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Evening Core Exam 5 May 7, 2008 Name ___________________________ Notes to Students: 1. Write your name on EACH PAGE including this one. The pages will be separated for grading. If your name is not on the page and we cannot identify your work you will not receive points for that page. 2. Space for each question is provided on the FRONT of the exam pages. You should not need to use the extra space on the back of the page. However, if you make a mistake on the front, you may cross it out and write your answer on the back. 3. Answer completely, but CONCISELY and clearly. One or a few words may be enough for some questions. Extraneous, unnecessary information will not gain you points. If the extra information is wrong, then it may cause points to be taken away. Diagrams, flow charts, and pictures are acceptable in addition to or in lieu of text. 4. There are 98 points on the exam; I will calculate your score as a percentage of the total points. There are 4 sections, and 15 pages including this one, on this exam. Dr. Levison’s questions are divided ‘approximately’ according to his lectures, but there is ‘overlap’. I’ve labeled the sections 3a-3d. It may be helpful to just ignore the sections in this case. 1 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 1 (Dr. David DeFouw; 11 points total) 1. Describe the molecular organization of a gap junction and a zonula adherens junction as might be found between adjacent cuboidal epithelial cells. Also describe how their molecular organizations relate to their respective functions. (8 points) 2. Epithelia are typically associated with basal laminae. Describe the interactions between epithelial cell transmembrane proteins and molecular constituents of the extracellular matrix that serve to create this association. (3 points) 2 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 2 (Dr. Stephen Garrett; 22 points total) 1. Describe how individual cyclins confer cell-cycle specificity to the cyclin-dependent protein kinase. (5 points) 2. What is the mechanism by which mammalian Rb protein (or Whi5 protein of yeast) inhibits the initiation of DNA synthesis? How is this inhibition relieved? (4 points) 3 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 2 (Dr. Stephen Garrett; continued) 3. Mitotic (B) cyclin levels oscillate throughout the cell cycle. On the graph below, accurately plot mitotic cyclin levels through two complete cycles. (4 points) Cyclin levels G1 S G2 M G1 S Cycles 4. What two mechanisms regulate cyclin accumulation? (4 points) 4 G2 M Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 2 (Dr. Stephen Garrett; continued) 5. Outline the observation that established the products of the CLN1, CLN2, and CLN3 genes of S. cerevisiae as G1 cyclins? (5 points) 5 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 3a (Dr. Steven Levison; 8 points total) 1. Assign the most appropriate epithelial type to these pictures (1/2 pt ea.) A. Stratified Squamous Epithelium B. Simple Squamous Epithelium C. Stratified Columnar Epithelium D. Transitional Epithelium E. Pseudostratified Epithelium F. Simple Cuboidal Epithelium 6 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 3a (Dr. Steven Levison; continued) 2. Use the diagram below, which is a schematic of the mucosa of the gastrointestinal tract to answer the following questions. Choose the best letter, i.e. A,B,C, or None to answer the question. A) Where would smooth muscle be most abundant? ( 1 pt) B) Where would collagen be most abundant? C) Which layer(s) is/are avascular? ( 1 pt) ( 1 pt) D) Which region has abundant tight junctions? ( 1 pt) E) Which layer harbors the neurons that innervate the smooth muscle? ( 1 pt) F) The dotted line in this diagram indicates the cell renewal occurs in this tissue. Draw an arrow on the diagram to indicate the approximate location of the stem cells (1 pt) 7 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 3b (Dr. Steven Levison; 9 points total) 3. What are 4 properties of a somatic stem cell (2 pts) A. B. C. D. 3E. How are stem cells different from progenitors (1pt)? 4. What is the most significant difference from the perspective of cell differentiation between a hematopoietic stem cell and an embryonic stem cell? (1 pt) 8 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 3b (Dr. Steven Levison; continued) 5. An experiment was performed where bone marrow stromal cells were transplanted into the adult mouse brain and it was observed that some neurons now expressed a marker that was uniquely expressed by the bone marrow stromal cells (EGFP). 5A. Based on your knowledge of stem cells, are you convinced based upon these data alone that the bone marrow cells transdifferented into new neurons? If not, what is an alternative explanation? (1pt) 5B. What is one simple experiment test that you could perform to rule out transdifferentiation?. (1 pt) 6. Where are stem cells frequently located and why aren’t stem cells distributed randomly throughout a tissue? Include in your answer a general description of the stem cell niche (3 pts). 