Life Sciences Commons^™

Xanthine Oxidoreductase, Uric Acid, And Iron Homeostasis: Discovering A Therapeutic Vulnerability In Breast Cancer, Matthew G. Chapa

Graduate Theses, Dissertations, and Problem Reports (ETD)

Breast cancer remains the most frequently diagnosed malignancy and the leading cause of cancer related deaths in women. This is primarily due to distant metastases, which highlight the necessity to understand factors that contribute to breast cancer progression. Emerging evidence associates decreased tumor xanthine oxidoreductase (XOR) expression with a poorer prognosis, increased recurrence, and a more aggressive phenotype. While healthy liver, intestines, kidneys, and breast tissue have robust XOR expression and activity, there is a tendency for this to be ablated in carcinogenesis. This dissertation investigates XOR's role in breast cancer and identifies its product, uric acid (UA), as possessing …

Expanding The Vibrating Sharp-Edge Spray Ionization Toolkit For Oligonucleotide Characterization, Sultan Mahmud

Graduate Theses, Dissertations, and Problem Reports (ETD)

A gentle or soft Ionization process is a critical component in native mass spectrometry (MS) to lift the biomolecules from the bulk solution into the gas phase environment of the mass spectrometer preserving their shape, topology and non-covalent interactions. Electrospray ionization (ESI) facilitates structural preservation of proteins, nucleic acids and their complexes and as a result it has been extensively used in native MS. However, in negative ion mode, ESI is somewhat limited in sensitivity due to corona discharge effect resulting from the requirement of a high amount of voltage. This often disrupts the ESI process and may not preserve …

Co-Transmission Is Co-Opted For The Coordination Of Auditory Sensory Integration, Marryn M. Bennett

Graduate Theses, Dissertations, and Problem Reports (ETD)

Corollary discharge circuits (CDCs) are conserved mechanisms for sensory modulation during species specific behavioral programs. Many behaviors require multiplexed differential sensory modulation for proper execution. Co-transmission of fast and slow neurotransmitters allows for distinct modulation of different downstream targets within one sensorimotor circuit. However, studying co-transmission within the context of modulatory circuits like CDCs requires complete knowledge of behavioral circuits and precise tools for individually determining the implications of each transmitter on its targets. In this dissertation, I used a conserved set of corollary discharge interneurons in Drosophila melanogaster as a model to study the intricacies of sensory modulation through …

Simulated Slot Machine Gambling In Relation To Sign-Tracking, Polina Krom

Graduate Theses, Dissertations, and Problem Reports (ETD)

The propensity to attribute incentive salience to reward-related cues, or sign-tracking (ST) has been linked to addiction in animal models and some initial human data. The current study explores the role of sign-tracking (ST), as a potential risk factor for problematic slot machine gambling, which abundantly features audiovisual reward-related cues, henceforth sensory features. A sample of healthy participants without gambling problems (n = 30) completed a Pavlovian-to-Instrumental Transfer (PIT) paradigm to assess ST propensity and played on a realistic slot machine simulator consisting of two versions: with sensory features (SF+) and without (SF-). Each game version had fixed bet sizes, …

Monitoring West Virginia Wastewater For Norovirus: A Test Case For Tracking Foodborne Illness Outbreaks In Rural Communities Using Wastewater, Haley M. Phillippi

Graduate Theses, Dissertations, and Problem Reports (ETD)

Foodborne illnesses are a global public health challenge. Foodborne illnesses, like norovirus, often have a large disease and societal burden. Norovirus is a single-stranded, positive-sense RNA virus, with 10 identified genogroups (GI-GX). Genogroups GI and GII are responsible for nearly all human cases of acute gastroenteritis worldwide. In the United States, HuNoV is not notifiable case-by-case. Instead, outbreaks are reported to national surveillance systems when two or more cases are epidemiologically linked. Most norovirus outbreaks occur during Winter to early Spring, however, certain individuals may still shed and transmit the virus without being detected or reported. Wastewater monitoring is a …

