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Transient Camk-Ii Activation Is Necessary For Left-Right Asymmetry In The Zebrafish Embryo, Ludmila Francescatto

Theses and Dissertations

Despite external bilateral symmetry, the internal organs of vertebrates are asymmetrically arranged. The development of Left-Right (LR) asymmetry is dependent on the activity of a ciliated organ known as the Kupffer’s vesicle (KV) or the embryonic node, in zebrafish and mouse, respectively. Cilia beating within the KV are essential to generate a counterclockwise flow of fluid, which leads to left-sided Ca2+ elevation. Ca2+ is a crucial morphogenic second messenger during vertebrate development. Ca2+ elevation activates targets, such as CaMK-II, which is also known as the multifunctional Ca2+/calmodulin-dependent protein kinase. Studies have linked CaMK-II to secretion (mediated through synapsin I) and …

Biochemical Actions Of A Novel Cis-Terpenone, Lin Zhang

Theses and Dissertations

Abstract BIOCHEMICAL ACTIONS OF A NOVEL CIS-TERPENONE By Lin Zhang, 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, 2012 Director: Qibing Zhou, Ph.D Assistant Professor Department of Chemistry

Quinone methides are reactive species due to their electrophilicity, and natural quinone methide analogs have broad biological activities. Based on known actions of cytochrome P450 enzymes, we hypothesized that trans-terpenones can be metabolized in cells to form a cascade of metabolite products, which may be biologically active due to the generation of quinine and quinone methide …

Role Of Lysophosphatidic Acid In Regulation Of Cancer Cell Metabolism, Abir Mukherjee

Theses and Dissertations

The simplest phospholipid, lysophosphatidic acid (LPA), is a heat stable component of serum known for its proliferative and migratory activities in cancer cells. Strong evidence suggests that LPA production and expression of its receptors are dysregulated in multiple human malignancies. The mechanism behind LPA-mediated tumor cell growth and oncogenesis remains poorly understood. In this thesis project I used ovarian and other cancer cells as a model system to examine the hypothesis that LPA present in the tumor microenvironment is a pathophysiological determinant of hyperactive de novo lipogenesis and aerobic glycolysis, two hallmarks of cancer cells. We demonstrated that LPA induced …

Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn

Theses and Dissertations

Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our …

Crosstalk Between Lysophospatidic Acid (Lpa) And Transforming Growth Factor Beta (Tgfβ) In Breast And Ovarian Cancer Cells, Jinhua Wu

Theses and Dissertations

Lysophosphatidic acid (LPA) and transforming growth factor beta (TGFβ) are platelet-derived intercellular mediators of cell proliferation and motility. LPA is a general growth, survival and motility-stimulating factor in mammalian cells. TGFβ prevents proliferation of normal epithelial cells. However, the growth-inhibitory effect of TGFβ is lost or reduced in most malignant cells. Instead, TGFβ promotes migration and invasion of advanced cancer cells. Since LPA and TGFβ are both present in the blood and tumor microenvironments, we were interested in signal integration and functional outcomes in malignant epithelial cells in an LPA and TGFβ co-stimulatory context. In a subset of breast and …

Adam10: A Novel Regulator Of Mast Cell Function And Activation, Travis Faber

Theses and Dissertations

In this study we show, to our knowledge, the first description of the role ADAM10 plays on mast cells. ADAM10 is abundantly expressed on mast cells both in vitro and in vivo. Its expression is inhibited by IL-10, a suppressive cytokine. siRNA depletion of ADAM10 on bone marrow-derived mast cells (BMMC) caused decreased IL-6 production following IgE cross-linking and also impaired BMMC stem cell factor (SCF)-induced migration through collagen IV. Mast cells and T helper cells (Th cells) in the peritoneum were reduced in ADAM10 KO mice. In addition, ADAM10 KO BMMC produced significantly less of all cytokines measured following …

Factors Influencing Pharmacists’ Decision To Report Adverse Events Related To Dietary Supplements, Ali M. Alhammad

Theses and Dissertations

Background: The increasing consumption of dietary supplements (DS) has drawn the attention of regulatory agencies, researchers and healthcare professionals. The US Food and Drug Administration (FDA) does not require premarketing assessment of DS considering them safe unless proven otherwise. However, the reporting rate of DS adverse events (DS-AE) is low. Objective: To describe pharmacists’ attitudes and knowledge of DS and DS information resources, and to determine the importance of selected attributes in pharmacists’ decisions to report a DS-AE. Methods: A convenience sample of practicing pharmacists in Virginia was surveyed using a web-based self-administered questionnaire. A conjoint analysis exercise was developed …

