Cell Adhesion Molecules in Olfactory Connection Formation

Cell Adhesion Molecules in Olfactory Connection Formation This dissertation study investigated expression, function and the regulatory mechanism of cell adhesion molecules in the formation of olfactory connections. Identification and characterization of a novel protocadherin, Pcdh20, provided additional evidence that multiple cell adhesion molecules are involved in the development of the olfactory system. In combination with several established studies by Sakano and Yoshihara’s group, my study further supports the neural identity model and provides a regulatory mechanism involving MeCP2 in the establishment and maintenance of this combinatory cell adhesion molecule expression in the olfactory sensory neurons. OR identity in correlation with cell adhesion molecule expression Though many cell adhesion molecule expression patterns were described, few of them were correlated with specific ORs. On the other side of the coin, it is also unknown whether a specific OR is correlated with a specific set of cell adhesion molecules throughout development. In adult mice, Pcdh20 expression is in a subpopulation of OSNs and their axons terminate in a small number of discrete Pcdh20-positive glomeruli in the OB. Interestingly, the distribution and numbers of Pcdh20-positive glomeruli are markedly different across gender. More Pcdh20-positive glomeruli with a wider distribution pattern are observed in the male OB, whereas fewer glomeruli with more restricted clustering of Pcdh20-positive glomeruli are found in female OB. The sexually dimorphic expression of Pcdh20 suggests that there may be different ORs associated with Pcdh20 in different sexes. 103 If Pcdh20 expression is correlated with specific OR expression, identification of Pcdh20 associated ORs could reveal possible sex-specific OR expression and aid in further investigation of OR-specific ligand function. In previous studies, cDNA libraries from a single OSN were obtained. OR expression in a single OSN can be identified by PCR using degenerate primers (Dulac and Axel, 1995). In collaboration with Dr. T. Cutforth from Stanford University, I have initiated this study by isolating single OSNs by dissociation of OE and attempting to identify Pcdh20 expressing cells by PCR. Several attempts were made to confirm OR expression using degenerate primers designed by L. Buck (Buck and Axel, 1989). Though I will not be able to complete this study during my dissertation research, identification of Pcdh20 associated ORs will provide important insight into not only OR and CAM association but also understanding of differential OR gene expression in different sexes and whether or not the main OB is related to pheromone recognition. Neuronal activity and regulation of cell adhesion molecule expression Neuronal activity results in long term changes in neurons by regulating gene expression. OSNs constantly respond to external stimuli throughout the life of the animal. Using genetic models and surgical manipulations, it is shown that blocking odorant evoked activity alters the expression of selected cell adhesion molecules. Even though regulation of cell adhesion molecule expression is important for the formation of olfactory axonal converge into glomeruli, the regulatory mechanism of gene expression is undetermined. I reported here that olfactory axon convergence is disrupted in MeCP2 null mice. Furthermore, I also obtained evidence that MeCP2 directly regulated Kirrel 2/3 expression. In MeCP2 KO mice, significant increases in Kirrel2/3 gene transcripts were observed in OE, suggesting that MeCP2 is a transcription suppressor for Kirrel 2/3 gene expression. In addition, my data provide evidence that MeCP2 function is regulated by neuronal activity. With the presence of odorant evoked 104 activity, MeCP2 is phosphorylated at Serine80 and also possesses enhanced binding affinity to promoters of Kirrel2 and Kirrel3 genes. Though MeCP2 increased its binding to promoters of both Kirrel2 and Kirrel3, transcript level changes are markedly different between Kirrel2 and Kirrel3 under odorant stimulation. Other transcription factors were shown to be regulated by neuronal activity. It is likely that both Kirrel2 and Kirrel3 are regulated under multiple neural activity dependent transcription factors. We propose a model in which a balanced transcriptional regulation from both repressors (like MeCP2) and enhancers (like CREB, MEF) determines the expression levels of Kirrel2 and Kirrel3. When both repressor and enhancer are under neural activity regulation, how the balance tilts will determine whether Kirrel2/3 expression will be up- or down-regulated in OSNs. In this study, the olfactory system serves as an excellent model system to study gene regulation of MeCP2 by neuronal activity at physiological levels. Previously, the mechanism of MeCP2 on gene expression regulation by neuronal activity was only studied in vitro. The brain is composed of heterogeneous cells and their neuronal circuits are extremely complex. In contrast, the OE is composed of a single type of neuron. This property provides an opportunity to study neuronal subtype specific MeCP2 function. In addition, the olfactory system provides an excellent system to study the effect of neuronal activity due to it accessibility. Odorant stimulation can be given to the OSNs in the nasal cavity to allow investigation of gene regulation under physiological level of stimulation. To further investigate the model we proposed, it is important to elucidate the full spectrum of MeCP2 target gene regulation. Future study should be done to screen MeCP2 target binding through ChIP-Chip analysi s. MeCP2 binding sequence will provide information in the target genes they regulate in the OSNs. To further provide or block odorant evoked activity, changes in MeCP2 binding will allow us to identify target genes that are activity dependent. Furthermore, identification of odorant evoked activity dependent transcription enhancers in OSNs will allow further  validation of the regulatory model we proposed here. Understanding neural activity dependent MeCP2 function is critical in elucidating the mechanisms of Rett Syndrome. Though rapid progress has been made in the identification of MeCP2 targeting genes, we still do not understand how changes in gene expression result in neuronal structural and functional changes. Rett Syndrome is exacerbated during the early postnatal period. Neural activity plays a critical role in this process. Understanding the relationship between physiological levels of neuronal activity and MeCP2 regulation is the obvious next challenge. The olfactory system provides an excellent model for the easy manipulation of activity stimulation and examination of subtle axonal targeting defects. This study established that cell adhesion molecules are regulated by MeCP2 in an activity dependent manner. Further genomic analysis will provide a comprehensive understanding of MeCP2 regulation of gene expression and could help in the development of treatment strategies for Rett Sy ndrome.

