Digital Commons Network^™

Novel Roles Of Tobacco-Associated Genes Underlying Disparate Survival In Appalachian Head And Neck Squamous Cell Carcinoma, Brenen William Papenberg

Graduate Theses, Dissertations, and Problem Reports

Head and neck squamous cell carcinoma (HNSCC) is an aggressive neoplasm primarily caused by tobacco consumption or human papillomavirus (HPV) infection. Incidence and mortality rates for HNSCC vary geographically. Appalachian residents consume tobacco products to a greater extent than national averages, a risk factor known to promote HPV-negative HNSCC through increased genomic instability. Male Appalachian patients display significantly worse relative survival than Appalachian females or non-Appalachian residents of either sex. Secondary analysis of available cancer registry outcome data from 2007-2013 indicates that white males with stage IV oral cavity/pharyngeal (OC/P) HNSCC are responsible for the decreased male survival observed within …

Cerebrovascular Dysfunction And Degeneration In Alzheimer’S Disease Pathophysiology, Dominic Dimitri Quintana

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a terminal illness and the most common form of dementia, which disproportionately affects the aged population. The pathophysiology of AD is characterized by neurodegeneration that slowly progresses, affecting regions of the brain that are involved in learning, memory, language, and executive function. In patients with the disease, early symptoms include non-disruptive forgetfulness that evolves into the inability to form new memories and ultimately the loss of autonomy at late stages. Histopathological hallmarks in the brain from patients with AD is the presence of amyloid-β (Aβ)-plaques and neurofibrillary tangles (NFT) deposited in the parenchyma. Since the discovery …

The Immunological Response To Chronic Stress In Obese Mice, Matthew Corey Parsley

Graduate Theses, Dissertations, and Problem Reports

Obesity and psychological stress are major risk factors for cardiovascular disease and have a positive correlation with vascular dysfunction. This functional deficit has been linked to a pro-inflammatory milieu, exacerbated by an upregulation of pro-inflammatory cytokines. Febuxostat, a xanthine oxidase inhibitor, has been shown to rescue vascular impairment in these models. The purpose of this study was to examine the individual and combined effects of obesity and chronic stress on neuroimmune cell populations, and assess if febuxostat is able mediate immune alterations.

Male mice (n=48) were assigned into either normal chow (lean) and high-fat diet (obese) groups. The lean animals …

Frontal Brain Injury: Effects On Flexibility, Impulse Control, And Attention, Christopher Matthew O'Hearn

Graduate Theses, Dissertations, and Problem Reports

Traumatic Brain Injury (TBI) is defined as an impact to the head, penetration of the skull, or rapid deceleration of the skull, resulting in an alteration of brain function or neurological deficit. Cognitive deficits are common following TBI and often go unresolved due to a lack of effective treatments. These deficits often perseverate into the chronic post injury phase, so the development of rehabilitative strategies is imperative. Behavioral flexibility, impulse control, and attention are a few cognitive processes that are commonly affected by TBI. The current research compares these processes between rats with and without a severe frontal brain injury …

Impact Of Sire Selection And Breed On Parasite Resistance In Sheep, Andrew Ryan Weaver

Graduate Theses, Dissertations, and Problem Reports

Selection within and among breeds are strategies to mitigate the impact of parasitism given failing chemotherapeutics. While Texels have improved marketability compared to other parasite-resistant breeds, the mechanism by which Texels reduce fecal egg count (FEC) is unclear. The immune response to Haemonchus contortus (Hc) was compared in Texel, parasite-resistant St. Croix, and parasite-susceptible Suffolk sheep. Adult worms exposed to St. Croix- and Texel-derived peripheral blood mononuclear cells and serum in vitro had greater binding around the reproductive structures than Suffolk and worm egg release tended to be affected by breed (P = 0.09). Resistance in Texels …

The Exploration Of Nanotoxicological Copper And Interspecific Saccharomyces Hybrids, Matthew Joseph Winans Phd

Graduate Theses, Dissertations, and Problem Reports

Nanotechnology takes advantage of cellular biology’s natural nanoscale operations by interacting with biomolecules differently than soluble or bulk materials, often altering normal cellular processes such as metabolism or growth. To gain a better understanding of how copper nanoparticles hybridized on cellulose fibers called carboxymethyl cellulose (CMC) affected growth of Saccharomyces cerevisiae, the mechanisms of toxicity were explored. Multiple methodologies covering genetics, proteomics, metallomics, and metabolomics were used during this investigation. The work that lead to this dissertation discovered that these cellulosic copper nanoparticles had a unique toxicity compared to copper. Further investigation suggested a possible ionic or molecular mimicry …

