Challenge responses:

Summary: Rather than regrade any of these specific questions, we will give a margin of 2 point (amounting to 4 questions missed) on the final grade thresholds to cover various minor sources of confusion.

#11 Which of the following hormones is classified as water-insoluble and endocrine?

Thyroxine is a hormone classified as water-insoluble and endocrine. “Thyroxin”, although now seen as simply a misspelling of “thyroxine”, was at the time of the exam, seen by some as an attempt to make up a false answer. Since ‘thyroxine’ is not an answer choice, this question has no right answer.

Credit should be given for all answers.

Response: While it's true that "thyroxin" is not the spelling that we used in the course, it's not plausible that any of the other options were intended to be water-insoluble endocrine hormones. Rather than regrade this, the margin we are giving on the grade thresholds is intended to compensate for confusion caused by these sorts of minor ambiguities.

#16 Lesch-Nyhan syndrome is caused by a defect in hypoxanthine phosphoribosyl transferase (HPRT) and involves a perturbation of ______.

Several students, especially those with English as there second language, did not know the meaning of the word ‘perturbation.’ Although probably unintentional, the use of this word makes this question confusing.

Credit should be given for all answers.

Response: While accepting that the word 'perturbation' may have unintentionally hindered some of the students, I think that students who knew that pathways a-c were all altered would not miss this question even if they never heard that word before.

#24 Which one of the following is NOT part of the delivery of fatty acids from the intestines to adipocytes?

The answer (d.) should also be accepted because fatty acids are NOT re-esterified to glycerol within the adipocytes for storage. They are re-esterified to glyerol-3-phophate within adipocytes. This is shown on slide 11 of the Ch. 24 Metabolism of Lipids power point presentation

Credit should also be given for D.

Response: Notwithstanding that glycerol-3-P is a substrate for the synthesis of triacylglycerol in adipocytes, triacylglycerol consists of glycerol with three esterified fatty acids. The actual point tested what that it could make no sense for insulin to inhibit fatty acid uptake by adipocytes.

#36 Which one of the following statements about PTH and PTHrP is FALSE?

PTH and PTHrP fluctuate in response to serum calcium levels. Literature shows that in cancer patients who were hypercalcemic, the levels of blood PTHrP were correspondingly elevated.

Mundy, G.R. & Edwards, J. R. “PTH-related peptide in hypercalcemia.” Journal of the American Society of Nephrology. 2008.

Many students do not come to class, but instead read the manual and rely on their previous knowledge and experience to answer questions. PTHrP is a known cancer marker that has been shown to alter its concentration in the blood along with serum Ca2+ levels. It would seem that this question has no right answer.

Therefore, credit should be given for all answer choices.

Response: It is true that bone cancers can ectopically express PTHrP and cause hypercalcemia. We discussed this also in class. That causes disease precisely because it is not regulated in response to calcium levels. It is just constitutively high, and this drives serum Ca+2 levels inappropriately high.

Students who don't come to class are responsible for the same level of comprehension as those that do come to class. Wholesale skipping of class causes lower grades. This was explained in writing at the beginning of the course.

#46 Which one of the following is incorrect regarding Vitamin D?

The answer choice C, stating that Vitamin D metabolism is catalyzed by a photosensitive reaction in the skin, is also false. The term metabolism implies breakdown of a substance. It is vitamin D synthesis that is catalyzed in the skin, not metabolism. Therefore, answer choice A should be accepted.

Response: There is nothing about the meaning of the word "metabolism" that excludes synthetic reactions.

Different Challenge for 46

In the Nutrition powerpoint, Slide 17, Dietary Lipids breakdown to Essential Fatty Acids, Cholesterol, and Fat Soluble Vitamins where it shows A, D, E, K.
The slide indicates that only Cholesterol is Not essential in the diet, indicating that the Vitamin D (and the fat soluble vitamins) with Essential Fatty Acids are essential in the diet. If the fat-soluble vitamins were not essential, it should have been noted (as the cholesterol was noted).

