Exam 3: Biology

Which of the following cell-cell junctions would help skin cells withstand mechanical stress by directly anchoring the intermediate filaments of adjacent cells?DesmosomesGap junctionsTight junctions

Passage Proteins known as cancer/testis antigens (CTAs) are normally expressed exclusively in germline cells but may become reactivated in cancer cells due to chromatin remodeling (eg, gene activation due to DNA demethylation).  Because of their normally restricted expression, CTAs can elicit an immune response when expressed by cancer cells derived from other tissue types.  Several CTAs are known to inhibit apoptosis or promote cell division in cancer cells, making them more resistant to traditional chemotherapy.  Accordingly, cancer research instead has focused on immunotherapy treatments targeting CTAs.In a study, researchers isolated peripheral blood lymphocytes (B lymphocytes, T lymphocytes, natural killer [NK] cells) from two healthy individuals.  These lymphocytes were cultured with signaling factors known to promote helper T cell (T_h cell) proliferation.  After 7 days, cultures from both individuals were enriched for T_h cells, which expressed proteins generally involved in activating other lymphocytes.  A subset of the cultures from each individual was treated with 5-Aza-CdR, a DNA-demethylating agent.  Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze expression of several CTAs (ie, MAGEs) in both untreated and 5-Aza-CdR-treated lymphocyte cultures, as well as in untreated melanoma (skin cancer) and breast cancer cell lines (Figure 1).  GAPDH, a protein expressed in most cell types, served as a control. Figure 1  Gels showing RT-PCR results for MAGE expressionAdditional peripheral blood lymphocytes were isolated from the same healthy individuals and incubated with the T_h cells that had been treated with 5-Aza-CdR.  After 11 days, these cultures consisted primarily of an increased number of NK cells and cytotoxic T lymphocytes (CTLs).  Researchers found that these CTLs were able to induce apoptosis in breast cancer cell lines but did not affect healthy cells.Researchers used a similar procedure to induce CTL proliferation in lymphocytes isolated from a breast cancer patient.  The CTLs were then incubated with cells obtained from a biopsy of the patient's cancerous tissue.  Following this experiment, researchers found that apoptosis was induced in the patient's cancer cells. Kirkin et al. Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. Nature Communications. 2018; 9:785 -CTLs incubated in the absence of 5-Aza-CdR-treated T_h cells were unable to induce apoptosis in the cancer cells described in the passage.  Given this, which of the following statements best describes why the 5-Aza-CdR-treated T_h cells were necessary to induce proliferation of functional CTLs?

Passage Obesity is a condition that affects over 30% of adults in the United States and is associated with comorbidities such as type 2 diabetes mellitus, heart disease, and cancer.  For individuals with clinically severe obesity, defined as having a body mass index above 40 kg/m², lifestyle interventions may produce insufficient weight reduction.  Weight loss surgery, such as Roux-en-Y gastric bypass (RYGB), has proved to be the most effective clinical intervention for facilitating massive and immediate weight loss in clinically obese patients.In RYGB, the stomach is first divided into a small gastric pouch and a distal gastric remnant, which remains attached to the duodenum.  Next, the jejunum is transected and its lower section is connected to the newly created gastric pouch to form the alimentary limb.  This connection is typically created with surgical staples.  The formation of the alimentary limb allows ingested food to bypass the region composed of the distal gastric remnant, the duodenum, and the upper jejunum; collectively termed the biliopancreatic limb.  Finally, the lumen of the upper jejunum is reconnected to the lumen of the lower jejunum to allow enzymes and compounds to flow freely from the biliopancreatic limb into the alimentary limb. Figure 1  RYGB surgically divides the digestive tract into the alimentary limb and the biliopancreatic limb, which then merge into the common limb.RYGB facilitates weight loss by reducing the functional volume of the stomach and altering intestinal anatomy to induce nutrient malabsorption.  However, the procedure is associated with several complications, such as steatorrhea, or fatty stools, due to disruption of lipid digestion.  Animal studies also suggest that RYGB promotes the growth of weight loss-inducing gut bacteria.  Researchers have found that transplanting gut microbiota of obese postoperative RYGB mice into nonoperated, obese mice lacking gut flora may reproduce the therapeutic effects of RYGB in transplant-recipient mice. Adapted from Bächler T, Le roux CW, Bueter M. How do patients' clinical phenotype and the physiological mechanisms of the operations impact the choice of bariatric procedure?. Clin Exp Gastroenterol. 2016;9:181-9. -All of the following are secreted by cells in the alimentary limb of RYGB patients EXCEPT:

