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Mitochondrial Morphology, Oxidative Stress Resistance, And Pathogenesis In Cryptococcus Neoformans, Andrew Lee Chang
Mitochondrial Morphology, Oxidative Stress Resistance, And Pathogenesis In Cryptococcus Neoformans, Andrew Lee Chang
Arts & Sciences Electronic Theses and Dissertations
Cryptococcus neoformans is an important pathogen that annually kills 200,000 people worldwide. It survives in the environment as a yeast or spore and can also proliferate within host macrophages after being inhaled into the lungs. In conditions of immunocompromise, cryptococcal cells can escape from the lungs to the brain, where they cause a deadly meningoencephalitis that is both difficult and expensive to treat. Cryptococcal adaptation to the harsh lung environment is a critical first step in its pathogenesis, and consequently a compelling topic of study. This adaptation is mediated by a complex transcriptional program that integrates cellular responses to environmental …
The Role Of Mitofusins In The Osteoclast Lineage, Anna Ballard
The Role Of Mitofusins In The Osteoclast Lineage, Anna Ballard
Arts & Sciences Electronic Theses and Dissertations
Mitochondria exist in a highly dynamic network in many cell types, and mutations in mitochondrial transmembrane GTPase mitofusin2 (MFN2), a key factor that mediates mitochondrial tethering, cause defects in the nervous system. Intriguingly, the skeleton has been overlooked in patients with such mutations. Because expression of MFN2 and its homolog, mitofusin1 (MFN1) increase with maturation of osteoclasts (OCs), which are rich in mitochondria, we sought to determine the role of mitofusins in the OC lineage. Double knockout of Mfn1 and Mfn2 in OC precursors by Lysozyme-M cre reveals that mitofusin activity is required for OC function and maintenance of bone …
Genetic Basis Of Thermal Divergence In Saccharomyces Species, Xueying C. Li
Genetic Basis Of Thermal Divergence In Saccharomyces Species, Xueying C. Li
Arts & Sciences Electronic Theses and Dissertations
The genetic architecture of phenotypic divergence is a central question in evolutionary biology. Genetic architecture is impacted by whether evolution occurs through accumulation of many small-effect or a few large-effect changes, the relative contribution of coding and cis-regulatory changes, and the prevalence of epistatic effects. Our empirical understanding of the genetic basis of evolutionary change remains incomplete, largely because reproductive barriers limit genetic analysis to those phenotypes that distinguish closely related species. In this dissertation, I use hybrid genetic analysis to examine the basis of thermal divergence between two post-zygotically isolated species, Saccharomyces cerevisiae and S. uvarum. S. cerevisiae is …
Functional And Skeletal Muscle Impairments In Progressive Diabetic Ckd, Daniel Bittel
Functional And Skeletal Muscle Impairments In Progressive Diabetic Ckd, Daniel Bittel
Arts & Sciences Electronic Theses and Dissertations
1-in-3 persons with type 2 diabetes (T2DM) develop chronic kidney disease (CKD), which is characterized by progressive renal dysfunction leading to end-stage renal disease. In response to elevated blood glucose and systemic inflammation of diabetes, a process of active thickening of the renal glomerular basement membrane ensues with concomitant damage to the structural supports (podocytes) of the kidneyճ filtration barrier. This results in impaired renal filtration. The metabolic sequelea of T2DM and CKD also, synergistically, alter skeletal muscleճ degradative pathways, satellite cell function (muscle reparative cells), and mitochondrial health (muscle energetic machinery) -- resulting in muscle breakdown, poor muscle quality, …
Mitochondrial Damage Accumulation In Oocytes – A Potential Link Between Maternal Obesity And Increased Cardiometabolic Disease Risk In Offspring., Anna Louise Boudoures
Mitochondrial Damage Accumulation In Oocytes – A Potential Link Between Maternal Obesity And Increased Cardiometabolic Disease Risk In Offspring., Anna Louise Boudoures
Arts & Sciences Electronic Theses and Dissertations
The developmental origins of health and disease (DoHAD) hypothesis suggests that negative maternal lifestyle choices, such as obesity, affect the health of her offspring. Clinical and laboratory studies support this hypothesis – offspring born to obese mothers are at increased risk for health conditions including cardiometabolic syndrome and congenital abnormalities. Maternal obesity damages the oocytes, contributing to the increased disease risk by transmitting damaged organelles and epigenetic modifications to the offspring. Mitochondria, the most abundant organelle in the oocyte, are damaged in oocytes from obese females. However, we do not understand if mitochondrial damage in oocytes is reversible nor why …
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Arts & Sciences Electronic Theses and Dissertations
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …
Evolution Of Ecological Dominance Of Yeast Species In High-Sugar Environments, Kathryn Marie Williams
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 …