athletes can pump blood more effectively at lower rates than those of nonathletes. Enlarged hearts are not always a result of exercise; they can result from pathologies, such as hypertrophic cardiomyopathy . The cause of an abnormally enlarged heart muscle is unknown, but the condition is often undiagnosed and can cause sudden death in apparently otherwise healthy young people. \n\n Chambers and Circulation through the Heart \n\n The human heart consists of four chambers: The left side and the right side each have one atrium and one ventricle . Each of the upper chambers, the right atrium (plural = atria) and the left atrium, acts as a receiving chamber and contracts to push blood into the lower chambers, the right ventricle and the left ventricle. The ventricles serve as the primary pumping chambers of the heart, propelling blood to the lungs or to the rest of the body. \n\n There are two distinct but linked circuits in the human circulation called the pulmonary and systemic circuits. Although both circuits transport blood and everything it carries, we can initially view the circuits from the point of view of gases. The pulmonary circuit transports blood to and from the lungs, where it picks up oxygen and delivers carbon dioxide for exhalation. The systemic circuit transports oxygenated blood to virtually all of the tissues of the body and returns relatively deoxygenated blood and carbon dioxide to the heart to be sent back to the pulmonary circulation. \n\n The right ventricle pumps deoxygenated blood into the pulmonary trunk , which leads toward the lungs and bifurcates into the left and right pulmonary arteries . These vessels in turn branch many times before reaching the pulmonary capillaries , where gas exchange occurs: Carbon dioxide exits the blood and oxygen enters. The pulmonary trunk arteries and their branches are the only arteries in the post-natal body that carry relatively deoxygenated blood. Highly oxygenated blood returning from the pulmonary capillaries in the lungs passes through a series of vessels that join together to form the pulmonary veins —the only post-natal veins in the body that carry highly oxygenated blood. The pulmonary veins conduct blood into the left atrium, which pumps the blood into the left ventricle, which in turn pumps oxygenated blood into the aorta and on to the many branches of the systemic circuit. Eventually, these vessels will lead to the systemic capillaries, where exchange with the tissue fluid and cells of the body occurs. In this case, oxygen and nutrients exit the systemic capillaries to be used by the cells in their metabolic processes, and carbon dioxide and waste products will enter the blood. \n\n The blood exiting the systemic capillaries is lower in oxygen concentration than when it entered. The capillaries will ultimately unite to form venules, joining to form ever-larger veins, eventually flowing into the two major systemic veins, the superior vena cava and the inferior vena cava , which return blood to the right atrium. The blood in the superior and inferior venae cavae flows into the right atrium, which pumps blood into the right ventricle. This process of blood circulation continues as long as the individual remains alive. Understanding the flow of blood through the pulmonary and systemic circuits is critical to all health professions ( Figure 19.4 ). \n\n Membranes, Surface Features, and Layers \n\n Our exploration of more in-depth heart structures begins by examining the membrane that surrounds the heart, the prominent surface features of the heart, and the layers that form the wall of the heart. Each of these components plays its own unique role in terms of function. \n\n Membranes \n\n The membrane that directly surrounds the heart and defines the pericardial cavity is called the pericardium or pericardial sac . It also surrounds the “roots” of the major vessels, or the areas of closest proximity to the heart. The pericardium, which literally translates as “around the heart,” consists of two distinct sublayers: the sturdy outer fibrous pericardium and the inner serous pericardium. The fibrous pericardium is made of tough, dense connective tissue that protects the heart and maintains its position in the thorax. The more delicate serous pericardium consists of two layers: the parietal pericardium, which is fused to the fibrous pericardium, and an inner visceral pericardium, or epicardium , which is fused to the heart and is part of the heart wall. The pericardial cavity, filled with lubricating serous fluid, lies between the epicardium and the pericardium. \n\n In most organs within the body, visceral serous membranes such as the epicardium are microscopic. However, in the case of the heart, it is not a microscopic layer but rather a macroscopic layer, consisting of a simple squamous epithelium called a mesothelium , reinforced with loose, irregular, or areolar connective tissue that attaches to the pericardium. This mesothelium secretes the lubricating serous fluid that fills the pericardial cavity and reduces friction as the heart contracts. Figure 19.5 illustrates the pericardial membrane and the layers of the heart. \n\n Disorders of the... Heart: Cardiac Tamponade \n\nIf excess fluid builds within the pericardial space, it can lead to a condition called cardiac tamponade, or pericardial tamponade. With each contraction of the heart, more fluid—in most instances, blood—accumulates within the pericardial cavity. In order to fill with blood for the next contraction, the heart must relax. However, the excess fluid in the pericardial cavity puts pressure on the heart and prevents full relaxation, so the chambers within the heart contain slightly less blood as they begin each heart cycle. Over time, less and less blood is ejected from the heart. If the fluid builds up slowly, as in hypothyroidism, the pericardial cavity may be able to expand gradually to accommodate this extra volume. Some cases of fluid in excess of one liter within the pericardial cavity have been reported. Rapid accumulation of as little as 100 mL of fluid following trauma may trigger cardiac tamponade. Other common causes include myocardial rupture, pericarditis, cancer, or even cardiac surgery. Removal of this excess fluid requires insertion of drainage tubes into the pericardial cavity. Premature removal of these drainage tubes, for example, following cardiac surgery, or clot formation within these tubes are causes of this condition. Untreated, cardiac tamponade can lead to death. \n\n Surface Features of the Heart \n\n Inside the pericardium, the surface features of the heart are visible, including the four chambers. There is a superficial leaf-like extension of the atria near the superior surface of the heart, one on each side, called an auricle —a name that means “ear like”—because its shape resembles the external ear of a human ( Figure 19.6 ). Auricles are relatively thin-walled structures that can fill with blood and empty into the atria or upper chambers of the heart. You may also hear them referred to as atrial appendages. Also prominent is a series of fat-filled grooves, each of which is known as a sulcus (plural = sulci), along the superior surfaces of the heart. Major coronary blood vessels are located in these sulci. The deep coronary sulcus is located between the atria and ventricles. Located between the left and right ventricles are two additional sulci that are not as deep as the coronary sulcus. The anterior interventricular sulcus is visible on the anterior surface of the heart, whereas the posterior interventricular sulcus is visible on the posterior surface of the heart. Figure 19.6 illustrates anterior and posterior views of the surface of the heart. \n\n Layers \n\n The wall of the heart is composed of three layers of unequal thickness. From superficial to deep, these are the epicardium, the myocardium, and the endocardium (see Figure 19.5 ). The outermost layer of the wall of the heart is also the innermost layer of the pericardium, the epicardium, or the visceral pericardium discussed earlier. \n\n The middle and thickest layer is the myocardium , made largely of cardiac muscle cells. It is built upon a framework of collagenous fibers, plus the blood vessels that supply the myocardium and the nerve fibers that help regulate the heart. It is the contraction of the myocardium that pumps blood through the heart and into the major arteries. The muscle pattern is elegant and complex, as the muscle cells swirl and spiral around the chambers of the heart. They form a figure 8 pattern around the atria and around the bases of the great vessels. Deeper ventricular muscles also form a figure 8 around the two ventricles and proceed toward the apex. More superficial layers of ventricular muscle wrap around both ventricles. This complex swirling pattern allows the heart to pump blood more effectively than a simple linear pattern would. Figure 19.7 illustrates the arrangement of muscle cells. \n\n Although the ventricles on the right and left sides pump the same amount of blood per contraction, the muscle of the left ventricle is much thicker and better developed than that of the right ventricle. In order to overcome the high resistance required to pump blood into the long systemic circuit, the left ventricle must generate a great amount of pressure. The right ventricle does not need to generate as much pressure, since the pulmonary circuit is shorter and provides less resistance. Figure 19.8 illustrates the differences in muscular thickness needed for each of the ventricles. \n\n The innermost layer of the heart wall, the endocardium , is joined to the myocardium with a thin layer of connective tissue. The endocardium lines the chambers where the blood circulates and covers the heart valves. It is made of simple squamous epithelium called endothelium , which is continuous with the endothelial lining of the blood vessels (see Figure 19.5 ). \n\n Once regarded as a simple lining layer, recent evidence indicates that the endothelium of the endocardium and the coronary capillaries may play active roles in regulating the contraction of the muscle within the myocardium. The endothelium may also regulate the growth patterns of the cardiac muscle cells throughout life, and the endothelins it secretes create an environment in the surrounding tissue fluids that regulates ionic concentrations and states of contractility. Endothelins are potent vasoconstrictors and, in a normal individual, establish a homeostatic balance with other vasoconstrictors and vasodilators. \n\n Internal Structure of the Heart \n\n Recall that the heart’s contraction cycle follows a dual pattern of circulation—the pulmonary and systemic circuits—because of the pairs of chambers that pump blood into the circulation. In order to develop a more precise understanding of cardiac function, it is first necessary to explore the internal anatomical structures in more detail. \n\n Septa of the Heart \n\n The word septum is derived from the Latin for “something that encloses;” in this case, a septum (plural = septa) refers to a wall or partition that divides the heart into chambers. The septa are physical extensions of the myocardium lined with endocardium. Located between the two atria is the interatrial septum . Normally in an adult heart, the interatrial septum bears an oval-shaped depression known as the fossa ovalis , a remnant of an opening in the fetal heart known as the foramen ovale . The foramen ovale allowed blood in the fetal heart to pass directly from the right atrium to the left atrium, allowing some blood to bypass the pulmonary circuit. Within seconds after birth, a flap of tissue known as the septum primum that previously acted as a valve closes the foramen ovale and establishes the typical cardiac circulation pattern. \n\n Between the two ventricles is a second septum known as the interventricular septum . Unlike the interatrial septum, the interventricular septum is normally intact after its formation during fetal development. It is substantially thicker than the interatrial septum, since the ventricles generate far greater pressure when they contract. \n\n The septum between the atria and ventricles is known as the atrioventricular septum . It is marked by the presence of four openings that allow blood to move from the atria into the ventricles and from the ventricles into the pulmonary trunk and aorta. Located in each of these openings between the atria and ventricles is a valve , a specialized structure that ensures one-way flow of blood. The valves between the atria and ventricles are known generically as atrioventricular valves . The valves at the openings that lead to the pulmonary trunk and aorta are known generically as semilunar valves . The interventricular septum is visible in Figure 19.9 . In this figure, the atrioventricular septum has been removed to better show the bicuspid and tricuspid valves; the interatrial septum is not visible, since its location is covered by the aorta and pulmonary trunk. Since these openings and valves structurally weaken the atrioventricular septum, the remaining tissue is heavily reinforced with dense connective tissue called the cardiac skeleton , or skeleton of the heart. It includes four rings that surround the openings between the atria and ventricles, and the openings to the pulmonary trunk and aorta, and serve as the point of attachment for the heart valves. The cardiac skeleton also provides an important boundary in the heart electrical conduction system. \n\n Disorders of the... Heart: Heart Defects \n\nOne very common form of interatrial septum pathology is patent foramen ovale, which occurs when the septum primum does not close at birth, and the fossa ovalis is unable to fuse. The word patent is from the Latin root patens for “open.” It may be benign or asymptomatic, perhaps never being diagnosed, or in extreme cases, it may require surgical repair to close the opening permanently. As much as 20–25 percent of the general population may have a patent foramen ovale, but fortunately, most have the benign, asymptomatic version. Patent foramen ovale is normally detected by auscultation of a heart murmur (an abnormal heart sound) and confirmed by imaging with an echocardiogram. Despite its prevalence in the general population, the causes of patent ovale are unknown, and there are no known risk factors. In nonlife-threatening cases, it is better to monitor the condition than to risk heart surgery to repair and seal the opening. \n\n Coarctation of the aorta is a congenital abnormal narrowing of the aorta that is normally located at the insertion of the ligamentum arteriosum, the remnant of the fetal shunt called the ductus arteriosus. If severe, this condition drastically restricts blood flow through the primary systemic artery, which is life threatening. In some individuals, the condition may be fairly benign and not detected until later in life. Detectable symptoms in an infant include difficulty breathing, poor appetite, trouble feeding, or failure to thrive. In older individuals, symptoms include dizziness, fainting, shortness of breath, chest pain, fatigue, headache, and nosebleeds. Treatment involves surgery to resect (remove) the affected region or angioplasty to open the abnormally narrow passageway. Studies have shown that the earlier the surgery is performed, the better the chance of survival. \n\n A patent ductus arteriosus is a congenital condition in which the ductus arteriosus fails to close. The condition may range from severe to benign. Failure of the ductus arteriosus to close results in blood flowing from the higher pressure aorta into the lower pressure pulmonary trunk. This additional fluid moving toward the lungs increases pulmonary pressure and makes respiration difficult. Symptoms include shortness of breath (dyspnea), tachycardia, enlarged heart, a widened pulse pressure, and poor weight gain in infants. Treatments include surgical closure (ligation), manual closure using platinum coils or specialized mesh inserted via the femoral artery or vein, or nonsteroidal anti-inflammatory drugs to block the synthesis of prostaglandin E2, which maintains the vessel in an open position. If untreated, the condition can result in congestive heart failure. \n\n Septal defects are not uncommon in individuals and may be congenital or caused by various disease processes. Tetralogy of Fallot is a congenital condition that may also occur from exposure to unknown environmental factors; it occurs when there is an opening in the interventricular septum caused by blockage of the pulmonary trunk, normally at the pulmonary semilunar valve. This allows blood that is relatively low in oxygen from the right ventricle to flow into the left ventricle and mix with the blood that is relatively high in oxygen. Symptoms include a distinct heart murmur, low blood oxygen percent saturation, dyspnea or difficulty in breathing, polycythemia, broadening (clubbing) of the fingers and toes, and in children, difficulty in feeding or failure to grow and develop. It is the most common cause of cyanosis following birth. The term “tetralogy” is derived from the four components of the condition, although only three may be present in an individual patient: pulmonary infundibular stenosis (rigidity of the pulmonary valve), overriding aorta (the aorta is shifted above both ventricles), ventricular septal defect (opening), and right ventricular hypertrophy (enlargement of the right ventricle). Other heart defects may also accompany this condition, which is typically confirmed by echocardiography imaging. Tetralogy of Fallot occurs in approximately 400 out of one million live births. Normal treatment involves extensive surgical repair, including the use of stents to redirect blood flow and replacement of valves and patches to repair the septal defect, but the condition has a relatively high mortality. Survival rates are currently 75 percent during the first year of life; 60 percent by 4 years of age; 30 percent by 10 years; and 5 percent by 40 years. \n\n In the case of severe septal defects, including both tetralogy of Fallot and patent foramen ovale, failure of the heart to develop properly can lead to a condition commonly known as a “blue baby.” Regardless of normal skin pigmentation, individuals with this condition have an insufficient supply of oxygenated blood, which leads to cyanosis, a blue or purple coloration of the skin, especially when active. \n\n Septal defects are commonly first detected through auscultation, listening to the chest using a stethoscope. In this case, instead of hearing normal heart sounds attributed to the flow of blood and closing of heart valves, unusual heart sounds may be detected. This is often followed by medical imaging to confirm or rule out a diagnosis. In many cases, treatment may not be needed. Some common congenital heart defects are illustrated in Figure 19.10 . \n\n Right Atrium \n\n The right atrium serves as the receiving chamber for blood returning to the heart from the systemic circulation. The two major systemic veins, the superior and inferior venae cavae, and the large coronary vein called the coronary sinus that drains the heart myocardium empty into the right atrium. The superior vena cava drains blood from regions superior to the diaphragm: the head, neck, upper limbs, and the thoracic region. It empties into the superior and posterior portions of the right atrium. The inferior vena cava drains blood from areas inferior to the diaphragm: the lower limbs and abdominopelvic region of the body. It, too, empties into the posterior portion of the atria, but inferior to the opening of the superior vena cava. Immediately superior and slightly medial to the opening of the inferior vena cava on the posterior surface of the atrium is the opening of the coronary sinus. This thin-walled vessel drains most of the coronary veins that return systemic blood from the heart. The majority of the internal heart structures discussed in this and subsequent sections are illustrated in Figure 19.9 . \n\n While the bulk of the internal surface of the right atrium is smooth, the depression of the fossa ovalis is medial, and the anterior surface demonstrates prominent ridges of muscle called the pectinate muscles . The right auricle also has pectinate muscles. The left atrium does not have pectinate muscles except in the auricle. \n\n The atria receive venous blood on a nearly continuous basis, preventing venous flow from stopping while the ventricles are contracting. While most ventricular filling occurs while the atria are relaxed, they do demonstrate a contractile phase and actively pump blood into the ventricles just prior to ventricular contraction. The opening between the atrium and ventricle is guarded by the tricuspid valve. \n\n Right Ventricle \n\n The right ventricle receives blood from the right atrium through the tricuspid valve. Each flap of the valve is attached to strong strands of connective tissue, the chordae tendineae , literally “tendinous cords,” or sometimes more poetically referred to as “heart strings.” There are several chordae tendineae associated with each of the flaps. They are composed of approximately 80 percent collagenous fibers with the remainder consisting of elastic fibers and endothelium. They connect each of the flaps to a papillary muscle that extends from the inferior ventricular surface. There are three papillary muscles in the right ventricle, called the anterior, posterior, and septal muscles, which correspond to the three sections of the valves. \n\n When the myocardium of the ventricle contracts, pressure within the ventricular chamber rises. Blood, like any fluid, flows from higher pressure to lower pressure areas, in this case, toward the pulmonary trunk and the atrium. To prevent any potential backflow, the papillary muscles also contract, generating tension on the chordae tendineae. This prevents the flaps of the valves from being forced into the atria and regurgitation of the blood back into the atria during ventricular contraction. Figure 19.11 shows papillary muscles and chordae tendineae attached to the tricuspid valve. \n\n The walls of the ventricle are lined with trabeculae carneae , ridges of cardiac muscle covered by endocardium. In addition to these muscular ridges, a band of cardiac muscle, also covered by endocardium, known as the moderator band (see Figure 19.9 ) reinforces the thin walls of the right ventricle and plays a crucial role in cardiac conduction. It arises from the inferior portion of the interventricular septum and crosses the interior space of the right ventricle to connect with the inferior papillary muscle. \n\n When the right ventricle contracts, it ejects blood into the pulmonary trunk, which branches into the left and right pulmonary arteries that carry it to each lung. The superior surface of the right ventricle begins to taper as it approaches the pulmonary trunk. At the base of the pulmonary trunk is the pulmonary semilunar valve that prevents backflow from the pulmonary trunk. \n\n Left Atrium \n\n After exchange of gases in the pulmonary capillaries, blood returns to the left atrium high in oxygen via one of the four pulmonary veins. While the left atrium does not contain pectinate muscles, it does have an auricle that includes these pectinate ridges. Blood flows nearly continuously from the pulmonary veins back into the atrium, which acts as the receiving chamber, and from here through an opening into the left ventricle. Most blood flows passively into the heart while both the atria and ventricles are relaxed, but toward the end of the ventricular relaxation period, the left atrium will contract, pumping blood into the ventricle. This atrial contraction accounts for approximately 20 percent of ventricular filling. The opening between the left atrium and ventricle is guarded by the mitral valve. \n\n Left Ventricle \n\n Recall that, although both sides of the heart will pump the same amount of blood, the muscular layer is much thicker in the left ventricle compared to the right (see Figure 19.8 ). Like the right ventricle, the left also has trabeculae carneae, but there is no moderator band. The mitral valve is connected to papillary muscles via chordae tendineae. There are two papillary muscles on the left—the anterior and posterior—as opposed to three on the right. \n\n The left ventricle is the major pumping chamber for the systemic circuit; it ejects blood into the aorta through the aortic semilunar valve. \n\n Heart Valve Structure and Function \n\n A transverse section through the heart slightly above the level of the atrioventricular septum reveals all four heart valves along the same plane ( Figure 19.12 ). The valves ensure unidirectional blood flow through the heart. Between the right atrium and the right ventricle is the right atrioventricular valve , or tricuspid valve . It typically consists of three flaps, or leaflets, made of endocardium reinforced with additional connective tissue. The flaps are connected by chordae tendineae to the papillary muscles, which control the opening and closing of the valves. Emerging from the right ventricle at the base of the pulmonary trunk is the pulmonary semilunar valve, or the pulmonary valve ; it is also known as the pulmonic valve or the right semilunar valve. The pulmonary valve is comprised of three small flaps of endothelium reinforced with connective tissue. When the ventricle relaxes, the pressure differential causes blood to flow back into the ventricle from the pulmonary trunk. This flow of blood fills the pocket-like flaps of the pulmonary valve, causing the valve to close and producing an audible sound. Unlike the atrioventricular valves, there are no papillary muscles or chordae tendineae associated with the pulmonary valve. \n\n Located at the opening between the left atrium and left ventricle is the mitral valve , also called the bicuspid valve or the left atrioventricular valve . Structurally, this valve consists of two cusps, compared to the three cusps of the tricuspid valve. In a clinical setting, the valve is referred to as the mitral valve, rather than the bicuspid valve. The two cusps of the mitral valve are attached by chordae tendineae to two papillary muscles that project from the wall of the ventricle. \n\n At the base of the aorta is the aortic semilunar valve, or the aortic valve , which prevents backflow from the aorta. It normally is composed of three flaps. When the ventricle relaxes and blood attempts to flow back into the ventricle from the aorta, blood will fill the cusps of the valve, causing it to close and producing an audible sound. \n\n In Figure 19.13 a , the two atrioventricular valves are open and the two semilunar valves are closed. This occurs when both atria and ventricles are relaxed and when the atria contract to pump blood into the ventricles. Figure 19.13 b shows a frontal view. Although only the left side of the heart is illustrated, the process is virtually identical on the right. \n\n Figure 19.14 a shows the atrioventricular valves closed while the two semilunar valves are open. This occurs when the ventricles contract to eject blood into the pulmonary trunk and aorta. Closure of the two atrioventricular valves prevents blood from being forced back into the atria. This stage can be seen from a frontal view in Figure 19.14 b . \n\n When the ventricles begin to contract, pressure within the ventricles rises and blood flows toward the area of lowest pressure, which is initially in the atria. This backflow causes the cusps of the tricuspid and mitral (bicuspid) valves to close. These valves are tied down to the papillary muscles by chordae tendineae. During the relaxation phase of the cardiac cycle, the papillary muscles are also relaxed and the tension on the chordae tendineae is slight (see Figure 19.13 b ). However, as the myocardium of the ventricle contracts, so do the papillary muscles. This creates tension on the chordae tendineae (see Figure 19.14 b ), helping to hold the cusps of the atrioventricular valves in place and preventing them from being blown back into the atria. \n\n The aortic and pulmonary semilunar valves lack the chordae tendineae and papillary muscles associated with the atrioventricular valves. Instead, they consist of pocket-like folds of endocardium reinforced with additional connective tissue. When the ventricles relax and the change in pressure forces the blood toward the ventricles, the blood presses against these cusps and seals the openings. \n\n Interactive Link \n\n Visit this site to observe an echocardiogram of actual heart valves opening and closing. Although much of the heart has been “removed” from this gif loop so the chordae tendineae are not visible, why is their presence more critical for the atrioventricular valves (tricuspid and mitral) than the semilunar (aortic and pulmonary) valves? \n\n Disorders of the... Heart Valves \n\nWhen heart valves do not function properly, they are often described as incompetent and result in valvular heart disease, which can range from benign to lethal. Some of these conditions are congenital, that is, the individual was born with the defect, whereas others may be attributed to disease processes or trauma. Some malfunctions are treated with medications, others require surgery, and still others may be mild enough that the condition is merely monitored since treatment might trigger more serious consequences. \n\n Valvular disorders are often caused by carditis, or inflammation of the heart. One common trigger for this inflammation is rheumatic fever, or scarlet fever, an autoimmune response to the presence of a bacterium, Streptococcus pyogenes , normally a disease of childhood. \n\n While any of the heart valves may be involved in valve disorders, mitral regurgitation is the most common, detected in approximately 2 percent of the population, and the pulmonary semilunar valve is the least frequently involved. When a valve malfunctions, the flow of blood to a region will often be disrupted. The resulting inadequate flow of blood to this region will be described in general terms as an insufficiency. The specific type of insufficiency is named for the valve involved: aortic insufficiency, mitral insufficiency, tricuspid insufficiency, or pulmonary insufficiency. \n\n If one of the cusps of the valve is forced backward by the force of the blood, the condition is referred to as a prolapsed valve. Prolapse may occur if the chordae tendineae are damaged or broken, causing the closure mechanism to fail. The failure of the valve to close properly disrupts the normal one-way flow of blood and results in regurgitation, when the blood flows backward from its normal path. Using a stethoscope, the disruption to the normal flow of blood produces a heart murmur. \n\n Stenosis is a condition in which the heart valves become rigid and may calcify over time. The loss of flexibility of the valve interferes with normal function and may cause the heart to work harder to propel blood through the valve, which eventually weakens the heart. Aortic stenosis affects approximately 2 percent of the population over 65 years of age, and the percentage increases to approximately 4 percent in individuals over 85 years. Occasionally, one or more of the chordae tendineae will tear or the papillary muscle itself may die as a component of a myocardial infarction (heart attack). In this case, the patient’s condition will deteriorate dramatically and rapidly, and immediate surgical intervention may be required. \n\n Auscultation, or listening to a patient’s heart sounds, is one of the most useful diagnostic tools, since it is proven, safe, and inexpensive. The term auscultation is derived from the Latin for “to listen,” and the technique has been used for diagnostic purposes as far back as the ancient Egyptians. Valve and septal disorders will trigger abnormal heart sounds. If a valvular disorder is detected or suspected, a test called an echocardiogram, or simply an “echo,” may be ordered. Echocardiograms are sonograms of the heart and can help in the diagnosis of valve disorders as well as a wide variety of heart pathologies. \n\n Interactive Link \n\n Visit this site for a free download, including excellent animations and audio of heart sounds. \n\n Career Connection Cardiologist \n\nCardiologists are medical doctors that specialize in the diagnosis and treatment of diseases of the heart. After completing 4 years of medical school, cardiologists complete a three-year residency in internal medicine followed by an additional three or more years in cardiology. Following this 10-year period of medical training and clinical experience, they qualify for a rigorous two-day examination administered by the Board of Internal Medicine that tests their academic training and clinical abilities, including diagnostics and treatment. After successful completion of this examination, a physician becomes a board-certified cardiologist. Some board-certified cardiologists may be invited to become a Fellow of the American College of Cardiology (FACC). This professional recognition is awarded to outstanding physicians based upon merit, including outstanding credentials, achievements, and community contributions to cardiovascular medicine. \n\n Interactive Link \n\n Visit this site to learn more about cardiologists. \n\n Career Connection Cardiovascular Technologist/Technician \n\nCardiovascular technologists/technicians are trained professionals who perform a variety of imaging techniques, such as sonograms or echocardiograms, used by physicians to diagnose and treat diseases of the heart. Nearly all of these positions require an associate degree, and these technicians earn a median salary of $49,410 as of May 2010, according to the U.S. Bureau of Labor Statistics. Growth within the field is fast, projected at 29 percent from 2010 to 2020. \n\n There is a considerable overlap and complementary skills between cardiac technicians and vascular technicians, and so the term cardiovascular technician is often used. Special certifications within the field require documenting appropriate experience and completing additional and often expensive certification examinations. These subspecialties include Certified Rhythm Analysis Technician (CRAT), Certified Cardiographic Technician (CCT), Registered Congenital Cardiac Sonographer (RCCS), Registered Cardiac Electrophysiology Specialist (RCES), Registered Cardiovascular Invasive Specialist (RCIS), Registered Cardiac Sonographer (RCS), Registered Vascular Specialist (RVS), and Registered Phlebology Sonographer (RPhS). \n\n Interactive Link \n\n Visit this site for more information on cardiovascular technologists/technicians. \n\n Coronary Circulation \n\n You will recall that the heart is a remarkable pump composed largely of cardiac muscle cells that are incredibly active throughout life. Like all other cells, a cardiomyocyte requires a reliable supply of oxygen and nutrients, and a way to remove wastes, so it needs a dedicated, complex, and extensive coronary circulation. And because of the critical and nearly ceaseless activity of the heart throughout life, this need for a blood supply is even greater than for a typical cell. However, coronary circulation is not continuous; rather, it cycles, reaching a peak when the heart muscle is relaxed and nearly ceasing while it is contracting. \n\n Coronary Arteries \n\n Coronary arteries supply blood to the myocardium and other components of the heart. The first portion of the aorta after it arises from the left ventricle gives rise to the coronary arteries. There are three dilations in the wall of the aorta just superior to the aortic semilunar valve. Two of these, the left posterior aortic sinus and anterior aortic sinus, give rise to the left and right coronary arteries, respectively. The third sinus, the right posterior aortic sinus, typically does not give rise to a vessel. Coronary vessel branches that remain on the surface of the artery and follow the sulci are called epicardial coronary arteries . \n\n The left coronary artery distributes blood to the left side of the heart, the left atrium and ventricle, and the interventricular septum. The circumflex artery arises from the left coronary artery and follows the coronary sulcus to the left. Eventually, it will fuse with the small branches of the right coronary artery. The larger anterior interventricular artery , also known as the left anterior descending artery (LAD), is the second major branch arising from the left coronary artery. It follows the anterior interventricular sulcus around the pulmonary trunk. Along the way it gives rise to numerous smaller branches that interconnect with the branches of the posterior interventricular artery, forming anastomoses. An anastomosis is an area where vessels unite to form interconnections that normally allow blood to circulate to a region even if there may be partial blockage in another branch. The anastomoses in the heart are very small. Therefore, this ability is somewhat restricted in the heart so a coronary artery blockage often results in death of the cells (myocardial infarction) supplied by the particular vessel. \n\n The right coronary artery proceeds along the coronary sulcus and distributes blood to the right atrium, portions of both ventricles, and the heart conduction system. Normally, one or more marginal arteries arise from the right coronary artery inferior to the right atrium. The marginal arteries supply blood to the superficial portions of the right ventricle. On the posterior surface of the heart, the right coronary artery gives rise to the posterior interventricular artery , also known as the posterior descending artery. It runs along the posterior portion of the interventricular sulcus toward the apex of the heart, giving rise to branches that supply the interventricular septum and portions of both ventricles. Figure 19.15 presents views of the coronary circulation from both the anterior and posterior views. \n\n Diseases of the... Heart: Myocardial Infarction \n\nMyocardial infarction (MI) is the formal term for what is commonly referred to as a heart attack. It normally results from a lack of blood flow (ischemia) and oxygen (hypoxia) to a region of the heart, resulting in death of the cardiac muscle cells. An MI often occurs when a coronary artery is blocked by the buildup of atherosclerotic plaque consisting of lipids, cholesterol and fatty acids, and white blood cells, primarily macrophages. It can also occur when a portion of an unstable atherosclerotic plaque travels through the coronary arterial system and lodges in one of the smaller vessels. The resulting blockage restricts the flow of blood and oxygen to the myocardium and causes death of the tissue. MIs may be triggered by excessive exercise, in which the partially occluded artery is no longer able to pump sufficient quantities of blood, or severe stress, which may induce spasm of the smooth muscle in the walls of the vessel. \n\n In the case of acute MI, there is often sudden pain beneath the sternum (retrosternal pain) called angina pectoris, often radiating down the left arm in males but not in female patients. Until this anomaly between the sexes was discovered, many female patients suffering MIs were misdiagnosed and sent home. In addition, patients typically present with difficulty breathing and shortness of breath (dyspnea), irregular heartbeat (palpations), nausea and vomiting, sweating (diaphoresis), anxiety, and fainting (syncope), although not all of these symptoms may be present. Many of the symptoms are shared with other medical conditions, including anxiety attacks and simple indigestion, so differential diagnosis is critical. It is estimated that between 22 and 64 percent of MIs present without any symptoms. \n\n An MI can be confirmed by examining the patient’s ECG, which frequently reveals alterations in the ST and Q components. Some classification schemes of MI are referred to as ST-elevated MI (STEMI) and non-elevated MI (non-STEMI). In addition, echocardiography or cardiac magnetic resonance imaging may be employed. Common blood tests indicating an MI include elevated levels of creatine kinase MB (an enzyme that catalyzes the conversion of creatine to phosphocreatine, consuming ATP) and cardiac troponin (the regulatory protein for muscle contraction), both of which are released by damaged cardiac muscle cells. \n\n Immediate treatments for MI are essential and include administering supplemental oxygen, aspirin that helps to break up clots, and nitroglycerine administered sublingually (under the tongue) to facilitate its absorption. Despite its unquestioned success in treatments and use since the 1880s, the mechanism of nitroglycerine is still incompletely understood but is believed to involve the release of nitric oxide, a known vasodilator, and endothelium-derived releasing factor, which also relaxes the smooth muscle in the tunica media of coronary vessels. Longer-term treatments include injections of thrombolytic agents such as streptokinase that dissolve the clot, the anticoagulant heparin, balloon angioplasty and stents to open blocked vessels, and bypass surgery to allow blood to pass around the site of blockage. If the damage is extensive, coronary replacement with a donor heart or coronary assist device, a sophisticated mechanical device that supplements the pumping activity of the heart, may be employed. Despite the attention, development of artificial hearts to augment the severely limited supply of heart donors has proven less than satisfactory but will likely improve in the future. \n\n MIs may trigger cardiac arrest, but the two are not synonymous. Important risk factors for MI include cardiovascular disease, age, smoking, high blood levels of the low-density lipoprotein (LDL, often referred to as “bad” cholesterol), low levels of high-density lipoprotein (HDL, or “good” cholesterol), hypertension, diabetes mellitus, obesity, lack of physical exercise, chronic kidney disease, excessive alcohol consumption, and use of illegal drugs. \n\n Coronary Veins \n\n Coronary veins drain the heart and generally parallel the large surface arteries (see Figure 19.15 ). The great cardiac vein can be seen initially on the surface of the heart following the interventricular sulcus, but it eventually flows along the coronary sulcus into the coronary sinus on the posterior surface. The great cardiac vein initially parallels the anterior interventricular artery and drains the areas supplied by this vessel. It receives several major branches, including the posterior cardiac vein, the middle cardiac vein, and the small cardiac vein. The posterior cardiac vein parallels and drains the areas supplied by the marginal artery branch of the circumflex artery. The middle cardiac vein parallels and drains the areas supplied by the posterior interventricular artery. The small cardiac vein parallels the right coronary artery and drains the blood from the posterior surfaces of the right atrium and ventricle. The coronary sinus is a large, thin-walled vein on the posterior surface of the heart lying within the atrioventricular sulcus and emptying directly into the right atrium. The anterior cardiac veins parallel the small cardiac arteries and drain the anterior surface of the right ventricle. Unlike these other cardiac veins, it bypasses the coronary sinus and drains directly into the right atrium. \n\n Disorders of the... Heart: Coronary Artery Disease \n\n Coronary artery disease is the leading cause of death worldwide. It occurs when the buildup of plaque—a fatty material including cholesterol, connective tissue, white blood cells, and some smooth muscle cells—within the walls of the arteries obstructs the flow of blood and decreases the flexibility or compliance of the vessels. This condition is called atherosclerosis, a hardening of the arteries that involves the accumulation of plaque. As the coronary blood vessels become occluded, the flow of blood to the tissues will be restricted, a condition called ischemia that causes the cells to receive insufficient amounts of oxygen, called hypoxia. Figure 19.16 shows the blockage of coronary arteries highlighted by the injection of dye. Some individuals with coronary artery disease report pain radiating from the chest called angina pectoris, but others remain asymptomatic. If untreated, coronary artery disease can lead to MI or a heart attack. \n\n The disease progresses slowly and often begins in children and can be seen as fatty “streaks” in the vessels. It then gradually progresses throughout life. Well-documented risk factors include smoking, family history, hypertension, obesity, diabetes, high alcohol consumption, lack of exercise, stress, and hyperlipidemia or high circulating levels of lipids in the blood. Treatments may include medication, changes to diet and exercise, angioplasty with a balloon catheter, insertion of a stent, or coronary bypass procedure. \n\n Angioplasty is a procedure in which the occlusion is mechanically widened with a balloon. A specialized catheter with an expandable tip is inserted into a superficial vessel, normally in the leg, and then directed to the site of the occlusion. At this point, the balloon is inflated to compress the plaque material and to open the vessel to increase blood flow. Then, the balloon is deflated and retracted. A stent consisting of a specialized mesh is typically inserted at the site of occlusion to reinforce the weakened and damaged walls. Stent insertions have been routine in cardiology for more than 40 years. \n\n Coronary bypass surgery may also be performed. This surgical procedure grafts a replacement vessel obtained from another, less vital portion of the body to bypass the occluded area. This procedure is clearly effective in treating patients experiencing a MI, but overall does not increase longevity. Nor does it seem advisable in patients with stable although diminished cardiac capacity since frequently loss of mental acuity occurs following the procedure. Long-term changes to behavior, emphasizing diet and exercise plus a medicine regime tailored to lower blood pressure, lower cholesterol and lipids, and reduce clotting are equally as effective. \n 19.2 Cardiac Muscle and Electrical Activity Learning Objectives By the end of this section, you will be able to: \n\n Describe the structure of cardiac muscle \n\n Identify and describe the components of the conducting system that distributes electrical impulses through the heart \n\n Compare the effect of ion movement on membrane potential of cardiac conductive and contractile cells \n\n Relate characteristics of an electrocardiogram to events in the cardiac cycle \n\n Identify blocks that can interrupt the cardiac cycle \n\n Recall that cardiac muscle shares a few characteristics with both skeletal muscle and smooth muscle, but it has some unique properties of its own. Not the least of these exceptional properties is its ability to initiate an electrical potential at a fixed rate that spreads rapidly from cell to cell to trigger the contractile mechanism. This property is known as autorhythmicity . Neither smooth nor skeletal muscle can do this. Even though cardiac muscle has autorhythmicity, heart rate is modulated by the endocrine and nervous systems. \n\n There are two major types of cardiac muscle cells: myocardial contractile cells and myocardial conducting cells. The myocardial contractile cells constitute the bulk (99 percent) of the cells in the atria and ventricles. Contractile cells conduct impulses and are responsible for contractions that pump blood through the body. The myocardial conducting cells (1 percent of the cells) form the conduction system of the heart. Except for Purkinje cells, they are generally much smaller than the contractile cells and have few of the myofibrils or filaments needed for contraction. Their function is similar in many respects to neurons, although they are specialized muscle cells. Myocardial conduction cells initiate and propagate the action potential (the electrical impulse) that travels throughout the heart and triggers the contractions that propel the blood. \n\n Structure of Cardiac Muscle Compared to the giant cylinders of skeletal muscle, cardiac muscle cells, or cardiomyocytes, are considerably shorter with much smaller diameters. Cardiac muscle also demonstrates striations, the alternating pattern of dark A bands and light I bands attributed to the precise arrangement of the myofilaments and fibrils that are organized in sarcomeres along the length of the cell ( Figure 19.17 a ). These contractile elements are virtually identical to skeletal muscle. T (transverse) tubules penetrate from the surface plasma membrane, the sarcolemma, to the interior of the cell, allowing the electrical impulse to reach the interior. The T tubules are only found at the Z discs, whereas in skeletal muscle, they are found at the junction of the A and I bands. Therefore, there are one-half as many T tubules in cardiac muscle as in skeletal muscle. In addition, the sarcoplasmic reticulum stores few calcium ions, so most of the calcium ions must come from outside the cells. The result is a slower onset of contraction. Mitochondria are plentiful, providing energy for the contractions of the heart. Typically, cardiomyocytes have a single, central nucleus, but two or more nuclei may be found in some cells. \n\n Cardiac muscle cells branch freely. A junction between two adjoining cells is marked by a critical structure called an intercalated disc , which helps support the synchronized contraction of the muscle ( Figure 19.17 b ). The sarcolemmas from adjacent cells bind together at the intercalated discs. They consist of desmosomes, specialized linking proteoglycans, tight junctions, and large numbers of gap junctions that allow the passage of ions between the cells and help to synchronize the contraction ( Figure 19.17 c ). Intercellular connective tissue also helps to bind the cells together. The importance of strongly binding these cells together is necessitated by the forces exerted by contraction. \n\n Cardiac muscle undergoes aerobic respiration patterns, primarily metabolizing lipids and carbohydrates. Myoglobin, lipids, and glycogen are all stored within the cytoplasm. Cardiac muscle cells undergo twitch-type contractions with long refractory periods followed by brief relaxation periods. The relaxation is essential so the heart can fill with blood for the next cycle. The refractory period is very long to prevent the possibility of tetany, a condition in which muscle remains involuntarily contracted. In the heart, tetany is not compatible with life, since it would prevent the heart from pumping blood. \n\n Everyday Connection Repair and Replacement \n\nDamaged cardiac muscle cells have extremely limited abilities to repair themselves or to replace dead cells via mitosis. Recent evidence indicates that at least some stem cells remain within the heart that continue to divide and at least potentially replace these dead cells. However, newly formed or repaired cells are rarely as functional as the original cells, and cardiac function is reduced. In the event of a heart attack or MI, dead cells are often replaced by patches of scar tissue. Autopsies performed on individuals who had successfully received heart transplants show some proliferation of original cells. If researchers can unlock the mechanism that generates new cells and restore full mitotic capabilities to heart muscle, the prognosis for heart attack survivors will be greatly enhanced. To date, myocardial cells produced within the patient ( in situ ) by cardiac stem cells seem to be nonfunctional, although those grown in Petri dishes ( in vitro ) do beat. Perhaps soon this mystery will be solved, and new advances in treatment will be commonplace. \n\n Conduction System of the Heart \n\n If embryonic heart cells are separated into a Petri dish and kept alive, each is capable of generating its own electrical impulse followed by contraction. When two independently beating embryonic cardiac muscle cells are placed together, the cell with the higher inherent rate sets the pace, and the impulse spreads from the faster to the slower cell to trigger a contraction. As more cells are joined together, the fastest cell continues to assume control of the rate. A fully developed adult heart maintains the capability of generating its own electrical impulse, triggered by the fastest cells, as part of the cardiac conduction system. The components of the cardiac conduction system include the sinoatrial node, the atrioventricular node, the atrioventricular bundle, the atrioventricular bundle branches, and the Purkinje cells ( Figure 19.18 ). \n\n Sinoatrial (SA) Node \n\n Normal cardiac rhythm is established by the sinoatrial (SA) node , a specialized clump of myocardial conducting cells located in the superior and posterior walls of the right atrium in close proximity to the orifice of the superior vena cava. The SA node has the highest inherent rate of depolarization and is known as the pacemaker of the heart. It initiates the sinus rhythm , or normal electrical pattern followed by contraction of the heart. \n\n This impulse spreads from its initiation in the SA node throughout the atria through specialized internodal pathways , to the atrial myocardial contractile cells and the atrioventricular node. The internodal pathways consist of three bands (anterior, middle, and posterior) that lead directly from the SA node to the next node in the conduction system, the atrioventricular node (see Figure 19.18 ). The impulse takes approximately 50 ms (milliseconds) to travel between these two nodes. The relative importance of this pathway has been debated since the impulse would reach the atrioventricular node simply following the cell-by-cell pathway through the contractile cells of the myocardium in the atria. In addition, there is a specialized pathway called Bachmann’s bundle or the interatrial band that conducts the impulse directly from the right atrium to the left atrium. Regardless of the pathway, as the impulse reaches the atrioventricular septum, the connective tissue of the cardiac skeleton prevents the impulse from spreading into the myocardial cells in the ventricles except at the atrioventricular node. Figure 19.19 illustrates the initiation of the impulse in the SA node that then spreads the impulse throughout the atria to the atrioventricular node. \n\n The electrical event, the wave of depolarization, is the trigger for muscular contraction. The wave of depolarization begins in the right atrium, and the impulse spreads across the superior portions of both atria and then down through the contractile cells. The contractile cells then begin contraction from the superior to the inferior portions of the atria, efficiently pumping blood into the ventricles. \n\n Atrioventricular (AV) Node \n\n The atrioventricular (AV) node is a second clump of specialized myocardial conductive cells, located in the inferior portion of the right atrium within the atrioventricular septum. The septum prevents the impulse from spreading directly to the ventricles without passing through the AV node. There is a critical pause before the AV node depolarizes and transmits the impulse to the atrioventricular bundle (see Figure 19.19 , step 3). This delay in transmission is partially attributable to the small diameter of the cells of the node, which slow the impulse. Also, conduction between nodal cells is less efficient than between conducting cells. These factors mean that it takes the impulse approximately 100 ms to pass through the node. This pause is critical to heart function, as it allows the atrial cardiomyocytes to complete their contraction