Passage Within the Actinopterygii (bony fish) lineage, marine teleosts (bony fish with mobile jaws) live in an aquatic environment where there is a higher external concentration of salt and a lower concentration of water relative to the internal concentrations.  Owing to these conditions, salt ions tend to diffuse into the teleost through its skin, whereas water molecules within the organism osmotically traverse the opposite path.Irrespective of lineage, many fish species actively assess their environment and regulate their internal concentration of fluids and electrolytes via a homeostatic process known as osmoregulation.  Teleosts with either glomerular kidneys (eg, eels, sculpin) or aglomerular kidneys that are purely tubular (eg, goosefish, toadfish) have served as experimental subjects for the study of marine teleost osmoregulation.  Analyzing the ionic (ie, Na⁺, Cl⁻, Mg²⁺, SO₄²⁻) concentration of intestinal fluids, urine, and plasma in each species led to the discovery that the renal tubule of the goosefish has both excretory and reabsorptive functions.Scientists have concluded that marine teleost osmoregulation involves the ingestion of seawater, retrieval of NaCl and water from the intestine, and primary excretion of divalent ions via urine and monovalent ions through the gills (thin barriers between the organism's blood and the aquatic environment).In an experiment to further study osmoregulatory mechanisms, researchers emptied the gut of an eel and sealed the anus to prevent fluid loss.  The eel was transported into seawater that had been treated with the volume marker phenol red.  After 20 hours, the eel's gut contained 2.3 mL of fluid but showed a phenol red concentration equivalent to 12.3 mL of ingested seawater.  Researchers found that the eel lost 2.3 g of weight due to urine output.  They ultimately reported that the eel had lost all the seawater it absorbed through the gut via various mechanisms. -Researchers studying marine teleosts claim that the glomerular kidney is 500 times as efficient as the aglomerular kidney in eliminating nontoxic substances.  Similar amounts of nontoxic ferrocyanide are intramuscularly injected into a sculpin and a goosefish of comparable weight.  Given this, which of the following tables showing renal elimination of ferrocyanide after 5 hours would support the researchers' claim?

Passage Lipopolysaccharides (LPS) found in gram-negative bacterial cells can elicit a lethal degree of adjuvanticity, or immune activation, in LPS-responsive host organisms.  In mice, responses may be modulated by abnormalities in the toll-like receptor (TLR) encoded by the Tlr4 gene closely linked to coat color on Chromosome 4.  To investigate the effect of a particular Tlr4 mutation on LPS response, three experiments were performed following a cross between fully responsive He-N mice [tlr4(+)/tlr4(+)] and He-J mice homozygous for the mutation [tlr4(d)/tlr4(d)].Experiment 1Researchers isolated spleen cells for analysis of protein expression and LPS response.  In cells isolated from F1 mice, both wild-type and mutant TLRs were distinguishable by protein electrophoresis.  Following this first analysis, spleen cells from each cohort were exposed to 2 × 10⁵ SRC, an antigen formed by sheep erythrocytes.  Cultures were then incubated in the presence or absence of Ph-LPS, with LPS extracted from Escherichia coli K345 cells using a phenol-water mixture.  Titers of anti-SRC antibody were recorded on incubation day 5, with the results shown in Table 1.Table 1  Mean anti-SRC titers with standard error Experiment 2Serum samples were assayed for interferon production 2 hours post LPS injection.  Interferon was quantified using a plaque reduction assay on mouse cells challenged with vesicular stomatitis virus. Figure 1  Average serum interferon levels in mice cohortsExperiment 3Mice were injected with varying doses of Ph-LPS and monitored for 4 days.  The lethal dose (LD₅₀) was defined as the minimum dose causing death in 50% of injected mice.  Compared to He-N mice, results reflected a 10-fold increase in LD₅₀ for F1 mice and a 100-fold increase in LD₅₀ for He-J mice. -In an isolated population of 10,000 mice, 1,600 are homozygous for a Tlr4 defect.  Assuming stable allele and genotype frequencies, how many mice are heterozygous for a Tlr4 defect?

