Digital Commons Network^™

The Role Of Toll-Like Receptor 9 In Periodontitis, Paul Kim

Theses and Dissertations

Periodontitis is a biofilm-initiated inflammatory disease, resulting in soft tissue damage and alveolar bone loss. A nucleic acid sensor, toll-like receptor 9 (TLR9), has been recently implicated in periodontal inflammation. This study utilized an in vivo periodontitis model using TLR9 knockout (TLR9-/-) mice to assess the role of TLR9 in periodontitis. Significant bone loss was observed in wild type, but not in TLR9-/- mice. Further experiments using ex vivo assays revealed significantly higher IL-6 production in splenocytes of wild type mice compared to knockout cells in response to Porphyromonas gingivalis (a keystone pathogen for periodontitis) challenge. In conclusion, TLR9 contributes …

Transitioning From A Traditional Nursing Home Environment To Green House Homes: What Are Stakeholders' Attitudes Toward And Satisfaction With The Small House Care Environment, Christine Harrop-Stein

Theses and Dissertations

This dissertation research was designed as two independent research studies. The first study, qualitative, and non-experimental, aimed to examine residents’, family members’, and staff members’ (stakeholders’) satisfaction with, and attitudes toward Green House living one month prior to moving and again at one and three months after moving. Focus groups were the primary method of data collection. Thirty residents and 40 staff members transitioned to one of three Green House homes beginning January, 2013. Data collected began in December, 2012. Following each focus group, tape recordings were transcribed, and coded. Using grounded theory and the constant comparative method of analysis, …

Long-Term Outcomes Of Prolonged Exposure And Naltrexone For Patients With Comorbid Posttraumatic Stress Disorder And Alcohol Dependence, Shelley Avny

Theses and Dissertations

A growing body of research is examining effective treatment(s) for individuals with comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). However, treatments for this comorbid population have been inadequately studied in the longer term. This study represents a long-term follow-up assessment of a randomized controlled trial that compared combined therapy (prolonged exposure + naltrexone) with monotherapies (prolonged exposure or naltrexone) for patients with PTSD and AD (see Foa, Yusko, McLean et al., 2013). Attempts were made to contact 120 participants 5-10 years after the original trial to assess the maintenance of treatment gains. Nineteen individuals were located and agreed …

The Role Of Nitric Oxide Scavenging In Hemoglobin-Based Oxygen Carrier Induced Hypertension: Systemic And Microvascular Effects, Alan Ottarson

Theses and Dissertations

The purpose of this study was to identify the effects of a hemoglobin-based oxygen carrier, HBOC-201, on the cardiovascular system. Systemic cardiovascular parameters of mean arterial pressure (MAP), pulse pressure, heart rate, and oxygen saturation, as well as vascular resistance, were examined. A murine model of the cardiovascular system and microvasculature was employed. Sprague-Dawley rats (male; 230-530g; N = 13) were anaesthetised and surgically prepared for intravital microscopy of the spinotrapezius muscle. Increasing doses of HBOC-201 (2 mg/kg, 22 mg/kg, 230 mg/kg, and 780 mg/kg) and an iso-oncotic volume control were administered to assess for a dose-response relationship. MAP displayed …

Reversed-Phase Ion-Pairing Ultra Performance Liquid Chromatography-Mass Spectrometry In Characterization Of Glycosaminoglycans, Alhumaidi Alabbas

Theses and Dissertations

Glycosaminoglycans (GAGs) are a family of linear bio-polysaccharides, which are heterogeneously modified with negatively charged sulfate and carboxylate groups. They are located on every cell surface, extracellular matrix or intracellular space in the body. GAGs are composed of alternating units of an amino sugars (glucosamine or galactosamine) and hexuronic acid/hexose (iduronic acid, glucoronic acid/ or galactose), which are linked by glycosidic bonds with different geometries. In recent years, GAGs have attracted considerable interest. GAGs play vital roles in fundamental biological processes, such as hemostasis, angiogenesis, cell signaling, growth and differentiation. Thus, GAGs contribute to a number of diseases such as …