The Case: No Dogs Allowed Essay

1. What economic questions does this case require the townb to ask? What is a dog park and how does it benefit the community? Can people or dogs get hurt at a dog park? How will dogs fight be avoided? If a dog park is built, will there be space available for an affordable recreation facility? 2. List the possible resources that the town would need to construct and maintain the park? Some possible resources that are needed to construct and manitain the dog park are: Secured fences to prevent loose dogs outside of the park area Trash cans and garbage removal material and equipment needed to clear the lan grass and lawn maintenance Fresh drinking water and field drainage system Lighting and benches for dog owners Pooper scooper stations Staff to construct and maintain the park 3. What town resources are scare? Limited public space and open space is dwindling in the town. 4. Who will be the consumers using this public good? The consumers this good would be the people who are the owners of dogs. 5. What is the opportunity cost of building this park? A. In terms of economics, opportunity cost is the value of the next-highest valued alternative use of that resource. In this case, the opportunity cost would be the offer of 850,000 dollars to purchase the land and build 40 new luxury homes. B. Identify at least one pro and one con for each of the following options. 1. Leaving the land undeveloped A pro in leaving the land undeveloped is saving the town resources and a con would be a waste of space that could be used for something to benefit the community. 2. Selling the land to real estate developers to build homes. A pro in selling the land to real estate developers would save the town’s resources and money to do other things within the coommunity. A con selling the land when it could be used for a dog park or a recreation facility, things that the community are asking for. 6. What if any, market failures might exist in this town? A market failure that could exist is the absence of private property rights, since the dog park would be directly behind a townhouse community, noise levels of barking dogs and fight risk could potentially disturb the neighborhood. 7. Create a chart that identifies the positive and negative externalities of building the park. Explain the effect of each externatality. 8. How could the town government counteract the negative externatalities? The town government can counteract the negative eternalities by ensuring that the dog park is securely fenced in with a double gated entry exit system so that the townhouse development would not have the cost in putting a fence around their development. The The town government can assess other available space for recreation since the town is growing. Dog owners will need to take responsibility for the full cost of the noise that their barking dogs create. The town government can make it illegal to disturb the peace by creating disturbing the peace laws. 9. Based on your studies of Unit 1, write a persuasive argument for or against the construction of the dog park. Should a dog park be constructed in Martinsville? Martinsville is a rapidly growing town, and statistics show that there are 7,000 licensed dogs in the town. Families who own dogs complain that there are no resources in the town for families with pets, and that since the recent creation of new apartments, condos, townhouses, and retail spaces that land space is scarce  and there is little to no land of their own for outdoor recreation. Developers want to purchase the land for $850, 000 to build 40 new luxury townhouses. After considering both sides of the issue, I strongly believe that a dog park should be constructed. The town of Martinsville has already added many new multi-family housing and these dwelling have very limited outdoor space. A national pet store chain is willing to give a grant to the town to partially fund the park and with the town’s budget surplus the cost of construction of the park will be covered, but a developer wishes to purchase the land to add more townhouses. The opprtunity cost will benefit the town in keeping them from using any of their resources, but the trade-off in this would be adding too many families yet again with limited space of their own, and some of these new families will have pets. Then, even more families will be complaining about space scarcity, therefore I disagree in building 40 new luxury townhouses on this particular land. All of the public spaces are not completely gone and developers can research other options. Families with pets have no outdoor space for their pets to play or exercise. There is only one local park in the area where no pets are allowed. A dog park can be a great addition to almost any community. First, it provides dogs with a chance to excercise and socialize with other dogs. Dogs like to be free, and they like to run and play instead of being chained down. Secondly, it provides dog owners with a chance to do things with their pets that they can’t do because of limited space. Lastly, having a dog park will prove that the town is family friendly, attracting more families to the town, and for all of the reasons, a dog park should be constructed in the town of Martinsville.