Role Of Extracytoplasmic Function Sigma Factors In Porphyromonas Gingivalis, Suhasini Yanamandra Sai

Theses and Dissertations

Porphyromonas gingivalis is a major etiological agent that is responsible for the cause and progression of periodontal diseases. The bacterium is exposed to various environmental conditions and oxidative stress conditions while it is in the oral cavity. So, P. gingivalis should have an efficient regulatory system in order to adjust and survive in the oral cavity. But little is known about the regulatory mechanisms that help the bacteria to survive in the oral cavity. So, it is essential to understand and characterize these regulatory mechanisms. The response and adaptation of P. gingivalis to environmental stress conditions occur at the level …

The Role Of R7 Regulators Of G Protein Signaling In The Retina, Hoon Shim

Theses and Dissertations

The R7 regulators of G protein signaling (R7 RGS), namely RGS6, RGS7, RGS9 and RGS11, are expressed in the retina along with its binding partner Gβ5. The RGS9-1 isoform is expressed only in retinal photoreceptors and rate-limits the recovery of rod phototransduction by acting as a member of the transducin GAP complex (RGS9-1/Gβ5L/R9AP). The Gβ5L isoform is also only expressed in retinal photoreceptors and acts by stabilizing the GAP complex. The Gβ5S isoform differs from Gβ5L by the absence of exon 1 due to alternative splicing and is expressed in many other retinal cells. Gβ5L is barely detectable in RGS9-/- …

Designing Direct And Indirect Factor Xa Inhibitors, Rami Al-Horani

Theses and Dissertations

Anticoagulants are the basis for treatment and prevention of thrombotic diseases. The currently available medicines are associated with a wide range of adverse reactions that mandates developing new anticoagulants. Several lines of evidence support the superiority of factor Xa (FXa) as a promising target to develop novel anticoagulants. This work focuses on the design of direct and indirect FXa inhibitors using an interdisciplinary approach. As indirect FXa inhibitors, a focused library of tetrasulfated N–arylacyl tetrahydroisoquinoline (THIQ) nonsaccharide allosteric antithrombin activators was designed, synthesized, and biochemically evaluated to establish their structure–activity relationship (SAR). An N–arylacyl THIQ analog having carboxylate at position–3, …

Investigating The Role Of Α6 And Α4 Containing Neuronal Nicotinic Acetylcholine Receptors In Nicotine And Cocaine Conditioned Place Preference Tests In Mice., Sarah Sanjakdar

Theses and Dissertations

Neuronal nicotinic acetylcholine receptors modulate both cholinergic and non-cholinergic synaptic transmission. Our research concerns α6 and α4 neuronal nicotinic subunits because they often co-assemble with the β2 subunit, which has abundant expression in the CNS and previous work has demonstrated that β2* nAChRs are involved in nicotine and cocaine reward. α6β2* and α4β2* nAChRs are highly expressed in midbrain, which is known to be critical for the incentive salience associated with natural and artificial (drug) reward. Our goal was to assess the role of α6β2* and α4β2* nAChRs in nicotine and cocaine reward using an unbiased conditioned place preference (CPP) …

Identifying Sortase A Variants With Higher Catalytic Effeciency, Muna Suliman

Theses and Dissertations

In the past two decades, the field of protein engineering has evolved rapidly to include new genetic and chemical techniques to alter protein function. Protein engineering seeks to improve enzyme properties through powerful methods that specifically incorporate novel or improved function in proteins. One such method is protein ligation, which is used to selectively link synthetic and recombinant polypeptides. Due to the limitations of current protein labeling techniques, simple site-specific modification methods remain in high demand. Use of enzyme-based labeling has been the focus of various studies because of its substrate specificity. Sortase-mediated transpeptidation is one approach that has been …

Regeneration Of Electrospun Bioresorbable Vascular Grafts: A Phenomenon Associated With Vascular Graft Properties And Macrophage Phenotypes (M1/M2), Koyal Garg

