Digital Commons Network^™

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 …

Analysis And Modeling Of The Roles Of Actin-Myosin Interactions In Bladder Smooth Muscle Biomechanics, Seyed Omid Komariza

Theses and Dissertations

Muscle mechanical behavior potentially plays an important role in some of the most common bladder disorders. These include overactive bladder, which can involve involuntary contractions during bladder filling, and impaired contractility or underactive bladder, which may involve weak or incomplete contractions during voiding. Actin-myosin cross-bridges in detrusor smooth muscle (DSM) are responsible for contracting and emptying the bladder. The total tension produced by muscle is the sum of its preload and active tensions. Studies suggest that actin-myosin cross-links are involved in adjustable preload stiffness (APS), which is characterized by a preload tension curve that can be shifted along the length …

Capillarity And Two-Phase Fluid Transport In Media With Fibers Of Dissimilar Properties, Thomas M. Bucher Jr.

Theses and Dissertations

Capillarity is a physical phenomenon that acts as a driving force in the displacement of one fluid by another within a porous medium. This mechanism operates on the micro and nanoscale, and is responsible for countless observable events. This can include applications such as absorption in various hygiene products, self-cleaning surfaces such as water beading up and rolling off a specially-coated windshield, anti-icing, and water management in fuel cells, among many others.

The most significant research into capillarity has occurred within the last century or so. Traditional formulations for fluid absorption include the Lucas–Washburn model for porous media, which is …

Where Does Electronic Aggression Fit?: A Comparison Of Dimensional And Categorical Models Of Adolescent Aggression, Krista R. Mehari

Theses and Dissertations

Electronic aggression is a rapidly growing focus of research, but it lacks a unifying theoretical framework that is necessary to advance the field. The lack of a theoretical framework has led to inconsistencies in measurement of electronic aggression, making it difficult to draw conclusions across studies. In general, researchers have assumed that electronic aggression constitutes a new form of aggression, a counterpart to physical, verbal, and relational aggression, due to unique features surrounding the perpetration of electronic aggression. Furthermore, researchers have treated electronic aggression as a categorical variable based on the assumption that “cyberbullies” constitute a distinct group of adolescents. …

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.

Side A, Side B, Hong Zhang

Theses and Dissertations

I believe that aural and visual language can contribute and inspire one another. Sound evokes the emotions and the senses. It is a catalyst for our imagination. It can be combined with imagery for the purpose of communication, harmoniously or contrastively. Both have corresponding characteristics—color/timbre, brightness/pitch, length/duration, scale/volume, composition/rhythm—and thus provide ways of transforming each other back and forth as input and output. Computer technology has increased the ease of transforming and manipulating the two. In my thesis project, I explore sound visualization, sound/image transformation and combination.

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 …

Regulation And Mechanistic Functions Of Caspase-9 Rna Splicing, Ngoc T. Vu

Theses and Dissertations

Caspase-9 has two splice variants, pro-apoptotic caspase-9a and anti-apoptotic caspase-9b, and dysregulation of caspase-9 splice variant ratio or expression of caspase-9b isoform has been linked to augmentation of the anchorage-independent growth and tumorigenic capacity of non-small cell lung cancer (NSCLC) cells. This study focuses on cell signaling pathway(s) regulating the alternative splicing of caspase-9 pre-mRNA and mechanistic roles of caspase-9b in a certain oncogenic/survival pathway. In regards to the former, we have identified hnRNP U as a novel splice-enhancer associated with exon 3 of caspase-9 (C9/E3). Moreover, hnRNP U binds specifically to C9/E3 at an RNA cis-element previously reported …

The Effect Of Fluvastatin On Mast Cell Function: Genotype Dependence, Elizabeth M. Kolawole

Theses and Dissertations

Fluvastatin, the HMG-CoA reductase inhibitor known for its role in the treatment of hypercholesterolemia and cardiovascular disease, has more recently been shown to play a role in the immune response. Given the critical role that mast cells play in allergy and inflammatory diseases such as asthma, which effects one third of America’s population, we assessed the effect of fluvastatin on mast cell and basophils function. We demonstrate that fluvastatin downregulated IgE-mediated cytokine production. Additionally, in vivo studies showed that fluvastatin suppressed IgE-mediated anaphylaxis. Interestingly, the effects of fluvastatin showed dependence on genetic background, as C57BL/6 mast cells were sensitive, while …

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, …

Story-Telling Through The Design Of A Permanent Mission Trip Training And Housing Facility, Betty L. Rowe

Theses and Dissertations

This mixed- assembly space is designed as a permanent mission trip training and housing facility. Predominately the space will be used by middle school and high school youth. By creating a modern experience, teens are given a better opportunity to engage in a space they can relate to. It becomes a space where young people feel encouraged to share their feelings, beliefs and desires as they journey into a closer, more intimate relationship with a higher being.

