Digital Commons Network^™

An Enzymology And Inhibition Study Of A Camp-Dependent Protein Kinase Linked To Acth-Independent Cushing's Syndrome, Nicole Luzi

Theses and Dissertations

Cyclic-AMP dependent protein kinase (PKA) is a key intracellular signal transduction kinase that is modulated by G_s- and G_i-coupled GPCRs. Under normal physiological conditions, PKA exists as an inactive holoenzyme made up of two catalytic subunits and two regulatory subunits. Upon cAMP binding to the regulatory subunits, the catalytic subunits (PKACa) are released to perform various downstream phosphorylation events. However, aberrant PKA activation can cause various diseases including Cushing’s Syndrome, which is an endocrine disorder caused by the overproduction of cortisol by the hypothalamus-pituitary-adrenal hormone system. This disorder can be caused by pituitary adenomas that release …

Using Lipidomics To Characterize The Inflammatory Mechanisms In Sepsis And Pre-Eclampsia, Daniel Stephenson

Theses and Dissertations

Lipidomics, a rapidly developing field of study, focuses on the classification and quantitation of lipid species. Lipidomics has emerged in the forefront of scientific research due to the key roles that lipids play in metabolism, cancer, and disease. Using mass spectrometry as a tool for analysis, understanding the role eicosanoids and sphingolipids play has advanced rapidly. Being able to observe these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and identification of eicosanoid and sphingolipid biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia. In the studies herein, we developed targeted mass spectrometric methods …

Spatial And Temporal Distributions Of Larval Clupeid Fishes In A Tidal Freshwater Marsh Complex, Philip Reid Anderson

Theses and Dissertations

Tidal freshwater wetlands provide valuable ecosystem services such as nutrient cycling, coastal flood control, and reproductive habitat for early life stages of economically and ecologically important fishes. The nutrient rich environments that tidal freshwater wetlands occur in support high levels of primary productivity of phytoplankton and vegetation that provide essential reproductive habitat for anadromous clupeid fishes (Alosa spp., Brevoortia tyrannus) in Chesapeake Bay tributaries. Seasonal retention of clupeid eggs and larvae within tidal freshwater habitats may enhance early growth, survival, and year class strength. The primary goal of the present study was to characterize the relative importance of …

Adaptation And Validation Of The Situation Awareness Global Assessment Technique For Student Registered Nurse Anesthetists, Deniz Dishman

Theses and Dissertations

Anesthesia is a health care specialty fraught with high workload demands, stressful work environments, increased production pressure, work areas with many distractions, an increasing use of advanced technology, and the constant need to prioritize work actions. Effective clinical judgment in this dynamic environment necessitates that the provider demonstrate the ability to project what may occur secondary to actual or potential condition changes. These key elements operationalize situation awareness (SA).

High level SA is an important characteristic for the successful development of student registered nurse anesthetists (SRNAs). With Endsley’s “Theory of Situation Awareness” as the foundation, the goal of this study …

Development Of Bivalent Ligands Targeting The Putative Mu Opioid Receptor And Chemokine Receptor Cxcr4 Heterodimer, Bethany A. Reinecke

Theses and Dissertations

Human immunodeficiency virus (HIV) and opioid abuse have been described as synergistic epidemics. Pharmacologically, it has been found that opioids have the capacity to enhance HIV infection and replication. Research has shown that activation of the mu-opioid receptor (MOR) elevates the expression of the HIV-1 entry co-receptor CXCR4 on T-lymphocytes in the peripheral nervous system, thus allowing for enhanced viral entry and invasion. Although the exact mechanism for opioid modulation of CXCR4 expression and subsequent exacerbation of HIV is unknown, several hypotheses exist. One hypothesis is that MOR and CXCR4 are functionally interacting through the formation of a heterodimer. This …

Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee

Theses and Dissertations

Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol …

Evaluating Predixcan’S Ability To Predict Differential Expression Between Alcoholics And Non-Alcoholics, John E. Drake Jr

Theses and Dissertations

PrediXcan is a recent software for the imputation of gene expression from genotype data alone. Using an overlapping set of transcriptome datasets from postmortem brain tissues of donors with alcohol use disorder and neurotypical controls, which were generated by two different platforms (e.g., Arraystar and Affymetrix), and an additional unrelated transcriptome dataset from lung tissue, we sought to evaluate PrediXcan’s ability to impute gene expression and identify differentially expressed genes. From the Arraystar platform, 1.3% of matched genes between the measured and imputed expression had a Pearson correlation ≥ 0.5. Our attempt to replicate this finding using the expression data …

Bantaba: Designing The Sacred Circle, Tashiara Scott

Theses and Dissertations

MOTIVATION In Richmond, there are 1.21 times as many African Americans as any other ethnic group. Yet 63.4% of African Americans live in poverty (Richmond, VA). African Americans face greater exposure to stress due to low socioeconomic status and poverty. In these communities, “discrimination and deprivation undermine individuals’ ability to accumulate the social and material resources to mitigate the effects of stress” (Brondolo, 2018). In this city’s African American community, where stress levels are high and consequential health concerns are prevalent, dance can be a remedy for managing stress and improving health (Hanna, 2006).