Evolutionary Genomics Of Dynamic Sex Chromosomes In The Salicaceae, Ran Zhou

Graduate Theses, Dissertations, and Problem Reports

Identifying the sex-determination region (SDR) and other genomic features of sex chromosomes are of great importance in the studies of the evolution of sex. However, the process of accurately identifying the size and location of the SDR is often difficult, even when a genomic sequence is available. This usually is hindered by large repetitive elements and a lack of recombination in the SDR. In this thesis, I assemble sex chromosomes with whole genomic sequencing data, identify SDRs and explore their genomic features in two sister species from the Salicaceae family. I also develop an interpretation of the lability of the …

Utilizing Conservation Genetics As A Strategy For Recovering The Endangered Candy Darter (Etheostoma Osburni) In West Virginia, Brin E. Kessinger

Graduate Theses, Dissertations, and Problem Reports

The Candy Darter (Etheostoma osburni) is a small freshwater fish native to the New River drainage in West Virginia and Virginia that was listed as endangered in November 2018. It has been extirpated from much of its historic range in West Virginia, restricting it to the Gauley and Greenbrier river drainages. In addition to extirpations, the species is threatened by introgressive hybridization with the invasive Variegate Darter (E. variatum). Previous research primarily focused on hybridization, but population genetic analyses were limited. Population genetic analyses aim to identify distinct populations through genetic structure and characterize the levels …

Evaluation Of The Performance Of Probabilistic Genotyping Software On Complex Mixture Samples, Kristen Newland

Graduate Theses, Dissertations, and Problem Reports

Probabilistic genotyping systems use sophisticated algorithms to aid DNA analysts with complex mixture interpretation. These systems are used to generate a likelihood ration (LR) which is used to provide the analyst with the statistical weight of the match between an evidence profile and a known contributor. Complex mixtures occur from samples consisting of more than two contributors and samples that have experienced degradation or consist of low template quantity.

This study was performed to compare the performance of three mixture analysis software tools on the same set of samples to determine the capabilities of each software, false inclusions, and false …

The Wiring Logic Of Identified Serotonergic Neurons Across Olfactory Networks In Drosophila, Kaylynn E. Coates

Graduate Theses, Dissertations, and Problem Reports

Serotonin is a ubiquitous neuromodulator that confers flexibility in networks to modulate a wide array of behavioral and physiological processes. However, due to the complexity and heterogeneity of serotonergic systems, it has been challenging to determine the patterns of connectivity as well as the physiological contexts that influence individual serotonin neurons. In this dissertation, I use two serotonergic neurons which innervate the Drosophila olfactory system, the CSDns, as a model to explore these broad questions comprehensively using anatomical approaches. I first show that the CSDns have distinct connectivity relationships with populations of antennal lobe principal olfactory neurons and that their …

Assessment Of Protein Quality, Lipid Metabolism, Hepatic Transcriptome And Safety Of A Silver Carp (Hypophthalmichthys Molitrix) Derived Sarcoplasmic Protein Powder., Derek Cole Warren

Graduate Theses, Dissertations, and Problem Reports

Fishery resources are currently operating either near optimal yield or at levels with elevated risk for fish stock depletion. A solution for overcoming limitations of natural fish resources is through utilization of less desirable fish species and fish processing by-products. Water-soluble sarcoplasm proteins consist of 25 – 30% of protein in carp, are lost in wash water during processing and can be recovered and freeze-dried to produce a protein-rich powder (CSP). The objective of this project was to evaluate the protein quality and safety of CSP, assess diets consisting of CSP or commercial milk proteins effects on lipid metabolism, and …

Improving The Biological Control Of Persicaria Perfoliata (Polygonaceae) Using Rhinoncomimus Latipes Korotyaev (Coleoptera: Curculionidae), Jaewon Kim

Graduate Theses, Dissertations, and Problem Reports

Persicaria perfoliata (L.) H. Gross (Polygonaceae; Mile-a-minute weed) is a rapid-growing invasive vine introduced from eastern Asia to northeastern United States in the 1930s. This vine has been invaded in disturbed areas and reforestation sites in 15 states in the U.S. and forms dense, monocultural patches that may inhibit natural forest regeneration. To control this weed, a host-specific biocontrol agent, Rhinoncomimus latipes Korotyaev (Coleoptera: Curculionidae) has been released in the P. perfoliata invaded states in the U.S. during the past 15 years. Currently, R. latipes is released by hand to the invaded area where the presence of the weed is …

Genetic And Biochemical Characterization Of Ergot Alkaloid Synthesizing Fungi And Their Symbionts, Matthew Duane Maust

