Digital Commons Network^™

Biochemical Analysis Of Putative Rna-Binding Proteins In Porphyromonas Gingivalis, Jacob Mirpanah

Theses and Dissertations

BIOCHEMICAL ANALYSIS OF PUTATIVE RNA-BINDING PROTEINS IN PORPHYROMONAS GINGIVALIS

By Jacob Mirpanah

Bachelor of Arts in Biology, University of Virginia, 2015

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Physiology and Biophysics at Virginia Commonwealth University

Virginia Commonwealth University, 2018

Major Director: Janina P. Lewis, Ph.D., Philips Institute for Oral Health Research

RNA-Binding Proteins (RBPs) play important regulatory roles in countless cellular processes. Often via the induction of a structural change in RNA’s secondary structure, RBPs are known to modulate protein expression through post-transcriptional regulation. In Escherichia coli, such RBPs have …

The Progress On Mapping Ubiquitin Signaling Using Photocrosslinking Mono And Di-Ubiquitin Probes And Other Ubiquitin Moieties, Courtney N. Braxton

Theses and Dissertations

Ubiquitin (Ub) is a small, 76 amino acid, and post-translational modification (PTM) protein in eukaryotes. Modification of a substrate protein via the covalent attachment of the C-terminal glycine of Ub to the ε-amino group of lysine residues in a substrate is termed ubiquitination. Unlike, other PTM proteins, Ub can form polyUb chains at one or more of its seven lysine residues. (K6, K11, K27, K29, K33, K48, and K68). The consequence of these different polymerization sites is altered biological response with different polyUb linkages conferring different fates to target proteins. Unfortunately, the study of these chains have been limited by …

Glycolytic Atp Production Is Required For Innate Mast Cell Activation And Is Limited By Lactic Acid, Which Effectively Reduces Lps-Induced Cytokine Production In Mast Cells And In Vivo, Heather Caslin

Theses and Dissertations

The metabolic pathways required for adenosine triphosphate (ATP) production within the cell are well understood, however recent publications suggest that metabolic pathways are closely linked to immune cell activation and inflammatory diseases. There has been little examination of the metabolic pathways that modulate mast cell activation and the feedback regulator lactic acid. Here we examine metabolic pathways and regulation within mast cells in the context of lipopolysaccharide (LPS) and interleukin (IL-33) activation, for which there has been little to no reported studies. First, we examine the effects of lactic acid, previously considered only a by-product of glycolysis and now understood …

Evolution And Niche Specialization Of Microbial Taxa In Vaginal Infection And Pregnancy, Abigail L. Glascock

Theses and Dissertations

The vaginal microbiome plays an important role in reproductive health and pregnancy. It has coevolved with humans and has direct effects on reproductive success, rendering selective pressure more pronounced at this site. Herein, we probe coevolution of the vaginal microbiome using a systems-level approach. In Chapter 2, we examine the evolutionary trajectory of two vaginal Veillonellaceae phylotypes evolved from an ancestral gastrointestinal lineage to inhabit the vaginal niche. We present evidence of their divergence and subniche specification and describe their differential associations with vaginal infection and pregnancy. In Chapter 3, we identify ten bacterial taxa, predicted to contribute to the …

The Role Of A Type Lamins In Regulating Myelination, Jacqueline M. Deloyht

Theses and Dissertations

Multiple sclerosis (MS), a demyelinating disorder of the central nervous system (CNS), affects approximately 400,000 individuals in the United States, and 2.5 million people worldwide. It is a leading cause of disability in young adults. Current treatments for MS target the inflammatory aspects of the disease, but do not aid in remyelination. To address remyelination as a therapeutic strategy, it is imperative to identify mechanisms that regulate myelin formation, including epigenetic targets. In this study, we investigate the role of the LMNA, a gene encoding Lamins A and C, intermediate filaments of the nuclear lamina, in regulating oligodendrocyte development and …

A Novel, Orally Active Hydrogen Sulfide-Releasing Compound, Sg1002, Improves Left Ventricular Function With An Associated Induction Of Angiogenesis In A Murine Model Of Ischemia/Reperfusion, Om A. Evani

