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Characterizing Stress Granule Regulation By Pas Kinase, Ataxin-2 And Ptc6 And Investigating The Lifespan Of Covid-19 Virus On Currency, Colleen R. Newey

Theses and Dissertations

The protein Ataxin-2 is a known positive regulator of stress granules in humans, mice and yeast (known as yeast PBP1). Due to the role that stress granules play in diseases including Amyotrophic Lateral Sclerosis (ALS) and cancer, this thesis investigates the role of Ataxin-2 and its protein binding partners in stress granule development and its effects on various metabolic phenotypes of the cell. PAS kinase is a sensory protein kinase, conserved from yeast to man, which regulates respiration and lipid biosynthesis. Our lab discovered that PAS kinase phosphorylates and activates Ataxin-2 in yeast, and that PAS kinase overexpression enhances localization …

Linking Microbial Community Assembly In Flowers With Function Under Diverse Environmental Conditions: A Case Study Involving Erwinia Amylovora, Christopher Skylar Mcdaniel

All Graduate Theses and Dissertations, Fall 2023 to Present

Fire blight, a devastating disease of pome fruit trees caused by the bacterium Erwinia amylovora, can cause millions of dollars in losses for producers each year around the globe. Management approaches that involve use of antibiotics, such as streptomycin, can be effective; although concerns exist over pollinator and crop health when using them regularly. Recently, there have been developments that allow for biological agents such as microbes to curtail fire blight infection. These agents work by competing with Erwinia for resources or space, producing antibacterial compounds, or even killing Erwinia cells on contact. Unfortunately, these agents do not yet …

The Effects Of Resistance Exercise Training On Insulin Resistance Development In Female Rodents With Type 1 Diabetes, Mitchell James Sammut

Electronic Thesis and Dissertation Repository

The etiology of insulin resistance (IR) development in type 1 diabetes mellitus (T1DM) remains unclear; however, impaired skeletal muscle metabolism may play a role. While IR development has been established in male T1DM rodents, female rodents have yet to be examined in this context. Resistance exercise training (RT) has been shown to improve IR and is associated with a lower risk of hypoglycemia onset in T1DM compared to aerobic exercise. Additionally, the molecular mechanisms mediating RT-induced improvements in insulin sensitivity remain unclear. Therefore, the purpose of this study was to investigate the effects of RT on IR development in female …

The Effects Of Ketones On Brain Metabolism And Cognition, Erin Reiko Saito

Theses and Dissertations

The brain is one of the most energetically demanding organs within the human body and is cognitively susceptible to energetic deficits such that the rise in obesity, insulin resistance, and Alzheimer’s disease in recent decades pose a substantial threat to cognitive longevity. The therapeutic efficacy of ketones are well-established in epilepsy and are currently being applied to other disease states. Alzheimer’s disease is characterized by impairments in brain glucose uptake and metabolism in regions relevant to learning, memory, and cognition that progress with the disease. While brain glucose uptake is impaired, ketone uptake is unaltered, potentially enabling ketones to fuel …

Gpr75 Deficiency Attenuates High Fat Diet-Driven Obesity And Glucose Intolerance, Sakib Hossain

NYMC Student Theses and Dissertations

Recently, a collaboration between Regeneron Pharmaceuticals and the Schwartzman-Garcia labs at New York Medical College published an exome sequencing study of individuals across the United Kingdom, United States, and Mexico which concluded that individuals possessing non-functioning, truncated mutations to the orphan g protein coupled receptor (GPCR), GPR75, had lower BMI and 54% reduced likelihood of obesity. The present study was undertaken to fully characterize the metabolic phenotype of Gpr75 deficient mice when fed a high fat diet (HFD) and explore potential mechanisms by which GPR75 activation links to increased adiposity and decreased glucose tolerance. After 14 weeks of HFD-feeding we …

Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie

Dissertations and Theses

Offspring of diabetic and obese mothers (ODOM) have greater risks of heart disease at birth and later in life. However, prevention is hindered because underlying mechanisms are poorly understood. Mounting studies in the Developmental Origins of Health and Disease field suggest that mitochondria play key roles in developmentally programmed heart disease similar to the roles they play in cardiomyopathy in adults with diabetes and obesity. However, whether mitochondria are responsible for the short[1]and long-term cardiac disease seen in ODOM remains unknown. Here, we sought to delineate the roles of mitochondria in the hearts of ODOM, determine whether mitochondria are playing …

