Digital Commons Network^™

Fluoxetine Attenuates Mast Cell Function By Targeting Purinergic Signaling, Tamara T. Haque

Theses and Dissertations

Mast cells are tissue resident, innate immune cells that provide protection against parasitic and bacterial infections and venom poisoning. Mast cells also play a pathogenic role in atopy and allergic diseases. Atopy and allergic diseases are increasing in the developed world and are predicted to continue to increase at an alarming rate. Current treatment options include corticosteroids, anti-histamines, anti-IgE and avoidance of allergen. These interventions have limitations: some patients are steroid resistant; anti-histamines have low efficacy since they need to be administered early during allergen exposure; and anti-IgE is costly. Thus there is a clinical need for new treatment options. …

Factors That Influence Mental Health Services Utilization By Children Who Have Experienced Adversity, Mary B. Stebbins

Theses and Dissertations

Adverse childhood experiences (ACEs) are linked to increased mental health problems in children, but their association with mental health services utilization is not well known. This secondary analysis used 2016 National Survey of Children’s Health data from two samples: children aged 6-17-years-old with a mental or behavioral condition in need of treatment or counseling (N = 5,723); and a subsample of children who experienced at least one ACE (n = 3,812). Multiple logistic regression and latent class analysis (LCA) were performed to examine the association between ACEs and mental health services utilization. Multiple logistic regressions also examined the …

Latent Growth Model Approach To Characterize Maternal Prenatal Dna Methylation Trajectories, Dana Lapato

Theses and Dissertations

Background. DNA methylation (DNAm) is a removable chemical modification to the DNA sequence intimately associated with genomic stability, cellular identity, and gene expression. DNAm patterning reflects joint contributions from genetic, environmental, and behavioral factors. As such, differences in DNAm patterns may explain interindividual variability in risk liability for complex traits like major depression (MD). Hundreds of significant DNAm loci have been identified using cross-sectional association studies. This dissertation builds on that foundational work to explore novel statistical approaches for longitudinal DNAm analyses. Methods. Repeated measures of genome-wide DNAm and social and environmental determinants of health were collected up to six …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …

Assessment Of Microbial Carbon Processing And Its Implications To The Carbon Budget Of Lake Superior, Lindsey Michelle Koren

Theses and Dissertations

Over the past few decades, there has been increased research focus on carbon cycling within aquatic systems, especially with the changing global climate. Inland waters play a major role in the global carbon cycle, but the fundamental features remain poorly understood, particularly the large lakes of the world. Our experimental approach assessing the carbon budget of Lake Superior, the largest freshwater lake by area, provides spatial and temporal variability that has been previously overlooked but may be critical to our understanding on the biogeochemical processes controlling the lake. Multiple stations were chosen across the lake, both nearshore and offshore, to …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

Cyclophilin A As A Molecular Switch Regulating Prolactin Receptor Mediated Signaling, Mammary Tumorigenesis And Metastasis, Shawn Hakim

Theses and Dissertations

Prolactin (PRL) and its receptor (PRLr) have been implicated in the development and progression of human breast cancer. PRL activates its receptor and induces activation of proximal Janus kinase 2 (Jak2) for signal transduction. Here, we sought to determine the role of PRLr-associated peptidyl-prolyl isomerase, cyclophilin A (CypA), in modulating structure/function relationships of the PRLr. It was demonstrated that CypA mediated PRL-induced conformational change of the CFP- and -YFP tagged forms of the PRLr cytoplasmic-tail, whereas CypA inhibition by NIM811 (N-methyl-4-isoleucine cyclosporin) or knockdown blocked the conformational change of the PRLr assessed by Fluorescence Resonance Energy Transfer (FRET) signal or …

Preconditioning Of The Tumor Microenvironment By Means Of Low Dose Chemotherapies For An Effective Immunotherapy Of Breast Cancer, Hussein F. Aqbi

