Characterization Of Mechanism Of Action Of Hydrogen Sulfide (H2s) In The Regulation Of Smooth Muscle Function, Ancy D. Nalli

Theses and Dissertations

Hydrogen sulfide (H₂S) is receiving increasing interest, as much as nitric oxide (NO) and carbon monoxide have received previously, to understand its physiological functions as it meets all the criteria to define as a third gasotransmitter. Endogenous synthesis from L-cysteine via cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) and the function of H₂S as an inhibitor of smooth muscle contraction in gastrointestinal tract are known. However, the loci of generation and action of H₂S, and the mechanism of inhibition of contraction are unknown. Hence, my aims in the present study are to: i) identify the expression …

Experimental Evolution Of An Rna Virus In Wild Birds: Evidence For Host-Dependent Impacts On Population Structure And Competitive Fitness, Nathan D. Grubaugh, Darci R. Smith, Doug E. Brackney, Angela M. Bosco-Lauth, Joseph R. Fauver, Corey L. Campbell, Todd A. Felix, Hannah Romo, Nisha K. Duggal, Elizabeth A. Dietrich, Tyler Eike, Jennifer E. Beane, Richard A. Bowen, William C. Black, Aaron C. Brault, Gregory D. Ebel

Journal Articles: Epidemiology

Within hosts, RNA viruses form populations that are genetically and phenotypically complex. Heterogeneity in RNA virus genomes arises due to error-prone replication and is reduced by stochastic and selective mechanisms that are incompletely understood. Defining how natural selection shapes RNA virus populations is critical because it can inform treatment paradigms and enhance control efforts. We allowed West Nile virus (WNV) to replicate in wild-caught American crows, house sparrows and American robins to assess how natural selection shapes RNA virus populations in ecologically relevant hosts that differ in susceptibility to virus-induced mortality. After five sequential passages in each bird species, we …

Does Human Papillomavirus Affect Pregnancy Outcomes? An Analysis Of Hospital Data 2012-2014, Harpriya Kaur, Delf Schmidt-Grimminger, Steven W. Remmenga, Baojiang Chen, K.M. M. Islam, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

Objective: To estimate the rate of Human Papillomavirus among pregnant women and its impact on the pregnancy outcomes.

Study design: This was a retrospective cohort study of women who sought prenatal care and later delivered at the Nebraska Medical Center from 2012-2014. Human Papillomavirus infection was based on a cytological cervicovaginal diagnosis (Pap test) report. Bivariate and multivariable analyzes were performed using SAS 9.3.

Results: Of the total sample size of 4824 women, 221 (4.4%) were HPV-positive. Women with Human Papillomavirus infection had increased risk of preeclampsia (adjusted OR: 2.83 95% CI: 1.28-6.26) and were also 1.8 times more likely …

Regulation Of Tie2 Extracellular Complex Formation In Angiogenesis, Annamarie Dalton

Theses and Dissertations

Pathological angiogenesis is an essential component of tumor growth, development, and metastasis for which few effective therapeutic options exist. Though many cancer therapies target the function of cell surface receptors, mechanisms regulating membrane receptor crosstalk remain unclear. Two important families of receptors in angiogenesis, the Ties and Integrins, respond to the extracellular environment via outside-in and, in the case of Integrins, also inside- out signaling. Recent reports showed that the endothelial specific tyrosine kinase receptor, Tie2, forms complexes with two of the endothelial Integrin heterodimers, α₅β₁ and α_Vβ₃, providing a convenient mechanism for …

Risperidone And Its Deconstructed Analogs: Functional Effects On The 5ht2ar, Sneha Shah

Theses and Dissertations

G protein-coupled receptors (GPCRs) are seven-transmembrane domain receptors that sense extracellular signal and activate intracellular signaling pathways. The serotonin 5HT2A receptor (or 2AR) is one of the GPCRs coupled to Gq proteins, activating PLC and hydrolyzing PIP2. This hydrolysis causes a diffusion of bound PIP2 away from the channel binding site resulting in G protein-gated inwardly rectifying K⁺ channel (GIRK) inhibition and a downstream stimulation of Ca²⁺ release from endoplasmic reticulum stores. Previous experiments have demonstrated that the serotonin 5HTA receptor is a target of serotonergic psychedelic drugs, such as LSD, and partially mediates the action of many …