that pumps blood into the ventricles before the impulse is transmitted to the cells of the ventricle itself. With extreme stimulation by the SA node, the AV node can transmit impulses maximally at 220 per minute. This establishes the typical maximum heart rate in a healthy young individual. Damaged hearts or those stimulated by drugs can contract at higher rates, but at these rates, the heart can no longer effectively pump blood. \n\n Atrioventricular Bundle (Bundle of His), Bundle Branches, and Purkinje Fibers \n\n Arising from the AV node, the atrioventricular bundle , or bundle of His , proceeds through the interventricular septum before dividing into two atrioventricular bundle branches , commonly called the left and right bundle branches. The left bundle branch has two fascicles. The left bundle branch supplies the left ventricle, and the right bundle branch the right ventricle. Since the left ventricle is much larger than the right, the left bundle branch is also considerably larger than the right. Portions of the right bundle branch are found in the moderator band and supply the right papillary muscles. Because of this connection, each papillary muscle receives the impulse at approximately the same time, so they begin to contract simultaneously just prior to the remainder of the myocardial contractile cells of the ventricles. This is believed to allow tension to develop on the chordae tendineae prior to right ventricular contraction. There is no corresponding moderator band on the left. Both bundle branches descend and reach the apex of the heart where they connect with the Purkinje fibers (see Figure 19.19 , step 4). This passage takes approximately 25 ms. \n\n The Purkinje fibers are additional myocardial conductive fibers that spread the impulse to the myocardial contractile cells in the ventricles. They extend throughout the myocardium from the apex of the heart toward the atrioventricular septum and the base of the heart. The Purkinje fibers have a fast inherent conduction rate, and the electrical impulse reaches all of the ventricular muscle cells in about 75 ms (see Figure 19.19 , step 5). Since the electrical stimulus begins at the apex, the contraction also begins at the apex and travels toward the base of the heart, similar to squeezing a tube of toothpaste from the bottom. This allows the blood to be pumped out of the ventricles and into the aorta and pulmonary trunk. The total time elapsed from the initiation of the impulse in the SA node until depolarization of the ventricles is approximately 225 ms. \n\n Membrane Potentials and Ion Movement in Cardiac Conductive Cells \n\n Action potentials are considerably different between cardiac conductive cells and cardiac contractive cells. While Na + and K + play essential roles, Ca 2+ is also critical for both types of cells. Unlike skeletal muscles and neurons, cardiac conductive cells do not have a stable resting potential. Conductive cells contain a series of sodium ion channels that allow a normal and slow influx of sodium ions that causes the membrane potential to rise slowly from an initial value of −60 mV up to about –40 mV. The resulting movement of sodium ions creates spontaneous depolarization (or prepotential depolarization ). At this point, calcium ion channels open and Ca 2+ enters the cell, further depolarizing it at a more rapid rate until it reaches a value of approximately +15 mV. At this point, the calcium ion channels close and K + channels open, allowing outflux of K + and resulting in repolarization. When the membrane potential reaches approximately −60 mV, the K + channels close and Na + channels open, and the prepotential phase begins again. This phenomenon explains the autorhythmicity properties of cardiac muscle ( Figure 19.20 ). \n\n Membrane Potentials and Ion Movement in Cardiac Contractile Cells \n\n There is a distinctly different electrical pattern involving the contractile cells. In this case, there is a rapid depolarization, followed by a plateau phase and then repolarization. This phenomenon accounts for the long refractory periods required for the cardiac muscle cells to pump blood effectively before they are capable of firing for a second time. These cardiac myocytes normally do not initiate their own electrical potential but rather wait for an impulse to reach them. Contractile cells demonstrate a much more stable resting phase than conductive cells at approximately −80 mV for cells in the atria and −90 mV for cells in the ventricles. Despite this initial difference, the other components of their action potentials are virtually identical. In both cases, when stimulated by an action potential, voltage-gated channels rapidly open, beginning the positive-feedback mechanism of depolarization. This rapid influx of positively charged ions raises the membrane potential to approximately +30 mV, at which point the sodium channels close. The rapid depolarization period typically lasts 3–5 ms. Depolarization is followed by the plateau phase, in which membrane potential declines relatively slowly. This is due in large part to the opening of the slow Ca 2+ channels, allowing Ca 2+ to enter the cell while few K + channels are open, allowing K + to exit the cell. The relatively long plateau phase lasts approximately 175 ms. Once the membrane potential reaches approximately zero, the Ca 2+ channels close and K + channels open, allowing K + to exit the cell. The repolarization lasts approximately 75 ms. At this point, membrane potential drops until it reaches resting levels once more and the cycle repeats. The entire event lasts between 250 and 300 ms ( Figure 19.21 ). \n\n The absolute refractory period for cardiac contractile muscle lasts approximately 200 ms, and the relative refractory period lasts approximately 50 ms, for a total of 250 ms. This extended period is critical, since the heart muscle must contract to pump blood effectively and the contraction must follow the electrical events. Without extended refractory periods, premature contractions would occur in the heart and would not be compatible with life. \n\n Calcium Ions \n\n Calcium ions play two critical roles in the physiology of cardiac muscle. Their influx through slow calcium channels accounts for the prolonged plateau phase and absolute refractory period that enable cardiac muscle to function properly. Calcium ions also combine with the regulatory protein troponin in the troponin-tropomyosin complex; this complex removes the inhibition that prevents the heads of the myosin molecules from forming cross bridges with the active sites on actin that provide the power stroke of contraction. This mechanism is virtually identical to that of skeletal muscle. Approximately 20 percent of the calcium required for contraction is supplied by the influx of Ca 2+ during the plateau phase. The remaining Ca 2+ for contraction is released from storage in the sarcoplasmic reticulum. \n\n Comparative Rates of Conduction System Firing \n\n The pattern of prepotential or spontaneous depolarization, followed by rapid depolarization and repolarization just described, are seen in the SA node and a few other conductive cells in the heart. Since the SA node is the pacemaker, it reaches threshold faster than any other component of the conduction system. It will initiate the impulses spreading to the other conducting cells. The SA node, without nervous or endocrine control, would initiate a heart impulse approximately 80–100 times per minute. Although each component of the conduction system is capable of generating its own impulse, the rate progressively slows as you proceed from the SA node to the Purkinje fibers. Without the SA node, the AV node would generate a heart rate of 40–60 beats per minute. If the AV node were blocked, the atrioventricular bundle would fire at a rate of approximately 30–40 impulses per minute. The bundle branches would have an inherent rate of 20–30 impulses per minute, and the Purkinje fibers would fire at 15–20 impulses per minute. While a few exceptionally trained aerobic athletes demonstrate resting heart rates in the range of 30–40 beats per minute (the lowest recorded figure is 28 beats per minute for Miguel Indurain, a cyclist), for most individuals, rates lower than 50 beats per minute would indicate a condition called bradycardia. Depending upon the specific individual, as rates fall much below this level, the heart would be unable to maintain adequate flow of blood to vital tissues, initially resulting in decreasing loss of function across the systems, unconsciousness, and ultimately death. \n\n Electrocardiogram \n\n By careful placement of surface electrodes on the body, it is possible to record the complex, compound electrical signal of the heart. This tracing of the electrical signal is the electrocardiogram (ECG) , also commonly abbreviated EKG (K coming kardiology, from the German term for cardiology). Careful analysis of the ECG reveals a detailed picture of both normal and abnormal heart function, and is an indispensable clinical diagnostic tool. The standard electrocardiograph (the instrument that generates an ECG) uses 3, 5, or 12 leads. The greater the number of leads an electrocardiograph uses, the more information the ECG provides. The term “lead” may be used to refer to the cable from the electrode to the electrical recorder, but it typically describes the voltage difference between two of the electrodes. The 12-lead electrocardiograph uses 10 electrodes placed in standard locations on the patient’s skin ( Figure 19.22 ). In continuous ambulatory electrocardiographs, the patient wears a small, portable, battery-operated device known as a Holter monitor, or simply a Holter, that continuously monitors heart electrical activity, typically for a period of 24 hours during the patient’s normal routine. \n\n A normal ECG tracing is presented in Figure 19.23 . Each component, segment, and interval is labeled and corresponds to important electrical events, demonstrating the relationship between these events and contraction in the heart. \n\n There are five prominent points on the ECG: the P wave, the QRS complex, and the T wave. The small P wave represents the depolarization of the atria. The atria begin contracting approximately 25 ms after the start of the P wave. The large QRS complex represents the depolarization of the ventricles, which requires a much stronger electrical signal because of the larger size of the ventricular cardiac muscle. The ventricles begin to contract as the QRS reaches the peak of the R wave. Lastly, the T wave represents the repolarization of the ventricles. The repolarization of the atria occurs during the QRS complex, which masks it on an ECG. \n\n The major segments and intervals of an ECG tracing are indicated in Figure 19.23 . Segments are defined as the regions between two waves. Intervals include one segment plus one or more waves. For example, the PR segment begins at the end of the P wave and ends at the beginning of the QRS complex. The PR interval starts at the beginning of the P wave and ends with the beginning of the QRS complex. The PR interval is more clinically relevant, as it measures the duration from the beginning of atrial depolarization (the P wave) to the initiation of the QRS complex. Since the Q wave may be difficult to view in some tracings, the measurement is often extended to the R that is more easily visible. Should there be a delay in passage of the impulse from the SA node to the AV node, it would be visible in the PR interval. Figure 19.24 correlates events of heart contraction to the corresponding segments and intervals of an ECG. \n\n Interactive Link \n\n Visit this site for a more detailed analysis of ECGs. \n\n Everyday Connection ECG Abnormalities \n\nOccassionally, an area of the heart other than the SA node will initiate an impulse that will be followed by a premature contraction. Such an area, which may actually be a component of the conduction system or some other contractile cells, is known as an ectopic focus or ectopic pacemaker. An ectopic focus may be stimulated by localized ischemia; exposure to certain drugs, including caffeine, digitalis, or acetylcholine; elevated stimulation by both sympathetic or parasympathetic divisions of the autonomic nervous system; or a number of disease or pathological conditions. Occasional occurances are generally transitory and nonlife threatening, but if the condition becomes chronic, it may lead to either an arrhythmia, a deviation from the normal pattern of impulse conduction and contraction, or to fibrillation, an uncoordinated beating of the heart. \n\n While interpretation of an ECG is possible and extremely valuable after some training, a full understanding of the complexities and intricacies generally requires several years of experience. In general, the size of the electrical variations, the duration of the events, and detailed vector analysis provide the most comprehensive picture of cardiac function. For example, an amplified P wave may indicate enlargement of the atria, an enlarged Q wave may indicate a MI, and an enlarged suppressed or inverted Q wave often indicates enlarged ventricles. T waves often appear flatter when insufficient oxygen is being delivered to the myocardium. An elevation of the ST segment above baseline is often seen in patients with an acute MI, and may appear depressed below the baseline when hypoxia is occurring. \n\n As useful as analyzing these electrical recordings may be, there are limitations. For example, not all areas suffering a MI may be obvious on the ECG. Additionally, it will not reveal the effectiveness of the pumping, which requires further testing, such as an ultrasound test called an echocardiogram or nuclear medicine imaging. It is also possible for there to be pulseless electrical activity, which will show up on an ECG tracing, although there is no corresponding pumping action. Common abnormalities that may be detected by the ECGs are shown in Figure 19.25 . \n\n Interactive Link \n\n Visit this site for a more complete library of abnormal ECGs. \n\n Everyday Connection External Automated Defibrillators \n\nIn the event that the electrical activity of the heart is severely disrupted, cessation of electrical activity or fibrillation may occur. In fibrillation, the heart beats in a wild, uncontrolled manner, which prevents it from being able to pump effectively. Atrial fibrillation (see Figure 19.25 b ) is a serious condition, but as long as the ventricles continue to pump blood, the patient’s life may not be in immediate danger. Ventricular fibrillation (see Figure 19.25 d ) is a medical emergency that requires life support, because the ventricles are not effectively pumping blood. In a hospital setting, it is often described as “code blue.” If untreated for as little as a few minutes, ventricular fibrillation may lead to brain death. The most common treatment is defibrillation, which uses special paddles to apply a charge to the heart from an external electrical source in an attempt to establish a normal sinus rhythm ( Figure 19.26 ). A defibrillator effectively stops the heart so that the SA node can trigger a normal conduction cycle. Because of their effectiveness in reestablishing a normal sinus rhythm, external automated defibrillators (EADs) are being placed in areas frequented by large numbers of people, such as schools, restaurants, and airports. These devices contain simple and direct verbal instructions that can be followed by nonmedical personnel in an attempt to save a life. \n\n A heart block refers to an interruption in the normal conduction pathway. The nomenclature for these is very straightforward. SA nodal blocks occur within the SA node. AV nodal blocks occur within the AV node. Infra-Hisian blocks involve the bundle of His. Bundle branch blocks occur within either the left or right atrioventricular bundle branches. Hemiblocks are partial and occur within one or more fascicles of the atrioventricular bundle branch. Clinically, the most common types are the AV nodal and infra-Hisian blocks. \n\n AV blocks are often described by degrees. A first-degree or partial block indicates a delay in conduction between the SA and AV nodes. This can be recognized on the ECG as an abnormally long PR interval. A second-degree or incomplete block occurs when some impulses from the SA node reach the AV node and continue, while others do not. In this instance, the ECG would reveal some P waves not followed by a QRS complex, while others would appear normal. In the third-degree or complete block, there is no correlation between atrial activity (the P wave) and ventricular activity (the QRS complex). Even in the event of a total SA block, the AV node will assume the role of pacemaker and continue initiating contractions at 40–60 contractions per minute, which is adequate to maintain consciousness. Second- and third-degree blocks are demonstrated on the ECG presented in Figure 19.25 . \n\n When arrhythmias become a chronic problem, the heart maintains a junctional rhythm, which originates in the AV node. In order to speed up the heart rate and restore full sinus rhythm, a cardiologist can implant an artificial pacemaker , which delivers electrical impulses to the heart muscle to ensure that the heart continues to contract and pump blood effectively. These artificial pacemakers are programmable by the cardiologists and can either provide stimulation temporarily upon demand or on a continuous basis. Some devices also contain built-in defibrillators. \n\n Cardiac Muscle Metabolism \n\n Normally, cardiac muscle metabolism is entirely aerobic. Oxygen from the lungs is brought to the heart, and every other organ, attached to the hemoglobin molecules within the erythrocytes. Heart cells also store appreciable amounts of oxygen in myoglobin. Normally, these two mechanisms, circulating oxygen and oxygen attached to myoglobin, can supply sufficient oxygen to the heart, even during peak performance. \n\n Fatty acids and glucose from the circulation are broken down within the mitochondria to release energy in the form of ATP. Both fatty acid droplets and glycogen are stored within the sarcoplasm and provide additional nutrient supply. (Seek additional content for more detail about metabolism.) \n 19.3 Cardiac Cycle Learning Objectives By the end of this section, you will be able to: \n\n Describe the relationship between blood pressure and blood flow \n\n Summarize the events of the cardiac cycle \n\n Compare atrial and ventricular systole and diastole \n\n Relate heart sounds detected by auscultation to action of heart’s valves \n\n The period of time that begins with contraction of the atria and ends with ventricular relaxation is known as the cardiac cycle ( Figure 19.27 ). The period of contraction that the heart undergoes while it pumps blood into circulation is called systole . The period of relaxation that occurs as the chambers fill with blood is called diastole . Both the atria and ventricles undergo systole and diastole, and it is essential that these components be carefully regulated and coordinated to ensure blood is pumped efficiently to the body. \n\n Pressures and Flow \n\n Fluids, whether gases or liquids, are materials that flow according to pressure gradients—that is, they move from regions that are higher in pressure to regions that are lower in pressure. Accordingly, when the heart chambers are relaxed (diastole), blood will flow into the atria from the veins, which are higher in pressure. As blood flows into the atria, the pressure will rise, so the blood will initially move passively from the atria into the ventricles. When the action potential triggers the muscles in the atria to contract (atrial systole), the pressure within the atria rises further, pumping blood into the ventricles. During ventricular systole, pressure rises in the ventricles, pumping blood into the pulmonary trunk from the right ventricle and into the aorta from the left ventricle. Again, as you consider this flow and relate it to the conduction pathway, the elegance of the system should become apparent. \n\n Phases of the Cardiac Cycle \n\n At the beginning of the cardiac cycle, both the atria and ventricles are relaxed (diastole). Blood is flowing into the right atrium from the superior and inferior venae cavae and the coronary sinus. Blood flows into the left atrium from the four pulmonary veins. The two atrioventricular valves, the tricuspid and mitral valves, are both open, so blood flows unimpeded from the atria and into the ventricles. Approximately 70–80 percent of ventricular filling occurs by this method. The two semilunar valves, the pulmonary and aortic valves, are closed, preventing backflow of blood into the right and left ventricles from the pulmonary trunk on the right and the aorta on the left. \n\n Atrial Systole and Diastole \n\n Contraction of the atria follows depolarization, represented by the P wave of the ECG. As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum, pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular (tricuspid, and mitral or bicuspid) valves. At the start of atrial systole, the ventricles are normally filled with approximately 70–80 percent of their capacity due to inflow during diastole. Atrial contraction, also referred to as the “atrial kick,” contributes the remaining 20–30 percent of filling (see Figure 19.27 ). Atrial systole lasts approximately 100 ms and ends prior to ventricular systole, as the atrial muscle returns to diastole. \n\n Ventricular Systole \n\n Ventricular systole (see Figure 19.27 ) follows the depolarization of the ventricles and is represented by the QRS complex in the ECG. It may be conveniently divided into two phases, lasting a total of 270 ms. At the end of atrial systole and just prior to ventricular contraction, the ventricles contain approximately 130 mL blood in a resting adult in a standing position. This volume is known as the end diastolic volume (EDV) or preload . \n\n Initially, as the muscles in the ventricle contract, the pressure of the blood within the chamber rises, but it is not yet high enough to open the semilunar (pulmonary and aortic) valves and be ejected from the heart. However, blood pressure quickly rises above that of the atria that are now relaxed and in diastole. This increase in pressure causes blood to flow back toward the atria, closing the tricuspid and mitral valves. Since blood is not being ejected from the ventricles at this early stage, the volume of blood within the chamber remains constant. Consequently, this initial phase of ventricular systole is known as isovolumic contraction , also called isovolumetric contraction (see Figure 19.27 ). \n\n In the second phase of ventricular systole, the ventricular ejection phase , the contraction of the ventricular muscle has raised the pressure within the ventricle to the point that it is greater than the pressures in the pulmonary trunk and the aorta. Blood is pumped from the heart, pushing open the pulmonary and aortic semilunar valves. Pressure generated by the left ventricle will be appreciably greater than the pressure generated by the right ventricle, since the existing pressure in the aorta will be so much higher. Nevertheless, both ventricles pump the same amount of blood. This quantity is referred to as stroke volume. Stroke volume will normally be in the range of 70–80 mL. Since ventricular systole began with an EDV of approximately 130 mL of blood, this means that there is still 50–60 mL of blood remaining in the ventricle following contraction. This volume of blood is known as the end systolic volume (ESV) . \n\n Ventricular Diastole \n\n Ventricular relaxation, or diastole, follows repolarization of the ventricles and is represented by the T wave of the ECG. It too is divided into two distinct phases and lasts approximately 430 ms. \n\n During the early phase of ventricular diastole, as the ventricular muscle relaxes, pressure on the remaining blood within the ventricle begins to fall. When pressure within the ventricles drops below pressure in both the pulmonary trunk and aorta, blood flows back toward the heart, producing the dicrotic notch (small dip) seen in blood pressure tracings. The semilunar valves close to prevent backflow into the heart. Since the atrioventricular valves remain closed at this point, there is no change in the volume of blood in the ventricle, so the early phase of ventricular diastole is called the isovolumic ventricular relaxation phase , also called isovolumetric ventricular relaxation phase (see Figure 19.27 ). \n\n In the second phase of ventricular diastole, called late ventricular diastole, as the ventricular muscle relaxes, pressure on the blood within the ventricles drops even further. Eventually, it drops below the pressure in the atria. When this occurs, blood flows from the atria into the ventricles, pushing open the tricuspid and mitral valves. As pressure drops within the ventricles, blood flows from the major veins into the relaxed atria and from there into the ventricles. Both chambers are in diastole, the atrioventricular valves are open, and the semilunar valves remain closed (see Figure 19.27 ). The cardiac cycle is complete. \n\n Figure 19.28 illustrates the relationship between the cardiac cycle and the ECG. \n\n Heart Sounds \n\n One of the simplest, yet effective, diagnostic techniques applied to assess the state of a patient’s heart is auscultation using a stethoscope. \n\n In a normal, healthy heart, there are only two audible heart sounds : S 1 and S 2 . S 1 is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as a “lub,” or first heart sound. The second heart sound, S 2 , is the sound of the closing of the semilunar valves during ventricular diastole and is described as a “dub” ( Figure 19.29 ). In both cases, as the valves close, the openings within the atrioventricular septum guarded by the valves will become reduced, and blood flow through the opening will become more turbulent until the valves are fully closed. There is a third heart sound, S 3 , but it is rarely heard in healthy individuals. It may be the sound of blood flowing into the atria, or blood sloshing back and forth in the ventricle, or even tensing of the chordae tendineae. S 3 may be heard in youth, some athletes, and pregnant women. If the sound is heard later in life, it may indicate congestive heart failure, warranting further tests. Some cardiologists refer to the collective S 1 , S 2 , and S 3 sounds as the “Kentucky gallop,” because they mimic those produced by a galloping horse. The fourth heart sound, S 4 , results from the contraction of the atria pushing blood into a stiff or hypertrophic ventricle, indicating failure of the left ventricle. S 4 occurs prior to S 1 and the collective sounds S 4 , S 1 , and S 2 are referred to by some cardiologists as the “Tennessee gallop,” because of their similarity to the sound produced by a galloping horse with a different gait. A few individuals may have both S 3 and S 4 , and this combined sound is referred to as S 7 . \n\n The term murmur is used to describe an unusual sound coming from the heart that is caused by the turbulent flow of blood. Murmurs are graded on a scale of 1 to 6, with 1 being the most common, the most difficult sound to detect, and the least serious. The most severe is a 6. Phonocardiograms or auscultograms can be used to record both normal and abnormal sounds using specialized electronic stethoscopes. \n\n During auscultation, it is common practice for the clinician to ask the patient to breathe deeply. This procedure not only allows for listening to airflow, but it may also amplify heart murmurs. Inhalation increases blood flow into the right side of the heart and may increase the amplitude of right-sided heart murmurs. Expiration partially restricts blood flow into the left side of the heart and may amplify left-sided heart murmurs. Figure 19.30 indicates proper placement of the bell of the stethoscope to facilitate auscultation. \n 19.4 Cardiac Physiology Learning Objectives By the end of this section, you will be able to: \n\n Relate heart rate to cardiac output \n\n Describe the effect of exercise on heart rate \n\n Identify cardiovascular centers and cardiac reflexes that regulate heart function \n\n Describe factors affecting heart rate \n\n Distinguish between positive and negative factors that affect heart contractility \n\n Summarize factors affecting stroke volume and cardiac output \n\n Describe the cardiac response to variations in blood flow and pressure \n\n The autorhythmicity inherent in cardiac cells keeps the heart beating at a regular pace; however, the heart is regulated by and responds to outside influences as well. Neural and endocrine controls are vital to the regulation of cardiac function. In addition, the heart is sensitive to several environmental factors, including electrolytes. \n\n Resting Cardiac Output \n\n Cardiac output (CO) is a measurement of the amount of blood pumped by each ventricle in one minute. To calculate this value, multiply stroke volume (SV) , the amount of blood pumped by each ventricle, by heart rate (HR) , in contractions per minute (or beats per minute, bpm). It can be represented mathematically by the following equation: \n\n CO = HR × SV \n\n SV is normally measured using an echocardiogram to record EDV and ESV, and calculating the difference: SV = EDV – ESV. SV can also be measured using a specialized catheter, but this is an invasive procedure and far more dangerous to the patient. A mean SV for a resting 70-kg (150-lb) individual would be approximately 70 mL. There are several important variables, including size of the heart, physical and mental condition of the individual, sex, contractility, duration of contraction, preload or EDV, and afterload or resistance. Normal range for SV would be 55–100 mL. An average resting HR would be approximately 75 bpm but could range from 60–100 in some individuals. \n\n Using these numbers, the mean CO is 5.25 L/min, with a range of 4.0–8.0 L/min. Remember, however, that these numbers refer to CO from each ventricle separately, not the total for the heart. Factors influencing CO are summarized in Figure 19.31 . \n\n SVs are also used to calculate ejection fraction , which is the portion of the blood that is pumped or ejected from the heart with each contraction. To calculate ejection fraction, SV is divided by EDV. Despite the name, the ejection fraction is normally expressed as a percentage. Ejection fractions range from approximately 55–70 percent, with a mean of 58 percent. \n\n Exercise and Maximum Cardiac Output \n\n In healthy young individuals, HR may increase to 150 bpm during exercise. SV can also increase from 70 to approximately 130 mL due to increased strength of contraction. This would increase CO to approximately 19.5 L/min, 4–5 times the resting rate. Top cardiovascular athletes can achieve even higher levels. At their peak performance, they may increase resting CO by 7–8 times. \n\n Since the heart is a muscle, exercising it increases its efficiency. The difference between maximum and resting CO is known as the cardiac reserve . It measures the residual capacity of the heart to pump blood. \n\n Heart Rates \n\n HRs vary considerably, not only with exercise and fitness levels, but also with age. Newborn resting HRs may be 120 bpm. HR gradually decreases until young adulthood and then gradually increases again with age. \n\n Maximum HRs are normally in the range of 200–220 bpm, although there are some extreme cases in which they may reach higher levels. As one ages, the ability to generate maximum rates decreases. This may be estimated by taking the maximal value of 220 bpm and subtracting the individual’s age. So a 40-year-old individual would be expected to hit a maximum rate of approximately 180, and a 60-year-old person would achieve a HR of 160. \n\n Disorders of the... Heart: Abnormal Heart Rates \n\nFor an adult, normal resting HR will be in the range of 60–100 bpm. Bradycardia is the condition in which resting rate drops below 60 bpm, and tachycardia is the condition in which the resting rate is above 100 bpm. Trained athletes typically have very low HRs. If the patient is not exhibiting other symptoms, such as weakness, fatigue, dizziness, fainting, chest discomfort, palpitations, or respiratory distress, bradycardia is not considered clinically significant. However, if any of these symptoms are present, they may indicate that the heart is not providing sufficient oxygenated blood to the tissues. The term relative bradycardia may be used with a patient who has a HR in the normal range but is still suffering from these symptoms. Most patients remain asymptomatic as long as the HR remains above 50 bpm. \n\n Bradycardia may be caused by either inherent factors or causes external to the heart. While the condition may be inherited, typically it is acquired in older individuals. Inherent causes include abnormalities in either the SA or AV node. If the condition is serious, a pacemaker may be required. Other causes include ischemia to the heart muscle or diseases of the heart vessels or valves. External causes include metabolic disorders, pathologies of the endocrine system often involving the thyroid, electrolyte imbalances, neurological disorders including inappropriate autonomic responses, autoimmune pathologies, over-prescription of beta blocker drugs that reduce HR, recreational drug use, or even prolonged bed rest. Treatment relies upon establishing the underlying cause of the disorder and may necessitate supplemental oxygen. \n\n Tachycardia is not normal in a resting patient but may be detected in pregnant women or individuals experiencing extreme stress. In the latter case, it would likely be triggered by stimulation from the limbic system or disorders of the autonomic nervous system. In some cases, tachycardia may involve only the atria. Some individuals may remain asymptomatic, but when present, symptoms may include dizziness, shortness of breath, lightheadedness, rapid pulse, heart palpations, chest pain, or fainting (syncope). While tachycardia is defined as a HR above 100 bpm, there is considerable variation among people. Further, the normal resting HRs of children are often above 100 bpm, but this is not considered to be tachycardia Many causes of tachycardia may be benign, but the condition may also be correlated with fever, anemia, hypoxia, hyperthyroidism, hypersecretion of catecholamines, some cardiomyopathies, some disorders of the valves, and acute exposure to radiation. Elevated rates in an exercising or resting patient are normal and expected. Resting rate should always be taken after recovery from exercise. Treatment depends upon the underlying cause but may include medications, implantable cardioverter defibrillators, ablation, or surgery. \n\n Correlation Between Heart Rates and Cardiac Output \n\n Initially, physiological conditions that cause HR to increase also trigger an increase in SV. During exercise, the rate of blood returning to the heart increases. However as the HR rises, there is less time spent in diastole and consequently less time for the ventricles to fill with blood. Even though there is less filling time, SV will initially remain high. However, as HR continues to increase, SV gradually decreases due to decreased filling time. CO will initially stabilize as the increasing HR compensates for the decreasing SV, but at very high rates, CO will eventually decrease as increasing rates are no longer able to compensate for the decreasing SV. Consider this phenomenon in a healthy young individual. Initially, as HR increases from resting to approximately 120 bpm, CO will rise. As HR increases from 120 to 160 bpm, CO remains stable, since the increase in rate is offset by decreasing ventricular filling time and, consequently, SV. As HR continues to rise above 160 bpm, CO actually decreases as SV falls faster than HR increases. So although aerobic exercises are critical to maintain the health of the heart, individuals are cautioned to monitor their HR to ensure they stay within the target heart rate range of between 120 and 160 bpm, so CO is maintained. The target HR is loosely defined as the range in which both the heart and lungs receive the maximum benefit from the aerobic workout and is dependent upon age. \n\n Cardiovascular Centers \n\n Nervous control over HR is centralized within the two paired cardiovascular centers of the medulla oblongata ( Figure 19.32 ). The cardioaccelerator regions stimulate activity via sympathetic stimulation of the cardioaccelerator nerves, and the cardioinhibitory centers decrease heart activity via parasympathetic stimulation as one component of the vagus nerve, cranial nerve X. During rest, both centers provide slight stimulation to the heart, contributing to autonomic tone . This is a similar concept to tone in skeletal muscles. Normally, vagal stimulation predominates as, left unregulated, the SA node would initiate a sinus rhythm of approximately 100 bpm. \n\n Both sympathetic and parasympathetic stimulations flow through a paired complex network of nerve fibers known as the cardiac plexus near the base of the heart. The cardioaccelerator center also sends additional fibers, forming the cardiac nerves via sympathetic ganglia (the cervical ganglia plus superior thoracic ganglia T1–T4) to both the SA and AV nodes, plus additional fibers to the atria and ventricles. The ventricles are more richly innervated by sympathetic fibers than parasympathetic fibers. Sympathetic stimulation causes the release of the neurotransmitter norepinephrine (NE) at the neuromuscular junction of the cardiac nerves. NE shortens the repolarization period, thus speeding the rate of depolarization and contraction, which results in an increase in HR. It opens chemical- or ligand-gated sodium and calcium ion channels, allowing an influx of positively charged ions. \n\n NE binds to the beta-1 receptor. Some cardiac medications (for example, beta blockers) work by blocking these receptors, thereby slowing HR and are one possible treatment for hypertension. Overprescription of these drugs may lead to bradycardia and even stoppage of the heart. \n\n Parasympathetic stimulation originates from the cardioinhibitory region with impulses traveling via the vagus nerve (cranial nerve X). The vagus nerve sends branches to both the SA and AV nodes, and to portions of both the atria and ventricles. Parasympathetic stimulation releases the neurotransmitter acetylcholine (ACh) at the neuromuscular junction. ACh slows HR by opening chemical- or ligand-gated potassium ion channels to slow the rate of spontaneous depolarization, which extends repolarization and increases the time before the next spontaneous depolarization occurs. Without any nervous stimulation, the SA node would establish a sinus rhythm of approximately 100 bpm. Since resting rates are considerably less than this, it becomes evident that parasympathetic stimulation normally slows HR. This is similar to an individual driving a car with one foot on the brake pedal. To speed up, one need merely remove one’s foot from the break and let the engine increase speed. In the case of the heart, decreasing parasympathetic stimulation decreases the release of ACh, which allows HR to increase up to approximately 100 bpm. Any increases beyond this rate would require sympathetic stimulation. Figure 19.33 illustrates the effects of parasympathetic and sympathetic stimulation on the normal sinus rhythm. \n\n Input to the Cardiovascular Center \n\n The cardiovascular center receives input from a series of visceral receptors with impulses traveling through visceral sensory fibers within the vagus and sympathetic nerves via the cardiac plexus. Among these receptors are various proprioreceptors, baroreceptors, and chemoreceptors, plus stimuli from the limbic system. Collectively, these inputs normally enable the cardiovascular centers to regulate heart function precisely, a process known as cardiac reflexes . Increased physical activity results in increased rates of firing by various proprioreceptors located in muscles, joint capsules, and tendons. Any such increase in physical activity would logically warrant increased blood flow. The cardiac centers monitor these increased rates of firing, and suppress parasympathetic stimulation and increase sympathetic stimulation as needed in order to increase blood flow. \n\n Similarly, baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including pulmonary vessels and the right side of the heart itself. Rates of firing from the baroreceptors represent blood pressure, level of physical activity, and the relative distribution of blood. The cardiac centers monitor baroreceptor firing to maintain cardiac homeostasis, a mechanism called the baroreceptor reflex . With increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centers decrease sympathetic stimulation and increase parasympathetic stimulation. As pressure and stretch decrease, the rate of baroreceptor firing decreases, and the cardiac centers increase sympathetic stimulation and decrease parasympathetic stimulation. \n\n There is a similar reflex, called the atrial reflex or Bainbridge reflex , associated with varying rates of blood flow to the atria. Increased venous return stretches the walls of the atria where specialized baroreceptors are located. However, as the atrial baroreceptors increase their rate of firing and as they stretch due to the increased blood pressure, the cardiac center responds by increasing sympathetic stimulation and inhibiting parasympathetic stimulation to increase HR. The opposite is also true. \n\n Increased metabolic byproducts associated with increased activity, such as carbon dioxide, hydrogen ions, and lactic acid, plus falling oxygen levels, are detected by a suite of chemoreceptors innervated by the glossopharyngeal and vagus nerves. These chemoreceptors provide feedback to the cardiovascular centers about the need for increased or decreased blood flow, based on the relative levels of these substances. \n\n The limbic system can also significantly impact HR related to emotional state. During periods of stress, it is not unusual to identify higher than normal HRs, often accompanied by a surge in the stress hormone cortisol. Individuals experiencing extreme anxiety may manifest panic attacks with symptoms that resemble those of heart attacks. These events are typically transient and treatable. Meditation techniques have been developed to ease anxiety and have been shown to lower HR effectively. Doing simple deep and slow breathing exercises with one’s eyes closed can also significantly reduce this anxiety and HR. \n\n Disorders of the... Heart: Broken Heart Syndrome \n\nExtreme stress from such life events as the death of a loved one, an emotional break up, loss of income, or foreclosure of a home may lead to a condition commonly referred to as broken heart syndrome. This condition may also be called Takotsubo cardiomyopathy, transient apical ballooning syndrome, apical ballooning cardiomyopathy, stress-induced cardiomyopathy, Gebrochenes-Herz syndrome, and stress cardiomyopathy. The recognized effects on the heart include congestive heart failure due to a profound weakening of the myocardium not related to lack of oxygen. This may lead to acute heart failure, lethal arrhythmias, or even the rupture of a ventricle. The exact etiology is not known, but several factors have been suggested, including transient vasospasm, dysfunction of the cardiac capillaries, or thickening of the myocardium—particularly in the left ventricle—that may lead to the critical circulation of blood to this region. While many patients survive the initial acute event with treatment to restore normal function, there is a strong correlation with death. Careful statistical analysis by the Cass Business School, a prestigious institution located in London, published in 2008, revealed that within one year of the death of a loved one, women are more than twice as likely to die and males are six times as likely to die as would otherwise be expected. \n\n Other Factors Influencing Heart Rate \n\n Using a combination of autorhythmicity and innervation, the cardiovascular center is able to provide relatively precise control over HR. However, there are a number of other factors that have an impact on HR as well, including epinephrine, NE, and thyroid hormones; levels of various ions including calcium, potassium, and sodium; body temperature; hypoxia; and pH balance ( Table 19.1 and Table 19.2 ). After reading this section, the importance of maintaining homeostasis should become even more apparent. \n\n Major Factors Increasing Heart Rate and Force of Contraction \n\n Factor \n\n Effect \n\n Cardioaccelerator nerves \n\n Release of norepinephrine by cardioinhibitory nerves \n\n Proprioreceptors \n\n Increased firing rates of proprioreceptors (e.g. during exercise) \n\n Chemoreceptors \n\n Chemoreceptors sensing decreased levels of O 2 or increased levels of H + , CO 2 and lactic acid \n\n Baroreceptors \n\n Decreased firing rates of baroreceptors (indicating falling blood volume/pressure) \n\n Limbic system \n\n Anticipation of physical exercise or strong emotions by the limbic system \n\n Catecholamines \n\n Decreased epinephrine and norepinephrine release by the adrenal glands \n\n Thyroid hormones \n\n Increased T 3 and T 4 in the blood (released by thyroid) \n\n Calcium \n\n Decrease in calcium ions in the blood \n\n Potassium \n\n Decrease in potassium ions in the blood \n\n Sodium \n\n Decrease in sodium ions in the blood \n\n Body temperature \n\n Increase in body temperature \n\n Nicotine and caffeine \n\n Presence of nicotine, caffeine or other stimulants \n\n Table 19.1 Factors Decreasing Heart Rate and Force of Contraction \n\n Factor \n\n Effect \n\n Cardioinhibitor nerves (vagus) \n\n Release of acetylcholine by cardioaccelerator nerves \n\n Proprioreceptors \n\n Decreased firing rates of proprioreceptors (e.g. during rest) \n\n Chemoreceptors \n\n Chemoreceptors sensing increased levels of O 2 or decreased levels of H + , CO 2 and lactic acid \n\n Baroreceptors \n\n Increased firing rates of baroreceptors (indicating rising blood volume/pressure) \n\n Limbic system \n\n Anticipation of relaxation by the limbic system \n\n Catecholamines \n\n Decreased epinephrine and norepinephrine release by the adrenal glands \n\n Thyroid hormones \n\n Decreased T 3 and T 4 in the blood (released by thyroid) \n\n Calcium \n\n Decrease in calcium ions in the blood \n\n Potassium \n\n Increase in potassium ions in the blood \n\n Sodium \n\n Increase in sodium ions in the blood \n\n Body temperature \n\n Decrease in body temperature \n\n Opiates and tranquilizers \n\n Presence of opiates (heroin), tranquilizers or other depressants \n\n Table 19.2 Epinephrine and Norepinephrine \n\n The catecholamines, epinephrine and NE, secreted by the adrenal medulla form one component of the extended fight-or-flight mechanism. The other component is sympathetic stimulation. Epinephrine and NE have similar effects: binding to the beta-1 receptors, and opening sodium and calcium ion chemical- or ligand-gated channels. The rate of depolarization is increased by this additional influx of positively charged ions, so the threshold is reached more quickly and the period of repolarization is shortened. However, massive releases of these hormones coupled with sympathetic stimulation may actually lead to arrhythmias. There is no parasympathetic stimulation to the adrenal medulla. \n\n Thyroid Hormones \n\n In general, increased levels of thyroid hormone, or thyroxin, increase cardiac rate and contractility. The impact of thyroid hormone is typically of a much longer duration than that of the catecholamines. The physiologically active form of thyroid hormone, T 3 or triiodothyronine, has been shown to directly enter cardiomyocytes and alter activity at the level of the genome. It also impacts the beta adrenergic response similar to epinephrine and NE described above. Excessive levels of thyroxin may trigger tachycardia. \n\n Calcium \n\n Calcium ion levels have great impacts upon both HR and contractility; as the levels of calcium ions increase, so do HR and contractility. High levels of calcium ions (hypercalcemia) may be implicated in a short QT interval and a widened T wave in the ECG. The QT interval represents the time from the start of depolarization to repolarization of the ventricles, and includes the period of ventricular systole. Extremely high levels of calcium may induce cardiac arrest. Drugs known as calcium channel blockers slow HR by binding to these channels and blocking or slowing the inward movement of calcium ions. \n\n Caffeine and Nicotine \n\n Caffeine and nicotine are not found naturally within the body. Both of these nonregulated drugs have an excitatory effect on membranes of neurons in general and have a stimulatory effect on the cardiac centers specifically, causing an increase in HR. Caffeine works by increasing the rates of depolarization at the SA node, whereas nicotine stimulates the activity of the sympathetic neurons that deliver impulses to the heart. \n\n Although it is the world’s most widely consumed psychoactive drug, caffeine is legal and not regulated. While precise quantities have not been established, “normal” consumption is not considered harmful to most people, although it may cause disruptions to sleep and acts as a diuretic. Its consumption by pregnant women is cautioned against, although no evidence of negative effects has been confirmed. Tolerance and even physical and mental addiction to the drug result in individuals who routinely consume the substance. Nicotine, too, is a stimulant and produces addiction. While legal and nonregulated, concerns about nicotine’s safety and documented links to respiratory and cardiac disease have resulted in warning labels on cigarette packages. \n\n Factors Decreasing Heart Rate \n\n HR can be slowed when a person experiences altered sodium and potassium levels, hypoxia, acidosis, alkalosis, and hypothermia (see Table 19.1 ). The relationship between electrolytes and HR is complex, but maintaining electrolyte balance is critical to the normal wave of depolarization. Of the two ions, potassium has the greater clinical significance. Initially, both hyponatremia (low sodium levels) and hypernatremia (high sodium levels) may lead to tachycardia. Severely high hypernatremia may lead to fibrillation, which may cause CO to cease. Severe hyponatremia leads to both bradycardia and other arrhythmias. Hypokalemia (low potassium levels) also leads to arrhythmias, whereas hyperkalemia (high potassium levels) causes the heart to become weak and flaccid, and ultimately to fail. \n\n Acidosis is a condition in which excess hydrogen ions are present, and the patient’s blood expresses a low pH value. Alkalosis is a condition in which there are too few hydrogen ions, and the patient’s blood has an elevated pH. Normal blood pH falls in the range of 7.35–7.45, so a number lower than this range represents acidosis and a higher number represents alkalosis. Recall that enzymes are the regulators or catalysts of virtually all biochemical reactions; they are sensitive to pH and will change shape slightly with values outside their normal range. These variations in pH and accompanying slight physical changes to the active site on the enzyme decrease the rate of formation of the enzyme-substrate complex, subsequently decreasing the rate of many enzymatic reactions, which can have complex effects on HR. Severe changes in pH will lead to denaturation of the enzyme. The last variable is body temperature. Elevated body temperature is called hyperthermia, and suppressed body temperature is called hypothermia. Slight hyperthermia results in increasing HR and strength of contraction. Hypothermia slows the rate and strength of heart contractions. This distinct slowing of the heart is one component of the larger diving reflex that diverts blood to essential organs while submerged. If sufficiently chilled, the heart will stop beating, a technique that may be employed during open heart surgery. In this case, the patient’s blood is normally diverted to an artificial heart-lung machine to maintain the body’s blood supply and gas exchange until the surgery is complete, and sinus rhythm can be restored. Excessive hyperthermia and hypothermia will both result in death, as enzymes drive the body systems to cease normal function, beginning with the central nervous system. \n\n Stroke Volume \n\n Many of the same factors that regulate HR also impact cardiac function by altering SV. While a number of variables are involved, SV is ultimately dependent upon the difference between EDV and ESV. The three primary factors to consider are preload, or the stretch on the ventricles prior to contraction; the contractility, or the force or strength of the contraction itself; and afterload, the force the ventricles must generate to pump blood against the resistance in the vessels. These factors are summarized in Table 19.1 and Table 19.2 . \n\n Preload \n\n Preload is another way of expressing EDV. Therefore, the greater the EDV is, the greater the preload is. One of the primary factors to consider is filling time , or the duration of ventricular diastole during which filling occurs. The more rapidly the heart contracts, the shorter the filling time becomes, and the lower the EDV and preload are. This effect can be partially overcome by increasing the second variable, contractility, and raising SV, but over time, the heart is unable to compensate for decreased filling time, and preload also decreases. \n\n With increasing ventricular filling, both EDV or preload increase, and the cardiac muscle itself is stretched to a greater degree. At rest, there is little stretch of the ventricular muscle, and the sarcomeres remain short. With increased ventricular filling, the ventricular muscle is increasingly stretched and the sarcomere length increases. As the sarcomeres reach their optimal lengths, they will contract more powerfully, because more of the myosin heads can bind to the actin on the thin filaments, forming cross bridges and increasing the strength of contraction and SV. If this process were to continue and the sarcomeres stretched beyond their optimal lengths, the force of contraction would decrease. However, due to the physical constraints of the location of the heart, this excessive stretch is not a concern. \n\n The relationship between ventricular stretch and contraction has been stated in the well-known Frank-Starling mechanism or simply Starling’s Law of the Heart. This principle states that, within physiological limits, the force of heart contraction is directly proportional to the initial length of the muscle fiber. This means that the greater the stretch of the ventricular muscle (within limits), the more powerful the contraction is, which in turn increases SV. Therefore, by increasing preload, you increase the second variable, contractility. \n\n Otto Frank (1865–1944) was a German physiologist; among his many published works are detailed studies of this important heart relationship. Ernest Starling (1866–1927) was an important English physiologist who also studied the heart. Although they worked largely independently, their combined efforts and similar conclusions have been recognized in the name “Frank-Starling mechanism.” \n\n Any sympathetic stimulation to the venous system will increase venous return to the heart, which contributes to ventricular filling, and EDV and preload. While much of the ventricular filling occurs while both atria and ventricles are in diastole, the contraction of the atria, the atrial kick, plays a crucial role