Life Sciences Commons^™

Mctr3 Mitigates Cigarette Smoke-Induced Pulmonary Inflammation And Damage, Yu Par Aung Myo

Theses and Dissertations

Smoking is deleterious to our lungs and can precipitate in a multitude of diseases, including chronic obstructive pulmonary disease (COPD). COPD is primarily caused by smoking cigarettes and is a major public health issue. Current therapies only treat symptoms without halting or reversing disease progression, thus highlighting a large unmet need to develop new therapies. We address this gap by investigating maresin conjugate in tissue regeneration 3 (MCTR3) which is a newly discovered specialized pro-resoling mediator (SPM) that has the novel property of promoting tissue repair and regeneration in addition to being anti-inflammatory and pro-resolving. For the first time, we …

Physiological Responses And Plant Trait Interactions With Coastal Dune And Swale Development, Emily C. Riffe

Theses and Dissertations

Vegetation is crucial to coastal ecosystems experiencing climate change and storm-induced disturbance. Plant species interact with the physical environment and are considered “ecosystem engineers.” Sand dunes and barrier islands are at the forefront of climate change impacts as they are barriers that protect landward habitat and communities. Nature based solutions are utilized to protect infrastructure on developed coastlines. Understanding how dominant plant species interact with and alter the physical environment enhances our understanding of the mechanisms of change and consequences to the system. The goal of this research was to quantify physiological and functional trait differences in dominant species found …

The Comparative Effects Of A Thermal Gradient On The Age And Growth Characteristics Of Largemouth Bass (Micropterus Nigricans), And Atlantic Cod (Gadus Morhua), Whitney Hall

Theses and Dissertations

Thermal gradients impact fishes differently, due to variations in ecological niches and physiological adaptations. I assessed the effects of temperature on Largemouth Bass (Micropterus nigricans) and Atlantic Cod (Gadus morhua) using data from peer-reviewed journals, state records, and fisheries agencies. For Largemouth Bass, I analyzed the relationships between air temperature (MAT_min°C, MAT24hr°C, and MAT_max°C), and growth parameters including maximum length and weight, growth rate (K), longevity, and total length-at-ages 3, 5, and 8 years (TLAge_3,5,8), using least squares regression. Significant correlations were found between all temperature and growth metrics. Positive correlations were found between …

Karyotyping As A Method To Verify Phylogenetic Relationships Among The Enneacanthus Species, Ophelia A. Anderson

Theses and Dissertations

The Enneacanthus genus consists of three species of freshwater fish endemic to eastern North America: E. obesus (Banded Sunfish), E. gloriosus (Blue Spotted Sunfish), and E. chaetodon (Black Banded Sunfish). Previous studies using molecular data suggest that E. obesus and E. gloriosus are more closely related, with E. chaetodon as the most distantly related species in the genus. This study investigates the phylogenetic relationship among the Enneacanthus species, using karyotype characteristics - chromosome number, morphology and fundamental number - as comparative metrics. Chromosome spreads were obtained from scale and gill epithelium samples collected between 1993 and 1994. Prepared slides …

Caspases Protect Against Hyperglycemia Induced Necroptosis-Like Cell Death In Brain Endothelial Cells, Aleena S. Mathew

Theses and Dissertations

Acute diabetes characterized by high spikes in blood glucose levels in association with severe hyperglycemia can lead to an increased risk of ischemic stroke in the brain. To better understand high blood glucose levels, hyperglycemia, in the brain we explored its effects on endothelial cells. Endothelial cells line the inner walls of blood vessels and are directly impacted in hyperglycemia. Brain endothelial cells are a major component of the blood brain barrier (BBB) which tightly regulates the brain’s microenvironment. The type of cell death such as apoptosis, caspase dependent, or necroptosis, caspase independent, can exacerbate diabetes associated complications. There is …

Targeting Als: A Multi-Cellular Study On The Potential Therapeutic Role Of Azole-Based Compounds, Alisha R. Kennedy

Theses and Dissertations

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder that leads to the degeneration of motor neurons, which control voluntary muscle movements such as eating, speaking, and breathing. As these neurons are damaged, voluntary movement ceases, leading to a fatal outcome. The survival time of ALS patients varies, ranging from a few months to up to 10 years. Chapter 1 of this thesis provides an overview of ALS, highlighting the role of transactive response DNA-binding protein 43 (TDP-43), a key feature in ALS and other neurodegenerative diseases. The aggregation of TDP-43, particularly due to …

Exploring The Role Of Transcription Factor Nrf1 In Autophagy And Inhibiting The Nrf1 Bounce-Back Response, Madison A. Ward