Graduate Theses, Dissertations, and Problem Reports

Ergot alkaloids are fungal tryptophan derived toxins which affect mammalian circulation and neurotransmission. These compounds are biosynthesized by a conserved genetic pathway, known as the ergot alkaloid synthesis (EAS) pathway by fungi belonging to the ascomycete families Trichocomaceae and Clavicipitaceae. Several Ipomoea species and related plants in the morning glory family harbor vertically transmitted symbiotic fungi in the genus Periglandula, also members of Clavicipitaceae, that produce ergot alkaloids. Metabolomic analysis of seeds identified a previously uncharacterized glycoside form of the pharmaceutically important ergot alkaloid, ergonovine. Several species belonging to the fungal genus Metarhizium have recently been shown to have the …

The Role Of Genotype In Saccharomyces Cerevisiae Resistance To 4-Methylcyclohexanemethanol, Michael C. Ayers

Graduate Theses, Dissertations, and Problem Reports

The chemical 4-methylcyclohexanemethanol (MCHM) spilled in the Elk River near Charleston, WV in January 2014, impacting the drinking water of 300,000 residents. Initial studies on MCHM following the spill attempted to characterize its toxicological effects in animals, but largely ignored characterization of its effects on cellular pathways and metabolism. In this study, I used this chemical as a novel stressor for the model eukaryote S. cerevisiae to explore the relationship of genotype and stress phenotypes. Initial exploration characterized the stress phenotype of MCHM in yeast through growth assays, cell cycle analysis, and transcriptomic data. MCHM exposure caused cells to arrest …

Haemonchus Contortus Antigen Identification And Use Of Tropomyosin In Ovine Vaccine Development, Brynnan P. Russ

Graduate Theses, Dissertations, and Problem Reports

Globally, the small ruminant industry loses hundreds of millions of dollars due to parasitism by the gastrointestinal nematode Haemonchus contortus. This parasite feeds on blood in the host’s abomasum leading to disease including anemia, hypoproteinemia, lethargy, and death. There have been exhaustive efforts to manage this parasite including different management applications, anthelmintic treatment, and now integration of resistance genetics into a flock. Like antibiotics, overuse of anthelmintics has led to resistance of H. contortus to these drugs. Therefore, other methods of control are the main focuses of many research initiatives. St. Croix are a resistant breed of sheep that mount …

Nitrogen Fertilization Decouples Roots And Microbes In Temperate Forests: Impacts On Soil Carbon And Nitrogen Cycling, Joseph E. Carrara

Graduate Theses, Dissertations, and Problem Reports

Since the start of the industrial revolution the burning of fossil fuels has resulted in enhanced nitrogen (N) inputs into temperate forests through atmospheric deposition. As N is the limiting nutrient for tree growth across most forests, these inputs have generally enhanced above-ground biomass accumulation. However, the impacts of added N on soil carbon storage (C) are less straightforward. While the mean N response across studies is an enhancement of soil C, these results are variable with some studies reporting net C losses. The classic paradigm posits that N enhances soil C through negative effects on fungal decomposers. However, some …

Comparison Of The Batch And Individual Log Study Methods For Use In Determining Log Breakeven Pricing, Levi Eric Sisler

Graduate Theses, Dissertations, and Problem Reports

Understanding log yields and overrun is critical to a profitable sawmill operation. Lumber yield and overrun data can be gathered through one of two types of sawmill studies: batch studies or individual log studies. Little to no research has previously been conducted to determine if one method provides more reliable results than the other method. For this effort, 16 batch studies were conducted. Individual log studies were also conducted on the same logs, allowing a direct comparison of the results from both study types. A breakeven analysis was conducted for each study type, which determined the amount of variability in …

Grainyhead-Like 2 Sensitizes Cells To Natural Killer Cell Cytotoxicity And Promotes The Interferon Response, Ian Philip Macfawn

Graduate Theses, Dissertations, and Problem Reports

Our research determined that the epithelial master transcription factor Grainyhead-like 2 (GRHL2) promotes sensitivity to Natural Killer (NK) cell-mediated killing, and modulates the interferon I (IFN-I) response of epithelial cells. Immune surveillance by NK cells constitutes a major selective pressure for circulating tumor cells. Epithelial (GRHL2-expressing) cells exhibited significantly higher rates of NK conjugation, a crucial step in direct cell-mediated cytotoxicity. Mechanistically, GRHL2 upregulates expression of intercellular adhesion molecule 1 (ICAM-1), a cell surface molecule critical for NK to target cell synaptogenesis. GRHL2 epigenetically regulates gene expression, and we found that GRHL2 mutant proteins unable to interact with the epigenetic …

