Life Sciences Commons^™

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 …

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …

Investigation Of Human N-Acetyltransferases (Nat1 And Nat2) Genetic Polymorphisms In Susceptibility To Aromatic Amine And Alkylaniline Genotoxicity., Mariam Habil

Electronic Theses and Dissertations

Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT1 and NAT2 genotypes. We hypothesize that different NATs alleles will impact levels of N-acetylation, HPRT mutations, DNA damage and oxidative stress induced by carcinogens. NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and NAT1*4, NAT1*14B, NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of benzidine, β-naphthylamine (BNA), and 4, 4’-methylene bis (2-chloroaniline) (MOCA) as aromatic amines and 3,4-dimethylaniline (3,4-DMA) as one of alkylanilines and their associated toxicity. Our …

Sequencing And Functional Characterization Of A Latrodectus Geometricus Defensin, Lg-Defensin, Jacklyn Victoria Thompson

Electronic Theses and Dissertations

Defensins are small, cysteine-rich, immune related proteins described to be the most widespread family of invertebrate antimicrobial peptides. Presently, there is limited information regarding spider defensins. In this study, a new defensin peptide was described in Latrodectus geometricus, Lg-defensin. The full open reading frame was resolved using RACE and de novo assembly, followed by a bioinformatical analysis and phylogenetic alignment to determine conserved sequence patterns and structural similarities to other defensins. Next, the functionality of Lg-defensin was determined using in vitro RNA interference to assess what impact silencing had on the spider’s ability to control a gram-positive and gram-negative bacterial …

The Mechanisms Of Mitochondrial Dysfunction In T Cell Aging During Chronic Viral Infection, Madison B. Schank

Electronic Theses and Dissertations

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections induce a myriad of disturbances to CD4 T cell functions, including mitochondrial compromise, excessive inflammation, increased telomeric DNA damage and attrition, cellular exhaustion and senescence, and accelerated aging. In this dissertation, the mechanisms underlying metabolic failure, accelerated aging, and cellular dysfunctions were evaluated in CD4 T cells from healthy subjects (HS) treated with a telomere-targeting drug (KML001) or HCV-infected individuals or people living with HIV (PLHIV) compared to HS. We observed that KML001-induced telomere injury resulted in mitochondrial swelling and decreased mitochondrial membrane potential, cellular respiration, mitochondrial DNA (mtDNA) copy …

Importance Of The Microhabitat And Microclimate Conditions In The Northern Gray-Cheeked Salamander (Plethodon Montanus) Across An Elevation Gradient, Trevor Chapman

Electronic Theses and Dissertations

The southern Appalachian Mountains have among the highest salamander diversity in the world, largely due to local speciation in the family Plethodontidae. Plethodontid salamanders (i.e., lungless salamanders) are particularly sensitive to habitat climate conditions due to their reliance on cutaneous respiration, and their immediate environmental conditions (microhabitat) likely influence their dispersion and activity more than the large-scale atmospheric conditions. The Northern Gray-cheeked salamander (Plethodon montanus) is restricted to high elevations in the Appalachian Mountains. Our goal was to investigate the relationship between P. montanus and its microhabitat by examining behavioral preference for climatic conditions, characterizing the microclimate with …

Voltage-Gated Potassium Channel Dependent Mechanisms Of Cardiovascular Adaptation To Chronic Exercise., Sean Raph

Electronic Theses and Dissertations

Exercise increases cardiac workload, escalating the demand for oxygen. The myocardial vasculature responds to the greater demand for oxygen by increasing blood flow to match the needs of the heart during augmented work. Increasing blood flow requires the coronary arteries dilate (a.k.a. vasodilation); this is mediated predominantly by vascular smooth muscle cell relaxation. Vasodilation is driven through inhibition of calcium influx into vascular smooth muscle cells. The prevention of calcium influx is largely mediated by efflux of potassium via potassium channels causing membrane hyperpolarization, which in turn closes voltage-dependent (or gated) calcium channels (VDCC). Changes in vascular smooth muscle cell …

Return-To-The-Platform: The Case Of A Collegiate Level Weightlifter Recovering From A Meniscus Injury, Nicholas Harden

Electronic Theses and Dissertations

The purpose of this study was to observe physiological metrics relative to training-induced adaptations in conjunction with laboratory- and competition-based performances in a super-heavyweight weightlifter recovering from a meniscus injury. A retrospective analysis was conducted on a collegiate level male weightlifter (23.2 yrs; 131.9 kg; 187.3 cm) over the course of 21-weeks post-meniscus surgery. Body mass, body fat percentage, hydration status, vastus lateralis muscle cross-sectional area, jump performance, and isometric midthigh pull were regularly assessed as part of an ongoing athlete monitoring program. Pre-injury baseline (T0) measurements were collected relative to a major national competition (COMP1). Post-injury measurements took place …