Passage Renal reabsorption of glucose is facilitated by sodium-glucose linked transporters (SGLTs), which are secondary active transport proteins located in the apical membrane of the proximal tubular cells in the kidney.  SGLT activity determines the transport maximum of glucose T_m, the maximum rate at which the kidneys can reabsorb glucose.Excretion of glucose in the urine (glycosuria) occurs when the glomerular filtration rate (GFR) of glucose exceeds the T_m.  Glycosuria is a symptom of diabetes mellitus, a disease marked by hyperglycemia (elevated serum glucose).  Uncontrolled hyperglycemia can damage the nerves that innervate urinary tract musculature, resulting in urinary retention (inability to fully empty the bladder) or incontinence (involuntary urine leakage).Canagliflozin is a SGLT inhibitor used for the treatment for diabetes.  The effect of canagliflozin on renal glucose reabsorption was tested in a glucose infusion experiment in patients with type 2 diabetes mellitus (T2DM).  First, researchers measured the participants' fasting serum glucose levels (average ~80 mg/dL) and then began a continuous intravenous infusion of a glucose solution.  The rate of glucose infusion was adjusted such that blood glucose concentration steadily rose to 300 mg/dL.  Blood and urine glucose concentrations were measured at 30-minute intervals.  The experiment was later repeated in the same patients following canagliflozin administration (100 mg, once a day for seven days).  The results of both trials are shown in Figure 1. Figure 1  Mean urine glucose excretion versus blood glucose concentration in patients with T2DM, with and without canagliflozin treatmentResearchers then estimated the new T_m of glucose following canagliflozin treatment (Figure 2).  Canagliflozin was found to also lower fasting blood glucose in individuals with T2DM.  Side effects included weight loss, increased urinary frequency, excessive thirst, and blood pressure reduction. Figure 2  Mean rate of renal glucose reabsorption versus plasma glucose concentration in patients with T2DM, with and without canagliflozin treatment -SGLT transports glucose against its concentration gradient across the luminal membrane of the proximal tubule.  The energy to drive this form of glucose transport is most likely directly provided by:

Which step(s) of the viral life cycle would most likely occur in lytic phages?Injection of viral genetic material into the bacterial hostIntegration of viral DNA into the bacterial genomeDegradation of the host genome

Camels inhabit water-deficient environments and exhibit an evolutionary adaptation that allows them to absorb more water than their ancestors that dwelled in water-rich environments.  The diagram below shows the structure of two nephron types present in the kidneys of camels and other mammals. How would the number of cortical nephrons differ from the number of juxtamedullary nephrons in camels and their ancestors?  Camels would be expected to have:

Passage The heart is a muscular organ comprising four chambers, two atria and two ventricles, that function synergistically to pump blood through a vast, closed network of blood vessels.  The chambers are separated by membranous muscular barriers known as septa.  Oxygenated blood returning from the lungs via the pulmonary veins fills the left atrium and enters the left ventricle, which then pumps the blood into the systemic arteries to supply other organs in the body.  By contrast, deoxygenated blood returning from systemic veins first enters the right atrium, then the right ventricle, and is ultimately siphoned into the pulmonary arteries leading to the lungs.  The necessary oxygen, nutrient, and waste exchange occurs between the thinnest blood vessels (capillaries) and neighboring tissues of the systemic and pulmonary circuits.Blood flow throughout the circulatory system is dictated by blood (hydrostatic) pressure, vascular resistance (force opposing blood flow through a vessel), and cardiac output (blood volume expelled from the ventricles per unit time).  When blood traverses a vessel, it exerts hydrostatic pressure on the vessel walls, which results in the forced movement of fluid out of the vessel and into the interstitial space.  The circulating plasma proteins cause the osmotic pressure within the vessel to be higher than that of the interstitial fluid.  In turn, osmotic pressure causes fluid to flow from the interstitial space into the blood vessel, opposing hydrostatic pressure.Cardiac output depends in part on heart rate, which is tightly regulated by the sinoatrial (SA) and atrioventricular (AV) nodes, specialized groups of self-depolarizing cells located in the upper right atrial wall and lower interatrial septum, respectively.  Action potentials (APs) generated by SA nodal cells stimulate atrial contraction as they travel to the AV node.  The AV node delays AP transmission to ventricular cells, ensuring ventricular filling is complete prior to heart contraction.A 63-year-old male patient collapsed while exercising and was hospitalized.  The patient presented with an elevated heart rate, low systemic blood pressure, and abnormally low blood oxygen levels.  In addition, x-rays revealed excess fluid in his lungs. -The systemic blood pressure gradient ΔP is equal to the mean pressure of blood exiting the heart through arteries minus the mean pressure of blood returning to the heart through veins.  The relationship of ΔP to cardiac output (CO) and vascular resistance (VR) is given by: ΔP=CO×VRGiven this, which of the following physiological changes would cause increased VR within vessels of the circulatory system?  (Note: Assume all other physiological factors remain constant.)