Response: Slide 41, chapter 23 says that vitamin D is " Derived from 7-dehydrocholesterol in light-dependent reaction in skin; required in diet for people with little sunlight exposure." I remember talking about the vitamin D supplementation story in at least 3 different class hours.
This question and answer is also in direct conflict with question 31, which asked for the identification of one of the following that are NOT absolutely required in the diet. Answer choice C was Fat-soluble Vitamins, which includes vitamin D. This was not the correct answer (it was glucose). So, there is a discrepancy on this question AND question 31. Due to the discrepancy and the fact that the slide does not state specifically that Vitamin D is not essential, only cholesterol, the question has no correct answer.

Response: The other fat soluble vitamins are absolutely required in the diet. Vitamin D is not required except in people with limited sunlight exposure.

#51 None of the following methods of protein trafficking are available in bacteria EXCEPT ______.

According to the manual and lecture material, "Bacteria are single cell organisms surrounded by a membrane and with no internal organelles surrounded by intracellular membranes" (p.7 of chapter 1 in our manual and page 12 of the .pdf from our lecture notes). Some students were taught in undergraduate study, and current literature shows, that bacteria can use endocytosis. Here is just one article published in academia that states bacteria can use endocytosis:

Fuerst, J.A. and Sagulenko, E. "Protein uptake by bacteria: An endocytosis process in the planctomycete Gemmata obscuriblobus." Communicative & Integrative Biology. 2010, 3(6), 572-575.

There are plenty other papers stating the same thing and a simple Google search illustrates that some bacteria are now found to use endocytosis for protein trafficking. Because it was not explicitly taught that bacteria cannot use endocytosis, students should not be punished for prior knowledge that bacteria have been found to use endocytosis.

Credit should also be given for D.

Response: The question hinged on the very simple relationship that bacteria, by definition, do not have internal membrane-bound organelles, and hence do not do any of the kinds of trafficking that eucaryotes do with membrane bound vesicles. That includes endocytosis. The challenge misquotes a literature reference to the contrary. The actual title of the paper is " Protein uptake by bacteria: An endocytosis-like process in the planctomycete Gemmata obscuriblobus". It's not endocytosis because it does not produce membrane bound vesicles. Instead, the bacteria highly invaginates its plasma membrane to give the appearance of internal membraneous structures. Furest and Sagulenko have, in fact, published a series of papers positing the controversial theory that this process has some molecular or ancestral relationship to endocytosis in eucaryotes. While I appreciate the industrious nature of the challenge, I don't seriously believe that students missed this question because of prior familiarity with the unusual biology of Gemmata obscuriblobus, or the belief that I could have possibly been asking about Gemmata obscuribiobus.

#53 Which of the following in NOT a component of both soft and mineralized connective tissue biology?

In the bone composition lecture, slide 26, it is stated that “Proteoglycan aggregate is major component of ground substance before mineralization.” This is further explained by the slide-by-slide summary provided that urges students to know that proteoglycan aggregate has to be turned over to replace cartilage with bone, and then degraded again to mineralize the bone. The question does not ask for a component not involved in production of these tissues. Instead, it asks for a component of mineralized tissue. Clearly, there is no proteoglycan aggregate in mineralized tissue, as it is degraded prior to mineralization.

Therefore, answer B should also be accepted.

Response: The question asks if it is a component of mineralized connective tissue biology, not a component of mineralized connective tissue. The biology of the tissue includes its generation.

#54 Which of the following occurring in a bone environment would typically (excluding hyperparathyroidism) trigger bone resorption NOT balanced by reformation?

IgG is expressed on B cells. The instructor used T lymphocytes to illustrate points involving periodontitis, as well as the point that T lymphocytes express RANKL, and are involved in inflammation. B cells express IgG, but T lymphocytes do not. If the answer choice would have stated “lymphocytes interacting with bacteria” or “T-lymphocytes interacting with bacteria”, this would be the correct choice. However, B cells express IgG, and from the slides, one can infer that B cells expressing IgG would not be involved in inflammation. This question, as stated, has no right answer.

Therefore, credit should be given for all answer choices.

