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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 …

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 …

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 …

Evolution And Selection: From Suppression Of Metabolic Deficiencies To Bacteriophage Host Range And Resistance, Daniel Kurt Arens

Theses and Dissertations

The evolution and adaptation of microorganisms is so rapid it can be seen in the time frame of days. The root cause for their evolution comes from selective environmental pressures that see organisms with beneficial mutations survive otherwise deadly encounters or outperform members of its population who fail to adapt. This does not always result in strict improvement of the individual as in the case of antibiotic resistant bacteria who often display fitness tradeoffs to avoid death (see Reviews [1-3]). For example, when an ampicillin resistance gene (ampC) containing plasmid that is occasionally found in the wild was transformed into …

Effect Of Water Consumption On Resting Metabolism In Adults, Brittany Leigh Murphy

Theses and Dissertations

This study analyzed the acute effect of water consumption on resting metabolic rate (RMR). It was hypothesized that water would have a small, nonclinically significant effect on RMR. Men and women ages 18–40 years participated in a crossover study in which each participant received a No Water and Water condition (order determined randomly) with a 7-day washout period between each condition. Both conditions began with visual analog scales to gauge hunger and thirst levels, urine spectrometry to quantify hydration status, and height and weight measurements. The No Water condition consisted of a 30-minute rest period followed by 45 minutes of …

The Role Of Beta-Hydroxybutyrate In Altering Adipose Mitochondrial Bioenergetics, Chase Mitchell Walton

Theses and Dissertations

The rampant growth of obesity worldwide has stimulated explosive research into human metabolism. Metabolic rate has been shown to be altered by diets differing in macronutrient composition, with low-carbohydrate, ketogenic diets eliciting a significant increase over other interventions. The purpose of this study was to determine the effects of the ketone β-hydroxybutyrate (βHB) on mitochondrial respiration and coupling status in adipose tissue. To explore this, we employed three distinct systems, namely cell, rodent, and human models. In every model, βHB robustly increased mitochondrial respiration. Furthermore, in cultured adipocytes and rodent adipose, we quantified the expression of genes involved in mitochondrial …

Genetic Determinants Of Variation In The Gh/Igf-1 Axis And Their Relationship To Cardiometabolic Health, Rafael Luis Aguirre Guillen

Theses and Dissertations

Background: In a study of Mexican Americans, we performed analyses of GEI and pleiotropy in the axis in relation to MS. GH/IGF-1 axis components were studied. Model parameters and likelihoods were estimated by maximum likelihood.

Results: Pleiotropy was observed for IGFBP3 (p

Conclusions: IGF-I and IGFBP3 are genetically correlated with MS whereas MS influences the additive genetic variance in IGFBP1 variables mainly but also in IGF-I somewhat by virtue of the VH exhibited by IGF-I/IGFBP1.

Investigation Of Therapeutic Immune Cell Metabolism, Josephine Anna Tueller

Theses and Dissertations

This thesis addresses multiple approaches to investigating mechanisms of immune linked disease. There are four projects outlined below which describe the work of these investigations. First, educating students about techniques to study disease and therapies is an important area of research. Flow cytometry is a common technique in immunology and its versatility and high throughput abilities can be applied to many fields. While it is very useful, flow cytometry is a complex technique that requires training to operate and understand, and there are very few reports about administering effective training. This thesis outlines the first report of a full semester …

Regulation Of Immune Cell Activation And Functionby The Nbmpp2 Protein Andthe Cd5 Co-Receptor, Claudia Mercedes Freitas

Theses and Dissertations

According to the centers for disease control and prevention (CDC) and the world healthorganization (WHO), heart disease and immune related diseases such as diabetes and cancer areamong the leading causes of death around the world. Thus, the regulation of the function ofimmune cell plays a key role in health and disease. Calcium (Ca2+) ions play a critical role inimmune cell activation, function and in a robust immune response. Defects in Ca2+ signalinginfluences the development of cardiac disease, Alzheimer disease, immune cell metabolism,muscle dysfunction, and cancer. Each immune cell is unique in its activation and function,making it relevant to understand how …

Assessment Of Microbial Carbon Processing And Its Implications To The Carbon Budget Of Lake Superior, Lindsey Michelle Koren

Theses and Dissertations

Over the past few decades, there has been increased research focus on carbon cycling within aquatic systems, especially with the changing global climate. Inland waters play a major role in the global carbon cycle, but the fundamental features remain poorly understood, particularly the large lakes of the world. Our experimental approach assessing the carbon budget of Lake Superior, the largest freshwater lake by area, provides spatial and temporal variability that has been previously overlooked but may be critical to our understanding on the biogeochemical processes controlling the lake. Multiple stations were chosen across the lake, both nearshore and offshore, to …