Mitochondrial Biogenesis And Electrical Properties Of Hpsc-Derived Motor Neurons, Laura O'Brien

Theses and Dissertations

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) hold great promise in the fields of drug development and regenerative medicine. If iPSCs reprogrammed from patient cells replicate what is seen in vivo they may be used as a model of disease. A process that is disrupted in many neurodegenerative diseases is mitochondrial biogenesis. One of these diseases is amyotrophic lateral sclerosis (ALS), which is characterized by loss of motor neurons in the brain and spinal cord. Differentiation of hPSCs into motor neurons offers a way to study a previous unavailable cell …

Development Of Non-Traditional Platinum Anticancer Agents: Trans-Platinum Planar Amine Compounds And Polynuclear Platinum Compounds, Daniel E. Lee

Theses and Dissertations

Development of Non-Traditional Platinum Anticancer Agents: trans-Platinum Planar Amine Compounds and Polynuclear Platinum Compounds

By Daniel E. Lee, 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, 2015

Major Director: Nicholas P Farrell, Ph.D., Professor, Department of Chemistry

Platinum anticancer compounds with cis geometry, similar to cisplatin, have been explored to circumvent the cisplatin resistance; however, they were not considered broadly active in cisplatin cells due to exhibiting similar or same cell death mechanism as cisplatin. Platinum compounds with trans geometry were less studied …

A Justification For The Trend Towards Indirect Pulp Therapy, Marissa Kuhnen

Theses and Dissertations

Purpose: The purpose of this retrospective chart review was to determine how primary molars needing vital pulp therapy have been treated in the past four years at Virginia Commonwealth University (VCU) and to determine which treatments: indirect pulp therapy (IPT), formocresol pulpotomy, and ferric sulfate pulpotomy have been successful. Methods: AxiUm records that contained the procedure codes D3120 (Pulp Cap – Indirect) or D3220 (Therapeutic Pulpotomy) were totaled by year. Visit records were queried again to identify treatment failures i.e. extractions or pulpectomy. Results: In 2010, 52% of vital pulp therapies were ferric sulfate pulpotomies and in …

Elucidating The Role Of Endogenous Electric Fields In Regulating The Astrocytic Response To Injury In The Mammalian Central Nervous System, Matthew L. Baer

Theses and Dissertations

Endogenous bioelectric fields guide morphogenesis during embryonic development and regeneration by directly regulating the cellular functions responsible for these phenomena. Although this role has been extensively explored in many peripheral tissues, the ability of electric fields to regulate wound repair and stimulate regeneration in the mammalian central nervous system (CNS) has not been convincingly established. This dissertation explores the role of electric fields in regulating the injury response and controlling the regenerative potential of the mammalian CNS. We place particular emphasis on their influence on astrocytes, as specific differences in their injury-induced behaviors have been associated with differences in the …

Identifying Problems During Transitions Of Care And Reasons For Emergency Department Utilization In Community-Dwelling Older Adults, Antoinette B. Coe

Theses and Dissertations

A mixed methods approach was used for this study. The setting was a low-income, subsidized housing apartment building for community-dwelling older and younger disabled adults identified as a health care hot spot due to high rates of ambulance use. The study purpose was to identify reasons for ED use and problems during transition from ED to home, predictors of zip code 23220 (health care hot spot) in emergent and non-emergent ED visits, and predictors of total ED costs in community-dwelling older adults living in a health care hot spot. Semi-structured interviews with residents who used the ED, an existing database …

Axon Initial Segment Stability In Multiple Sclerosis, Suneel K. Thummala

Theses and Dissertations

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by inflammation and demyelination. In addition to these hallmark features, MS also presents with axonal pathology, which is likely responsible for the signs and symptoms of the disease. Although prominent in MS, axonal pathology is frequently considered a consequence of demyelination and not a primary event. This conclusion is consistent with demyelination inducing the loss of specific axonal domains, known as the nodes of Ranvier that are responsible for the propagation of action potentials along the axon. In contrast, we propose that axonal pathology associated with MS …

Mysteries Of The Trypanosomatid Maxicircles: Characterization Of The Maxicircle Genomes And The Evolution Of Rna Editing In The Order Kinetoplastida, Preethi Ranganathan Iyengar

Theses and Dissertations

The trypanosomatid protists belonging to Order Kinetoplastida are some of the most successful parasites ever known to mankind. Their extreme physiological diversity and adaptability to different environmental conditions and host systems make them some of the most widespread parasites, causing deadly diseases in humans and other vertebrates.