Parental Effects On Offspring Reaction Norms: Consequences For Complex Phenotypes In Variable Environments, Alexandra G. Cones

Theses and Dissertations--Biology

Organismal traits all exhibit some degree of environmental sensitivity, and both the strength and direction of these phenotypically plastic responses to the environment can evolve in adaptive ways. For example, parents can use information about their own environment to precondition the traits of their offspring so that they thrive in their future environment. This transgenerational plasticity can also alter the plasticity of offspring, but explicit investigations of this specific phenomenon are rare. I begin with a review of the literature and provide a quantitative genetic framework to investigate this phenomenon, which I then explore empirically using avian embryos. The metabolic …

Rewired Metabolism In Apoe4 Microglia: Implications For Inflammation And Neurodegeneration, Nicholas A. Devanney

Theses and Dissertations--Physiology

Among the earliest changes to occur in Alzheimer’s disease, metabolic dysfunction and chronic neuroinflammation are now known to be major driving forces in disease progression. The paradigm of ‘immunometabolism’ seeks to bridge these two facets, positing that metabolic transformations are indispensable in determining the response of immune cells, such as microglia – the brain’s resident immune population. Proinflammatory stimulation of microglia leads to a shift away from mitochondrial respiration towards a dramatic upregulation of the glycolysis pathway for energy production. This glycolytic burst provides microglia with a rapid supply of ATP, but comes at a cost, as utilizing glucose to …

Multilevel Phenotypic Integration Of Metabolism And Behavior In House Sparrows And Mice, Tim Salzman

Theses and Dissertations--Biology

Patterns of multilevel variation in behavior, both within and among individuals, raise challenging questions about underlying mechanisms and the selective pressures acting on them. One intriguing hypothesis is that physiology shows parallel multilevel variation, and so might represent a latent trait that integrates multilevel behavioral responses. For example, foraging acquires the fuel needed to maintain metabolism, and in turn, an individual’s metabolism affects expression of foraging, and other, behaviors. Metabolism and behavior thus might coevolve to become integrated traits. Despite the appeal of this hypothesis, numerous investigations into the link between metabolism and behavior have yielded largely equivocal results.

To …

A Metagenomic Analysis Of The Microbial Communities Associated With Different Hydrothermal Vent Chimneys, Laura Murray

WWU Graduate School Collection

Hydrothermal vents host a diverse community of microorganisms that utilize chemical gradients from the venting fluid for their metabolisms. The venting fluid can solidify to form chimney structures that these microbes adhere to and colonize. These chimney structures are found throughout many different locations in the world’s oceans. In this study, comparative metagenomic analyses of microbial communities on five chimney structures from around the Pacific Ocean were elucidated focusing on the core taxa and genes that are characteristic for each of these hydrothermal vent chimneys, as well as highlighting differences among the taxa and genes found at each chimney due …

How Aquatic Insects Mitigate Temperature-Oxygen Challenges Via Behavioral, Morphological, And Physiological Plasticity, Jackson H. Birrell

Graduate Student Theses, Dissertations, & Professional Papers

How do organisms respond to environmental challenges and to environmental change? These questions occupy a central place in ecology and answering them will help us to understand why species live where they do, how organisms are affected by human activities, and, ultimately, how to choose among alternative conservation strategies. These questions are difficult, however, for two reasons. First, environmental challenges often involve multiple, interacting stressors. Second, individual responses can be modified by behavioral, morphological, and physiological plasticity. My dissertation investigates how interactions between temperature and oxygen influence the performance and survival of aquatic insects and how plasticity allows individuals to …

A Long‐Term Obesogenic High‐Fat Diet In Mice Partially Dampens The Anti‐Frailty Benefts Of Late‐Life Intermittent Fasting, Yoko Henderson, Nazmin Bithi, Jie Yang, Christopher Link, Aili Zhang, Benjamin Baron, Eran Maina, Christopher Hine