Theses and Dissertations

Hydrogen sulfide (H₂S) is the newest member of the gasotransmitter family and is becoming well known for its cardioprotective effects in preclinical trials. Many recent studies have shown the benefits of exogenous H₂S in the setting of acute myocardial infarction (AMI) and pressure overload-induced heart failure, but current formulations are derived from inorganic salts which have shortcomings in the precision and control of release of H₂S. The main objective of this thesis was to determine if the novel, orally active, slow-releasing compound, SG1002, can attenuate the severity of damage and adverse remodeling caused by …

A Familiar House, William Lenard

Theses and Dissertations

The landscapes of my home in Connecticut are important to me. When I was young, I went to the woods for seclusion and comfort. While I wandered through the woods, I discovered a passion for storytelling. Now that I no longer live in New England, I miss the familiar landscapes of home. As a way to portray my sentiment, I write poetic narratives and create objects to illustrate natural landscapes.

I combine my interests of classic Americana art and literature with brutalist architecture and modern furniture to create immersive installations. I work with concrete and hardwood to materially bridge the …

There Is Someone In This Dress, George, Michael S. Royce

Theses and Dissertations

Questions surrounding queer subjectivity—including shame, the closet, and celebration—are at the core of my interests as a painter and image maker. Mining the history of religious iconography, including annunciation paintings, scenes of the crucifixion, and other notable works of this ilk, my paintings seek to explore the intricacies of sexuality and the workings of shame and celebration at play in the life of the queer-identified.

Nam June Paik As A Pioneer Of Interactive Art, Byeongwon Ha

Theses and Dissertations

Nam June Paik (1932-2006) is well known as the father of video art. However, this study demonstrates the importance of his earlier interactive art (1961-63), which historically has been overshadowed by his video art. At the climax of his career in interactive art, Paik introduced his two-way art to the public at his first solo exhibition in Wuppertal, West Germany, in 1963. Interactive art itself has been a peripheral area in the history of art, and it has plural pioneers across disciplinary boundaries. Among the several origins of interactive art, Nam June Paik utilized music as a fundamental approach to …

Cellular Inhibitor Of Apoptosis Protein2 – A Critical Regulator Of Neuroinflammation, Debolina Dipankar Biswas

Theses and Dissertations

Inhibitors of apoptosis (IAPs) modulate cell death and play critical role in signal transduction that promotes inflammation. Recently, Smac mimetics, which are IAP antagonists, have attracted attention as novel cancer therapeutics. Cellular Inhibitor of Apoptosis 2 (cIAP2), a member of IAP family, positively affects both NF-κB and MAPK activation in response to many inflammatory stimuli. We observed that the lack of cIAP2 ablates LPS-induced neuroinflammation. Also, cIAP2^-/- macrophages demonstrated diminished antigen presentation potential that could contribute to ablated immunity. In addition to these functions, we have previously reported that cIAP2 also regulates the activation of Interferon Regulatory Factor 1 …

Abuse Liability Of An Electronic Cigarette In Traditional Cigarette Smokers, Sarah F. Maloney

Theses and Dissertations

Electronic cigarettes have grown in popularity across the U.S. and concerns have been raised about their abuse liability. The purpose of the current study was to evaluate and compare the abuse liability of an electronic cigarette with and without nicotine to a nicotine inhaler (the Nicotrol inhaler) and participants’ own brand of cigarettes. A total of 24 smokers attended four sessions in which the abuse liability of each product was examined using the Multiple-Choice Procedure (MCP), nicotine delivery, nicotine abstinence symptom suppression, and subjective reinforcing effects. Results revealed that the nicotine containing and non-nicotine containing electronic cigarette had a higher …

Social Soul, Norah Alshammari

Theses and Dissertations

Twitter has over 313 million users, with 500 million tweets produced each day.