Theses and Dissertations

Breast cancer mortality is mainly due to distant recurrence of the disease arising from dormant tumor cells established by cancer therapies. Patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting …

Dating Violence And Latina/O Emerging Adult’S Attitudes Towards Condoms And Condom Use Behaviors: Examining The Role Of Culture, Melissa Avila

Theses and Dissertations

Latina/o emerging adults living in southern states may be especially at risk of being disproportionately affected by HIV. In 2015, Latina/os aged 20 to 24 accounted for 14.7% of all 20-24-year old’s living with HIV in southern states, despite the fact that 20 to 24-year-olds make up 3.7% of the region’s overall population of individuals living with HIV (CDC, 2016; U.S. Census Bureau, 2017). Specifically, there continues to be groups of Latina/o emerging adults who do not use condoms when they are sexually active and who are not using condoms consistently. Condom use literature suggests that relationship factors, such as …

Mechanochemical Regulation Of Epithelial Tissue Remodeling: A Multiscale Computational Model Of The Epithelial-Mesenchymal Transition Program, Lewis Scott

Theses and Dissertations

Epithelial-mesenchymal transition (EMT) regulates the cellular processes of migration, growth, and proliferation - as well as the collective cellular process of tissue remodeling - in response to mechanical and chemical stimuli in the cellular microenvironment. Cells of the epithelium form cell-cell junctions with adjacent cells to function as a barrier between the body and its environment. By distributing localized stress throughout the tissue, this mechanical coupling between cells maintains tensional homeostasis in epithelial tissue structures and provides positional information for regulating cellular processes. Whereas in vitro and in vivo models fail to capture the complex interconnectedness of EMT-associated signaling networks, …

The Role Of Cellular Aging In The Regulation Of Free Fatty Acid Induced Cellular Inflammation By Liver X Receptor Alpha, Charles S. Schwartz

Theses and Dissertations

Purpose: This study examined the impact of an acute bout of exercise on LXRα mRNA expression in isolated PBMCs from aerobically fit middle-aged males, and its associations with cellular inflammation. Furthermore, association between cellular age and LXRα were investigated. Methods: LXRα mRNA, plasma free fatty acids, IL-6, and MCP-1 responses were quantified following acute moderate intensity exercise and throughout recovery. To examine LXRα’s associations with cellular inflammation, PBMCs were stimulated with palmitate. Finally, telomere length was quantified as an indicator of cellular age. Results: LXRα mRNA expression was reduced at 90 minutes of recovery and did not influence systemic inflammation. …

Energy Efficient Spintronic Device For Neuromorphic Computation, Md Ali Azam

Theses and Dissertations

Future computing will require significant development in new computing device paradigms. This is motivated by CMOS devices reaching their technological limits, the need for non-Von Neumann architectures as well as the energy constraints of wearable technologies and embedded processors. The first device proposal, an energy-efficient voltage-controlled domain wall device for implementing an artificial neuron and synapse is analyzed using micromagnetic modeling. By controlling the domain wall motion utilizing spin transfer or spin orbit torques in association with voltage generated strain control of perpendicular magnetic anisotropy in the presence of Dzyaloshinskii-Moriya interaction (DMI), different positions of the domain wall are realized …

An Autoethnographic Journey Through Craftivism: Making With/For Meaning, Virginia H. Brinn

Theses and Dissertations

Through this dissertation, I set out to investigate how craftivism as a way of making with/for meaning might foster transformative experiences within the discipline of art education. My motivating questions for this research project as I began my qualitative process follow. In what ways does my art-making inform my teaching practice? How do both my art and teaching practice inform my research practice? In what ways does my feminist identity impact these practices, ways of thinking and knowing, and the process of becoming who I am? And why is this research relevant to the field of art education? Given the …

Response And Recovery Of Syntrophic And Methanogenic Activity To Saltwater Intrusion In A Tidal Freshwater Marsh Soil, David J. Berrier Jr.