Stenosis is the abnormal narrowing of a tubular structure in the body, such as a blood vessel.  Stenosis of the afferent arterioles in the kidney would be expected to:

Passage Hematological anomalies have been observed in patients with prolonged liver damage.  For example, patients with chronic cirrhosis (scarring of the liver) often develop anemia and other blood disorders.  Hemoglobin is the metalloprotein within red blood cells that is responsible for the oxygen-carrying capacity of blood, and its function may be affected by liver damage.  The poor prognosis of patients with cirrhosis and anemia has stimulated further study of hemoglobin function and oxygen saturation.Blood samples from both cirrhotic patients and healthy individuals at rest and after exercise were exposed to varying partial pressures of oxygen.  Measurement of oxyhemoglobin dissociation curves (ODCs [Figure 1]) from the blood samples revealed significant functional differences in the hemoglobin from cirrhotic patients relative to control subjects. Figure 1  Oxyhemoglobin dissociation curve for cirrhotic patients (CP) at rest and for healthy controls (HC) at rest and after 20 minutes of exerciseVitamins are considered nontoxic supplements and are frequently provided to anemic patients to increase red blood cell production.  They may therefore have therapeutic benefits for cirrhotic patients.  However, some studies indicate that excessive vitamin consumption may lead to oxidative stress that could induce anemia through hemolysis (red blood cell rupturing).  Hemoglobin strongly absorbs light at 577 nm, and researchers conducted hemolysis assays by spinning down red blood cells and measuring absorbance (Abs) of the supernatant at 577 nm to determine how much hemoglobin was released.  The assay was carried out in the presence of four vitamins to determine their potential as oxidizing agents, and results are shown in Table 1.Table 1  Hemolysis of Red Blood Cells from Healthy Donors Treated With Vitamins [2 mM] for 30 Minutes, Measured by Absorbance at 577 nm Adapted from Clerbaux T, Detry B, Geubel A, et al. The oxyhemoglobin dissociation curve in liver cirrhosis. Chest. 2006;129(2):438-45. -Upregulation of which enzyme could improve oxygen release into the tissues of cirrhotic patients?

Passage Viruses are known as obligate intracellular parasites because they cannot reproduce independently (outside of a host cell).  Viral genomes (RNA or DNA) are enclosed by a protein shell known as the capsid.  Some viruses, known as enveloped viruses, have an additional phospholipid bilayer that fully envelops the capsid.  Viruses that lack this outermost phospholipid covering are labeled non-enveloped.  The entry of either enveloped or nonenveloped viruses into a host cell enables the production of viral proteins and the subsequent assembly of viral progeny.Immune cells (B and T cells) protect host organisms against viral infections by recognizing viral particles (antigens) as foreign.  In response to the recognition of foreign particles, antigen-presenting cells display cleaved antigens (also known as antigen fragments) on their surface, which enable the activation of other immune cells that stimulate an immune response, including the production of neutralizing antibodies.An example of an infectious disease is viral hepatitis (inflammation of the liver), which can be caused by any one of five distinct hepatitis viruses (A-E) that infect hepatocytes (liver cells).  HAV, HCV, and HEV contain positive-sense, single-stranded RNA (+ssRNA) as genetic material.  In contrast, HBV has a partially double-stranded circular DNA genome.  HDV is unique because it has a negative-sense, single-stranded RNA (−ssRNA) genome.Researchers hypothesized that synthetic antibodies could be used to treat viral hepatitis in patients with compromised immune systems.  Fluorescent antibodies, designed to bind the capsid proteins of the five hepatitis viruses, were added to separate wells containing each type of virus.  The fluorescence assay that was performed detected only bound antibodies in media with HAV or HEV. Adapted from Shin EC, Sung PS, Park SH. Immune responses and immunopathology in acute and chronic viral hepatitis. Nat Rev Immunol. 2016;16(8):509-23. -Based on the passage, which of the following viruses does NOT have an outer phospholipid bilayer?