Gut Microbiota Regulates The Interplay Between Diet And Genetics To Influence Insulin Resistance, Jeralyn Jones Franson

Theses and Dissertations

Insulin resistance and obesity are major public health concerns. The impact of diet and genetics on insulin resistance and obesity is well accepted. Additionally, the gut microbiota has been shown to influence obesity and metabolic disorders. However, much remains to be understood about the role of gut microbiota in the development of insulin resistance and obesity. We utilized a mouse model lacking PAS kinase, a protein involved in cellular metabolism, in order to better understand the relationship between diet, genetics and the gut microbiota. Previous research has shown that mice lacking PAS kinase were protected from the effects of a …

Metabolic Dysregulation: An Investigation Of The Role Of Foxo3 In Gluconeogensis In Pten-Null Glioblastomas, Victor Fanniel

Theses and Dissertations

Many processes are regulated by the Phosphatidylinositol 3 kinase (PI3K) pathway in the cell including cell survival, metabolism, and apoptosis. Increased activation of the PI3K pathway is a hallmark of many cancers which can be oftentimes attributed to the mutation of PTEN, which encodes an enzyme that performs the reverse reaction of PI3K. When PTEN is null-mutated, this creates a constitutively active PI3K pathway and constitutively active AKT. Since AKT phosphorylates conserved residues on FOXO transcription factors to mark them for nuclear export, this renders FOXO inactive. However, new research has provided evidence that FOXO is still present in …

Monitoring Expression Of Metabolic Genes During The Hypoxic Response Of S. Cerevisae, Nikkoli Lueder

Theses and Dissertations

All organisms appear to have the ability to sense and respond to changes in their environment. Hypoxia, or low oxygen, is experienced by many organisms at some point in their life cycle. Some organisms such as S. cerevisiae, a species of yeast, respond by dramatically altering gene expression. The result is that genes needed in the new environment are turned on and unneeded genes are turned off. S. cerevisiae has been used in our study because it shares many genes with other eukaryotes, including humans, so many of our findings are applicable to these organisms. Here, we tried to understand …

Glycolytic Atp Production Is Required For Innate Mast Cell Activation And Is Limited By Lactic Acid, Which Effectively Reduces Lps-Induced Cytokine Production In Mast Cells And In Vivo, Heather Caslin

Theses and Dissertations

The metabolic pathways required for adenosine triphosphate (ATP) production within the cell are well understood, however recent publications suggest that metabolic pathways are closely linked to immune cell activation and inflammatory diseases. There has been little examination of the metabolic pathways that modulate mast cell activation and the feedback regulator lactic acid. Here we examine metabolic pathways and regulation within mast cells in the context of lipopolysaccharide (LPS) and interleukin (IL-33) activation, for which there has been little to no reported studies. First, we examine the effects of lactic acid, previously considered only a by-product of glycolysis and now understood …

Discovery And Characterization Of Bile Acid And Steroid Metabolism Pathways In Gut-Associated Microbes, Spencer Harris

Theses and Dissertations

The human gut microbiome is a complex microbial ecosystem residing in the lumen of our gastrointestinal tract. The type and amounts of microbes present in this ecosystem varies based on numerous factors, including host genetics, diet, and environmental factors. The human gut microbiome plays an important role in normal host physiological functions, including providing energy to colonocytes in the form of short-chain fatty acids. However, gut microbial metabolites have also been associated with numerous disease states. Current tools for analyzing the gut microbiome, such as high-throughput sequencing techniques, are limited in their predictive ability. Additionally, “-omic” approaches of studying the …

A Comparison Of Computational Methods For Estimating Estuarine Production And Respiration From Diel Open Water Dissolved Oxygen Measurements, Spencer Tassone

Theses and Dissertations

Diel dissolved oxygen (DO) data were used to characterize seasonal, inter-annual, and longitudinal variation in production and respiration for the James River Estuary. Two computational methods (Bayesian and bookkeeping) were applied to these data to determine whether inferences regarding DO metabolism are sensitive to methodology. Net metabolism was sensitive to methodology as Bayesian results indicated net heterotrophy (production < respiration) while bookkeeping results indicated net autotrophy (production > respiration). Differences in net metabolism among the methods was due to low seasonal variation in respiration using the Bayesian method, whereas bookkeeping results showed a strong correlation between production and respiration. Bayesian results suggest a dependence on allochthonous organic matter (OM) whereas …

The Role Of Hypoxia On Pyruvate Kinase M2, Mammalian Target Of Rapamycin, Mitochondrial Function, And Cell Invasion In The Trophoblast, Rebecca Lutz Kimball