Evaluation And Identification Of Novel Viruses In Wild Fishes Using Varied Molecular Biology Techniques, Clayton Douglas Raines

Graduate Theses, Dissertations, and Problem Reports (ETD)

Viruses are among the most abundant biological entities on Earth, yet their diversity and ecological roles in aquatic vertebrates, particularly fishes, remain poorly characterized. This dissertation advances fish virology through integrative approaches that combine historical context, molecular diagnostics, and genomic discovery. A novel hepadnavirus (ApHBV) was identified in asymptomatic Alosa pseudoharengus, emphasizing the prevalence of subclinical infections in migratory forage species. In Catostomus commersonii, transcriptomic profiling revealed sexually dimorphic immune responses to hepatitis B and C-like viruses, highlighting complex host-pathogen dynamics. In Micropterus nigricans, next-generation sequencing uncovered a novel nackednavirus and multiple adomaviruses within hyperpigmented lesions, expanding …

Ciliary Arl14b In Vision, Alexis Breann Crockett

Graduate Theses, Dissertations, and Problem Reports (ETD)

Primary cilia are highly specialized organelles that regulate signaling, trafficking, and sensory perception across multiple tissues, including the retina. The small GTPase ADP Ribosylation Factor-Like Protein 13B (ARL13B) is an atypical ARF-family protein enriched in cilia. ARL13B acts as a guanine exchange factor (GEF) for another small GTPase ARF-like Protein 3 (ARL3). Mutations in ARL13B cause Joubert syndrome, a ciliopathy characterized by brain malformation, developmental delays, and retinal degeneration. Despite ARL13B’s known ciliary localization and clinical relevance, ARL13B’s precise functions in cilia remain poorly defined. This dissertation investigates the cilia-specific roles and GEF-specific roles of ARL13B in photoreceptors using two …

Exploring The Ruminal Microbiome And Its Impacts On Feed Efficiency In Beef Cattle, Taylor Simone Sidney

Graduate Theses, Dissertations, and Problem Reports (ETD)

The ability for beef cattle to utilize feed efficiently is a critical determinant for both economic and environmental sustainability in livestock production. However, despite extensive research, the complex microbial ecosystem within the rumen and its relationship to feed efficiency remain incompletely understood. This dissertation explores the physiological and microbial foundations of feed efficiency by characterizing how rumen microbial communities and their functions differ among beef cattle with divergent residual feed intake (RFI) phenotypes and how the RFI status of beef cattle influenced their response to dietary interventions such as supplementation with a Bacillus-based feed additive. In the first study, …

Sleep, Endocannabinoid Signaling, And Cortical Processing In Mouse Models Of Autism Spectrum Disorder, Bryan Rodriguez

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sleep plays a crucial role in memory consolidation, neuronal plasticity, and cognitive function. Individuals with autism spectrum disorder (ASD) often experience sleep disturbances, which are positively correlated with symptom severity. However, on the surface, sleep architecture is remarkably normal under baseline conditions in many rodent models of ASD. The goals if this dissertation were to investigate whether regulation of sleep, biochemical signaling during sleep, and downstream consequences of sleep on behavior are altered in two mouse models of ASD. In Aim 1, we tested the hypothesis that sleep phenotypes emerge in ASD models under conditions of high sleep pressure. We …

Bridging The Gap Between Structural And Cellular Biology: Insight Into The Organization Of Glycolytic Enzymes In Cells, Heather Hansen

Graduate Theses, Dissertations, and Problem Reports (ETD)