This project focuses on their unique mitochondrion, called the kinetoplast, and more specifically involves the characterization of a part of their mitochondrial DNA (also called kinetoplast DNA or kDNA), the maxicircles, which are functional homologs of eukaryotic mitochondrial DNA in the kinetoplastid protists. We have sequenced and characterized the maxicircle genomes of 20 …

Role Of Extracytoplasmic Rna Polymerase Sigma 70 Factor, Pg0214, In The Survival Of Porphyromonas Gingivalis And In Adaptation To Environmental Stress., David M. Smith

Theses and Dissertations

Porphyromonas gingivalis, a gram-negative anaerobic, pathogenic bacterium is a major etiological agent in the initiation and progression of periodontal disease. Due to the ever-changing environment of the oral cavity, inhabitants like Porphyromonas gingivalis must possess the ability to adapt to changes in environmental conditions like pH, temperature, oxygen tension, and metal concentration. P. gingivalis should therefore have an efficient regulatory system in order to adapt and survive in the oral cavity. This response adaptation occurs at the transcriptional level, which involves alternative sigma factors. Extracytoplasmic function sigma (ECF-s) factors are the largest group of alternative sigma factors that play …

The Effects Of Hydropeaking On Lotic Benthic Macroinvertebrate Assemblages, Andrew L. Garey

Theses and Dissertations

The term hydropeaking refers to anthropogenically induced, short-duration, high-magnitude discharge pulses that are generated in lotic systems for electricity production. The practice of hydropeaking produces the largest source of renewable energy worldwide, and its use is projected to increase through the year 2040. The primary objective of this work was to evaluate the effects of hydropeaking on benthic macroinvertebrate assemblages, which are important components of lotic ecosystems. Results of this work show that, across a wide range of impacted systems worldwide, the consistently observed patterns of elevated benthic macroinvertebrate drift in response to hydropeaking pulses are primarily related to the …

Sexual Behavior And Hiv Risk In Black College Women: The Influence Of Gender, Peer, And Relationship Beliefs, Melanie P. Moore

Theses and Dissertations

Black women in the United States disproportionately represent 64% of women with an HIV infection (CDC, 2013). Research is needed to better understand gender and culturally-specific factors that contribute to Black women’s HIV risk. The Theory of Gender and Power and the Theory of Planned behavior were used as theoretical frameworks in examining the effect of attitudinal beliefs (gender related beliefs), subjective norm beliefs (peer norms), and perceived behavioral control beliefs (relationship power) on sexual behavior in Black college women. Condom use and assertiveness in sexual communication were the dependent variables. Participants included 136 Black college women recruited through the …

Workplace Discrimination And Visual Impairment: An Analysis Of Eeoc Charges And Resolutions, Jane Mcneil

Theses and Dissertations

Workplace discrimination for individuals with visual impairments in the U.S. is an ongoing issue dating before the founding of the EEOC and the enactment of the ADA. Despite laws enacted to protect against unequal treatment in the workplace, the EEOC continues to receive submissions of formal discrimination charges from individuals with visual impairments.

The workplace is experiencing changes with increasing amounts of older adults, women, minorities, and the use of technology and the Internet. By examining characteristics of the discrimination charges and the resulting outcomes, the knowledge gained can describe the current situation and the historical progression of workplace discrimination …

Working Together: Using Protein Networks Of Bacterial Species To Compare Essentiality, Centrality, And Conservation In Escherichia Coli., Christopher Wimble

Theses and Dissertations

Proteins in Escherichia coli were compared in terms of essentiality, centrality, and conservation. The hypotheses of this study are: for proteins in Escherichia coli, (1) there is a positive, measureable correlation between protein conservation and essentiality, (2) there is a positive relationship between conservation and degree centrality, and (3) essentiality and centrality also have a positive correlation. The third hypothesis was supported by a moderate correlation, the first with a weak correlation, and the second hypotheis was not supported. When proteins that did not map to orthologous groups and proteins that had no interactions were removed, the relationship between essentality …

