Digital Commons Network^™

Diuretic, Natriuretic, And Vasodepressor Activity Of A Lipid Fraction Enhanced In Medium Of Cultured Mouse Medullary Interstitial Cells By A Selective Faah Inhibitor, Zdravka P. Daneva

Theses and Dissertations

The relationship between the endocannabinoid system in the renal medulla and the long-term regulation of blood pressure is not well understood. To investigate the possible role of the endocannabinoid system in renomedullary interstitial cells, mouse medullary interstitial cells (MMICs) were obtained, cultured and characterized for their responses to treatment with a selective inhibitor of fatty acid amide hydrolase (FAAH), PF-3845. Treatment of MMICs with PF-3845 increased cytoplasmic lipid granules detected by Sudan Black B staining and multilamellar bodies identified by transmission electron microscopy. HPLC analyses of lipid extracts of MMIC culture medium revealed a 205nm-absorbing peak that showed responsiveness to …

National And Local Antibiotic Prescribing Trends And Prescribing Appropriateness In Older Adults, Fawaz M. Alotaibi

Theses and Dissertations

Background: Antibiotic overuse/misuse has been documented in several reports to increase the risk of Clostridioides difficile (C.diff) infection and antibiotic resistance. The older adult population is more prone to use antibiotic medications than any other age group due to decreased immune function, use of urinary catheters, ventilation during hospitalization and other factors. Antibiotic resistance and C.diff are major public health problems. However, studies examining the trends of antibiotic use and the association between the antibiotic use and negative health outcomes among older adults in the outpatient and emergency department settings are limited.

Objectives: The main objectives of this …

Conjugated Bile Acid And Sphingosine 1-Phosophate Prompt Cholangiocarcinoma Cell Growth Via Releasing Exosomes, Waad A. Alruwaili

Theses and Dissertations

Cholangiocarcinoma (CCA) is a fatal primary malignancy that is formed in the bile ducts. Cancer-associated myofibroblasts play a crucial role in CCA proliferation and invasion. Furthermore, there is a growing interest in the role of the exosome in the interaction between the cancer-associated myofibroblasts and cholangiocarcinoma which lead to CCA growth. However how cholangiocarcinoma-derived exosome affect the cancer-associated myofibroblasts in the tumor microenvironment remain unknown. In this study, we examined whether exosome produced by cholangiocarcinoma could involve in the prompt of CCA cells growth by regulation of myofibroblast. We found that cholangiocarcinoma-derived exosome could prompt elevated α-smooth muscle actin and …

Perceived Stress, Salivary Cortisol, And Depression In Adults Diagnosed With Postconcussion Syndrome; A Pilot Study, Christine Fish-Huson

Theses and Dissertations

Traumatic Brain Injury (TBI) affects approximately 1.7 million persons in the United States annually, 75% are categorized as mild (mTBI). Most persons who experience mTBI will recover, however an estimated 10% will develop Postconcussion Syndrome (PCS). Evidence supports a relationship between perceived stress, salivary cortisol, and depressive symptoms in persons after TBI; however, there are no known studies exploring these relationships in the PCS patient population. A sample of 17 men and women diagnosed with PCS were recruited from Southwest and Central Virginia. Data collection included the Rivermead Postconcussion Questionnaire, Perceived Stress Scale-10, Center for Epidemiological Studies-Depression Scale and the …

Characterization Of The Novel Interaction Between Neisseria Gonorrhoeae Tdfj And Its Human Ligand S100a7, Stavros Maurakis

Theses and Dissertations

Neisseria gonorrhoeae is an obligate human pathogen that causes the common STI gonorrhea, which presents a growing threat to global health. The WHO estimated 78 million new cases of gonorrhea worldwide in 2017, with estimates of 820,000 new cases in the United States alone according to the CDC. High-frequency phase and antigenic variation inherent in N. gonorrhoeae, coupled with its natural ability to rapidly acquire and stably integrate antimicrobial resistance factors into its genome, have culminated in an infection against which there is no effective vaccine, and for which the list of viable therapeutic options is quickly shrinking. Moreover, no …