Glycolytic enzymes are spatially organized in the cytoplasm, and are shown to localize with cellular structures such as the plasma membrane, F-actin, mitochondria, or associate independently within the cytosol. The assembly of these enzymes is hypothesized to regulate pathway flux to meet the energetic needs of the cell. However, it is unclear whether all of these assemblies have the same mechanism of formation or function in the cell. We investigated the role of glycolytic enzyme assemblies in cells, using the glycolytic “gatekeeper” enzyme phosphofructokinase-1 (PFK1). PFK1 is extensively regulated by multiple mechanisms, including over 20 allosteric ligands, post translational modifications, …

Probing The 10-23 Dnazyme Catalytic Core: Insights From Structural And Mechanistic Studies, Evan Rhyse Cramer

Graduate Theses, Dissertations, and Problem Reports (ETD)

The 10-23 DNAzyme is a catalytically active DNA oligonucleotide capable of cleaving RNA at purine-pyrimidine junctions in the presence of divalent metal ions, most notably magnesium. Despite its promise as a programmable RNA knockdown tool, its clinical and biotechnical utility has been hampered by limited structural characterization, low catalytic efficiency under physiological conditions, and poor understanding of its in-cell activity. This dissertation presents a comprehensive framework for the structural and functional analysis of DNAzymes using the 10-23 DNAzyme as a model system. In the absence of high-resolution structures, we first employed detailed in vitro biochemical assays to map essential residues …

Effects Of Environmental And Anthropogenic Gradients On Fish Beta Diversity In Central Appalachian Streams, Alanna Kaylee Lowther Smith

Graduate Theses, Dissertations, and Problem Reports (ETD)

Understanding the environmental and spatial drivers of community composition is essential for conserving freshwater biodiversity. We examined how environmental gradients, land cover, and spatial structure influence fish beta diversity in wadeable streams across West Virginia, USA. We quantified total beta diversity and partitioned it into species replacement and richness difference components and used local contributions to beta diversity (LCBD) to identify compositionally unique sites. Community–environment relationships were evaluated with distance-based redundancy analysis (dbRDA), and a beta regression GLMM was used to test how elevation, slope, land cover, and stream order (factor) predicted LCBD while accounting for spatial structure (dbMEMs) and …

Identification, Mapping And Treatment Of The Invasive Rosa Multiflora Using Unmanned Aerial Systems And Machine Learning Models, Kylie Virginia Shaw

Graduate Theses, Dissertations, and Problem Reports (ETD)

Invasive species are introduced species that cause detrimental impacts to the native ecosystem or cause harm to human health. The work necessary for land managers to survey for and treat invasive species takes up limited time, labor, and financial resources. This study assesses how Unmanned Aerial Systems (UAS) and machine learning models can be used to make the identification, mapping, and treatment of invasive vegetation more efficient and effective. A UAS-mounted multispectral camera captured images of our target species, Rosa multiflora (multiflora rose), throughout its growing season in southwest Pennsylvania. A random forest machine learning model was trained on these …

Watershed-Level Survey Of Antimicrobial Resistance From Onsite Wastewater Systems, Trey Franklin Clark

Graduate Theses, Dissertations, and Problem Reports (ETD)

The emergence of antimicrobial resistance (AMR) has quickly become one of the largest global health and development threats. Research related to environmental modes of transmission of AMR has accelerated in recent years, and the US Environmental Protection Agency is particularly interested in this emerging contaminant. Knowledge of how onsite (decentralized) wastewater treatment systems contribute to this issue is lacking, so this research serves to analyze and quantify the environmental dissemination of AMR and fecal contamination from these sources at a watershed level while using statistical analysis to assess relationships between physiochemical, spatial, and sampling parameters. This research surveyed four watersheds …

Canine Agility On The A-Frame Obstacle, Derek Wheeler

Williams Honors College, Honors Research Projects

Agility dogs rely on speed, strength, and precision to safely complete obstacles, such as the A-frame. These athletes can experience injuries in training or competition and the variability in multiple repetitions is undocumented. The purpose of this study was to evaluate whether canine mass and trained contact behavior affected performance variables, including number of footfalls, obstacle completion time, and velocity between repetitions. Twenty-one actively competing dogs, at the masters level in American Kennel Club agility, were recorded completing two repetitions of the A-frame under standardized conditions. Paw placements were tracked manually frame by frame in XMALab and statistical analyses including …