by providing the last 20–30 percent of ventricular filling. \n\n Contractility \n\n It is virtually impossible to consider preload or ESV without including an early mention of the concept of contractility. Indeed, the two parameters are intimately linked. Contractility refers to the force of the contraction of the heart muscle, which controls SV, and is the primary parameter for impacting ESV. The more forceful the contraction is, the greater the SV and smaller the ESV are. Less forceful contractions result in smaller SVs and larger ESVs. Factors that increase contractility are described as positive inotropic factors , and those that decrease contractility are described as negative inotropic factors (ino- = “fiber;” -tropic = “turning toward”). \n\n Not surprisingly, sympathetic stimulation is a positive inotrope, whereas parasympathetic stimulation is a negative inotrope. Sympathetic stimulation triggers the release of NE at the neuromuscular junction from the cardiac nerves and also stimulates the adrenal cortex to secrete epinephrine and NE. In addition to their stimulatory effects on HR, they also bind to both alpha and beta receptors on the cardiac muscle cell membrane to increase metabolic rate and the force of contraction. This combination of actions has the net effect of increasing SV and leaving a smaller residual ESV in the ventricles. In comparison, parasympathetic stimulation releases ACh at the neuromuscular junction from the vagus nerve. The membrane hyperpolarizes and inhibits contraction to decrease the strength of contraction and SV, and to raise ESV. Since parasympathetic fibers are more widespread in the atria than in the ventricles, the primary site of action is in the upper chambers. Parasympathetic stimulation in the atria decreases the atrial kick and reduces EDV, which decreases ventricular stretch and preload, thereby further limiting the force of ventricular contraction. Stronger parasympathetic stimulation also directly decreases the force of contraction of the ventricles. \n\n Several synthetic drugs, including dopamine and isoproterenol, have been developed that mimic the effects of epinephrine and NE by stimulating the influx of calcium ions from the extracellular fluid. Higher concentrations of intracellular calcium ions increase the strength of contraction. Excess calcium (hypercalcemia) also acts as a positive inotropic agent. The drug digitalis lowers HR and increases the strength of the contraction, acting as a positive inotropic agent by blocking the sequestering of calcium ions into the sarcoplasmic reticulum. This leads to higher intracellular calcium levels and greater strength of contraction. In addition to the catecholamines from the adrenal medulla, other hormones also demonstrate positive inotropic effects. These include thyroid hormones and glucagon from the pancreas. \n\n Negative inotropic agents include hypoxia, acidosis, hyperkalemia, and a variety of synthetic drugs. These include numerous beta blockers and calcium channel blockers. Early beta blocker drugs include propranolol and pronethalol, and are credited with revolutionizing treatment of cardiac patients experiencing angina pectoris. There is also a large class of dihydropyridine, phenylalkylamine, and benzothiazepine calcium channel blockers that may be administered decreasing the strength of contraction and SV. \n\n Afterload \n\n Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system. Any condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood. Damage to the valves, such as stenosis, which makes them harder to open will also increase afterload. Any decrease in resistance decreases the afterload. Figure 19.34 summarizes the major factors influencing SV, Figure 19.35 summarizes the major factors influencing CO, and Table 19.3 and Table 19.4 summarize cardiac responses to increased and decreased blood flow and pressure in order to restore homeostasis. \n\n Cardiac Response to Decreasing Blood Flow and Pressure Due to Decreasing Cardiac Output \n\n Baroreceptors (aorta, carotid arteries, venae cavae, and atria) \n\n Chemoreceptors (both central nervous system and in proximity to baroreceptors) \n\n Sensitive to \n\n Decreasing stretch \n\n Decreasing O 2 and increasing CO 2 , H + , and lactic acid \n\n Target \n\n Parasympathetic stimulation suppressed \n\n Sympathetic stimulation increased \n\n Response of heart \n\n Increasing heart rate and increasing stroke volume \n\n Increasing heart rate and increasing stroke volume \n\n Overall effect \n\n Increasing blood flow and pressure due to increasing cardiac output; homeostasis restored \n\n Increasing blood flow and pressure due to increasing cardiac output; homeostasis restored \n\n Table 19.3 \n\n Cardiac Response to Increasing Blood Flow and Pressure Due to Increasing Cardiac Output \n\n Baroreceptors (aorta, carotid arteries, venae cavae, and atria) \n\n Chemoreceptors (both central nervous system and in proximity to baroreceptors) \n\n Sensitive to \n\n Increasing stretch \n\n Increasing O 2 and decreasing CO 2 , H + , and lactic acid \n\n Target \n\n Parasympathetic stimulation increased \n\n Sympathetic stimulation suppressed \n\n Response of heart \n\n Decreasing heart rate and decreasing stroke volume \n\n Decreasing heart rate and decreasing stroke volume \n\n Overall effect \n\n Decreasing blood flow and pressure due to decreasing cardiac output; homeostasis restored \n\n Decreasing blood flow and pressure due to decreasing cardiac output; homeostasis restored \n\n Table 19.4 \n 19.5 Development of the Heart Learning Objectives By the end of this section, you will be able to: \n\n Describe the embryological development of heart structures \n\n Identify five regions of the fetal heart \n\n Relate fetal heart structures to adult counterparts \n\n The human heart is the first functional organ to develop. It begins beating and pumping blood around day 21 or 22, a mere three weeks after fertilization. This emphasizes the critical nature of the heart in distributing blood through the vessels and the vital exchange of nutrients, oxygen, and wastes both to and from the developing baby. The critical early development of the heart is reflected by the prominent heart bulge that appears on the anterior surface of the embryo. \n\n The heart forms from an embryonic tissue called mesoderm around 18 to 19 days after fertilization. Mesoderm is one of the three primary germ layers that differentiates early in development that collectively gives rise to all subsequent tissues and organs. The heart begins to develop near the head of the embryo in a region known as the cardiogenic area . Following chemical signals called factors from the underlying endoderm (another of the three primary germ layers), the cardiogenic area begins to form two strands called the cardiogenic cords ( Figure 19.36 ). As the cardiogenic cords develop, a lumen rapidly develops within them. At this point, they are referred to as endocardial tubes . The two tubes migrate together and fuse to form a single primitive heart tube . The primitive heart tube quickly forms five distinct regions. From head to tail, these include the truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, and the sinus venosus. Initially, all venous blood flows into the sinus venosus, and contractions propel the blood from tail to head, or from the sinus venosus to the truncus arteriosus. This is a very different pattern from that of an adult. \n\n The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart. The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk. The bulbus cordis develops into the right ventricle. The primitive ventricle forms the left ventricle. The primitive atrium becomes the anterior portions of both the right and left atria, and the two auricles. The sinus venosus develops into the posterior portion of the right atrium, the SA node, and the coronary sinus. \n\n As the primitive heart tube elongates, it begins to fold within the pericardium, eventually forming an S shape, which places the chambers and major vessels into an alignment similar to the adult heart. This process occurs between days 23 and 28. The remainder of the heart development pattern includes development of septa and valves, and remodeling of the actual chambers. Partitioning of the atria and ventricles by the interatrial septum, interventricular septum, and atrioventricular septum is complete by the end of the fifth week, although the fetal blood shunts remain until birth or shortly after. The atrioventricular valves form between weeks five and eight, and the semilunar valves form between weeks five and nine. "}}},{"rowIdx":191,"cells":{"bname":{"kind":"string","value":"microbiology"},"keyterm":{"kind":"string","value":""},"summary":{"kind":"string","value":" Summary 14.1 History of Chemotherapy and Antimicrobial Discovery \n\n Antimicrobial drugs produced by purposeful fermentation and/or contained in plants have been used as traditional medicines in many cultures for millennia. \n\n The purposeful and systematic search for a chemical “magic bullet” that specifically target infectious microbes was initiated by Paul Ehrlich in the early 20th century. \n\n The discovery of the natural antibiotic , penicillin, by Alexander Fleming in 1928 started the modern age of antimicrobial discovery and research. \n\n Sulfanilamide, the first synthetic antimicrobial , was discovered by Gerhard Domagk and colleagues and is a breakdown product of the synthetic dye, prontosil. \n\n 14.2 Fundamentals of Antimicrobial Chemotherapy \n\n Antimicrobial drugs can be bacteriostatic or bactericidal , and these characteristics are important considerations when selecting the most appropriate drug. \n\n The use of narrow-spectrum antimicrobial drugs is preferred in many cases to avoid superinfection and the development of antimicrobial resistance. \n\n Broad-spectrum antimicrobial use is warranted for serious systemic infections when there is no time to determine the causative agent, when narrow-spectrum antimicrobials fail, or for the treatment or prevention of infections with multiple types of microbes. \n\n The dosage and route of administration are important considerations when selecting an antimicrobial to treat and infection. Other considerations include the patient’s age, mass, ability to take oral medications, liver and kidney function, and possible interactions with other drugs the patient may be taking. \n\n 14.3 Mechanisms of Antibacterial Drugs \n\n Antibacterial compounds exhibit selective toxicity , largely due to differences between prokaryotic and eukaryotic cell structure. \n\n Cell wall synthesis inhibitors, including the β-lactams , the glycopeptides , and bacitracin , interfere with peptidoglycan synthesis, making bacterial cells more prone to osmotic lysis. \n\n There are a variety of broad-spectrum, bacterial protein synthesis inhibitors that selectively target the prokaryotic 70S ribosome, including those that bind to the 30S subunit ( aminoglycosides and tetracyclines ) and others that bind to the 50S subunit ( macrolides , lincosamides , chloramphenicol , and oxazolidinones ). \n\n Polymyxins are lipophilic polypeptide antibiotics that target the lipopolysaccharide component of gram-negative bacteria and ultimately disrupt the integrity of the outer and inner membranes of these bacteria. \n\n The nucleic acid synthesis inhibitors rifamycins and fluoroquinolones target bacterial RNA transcription and DNA replication, respectively. \n\n Some antibacterial drugs are antimetabolites , acting as competitive inhibitors for bacterial metabolic enzymes. Sulfonamides and trimethoprim are antimetabolites that interfere with bacterial folic acid synthesis. Isoniazid is an antimetabolite that interferes with mycolic acid synthesis in mycobacteria. \n\n 14.4 Mechanisms of Other Antimicrobial Drugs \n\n Because fungi, protozoans, and helminths are eukaryotic organisms like human cells, it is more challenging to develop antimicrobial drugs that specifically target them. Similarly, it is hard to target viruses because human viruses replicate inside of human cells. \n\n Antifungal drugs interfere with ergosterol synthesis, bind to ergosterol to disrupt fungal cell membrane integrity, or target cell wall-specific components or other cellular proteins. \n\n Antiprotozoan drugs increase cellular levels of reactive oxygen species, interfere with protozoal DNA replication (nuclear versus kDNA, respectively), and disrupt heme detoxification. \n\n Antihelminthic drugs disrupt helminthic and protozoan microtubule formation; block neuronal transmissions; inhibit anaerobic ATP formation and/or oxidative phosphorylation; induce a calcium influx in tapeworms, leading to spasms and paralysis; and interfere with RNA synthesis in schistosomes. \n\n Antiviral drugs inhibit viral entry, inhibit viral uncoating, inhibit nucleic acid biosynthesis, prevent viral escape from endosomes in host cells, and prevent viral release from infected cells. \n\n Because it can easily mutate to become drug resistant, HIV is typically treated with a combination of several antiretroviral drugs , which may include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors , and drugs that interfere with viral binding and fusion to initiate infection. \n\n 14.5 Drug Resistance \n\n Antimicrobial resistance is on the rise and is the result of selection of drug-resistant strains in clinical environments, the overuse and misuse of antibacterials, the use of subtherapeutic doses of antibacterial drugs, and poor patient compliance with antibacterial drug therapies. \n\n Drug resistance genes are often carried on plasmids or in transposons that can undergo vertical transfer easily and between microbes through horizontal gene transfer. \n\n Common modes of antimicrobial drug resistance include drug modification or inactivation, prevention of cellular uptake or efflux, target modification, target overproduction or enzymatic bypass, and target mimicry. \n\n Problematic microbial strains showing extensive antimicrobial resistance are emerging; many of these strains can reside as members of the normal microbiota in individuals but also can cause opportunistic infection. The transmission of many of these highly resistant microbial strains often occurs in clinical settings, but can also be community-acquired. \n\n 14.6 Testing the Effectiveness of Antimicrobials \n\n The Kirby-Bauer disk diffusion test helps determine the susceptibility of a microorganism to various antimicrobial drugs. However, the zones of inhibition measured must be correlated to known standards to determine susceptibility and resistance, and do not provide information on bactericidal versus bacteriostatic activity, or allow for direct comparison of drug potencies. \n\n Antibiograms are useful for monitoring local trends in antimicrobial resistance/susceptibility and for directing appropriate selection of empiric antibacterial therapy. \n\n There are several laboratory methods available for determining the minimum inhibitory concentration (MIC) of an antimicrobial drug against a specific microbe. The minimal bactericidal concentration (MBC) can also be determined, typically as a follow-up experiment to MIC determination using the tube dilution method. \n\n 14.7 Current Strategies for Antimicrobial Discovery \n\n Current research into the development of antimicrobial drugs involves the use of high-throughput screening and combinatorial chemistry technologies. \n\n New technologies are being developed to discover novel antibiotics from soil microorganisms that cannot be cultured by standard laboratory methods. \n\n Additional strategies include searching for antibiotics from sources other than soil, identifying new antibacterial targets, using combinatorial chemistry to develop novel drugs, developing drugs that inhibit resistance mechanisms, and developing drugs that target virulence factors and hold infections in check. "},"intro":{"kind":"string","value":" Chapter Outline 14.1 History of Chemotherapy and Antimicrobial Discovery 14.2 Fundamentals of Antimicrobial Chemotherapy 14.3 Mechanisms of Antibacterial Drugs 14.4 Mechanisms of Other Antimicrobial Drugs 14.5 Drug Resistance 14.6 Testing the Effectiveness of Antimicrobials 14.7 Current Strategies for Antimicrobial Discovery Introduction In nature, some microbes produce substances that inhibit or kill other microbes that might otherwise compete for the same resources. Humans have successfully exploited these abilities, using microbes to mass-produce substances that can be used as antimicrobial drugs. Since their discovery, antimicrobial drugs have saved countless lives, and they remain an essential tool for treating and controlling infectious disease. But their widespread and often unnecessary use has had an unintended side effect: the rise of multidrug-resistant microbial strains. In this chapter, we will discuss how antimicrobial drugs work, why microbes develop resistance, and what health professionals can do to encourage responsible use of antimicrobials. "},"questions":{"kind":"list like","value":[{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"A few decades later , German scientists Josef Klarer , Fritz Mietzsch , and Gerhard Domagk discovered the antibacterial activity of a synthetic dye , prontosil , that could treat streptococcal and staphylococcal infections in mice . Domagk ’ s own daughter was one of the first human recipients of the drug , which completely cured her of a severe streptococcal infection that had resulted from a poke with an embroidery needle . Gerhard Domagk ( 1895 – 1964 ) was awarded the Nobel Prize in Medicine in 1939 for his work with prontosil and sulfanilamide , the active breakdown product of prontosil in the body . <hl> Sulfanilamide , the first synthetic antimicrobial created , served as the foundation for the chemical development of a family of sulfa drugs . <hl> A synthetic antimicrobial is a drug that is developed from a chemical not found in nature . The success of the sulfa drugs led to the discovery and production of additional important classes of synthetic antimicrobials , including the quinolines and oxazolidinones .","hl_sentences":"Sulfanilamide , the first synthetic antimicrobial created , served as the foundation for the chemical development of a family of sulfa drugs .","question":{"cloze_format":"The antimicrobial drug ___ is synthetic.","normal_format":"Which of the following antimicrobial drugs is synthetic?","question_choices":["sulfanilamide","penicillin","actinomycin","neomycin"],"question_id":"fs-id1167659391042","question_text":"Which of the following antimicrobial drugs is synthetic?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"<hl> The risk associated with using broad-spectrum antimicrobials is that they will also target a broad spectrum of the normal microbiota , increasing the risk of a superinfection , a secondary infection in a patient having a preexisting infection . <hl> <hl> A superinfection develops when the antibacterial intended for the preexisting infection kills the protective microbiota , allowing another pathogen resistant to the antibacterial to proliferate and cause a secondary infection ( Figure 14.6 ) . <hl> Common examples of superinfections that develop as a result of antimicrobial usage include yeast infections ( candidiasis ) and pseudomembranous colitis caused by Clostridium difficile , which can be fatal .","hl_sentences":"The risk associated with using broad-spectrum antimicrobials is that they will also target a broad spectrum of the normal microbiota , increasing the risk of a superinfection , a secondary infection in a patient having a preexisting infection . A superinfection develops when the antibacterial intended for the preexisting infection kills the protective microbiota , allowing another pathogen resistant to the antibacterial to proliferate and cause a secondary infection ( Figure 14.6 ) .","question":{"cloze_format":"The combination that would most likely contribute to the development of a superinfection is the ___ .","normal_format":"Which of the following combinations would most likely contribute to the development of a superinfection?","question_choices":["long-term use of narrow-spectrum antimicrobials","long-term use of broad-spectrum antimicrobials","short-term use of narrow-spectrum antimicrobials","short-term use of broad-spectrum antimicrobials"],"question_id":"fs-id1167660261866","question_text":"Which of the following combinations would most likely contribute to the development of a superinfection?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> The route of administration , the method used to introduce a drug into the body , is also an important consideration for drug therapy . <hl> <hl> Drugs that can be administered orally are generally preferred because patients can more conveniently take these drugs at home . <hl> However , some drugs are not absorbed easily from the gastrointestinal ( GI ) tract into the bloodstream . These drugs are often useful for treating diseases of the intestinal tract , such as tapeworms treated with niclosamide , or for decontaminating the bowel , as with colistin . Some drugs that are not absorbed easily , such as bacitracin , polymyxin , and several antifungals , are available as topical preparations for treatment of superficial skin infections . Sometimes , patients may not initially be able to take oral medications because of their illness ( e . g . , vomiting , intubation for respirator ) . When this occurs , and when a chosen drug is not absorbed in the GI tract , administration of the drug by a parenteral route ( intravenous or intramuscular injection ) is preferred and typically is performed in health-care settings . For most drugs , the plasma levels achieved by intravenous administration is substantially higher than levels achieved by oral or intramuscular administration , and this can also be an important consideration when choosing the route of administration for treating an infection ( Figure 14.7 ) .","hl_sentences":"The route of administration , the method used to introduce a drug into the body , is also an important consideration for drug therapy . Drugs that can be administered orally are generally preferred because patients can more conveniently take these drugs at home .","question":{"cloze_format":"The route of administration that would be appropriate and convenient for home administration of an antimicrobial to treat a systemic infection is ___.","normal_format":"Which of the following routes of administration would be appropriate and convenient for home administration of an antimicrobial to treat a systemic infection?","question_choices":["oral","intravenous","topical","parenteral"],"question_id":"fs-id1167660323716","question_text":"Which of the following routes of administration would be appropriate and convenient for home administration of an antimicrobial to treat a systemic infection?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"The spectrum of activity of an antibacterial drug relates to diversity of targeted bacteria . A narrow-spectrum antimicrobial targets only specific subsets of bacterial pathogens . For example , some narrow-spectrum drugs only target gram-positive bacteria , whereas others target only gram-negative bacteria . <hl> If the pathogen causing an infection has been identified , it is best to use a narrow-spectrum antimicrobial and minimize collateral damage to the normal microbiota . <hl> A broad-spectrum antimicrobial targets a wide variety of bacterial pathogens , including both gram-positive and gram-negative species , and is frequently used as empiric therapy to cover a wide range of potential pathogens while waiting on the laboratory identification of the infecting pathogen . Broad-spectrum antimicrobials are also used for polymicrobic infections ( mixed infection with multiple bacterial species ) , or as prophylactic prevention of infections with surgery / invasive procedures . Finally , broad-spectrum antimicrobials may be selected to treat an infection when a narrow-spectrum drug fails because of development of drug resistance by the target pathogen . Most people associate the term chemotherapy with treatments for cancer . However , chemotherapy is actually a broader term that refers to any use of chemicals or drugs to treat disease . Chemotherapy may involve drugs that target cancerous cells or tissues , or it may involve antimicrobial drugs that target infectious microorganisms . <hl> Antimicrobial drugs typically work by destroying or interfering with microbial structures and enzymes , either killing microbial cells or inhibiting of their growth . <hl> But before we examine how these drugs work , we will briefly explore the history of humans ’ use of antimicrobials for the purpose of chemotherapy .","hl_sentences":"If the pathogen causing an infection has been identified , it is best to use a narrow-spectrum antimicrobial and minimize collateral damage to the normal microbiota . Antimicrobial drugs typically work by destroying or interfering with microbial structures and enzymes , either killing microbial cells or inhibiting of their growth .","question":{"cloze_format":"The clinical situation that would be appropriate for treatment with a narrow-spectrum antimicrobial drug is ___ .","normal_format":"Which clinical situation would be appropriate for treatment with a narrow-spectrum antimicrobial drug?","question_choices":["treatment of a polymicrobic mixed infection in the intestine","prophylaxis against infection after a surgical procedure","treatment of strep throat caused by culture identified Streptococcus pyogenes","empiric therapy of pneumonia while waiting for culture results"],"question_id":"fs-id1167660131926","question_text":"Which clinical situation would be appropriate for treatment with a narrow-spectrum antimicrobial drug?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> An important quality for an antimicrobial drug is selective toxicity , meaning that it selectively kills or inhibits the growth of microbial targets while causing minimal or no harm to the host . <hl> Most antimicrobial drugs currently in clinical use are antibacterial because the prokaryotic cell provides a greater variety of unique targets for selective toxicity , in comparison to fungi , parasites , and viruses . Each class of antibacterial drugs has a unique mode of action ( the way in which a drug affects microbes at the cellular level ) , and these are summarized in Figure 14.9 and Table 14.1 .","hl_sentences":"An important quality for an antimicrobial drug is selective toxicity , meaning that it selectively kills or inhibits the growth of microbial targets while causing minimal or no harm to the host .","question":{"cloze_format":"The terms that refers to the ability of an antimicrobial drug to harm the target microbe without harming the host is ___.","normal_format":"Which of the following terms refers to the ability of an antimicrobial drug to harm the target microbe without harming the host?","question_choices":["mode of action","therapeutic level","spectrum of activity","selective toxicity"],"question_id":"fs-id1167661429067","question_text":"Which of the following terms refers to the ability of an antimicrobial drug to harm the target microbe without harming the host?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"<hl> Similar to the penicillins , cephalosporins contain a β-lactam ring ( Figure 14.10 ) and block the transpeptidase activity of penicillin-binding proteins . <hl> However , the β-lactam ring of cephalosporins is fused to a six-member ring , rather than the five-member ring found in penicillins . This chemical difference provides cephalosporins with an increased resistance to enzymatic inactivation by β-lactamases . The drug cephalosporin C was originally isolated from the fungus Cephalosporium acremonium in the 1950s and has a similar spectrum of activity to that of penicillin against gram-positive bacteria but is active against more gram-negative bacteria than penicillin . Another important structural difference is that cephalosporin C possesses two R groups , compared with just one R group for penicillin , and this provides for greater diversity in chemical alterations and development of semisynthetic cephalosporins . The family of semisynthetic cephalosporins is much larger than the penicillins , and these drugs have been classified into generations based primarily on their spectrum of activity , increasing in spectrum from the narrow-spectrum , first-generation cephalosporins to the broad-spectrum , fourth-generation cephalosporins . A new fifth-generation cephalosporin has been developed that is active against methicillin-resistant Staphylococcus aureus ( MRSA ) . <hl> Penicillin , the first antibiotic discovered , is one of several antibacterials within a class called β-lactams . <hl> <hl> This group of compounds includes the penicillins , cephalosporins , monobactams , and carbapenems , and is characterized by the presence of a β-lactam ring found within the central structure of the drug molecule ( Figure 14.10 ) . <hl> The β-lactam antibacterials block the crosslinking of peptide chains during the biosynthesis of new peptidoglycan in the bacterial cell wall . They are able to block this process because the β-lactam structure is similar to the structure of the peptidoglycan subunit component that is recognized by the crosslinking transpeptidase enzyme , also known as a penicillin-binding protein ( PBP ) . Although the β-lactam ring must remain unchanged for these drugs to retain their antibacterial activity , strategic chemical changes to the R groups have allowed for development of a wide variety of semisynthetic β-lactam drugs with increased potency , expanded spectrum of activity , and longer half-lives for better dosing , among other characteristics .","hl_sentences":"Similar to the penicillins , cephalosporins contain a β-lactam ring ( Figure 14.10 ) and block the transpeptidase activity of penicillin-binding proteins . Penicillin , the first antibiotic discovered , is one of several antibacterials within a class called β-lactams . This group of compounds includes the penicillins , cephalosporins , monobactams , and carbapenems , and is characterized by the presence of a β-lactam ring found within the central structure of the drug molecule ( Figure 14.10 ) .","question":{"cloze_format":"___ is not a type of β-lactam antimicrobial.","normal_format":"Which of the following is not a type of β-lactam antimicrobial?","question_choices":["penicillins","glycopeptides","cephalosporins","monobactams"],"question_id":"fs-id1167661298496","question_text":"Which of the following is not a type of β-lactam antimicrobial?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> The drug chloramphenicol represents yet another structurally distinct class of antibacterials that also bind to the 50S ribosome , inhibiting peptide bond formation . <hl> Chloramphenicol , produced by Streptomyces venezuelae , was discovered in 1947 ; in 1949 , it became the first broad-spectrum antibiotic that was approved by the FDA . Although it is a natural antibiotic , it is also easily synthesized and was the first antibacterial drug synthetically mass produced . As a result of its mass production , broad-spectrum coverage , and ability to penetrate into tissues efficiently , chloramphenicol was historically used to treat a wide range of infections , from meningitis to typhoid fever to conjunctivitis . Unfortunately , serious side effects , such as lethal gray baby syndrome , and suppression of bone marrow production , have limited its clinical role . Chloramphenicol also causes anemia in two different ways . <hl> One mechanism involves the targeting of mitochondrial ribosomes within hematopoietic stem cells , causing a reversible , dose-dependent suppression of blood cell production . <hl> Once chloramphenicol dosing is discontinued , blood cell production returns to normal . This mechanism highlights the similarity between 70S ribosomes of bacteria and the 70S ribosomes within our mitochondria . The second mechanism of anemia is idiosyncratic ( i . e . , the mechanism is not understood ) , and involves an irreversible lethal loss of blood cell production known as aplastic anemia . This mechanism of aplastic anemia is not dose dependent and can develop after therapy has stopped . Because of toxicity concerns , chloramphenicol usage in humans is now rare in the United States and is limited to severe infections unable to be treated by less toxic antibiotics . Because its side effects are much less severe in animals , it is used in veterinary medicine . <hl> The lincosamides include the naturally produced lincomycin and semisynthetic clindamycin . <hl> <hl> Although structurally distinct from macrolides , lincosamides are similar in their mode of action to the macrolides through binding to the 50S ribosomal subunit and preventing peptide bond formation . <hl> Lincosamides are particularly active against streptococcal and staphylococcal infections .","hl_sentences":"The drug chloramphenicol represents yet another structurally distinct class of antibacterials that also bind to the 50S ribosome , inhibiting peptide bond formation . One mechanism involves the targeting of mitochondrial ribosomes within hematopoietic stem cells , causing a reversible , dose-dependent suppression of blood cell production . The lincosamides include the naturally produced lincomycin and semisynthetic clindamycin . Although structurally distinct from macrolides , lincosamides are similar in their mode of action to the macrolides through binding to the 50S ribosomal subunit and preventing peptide bond formation .","question":{"cloze_format":"___ does not bind to the 50S ribosomal subunit.","normal_format":"Which of the following does not bind to the 50S ribosomal subunit?","question_choices":["tetracyclines","lincosamides","macrolides","chloramphenicol"],"question_id":"fs-id1167661403800","question_text":"Which of the following does not bind to the 50S ribosomal subunit?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"One member of the quinolone family , a group of synthetic antimicrobials , is nalidixic acid . It was discovered in 1962 as a byproduct during the synthesis of chloroquine , an antimalarial drug . <hl> Nalidixic acid selectively inhibits the activity of bacterial DNA gyrase , blocking DNA replication . <hl> Chemical modifications to the original quinolone backbone have resulted in the production of fluoroquinolones , like ciprofloxacin and levofloxacin , which also inhibit the activity of DNA gyrase . Ciprofloxacin and levofloxacin are effective against a broad spectrum of gram-positive or gram-negative bacteria , and are among the most commonly prescribed antibiotics used to treat a wide range of infections , including urinary tract infections , respiratory infections , abdominal infections , and skin infections . However , despite their selective toxicity against DNA gyrase , side effects associated with different fluoroquinolones include phototoxicity , neurotoxicity , cardiotoxicity , glucose metabolism dysfunction , and increased risk for tendon rupture .","hl_sentences":"Nalidixic acid selectively inhibits the activity of bacterial DNA gyrase , blocking DNA replication .","question":{"cloze_format":"The antimicrobial that inhibits the activity of DNA gyrase is ___ .","normal_format":"Which of the following antimicrobials inhibits the activity of DNA gyrase?","question_choices":["polymyxin B","clindamycin","nalidixic acid","rifampin"],"question_id":"fs-id1167661401393","question_text":"Which of the following antimicrobials inhibits the activity of DNA gyrase?"},"references_are_paraphrase":null},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"<hl> Beyond targeting ergosterol in fungal cell membranes , there are a few antifungal drugs that target other fungal structures ( Figure 14.14 ) . <hl> The echinocandins , including caspofungin , are a group of naturally produced antifungal compounds that block the synthesis of β ( 1 → 3 ) glucan found in fungal cell walls but not found in human cells . This drug class has the nickname “ penicillin for fungi . ” Caspofungin is used for the treatment of aspergillosis as well as systemic yeast infections . The most common mode of action for antifungal drugs is the disruption of the cell membrane . Antifungals take advantage of small differences between fungi and humans in the biochemical pathways that synthesize sterols . The sterols are important in maintaining proper membrane fluidity and , hence , proper function of the cell membrane . For most fungi , the predominant membrane sterol is ergosterol . <hl> Because human cell membranes use cholesterol , instead of ergosterol , antifungal drugs that target ergosterol synthesis are selectively toxic ( Figure 14.13 ) . <hl>","hl_sentences":"Beyond targeting ergosterol in fungal cell membranes , there are a few antifungal drugs that target other fungal structures ( Figure 14.14 ) . Because human cell membranes use cholesterol , instead of ergosterol , antifungal drugs that target ergosterol synthesis are selectively toxic ( Figure 14.13 ) .","question":{"cloze_format":"___ is not an appropriate target for antifungal drugs.","normal_format":"Which of the following is not an appropriate target for antifungal drugs?","question_choices":["ergosterol","chitin","cholesterol","β(1→3) glucan"],"question_id":"fs-id1167661364965","question_text":"Which of the following is not an appropriate target for antifungal drugs?"},"references_are_paraphrase":null},{"answer":{"ans_choice":1,"ans_text":"B"},"bloom":null,"hl_context":"<hl> The avermectins are members of the macrolide family that were first discovered from a Japanese soil isolate , Streptomyces avermectinius . <hl> <hl> A more potent semisynthetic derivative of avermectin is ivermectin , which binds to glutamate-gated chloride channels specific to invertebrates including helminths , blocking neuronal transmission and causing starvation , paralysis , and death of the worms . <hl> Ivermectin is used to treat roundworm diseases , including onchocerciasis ( also called river blindness , caused by the worm Onchocerca volvulus ) and strongyloidiasis ( caused by the worm Strongyloides stercoralis or S . fuelleborni ) . Ivermectin also can also treat parasitic insects like mites , lice , and bed bugs , and is nontoxic to humans .","hl_sentences":"The avermectins are members of the macrolide family that were first discovered from a Japanese soil isolate , Streptomyces avermectinius . A more potent semisynthetic derivative of avermectin is ivermectin , which binds to glutamate-gated chloride channels specific to invertebrates including helminths , blocking neuronal transmission and causing starvation , paralysis , and death of the worms .","question":{"cloze_format":"The drug class that specifically inhibits neuronal transmission in helminths is ___.","normal_format":"Which of the following drug classes specifically inhibits neuronal transmission in helminths?","question_choices":["quinolines","avermectins","amantadines","imidazoles"],"question_id":"fs-id1167664003689","question_text":"Which of the following drug classes specifically inhibits neuronal transmission in helminths?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> The reverse transcriptase inhibitors block the early step of converting viral RNA genome into DNA , and can include competitive nucleoside analog inhibitors ( e . g . , azidothymidine / zidovudine , or AZT ) and non-nucleoside noncompetitive inhibitors ( e . g . , etravirine ) that bind reverse transcriptase and cause an inactivating conformational change . <hl> Drugs called protease inhibitors ( e . g . , ritonavir ) block the processing of viral proteins and prevent viral maturation . Protease inhibitors are also being developed for the treatment of other viral types . 18 For example , simeprevir ( Olysio ) has been approved for the treatment of hepatitis C and is administered with ribavirin and interferon in combination therapy . The integrase inhibitors ( e . g . , raltegravir ) , block the activity of the HIV integrase responsible for the recombination of a DNA copy of the viral genome into the host cell chromosome . Additional drug classes for HIV treatment include the CCR 5 antagonists and the fusion inhibitors ( e . g . , enfuviritide ) , which prevent the binding of HIV to the host cell coreceptor ( chemokine receptor type 5 [ CCR 5 ] ) and the merging of the viral envelope with the host cell membrane , respectively . Table 14.10 shows the various therapeutic classes of antiviral drugs , categorized by mode of action , with examples of each . 18 B . L . Pearlman . “ Protease Inhibitors for the Treatment of Chronic Hepatitis C Genotype - 1 Infection : The New Standard of Care . ” Lancet Infectious Diseases 12 no . 9 ( 2012 ): 717 – 728 .","hl_sentences":"The reverse transcriptase inhibitors block the early step of converting viral RNA genome into DNA , and can include competitive nucleoside analog inhibitors ( e . g . , azidothymidine / zidovudine , or AZT ) and non-nucleoside noncompetitive inhibitors ( e . g . , etravirine ) that bind reverse transcriptase and cause an inactivating conformational change .","question":{"cloze_format":"___ is a nucleoside analog commonly used as a reverse transcriptase inhibitor in the treatment of HIV.","normal_format":"Which of the following is a nucleoside analog commonly used as a reverse transcriptase inhibitor in the treatment of HIV?","question_choices":["acyclovir","ribavirin","adenine-arabinoside","azidothymidine"],"question_id":"fs-id1167661294856","question_text":"Which of the following is a nucleoside analog commonly used as a reverse transcriptase inhibitor in the treatment of HIV?"},"references_are_paraphrase":null},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> Artemisinin , a plant-derived antifungal first discovered by Chinese scientists in the 1970s , is quite effective against malaria . <hl> Semisynthetic derivatives of artemisinin are more water soluble than the natural version , which makes them more bioavailable . <hl> Although the exact mechanism of action is unclear , artemisinins appear to act as prodrugs that are metabolized by target cells to produce reactive oxygen species ( ROS ) that damage target cells . <hl> Due to the rise in resistance to antimalarial drugs , artemisinins are also commonly used in combination with other antimalarial compounds in artemisinin-based combination therapy ( ACT ) .","hl_sentences":"Artemisinin , a plant-derived antifungal first discovered by Chinese scientists in the 1970s , is quite effective against malaria . Although the exact mechanism of action is unclear , artemisinins appear to act as prodrugs that are metabolized by target cells to produce reactive oxygen species ( ROS ) that damage target cells .","question":{"cloze_format":"___ is an antimalarial drug that is thought to increase ROS levels in target cells.","normal_format":"Which of the following is an antimalarial drug that is thought to increase ROS levels in target cells?","question_choices":["artemisinin","amphotericin b","praziquantel","pleconaril"],"question_id":"fs-id1167659329127","question_text":"Which of the following is an antimalarial drug that is thought to increase ROS levels in target cells?"},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"<hl> Resistance genes may code for enzymes that chemically modify an antimicrobial , thereby inactivating it , or destroy an antimicrobial through hydrolysis . <hl> Resistance to many types of antimicrobials occurs through this mechanism . For example , aminoglycoside resistance can occur through enzymatic transfer of chemical groups to the drug molecule , impairing the binding of the drug to its bacterial target . For β-lactams , bacterial resistance can involve the enzymatic hydrolysis of the β-lactam bond within the β-lactam ring of the drug molecule . Once the β-lactam bond is broken , the drug loses its antibacterial activity . <hl> This mechanism of resistance is mediated by β-lactamases , which are the most common mechanism of β-lactam resistance . <hl> <hl> Inactivation of rifampin commonly occurs through glycosylation , phosphorylation , or adenosine diphosphate ( ADP ) ribosylation , and resistance to macrolides and lincosamides can also occur due to enzymatic inactivation of the drug or modification . <hl>","hl_sentences":"Resistance genes may code for enzymes that chemically modify an antimicrobial , thereby inactivating it , or destroy an antimicrobial through hydrolysis . This mechanism of resistance is mediated by β-lactamases , which are the most common mechanism of β-lactam resistance . Inactivation of rifampin commonly occurs through glycosylation , phosphorylation , or adenosine diphosphate ( ADP ) ribosylation , and resistance to macrolides and lincosamides can also occur due to enzymatic inactivation of the drug or modification .","question":{"cloze_format":"The resistance mechanism that describes the function of β-lactamase is the ___ .","normal_format":"Which of the following resistance mechanisms describes the function of β-lactamase?","question_choices":["efflux pump","target mimicry","drug inactivation","target overproduction"],"question_id":"fs-id1167661397905","question_text":"Which of the following resistance mechanisms describes the function of β-lactamase?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"From a clinical perspective , our greatest concerns are multidrug-resistant microbes ( MDRs ) and cross resistance . MDRs are colloquially known as “ superbugs ” and carry one or more resistance mechanism ( s ) , making them resistant to multiple antimicrobials . <hl> In cross-resistance , a single resistance mechanism confers resistance to multiple antimicrobial drugs . <hl> <hl> For example , having an efflux pump that can export multiple antimicrobial drugs is a common way for microbes to be resistant to multiple drugs by using a single resistance mechanism . <hl> In recent years , several clinically important superbugs have emerged , and the CDC reports that superbugs are responsible for more than 2 million infections in the US annually , resulting in at least 23,000 fatalities . 19 Several of the superbugs discussed in the following sections have been dubbed the ESKAPE pathogens . This acronym refers to the names of the pathogens ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa and Enterobacter spp . ) but it is also fitting in that these pathogens are able to “ escape ” many conventional forms of antimicrobial therapy . As such , infections by ESKAPE pathogens can be difficult to treat and they cause a large number of nosocomial infections . 19 Centers for Disease Control and Prevention . “ Antibiotic / Antimicrobial Resistance . ” http://www.cdc.gov/drugresistance/index.html . Accessed June 2 , 2016 .","hl_sentences":"In cross-resistance , a single resistance mechanism confers resistance to multiple antimicrobial drugs . For example , having an efflux pump that can export multiple antimicrobial drugs is a common way for microbes to be resistant to multiple drugs by using a single resistance mechanism .","question":{"cloze_format":"The resistance mechanism that is commonly effective against a wide range of antimicrobials in multiple classes is the ___.","normal_format":"Which of the following resistance mechanisms is commonly effective against a wide range of antimicrobials in multiple classes?","question_choices":["efflux pump","target mimicry","target modification","target overproduction"],"question_id":"fs-id1167661424151","question_text":"Which of the following resistance mechanisms is commonly effective against a wide range of antimicrobials in multiple classes?"},"references_are_paraphrase":0},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"Microbes may develop resistance mechanisms that involve inhibiting the accumulation of an antimicrobial drug , which then prevents the drug from reaching its cellular target . This strategy is common among gram-negative pathogens and can involve changes in outer membrane lipid composition , porin channel selectivity , and / or porin channel concentrations . For example , a common mechanism of carbapenem resistance among Pseudomonas aeruginosa is to decrease the amount of its OprD porin , which is the primary portal of entry for carbapenems through the outer membrane of this pathogen . <hl> Additionally , many gram-positive and gram-negative pathogenic bacteria produce efflux pump s that actively transport an antimicrobial drug out of the cell and prevent the accumulation of drug to a level that would be antibacterial . <hl> <hl> For example , resistance to β-lactams , tetracyclines , and fluoroquinolones commonly occurs through active efflux out of the cell , and it is rather common for a single efflux pump to have the ability to translocate multiple types of antimicrobials . <hl>","hl_sentences":"Additionally , many gram-positive and gram-negative pathogenic bacteria produce efflux pump s that actively transport an antimicrobial drug out of the cell and prevent the accumulation of drug to a level that would be antibacterial . For example , resistance to β-lactams , tetracyclines , and fluoroquinolones commonly occurs through active efflux out of the cell , and it is rather common for a single efflux pump to have the ability to translocate multiple types of antimicrobials .","question":{"cloze_format":"The resistance mechanism that is the most nonspecific to a particular class of antimicrobials is the ___.","normal_format":"Which of the following resistance mechanisms is the most nonspecific to a particular class of antimicrobials?","question_choices":["drug modification","target mimicry","target modification","efflux pump"],"question_id":"fs-id1167661737849","question_text":"Which of the following resistance mechanisms is the most nonspecific to a particular class of antimicrobials?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> The occurrence of carbapenem-resistant Enterobacteriaceae ( CRE ) and carbapenem resistance among other gram-negative bacteria ( e . g . , P . aeruginosa , Acinetobacter baumannii , Stenotrophomonas maltophila ) is a growing health-care concern . <hl> These pathogens develop resistance to carbapenems through a variety of mechanisms , including production of carbapenemases ( broad-spectrum β-lactamases that inactivate all β-lactams , including carbapenems ) , active efflux of carbapenems out of the cell , and / or prevention of carbapenem entry through porin channels . Similar to concerns with ESBLs , carbapenem-resistant , gram-negative pathogens are usually resistant to multiple classes of antibacterials , and some have even developed pan-resistance ( resistance to all available antibacterials ) . Infections with carbapenem-resistant , gram-negative pathogens commonly occur in health-care settings through interaction with contaminated individuals or medical devices , or as a result of surgery . <hl> Gram-negative pathogens that produce extended-spectrum β-lactamases ( ESBLs ) show resistance well beyond just penicillins . <hl> The spectrum of β-lactams inactivated by ESBLs provides for resistance to all penicillins , cephalosporins , monobactams , and the β-lactamase-inhibitor combinations , but not the carbapenems . An even greater concern is that the genes encoding for ESBLs are usually found on mobile plasmids that also contain genes for resistance to other drug classes ( e . g . , fluoroquinolones , aminoglycosides , tetracyclines ) , and may be readily spread to other bacteria by horizontal gene transfer . <hl> These multidrug-resistant bacteria are members of the intestinal microbiota of some individuals , but they are also important causes of opportunistic infections in hospitalized patients , from whom they can be spread to other people . <hl> <hl> Vancomycin is only effective against gram-positive organisms , and it is used to treat wound infections , septic infections , endocarditis , and meningitis that are caused by pathogens resistant to other antibiotics . <hl> It is considered one of the last lines of defense against such resistant infections , including MRSA . With the rise of antibiotic resistance in the 1970s and 1980s , vancomycin use increased , and it is not surprising that we saw the emergence and spread of vancomycin-resistant enterococci ( VRE ) , vancomycin-resistant S . aureus ( VRSA ) , and vancomycin-intermediate S . aureus ( VISA ) . The mechanism of vancomycin resistance among enterococci is target modification involving a structural change to the peptide component of the peptidoglycan subunits , preventing vancomycin from binding . These strains are typically spread among patients in clinical settings by contact with health-care workers and contaminated surfaces and medical equipment . Methicillin , a semisynthetic penicillin , was designed to resist inactivation by β-lactamases . Unfortunately , soon after the introduction of methicillin to clinical practice , methicillin-resistant strains of S . aureus appeared and started to spread . The mechanism of resistance , acquisition of a new low-affinity PBP , provided S . aureus with resistance to all available β-lactams . <hl> Strains of methicillin-resistant S . aureus ( MRSA ) are widespread opportunistic pathogens and a particular concern for skin and other wound infections , but may also cause pneumonia and septicemia . <hl> <hl> Although originally a problem in health-care settings ( hospital-acquired MRSA [ HA-MRSA ] ) , MRSA infections are now also acquired through contact with contaminated members of the general public , called community-associated MRSA ( CA-MRSA ) . <hl> Approximately one-third of the population carries S . aureus as a member of their normal nasal microbiota without illness , and about 6 % of these strains are methicillin resistant . 20 21 20 A . S . Kalokhe et al . “ Multidrug-Resistant Tuberculosis Drug Susceptibility and Molecular Diagnostic Testing : A Review of the Literature . American Journal of the Medical Sciences 345 no . 2 ( 2013 ): 143 – 148 . 21 Centers for Disease Control and Prevention . “ Methicillin-Resistant Staphylococcus aureus ( MRSA ): General Information About MRSA in the Community . ” http://www.cdc.gov/mrsa/community/index.html . Accessed June 2 , 2016","hl_sentences":"The occurrence of carbapenem-resistant Enterobacteriaceae ( CRE ) and carbapenem resistance among other gram-negative bacteria ( e . g . , P . aeruginosa , Acinetobacter baumannii , Stenotrophomonas maltophila ) is a growing health-care concern . Gram-negative pathogens that produce extended-spectrum β-lactamases ( ESBLs ) show resistance well beyond just penicillins . These multidrug-resistant bacteria are members of the intestinal microbiota of some individuals , but they are also important causes of opportunistic infections in hospitalized patients , from whom they can be spread to other people . Vancomycin is only effective against gram-positive organisms , and it is used to treat wound infections , septic infections , endocarditis , and meningitis that are caused by pathogens resistant to other antibiotics . Strains of methicillin-resistant S . aureus ( MRSA ) are widespread opportunistic pathogens and a particular concern for skin and other wound infections , but may also cause pneumonia and septicemia . Although originally a problem in health-care settings ( hospital-acquired MRSA [ HA-MRSA ] ) , MRSA infections are now also acquired through contact with contaminated members of the general public , called community-associated MRSA ( CA-MRSA ) .","question":{"cloze_format":"The type of drug-resistant bacteria that does not typically persist in individuals as a member of their intestinal microbiota is ___.","normal_format":"Which of the following types of drug-resistant bacteria do not typically persist in individuals as a member of their intestinal microbiota?","question_choices":["MRSA","VRE","CRE","ESBL-producing bacteria"],"question_id":"fs-id1167663931670","question_text":"Which of the following types of drug-resistant bacteria do not typically persist in individuals as a member of their intestinal microbiota?"