Translational Insights Into The Genetic Etiology Of Mental Health Disorders: Examining Risk Factor Models, Neuroimaging, And Current Dissemination Practices, Jessica L. Bourdon

Theses and Dissertations

Psychiatric genetics is a basic science field that has potential for practical application and effective translation. To date, translational frameworks utilized by this field have been linear (e.g., sequential) in nature, focusing on molecular genetic information. It is proposed that non-linear (e.g., socio-ecological) frameworks are a better way to immediately translate non-molecular genetic information. This dissertation explored the translation of psychiatric genetic information in two ways. First, a survey was sent to academic stakeholders to assess the state of the science regarding the translation of genetic information to the clinical care of mental health disorders. Findings from this indicate a …

Social Jetlag, Depressive Symptoms, And Longitudinal Outcomes In College Students, Morgan P. Reid

Theses and Dissertations

Social jetlag refers to the chronic shift in sleep timing between work and free days and has been associated with a variety of negative physical and psychological outcomes. Existing research on social jetlag has relied heavily on cross-sectional studies, preventing researchers and practitioners from assessing the effects of social jetlag over time. The current study used longitudinal data to explore the directionality of the association between social jetlag and depressive symptoms as well as the longitudinal associations between social jetlag, academic performance, and wellbeing in college students. Gender and race were also assessed as potential moderators of these associations. Cross-lagged …

Race, Health, And Social Support On Campus: An Exploration Of Discrimination On Health And Fraternity/Sorority Membership For African American College Students, Alexandra M. Munson

Theses and Dissertations

African American college students face a myriad of unique race related stressors on campus, yet there is a gap of knowledge on how these experiences may impact overall health as well as what may mediate these effects. The goal of the current study was threefold. First, it was to better understand the relationship between health outcomes and the experience of discrimination on college campuses for African American students. Second, it further investigated the research of Pieterse & Carter (2007), to explore if perceived discrimination influences health outcomes above and beyond general life stress in the emerging adult population. Lastly, it …

Co-Localization Of Polycystic Ovary Syndrome Candidate Gene Products In Human Theca Cells Suggests Novel Signaling Pathways, Rewa M. Kulkarni

Theses and Dissertations

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility and the most common endocrinopathy of women of reproductive age. Genome-wide association studies (GWAS) identified a number of loci associated PCOS in different ethnic populations, including women with Asian and European ancestry. Replication studies have confirmed some of these associations. Among the loci identified are those located near the LH receptor gene (LHCGR), a clathrin-binding protein gene (DENND1A) that also functions as a guanine nucleotide exchange factor, and the gene encoding RAB5B, a GTPase and protein involved in vesicular trafficking. The functional significance of one …

A Contextual Approach To Understanding Psychiatric Comorbidities In Adolescents With Autism Spectrum Disorder: Individual, Peer, And Family Factors, Jessica L. Greenlee

Theses and Dissertations

Psychiatric comorbidities are common in youth with Autism Spectrum Disorders (ASD) and can have a negative impact on adaptive functioning and quality of life. Research has primarily focused on individual characteristics associated with internalizing problems such as age, intelligence, and social functioning. However, developmental theory supports the notion that individual level factors are necessary but not sufficient to understand the mental health of youth with ASD. Using the Family Ecology Framework as a guide, the purpose of this study was to examine how peer and family contexts are associated with anxiety and depression symptoms of adolescents with ASD. Using data …

Role Of Sarm1 In Chronic Immune-Mediated Central Nervous System Inflammation, Kenneth E. Viar Ii

Theses and Dissertations

SARM1 is an injury-induced nicotinamide adenine dinucleotide nucleosidase (NADase) that was previously shown to promote axonal degeneration in response to traumatic, toxic, and excitotoxic stressors. This raises the question of whether a SARM1-dependent program of axonal degeneration is central to a common pathway contributing to disease burden in neurological disorders. The degree to and mechanism by which SARM1 inactivation decreases the pathophysiology of such disorders is of interest to establish the rationale to pursue SARM1 as a therapeutic target. In this study, we compare the course and pathology of experimental autoimmune encephalomyelitis (EAE) in Sarm1-knockout (KO) mice and wild-type …