Theses and Dissertations

Tidal freshwater wetland soils contain large amounts of organic carbon, some of which is mineralized to carbon dioxide (CO₂) and methane (CH₄) by a diverse consortium of anaerobic microorganisms that includes fermenters, syntrophs, and methanogens (MG). These microbial groups are tightly linked and often rely on cooperative interspecies metabolisms (i.e., syntrophy) to survive. Environmental perturbations can disrupt these interactions and thus alter the rates and pathways of carbon cycling. One environmental change of particular concern in coastal wetlands is sea level rise, which can result in increased episodic saltwater intrusion events into these ecosystems. These events …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Electrostatic Networks And Mechanisms Of Δph-Dependent Gating In The Human Voltage-Gated Proton Channel Hv1, Ashley L. Bennett

Theses and Dissertations

The structure of the voltage-gated proton (H⁺) channel Hv1 is homologous to the voltage sensor domain (VSD) of tetrameric voltage-gated Na⁺, K⁺ and Ca²⁺ channels (VGCs), but lacks a pore domain and instead forms a homodimer. Similar to other VSD proteins, Hv1 is gated by changes in membrane potential (V), but unlike VGCs, voltage-dependent gating in Hv1 is modulated by changes in the transmembrane pH gradient (DpH = pH_o - pH_i). In Hv1, pH_o or pH_i changes shift the open probability (P_OPEN)-V relation by ~40 mV per …

Mathematics Identity Construction In Successful African Americans: Reflections On Mathematics Experiences During Adolescence, Teri N. Johnson

Theses and Dissertations

This project used narrative inquiry to examine adolescent experiences that contributed to the development of positive mathematics identities in successful African Americans. Ten African Americans, who had worked in a STEM-related occupation for at least two years, were asked to reflect on in- and out-of-school experiences with mathematics during their middle and high school years. Data collection included individual interviews and one focus group discussion. A combination of internal and external factors emerged as contributors to participants’ adolescent mathematics identities. Internal factors included early career interest, finding enjoyment in the challenges associated with learning mathematics, or facing setbacks they were …

The Increased Frequency Of Micronuclei Seen In Women With A History Of Childhood Sexual Abuse Reflects More Numerical Than Structural Acquired Chromosomal Events: A Discordant Identical Co-Twin Study, Kaitlyn M. Dochelli

Theses and Dissertations

Childhood sexual abuse (CSA) is a stressful life experience with lasting/far-reaching health and psychopathological consequences. Our laboratory recently identified a significantly increased frequency of acquired chromosomal anomalies (assessed using the cytokinesis-blocked micronucleus assay) in adult female twins exposed to CSA when compared to their unexposed co-twin. The primary aim of this study was to evaluate potential mechanism(s) underlying the observed increases in levels of micronuclei in an expanded group of 90 female identical twins (61 CSA+ females and 29 CSA- females [including a total of 27 MZ co-twin pairs]) using fluorescence in situ hybridization (FISH) methodologies, with PNA probes specific …

Modulation Of Autophagy And Senescence To Enhance The Response To Therapy In Triple Negative Breast Cancer, Liliya Tyutyunyk-Massey

Theses and Dissertations

Abstract

Although great strides have been made over the decades in development and optimization of anti-cancer therapies, even highly effective drugs often fail to completely eliminate tumors. Residual tumor cells can enter into a state of dormancy for prolonged periods of time but eventually are able to regain proliferative capacity and reemerge as chemotherapy-resistant disease. Because recurrent disease is a leading contributor to patient’s mortality, it is paramount to identify strategies for effectively destroying residual tumor cells.