Theses and Dissertations

Cells exposed to proteotoxic stress invoke adaptive responses aimed at restoring proteostasis. Our previous studies have established a firm role for the transcription factor Nuclear factor-erythroid derived-2-related factor-1 (Nrf1) in responding to proteotoxic stress elicited by inhibition of cellular proteasome. Following proteasome inhibition, Nrf1 mediates the synthesis of new proteasomes, thus enabling cells to mitigate proteotoxic stress. Here, we report that under similar circumstances, multiple components of the autophagy-lysosomal pathway (ALP) were transcriptionally upregulated in an Nrf1-dependent fashion, thus providing the cells with an additional route to cope with proteasome insufficiency. In response to proteasome inhibitors, Nrf1-deficient cells exhibited profound …

Utilization Of Golden Pennycress In Broiler Diets, Marley M. Knowles

Theses and Dissertations

The objective of this study was to evaluate performance in broiler chickens fed diets containing golden pennycress meal (GPCM), with and without a flavor additive. Golden pennycress (Thlaspi arvense) is a winter cover crop grown in the Midwest that is rising in popularity as a cash crop used for biofuel production. After oil is pressed out of the seeds, a meal remains that is usually discarded. Incorporation of this meal (23% protein, 15% fat) into feedstuffs for broilers would be an efficient way to make biofuel production more sustainable. In one study, Cornish Cross three-day-old chicks (n=12) were …

Scrolling For Two: An Exploration Of Pregnant Women's Social Support And Information Seeking Behaviors Using Technology During The Covid-19 Pandemic, Sarah Knowlton

Theses and Dissertations

Pregnant women faced additional challenges in accessing reliable support and pregnancy- related information, leading to increased distress during the COVID-19 pandemic. Quarantine measures limited doctor’s appointments and isolated pregnant women from their families, which meant that meaningful connections and convenient information was important.

The purpose of this study is to explore the implications of COVID-19 social distancing on pregnant women, with a focus on three questions: 1) what digital technologies did pregnant women use for support and information seeking purposes during the pandemic? 2) how did pregnant women use technology to seek social support during the pandemic? 3) how did …

Boys Build, Girls Glam: An Examination Of Adult Language Use In Informal Steam Education Settings, Alexandra Horton

Theses and Dissertations

Research on STEAM education has primarily focused on formal education settings such as schools, with more research needed in informal or non-traditional education settings. As children frequently engage with informal and non-traditional education settings, it is important to understand how we can transmit information in these settings to bolster and further the learning process and increase engagement. STEAM fields have been plagued by racial and gender inequities that have led to these groups being marginalized and excluded (Blair et al., 2017; Eaton et al., 2020; Martin, 2018; Martin & Phillips, 2019; Miller et al., 2018; Newall et al., 2018, Sheffield …

Examining The Distribution And Predictability Of Population Dynamics Across Geographic Space, Cleber Ten Caten

Theses and Dissertations

Populations occupy different regions of the geographic space and may experience distinct conditions over time that can cause fluctuations in their number of individuals. Environmental conditions, dispersal events, and resource availability are some of the factors that influence populations. A central goal in ecology has been to develop generalizations about how these factors that affect population dynamics are structured in geographic space. However, limited knowledge about where species occur and a lack of long-term surveys of populations has hindered the development, and validation, of such generalizations. In this dissertation, I use a combination of observational data, simulations, and experimental approaches …

Factors Influencing Adherence To Surveillance Guidelines In Individuals With Tuberous Sclerosis Complex, Kashish Khanna

Theses and Dissertations

Tuberous Sclerosis Complex (TSC) is a genetic condition that is caused by pathogenic changes in either the TSC1 or TSC2 gene and is characterized by multiple benign tumors, otherwise known as hamartomas, in various organs such as the brain, skin, lungs, and kidneys. Because of the many different clinical manifestations of TSC, extensive surveillance guidelines are recommended for individuals with TSC. Past studies have shown that there has been a gap in knowledge of these surveillance guidelines. These studies also suggest projects that measure adherence to surveillance guidelines and address specific challenges hindering surveillance guideline adherence. This study aims to …

The Relationship Between Cardiac Patient Beliefs And Experiences With Insurability And Their Decisions On Whether Or Not To Pursue Genetic Testing, Julia Schoeni

Theses and Dissertations

Since the enactment of the Genetic Information Non-Discrimination Act (GINA) in 2008, genetics providers have been incorporating conversations about GINA in pre-test counseling. There is currently limited evidence of the effects of personal or family histories of cardiomyopathy or aortopathy and associated genetic testing on patients seeking insurance policies not protected by GINA, including life, long term care, and disability insurance. This study aimed to determine whether individuals with a personal or family history of cardiomyopathy or aortopathy are having conversations about future insurability with their healthcare providers and how they perceive their ability to get these insurances when deciding …

