Review questions for the last part of the course The final exam will be cumulative (in the sense of including questions from all parts of the course). So please study the previous lists of review questions, in addition to this new one. You are also responsible for the figures and illustrations posted on the course web pages. ************************************************************************* Before birth, the heart muscle tissue of both right and left ventricles have the same thickness, curvature and strength. (And exert the same pressure) Please explain why? Hint: Compare the amount of force exerted by the two ventricles before birth. After birth, which ventricle exerts the stronger force? And why? Suggest why the muscles of the left ventricle become thicker and stronger in the weeks and months after birth, as compared with the muscles of the walls of the right ventricle? Hint: Does lifting weights cause skeletal muscles to get stronger and thicker? If both the foramen ovale and the ductus arteriosus somehow closed long before birth, then which ventricle would have to exert the stronger force? (And become thicker and stronger) The curvature of both ventricles is the same before birth. How is curvature related to pressure? After birth, the curvature of the left ventricle becomes much more than the curvature of the right ventricle. Explain how these differences in curvature contribute to pressure differences? Hint: T x C = what?? Consider whether the curvature difference between the two ventricles is a method for increasing the pressure inside the left ventricle, as compared with being a side effect of the weaker strength of the muscles squeezing the right ventricle? Explain your ideas. Do you think that individual heart muscles detect tension and grow thicker and stronger as a direct local response to increases in tension? What phenomena would this explain? Please design some experiments to test this possibility (growth in response to tension). Imagine a genetic disease that decreased this apparent ability of heart muscles to detect tension and become more strongly contractile where tension is stronger. What structural abnormalities would be produced, especially in the years after birth? What would be the effect on curvature and tension if increased blood pressure caused the outer walls of both right and left ventricles to bulge outward? ************************************************************************* How does sex determination work in Drosophila, and how is it different from sex determination in mammals? Hint: both have X and Y chromosomes but the mechanisms by which sex is determined are very different. Be prepared to explain this. What controls whether turtle and alligator embryos will develop into males or females? What is unusual about sex determination in fish? What tissues are the testis and the ovary and the sex ducts derived from? What is the Müllerian duct? What is the Wolffian duct? What happens to them in embryonic development? Where do the testes originate in development of mammals, and what happens to them during development? What is different about the position of the testes in birds? What is another example of organ migration in mammals? Contrast the internal histology of the testes and the ovaries. What is meant by dosage compensation in mammals? ************************************************************************* What is metamorphosis? What are at least three different examples of metamorphosis (e.g. caterpillars change into what? Plutei change into what? Tadpoles change into what?) What are at least 7 different changes that occur when a tadpole metamorphoses into a frog? What is thyroxine? What functions does it serve? (You don't need to know the molecular structure) What is ecdysone? What is meant by molting, in relation to the growth of insects and other arthropods? What is Juvenile Hormone? (again, function, not chemical structure) Does Juvenile Hormone participate in the control of molting and metamorphosis of insects? What does it cause? What does it prevent? A common misconception is that people today live much longer than they did a few hundred years ago. Explain why they are wrong. Hint: What is the meaning of "life expectancy"? ************************************************************************* Antibodies are synthesized by which particular kind of cells? Suggest why it's necessary that the great majority of lymphocytes undergo apoptosis. (Hint: Remember the randomness of the VDJ recombination of lymphocyte DNA! This is important!) Which of the following is closest to the reason that people don't normally make antibodies against their bodies' own antigens? a) Because every molecule in the body is labeled with special molecules that are special for them, and which lymphocytes recognize as "self", in the sense of avoiding attacks or binding to any molecule with that "self" label. b) Genetic linkage prevents anybody who inherits the gene for the A antigen from also inheriting the gene for antibodies that bind to the A antigen, and likewise for every combination of antigens and antibodies. c) Transcription of RNA is selectively inhibited for any antibody whose binding site would fit any of a person's own antigens. d) Because some mechanism weeds out those V, D and J regions of DNA that would code for antibodies that would fit any of that person's own antigens. e) Some mechanism