},"references_are_paraphrase":0},{"answer":{"ans_choice":0,"ans_text":"A"},"bloom":null,"hl_context":"<hl> The Kirby-Bauer disk diffusion test has long been used as a starting point for determining the susceptibility of specific microbes to various antimicrobial drugs . <hl> The Kirby-Bauer assay starts with a Mueller-Hinton agar plate on which a confluent lawn is inoculated with a patient ’ s isolated bacterial pathogen . Filter paper disks impregnated with known amounts of antibacterial drugs to be tested are then placed on the agar plate . As the bacterial inoculum grows , antibiotic diffuses from the circular disk into the agar and interacts with the growing bacteria . Antibacterial activity is observed as a clear circular zone of inhibition around the drug-impregnated disk , similar to the disk-diffusion assay depicted in Figure 13.31 . <hl> The diameter of the zone of inhibition , measured in millimeters and compared to a standardized chart , determines the susceptibility or resistance of the bacterial pathogen to the drug . <hl>","hl_sentences":"The Kirby-Bauer disk diffusion test has long been used as a starting point for determining the susceptibility of specific microbes to various antimicrobial drugs . The diameter of the zone of inhibition , measured in millimeters and compared to a standardized chart , determines the susceptibility or resistance of the bacterial pathogen to the drug .","question":{"cloze_format":"In the Kirby-Bauer disk diffusion test, the _______ of the zone of inhibition is measured and used for interpretation.","normal_format":"In the Kirby-Bauer disk diffusion test, what of the zone of inhibition is measured and used for interpretation?","question_choices":["diameter","microbial population","circumference","depth"],"question_id":"fs-id1167659011346","question_text":"In the Kirby-Bauer disk diffusion test, the _______ of the zone of inhibition is measured and used for interpretation."},"references_are_paraphrase":0},{"answer":{"ans_choice":2,"ans_text":"C"},"bloom":null,"hl_context":"<hl> As discussed , the limitations of the Kirby-Bauer disk diffusion test do not allow for a direct comparison of antibacterial potencies to guide selection of the best therapeutic choice . <hl> <hl> However , antibacterial dilution tests can be used to determine a particular drug ’ s minimal inhibitory concentration ( MIC ) , the lowest concentration of drug that inhibits visible bacterial growth , and minimal bactericidal concentration ( MBC ) , the lowest drug concentration that kills ≥ 99.9 % of the starting inoculum . <hl> Determining these concentrations helps identify the correct drug for a particular pathogen . For the macrobroth dilution assay , a dilution series of the drug in broth is made in test tubes and the same number of cells of a test bacterial strain is added to each tube ( Figure 14.19 ) . The MIC is determined by examining the tubes to find the lowest drug concentration that inhibits visible growth ; this is observed as turbidity ( cloudiness ) in the broth . Tubes with no visible growth are then inoculated onto agar media without antibiotic to determine the MBC . Generally , serum levels of an antibacterial should be at least three to five times above the MIC for treatment of an infection .","hl_sentences":"As discussed , the limitations of the Kirby-Bauer disk diffusion test do not allow for a direct comparison of antibacterial potencies to guide selection of the best therapeutic choice . However , antibacterial dilution tests can be used to determine a particular drug ’ s minimal inhibitory concentration ( MIC ) , the lowest concentration of drug that inhibits visible bacterial growth , and minimal bactericidal concentration ( MBC ) , the lowest drug concentration that kills ≥ 99.9 % of the starting inoculum .","question":{"cloze_format":"The technique that cannot be used to determine the minimum inhibitory concentration of an antimicrobial drug against a particular microbe is the ___.","normal_format":"Which of the following techniques cannot be used to determine the minimum inhibitory concentration of an antimicrobial drug against a particular microbe?","question_choices":["Etest","microbroth dilution test","Kirby-Bauer disk diffusion test","macrobroth dilution test"],"question_id":"fs-id1167663964408","question_text":"Which of the following techniques cannot be used to determine the minimum inhibitory concentration of an antimicrobial drug against a particular microbe?"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"Recently , studies have shown that antibiograms are useful tools in the decision-making process of selecting appropriate empiric therapy . <hl> An antibiogram is a compilation of local antibiotic susceptibility data broken down by bacterial pathogen . <hl> In a November 2014 study published in the journal Infection Control and Hospital Epidemiology , researchers determined that 85 % of the prescriptions ordered in skilled nursing facilities were decided upon empirically , but only 35 % of those prescriptions were deemed appropriate when compared with the eventual pathogen identification and susceptibility profile obtained from the clinical laboratory . However , in one nursing facility where use of antibiograms was implemented to direct selection of empiric therapy , appropriateness of empiric therapy increased from 32 % before antibiogram implementation to 45 % after implementation of antibiograms . 24 Although these data are preliminary , they do suggest that health-care facilities can reduce the number of inappropriate prescriptions by using antibiograms to select empiric therapy , thus benefiting patients and minimizing opportunities for antimicrobial resistance to develop . 24 J . P . Furuno et al . “ Using Antibiograms to Improve Antibiotic Prescribing in Skilled Nursing Facilities . ” Infection Control and Hospital Epidemiology 35 no . Suppl S3 ( 2014 ): S56 – 61 .","hl_sentences":"An antibiogram is a compilation of local antibiotic susceptibility data broken down by bacterial pathogen .","question":{"cloze_format":"The utility of an antibiogram is that it shows antimicrobial susceptibility trends ___ .","normal_format":"How the utility of an antibiogram shows antimicrobial susceptibility trends?","question_choices":["over a large geographic area.","for an individual patient.","in research laboratory strains.","in a localized population."],"question_id":"fs-id1167661481139","question_text":"The utility of an antibiogram is that it shows antimicrobial susceptibility trends"},"references_are_paraphrase":null},{"answer":{"ans_choice":3,"ans_text":"D"},"bloom":null,"hl_context":"<hl> Although soils have been widely examined , other environmental niches have not been tested as fully . <hl> Since 70 % of the earth is covered with water , marine environments could be mined more fully for the presence of antimicrobial-producing microbes . <hl> In addition , researchers are using combinatorial chemistry , a method for making a very large number of related compounds from simple precursors , and testing them for antimicrobial activity . <hl> An additional strategy that needs to be explored further is the development of compounds that inhibit resistance mechanisms and restore the activity of older drugs , such as the strategy described earlier for β-lactamase inhibitors like clavulanic acid . Finally , developing inhibitors of virulence factor production and function could be a very important avenue . Although this strategy would not be directly antibacterial , drugs that slow the progression of an infection could provide an advantage for the immune system and could be used successfully in combination with antimicrobial drugs .","hl_sentences":"Although soils have been widely examined , other environmental niches have not been tested as fully . In addition , researchers are using combinatorial chemistry , a method for making a very large number of related compounds from simple precursors , and testing them for antimicrobial activity .","question":{"cloze_format":"___ has/have yielded compounds with the most antimicrobial activity.","normal_format":"Which of the following has yielded compounds with the most antimicrobial activity?","question_choices":["water","air","volcanoes","soil"],"question_id":"fs-id1167661463241","question_text":"Which of the following has yielded compounds with the most antimicrobial activity?"},"references_are_paraphrase":null}],"string":"[\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"A few decades later , German scientists Josef Klarer , Fritz Mietzsch , and Gerhard Domagk discovered the antibacterial activity of a synthetic dye , prontosil , that could treat streptococcal and staphylococcal infections in mice . Domagk ’ s own daughter was one of the first human recipients of the drug , which completely cured her of a severe streptococcal infection that had resulted from a poke with an embroidery needle . Gerhard Domagk ( 1895 – 1964 ) was awarded the Nobel Prize in Medicine in 1939 for his work with prontosil and sulfanilamide , the active breakdown product of prontosil in the body . <hl> Sulfanilamide , the first synthetic antimicrobial created , served as the foundation for the chemical development of a family of sulfa drugs . <hl> A synthetic antimicrobial is a drug that is developed from a chemical not found in nature . The success of the sulfa drugs led to the discovery and production of additional important classes of synthetic antimicrobials , including the quinolines and oxazolidinones .\",\n \"hl_sentences\": \"Sulfanilamide , the first synthetic antimicrobial created , served as the foundation for the chemical development of a family of sulfa drugs .\",\n \"question\": {\n \"cloze_format\": \"The antimicrobial drug ___ is synthetic.\",\n \"normal_format\": \"Which of the following antimicrobial drugs is synthetic?\",\n \"question_choices\": [\n \"sulfanilamide\",\n \"penicillin\",\n \"actinomycin\",\n \"neomycin\"\n ],\n \"question_id\": \"fs-id1167659391042\",\n \"question_text\": \"Which of the following antimicrobial drugs is synthetic?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The risk associated with using broad-spectrum antimicrobials is that they will also target a broad spectrum of the normal microbiota , increasing the risk of a superinfection , a secondary infection in a patient having a preexisting infection . <hl> <hl> A superinfection develops when the antibacterial intended for the preexisting infection kills the protective microbiota , allowing another pathogen resistant to the antibacterial to proliferate and cause a secondary infection ( Figure 14.6 ) . <hl> Common examples of superinfections that develop as a result of antimicrobial usage include yeast infections ( candidiasis ) and pseudomembranous colitis caused by Clostridium difficile , which can be fatal .\",\n \"hl_sentences\": \"The risk associated with using broad-spectrum antimicrobials is that they will also target a broad spectrum of the normal microbiota , increasing the risk of a superinfection , a secondary infection in a patient having a preexisting infection . A superinfection develops when the antibacterial intended for the preexisting infection kills the protective microbiota , allowing another pathogen resistant to the antibacterial to proliferate and cause a secondary infection ( Figure 14.6 ) .\",\n \"question\": {\n \"cloze_format\": \"The combination that would most likely contribute to the development of a superinfection is the ___ .\",\n \"normal_format\": \"Which of the following combinations would most likely contribute to the development of a superinfection?\",\n \"question_choices\": [\n \"long-term use of narrow-spectrum antimicrobials\",\n \"long-term use of broad-spectrum antimicrobials\",\n \"short-term use of narrow-spectrum antimicrobials\",\n \"short-term use of broad-spectrum antimicrobials\"\n ],\n \"question_id\": \"fs-id1167660261866\",\n \"question_text\": \"Which of the following combinations would most likely contribute to the development of a superinfection?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The route of administration , the method used to introduce a drug into the body , is also an important consideration for drug therapy . <hl> <hl> Drugs that can be administered orally are generally preferred because patients can more conveniently take these drugs at home . <hl> However , some drugs are not absorbed easily from the gastrointestinal ( GI ) tract into the bloodstream . These drugs are often useful for treating diseases of the intestinal tract , such as tapeworms treated with niclosamide , or for decontaminating the bowel , as with colistin . Some drugs that are not absorbed easily , such as bacitracin , polymyxin , and several antifungals , are available as topical preparations for treatment of superficial skin infections . Sometimes , patients may not initially be able to take oral medications because of their illness ( e . g . , vomiting , intubation for respirator ) . When this occurs , and when a chosen drug is not absorbed in the GI tract , administration of the drug by a parenteral route ( intravenous or intramuscular injection ) is preferred and typically is performed in health-care settings . For most drugs , the plasma levels achieved by intravenous administration is substantially higher than levels achieved by oral or intramuscular administration , and this can also be an important consideration when choosing the route of administration for treating an infection ( Figure 14.7 ) .\",\n \"hl_sentences\": \"The route of administration , the method used to introduce a drug into the body , is also an important consideration for drug therapy . Drugs that can be administered orally are generally preferred because patients can more conveniently take these drugs at home .\",\n \"question\": {\n \"cloze_format\": \"The route of administration that would be appropriate and convenient for home administration of an antimicrobial to treat a systemic infection is ___.\",\n \"normal_format\": \"Which of the following routes of administration would be appropriate and convenient for home administration of an antimicrobial to treat a systemic infection?\",\n \"question_choices\": [\n \"oral\",\n \"intravenous\",\n \"topical\",\n \"parenteral\"\n ],\n \"question_id\": \"fs-id1167660323716\",\n \"question_text\": \"Which of the following routes of administration would be appropriate and convenient for home administration of an antimicrobial to treat a systemic infection?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"The spectrum of activity of an antibacterial drug relates to diversity of targeted bacteria . A narrow-spectrum antimicrobial targets only specific subsets of bacterial pathogens . For example , some narrow-spectrum drugs only target gram-positive bacteria , whereas others target only gram-negative bacteria . <hl> If the pathogen causing an infection has been identified , it is best to use a narrow-spectrum antimicrobial and minimize collateral damage to the normal microbiota . <hl> A broad-spectrum antimicrobial targets a wide variety of bacterial pathogens , including both gram-positive and gram-negative species , and is frequently used as empiric therapy to cover a wide range of potential pathogens while waiting on the laboratory identification of the infecting pathogen . Broad-spectrum antimicrobials are also used for polymicrobic infections ( mixed infection with multiple bacterial species ) , or as prophylactic prevention of infections with surgery / invasive procedures . Finally , broad-spectrum antimicrobials may be selected to treat an infection when a narrow-spectrum drug fails because of development of drug resistance by the target pathogen . Most people associate the term chemotherapy with treatments for cancer . However , chemotherapy is actually a broader term that refers to any use of chemicals or drugs to treat disease . Chemotherapy may involve drugs that target cancerous cells or tissues , or it may involve antimicrobial drugs that target infectious microorganisms . <hl> Antimicrobial drugs typically work by destroying or interfering with microbial structures and enzymes , either killing microbial cells or inhibiting of their growth . <hl> But before we examine how these drugs work , we will briefly explore the history of humans ’ use of antimicrobials for the purpose of chemotherapy .\",\n \"hl_sentences\": \"If the pathogen causing an infection has been identified , it is best to use a narrow-spectrum antimicrobial and minimize collateral damage to the normal microbiota . Antimicrobial drugs typically work by destroying or interfering with microbial structures and enzymes , either killing microbial cells or inhibiting of their growth .\",\n \"question\": {\n \"cloze_format\": \"The clinical situation that would be appropriate for treatment with a narrow-spectrum antimicrobial drug is ___ .\",\n \"normal_format\": \"Which clinical situation would be appropriate for treatment with a narrow-spectrum antimicrobial drug?\",\n \"question_choices\": [\n \"treatment of a polymicrobic mixed infection in the intestine\",\n \"prophylaxis against infection after a surgical procedure\",\n \"treatment of strep throat caused by culture identified Streptococcus pyogenes\",\n \"empiric therapy of pneumonia while waiting for culture results\"\n ],\n \"question_id\": \"fs-id1167660131926\",\n \"question_text\": \"Which clinical situation would be appropriate for treatment with a narrow-spectrum antimicrobial drug?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> An important quality for an antimicrobial drug is selective toxicity , meaning that it selectively kills or inhibits the growth of microbial targets while causing minimal or no harm to the host . <hl> Most antimicrobial drugs currently in clinical use are antibacterial because the prokaryotic cell provides a greater variety of unique targets for selective toxicity , in comparison to fungi , parasites , and viruses . Each class of antibacterial drugs has a unique mode of action ( the way in which a drug affects microbes at the cellular level ) , and these are summarized in Figure 14.9 and Table 14.1 .\",\n \"hl_sentences\": \"An important quality for an antimicrobial drug is selective toxicity , meaning that it selectively kills or inhibits the growth of microbial targets while causing minimal or no harm to the host .\",\n \"question\": {\n \"cloze_format\": \"The terms that refers to the ability of an antimicrobial drug to harm the target microbe without harming the host is ___.\",\n \"normal_format\": \"Which of the following terms refers to the ability of an antimicrobial drug to harm the target microbe without harming the host?\",\n \"question_choices\": [\n \"mode of action\",\n \"therapeutic level\",\n \"spectrum of activity\",\n \"selective toxicity\"\n ],\n \"question_id\": \"fs-id1167661429067\",\n \"question_text\": \"Which of the following terms refers to the ability of an antimicrobial drug to harm the target microbe without harming the host?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Similar to the penicillins , cephalosporins contain a β-lactam ring ( Figure 14.10 ) and block the transpeptidase activity of penicillin-binding proteins . <hl> However , the β-lactam ring of cephalosporins is fused to a six-member ring , rather than the five-member ring found in penicillins . This chemical difference provides cephalosporins with an increased resistance to enzymatic inactivation by β-lactamases . The drug cephalosporin C was originally isolated from the fungus Cephalosporium acremonium in the 1950s and has a similar spectrum of activity to that of penicillin against gram-positive bacteria but is active against more gram-negative bacteria than penicillin . Another important structural difference is that cephalosporin C possesses two R groups , compared with just one R group for penicillin , and this provides for greater diversity in chemical alterations and development of semisynthetic cephalosporins . The family of semisynthetic cephalosporins is much larger than the penicillins , and these drugs have been classified into generations based primarily on their spectrum of activity , increasing in spectrum from the narrow-spectrum , first-generation cephalosporins to the broad-spectrum , fourth-generation cephalosporins . A new fifth-generation cephalosporin has been developed that is active against methicillin-resistant Staphylococcus aureus ( MRSA ) . <hl> Penicillin , the first antibiotic discovered , is one of several antibacterials within a class called β-lactams . <hl> <hl> This group of compounds includes the penicillins , cephalosporins , monobactams , and carbapenems , and is characterized by the presence of a β-lactam ring found within the central structure of the drug molecule ( Figure 14.10 ) . <hl> The β-lactam antibacterials block the crosslinking of peptide chains during the biosynthesis of new peptidoglycan in the bacterial cell wall . They are able to block this process because the β-lactam structure is similar to the structure of the peptidoglycan subunit component that is recognized by the crosslinking transpeptidase enzyme , also known as a penicillin-binding protein ( PBP ) . Although the β-lactam ring must remain unchanged for these drugs to retain their antibacterial activity , strategic chemical changes to the R groups have allowed for development of a wide variety of semisynthetic β-lactam drugs with increased potency , expanded spectrum of activity , and longer half-lives for better dosing , among other characteristics .\",\n \"hl_sentences\": \"Similar to the penicillins , cephalosporins contain a β-lactam ring ( Figure 14.10 ) and block the transpeptidase activity of penicillin-binding proteins . Penicillin , the first antibiotic discovered , is one of several antibacterials within a class called β-lactams . This group of compounds includes the penicillins , cephalosporins , monobactams , and carbapenems , and is characterized by the presence of a β-lactam ring found within the central structure of the drug molecule ( Figure 14.10 ) .\",\n \"question\": {\n \"cloze_format\": \"___ is not a type of β-lactam antimicrobial.\",\n \"normal_format\": \"Which of the following is not a type of β-lactam antimicrobial?\",\n \"question_choices\": [\n \"penicillins\",\n \"glycopeptides\",\n \"cephalosporins\",\n \"monobactams\"\n ],\n \"question_id\": \"fs-id1167661298496\",\n \"question_text\": \"Which of the following is not a type of β-lactam antimicrobial?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The drug chloramphenicol represents yet another structurally distinct class of antibacterials that also bind to the 50S ribosome , inhibiting peptide bond formation . <hl> Chloramphenicol , produced by Streptomyces venezuelae , was discovered in 1947 ; in 1949 , it became the first broad-spectrum antibiotic that was approved by the FDA . Although it is a natural antibiotic , it is also easily synthesized and was the first antibacterial drug synthetically mass produced . As a result of its mass production , broad-spectrum coverage , and ability to penetrate into tissues efficiently , chloramphenicol was historically used to treat a wide range of infections , from meningitis to typhoid fever to conjunctivitis . Unfortunately , serious side effects , such as lethal gray baby syndrome , and suppression of bone marrow production , have limited its clinical role . Chloramphenicol also causes anemia in two different ways . <hl> One mechanism involves the targeting of mitochondrial ribosomes within hematopoietic stem cells , causing a reversible , dose-dependent suppression of blood cell production . <hl> Once chloramphenicol dosing is discontinued , blood cell production returns to normal . This mechanism highlights the similarity between 70S ribosomes of bacteria and the 70S ribosomes within our mitochondria . The second mechanism of anemia is idiosyncratic ( i . e . , the mechanism is not understood ) , and involves an irreversible lethal loss of blood cell production known as aplastic anemia . This mechanism of aplastic anemia is not dose dependent and can develop after therapy has stopped . Because of toxicity concerns , chloramphenicol usage in humans is now rare in the United States and is limited to severe infections unable to be treated by less toxic antibiotics . Because its side effects are much less severe in animals , it is used in veterinary medicine . <hl> The lincosamides include the naturally produced lincomycin and semisynthetic clindamycin . <hl> <hl> Although structurally distinct from macrolides , lincosamides are similar in their mode of action to the macrolides through binding to the 50S ribosomal subunit and preventing peptide bond formation . <hl> Lincosamides are particularly active against streptococcal and staphylococcal infections .\",\n \"hl_sentences\": \"The drug chloramphenicol represents yet another structurally distinct class of antibacterials that also bind to the 50S ribosome , inhibiting peptide bond formation . One mechanism involves the targeting of mitochondrial ribosomes within hematopoietic stem cells , causing a reversible , dose-dependent suppression of blood cell production . The lincosamides include the naturally produced lincomycin and semisynthetic clindamycin . Although structurally distinct from macrolides , lincosamides are similar in their mode of action to the macrolides through binding to the 50S ribosomal subunit and preventing peptide bond formation .\",\n \"question\": {\n \"cloze_format\": \"___ does not bind to the 50S ribosomal subunit.\",\n \"normal_format\": \"Which of the following does not bind to the 50S ribosomal subunit?\",\n \"question_choices\": [\n \"tetracyclines\",\n \"lincosamides\",\n \"macrolides\",\n \"chloramphenicol\"\n ],\n \"question_id\": \"fs-id1167661403800\",\n \"question_text\": \"Which of the following does not bind to the 50S ribosomal subunit?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"One member of the quinolone family , a group of synthetic antimicrobials , is nalidixic acid . It was discovered in 1962 as a byproduct during the synthesis of chloroquine , an antimalarial drug . <hl> Nalidixic acid selectively inhibits the activity of bacterial DNA gyrase , blocking DNA replication . <hl> Chemical modifications to the original quinolone backbone have resulted in the production of fluoroquinolones , like ciprofloxacin and levofloxacin , which also inhibit the activity of DNA gyrase . Ciprofloxacin and levofloxacin are effective against a broad spectrum of gram-positive or gram-negative bacteria , and are among the most commonly prescribed antibiotics used to treat a wide range of infections , including urinary tract infections , respiratory infections , abdominal infections , and skin infections . However , despite their selective toxicity against DNA gyrase , side effects associated with different fluoroquinolones include phototoxicity , neurotoxicity , cardiotoxicity , glucose metabolism dysfunction , and increased risk for tendon rupture .\",\n \"hl_sentences\": \"Nalidixic acid selectively inhibits the activity of bacterial DNA gyrase , blocking DNA replication .\",\n \"question\": {\n \"cloze_format\": \"The antimicrobial that inhibits the activity of DNA gyrase is ___ .\",\n \"normal_format\": \"Which of the following antimicrobials inhibits the activity of DNA gyrase?\",\n \"question_choices\": [\n \"polymyxin B\",\n \"clindamycin\",\n \"nalidixic acid\",\n \"rifampin\"\n ],\n \"question_id\": \"fs-id1167661401393\",\n \"question_text\": \"Which of the following antimicrobials inhibits the activity of DNA gyrase?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Beyond targeting ergosterol in fungal cell membranes , there are a few antifungal drugs that target other fungal structures ( Figure 14.14 ) . <hl> The echinocandins , including caspofungin , are a group of naturally produced antifungal compounds that block the synthesis of β ( 1 → 3 ) glucan found in fungal cell walls but not found in human cells . This drug class has the nickname “ penicillin for fungi . ” Caspofungin is used for the treatment of aspergillosis as well as systemic yeast infections . The most common mode of action for antifungal drugs is the disruption of the cell membrane . Antifungals take advantage of small differences between fungi and humans in the biochemical pathways that synthesize sterols . The sterols are important in maintaining proper membrane fluidity and , hence , proper function of the cell membrane . For most fungi , the predominant membrane sterol is ergosterol . <hl> Because human cell membranes use cholesterol , instead of ergosterol , antifungal drugs that target ergosterol synthesis are selectively toxic ( Figure 14.13 ) . <hl>\",\n \"hl_sentences\": \"Beyond targeting ergosterol in fungal cell membranes , there are a few antifungal drugs that target other fungal structures ( Figure 14.14 ) . Because human cell membranes use cholesterol , instead of ergosterol , antifungal drugs that target ergosterol synthesis are selectively toxic ( Figure 14.13 ) .\",\n \"question\": {\n \"cloze_format\": \"___ is not an appropriate target for antifungal drugs.\",\n \"normal_format\": \"Which of the following is not an appropriate target for antifungal drugs?\",\n \"question_choices\": [\n \"ergosterol\",\n \"chitin\",\n \"cholesterol\",\n \"β(1→3) glucan\"\n ],\n \"question_id\": \"fs-id1167661364965\",\n \"question_text\": \"Which of the following is not an appropriate target for antifungal drugs?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 1,\n \"ans_text\": \"B\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The avermectins are members of the macrolide family that were first discovered from a Japanese soil isolate , Streptomyces avermectinius . <hl> <hl> A more potent semisynthetic derivative of avermectin is ivermectin , which binds to glutamate-gated chloride channels specific to invertebrates including helminths , blocking neuronal transmission and causing starvation , paralysis , and death of the worms . <hl> Ivermectin is used to treat roundworm diseases , including onchocerciasis ( also called river blindness , caused by the worm Onchocerca volvulus ) and strongyloidiasis ( caused by the worm Strongyloides stercoralis or S . fuelleborni ) . Ivermectin also can also treat parasitic insects like mites , lice , and bed bugs , and is nontoxic to humans .\",\n \"hl_sentences\": \"The avermectins are members of the macrolide family that were first discovered from a Japanese soil isolate , Streptomyces avermectinius . A more potent semisynthetic derivative of avermectin is ivermectin , which binds to glutamate-gated chloride channels specific to invertebrates including helminths , blocking neuronal transmission and causing starvation , paralysis , and death of the worms .\",\n \"question\": {\n \"cloze_format\": \"The drug class that specifically inhibits neuronal transmission in helminths is ___.\",\n \"normal_format\": \"Which of the following drug classes specifically inhibits neuronal transmission in helminths?\",\n \"question_choices\": [\n \"quinolines\",\n \"avermectins\",\n \"amantadines\",\n \"imidazoles\"\n ],\n \"question_id\": \"fs-id1167664003689\",\n \"question_text\": \"Which of the following drug classes specifically inhibits neuronal transmission in helminths?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The reverse transcriptase inhibitors block the early step of converting viral RNA genome into DNA , and can include competitive nucleoside analog inhibitors ( e . g . , azidothymidine / zidovudine , or AZT ) and non-nucleoside noncompetitive inhibitors ( e . g . , etravirine ) that bind reverse transcriptase and cause an inactivating conformational change . <hl> Drugs called protease inhibitors ( e . g . , ritonavir ) block the processing of viral proteins and prevent viral maturation . Protease inhibitors are also being developed for the treatment of other viral types . 18 For example , simeprevir ( Olysio ) has been approved for the treatment of hepatitis C and is administered with ribavirin and interferon in combination therapy . The integrase inhibitors ( e . g . , raltegravir ) , block the activity of the HIV integrase responsible for the recombination of a DNA copy of the viral genome into the host cell chromosome . Additional drug classes for HIV treatment include the CCR 5 antagonists and the fusion inhibitors ( e . g . , enfuviritide ) , which prevent the binding of HIV to the host cell coreceptor ( chemokine receptor type 5 [ CCR 5 ] ) and the merging of the viral envelope with the host cell membrane , respectively . Table 14.10 shows the various therapeutic classes of antiviral drugs , categorized by mode of action , with examples of each . 18 B . L . Pearlman . “ Protease Inhibitors for the Treatment of Chronic Hepatitis C Genotype - 1 Infection : The New Standard of Care . ” Lancet Infectious Diseases 12 no . 9 ( 2012 ): 717 – 728 .\",\n \"hl_sentences\": \"The reverse transcriptase inhibitors block the early step of converting viral RNA genome into DNA , and can include competitive nucleoside analog inhibitors ( e . g . , azidothymidine / zidovudine , or AZT ) and non-nucleoside noncompetitive inhibitors ( e . g . , etravirine ) that bind reverse transcriptase and cause an inactivating conformational change .\",\n \"question\": {\n \"cloze_format\": \"___ is a nucleoside analog commonly used as a reverse transcriptase inhibitor in the treatment of HIV.\",\n \"normal_format\": \"Which of the following is a nucleoside analog commonly used as a reverse transcriptase inhibitor in the treatment of HIV?\",\n \"question_choices\": [\n \"acyclovir\",\n \"ribavirin\",\n \"adenine-arabinoside\",\n \"azidothymidine\"\n ],\n \"question_id\": \"fs-id1167661294856\",\n \"question_text\": \"Which of the following is a nucleoside analog commonly used as a reverse transcriptase inhibitor in the treatment of HIV?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Artemisinin , a plant-derived antifungal first discovered by Chinese scientists in the 1970s , is quite effective against malaria . <hl> Semisynthetic derivatives of artemisinin are more water soluble than the natural version , which makes them more bioavailable . <hl> Although the exact mechanism of action is unclear , artemisinins appear to act as prodrugs that are metabolized by target cells to produce reactive oxygen species ( ROS ) that damage target cells . <hl> Due to the rise in resistance to antimalarial drugs , artemisinins are also commonly used in combination with other antimalarial compounds in artemisinin-based combination therapy ( ACT ) .\",\n \"hl_sentences\": \"Artemisinin , a plant-derived antifungal first discovered by Chinese scientists in the 1970s , is quite effective against malaria . Although the exact mechanism of action is unclear , artemisinins appear to act as prodrugs that are metabolized by target cells to produce reactive oxygen species ( ROS ) that damage target cells .\",\n \"question\": {\n \"cloze_format\": \"___ is an antimalarial drug that is thought to increase ROS levels in target cells.\",\n \"normal_format\": \"Which of the following is an antimalarial drug that is thought to increase ROS levels in target cells?\",\n \"question_choices\": [\n \"artemisinin\",\n \"amphotericin b\",\n \"praziquantel\",\n \"pleconaril\"\n ],\n \"question_id\": \"fs-id1167659329127\",\n \"question_text\": \"Which of the following is an antimalarial drug that is thought to increase ROS levels in target cells?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Resistance genes may code for enzymes that chemically modify an antimicrobial , thereby inactivating it , or destroy an antimicrobial through hydrolysis . <hl> Resistance to many types of antimicrobials occurs through this mechanism . For example , aminoglycoside resistance can occur through enzymatic transfer of chemical groups to the drug molecule , impairing the binding of the drug to its bacterial target . For β-lactams , bacterial resistance can involve the enzymatic hydrolysis of the β-lactam bond within the β-lactam ring of the drug molecule . Once the β-lactam bond is broken , the drug loses its antibacterial activity . <hl> This mechanism of resistance is mediated by β-lactamases , which are the most common mechanism of β-lactam resistance . <hl> <hl> Inactivation of rifampin commonly occurs through glycosylation , phosphorylation , or adenosine diphosphate ( ADP ) ribosylation , and resistance to macrolides and lincosamides can also occur due to enzymatic inactivation of the drug or modification . <hl>\",\n \"hl_sentences\": \"Resistance genes may code for enzymes that chemically modify an antimicrobial , thereby inactivating it , or destroy an antimicrobial through hydrolysis . This mechanism of resistance is mediated by β-lactamases , which are the most common mechanism of β-lactam resistance . Inactivation of rifampin commonly occurs through glycosylation , phosphorylation , or adenosine diphosphate ( ADP ) ribosylation , and resistance to macrolides and lincosamides can also occur due to enzymatic inactivation of the drug or modification .\",\n \"question\": {\n \"cloze_format\": \"The resistance mechanism that describes the function of β-lactamase is the ___ .\",\n \"normal_format\": \"Which of the following resistance mechanisms describes the function of β-lactamase?\",\n \"question_choices\": [\n \"efflux pump\",\n \"target mimicry\",\n \"drug inactivation\",\n \"target overproduction\"\n ],\n \"question_id\": \"fs-id1167661397905\",\n \"question_text\": \"Which of the following resistance mechanisms describes the function of β-lactamase?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"From a clinical perspective , our greatest concerns are multidrug-resistant microbes ( MDRs ) and cross resistance . MDRs are colloquially known as “ superbugs ” and carry one or more resistance mechanism ( s ) , making them resistant to multiple antimicrobials . <hl> In cross-resistance , a single resistance mechanism confers resistance to multiple antimicrobial drugs . <hl> <hl> For example , having an efflux pump that can export multiple antimicrobial drugs is a common way for microbes to be resistant to multiple drugs by using a single resistance mechanism . <hl> In recent years , several clinically important superbugs have emerged , and the CDC reports that superbugs are responsible for more than 2 million infections in the US annually , resulting in at least 23,000 fatalities . 19 Several of the superbugs discussed in the following sections have been dubbed the ESKAPE pathogens . This acronym refers to the names of the pathogens ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa and Enterobacter spp . ) but it is also fitting in that these pathogens are able to “ escape ” many conventional forms of antimicrobial therapy . As such , infections by ESKAPE pathogens can be difficult to treat and they cause a large number of nosocomial infections . 19 Centers for Disease Control and Prevention . “ Antibiotic / Antimicrobial Resistance . ” http://www.cdc.gov/drugresistance/index.html . Accessed June 2 , 2016 .\",\n \"hl_sentences\": \"In cross-resistance , a single resistance mechanism confers resistance to multiple antimicrobial drugs . For example , having an efflux pump that can export multiple antimicrobial drugs is a common way for microbes to be resistant to multiple drugs by using a single resistance mechanism .\",\n \"question\": {\n \"cloze_format\": \"The resistance mechanism that is commonly effective against a wide range of antimicrobials in multiple classes is the ___.\",\n \"normal_format\": \"Which of the following resistance mechanisms is commonly effective against a wide range of antimicrobials in multiple classes?\",\n \"question_choices\": [\n \"efflux pump\",\n \"target mimicry\",\n \"target modification\",\n \"target overproduction\"\n ],\n \"question_id\": \"fs-id1167661424151\",\n \"question_text\": \"Which of the following resistance mechanisms is commonly effective against a wide range of antimicrobials in multiple classes?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"Microbes may develop resistance mechanisms that involve inhibiting the accumulation of an antimicrobial drug , which then prevents the drug from reaching its cellular target . This strategy is common among gram-negative pathogens and can involve changes in outer membrane lipid composition , porin channel selectivity , and / or porin channel concentrations . For example , a common mechanism of carbapenem resistance among Pseudomonas aeruginosa is to decrease the amount of its OprD porin , which is the primary portal of entry for carbapenems through the outer membrane of this pathogen . <hl> Additionally , many gram-positive and gram-negative pathogenic bacteria produce efflux pump s that actively transport an antimicrobial drug out of the cell and prevent the accumulation of drug to a level that would be antibacterial . <hl> <hl> For example , resistance to β-lactams , tetracyclines , and fluoroquinolones commonly occurs through active efflux out of the cell , and it is rather common for a single efflux pump to have the ability to translocate multiple types of antimicrobials . <hl>\",\n \"hl_sentences\": \"Additionally , many gram-positive and gram-negative pathogenic bacteria produce efflux pump s that actively transport an antimicrobial drug out of the cell and prevent the accumulation of drug to a level that would be antibacterial . For example , resistance to β-lactams , tetracyclines , and fluoroquinolones commonly occurs through active efflux out of the cell , and it is rather common for a single efflux pump to have the ability to translocate multiple types of antimicrobials .\",\n \"question\": {\n \"cloze_format\": \"The resistance mechanism that is the most nonspecific to a particular class of antimicrobials is the ___.\",\n \"normal_format\": \"Which of the following resistance mechanisms is the most nonspecific to a particular class of antimicrobials?\",\n \"question_choices\": [\n \"drug modification\",\n \"target mimicry\",\n \"target modification\",\n \"efflux pump\"\n ],\n \"question_id\": \"fs-id1167661737849\",\n \"question_text\": \"Which of the following resistance mechanisms is the most nonspecific to a particular class of antimicrobials?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The occurrence of carbapenem-resistant Enterobacteriaceae ( CRE ) and carbapenem resistance among other gram-negative bacteria ( e . g . , P . aeruginosa , Acinetobacter baumannii , Stenotrophomonas maltophila ) is a growing health-care concern . <hl> These pathogens develop resistance to carbapenems through a variety of mechanisms , including production of carbapenemases ( broad-spectrum β-lactamases that inactivate all β-lactams , including carbapenems ) , active efflux of carbapenems out of the cell , and / or prevention of carbapenem entry through porin channels . Similar to concerns with ESBLs , carbapenem-resistant , gram-negative pathogens are usually resistant to multiple classes of antibacterials , and some have even developed pan-resistance ( resistance to all available antibacterials ) . Infections with carbapenem-resistant , gram-negative pathogens commonly occur in health-care settings through interaction with contaminated individuals or medical devices , or as a result of surgery . <hl> Gram-negative pathogens that produce extended-spectrum β-lactamases ( ESBLs ) show resistance well beyond just penicillins . <hl> The spectrum of β-lactams inactivated by ESBLs provides for resistance to all penicillins , cephalosporins , monobactams , and the β-lactamase-inhibitor combinations , but not the carbapenems . An even greater concern is that the genes encoding for ESBLs are usually found on mobile plasmids that also contain genes for resistance to other drug classes ( e . g . , fluoroquinolones , aminoglycosides , tetracyclines ) , and may be readily spread to other bacteria by horizontal gene transfer . <hl> These multidrug-resistant bacteria are members of the intestinal microbiota of some individuals , but they are also important causes of opportunistic infections in hospitalized patients , from whom they can be spread to other people . <hl> <hl> Vancomycin is only effective against gram-positive organisms , and it is used to treat wound infections , septic infections , endocarditis , and meningitis that are caused by pathogens resistant to other antibiotics . <hl> It is considered one of the last lines of defense against such resistant infections , including MRSA . With the rise of antibiotic resistance in the 1970s and 1980s , vancomycin use increased , and it is not surprising that we saw the emergence and spread of vancomycin-resistant enterococci ( VRE ) , vancomycin-resistant S . aureus ( VRSA ) , and vancomycin-intermediate S . aureus ( VISA ) . The mechanism of vancomycin resistance among enterococci is target modification involving a structural change to the peptide component of the peptidoglycan subunits , preventing vancomycin from binding . These strains are typically spread among patients in clinical settings by contact with health-care workers and contaminated surfaces and medical equipment . Methicillin , a semisynthetic penicillin , was designed to resist inactivation by β-lactamases . Unfortunately , soon after the introduction of methicillin to clinical practice , methicillin-resistant strains of S . aureus appeared and started to spread . The mechanism of resistance , acquisition of a new low-affinity PBP , provided S . aureus with resistance to all available β-lactams . <hl> Strains of methicillin-resistant S . aureus ( MRSA ) are widespread opportunistic pathogens and a particular concern for skin and other wound infections , but may also cause pneumonia and septicemia . <hl> <hl> Although originally a problem in health-care settings ( hospital-acquired MRSA [ HA-MRSA ] ) , MRSA infections are now also acquired through contact with contaminated members of the general public , called community-associated MRSA ( CA-MRSA ) . <hl> Approximately one-third of the population carries S . aureus as a member of their normal nasal microbiota without illness , and about 6 % of these strains are methicillin resistant . 20 21 20 A . S . Kalokhe et al . “ Multidrug-Resistant Tuberculosis Drug Susceptibility and Molecular Diagnostic Testing : A Review of the Literature . American Journal of the Medical Sciences 345 no . 2 ( 2013 ): 143 – 148 . 21 Centers for Disease Control and Prevention . “ Methicillin-Resistant Staphylococcus aureus ( MRSA ): General Information About MRSA in the Community . ” http://www.cdc.gov/mrsa/community/index.html . Accessed June 2 , 2016\",\n \"hl_sentences\": \"The occurrence of carbapenem-resistant Enterobacteriaceae ( CRE ) and carbapenem resistance among other gram-negative bacteria ( e . g . , P . aeruginosa , Acinetobacter baumannii , Stenotrophomonas maltophila ) is a growing health-care concern . Gram-negative pathogens that produce extended-spectrum β-lactamases ( ESBLs ) show resistance well beyond just penicillins . These multidrug-resistant bacteria are members of the intestinal microbiota of some individuals , but they are also important causes of opportunistic infections in hospitalized patients , from whom they can be spread to other people . Vancomycin is only effective against gram-positive organisms , and it is used to treat wound infections , septic infections , endocarditis , and meningitis that are caused by pathogens resistant to other antibiotics . Strains of methicillin-resistant S . aureus ( MRSA ) are widespread opportunistic pathogens and a particular concern for skin and other wound infections , but may also cause pneumonia and septicemia . Although originally a problem in health-care settings ( hospital-acquired MRSA [ HA-MRSA ] ) , MRSA infections are now also acquired through contact with contaminated members of the general public , called community-associated MRSA ( CA-MRSA ) .\",\n \"question\": {\n \"cloze_format\": \"The type of drug-resistant bacteria that does not typically persist in individuals as a member of their intestinal microbiota is ___.\",\n \"normal_format\": \"Which of the following types of drug-resistant bacteria do not typically persist in individuals as a member of their intestinal microbiota?\",\n \"question_choices\": [\n \"MRSA\",\n \"VRE\",\n \"CRE\",\n \"ESBL-producing bacteria\"\n ],\n \"question_id\": \"fs-id1167663931670\",\n \"question_text\": \"Which of the following types of drug-resistant bacteria do not typically persist in individuals as a member of their intestinal microbiota?\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 0,\n \"ans_text\": \"A\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> The Kirby-Bauer disk diffusion test has long been used as a starting point for determining the susceptibility of specific microbes to various antimicrobial drugs . <hl> The Kirby-Bauer assay starts with a Mueller-Hinton agar plate on which a confluent lawn is inoculated with a patient ’ s isolated bacterial pathogen . Filter paper disks impregnated with known amounts of antibacterial drugs to be tested are then placed on the agar plate . As the bacterial inoculum grows , antibiotic diffuses from the circular disk into the agar and interacts with the growing bacteria . Antibacterial activity is observed as a clear circular zone of inhibition around the drug-impregnated disk , similar to the disk-diffusion assay depicted in Figure 13.31 . <hl> The diameter of the zone of inhibition , measured in millimeters and compared to a standardized chart , determines the susceptibility or resistance of the bacterial pathogen to the drug . <hl>\",\n \"hl_sentences\": \"The Kirby-Bauer disk diffusion test has long been used as a starting point for determining the susceptibility of specific microbes to various antimicrobial drugs . The diameter of the zone of inhibition , measured in millimeters and compared to a standardized chart , determines the susceptibility or resistance of the bacterial pathogen to the drug .\",\n \"question\": {\n \"cloze_format\": \"In the Kirby-Bauer disk diffusion test, the _______ of the zone of inhibition is measured and used for interpretation.\",\n \"normal_format\": \"In the Kirby-Bauer disk diffusion test, what of the zone of inhibition is measured and used for interpretation?\",\n \"question_choices\": [\n \"diameter\",\n \"microbial population\",\n \"circumference\",\n \"depth\"\n ],\n \"question_id\": \"fs-id1167659011346\",\n \"question_text\": \"In the Kirby-Bauer disk diffusion test, the _______ of the zone of inhibition is measured and used for interpretation.\"\n },\n \"references_are_paraphrase\": 0\n },\n {\n \"answer\": {\n \"ans_choice\": 2,\n \"ans_text\": \"C\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> As discussed , the limitations of the Kirby-Bauer disk diffusion test do not allow for a direct comparison of antibacterial potencies to guide selection of the best therapeutic choice . <hl> <hl> However , antibacterial dilution tests can be used to determine a particular drug ’ s minimal inhibitory concentration ( MIC ) , the lowest concentration of drug that inhibits visible bacterial growth , and minimal bactericidal concentration ( MBC ) , the lowest drug concentration that kills ≥ 99.9 % of the starting inoculum . <hl> Determining these concentrations helps identify the correct drug for a particular pathogen . For the macrobroth dilution assay , a dilution series of the drug in broth is made in test tubes and the same number of cells of a test bacterial strain is added to each tube ( Figure 14.19 ) . The MIC is determined by examining the tubes to find the lowest drug concentration that inhibits visible growth ; this is observed as turbidity ( cloudiness ) in the broth . Tubes with no visible growth are then inoculated onto agar media without antibiotic to determine the MBC . Generally , serum levels of an antibacterial should be at least three to five times above the MIC for treatment of an infection .\",\n \"hl_sentences\": \"As discussed , the limitations of the Kirby-Bauer disk diffusion test do not allow for a direct comparison of antibacterial potencies to guide selection of the best therapeutic choice . However , antibacterial dilution tests can be used to determine a particular drug ’ s minimal inhibitory concentration ( MIC ) , the lowest concentration of drug that inhibits visible bacterial growth , and minimal bactericidal concentration ( MBC ) , the lowest drug concentration that kills ≥ 99.9 % of the starting inoculum .\",\n \"question\": {\n \"cloze_format\": \"The technique that cannot be used to determine the minimum inhibitory concentration of an antimicrobial drug against a particular microbe is the ___.\",\n \"normal_format\": \"Which of the following techniques cannot be used to determine the minimum inhibitory concentration of an antimicrobial drug against a particular microbe?\",\n \"question_choices\": [\n \"Etest\",\n \"microbroth dilution test\",\n \"Kirby-Bauer disk diffusion test\",\n \"macrobroth dilution test\"\n ],\n \"question_id\": \"fs-id1167663964408\",\n \"question_text\": \"Which of the following techniques cannot be used to determine the minimum inhibitory concentration of an antimicrobial drug against a particular microbe?\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"Recently , studies have shown that antibiograms are useful tools in the decision-making process of selecting appropriate empiric therapy . <hl> An antibiogram is a compilation of local antibiotic susceptibility data broken down by bacterial pathogen . <hl> In a November 2014 study published in the journal Infection Control and Hospital Epidemiology , researchers determined that 85 % of the prescriptions ordered in skilled nursing facilities were decided upon empirically , but only 35 % of those prescriptions were deemed appropriate when compared with the eventual pathogen identification and susceptibility profile obtained from the clinical laboratory . However , in one nursing facility where use of antibiograms was implemented to direct selection of empiric therapy , appropriateness of empiric therapy increased from 32 % before antibiogram implementation to 45 % after implementation of antibiograms . 24 Although these data are preliminary , they do suggest that health-care facilities can reduce the number of inappropriate prescriptions by using antibiograms to select empiric therapy , thus benefiting patients and minimizing opportunities for antimicrobial resistance to develop . 24 J . P . Furuno et al . “ Using Antibiograms to Improve Antibiotic Prescribing in Skilled Nursing Facilities . ” Infection Control and Hospital Epidemiology 35 no . Suppl S3 ( 2014 ): S56 – 61 .\",\n \"hl_sentences\": \"An antibiogram is a compilation of local antibiotic susceptibility data broken down by bacterial pathogen .\",\n \"question\": {\n \"cloze_format\": \"The utility of an antibiogram is that it shows antimicrobial susceptibility trends ___ .\",\n \"normal_format\": \"How the utility of an antibiogram shows antimicrobial susceptibility trends?\",\n \"question_choices\": [\n \"over a large geographic area.\",\n \"for an individual patient.