Researchers analyzing gene expression in connective tissue samples are likely to obtain gene expression profiles for all of the following tissues EXCEPT:

Passage Trypanosoma brucei is a eukaryotic parasite that causes sleeping sickness in Sub-Saharan Africa.  The cell cycle of T. brucei differs from that of higher eukaryotes.  For example, the chromatin does not condense during mitosis, and the nuclear envelope remains intact.  In addition, the nucleus divides before cell division, and the cell divides along the longitudinal axis (Figure 1). Figure 1  Mitosis in T. bruceiA culture of T. brucei was arrested in S phase of the cell cycle by overnight incubation with the reversible inhibitor hydroxyurea.  The cells were then washed, and their progression through the cell cycle was monitored by flow cytometry and microscopy.  A subset of the culture was first exposed to the drug VX-680, which arrests cells upon completion of metaphase.  The results are shown in Figure 2. Figure 2  Percentages of a population of T. brucei cells in each phase of the cell cycle, measured at different time points in the (A) absence and (B) presence of VX-680 Adapted from Li Z, Umeyama T, Wang CC. The Aurora Kinase in Trypanosoma brucei plays distinctive roles in metaphase-anaphase transition and cytokinetic initiation. PLoS Pathog. 2009;5(9):e1000575. -Based on the passage, VX-680 most likely inhibits:

Passage Endometriosis is a chronic, treatable disease of the female reproductive tract associated with infertility and pelvic pain in women of reproductive age.  The endometrium, a layer of epithelial tissue that grows and sheds during the menstrual cycle, normally makes up the interior lining of the uterus.  In individuals with endometriosis, endometrial tissue is also found ectopically (outside the uterine cavity).The mechanism by which endometrial tissue successfully implants outside the uterine cavity is thought to be dependent on signaling molecules that promote the formation of blood vessels locally.  One of these signaling molecules is vascular endothelial growth factor (VEGF), a protein that is normally synthesized and secreted by various tissues in response to reduced oxygen levels.  Because VEGF is thought to be implicated in ectopic endometrial tissue growth, researchers hypothesize that the abdominal and pelvic structures of women with endometriosis would contain higher levels of VEGF compared to women without endometriosis.In an experiment, women ages 25-40 were divided into groups based on endometriosis disease status.  Individuals on any type of medication were excluded from the study.  Using minimally invasive surgery, samples of peritoneal fluid were taken from healthy subjects (n = 19) and from subjects diagnosed with endometriosis (n = 30).  An enzyme-linked immunosorbent assay (ELISA) was used to characterize the concentration of VEGF protein present within these samples.In a separate procedure that took place five days after peritoneal fluid collection, uterine endometrial samples were obtained from all subjects and visualized under a microscope to determine the menstrual cycle phase of each participant.  Figure 1 shows the level of VEGF in the abdominal fluid categorized by disease status and menstrual cycle phase. Figure 1  VEGF concentration in sampled peritoneal fluid (Note:  * = p < 0.05; Proliferative phase = stage immediately preceding ovulation; Secretory phase = stage immediately following ovulation) -A scientist proposed that ectopic endometrial cells contain extra copies of the VEGF gene.  Given this information, which of the following techniques can be used to analyze VEGF gene count?DNA sequencingNorthern blotSouthern blot