Senior Honors Projects

The global obesity pandemic coupled with ever-growing life expectancies equates to hundreds of millions of individuals with potentially longer but not healthier lives. Aging is one of the risk factors for numerous maladies such as metabolic dis- order and frailty, which are exacerbated under obesity. Thus, therapeutic approaches that address obesity to ultimately improve afected individuals’ quality of life and extend their lifespan are needed. We previously reported that the every other day (EOD) fasting initiated late-life improved metabolic, musculoskeletal, and cognitive endpoints in standard rodent diet-fed mice. In the present study, using the same dietary intervention methodology, we tested …

Specialized Metabolism In Retina, Retinal Pigmented Epithelium, And Testis, Siyan Zhu

Graduate Theses, Dissertations, and Problem Reports

The retina and its neighboring retinal pigmented epithelium (RPE) are high energy-demanding and metabolically active tissues with specialized and complementary metabolism. They are metabolically interdependent and impact each other’s viability. Interestingly, many of the metabolic features in the retina and RPE are shared with the testis. For example, testis is also energy costly due to continuous sperm differentiation and it has similar metabolic inter-dependence between different testis cells. Both the retina and testis are vulnerable to mitochondrial metabolic impairments.

We conducted three research projects to understand 1) the nutrient utilization and communication in retina and RPE; 2) The profiling of …

Investigating The Relationship Between Metabolic Reprogramming And Peripheral Cd4+ T-Cell Inflammation In Human Type 2 Diabetes Pathogenesis, Gabriella Kalantar

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Chronic, low-grade systemic inflammation rises in obesity and promotes type 2 diabetes (T2D). Circulating immune cells are key indicators of obesity and T2D pathogenesis. T cells outnumber monocytes, in blood, suggesting that T cells might fuel peripheral inflammation in obesity/T2D. Our lab’s work supports this idea by identification of a Th17 cytokine profile in T2D from T-cell stimulated peripheral blood mononuclear cells. Work described herein further supported this work by demonstrating that T cells dominate peripheral inflammation over monocytes across the spectrum of obesity and glycemic control. Our lab has also recently shown that inflammation changes during prediabetes (preT2D), identified …

The Effects Of Sex On Zebrafish Bone Metabolism, Simon Bagatto

Williams Honors College, Honors Research Projects

I investigated the effects of diet and sex on zebrafish bone metabolism. Zebrafish were subjected to either a high-calorie or low-calorie diet over a five-week period. After this diet, zebrafish scales were used to measure alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) enzyme activity with a fluorescent substrate. The enzyme activities were markers of the osteoblasts (ALP) and the osteoclasts (TRAP). These data were compared among sex and diet of the zebrafish using a repeated measures ANOVA statistical test. I also measured the number of resorption lacunae per scale (another indicator of osteoclast activity). The results showed higher TRAP …

Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam

Dissertations & Theses (Open Access)

ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

Regulation Of T Cell Activation By The Cd5 Co-Receptor And Altered Peptides, Characterization Of Thymidine Kinase-Specific Antibodies, And Integrating Genomics Education In Society, Kiara Vaden Whitley

Theses and Dissertations

Helper T cells (Th) are a vital component of the immune system responsible for directing other immune cells to eliminate pathogens and cancer. Specifically, Th cells facilitate B cell and cytotoxic T cell (Tc) activation and recruitment and enhance their function against cancer and infectious diseases. Th cells are a valuable resource for improving Tc responses in cancer treatment and have become a focus of immunotherapeutic research. While it is increasingly clear that helper T cells serve an important role, the details about which entities produce an effective Th cell response remain unclear. CD5 is a T cell co-receptor that …

The Effects Of Moderate And High Temperatures On Growth, Metabolism, And Blood-Oxygen Affinity In Ictalurus Spp., Brandon Gerhart

Theses and Dissertations

Despite the growing use of hybrid catfish (Ictalurus furcatus × I. punctatus) in aquaculture, few studies have investigated the comparative effects of temperature on physiological performance with other cultured catfish. Therefore, growth, metabolism, and blood-oxygen affinity of blue (I. furcatus), channel (I. punctatus), and hybrid catfish were compared at moderate (23°C) and high (33°C) water temperatures. Channel catfish had the greatest growth and were in better condition compared to blue and hybrid catfish. Hybrid catfish standard metabolic rates did not differ from blue or channel catfish, while hybrid catfish had higher maximum metabolic rates, …