DESIGN PROBLEM How can an intentionally …

Upper Thermal Limits Vary Among And Within Native Bee Species In Relation To Season, Voltinism, And Nest Type, Kálmán K. Csigi Xiv

Theses and Dissertations

Native bees are only recently gaining attention for the extent to which they aid in pollination and ecosystem services. These services are threatened by predictions of warming temperatures if bees are not able to respond. Voltinism - the number of generations produced annually- can strongly influence thermal conditions experienced by both developing and adult bees based on emergence strategies for each voltinism type. Differences in experienced thermal conditions brought on by climate change could therefore affect upper thermal limits (UTL) in bees. This study observes UTLs across a foraging season within and among native bee species vi to elucidate the …

Facilitative And Competitive Tradeoffs Between Morella Cerifera Seedlings And Coastal Grasses, Michael N. Sinclair

Theses and Dissertations

Morella cerifera is a rapidly expanding native shrub on the Virginia barrier islands which displaces other native coastal species and may interrupt normal sediment dynamics. Barrier islands are considered stressful environments with low nutrients, high solar load, and frequent drought and salt exposure; facilitation often dominates in stressful environments according to the Stress Gradient Hypothesis. The objective of this project was to understand the importance of species interactions with grasses on the growth and physiology of M. cerifera at the seedling life stage through both field and lab experiments. Grasses provided ~1.3°C insulation to shrubs during winter freeze events and …

Determination Of Optimal Parameter Estimates For Medical Interventions In Human Metabolism And Inflammation, Marcella Torres

Theses and Dissertations

In this work we have developed three ordinary differential equation models of biological systems: body mass change in response to exercise, immune system response to a general inflammatory stimulus, and the immune system response in atherosclerosis. The purpose of developing such computational tools is to test hypotheses about the underlying biological processes that drive system outcomes as well as possible real medical interventions. Therefore, we focus our analysis on understanding key interactions between model parameters and outcomes to deepen our understanding of these complex processes as a means to developing effective treatments in obesity, sarcopenia, and inflammatory diseases.

We develop …

Expansion Of The Genetic Code To Include Acylated Lysine Derivatives And Photocaged Histidine, William D. Kinney

Theses and Dissertations

The genetic code of all known organisms is comprised of the 20 proteinogenic amino acids that serve as building blocks on a peptide chain to form a vast array of proteins. Proteins are responsible for virtually every biological process in all organisms; however, the 20 amino acids contain a limited number of functional groups that often leaves much to be desired. The lack of diversity addresses the need to increase the genetic repertoire of living cells to include a variety of amino acids with novel structural, chemical, and physical properties not found in the common 20 amino acids. In order …

(And I Can't Stress This Enough) In My Mouth: Extradiegetic Affect As Material, C. Klockner

Theses and Dissertations

(and i can’t stress this enough) in my mouth: Extradiegetic Affect as Material is a non-linear exploration into the structures of feeling that exist in relation to cinema in its role as a technology for generating subjectivity. In the development of this research, a proposal of cinema’s likeness to the ecological circulation of microplastics is drawn in order to illustrate cinema’s materiality and nearly invisible ubiquity. The notion of extradiegetic affect is outlined as a post-cinematic condition in which lived experience becomes secondary to cinematic representation and which, simultaneously, becomes directly shaped by engaging with these representations.