selectively kills, inactivates or sequesters all B and T lymphocytes whose combinations of V, D and J regions of DNA actually do code for antibodies (or T-cell receptors) that actually do fit any of that person's own antigens. f) When antibodies bind to antigens that are present in large enough amounts, then those antibodies are quickly filtered out of the blood.) g) Some other mechanism? Put it in your own words. You should be able to write a few sentences about each of the following: antibodies VDJ recombination autoimmune disease immune tolerance vaccination Pasteur What are the names of at least 4 autoimmune diseases? Multiple Sclerosis, Lupus, Childhood Diabetes, Pernicious Anemia, Rheumatoid Arthritis Explain the errors in the following misleading statements: Autoimmune diseases result from failure of lymphocytes to distinguish between "self" and "non-self" histocompatibility antigens. Autoimmune diseases are caused by excess strength of the immune system. Which of the following are already known? (And briefly explain the known mechanism). Also tell which of the following are not known. a) How does the immune system produce genes for antibodies that fit (="recognize"="selectively bind to") molecules of your own body. Hint: Explain VDJ recombination. b) Does your immune system ever contain genes for antibodies that selectively bind ("recognize") molecules that neither you nor any of your ancestors have ever encountered? (same hint) c) How does the immune system (or any system) "recognize" something that it hasn't encountered before. (same hint) If a B lymphocyte's antibody binding sites fit a certain molecule, then based on what criterion does the lymphocyte "recognize" whether the bound molecule is "self" or "non-self"? a) If the molecule had been self, then that lymphocyte would have been weeded out = induced to die) during embryonic development. Therefore if a lymphocyte still exists, then whatever antigen it binds to must be non-self. b) All your cells have the equivalent of identification badges, and if a lymphocyte's badge matches the badge of another cells, then the latter must be "self" If immune tolerance really did work by means of matching badges, then by what means would you treat, or try to treat, autoimmune diseases? People who have type A blood somehow avoid making antibodies whose binding sites fit the type A blood group antigen. If they did make such antibodies, that would cause a very severe autoimmune disease. How do their lymphocytes avoid making antibodies with that specificity? Which of the following is closest to the reason that people don't normally make antibodies against their bodies' own antigens? a) Because every molecule in the body is labeled with special molecules that are special for them, and which lymphocytes recognize as "self", in the sense of avoiding attacks or binding to any molecule with that "self" label. b) Genetic linkage prevents anybody who inherits the gene for the A antigen from also inheriting the gene for antibodies that bind to the A antigen, and likewise for every combination of antigens and antibodies. c) Transcription of RNA is selectively inhibited for any antibody whose binding site would fit any of a person's own antigens. d) Because some mechanism weeds out those V, D and J regions of DNA that would code for antibodies that would fit any of that person's own antigens. e) Some mechanism selectively kills, inactivates or sequesters all B and T lymphocytes whose combinations of V, D and J regions of DNA actually do code for antibodies (or T-cell receptors) that actually do fit any of that person's own antigens. f) When antibodies bind to antigens that are present in large enough amounts, then those antibodies are quickly filtered out of the blood.) g) Some other mechanism? Put it in your own words. Tens of thousands of people become autoimmune to the special kind of myelin made by oligodendrocyte cells inside the central nervous system. (Many more than become autoimmune to any other differentiated cell type). Absolutely nobody develops autoimmunity to Schwann cell myelin! Can you invent some possible reasons for these facts? Explain why the following would be a possibility. Perhaps oligodendrocytes differentiate later during embryonic development than Schwann cells. (After the process of weeding out lymphocytes whose randomly-generated binding sites fit "anti-self" binding sites?) ************************************************************************* What are at least two connections between cancer and apoptosis? If a drug activated caspases when stimulated by an over-active oncogene protein, would this be useful? What is metastasis? Please invent several more new methods for taking advantage of (1) The abnormalities observed in cancer cells, (2) The biochemical effects of oncogenes, (3) And the mechanism of apoptosis for the purpose of selective killing of cancer cells, while harming normal cells as little as possible. What are the major weaknesses of current methods of cancer chemotherapy? (Specificity, or lack of specificity? Side effects? Failure to take advantage of apoptosis? The fact that many cancers are slow-growing?) What if a certain kind of cancer cells grew at the same rate as equivalent normal cells, except during treatment with anti-DNA or anti-microtubule chemotherapy drugs, during which time the normal cells slowed down, but the cancer cells continued