Fabrication Of Nanoporous Gold And Biological Applications, Badharinadh Uppalapati

Theses and Dissertations

FABRICATION OF NANOPOROUS GOLD AND BIOLOGICAL APPLICATIONS By Badharinadh Uppalapati A Dissertation submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2014 Major Director: Maryanne M. Collinson, Professor, Department of Chemistry Fabrication of nanoporous gold electrodes by dealloying Au:Ag alloys has attracted much attention in sensing applications. In the first part of this work, the electrochemical response of the redox active molecule, potassium ferricyanide, in a solution of bovine serum albumin in buffer, serum or blood was studied using nanoporous gold and comparisons made to planar gold. Nanoporous …

Fabrication Of Micropatterns For The Spatial Control Of Cell Propagation And Differentiation, Mahmoud Moustafa

Theses and Dissertations

Challenges in the development of successful cell therapies involve engineering and control of cues to regulate the balance between differentiation and self-renewal. However, the complexity of architecture and function make this an intriguing problem in the context of forming functional connections. Here we present the design and fabrication of microstructured scaffolds that present a biomimetic framework along which neural cell lines can organize into oriented constructs. Specifically, we show microfabricated non-linear architectures that promote cellular fate related to propagation of human neuroblastoma cells and directed differentiation towards neurons. By mimicking biological networks that allow for spreading of the cells instead …

Affinity Enrichment And Mass Spectrometric Quantitation Of Protein Carbonyls, Suresh Narayanasamy

Theses and Dissertations

The importance of the role of oxidative stress in aging and numerous age-related diseases has become undeniable due to enormous weight of supporting evidence from the field of free radical biology. One of the most prominent oxidative modifications of proteins is the introduction of carbonyl groups. As with oxidative stress, protein carbonylation has been correlated with various disease states and natural aging. While protein carbonyls are relatively stable, reproducible detection and modification site localization are still challenging. This thesis details attempts to improve the analytical methodology used for the identification and quantitation of carbonylated proteins. We have studied the impact …

Novel 3d Head And Neck Cancer Model To Evaluate Chemotherapeutic Efficacy, Kelly Morgan

Theses and Dissertations

HNSCC accounts for 7 percent of all new cancer occurrences. Despite currently available treatments, there continues to be a high mortality and recurrence rate in HNSCC. Well over 50 percent of all cancer patients receive chemotherapy as a standard treatment. However, only 5 percent of these cases have been shown to help with treatment of the disease. Formerly, two options were available for drug testing: in vivo animal models, and in vitro two-dimensional models. While in vivo models remain the most representative, their use is burdened by high costs, time constraints, and ethical concerns. 2D models are simple to use …

Acquired Epigenetic And Chromosomal Changes In Women Treated For Breast Cancer, Noran Aboalela

Theses and Dissertations

Improved survival for women receiving chemotherapy for breast cancer (BC) has been accompanied by the development/persistence of psychoneurological symptoms (PNS) that compromise their quality of life. The biological basis for these PNS is unknown, but could reflect the acquisition of soma-wide chromosomal/epigenetic alterations. An important first step in testing this hypothesis is to determine if somatic genetic/epigenetic changes arise and persist following treatment. To answer this question we longitudinally studied 71 women (ages 23-71) with early-stage BC and collected measures before chemotherapy (baseline), and 4 weeks (mid-chemo); six months (during radiation therapy for a subset of women); and one year …

Structural Studies Of Interferon Regulatory Factor 4: A Molecular Perspective Of Its Regulatory Mechanism, Soumya Govinda Remesh

Theses and Dissertations

Interferon (IFN) regulatory factor family member 4 (IRF4) is a transcription factor that serves specific roles in transcriptional regulation of IFN responsive genes and is indispensable in B- & T-cell differentiation. IRF4 like the other members of the family has two major domains- the N-terminal DNA binding domain (DBD) essential for its recognition and binding to the Interferon Stimulated Response Element DNA sequence and a C-terminal Interferon activation domain (IAD) thought to maintain IRF4 in an auto-inhibited inactive state and is also critical in its activation. A putative unstructured linker connects the DBD and IAD. Activation in most members of …