Utilizing Evisits To Increase Access To Genetic Services For The Hearing Loss Population: A Tailored Service Delivery Model, Ansley Roberts

Theses and Dissertations

Purpose: Patients referred for genetics services have specific barriers decreasing accessibility, such as communication difficulties, long wait times, and misconceptions about the utility of genetic testing. We assessed a new tailored service delivery model used by the Greenwood Genetic Center to evaluate patients referred for hearing loss to determine if this model increases access to genetics services for individuals with hearing loss. Methods: Data points such as wait times, testing plan, and diagnostic yield were compiled from patient medical records. Comparison and analysis of data was completed by visit type, in-person, virtual, and electronic visits (eVisits), between October 2023 – …

Involvement Of Integrated Stress Response In Primary And Secondary Dystonia, Tricia Aleena Dulice Simon

Theses and Dissertations

ABSTRACT Dystonia is the third most common movement disorder in the United States of America , the first two being essential tremor and Parkinson’s disease. Gaining mechanistic knowledge about pathobiology of dystonia is essential for development of effective therapies. As the only therapies currently available are invasive procedures such as deep brain stimulation (DBS) or frequent botulinum toxin injections, it is critical to understand the underlying molecular mechanisms leading to dystonia. A maladaptive integrated stress response (ISR) involving dysregulation of the eukaryotic translation initiation factor  (eIF2) mediated signaling is observed in DYT-PRKRA patient cells. Mutations in PRKRA gene, which …

Bugs In The Flux: Links Between Arthropod Diversity And Spatial Variation Of Soil Respiration In A Temperate Forest, Erin-Darby H. Mcclain

Theses and Dissertations

Soil respiration (Rs) is the largest terrestrial flux of carbon (C) to the atmosphere, with heterotrophic contributions to Rs varying spatially and temporally. While microbes are the primary and most thoroughly studied source of soil heterotrophic respiration (Rh), contributions from higher trophic organisms, including arthropods, are rarely quantified and poorly understood. Arthropod abundance and diversity correspond with variation in soil microclimate, which is influenced by site factors including canopy structure, site productivity, and disturbance. However, the extent to which these site factors influence arthropod abundance and diversity, and consequently, spatial variation in Rs is not known. The objective of our …

Mdma Enantiomers: An Exploration Into 5-Ht2ar Necessity In Non-Hallucinogen Induced Frontal Cortex Plasticity, Maya C. Gaines-Smith

Theses and Dissertations

Entactogen 3,4-methylenedioxymethamphetamine (MDMA) has gained increasing attention as a potential psychotherapeutic, particularly for psychiatric disorders that have proven to be resistant to traditional treatments. Despite its growing popularity, the complete neurobiological mechanism of MDMA enantiomers, as well as the role of sex in these mechanisms, remains to be fully elucidated. Current ongoing research implicates agonism of the serotonin (5-HT) 2A receptor (5-HT_2AR) and neuroplastic growth in the success of other psychoactive and hallucinogenic pharmacotherapeutics, highlighting the importance of understanding the role that the 5-HT_2AR plays in the therapeutic mechanism of action of MDMA enantiomers. The culmination …

Scopolamine-Induced Modulation Of Serotonin And Dopamine Transporters Activity: Behavioral And Molecular Insights Into Rapid Antidepressant Action, Deepak Karunakaran

Theses and Dissertations

Major depressive disorder (MDD) affects over 350 million individuals worldwide and is characterized by profound dysregulation of serotonin (5-HT) and dopamine (DA) systems that govern mood, reward processing, and motivation. The serotonin transporter (SERT) and dopamine transporter (DAT), both dynamically regulated through phosphorylation, serve as critical determinants of synaptic monoamine signaling. Despite decades of therapeutic development, current antidepressants require 4-6 weeks to achieve efficacy, and approximately one-third to half of patients develop treatment-resistant depression. The emergence of rapid-acting antidepressants like ketamine represents a paradigmatic shift, demonstrating symptom relief within hours; however, ketamine's therapeutic potential remains constrained by abuse liability, dissociative …

Exploring The Role Of Host Immune Responses And Bacterial Sensory Pathways In The Development Of Treponema Denticola-Mediated Periodontal Disease, Annie N. Hinson