\",\n \"in research laboratory strains.\",\n \"in a localized population.\"\n ],\n \"question_id\": \"fs-id1167661481139\",\n \"question_text\": \"The utility of an antibiogram is that it shows antimicrobial susceptibility trends\"\n },\n \"references_are_paraphrase\": null\n },\n {\n \"answer\": {\n \"ans_choice\": 3,\n \"ans_text\": \"D\"\n },\n \"bloom\": null,\n \"hl_context\": \"<hl> Although soils have been widely examined , other environmental niches have not been tested as fully . <hl> Since 70 % of the earth is covered with water , marine environments could be mined more fully for the presence of antimicrobial-producing microbes . <hl> In addition , researchers are using combinatorial chemistry , a method for making a very large number of related compounds from simple precursors , and testing them for antimicrobial activity . <hl> An additional strategy that needs to be explored further is the development of compounds that inhibit resistance mechanisms and restore the activity of older drugs , such as the strategy described earlier for β-lactamase inhibitors like clavulanic acid . Finally , developing inhibitors of virulence factor production and function could be a very important avenue . Although this strategy would not be directly antibacterial , drugs that slow the progression of an infection could provide an advantage for the immune system and could be used successfully in combination with antimicrobial drugs .\",\n \"hl_sentences\": \"Although soils have been widely examined , other environmental niches have not been tested as fully . In addition , researchers are using combinatorial chemistry , a method for making a very large number of related compounds from simple precursors , and testing them for antimicrobial activity .\",\n \"question\": {\n \"cloze_format\": \"___ has/have yielded compounds with the most antimicrobial activity.\",\n \"normal_format\": \"Which of the following has yielded compounds with the most antimicrobial activity?\",\n \"question_choices\": [\n \"water\",\n \"air\",\n \"volcanoes\",\n \"soil\"\n ],\n \"question_id\": \"fs-id1167661463241\",\n \"question_text\": \"Which of the following has yielded compounds with the most antimicrobial activity?\"\n },\n \"references_are_paraphrase\": null\n }\n]","isConversational":false},"chapter":{"kind":"number","value":14,"string":"14"},"chapter_text":{"kind":"string","value":" 14.1 History of Chemotherapy and Antimicrobial Discovery \n\n Learning Objectives \n\n Compare and contrast natural, semisynthetic, and synthetic antimicrobial drugs \n\n Describe the chemotherapeutic approaches of ancient societies \n\n Describe the historically important individuals and events that led to the development of antimicrobial drugs \n\n Clinical Focus Part 1 Marisa, a 52-year-old woman, was suffering from severe abdominal pain, swollen lymph nodes, fatigue, and a fever. She had just returned home from visiting extended family in her native country of Cambodia. While abroad, she received medical care in neighboring Vietnam for a compressed spinal cord. She still had discomfort when leaving Cambodia, but the pain increased as her trip home continued and her husband drove her straight from the airport to the emergency room. \n\n Her doctor considers whether Marisa could be suffering from appendicitis, a urinary tract infection (UTI), or pelvic inflammatory disease (PID). However, each of those conditions is typically preceded or accompanied by additional symptoms. He considers the treatment she received in Vietnam for her compressed spinal cord, but abdominal pain is not usually associated with spinal cord compression. He examines her health history further. \n\n What type of infection or other condition may be responsible? \n\n What type of lab tests might the doctor order? \n\n Jump to the next Clinical Focus box. \n\n Most people associate the term chemotherapy with treatments for cancer. However, chemotherapy is actually a broader term that refers to any use of chemicals or drugs to treat disease. Chemotherapy may involve drugs that target cancerous cells or tissues, or it may involve antimicrobial drugs that target infectious microorganisms. Antimicrobial drugs typically work by destroying or interfering with microbial structures and enzymes, either killing microbial cells or inhibiting of their growth. But before we examine how these drugs work, we will briefly explore the history of humans’ use of antimicrobials for the purpose of chemotherapy. \n\n Use of Antimicrobials in Ancient Societies \n\n Although the discovery of antimicrobials and their subsequent widespread use is commonly associated with modern medicine, there is evidence that humans have been exposed to antimicrobial compounds for millennia. Chemical analyses of the skeletal remains of people from Nubia 2 (now found in present-day Sudan) dating from between 350 and 550 AD have shown residue of the antimicrobial agent tetracycline in high enough quantities to suggest the purposeful fermentation of tetracycline-producing Streptomyces during the beer-making process. The resulting beer , which was thick and gruel-like, was used to treat a variety of ailments in both adults and children, including gum disease and wounds. The antimicrobial properties of certain plants may also have been recognized by various cultures around the world, including Indian and Chinese herbalists ( Figure 14.2 ) who have long used plants for a wide variety of medical purposes. Healers of many cultures understood the antimicrobial properties of fungi and their use of moldy bread or other mold-containing products to treat wounds has been well documented for centuries. 3 Today, while about 80% of the world’s population still relies on plant-derived medicines, 4 scientists are now discovering the active compounds conferring the medicinal benefits contained in many of these traditionally used plants. 2 M.L. Nelson et al. “Brief Communication: Mass Spectroscopic Characterization of Tetracycline in the Skeletal Remains of an Ancient Population from Sudanese Nubia 350–550 CE.” American Journal of Physical Anthropology 143 no. 1 (2010):151–154. 3 M. Wainwright. “Moulds in Ancient and More Recent Medicine.” Mycologist 3 no. 1 (1989):21–23. 4 S. Verma, S.P. Singh. “Current and Future Status of Herbal Medicines.” Veterinary World 1 no. 11 (2008):347–350. \n\n Check Your Understanding \n\n Give examples of how antimicrobials were used in ancient societies. \n\n The First Antimicrobial Drugs \n\n Societies relied on traditional medicine for thousands of years; however, the first half of the 20th century brought an era of strategic drug discovery. In the early 1900s, the German physician and scientist Paul Ehrlich (1854–1915) set out to discover or synthesize chemical compounds capable of killing infectious microbes without harming the patient. In 1909, after screening more than 600 arsenic-containing compounds, Ehrlich’s assistant Sahachiro Hata (1873–1938) found one such “magic bullet.” Compound 606 targeted the bacterium Treponema pallidum , the causative agent of syphilis. Compound 606 was found to successfully cure syphilis in rabbits and soon after was marketed under the name Salvarsan as a remedy for the disease in humans ( Figure 14.3 ). Ehrlich’s innovative approach of systematically screening a wide variety of compounds remains a common strategy for the discovery of new antimicrobial agents even today. \n\n A few decades later, German scientists Josef Klarer , Fritz Mietzsch , and Gerhard Domagk discovered the antibacterial activity of a synthetic dye, prontosil , that could treat streptococcal and staphylococcal infections in mice. Domagk’s own daughter was one of the first human recipients of the drug, which completely cured her of a severe streptococcal infection that had resulted from a poke with an embroidery needle. Gerhard Domagk (1895–1964) was awarded the Nobel Prize in Medicine in 1939 for his work with prontosil and sulfanilamide , the active breakdown product of prontosil in the body. Sulfanilamide, the first synthetic antimicrobial created, served as the foundation for the chemical development of a family of sulfa drugs. A synthetic antimicrobial is a drug that is developed from a chemical not found in nature. The success of the sulfa drugs led to the discovery and production of additional important classes of synthetic antimicrobials, including the quinolines and oxazolidinones . \n\n A few years before the discovery of prontosil, scientist Alexander Fleming (1881–1955) made his own accidental discovery that turned out to be monumental. In 1928, Fleming returned from holiday and examined some old plates of staphylococci in his research laboratory at St. Mary’s Hospital in London. He observed that contaminating mold growth (subsequently identified as a strain of Penicillium notatum ) inhibited staphylococcal growth on one plate. Fleming, therefore, is credited with the discovery of penicillin , the first natural antibiotic , ( Figure 14.4 ). Further experimentation showed that penicillin from the mold was antibacterial against streptococci, meningococci, and Corynebacterium diphtheriae , the causative agent of diphtheria. \n\n Fleming and his colleagues were credited with discovering and identifying penicillin, but its isolation and mass production were accomplished by a team of researchers at Oxford University under the direction of Howard Florey (1898–1968) and Ernst Chain (1906–1979) ( Figure 14.4 ). In 1940, the research team purified penicillin and reported its success as an antimicrobial agent against streptococcal infections in mice. Their subsequent work with human subjects also showed penicillin to be very effective. Because of their important work, Fleming, Florey, and Chain were awarded the Nobel Prize in Physiology and Medicine in 1945. \n\n In the early 1940s, scientist Dorothy Hodgkin (1910–1994), who studied crystallography at Oxford University, used X-rays to analyze the structure of a variety of natural products. In 1946, she determined the structure of penicillin, for which she was awarded the Nobel Prize in Chemistry in 1964. Once the structure was understood, scientists could modify it to produce a variety of semisynthetic penicillins. A semisynthetic antimicrobial is a chemically modified derivative of a natural antibiotic. The chemical modifications are generally designed to increase the range of bacteria targeted, increase stability, decrease toxicity, or confer other properties beneficial for treating infections. \n\n Penicillin is only one example of a natural antibiotic. Also in the 1940s, Selman Waksman (1888–1973) ( Figure 14.5 ), a prominent soil microbiologist at Rutgers University, led a research team that discovered several antimicrobials, including actinomycin , streptomycin , and neomycin . The discoveries of these antimicrobials stemmed from Waksman’s study of fungi and the Actinobacteria , including soil bacteria in the genus Streptomyces , known for their natural production of a wide variety of antimicrobials. His work earned him the Nobel Prize in Physiology and Medicine in 1952. The actinomycetes are the source of more than half of all natural antibiotics 5 and continue to serve as an excellent reservoir for the discovery of novel antimicrobial agents. Some researchers argue that we have not yet come close to tapping the full antimicrobial potential of this group. 6 5 J. Berdy. “Bioactive Microbial Metabolites.” The Journal of Antibiotics 58 no. 1 (2005):1–26. 6 M. Baltz. “Antimicrobials from Actinomycetes: Back to the Future.” Microbe 2 no. 3 (2007):125–131. \n\n Check Your Understanding \n\n Why is the soil a reservoir for antimicrobial resistance genes? \n 14.2 Fundamentals of Antimicrobial Chemotherapy \n\n Learning Objectives \n\n Contrast bacteriostatic versus bactericidal antibacterial activities \n\n Contrast broad-spectrum drugs versus narrow-spectrum drugs \n\n Explain the significance of superinfections \n\n Discuss the significance of dosage and the route of administration of a drug \n\n Identify factors and variables that can influence the side effects of a drug \n\n Describe the significance of positive and negative interactions between drugs \n\n Several factors are important in choosing the most appropriate antimicrobial drug therapy, including bacteriostatic versus bactericidal mechanisms, spectrum of activity , dosage and route of administration , the potential for side effects , and the potential interactions between drugs. The following discussion will focus primarily on antibacterial drugs , but the concepts translate to other antimicrobial classes. \n\n Bacteriostatic Versus Bactericidal \n\n Antibacterial drugs can be either bacteriostatic or bactericidal in their interactions with target bacteria. Bacteriostatic drugs cause a reversible inhibition of growth, with bacterial growth restarting after elimination of the drug. By contrast, bactericidal drugs kill their target bacteria. The decision of whether to use a bacteriostatic or bactericidal drugs depends on the type of infection and the immune status of the patient. In a patient with strong immune defenses, bacteriostatic and bactericidal drugs can be effective in achieving clinical cure. However, when a patient is immunocompromised, a bactericidal drug is essential for the successful treatment of infections. Regardless of the immune status of the patient, life-threatening infections such as acute endocarditis require the use of a bactericidal drug. \n\n Spectrum of Activity \n\n The spectrum of activity of an antibacterial drug relates to diversity of targeted bacteria. A narrow-spectrum antimicrobial targets only specific subsets of bacterial pathogens. For example, some narrow-spectrum drugs only target gram-positive bacteria , whereas others target only gram-negative bacteria . If the pathogen causing an infection has been identified, it is best to use a narrow-spectrum antimicrobial and minimize collateral damage to the normal microbiota. A broad-spectrum antimicrobial targets a wide variety of bacterial pathogens, including both gram-positive and gram-negative species, and is frequently used as empiric therapy to cover a wide range of potential pathogens while waiting on the laboratory identification of the infecting pathogen. Broad-spectrum antimicrobials are also used for polymicrobic infections (mixed infection with multiple bacterial species), or as prophylactic prevention of infections with surgery/invasive procedures. Finally, broad-spectrum antimicrobials may be selected to treat an infection when a narrow-spectrum drug fails because of development of drug resistance by the target pathogen. \n\n The risk associated with using broad-spectrum antimicrobials is that they will also target a broad spectrum of the normal microbiota, increasing the risk of a superinfection , a secondary infection in a patient having a preexisting infection. A superinfection develops when the antibacterial intended for the preexisting infection kills the protective microbiota , allowing another pathogen resistant to the antibacterial to proliferate and cause a secondary infection ( Figure 14.6 ). Common examples of superinfections that develop as a result of antimicrobial usage include yeast infections ( candidiasis ) and pseudomembranous colitis caused by Clostridium difficile , which can be fatal. \n\n Check Your Understanding \n\n What is a superinfection and how does one arise? \n\n Dosage and Route of Administration \n\n The amount of medication given during a certain time interval is the dosage , and it must be determined carefully to ensure that optimum therapeutic drug levels are achieved at the site of infection without causing significant toxicity ( side effects ) to the patient. Each drug class is associated with a variety of potential side effects, and some of these are described for specific drugs later in this chapter. Despite best efforts to optimize dosing, allergic reactions and other potentially serious side effects do occur. Therefore, the goal is to select the optimum dosage that will minimize the risk of side effects while still achieving clinical cure, and there are important factors to consider when selecting the best dose and dosage interval. For example, in children, dose is based upon the patient’s mass. However, the same is not true for adults and children 12 years of age and older, for which there is typically a single standard dose regardless of the patient’s mass. With the great variability in adult body mass, some experts have argued that mass should be considered for all patients when determining appropriate dosage. 7 An additional consideration is how drugs are metabolized and eliminated from the body. In general, patients with a history of liver or kidney dysfunction may experience reduced drug metabolism or clearance from the body, resulting in increased drug levels that may lead to toxicity and make them more prone to side effects. 7 M.E. Falagas, D.E. Karageorgopoulos. “Adjustment of Dosing of Antimicrobial Agents for Bodyweight in Adults.” The Lancet 375 no. 9710 (2010):248–251. \n\n There are also some factors specific to the drugs themselves that influence appropriate dose and time interval between doses. For example, the half-life , or rate at which 50% of a drug is eliminated from the plasma, can vary significantly between drugs. Some drugs have a short half-life of only 1 hour and must be given multiple times a day, whereas other drugs have half-lives exceeding 12 hours and can be given as a single dose every 24 hours. Although a longer half-life can be considered an advantage for an antibacterial when it comes to convenient dosing intervals, the longer half-life can also be a concern for a drug that has serious side effects because drug levels may remain toxic for a longer time. Last, some drugs are dose dependent, meaning they are more effective when administered in large doses to provide high levels for a short time at the site of infection. Others are time dependent, meaning they are more effective when lower optimum levels are maintained over a longer period of time. \n\n The route of administration , the method used to introduce a drug into the body, is also an important consideration for drug therapy. Drugs that can be administered orally are generally preferred because patients can more conveniently take these drugs at home. However, some drugs are not absorbed easily from the gastrointestinal (GI) tract into the bloodstream. These drugs are often useful for treating diseases of the intestinal tract, such as tapeworms treated with niclosamide , or for decontaminating the bowel, as with colistin . Some drugs that are not absorbed easily, such as bacitracin , polymyxin , and several antifungals, are available as topical preparations for treatment of superficial skin infections. Sometimes, patients may not initially be able to take oral medications because of their illness (e.g., vomiting, intubation for respirator). When this occurs, and when a chosen drug is not absorbed in the GI tract, administration of the drug by a parenteral route (intravenous or intramuscular injection) is preferred and typically is performed in health-care settings. For most drugs, the plasma levels achieved by intravenous administration is substantially higher than levels achieved by oral or intramuscular administration, and this can also be an important consideration when choosing the route of administration for treating an infection ( Figure 14.7 ). \n\n Check Your Understanding \n\n List five factors to consider when determining the dosage of a drug. \n\n Name some typical side effects associated with drugs and identify some factors that might contribute to these side effects. \n\n Drug Interactions \n\n For the optimum treatment of some infections, two antibacterial drugs may be administered together to provide a synergistic interaction that is better than the efficacy of either drug alone. A classic example of synergistic combinations is trimethoprim and sulfamethoxazole ( Bactrim ). Individually, these two drugs provide only bacteriostatic inhibition of bacterial growth, but combined, the drugs are bactericidal . \n\n Whereas synergistic drug interactions provide a benefit to the patient, antagonistic interactions produce harmful effects. Antagonism can occur between two antimicrobials or between antimicrobials and nonantimicrobials being used to treat other conditions. The effects vary depending on the drugs involved, but antagonistic interactions may cause loss of drug activity, decreased therapeutic levels due to increased metabolism and elimination, or increased potential for toxicity due to decreased metabolism and elimination. As an example, some antibacterials are absorbed most effectively from the acidic environment of the stomach. If a patient takes antacids, however, this increases the pH of the stomach and negatively impacts the absorption of these antimicrobials, decreasing their effectiveness in treating an infection. Studies have also shown an association between use of some antimicrobials and failure of oral contraceptives. 8 8 B.D. Dickinson et al. “Drug Interactions between Oral Contraceptives and Antibiotics.” Obstetrics & Gynecology 98, no. 5 (2001):853–860. \n\n Check Your Understanding \n\n Explain the difference between synergistic and antagonistic drug interactions. \n\n Eye on Ethics Resistance Police In the United States and many other countries, most antimicrobial drugs are self-administered by patients at home. Unfortunately, many patients stop taking antimicrobials once their symptoms dissipate and they feel better. If a 10-day course of treatment is prescribed, many patients only take the drug for 5 or 6 days, unaware of the negative consequences of not completing the full course of treatment. A shorter course of treatment not only fails to kill the target organisms to expected levels, it also selects for drug-resistant variants within the target population and within the patient’s microbiota. \n\n Patients’ nonadherence especially amplifies drug resistance when the recommended course of treatment is long. Treatment for tuberculosis (TB) is a case in point, with the recommended treatment lasting from 6 months to a year. The CDC estimates that about one-third of the world’s population is infected with TB, most living in underdeveloped or underserved regions where antimicrobial drugs are available over the counter. In such countries, there may be even lower rates of adherence than in developed areas. Nonadherence leads to antibiotic resistance and more difficulty in controlling pathogens. As a direct result, the emergence of multidrug-resistant and extensively drug-resistant strains of TB is becoming a huge problem. \n\n Overprescription of antimicrobials also contributes to antibiotic resistance. Patients often demand antibiotics for diseases that do not require them, like viral colds and ear infections. Pharmaceutical companies aggressively market drugs to physicians and clinics, making it easy for them to give free samples to patients, and some pharmacies even offer certain antibiotics free to low-income patients with a prescription. \n\n In recent years, various initiatives have aimed to educate parents and clinicians about the judicious use of antibiotics. However, a recent study showed that, between 2000 and 2013, the parental expectation for antimicrobial prescriptions for children actually increased ( Figure 14.8 ). \n\n One possible solution is a regimen called directly observed therapy (DOT) , which involves the supervised administration of medications to patients. Patients are either required to visit a health-care facility to receive their medications, or health-care providers must administer medication in patients’ homes or another designated location. DOT has been implemented in many cases for the treatment of TB and has been shown to be effective; indeed, DOT is an integral part of WHO’s global strategy for eradicating TB. 9 , 10 But is this a practical strategy for all antibiotics? Would patients taking penicillin, for example, be more or less likely to adhere to the full course of treatment if they had to travel to a health-care facility for each dose? And who would pay for the increased cost associated with DOT? When it comes to overprescription, should someone be policing physicians or drug companies to enforce best practices? What group should assume this responsibility, and what penalties would be effective in discouraging overprescription? 9 Centers for Disease Control and Prevention. “Tuberculosis (TB).” http://www.cdc.gov/tb/education/ssmodules/module9/ss9reading2.htm. Accessed June 2, 2016. 10 World Health Organization. “Tuberculosis (TB): The Five Elements of DOTS.” http://www.who.int/tb/dots/whatisdots/en/. Accessed June 2, 2016. \n 14.3 Mechanisms of Antibacterial Drugs \n\n Learning Objective \n\n Describe the mechanisms of action associated with drugs that inhibit cell wall biosynthesis, protein synthesis, membrane function, nucleic acid synthesis, and metabolic pathways \n\n An important quality for an antimicrobial drug is selective toxicity , meaning that it selectively kills or inhibits the growth of microbial targets while causing minimal or no harm to the host. Most antimicrobial drugs currently in clinical use are antibacterial because the prokaryotic cell provides a greater variety of unique targets for selective toxicity, in comparison to fungi, parasites, and viruses. Each class of antibacterial drugs has a unique mode of action (the way in which a drug affects microbes at the cellular level), and these are summarized in Figure 14.9 and Table 14.1 . \n\n Common Antibacterial Drugs by Mode of Action \n\n Mode of Action \n\n Target \n\n Drug Class \n\n Inhibit cell wall biosynthesis \n\n Penicillin-binding proteins \n\n β-lactams: penicillins, cephalosporins, monobactams, carbapenems \n\n Peptidoglycan subunits \n\n Glycopeptides \n\n Peptidoglycan subunit transport \n\n Bacitracin \n\n Inhibit biosynthesis of proteins \n\n 30S ribosomal subunit \n\n Aminoglycosides, tetracyclines \n\n 50S ribosomal subunit \n\n Macrolides, lincosamides, chloramphenicol, oxazolidinones \n\n Disrupt membranes \n\n Lipopolysaccharide, inner and outer membranes \n\n Polymyxin B, colistin, daptomycin \n\n Inhibit nucleic acid synthesis \n\n RNA \n\n Rifamycin \n\n DNA \n\n Fluoroquinolones \n\n Antimetabolites \n\n Folic acid synthesis enzyme \n\n Sulfonamides, trimethoprim \n\n Mycolic acid synthesis enzyme \n\n Isonicotinic acid hydrazide \n\n Mycobacterial adenosine triphosphate (ATP) synthase inhibitor \n\n Mycobacterial ATP synthase \n\n Diarylquinoline \n\n Table 14.1 \n\n Inhibitors of Cell Wall Biosynthesis \n\n Several different classes of antibacterials block steps in the biosynthesis of peptidoglycan , making cells more susceptible to osmotic lysis ( Table 14.2 ). Therefore, antibacterials that target cell wall biosynthesis are bactericidal in their action. Because human cells do not make peptidoglycan, this mode of action is an excellent example of selective toxicity. \n\n Penicillin, the first antibiotic discovered, is one of several antibacterials within a class called β-lactams . This group of compounds includes the penicillins , cephalosporins , monobactams , and carbapenems , and is characterized by the presence of a β-lactam ring found within the central structure of the drug molecule ( Figure 14.10 ). The β-lactam antibacterials block the crosslinking of peptide chains during the biosynthesis of new peptidoglycan in the bacterial cell wall. They are able to block this process because the β-lactam structure is similar to the structure of the peptidoglycan subunit component that is recognized by the crosslinking transpeptidase enzyme, also known as a penicillin-binding protein (PBP) . Although the β-lactam ring must remain unchanged for these drugs to retain their antibacterial activity, strategic chemical changes to the R groups have allowed for development of a wide variety of semisynthetic β-lactam drugs with increased potency , expanded spectrum of activity , and longer half-lives for better dosing, among other characteristics. \n\n Penicillin G and penicillin V are natural antibiotics from fungi and are primarily active against gram-positive bacterial pathogens, and a few gram-negative bacterial pathogens such as Pasteurella multocida . Figure 14.10 summarizes the semisynthetic development of some of the penicillins. Adding an amino group (-NH 2 ) to penicillin G created the aminopenicillins (i.e., ampicillin and amoxicillin ) that have increased spectrum of activity against more gram-negative pathogens. Furthermore, the addition of a hydroxyl group (-OH) to amoxicillin increased acid stability, which allows for improved oral absorption. Methicillin is a semisynthetic penicillin that was developed to address the spread of enzymes ( penicillinases ) that were inactivating the other penicillins. Changing the R group of penicillin G to the more bulky dimethoxyphenyl group provided protection of the β-lactam ring from enzymatic destruction by penicillinases, giving us the first penicillinase-resistant penicillin. \n\n Similar to the penicillins, cephalosporins contain a β-lactam ring ( Figure 14.10 ) and block the transpeptidase activity of penicillin-binding proteins. However, the β-lactam ring of cephalosporins is fused to a six-member ring, rather than the five-member ring found in penicillins. This chemical difference provides cephalosporins with an increased resistance to enzymatic inactivation by β-lactamases . The drug cephalosporin C was originally isolated from the fungus Cephalosporium acremonium in the 1950s and has a similar spectrum of activity to that of penicillin against gram-positive bacteria but is active against more gram-negative bacteria than penicillin . Another important structural difference is that cephalosporin C possesses two R groups, compared with just one R group for penicillin, and this provides for greater diversity in chemical alterations and development of semisynthetic cephalosporins. The family of semisynthetic cephalosporins is much larger than the penicillins, and these drugs have been classified into generations based primarily on their spectrum of activity, increasing in spectrum from the narrow-spectrum, first-generation cephalosporins to the broad-spectrum, fourth-generation cephalosporins. A new fifth-generation cephalosporin has been developed that is active against methicillin-resistant Staphylococcus aureus (MRSA) . \n\n The carbapenems and monobactams also have a β-lactam ring as part of their core structure, and they inhibit the transpeptidase activity of penicillin-binding proteins. The only monobactam used clinically is aztreonam . It is a narrow-spectrum antibacterial with activity only against gram-negative bacteria. In contrast, the carbapenem family includes a variety of semisynthetic drugs ( imipenem , meropenem , and doripenem ) that provide very broad-spectrum activity against gram-positive and gram-negative bacterial pathogens. \n\n The drug vancomycin , a member of a class of compounds called the glycopeptides , was discovered in the 1950s as a natural antibiotic from the actinomycete Amycolatopsis orientalis . Similar to the β-lactams, vancomycin inhibits cell wall biosynthesis and is bactericidal. However, in contrast to the β-lactams, the structure of vancomycin is not similar to that of cell-wall peptidoglycan subunits and does not directly inactivate penicillin-binding proteins. Rather, vancomycin is a very large, complex molecule that binds to the end of the peptide chain of cell wall precursors, creating a structural blockage that prevents the cell wall subunits from being incorporated into the growing N-acetylglucosamine and N-acetylmuramic acid (NAM-NAG) backbone of the peptidoglycan structure ( transglycosylation ). Vancomycin also structurally blocks transpeptidation . Vancomycin is bactericidal against gram-positive bacterial pathogens, but it is not active against gram-negative bacteria because of its inability to penetrate the protective outer membrane. \n\n The drug bacitracin consists of a group of structurally similar peptide antibiotics originally isolated from Bacillus subtilis . Bacitracin blocks the activity of a specific cell-membrane molecule that is responsible for the movement of peptidoglycan precursors from the cytoplasm to the exterior of the cell, ultimately preventing their incorporation into the cell wall. Bacitracin is effective against a wide range of bacteria, including gram-positive organisms found on the skin, such as Staphylococcus and Streptococcus . Although it may be administered orally or intramuscularly in some circumstances, bacitracin has been shown to be nephrotoxic (damaging to the kidneys). Therefore, it is more commonly combined with neomycin and polymyxin in topical ointments such as Neosporin . \n\n Drugs that Inhibit Bacterial Cell Wall Synthesis \n\n Mechanism of Action \n\n Drug Class \n\n Specific Drugs \n\n Natural or Semisynthetic \n\n Spectrum of Activity \n\n Interact directly with PBPs and inhibit transpeptidase activity \n\n Penicillins \n\n Penicillin G, penicillin V \n\n Natural \n\n Narrow-spectrum against gram-positive and a few gram-negative bacteria \n\n Ampicillin, amoxicillin \n\n Semisynthetic \n\n Narrow-spectrum against gram-positive bacteria but with increased gram-negative spectrum \n\n Methicillin \n\n Semisynthetic \n\n Narrow-spectrum against gram-positive bacteria only, including strains producing penicillinase \n\n Cephalosporins \n\n Cephalosporin C \n\n Natural \n\n Narrow-spectrum similar to penicillin but with increased gram-negative spectrum \n\n First-generation cephalosporins \n\n Semisynthetic \n\n Narrow-spectrum similar to cephalosporin C \n\n Second-generation cephalosporins \n\n Semisynthetic \n\n Narrow-spectrum but with increased gram-negative spectrum compared with first generation \n\n Third- and fourth-generation cephalosporins \n\n Semisynthetic \n\n Broad-spectrum against gram-positive and gram-negative bacteria, including some β-lactamase producers \n\n Fifth-generation cephalosporins \n\n Semisynthetic \n\n Broad-spectrum against gram-positive and gram-negative bacteria, including MRSA \n\n Monobactams \n\n Aztreonam \n\n Semisynthetic \n\n Narrow-spectrum against gram-negative bacteria, including some β-lactamase producers \n\n Carbapenems \n\n Imipenem, meropenem, doripenem \n\n Semisynthetic \n\n Broadest spectrum of the β-lactams against gram-positive and gram-negative bacteria, including many β-lactamase producers \n\n Large molecules that bind to the peptide chain of peptidoglycan subunits, blocking transglycosylation and transpeptidation \n\n Glycopeptides \n\n Vancomycin \n\n Natural \n\n Narrow spectrum against gram-positive bacteria only, including multidrug-resistant strains \n\n Block transport of peptidoglycan subunits across cytoplasmic membrane \n\n Bacitracin \n\n Bacitracin \n\n Natural \n\n Broad-spectrum against gram-positive and gram-negative bacteria \n\n Table 14.2 \n\n Check Your Understanding \n\n Describe the mode of action of β-lactams. \n\n Inhibitors of Protein Biosynthesis \n\n The cytoplasmic ribosomes found in animal cells (80S) are structurally distinct from those found in bacterial cells (70S), making protein biosynthesis a good selective target for antibacterial drugs. Several types of protein biosynthesis inhibitors are discussed in this section and are summarized in Figure 14.11 . \n\n Protein Synthesis Inhibitors That Bind the 30S Subunit \n\n Aminoglycosides are large, highly polar antibacterial drugs that bind to the 30S subunit of bacterial ribosomes, impairing the proofreading ability of the ribosomal complex. This impairment causes mismatches between codons and anticodons, resulting in the production of proteins with incorrect amino acids and shortened proteins that insert into the cytoplasmic membrane. Disruption of the cytoplasmic membrane by the faulty proteins kills the bacterial cells. The aminoglycosides , which include drugs such as streptomycin , gentamicin , neomycin , and kanamycin , are potent broad-spectrum antibacterials. However, aminoglycosides have been shown to be nephrotoxic (damaging to kidney), neurotoxic (damaging to the nervous system), and ototoxic (damaging to the ear). \n\n Another class of antibacterial compounds that bind to the 30S subunit is the tetracyclines . In contrast to aminoglycosides, these drugs are bacteriostatic and inhibit protein synthesis by blocking the association of tRNAs with the ribosome during translation. Naturally occurring tetracyclines produced by various strains of Streptomyces were first discovered in the 1940s, and several semisynthetic tetracyclines, including doxycycline and tigecycline have also been produced. Although the tetracyclines are broad spectrum in their coverage of bacterial pathogens, side effects that can limit their use include phototoxicity , permanent discoloration of developing teeth, and liver toxicity with high doses or in patients with kidney impairment. \n\n Protein Synthesis Inhibitors That Bind the 50S Subunit \n\n There are several classes of antibacterial drugs that work through binding to the 50S subunit of bacterial ribosomes. The macrolide antibacterial drugs have a large, complex ring structure and are part of a larger class of naturally produced secondary metabolites called polyketides , complex compounds produced in a stepwise fashion through the repeated addition of two-carbon units by a mechanism similar to that used for fatty acid synthesis. Macrolides are broad-spectrum, bacteriostatic drugs that block elongation of proteins by inhibiting peptide bond formation between specific combinations of amino acids. The first macrolide was erythromycin . It was isolated in 1952 from Streptomyces erythreus and prevents translocation. Semisynthetic macrolides include azithromycin and telithromycin. Compared with erythromycin, azithromycin has a broader spectrum of activity, fewer side effects, and a significantly longer half-life (1.5 hours for erythromycin versus 68 hours for azithromycin) that allows for once-daily dosing and a short 3-day course of therapy (i.e., Zpac formulation) for most infections. Telithromycin is the first semisynthetic within the class known as ketolides. Although telithromycin shows increased potency and activity against macrolide-resistant pathogens, the US Food and Drug Administration (FDA) has limited its use to treatment of community-acquired pneumonia and requires the strongest “black box warning” label for the drug because of serious hepatotoxicity. \n\n The lincosamides include the naturally produced lincomycin and semisynthetic clindamycin . Although structurally distinct from macrolides, lincosamides are similar in their mode of action to the macrolides through binding to the 50S ribosomal subunit and preventing peptide bond formation. Lincosamides are particularly active against streptococcal and staphylococcal infections. \n\n The drug chloramphenicol represents yet another structurally distinct class of antibacterials that also bind to the 50S ribosome, inhibiting peptide bond formation. Chloramphenicol, produced by Streptomyces venezuelae , was discovered in 1947; in 1949, it became the first broad-spectrum antibiotic that was approved by the FDA. Although it is a natural antibiotic, it is also easily synthesized and was the first antibacterial drug synthetically mass produced. As a result of its mass production, broad-spectrum coverage, and ability to penetrate into tissues efficiently, chloramphenicol was historically used to treat a wide range of infections, from meningitis to typhoid fever to conjunctivitis . Unfortunately, serious side effects, such as lethal gray baby syndrome , and suppression of bone marrow production, have limited its clinical role. Chloramphenicol also causes anemia in two different ways. One mechanism involves the targeting of mitochondrial ribosomes within hematopoietic stem cells, causing a reversible, dose-dependent suppression of blood cell production. Once chloramphenicol dosing is discontinued, blood cell production returns to normal. This mechanism highlights the similarity between 70S ribosomes of bacteria and the 70S ribosomes within our mitochondria. The second mechanism of anemia is idiosyncratic (i.e., the mechanism is not understood), and involves an irreversible lethal loss of blood cell production known as aplastic anemia . This mechanism of aplastic anemia is not dose dependent and can develop after therapy has stopped. Because of toxicity concerns, chloramphenicol usage in humans is now rare in the United States and is limited to severe infections unable to be treated by less toxic antibiotics. Because its side effects are much less severe in animals, it is used in veterinary medicine. \n\n The oxazolidinones , including linezolid , are a new broad-spectrum class of synthetic protein synthesis inhibitors that bind to the 50S ribosomal subunit of both gram-positive and gram-negative bacteria. However, their mechanism of action seems somewhat different from that of the other 50S subunit-binding protein synthesis inhibitors already discussed. Instead, they seem to interfere with formation of the initiation complex (association of the 50S subunit, 30S subunit, and other factors) for translation, and they prevent translocation of the growing protein from the ribosomal A site to the P site. Table 14.3 summarizes the protein synthesis inhibitors. \n\n Drugs That Inhibit Bacterial Protein Synthesis \n\n Molecular Target \n\n Mechanism of Action \n\n Drug Class \n\n Specific Drugs \n\n Bacteriostatic or Bactericidal \n\n Spectrum of Activity \n\n 30S subunit \n\n Causes mismatches between codons and anticodons, leading to faulty proteins that insert into and disrupt cytoplasmic membrane \n\n Aminoglycosides \n\n Streptomycin, gentamicin, neomycin, kanamycin \n\n Bactericidal \n\n Broad spectrum \n\n Blocks association of tRNAs with ribosome \n\n Tetracyclines \n\n Tetracycline, doxycycline, tigecycline \n\n Bacteriostatic \n\n Broad spectrum \n\n 50S subunit \n\n Blocks peptide bond formation between amino acids \n\n Macrolides \n\n Erythromycin, azithromycin, telithromycin \n\n Bacteriostatic \n\n Broad spectrum \n\n Lincosamides \n\n Lincomycin, clindamycin \n\n Bacteriostatic \n\n Narrow spectrum \n\n Not applicable \n\n Chloramphenicol \n\n Bacteriostatic \n\n Broad spectrum \n\n Interferes with the formation of the initiation complex between 50S and 30S subunits and other factors. \n\n Oxazolidinones \n\n Linezolid \n\n Bacteriostatic \n\n Broad spectrum \n\n Table 14.3 \n\n Check Your Understanding \n\n Compare and contrast the different types of protein synthesis inhibitors. \n\n Inhibitors of Membrane Function \n\n A small group of antibacterials target the bacterial membrane as their mode of action ( Table 14.4 ). The polymyxins are natural polypeptide antibiotics that were first discovered in 1947 as products of Bacillus polymyxa ; only polymyxin B and polymyxin E ( colistin ) have been used clinically. They are lipophilic with detergent-like properties and interact with the lipopolysaccharide component of the outer membrane of gram-negative bacteria, ultimately disrupting both their outer and inner membranes and killing the bacterial cells. Unfortunately, the membrane-targeting mechanism is not a selective toxicity , and these drugs also target and damage the membrane of cells in the kidney and nervous system when administered systemically. Because of these serious side effects and their poor absorption from the digestive tract, polymyxin B is used in over-the-counter topical antibiotic ointments (e.g., Neosporin ), and oral colistin was historically used only for bowel decontamination to prevent infections originating from bowel microbes in immunocompromised patients or for those undergoing certain abdominal surgeries. However, the emergence and spread of multidrug-resistant pathogens has led to increased use of intravenous colistin in hospitals, often as a drug of last resort to treat serious infections. The antibacterial daptomycin is a cyclic lipopeptide produced by Streptomyces roseosporus that seems to work like the polymyxins, inserting in the bacterial cell membrane and disrupting it. However, in contrast to polymyxin B and colistin, which target only gram-negative bacteria, daptomycin specifically targets gram-positive bacteria. It is typically administered intravenously and seems to be well tolerated, showing reversible toxicity in skeletal muscles. \n\n Drugs That Inhibit Bacterial Membrane Function \n\n Mechanism of Action \n\n Drug Class \n\n Specific Drugs \n\n Spectrum of Activity \n\n Clinical Use \n\n Interacts with lipopolysaccharide in the outer membrane of gram-negative bacteria, killing the cell through the eventual disruption of the outer membrane and cytoplasmic membrane \n\n Polymyxins \n\n Polymyxin B \n\n Narrow spectrum against gram-negative bacteria, including multidrug-resistant strains \n\n Topical preparations to prevent infections in wounds \n\n Polymyxin E (colistin) \n\n Narrow spectrum against gram-negative bacteria, including multidrug-resistant strains \n\n Oral dosing to decontaminate bowels to prevent infections in immunocompromised patients or patients undergoing invasive surgery/procedures. \n\n Intravenous dosing to treat serious systemic infections caused by multidrug-resistant pathogens \n\n Inserts into the cytoplasmic membrane of gram-positive bacteria, disrupting the membrane and killing the cell \n\n Lipopeptide \n\n Daptomycin \n\n Narrow spectrum against gram-positive bacteria, including multidrug-resistant strains \n\n Complicated skin and skin-structure infections and bacteremia caused by gram-positive pathogens, including MRSA \n\n Table 14.4 \n\n Check Your Understanding \n\n How do polymyxins inhibit membrane function? \n\n Inhibitors of Nucleic Acid Synthesis \n\n Some antibacterial drugs work by inhibiting nucleic acid synthesis ( Table 14.5 ). For example, metronidazole is a semisynthetic member of the nitroimidazole family that is also an antiprotozoan. It interferes with DNA replication in target cells. The drug rifampin is a semisynthetic member of the rifamycin family and functions by blocking RNA polymerase activity in bacteria. The RNA polymerase enzymes in bacteria are structurally different from those in eukaryotes, providing for selective toxicity against bacterial cells. It is used for the treatment of a variety of infections, but its primary use, often in a cocktail with other antibacterial drugs, is against mycobacteria that cause tuberculosis . Despite the selectivity of its mechanism, rifampin can induce liver enzymes to increase metabolism of other drugs being administered (antagonism), leading to hepatotoxicity (liver toxicity) and negatively influencing the bioavailability and therapeutic effect of the companion drugs. \n\n One member of the quinolone family, a group of synthetic antimicrobials, is nalidixic acid . It was discovered in 1962 as a byproduct during the synthesis of chloroquine , an antimalarial drug. Nalidixic acid selectively inhibits the activity of bacterial DNA gyrase, blocking DNA replication. Chemical modifications to the original quinolone backbone have resulted in the production of fluoroquinolones , like ciprofloxacin and levofloxacin , which also inhibit the activity of DNA gyrase. Ciprofloxacin and levofloxacin are effective against a broad spectrum of gram-positive or gram-negative bacteria, and are among the most commonly prescribed antibiotics used to treat a wide range of infections, including urinary tract infections, respiratory infections, abdominal infections, and skin infections. However, despite their selective toxicity against DNA gyrase, side effects associated with different fluoroquinolones include phototoxicity , neurotoxicity , cardiotoxicity , glucose metabolism dysfunction, and increased risk for tendon rupture. \n\n Drugs That Inhibit Bacterial Nucleic Acid Synthesis \n\n Mechanisms of Action \n\n Drug Class \n\n Specific Drugs \n\n Spectrum of activity \n\n Clinical Use \n\n Inhibits bacterial RNA polymerase activity and blocks transcription, killing the cell \n\n Rifamycin \n\n Rifampin \n\n Narrow spectrum with activity against gram-positive and limited numbers of gram-negative bacteria. Also active against Mycobacterium tuberculosis. \n\n Combination therapy for treatment of tuberculosis \n\n Inhibits the activity of DNA gyrase and blocks DNA replication, killing the cell \n\n Fluoroquinolones \n\n Ciprofloxacin, ofloxacin, moxifloxacin \n\n Broad spectrum against gram-positive and gram-negative bacteria \n\n Wide variety of skin and systemic infections \n\n Table 14.5 \n\n Check Your Understanding \n\n Why do inhibitors of bacterial nucleic acid synthesis not target host cells? \n\n Inhibitors of Metabolic Pathways \n\n Some synthetic drugs control bacterial infections by functioning as antimetabolites , competitive inhibitors for bacterial metabolic enzymes ( Table 14.6 ). The sulfonamides ( sulfa drugs ) are the oldest synthetic antibacterial agents and are structural analogues of para -aminobenzoic acid (PABA), an early intermediate in folic acid synthesis ( Figure 14.12 ). By inhibiting the enzyme involved in the production of dihydrofolic acid, sulfonamides block bacterial biosynthesis of folic acid and, subsequently, pyrimidines and purines required for nucleic acid synthesis. This mechanism of action provides bacteriostatic inhibition of growth against a wide spectrum of gram-positive and gram-negative pathogens. Because humans obtain folic acid from food instead of synthesizing it intracellularly, sulfonamides are selectively toxic for bacteria. However, allergic reactions to sulfa drugs are common. The sulfones are structurally similar to sulfonamides but are not commonly used today except for the treatment of Hansen’s disease ( leprosy ). \n\n Trimethoprim is a synthetic antimicrobial compound that serves as an antimetabolite within the same folic acid synthesis pathway as sulfonamides. However, trimethoprim is a structural analogue of dihydrofolic acid and inhibits a later step in the metabolic pathway ( Figure 14.12 ). Trimethoprim is used in combination with the sulfa drug sulfamethoxazole to treat urinary tract infection s, ear infection s, and bronchitis . As discussed, the combination of trimethoprim and sulfamethoxazole is an example of antibacterial synergy. When used alone, each antimetabolite only decreases production of folic acid to a level where bacteriostatic inhibition of growth occurs. However, when used in combination, inhibition of both steps in the metabolic pathway decreases folic acid synthesis to a level that is lethal to the bacterial cell. Because of the importance of folic acid during fetal development, sulfa drugs and trimethoprim use should be carefully considered during early pregnancy. \n\n The drug isoniazid is an antimetabolite with specific toxicity for mycobacteria and has long been used in combination with rifampin or streptomycin in the treatment of tuberculosis . It is administered as a prodrug, requiring activation through the action of an intracellular bacterial peroxidase enzyme, forming isoniazid-nicotinamide adenine dinucleotide (NAD) and isoniazid-nicotinamide adenine dinucleotide phosphate (NADP), ultimately preventing the synthesis of mycolic acid, which is essential for mycobacterial cell walls. Possible side effects of isoniazid use include hepatotoxicity , neurotoxicity , and hematologic toxicity ( anemia ). \n\n Antimetabolite Drugs \n\n Metabolic Pathway Target \n\n Mechanism of Action \n\n Drug Class \n\n Specific Drugs \n\n Spectrum of Activity \n\n Folic acid synthesis \n\n Inhibits the enzyme involved in production of dihydrofolic acid \n\n Sulfonamides \n\n Sulfamethoxazole \n\n Broad spectrum against gram-positive and gram-negative bacteria \n\n Sulfones \n\n Dapsone \n\n Inhibits the enzyme involved in the production of tetrahydrofolic acid \n\n Not applicable \n\n Trimethoprim \n\n Broad spectrum against gram-positive and gram-negative bacteria \n\n Mycolic acid synthesis \n\n Interferes with the synthesis of mycolic acid \n\n Not applicable \n\n Isoniazid \n\n Narrow spectrum against Mycobacterium spp., including M. tuberculosis \n\n Table 14.6 \n\n Check Your Understanding \n\n How do sulfonamides and trimethoprim selectively target bacteria? \n\n Inhibitor of ATP Synthase \n\n Bedaquiline, representing the synthetic antibacterial class of compounds called the diarylquinolines , uses a novel mode of action that specifically inhibits mycobacterial growth. Although the specific mechanism has yet to be elucidated, this compound appears to interfere with the function of ATP synthases, perhaps by interfering with the use of the hydrogen ion gradient for ATP synthesis by oxidative phosphorylation , leading to reduced ATP production. Due to its side effects , including hepatotoxicity and potentially lethal heart arrhythmia, its use is reserved for serious, otherwise untreatable cases of tuberculosis . Link to Learning \n\nTo learn more about the general principles of antimicrobial therapy and bacterial modes of action, read this article for a general overview of antimicrobial therapy strategies and read this article on the mechanism of action of antimicrobial classes.