Characterization Of The Biochemical Properties Of Nudt8, A Novel Coa-Degrading Enzyme That Localizes To The Mitochondria, Evan W. Kerr

Graduate Theses, Dissertations, and Problem Reports

Coenzyme A (CoA) is a vital cofactor that is required for a variety of metabolic reactions including the TCA cycle and the synthesis and oxidation of fatty acids, amino acids and ketone bodies. The importance of CoA is underscored by its tight regulation, as prolonged elevations or inability to synthesize adequate amounts of this cofactor lead to severe metabolic dysfunction. Regulation of CoA biosynthesis has been extensively characterized, however less is known about regulation of CoA and its thioesters via degradation. Presently, two CoA-degrading enzymes, Nudt7 and Nudt19 have been identified as regulators of the peroxisomal pool of (acyl-)CoA in …

Avian And Salamander Response To Young Forest Management In West Virginia, Eric L. Margenau

Graduate Theses, Dissertations, and Problem Reports

This dissertation focuses on the effects of various young forest habitat management techniques on the avian and salamander community in West Virginia. Wildlife species associated with the nascent stage of forest succession are experiencing precipitous population declines throughout much of the eastern United States due to decreases in the amount of young forest area which have been brought on by changes in disturbance regimes over the past century. As a result, the need to find novel approaches for creating young forest habitats to sustain young forest wildlife populations is necessary. However, young forest habitat creation often negatively affects species that …

The Morphological, Physiological, And Genetic Underpinnings Of Intraspecific Salinity Tolerance In Sorghum Bicolor, Ashley N. Henderson

Graduate Theses, Dissertations, and Problem Reports

Decreases in land quality and quantity threaten the efficient production of agriculturally and economically pivotal crops. Such reductions in arable lands are a consequence of population growth and urbanization, and often result in the introduction of various abiotic stresses. The most common abiotic stressors include water limitation (drought), water logging (over watering), poor water quality (salinity), and extreme temperatures (cold, frost, heat). Each of these stressors negatively impact plant growth, development, and yield. Soil salinity, specifically, is a considerable constraint affecting lands used in agriculture. Salts in the soil rise both naturally and through anthropogenic factors making the abundance a …

Enabling And Threatening Factors Affecting Persistence. A Qualitative And Quantitative Study On Rural First-Generation Stem Students’ And Stem Faculty's Perspectives., Travis A. Miller

Graduate Theses, Dissertations, and Problem Reports

This study focuses on the factors that enable and threaten rural first-generation STEM students’ persistence. Limited empirical studies are available that focus on rural first-generation STEM majors’ persistence. Quantitative analysis was conducted using Kruskal Wallis H and Mann-Whitney U tests to determine any significant differences with the survey results. Content and thematic analysis was conducted on the student and faculty interviews to determine themes of enabling and threatening factors affecting persistence.

Enabling factors affecting persistence were found to be: Drive or Motivation, Experiences and skills, and Support. These were both faculty and student interview themes whereas a …

Stable Aggregate Dynamics And Carbon Storage In Acidified Forest Soils: Influence Of Atmospheric Deposition And Conifer Conversion At The Fernow Experimental Forest, J E. Kemner

Graduate Theses, Dissertations, and Problem Reports

This research explored effects of ecosystem change from increased atmospheric nitrogen (N) deposition and stand conversion from mixed-species hardwood to Norway spruce in three experimental watersheds at the Fernow Experimental Forest (FEF). I measured soil aggregation and organic matter (OM) content to investigate the influence of forest fertilization in Watershed 3 (WS3), a hardwood forest receiving (NH₄)₂SO₄ fertilizer, versus Watershed 7 (WS7), a natural hardwood forest. I compared WS7 to Watershed 6 (WS6), a converted Norway spruce (Picea abies) monoculture. I quantified WS6 and WS7 C and N ecosystem pools, including vegetation biomass, …

Comparing And Linking Organic Carbon And Iron In Soil And Headwater Stream In A Pasture And A Forest Catchment In A Central Appalachian Region, West Virginia, Lili Lei

Graduate Theses, Dissertations, and Problem Reports

Continued global warming and surface water brownification are two main environmental issues which have attracted attention and are related to soil organic carbon (SOC) cycling. Iron oxides differ in reducibility and thus have essential roles in regulating SOC preservation and remineralization in soil and transport of dissolved organic carbon (DOC) from soil to surface water. In the central Appalachian region, anthropogenic disturbances are increasing, which leads to major issues of soil degradation and depletion of SOC concentrations. Cropland and pasture soils are subject to intense disturbances compared to the forest soil, which may lead to differences in SOC fractions and …