Cytotoxic drugs and ionizing radiation are used as standard therapies in a variety of cancers. These modalities induce apoptosis, autophagy and senescence. Senescence …

Eternal Enemies, Or Incidental Encounters? Structure And Patterns Of Interspecific Killing In Carnivora, Tor G. Bertin

Theses and Dissertations

Lethal interactions between carnivorans (interspecific killing) may influence their population dynamics, behavior, and other important aspects of their ecology. In this study, I expand upon previous research on the broad-scale patterns of interspecific killing in Carnivora (Palomares & Caro 1999, Donadio & Buskirk 2006) with a greatly expanded dataset (inclusion of scat and stomach data and more intensive sampling of the literature), and suggest avenues for future research. While like previous studies, I found a positive effect of relative body size between killer species and killed species on the likelihood of forming a killing interaction, I failed to find evidence …

Cold X-Ray Effects On Satellite Solar Panels In Orbit, Myles Fogleman

Theses and Dissertations

An exo-atmospheric nuclear detonation releases up to 80 percent of its’ energy as X-rays. Satellite’s solar cells and their protective coatings are vulnerable to low energy X-ray radiation. Cold X-rays (~1-1.5 keV) are absorbed close to the surface of materials causing the blow-off and rapid formation of Warm Dense Plasmas (WDPs), particularly in a gap between the unshielded active elements of solar cells. To understand how WDPs are created, it is necessary to investigate the power density distribution produced by cold X-rays for typical solar panel surface materials. The Monte Carlo stepping model implemented in the GEANT4 software toolkit is …

Targeting Sphingosine Kinase 2 As A Treatment For Cholangiocarcinoma, Anthony D. Stillman

Theses and Dissertations

Cholangiocarcinoma (CCA) has a high mortality rate and its occurrence is rising. This increase prompts the need for improved CCA treatments. Studies have suggested that CCA is highly reliant on the sphingosine-1-phosphate-receptor-2 (S1PR2) and sphingosine kinase 2 (SphK2). Recently, a competitive SphK2 inhibitor, ABC294640, has been approved for clinical trial. ABC294640 has the potential to treat CCA, which is support by a phase I clinical study that was able to temporarily treat a patient suffering from metastasized CCA with ABC294640. To determine the viability of ABC294640 as a treatment for CCA, this study focused on determining the effects of ABC294640 …

Planting Density Effects On The Growth Of Dune Grasses., Audrey Kirschner

Theses and Dissertations

Coastal dune vegetation plays a key role in dune formation and stabilization through sediment trapping and erosion control. To restore degraded dunes, revegetation of dune building species is critical. Planting density has been found to effect growth of marsh species, with closer plantings alleviating stress through facilitation. As coastal dunes are high stress environments, it is expected that dune species may also exhibit facilitative interactions based on the Stress Gradient Hypothesis. Therefore, planting grasses in clumped configurations may lead to more successful dune revegetation. The objective of this research was to determine how planting density affects the growth of two …

2nd Tier Assay For The Detection Of Congenital Adrenal Hyperplasia By Virginia’S Newborn Screening Laboratory: Steroid Profile By Hplc-Ms/Ms, Christopher E. Nixon

Theses and Dissertations

Congenital Adrenal Hyperplasia (CAH) encompasses several disorders related to disruptions in the adrenal steroid production pathway. These disruptions may cause virilization of the external female sex organs, incorrect gender assignment, precocious puberty, and in the most severe form, may cause life-threatening salt wasting and adrenal crisis if not detected and treated early in the newborn period.

17α-Hydroxyprogesterone (17-OHP) is the primary target for immunofluorescence detection of CAH from dried blood spots in newborn screening (NBS). Unfortunately, current immunoassay techniques for the detection of CAH suffer from high false positive rates. The primary factors contributing to false positive determinations can include …

An Investigation On The Role Of Β-Arrestin 2, Protein Kinase C And Sex On The Mechanism Of Morphine Tolerance In The Mouse Ileum, Karan Hitesh Muchhala

Theses and Dissertations

Opioids such as morphine are frequently used in the clinic to treat pain. However, the perennial bane of chronic opioid use is the rapid development of tolerance to the analgesic effects but delayed development of tolerance to the respiratory depressant and constipating effects. As constipation is one of the most common opioid-related adverse effects in humans, it is important to delineate mechanisms that drive opioid tolerance in the ileum and lack of it in the colon. The overarching goal of this thesis was to investigate mechanisms of morphine tolerance in the ileum by comparing the mechanism of morphine tolerance in …