Society’s growing dependence on the internet for self-expression shows no

sign of abating. However, recent research warns that social media perpetuates

loneliness, caused by reduced face-to-face interaction. My thesis analyzes and

demonstrates the important role facial expressions play in a conversation’s

progress, impacting how people process and relate to what is being said. My

work critically assesses communication problems associated with Twitter. By

isolating and documenting expressive facial reactions to a curated selection

of tweets, the exhibition creates a commentary on our contemporary digital

existence, specifically articulating …

Lps-Induced Inos Mrna And The Pro-Apoptotic Signaling Pathway In Leukocytes Of Fit And Unfit Males, Tiffany M. Zuniga

Theses and Dissertations

Overexpression of the enzyme iNOS induces apoptotic cellular death by increasing indices of pro-inflammation and oxidative stress. Aerobic physical activity has been known to have anti- inflammatory benefits and reduce oxidative stress. Purpose: Therefore, this study aimed to examine the impact of aerobic fitness on LPS-induced iNOS mRNA expression and the relationship of this expression with indices of oxidative stress, pro-inflammation and apoptosis in isolated leukocytes. Methods: Whole blood samples from aerobically fit and unfit males were stimulated with and without LPS. Thereafter, iNOS mRNA expression and MDA, TNF-α and p53 concentrations were analyzed. Results: iNOS mRNA expression levels following …

Redox Reactions At Oil-Water Interface By Particle Collision Electroanalysis, Dilip K. Paul

Theses and Dissertations

Particle Collision Electrochemistry (PCE) has gained considerable attention in heterogeneous catalysis, petroleum chemistry and pharmaceutical fields. The PCE refers to a phenomenon in which a particle strikes on an inert electrode surface as a consequence of its Brownian motion and produces a spike of current for the direct oxidation/reduction of the individual particle. This method allows us characterization of individual particles and in-situ study of electrochemical reactions coupled to the particle.

Herein, emulsion droplets were studied by PCE where toluene droplets contained hydrophobic tetrachloro-1,4-benzoquinone (Q). This was investigated as a model system to study the molecular effects that arise due …

Detection Of Genetic Abnormalities Using High Speed Atomic Force Microscopy, Anita J. Olsen

Theses and Dissertations

Genetic mutations in the regulatory genes responsible for cell proliferation, differentiation, and death play a significant role in cancer. Molecular diagnostic and sequencing techniques used to detect these abnormalities have limitations that need to be overcome. These issues can be addressed with the use of a novel High-Speed Atomic Force Microscope (HS-AFM) taking physical measurement of molecules labeled with a programmable nanoparticle (Cas9). This technique was used to demonstrate proof-of-concept using genetic mutations found in breast cancer and follicular lymphoma.

Current quantification methods for copy number variation (gene duplication) and gene expression analysis are based on amplification and fluorescence-based techniques …

Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy

Theses and Dissertations

Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT_2A-dependent upregulation of histone deacetylase 2 …

Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter

Theses and Dissertations

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting …

Migratory Patterns And Population Genetic Structure In A Declining Wetland-Dependent Songbird, Matthew G. Desaix

Theses and Dissertations

Understanding migratory connectivity is essential for assessing the drivers behind population dynamics and for implementing effective management in migratory species. Genetic markers provide a means to describe migratory connectivity, as well as incorporate population genetic analyses, however genetic markers can be uninformative for species with weak genetic structure. In this study, we evaluate range-wide population genetic structure and migratory connectivity in the prothonotary warbler, Protonotaria citrea, a wetland-dependent neotropical migratory songbird, using high-resolution genetic markers. We reveal regional genetic structure between sampling sites in the Mississippi River Valley and the Atlantic Seaboard with overall weak genetic differentiation among populations …

Ultrasound—Re:Viewing Bodies, Minjee Jeon

Theses and Dissertations

A medical evaluation of physical impairment imposes the additional burden of “labeling” the patient with the condition. The binary nature of the normal versus abnormal label emphasizes difference and can lead to trauma. Understanding differences, however, can lead to the generation of new forms and thus, more sensitive differentiation and representation. Tension is created by exploring different bodily forms—a dialectic between form and essence. I am designing a space that visualizes and illuminates difference as a source of trauma and amplifying the tension by comparing figures that represent varying degrees of normalcy. This forms a critique of idealized form and …

Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., James A. Ratti

Theses and Dissertations

COPD is characterized by tissue inflammation and impaired remodeling that suggests fibroblast maintenance of structural homeostasis is dysregulated. Thus, we performed in vitro wound healing experiments on normal and diseased human lung fibroblasts and developed an ABM of fibroblasts closing a scratched monolayer using NetLogo to evaluate differences due to COPD or cigarette smoke condensate exposure. This ABM consists of a rule-set governing the healing response, accounting for cell migration, proliferation, death, activation and senescence rates; along with the effects of heterogeneous activation, phenotypic changes, serum deprivation and exposure to cigarette smoke condensate or bFGF. Simulations were performed to calibrate …

Consuming Digital Debris In The Plasticene, Stephen R. Parks

Theses and Dissertations

Claims of customization and control by socio-technical industries are altering the role of consumer and producer. These narratives are often misleading attempts to engage consumers with new forms of technology. By addressing capitalist intent, material, and the reproduction limits of 3-D printed objects’, I observe the aspirational promise of becoming a producer of my own belongings through new networks of production. I am interested in gaining a better understanding of the data consumed that perpetuates hyper-consumptive tendencies for new technological apparatuses. My role as a designer focuses on the resolution of not only the surface of the object through 3-D …

Advances In Dual-Energy Computed Tomography Imaging Of Radiological Properties, Dong Han

Theses and Dissertations

Dual-energy computed tomography (DECT) has shown great potential in the reduction of uncertainties of proton ranges and low energy photon cross section estimation used in radiation therapy planning. The work presented herein investigated three contributions for advancing DECT applications. 1) A linear and separable two-parameter DECT, the basis vector model (BVM) was used to estimate proton stopping power. Compared to other nonlinear two-parameter models in the literature, the BVM model shows a comparable accuracy achieved for typical human tissues. This model outperforms other nonlinear models in estimations of linear attenuation coefficients. This is the first study to clearly illustrate the …

Rational Design Of Allosteric Modulators Of Hemoglobin As Dual Acting Antisickling Agents, Piyusha P. Pagare

Theses and Dissertations

Intracellular polymerization of deoxygenated sickle hemoglobin (Hb S) remains the principal cause of the pathophysiology associated with sickle cell disease (SCD). Naturally occurring and synthetic allosteric effectors of hemoglobin (AEH) have been investigated as potential therapeutic agents for the treatment of SCD. Several aromatic aldehydes, including vanillin, have been studied previously as AEHs for their antisickling activities. Specifically, these compounds form Schiff- base adduct with Hb to stabilize the oxygenated (R) state, increase Hb affinity for O2 and concomitantly prevent the hypoxia-induced primary pathophysiology of Hb S polymerization and RBC sickling, in turn, ameliorating several of the cascading secondary adverse …

The Development Of Novel Inhibitors Of The Nlrp3 Inflammasome, Jacob W. Fulp

Theses and Dissertations

Inflammasomes are intracellular multimeric protein complexes that regulate inflammation by controlling the maturation of cytokines, interleukin-1β (IL-1β) and interleukin-18 (IL-18). Additionally, activation of these inflammasome complexes has been implicated in an inflammatory form of death known as proptosis. Of the known inflammasomes, the NOD-like receptor family pyrin domain containing 3 (NLPP3) inflammasome, is the most elucidated. Under physiological conditions, NLRP3-mediated inflammation promotes healing and the elimination of cellular debris and pathogens. However, the dysregulation of IL-1β, IL-18 and pyroptosis are instrumental in the development of multiple pathologies. Furthermore, studies suggest that the NLRP3 inflammasome mediates detrimental neuroinflammation and …

Heparan Sulfate, A New Target For Platinum In Metastatic Tnbc, Samantha J. Katner

Theses and Dissertations

Abstract

Heparan Sulfate, A New Target for Platinum in Metastatic TNBC

Author: Samantha J. Katner, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy

Virginia Commonwealth University, 2018

Advisor: Dr. Nicholas Farrell, Professor, Chemistry Department

Heparan sulfate proteoglycans (HSPGs), composed of the linear polysaccharide heparan sulfate (HS) conjugated to a protein core, are located on the cell surface and extracellular matrix. The HS chains display varying degrees of sulfation, which constitutes the molecular recognition motif for many HS-protein interactions. HSPGs, associated growth factors, and heparanase promote tumor progression by facilitating invasion, angiogenesis, …

Development And Validation Of A Semi-Physiological Pharmacokinetic (Pbpk) Model To Predict Systemic And Pulmonary Exposures After Intravenous, Oral Administration And Pulmonary Inhalation Of Selected Drugs, Budesonide, Tobramycin And Ciprofloxacin, In Humans, Bishoy Hanna

Theses and Dissertations

Using a semi-PBPK modeling/quantitative meta-analysis approach, this project investigated what factors affect pulmonary and systemic exposures of Budesonide (BUD), Tobramycin (TOB), and Ciprofloxacin (CIP) after inhalation:

Three structurally different pulmonary disposition models were developed for each drug, including pulmonary absorption (all three), excretion (TOB and CIP) and sequestration (TOB) in a peripheral and central lung compartment. Systemic disposition parameters were estimated using available human mean plasma (c_p(t)) and sputum (c_s(t)) concentration profiles after IV administration, and GI absorption parameters were estimated from these profiles after oral administration. Pulmonary disposition parameters were estimated from c_p(t) …

The Break, Ian Gerson

Theses and Dissertations

The Break is a personal investigation into problems and possibilities of representing my specific transgender identity.

Trans as a tactic to speak about a state of forever becoming, forever in between, outside of and in opposition to dominant social norms of being.

Trans as a model for a different way of viewing and being in the world.

Can we form a different kind of horizontal shared power though a collective refusal to play into existing structures from which we have been excluded? What are the potentials for modeling other ways of being, other ways of (dis)engaging, other ways to be …

Nuclear Rupture In Progeria Expressing Cells, Kranthidhar Bathula

Theses and Dissertations

Cells regularly take on various types of force in the body. They have structures that are able to mediate, transfer and respond to the forces. A mutation in force regulating proteins such as lamin in the nucleus or the KASH domain which connects the nucleus to the cytoskeleton of the cell can cause catastrophic events to occur. The aims of this study were to better understand the response of the nucleus when structural proteins are mutated or are not present while under force. Progeria, a rare disease where an additional farnesyl group is attached to lamin was used in this …

Enhancing Adherence To Prescribed Opioids Using A Mobile-Base Application: A Pilot Study Of Feasibility In Chronic Non-Cancer Pain, Daniel M. Sop

Theses and Dissertations

In this study we present feasibility of a mobile monitoring and reporting system that would provide an accurate unbiased screening tool to systematically analyze opioid adherence in Sickle cell disease patients. In addition, the software simultaneously measures pain. The Mobile Applications Rating Scale: a new and validated tool for assessing the quality of health mobile apps for engagement, functionality, aesthetics, information quality, subjective quality, relevance and overall impact was administered post usage to evaluate the application.

A total of 28 patients were recruited to review and test the software at one sitting. The majority of the population found the application …

Graphene As A Solid-State Ligand For Palladium Catalyzed Cross-Coupling Reactions, Yuan Yang

Theses and Dissertations

Palladium-catalyzed carbon-carbon cross-coupling reactions have emerged a broadly useful, selective and widely applicable method to synthesize pharmaceutical active ingredients. As currently practiced in the pharmaceutical industry, homogeneous Pd catalysts are typically used in cross-coupling reactions. The rational development of heterogeneous catalysts for cross-coupling reactions is critical for overcoming the major drawbacks of homogeneous catalysis including difficulties in the separation, purification, and quality control process in drug production. In order to apply heterogeneous catalysis to flow reactors that may overcome this limitation, the catalyst must be strongly bound to a support, highly stable with respect to leaching, and highly active. While …