Response: This question tests elements of chapters 9 and 10, which are that one of the fundamental functions of IgG is to trigger inflammation when bound to bacteria, and that inflammation, as exemplified by periodontitis, causes bone loss. The bone lecture listed both inflammatory responses driven through RANKL expression and others that were not. I twice summarized this by saying that, rather than focuing on specific molecular pathways, to understand that anything that causes inflammation in the vicinity of bone can cause bone loss.

#55 As Inflammation proceeds to its macrophagic stage, the pH of the site drops. This can often cause a problem with the action of ______.

Inflammation enters the macrophagic stage after already being infiltrated with neutrophils. Neutrophils cannot survive the acidic condition the macrophages create (Manual Ch. 10 pg. 6). NSAIDs are a treatment option listed on slide 16 of the Biosynthesis of Nucleotides power point presentation. It helps to alleviate the acute symptoms of gout caused by neutrophil action. The NSAIDs treat gout by inhibiting the neutrophils. The drop in pH creates an environment where neutrophils cannot survive, therefore neutrophils would not be present for the NSAIDs to inhibit. This would “cause a problem” in this particular situation of inflammation with the action of NSAIDs used to treat inflammation related to Gout.

Therefore, A should also be accepted.

Response: Lest we completely lose sight of the point of the question: the topical anethetics that you rely upon are pH dependent and won't work if you inject them into a highly inflamed site. The challenge tries to to synthesize a pH effect on NSAIDs with a number of assertions that don't quite fit together. It is true that NSAIDs are used to treat gout, and gout is an inflammation. It is not true that NSAIDs only act on neutrophils. NSAIDs act on cyclooxygenase with synthesizes inflammatory signals in many cell types. This was apparently a confused reference to the fact that cholchicine is also used to treat gout, and cholchicine targets neutrophil migratory behaviour.

#73 Which of the following is a cytokine that can induce the differentiation of a pre-osteoblast from a mesenchymal osteoprogenitor?

In Chapter 33 on page 6, it says "BMP is a member of the TGF-beta family". This implies that BMP is a type of TGF-beta. Furthermore, on the resorption and formation powerpoint (slide 22), it list molecules TGF-beta and BMPs as molecules involved in promoting osteoblast proliferation and differentiation. These bullet points in both the manual and lecture imply that TGF-beta is associated with differentiation. It seems that if a member of a family is responsible for an action, then the family in general, should also be attributed that quality.

Therefore, answer B should also be accepted.

Response: It is true that most of the BMPs are members of the TGF-beta family. BMPs, by definition, are those cytokines that cause ectopic bone formation when injected in a non-boney site. TGF-beta itself does not do that. It is true that TGF-beta promotes osteoblast proliferation and differentiation, but it cannot by itself induce this action. The way to think of TGF-beta is that it encourages switching from the destructive to the healing stages of an inflammation, but does not carry the information as to which kinds of tissue to produce. It functions much the same in bone as in soft connective tissue.

#92 Which of the following statements about enzyme kinetics is correct?

The Km value is the concentration of the substrateat one-half the Vmax value. Several students inferred the word “concentration” when answering. The fact that students chose answer choice A, which states that the Km value is ½ the Vmax value, shows that they understand the concept.

This question was not designed to test knowledge of the material, but was intentionally designed to mislead students.

Response: The point of the question was in fact to test whether a student understood that the Km value is a concentration rather than just memorizing that it had something to do with 1/2 the Vmax.

#96 Which one of the following statements regarding acetyl-CoA is False?

Answer choice A is also false. “It is formed from pyruvate in a manner that is dependent upon an enzyme that has NAD+ and coenzyme A as substrates." It is, in fact, two different enzymes in the pyruvate dehydrogenase complex, that complete this process. In chapter 16 p.4-6, pyruvate dehydrogenase is defined as a multienzyme complex (indicating more than one enzyme) and a table clearly shows the enzyme Dihydrolipoyl transacetylase uses coenzyme A whereas Dihydrolipoyl dehydrogenase uses NAD+ as substrates. Clearly, to say “an” enzyme does this is inaccurate.

Therefore, answer A should also be accepted.

Response: Pyruvate dehydrogenase is commonly called an enzyme irrespective of the fact that its subunits can independently be called enzymes.