Theses and Dissertations

Macrophages (MФ) and mast cells are important cell types in the context of tissue remodeling and regeneration. Mast cells participate in the early stages of wound healing and modulate the acute inflammatory responses to biomaterials. Mast cells can secrete a myriad of different cytokines by the process of degranulation; the process of regulated secretion in which preformed contents stored in their granules are rapidly released by exocytosis. Some of these cytokines such as IL-4, IL-13 and TNF-α can modulate the MФ phenotype. Macrophages (MΦ) are innate immune cells, crucial for tissue homeostasis, presentation of foreign and self-antigens following infection/injury, pathogen …

Novel Fluorous Hybrid Surface Modification Characterized By Wetting Dynamics, Morphology And Nanomechanics, Sithara Nair

Theses and Dissertations

The surface response of a polymer substrate to external stimuli such as initial wetting is controlled by the outermost molecular layer. Thus, changes on the nanoscale may be engaged to control macroscale wetting behavior. Our work has predominantly focused on surface modification of conventional polyurethane coatings (HMDI-BD-PTMO). Studies on network constrained phase separation and facile polydimethylsiloxane surface functionalization led to the discovery of a simpler one-step and more general approach to functional polymer surfaces that we have designated as “Bottle-Brush Nanoglass” (BB-NG) after the two principle components: (a) a polyoxetane soft block “spine” with side chain “A” bristles and triethoxysilyl …

Development Of Dual-Pathway Inhibitors Of Raf/Mek/Erk And Pi3k/Akt Signaling Pathways., Sasha Fraser

Theses and Dissertations

In the present study, we designed a new chemical template that contains an oxindole moiety as potential dual-pathway inhibitors of the Raf/MEK/ERK and PI3K/Akt signaling pathways. The design hypothesis is to evaluate whether the oxindole ring system will approximately orient functional groups in a similar manner to the thiazolidinedione moiety, and thus maintain biological activity as dual-pathway inhibitors of the Raf/MEK/ERK and PI3K/Akt signaling pathways. Furthermore, the oxindole ring will provide the flexibility to allow the introduction of various substituents on the oxindole moiety, thereby facilitating comprehensive SAR studies to further explore the biological activity.

Species Level Differences In The Ecology Of Two Neotropical Tadpole Species: Responses To Nonlethal Predators And The Roles Of Competition And Resource Use, Zacharia Costa

Theses and Dissertations

Closely related species at the same trophic level are often considered to be ecologically equivalent. However, it is clear that individuals species can have unique functional roles that drive community and ecosystem processes. In this study we examine the growth responses of two Neotropical hylid tadpole species, Agalychnis callidryas and Dendropsophus ebraccatus, to intraspecific and interspecific competition. We also look at density-dependent effects of each on phytoplankton, periphyton and zooplankton, as well as their responses to a caged dragonfly predator through ontogeny. Intraspecific competition affected both species similarly, and their effects on resources were qualitatively similar but quantitatively different. Predators …

Medication-Related Problems In Older Adults: A Focus On Underuse Of Warfarin And Warfarin-Antibiotic Interactions, Parinaz K. Ghaswalla

Theses and Dissertations

The work presented in this dissertation focuses on two important medication-related problems in older adults, that is, untreated indication and drug-drug interactions, specifically with respect to a high-risk medication such as warfarin. Warfarin is a challenge to use in clinical practice due to its narrow therapeutic index, variability in dose-response and its interactions with numerous foods and drugs. This dissertation presents the research from two projects. In the first project the prevalence and predictors of warfarin use in nursing home (NH) residents with atrial fibrillation (AF), and use of secondary stroke prevention strategies was determined, in order to understand the …

Assessing Parental Involvement In Type 1 Diabetes Management During Adolescence, Elizabeth M. Robinson

Theses and Dissertations

Type 1 diabetes is one of the most common pediatric chronic illnesses. Adolescents are at risk for poorer glycemic control; however, youth whose parents remain involved in diabetes care are in better control. The current study examined parental involvement (PI) using a multi-method, multi-source approach in a sample of 255 youth (Age M = 12.83). The Diabetes Family Responsibility Questionnaire, Parental Monitoring of Diabetes Care Scale, and 24-Hour Diabetes Interview assessed two types of PI, parental responsibility and parental monitoring. Global and specific assessment served to cross-corroborate indicators of PI related to HbA1c. Higher levels of monitoring related to lower …