Effects Of Prescribed Fire Regimes On White-Tailed Deer (Odocoileus Virginianus) Browse, Forage, And Nutrient Availability In The Pineywoods Ecoregion Of Texas, Wyatt L. Bagwell

Electronic Theses and Dissertations

Fire is a management tool for white-tailed deer (Odocoileus virginianus) habitat, influencing browse availability, herbaceous production, and nutrient content. In 2020 and 2021, this study utilized 46 plots across East Texas to assess these habitat components. A stem count index survey method was used to assess browse utilization prior to April in both years, and preferred browse species were clipped and analyzed for nutrient availability, and herbaceous production was also measured. Additionally, white-tailed deer population data, browse survey data, and recent fire history were obtained from five different wildlife management areas to examine their relationship. Deer had preferences …

Death Of A Bacterium: Exploring The Inhibition Of Staphylococcus Aureus By Burkholderia Cenocepacia., Tiffany Brandt

Electronic Theses and Dissertations

Antimicrobial resistance is a phenomenon of increasing concern as antimicrobial overuse and misuse eliminate current therapeutic options, ushering society into a post-antimicrobial era. Antibiotic discovery and synthesis efforts are urgently needed to counter the increasing burden of antimicrobial resistance. Staphylococcus aureus is a causative agent of a variety of clinical manifestations including bacteremia, endocarditis, soft tissue infection, osteomyelitis, and device-related infections. S. aureus infection presents additional treatment challenges due to its capacity for biofilm formation, which is a mode of growth that confers protection from antibiotics and physical elimination, and the emergence of antibiotic resistant strains, including methicillin-resistant S. aureus …

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller

Electronic Theses and Dissertations

28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …

Alcohol, Stress, And Sex In The Bed Nucleus Of The Stria Terminalis, Nicholas Burski

Electronic Theses and Dissertations

Alcohol use disorder (AUD) costs the U.S. billions of dollars each year and is a leading cause of preventable death. AUD leads to many health complications, and those who suffer from AUD will often have stress and anxiety disorder comorbidities. To better understand this connection between AUD and stress and anxiety disorders, restraint stress (RS) and chronic-intermittent ethanol exposure (CIE) procedures were used on rats to analyze neuroinflammation via ELISA in the infralimbic and prelimbic cortices, and the bed nucleus of the stria terminalis (BNST). Levels of proinflammatory cytokines, TNF-α and IL-1β, were found to be elevated across different tests …

The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall

Electronic Theses and Dissertations

Volatile organic compounds (VOCs) are a group of pervasive air pollutants that are released into the atmosphere from both anthropogenic and environmental sources. Recent epidemiological studies suggest that exposure to various VOCs is associated with an increased risk of cardiovascular disease. However, the relationship between VOCs and cardiovascular disease is not well-studied. Using animal models and three select VOCs, benzene, xylene, and trichloroethylene, we studied the effects of VOCs on endothelial injury and benzene-induced atherogenesis. We found that exposure to benzene and xylene increased circulating endothelial microparticles, depleted progenitor cells, and increased platelet activation. Following the exposure to the representative …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

A Functional Study Of Topological Dna Problem In Human T Cells During Chronic Viral Infection, Xindi Dang

Electronic Theses and Dissertations

T cells play an important role in adaptive immune system against viral infections, while premature aging and dysfunction of T cells induced by unrepaired DNA damages are always non-negligible snags during the long-term of fighting with chronic viral infections, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV) infection. In this dissertation, we investigated the role of topological DNA damage in reprogramming telomeric DNA damage responses (DDR), mitochondrial metabolisms, and T cell functions using CD4+ T cells derived from individuals with chronic viral infections or healthy subjects treated with topoisomerase inhibitors. The healthy human …

Light And Temperature Entrainment Of Two Circadian-Driven Behaviors In The Flesh Fly Sarcophaga Crassipalpis, Raven Ragsdale

Electronic Theses and Dissertations

Circadian rhythms dictate the timing of both once-in-a-lifetime adult emergence (eclosion) and daily locomotor activity rhythms in the flesh fly S. crassipalpis. Light cycles are considered the primary environmental time cue (zeitgeber), but the life history of S. crassipalpis suggests that temperature cycles (thermocycles) may also play a key role. This work evaluates the efficacy of thermocycling as a zeitgeber in S. crassipalpis. We found that shifting both light and temperature cycles of sufficient amplitude affect the phasing of eclosion and locomotor activity, but result in different patterns. Additional experiments suggest greater thermocycle sensitivity during the late metamorphic …