Analysis Of The Role Of Astrocyte Elevated Gene-1 In Normal Liver Physiology And In The Onset And Progression Of Hepatocellular Carcinoma, Chadia L. Robertson

Theses and Dissertations

First identified over a decade ago, Astrocyte Elevated Gene-1 (AEG-1) has been studied extensively due to early reports of its overexpression in various cancer cell lines. Research groups all over the globe including our own have since identified AEG-1 overexpression in cancers of diverse lineages including cancers of the liver, colon, skin, prostate, breast, lung, esophagus, neurons and neuronal glia as compared to matched normal tissue. A comprehensive and convincing body of data currently points to AEG-1 as an essential component, critical to the progression and perhaps onset of cancer. AEG-1 is a potent activator of multiple pro-tumorigenic signal transduction …

Perceptions Of Acupuncture And Acupressure By Anesthesia Providers, Amanda Faircloth

Theses and Dissertations

BACKGROUND: Randomized controlled trials show acupuncture and acupressure support anesthesia management by decreasing anxiety, opioid requirements and treating post-operative nausea and vomiting. Acupuncture and acupressure have demonstrated clinical usefulness and received governmental support (NIH, PPACA, WHO, U.S. Military), but have not yet diffused into mainstream anesthesia practice. This study examined US anesthesia providers' perceptions of acupuncture and acupressure.

METHODS: Ninety-six anesthesiology departments stratified by geographic region (Northeast, South, West, and Midwest) and institution type (university medical centers, community hospitals, children’s hospitals, and VA hospitals) were selected for participation in an anonymous, online survey. The target sample was 1,728 providers …

Regulation Of Pancreatic Α And Β Cell Function By The Bile Acid Receptor Tgr5, Divya Prasanna Kumar

Theses and Dissertations

The discovery that bile acids act as endogenous ligands of the membrane receptor TGR5 and the nuclear receptor FXR increased their significance as regulators of cholesterol, glucose and energy metabolism. Activation of TGR5, expressed on enteroendocrine L cells, by bile acids caused secretion of GLP-1, which stimulates insulin secretion from pancreatic β cells. Expression of TGR5 on pancreatic islet cells and the direct effect of bile acids on the endocrine functions of pancreas, however, are not fully understood. The aim of this study was to identify expression of TGR5 in pancreatic islet cells and determine the effect of bile acids …

Characterization Of The Discriminative Stimulus Properties Of The Atypical Antipsychotic Amisulpride In C57bl/6 Mice, Timothy J. Donahue

Theses and Dissertations

Amisulpride, a benzamide derivative, is an atypical antipsychotic drug used to treat both schizophrenia and depression. Amisulpride is a selective antagonist at dopamine D₂ and D₃ receptors and at serotonin 5-HT_2B and 5-HT₇ receptors and displays an atypical clinical profile with reduced extrapyramidal motor effects. The drug has a chiral center and is a mixture of two optical isomers: (S)-amisulpride and (R)-amisulpride. The present study used a two-lever drug discrimination assay to allow a direct comparison between amisulpride and its two isomers. Additionally, substitution testing was conducted with the typical antipsychotics, atypical antipsychotics, antidepressants, …

A Pollination Network Of Cornus Florida, James H. Lee

Theses and Dissertations

From the agent-based, correlated random walk model presented, we observe the effects of varying the parameter values of maximum insect turning area, ��_max, density of trees, ω, maximum pollen carryover, ��_max, and probability of fertilization, P_��, on the distribution of pollen within a population of Cornus florida (flowering dogwood). We see that varying ��_max and ��_max changes the dispersal distance of pollen, which greatly affects many measures of connectivity. The clustering coefficient of fathers is maximized when ��_max is between 60° and 90°. Varying ω does not have a major …

Enhancing Critical Thinking In Clinical Laboratory Students: A Multimodal Model, Denise Marie Juroske Short