to grow at the normal rate. Suggest an explanation for the slowing of normal cells, but not cancer cells. Explain how your explanation is related to how cancer can sometimes be cured by anti-growth chemotherapy drugs. Hint: Suppose that someone invented a drug that selectively stopped the growth of normal cells, but had no effect at all on cancerous cells. Propose how such an anti-growth drug could be used to cure cancer (Hint: In combination with other drugs that are now available) even though the new drug has absolutely no effect on normal cells (Hint: Except in combination with other drugs.) Suppose that somebody invented a drug that speeds up the growth rate of normal cells and also cancer cells. Suggest how this drug could increase the killing selectivity of other drugs that either damage mitotic spindles or DNA structure. In those particular cases of cancers that result from over-sensitive receptors for receptors of growth factors, why might treatment with traditional anti-DNA and anti-mitosis drugs have increased effectiveness when combined with treatment of the cancer with the same growth factors to which they are over-sensitive? Hint: This is analogous to the preceding question, in that the growth factor would have the same effect as a drug that speeds up growth rates, even in non cancerous cells. List and describe at least five abnormalities (Other than growth rates) by which malignant cancer cells are routinely distinguished from non-cancerous cells **** By what alternative method could pathologists distinguish between fast-growing and slow-growing cells? Hint: Rate of synthesis of DNA, as measured by incorporation of tritiated thymidine, for example. OR treatment of tissues with any of the many drugs that prevent completion of mitosis, so that dividing cells are trapped in mitosis, followed by counting the percentage of nuclei. **** Given that pathologists never even try to diagnose cancer using any of the cheap and easy methods for measuring growth rates, does that mean they don't really believe that cancer cells grow faster than normal cells? Why do they tell Aesop's fables to their patients? The patient wouldn't understand if you told them the truth? Pathologists are unsure of their own knowledge? To give patients the impression that researchers are making lots of progress? Until two years ago, the NIH information web site about cancer said that cancer is caused by cells growing and dividing too fast, and that chemotherapy works by slowing them down. Summarize the errors in the NIH statement. If a researcher actually believed this false statement, the belief would greatly reduce his or her chance of discovering an actual cure; Please explain how. For example, what would they fail to look for? What would they look for instead? -- Sometimes articles about oncogenes say that if only all the oncogenes were eliminated from the genome, then cancer would not be able to occur. Explain why this is a misguided idea. Imagine a drug that has many -OH groups that can be phosphorylated, and that (when over-phosphorylated) becomes able to activate caspase enzymes. Explain how such a drug might cure several kinds of cancer. A very large percentage of human cancer deaths result from mutations in a Ras gene that, slows, reduces or eliminates a ras protein's ability to convert bound GTP to GDP. What might be a specific cure for this type of cancer? Hints: Imagine a chemical analog to GDP that binds irreversibly to all ras proteins. Imagine a chemical analog to GTP that breaks down very quickly, even when bound to a weakened or inactivated ras protein. Imagine how to stimulate apoptosis in any cells in which ras proteins remain bound to the same GTP molecule for very long periods of time. Many cancers result from genetic translocations, which is to say breakage of chromosomes and rejoining an oncogene to a location next to a "luxury" gene (that is transcribed only by cells that have differentiated into a particular cell type.) For example, lymphomas result from translocation of antibody genes to positions next to some oncogene. If you could induce dedifferentiation of such cells, why would they cease to be cancerous? Or would they be? Why are lymphocytes much more likely than any other differentiated cell type to undergo chromosome breaks right next to the genes that code for antibody proteins? Hint: VDJ recombination is the mechanism for creating genes for antibody binding sites. Fusing two cells that are differentiated into different types usually results in complete dedifferentiation, because of reduced transcription of all luxury genes. Explain how you could potentially cure cancer and autoimmune disease by means of cell fusion-induced dedifferentiation. Hint: For example, imagine stimulating macrophages to fuse selectively with liver carcinoma cells, or pancreatic sarcoma cells, or leukemia cells. Explain some of the errors and false assumptions in this quote from a Wikipedia illustration: "Macrophages have identified a cancer cell (the large, spiky mass). Upon fusing with the cancer cell, the macrophages (smaller white cells) inject toxins that kill the tumor cell." ************************************************************************* Describe at least two phenomena in the area of evo-devo that surprised you, and explain why. SOME MORE QUESTIONS WILL BE ADDED.

 

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