Life Sciences Commons^™

Impairment Of The Glial Phagolysosomal System Drives Prion-Like Propagation Of Huntington’S Disease, Graham Davis

Theses and Dissertations

The ability of glia to tightly regulate neuronal health and homeostasis in the CNS is conserved across species. Yet, despite the ability to degrade protein aggregates, glia are vulnerable to the accumulation of neurotoxic amyloid aggregates during neurodegenerative disease progress, and even exacerbate their spread. A developing narrative highlights glia as a double-edged sword in neurodegenerative diseases: initially capable of dynamically responding to amyloid aggregate-ladened dying neurons but also capable of inducing chronic inflammation and creating seeding-competent amyloid oligomers. Thus, uncovering the mechanisms that allow glia to control aggregate deposition while preventing the neurotoxic effects and seed generation is vital …

Dynamic Regulation Of Store-Operated Calcium Entry By Protein S-Acylation, Goutham Kodakandla

Theses and Dissertations

Calcium plays a pivotal role in many physiological functions in cells. Cytosolic calcium levels are finely tuned by calcium ion channels, pumps, and intracellular organelles. Store-operated calcium entry (SOCE) is when depletion of endoplasmic reticulum (ER) calcium stores activates a calcium sensor known as stromal interaction molecule 1 (STIM1). Activation of STIM1 leads to a conformational change from a compact state to an extended state. This extended state of STIM1 allows it to bind to a calcium channel in the plasma membrane (PM) known as Orai1. The binding of Orai1 and STIM1 leads to opening of Orai1 channels and calcium …

Sctiger: A Deep-Learning Method For Inferring Gene Regulatory Networks From Single-Cell Gene Expression Data, Madison Dautle

Theses and Dissertations

Inferring gene regulatory networks (GRNs) from single-cell RNA-sequencing (scRNA-seq) data is an important computational question to reveal fundamental regulatory mechanisms. Although many computational methods have been designed to predict GRNs, none work on condition specific GRNs by directly using paired datasets of case versus control experiments, common in diverse biological research projects. We present a novel deep-learning based method, scTIGER, for GRN detection by using the co-dynamics of gene expression. scTIGER also employs cell type-based pseudotiming, an attention-based convolutional neural network method, and permutation-based significance testing to infer GRNs from gene modules. We first applied scTIGER to scRNA-seq datasets of …

Evaluation Of The Virulence Potential Of Avian Pathogenic Escherichia Coli Isolated From Broiler Breeders With Colibacillosis In Mississippi, Jiddu Joseph

Theses and Dissertations

Avian pathogenic Escherichia coli (APEC) is a bacterium that is responsible for colibacillosis in birds. However, information about broiler breeder APEC isolates is limited, but the data is critical due to the transfer of this bacteria down the production pyramid to progenies resulting in high mortality. Therefore, we evaluated the phenotypic virulence characteristics of 28 isolates using embryo lethality and day-old chick challenge assays. Also, the in vitro adhesion and invasion potential of selected nine isolates were identified. Results showed more than 1/3^rd of the isolates were highly virulent and the virulence increased as the number of virulence-associated genes …

Effectiveness Of Intervention Studies Based On Diet And/Or Physical Activity In Treatment, Prevention, And Management Of Diabetes Among South Asians: A Systematic Review, Ishaan Arora

Theses and Dissertations

The purpose of this study was to describe diet and/or physical activity-based interventions and their control in cardiometabolic risk factors of diabetes for the South Asian (SA) population. A systematic review was conducted in accordance with the PRISMA guidelines. Seventeen randomized control trials meeting the inclusion criteria were included for analysis. Interventions with type-2 diabetic SA showed significant improvements in HbA1c% (4/5 studies), fasting blood glucose (3/4 studies), and postprandial glucose (2/2 studies). Interventions with at-risk/prediabetic and non-diabetic SA showed a modest change in overall outcomes, with significant change reported for post-prandial insulin (3/4 studies), BMI and weight (2/4 studies), …