Theses and Dissertations

This thesis will be organized into two chapters discussing the role of hypoxia in the human placenta. The goal of this thesis is to characterize pyruvate kinase M2, mammalian target of rapamycin, mitochondrial function, and cell invasion in hypoxic conditions in the trophoblast. Understanding the mechanisms of placental metabolism can lead to further treatments for placental diseases. Chapter one covers the background of intrauterine growth restriction, hypoxia, placental metabolism, and pyruvate kinase M2 (PKM2). Little is currently understood about the role of the mitochondria in placental diseases. Expression of PKM2, trophoblast cell invasion, and mitochondrial function is shown to be …

Identifying And Characterizing Yeast Pas Kinase 1 Substrates Reveals Regulation Of Mitochondrial And Cell Growth Pathways, Desiree Demille

Theses and Dissertations

Glucose allocation is an important cellular process that is misregulated in the interrelated diseases obesity, diabetes and cancer. Cells have evolved critical mechanisms for regulating glucose allocation, one of which is sensory protein kinases. PAS kinase is a key sensory protein kinase that regulates glucose allocation in yeast, mice and man; and is a novel therapeutic target for the treatment of metabolic diseases such as obesity, diabetes and cancer. Despite its importance, the molecular mechanisms of PAS kinase function are largely unknown. Through large-scale protein-interaction studies, we have identified 93 novel binding partners for PAS kinase which help to expand …

Global Climate Change And The Southern Ocean: How Antarctic Fishes Physiologically Respond To A Changing Environment From The Cellular To The Organismal Level, Laura A. Enzor

Theses and Dissertations

Studies have projected that future changes in sea surface temperature and pCO2 levels will impact higher latitudes to a greater extent than in temperate regions. For notothenioid fishes of the Southern Ocean, evolution in extremely stable, cold waters has resulted in several adaptations which have left these fishes poorly prepared for global climate change. I have analyzed the metabolic and cellular response of Trematomus bernacchii, Pagothenia borchgrevinki and Trematomus newnesi to a long-term, multi-stressor scenario relevant to the predicted changes in the Southern Ocean. By combining whole animal respirometry with cellular level analysis of energy allocation, osmoregulatory mechanisms and cellular …

Different Expression Of Placental Pyruvate Kinase M2 In Normal, Preeclamptic, And Intrauterine Growth Restriction Pregnancies, Brigham L. Bahr

Theses and Dissertations

This thesis will be organized into two chapters discussing the placental expression of two proteins, pyruvate kinase M2 (PKM2) and heat shock protein 27 (HSP 27), in human placentas. Understanding the mechanisms of placental metabolism in healthy and diseased placentas helps us understand how placenta disorders occur and how we can treat these disorders. The goal is to investigate these proteins to gain an understanding of their roles in placental disorders and help decrease maternal and fetal mortality rates. Chapter one covers the background of pyruvate kinase M2 (PKM2) in cancer and embryonic tissues, and the expression of PKM2 in …

The Effects Of Aging On Skeletal Muscle Ampk Activation And An Analysis Of Chronic Aicar Treatment On The Aging Phenotype, Shalene E. Hardman

Theses and Dissertations

AMP-activated protein kinase (AMPK), a metabolic regulator, acts in opposition to many of the effects of aging and may provide insights into the development of sarcopenia. However, the effect of aging on AMPK activation is unclear. The purpose of this dissertation was to: 1) clarify the controversy concerning the activation of AMPK in response to endurance-like exercise in aged skeletal muscle; 2) address mechanisms for the age-associated alterations in AMPK activation; and 3) address the known benefits of chronic AICAR treatment in aged skeletal muscle. First, to clarify the effect of age on AMPK activation, young adult (YA) (8 mo.) …

Cellular Metabolism And Its Effect On The Type Iii Secretion System Of Dickeya Dadantii 3937, William Cortrell Hutchins

Theses and Dissertations

Nutrition, in both eukaryotes and prokaryotes, is vital to the life and well-being of the species. In organisms such as Escherichia coli, metabolism and its regulation have been well established, whereas in Dickeya dadantii 3937, the metabolic pathways and their effects on other processes have not been elucidated. Little is known is how carbon metabolism is able to regulate virulence and pathogenicity in this organism. In this work, we have investigated how the metabolic network contributes to positively and negatively regulating the pathogenicity of Dickeya dadantii 3937.