Adhesion At Solid/Liquid Interfaces, Neda Ojaghlou

Theses and Dissertations

The adhesion at solid/liquid interface plays a fundamental role in diverse fields and helps explain the structure and physical properties of interfaces, at the atomic scale, for example in catalysis, crystal growth, lubrication, electrochemistry, colloidal system, and in many biological reactions. Unraveling the atomic structure at the solid/liquid interface is, therefore, one of the major challenges facing the surface science today to understand the physical processes in the phenomena such as surface coating, self-cleaning, and oil recovery applications. In this thesis, a variety of theory/computational methods in statistical physics and statistical mechanics are used to improve understanding of water adhesion …

Adverse Childhood Experiences, Neighborhood Disorganization, Co-Parenting: The Impact On College Student Mental Health, Mona L. Quarless

Theses and Dissertations

Though mental health issues are prevalent amongst college students, pre-college environment and experiences are largely overlooked as potential factors in scientific literature. The current study examined the association of neighborhood disorganization, Adverse Childhood Experiences (ACEs) and mental health outcomes in a sample of college students. Utilizing the ecological model of human development and risk-resilience framework, I examined co-parenting quality as a plausible protective factor against the negative effects of adverse childhood experiences and neighborhood disorder. Self-report measures of ACEs, co-parenting quality, neighborhood disorder, anxiety, and depression were completed by a sample of college students (N = 259; mean age = …

Stat5b And Stat5 Tetramers Are Essential For Ige-Mediated Mast Cell Function, Kasalina N. Kiwanuka

Theses and Dissertations

Signal Transducers and Activators of Transcription (STATs) are latent transcription factors that mediate several cellular responses. This protein family consists of seven members, STAT1 – 6 including two closely related molecules, STAT5a and STAT5b, that show 96% amino acid sequence homology and are critical for lymphoid, myeloid and erythroid cell development and function. Activated STAT proteins dimerize and translocate to the nucleus, where they bind to high-affinity DNA motifs to modulate gene expression. We recently identified STAT5b as the critical regulator of IgE-mediated cytokine production in mast cells. STAT5b knockout (KO) cells show decreased sensitivity to IgE-mediated passive systemic anaphylaxis …

Phenotypic Characterization Of Pnpase Mutation And Overexpression In C. Elegans, Brian J. Hur

Theses and Dissertations

PNPase, polynucleotide phosphorylase, is a multifunctional exoribonuclease protein with 3` terminal oligonucleotide polymerase activity. Coded by the PNPT1 gene, the protein is associated with mitochondrial homeostasis and functions as a possible target for cancer therapy. In this study, C. elegans was used to investigate the effect of mutation and overexpression of pnpt-1, the gene that encodes PNPase. It was determined that two specific mutations in pnpt-1 did not affect PNPase expression nor did they produce deleterious phenotypes that affected polycistronic transcript accumulation or ROS production. Creation of a stable overexpression model was achieved through Fusion PCR. However, different transgenic …

Spectral Methods For The Detection And Characterization Of Topologically Associated Domains, Kellen Garrison Cresswell

Theses and Dissertations

The three-dimensional (3D) structure of the genome plays a crucial role in gene expression regulation. Chromatin conformation capture technologies (Hi-C) have revealed that the genome is organized in a hierarchy of topologically associated domains (TADs), sub-TADs, and chromatin loops which is relatively stable across cell-lines and even across species. These TADs dynamically reorganize during development of disease, and exhibit cell- and conditionspecific differences. Identifying such hierarchical structures and how they change between conditions is a critical step in understanding genome regulation and disease development. Despite their importance, there are relatively few tools for identification of TADs and even fewer for …