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An Essential Role For Self-Pmhc Throughout The Life Of A Cd4 T Cell: Contributions In The Thymus And Periphery, Stephanie Rodriguez

Arts & Sciences Electronic Theses and Dissertations

It is well established that self-peptide Major Histocompatibility Complexes (hereafter self-pMHC) are essential for the development of a broad repertoire of mature, self-tolerant CD4 and CD8 T cells. Despite clear knowledge that the pool of self-ligands is critical for positive and negative selection, the exact kinetics and dynamic nature of thymocyte interaction with self-pMHC class II (self-pMHCII) bearing antigen-presenting cells (APCs) during development is still largely a mystery. The enigmatic nature of selecting self-pMHC is not unique to the thymic environment; increasingly evident is the dependence of peripheral T cells on extra-thymic self-pMHC expression, specifically selecting self-pMHC, for their homeostatic …

Evolution Of Ecological Dominance Of Yeast Species In High-Sugar Environments, Kathryn Marie Williams

Arts & Sciences Electronic Theses and Dissertations

Two challenging goals of evolutionary biology are to understand how evolutionary innovations evolve and how they contribute to the success of lineages. Evolutionary innovations may arise following whole genome duplication (WGD) events and they are suspected to contribute to the success of lineages by creating ecological opportunity. However, direct evidence for duplicated genes involved in evolutionary innovations remains rare, and the relationship between evolutionary innovations and the success of lineages may be very complex. In this study, I explore the relationship of evolutionary innovation, WGD, and the ecological dominance of yeast species in high-sugar environments. In budding yeast, a major …

Origin Of Maternal Age Effect In Congenital Heart Disease Risk For Offspring, Claire Elaine Schulkey

Arts & Sciences Electronic Theses and Dissertations

Increasing maternal age is widely acknowledged to lead to greater likelihood of pregnancy complications and congenital abnormalities, but the basis of this effect has not been well studied. Often dismissed as the product of oocyte ageing, the mechanistic basis of this maternal age effect is likely more complex.

Congenital heart disease is a classic complex disease with multiple genetic and environmental modifiers, including maternal age. Maternal ageing is a known risk-factor in humans, and has been shown to exist in an Nkx2-5 haploinsufficient mouse model for the disease. This mouse model's maternal age risk is dependent upon strain background, with …

Characterizing The Fitness Landscapes Of Gut Symbionts In Defined Community And Diet Contexts, Meng Wu

Arts & Sciences Electronic Theses and Dissertations

A species' niche is the description of all the environmental conditions required to permit a population of that species to persist, including the effects of the population on those conditions. This definition includes the species' resource requirements, as well as stress tolerances and interactions with other species acting as competitors, predators, parasites, and mutualists. The human gut microbiota serves as a microbial `metabolic organ' tasked in part with the biotransformation of many components of our diet. Relatively little is known about the factors that allow members of the human gut microbiota to persist in a habitat that experiences marked changes …

The Influence Of Metacommunity Size On Species Diversity Across Spatial Scales, Lauren Woods

Arts & Sciences Electronic Theses and Dissertations

This dissertation explores the influence of metacommunity size and landscape level processes, such as dispersal, on species diversity. A metacommunity is a group of local communities, or patches, connected by dispersal, and metacommunity size can be defined as the number of discrete local patches within a metacommunity. In chapter 1, I developed a framework to predict the effects of habitat destruction, or a reduction in metacommunity size, on the species richness of local patches of different sizes by integrating metacommunity theory with the equilibrium theory of island biogeography. The effect of metacommunity size on species richness in small and large …

Modulation Of Nmda Receptor Activity During Physiological And Pathophysiological Events, Christine Marie Emnett

Arts & Sciences Electronic Theses and Dissertations

N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that serve crucial signaling and neurotrophic functions throughout the central nervous system. Both hyperfunction and hypofunction of NMDARs are associated with neurological and neuropsychiatric conditions. Thus, both positive and negative pharmacological NMDAR modulators are of clinical interest as treatments. Understanding drug mechanisms could lead to more rational drug design. Memantine and ketamine are NMDAR open channel blockers that exhibit similar pharmacodynamics at NMDARs but have different clinical uses. Memantine improves cognitive decline during Alzheimer's disease. Ketamine is an anesthetic and analgesic with psychotomimetic effects, but it is also a rapid acting and long-lived …