Theses and Dissertations

The purpose of this study was to improve critical thinking skills in clinical laboratory technologists through the development, implementation, and assessment of a multimodal model targeting critical thinking skills. Clinical laboratory technologists influence patient care through the testing of laboratory samples. Employers of these entry level professionals identified a need for improved critical thinking skills. This quasi-experimental study aimed to design a multimodal critical thinking model, implement the model into the clinical laboratory educational curriculum, and assesses this skill set for students in a pre-test / post-test format. The model was delivered and assessed for 47 clinical laboratory students at …

"Mining" For A Reference Condition In Southern West Virginia Streams, Matthew Rouch

Theses and Dissertations

Quarterly samples were used to estimate assemblage-level (all species combined) fish production within three minimally-impacted, southern West Virginia streams. The total annual fish production estimate was highest in Slaunch Fork (37.52 kg∙ha^-1∙y^-1), a tributary of the Tug Fork River, and lowest in Cabin Creek (10.59 kg∙ha^-1∙y^-1), a Guyandotte River tributary. Creek Chub Semotilus atromaculatus, Mottled Sculpin Cottus bairdii and Blacknose Dace Rhinicthys atratulus were the most abundant species among sites, accounting for >90% of all sampled individuals. Reference condition criteria were also selected and metrics calculated for each of the three …

Novel Compounds As Potential Alzheimer's Disease Therapeutics And Inhibitors Of The Nlrp3 Inflammasome, Jeremy E. Chojnacki

Theses and Dissertations

Alzheimer’s disease is a devastating neurodegenerative disorder and the leading cause of dementia. The disease manifests via several pathologies including neuroinflammation, oxidative stress, metal ion dyshomeostasis, and cell death. To address the multifaceted nature of this disorder, the design of several diverse compounds, targeting many pathological effects, was generated. First, a series of compounds based on curcumin and diosgenin were synthesized following the bivalent design strategy. Two compounds were discovered to have neuroprotective ability, anti-oxidative function, and anti-Aß oligomerization (AßO) properties. A second set of molecules was also designed, wherein a hybrid compound strategy was utilized. Three hybrids were to …

Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli

Theses and Dissertations

Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a …

Nf-Κb P50: The Role Of Redox Signaling And Loss Of Function In Dysregulated Microglial Activation, Thomas Taetzsch

Theses and Dissertations

Abstract

NF-κB p50: THE ROLE OF REDOX SIGNALING AND LOSS OF FUNCTION IN DYSREGULATED MICROGLIAL ACTIVATION

By Thomas J Taetzsch 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, 2014

Major Director: Michelle L Block PhD,

IUPUI Associate Professor

Department of Anatomy and Neurobiology

Oxidative stress and chronic microglia-mediated inflammation are well characterized underlying factors in neurodegenerative disease. While it is clear that increased levels of inflammation and augmented oxidative stress in the aged brain create an environment that is particularly harmful to neurons, little …

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Exploring Environments, Idil Cilingiroglu

Theses and Dissertations

My search for creative inspiration often leads to explorations in natural and built environments. Being physically immersed in an environment offers endless vantage points, as well as points of focus; allowing all senses to function as receptors of surrounding data. Observations stimulate thoughts and ideas, which inspire experiments. Projects are born, sometimes out of the smallest details. In a series of projects I explore the possibilities of using physical environments as primary source of inspiration and input in the creation of tools that function in design contexts.

Designing Connection, Laurie K. Culshaw

Theses and Dissertations

Social connection is an essential human need. Personal connections exist at a variety of depths and within different types of relationships. Small daily choices determine the strength of those connections and their impact on our well-being as individuals and as a community. Modern society and technology have altered the speed and channels of connection, increasing communication but decreasing meaningful connection. It is critical to understand how the methods of communication affect the depth of connections. Through a series of participatory graphic design projects, I analyze the strengths and weaknesses of one-on-one, small group and community connections within an established taxonomy …

Atm, Brca1, And Aurora A: Mechanisms Of G2/M Checkpoint Control In Human Embryonic Stem Cells, Jason Beckta