Biometal-Induced Structural Consequences Of Α-Synuclein – The Parkinson’S Disease Protein, Dinendra L. Abeyawardhane

Theses and Dissertations

The pre-synaptic protein α-Synuclein (αS) is often linked to the pathology of Parkinson’s disease (PD), an age-related neurodegenerative disorder. Lewy bodies, the cytopathological hallmarks of PD, are found to be rich in aggregates of misfolded αS protein. Metal dyshomeostasis has also been linked to PD due to the accumulation of iron in the substantia nigra pars compacta, and diminished copper levels reported in this same region. Metal dyshomeostasis in the brain coupled with oxidative stress can enhance the aggregation of αS. Recently, it was confirmed that mammalian αS is universally acetylated at the N-terminus, a common post-translational modification in …

The Development Of Intrinsically Cell-Permeable Peptide Libraries Using Mrna Display, Nicolas A. Abrigo

Theses and Dissertations

Peptides are emerging as promising therapeutics due to their inhibitory affinity towards protein-protein interactions (PPI). However, peptides have been limited mainly by their poor bio-stability and lack of cell permeability. Efforts to generate drug-like peptides have led to the development of macrocyclic peptides, which exhibit improved stability. Yet, most macrocyclic peptides still require the assistance of a cell penetrating peptide (CPP) for cellular entry.

High throughput technologies have been exceptional tools for the discovery of peptides to interrupt PPIs. This work details the recent advancements we have made to improve our high throughput technique, mRNA display, to yield more therapeutically …

Erbb3 Signaling And Its Effect On Spheroid Formation In Ovarian Cancer, Muskan Bansal, Danielle Burke, Mara P. Steinkamp

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

ErbB3 is a receptor tyrosine kinase in the epidermal growth factor receptor (EGFR) family. Like other family members, it has an extracellular ligand-binding domain, a transmembrane domain, and an intracellular kinase domain. ErbB3 requires interactions with other receptors and dimerizes with ErbB2 and MET, to activate downstream signaling pathways. Mutations in the ErbB3 gene within the extracellular and kinase domains have been identified in many cancer types. To understand the impact of ErbB3 on cancer growth and metastasis, the human ovarian cancer cell line, OVCAR8, was used as a model. Parental OVCAR8 cells that express ErbB2 and ErbB3 were compared …

Therapeutic Targeting Of Relaxin Signaling In Ischemic Heart Disease, Siva Teja Vk Devarakonda

Theses and Dissertations

Ischemic heart disease is characterized by reduced perfusion of oxygenated blood to the myocardium, potentially resulting in infarction upon occlusion of coronary arteries. While prompt reperfusion and advances in in-hospital care have led to a decline in short term mortality, sustained damage to the ventricle, along with reperfusion injury, can lead to progressive deterioration in cardiac function. Limiting the extent of this initial ischemia-reperfusion injury and combating the course of adverse remodeling remains the scope of several preclinical studies geared towards improving cardiac health after MI. To this, relaxin-2 – the peptide hormone that regulates maternal hemodynamic function during pregnancy …

Glycosaminoglycan Mimetics For The Treatment Of Cancer And Lung Inflammation, Shravan Morla

Theses and Dissertations

Glycosaminoglycans (GAGs) are linear polysaccharides whose disaccharide building blocks consist of an amino sugar and either uronic acid or galactose. They are expressed on virtually all mammalian cells, usually covalently attached to proteins, forming proteoglycans. GAGs are highly negatively charged due to an abundance of sulfate and carboxylic acid groups, and are structurally very diverse, with differences arising from chain length, the type of monomeric units, the linkages between each monomeric unit, the position of sulfate groups, and the degree of sulfation. GAGs are known to interact with a multitude of proteins, impacting diverse physiological and pathological processes. In addition, …

Berthe Morisot: Woman Impressionist, Kathryn Mcfadden

Art Inquiries

No abstract provided.

Action Forms: Retrospective: Exhibition Of Ilija Šoškić, Rachel Klipa

Art Inquiries

No abstract provided.

Designing Biomimetic Implant Surfaces To Promote Osseointegration Under Osteoporotic Conditions By Revitalizing Mechanisms Coupling Bone Resorption To Formation, Ethan M. Lotz

Theses and Dissertations

In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, …

The Compass, Summer 2019

The Compass, 2018-

The Compass is an annual orientation guide for VCU students produced by the Student Media Collective in the VCU Student Media Centered. The guide is distributed physically during summer orientation sessions for new and transfer students. The publication includes short articles, illustrations, letters of welcome from students and administrators, comics, and advertisements from VCU and Richmond organizations.

Virginia Dental Journal (Vol. 96, No. 1, 2019)

Virginia Dental Journal

No abstract provided.