9 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 3c (Dr. Steven Levison; 9 points total) 7) Your colleague Dr C. Mel deRoses has been fate mapping cells in Drosophila that go on to form the Sniff ganglion. The neurons of this ganglion are sensory neurons involved in olfaction and they are surrounded by a connective tissue capsule. Below is a diagram illustrating the lineage relationships that he has observed. The final ganglion has 3 cells which consist of 1 B cell and 2 C cells. Based on the diagram below answer the following questions. Hint: this is a multi-multi- part question, so you are advised to read the whole question before answering to avoid redundancy in your answers. AB A B C C 7A. Based on the diagram, which precursor divides in an asymmetric fashion? (1pt) 7B. Which precursor divides in a symmetric fashion? (1pt) 10 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 3c (Dr. Steven Levison; continued) 7C. When cell B divides in vivo, it produces two identical daughter cells – both are neurons. However, when Dr. DeRoses transplants cell B into presumptive skin, the C cells become epithelium. In 2-3 sentences describe a simple in vitro experiment that you could perform to determine whether the neuronal or epithelial fate is the default, and predict the result of your experiment. (2 pts) 7D. Cell fates can be influenced by environmental signals. Name 2 general types of signals that the C cells could receive that would determine their fate. A. (1 pt) B. (1 pt) 7E. Adjacent cells can laterally signal to affect cell fate. Which molecules are involved in lateral signaling? (1 pt) 7F. In 2-3 sentences describe an experiment to test whether that signal is operating on these cells. (2 pts) 11 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 3d (Dr. Steven Levison; 15 points total) 7G. Dr. DeRoses used Nomarski optics (light microscopy using polarized light) to demonstrate that cell AB divides to produce two daughters A and B. However, when he observes the ganglion just a few hours after cell AB has divided, he finds only one daughter. He suspects that cell A is undergoing programmed cell death. If his hypothesis is correct, name 2 characteristics that he would observe were he to examine the dying cell A under the electron microscope. 1. (1 pt) 2. (1 pt) 7H. Using biochemical methods, what are two read-outs that Dr. DeRoses could use to establish whether cell A is dying by apoptosis? 1. (1 pt) 2. (1 pt) 7I. In 2-3 sentences briefly describe an in vitro experiment that you could perform to prove that cell A was not being murdered by the C cells, but rather that it was destined to die? (2 pts) 12 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 3d (Dr. Steven Levison; continued) 7J. Suppose that cell A is dying because it has inherited high levels of an enzyme that spontaneously generate high concentrations of free radicals resulting in oxidative stress and DNA damage. Please draw the major components of the signaling cascade that would become activated leading to the apoptotic death of this cell (4 pts). 7K. Suppose that instead your experiments suggest that that the C cells produce high levels of Fas ligand. Please draw the signaling cascade upstream of the executor caspases that would become activated leading to the apoptotic death of cell A (3 pts). 13 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 3d (Dr. Steven Levison; continued) 8. The unprocessed form of NGF as it turns out can promote cell death by signaling through the same receptor that can promote survival. Which receptor subunits do pro-neurotrophins signal through and why is it not so surprising that one of these subunits can promote cell death? (2 pts). 14 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 4 (Dr. Ian Whitehead; 24 points total) 1. Briefly describe the difference between an oncogene and a tumor suppressor gene. Provide one example of each that is associated with a specific human malignancy (8 pts) 2. Although naturally occurring oncogenes that encode growth factors are rare, it is relatively easy to experimentally manipulate the expression of a growth factor such that it becomes oncogenic. Briefly describe how you would do this. (6 pts) 15 Evening Core Exam 5 May 7, 2008 Name ___________________________ Section 4 (Dr. Ian Whitehead; continued) 3. Mutations associated with tumor suppressors often impinge upon the Restriction Point in the mammalian cell cycle. Provide an example of a tumor suppressor gene whose product regulates the Restriction Point. Describe the mechanism through which loss-of-function at this locus triggers deregulated proliferation. (10 pts) 16