Radiotherapy Response Using Intravoxel Incoherent Motion Magnetic Resonance Imaging In Liver Patients Treated With Stereotactic Body Radiotherapy, Benjamin C. Lewis

Theses and Dissertations

Magnetic resonance imaging is utilized as an important tool in radiation oncology for delineation of healthy and cancerous tissues, and evaluating the functionality of those tissues, structures, and organs. Currently, the clinical imaging protocol at Virginia Commonwealth University includes anatomical imaging for tissue and structure delineation, and to observe treatment induced changes. Diffusion weighted imaging (DWI) is also acquired for calculation of apparent diffusion coefficient (ADC) values to provide quantitative information on tissue diffusivity and microstructure. However, anatomical images and ADC values may not display the true extent of changes in tissue. This work seeks to further utilize the capabilities …

The Structure And Stability Of Cationic Metal-Benzene Clusters, Daniel P. Rabayda

Theses and Dissertations

We have investigated the size-dependent stability and structure of benzene, aluminum-benzene, and vanadium-benzene clusters. Motivated by gas-phase experimental studies performed by an experimental collaborator, we have used first-principle electronic structure methods to identify the structure of Al⁺(Bz)_n, V⁺(Bz)_n, and Bz_n clusters. Our studies reveal that cationic aluminum-benzene clusters have a magic number of 13, and that its high stability may be understood by analyzing the structure of the cluster. We also investigate the structure of vanadium-benzene clusters which have a magic number of 2. Here I examine the benzene-cation and benzene-benzene …

The Role Of Sphingosine Kinase 2 In Alcoholic Liver Disease, Eric K. Kwong

Theses and Dissertations

Alcoholic liver disease (ALD) is one of the most common liver diseases worldwide characterized by the accumulation of lipids within the liver, inflammation and the possibility of progressing to cirrhosis and liver failure. More importantly, there are currently no effective treatments for ALD and liver transplantation remains the only therapeutic option for end-stage liver disease. Previous studies have shown that ALD is a result of a combination of endoplasmic reticulum (ER) stress, lipid metabolism dysregulation and inflammation. It has been previously reported that alcohol disrupts gut microbiota homeostasis and causes increased endotoxins that contribute to the pathology of ALD. However, …

Behavioral And Immune Implications Of Chronic Predator Exposure In Adolescent Mice, Kimaya R. Council

Theses and Dissertations

Evidence suggests that toxic stressors introduced early in development have prolonged effects on neuronal function due, in part, to the maturation of the hypothalamic- pituitary- adrenal (HPA) axis during adolescence. Early life stress has been implicated as a driver of mood and anxiety disorders, like depression and post-traumatic stress disorder - the extent to which appears to be sex dependent. While it is known that early life stress results in several consequences in adulthood, the mechanisms by which these changes manifest are unclear. Stress-induced changes in mood and behavior are often associated with alterations in inflammatory reactivity in both the …

A High Fructose Diet Alters Affective-Like Behavior And Metrics Of Synaptic Mitochondrial Function Differentially In Male And Female Rats, Alix H. Kloster

Theses and Dissertations

Fructose consumption has become a normalized part of the standard American diet over the past 40 years. While fructose consumption is a known risk factor of metabolic syndrome, there is increasing evidence that fructose consumption influences brain and behavior. Recently, more interest has been focused on mitochondrial dysfunction as a potential link between metabolic stress and modifications of the central nervous system. Mitochondria are in the unique position of both regulating and being vulnerable to alterations in energy homeostasis. Sex-differences are well categorized in the presentation of metabolic symptoms associated with excessive fructose consumption. Thus, it is important to characterize …

Groundwater Quality Assessment Of The Piney Point Aquifer In The Virginia Coastal Plain, Elizabeth J. Keily

Theses and Dissertations

The solid phase of an aquifer has an effect on the aqueous phase; if groundwater quality is degraded by the solid phase of an aquifer this is referred to as geogenic pollution. In this study, the Piney Point aquifer in the Virginia Coastal Plain was assessed for mechanisms that may release anions from the solid to aqueous phases and effect water quality. This was done by conducting leaching experiments modified from Balintova et al. (2013). Piney Point aquifer sediments and groundwaters were also analyzed to give a baseline for these experiments. Sedimentary analysis was found to be consistent with McFarland …

Lifetime, Emily E. Kuchenbecker

Theses and Dissertations

Time is my bully. Time marks the start of something, as well as the end. We are all carrying out the inexorable passing of time as it relates to our impending mortalities.