Effects Of Temperature On Growth, Metabolic Rate, And Lower Dissolved Oxygen Tolerance Of Speckled Peacock Bass Cichla Temensis, Manuel E. Coffill-Rivera

Theses and Dissertations

I examined the effects of temperature (25, 30, and 35°C) on growth, standard metabolic rate (SMR), and lower dissolved oxygen tolerance (LDOT) of juvenile Speckled Peacock Bass Cichla temensis. Fish were acclimated to 150-L aquaria for 7 weeks before the growth, SMR, and LDOT experiments. The growth study lasted 58 days and fish acclimated to 25 and 30°C displayed similar growth rates, while fish acclimated to 35°C had very poor growth rates. The SMR and LDOT experiments were performed using intermittent respirometers. Fish acclimated to 25°C had the lowest SMR, followed by 30°C, and finally 35°C. The highest LDOT …

Eluication Of Lipid Metabolic Pathways In Differentiating Giardia Lamblia Using High Resolution Mass Spectrometry, Cameron Ellis

Open Access Theses & Dissertations

Giardia lamblia is an intestinal protozoan found worldwide, including the U.S. This parasite exists in two morphologic stages - a replicative trophozoite and a relatively dormant yet viable cyst. While exposures of cysts to gastric acid during passage through the human stomach induces excystation, factors in the small intestine, where trophozoites colonize trigger encystation or cyst formation. Transformation into cyst stage is essential for Giardia to survive in the environment for months before infecting new hosts. Because of its small genome size (11.7 Mb), metabolic pathways in Giardia are highly reduced. As far as lipid metabolism is concerned, only limited …

A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin

Electronic Theses and Dissertations

Computational modeling of metabolic reactions and cellular systems is evolving as a tool for quantitative prediction of metabolic parameters and reaction pathway analysis. In this work, the basics of computational cell biology are presented as well as a summary of physical processes within the cell, and the algorithmic methods used to find time dependent solutions. Protein-protein and enzyme-substrate interactions are mathematically represented via mass action kinetics to construct sets of linear differential equations that describe reaction rates and formation of protein complexes. Using mass action methods, examples of reaction networks and their solutions are presented within the Virtual Cell simulation …

The Role Of L-Alanine Signaling In Aspergillus Fumigatus Biofilm Adherence, Carbon Catabolism, And Echinocandin Susceptibility., Joshua D. Kerkaert

Dartmouth College Ph.D Dissertations

Aspergillus fumigatus is a saprophytic filamentous fungus that participates in environmental carbon and nitrogen cycles through the degradation of complex organic substrates. In addition to its ecological role, A. fumigatus is the primary causative agent of a spectrum of diseases depending on the immune status of the individual, the most lethal of which is invasive aspergillosis (IA). Treatment strategies for IA are limited and far too frequently fail. Despite the high rates of treatment failure, antifungal resistance remains relatively low, albeit rising at a concerning rate. Insights into this discrepancy between the rate of treatment failure and the rate of …

The Regulation Of Atg9a-Mediated Aggrephagy By An Ulk1-Independent Atg13-Atg101 Complex, Joshua Youngs

Undergraduate Honors Theses

Aggrephagy, a type of autophagy, is an essential cellular process by which protein aggregates are collected and broken down in the lysosome. Protein aggregates are implicated in several diseases including Alzheimer’s disease, diabetes, and cancer. Here, we investigate the ATG13-ATG101 protein complex, a sub-complex of the canonical ULK1 complex whose regulatory role in aggrephagy is not completely understood. We also develop a protein fragment complementation (PFC) assay using the biotin ligase TurboID to study the functions of the ATG13-ATG101 complex with increased specificity. We demonstrate that ATG13 is required for optimal degradation of p62-ubiquitin condensates. We also show that a …

