thesis

The dauer larva is an alternate larval stage which allows the nematode C. elegans to survive environmestress during development. Dauer formation requires autophagy, a cellular process responsible for degrading and recycling cytoplasmic components. I investigated the role of a spinster orthiolog, C13C4.5, by examining the effects of C13C4.5 loss-of-function and by generating a transgenic strain which expressed a C13C4.5::GFP fusion protein. Under normal conditions C13C4.5::GFP is expressed diffusely in the intestine, but under autophagy-promoting conditions the expression pattern becomes more punctate. This is consistent with localization of C13C4.5 to autophagolysomoes during autophagy, as has been shown for spinster in D. melanogaster. Loss of C13C4.5 function in a dauer-constitutive mutant resulted in a reduction in the proportion of animals entering into the dauer stage. Together these data suggest that C13C4.5 is involved in dauer formation and the autophagy pathway.

The Supreme Court's Ruling in DeShaney v. Winnebago County Department of Social Services (1989) eld that "A State's failure to protect an individual against private violence simply does not constitute a violation of the Due Process Clause." (489 U.S. 189 at 197). A state child protection agency's failure to prevent near-fatal abuse of a four year old child under its supervision was not considered a violation of the child's fourteenth amendment rights. This thesis critcally examines the reasoning behind the majority decision in DeShaney ; and using feminist legal theory, discusses ways to effectively address state policy and liability when private violence is used on vulnerable citizens, challenging the arbitrary dichotomy between the public and private spheres.

DNA methylation, the addition of a methyl group to the 5' position of DNA cytosines (5mC), is generally associated with transcriptional repression during early embryo formation ; however, in the adult brain, it is dynamically regulated and plays an important role in the formation and maintenance of memory. Very recently, it has been hypothesized that DNA hydroxymethylation, the addition of a hydroxyl group to methylated cytosines (5mC), serves as an intermediate in the DNA demethylation pathway. GIven its recent discovery, the role of DNA hydroxymethylation in memory has not yet been explored. In this study, we developed an immunofluorescent triple labeling protocol in order to begin examining the involvement of 5mC and 5hmC in neurons activated by consolidation of a contextual memory associated with methamphetamine in the brain's reward center, the nucleus accumbens.

Is beauty really in the eye of the beholder? Historically, philosophers, poets, artists, and scientists have striven to define and express one of the most complex words in the English language : beauty. In contemporary society we tend to casually ascribe the word beauty to many various objects,paintings, sounds, and ideas. Its meaning can adhere to a stone, to the oscillating waves of an ocean, to the nonorganic as to the organic. Perceptions of Beauty is a project the follows my journey as an artist and how my perception of beauty has changed over the past four years. Using examples from select artists, philosophers, and scientific studies, I will contend that Beauty is not "in the eye of the beholder," but is a complex and formulated characteristic that inspires not only an emotional response, but evokes mechanisms that defy our understanding of ourselves.

Caloric restriction (CR), the reduction of nutrient intake short of malnutrition, extends the lifespan of various organisms and can improve measures of human health. Whether mechanisms of lifespan extension are conserved between humans and model organisms is unknown. In mammals, implementing CR is easily achieved by providing a restricted group with a fraction of the food consumed by an "ad libitum" fed group, which has unlimited food access. Due to the difficulty in directly controlling Drosophila food intake, caloric restriction, performed similarly to the mammalian paradigm, has never been tested in flies. Here, we demonstrate a system that allows measurement of food intake throughout life. This system will be used to measure fly lifespan under caloric restriction analogous to current mammalian studies. Our work will help tease apart the differences between the various caloric and dietary restriction paradigms in Drosophila, strengthening our understanding of how fly models relate to mammalian systems.

Alzheimer's disease (AD) is an increasingly common neurological disorder that mainly affects memory formation and retention. It is characterized by unique intercellular neurofibrillary tangles and extracellular beta-amyloid plaques. Histone deacetylase inhibitors (HDACi's) are competitive antagonists against histone deacetylases, causing histone acetyltransferases to acetylate the genome unregulated. This thesis investigates the use of new histone deacetylase inhibitors on recovering memory in a mouse model of Alzheimer's disease. By use of a fear conditioning paradigm, we have shown that these HDACI's increase memory in AD mice, but show either no effect or a positive effect in wild-type mice. Future experiments will investigate the efficacy of compound 966 and the spine density of hippocampal brain slices after fear conditioning trials.

HIV-1 is the human immunodeficiency virus that can lead to acquired immune deficiency syndrome, or AIDS. Multiple cellular proteins have been identified as playing a critical role in all steps of HIV-1 replication. The heterogeneous nuclear ribonuclear protein U, or hnRNPU is a RNA and DNA binding protein known to influence pre-mRNA processsing, transport to the cytoplasm, intracellular localization, translation and turnover of mRNAs. Recently, the expression of N86-hnRNPU, an N-terminal fragment of hnRNPU, was found to inhibit HIV-1 mRNA export (6). This study primarily aims at identifying proteins that associate with the fragment (N86-hnRNPU) also called H1, and secondarily aims to exclude the possibility that N86-hnRNPU transcripts act as microRNAs.

Aging is a process characterized by accumulated oxidative damage to DNA, proteins, and lipids,which leads to the gradual degeneration of cellular activity. Mitochondria play a central role in aging because they produce both cellular energy and oxidative stress. As resultof accumulated oxidative damage, mitochondria function decays, which leads to a cellular energy deficit and compromises cellular function. Iron is an essential nutrient reequired by mitodhondria to function optimally. It has been proved that iron supplementation increases the lifespan of several yeast strains, including superoxide dismutase mutants. We are interested in finding where the iron is going and what it might be doing that is beneficial to the cell. We have used Saccharomyces cerevisiae as our molecular model of aging. Our results indicate that the extra iron is being transported into the mitochoindria.

Hosting an Olympic Games has a major impact on the city and its people. I compared the Barcelona 1992 and Athens 2004 approaches to "legacy," the lasting impacts of a Games. I grouped my comparison into three categories : Economic, Urban and Environmental Impacts, and Global and Social Identity. In Olympic circles, few cities live up to the long-term planning standard set by Barcelona, especially in urban regeneration. However, most scholars agree that Athens did not plan for the post-Games period as effectively as they could have. Barcelona had better organization and cooperation, while the Athens organizers and the government disagreed on various issues. Though Athens wanted to leave a positive legacy and did in many ways, they were not as focused on that aspect. Athens shined in the concept of "heritage," which encompasses bringing the past into the present as a "legacy." Because of their h istory, they were able to bring historical meaning to their Games.

This experiment tested 3 to 5-year-old children's (n=18) abilities to learn a novel verb in the context of one or two novel objects. We showed the children claymation videos of novel creatures performing two novel actions. They were then tested on whether they could correctly identify the action that a creature was performing in the form of a 'yes' or 'no' response. Children in the blocked condition, who learned the verbs in the context of one creature, responded correctly more often (p=.01) than children in the grouped condition, who learned the verbs in the context of two creatures. Results were similar when tested again one week later. These findings suggest that when teaching young children verbs, it may be more effective to first teach in the context of one object so that the children have a more confident understanding of the verb meaning.