I do not fear death.

The awareness of my body’s impermanence employs me to feel that much more connected to the vessel containing that of which I am.

But what am I? Am I my body- or is it much deeper?

Through the work executed during my graduate research, I have attempted to quantify my existence through the archiving my time and body. This document ushers you through …

Connecting The Dots: Investigating The Effects Of Trans-Synaptic Tau Transmission In The Hippocampus, Michael Bamisile

Theses and Dissertations

Tauopathy, which results from the oligomerization of misfolded tau protein in neurons, is a feature present in a number of neurodegenerative diseases and a hallmark of Alzheimer’s Disease (AD). Tau is an important phosphoprotein that regulates the assembly of microtubules, but tauopathy can occur when tau becomes hyperphosphorylated. Phosphorylation prevents tau from binding to tubulin, which results in cytosolic accumulation of tau and eventual oligomerization. This abnormal accumulation of tau leads to the spreading of hyperphosphorylated tau to downstream synaptically connected neurons through an unknown mechanism. In AD, the hippocampus is one of the first brain structures to be affected …

A Mathematics Workshop For Parents: Exploring Content Knowledge And Perceptions Of Parental Involvement, Kristina C. Anthony

Theses and Dissertations

This qualitative study explored a mathematics workshop for parents and the impact on a parent’s mathematical content knowledge in rational numbers, perceptions of current instructional practices, and parental beliefs in supporting their children in learning mathematics. A 6-week parent workshop on rational numbers was offered in a rural middle school. Data sources included interviews and workshop audio transcriptions. This study concluded that a mathematics workshop supports parents in developing a conceptual understanding of rational numbers and rational number operations. Furthermore, parents recognized the importance of discourse, representation, and justification for building conceptual understanding in mathematics. Parents, who participated in the …

At The Table; An Investigation Of How Growing, Cooking, And Sharing Food Together Can Bring A Wealth Of Benefits, Angeline M. Troilo

Theses and Dissertations

MOTIVATION: The value of family mealtime has been well documented by decades of academic research. Children from families, (regardless of race, class or income), that routinely sit down to a meal together, suffer less depression, obesity and substance abuse. They also stay healthier and do better in school (Benefits 2018). There are nutrition, health, social, and mental benefits to eating with others. Research has shown that people eat more fruits and vegetables and other nutrient-rich foods when they share a meal with others. They also drink less soda and eat less fried foods (Benefits 2018). Eating meals together teaches children …

Regulatory T Cells Promote Breast Cancer Progression Through Inhibiting Classical Activation Of Macrophages, Nicholas M. Clark

Theses and Dissertations

Transient ablation of regulatory T cells has been shown to be effective at hindering tumor growth and metastasis in murine breast cancer model. Based on our lab’s previous work, we have demonstrated that NK cells and CD8+ cytotoxic T cells were not required for the protective effect of Treg cell ablation. However, we also reported that CD4+ helper T cells and IFN-γ were required for the protective effect of Treg cell ablation. Furthermore, we observed that CD11B+ cells responded to Treg ablation therapy by up-regulating target genes of IFN-γ. Therefore, this study aimed to investigate the connection between the myeloid …

Aeg-1 Knockout Sensitizes Hepatocellular Carcinoma (Hcc) Cells To Ionizing Radiation, Maheen Khan