The Role Of Irf1 In The Brain And In Adaptive Responses Of Astrocytes, Andrew Hoskins

Theses and Dissertations

In neurodegenerative diseases, the CNS becomes inflamed through activation of pathways, including the NF-B pathway. Some of the therapies for those diseases target neuroinflammatory pathways. Here, we explore the mechanisms for the upregulation of a subset of genes following a restimulation of the NF-B pathway. We discover that this upregulation occurs independent of IRF1 expression and type 1 interferon signaling. A knockdown of IRF1 using siRNA and an inhibition of JAK proteins using inhibitor AG490 both had no effect on priming. A secreted factor was found to upregulate the expression of both this subset of genes and genes encoding pro-inflammatory …

Management Of The Open Apex Using A Bioceramic Apical Barrier: Success And Survival Rates At Virginia Commonwealth University, Adam Sarnowski

Theses and Dissertations

Purpose: The aim of this study was to assess the outcome of treatment of teeth with open apices managed by the orthograde placement of a bioceramic apical barrier as well as to identify potential outcome factors for this type of treatment. Methods: Patient records were pooled from graduate resident cases completed at Virginia Commonwealth University between January 1, 2010 and May 31, 2018. A total of 515 patients were identified using relevant ADA codes and a key word search within the patient record database. A total of 104 patients (119 teeth) had an open apex that had NSRCT utilizing a …

Adverse Childhood Experiences Indirectly Affect Child Telomere Length Through Self-Regulation, David Sosnowski

Theses and Dissertations

The goals of present study were: (a) to examine associations between adverse childhood experiences (ACEs) and telomere length during childhood using ACE composite scores both with and without “new” adversities (i.e., parental death and poverty), and (b) to determine if ACEs indirectly affect telomere length through children’s self-regulatory abilities (i.e., effortful control and self-control). The analytic sample consisted of national data from teachers, biological parents, and their children (N = 2,527; M_age = 9.35, SD = .36 years; 52% male; 45% Black). Results from linear regression analyses revealed a statistically significant main effect of updated (but not traditional) …

Effect Of Manipulation Of Notch Signaling Pathway On Neural Stem Cell Proliferation In The Hippocampus Following Traumatic Brain Injury, Seung L. Kim

Theses and Dissertations

Effect of Manipulation of Notch Signaling Pathway on Neural Stem Cell Proliferation in the Hippocampus Following Traumatic Brain Injury

By Seung L. Kim A thesis statement submitted for degree requirement in Mater of Science Virginia Commonwealth University, 2019 Advisor: Dong Sun, MD. PhD. Department of Anatomy & Neurobiology

The Notch signaling pathway is known as a core signaling system in maintaining neural stem cells (NSCs) in embryonic development and adulthood including cell proliferation, maturation, and cell fate decision. Proliferation of NSCs persists throughout lifespan in neurogenic niches and is often upregulated following neurological insults including traumatic brain injury (TBI). Therefore, …

Cell Type And Substrate Dependence Of Fibronectin Properties And Mechanotransduction, Navpreet S. Saini

Theses and Dissertations

Fibronectin is an important protein that is able to bind to other fibronectin molecules and to cell surface receptors. In doing so, the interactions fibronectin can perform is important for the processes of cell migration and tissue formation. Understanding the properties of fibronectin and fibril assembly is useful for areas such as wound healing, where fibronectin molecules are assembled to protect the tissue and to perform other tasks. Because of these reasons, it is important to understand how fibronectin is assembled and how its properties affect the fibril assembly, which in return affects the way the cell matrix operates. Previously …

The Effect Of Repeated Opioid Dosing On The Gut Microbiome, Anne K. Rowe

Theses and Dissertations

Opioids are prescribed to millions of people each year, especially to help patients cope with chronic pain, something from which more than a fifth of U.S. adults suffer (CDC). Unfortunately, opioid use and abuse has become a national emergency as the number of opioid prescriptions, opioid misuse, and opioid-related drug overdoses and death have drastically increased in the last twenty years (HHS). Because of the emergent state surrounding opioid use and misuse, the effects of opioids on all aspects of the human body has been an increasingly large focus of research scientists. This study focuses on the possible effect of …

The Walls We Put Up - Loneliness And Belonging In Urban Co-Living, Richard Rozewski

Theses and Dissertations

ABSTRACT

Concurrent issues of social isolation and loneliness have long been recognized as problems that affect seniors but it is also being proven to affect young people as well, specifically with the rise of new technologies and a perception of connectedness. Co-living provides one alternative design solution to traditional housing models which can unlock a range of social benefits.

MOTIVATION

Loneliness is an unfortunate reality of modern life and it is something that most people experience at least once in their life (Cacioppo & Patrick, 2008). A study carried out by Berguno, Leroux McAinsh, Shaikh (2004), showed that 80% of …