Theses and Dissertations

Periodontitis is a chronic inflammatory disease driven by dysbiotic microbial communities and maladaptive host responses. Treponema denticola, a spirochete pathobiont, is strongly associated with disease severity. However, the molecular mechanisms underlying its interaction with host tissues and regulation of virulence remain incompletely understood. This work examines both the epithelial immune responses and bacterial transduction systems that shape T. denticola pathogenesis. Transcriptomic analysis of gingival keratinocytes revealed IL-36γ as the most highly induced cytokine following infection with T. denticola. Functional studies demonstrated that IL-36γ induction occurs in a dose- and time-dependent manner through TLR2/6 signaling, requiring the NF-κB, PI3K/Akt, and …

Functional Analysis Of Ligand Binding Domain 2 Of Outer Surface Protein C Of Borreliella Burgdorferi, Gavin Z. Chambers

Theses and Dissertations

Lyme disease, caused by the spirochete Borreliella burgdorferi, is the most common vector-borne infection in North America. A critical determinant of early mammalian infection is outer surface protein C (OspC), a highly variable lipoprotein that is indispensable for spirochete survival but whose precise function remains unresolved. OspC has been proposed to mediate diverse roles, including complement evasion, adhesion, tissue dissemination, and antiphagocytic activity, supporting the view that it is a multifunctional virulence factor. Structural studies have identified two putative ligand-binding domains (LBD1 and LBD2), with LBD2 forming a solvent-exposed crown at the membrane-distal end of the OspC dimer.

To …

The Bacteriostatic, Regenerative, And Immunomodulatory Properties Of Extracellular Matrix Particles For Lung Injury, Keera P. Rhoads

Theses and Dissertations

Acute respiratory distress syndrome (ARDS) is a prevalent, life-threatening lung condition, affecting nearly 200,000 Americans annually, with a 40% international mortality rate. There is no cure for ARDS, and current pharmacological treatments have limited effectiveness. Symptoms can be mitigated with mechanical ventilation, though this often leads to ventilator-induced lung injuries (VILI) and puts critically ill patients at risk of infections, including ventilator-associated pneumonia (VAP). A promising therapeutic is the extracellular matrix (ECM), a complex network of structural proteins and bioactive molecules that has been shown to have anti-inflammatory properties and prevent fibrosis. We aim to utilize the regenerative and immunomodulatory …

Enhancing Clinical Trial Matching In Molecular Diagnostics: Using Natural Language Processing And Clustering Approaches In Hematological Malignancies, Gillian Fanning

Theses and Dissertations

Clinical trial matching is a critical component of personalized medicine, particularly in the management of hematologic malignancies. At Virginia Commonwealth University (VCU) Health, the Molecular Diagnostics (MDX) Lab produces somatic variant reports and recommends clinical trials based on the presence of clinically significant mutations. However, the current manual trial recommendation process is time-intensive and lacks scalability.

This study introduces a computational framework to streamline and standardize clinical trial matching using natural language processing (NLP) and unsupervised clustering. Trial brief descriptions were analyzed to extract frequent terms, and trials were grouped based on term similarity using joint dimensionality reduction and clustering. …

Dickkopf1(Dkk1): A Novel Endogenous Ligand To Prime Nlrp3 Inflammasome Via Tlr4, Theingi Aung

Theses and Dissertations

Dickkopf1(DKK1) is a quintessential Wnt antagonist and immunomodulator in various inflammatory diseases. The underlying molecular mechanisms of DKK1-mediated immunomodulation remain elusive. Here, we identified TLR4 as a new receptor for DKK1 to activate NFκΒ pathway-mediated gene expression and pyroptosis via NLRP3 inflammasome in human and mouse macrophages.

DKK1 employed TLR4 to initiate NFκB signaling cascade via MyD88. MyD88-TAK1-NFκΒ pathway activation by DKK1 increased HIF1α, NFκB, and NLRP3 protein expression levels, leading to pyroptosis. Unlike LPS, DKK1 did not induce IRAK4 phosphorylation, while the interaction between MyD88 and IRAK4 was maintained for downstream signaling activation. DKK1 did not induce IRF3 phosphorylation …

Isolating Confounding Abiotic And Biotic Effects On The Phenotype On Physa Acuta Snails, Ashley M. Bauer

Theses and Dissertations

Organisms match their phenotypes to prevailing environmental conditions leading to habitat specific polymorphisms. Polymorphisms arise from genetic divergence, phenotypic plasticity, or a combination of both processes. I examined the presence of habitat-specific polymorphism in Physa acuta snails collected from three streams and their corresponding downstream reservoir. In lotic systems shells were rotund with larger apertures, while those from lentic systems were more elongate with smaller apertures. In a reciprocal transplant lab experiment that crossed flow regime and crayfish predator cues, I tested for the underlying mechanisms responsible for the observed phenotypic differences. I found no evidence for plasticity in relation …