Theses and Dissertations

Liver cancer is the fourth leading cause of cancer-associated deaths globally, and among primary liver cancers, hepatocellular carcinoma (HCC) encompasses 75-85% of all cases. HCC is a highly lethal disease due to limited treatment options – only a small subset of patients qualify for surgical resection or transplantation; the remaining patients often display resistance to radiation therapy or chemotherapy. Overexpression of the oncogene astrocyte elevated gene-1 (AEG-1) is associated with poorer survival and increased tumor recurrence in HCC, and numerous studies show its role in initiation of hepatocarcinogenesis. A prior study also demonstrated AEG-1 expression inhibits senescence by diminishing the …

Regenerative Potential Of Mesenchymal Stem Cell Derived Exosomes, Andrew P. Wong

Theses and Dissertations

Bone defects are a pervasive complication arising from many clinical conditions, both mechanical and pathological. Current treatments for large bony defects focus on applying bone grafts or synthetic materials to the defect area. Cell-based—and especially stem-cell—therapies have advanced greatly thanks to increasing attention focused on their ability to generate new tissues in situ with biomechanical properties approaching that of native tissue, but they suffer from their own shortcomings as well. Exosomes have been shown to play critical roles in cell-signaling and tissue regeneration and are therefore potentially ideal therapeutic vehicles for treating bone defects. Exosomes are small microvesicles counted amongst …

Fluvastatin And Microrna-146a Alter Interleukin-33 Mediated Mast Cell Functions., Marcela Taruselli

Theses and Dissertations

Mast cells are tissue-resident immune cells known as effector cells for the innate and adaptive immune systems. Mast cells contribute to host defenses against parasites such as large roundworm parasites, bacterial pathogens, and toxins, and participate in wound healing, but they are mostly known for their role in allergic diseases. It has been well established that during allergic diseases, mast cells are stimulated by IgE cross-linkage to release proinflammatory mediators. However, a newly discovered cytokine, IL-33 has also been implicated in allergic disease. Recently, IL-33 has been implicated as a driver of several Type I sensitivities and previous studies have …

I Thought The Earth Remembered Me, Hannah Bates

Theses and Dissertations

The forest is teeming with activity: fungi transform dead logs into nutrients, roots entangle themselves with the earth, and strong winds break resilient boughs. Like the forest, the human body functions according to a complex system of agents - from the micro bacteria in the gut to the pores of the skin. The built world has often been rendered in opposition to these processes of nature. As a vessel through which the world is experienced, the body is an intermediary between raw matter and fabricated things. The planet is suffused with human life, and there is a critical tension between …

In A Building, A Stairwell, A Room Speaks, Tsz Wai Wallis Cheung

Theses and Dissertations

Working toward a personal definition of womanhood while progressing with my research in feminist discourse, I frame biographical events alongside the intricate use of language surrounding feminist theory. Experimenting with material specificities that speak to my personal narratives and cultural significance, my work seeks to address the interlacing operations of subjectivity expanding on the intersection of class, gender and race.

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) …

Spag17 Deficiency Impairs Neuronal Cell Differentiation In Developing Brain, Olivia J. Choi

Theses and Dissertations

The development of the nervous system is a multi-level, time-sensitive process that relies heavily on cell differentiation. However, the molecular mechanisms that control brain development remain poorly understood. We generated a knockout (KO) mouse for the cilia associated gene Spag17. These animals develop hydrocephalus and enlarged ventricles consistent with the role of Spag17 in the motility of ependymal cilia. However, other phenotypes that cannot be explained by this role were also present. Recently, a mutation in Spag17 has been associated with brain malformations and severe intellectual disability in humans. Therefore, we hypothesized that Spag17 plays a crucial role in …

Pharmacodynamics Of Monoamine Transporter Releasing Agents And Reuptake Inhibitors, Alexa Holloway

Theses and Dissertations

Ligands of the human monoamine transporters encompass a wide range of both illicit and therapeutic drugs that act upon neural circuitry related to reward, motivation, and the processing of salient stimuli. The present study utilizes two methods for analyzing transporter substrates and inhibitors in order to characterize activity and assess potency. The first measures transient changes in intracellular calcium as a surrogate for transporter activity by harnessing the electrical coupling of monoamine transporters and L-type calcium channels. This is used to analyze novel chimera of the strong hDAT inhibitors methylphenidate and ��-PPP in order to assess the contribution of specific …