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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 …

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 …

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 …

Relating Metabolic Phenotypes To Movement Behavior In Brook Trout, Jacob E. Bowman

All NMU Master's Theses

Brook trout movement-related life history strategies vary considerably and range from individuals that stay within the same 100 meters their entire life to individuals that are potamodromous or anadromous. Potential drivers of movement life histories have been the subject of much research in fish, with genetic subpopulation explanations often failing to explain the phenomenon. Metabolic phenotypes have been suggested as a possible driver for expression of different movement life histories. I investigated if metabolic phenotypes are related to movement strategies within a population of brook trout (Salvelinus fontinalis) in Unnamed Creek, a tributary to the Rock River, Alger …

Keeping Your Cool: Thermoregulatory Performance And Plasticity In Desert Cricetid Rodents, Richard W. Ramirez, Eric A. Riddell, Steven R. Beissinger, Blair W. Wolf

Biology ETDs

Small mammals in hot deserts often avoid heat via nocturnality and fossoriality and are thought to have a limited capacity to dissipate heat using evaporative cooling. Research to date has focused on thermoregulatory responses to air temperatures (T_a) below body temperature (T_b). Consequently, the thermoregulatory performance of small mammals exposed to high air temperatures is poorly understood, particularly responses across geographic and seasonal scales. We quantified the seasonal thermoregulatory performance of four cricetid rodents (Neotoma albigula, N. lepida, Peromyscus eremicus, P. crinitus) exposed to high T_a, at four sites …

Links Between Electrophilic Stress And Antifungal Resistance In Pathogenic Candida Species, Amy R. Biermann

Dartmouth College Ph.D Dissertations

Collectively, Candida species are the most prevalent cause of both superficial and invasive fungal infections worldwide. Invasive Candida infections have a high mortality rate and predominantly affect individuals with underlying diseases, such as diabetes, HIV, or cancer. Unfortunately, many invasive Candida infections are recalcitrant to antifungal treatment, while intrinsically multidrug-resistant pathogens, like Candida auris, are increasing in prevalence. Although the canonical mechanisms of antifungal resistance in Candida species are well established, i.e., overexpression of efflux pumps and overexpression of or mutations in genes encoding drug targets, factors affecting the natural evolution and regulation of resistance mechanisms remain poorly understood. …

Beyond Cortisol: Indicators Of Stress And Negative Feedback In Plasma And Blubber Of Marine Mammals, Jessica Avalos

University of the Pacific Theses and Dissertations

Marine mammals play an important role in ecosystem stability. However, anthropogenic activity is compounding pressure on many already vulnerable populations. A potential consequence of anthropogenic disturbance is physiological stress, which can impact metabolism, immunity, and reproduction, especially if it occurs repeatedly. Previous studies on marine mammals have focused on acute stress, but the impacts of repeated stress are poorly understood. Due to its accessibility on land during haul-outs, the northern elephant seal (Mirounga angustirostris) is a good system in which to study the effects of stress in marine mammals. Stress stimulates the release of glucocorticoid hormones, primarily cortisol. Elevated cortisol …

Characterization And Manipulation Of O-Glcnacylation In Granulosa Cells Of Bovine Ovarian Antral Follicles, Abigail Marie Maucieri

Graduate College Dissertations and Theses

Glucose is widely recognized as the preferred energy substrate for metabolism by granulosa cells (GCs). Yet in most cells, 2-5% of glucose is shunted through the hexosamine biosynthesis pathway (HBP) for O-linked N-acetylglucosaminylation (O-GlcNAcylation). O-GlcNAcylation is an evolutionarily-conserved, post-translational process that modifies serine and threonine residues on a variety of proteins. O-GlcNAcylation is also considered a nutrient sensor that can regulate cellular processes such as metabolism, signal transduction, and proliferation. In this respect, O-GlcNAcylation may be similar to, and possibly mediate, AMP-activated protein kinase (AMPK) signaling and its nutrient-sensing actions. However, the occurrence of O-GlcNAcylation and its relative importance to …

The Impact Of Nitric Oxide On Dendritic Cell Metabolism, Julia Priscilla Snyder

Graduate College Dissertations and Theses

Dendritic cells (DCs) are sentinel immune cells capable of directly sensing and responding to pathogens. Upon pathogen recognition, DCs undergo a process of activation that allows them to participate in the proinflammatory response at the site of infection and to initiate the adaptive immune response through antigen presentation to T cells. Because activated DCs serve as the critical link between innate and adaptive immunity, modulating DC activation could be a powerful tool in various clinical contexts such as vaccine design. DC activation is accompanied by widespread changes in metabolism including the rapid upregulation of glycolysis, which is sustained in DCs …

Validation Of Prmr Equations In A Non-Caucasian Sample – Ethnicity As A Variable In Predicting Resting Metabolic Rate, Erin N. Bannister

Graduate Research Theses & Dissertations

This study intends to identify a predictive resting metabolic rate (pRMR) equation that is predictive of the measured resting metabolic rate (mRMR) in a sample that includes a group of Black Americans. The handful of commonly used pRMR equations, such as the Mifflin- St. Jeor or Harris-Benedict equations, were created without defining the demographics of their populations, while validation of these equations is typically done with almost exclusively Caucasian subjects. Black and brown Americans require the same evidence of precision in predictions of daily energy needs as Caucasian Americans. When applied to non-Caucasian samples, these equations appear in the literature …

Regulation Of Skeletal Muscle Plasticity By The Gut Microbiome, Taylor R. Valentino

Theses and Dissertations--Physiology

Recent evidence suggests that the gut microbiome could play a role in skeletal muscle plasticity, providing novel treatments for muscle wasting diseases and/or performance enhancements. I first sought to determine if the gut microbiome is necessary for skeletal muscle adaptation to exercise. Forty-two, four-month old, female C57Bl/6J underwent nine weeks of weighted wheel running or remained in cage with a locked wheel, without or without the administration of antibiotics (treated). In response to wheel running, I found that antibiotic depletion of the microbiome led to a blunted hypertrophic response in the soleus muscle as measured by normalized muscle wet weight …

Metabolic Diversity Among Fibroblasts From Regenerating And Non-Regenerating Mammals, Ebenezer Aryee

Theses and Dissertations--Biology

Regeneration is a wound repair process that terminates in the restoration of tissue function and structure. Fibroblasts play pivotal roles in regenerative and fibrotic wound repair. Reports of extensive regenerative ability in mammals have been historically rare, but more recently spiny mice (Acomys) have emerged as a bona fide model of complex tissue regeneration. Recent work has indicated that fibroblasts from regenerators (Acomys and Oryctolagus) are more resistant to reactive oxygen species (ROS)-induced senescence compared to non-regenerating species, suggesting the influence of intrinsic cellular states on the fate of wound repair. Determining the basal metabolic signature …