Speed And Resolution In The Age Of Technological Reproducibility, Shawn Taylor

Theses and Dissertations

The rate of acceleration of the biologic and synthetic world has for a while now, been in the process of exponentially speeding up, maxing out servers and landfills, merging with each other, destroying each other. The last prehistoric relics on Earth are absorbing the same oxygen, carbon dioxide and electronic waves in our biosphere as us. A degraded .jpeg enlarged to full screen on a Samsung 4K UHD HU8550 Series Smart TV - 85” Class (84.5” diag.). Within this composite ecology, the ancient limestone of the grand canyon competes with the iMax movie of itself, the production of Mac pros, …

Crown Size Comparisons In Patients With Unilateral Palatally Displaced Canines, Joseph Eliason, Steven J. Lindauer

Theses and Dissertations

Abstract

CROWN SIZE COMPARISONS IN PATIENTS WITH PALATALLY DISPLACED CANINES

By Joseph L. Eliason, D.D.S.

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Dentistry at Virginia Commonwealth University.

Virginia Commonwealth University, 2015

Thesis Director: Steven J. Lindauer, D.M.D., M.Dent.Sc.

Professor and Chair, Department of Orthodontics

There has been significant debate over the past decades regarding the etiology of palatally displaced canines. Theorized risk factors include agenesis or malformation of the lateral incisors, incisor retroclination, transverse deficiency, or genetic predisposition. The purpose of this study is to compare the linear and volumetric …

Understanding The Function Of Dyrk1a Through Characterization Of Its Interacting Proteins, Varsha Ananthapadmanabhan

Theses and Dissertations

DYRK1A is a protein kinase encoded by a gene implicated in Down syndrome pathogenesis. Loss of DYRK1A could promote oncogenic transformation. However, the regulation and substrates of DYRK1A are not fully understood. MudPIT proteomic analysis revealed novel DYRK1A interacting proteins with poorly characterized or even unknown functions. Therefore, the aim of this thesis was to understand the function of DYRK1A through the characterization of its interacting proteins. To achieve this aim, we established stable cell lines expressing these proteins and confirmed the interactions between DYRK1A and seven candidate binding partners. Furthermore, we found that all novel DYRK1A-interacting proteins also bind …

Kensington Center For Health: An Exploration Of Health, Wellness And The Built Environment., Rose Peck

Theses and Dissertations

This is a project that explores how design can integrate medical treatment and community support. The high prevalence of chronic disease is creating a national healthcare crisis. Chronic disease is the leading cause of death and disability in the United States. Consideration of a holistic sense of well-being that focuses on disease resistance, resilience, and self-management is necessary to realize and sustain health outcomes. Community engagement is imperative to improve adherence rates for lifestyle changes. This project aims to design a community wellness space that is focused on prevention, resilience and self-management. A new typology of a community-anchored wellness clinic …

Characterization Of The Interactions Between Staphylococcal Phage 80 Alpha Scaffold And Capsid Proteins, Laura Klenow

Theses and Dissertations

Staphylococcal phage 80α can serve as a helper bacteriophage for a family of mobile genetic elements called Staphylococcus aureus pathogenicity islands (SaPIs). The prototype island, SaPI1, is able to hijack the 80α capsid assembly process and redirect capsid formation to yield smaller, phage-like transducing particles carrying SaPI DNA. Capsid size redirection is accomplished through two SaPI1-encoded gene products, CpmA and an alternate scaffold protein, CpmB. The normal 80α scaffold and the SaPI1 CpmB scaffold share a small block of conserved residues at their C-termini, several of which had been shown to be essential for CpmB function. This led to the …

Forbearance Across Culture, Yin Lin

Theses and Dissertations

Forbearance is defined for the purpose of the present dissertation as, “the attempt to suppress the visible signs of negative emotion (i.e., emotional expression) and visible behaviors (i.e., the expression of negative vengeful or avoidant motives) in response to a hurt or offense, often (but not always) for the sake of group harmony.” I reviewed the literature on forbearance and cross-cultural studies in suppression of emotion or emotional expression under the framework of New Big Five personality processes and cultural models of self and relating. Then I offered three propositions about forbearance. Furthermore, I collected three samples and …

Development And Validation Of A Discrete Event Simulation Model To Evaluate The Long Term Use Of Electronic Cigarettes In Us Population, Kunal Saxena

Theses and Dissertations

Introduction: Cigarette smoking is associated with lung cancer, cardiovascular disease, and chronic respiratory conditions. It is responsible for high mortality and morbidity risk in the US population. Smokers find sudden quitting difficult and it is reported that a large number of unassisted quitting attempts are eventually unsuccessful. Electronic cigarette or e-cig is a novel battery-driven, nicotine delivery product, currently being used as a smoking cessation tool by current and former smokers. Since its resemblance to a conventional cigarette, and its non-combustible nature, e-cig use has risen exponentially in the last few years. To address such public health issues, the US …

Characterization Of A Novel Protease In Staphylococcus Aureus, Adam L. Johnson

Theses and Dissertations

A newly discovered cysteine protease, Prp, has been shown to perform an essential, site-specific cleavage of ribosomal protein L27 in Staphylococcus aureus. In Firmicutes and related bacteria, ribosomal protein L27 is encoded with a conserved N-terminal extension that must be removed to expose residues critical for ribosome function. Uncleavable and pre-cleaved variants were unable to complement an L27 deletion in S. aureus, indicating that this N-terminal processing event is essential and likely plays an important regulatory role. The gene encoding the responsible protease (prp) has been shown to be essential, and is found in all organisms …

High-Throughput Data Analysis: Application To Micronuclei Frequency And T-Cell Receptor Sequencing, Mateusz Makowski

Theses and Dissertations

The advent of high-throughput sequencing has brought about the creation of an unprecedented amount of research data. Analytical methodology has not been able to keep pace with the plethora of data being produced. Two assays, ImmunoSEQ and the cytokinesisblock micronucleus (CBMN), that both produce count data and have few methods available to analyze them are considered.

ImmunoSEQ is a sequencing assay that measures the beta T-cell receptor (TCR) repertoire. The ImmunoSEQ assay was used to describe the TCR repertoires of patients that have undergone hematopoietic stem cell transplantation (HSCT). Several different methods for spectratype analysis were extended to the TCR …

An Association Study Between Adult Blood Pressure And Time To First Cardiovascular Disease, Yongjia Pu

Theses and Dissertations

BACKGROUND: Several studies have demonstrated the association between the time to hypertension event and multiple baseline measurements for adults, yet other survival cardiovascular disease (CVD) outcomes such as high cholesterol and heart attack have been somewhat less considered. The Fels Longitudinal Study (FLS) provides us an opportunity to connect adult blood pressure (BP) at certain ages to the time to first CVD outcomes. The availability of long-term serial BP measurements from FLS also potentially allows us to evaluate if the trend of the measured BP biomarkers over time predicts survival outcomes in adulthood through statistical modeling.

METHODS: When the reference …

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

Development Of Irreversible Substrate Competitive Probes For Pka Activity, Robert A. Coover

Theses and Dissertations

The current environment for drug discovery and disease treatment relies heavily on genomic analysis, structural biology and chemical biology techniques. With the enormous advances in genomic analysis and structural biology, the use of and desire for targeted therapies has increased. However, as more genomic data for cancer disease state pathology becomes available we must ask increasingly difficult questions and even produce new technologies, such as activity-based probes, to answer these questions.

In particular, targeted kinase inhibitors for the treatment of cancer has become a mainstay for drug development for both industry and academia, but it is evident that the genomic …

A Comparison Of Vitamin D Levels In Children With Early Childhood Caries, Vanessa O. Hofilena

Theses and Dissertations

Purpose: To determine if there is an association between early childhood caries (ECC) and vitamin D deficiency, as measured via a serum sample. An exploratory goal was to investigate the possibility of measuring vitamin D with a salivary assay. Methods: Serum samples of patients who were scheduled for a dental or otolaryngology procedure under general anesthesia were assessed for 25-hydroxyvitamin D (25(OH)D), parathyroid hormone and calcium. Results: Our analysis indicates that the vitamin D levels of the controls and ECC group were significantly different. There were significant inverse correlations between: 1) PTH levels and vitamin D and 2) decayed, missing, …