A Comparison Of Ground Reaction Forces And Muscle Activity Of The Tsunami Bar® Against A Rigid Barbell During Back Squat Phases, John Carver Middleton

Theses and Dissertations

An Institutional Review Board (IRB)-approved study was conducted to investigate the effects of the Tsunami Bar® (TB), a flexible barbell, on ground reaction force (GRF) production and muscle activity in the quadricep, hamstring, and gluteal muscle groups during phases of the squat exercise and compare the effects to the effects to using a rigid barbell (RB). A two-by-two repeated measures Analysis of Variance (ANOVA) test was used to compare the results. Descriptive statistics showed significantly higher GRFs for the TB during the unweighting phase, significant differences in GRFs between speeds for each phase, significantly higher forces on average with the …

Using Music To Modify Step-Rate And Running Biomechanics In Healthy Runners, Erin Marie Lally

Theses and Dissertations

Context: Running-related injury (RRI) is a significant public health issue that may be caused by injurious running biomechanics. Increasing step-rate (SR) using gait retraining may prevent and treat RRI. The Optimizing Performance Through Intrinsic Motivation and Attention for Learning (OPTIMAL) theory indicates enhanced expectancies, autonomy, and external focus of attention will optimize motor learning. Music has been shown to create enhanced expectancies, can provide incidental choices (autonomy), directs attention externally, and may increase compliance. No studies have investigated if music can be used to alter SR and running biomechanics or strategies that may improve compliance to gait retraining. Objective: The …

Artemisinin And Its Derivatives Reactions: Characterization Of The Reaction Products Using Lc/Tof Ms, Kogila Vijayan

Theses and Dissertations

Artemisinin (ART) is a sesquiterpene lactone and a popular malaria drug with potential anticancer properties. In this work, LC/TOF MS was used to investigate the reaction of ART with DNA bases and estradiol. ART-deoxyadenosine and ART-deoxycytidine interactions were studied in the presence of Fe (II) ions. ART-deoxyadenosine and ART-deoxycytidine reaction mixtures gave chromatographic signatures that remained unchanged at room temperature but grew after incubation at 37°C. The change in temperature from room temperature to 37°C was the main driver of adduct formation in these reactions. ART was found to react with Fe (II) ions as observed from several new chromatographic …

Identifying Barriers To Data Use On U.S. Beef Cow-Calf Operations And Developing Solutions To Improve Cow-Calf Record-Keeping, William Isaac Jumper

Theses and Dissertations

Cattle health and production records (CHPR) are data collected by cattle producers and veterinarians in the form of measurements, observations, counts of events over time, and physiologic attributes that describe individual and group-level health and production. These data are useful to both veterinarians and cattle producers for making evidence-based decisions on cow-calf operations. Currently, there are no uniform, industry-wide methods of capturing and recording CHPR in the U.S. cow-calf industry. Although many cow-calf producers in the U.S. are thought to collect some form of CHPR, it is believed that relatively few are doing so in an electronic manner that facilitates …

Educational Environments And Children's Physical Activity And Sedentary Behaviors, Nathan R. Tokarek

Theses and Dissertations

Children and adolescents spend the majority of their day engaged in sedentary behaviors (SB), while also not meeting physical activity (PA) recommendations. The failure to develop and maintain health enhancing behaviors from a young age may impact an individual throughout their life. With children and adolescents spending a large proportion of their waking hours in a school setting, the educational environment presents an opportunity in which children and adolescents’ PA and SB can be positively influenced. Therefore, the purpose of this dissertation was to explore how children and adolescent’s school time PA and SB are associated with the educational setting, …

Protacs – A Novel And Rapidly Developing Field Of Targeted Protein Degradation, Hannah R. Gatley