Ingestion Of Expanded Polystyrene By Procambarus Spp: A Toxicology Report, Garrik Neill Catania, Panagiotis Antonios Tsarouhas

Williams Honors College, Honors Research Projects

This project aims to be a toxicology report into the ingestion of expanded polystyrene by Procambarus spp. The goal would be to prove that ingestion of this plastic could lead to harm of the crayfish and that its presence in the environment of the crayfish could be a serious ecological problem. This project will take three groups of ten crayfish each and over a period of approximately seven weeks the crayfish will be monitored for changes due to their respective treatments. One group will serve as the control and will have nothing unique happen to them, one will serve as …

Hip Strengthening In Female Collegiate Soccer Players: Effects Of Gluteus Medius Strengthening On Biodex Balance Scores, Caitlin Bruni, Morgan Shansky

Williams Honors College, Honors Research Projects

The purpose of this study is to examine the effects of gluteus medius (Gmed) strengthening program on single leg stability in collegiate female soccer players. Given the role of Gmed in stabilizing the hip, improving its strength may reduce lower extremity injury risk. Weakness in Gmed has been linked to conditions such as Anterior Cruciate Ligament (ACL) tears and Patellofemoral pain syndrome (PFPS). This study investigates whether an 8-week strength program improves single-leg stability, measured using the Biodex Balance System. Thirty-three female soccer players (18-23 years) from The University of Akron were recruited, with 22 completing the study. Participants underwent …

Perceived Shoulder Discomfort In Adolescent Swimmers, Abigail Daniel

Williams Honors College, Honors Research Projects

Competitive swimming is a sport that athletes traditionally start at a young age, training for many years to build up an aerobic base, learn the best techniques of the sport, and gain experience racing. While this increases the ability to perform and adapt to training in the sport, it also can lead to shoulder tightness, soreness, and even injury. PURPOSE: To investigate any correlation between the perceived shoulder discomfort of adolescents to flexion and extension measurements. METHODS: Participants (N=25) were recruited in person from a swimming club. Swimmers were between 13-18 years old and varied in participation level from recreational …

Review Of Research On Relative Energy Deficiency In Sport (Red-S), Paige Mcmaster

Williams Honors College, Honors Research Projects

The following research article review serves to summarize and evaluate peer-reviewed research articles on the topic of Relative Energy Deficiency in Sport (RED-S). The paper will cover RED-S's effect on males versus females, endurance athletes versus non-endurance athletes, recreational athletes versus competitive athletes, and different age groups. Methodology includes strategically reviewing current literature and providing common themes or key points. The goal is to effectively summarize the subject of RED-S, provide in-depth understanding of the condition, and establish the need for education to prevent or reduce the incidence of RED-S.

Leveraging Large-Language Models As Collaborative Reasoning Partners To Enhance Scientific Workflow, Douglas B. Craig

Wayne State University Dissertations

The rise of Large Language Models (LLMs) has transformed artificial intelligence, offering advanced capabilities in text generation, natural language understanding, and multi-modal interactions. However, their use as standalone tools or as perceived repositories of static knowledge has limited their potential in real-world applications, especially in critical domains like healthcare and scientific research, where transparency, explainability, and accountability are paramount. This research addresses these limitations by conceptualizing LLMs as reasoning engines within a hybrid framework that integrates retrieval-augmented generation (RAG) and case-based reasoning (CBR) within a note-taking application.