Theses and Dissertations

When cultured in vitro, human embryonic stem cells (hESCs) acquire genetic abnormalities that have slowed their therapeutic use. As hESCs have a “leaky” G1/S boundary, the pressure of ensuring genetic integrity falls on the G2/M checkpoint, which can be activated by failed chromosomal decatenation (among other stimuli). It is hypothesized that hESCs have a deficient decatenation checkpoint, but little data supports this. Evidence suggests that the ataxia telangiectasia mutated (ATM) kinase controls the G2/M decatenation and DNA damage checkpoints, though previous reports are conflicting on this point. My work demonstrates that inhibition of decatenation activates ATM and arrests hESCs in …

An Analysis Of Fatty Acid Metabolism’S Role In The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans, Richard Raabe

Theses and Dissertations

An individual’s naïve level of response (LR) to ethanol is predictive of their lifetime likelihood to abuse alcohol. LR is heavily genetically influenced, suggesting that the genes responsible for LR may also be central to the development of abuse disorders. Our laboratory uses the model organism C. elegans to investigate the genetic influences on responses to acute ethanol exposure. We recently found that changes in TAG levels can alter LR. From this result we investigated the role of long-chain polyunsaturated fatty acids (LC-PUFAs) as well enzymes involved in lipid modifications of proteins. We found that LC-PUFAs are necessary for acute …

Characterization Of Complement Evasion Of The Periopathogen, Treponema Denticola, Daniel Patrick Miller

Theses and Dissertations

Periodontitis is a polymicrobially-induced, chronic inflammatory disease of the tissues that support and surround the tooth. While greater than 500 organisms are found in dental plaque, Treponema denticola is one of only a few species associated with disease. It has been hypothesized that oral bacteria disrupt host homeostasis through manipulation of the innate immune system. In this study, we examine the impact of binding and subsequent cleavage of factor H, a complement regulator, by T. denticola in the evasion and subversion of complement. The molecular interaction between the sole FH-binding protein, FhbB, and FH was detailed by x-ray crystallography, site-directed …

Hiv And Opiates-Mediated Neurotoxicity: Gsk3Β Is A Potential Therapeutic Target, Ruturaj Masvekar

Theses and Dissertations

HIV-1 enters the CNS soon after initial systemic infection. HIV-1 can induce a wide range of neurological deficits, collectively known as HIV-1-associated neurocognitive disorders (HAND). Mature neurons are not infected by HIV-1; instead, infected and/or activated glial cells release various viral and cellular factors that induce direct and/or indirect neuronal toxicity, leading to HAND. Injection drug abuse is a significant risk factor for HIV-infection, and opiate drug abusers show increased HIV-neuropathology, even with anti-retroviral treatments. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes …

Folate Conjugated Dendrimers For Targeted Anticancer Therapy, Shannon Andrews

Theses and Dissertations

Anticancer therapeutics are often limited to suboptimal doses due to their lack of selectivity for tumor cells and resultant damage to healthy tissue. These limitations motivated researchers to develop tumor-specific delivery systems for improved therapeutic efficacy and reduced unintended cytotoxicity. Polyamidoamine dendrimers offer an ideal platform for designing targeted therapeutics with tunable characteristics that optimize pharmacokinetic behavior and targeting specificity. Ligand conjugation to dendrimer provides the biochemical interaction necessary to activate tumor-specific receptors for receptor-mediated endocytosis and effective internalization of polyplexes. Tumor-specific receptors overexpressed in carcinomas, like folate receptor-alpha (FOLRα), are targeted by ligand-conjugated dendrimer to allow enhanced internalization of …

Multi-Species Gene Networks And Drosophila Ethanol Sedation, Arnavaz Kollah

Theses and Dissertations

Alcohol use disorders (AUDs) are major health issues with few known genetic explanations. This project used the fruit fly (Drosophila melanogaster) model to identify genes and gene networks that influence alcohol intoxication, a phenotype related to alcohol abuse in humans. We used bioinformatic tools to build gene networks based on 24 published Drosophila ethanol-responsive genes with human orthologs. We then assessed the role of these networks in ethanol sedation by testing two of the networks seeded on IP3K2, a gene that regulates calcium signaling, and CG14630, a gene involved in carnitine biosynthesis. We knocked down several genes in each of …