Theses and Dissertations

There is a continued need for new technology and strategies for tackling cancer and other diseases, and within the current century a novel therapeutic strategy has emerged in the realm of targeted protein degradation called Proteolysis-Targeting Chimeras (PROTACs). This technology specifically targets and degrades disease-causing proteins via the ubiquitin-proteasome system, and has seen an explosion of research and intrigue in both academia and industry over the past two decades. The diversity of PROTAC classes based on the E3 ligase recruiting ligand and the target protein allows for a universal molecular structure that can be customized for a specific target and …

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …

Evaluation Of Spliceai For Improved Genetic Variant Classification In Inherited Ophthalmic Disease Genes, Melissa Reeves

Theses and Dissertations

ABSTRACT

EVALUATION OF SPLICEAI FOR IMPROVED GENETIC VARIANT CLASSIFICATION IN INHERITED OPHTHALMIC DISEASE GENES

By Melissa Jean Reeves, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2023

Major Director: Melissa Jamerson, PhD, MLS(ASCP)

Associate Professor, Department of Medical Laboratory Sciences

Inherited ophthalmic diseases impact individuals around the globe. Inherited retinal diseases (IRDs) are the leading cause of blindness in individuals aged 15 to 45. The personal, social, and economic impact of vision loss is profound. Due to individual differences, symptoms can be variable, and …

The Influence Of Taste Sensitivity To 6-N-Propylthiouracil (Prop) On Anthropometric Measurements, Body Composition, And Eating Behaviors Among Female College Students, Abeer Mohammedsharief Alardawi

Theses and Dissertations

Taste is one of the crucial factors that contributes to shaping eating behaviors and is also one of the leading reasons that affects our preferences to like or dislike some foods that mainly have a bitter taste. Variation in bitter phenotype (tasters and non-tasters) could influence diet quality and in turn body weight, which overall influenced health outcomes. The objective of this study was to identify whether bitter taste phenotype status influences anthropometric measurements, body fat percentage, and eating behaviors (liking and intake) in female college students. In this cross-sectional study (n = 86), female college students aged 18 to …

Targeting Ribosome Biogenesis For Pancreatic Cancer Treatment, Carlos Perez Iii

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related death in the United States. Currently, PanCa is one of the recalcitrant cancers that has very limited therapeutic options available for its treatment. The current standard care of PanCa is gemcitabine (GEM) alone or in combination with FOLFIRINOX, nab-paclitaxel, erlotinib, or 5-FU PanCa, which often show poor response. Therefore, new treatment strategies are required for the prevention and treatment of cancer. Ribosome biogenesis process is dysregulated in most of the cancer types of results in production of more ribosomes and synthesis of oncoproteins which lead to the induction, progression, …

Influence Of Paclitaxel Nanomedicine On The Pancreatic Tumor Immune Components, Godwin Peasah-Darkwah

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortalities in the U.S due to ineffective therapeutic options. Pancreatic tumors are highly desmoplastic and inhibit efficient uptake of therapeutic payloads. Paclitaxel (PTX) has been tested in PanCa therapy with marginally better clinical outcomes, but remain limited by its poor hemocompatibility, biodistribution and intracellular accumulation in tumor cells. Thus, we synthesized a next generation nanoparticle system for PTX to improve its pharmacokinetics and pharmacodynamics (PKPD) in treating PanCa. We also examined ability of the nano formulation to potentiate gemcitabine (GEM) activity in combating chemoresistance in the pancreatic tumor microenvironment …

Development Of Enhanced Food Packaging Systems Based On Blends Of Bio-Based And Biodegradable Polymers Exhibiting Antimicrobial Properties, Aishat Agboluaje

Theses and Dissertations

Food packaging is one of the important aspects of food processing, which contributes greatly to decreasing post-harvest food losses. While ensuring that foods are adequately packaged, it is also important to consider the impact of these food packaging materials on the environment. Accordingly, this research work was aimed at investigating the potential of bio-based and biodegradable blends of polyvinyl alcohol (PVA) and chitosan loaded with antimicrobial agents such as turmeric, clove, and cinnamon for use in food packaging applications. The methodology involved creating PVA/chitosan films with varying compositions via solvent casting method and selecting the best composition exhibiting the highest …