The Nuiances of Social Justice Topics for Essay

The Nuiances of Social Justice Topics for Essay The Hidden Truth on Social Justice Topics for Essay Schools do their very best to prevent students from getting bullied, but it isn't enough. Students lead busy lives and frequently forget about an approaching deadline. Know that not all students feel exactly the same way about those difficulties. Even young students may use photography and video for social shift. The Bad Secret of Social Justice Topics for Essay This collection doesn't consist of explicit teachings in any type of civics or grassroots activism, but nevertheless, it will provide students with a deep comprehension of lives completely unlike their own. Basically, possession of the 2 morals which include a feeling of justice and conception of good, constitute freedom. Frequently, the wealthy influence country laws that do function to safeguard their interest, rarely addressing the requirements of the poor. The aim of this assignment is to learn more about the significance of justice. Ethnocentrism is a system which elevates one particular culture above another, judging different groups as inferior depending on the standards and values of a person's own culture. Students who respected the social justice mission proved much more inclined to state they intended to work for social justice later on and felt they possessed the skills to effect positive shift. Social Justice Topics for Essay: No Longer a Mystery You want to reveal the readers that you master of this issue and not a confused newbie who doesn't understand what he or she's discussing. Some teens are so involved in the digital world of internet gaming and media they don't really look closely at things and issues around them. The multiple topics could be found, for instance, in the diss ertation abstracts international database. It is possible to view an assortment of trailers for student-created documentaries here. When you get a task to compose an essay on a social issue, you're given a chance to open an exciting discourse. It takes a couple minutes to put your purchase, and you will get an original and authentic essay about the hottest topics. There are a few critical things you want to understand as a way to write up an exemplary essay. When prior brainstorming is finished, you can begin drafting your essay. With a little bit of zeal and hard work, you are certain to develop an impressive unlawful justice essay. Don't be worried about the originality. Wait around for expert feedback to enhance the standard of your writing. Getting the Best Social Justice Topics for Essay The school to prison pipeline is a true thing. Help your son or daughter analyze the positive and negative points of each possibility and select the 1 problem he would like to work on most. The very first step is to assist your son or daughter choose something which he is good at and enjoys doing. Often the toughest part of getting your kid to become involved in a social justice project is knowing where to start. General information Students that are new to the topic of social studies must be ready for in-depth education at their initial lessons. Inexpensive Labor Debate research papers explore either side of the low-cost labor debate. Teachers might take a topic from the current curriculum and offer several choices for projects. Find out more about Public Interest Tech. When you compose a social issue essay, it is very important to clearly show your private view of the issue. You could possibly be given the topic straight away by your professor, or you can be free to select the topic yourself. Sociology is, undoubtedly, a fascinating subject, particularly if you're fortunate enough to find a progressive-thinking professor. To start with, your essay is supposed to tackle a particular social, psychological or anthropological matter. Top Choices of Social Justice Topics for Essay There's well-known that you aren't going to have the ability to write a very good insightful research paper if you're not interested in the subject overall and in the subject specifically. It's also wise to know that any prudent writer won't ever supply you with a comprehensive sample term paper. It's also important that you know the source of these term papers. You are going to have brief feel of the expression paper, which will act as an inducement for you to buy the entire term paper. There's also lots of information on the best way to compose an essay and how to prevent the most typical mistakes, but should you need assistance, you can refer to this video. This advice might seem dull if you're working on historical paper. These topics are designed to help students identify some helpful sources. They will be useful for people who want to write essays about the subject mentioned above in the form of a regular job.

Powers of the United States Congress as Established by the...

The United States Congress was established by the Constitution to be the legislature branch of the Government as distinguished from the executive branch which is headed by the President and the judiciary. The system is organized in order for each of the branches to act as a check and balance on each of the other branches (Moyers, 1987). This check and balance nature of the system often results in creating friction between the branches but this was precisely the purpose behind the Founding Fathers setting the system up in this manner. The theory was that this would diminish the possibility of any one branch becoming too powerful in relation to the other branches. Congress, like the other two branches of the U.S. government, is limited to exercising only the powers specifically granted the Constitution. The powers granted Congress are enumerated in several different locations in the Constitution but the majority of its powers are set forth in Article I. The first of Congress enumerated powers is its authority to regulate commerce among the several states. Since first being addressed by the U.S. Supreme Court in the landmark case of Gibbons v. Ogden (Gibbons v. Ogden, 1824) the power of Congress to engage itself in the operation of interstate commerce has been expanded, over time, to the point where Congress power to regulate commerce now includes any activities that substantially affects interstate commerce. One of Congress most significant powers is the authorityShow MoreRelatedThe Articles Of Confederation And The Constitution1115 Words   |  5 PagesThe Articles of Confederation were the earliest constitution of the United States. After the United States became fully independent from Great Britain, following the Revolutionary War, the document was created to outline the functions and management of new nation. However, the document established a very weak central government, instead giving the power to the states. 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