The study introduces a novel system, LmRaC, designed to enhance the reliability, explainability, …

Using Genetically Heterogenous Mice To Identify Regulators Of Immune Checkpoint Blockade Response, Justin Hackett

Wayne State University Dissertations

Immune Checkpoint Inhibitors (ICI) have dramatically improved patient outcomes in metastatic lung cancer, metastatic melanoma, subtypes of renal cancer and others. However, despite the clinical success, most patients still fail to have a durable response. Understanding what determines response and predicting who will respond to therapy is essential to improving patient outcomes. To investigate genetic underpinnings of ICI response we utilized F1 crosses of C57Bl/6 with Diversity Outbred mice (DOB6F1) and multiple Collaborative Cross (CC) strains to identify and validate (respectively) genetic loci that associated with response to ICI. The genomic data suggested that the lactation and immunomodulatory peptide prolactin …

The Role Of Fruiting Bodies In Protecting A Community Of Myxococcus Xanthus Spores From The Environment, Dave Lall

Wayne State University Dissertations

Environmental microorganisms have evolved a variety of strategies to survive fluctuations in environmental conditions, including the production of biofilms and differentiation into spores. Myxococcus xanthus are ubiquitous soil bacteria that produce starvation-induced multicellular fruiting bodies filled with environmentally resistant spores (a specialized biofilm). Isolated spores have been shown to be more resistant than vegetative cells to heat, ultraviolet radiation, and desiccation. The evolutionary advantage of producing spores inside of fruiting bodies is not clear. Here, we examine a hypothesis that the fruiting body provides additional protection from environmental insults. We developed a high-throughput method to compare the recovery (outgrowth) of …

Environmental Pollution And Early-Life Metabolic Programming, Lisa Koshko

Wayne State University Dissertations

Substantial evidence demonstrates that parental pollutant exposures can induce harmful health effects in the offspring, including the predisposition to Type II Diabetes. As rates of Type II Diabetes continue to rise in younger populations, a crucial gap lies in understanding the role of parental influence in the etiology of later-life metabolic disease. Therefore, the central goal of this work was to determine how early life exposure to smoking level benzene, an endocrine-disrupting air pollutant, affects the metabolic health of offspring, and to identify potential developmental mechanisms involved in disease susceptibility. This goal was achieved using two models of early life …

Assessing Genetic Diversity And Population Structure In The Imperiled Aconitum Reclinatum (White Monkshood), An Endemic Wildflower Of Central Appalachia, Diamanda A. Zizis

Master’s Theses

Aconitum reclinatum, white monkshood (Ranunculaceae), is a Pennsylvania critically imperiled plant species found in five states of the Appalachian region of the United States: Pennsylvania, West Virginia, Virginia, North Carolina, and Tennessee. This plant is adapted to cool, moist environments but faces threats from increasing habitat loss, deer browse, logging, and changes in rainfall and temperature associated with climate change. Comprehensive knowledge of A. reclinatum genetic population structure remains limited. To address this, we collaborated with Natural Heritage programs within the range of A. reclinatum to sample populations across the species distribution and generate a genotyping-by-sequencing data set of …

Assessing Arbuscular Mycorrhizal Fungal Community Composition And Diversity Across A Land-Use Gradient In Eastern Washington Prairies, Katherine I. Cole

EWU Masters Thesis Collection

Arbuscular mycorrhizal fungi (AMF) are key to healthy, functioning terrestrial ecosystems worldwide. Associating with over 80% of all extant land plants, they play a pivotal role in nutrient cycling, and contribute to overall plant health. Given their significance to terrestrial ecosystems, AMF have a crucial role to play in the successful restoration of Eastern Washington’s native prairies. However, AMF community composition is significantly altered by the commercial agricultural practices used extensively in this region for over 100 years. The Eastern Washington University (EWU) Prairie Restoration Project aims to restore ~120 acres of farmland to native prairie. This research provides insight …

Effects Of Variable Nitrogen Fertilization Rates And Dried Distillers Grains Plus Solubles Supplementation On Forage Use, Animal Performance, And Economic Outcomes Of Steer Calves Grazing Winter Wheat Pastures, Cody E. Gruber, Miriam A. Snider, Michelle L. Johnson, Tom Hess, Elizabeth B. Kegley, J. Daniel Rivera, James A. Mitchell, M. Shane Gadberry