Development Of A Novel Approach To Assess Qualitative And Quantitative Dynamics Associated With The Subcutaneous Or Intramuscular Administration Of Pharmaceuticals And Associated Parenteral Delivery Systems, Eric Edwards

Theses and Dissertations

There has been a significant increase in the number of injectable pharmaceutical products over the last decade that have been incorporated into unique delivery systems such as pen injectors, auto-injectors, or pre-filled syringes. The advancement of these delivery systems and the paradigm shift towards administration of injectables in the out-of-hospital or home setting have introduced variables that can affect the bioavailability of injectable drugs and potential pharmacologic outcomes. An approach that allows for the qualitative and quantitative dispersion assessment of an injectable at the moment of tissue deposition coupled with an assessment of systemic exposure parameters could provide substantial information …

Evaluation Of Brook Trout (Salvelinus Fontinalis) Introductions And Re-Introductions Into Four Virginia Blue Ridge Mountain Streams, Michael Isel Iii

Theses and Dissertations

Approximately 100 brook trout were transplanted into each of four Virginia streams in September 2008. Garth Run and Kinsey Run were re-introductions, and Wildcat Hollow and Sweet Run were new introductions. Single pass electrofishing (EF) surveys were conducted with a backpack electrofisher five times during the study. Selected trout > 70 mm but < 100 mm and all trout > 100 mm received a Biomark® 134.2 kHz passive integrated transponder (PIT) tag to identify individual fish upon recapture. Trout were present in all streams almost three years post introductions. Catches decreased across the first four surveys. Young of year catch rates severely decreased from June 2009 (n = …

Synthesis And Characterization Of Highly Porous Borazine-Linked Polymers Via Dehydrogenation/Dehydrocoupling Of Borane-Amine Adducts And Their Applications To Gas Storage, Karl Jackson

Theses and Dissertations

A new class of porous polymers has been designed and successfully synthesized by thermal dehydrogenation of several polytopic arylamine-borane adducts and has been designated Borazine-Linked Polymers (BLPs). The polymers reported are constructed of linear, triangular, and tetrahedral amine building units to form 2D and 3D frameworks. The boron sites of the pores are aligned with hydrogen atoms contrasted with the recently reported halogenated BLPs which consist of pore channels aligned with bromine or chlorine atoms. One of the reported BLPs, BLP-2(H), was proven to be crystalline by PXRD, matching the experimental pattern to theoretical patterns calculated from modeled structures. BLPs …

The Impact Of Race And Interactions Between Student-Faculty On Undergraduate Student Learning And Multicultural Perceptions, Yun Zhu

Theses and Dissertations

As enrollment of minority students and recruitment of minority faculty in higher education increase, opportunities for students to interact with racially and ethnically different faculty will become more frequent and pronounced. Also, there may be expectations that these interactions will produce greater educational gains and sensitivity to racial issues. A quantitative research methodology was employed to measure the nature of the student-faculty interactions across race and to explore factors that influence undergraduate students’ GPA and multicultural perceptions in order to identify ways in which student-faculty interactions might better serve the students. Mainly, this study focused on the quantity, quality, and …

Teachers' Perception Of Computer Use And Technical Support In A Rural Virginia School Division: A Case Study, Rodney Berry

Theses and Dissertations

The purpose of this study was to investigate teacher perceptions of computer-based technology and technology support provided by a rural school division; the extent of teachers’ self reported computer skills, comfort levels, perception of obstacles; and the amount of support, time, and training available to them to accomplish the integration during the course of instruction. This research was conducted during the 2010-2011 school term as a case study of a small rural K-12 school division in southern Virginia, consisting of teachers from each core curriculum from each of the three schools, selected deliberately. The study was divided into three phases: …

Identifying Modulators Of The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans., Ka-Po Leung

Theses and Dissertations

Alcohol abuse is a problem in our society. There are few treatments available, in part due to the unclear molecular mechanisms of ethanol’s effects. Human studies indicate that there is a genetic component influencing disease susceptibility, and that an individual’s initial response to alcohol can predict their development of addiction. We have taken a forward genetics approach to study one component of initial response, acute functional tolerance (AFT), in Caenorhabditis elegans. We identified bet11, a mutation that causes animals to be defective in the development of AFT. Genetic analysis suggested that the gene that bet11 disrupts participates in a synthetic …

Woody Encroachment Mechanisms Of A Symbiotic N-Fixing Shrub: Ecophysiology, Facilitation, And Resource Use Efficiency, Jaclyn Vick