Chapter 1 provides an overview of the history and virulence processes in …

Plasma Lactate Accumulation During Running With Body Weight Unloading By Lbpp, Nicole Nevitt Rasmussen

Theses and Dissertations

At any given running speed, weight support with a lower body positive pressure (LBPP) device (i.e. Alter-G treadmill) reduces V̇O2. However, it is unknown how application of LBPP during running impacts lactate metabolism, specifically lactate threshold. Purpose: To determine if body weight unloading with the Alter-G treadmill alters lactate threshold. Methods. Maximal aerobic capacity (V̇O2max) and lactate threshold (LT) was determined in 8 male subjects on an Alter-G treadmill at 100% and 80% body weight loading at 0% grade in a randomized crossover design. V̇O2max tests started at 7 mile h-1 and increase speed by 1 mile h-1 every 2 …

The Effects Of A High Fat Diet On Mitochondrial Biogenesis And Inflammation In The Brain., Lauren Suzanne Vervaecke

Theses and Dissertations

INTRO: High fat diets (HFD) ingested over long periods of time have been shown to cause diet induced obesity leading to excessive adiposity and chronic low grade inflammation. Here we have shown how differing levels of saturated fats (SF), which are common storage fats, affect markers of inflammation and mitochondrial biogenesis. IL-1â and TNF-alpha are pro-inflammatory cytokines that have been shown to increase with a HFD, while molecular signalers, PGC-1alpha, cyt c, and SIRT1, related to mitochondrial biogenesis have been shown to decrease. Despite the risks of consuming a diet high in SF's, consumers continue to buy energy dense foods …

Factors Affecting Dissolved Oxygen Metabolism In Coastal Plain Streams Of Virginia, Julie Frank

Theses and Dissertations

I investigated seasonal and inter-site variation in factors influencing diel dissolved oxygen (DO) metabolism at four streams in the Virginia Coastal Plain. Data were collected monthly from January to August 2008 to characterize DO metabolism (diel DO amplitude, production, respiration), incident solar radiation (PAR), dissolved nutrients, fine benthic materials (mass, C:N, Chlα) and hydrology (discharge, water transit time, transient storage). Reach-scale metabolism estimates were determined using the one-station diurnal DO technique and transit time and transient storage were determined by conservative tracer additions. Incident solar radiation was the primary determinant of DO metabolism as streams experiencing higher light levels (Herring …

The Effects Of 3-Phosphoglycerate And Other Metabolites On The Activation Of Amp-Activated Protein Kinase By Lkb1/Strad/Mo25, William John Ellingson

Theses and Dissertations

Skeletal muscle contraction results in the phosphorylation and activation of the AMP-activated protein kinase (AMPK) by an upstream kinase, AMPKK. The LKB1-STRAD-MO25 complex is the major AMPKK in skeletal muscle; however, LKB1-STRAD-MO25 activity is not increased by muscle contraction. This relationship suggests that phosphorylation of AMPK by LKB1-STRAD-MO25 during skeletal muscle contraction may be regulated by allosteric mechanisms. In this study we tested an array of metabolites including glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), fructose 1,6-bisphosphate (F1,6-P2), 3-phosphoglycerate (3PG), glucose-1-phosphate (G1P), glucose-1,6-bisphosphate (G1,6-P2), adenosine diphosphate (ADP), carnitine (Carn), acetyl-carnitine (Acarn), inosine monophosphate (IMP), inosine, and ammonia for allosteric regulation. We found that …

Effect Of Nitric Oxide On Oxygen Consumption Of Skeletal Muscle, Christina Lyn Cox

Theses and Dissertations

Mammalian cells require a continuous and sufficient supply of oxygen to carry out their functions. The oxygen pathway has an overall direction taking O2 from the air to the mitochondria, which is a result of the mitochondrial O2 consumption (VO2) NO various effects on the mitochondria: at low concentrations for short periods NO specifically and irreversibly inhibits cytochrome c and reversibly inhibits cytochrome c oxidase, to decrease VO2. Thus, NO can modulate VO2 of skeletal muscle. The purpose of the present study was to measure VO2 of the rat spinotrapezius muscle under conditions of altered NO. The methods used provide …

Metabolic Inhibition Of A Toluene-Enriched Microbial Population Due To Lead (Pb2+): Verification Of A Free Metal Ion Toxicity Model, Patrick J. S. Marbas

Theses and Dissertations

A dissolved oxygen probe and an ion specific electrode were used to study the lead-induced metabolic inhibition in a toluene-enriched microbial population. Predicted toxicity values were compared to the actual toxicity responses using a free metal ion toxicity model (TM) which linked metabolic inhibition with lead activity. Experimentally derived values for the model parameters (lead activity and a lead distribution coefficient) were used in the TM. It was postulated that cellular metabolism is disrupted by the conformational changes to the cell's plasma membrane produced by lead ion adsorption. The predicted toxicity values were higher than the actual toxicity response. This …