Passage Proteins known as cancer/testis antigens (CTAs) are normally expressed exclusively in germline cells but may become reactivated in cancer cells due to chromatin remodeling (eg, gene activation due to DNA demethylation).  Because of their normally restricted expression, CTAs can elicit an immune response when expressed by cancer cells derived from other tissue types.  Several CTAs are known to inhibit apoptosis or promote cell division in cancer cells, making them more resistant to traditional chemotherapy.  Accordingly, cancer research instead has focused on immunotherapy treatments targeting CTAs.In a study, researchers isolated peripheral blood lymphocytes (B lymphocytes, T lymphocytes, natural killer [NK] cells) from two healthy individuals.  These lymphocytes were cultured with signaling factors known to promote helper T cell (T_h cell) proliferation.  After 7 days, cultures from both individuals were enriched for T_h cells, which expressed proteins generally involved in activating other lymphocytes.  A subset of the cultures from each individual was treated with 5-Aza-CdR, a DNA-demethylating agent.  Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze expression of several CTAs (ie, MAGEs) in both untreated and 5-Aza-CdR-treated lymphocyte cultures, as well as in untreated melanoma (skin cancer) and breast cancer cell lines (Figure 1).  GAPDH, a protein expressed in most cell types, served as a control. Figure 1  Gels showing RT-PCR results for MAGE expressionAdditional peripheral blood lymphocytes were isolated from the same healthy individuals and incubated with the T_h cells that had been treated with 5-Aza-CdR.  After 11 days, these cultures consisted primarily of an increased number of NK cells and cytotoxic T lymphocytes (CTLs).  Researchers found that these CTLs were able to induce apoptosis in breast cancer cell lines but did not affect healthy cells.Researchers used a similar procedure to induce CTL proliferation in lymphocytes isolated from a breast cancer patient.  The CTLs were then incubated with cells obtained from a biopsy of the patient's cancerous tissue.  Following this experiment, researchers found that apoptosis was induced in the patient's cancer cells. Kirkin et al. Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. Nature Communications. 2018; 9:785 -Treating DNA with the compound bisulfite converts any unmethylated cytosines into uracils.  Bisulfite sequencing, which takes advantage of this mechanism, was used to compare DNA methylation of the MAGE-A1 gene in healthy cells and melanoma cells.  Based on the passage, which of the following graphs most likely represents the percentage of cytosines converted to uracils in the MAGE-A1 gene after treating DNA from these cells with bisulfite?

Passage The heart is a muscular organ comprising four chambers, two atria and two ventricles, that function synergistically to pump blood through a vast, closed network of blood vessels.  The chambers are separated by membranous muscular barriers known as septa.  Oxygenated blood returning from the lungs via the pulmonary veins fills the left atrium and enters the left ventricle, which then pumps the blood into the systemic arteries to supply other organs in the body.  By contrast, deoxygenated blood returning from systemic veins first enters the right atrium, then the right ventricle, and is ultimately siphoned into the pulmonary arteries leading to the lungs.  The necessary oxygen, nutrient, and waste exchange occurs between the thinnest blood vessels (capillaries) and neighboring tissues of the systemic and pulmonary circuits.Blood flow throughout the circulatory system is dictated by blood (hydrostatic) pressure, vascular resistance (force opposing blood flow through a vessel), and cardiac output (blood volume expelled from the ventricles per unit time).  When blood traverses a vessel, it exerts hydrostatic pressure on the vessel walls, which results in the forced movement of fluid out of the vessel and into the interstitial space.  The circulating plasma proteins cause the osmotic pressure within the vessel to be higher than that of the interstitial fluid.  In turn, osmotic pressure causes fluid to flow from the interstitial space into the blood vessel, opposing hydrostatic pressure.Cardiac output depends in part on heart rate, which is tightly regulated by the sinoatrial (SA) and atrioventricular (AV) nodes, specialized groups of self-depolarizing cells located in the upper right atrial wall and lower interatrial septum, respectively.  Action potentials (APs) generated by SA nodal cells stimulate atrial contraction as they travel to the AV node.  The AV node delays AP transmission to ventricular cells, ensuring ventricular filling is complete prior to heart contraction.A 63-year-old male patient collapsed while exercising and was hospitalized.  The patient presented with an elevated heart rate, low systemic blood pressure, and abnormally low blood oxygen levels.  In addition, x-rays revealed excess fluid in his lungs. -As shown below, CO₂ reacts with water in the blood to form H₂CO₃, a weak acid that can reversibly dissociate to form HCO₃⁻ and a free H⁺ ion. CO2+H2O⇋H2CO3⇋HCO3-+H+The patient is noted to have decreased pulmonary gas exchange.  Given this, which of the following is most likely to occur in the patient's blood if this condition is left untreated?

Which statement best describes the characteristics of hormones secreted from the pituitary gland?

