BIOLOGY 101 –

AP Biology. I would be so grateful if someone could complete this. It does not have to be A+ material, just try to answer the questions short and to the point. No to lengthy answers are necessary. I will give a good tip and refer to you for future Biology help 🙂 Thanks! 1.Summarize the two articles, including background information as well as experimental results. Students should provide adequate summaries for these articles: http://cancerres.aacrjournals.org/content/64/20/7545.full http://genesdev.cshlp.org/content/16/21/2743.full2.Use the e-text, http://www.cancerquest.org, and other sources to answer the following question: What is cancer and what are some of the causes of cancer?3.Figure 2 in the Athar et al. (2004) article shows a line graph (A) depicting percent increase in number of tumors per mouse over the 52 weeks of the experiment. This line graph compares the tumors found in the mice given cyclopamine compared to those given plain water. It also includes a bar graph (C) that shows the average number of tumors per irradiated mouse with and without cyclopamine. Examine these graphs and then answer the following questions.a.Compare the overall percentage increase in tumors for control vs. experimental mice shown in the line graph.b.Using the Basal-cell carcinoma (BCC) bar graph as a reference, how effective was cyclopamine in treating BCC in the mice?4.The hedgehog gene family codes for signaling proteins. These proteins serve as ligands binding to receptors in nearby target cells, activating the hedgehog pathway. The hedgehog pathway in the target cells has two membrane proteins named Patched (Ptch) and Smoothened (Smo), as well as several intracellular proteins.When Shh (Sonic hedgehog) ligand binds to Ptch, it activates Smo. This causes the signal to be transduced, resulting in transcription and cell division. In the absence of the hedgehog signaling protein (Shh), Ptch inhibits Smo. This means no signal is sent to the intracellular components of the hedgehog pathway. Therefore, transcription and cell division do not occur. Smo and the subsequent intracellular pathway could also be turned on by mutations that inactivate Ptch.Based on what you’ve read, do you think that the hedgehog signaling pathway is a local or long-distance type of signaling? Explain your answer.5.Cyclopamine is a known antagonist of Smo. Describe how cyclopamine reduces the number of BCCs in UV-irradiated mice.6.Scientists have found that the hedgehog signaling pathway is active in embryos during the early development of the neural tube, motor neuron specification, left-right symmetry, body plan, limbs, and retinas.In the 1950s, sheep feeding on the corn lily (Veratrum species) in mountain pastures gave birth to a number of lambs with only one eye. These one-eyed lambs were explained when the compound, now known as cyclopamine, was discovered in the corn lily.Explain how a failure to have cell division occurs at a critical time during development could lead to lambs with one eye. Refer to Section 18.4 of your e-text to read about critical events in the development of left-right symmetry and body plan.7.The Nobel Prize-winning researchers Christiane Nüsslein-Volhard and Eric Wieschaus investigated fruit fly mutations to study the roles of genes active in the development of fly embryos. They mutated one gene, later named “hedgehog” because it resulted in dense spines in shortened fly larvae. Homologous hedgehog genes were later discovered in vertebrates. After these genes were sequenced in several different kinds of animals, they were compared and used to determine the phylogenetic relatedness of various species. Refer to the phylogram in Figure 26.12 in your e-text (in Section 26.3) to answer the following questions.a.Why do you think fruit flies, Drosophila, were used as the outgroup in this phylogram?b.What does the phylogram tell us about the hedgehog gene in mammals and birds as compared to the hedgehog gene in mammals and amphibians?c.How do phylograms and ultrametric trees confirm the relevance of research on flies or mice when studying something like the hedgehog pathway?8.Western blots and immunohistochemistry are scientific techniques that use the highly specific binding of antibodies with target molecules to act as molecular probes in cells and tissues.a.Explain how an antibody is able to recognize a specific antigen. (Include an explanation of an epitope in your answer.)b.Antibodies can be used to find, bind, and tag specific molecules of interest. Antibodies are Y-shaped molecules, with the tips of the Y containing unique amino acid sequences that bind the antigen. These variable portions of antibody molecules convey the high specificity for a target molecule. The large tail or base of the Y is much less variable. In fact, all antibodies within a species have tail regions that are very similar in sequence and shape. By inserting compounds that fluoresce, meaning they produce radiation or produce a color change in the tail region of these molecules, researchers can use antibodies as marker molecules.Researchers often use two different antibodies: a primary antibody for targeting the molecule of interest and a secondary antibody with active sites to bind the primary antibody’s tail and act as a marker. Western blots are used to detect the presence of a known protein in a given sample. The proteins are first separated by molecular weight using gel electrophoresis. Next, the proteins are transferred from the gel to a nitrocellose membrane in a process called blotting. The nitrocellulose membrane is then incubated with a primary antibody that combines with the protein of interest. Then an enzyme coupled with a secondary antibody is used to produce a detectable color change when the protein of interest is present. The intensity of the color change indicates the quantity of the protein.Immunohistochemistry uses antibodies to detect the presence of specific molecules, usually proteins, within tissues and cells. Thin sections of a biological sample are fixed to a glass slide, incubated with primary and secondary antibodies, and examined microscopically. Secondary antibodies used in immunohistochemistry are frequently fluorescent, in which case a fluorescent microscope is used to read the results.Briefly describe what you can learn about a target protein by using these two techniques.c.In 1996, it was discovered that a mutation in the Patched gene in the hedgehog pathway wasinvolved in almost all cases of basal cell nevus syndrome, a rare hereditary syndrome of birth defects and multiple BCC starting early in life. This autosomal recessive mutation was identified in families affected by the syndrome. The Patched mutation resulted in a nonfunctional Patched protein.Refer to the description in question #4 and explain what happens when the Patched protein is nonfunctional. Then explain how a nonfunctioning Patched protein could lead to cancer.9.Soon after the above discoveries, researchers began looking at inhibitors that might serve as chemotherapy for this common cancer. Cyclopamine, the plant teratogen known to interfere with the hedgehog signaling pathway in early development, showed potential as a cancer treatment.The exact mechanism by which cyclopamine inhibits hedgehog pathway signaling is still unknown. One hypothesis is that cyclopamine prevents the secretion of Shh from Shh-producing cells. In this case, the protein is expressed but without its normal cholesterol addition. As a result, Shh cannot leave the cell to act as a signaling protein.If you were asked to test this hypothesis, which technique do you think would be more useful: Western blots or immunohistochemistry? Explain your choice.li>Explore a known hedgehog pathway antagonist other than cyclopamine, such as Vismodegib (GDC-0449) or LY2940680. For the chosen antagonist, provide detailed descriptions for each of the following:Describe the antagonist, giving some background information.How does this antagonist disrupt the pathway?Does the antagonist have potential as a chemotherapeutic drug?