Identification Of Pneumococcal Membrane Proteins Involved In Colonization/Biofilm Formation And Cognate Host Cellular Receptors, Yoonsung Hu

Theses and Dissertations

Colonization is prerequisite for infection and transmission of Streptococcus pneumoniae, or pneumococcus. Currently available pneumococcal conjugate and pneumococcal polysaccharide vaccines can provide protection against a limited number of capsular serotypes. Implementation of vaccines has decreased the frequency of invasive pneumococcal disease and their colonization rates, but only in a serotype-dependent manner. This has led to serotype replacement in pneumococcal ecology and increased invasive disease caused by non-vaccine serotypes. Development of conserved protein-based vaccine that can provide protection against all pneumococcal serotypes is needed. Numerous surface proteins are conserved in all serotypes, and some are known to be involved in …

Bodyverse, Colin B. Stilwell

Theses and Dissertations

This paper supports the MFA dance thesis film BodyVerse. Exploring the intertwining relationship of body systems with the natural world, it brings somatic principles such as Body Mind Centering and dance improvisation together with film legacies and digital platforms.

Full-Body Biomechanical Characterization Of Children With Hypermobile Ehlers-Danlos Syndrome During Gait And Activities Of Daily Living, Anahita Alahmoradiqashqai

Theses and Dissertations

Hypermobile Ehlers-Danlos syndrome (hEDS) is an inherited connective tissue disorder, often under-diagnosed, and presenting with frequent chronic pain and severe musculoskeletal symptoms that can drastically reduce the quality of life during one’s life span. While there are limited quantitative approaches in the literature on adult movements, the biomechanics of movements during activities of daily living (ADLs) in children have not been investigated comprehensively. Therefore, the primary purpose of this dissertation was to characterize the biomechanics of the musculoskeletal system and investigate the biomechanics of hEDS by quantifying joint dynamics and muscle activations during ADLs and gait in the pediatric population. …

Development Of New Treatments For Asthma And Neuropathic Pain Based On Ɣ-Aminobutyric Acid A Receptor (Gabaar) Ligands, Nicolas Mark Zahn

Theses and Dissertations

The γ-aminobutyric acid A receptor (GABAAR) is a ligand-gated pentameric chloride channel consisting of several identified subunits: α1-6, β1-3, γ1-3, δ, ε, π, θ, ρ1-3.1-2 Typical arrangement of subunits consists of two α subunits, two β subunits, and one γ subunit.3 GABAARs have two binding sites for the endogenous ligand γ-aminobutyric acid (GABA), between the α and β subunits. GABAARs also have a binding site for positive allosteric modulators, such as benzodiazepines, between the α and γ subunits.4-5 Due to their ability to treat anxiety, epilepsy, insomnia, and muscle relaxation, benzodiazepines are widely prescribed pharmaceuticals.6-7 Still, adverse effects result from …

A Predictive Model For Geographical Location Using Microbiome Composition And Covid-19 Based Analysis, Ahmed Adel Aboushanab

Theses and Dissertations

The human microbiome is a main contributor for the health and welfare of the human body. It is affected by many factors like diet and hygiene. These factors differ between different populations. Testing the population-microbiome differences using healthy samples from different countries is the first objective of this study. This data was then used in training and testing machine learning models (Random Forest and L2-logistic Regression Classifiers) for the prediction of the geographical location based on the microbiome data. Random Forest Classifier had the highest accuracy. Feature importance analysis showed that the data for Proteobacteria, Actinobacteria, and Bacteroidetes improved the …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …

The Role Of Human Dopamine Transporter Threonine 261 And Serine 262 In Amphetamine Regulation Of Transporter Function And Surface Expression, Sina Abdollahi