\n\n Clinical Focus Part 2 Reading thorough Marisa’s health history, the doctor noticed that during her hospitalization in Vietnam, she was catheterized and received the antimicrobial drugs ceftazidime and metronidazole . Upon learning this, the doctor ordered a CT scan of Marisa’s abdomen to rule out appendicitis; the doctor also requested blood work to see if she had an elevated white blood cell count, and ordered a urine analysis test and urine culture to look for the presence of white blood cells, red blood cells, and bacteria. \n\n Marisa’s urine sample came back positive for the presence of bacteria, indicating a urinary tract infection (UTI). The doctor prescribed ciprofloxacin. In the meantime, her urine was cultured to grow the bacterium for further testing. \n\n What types of antimicrobials are typically prescribed for UTIs? \n\n Based upon the antimicrobial drugs she was given in Vietnam, which of the antimicrobials for treatment of a UTI would you predict to be ineffective? \n\n Jump to the next Clinical Focus box. Go back to the previous Clinical Focus box. \n 14.4 Mechanisms of Other Antimicrobial Drugs \n\n Learning Objective \n\n Explain the differences between modes of action of drugs that target fungi, protozoa, helminths, and viruses \n\n Because fungi, protozoa, and helminths are eukaryotic, their cells are very similar to human cells, making it more difficult to develop drugs with selective toxicity. Additionally, viruses replicate within human host cells, making it difficult to develop drugs that are selectively toxic to viruses or virus-infected cells. Despite these challenges, there are antimicrobial drugs that target fungi, protozoa, helminths, and viruses, and some even target more than one type of microbe. Table 14.7 , Table 14.8 , Table 14.9 , and Table 14.10 provide examples for antimicrobial drugs in these various classes. \n\n Antifungal Drugs \n\n The most common mode of action for antifungal drugs is the disruption of the cell membrane. Antifungals take advantage of small differences between fungi and humans in the biochemical pathways that synthesize sterols. The sterols are important in maintaining proper membrane fluidity and, hence, proper function of the cell membrane. For most fungi, the predominant membrane sterol is ergosterol . Because human cell membranes use cholesterol , instead of ergosterol, antifungal drugs that target ergosterol synthesis are selectively toxic ( Figure 14.13 ). \n\n The imidazoles are synthetic fungicides that disrupt ergosterol biosynthesis; they are commonly used in medical applications and also in agriculture to keep seeds and harvested crops from molding. Examples include miconazole , ketoconazole , and clotrimazole , which are used to treat fungal skin infections such as ringworm , specifically tinea pedis ( athlete’s foot ), tinea cruris ( jock itch ), and tinea corporis . These infections are commonly caused by dermatophytes of the genera Trichophyton , Epidermophyton , and Microsporum . Miconazole is also used predominantly for the treatment of vaginal yeast infections caused by the fungus Candida , and ketoconazole is used for the treatment of tinea versicolor and dandruff , which both can be caused by the fungus Malassezia . \n\n The triazole drugs, including fluconazole , also inhibit ergosterol biosynthesis. However, they can be administered orally or intravenously for the treatment of several types of systemic yeast infections, including oral thrush and cryptococcal meningitis , both of which are prevalent in patients with AIDS. The triazoles also exhibit more selective toxicity , compared with the imidazoles, and are associated with fewer side effects. \n\n The allylamines , a structurally different class of synthetic antifungal drugs, inhibit an earlier step in ergosterol biosynthesis. The most commonly used allylamine is terbinafine (marketed under the brand name Lamisil ), which is used topically for the treatment of dermatophytic skin infections like athlete’s foot , ringworm , and jock itch . Oral treatment with terbinafine is also used for the treatment of fingernail and toenail fungus, but it can be associated with the rare side effect of hepatotoxicity . \n\n The polyenes are a class of antifungal agents naturally produced by certain actinomycete soil bacteria and are structurally related to macrolides . These large, lipophilic molecules bind to ergosterol in fungal cytoplasmic membranes, thus creating pores. Common examples include nystatin and amphotericin B . Nystatin is typically used as a topical treatment for yeast infections of the skin, mouth, and vagina, but may also be used for intestinal fungal infections. The drug amphotericin B is used for systemic fungal infections like aspergillosis , cryptococcal meningitis , histoplasmosis , blastomycosis , and candidiasis . Amphotericin B was the only antifungal drug available for several decades, but its use is associated with some serious side effects, including nephrotoxicity (kidney toxicity). \n\n Amphotericin B is often used in combination with flucytosine , a fluorinated pyrimidine analog that is converted by a fungal-specific enzyme into a toxic product that interferes with both DNA replication and protein synthesis in fungi. Flucytosine is also associated with hepatotoxicity (liver toxicity) and bone marrow depression. \n\n Beyond targeting ergosterol in fungal cell membranes, there are a few antifungal drugs that target other fungal structures ( Figure 14.14 ). The echinocandins , including caspofungin, are a group of naturally produced antifungal compounds that block the synthesis of β(1→3) glucan found in fungal cell walls but not found in human cells. This drug class has the nickname “penicillin for fungi.” Caspofungin is used for the treatment of aspergillosis as well as systemic yeast infections. \n\n Although chitin is only a minor constituent of fungal cell walls, it is also absent in human cells, making it a selective target. The polyoxins and nikkomycins are naturally produced antifungals that target chitin synthesis. Polyoxins are used to control fungi for agricultural purposes, and nikkomycin Z is currently under development for use in humans to treat yeast infections and Valley fever ( coccidioidomycosis ), a fungal disease prevalent in the southwestern US. 12 12 Centers for Disease Control and Prevention. “Valley Fever: Awareness Is Key.” http://www.cdc.gov/features/valleyfever/. Accessed June 1, 2016. \n\n The naturally produced antifungal griseofulvin is thought to specifically disrupt fungal cell division by interfering with microtubules involved in spindle formation during mitosis. It was one of the first antifungals, but its use is associated with hepatotoxicity . It is typically administered orally to treat various types of dermatophytic skin infections when other topical antifungal treatments are ineffective. \n\n There are a few drugs that act as antimetabolites against fungal processes. For example, atovaquone , a representative of the naphthoquinone drug class, is a semisynthetic antimetabolite for fungal and protozoal versions of a mitochondrial cytochrome important in electron transport. Structurally, it is an analog of coenzyme Q , with which it competes for electron binding. It is particularly useful for the treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii . The antibacterial sulfamethoxazole-trimethoprim combination also acts as an antimetabolite against P. jirovecii . \n\n Table 14.7 shows the various therapeutic classes of antifungal drugs, categorized by mode of action, with examples of each. \n\n Common Antifungal Drugs \n\n Mechanism of Action \n\n Drug Class \n\n Specific Drugs \n\n Clinical Uses \n\n Inhibit ergosterol synthesis \n\n Imidazoles \n\n Miconazole, ketoconazole, clotrimazole \n\n Fungal skin infections and vaginal yeast infections \n\n Triazoles \n\n Fluconazole \n\n Systemic yeast infections, oral thrush, and cryptococcal meningitis \n\n Allylamines \n\n Terbinafine \n\n Dermatophytic skin infections (athlete’s foot, ring worm, jock itch), and infections of fingernails and toenails \n\n Bind ergosterol in the cell membrane and create pores that disrupt the membrane \n\n Polyenes \n\n Nystatin \n\n Used topically for yeast infections of skin, mouth, and vagina; also used for fungal infections of the intestine \n\n Amphotericin B \n\n Variety systemic fungal infections \n\n Inhibit cell wall synthesis \n\n Echinocandins \n\n Caspofungin \n\n Aspergillosis and systemic yeast infections \n\n Not applicable \n\n Nikkomycin Z \n\n Coccidioidomycosis (Valley fever) and yeast infections \n\n Inhibit microtubules and cell division \n\n Not applicable \n\n Griseofulvin \n\n Dermatophytic skin infections \n\n Table 14.7 \n\n Check Your Understanding \n\n How is disruption of ergosterol biosynthesis an effective mode of action for antifungals? \n\n Case in Point Treating a Fungal Infection of the Lungs Jack, a 48-year-old engineer, is HIV positive but generally healthy thanks to antiretroviral therapy (ART) . However, after a particularly intense week at work, he developed a fever and a dry cough. He assumed that he just had a cold or mild flu due to overexertion and didn’t think much of it. However, after about a week, he began to experience fatigue, weight loss, and shortness of breath. He decided to visit his physician, who found that Jack had a low level of blood oxygenation. The physician ordered blood testing, a chest X-ray, and the collection of an induced sputum sample for analysis. His X-ray showed a fine cloudiness and several pneumatoceles (thin-walled pockets of air), which indicated Pneumocystis pneumonia (PCP), a type of pneumonia caused by the fungus Pneumocystis jirovecii . Jack’s physician admitted him to the hospital and prescribed Bactrim , a combination of sulfamethoxazole and trimethoprim , to be administered intravenously. \n\n P. jirovecii is a yeast-like fungus with a life cycle similar to that of protozoans. As such, it was classified as a protozoan until the 1980s. It lives only in the lung tissue of infected persons and is transmitted from person to person, with many people exposed as children. Typically, P. jirovecii only causes pneumonia in immunocompromised individuals. Healthy people may carry the fungus in their lungs with no symptoms of disease. PCP is particularly problematic among HIV patients with compromised immune systems. \n\n PCP is usually treated with oral or intravenous Bactrim, but atovaquone or pentamidine (another antiparasitic drug) are alternatives. If not treated, PCP can progress, leading to a collapsed lung and nearly 100% mortality. Even with antimicrobial drug therapy, PCP still is responsible for 10% of HIV-related deaths. \n\n The cytological examination, using direct immunofluorescence assay (DFA), of a smear from Jack’s sputum sample confirmed the presence of P. jirovecii ( Figure 14.15 ). Additionally, the results of Jack’s blood tests revealed that his white blood cell count had dipped, making him more susceptible to the fungus. His physician reviewed his ART regimen and made adjustments. After a few days of hospitalization, Jack was released to continue his antimicrobial therapy at home. With the adjustments to his ART therapy, Jack’s CD4 counts began to increase and he was able to go back to work. \n\n Antiprotozoan Drugs \n\n There are a few mechanisms by which antiprotozoan drugs target infectious protozoans ( Table 14.9 ). Some are antimetabolites , such as atovaquone , proguanil , and artemisinins. Atovaquone, in addition to being antifungal, blocks electron transport in protozoans and is used for the treatment of protozoan infections including malaria , babesiosis , and toxoplasmosis . Proguanil is another synthetic antimetabolite that is processed in parasitic cells into its active form, which inhibits protozoan folic acid synthesis. It is often used in combination with atovaquone, and the combination is marketed as Malarone for both malaria treatment and prevention. \n\n Artemisinin, a plant-derived antifungal first discovered by Chinese scientists in the 1970s, is quite effective against malaria. Semisynthetic derivatives of artemisinin are more water soluble than the natural version, which makes them more bioavailable. Although the exact mechanism of action is unclear, artemisinins appear to act as prodrugs that are metabolized by target cells to produce reactive oxygen species (ROS) that damage target cells. Due to the rise in resistance to antimalarial drugs, artemisinins are also commonly used in combination with other antimalarial compounds in artemisinin-based combination therapy (ACT). \n\n Several antimetabolites are used for the treatment of toxoplasmosis caused by the parasite Toxoplasma gondii . The synthetic sulfa drug sulfadiazine competitively inhibits an enzyme in folic acid production in parasites and can be used to treat malaria and toxoplasmosis. Pyrimethamine is a synthetic drug that inhibits a different enzyme in the folic acid production pathway and is often used in combination with sulfadoxine (another sulfa drug) for the treatment of malaria or in combination with sulfadiazine for the treatment of toxoplasmosis . Side effects of pyrimethamine include decreased bone marrow activity that may cause increased bruising and low red blood cell counts. When toxicity is a concern, spiramycin , a macrolide protein synthesis inhibitor, is typically administered for the treatment of toxoplasmosis. \n\n Two classes of antiprotozoan drugs interfere with nucleic acid synthesis: nitroimidazoles and quinolines . Nitroimidazoles, including semisynthetic metronidazole , which was discussed previously as an antibacterial drug, and synthetic tinidazole , are useful in combating a wide variety of protozoan pathogens, such as Giardia lamblia , Entamoeba histolytica , and Trichomonas vaginalis . Upon introduction into these cells in low-oxygen environments, nitroimidazoles become activated and introduce DNA strand breakage, interfering with DNA replication in target cells. Unfortunately, metronidazole is associated with carcinogenesis (the development of cancer) in humans. \n\n Another type of synthetic antiprotozoan drug that has long been thought to specifically interfere with DNA replication in certain pathogens is pentamidine . It has historically been used for the treatment of African sleeping sickness (caused by the protozoan Trypanosoma brucei ) and leishmaniasis (caused by protozoa of the genus Leishmania ), but it is also an alternative treatment for the fungus Pneumocystis . Some studies indicate that it specifically binds to the DNA found within kinetoplasts (kDNA; long mitochondrion-like structures unique to trypanosomes ), leading to the cleavage of kDNA. However, nuclear DNA of both the parasite and host remain unaffected. It also appears to bind to tRNA, inhibiting the addition of amino acids to tRNA, thus preventing protein synthesis. Possible side effects of pentamidine use include pancreatic dysfunction and liver damage. \n\n The quinolines are a class of synthetic compounds related to quinine , which has a long history of use against malaria. Quinolines are thought to interfere with heme detoxification, which is necessary for the parasite’s effective breakdown of hemoglobin into amino acids inside red blood cells. The synthetic derivatives chloroquine, quinacrine (also called mepacrine ), and mefloquine are commonly used as antimalarials, and chloroquine is also used to treat amebiasis typically caused by Entamoeba histolytica . Long-term prophylactic use of chloroquine or mefloquine may result in serious side effects, including hallucinations or cardiac issues. Patients with glucose-6-phosphate dehydrogenase deficiency experience severe anemia when treated with chloroquine. \n\n Common Antiprotozoan Drugs \n\n Mechanism of Action \n\n Drug Class \n\n Specific Drugs \n\n Clinical Uses \n\n Inhibit electron transport in mitochondria \n\n Naphthoquinone \n\n Atovaquone \n\n Malaria, babesiosis, and toxoplasmosis \n\n Inhibit folic acid synthesis \n\n Not applicable \n\n Proquanil \n\n Combination therapy with atovaquone for malaria treatment and prevention \n\n Sulfonamide \n\n Sulfadiazine \n\n Malaria and toxoplasmosis \n\n Not applicable \n\n Pyrimethamine \n\n Combination therapy with sulfadoxine (sulfa drug) for malaria \n\n Produces damaging reactive oxygen species \n\n Not applicable \n\n Artemisinin \n\n Combination therapy to treat malaria \n\n Inhibit DNA synthesis \n\n Nitroimidazoles \n\n Metronidazole, tinidazole \n\n Infections caused by Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis \n\n Not applicable \n\n Pentamidine \n\n African sleeping sickness and leishmaniasis \n\n Inhibit heme detoxification \n\n Quinolines \n\n Chloroquine \n\n Malaria and infections with E. histolytica \n\n Mepacrine, mefloquine \n\n Malaria \n\n Table 14.8 \n\n Check Your Understanding \n\n List two modes of action for antiprotozoan drugs. \n\n Antihelminthic Drugs \n\n Because helminths are multicellular eukaryotes like humans, developing drugs with selective toxicity against them is extremely challenging. Despite this, several effective classes have been developed ( Table 14.9 ). Synthetic benzimidazoles , like mebendazole and albendazole , bind to helminthic β-tubulin, preventing microtubule formation. Microtubules in the intestinal cells of the worms seem to be particularly affected, leading to a reduction in glucose uptake. Besides their activity against a broad range of helminths, benzimidazoles are also active against many protozoans, fungi, and viruses, and their use for inhibiting mitosis and cell cycle progression in cancer cells is under study. 13 Possible side effects of their use include liver damage and bone marrow suppression. 13 B. Chu et al. “A Benzimidazole Derivative Exhibiting Antitumor Activity Blocks EGFR and HER2 Activity and Upregulates DR5 in Breast Cancer Cells.” Cell Death and Disease 6 (2015):e1686 \n\n The avermectins are members of the macrolide family that were first discovered from a Japanese soil isolate, Streptomyces avermectinius . A more potent semisynthetic derivative of avermectin is ivermectin , which binds to glutamate-gated chloride channels specific to invertebrates including helminths, blocking neuronal transmission and causing starvation, paralysis, and death of the worms. Ivermectin is used to treat roundworm diseases, including onchocerciasis (also called river blindness , caused by the worm Onchocerca volvulus ) and strongyloidiasis (caused by the worm Strongyloides stercoralis or S. fuelleborni ). Ivermectin also can also treat parasitic insects like mites, lice, and bed bugs, and is nontoxic to humans. \n\n Niclosamide is a synthetic drug that has been used for over 50 years to treat tapeworm infections. Although its mode of action is not entirely clear, niclosamide appears to inhibit ATP formation under anaerobic conditions and inhibit oxidative phosphorylation in the mitochondria of its target pathogens. Niclosamide is not absorbed from the gastrointestinal tract, thus it can achieve high localized intestinal concentrations in patients. Recently, it has been shown to also have antibacterial, antiviral, and antitumor activities. 14 15 16 14 J.-X. Pan et al. “Niclosamide, An Old Antihelminthic Agent, Demonstrates Antitumor Activity by Blocking Multiple Signaling Pathways of Cancer Stem Cells.” Chinese Journal of Cancer 31 no. 4 (2012):178–184. 15 F. Imperi et al. “New Life for an Old Drug: The Anthelmintic Drug Niclosamide Inhibits Pseudomonas aeruginosa Quorum Sensing.” Antimicrobial Agents and Chemotherapy 57 no. 2 (2013):996-1005. 16 A. Jurgeit et al. “Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects.” PLoS Pathogens 8 no. 10 (2012):e1002976. \n\n Another synthetic antihelminthic drug is praziquantel , which used for the treatment of parasitic tapeworms and liver flukes , and is particularly useful for the treatment of schistosomiasis (caused by blood flukes from three genera of Schistosoma ). Its mode of action remains unclear, but it appears to cause the influx of calcium into the worm, resulting in intense spasm and paralysis of the worm. It is often used as a preferred alternative to niclosamide in the treatment of tapeworms when gastrointestinal discomfort limits niclosamide use. \n\n The thioxanthenones , another class of synthetic drugs structurally related to quinine , exhibit antischistosomal activity by inhibiting RNA synthesis. The thioxanthenone lucanthone and its metabolite hycanthone were the first used clinically, but serious neurological, gastrointestinal, cardiovascular, and hepatic side effects led to their discontinuation. Oxamniquine, a less toxic derivative of hycanthone, is only effective against S. mansoni , one of the three species known to cause schistosomiasis in humans. Praziquantel was developed to target the other two schistosome species, but concerns about increasing resistance have renewed interest in developing additional derivatives of oxamniquine to target all three clinically important schistosome species. \n\n Common Antihelminthic Drugs \n\n Mechanism of Action \n\n Drug Class \n\n Specific Drugs \n\n Clinical Uses \n\n Inhibit microtubule formation, reducing glucose uptake \n\n Benzimidazoles \n\n Mebendazole, albendazole \n\n Variety of helminth infections \n\n Block neuronal transmission, causing paralysis and starvation \n\n Avermectins \n\n Ivermectin \n\n Roundworm diseases, including river blindness and strongyloidiasis, and treatment of parasitic insects \n\n Inhibit ATP production \n\n Not applicable \n\n Niclosamide \n\n Intestinal tapeworm infections \n\n Induce calcium influx \n\n Not applicable \n\n Praziquantel \n\n Schistosomiasis (blood flukes) \n\n Inhibit RNA synthesis \n\n Thioxanthenones \n\n Lucanthone, hycanthone, oxamniquine \n\n Schistosomiasis (blood flukes) \n\n Table 14.9 \n\n Check Your Understanding \n\n Why are antihelminthic drugs difficult to develop? \n\n Antiviral Drugs \n\n Unlike the complex structure of fungi, protozoa, and helminths, viral structure is simple, consisting of nucleic acid, a protein coat, viral enzymes, and, sometimes, a lipid envelope. Furthermore, viruses are obligate intracellular pathogens that use the host’s cellular machinery to replicate. These characteristics make it difficult to develop drugs with selective toxicity against viruses. \n\n Many antiviral drugs are nucleoside analogs and function by inhibiting nucleic acid biosynthesis. For example, acyclovir (marketed as Zovirax ) is a synthetic analog of the nucleoside guanosine ( Figure 14.16 ). It is activated by the herpes simplex viral enzyme thymidine kinase and, when added to a growing DNA strand during replication, causes chain termination. Its specificity for virus-infected cells comes from both the need for a viral enzyme to activate it and the increased affinity of the activated form for viral DNA polymerase compared to host cell DNA polymerase. Acyclovir and its derivatives are frequently used for the treatment of herpes virus infections, including genital herpes , chickenpox , shingles , Epstein-Barr virus infections, and cytomegalovirus infections. Acyclovir can be administered either topically or systemically, depending on the infection. One possible side effect of its use includes nephrotoxicity . The drug adenine-arabinoside , marketed as vidarabine , is a synthetic analog to deoxyadenosine that has a mechanism of action similar to that of acyclovir. It is also effective for the treatment of various human herpes viruses. However, because of possible side effects involving low white blood cell counts and neurotoxicity , treatment with acyclovir is now preferred. \n\n Ribavirin, another synthetic guanosine analog, works by a mechanism of action that is not entirely clear. It appears to interfere with both DNA and RNA synthesis, perhaps by reducing intracellular pools of guanosine triphosphate (GTP). Ribavarin also appears to inhibit the RNA polymerase of hepatitis C virus. It is primarily used for the treatment of the RNA viruses like hepatitis C (in combination therapy with interferon) and respiratory syncytial virus . Possible side effects of ribavirin use include anemia and developmental effects on unborn children in pregnant patients. In recent years, another nucleotide analog, sofosbuvir ( Solvaldi ), has also been developed for the treatment of hepatitis C. Sofosbuvir is a uridine analog that interferes with viral polymerase activity. It is commonly coadministered with ribavirin, with and without interferon . \n\n Inhibition of nucleic acid synthesis is not the only target of synthetic antivirals. Although the mode of action of amantadine and its relative rimantadine are not entirely clear, these drugs appear to bind to a transmembrane protein that is involved in the escape of the influenza virus from endosomes. Blocking escape of the virus also prevents viral RNA release into host cells and subsequent viral replication. Increasing resistance has limited the use of amantadine and rimantadine in the treatment of influenza A. Use of amantadine can result in neurological side effects, but the side effects of rimantadine seem less severe. Interestingly, because of their effects on brain chemicals such as dopamine and NMDA (N-methyl D-aspartate), amantadine and rimantadine are also used for the treatment of Parkinson’s disease . \n\n Neuraminidase inhibitors, including olsetamivir ( Tamiflu ), zanamivir ( Relenza ), and peramivir ( Rapivab ), specifically target influenza viruses by blocking the activity of influenza virus neuraminidase , preventing the release of the virus from infected cells. These three antivirals can decrease flu symptoms and shorten the duration of illness, but they differ in their modes of administration: olsetamivir is administered orally, zanamivir is inhaled, and peramivir is administered intravenously. Resistance to these neuraminidase inhibitors still seems to be minimal. \n\n Pleconaril is a synthetic antiviral under development that showed promise for the treatment of picornaviruses . Use of pleconaril for the treatment of the common cold caused by rhinoviruses was not approved by the FDA in 2002 because of lack of proven effectiveness, lack of stability, and association with irregular menstruation. Its further development for this purpose was halted in 2007. However, pleconaril is still being investigated for use in the treatment of life-threatening complications of enteroviruses , such as meningitis and sepsis . It is also being investigated for use in the global eradication of a specific enterovirus, polio . 17 Pleconaril seems to work by binding to the viral capsid and preventing the uncoating of viral particles inside host cells during viral infection. 17 M.J. Abzug. “The Enteroviruses: Problems in Need of Treatments.” Journal of Infection 68 no. S1 (2014):108–14. \n\n Viruses with complex life cycles, such as HIV , can be more difficult to treat. First, HIV targets CD4-positive white blood cells, which are necessary for a normal immune response to infection. Second, HIV is a retrovirus , meaning that it converts its RNA genome into a DNA copy that integrates into the host cell’s genome, thus hiding within host cell DNA. Third, the HIV reverse transcriptase lacks proofreading activity and introduces mutations that allow for rapid development of antiviral drug resistance. To help prevent the emergence of resistance, a combination of specific synthetic antiviral drugs is typically used in ART for HIV ( Figure 14.17 ). \n\n The reverse transcriptase inhibitors block the early step of converting viral RNA genome into DNA, and can include competitive nucleoside analog inhibitors (e.g., azidothymidine/zidovudine , or AZT) and non-nucleoside noncompetitive inhibitors (e.g., etravirine ) that bind reverse transcriptase and cause an inactivating conformational change. Drugs called protease inhibitors (e.g., ritonavir ) block the processing of viral proteins and prevent viral maturation. Protease inhibitors are also being developed for the treatment of other viral types. 18 For example, simeprevir ( Olysio ) has been approved for the treatment of hepatitis C and is administered with ribavirin and interferon in combination therapy. The integrase inhibitors (e.g., raltegravir ), block the activity of the HIV integrase responsible for the recombination of a DNA copy of the viral genome into the host cell chromosome. Additional drug classes for HIV treatment include the CCR5 antagonists and the fusion inhibitors (e.g., enfuviritide ), which prevent the binding of HIV to the host cell coreceptor (chemokine receptor type 5 [CCR5]) and the merging of the viral envelope with the host cell membrane, respectively. Table 14.10 shows the various therapeutic classes of antiviral drugs, categorized by mode of action, with examples of each. 18 B.L. Pearlman. “Protease Inhibitors for the Treatment of Chronic Hepatitis C Genotype-1 Infection: The New Standard of Care.” Lancet Infectious Diseases 12 no. 9 (2012):717–728. \n\n Common Antiviral Drugs \n\n Mechanism of Action \n\n Drug \n\n Clinical Uses \n\n Nucleoside analog inhibition of nucleic acid synthesis \n\n Acyclovir \n\n Herpes virus infections \n\n Azidothymidine/zidovudine (AZT) \n\n HIV infections \n\n Ribavirin \n\n Hepatitis C virus and respiratory syncytial virus infections \n\n Vidarabine \n\n Herpes virus infections \n\n Sofosbuvir \n\n Hepatitis C virus infections \n\n Non-nucleoside noncompetitive inhibition \n\n Etravirine \n\n HIV infections \n\n Inhibit escape of virus from endosomes \n\n Amantadine, rimantadine \n\n Infections with influenza virus \n\n Inhibit neuraminadase \n\n Olsetamivir, zanamivir, peramivir \n\n Infections with influenza virus \n\n Inhibit viral uncoating \n\n Pleconaril \n\n Serious enterovirus infections \n\n Inhibition of protease \n\n Ritonavir \n\n HIV infections \n\n Simeprevir \n\n Hepatitis C virus infections \n\n Inhibition of integrase \n\n Raltegravir \n\n HIV infections \n\n Inhibition of membrane fusion \n\n Enfuviritide \n\n HIV infections \n\n Table 14.10 \n\n Check Your Understanding \n\n Why is HIV difficult to treat with antivirals? \n\n Link to Learning \n\n To learn more about the various classes of antiretroviral drugs used in the ART of HIV infection, explore each of the drugs in the HIV drug classes provided by US Department of Health and Human Services at this website. \n 14.5 Drug Resistance \n\n Learning Objectives \n\n Explain the concept of drug resistance \n\n Describe how microorganisms develop or acquire drug resistance \n\n Describe the different mechanisms of antimicrobial drug resistance \n\n Antimicrobial resistance is not a new phenomenon. In nature, microbes are constantly evolving in order to overcome the antimicrobial compounds produced by other microorganisms. Human development of antimicrobial drugs and their widespread clinical use has simply provided another selective pressure that promotes further evolution. Several important factors can accelerate the evolution of drug resistance . These include the overuse and misuse of antimicrobials, inappropriate use of antimicrobials, subtherapeutic dosing, and patient noncompliance with the recommended course of treatment. \n\n Exposure of a pathogen to an antimicrobial compound can select for chromosomal mutations conferring resistance, which can be transferred vertically to subsequent microbial generations and eventually become predominant in a microbial population that is repeatedly exposed to the antimicrobial. Alternatively, many genes responsible for drug resistance are found on plasmids or in transposons that can be transferred easily between microbes through horizontal gene transfer (see How Asexual Prokaryotes Achieve Genetic Diversity ). Transposons also have the ability to move resistance genes between plasmids and chromosomes to further promote the spread of resistance. \n\n Mechanisms for Drug Resistance \n\n There are several common mechanisms for drug resistance, which are summarized in Figure 14.18 . These mechanisms include enzymatic modification of the drug, modification of the antimicrobial target, and prevention of drug penetration or accumulation. \n\n Drug Modification or Inactivation \n\n Resistance genes may code for enzymes that chemically modify an antimicrobial, thereby inactivating it, or destroy an antimicrobial through hydrolysis. Resistance to many types of antimicrobials occurs through this mechanism. For example, aminoglycoside resistance can occur through enzymatic transfer of chemical groups to the drug molecule, impairing the binding of the drug to its bacterial target. For β-lactams , bacterial resistance can involve the enzymatic hydrolysis of the β-lactam bond within the β-lactam ring of the drug molecule. Once the β-lactam bond is broken, the drug loses its antibacterial activity. This mechanism of resistance is mediated by β-lactamases , which are the most common mechanism of β-lactam resistance. Inactivation of rifampin commonly occurs through glycosylation , phosphorylation , or adenosine diphosphate (ADP) ribosylation, and resistance to macrolides and lincosamides can also occur due to enzymatic inactivation of the drug or modification. \n\n Prevention of Cellular Uptake or Efflux \n\n Microbes may develop resistance mechanisms that involve inhibiting the accumulation of an antimicrobial drug, which then prevents the drug from reaching its cellular target. This strategy is common among gram-negative pathogens and can involve changes in outer membrane lipid composition, porin channel selectivity, and/or porin channel concentrations. For example, a common mechanism of carbapenem resistance among Pseudomonas aeruginosa is to decrease the amount of its OprD porin, which is the primary portal of entry for carbapenems through the outer membrane of this pathogen. Additionally, many gram-positive and gram-negative pathogenic bacteria produce efflux pump s that actively transport an antimicrobial drug out of the cell and prevent the accumulation of drug to a level that would be antibacterial. For example, resistance to β-lactams, tetracyclines , and fluoroquinolones commonly occurs through active efflux out of the cell, and it is rather common for a single efflux pump to have the ability to translocate multiple types of antimicrobials. \n\n Target Modification \n\n Because antimicrobial drugs have very specific targets, structural changes to those targets can prevent drug binding, rendering the drug ineffective. Through spontaneous mutations in the genes encoding antibacterial drug targets, bacteria have an evolutionary advantage that allows them to develop resistance to drugs. This mechanism of resistance development is quite common. Genetic changes impacting the active site of penicillin-binding proteins (PBPs) can inhibit the binding of β-lactam drugs and provide resistance to multiple drugs within this class. This mechanism is very common among strains of Streptococcus pneumoniae , which alter their own PBPs through genetic mechanisms. In contrast, strains of Staphylococcus aureus develop resistance to methicillin ( MRSA ) through the acquisition of a new low-affinity PBP, rather than structurally alter their existing PBPs. Not only does this new low-affinity PBP provide resistance to methicillin but it provides resistance to virtually all β-lactam drugs, with the exception of the newer fifth-generation cephalosporins designed specifically to kill MRSA. Other examples of this resistance strategy include alterations in \n\n ribosome subunits, providing resistance to macrolides, tetracyclines, and aminoglycosides; \n\n lipopolysaccharide (LPS) structure, providing resistance to polymyxins ; \n\n RNA polymerase, providing resistance to rifampin ; \n\n DNA gyrase, providing resistance to fluoroquinolones; \n\n metabolic enzymes, providing resistance to sulfa drugs , sulfones , and trimethoprim ; and \n\n peptidoglycan subunit peptide chains, providing resistance to glycopeptides . \n\n Target Overproduction or Enzymatic Bypass \n\n When an antimicrobial drug functions as an antimetabolite, targeting a specific enzyme to inhibit its activity, there are additional ways that microbial resistance may occur. First, the microbe may overproduce the target enzyme such that there is a sufficient amount of antimicrobial-free enzyme to carry out the proper enzymatic reaction. Second, the bacterial cell may develop a bypass that circumvents the need for the functional target enzyme. Both of these strategies have been found as mechanisms of sulfonamide resistance . Vancomycin resistance among S. aureus has been shown to involve the decreased cross-linkage of peptide chains in the bacterial cell wall, which provides an increase in targets for vancomycin to bind to in the outer cell wall. Increased binding of vancomycin in the outer cell wall provides a blockage that prevents free drug molecules from penetrating to where they can block new cell wall synthesis. \n\n Target Mimicry \n\nA recently discovered mechanism of resistance called target mimicry involves the production of proteins that prevent drugs from binding to their bacterial cellular targets. For example, fluoroquinolone resistance by Mycobacterium tuberculosis can involve the production of a protein that resembles DNA. This protein is called MfpA (Mycobacterium fluoroquinolone resistance protein A). The mimicry of DNA by MfpA results in DNA gyrase binding to MfpA, preventing the binding of fluoroquinolones to DNA gyrase.\n\n Check Your Understanding \n\n List several mechanisms for drug resistance. \n\n Multidrug-Resistant Microbes and Cross Resistance \n\n From a clinical perspective, our greatest concerns are multidrug-resistant microbes (MDRs) and cross resistance. MDRs are colloquially known as “ superbugs ” and carry one or more resistance mechanism(s), making them resistant to multiple antimicrobials. In cross-resistance , a single resistance mechanism confers resistance to multiple antimicrobial drugs. For example, having an efflux pump that can export multiple antimicrobial drugs is a common way for microbes to be resistant to multiple drugs by using a single resistance mechanism. In recent years, several clinically important superbugs have emerged, and the CDC reports that superbugs are responsible for more than 2 million infections in the US annually, resulting in at least 23,000 fatalities. 19 Several of the superbugs discussed in the following sections have been dubbed the ESKAPE pathogens . This acronym refers to the names of the pathogens ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa and Enterobacter spp. ) but it is also fitting in that these pathogens are able to “escape” many conventional forms of antimicrobial therapy. As such, infections by ESKAPE pathogens can be difficult to treat and they cause a large number of nosocomial infections. 19 Centers for Disease Control and Prevention. “Antibiotic/Antimicrobial Resistance.” http://www.cdc.gov/drugresistance/index.html. Accessed June 2, 2016. \n\n Methicillin-Resistant Staphylococcus aureus (MRSA) \n\n Methicillin, a semisynthetic penicillin, was designed to resist inactivation by β-lactamases. Unfortunately, soon after the introduction of methicillin to clinical practice, methicillin-resistant strains of S. aureus appeared and started to spread. The mechanism of resistance, acquisition of a new low-affinity PBP, provided S. aureus with resistance to all available β-lactams. Strains of methicillin-resistant S. aureus (MRSA) are widespread opportunistic pathogens and a particular concern for skin and other wound infections, but may also cause pneumonia and septicemia . Although originally a problem in health-care settings (hospital-acquired MRSA [HA-MRSA]), MRSA infections are now also acquired through contact with contaminated members of the general public, called community-associated MRSA (CA-MRSA). Approximately one-third of the population carries S. aureus as a member of their normal nasal microbiota without illness, and about 6% of these strains are methicillin resistant. 20 21 20 A.S. Kalokhe et al. “Multidrug-Resistant Tuberculosis Drug Susceptibility and Molecular Diagnostic Testing: A Review of the Literature. American Journal of the Medical Sciences 345 no. 2 (2013):143–148. 21 Centers for Disease Control and Prevention. “Methicillin-Resistant Staphylococcus aureus (MRSA): General Information About MRSA in the Community.” http://www.cdc.gov/mrsa/community/index.html. Accessed June 2, 2016 \n\n Micro Connections Clavulanic Acid: Penicillin’s Little Helper With the introduction of penicillin in the early 1940s, and its subsequent mass production, society began to think of antibiotics as miracle cures for a wide range of infectious diseases. Unfortunately, as early as 1945, penicillin resistance was first documented and started to spread. Greater than 90% of current S. aureus clinical isolates are resistant to penicillin. 22 22 F.D. Lowy. “Antimicrobial Resistance: The Example of Staphylococcus aureus .” Journal of Clinical Investigation 111 no. 9 (2003):1265–1273. \n\n Although developing new antimicrobial drugs is one solution to this problem, scientists have explored new approaches, including the development of compounds that inactivate resistance mechanisms. The development of clavulanic acid represents an early example of this strategy. Clavulanic acid is a molecule produced by the bacterium Streptococcus clavuligerus . It contains a β-lactam ring , making it structurally similar to penicillin and other β-lactams , but shows no clinical effectiveness when administered on its own. Instead, clavulanic acid binds irreversibly within the active site of β-lactamases and prevents them from inactivating a coadministered penicillin. \n\n Clavulanic acid was first developed in the 1970s and was mass marketed in combination with amoxicillin beginning in the 1980s under the brand name Augmentin. As is typically the case, resistance to the amoxicillin-clavulanic acid combination soon appeared. Resistance most commonly results from bacteria increasing production of their β-lactamase and overwhelming the inhibitory effects of clavulanic acid, mutating their β-lactamase so it is no longer inhibited by clavulanic acid, or from acquiring a new β-lactamase that is not inhibited by clavulanic acid. Despite increasing resistance concerns, clavulanic acid and related β-lactamase inhibitors (sulbactam and tazobactam) represent an important new strategy: the development of compounds that directly inhibit antimicrobial resistance-conferring enzymes. \n\n Vancomycin-Resistant Enterococci and Staphylococcus aureus \n\n Vancomycin is only effective against gram-positive organisms, and it is used to treat wound infections, septic infections, endocarditis, and meningitis that are caused by pathogens resistant to other antibiotics. It is considered one of the last lines of defense against such resistant infections, including MRSA. With the rise of antibiotic resistance in the 1970s and 1980s, vancomycin use increased, and it is not surprising that we saw the emergence and spread of vancomycin-resistant enterococci (VRE) , vancomycin-resistant S. aureus (VRSA) , and vancomycin-intermediate S. aureus (VISA) . The mechanism of vancomycin resistance among enterococci is target modification involving a structural change to the peptide component of the peptidoglycan subunits, preventing vancomycin from binding. These strains are typically spread among patients in clinical settings by contact with health-care workers and contaminated surfaces and medical equipment. \n\n VISA and VRSA strains differ from each other in the mechanism of resistance and the degree of resistance each mechanism confers. VISA strains exhibit intermediate resistance, with a minimum inhibitory concentration (MIC) of 4–8 μg/mL, and the mechanism involves an increase in vancomycin targets. VISA strains decrease the crosslinking of peptide chains in the cell wall, providing an increase in vancomycin targets that trap vancomycin in the outer cell wall. In contrast, VRSA strains acquire vancomycin resistance through horizontal transfer of resistance genes from VRE, an opportunity provided in individuals coinfected with both VRE and MRSA. VRSA exhibit a higher level of resistance, with MICs of 16 μg/mL or higher. 23 In the case of all three types of vancomycin-resistant bacteria, rapid clinical identification is necessary so proper procedures to limit spread can be implemented. The oxazolidinones like linezolid are useful for the treatment of these vancomycin-resistant, opportunistic pathogens, as well as MRSA. 23 Centers for Disease Control and Prevention. “Healthcare-Associated Infections (HIA): General Information about VISA/VRSA.” http://www.cdc.gov/HAI/organisms/visa_vrsa/visa_vrsa.html. Accessed June 2, 2016. \n\n Extended-Spectrum β-Lactamase–Producing Gram-Negative Pathogens \n\n Gram-negative pathogens that produce extended-spectrum β-lactamases (ESBLs) show resistance well beyond just penicillins. The spectrum of β-lactams inactivated by ESBLs provides for resistance to all penicillins , cephalosporins , monobactams , and the β-lactamase-inhibitor combinations, but not the carbapenems . An even greater concern is that the genes encoding for ESBLs are usually found on mobile plasmids that also contain genes for resistance to other drug classes (e.g., fluoroquinolones , aminoglycosides , tetracyclines ), and may be readily spread to other bacteria by horizontal gene transfer . These multidrug-resistant bacteria are members of the intestinal microbiota of some individuals, but they are also important causes of opportunistic infections in hospitalized patients, from whom they can be spread to other people. \n\n Carbapenem-Resistant Gram-Negative Bacteria \n\n The occurrence of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem resistance among other gram-negative bacteria (e.g., P. aeruginosa , Acinetobacter baumannii , Stenotrophomonas maltophila ) is a growing health-care concern. These pathogens develop resistance to carbapenems through a variety of mechanisms, including production of carbapenemases (broad-spectrum β-lactamases that inactivate all β-lactams, including carbapenems), active efflux of carbapenems out of the cell, and/or prevention of carbapenem entry through porin channels . Similar to concerns with ESBLs, carbapenem-resistant, gram-negative pathogens are usually resistant to multiple classes of antibacterials, and some have even developed pan-resistance (resistance to all available antibacterials). Infections with carbapenem-resistant, gram-negative pathogens commonly occur in health-care settings through interaction with contaminated individuals or medical devices, or as a result of surgery. \n\n Multidrug-Resistant Mycobacterium tuberculosis \n\n The emergence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant Mycobacterium tuberculosis ( XDR-TB ) is also of significant global concern. MDR-TB strains are resistant to both rifampin and isoniazid , the drug combination typically prescribed for treatment of tuberculosis. XDR-TB strains are additionally resistant to any fluoroquinolone and at least one of three other drugs ( amikacin , kanamycin , or capreomycin ) used as a second line of treatment, leaving these patients very few treatment options. Both types of pathogens are particularly problematic in immunocompromised persons, including those suffering from HIV infection. The development of resistance in these strains often results from the incorrect use of antimicrobials for tuberculosis treatment, selecting for resistance. \n\n Check Your Understanding \n\n How does drug resistance lead to superbugs? \n\n Link to Learning \n\n To learn more about the top 18 drug-resistant threats to the US, visit the CDC’s website. \n\n Micro Connections Factory Farming and Drug Resistance Although animal husbandry has long been a major part of agriculture in America, the rise of concentrated animal feeding operations (CAFOs) since the 1950s has brought about some new environmental issues, including the contamination of water and air with biological waste, and ethical issues regarding animal rights also are associated with growing animals in this way. Additionally, the increase in CAFOs involves the extensive use of antimicrobial drugs in raising livestock. Antimicrobials are used to prevent the development of infectious disease in the close quarters of CAFOs; however, the majority of antimicrobials used in factory farming are for the promotion of growth—in other words, to grow larger animals. \n\n The mechanism underlying this enhanced growth remains unclear. These antibiotics may not necessarily be the same as those used clinically for humans, but they are structurally related to drugs used for humans. As a result, use of antimicrobial drugs in animals can select for antimicrobial resistance, with these resistant bacteria becoming cross-resistant to drugs typically used in humans. For example, tylosin use in animals appears to select for bacteria also cross-resistant to other macrolides, including erythromycin, commonly used in humans. \n\n Concentrations of the drug-resistant bacterial strains generated by CAFOs become increased in water and soil surrounding these farms. If not directly pathogenic in humans, these resistant bacteria may serve as a reservoir of mobile genetic elements that can then pass resistance genes to human pathogens. Fortunately, the cooking process typically inactivates any antimicrobials remaining in meat, so humans typically are not directly ingesting these drugs. Nevertheless, many people are calling for more judicious use of these drugs, perhaps charging farmers user fees to reduce indiscriminate use. In fact, in 2012, the FDA published guidelines for farmers who voluntarily phase out the use of antimicrobial drugs except under veterinary supervision and when necessary to ensure animal health. Although following the guidelines is voluntary at this time, the FDA does recommend what it calls “judicious” use of antimicrobial drugs in food-producing animals in an effort to decrease antimicrobial resistance. \n\n Clinical Focus Part 3 Unfortunately, Marisa’s urinary tract infection did not resolve with ciprofloxacin treatment. Laboratory testing showed that her infection was caused by a strain of Klebsiella pneumoniae with significant antimicrobial resistance. The resistance profile of this K. pneumoniae included resistance to the carbapenem class of antibacterials, a group of β-lactams that is typically reserved for the treatment of highly resistant bacteria. K. pneumoniae is an opportunistic, capsulated, gram-negative rod that may be a member of the normal microbiota of the intestinal tract, but may also cause a number of diseases, including pneumonia and UTIs. \n\n Specific laboratory tests looking for carbapenemase production were performed on Marisa’s samples and came back positive. Based upon this result, in combination with her health history, production of a carbapenemase known as the New Delhi Metallo-β-lactamase (NDM) was suspected. Although the origin of the NDM carbapenemase is not completely known, many patients infected with NDM-containing strains have travel histories involving hospitalizations in India or surrounding countries. \n\n How would doctors determine which types of antimicrobial drugs should be administered? \n\n Jump to the next Clinical Focus box. Go back to the previous Clinical Focus box. \n 14.6 Testing the Effectiveness of Antimicrobials \n\n Learning Objectives \n\n Describe how the Kirby-Bauer disk diffusion test determines the susceptibility of a microbe to an antibacterial drug. \n\n Explain the significance of the minimal inhibitory concentration and the minimal bactericidal concentration relative to the effectiveness of an antimicrobial drug. \n\n Testing the effectiveness of antimicrobial drugs against specific organisms is important in identifying their spectrum of activity and the therapeutic dosage . This type of test, generally described as antimicrobial susceptibility testing (AST) , is commonly performed in a clinical laboratory. In this section, we will discuss common methods of testing the effectiveness of antimicrobials. \n\n The Kirby-Bauer Disk Diffusion Test \n\n The Kirby-Bauer disk diffusion test has long been used as a starting point for determining the susceptibility of specific microbes to various antimicrobial drugs. The Kirby-Bauer assay starts with a Mueller-Hinton agar plate on which a confluent lawn is inoculated with a patient’s isolated bacterial pathogen. Filter paper disks impregnated with known amounts of antibacterial drugs to be tested are then placed on the agar plate. As the bacterial inoculum grows, antibiotic diffuses from the circular disk into the agar and interacts with the growing bacteria. Antibacterial activity is observed as a clear circular zone of inhibition around the drug-impregnated disk, similar to the disk-diffusion assay depicted in Figure 13.31 . The diameter of the zone of inhibition, measured in millimeters and compared to a standardized chart, determines the susceptibility or resistance of the bacterial pathogen to the drug. \n\n There are multiple factors that determine the size of a zone of inhibition in this assay, including drug solubility, rate of drug diffusion through agar, the thickness of the agar medium, and the drug concentration impregnated into the disk. Due to a lack of standardization of these factors, interpretation of the Kirby-Bauer disk diffusion assay provides only limited information on susceptibility and resistance to the drugs tested. The assay cannot distinguish between bacteriostatic and bactericidal activities, and differences in zone sizes cannot be used to compare drug potencies or efficacies. Comparison of zone sizes to a standardized chart will only provide information on the antibacterials to which a bacterial pathogen is susceptible or resistant. \n\n Check Your Understanding \n\n How does one use the information from a Kirby-Bauer assay to predict the therapeutic effectiveness of an antimicrobial drug in a patient? \n\n Micro Connections Antibiograms: Taking Some of the Guesswork Out of Prescriptions Unfortunately, infectious diseases don’t take a time-out for lab work. As a result, physicians rarely have the luxury of conducting susceptibility testing before they write a prescription. Instead, they rely primarily on the empirical evidence (i.e., the signs and symptoms of disease) and their professional experience to make an educated guess as to the diagnosis, causative agent(s), and drug most likely to be effective. This approach allows treatment to begin sooner so the patient does not have to wait for lab test results. In many cases, the prescription is effective; however, in an age of increased antimicrobial resistance, it is becoming increasingly more difficult to select the most appropriate empiric therapy. Selecting an inappropriate empiric therapy not only puts the patient at risk but may promote greater resistance to the drug prescribed. \n\n Recently, studies have shown that antibiograms are useful tools in the decision-making process of selecting appropriate empiric therapy. An antibiogram is a compilation of local antibiotic susceptibility data broken down by bacterial pathogen. In a November 2014 study published in the journal Infection Control and Hospital Epidemiology , researchers determined that 85% of the prescriptions ordered in skilled nursing facilities were decided upon empirically, but only 35% of those prescriptions were deemed appropriate when compared with the eventual pathogen identification and susceptibility profile obtained from the clinical laboratory. However, in one nursing facility where use of antibiograms was implemented to direct selection of empiric therapy, appropriateness of empiric therapy increased from 32% before antibiogram implementation to 45% after implementation of antibiograms. 24 Although these data are preliminary, they do suggest that health-care facilities can reduce the number of inappropriate prescriptions by using antibiograms to select empiric therapy, thus benefiting patients and minimizing opportunities for antimicrobial resistance to develop. 