Theses and Dissertations

Causes and consequences of woody encroachment into grass dominated systems have been widely studied, however functional mechanisms which promote encroachment are largely unknown. Many expansive woody species are shrubs with rhizobial or actinorhizal N-fixing symbiotic associations. Morella cerifera L. (Myricaceae) is an actinorhizal N-fixing shrub which rapidly expands into grasslands on the barrier islands off the coast of Virginia, USA. The objective of this research was to determine physiological drivers of woody encroachment resulting in increased woody cover of M. cerifera on Southeastern, US barrier islands. Variations in physiology and resource use efficiencies (RUE) of M. cerifera and co-occurring shrubs …

Characterizing The Phosphorylation State Of Tie2 Using Sh2 Domain Fusion Proteins, Kenneth Yuth

Theses and Dissertations

The cardiovascular system develops through two distinct processes in embryogenesis: vasculogenesis, whereby the primary plexus in the heart is formed along with embryonic and extraembryonic vasculature, and angiogenesis, which begins after vasculogenesis and results in the refinement and maturation of the branched vessel system. In pathological angiogenesis, tumors expand by releasing pro-angiogenic factors in response to hypoxic conditions. The Tie receptors, Tie1 and Tie2, are receptor tyrosine kinases that are integral to angiogenic pathways. A family of Angiopoietins, Ang1-4, have been shown to act as ligands for Tie2, of which Ang1 and Ang2 are best characterized. Activation of the receptor …

Healthcare Acquired Infection Risk And Toothbrush Contamination In The Icu., Michelle Frazelle

Theses and Dissertations

Healthcare acquired infections (HAIs) are a complex and multi-factorial problem associated with high morbidity, mortality, and cost. Toothbrushes (TBs) may be at risk for contamination with potential pathogenic microorganisms (PPMs) from the patient care environment or autoinnoculation from the patient. We focused on three PPMs: multiply resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE), and Acinetobacter. Specific aims were to (1) describe environmental factors associated with TB contamination in the ICU; (2) describe the relationship between TB contamination and oral colonization in critically ill adults.

Factors Controlling Dissolved Organic Carbon Lability And Ecological Fate In The East Branch Swift River, Massachusettes, Hall Eric

Theses and Dissertations

Fluvial systems have been estimated to transform, transport, or store 2.75 petagrams (Pg) of Organic Carbon (OC) per year. Although approximately 1Pg per year of terrestrial carbon is fluxed to the atmosphere through inland waters, little is known about the factors regulating its eventual ecological fate. 28 day lability incubations were conducted concurrent with the measurement of several environmental parameters including discharge, nutrient concentration, DO13C, and DOC:DON at several sites along Bigelow Brook and the East Branch of the Swift River, Massachusetts. Temporal and spatial variation of DOC, DOC:DON and DO13C were explored. Two distinct DOC consumption rates, short and …

Sensory Modulation Disorder In Puerto Rican Preschoolers: Associated Risk Factors, Rosa L. Roman-Oyola

Theses and Dissertations

Sensory Modulation Disorder (SMD) reduces a child’s ability to respond to sensory stimuli in the environment in a manner that corresponds to the nature or intensity of the stimulus; this disorder therefore significantly can impact participation in developmentally appropriate play and functional activities. More studies are needed to enhance research in the field of SMD and aid the general community in understanding the disorder and its causes. The purpose of this study was to characterize the prevalence of SMD among Puerto Rican preschoolers and examine the relationship between specific risk factors (socioeconomic status, pre-natal alcohol exposure, low birth weight, preterm …

Comparing The Efficacy Of Two Cognitive Dissonance Interventions For Eating Pathology: Are Online And Face-To-Face Interventions Equally Effective?, Kasey Serdar

Theses and Dissertations

Clinical and subclinical eating pathology are common, especially among female undergraduates. Such problems are often chronic and associated with a range of negative medical and psychological outcomes. Thus, it is important to develop effective prevention programs to reduce eating disorder risk. Numerous studies suggest that dissonance-based prevention programs are the most successful in reducing eating disorder risk factors, however, such programs might not be convenient for students limited by scheduling restraints or geographic proximity. Further, some students may be reluctant to attend such groups due to lack of anonymity. One way to address these potential barriers is to adapt dissonance-based …