Animal Science Faculty Publications and Presentations

With the continued increase of fertilizer prices, stocker cattle producers may utilize alternative management strategies to mitigate costs and extend the grazing season to achieve better utilization of a wheat (Triticum aestivum L.) crop. One potential strategy is to reduce pasture nitrogen (N) fertilization rates combined with animal dietary supplementation. In this 3-year (yr) study, wheat pastures (1.62-hectare (ha)) were stocked at fixed rates of 2.47 and 4.94 steer/ha in the fall and spring respectively. Nitrogen was applied as urea to experimental pastures at three different rates: 1) 100.9 (100N), 2) 134.5 (135N), and 3) 168.1 kg N/ha (168N). These …

Investigating The Role Of Prostasin In Angiogenesis: A Chorioallantoic Membrane Model Approach, Zaima Aline

Honors Undergraduate Theses

Prostasin, also known as PRSS8 or CAP1, is a glycosylphosphatidylinositol (GPI)-anchored extracellular serine protease involved in various physiological and pathophysiological processes. Prostasin expression is observed during key phases of trophoblast invasion and placental development, critical steps in embryo implantation in Rhesus monkeys. This suggests a role for prostasin in extracellular matrix remodeling and tissue invasion, both essential for a healthy pregnancy. Moreover, prostasin appears vital for development as studies in mice show that a germline knockout of the gene leads to significant placental defects and eventual embryonic death, highlighting its importance in vascular and structural development within the placenta.

Building …

Examining The Effect Of A High Fat Diet On The Expression Of Adipokines In A Murine Model Of Barrett's Esophagus, Saagar A. Shah

Honors Undergraduate Theses

Chronic acid reflux results in injury to the esophagus and the development of Barrett’s Esophagus (BE). BE elevates the lifetime risk for a patient to develop Esophageal Adenocarcinoma (EAC). Clinically, one of the main risk factors for BE and EAC is obesity, which alters the secretion of inflammatory cytokines by adipocytes, also referred to as adipokines. Conflicting reports have been made to the expression of adipokines and their receptors in the progression to esophageal cancer. Utilizing an inflammation-based mouse model for BE, we hypothesize that alterations in the expression of adipokines and their receptors favor an inflammatory environment associated with …

Unravelling The Role Of Two-Component Systems In Mycobacterium Abscessus, Andrea C. Molero Perez

Honors Undergraduate Theses

Mycobacterium abscessus (Mab) is an emerging pathogen within the nontuberculous bacteria (NTM) which poses a threat due to its complex multi-drug resistance and opportunistic nature. It is predicted that only 45.6% of patients will have successful treatment, with immunocompromised and cystic fibrosis patients being the most threatened. Moreover, investigating new treatment approaches is key to responding to this public health issue. Two-component systems (TCS) are regulatory pathways that play a pivotal role in bacterial survival and virulence. These systems are composed of a sensor histidine kinase (HK) and cognate response regulator (RR) protein that senses environmental cues and triggers specific …

A Tail Of Two Fishes: Exploring Population Structure In Two Species Of Fishes Across The Galápagos Islands, Hillary Quach

Honors Undergraduate Theses

The Galápagos Islands, a UNESCO World Heritage Site and a biodiversity hotspot with high levels of endemism, is home to over 440 species of fishes. Marine conditions across the Archipelago are greatly influenced by ocean currents in the region. The Pacific Equatorial Undercurrent, South Equatorial Current, and the Humboldt Current deliver waters rich in nutrients across the three major regions within the Galápagos (central, north, and west). These conditions create a dynamic environment close to the equator, enabling diverse species to thrive in distinct parts of the Galápagos. Despite the rich biodiversity in the region and diverse oceanographic conditions, there …