The space is intended to serve a transient population. A large portion of the first floor is devoted to communal gathering which provides …

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 …

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 …

Fathering And Child Maltreatment: A Grounded Theory Study, Jennifer Shadik

Theses and Dissertations

Literature related to fathers and child physical abuse and neglect is lacking (Guterman & Lee, 2005; Lee, Bellamy, & Guterman, 2009). The purpose of this study was to better understand several pertinent aspects of fathering related to maltreatment. Three research questions were examined: 1.What are the attitudes, behaviors and contexts of fathers who have abused or neglected a child that relate to maltreatment? 2. What are the resources and capacities of these fathers which could be capitalized on? 3. How does goodness-of-fit or a poor fit between the father and child impact the parenting relationships of these fathers? Fifteen fathers …

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 …

Investigating The Effects Of Applied Electric Fields On Microglial Cell Behaviour, Eman Bani

Theses and Dissertations

As surveyors of the central nervous system (CNS), microglial cells play an integral part in the inflammatory response following traumatic injuries. Thus, they have been implicated in the limited capability of neurons to regenerate in the CNS. Additionally, the roles of endogenous electric fields in the regenerative process of neurons in the mammalian peripheral nervous system (PNS) or amphibian CNS have long been studied. Further, previous studies in our lab have shown that physiological electric fields are capable of directing behaviours in astrocytes and schwann cells. Therefore in this study, a BV-2 microglia cell line was utilized to investigate whether …

Reproductive Success In Hatchery-Produced Eastern Oyster, Crassostrea Virginica (Gmelin), April Piggott

Theses and Dissertations

The eastern oyster (Crassostrea virginica Gmelin 1791) has great ecological and economic importance but populations have declined, especially in Chesapeake Bay, to historically low numbers. Hatcheries strive to produce oysters with beneficial characteristics for supplementation and commercial purposes, both natural and stimulated mass spawning. Unequal contribution of parents in mass spawnings potentially can lead to high levels of inbreeding and a loss of beneficial characteristics in offspring. In this study, we determined microsatellite genotypes for parents (n^parents =24, 49, and 77 parents) and progeny (n=96 each) of three hatchery-produced families and used the data for parental assignment. We observed the …

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 …

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 …

Identification Of Peptidases In Highly-Pathogenic Versus Weakly-Pathogenic Naegleria Fowleri Amebae, Ishan Vyas

Theses and Dissertations

Naegleria fowleri, a free-living ameba, is the causative agent of Primary Amebic Meningoencephalitis. Highly-pathogenic mouse-passaged amebae (Mp) and weakly-pathogenic axenically-grown (Ax) N. fowleri were examined for peptidase activity. Zymography and azocasein peptidase activity assays demonstrated that Mp and Ax N. fowleri exhibited a similar peptidase pattern. Prominent for whole cell lysates, membranes and conditioned medium from Mp and Ax amebae were the presence of an activity band of approximately 58kDa and 100 kDa bands susceptible to the action of cysteine and metallopeptidase inhibitors, respectively. Further roles of the peptidases during the invasion process were examined by in vitro invasion assays …

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 …

Identification Of Micro-Rnas And Their Messenger Rna Targets In Prostate Cancer And Biological Fluids, Kanika Sharma

Theses and Dissertations

Prostate cancer is the second most common cancer in the United States that affects men today. To better treat this disease accurate biomarkers and successful therapeutic treatments are needed. A novel approach to understand the mechanisms behind prostate cancer tumor formation lies in identifying dysregulated micro-RNAs (miRNAs), which are a class of small (18-24 nucleotides) non-coding RNAs that regulate gene expression posttranscriptionally by either inhibiting protein synthesis or signaling messenger-RNA for degradation. Multiple miRNAs were discovered in our highly tumorigenic and metastatic prostate cancer progression model M12 cell line compared to its weakly tumorigenic P69 parental cell line. Various analyses …

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 …

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 …

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 …

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 …

Parental Mediation Of Adolescent Movie Viewing, Larry James Webster Jr.

Theses and Dissertations

Parental mediation of media use by children has been studied extensively as it applies to television and children 12 years old and younger. This study expands the scope of Parental Mediation Theory by applying it to adolescents (age 13-17 years old) and movie viewing. The results of this study show overall parental mediation of adolescent movie viewing is negatively associated with the age of the child. The results show that among parents who mediate movie viewing, restrictive, instructive and social co-viewing mediation strategies are negatively correlated with the age of the adolescent. Third Person Effect is also examined as parental …