Determining The Role Of Mir-133a In The Diabetic Heart, Tyler Kambis

Theses & Dissertations

Diabetes mellitus (DM) is characterized by hyperglycemia, hyperlipidemia, and hypoinsulemia, each of which disrupt intracellular mechanisms in the heart. DM is a chronic metabolic disease delineated into two categories: insulin deficient-type 1 DM and insulin resistant-type 2 DM. Although they differ in underlying genetic and physiological factors, both significantly increase the risk of heart failure. Impaired insulin signaling shifts energy dependency from glycolysis towards fatty acid β-oxidation in the DM heart. This DM-induced metabolic shift increases mitochondrial stress leading to mitochondrial dysfunction and cell death in the heart. The metabolically entwined ferroptosis is a novel form of myocardial cell death …

Characterizing The Roles Of Cannabinoid Receptor 1 & 2 In Zebrafish Behavior, Metabolism, And Seizure-Induced Activity, Kayci Kimmons

Honors Theses

Epileptic disorders like Dravet Syndrome require novel studies to determine the most ideal treatment. New research linking the endocannabinoid system (ECS) to epileptic disorders is arising, but there is still much to be discovered about the function and regulatory impact of the endocannabinoid system and its receptors in epilepsies like Dravet. In this study, knockout models of larval and adult zebrafish (Danio rerio) were used to investigate the roles of cannabinoid receptors 1 & 2 in behavior, brain mitochondrial metabolism, and seizure-induced activity following exposure to THC and CBD. Larval zebrafish which lacked cannabinoid receptor 1 exhibited increased …

Role Of Fasting In Caloric Restriction Improved Glucose Tolerance, Makayla M. Dillon

ETD Archive

The Caloric Restriction (CR) diet in mammals has been shown to increase longevity and prevent metabolic disorders. Some of the benefits of CR include improved glucose homeostasis, namely improvements in glucose tolerance. Mice on the CR diet have a 30% reduction in food provided, as well as a fasting period between meals as they are only fed once a day. Hence the benefits of CR stem from both fasting and reduced calorie intake. In this study, we investigated if the fasting component of CR is responsible for the benefits of this diet in improving glucose homeostasis. In particular, we used …

An Investigation Into The Roles Of Aldose Reductase And Acetate Kinase In The Metabolism Of Entamoeba Histolytica, Matthew B. Angel

All Dissertations

Entamoeba histolytica is an amoebic parasite that infects an estimated 90 million people worldwide and causes approximately 100,000 deaths per year. As the causative agent of amoebic dysentery, this food- and water-borne pathogen represents a significant public health burden worldwide, particularly in areas with poor sanitation. While treatments for amoebiasis exist, they are often limited in their effectiveness. Thus, efforts to better understand the biology and physiology of this organism are vital to the development of novel treatments for this disease.

E. histolytica lacks the enzymes for many common metabolic pathways such as the citric acid cycle and oxidative phosphorylation …

Assessing Dietary Nutrient Adequacy And The Effects Of Season-Long Training On Body Composition And Metabolic Rates Of Men's Division I Collegiate Basketball Player, Morgan M. Nishisaka

Master's Theses

The success of performance in basketball may rely on both optimal body composition and nutrient intake. To our knowledge this is the first study to examine dietary intake adequacy and season-long effects on body composition and metabolism. The purpose of this study was to examine seasonal changes in body composition (BC), resting metabolic rate (RMR) and respiratory quotient (RQ), while also examining the dietary intake adequacy of NCAA DI male basketball players. BC, RMR and RQ were assessed during pre-season, in-season, and post-season (September, December, and March), while dietary assessment was collected in September and February. Results of this study …

Severe Hypoxia Up-Regulates Gluconeogenesis In Daphnia, Morad C. Malek

Undergraduate Honors Theses

Hypoxia is a significant low oxygen state that has complex and diverse impacts on organisms. In aerobes, various adaptive responses to hypoxia are observed that vary depending on the level of oxygen depletion and previous adaptation, hence the continued attention to hypoxia as an important abiotic stressor. Adaptive responses to hypoxia are primarily governed by the hypoxia-inducible factors (HIFs), which activate downstream genetic pathways responsible for oxygen transport and metabolic plasticity. In aquatic habitats, oxygen availability can vary greatly over time and space. Therefore, aquatic organisms’ adaptation to hypoxia is likely pervasive, especially in genotypes originating from waterbodies prone to …