24 J.P. Furuno et al. “Using Antibiograms to Improve Antibiotic Prescribing in Skilled Nursing Facilities.” Infection Control and Hospital Epidemiology 35 no. Suppl S3 (2014):S56–61. \n\n Link to Learning \n\n Visit this website to view an interactive antibiogram provided by Stanford University. \n\n Dilution Tests \n\n As discussed, the limitations of the Kirby-Bauer disk diffusion test do not allow for a direct comparison of antibacterial potencies to guide selection of the best therapeutic choice. However, antibacterial dilution tests can be used to determine a particular drug’s minimal inhibitory concentration (MIC) , the lowest concentration of drug that inhibits visible bacterial growth, and minimal bactericidal concentration (MBC) , the lowest drug concentration that kills ≥99.9% of the starting inoculum. Determining these concentrations helps identify the correct drug for a particular pathogen. For the macrobroth dilution assay, a dilution series of the drug in broth is made in test tubes and the same number of cells of a test bacterial strain is added to each tube ( Figure 14.19 ). The MIC is determined by examining the tubes to find the lowest drug concentration that inhibits visible growth; this is observed as turbidity (cloudiness) in the broth. Tubes with no visible growth are then inoculated onto agar media without antibiotic to determine the MBC. Generally, serum levels of an antibacterial should be at least three to five times above the MIC for treatment of an infection. \n\n The MIC assay can also be performed using 96-well microdilution trays, which allow for the use of small volumes and automated dispensing devices, as well as the testing of multiple antimicrobials and/or microorganisms in one tray ( Figure 14.20 ). MICs are interpreted as the lowest concentration that inhibits visible growth, the same as for the macrobroth dilution in test tubes. Growth may also be interpreted visually or by using a spectrophotometer or similar device to detect turbidity or a color change if an appropriate biochemical substrate that changes color in the presence of bacterial growth is also included in each well. \n\n The Etest is an alternative method used to determine MIC, and is a combination of the Kirby-Bauer disk diffusion test and dilution methods. Similar to the Kirby-Bauer assay, a confluent lawn of a bacterial isolate is inoculated onto the surface of an agar plate. Rather than using circular disks impregnated with one concentration of drug, however, commercially available plastic strips that contain a gradient of an antibacterial are placed on the surface of the inoculated agar plate ( Figure 14.21 ). As the bacterial inoculum grows, antibiotic diffuses from the plastic strips into the agar and interacts with the bacterial cells. Because the rate of drug diffusion is directly related to concentration, an elliptical zone of inhibition is observed with the Etest drug gradient, rather than a circular zone of inhibition observed with the Kirby-Bauer assay. To interpret the results, the intersection of the elliptical zone with the gradient on the drug-containing strip indicates the MIC. Because multiple strips containing different antimicrobials can be placed on the same plate, the MIC of multiple antimicrobials can be determined concurrently and directly compared. However, unlike the macrobroth and microbroth dilution methods, the MBC cannot be determined with the Etest. \n\n Check Your Understanding \n\n Compare and contrast MIC and MBC. \n\n Clinical Focus Resolution Marisa’s UTI was likely caused by the catheterizations she had in Vietnam. Most bacteria that cause UTIs are members of the normal gut microbiota, but they can cause infections when introduced to the urinary tract, as might have occurred when the catheter was inserted. Alternatively, if the catheter itself was not sterile, bacteria on its surface could have been introduced into Marisa’s body. The antimicrobial therapy Marisa received in Cambodia may also have been a complicating factor because it may have selected for antimicrobial-resistant strains already present in her body. These bacteria would have already contained genes for antimicrobial resistance, either acquired by spontaneous mutation or through horizontal gene transfer, and, therefore, had the best evolutionary advantage for adaptation and growth in the presence of the antimicrobial therapy. As a result, one of these resistant strains may have been subsequently introduced into her urinary tract. \n\n Laboratory testing at the CDC confirmed that the strain of Klebsiella pneumoniae from Marisa’s urine sample was positive for the presence of NDM, a very active carbapenemase that is beginning to emerge as a new problem in antimicrobial resistance. While NDM-positive strains are resistant to a wide range of antimicrobials, they have shown susceptibility to tigecycline (structurally related to tetracycline ) and the polymyxins B and E ( colistin ). \n\n To prevent her infection from spreading, Marisa was isolated from the other patients in a separate room. All hospital staff interacting with her were advised to follow strict protocols to prevent surface and equipment contamination. This would include especially stringent hand hygiene practices and careful disinfection of all items coming into contact with her. \n\n Marisa’s infection finally responded to tigecycline and eventually cleared. She was discharged a few weeks after admission, and a follow-up stool sample showed her stool to be free of NDM-containing K. pneumoniae , meaning that she was no longer harboring the highly resistant bacterium. \n\n Go back to the previous Clinical Focus box. \n 14.7 Current Strategies for Antimicrobial Discovery \n\n Learning Objectives \n\n Describe the methods and strategies used for discovery of new antimicrobial agents. \n\n With the continued evolution and spread of antimicrobial resistance, and now the identification of pan-resistant bacterial pathogens, the search for new antimicrobials is essential for preventing the postantibiotic era. Although development of more effective semisynthetic derivatives is one strategy, resistance to them develops rapidly because bacterial pathogens are already resistant to earlier-generation drugs in the family and can easily mutate and develop resistance to the new semisynthetic drugs. Today, scientists continue to hunt for new antimicrobial compounds and explore new avenues of antimicrobial discovery and synthesis. They check large numbers of soils and microbial products for antimicrobial activity by using high-throughput screening methods , which use automation to test large numbers of samples simultaneously. The recent development of the iChip 25 allows researchers to investigate the antimicrobial-producing capabilities of soil microbes that are difficult to grow by standard cultivation techniques in the laboratory. Rather than grow the microbes in the laboratory, they are grown in situ—right in the soil. Use of the iChip has resulted in the discovery of teixobactin , a novel antimicrobial from Mount Ararat, Turkey. Teixobactin targets two distinct steps in gram-positive cell wall synthesis and for which antimicrobial resistance appears not yet to have evolved. 25 L. Losee et al. “A New Antibiotic Kills Pathogens Without Detectable Resistance.” Nature 517 no. 7535 (2015):455–459. \n\n Although soils have been widely examined, other environmental niches have not been tested as fully. Since 70% of the earth is covered with water, marine environments could be mined more fully for the presence of antimicrobial-producing microbes. In addition, researchers are using combinatorial chemistry, a method for making a very large number of related compounds from simple precursors, and testing them for antimicrobial activity. An additional strategy that needs to be explored further is the development of compounds that inhibit resistance mechanisms and restore the activity of older drugs, such as the strategy described earlier for β-lactamase inhibitors like clavulanic acid . Finally, developing inhibitors of virulence factor production and function could be a very important avenue. Although this strategy would not be directly antibacterial, drugs that slow the progression of an infection could provide an advantage for the immune system and could be used successfully in combination with antimicrobial drugs. \n\n Check Your Understanding \n\n What are new sources and strategies for developing drugs to fight infectious diseases? \n\n Eye on Ethics The (Free?) Market for New Antimicrobials There used to be plenty of antimicrobial drugs on the market to treat infectious diseases. However, the spread of antimicrobial resistance has created a need for new antibiotics to replace those that are no longer as effective as they once were. Unfortunately, pharmaceutical companies are not particularly motivated to fill this need. As of 2009, all but five pharmaceutical companies had moved away from antimicrobial drug development. 26 As a result, the number of FDA approvals of new antimicrobials has fallen drastically in recent decades ( Figure 14.22 ). 26 H.W. Boucher et al. “Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America.” Clinical Infectious Diseases 48 no. 1 (2009):1–12. \n\n Given that demand usually encourages supply, one might expect pharmaceutical companies to be rushing to get back in the business of developing new antibiotics. But developing new drugs is a lengthy process and requires large investments in research and development. Pharmaceutical companies can typically get a higher return on their investment by developing products for chronic, nonmicrobial diseases like diabetes; such drugs must be taken for life, and therefore generate more long-term revenue than an antibiotic that does its job in a week or two. But what will happen when drugs like vancomycin, a superantimicrobial reserved for use as a last resort, begin to lose their effectiveness against ever more drug-resistant superbugs? Will drug companies wait until all antibiotics have become useless before beginning to look for new ones? \n\n Recently, it has been suggested that large pharmaceutical companies should be given financial incentives to pursue such research. In September 2014, the White House released an executive order entitled “Combating Antibiotic Resistant Bacteria,” calling upon various government agencies and the private sector to work together to “accelerate basic and applied research and development for new antimicrobials, other therapeutics, and vaccines.” 27 As a result, as of March 2015, President Obama’s proposed fiscal year 2016 budget doubled the amount of federal funding to $1.2 billion for “combating and preventing antibiotic resistance,” which includes money for antimicrobial research and development. 28 Similar suggestions have also been made on a global scale. In December 2014, a report chaired by former Goldman Sachs economist Jim O’Neill was published in The Review on Antimicrobial Resistance . 29 27 The White House. National Action Plan for Combating Antibiotic-Resistant Bacteria. Washington, DC: The White House, 2015. 28 White House Office of the Press Secretary. “Fact Sheet: Obama Administration Releases National Action Plan to Combat Antibiotic-Resistant Bacteria.” March 27, 2015. https://www.whitehouse.gov/the-press-office/2015/03/27/fact-sheet-obama-administration-releases-national-action-plan-combat-ant 29 Review on Antimicrobial Resistance. http://amr-review.org. Accessed June 1, 2016. \n\n These developments reflect the growing belief that for-profit pharmaceutical companies must be subsidized to encourage development of new antimicrobials. But some ask whether pharmaceutical development should be motivated by profit at all. Given that millions of lives may hang in the balance, some might argue that drug companies have an ethical obligation to devote their research and development efforts to high-utility drugs, as opposed to highly profitable ones. Yet this obligation conflicts with the fundamental goals of a for-profit company. Are government subsidies enough to ensure that drug companies make the public interest a priority, or should government agencies assume responsibility for developing critical drugs that may have little or no return on investment? \n\n Link to Learning \n\n To further examine the scope of the problem, view this video. \n\n To learn more about the history of antimicrobial drug discovery, visit Michigan State University’s Antimicrobial Resistance Learning Site. 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principles_of_accounting,_volume_1:_financial_accounting | Summary 9.1 Explain the Revenue Recognition Principle and How It Relates to Current and Future Sales and Purchase Transactions
According to the revenue recognition principle, a company will recognize revenue when a product or service is provided to a client. The revenue must be reported in the period when the ear... | Chapter Outline 9.1 Explain the Revenue Recognition Principle and How It Relates to Current and Future Sales and Purchase Transactions 9.2 Account for Uncollectible Accounts Using the Balance Sheet and Income Statement Approaches 9.3 Determine the Efficiency of Receivables Management Using Financial Ratios 9.4 ... | [
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"hl_context": "<hl> The revenue recognition principle , which states that companies must recognize revenue in the period in which it is earned , instructs companies to recognize revenue when a four-step process is completed... | 9 | 9.1 Explain the Revenue Recognition Principle and How It Relates to Current and Future Sales and Purchase Transactions
You own a small clothing store and offer your customers cash, credit card, or in-house credit payment options. Many of your customers choose to pay with a credit card or charge the purchase to th... | |
u.s._history | Summary 24.1 Prosperity and the Production of Popular Entertainment For many middle-class Americans, the 1920s was a decade of unprecedented prosperity. Rising earnings generated more disposable income for the consumption of entertainment, leisure, and consumer goods. This new wealth coincided with and fueled techno... | Chapter Outline 24.1 Prosperity and the Production of Popular Entertainment 24.2 Transformation and Backlash 24.3 A New Generation 24.4 Republican Ascendancy: Politics in the 1920s Introduction
Following the hardships of the immediate postwar era, the United States embarked upon one of the most prosperous d... | [
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"hl_context": "<hl> In 1927 , the world of the silent movie began to wane with the New York release of the first “ talkie ” : The Jazz Singer . <hl> The plot of this film , which starred Al Jolson , told a distinctively Ame... | 24 | 24.1 Prosperity and the Production of Popular Entertainment Learning Objectives By the end of this section, you will be able to:
Discuss the role of movies in the evolution of American culture
Explain the rise of sports as a dominant social force
Analyze the ways in which the automobile, especially the Mode... | |
psychology | Summary 15.1 What Are Psychological Disorders? Psychological disorders are conditions characterized by abnormal thoughts, feelings, and behaviors. Although challenging, it is essential for psychologists and mental health professionals to agree on what kinds of inner experiences and behaviors constitute the presence ... | Chapter Outline 15.1 What Are Psychological Disorders? 15.2 Diagnosing and Classifying Psychological Disorders 15.3 Perspectives on Psychological Disorders 15.4 Anxiety Disorders 15.5 Obsessive-Compulsive and Related Disorders 15.6 Posttraumatic Stress Disorder 15.7 Mood Disorders 15.8 Schizophrenia 15... | [
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"hl_context": "If none of the criteria discussed so far is adequate by itself to define the presence of a psychological disorder , how can a disorder be conc... | 15 | 15.1 What Are Psychological Disorders? Learning Objectives By the end of this section, you will be able to:
Understand the problems inherent in defining the concept of psychological disorder
Describe what is meant by harmful dysfunction
Identify the formal criteria that thoughts, feelings, and behaviors must... | |
anatomy_and_physiology | Chapter Objectives
After studying this chapter, you will be able to:
Describe the components of the autonomic nervous system
Differentiate between the structures of the sympathetic and parasympathetic divisions in the autonomic nervous system
Name the components of a visceral reflex specific to the autonom... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "increased stomach motility"
},
"bloom": "1",
"hl_context": "In addition to its association with the fight-or-flight response and rest-and-digest functions , the autonomic system is responsible for certain everyday functions . For example , it c... | 15 | 15.1 Divisions of the Autonomic Nervous System Learning Objectives By the end of this section, you will be able to:
Name the components that generate the sympathetic and parasympathetic responses of the autonomic nervous system
Explain the differences in output connections within the two divisions of the auto... | ||
business_ethics | Summary 3.1 Adopting a Stakeholder Orientation
An organization has duties and responsibilities with regard to each stakeholder; however, the implicit social contract between business and society means that meeting legal requirements might support only minimal ethical standards. Society on the whole and in the lon... | Chapter Outline 3.1 Adopting a Stakeholder Orientation 3.2 Weighing Stakeholder Claims 3.3 Ethical Decision-Making and Prioritizing Stakeholders 3.4 Corporate Social Responsibility (CSR) Introduction
In May 2018, in the wake of a global uproar after two Black men in a Philadelphia Starbucks were arrested wh... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "D"
},
"bloom": null,
"hl_context": "<hl> When a product does not live up to its maker ’ s claims for whatever reason , the manufacturer needs to correct the problem to retain or regain customers ’ trust . <hl> <hl> Without this trust , the inte... | 3 | 3.1 Adopting a Stakeholder Orientation
Learning Objectives
By the end of this section, you will be able to:
Identify key types of business-stakeholder relationships
Explain why laws do not dictate every ethical responsibility a company may owe key stakeholders
Discuss why stakeholders’ welfare must be... | |
biology | Chapter Outline 8.1 Overview of Photosynthesis 8.2 The Light-Dependent Reactions of Photosynthesis 8.3 Using Light Energy to Make Organic Molecules Introduction The processes in all organisms—from bacteria to humans—require energy. To get this energy, many organisms access stored energy by eating, that is, by in... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "chloroplasts"
},
"bloom": "2",
"hl_context": "<hl> In plants , carbon dioxide ( CO 2 ) enters the leaves through stomata , where it diffuses over short distances through intercellular spaces until it reaches the mesophyll cells . <hl> <hl> Once... | 8 | 8.1 Overview of Photosynthesis Learning Objectives By the end of this section, you will be able to:
Explain the relevance of photosynthesis to other living things
Describe the main structures involved in photosynthesis
Identify the substrates and products of photosynthesis
Summarize the process of photosyn... | ||
business_law_i_essentials | Chapter Outline 13.1 Introduction to International Law 13.2 Sources and Practice of International Law Introduction
Learning Outcome Explain international law and its role in business. | [
{
"answer": {
"ans_choice": 2,
"ans_text": "Both a and b."
},
"bloom": null,
"hl_context": "<hl> The second important clause related to international law is the Treaty Clause , which states that the president has the power “ by and with the advice and consent of the senate ” to create tr... | 13 | 13.1 Introduction to International Law
In 1945, President Harry Truman stated, “When Kansas and Colorado have a quarrel over the water in the Arkansas River they don’t call out the National Guard in each state and go to war over it. They bring a suit in the Supreme Court of the United States and abide by the deci... | ||
biology | Chapter Outline 16.1 Regulation of Gene Expression 16.2 Prokaryotic Gene Regulation 16.3 Eukaryotic Epigenetic Gene Regulation 16.4 Eukaryotic Transcription Gene Regulation 16.5 Eukaryotic Post-transcriptional Gene Regulation 16.6 Eukaryotic Translational and Post-translational Gene Regulation 16.7 Cance... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels"
},
"bloom": "2",
"hl_context": "Cancer can be described as a disease of altered gene expression . There are many proteins that are turned on or off... | 16 | 16.1 Regulation of Gene Expression Learning Objectives By the end of this section, you will be able to:
Discuss why every cell does not express all of its genes
Describe how prokaryotic gene regulation occurs at the transcriptional level
Discuss how eukaryotic gene regulation occurs at the epigenetic, transcr... | ||
microbiology | Summary 6.1 Viruses
Viruses are generally ultramicroscopic, typically from 20 nm to 900 nm in length. Some large viruses have been found.
Virions are acellular and consist of a nucleic acid, DNA or RNA, but not both, surrounded by a protein capsid . There may also be a phospholipid membrane surrounding the c... | Chapter Outline 6.1 Viruses 6.2 The Viral Life Cycle 6.3 Isolation, Culture, and Identification of Viruses 6.4 Viroids, Virusoids, and Prions Introduction Public health measures in the developed world have dramatically reduced mortality from viral epidemics. But when epidemics do occur, they can spread quickly... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "Extending outward and away from the capsid on some naked viruses and enveloped viruses are protein structures called spike s . <hl> At the tips of these spikes are structures that allow the virus to attach an... | 6 | 6.1 Viruses
Learning Objectives
Describe the general characteristics of viruses as pathogens
Describe viral genomes
Describe the general characteristics of viral life cycles
Differentiate among bacteriophages, plant viruses, and animal viruses
Describe the characteristics used to identify viruses a... | |
anatomy_and_physiology | Chapter Objectives
After studying this chapter, you will be able to:
List the structures of the respiratory system
List the major functions of the respiratory system
Outline the forces that allow for air movement into and out of the lungs
Outline the process of gas exchange
Summarize the process of ox... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "increase surface area"
},
"bloom": "1",
"hl_context": "The external nose consists of the surface and skeletal structures that result in the outward appearance of the nose and contribute to its numerous functions ( Figure 22.3 ) . The root is th... | 22 | 22.1 Organs and Structures of the Respiratory System Learning Objectives By the end of this section, you will be able to:
List the structures that make up the respiratory system
Describe how the respiratory system processes oxygen and CO 2
Compare and contrast the functions of upper respiratory tract with ... | ||
biology | Chapter Outline 12.1 Mendel’s Experiments and the Laws of Probability 12.2 Characteristics and Traits 12.3 Laws of Inheritance Introduction Genetics is the study of heredity. Johann Gregor Mendel set the framework for genetics long before chromosomes or genes had been identified, at a time when meiosis was not w... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "anther"
},
"bloom": null,
"hl_context": "<hl> Mendel performed hybridizations , which involve mating two true-breeding individuals that have different traits . <hl> <hl> In the pea , which is naturally self-pollinating , this is done by manuall... | 12 | 12.1 Mendel’s Experiments and the Laws of Probability Learning Objectives By the end of this section, you will be able to:
Describe the scientific reasons for the success of Mendel’s experimental work
Describe the expected outcomes of monohybrid crosses involving dominant and recessive alleles
Apply the sum a... | ||
american_government | Summary 2.1 The Pre-Revolutionary Period and the Roots of the American Political Tradition
For many years the British colonists in North America had peacefully accepted rule by the king and Parliament. They were proud to be Englishmen. Much of their pride, however, stemmed from their belief that they were heirs to... | Chapter Outline 2.1 The Pre-Revolutionary Period and the Roots of the American Political Tradition 2.2 The Articles of Confederation 2.3 The Development of the Constitution 2.4 The Ratification of the Constitution 2.5 Constitutional Change Introduction
The U.S. Constitution , see Figure 2.1 , is one of t... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "C"
},
"bloom": null,
"hl_context": "The beliefs and attitudes that led to the call for independence had long been an important part of colonial life . <hl> Of all the political thinkers who influenced American beliefs about government , the mos... | 2 | 2.1 The Pre-Revolutionary Period and the Roots of the American Political Tradition
Learning Objectives
By the end of this section, you will be able to:
Identify the origins of the core values in American political thought, including ideas regarding representational government
Summarize Great Britain’s act... | |
anatomy_and_physiology | Chapter Objectives After studying this chapter, you will be able to:
Identify the main tissue types and discuss their roles in the human body
Identify the four types of tissue membranes and the characteristics of each that make them functional
Explain the functions of various epithelial tissues and how their ... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "embryonic"
},
"bloom": null,
"hl_context": "The next level of organization is the organ , where several types of tissues come together to form a working unit . Just as knowing the structure and function of cells helps you in your study of tissu... | 4 | 4.1 Types of Tissues Learning Objectives By the end of this section, you will be able to:
Identify the four main tissue types
Discuss the functions of each tissue type
Relate the structure of each tissue type to their function
Discuss the embryonic origin of tissue
Identify the three major germ layer... | ||
u.s._history | Summary 4.1 Charles II and the Restoration Colonies
After the English Civil War and interregnum, England began to fashion a stronger and larger empire in North America. In addition to wresting control of New York and New Jersey from the Dutch, Charles II established the Carolinas and Pennsylvania as proprietary c... | Chapter Outline 4.1 Charles II and the Restoration Colonies 4.2 The Glorious Revolution and the English Empire 4.3 An Empire of Slavery and the Consumer Revolution 4.4 Great Awakening and Enlightenment 4.5 Wars for Empire Introduction
The eighteenth century witnessed the birth of Great Britain (after the ... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "C"
},
"bloom": null,
"hl_context": "Though Cromwell enjoyed widespread popularity at first , over time he appeared to many in England to be taking on the powers of a military dictator . Dissatisfaction with Cromwell grew . When he died in 1658 ... | 4 | 4.1 Charles II and the Restoration Colonies Learning Objectives By the end of this section, you will be able to:
Analyze the causes and consequences of the Restoration
Identify the Restoration colonies and their role in the expansion of the Empire
When Charles II ascended the throne in 1660, English subject... | |
microbiology | Summary 17.1 Physical Defenses
Nonspecific innate immunity provides a first line of defense against infection by nonspecifically blocking entry of microbes and targeting them for destruction or removal from the body.
The physical defenses of innate immunity include physical barriers, mechanical actions that r... | Chapter Outline 17.1 Physical Defenses 17.2 Chemical Defenses 17.3 Cellular Defenses 17.4 Pathogen Recognition and Phagocytosis 17.5 Inflammation and Fever Introduction Despite relatively constant exposure to pathogenic microbes in the environment, humans do not generally suffer from constant infection or di... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "<hl> Nonspecific innate immunity can be characterized as a multifaceted system of defenses that targets invading pathogens in a nonspecific manner . <hl> In this chapter , we have divided the numerous defense... | 17 | 17.1 Physical Defenses
Learning Objectives
Describe the various physical barriers and mechanical defenses that protect the human body against infection and disease
Describe the role of microbiota as a first-line defense against infection and disease
Clinical Focus Part 1 Angela, a 25-year-old female pati... | |
biology | Chapter Outline 22.1 Prokaryotic Diversity 22.2 Structure of Prokaryotes 22.3 Prokaryotic Metabolism 22.4 Bacterial Diseases in Humans 22.5 Beneficial Prokaryotes Introduction In the recent past, scientists grouped living things into five kingdoms—animals, plants, fungi, protists, and prokaryotes—based on se... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "prokaryotes"
},
"bloom": null,
"hl_context": "When and where did life begin ? What were the conditions on Earth when life began ? <hl> Prokaryotes were the first forms of life on Earth , and they existed for billions of years before plants and ... | 22 | 22.1 Prokaryotic Diversity Learning Objectives By the end of this section, you will be able to:
Describe the evolutionary history of prokaryotes
Discuss the distinguishing features of extremophiles
Explain why it is difficult to culture prokaryotes
Prokaryotes are ubiquitous. They cover every imaginable su... | ||
principles_of_accounting,_volume_2:_managerial_accounting | Summary 3.1 Explain Contribution Margin and Calculate Contribution Margin per Unit, Contribution Margin Ratio, and Total Contribution Margin
Contribution margin can be used to calculate how much of every dollar in sales is available to cover fixed expenses and contribute to profit.
Contribution margin can be e... | Chapter Outline 3.1 Explain Contribution Margin and Calculate Contribution Margin per Unit, Contribution Margin Ratio, and Total Contribution Margin 3.2 Calculate a Break-Even Point in Units and Dollars 3.3 Perform Break-Even Sensitivity Analysis for a Single Product Under Changing Business Situations 3.4 Perf... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "A"
},
"bloom": null,
"hl_context": "<hl> The contribution margin ratio is the percentage of a unit ’ s selling price that exceeds total unit variable costs . <hl> In other words , contribution margin is expressed as a percentage of sales price ... | 3 | 3.1 Explain Contribution Margin and Calculate Contribution Margin per Unit, Contribution Margin Ratio, and Total Contribution Margin
Before examining contribution margins, let’s review some key concepts: fixed costs, relevant range, variable costs, and contribution margin. Fixed costs are those costs that will ... | |
introduction_to_sociology | Learning Objectives 15.1 The Sociological Approach to Religion
Discuss historical view of religion from a sociological perspective
Understand how the major sociological paradigms view religion
15.2 World Religions
Explain the differences between various types of religious organizations
Understand cla... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "All of the above"
},
"bloom": null,
"hl_context": "<hl> Functionalists contend that religion serves several functions in society . <hl> Religion , in fact , depends on society for its existence , value , and significance , and vice versa . <hl>... | 15 | 15.1 The Sociological Approach to Religion
From the Latin religio (respect for what is sacred) and religare (to bind, in the sense of an obligation), the term religion describes various systems of belief and practice concerning what people determine to be sacred or spiritual (Fasching and deChant 2001; Durkhei... | ||
anatomy_and_physiology | Chapter Objectives
After studying this chapter, you will be able to:
Describe the composition of urine
Label structures of the urinary system
Characterize the roles of each of the parts of the urinary system
Illustrate the macroscopic and microscopic structures of the kidney
Trace the flow of blood t... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "polyuria"
},
"bloom": null,
"hl_context": "Urine volume varies considerably . The normal range is one to two liters per day ( Table 25.2 ) . The kidneys must produce a minimum urine volume of about 500 mL / day to rid the body of wastes . Outpu... | 25 | 25.1 Physical Characteristics of Urine Learning Objectives By the end of this section, you will be able to:
Compare and contrast blood plasma, glomerular filtrate, and urine characteristics
Describe the characteristics of a normal urine sample, including normal range of pH, osmolarity, and volume
The urina... | ||
introduction_to_sociology | Learning Objectives 20.1 Demography and Population
Understand demographic measurements like fertility and mortality rates
Describe a variety of demographic theories, such as Malthusian, cornucopian, zero population growth, and demographic transition theories
Be familiar with current population trends and pat... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "6 billion"
},
"bloom": null,
"hl_context": "As mentioned earlier , the earth ’ s population is seven billion . That number might not seem particularly jarring on its own ; after all , we all know there are lots of people around . <hl> But consi... | 20 | 20.1 Demography and Population
We recently hit a population milestone of seven billion humans on the earth’s surface. The rapidity with which this happened demonstrated an exponential increase from the time it took to grow from five billion to six billion people. In short, the planet is filling up. How quickly wil... | ||
biology | Chapter Outline 18.1 Understanding Evolution 18.2 Formation of New Species 18.3 Reconnection and Rates of Speciation Introduction All species of living organisms, from bacteria to baboons to blueberries, evolved at some point from a different species. Although it may seem that living things today stay much the s... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "natural selection"
},
"bloom": "1",
"hl_context": "<hl> Wallace and Darwin both observed similar patterns in other organisms and they independently developed the same explanation for how and why such changes could take place . <hl> <hl> Darwin ... | 18 | 18.1 Understanding Evolution Learning Objectives By the end of this section, you will be able to:
Describe how the present-day theory of evolution was developed
Define adaptation
Explain convergent and divergent evolution
Describe homologous and vestigial structures
Discuss misconceptions about the theo... | ||
anatomy_and_physiology | Chapter Objectives After studying this chapter, you will be able to:
Describe the structure and function of the cell membrane, including its regulation of materials into and out of the cell
Describe the functions of the various cytoplasmic organelles
Explain the structure and contents of the nucleus, as well a... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "integral proteins"
},
"bloom": "1",
"hl_context": "The lipid bilayer forms the basis of the cell membrane , but it is peppered throughout with various proteins . Two different types of proteins that are commonly associated with the cell membran... | 3 | 3.1 The Cell Membrane Learning Objectives By the end of this section, you will be able to:
Describe the molecular components that make up the cell membrane
Explain the major features and properties of the cell membrane
Differentiate between materials that can and cannot diffuse through the lipid bilayer
... | ||
business_ethics | Summary 2.1 The Concept of Ethical Business in Ancient Athens
The role of ethics in Athens during Greece’s Golden Age (fifth century BCE) was substantial. Aristotle focused on the role of virtue in developing individual character and social stability. He believed a person’s actions determined whether he or she wa... | Chapter Outline 2.1 The Concept of Ethical Business in Ancient Athens 2.2 Ethical Advice for Nobles and Civil Servants in Ancient China 2.3 Comparing the Virtue Ethics of East and West 2.4 Utilitarianism: The Greatest Good for the Greatest Number 2.5 Deontology: Ethics as Duty 2.6 A Theory of Justice Intro... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "A"
},
"bloom": null,
"hl_context": "Aristotle identified two types of virtues , which the philosophical community of his day agreed were objective and not subjective . The two types were intellectual and moral . <hl> Intellectual virtues — incl... | 2 | 2.1 The Concept of Ethical Business in Ancient Athens
Learning Objectives
By the end of this section, you will be able to:
Identify the role of ethics in ancient Athens
Explain how Aristotelian virtue ethics affected business practices
It would be hard to overstate the influence of ancient Athens on W... | |
biology | Chapter Outline 3.1 Synthesis of Biological Macromolecules 3.2 Carbohydrates 3.3 Lipids 3.4 Proteins 3.5 Nucleic Acids Introduction Food provides the body with the nutrients it needs to survive. Many of these critical nutrients are biological macromolecules, or large molecules, necessary for life. These macr... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "water and polymers"
},
"bloom": null,
"hl_context": "Most macromolecules are made from single subunits , or building blocks , called monomers . <hl> The monomers combine with each other using covalent bonds to form larger molecules known as pol... | 3 | 3.1 Synthesis of Biological Macromolecules Learning Objectives By the end of this section, you will be able to:
Understand the synthesis of macromolecules
Explain dehydration (or condensation) and hydrolysis reactions
As you’ve learned, biological macromolecules are large molecules, necessary for life, that... | ||
u.s._history | Summary 8.1 Competing Visions: Federalists and Democratic-Republicans
While they did not yet constitute distinct political parties, Federalists and Anti-Federalists, shortly after the Revolution, found themselves at odds over the Constitution and the power that it concentrated in the federal government. While man... | Chapter Outline 8.1 Competing Visions: Federalists and Democratic-Republicans 8.2 The New American Republic 8.3 Partisan Politics 8.4 The United States Goes Back to War Introduction
The partisan political cartoon above ( Figure 8.1 ) lampoons Thomas Jefferson’s 1807 Embargo Act, a move that had a devastatin... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "<hl> Right to a jury trial in civil cases <hl> <hl> Amendment 7 <hl> <hl> Right to a speedy trial by an impartial jury <hl> <hl> Amendment 6 <hl> <hl> Right to keep and bear arms to maintain a well-regulated ... | 8 | 8.1 Competing Visions: Federalists and Democratic-Republicans Learning Objectives By the end of this section, you will be able to:
Describe the competing visions of the Federalists and the Democratic-Republicans
Identify the protections granted to citizens under the Bill of Rights
Explain Alexander Hamilton... | |
anatomy_and_physiology | Chapter Objectives After studying this chapter, you will be able to:
Describe the actions and roles of agonists and antagonists
Explain the structure and organization of muscle fascicles and their role in generating force
Explain the criteria used to name skeletal muscles
Identify the skeletal muscles and ... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "They insert into the skin."
},
"bloom": null,
"hl_context": "The origins of the muscles of facial expression are on the surface of the skull ( remember , the origin of a muscle does not move ) . <hl> The insertions of these muscles have fibers ... | 11 | 11.1 Interactions of Skeletal Muscles, Their Fascicle Arrangement, and Their Lever Systems Learning Objectives By the end of this section, you will be able to:
Compare and contrast agonist and antagonist muscles
Describe how fascicles are arranged within a skeletal muscle
Explain the major events of a skel... | ||
microbiology | Summary 22.1 Anatomy and Normal Microbiota of the Respiratory Tract
The respiratory tract is divided into upper and lower regions at the epiglottis .
Air enters the upper respiratory tract through the nasal cavity and mouth, which both lead to the pharynx . The lower respiratory tract extends from the lar... | Chapter Outline 22.1 Anatomy and Normal Microbiota of the Respiratory Tract 22.2 Bacterial Infections of the Respiratory Tract 22.3 Viral Infections of the Respiratory Tract 22.4 Respiratory Mycoses Introduction The respiratory tract is one of the main portals of entry into the human body for microbial pathoge... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "C"
},
"bloom": null,
"hl_context": "The respiratory system can be conceptually divided into upper and lower regions at the point of the epiglottis , the structure that seals off the lower respiratory system from the pharynx during swallowing ( ... | 22 | 22.1 Anatomy and Normal Microbiota of the Respiratory Tract
Learning Objectives
Describe the major anatomical features of the upper and lower respiratory tract
Describe the normal microbiota of the upper and lower respiratory tracts
Explain how microorganisms overcome defenses of upper and lower respirat... | |
microbiology | Summary 3.1 Spontaneous Generation
The theory of spontaneous generation states that life arose from nonliving matter. It was a long-held belief dating back to Aristotle and the ancient Greeks.
Experimentation by Francesco Redi in the 17th century presented the first significant evidence refuting spontaneous ... | Chapter Outline 3.1 Spontaneous Generation 3.2 Foundations of Modern Cell Theory 3.3 Unique Characteristics of Prokaryotic Cells 3.4 Unique Characteristics of Eukaryotic Cells Introduction Life takes many forms, from giant redwood trees towering hundreds of feet in the air to the tiniest known microbes, which ... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "C"
},
"bloom": null,
"hl_context": "<hl> In 1745 , John Needham ( 1713 – 1781 ) published a report of his own experiments , in which he briefly boiled broth infused with plant or animal matter , hoping to kill all preexisting microbes . <hl> 2 ... | 3 | 3.1 Spontaneous Generation
Learning Objectives
Explain the theory of spontaneous generation and why people once accepted it as an explanation for the existence of certain types of organisms
Explain how certain individuals (van Helmont, Redi, Needham, Spallanzani, and Pasteur) tried to prove or disprove spon... | |
business_ethics | Summary 5.1 The Relationship between Business Ethics and Culture
Culture has a tremendous influence on ethics and its application in a business setting. In fact, we can argue that culture and ethics cannot be separated, because ethical norms have been established over time by and make sense to people who share th... | Chapter Outline 5.1 The Relationship between Business Ethics and Culture 5.2 Business Ethics over Time 5.3 The Influence of Geography and Religion 5.4 Are the Values Central to Business Ethics Universal? Introduction
Ethics is a construct of considerable significance to human beings. Some suggest ethics eme... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "A"
},
"bloom": null,
"hl_context": "In the West , we typically think of these beliefs in Western terms . This worldview explains the misunderstanding between Minuit , who assumed he was buying Manhattan , and the tribal leaders , who may have h... | 5 | 5.1 The Relationship between Business Ethics and Culture
Learning Objectives
By the end of this section, you will be able to:
Describe the processes of acculturation and enculturation
Explain the interaction of business and culture from an ethical perspective
Analyze how consumerism and the global mar... | |
psychology | Summary 5.1 Sensation versus Perception
Sensation occurs when sensory receptors detect sensory stimuli. Perception involves the organization, interpretation, and conscious experience of those sensations. All sensory systems have both absolute and difference thresholds, which refer to the minimum amount of stimulu... | Chapter Outline 5.1 Sensation versus Perception 5.2 Waves and Wavelengths 5.3 Vision 5.4 Hearing 5.5 The Other Senses 5.6 Gestalt Principles of Perception Introduction
Imagine standing on a city street corner. You might be struck by movement everywhere as cars and people go about their business, by the ... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "absolute threshold"
},
"bloom": null,
"hl_context": "The sensitivity of a given sensory system to the relevant stimuli can be expressed as an absolute threshold . <hl> Absolute threshold refers to the minimum amount of stimulus energy that must... | 5 | 5.1 Sensation versus Perception Learning Objectives By the end of this section, you will be able to:
Distinguish between sensation and perception
Describe the concepts of absolute threshold and difference threshold
Discuss the roles attention, motivation, and sensory adaptation play in perception
Sensatio... | |
introduction_to_sociology | Learning Objectives 16.1 Education around the World
Identify differences in educational resources around the world
Describe the concept of universal access to education
16.2 Theoretical Perspectives on Education
Define manifest and latent functions of education
Explain and discuss how functionalism, ... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "Resources and money"
},
"bloom": null,
"hl_context": "Education is a social institution through which a society ’ s children are taught basic academic knowledge , learning skills , and cultural norms . Every nation in the world is equipped with... | 16 | 16.1 Education around the World
Education is a social institution through which a society’s children are taught basic academic knowledge, learning skills, and cultural norms. Every nation in the world is equipped with some form of education system, though those systems vary greatly. The major factors affecting ed... | ||
microbiology | Summary 1.1 What Our Ancestors Knew
Microorganisms (or microbes ) are living organisms that are generally too small to be seen without a microscope.
Throughout history, humans have used microbes to make fermented foods such as beer, bread, cheese, and wine.
Long before the invention of the microscope, som... | Chapter Outline 1.1 What Our Ancestors Knew 1.2 A Systematic Approach 1.3 Types of Microorganisms Introduction From boiling thermal hot springs to deep beneath the Antarctic ice, microorganisms can be found almost everywhere on earth in great quantities. Microorganisms (or microbes, as they are also called) are ... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "D"
},
"bloom": null,
"hl_context": "Production of these foods and beverages requires microbial fermentation , a process that uses bacteria , mold , or yeast to convert sugars ( carbohydrates ) to alcohol , gases , and organic acids ( Figure 1.3... | 1 | 1.1 What Our Ancestors Knew
Learning Objectives
Describe how our ancestors improved food with the use of invisible microbes
Describe how the causes of sickness and disease were explained in ancient times, prior to the invention of the microscope
Describe key historical events associated with the birth of... | |
u.s._history | Summary 9.1 Early Industrialization in the Northeast
Industrialization led to radical changes in American life. New industrial towns, like Waltham, Lowell, and countless others, dotted the landscape of the Northeast. The mills provided many young women an opportunity to experience a new and liberating life, and t... | Chapter Outline 9.1 Early Industrialization in the Northeast 9.2 A Vibrant Capitalist Republic 9.3 On the Move: The Transportation Revolution 9.4 A New Social Order: Class Divisions Introduction
By the 1830s, the United States had developed a thriving industrial and commercial sector in the Northeast. Farme... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "C"
},
"bloom": null,
"hl_context": "The success of Slater and his partners Smith Brown and William Almy , relatives of Moses Brown , inspired others to build additional mills in Rhode Island and Massachusetts . By 1807 , thirteen more mills had... | 9 | 9.1 Early Industrialization in the Northeast Learning Objectives By the end of this section, you will be able to:
Explain the role of the putting-out system in the rise of industrialization
Understand industrialization’s impact on the nature of production and work
Describe the effect of industrialization on... | |
u.s._history | Summary 14.1 The Compromise of 1850
The difficult process of reaching a compromise on slavery in 1850 exposed the sectional fault lines in the United States. After several months of rancorous debate, Congress passed five laws—known collectively as the Compromise of 1850—that people on both sides of the divide hop... | Chapter Outline 14.1 The Compromise of 1850 14.2 The Kansas-Nebraska Act and the Republican Party 14.3 The Dred Scott Decision and Sectional Strife 14.4 John Brown and the Election of 1860 Introduction
The heated sectional controversy between the North and the South reached new levels of intensity in the 18... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "A"
},
"bloom": null,
"hl_context": "<hl> As president , Taylor sought to defuse the sectional controversy as much as possible , and , above all else , to preserve the Union . <hl> Although Taylor was born in Virginia before relocating to Kentuc... | 14 | 14.1 The Compromise of 1850 Learning Objectives By the end of this section, you will be able to:
Explain the contested issues that led to the Compromise of 1850
Describe and analyze the reactions to the 1850 Fugitive Slave Act
At the end of the Mexican-American War, the United States gained a large expanse ... | |
biology | Chapter Outline 28.1 Phylum Porifera 28.2 Phylum Cnidaria 28.3 Superphylum Lophotrochozoa 28.4 Superphylum Ecdysozoa 28.5 Superphylum Deuterostomia Introduction A brief look at any magazine pertaining to our natural world, such as National Geographic , would show a rich variety of vertebrates, especially ma... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "a collagen-like gel and suspended cells for various functions"
},
"bloom": null,
"hl_context": "While sponges ( excluding the hexactinellids ) do not exhibit tissue-layer organization , they do have different cell types that perform distinct fu... | 28 | 28.1 Phylum Porifera Learning Objectives By the end of this section, you will be able to:
Describe the organizational features of the simplest multicellular organisms
Explain the various body forms and bodily functions of sponges
The invertebrates, or invertebrata , are animals that do not contain bony struc... | ||
introduction_to_sociology | Learning Objectives 3.1 What Is Culture?
Differentiate between culture and society
Explain material versus nonmaterial culture
Discuss the concept of cultural universalism as it relates to society
Compare and contrast ethnocentrism and xenocentrism
3.2 Elements of Culture
Understand how values and... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "culture and society"
},
"bloom": "1",
"hl_context": "<hl> In everyday conversation , people rarely distinguish between the terms culture and society , but the terms have slightly different meanings , and the distinction is important to a sociol... | 3 | 3.1 What Is Culture?
Humans are social creatures. Since the dawn of
Homo sapiens
nearly 250,000 years ago, people have grouped together into communities in order to survive. Living together, people form common habits and behaviors—from specific methods of childrearing to preferred techniques fo... | ||
principles_of_accounting,_volume_2:_managerial_accounting | Summary 1.1 Define Managerial Accounting and Identify the Three Primary Responsibilities of Management
The purpose of managerial accounting is to supply financial and nonfinancial information to the organization’s management and other internal decision makers.
Most of the job responsibilities of a manager fit ... | Chapter Outline 1.1 Define Managerial Accounting and Identify the Three Primary Responsibilities of Management 1.2 Distinguish between Financial and Managerial Accounting 1.3 Explain the Primary Roles and Skills Required of Managerial Accountants 1.4 Describe the Role of the Institute of Management Accountants... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "D"
},
"bloom": null,
"hl_context": "To put this in context , think about how you will spend your weekend . <hl> First , you are the manager of your own time . <hl> You must plan based on your workload and on how much time you will spend studyin... | 1 | 1.1 Define Managerial Accounting and Identify the Three Primary Responsibilities of Management
Financial accounting process provides a useful level of detail for external users, such as investors and creditors, but it does not provide enough detailed information for the types of decisions made in the day-to-day o... | |
u.s._history | Summary 18.1 Inventors of the Age
Inventors in the late nineteenth century flooded the market with new technological advances. Encouraged by Great Britain’s Industrial Revolution, and eager for economic development in the wake of the Civil War, business investors sought the latest ideas upon which they could capi... | Chapter Outline 18.1 Inventors of the Age 18.2 From Invention to Industrial Growth 18.3 Building Industrial America on the Backs of Labor 18.4 A New American Consumer Culture Introduction
“The electric age was ushered into being in this last decade of the nineteenth century today when President Cleveland, b... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "<hl> In offices , worker productivity benefited from the typewriter , invented in 1867 , the cash register , invented in 1879 , and the adding machine , invented in 1885 . <hl> These tools made it easier than... | 18 | 18.1 Inventors of the Age Learning Objectives By the end of this section, you will be able to:
Explain how the ideas and products of late nineteenth-century inventors contributed to the rise of big business
Explain how the inventions of the late nineteenth century changed everyday American life
The late nin... | |
anatomy_and_physiology | Chapter Objectives After studying this chapter, you will be able to:
List and describe the functions of bones
Describe the classes of bones
Discuss the process of bone formation and development
Explain how bone repairs itself after a fracture
Discuss the effect of exercise, nutrition, and hormones on ... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "protection of internal organs"
},
"bloom": "1",
"hl_context": "<hl> Bones also protect internal organs from injury by covering or surrounding them . <hl> For example , your ribs protect your lungs and heart , the bones of your vertebral column ... | 6 | 6.1 The Functions of the Skeletal System Learning Objectives By the end of this section, you will be able to:
Define bone, cartilage, and the skeletal system
List and describe the functions of the skeletal system
Bone , or osseous tissue , is a hard, dense connective tissue that forms most of the adult sk... | ||
biology | Chapter Outline 41.1 Osmoregulation and Osmotic Balance 41.2 The Kidneys and Osmoregulatory Organs 41.3 Excretion Systems 41.4 Nitrogenous Wastes 41.5 Hormonal Control of Osmoregulatory Functions Introduction The daily intake recommendation for human water consumption is eight to ten glasses of water. In ord... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "shrink due to water loss"
},
"bloom": null,
"hl_context": "Osmosis is the diffusion of water across a membrane in response to osmotic pressure caused by an imbalance of molecules on either side of the membrane . Osmoregulation is the process of... | 41 | 41.1 Osmoregulation and Osmotic Balance Learning Objectives By the end of this section, you will be able to:
Define osmosis and explain its role within molecules
Explain why osmoregulation and osmotic balance are important body functions
Describe active transport mechanisms
Explain osmolarity and the way i... | ||
introduction_to_sociology | Learning Objectives 8.1 Technology Today
Define technology and describe its evolution
Understand technological inequality and issues related to unequal access to technology
Describe the role of planned obsolescence in technological development
8.2 Media and Technology in Society
Describe the evolutio... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "knowledge gap "
},
"bloom": "1",
"hl_context": "There are two forms of technological stratification . The first is differential class-based access to technology in the form of the digital divide . <hl> This digital divide has led to the second ... | 8 | 8.1 Technology Today
It is easy to look at the latest sleek tiny Apple product and think that technology is only recently a part of our world. But from the steam engine to the most cutting-edge robotic surgery tools, technology describes the application of science to address the problems of daily life. We might ... | ||
principles_of_accounting,_volume_2:_managerial_accounting | Summary 4.1 Distinguish between Job Order Costing and Process Costing
Job order costing (JOC) is the optimal costing method for producing custom goods or when it is easy to identify the cost directly with the product.