Doves And Symbiotic Bacteria: Whole-Genome Assembly And Phylogenomic Inference, Mariam Topchyan

Theses and Dissertations

Part 1

I examined a potential source of variation in phylogenetic inference, investigating whether handling single-nucleotide polymorphisms (SNPs) through different methods during reference-guided genome assembly of pigeon and dove species impacts phylogenetic reconstruction and inference. Specifically, I created a custom consensus base calling tool that handles allelic variation through two different approaches, either ignoring heterozygous sites by denoting them as an ambiguous character “N,” or using a pseudo-random choice between supported base variants. Through reference-guided assembly of 108 dove species, I generated two datasets of alignments using both consensus calling methods, created two trees from both datasets via supermatrix and …

Targeting The Achilles’ Heel Of Lung Cancer Induced By Oncogenic P53, Brandon G. Velasco

Theses and Dissertations

Mutations of the tumor suppressor gene, TP53, are the most prevalent oncogenic mutations in lung cancer, occurring in up to 70% of human non-small cell lung cancer (NSCLC). The majority of mutations in p53 are missense mutations that cause not only a loss of tumor suppressor function, but also gain of oncogenic functions, like tumorigenicity, immune suppression, and chemoresistance. Previous studies have shown that the depletion of gain-of-function (GOF) p53 or disruption of its ability to transactivate the expression of genes related to oncogenesis eliminates its tumorigenic properties indicating a dependency of human lung cancer cells expressing GOF p53 …

Linking Disturbance & Macrophyte Colonization–Extinction Dynamics To Invasion Success & Community Assembly: Integrating Population, Community, & Landscape Perspectives, Joshua T. Armstrong

Theses and Dissertations

Aquatic plants, macrophytes, are foundational components of freshwater ecosystems, influencing abiotic conditions, providing habitat structure, and shaping biodiversity and community assembly processes. Their role is particularly critical in dynamic systems where disturbance regimes and colonization processes interact to shape community patterns and species distributions. Despite their ecological importance, macrophytes remain underrepresented in theoretical and applied studies of metacommunity dynamics and invasion ecology, especially in natural systems experiencing frequent environmental fluctuations. Here we aim to elucidate how macrophytes influence and respond to spatial and temporal variation in aquatic ecosystems, with a particular focus on colonization-extinction dynamics, invasion success, and community assembly. …

Investigating Mitochondrial Stress Response Mechanisms In Aging, Aileigh E. Daniel

Theses and Dissertations

Mitochondrial dysfunction is widely recognized as a key contributor to aging and age-related diseases. The concept of mitohormesis suggests that low levels of ROS can activate stress-responsive transcription factors, promoting adaptive mechanisms that enhance longevity. We hypothesized that changes in protein abundance under conditions of mild mitochondrial stress reflect an adaptive response, and that commonly altered proteins across diverse genetic backgrounds of mitochondrial stress can help identify key regulators of stress resilience and aging. Our study identified conserved mitochondrial stress response pathways and highlighted candidate regulators for further investigation. These regulators appear to impair mitochondrial energy production by downregulating ATP …

Unleashing Serine Palmitoyltransferase In Test Tubes And Mice, Matthew W. Peart

Theses and Dissertations

Canonically known both for structural contributions to lipid bilayers and roles in cell signaling, the sphingolipids comprise a dynamic, multifaceted class of molecules which are studied to understand homeostatic cell biology as well as pathophysiology. Sphingolipids contribute to tissue-specific structures such as myelin, a multilayer membrane that allows for rapid conduction of action potentials along neuronal axons. All sphingolipids are downstream products of the rate-limiting and initiating enzyme in the de novo sphingolipid synthesis pathway, Serine palmitoyltransferase (SPT). Demonstrative of its status as the enzyme that catalyzes a crucial step in a biochemical pathway, SPT activity is strictly regulated. This …

Climate Change-Induced Shifts In Mediterranean Fungal Fruiting Phenology And Productivity, Rachel Demay

Theses and Dissertations

We used a 29-year dataset of mushroom fruiting from the Pinar Grande forest in northern Spain to investigate the effects of climate change on the phenology, productivity, and diversity of mycorrhizal and saprotrophic mushrooms. We investigated the long-term trends in fruiting season length, yield (by count, total weight, and average weight), and genus richness. Additionally, we identified associations between monthly temperature and monthly precipitation with these fungal responses across functional groups: mycorrhizal, saprotrophic, litter-decaying saprotrophic, and wood-decaying saprotrophic mushrooms, and the economically-important edible genera Boletus and Lactarius. We found that autumnal season length in the Pinar Grande has shortened over …