Novel Signal Sequences And Fusion Partners For Paratransgenesis In Asaia, Christina Grogan

Electronic Theses and Dissertations

Mosquitoes transmit many pathogens that cause human disease. One such disease, malaria, is caused by parasites in the genus Plasmodium, infecting over 200 million people and killing over 600,000 per year. Current strategies to control vector-transmitted diseases are increasingly undermined by mosquito and pathogen resistance. Research has turned to additional and novel methods of control, such as altering the microbiota of the vectors. In this method, called paratransgenesis, symbiotic bacteria are genetically modified to affect the mosquito’s phenotype by engineering them to deliver antiplasmodial molecules into the midgut to kill parasites. These molecules must be released by the …

Identification And Characterization Of Genetic Elements That Regulate A C-Di-Gmp Mediated Multicellular Trait In Pseudomonas Fluorescens, Collin Kessler

Electronic Theses and Dissertations

Microbial communities contain densely packed cells where competition for space and resources are fierce. These communities are generally referred to as biofilms and provide advantages to individual cells against immunological and antimicrobial intervention, dehydration, and predation. High intracellular pools of cyclic diguanylate monophosphate (c-di-GMP) cause cells to aggregate during biofilm formation through the production of diverse extracellular polymers. Genes that encode c-di-GMP catalytic enzymes are commonly mutated during chronic infections where opportunists display enhanced resistance to phagocytosis and antibiotics. Our lab uses an emergent multicellular trait in the model organism Pseudomonas fluorescens Pf0-1 to study the emergence of c-di-GMP mutations …

Investigating Host Defenses Of North American Salamanders Against The Recently Emerged Chytrid Pathogen, Batrachochytrium Salamandrivorans, Kenzie Pereira

Electronic Theses and Dissertations

A recently emerged chytrid fungal pathogen, Batrachochytrium salamandrivorans (Bsal) threatens salamander biodiversity. Bsal susceptibility varies between and within salamander species, but little is known about the mechanisms underlying these differences. Susceptibility is likely influenced by numerous interacting factors, but my dissertation studied the role of host immune responses.

My first aim investigated between species differences by studying the bioactive properties of salamander skin peptides against Bsal and the related pathogen, B. dendrobatidis (Bd). Skin peptides were collected from five salamander species, used for in vitro assays, and analyzed by RP-HPLC. While skin peptides from one …

Neural Stem Cells: Age-Dependent Outcomes During Viral Infections In The Central Nervous System, Manisha N. Chandwani

Electronic Theses and Dissertations

Viral infections in the central nervous system (CNS) are associated with neurodevelopmental and neurobehavioral deficits. The outcomes of viral infections can be driven by damage and death of neurons. Neural stem cells (NSCs) play key roles in neurodevelopment, repair, and physiological brain function. During a viral infection, NSC activity can disturbed by direct infection of NSCs by the virus or by anti-viral immune response. Here, we aimed to assess whether the anti-viral immune response can impact NSC activity during an immunocompetent response in the adult brain. We utilized a transgenic mouse model of Measles virus infection where only the CNS …

Characterization Of Microbotryum Lychnidis-Dioicae Secreted Effector Proteins That Manipulate Its Host Plant, Silene Latifolia., Ming-Chang Tsai

Electronic Theses and Dissertations

The smut fungal species Microbotryum lychnidis-dioicae is an obligate phytopathogen colonizing the plant host, Silene latifolia. A significant feature of M. lychnidis-dioicae infection is that the fungus can replace pollen on the anthers of susceptible host plants with fungal teliospores, thus earning the fungus the name: anther smut disease of flowers. The fungus synthesizes and secretes effector proteins into the cells of the plant host during infection, and the protein-protein interactions may interfere with and modify metabolism, plant development, and gene expression of the host to allow fungal colonization. Two potential fungal effector proteins, MVLG_06175 and MVLG_05122, were identified …

Community Structure Analysis Of Turtles With Application To The Early Pliocene Gray Fossil Site, Julian Conley

Electronic Theses and Dissertations

Turtles are important components of ecosystems around the world, with diverse ecological niches and adaptations. However, there are few detailed studies of how turtle community structure reflects local environments. This project applied techniques of community structure analysis to sites across the United States to infer past ecosystem and environmental conditions of the early Pliocene Gray Fossil Site (GFS) in northeastern Tennessee based on the ancient turtle community. Results indicate extant turtle community structure closely reflects environmental conditions, and that ancient turtle communities can be used to infer climate and habitat conditions of past ecosystems. Application to the GFS turtle community …