A JOC system assigns costs to each individual job as the costs are incurred, so that at all p... | Chapter Outline 4.1 Distinguish between Job Order Costing and Process Costing 4.2 Describe and Identify the Three Major Components of Product Costs under Job Order Costing 4.3 Use the Job Order Costing Method to Trace the Flow of Product Costs through the Inventory Accounts 4.4 Compute a Predetermined Overhead... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "<hl> Both job order costing and process costing track the costs of materials , labor , and overhead as components of virtually all products . <hl> The process of production does not change because of the cost... | 4 | 4.1 Distinguish between Job Order Costing and Process Costing
Pet Smart , H&R Block , Chili’s , and Marshalls are popular chains often found at the same shopping center, even though they are very different businesses. Although they have a retail store, the Pet Smart Corporation also manufactures large volumes... | |
business_law_i_essentials | Chapter Outline 8.1 The Nature and Origins of Sales Contracts 8.2 Warranties and Sales Contracts Introduction
Learning Outcome
Recognize nuances of contracts pertaining to sales. | [
{
"answer": {
"ans_choice": 2,
"ans_text": "Cumulative."
},
"bloom": null,
"hl_context": "<hl> Principal : the validity does not depend upon the existence of other contracts <hl> <hl> Bilateral : both parties in the contract are bound to fulfill reciprocal obligations toward each other <... | 8 | 8.1 The Nature and Origins of Sales Contracts
Features of Sales Contracts
Commercial enterprises that engage in buying and selling practices need to be aware of the features and nature of sales contracts . A contract of sale is a specific type of contract in which one party is obligated to deliver and transfe... | ||
introduction_to_sociology | Learning Objectives 18.1 Economic Systems
Understand types of economic systems and their historical development
Describe capitalism and socialism both in theory and in practice
Discussion how functionalists, conflict theorists, and symbolic interactionists view the economy and work
18.2 Globalization an... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "Corn"
},
"bloom": null,
"hl_context": "<hl> Globalization has also led to the development of global commodity chains , where internationally integrated economic links connect workers and corporations for the purpose of manufacture and marketing... | 18 | 18.1 Economic Systems
The dominant economic systems of the modern era have been capitalism and socialism, and there have been many variations of each system across the globe. Countries have switched systems as their rulers and economic fortunes have changed. For example, Russia has been transitioning to a market-b... | ||
biology | Chapter Outline 32.1 Reproductive Development and Structure 32.2 Pollination and Fertilization 32.3 Asexual Reproduction Introduction Plants have evolved different reproductive strategies for the continuation of their species. Some plants reproduce sexually, and others asexually, in contrast to animal species, w... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "microsporangium"
},
"bloom": null,
"hl_context": "The male gametophyte develops and reaches maturity in an immature anther . <hl> In a plant ’ s male reproductive organs , development of pollen takes place in a structure known as the microspora... | 32 | 32.1 Reproductive Development and Structure Learning Objectives By the end of this section, you will be able to:
Describe the two stages of a plant’s lifecycle
Compare and contrast male and female gametophytes and explain how they form in angiosperms
Describe the reproductive structures of a plant
Describ... | ||
biology | Chapter Outline 23.1 Eukaryotic Origins 23.2 Characteristics of Protists 23.3 Groups of Protists 23.4 Ecology of Protists Introduction Humans have been familiar with macroscopic organisms (organisms big enough to see with the unaided eye) since before there was a written history, and it is likely that most cul... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "oxygenation of the atmosphere"
},
"bloom": "3",
"hl_context": "<hl> Recall that the first fossils that we believe to be eukaryotes date to about 2 billion years old , so they appeared as oxygen levels were increasing . <hl> Also , recall that a... | 23 | 23.1 Eukaryotic Origins Learning Objectives By the end of this section, you will be able to:
List the unifying characteristics of eukaryotes
Describe what scientists know about the origins of eukaryotes based on the last common ancestor
Explain endosymbiotic theory
Living things fall into three large grou... | ||
microbiology | Summary 19.1 Hypersensitivities
An allergy is an adaptive immune response, sometimes life-threatening, to an allergen .
Type I hypersensitivity requires sensitization of mast cells with IgE, involving an initial IgE antibody response and IgE attachment to mast cells. On second exposure to an allergen, cros... | Chapter Outline 19.1 Hypersensitivities 19.2 Autoimmune Disorders 19.3 Organ Transplantation and Rejection 19.4 Immunodeficiency 19.5 Cancer Immunobiology and Immunotherapy Introduction An allergic reaction is an immune response to a type of antigen called an allergen . Allergens can be found in many differ... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "<hl> Late-phase reactions in type I hypersensitivities may develop 4 – 12 hours after the early phase and are mediated by eosinophil s , neutrophil s , and lymphocytes that have been recruited by chemotactic ... | 19 | 19.1 Hypersensitivities
Learning Objectives
Identify and compare the distinguishing characteristics, mechanisms, and major examples of type I, II, III, and IV hypersensitivities
Clinical Focus Part 1 Kerry, a 40-year-old airline pilot, has made an appointment with her primary care physician to discuss a ras... | |
biology | Chapter Outline 19.1 Population Evolution 19.2 Population Genetics 19.3 Adaptive Evolution Introduction All life on Earth is related. Evolutionary theory states that humans, beetles, plants, and bacteria all share a common ancestor, but that millions of years of evolution have shaped each of these organisms into... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "Microevolution describes the evolution of organisms in populations, while macroevolution describes the evolution of species over long periods of time."
},
"bloom": null,
"hl_context": "The mechanisms of inheritance , or genetics , were not unde... | 19 | 19.1 Population Evolution Learning Objectives By the end of this section, you will be able to:
Define population genetics and describe how population genetics is used in the study of the evolution of populations
Define the Hardy-Weinberg principle and discuss its importance
The mechanisms of inheritance, or g... | ||
business_law_i_essentials | Chapter Outline 11.1 History of Antitrust Law 11.2 Antitrust Laws Introduction
Learning Outcome Analyze the tenets of antitrust laws in the United States. | [
{
"answer": {
"ans_choice": 1,
"ans_text": "b"
},
"bloom": null,
"hl_context": "During the late 1800s , the United States became concerned about the development of corporate monopolies dominating the manufacturing and mining industries ( Jurist , n . d . ) . The end of the Civil War mark... | 11 | 11.1 History of Antitrust Law
What if the two largest manufacturers of soft drinks, Coca Cola Co. and PepsiCo, merged? It is likely that the mega-company that resulted would dominate the soft drink industry, squeezing out all of the other smaller competitors.
In the late 1800s, concern over this kind of merger... | ||
anatomy_and_physiology | Chapter Objectives After studying this chapter, you will be able to:
Describe the components of the somatic nervous system
Name the modalities and submodalities of the sensory systems
Distinguish between general and special senses
Describe regions of the central nervous system that contribute to somatic fu... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "nociceptor"
},
"bloom": "1",
"hl_context": "Receptor cells can be further categorized on the basis of the type of stimuli they transduce . Chemical stimuli can be interpreted by a chemoreceptor that interprets chemical stimuli , such as an obje... | 14 | 14.1 Sensory Perception Learning Objectives By the end of this section, you will be able to:
Describe different types of sensory receptors
Describe the structures responsible for the special senses of taste, smell, hearing, balance, and vision
Distinguish how different tastes are transduced
Describe the... | ||
business_law_i_essentials | Chapter Outline 12.1 Unfair Trade Practices 12.2 The Federal Trade Commission Introduction
Learning Outcomes Analyze laws pertaining to unfair trade practices and the agency that scrutinizes them. | [
{
"answer": {
"ans_choice": 1,
"ans_text": "Charging extremely high prices."
},
"bloom": null,
"hl_context": "<hl> Unfair trade practices include false representation of a good or service , targeting vulnerable populations , false advertising , tied selling , false free prize or gift off... | 12 | 12.1 Unfair Trade Practices
The term “unfair trade practice” describes the use of deceptive, fraudulent, or unethical methods to gain business advantage or to cause injury to a consumer. Unfair trade practices are considered unlawful under the Consumer Protection Act. The purpose of the law is to ensure that cons... | ||
business_law_i_essentials | Chapter Outline 1.1 Basic American Legal Principles 1.2 Sources and Types of Law 1.3 Important Business Laws and Regulations Introduction
Learning Outcome
Describe the foundation and sources that establish American law. | [
{
"answer": {
"ans_choice": 1,
"ans_text": "b"
},
"bloom": null,
"hl_context": "<hl> Based on the British legal system , the American legal system is divided into a federal system and a state and local system . <hl> The overall goal of both systems is to provide order and a means of disp... | 1 | 1.1 Basic American Legal Principles
The American legal system has its roots in the British legal system. It was developed with the purpose of establishing standards for acceptable conduct, proscribing punishment for violations as a deterrent, establishing systems for enforcement, and peacefully resolving disputes... | ||
psychology | Summary 13.1 What Is Industrial and Organizational Psychology?
The field of I-O psychology had its birth in industrial psychology and the use of psychological concepts to aid in personnel selection. However, with research such as the Hawthorne study, it was found that productivity was affected more by human inter... | Chapter Outline 13.1 What Is Industrial and Organizational Psychology? 13.2 Industrial Psychology: Selecting and Evaluating Employees 13.3 Organizational Psychology: The Social Dimension of Work 13.4 Human Factors Psychology and Workplace Design Introduction
In July 2012, Yahoo!, one of the largest and olde... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "Walter Dill Scott"
},
"bloom": null,
"hl_context": "<hl> Scott was one of the first psychologists to apply psychology to advertising , management , and personnel selection . <hl> In 1903 , Scott published two books : The Theory of Advertising a... | 13 | 13.1 What Is Industrial and Organizational Psychology? Learning Objectives By the end of this section, you will be able to:
Understand the scope of study in the field of industrial and organizational psychology
Describe the history of industrial and organizational psychology
In 2012, people who worked in the... | |
introduction_to_sociology | Learning Objectives 9.1 What Is Social Stratification?
Differentiate between open and closed stratification systems
Distinguish between caste and class systems
Understand meritocracy as an ideal system of stratification
9.2 Social Stratification and Mobility in the United States
Understand America’s ... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "People cannot change their social standings."
},
"bloom": "1",
"hl_context": "<hl> In the Hindu caste tradition , people were expected to work in the occupation of their caste and to enter into marriage according to their caste . <hl> <hl> Acce... | 9 | 9.1 What Is Social Stratification?
In the opening story, two siblings chose different life paths. Michael stayed within his parents’ social realm, achieving similar levels of education, occupation, and income. He retained social ties with community members. Lisa, however, rose from her parents’ social position, ac... | ||
anatomy_and_physiology | Chapter Objectives After this chapter, you will be able to:
Discuss both functional and structural classifications for body joints
Describe the characteristic features for fibrous, cartilaginous, and synovial joints and give examples of each
Define and identify the different body movements
Discuss the stru... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "amphiarthrosis"
},
"bloom": "1",
"hl_context": "<hl> An amphiarthrosis is a joint that has limited mobility . <hl> <hl> An example of this type of joint is the cartilaginous joint that unites the bodies of adjacent vertebrae . <hl> <hl> Filling... | 9 | 9.1 Classification of Joints Learning Objectives By the end of this section, you will be able to:
Distinguish between the functional and structural classifications for joints
Describe the three functional types of joints and give an example of each
List the three types of diarthrodial joints
A joint , ... | ||
biology | Chapter Outline 27.1 Features of the Animal Kingdom 27.2 Features Used to Classify Animals 27.3 Animal Phylogeny 27.4 The Evolutionary History of the Animal Kingdom Introduction Animal evolution began in the ocean over 600 million years ago with tiny creatures that probably do not resemble any living organism ... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "asexual reproduction"
},
"bloom": null,
"hl_context": "<hl> Most animals are diploid organisms , meaning that their body ( somatic ) cells are diploid and haploid reproductive ( gamete ) cells are produced through meiosis . <hl> Some exceptions... | 27 | 27.1 Features of the Animal Kingdom Learning Objectives By the end of this section, you will be able to:
List the features that distinguish the kingdom Animalia from other kingdoms
Explain the processes of animal reproduction and embryonic development
Describe the roles that Hox genes play in development
E... | ||
biology | Chapter Outline 17.1 Biotechnology 17.2 Mapping Genomes 17.3 Whole-Genome Sequencing 17.4 Applying Genomics 17.5 Genomics and Proteomics Introduction
The study of nucleic acids began with the discovery of DNA, progressed to the study of genes and small fragments, and has now exploded to the field of genomi... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "introducing recombinant DNA into an organism by any means"
},
"bloom": null,
"hl_context": "<hl> Genetic engineering is the alteration of an organism ’ s genotype using recombinant DNA technology to modify an organism ’ s DNA to achieve desirab... | 17 | 17.1 Biotechnology Learning Objectives By the end of this section, you will be able to:
Describe gel electrophoresis
Explain molecular and reproductive cloning
Describe uses of biotechnology in medicine and agriculture
Biotechnology is the use of biological agents for technological advancement. Biotechnol... | ||
business_ethics | Summary 10.1 More Telecommuting or Less?
Remote workers save themselves the time and cost of a commute and are better able to balance work and home life. Companies often benefit from the higher productivity and lower turnover of telecommuting employees, and they can also provide a social benefit by permitting emp... | Chapter Outline 10.1 More Telecommuting or Less? 10.2 Workplace Campuses 10.3 Alternatives to Traditional Patterns of Work 10.4 Robotics, Artificial Intelligence, and the Workplace of the Future Introduction
Beginning in the eighteenth century, in much of the Western world, the Industrial Revolution transfo... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "<hl> More broadly , there is a good deal of evidence suggesting that telecommuting has beneficial effects on worker productivity . <hl> <hl> For example , a call-center study reported in the Harvard Business ... | 10 | 10.1 More Telecommuting or Less?
Learning Objectives
By the end of this section, you will be able to:
Identify the benefits of permitting employees to work from home
Explain the drawbacks of telecommuting for the business and for employees
Discuss the ethical dilemmas related to telecommuting and some... | |
u.s._history | Summary 22.1 Turner, Mahan, and the Roots of Empire
In the last decades of the nineteenth century, after the Civil War, the United States pivoted from a profoundly isolationist approach to a distinct zeal for American expansion. The nation’s earlier isolationism originated from the deep scars left by the Civil Wa... | Chapter Outline 22.1 Turner, Mahan, and the Roots of Empire 22.2 The Spanish-American War and Overseas Empire 22.3 Economic Imperialism in East Asia 22.4 Roosevelt’s “Big Stick” Foreign Policy 22.5 Taft’s “Dollar Diplomacy” Introduction
As he approached the rostrum to speak before historians gathered in C... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "On the eve of the Civil War , the country lacked the means to establish a strong position in international diplomacy . <hl> As of 1865 , the U . S . State Department had barely sixty employees and no ambassad... | 22 | 22.1 Turner, Mahan, and the Roots of Empire Learning Objectives By the end of this section, you will be able to:
Explain the evolution of American interest in foreign affairs from the end of the Civil War through the early 1890s
Identify the contributions of Frederick Jackson Turner and Alfred Thayer Mahan to ... | |
biology | Chapter Outline 26.1 Evolution of Seed Plants 26.2 Gymnosperms 26.3 Angiosperms 26.4 The Role of Seed Plants Introduction The lush palms on tropical shorelines do not depend on water for the dispersal of their pollen, fertilization, or the survival of the zygote—unlike mosses, liverworts, and ferns of the terr... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "all heterosporous."
},
"bloom": null,
"hl_context": "In seed plants , the evolutionary trend led to a dominant sporophyte generation , and at the same time , a systematic reduction in the size of the gametophyte : from a conspicuous structure t... | 26 | 26.1 Evolution of Seed Plants Learning Objectives By the end of this section, you will be able to:
Explain when seed plants first appeared and when gymnosperms became the dominant plant group
Describe the two major innovations that allowed seed plants to reproduce in the absence of water
Discuss the purpose o... | ||
introduction_to_intellectual_property | Chapter Outline 1.1 The Foundations of Patent Protection 1.2 The Weakness of Early Patent Systems 1.3 America’s Uniquely Democratic Patent System 1.4 The Role of the U.S. Legal System 1.5 What the U.S. Patent System Wrought 1.6 Patent-Eligible Inventions 1.7 Criteria for Patenting 1.8 Other Types of Pa... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B."
},
"bloom": null,
"hl_context": "<hl> utility patents , which preclude others from making , using , or selling the invention during the term of the patent , which begins on the grant date and ends 20 years from the filing date ( for an aver... | 1 | 1.1 The Foundations of Patent Protection
Learning Objectives
After completing this section, you will be able to
Describe the philosophical logic behind granting patents.
Describe the role of patents in fostering invention.
Do Patents Really Promote Innovation?
Before reading this section, please wa... | ||
american_government | Summary 17.1 Defining Foreign Policy
As the president, Congress, and others carry out U.S. foreign policy in the areas of trade, diplomacy, defense, intelligence, foreign aid, and global environmental policy, they pursue a variety of objectives and face a multitude of challenges. The four main objectives of U.S. f... | Chapter Outline 17.1 Defining Foreign Policy 17.2 Foreign Policy Instruments 17.3 Institutional Relations in Foreign Policy 17.4 Approaches to Foreign Policy Introduction
The U.S. government interacts with a large number of international actors, from other governments to private organizations, to fight globa... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "bureaucratic oversight"
},
"bloom": null,
"hl_context": "Besides participating in the UN and NATO , the United States also distributes hundreds of millions of dollars each year in foreign aid to improve the quality of life of citizens in develo... | 17 | 17.1 Defining Foreign Policy
Learning Objectives
By the end of this section, you will be able to:
Explain what foreign policy is and how it differs from domestic policy
Identify the objectives of U.S. foreign policy
Describe the different types of foreign policy
Identify the U.S. government’s main c... | |
psychology | Summary 9.1 What Is Lifespan Development?
Lifespan development explores how we change and grow from conception to death. This field of psychology is studied by developmental psychologists. They view development as a lifelong process that can be studied scientifically across three developmental domains: physical, ... | Chapter Outline 9.1 What Is Lifespan Development? 9.2 Lifespan Theories 9.3 Stages of Development 9.4 Death and Dying Introduction
Welcome to the story of your life. In this chapter we explore the fascinating tale of how you have grown and developed into the person you are today. We also look at some ideas ... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "continuous development"
},
"bloom": null,
"hl_context": "<hl> Continuous development views development as a cumulative process , gradually improving on existing skills ( Figure 9.2 ) . <hl> With this type of development , there is gradual chang... | 9 | 9.1 What Is Lifespan Development? Learning Objectives By the end of this section, you will be able to:
Define and distinguish between the three domains of development: physical, cognitive and psychosocial
Discuss the normative approach to development
Understand the three major issues in development: continui... | |
anatomy_and_physiology | Chapter Objectives
After studying this chapter, you will be able to:
Describe the anatomy of the male and female reproductive systems, including their accessory structures
Explain the role of hypothalamic and pituitary hormones in male and female reproductive function
Trace the path of a sperm cell from its i... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "sperm"
},
"bloom": "1",
"hl_context": "Unique for its role in human reproduction , a gamete is a specialized sex cell carrying 23 chromosomes — one half the number in body cells . <hl> At fertilization , the chromosomes in one male gamete , cal... | 27 | 27.1 Anatomy and Physiology of the Male Reproductive System Learning Objectives By the end of this section, you will be able to:
Describe the structure and function of the organs of the male reproductive system
Describe the structure and function of the sperm cell
Explain the events during spermatogenesis ... | ||
business_law_i_essentials | Chapter Outline 3.1 Business Ethics 3.2 Social Responsibility Introduction
Learning Outcome
Analyze the role of ethics and social responsibility in business. | [
{
"answer": {
"ans_choice": 2,
"ans_text": "Leadership."
},
"bloom": null,
"hl_context": "<hl> The idea of business ethics may seem subjective , but it comes down to acceptable levels of behavior for each individual who makes up the organization . <hl> <hl> This behavior must start at th... | 3 | 3.1 Business Ethics
Businesses must establish a clear set of values that promote ethical practices and social responsibility. In today’s business climate, companies are increasingly under scrutiny by private citizens. A company that builds its foundation on sound principles will have a better chance of staying co... | ||
principles_of_accounting,_volume_1:_financial_accounting | Summary 15.1 Describe the Advantages and Disadvantages of Organizing as a Partnership
There are many advantages and disadvantages of partnership as a form of business entity and they should be carefully considered.
The most significant advantage of partnerships is the exemption from tax at the business level. ... | Chapter Outline 15.1 Describe the Advantages and Disadvantages of Organizing as a Partnership 15.2 Describe How a Partnership Is Created, Including the Associated Journal Entries 15.3 Compute and Allocate Partners’ Share of Income and Loss 15.4 Prepare Journal Entries to Record the Admission and Withdrawal of ... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "D"
},
"bloom": null,
"hl_context": "<hl> A general partnership is an association in which each partner is personally liable to the partnership ’ s creditors if the partnership has insufficient assets to pay its creditors . <hl> <hl> These partn... | 15 | 15.1 Describe the Advantages and Disadvantages of Organizing as a Partnership
A partnership is legal business structure consisting of an association of two or more people who contribute money, property, or services to operate as co-owners of a business. When discussing partnerships as a form of business ownersh... | |
biology | Chapter Outline 6.1 Energy and Metabolism 6.2 Potential, Kinetic, Free, and Activation Energy 6.3 The Laws of Thermodynamics 6.4 ATP: Adenosine Triphosphate 6.5 Enzymes Introduction Virtually every task performed by living organisms requires energy. Energy is needed to perform heavy labor and exercise, but h... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "glucose : ATP"
},
"bloom": null,
"hl_context": "Solar energy is required to synthesize a molecule of glucose during the reactions of photosynthesis . <hl> In photosynthesis , light energy from the sun is initially transformed into chemical ener... | 6 | 6.1 Energy and Metabolism Learning Objectives By the end of this section, you will be able to:
Explain what metabolic pathways are and describe the two major types of metabolic pathways
Discuss how chemical reactions play a role in energy transfer
Scientists use the term bioenergetics to discuss the concept... | ||
american_government | Summary 14.1 State Power and Delegation
The power structure of government established in the Articles of Confederation was rebalanced in the Constitution to ensure that both the central and the regional governments had some degree of authority and autonomy. Federal and state governments have managed to work out sh... | Chapter Outline 14.1 State Power and Delegation 14.2 State Political Culture 14.3 Governors and State Legislatures 14.4 State Legislative Term Limits 14.5 County and City Government Introduction
Controversial national policy decisions by lawmakers and justices tend to grab headlines and dominate social med... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "A"
},
"bloom": null,
"hl_context": "Growing financial resources gave the federal government increased power over subnational governments . <hl> This increased power was because it could use categorical grants to dictate the terms and conditions... | 14 | 14.1 State Power and Delegation
Learning Objectives
By the end of this section, you will be able to:
Explain how the balance of power between national and state governments shifted with the drafting and ratification of the Constitution
Identify parts of the Constitution that grant power to the national go... | |
psychology | Summary 2.1 Why Is Research Important?
Scientists are engaged in explaining and understanding how the world around them works, and they are able to do so by coming up with theories that generate hypotheses that are testable and falsifiable. Theories that stand up to their tests are retained and refined, while tho... | Chapter Outline 2.1 Why Is Research Important? 2.2 Approaches to Research 2.3 Analyzing Findings 2.4 Ethics Introduction
Have you ever wondered whether the violence you see on television affects your behavior? Are you more likely to behave aggressively in real life after watching people behave violently in ... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "testable"
},
"bloom": null,
"hl_context": "<hl> Scientific research ’ s dependence on falsifiability allows for great confidence in the information that it produces . <hl> <hl> Typically , by the time information is accepted by the scientific c... | 2 | 2.1 Why Is Research Important? Learning Objectives By the end of this section, you will be able to:
Explain how scientific research addresses questions about behavior
Discuss how scientific research guides public policy
Appreciate how scientific research can be important in making personal decisions
Scien... | |
u.s._history | Summary 2.1 Portuguese Exploration and Spanish Conquest
Although Portugal opened the door to exploration of the Atlantic World, Spanish explorers quickly made inroads into the Americas. Spurred by Christopher Columbus’s glowing reports of the riches to be found in the New World, throngs of Spanish conquistadors s... | Chapter Outline 2.1 Portuguese Exploration and Spanish Conquest 2.2 Religious Upheavals in the Developing Atlantic World 2.3 Challenges to Spain’s Supremacy 2.4 New Worlds in the Americas: Labor, Commerce, and the Columbian Exchange Introduction
The story of the Atlantic World is the story of global migrati... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "D"
},
"bloom": null,
"hl_context": "<hl> Portuguese colonization of Atlantic islands in the 1400s inaugurated an era of aggressive European expansion across the Atlantic . <hl> In the 1500s , Spain surpassed Portugal as the dominant European po... | 2 | 2.1 Portuguese Exploration and Spanish Conquest Learning Objectives By the end of this section, you will be able to:
Describe Portuguese exploration of the Atlantic and Spanish exploration of the Americas, and the importance of these voyages to the developing Atlantic World
Explain the importance of Spanish ex... | |
biology | Chapter Outline 21.1 Viral Evolution, Morphology, and Classification 21.2 Virus Infections and Hosts 21.3 Prevention and Treatment of Viral Infections 21.4 Other Acellular Entities: Prions and Viroids Introduction No one knows exactly when viruses emerged or from where they came, since viruses do not leave his... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "Viruses are acellular."
},
"bloom": null,
"hl_context": "Chapter Outline 21.1 Viral Evolution , Morphology , and Classification 21.2 Virus Infections and Hosts 21.3 Prevention and Treatment of Viral Infections 21.4 Other Acellular Entities : Pr... | 21 | 21.1 Viral Evolution, Morphology, and Classification Learning Objectives By the end of this section, you will be able to:
Describe how viruses were first discovered and how they are detected
Discuss three hypotheses about how viruses evolved
Recognize the basic shapes of viruses
Understand past and emergin... | ||
american_government | Summary 6.1 The Nature of Public Opinion
Public opinion is more than a collection of answers to a question on a poll; it represents a snapshot of how people’s experiences and beliefs have led them to feel about a candidate, a law, or a social issue. Our attitudes are formed in childhood as part of our upbringing. ... | Chapter Outline 6.1 The Nature of Public Opinion 6.2 How Is Public Opinion Measured? 6.3 What Does the Public Think? 6.4 The Effects of Public Opinion Introduction
On November 7, 2012, the day after the presidential election, journalists found Mitt Romney’s transition website, detailing the Republican candid... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "D"
},
"bloom": null,
"hl_context": "<hl> The most prominent agents of socialization are family and school . <hl> <hl> Other influential agents are social groups , such as religious institutions and friends , and the media . <hl> Political socia... | 6 | 6.1 The Nature of Public Opinion
Learning Objectives
By the end of this section, you will be able to:
Define public opinion and political socialization
Explain the process and role of political socialization in the U.S. political system
Compare the ways in which citizens learn political information
... | |
principles_of_accounting,_volume_1:_financial_accounting | Summary 16.1 Explain the Purpose of the Statement of Cash Flows
The statement of cash flows presents the sources and uses of cash.
The statement of cash flows is used to predict future cash flows and to assess the quality of an entity’s earnings.
There are two approaches utilized to prepare the statement of... | Chapter Outline 16.1 Explain the Purpose of the Statement of Cash Flows 16.2 Differentiate between Operating, Investing, and Financing Activities 16.3 Prepare the Statement of Cash Flows Using the Indirect Method 16.4 Prepare the Completed Statement of Cash Flows Using the Indirect Method 16.5 Use Informatio... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "C"
},
"bloom": null,
"hl_context": "<hl> Gains and / or losses on the disposal of long-term assets are included in the calculation of net income , but cash obtained from disposing of long-term assets is a cash flow from an investing activity . ... | 16 | 16.1 Explain the Purpose of the Statement of Cash Flows
The statement of cash flows is a financial statement listing the cash inflows and cash outflows for the business for a period of time. Cash flow represents the cash receipts and cash disbursements as a result of business activity. The statement of cash f... | |
american_government | Summary 8.1 What Is the Media?
The media encompass all communications that transmit facts or information to citizens and includes the mass media in print and on the radio, television, and Internet. Television takes many forms, such as local, network, cable, or satellite. Historically, programming was transmitted f... | Chapter Outline 8.1 What Is the Media? 8.2 The Evolution of the Media 8.3 Regulating the Media 8.4 The Impact of the Media Introduction
Democratic primary candidate Bernie Sanders arrived in Seattle on August 8, 2015, to give a speech at a rally to promote his presidential campaign. Instead, the rally was ... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "A"
},
"bloom": null,
"hl_context": "<hl> Most affiliate stations will show local news before and after network programming to inform local viewers of events and issues . <hl> Network news has a national focus on politics , international events ... | 8 | 8.1 What Is the Media?
Learning Objectives
By the end of this section, you will be able to:
Explain what the media are and how they are organized
Describe the main functions of the media in a free society
Compare different media formats and their respective audiences
Ours is an exploding media syste... | |
microbiology | Summary 15.1 Characteristics of Infectious Disease
In an infection , a microorganism enters a host and begins to multiply. Some infections cause disease , which is any deviation from the normal function or structure of the host.
Signs of a disease are objective and are measured. Symptoms of a disease are ... | Chapter Outline 15.1 Characteristics of Infectious Disease 15.2 How Pathogens Cause Disease 15.3 Virulence Factors of Bacterial and Viral Pathogens 15.4 Virulence Factors of Eukaryotic Pathogens Introduction Jane woke up one spring morning feeling not quite herself. Her throat felt a bit dry and she was sniffl... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "C"
},
"bloom": null,
"hl_context": "<hl> Unlike signs , symptom s of disease are subjective . <hl> <hl> Symptoms are felt or experienced by the patient , but they cannot be clinically confirmed or objectively measured . <hl> <hl> Examples of sy... | 15 | 15.1 Characteristics of Infectious Disease
Learning Objectives
Distinguish between signs and symptoms of disease
Explain the difference between a communicable disease and a noncommunicable disease
Compare different types of infectious diseases, including iatrogenic, nosocomial, and zoonotic diseases
I... | |
microbiology | Summary 11.1 The Functions of Genetic Material
DNA serves two important cellular functions: It is the genetic material passed from parent to offspring and it serves as the information to direct and regulate the construction of the proteins necessary for the cell to perform all of its functions.
The central do... | Chapter Outline 11.1 The Functions of Genetic Material 11.2 DNA Replication 11.3 RNA Transcription 11.4 Protein Synthesis (Translation) 11.5 Mutations 11.6 How Asexual Prokaryotes Achieve Genetic Diversity 11.7 Gene Regulation: Operon Theory Introduction In 1954, French scientist and future Nobel laureat... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "D"
},
"bloom": null,
"hl_context": "<hl> In addition to the mRNA template , many molecules and macromolecules contribute to the process of translation . <hl> <hl> The composition of each component varies across taxa ; for instance , ribosomes m... | 11 | 11.1 The Functions of Genetic Material
Learning Objectives
Explain the two functions of the genome
Explain the meaning of the central dogma of molecular biology
Differentiate between genotype and phenotype and explain how environmental factors influence phenotype
Clinical Focus Part 1 Mark is 60-year-... | |
principles_of_accounting,_volume_1:_financial_accounting | Summary 2.1 Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate
Financial statements provide financial information to stakeholders to help them in making decisions.
There are four financial statements: income statement, statement of o... | Chapter Outline 2.1 Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate 2.2 Define, Explain, and Provide Examples of Current and Noncurrent Assets, Current and Noncurrent Liabilities, Equity, Revenues, and Expenses 2.3 Prepare an Income... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "D"
},
"bloom": null,
"hl_context": "In Describe the Income Statement , Statement of Owner ’ s Equity , Balance Sheet , and Statement of Cash Flows , and How They Interrelate , we discussed the function of and the basic characteristics of the st... | 2 | 2.1 Describe the Income Statement, Statement of Owner’s Equity, Balance Sheet, and Statement of Cash Flows, and How They Interrelate
The study of accounting requires an understanding of precise and sometimes complicated terminology, purposes, principles, concepts, and organizational and legal structures. Typicall... | |
business_ethics | Summary 9.1 Entrepreneurship and Start-Up Culture
The atmosphere surrounding entrepreneurs and their start-ups can provide a dizzying rush. The opportunities to create a company, be your own boss, make a dramatic impact on business, establish an entrepreneurial culture that will be adopted by others, and possibly... | Chapter Outline 9.1 Entrepreneurship and Start-Up Culture 9.2 The Influence of Advertising 9.3 The Insurance Industry 9.4 Ethical Issues in the Provision of Health Care Introduction
As consumers, employees, and community members, we see everywhere the extent to which business can contribute to either social... | [
{
"answer": {
"ans_choice": 2,
"ans_text": "C"
},
"bloom": null,
"hl_context": "<hl> A fairly common characteristic of successful start-ups is charismatic , driven founders with take-no-prisoner competitive mentalities , as was illustrated earlier in this chapter in the example of Kalani... | 9 | 9.1 Entrepreneurship and Start-Up Culture
Learning Objectives
By the end of this section, you will be able to:
Identify ethical challenges relating to entrepreneurial start-ups
Describe positive and negative effects of growth in a start-up
Discuss the role of the founder in instilling an ethical cultu... | |
business_law_i_essentials | Chapter Outline 14.1 Liability Under the Securities Act 14.2 The Framework of Securities Regulation Introduction
Learning Outcome
Describe the Securities Exchange Act of 1934 and its impact on business. | [
{
"answer": {
"ans_choice": 0,
"ans_text": "The New York Stock Exchange."
},
"bloom": null,
"hl_context": "The SEC also oversees self-regulatory organizations ( SROs ) , or private organizations that create and enforce industry standards . These organizations are allowed to “ police ” th... | 14 | 14.1 Liability Under the Securities Act
As explained in the previous section, many companies were initially irritated by the creation of the Securities Exchange Act of 1934, as it created a myriad of legal responsibilities and potential liabilities that impacted their business models. Companies came to recognize ... | ||
biology | Chapter Outline 43.1 Reproduction Methods 43.2 Fertilization 43.3 Human Reproductive Anatomy and Gametogenesis 43.4 Hormonal Control of Human Reproduction 43.5 Human Pregnancy and Birth 43.6 Fertilization and Early Embryonic Development 43.7 Organogenesis and Vertebrate Formation Introduction Animal repr... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "asexual"
},
"bloom": null,
"hl_context": "Animals produce offspring through asexual and / or sexual reproduction . Both methods have advantages and disadvantages . Asexual reproduction produces offspring that are genetically identical to the pa... | 43 | 43.1 Reproduction Methods Learning Objectives By the end of this section, you will be able to:
Describe advantages and disadvantages of asexual and sexual reproduction
Discuss asexual reproduction methods
Discuss sexual reproduction methods
Animals produce offspring through asexual and/or sexual reproducti... | ||
introduction_to_sociology | Learning Objectives 11.1 Racial, Ethnic, and Minority Groups
Understand the difference between race and ethnicity
Define a majority group (dominant group)
Define a minority group (subordinate group)
11.2 Stereotypes, Prejudice, and Discrimination
Explain the difference between stereotypes, prejudice,... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "any of the above"
},
"bloom": "1",
"hl_context": "<hl> The next 150 years saw the rise of American slavery , with black Africans being kidnapped from their own lands and shipped to the New World on the trans-Atlantic journey known as the Middle... | 11 | 11.1 Racial, Ethnic, and Minority Groups
While many students first entering a sociology classroom are accustomed to conflating the terms “race,” “ethnicity,” and “minority group,” these three terms have distinct meanings for sociologists. The idea of race refers to superficial physical differences that a particula... | ||
introduction_to_sociology | Learning Objectives 7.1 Deviance and Control
Define deviance and explain the nature of deviant behavior
Differentiate between methods of social control
7.2 Theoretical Perspectives on Deviance
Describe the functionalist view of deviance in society through four sociologist’s theories
Explain how confl... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "Deviance is socially defined."
},
"bloom": "1",
"hl_context": "What , exactly , is deviance ? And what is the relationship between deviance and crime ? <hl> As Philip Hudson found out , some behaviors , such as wearing clothes of the opposite s... | 7 | 7.1 Deviance and Control
What, exactly, is deviance? And what is the relationship between deviance and crime? As Philip Hudson found out, some behaviors, such as wearing clothes of the opposite sex, can be deviant in certain places, criminal in some places, and perfectly acceptable elsewhere. According to sociolog... | ||
principles_of_accounting,_volume_1:_financial_accounting | Summary 7.1 Define and Describe the Components of an Accounting Information System
An accounting information system is a set of business processes that record transactions using journals and ledgers (a paper-based system) or computer files (using a computerized system) to keep track of a company’s money and other... | Chapter Outline 7.1 Define and Describe the Components of an Accounting Information System 7.2 Describe and Explain the Purpose of Special Journals and Their Importance to Stakeholders 7.3 Analyze and Journalize Transactions Using Special Journals 7.4 Prepare a Subsidiary Ledger 7.5 Describe Career Paths Ope... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "D"
},
"bloom": null,
"hl_context": "Firms are also developing and using artificial intelligence ( AI ) systems to perform tasks previously performed by accounting professionals , but now are freeing up the professionals to perform higher-level ... | 7 | 7.1 Define and Describe the Components of an Accounting Information System
Today, when we refer to an accounting information system (AIS) , we usually mean a computerized accounting system, because computers and computer software that help us process accounting transactions have become relatively inexpensive. Th... | |
psychology | Summary 16.1 Mental Health Treatment: Past and Present
It was once believed that people with psychological disorders, or those exhibiting strange behavior, were possessed by demons. These people were forced to take part in exorcisms, were imprisoned, or executed. Later, asylums were built to house the mentally il... | Chapter Outline 16.1 Mental Health Treatment: Past and Present 16.2 Types of Treatment 16.3 Treatment Modalities 16.4 Substance-Related and Addictive Disorders: A Special Case 16.5 The Sociocultural Model and Therapy Utilization Introduction
What comes to mind when you think about therapy for psychologica... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "medieval priests"
},
"bloom": null,
"hl_context": "<hl> In the 19th century , Dorothea Dix led reform efforts for mental health care in the United States ( Figure 16.6 ) . <hl> She investigated how those who are mentally ill and poor were cared... | 16 | 16.1 Mental Health Treatment: Past and Present Learning Objectives By the end of this section, you will be able to:
Explain how people with psychological disorders have been treated throughout the ages
Discuss deinstitutionalization
Discuss the ways in which mental health services are delivered today
Dist... | |
u.s._history | Summary 21.1 The Origins of the Progressive Spirit in America
In its first decade, the Progressive Era was a grassroots effort that ushered in reforms at state and local levels. At the beginning of the twentieth century, however, Progressive endeavors captured the attention of the federal government. The challeng... | Chapter Outline 21.1 The Origins of the Progressive Spirit in America 21.2 Progressivism at the Grassroots Level 21.3 New Voices for Women and African Americans 21.4 Progressivism in the White House Introduction
Women’s suffrage was one of many causes that emerged in the Progressive Era, as Americans confro... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "Beginning in the second half of the nineteenth century , these Progressive journalists sought to expose critical social problems and exhort the public to take action . In his book , How the Other Half Lives (... | 21 | 21.1 The Origins of the Progressive Spirit in America Learning Objectives By the end of this section, you will be able to:
Describe the role that muckrakers played in catalyzing the Progressive Era
Explain the main features of Progressivism
The Progressive Era was a time of wide-ranging causes and varied mo... | |
anatomy_and_physiology | Chapter Objectives
After studying this chapter, you will be able to:
List and explain the steps involved in fertilization
Describe the major events in embryonic development
Describe the major events in fetal development
Discuss the adaptations of a woman’s body to pregnancy
Describe the physiologic a... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "most do not reach the oocyte"
},
"bloom": "1",
"hl_context": "Fertilization is a numbers game . <hl> During ejaculation , hundreds of millions of sperm ( spermatozoa ) are released into the vagina . <hl> <hl> Almost immediately , millions of th... | 28 | 28.1 Fertilization Learning Objectives By the end of this section, you will be able to:
Describe the obstacles that sperm must overcome to reach an oocyte
Explain capacitation and its importance in fertilization
Summarize the events that occur as a sperm fertilizes an oocyte
Fertilization occurs when a... | ||
biology | Chapter Outline 40.1 Overview of the Circulatory System 40.2 Components of the Blood 40.3 Mammalian Heart and Blood Vessels 40.4 Blood Flow and Blood Pressure Regulation Introduction Most animals are complex multicellular organisms that require a mechanism for transporting nutrients throughout their bodies and... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "They use less metabolic energy."
},
"bloom": null,
"hl_context": "The circulatory system is effectively a network of cylindrical vessels : the arteries , veins , and capillaries that emanate from a pump , the heart . In all vertebrate organisms... | 40 | 40.1 Overview of the Circulatory System Learning Objectives By the end of this section, you will be able to:
Describe an open and closed circulatory system
Describe interstitial fluid and hemolymph
Compare and contrast the organization and evolution of the vertebrate circulatory system.
In all animals, exc... | ||
microbiology | Summary 18.1 Overview of Specific Adaptive Immunity
Adaptive immunity is an acquired defense against foreign pathogens that is characterized by specificity and memory. The first exposure to an antigen stimulates a primary response , and subsequent exposures stimulate a faster and strong secondary response.... | Chapter Outline 18.1 Overview of Specific Adaptive Immunity 18.2 Major Histocompatibility Complexes and Antigen-Presenting Cells 18.3 T Lymphocytes and Cellular Immunity 18.4 B Lymphocytes and Humoral Immunity 18.5 Vaccines Introduction People living in developed nations and born in the 1960s or later may ha... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "A"
},
"bloom": null,
"hl_context": "Once a B cell is activated , it undergoes clonal proliferation and daughter cells differentiate into plasma cells . <hl> Plasma cells are antibody factories that secrete large quantities of antibodies . <hl> ... | 18 | 18.1 Overview of Specific Adaptive Immunity
Learning Objectives
Define memory, primary response, secondary response, and specificity
Distinguish between humoral and cellular immunity
Differentiate between antigens, epitopes, and haptens
Describe the structure and function of antibodies and distinguish... | |
u.s._history | Summary 15.1 The Origins and Outbreak of the Civil War
The election of Abraham Lincoln to the presidency in 1860 proved to be a watershed event. While it did not cause the Civil War, it was the culmination of increasing tensions between the proslavery South and the antislavery North. Before Lincoln had even taken... | Chapter Outline 15.1 The Origins and Outbreak of the Civil War 15.2 Early Mobilization and War 15.3 1863: The Changing Nature of the War 15.4 The Union Triumphant Introduction
In May 1864, General Ulysses S. Grant ordered the Union’s Army of the Potomac to cross the Rapidan River in Virginia. Grant knew tha... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "that the Five Civilized Tribes would be admitted into the Confederacy"
},
"bloom": null,
"hl_context": "<hl> The Confederacy also gained the backing of the Five Civilized Tribes , as they were called , in the Indian Territory . <hl> The Five Ci... | 15 | 15.1 The Origins and Outbreak of the Civil War Learning Objectives By the end of this section, you will be able to:
Explain the major events that occurred during the Secession Crisis
Describe the creation and founding principles of the Confederate States of America
The 1860 election of Abraham Lincoln was a... | |
microbiology | Summary 4.1 Prokaryote Habitats, Relationships, and Microbiomes
Prokaryotes are unicellular microorganisms whose cells have no nucleus.
Prokaryotes can be found everywhere on our planet, even in the most extreme environments.
Prokaryotes are very flexible metabolically, so they are able to adjust their feed... | Chapter Outline 4.1 Prokaryote Habitats, Relationships, and Microbiomes 4.2 Proteobacteria 4.3 Nonproteobacteria Gram-Negative Bacteria and Phototrophic Bacteria 4.4 Gram-Positive Bacteria 4.5 Deeply Branching Bacteria 4.6 Archaea Introduction Scientists have studied prokaryotes for centuries, but it was... | [
{
"answer": {
"ans_choice": 1,
"ans_text": "B"
},
"bloom": null,
"hl_context": "All living organisms are classified into three domains of life : Archaea , Bacteria , and Eukarya . In this chapter , we will focus on the domains Archaea and Bacteria . <hl> Archaea and bacteria are unicellu... | 4 | 4.1 Prokaryote Habitats, Relationships, and Microbiomes
Learning Objectives
Identify and describe unique examples of prokaryotes in various habitats on earth
Identify and describe symbiotic relationships
Compare normal/commensal/resident microbiota to transient microbiota
Explain how prokaryotes are c... | |
anatomy_and_physiology | Chapter Objectives
After studying this chapter, you will be able to:
Identify and describe the interior and exterior parts of the human heart
Describe the path of blood through the cardiac circuits
Describe the size, shape, and location of the heart
Compare cardiac muscle to skeletal and smooth muscle
... | [
{
"answer": {
"ans_choice": 3,
"ans_text": "endocardium"
},
"bloom": "1",
"hl_context": "When the myocardium of the ventricle contracts , pressure within the ventricular chamber rises . Blood , like any fluid , flows from higher pressure to lower pressure areas , in this case , toward th... | 19 | 19.1 Heart Anatomy Learning Objectives By the end of this section, you will be able to:
Describe the location and position of the heart within the body cavity
Describe the internal and external anatomy of the heart
Identify the tissue layers of the heart
Relate the structure of the heart to its function... | ||
microbiology | Summary 14.1 History of Chemotherapy and Antimicrobial Discovery
Antimicrobial drugs produced by purposeful fermentation and/or contained in plants have been used as traditional medicines in many cultures for millennia.
The purposeful and systematic search for a chemical “magic bullet” that specifically targe... | Chapter Outline 14.1 History of Chemotherapy and Antimicrobial Discovery 14.2 Fundamentals of Antimicrobial Chemotherapy 14.3 Mechanisms of Antibacterial Drugs 14.4 Mechanisms of Other Antimicrobial Drugs 14.5 Drug Resistance 14.6 Testing the Effectiveness of Antimicrobials 14.7 Current Strategies for An... | [
{
"answer": {
"ans_choice": 0,
"ans_text": "A"
},
"bloom": null,
"hl_context": "A few decades later , German scientists Josef Klarer , Fritz Mietzsch , and Gerhard Domagk discovered the antibacterial activity of a synthetic dye , prontosil , that could treat streptococcal and staphylococ... | 14 | 14.1 History of Chemotherapy and Antimicrobial Discovery
Learning Objectives
Compare and contrast natural, semisynthetic, and synthetic antimicrobial drugs
Describe the chemotherapeutic approaches of ancient societies
Describe the historically important individuals and events that led to the development ... |
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