Passage Parathyroid hormone (PTH) is an important regulator of calcium and phosphate homeostasis.  Specifically, PTH functions to increase plasma calcium concentration and reduce plasma phosphate levels.  PTH secretion is closely regulated by changes in plasma calcium concentration, which are detected by the human calcium-sensing receptor (hCaSR), a G protein-coupled receptor located on chief cells of the parathyroid gland.  hCaSR activation ultimately inhibits PTH release by inducing a second messenger cascade in which intracellular calcium levels rise due to the hydrolysis of the membrane phospholipid phosphatidylinositol bisphosphate (PIP₂) into inositol trisphosphate (IP₃) and diacylglycerol (DAG) by the membrane-bound enzyme phospholipase C (PLC).Secondary hyperparathyroidism is a condition characterized by excessive PTH release in response to depressed serum calcium or elevated serum phosphate levels.  The novel peptide AMG 416, an hCaSR agonist, is being investigated as a possible treatment for secondary hyperparathyroidism caused by end-stage renal disease (ESRD).  IP-1, a downstream metabolite of IP₃, is a marker of hCaSR activity.  Researchers used embryonic kidney cells lacking hCaSR (HEK-293T) and HEK-293T clone cells stably transfected with hCaSR (hCaSR) to measure IP-1 levels following AMG 416 treatment (Figure 1). Figure 1  IP-1 concentration in embryonic kidney cells lacking hCaSR (HEK-293T) and HEK-293T clone cells transfected with hCaSR (hCaSR) following AMG 416 treatmentThe dependence of AMG 416 on extracellular calcium was investigated by incubating hCaSR cells with increasing concentrations of AMG 416 in the presence or absence of calcium treatment (Figure 2). Figure 2  IP-1 levels in hCaSR cells incubated with and without calcium and AMG 416 peptide  (Note:  IP-1 levels are normalized to the number of cells present in each culture.)In addition, PTH concentration was measured in 5/6 Nx mice, an animal model of secondary hyperparathyroidism in human ESRD.  Blood samples were taken from male and female 5/6 Nx mice for 8 hours following administration of varying concentrations of AMG 416 (Figure 3), and PTH levels were measured. Figure 3  Serum PTH concentration following administration of AMG 416 to 5/6 Nx mice -Secondary hyperparathyroidism may result from:increased intestinal calcium absorption.impaired renal phosphate reabsorption.deficient renal calcitriol synthesis.

Passage Osteoarthritis (OA) is a disorder marked by the deterioration of articular (hyaline) cartilage, the connective tissue lining the ends of bones at most movable joints.  The progressive erosion of articular cartilage in OA is thought to be caused by an inflammatory response induced by years of biomechanical stress due to excessive compression and friction.  This response involves the release of proteolytic enzymes that break down cartilaginous proteins.  The progressive breakdown of articular cartilage ultimately results in complete exposure of the cortical portion of the underlying subchondral bone with narrowing of the joint space.  Repeated and abnormal joint stress can also cause the development of osteophytes, or bony growths, that form on the subchondral bone.  These degenerative processes cause pain and restrict joint movement.Stem cell therapy, in which injected or grafted stem cells are induced to differentiate into chondrocytes (cartilage cells), is a potential new treatment for OA.  To further understand chondrogenesis, researchers have been studying the molecules that regulate the expression and activity of the transcription factor Sox9, which has been shown to promote chondrocyte differentiation.  For example, researchers have found that binding of the growth factor TGF-β to its receptor results in Sox9 activation.MicroRNAs (miRNAs), which are known to alter gene expression by acting at the translational level, are also potential regulators of Sox9.  In particular, miRNA-145 is thought to regulate Sox9 expression by binding to the 3′-UTR of the Sox9 mRNA transcript.  After chondrocyte differentiation was induced using TGF-β, researchers used Western blotting to generate an expression profile of Sox9 and β-actin (a protein not regulated by miRNA-145) in mouse stem cells transfected with miRNA-145, anti-miRNA-145, or neither (Figure 1). Figure 1  Expression of Sox9 in the presence and absence of miRNA-145 or anti-miRNA-145 following induction of chondrocyte differentiation Adapted from Yang B, Guo H, Zhang Y, Chen L, Ying D, Dong S. MicroRNA-145 regulates chondrogenic differentiation of mesenchymal stem cells by targeting Sox9. PLoS ONE. 2011;6(7):e21679. -Luciferase is an enzyme responsible for bioluminescence (light emission).  Researchers engineered a reporter vector (shown below) that results in the expression of a hybrid transcript containing luciferase and the Sox9 3′- UTR. The vector was transfected into two groups of mouse stem cells, Group A and Group B.  Cells in Group B were also transfected with a miR-145 mimic, which was designed to imitate mature endogenous miRNA in the cell.  Given this information, luciferase bioluminescence will most likely be detected in: