Life Sciences Commons^™

Emergent Non-Consumptive Predator Effects Alter Habitat Colonization By Dipteran Prey, Ethan G. Staats

Theses and Dissertations

When ovipositing, prey organisms avoid habitat patches containing predator cues because predators consume, and negatively affect the fitness of their prey. Richness of predator species often enhances the strength of consumptive predator effects, but little is known about how multiple predators combined affect prey non-consumptively. We quantified dipteran colonization in aquatic mesocosms in response to varied predator richness. Multiple predator species combined reduced oviposition by Culex mosquitoes, chironomid midges, and the general colonizing dipteran community more than predicted by the effects of the independent predator species. Previous research which quantifies effects of multiple predators on prey as prey abundance, but …

Dysregulation Of Micrornas In Blood As Biomarkers For Diagnosing Prostate Cancer, Rhonda W. Daniel

Theses and Dissertations

Prostate cancer is the most common noncutaneous cancer among men, yet current diagnostic methods are insufficient and more reliable diagnostic markers need to be developed. The answer that can bridge this gap and enable more efficient diagnoses may lie in microRNAs. These small, single stranded RNA molecules impact protein expression at the translational level and regulate important cellular pathways. Dysregulation of these small RNA molecules can have tumorigenic effects on cells and lead to many types of cancers.

Currently the Prostate-Stimulating Antigen (PSA) is used as a diagnostic marker for prostate cancer. However, many factors can elevate PSA levels such …

The Characterization Of A Putative Virulence Factor Expressed By Sneathia Amnii, Amy Sanford

Theses and Dissertations

Preterm birth, defined at birth before 37 weeks gestation, affects millions of newborns worldwide every year. Preterm birth is a leading cause of infant morbidity and mortality. One major cause of preterm birth is preterm premature rupture of membranes (PPROM), which can be triggered by bacterial infection and inflammation. A bacterial species that has been implicated in preterm birth and other obstetric complications is Sneathia amnii. The goals of this study were to observe cytopathogenic effects caused by S. amnii strain Sn35 and identify putative virulence factors causing those effects. Sn35 was able to adhere to, invade, and damage/kill …

Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal

Theses and Dissertations

New drug discoveries and new approaches towards diagnosis and treatment have improved cancer therapeutics remarkably. One of the most influential and effective discoveries in the field of cancer therapeutics was antimetabolites, such as the antifolates. The interest in antifolates increased as some of the antifolates showed responses in cancers, such as mesothelioma, leukemia, and breast cancers. When pemetrexed (PTX) was discovered, our laboratory had established that the primary mechanism of action of pemetrexed is to inhibit thymidylate 22 synthase (TS) (E. Taylor et al., 1992). Preclinical studies have shown that PTX has a broad range of antitumor activity in human …

Investigating The Role Of The Nucleosome Remodeling Factor Nurf As A Regulator Of Gene Expression, Aiman S. Alhazmi

Theses and Dissertations

The nucleosome remodeling factor (NURF) is an evolutionary conserved ATP-dependent chromatin remodeling factor. It was first isolated from Drosophila as a complex with enzymatic activity that once recruited to nucleosome, it slides the nucleosome to provide accessibility for transcription factors. Since then, numerous works from animal models and cell lines show the role of NURF as a regulator of gene expression. NURF interacts with H3K4me3 and sequence specific transcription factors that recruit the complex to promoter regions. Whether this is the only mechanism by which NURF regulates gene expression is not known. However, other ATP-dependent chromatin remodeling complexes are known …

A Novel Antimicrobial Drug Discovery Approach For The Periodontal Pathogen Porphyromonas Gingivalis, Victoria N. Stone

Theses and Dissertations

The human body is colonized by more than 100 trillion microbes which make up an essential part of the body and plays a significant role in health. We now know the over use and misuse of broad-spectrum antibiotics can disrupt this microbiome contributing to the onset of disease and runs the risk of promoting antibiotic resistance. With antibiotic research still on the decline, new strategies are greatly needed to combat emerging pathogens while maintaining a healthy microbiome. We therefore set out to present a novel species-selective antimicrobial drug discovery strategy.

Disruption of the homeostasis within the oral cavity can trigger …

Development Of Clinically Relevant In Vitro Performance Tests For Powder Inhalers, Xiangyin Wei

Theses and Dissertations

While realistic in vitro testing of dry powder inhalers (DPIs) can be used to establish in vitro–in vivo correlations (IVIVCs) and predict in vivo lung doses, the aerodynamic particle size distributions (APSDs) of those doses and their regional lung deposition remains unclear. Four studies were designed to improve testing centered on the behavior of Novolizer®. Different oropharyngeal geometries were assessed by testing different mouth-throat (MT) models across a realistic range of inhalation profiles (IPs) with Salbulin® Novolizer®. Small and large Virginia Commonwealth University (VCU) and Oropharyngeal Consortium (OPC) models produced similar ranges for total lung dose in vitro (TLD …

Orientia Tsutsugamushi Ankyrin-Repeat Protein Family Targeting Of The Host Endoplasmic Reticulum, Lauren Viebrock

Theses and Dissertations

Abstract

ORIENTIA TSUTSUGAMUSHI ANKYRIN REPEAT-PROTEIN FAMILY TARGETING OF THE HOST ENDOPLASMIC RETICULUM

By Lauren VieBrock, B.S.

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

Virginia Commonwealth University, 2015

Director: Jason A. Carlyon, Ph.D.

Professor

Microbiology and Immunology

Scrub typhus is an understudied, potentially fatal febrile illness, which poses threat to one billion people annually in the Asia-Pacific region. The host-pathogen interactions that facilitate the intracellular survival of the etiologic agent, Orientia tsutsugamushi, are not well understood. The Orientia tsutsugamushi genome encodes a large number of ankyrin repeat-containing proteins …

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 …

Clinical And Genomic Characterization Of Two Vaginal Megasphaera Species, Abigail L. Glascock

Theses and Dissertations

Two vaginal phylotypes of the genus Megasphaera (phylotype 1 and phylotype 2) were recently associated with bacterial vaginosis (BV), an infection characterized by vaginal dysbiosis. Through an analysis of 16S rRNA profiles of 3,986 women enrolled in the Vaginal Human Microbiome Project, we confirmed that while both phylotypes were associated with BV, Megaspheara phylotype 1 had higher specificity for the condition. Megasphaera phylotype 2 was strongly associated with trichomoniasis. Previous studies have reported that BV-associated organisms are excluded in pregnancy. We observed that Megasphaera phylotype 1, which has been associated with adverse pregnancy outcomes, exhibited a trend of increased prevalence …

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 …

In-Silico Models For Capturing The Static And Dynamic Characteristics Of Robustness Within Complex Networks, Bhanu K. Kamapantula

Theses and Dissertations

Understanding the role of structural patterns within complex networks is essential to establish the governing principles of such networks. Social networks, biological networks, technological networks etc. can be considered as complex networks where information processing and transport plays a central role. Complexity in these net works can be due to abstraction, scale, functionality and structure. Depending on the abstraction each of these can be categorized further. Gene regulatory networks are one such category of biological networks. Gene regulatory networks (GRNs) are assumed to be robust under internal and external perturbations. Network motifs such as feed-forward loop motif and bifan motif …

Integrated Nanoscale Imaging And Spatial Recognition Of Biomolecules On Surfaces, Congzhou Wang

Theses and Dissertations

Biomolecules on cell surfaces play critical roles in diverse biological and physiological processes. However, conventional bulk scale techniques are unable to clarify the density and distribution of specific biomolecules in situ on single, living cell surfaces at the micro or nanoscale. In this work, a single cell analysis technique based on Atomic Force Microscopy (AFM) is developed to spatially identify biomolecules and characterize nanomechanical properties on single cell surfaces. The unique advantage of these AFM-based techniques lies in the ability to operate in situ (in a non-destructive fashion) and in real time, under physiological conditions or controlled micro-environments.

First, AFM-based …

A Preliminary Study On External Counterpulsation System: An Alternative Therapeutic Option For Fontan Patients, Joseph Hernandez

Theses and Dissertations

In order to address the long-term complications that arise from poor venous return, a hallmark of the Fontan physiology, we assessed the feasibility of a non-invasive, home therapy that will improve the health of the patient during the heart transplant waiting period and ameliorate the quality of life. In order to achieve this goal we tested a device that applies pressure to the lower extremities of the body (legs and abdomen) in a pulsating fashion with the goal of augmenting systemic blood flow to the pulmonary arteries. This treatment will enhance flow from the great veins and through the lungs …

Mitochondrial Therapeutics During Ischemia-Reperfusion; Modulation Of Complex I: Effect Of Metformin., Shawn Y. Sunu

Theses and Dissertations

The modulation of the electron transport during ischemia-reperfusion has been shown to be protective. We hypothesized that metformin, a Complex I inhibitor, may exhibit characteristics of a pharmacological agent that could achieve long-term therapeutic intervention against ischemia-reperfusion injury. Mitochondria were harvested from adult male mice and incubated with or without metformin at 30^oC for 15 minutes, while being shaken at 300 rpm. Metformin decreased Complex I oxidative phosphorylation and Complex I activity. However, metformin also increased injury and decreased the maximum membrane potential. Even though there was a decrease in maximum membrane potential, the proton motive force (PMF) …

Cyclic Gmp: A Satiety Signal In C. Elegans, Ji S. Park

Theses and Dissertations

Appetite control and satiety mechanisms help animals maintain energy homeostasis; however, these mechanisms can be misregulated, leading to overweight and obesity. Caenorhabditis elegans is an excellent model system to study appetite and satiety because of its conserved behavioral aspects of satiety and conserved molecular mechanisms. ASI senses nutrition and its activity is required for the behavioral state of satiety quiescence. The purpose of this thesis project was to elucidate the function of cGMP signaling in ASI by looking at behavioral effects from the pharmacological use of sildenafil (Viagra), a PDE inhibitor, and the effects on ASI activation from mutating guanylyl …

Effects Of Hiv-1 Tat On The Enteric Nervous, Joy Ngwainmbi

Theses and Dissertations

More than 1.2 million people are estimated to be currently living with the human immunodeficiency virus (HIV) in the United States of America. The gastrointestinal (GI) tract is both a major target and an important component of HIV pathogenesis. The GI processes that are dysregulated during HIV infection are controlled by the enteric nervous system (ENS). Indeed, both clinical and experimental studies have implicated the ENS in HIV and simian immunodeficiency virus (SIV) pathogenesis. In addition to direct viral effects, the HIV virus also indirectly affects the GI tract via cellular and/or viral toxins released by infected cells. Trans-activator of …

The Role Of Tfec In Zebrafish Neural Crest Cell And Rpe Development., Samantha A. Spencer

Theses and Dissertations

Zebrafish (Danio rerio) show a unique pigmentation pattern comprised of three pigment cell types: melanophores, iridophores and xanthophores. Other pigmented cells include the retinal pigmented epithelium (rpe) which absorbs excess light in the eye and maintain the extracellular environment around the photoreceptors. While previous mutations in mitfa showed a role in regulating trunk melanophores, the rpe was not affected. TALENs and CRISPR-Cas9 systems were used to generate mutant zebrafish for tfec, a transcription factor expressed in both neural crest and rpe. Embryos with tfec mutations showed a loss of iridophore pigmentation, and delays in the pigmentation of …

Behavioral Responses Of Male Parasitic Wasps To Plant Cues: A Comparison Of Two Host-Plant Complex Sources Of Cotesia Congregata (Say), Megan Ayers

Theses and Dissertations

Prior exposure to plants cues can enhance assortative mating in insects. We hypothesized that, as previously reported for females, males of Cotesia congregata would display inherent responses to plant cues that could be modified by postemergence experience and further, that males originating from two different host-plant complexes (HPCs) would display different behavioral responses to these HPCs. In no-choice contact assays with a non-host plant, searching responses of males and females increased sharply at Day 2 and remained stable through Day 4. In no-choice assays with potential host plants, males searched longer on catalpa than tobacco; responses were not modified by …

Responses Of The Catalpa Sphinx, Ceratomia Catalpae, And Its Primary Parasitoid, Cotesia Congregata, To Varying Levels Of Iridoid Glycosides In Catalpa, Jessica L. Bray

Theses and Dissertations

The catalpa sphinx, Ceratomia catalpae, is a specialist on Catalpa trees, which produce iridoid glycosides (IGs). Whereas some trees are defoliated every year, others escape herbivory. Caterpillar populations are either heavily parasitized by the braconid wasp, Cotesia congregata, or remain unparasitized. We hypothesized that these patterns could be explained by variable IG concentrations among trees and insect responses to these chemicals. IG concentrations varied among trees. Percent defoliation was positively related to IG concentration. In comparisons of insect responses to relatively high or low IG concentrations, moths preferred to oviposit on trees with high IG concentrations. Caterpillars did …

The Effect Of Dexamethasone On Il-33-Mediated Mast Cell Activation, Oksana I. Chernushevich

Theses and Dissertations

Dexamethasone has been shown to inhibit IgE-mediated mast cell activation, and the present research investigated its role in suppressing IL-33-mediated mast cell activation. We have found that micromolar concentrations of Dexamethasone are capable of suppressing IL-33-mediated mast cell cytokine production, on several genetic backgrounds, and in not only bone marrow derived mast cells, but also peritoneal mast cells. Intracellular staining demonstrated that Dexamethasone significantly reduces expression of the IL-33 receptor, T1/ST2, in mast cells; however, the cytokine suppression is independent of T1/ST2 downregulation. At the same time, Dexamethasone pretreatment significantly reduced ERK phosphorylation, but our data suggests that inhibition occurs …

The Genetic Architecture Of Water-Use Efficiency Within And Between Two Natural Populations Of Foxtail Pine, Douglas E. Harwood

Theses and Dissertations

The goal of this project was to determine the genetic architecture of water-use efficiency (WUE) for foxtail pine, which included genomic loci, and effect sizes of this trait. Foxtail pine is a subalpine endemic conifer that inhabits two distinct regional populations separated by 500 km in the mountains of California. In order to achieve this goal, a robust linkage map containing thousands of genetic markers was created using four megagametophyte arrays ranging in size from approximately 70 to 95 megagametophytes. Quantitative trait loci (QTL) discovered for WUE were mapped along the linkage map using linear mixed models and five half-sibling …

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 …

The Role Of Adam10, Adam17, And Spag6 In Humoral Immunity And Secondary Lymphoid Tissue Architecture, Lauren Folgosa Cooley

Theses and Dissertations

ADAM10, ADAM17, and SPAG6 contribute significantly to humoral immunity and secondary lymphoid tissue architecture. ADAM10 and ADAM17 are two closely related zinc-metalloproteinases. Through cleavage of their ligands CD23 and TNF, respectively, they greatly influence IgE production and secondary lymphoid tissue architecture maintenance. Th1 prone WT strains initially exhibit increased ADAM17 and TNF yet reduced ADAM10 relative to Th2 prone WT strains. In the absence of B cell ADAM10, a compensatory increase in ADAM17 and TNF cleavage is noted only in Th1 prone C57Bl/6, not Th2 prone Balb/c. B cell TNF homeostasis is important for maintaining secondary lymphoid tissue architecture. We …

Relationship Between Autophagy, Senescence, And Dna Damage In Radiation Sensitization By Parp Inhibition, Moureq Alotaibi

Theses and Dissertations

Radiotherapy continues to be a primary modality in the treatment of cancer. DNA damage induced by radiation can promote apoptosis as well as both autophagy and senescence, where autophagy and senescence can theoretically function to prolong tumor survival. A primary aim of this work was to investigate the hypothesis that autophagy and/or senescence could be permissive for DNA repair, thereby facilitating tumor cell recovery from radiation-induced growth arrest and/or cell death. In addition, studies were designed to elucidate the involvement of autophagy and senescence in radiation sensitization by PARP inhibitors and the re-emergence of a proliferating tumor cell population. In …

Expanding Eco-Visualization: Sculpting Corn Production, Jennifer E. Figg

Theses and Dissertations

This dissertation expands upon the definition of eco-visualization artwork. EV was originally defined in 2006 by Tiffany Holmes as a way to display the real time consumption statistics of key environmental resources for the goal of promoting ecological literacy. I assert that the final forms of EV artworks are not necessarily dependent on technology, and can differ in terms of media used, in that they can be sculptural, video-based, or static two-dimensional forms that communicate interpreted environmental information. There are two main categories of EV: one that is predominantly screen-based and another that employs a variety of modes of representation …

Rheb Dynamics On Lysosomal Membranes Determines Mtorc1 Activity After Loss Of P53 Or Activation Of Ampk, Catherine M. Bell

Theses and Dissertations

The tumor suppressor TP53 is the most frequently altered gene in human cancers. The growth-promoting complex, mTORC1 plays a part of the oncogenic profile caused by dysfunctional p53. mTORC1 sits downstream of AMPK and other crucial tumor suppressors/oncogenes, PTEN, LKB1, and Akt. The antifolate pemetrexed was found by this laboratory to activate AMPK via the inhibition of the enzyme AICART in de novo purine synthesis. This work presents a mechanism of mTORC1 activation with p53 loss, as well as of mTORC1 inhibition by pemetrexed-induced AMPK. We have found that mTORC1 activity was substantially upregulated by the loss …

Synthetic Cannabinoids Versus Delta-9-Tetrahydrocannabinol: Abuse-Related Consequences Of Enhanced Efficacy At The Cannabinoid 1 Receptor, Travis Grim

Theses and Dissertations

In the past ten years, synthetic cannabinoids (SC) have emerged as drugs of abuse. Unlike D⁹-tetrahydrocannabinol (THC), many SCs are associated with serious health complications and death. One way in which THC and SCs differ lies with their enhanced potency and efficacy at the CB₁ receptor. No current methods exist to measure efficacy at the CB₁ receptor in vivo, and the abuse-related properties of SC cannabinoids are not well explored. Here, we utilized CB₁ wild type (WT), heterozygous (HET), and knockout (KO) mice. By employing CB₁ ligands which differ in efficacy we have …

Meta-Analysis Of Gene Expression Studies, Umaporn Siangphoe

Theses and Dissertations

Combining effect sizes from individual studies using random-effects models are commonly applied in high-dimensional gene expression data. However, unknown study heterogeneity can arise from inconsistency of sample qualities and experimental conditions. High heterogeneity of effect sizes can reduce statistical power of the models. We proposed two new methods for random effects estimation and measurements for model variation and strength of the study heterogeneity. We then developed a statistical technique to test for significance of random effects and identify heterogeneous genes. We also proposed another meta-analytic approach that incorporates informative weights in the random effects meta-analysis models. We compared the proposed …

Nitric Oxide Synthase Activity And Its Modulation In The Treatment Of Colorectal Cancer, Asim Alam

Theses and Dissertations

The American Cancer Society estimates more than 141,000 new cases of and about 50,000 deaths from colorectal cancer every year. Treatment options include surgery, radiation therapy and targeted therapies such as anti-angiogenics. However, no therapies address the key driving factor of colorectal cancer: inflammation. It is well known that chronic inflammatory conditions such as Crohn’s Disease, ulcerative colitis, diabetes, obesity and cigarette smoking all elevate the risk of developing colorectal cancer. One of the hallmarks of chronic inflammation is the elevated levels of reactive oxygen/nitrogen species (ROS/RNS). A primary source of these ROS/RNS is uncoupled Nitric Oxide Synthase (NOS). Under …