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 …

Dibutyl Amine Detection, Quantification, And Removal With Iron(Ii)Tetrasulfophthalocyanine (Fetspc), Kyle Bittner

Electronic Theses and Dissertations

Pesticide testing is of practical interest in various areas of today’s world due to their prevalence and toxicity. These areas include agriculture, environmental, chemical plants, and many others. Herbicides, like Roundup, contain secondary amines such as glyphosate. The ability to detect secondary amines could offer a method for glyphosate detection in agricultural and environmental samples. Secondary amines can interact with metal complexes through electron charge transfer. Such interactions can cause a change in the metal’s electron configuration and energy state and can be seen in the UV-Vis spectrum. Metal phthalocyanines (MPc’s) and other organometallic complexes have been of interest for …

Validation Of The 40 Hz Auditory Steady State Response As A Pharmacodynamic Biomarker Of Evoked Neural Synchrony, Muhammad Ummear Raza

Electronic Theses and Dissertations

Schizophrenia is a troubling and severe mental illness that is only incompletely treated by currently available drugs. New drug development is hindered by a scarcity of functionally relevant pharmacodynamic biomarkers that are translatable across preclinical and human subjects. Although psychosis is a major feature of schizophrenia, cognitive and negative symptoms determine the long-term functional outcomes for patients. Stimulus-evoked neural synchrony at gamma (~ 40 Hz) frequency plays an important role in the processing and integration of sensory information. Not surprisingly, schizophrenia patients show deficits in gamma oscillations. NMDA receptor (NMDAR) activation on fast-spiking parvalbumin-positive interneurons is deemed important for the …

The Paleoecology Of High-Elevation Bison In The Greater Yellowstone Ecosystem And Implications For Modern Bison Conservation, Darian Bouvier

Electronic Theses and Dissertations

The national mammal of the United States, the American Bison (Bison bison) was once nearly extinct. Populations have recovered to the degree that thousands roam the Great Plains today. Due to their large numbers and body size, this species has an oversized impact on the ecological communities where it lives and is considered a keystone herbivore in modern North American grasslands. This study explores the detailed, seasonally resolved, paleoecology of seven bison from the Greater Yellowstone Ecosystem during the Late Holocene through stable isotope analyses and species niche modeling. Isotopic analyses of δ¹³C, δ¹⁵N, …

Flora Of Doe Mountain Recreation Area, Johnson County, Tennessee, Benjamin Mccullough

Electronic Theses and Dissertations

A botanical inventory of Doe Mountain Recreation Area (DMRA) in northeastern Tennessee was conducted to help guide conservation-based management. A total of 484 species were found in DMRA, comprising 94 families, and 285 genera, 10 species listed in the state rare plant list, and 76 exotic species. Two species, Liatris virgata and Lycopodiella inundata, were new state records. Water in the Lycopodiella seep was an order of magnitude more acid than at other sites. An analysis of the wildland-urban interface showed that only 13% of the area was classified as uninhabited. The inventory-invasion index, introduced to quantify the relative …

Evaluating Bat Roost Abundance: A Comparison Of Drone-Acquired Thermal Imagery And Acoustic Estimates With Visual Observations, Karah Jaffe

Electronic Theses and Dissertations

Roosts provide an opportunity to census philopatric populations of bats. Comparing the efficacy of traditional methods with novel methods can provide guidance on the use of new technologies in the field. This project aims to compare the count efficacy of external emergence methodologies, i.e., drone-acquired thermal imagery, acoustic estimates, and visual counts. Surveys were conducted ten nights at two emergence sites and synchronized to compare counts. Acoustic estimates could not be established as there was a weak prediction of the linear relationship between root-mean-square pressure and emergence count; therefore, this method was removed from the comparative analysis. A linear mixed-effects …

Determination Of The Functional Role Of Rab-Ggt In Physcomitrium Patens., Hyun Jin Jung

Electronic Theses and Dissertations

Protein prenylation, a common lipid post-translational modification, is required for growth and development in eukaryotes. Rab geranylgeranylation involves the addition of one or two 20-carbon geranylgeranyl moieties to Rab-GTPase target proteins, which regulate intracellular vesicle trafficking. The reaction is carried out by heterodimeric Rab geranylgeranyltransferase (Rab-GGT), which is composed of two associated α- and β-subunits, with the assistance of an additional protein called Rab escort protein (REP). Loss of function of the Rab-GGT α subunit RGTA1 has not been reported in any plant. While knockout of either of the two β subunits RGTB1 or RGTB2 results in …