Theses and Dissertations

Amphetamine (AMPH) has been used clinically and recreationally around the world for years. A 2021 study reports a 67.5% rise in AMPH use from 2010-2017 across all fifty states. Study also shows that 30% of patients with AMPH-induced psychosis end up with primary psychosis over time. AMPH works by inhibiting monoamine (Norepinephrine (NE), Serotonin (5-HT), and Dopamine (DA) reuptake followed by triggering transporter mediated monoamine release and consequently increases monoamine concentrations in extracellular synaptic space. AMPH also works as a substrate for monoamine transporters, enters the neuron, and once its inside the neuron, it will prevent the storage of monoamines …

Estimating Weighted Panel Sizes For Primary Care Providers: An Assessment Of Clustering And Novel Methods Of Panel Size Estimation On Electronic Medical Records, Martin A. Lavallee

Theses and Dissertations

Primary Care is on the frontlines of healthcare, thus they see the most diverse set of patients. In order to achieve high functioning primary care, a practice must establish empanelment, the pairing of patients to providers. Enumeration of empanelment, or estimating panel sizes, helps ensure that the demands of the patients demand the supply of providers and optimize the balance of primary care resources to improve quality of care. Further we can adjust panel sizes by using patient-level data on healthcare utilization and complexity extracted from the electronic medial record to determine the amount of care or burden of work …

Chronic Adolescent Stress As A Predictive Factor For The Risk Of Developing Ptsd-Like Symptoms In Adulthood, Grace K. Young

Theses and Dissertations

Post-traumatic stress disorder is a stress and trauma based psychological disorder that is defined by the DSM-IV as an anxiety disorder that affects approximately 7.8% of people in the United States. PTSD is when those who suffer a traumatic event have intense and distressing feelings, emotions, and memories for a prolonged period of time after the event. A prominent feature of PTSD is the impaired ability to properly extinguish a fear response after a dangerous trigger or stressor is no longer present, also known as safety learning. Stressors are threats perceived within the environment that activate a response within the …

Protein Structure And Interaction: The Role Of Aromatic Residues In Protein Structure And Interactions Between Pyridoxine 5'-Phosphate Oxidase/Dopa Decarboxylase, Mohammed H. Al Mughram

Theses and Dissertations

Naturally developed proteins are capable of carrying out a wide variety of molecular functions due to their highly precise three-dimensional structures, which are determined by their genetically encoded sequences of amino acids. A thorough knowledge of protein structures and interactions at the atomic level will enable researchers to get a deep foundational understanding of the molecular interactions and enzymatic processes required for cells, resulting in more effective therapeutic interventions. This dissertation intends to use structural knowledge from solved protein structures for two distinct objectives.

In the first project, we conducted a bioinformatics structural analysis of experimental protein structures using our …

Behavioral Screening And Chiral Bioanalysis Of Emerging Stimulant-Type Drugs In Rats, Tyson R. Baird

Theses and Dissertations

The epidemic of drug use in the United States and elsewhere in the world has resulted in tragic loss of life and substantial economic costs. Novel psychoactive substances (NPS) are one of the contributors to this problem, and the lack of information about many of these drugs compounds their risk. This dissertation proposes a strategy to use intracranial self-stimulation (ICSS) as a behavioral screening tool to assess emerging drugs of abuse for their abuse potential in order to generate a proactive threat assessment. A series of stimulant-type drugs including methcathinone, α-pyrrolidinohexanophenone (α-PHP), cocaine, and the phenyltropane analogs of cocaine WIN35428 …

Examination Of Common And Rare Variant Genetic Architecture Of Psychiatric Disorders, Mohammad Ahangari

Theses and Dissertations

Psychiatric disorders are often heterogenous in their manifestation and genome-wide association studies have identified many common risk variants involved in their polygenic architectures with varying degrees of pleiotropy. In recent years, large-scale biobanks have also begun sequencing the genome of their participants to elucidate the role of rare risk variation in the genetic architecture of complex phenotypes, including psychiatric traits. This dissertation sought to better understand the role of both common and rare risk variation in the genetic architecture of psychiatric disorders with a particular focus on schizophrenia and alcohol problems. In the first three analyses, we focused on characterizing …