Breast Cancer Associated Muscle Fatigue: Novel Targets To Improve Survival And Quality Of Life, Hannah Elizabeth Wilson

Graduate Theses, Dissertations, and Problem Reports

Women diagnosed with breast cancer (BC) currently represent the largest group of cancer survivors in the United States, accounting for over 20% of those living after a cancer diagnosis. Most BC survivors report an unusual degree of fatigue, which can present prior to diagnosis and continue for many years after treatment cessation. Recent studies show that deficits in muscle function predict shorter survival in cancer, perhaps due to the fact that fatigue is known to reduce a patient’s tolerance to anti-cancer therapies. Therefore, improving muscle function in BC patients has the potential to improve both quality of life and survival …

Evidence Of Y Chromosome Long Non-Coding Rnas Involved In The Radiation Response Of Male Non-Small Cell Lung Cancer Cells, Tayvia Brownmiller

Graduate Theses, Dissertations, and Problem Reports

Non-small cell lung cancer (NSCLC) is the number one cause of cancer related mortality in the United States and worldwide. Advanced and therapeutically resistant lung tumors contribute to the high rate of mortality from NSCLC, therefore there is a need for new methods of diagnosing and treating this disease. Long non-coding RNAs (lncRNAs) have been shown to be a crucial component of human molecular biology, regulating nearly every cellular pathway from chromatin condensation to transcription and translation. Furthermore, many lncRNAs have been classified as oncogenes or tumor suppressors, highlighting the various molecular mechanisms they are involved in regarding the formation …

Pulmonary Immune Responses To Respirable Elongate Mineral Particles Of Asbestiform And Non-Asbestiform Morphologies, Timur Khaliullin

Graduate Theses, Dissertations, and Problem Reports

Inhalation exposure to asbestiform elongate mineral particles (EMPs) may cause pulmonary fibrosis, lung and pleural cancer. At the same time, epidemiological evidence for non-asbestiform EMP pathogenicity is scarce, with little if any risk of cancer, but consistent findings of pneumoconiosis and increased mortality. Globally, conditions caused by asbestos exposures contribute most to the occupational cancer burden and are responsible for the increasing mortality for occupational respiratory diseases. Immunological components of the fiber-induced lesions are extremely understudied, partly due to the lack of comparable test articles. In this study I utilized respirable preparations of asbestiform and non-asbestiform riebeckite and tremolite to …

Central Appalachian Understory Red Spruce (Picea Rubens Sarg.) Growth Rates And Allometric Relationships, Joseph M. Gray

Graduate Theses, Dissertations, and Problem Reports

Red spruce (Picea rubens) was a prized timber species in West Virginia during the era of resource exploitation in the late 1800s and early 1900s. Consequently, Central Appalachian red spruce has faced large reductions in range and changes in stand composition. This region is relatively underrepresented in literature partially due to these constrictions. Investigating how stem growth occurs in young individuals can fill in some of our gaps in understanding the species and aid in restoration efforts. We sampled an array of high elevation sites on federal and state lands in West Virginia to analyze understory spruce growth …

Microbial Responses To Unconventional Oil And Gas Development May Alter Ecosystem Function In Headwater Streams, Rachel Michaels

Graduate Theses, Dissertations, and Problem Reports

The demand for natural gas, and the need for efficient extraction, has led to the development of unconventional oil and natural gas (UOG) techniques. Due to the novelty of UOG, the potential impacts to freshwater ecosystems are not fully understood. We used a dual pronged approach to study the effects of UOG development on microbial biodiversity and function via a laboratory microcosm experiment and a survey study of streams with and without UOG development within their watersheds. The laboratory microcosm study simulated stream contamination with produced water, a byproduct of UOG operation, using sediment collected from one high water-quality stream …

Targeting The Nt17 Of The Huntingtin Protein Via Natural And Chemical Modifications: Impact On Aggregation And Membrane Interactions, Faezeh Sedighi

Graduate Theses, Dissertations, and Problem Reports

Huntington Disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine domain (polyQ) in the first exon of the huntingtin protein (htt-exon1). The major hallmark of HD is the accumulation of aggregates into proteinaceous inclusion bodies. PolyQ expansion in huntingtin promotes self-assembly into a variety of toxic aggregates such as oligomers, fibrils, and amorphous aggregates. The resulting heterogeneous mixture of distinct species makes it difficult to assign a toxic function to specific aggregate structures. In addition, htt interacts with a variety of membranous surfaces. The first 17 amino acids (Nt17) of htt directly flanking the polyQ domain functions …