Digital Commons Network^™

The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers

Electronic Theses and Dissertations

Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and …

Porphyromonas Gingivalis Infection In Gestational Diabetes Mellitus And Survival In Tobacco Smokers., Himabindu Gogeneni

Electronic Theses and Dissertations

This thesis contains a clinical project and distinct basic science project. Gestational diabetes mellitus occurs in 4% of pregnancies and increases the risk of birth defects, pre-term birth, and miscarriage. Gingivitis during pregnancy also increases the risk for poor pregnancy outcome. Gingivitis is a bacterial-induced disease, and specific plaque pathogens have been associated with systemic sequelae to periodontal inflammation. Therefore, we set out to monitor oral infection with three key periodontopathogens (Porphyromonas gingivalis, Filifactor alocis, and Treponema denticola) and the systemic inflammatory burden [C-reactive protein (CRP) in pregnant women with and without gingivitis and gestational diabetes. Gingivitis …

Ubqln1 : A Multi-Domain Protein With Multiple Functions., Zimple Kurlawala

Electronic Theses and Dissertations

There are 5 Ubiquilin proteins (UBQLN1-4, UBQLN-L), which are evolutionarily conserved and structurally similar. UBQLN proteins have 3 functional domains: N-terminal ubiquitin-like domain (UBL), C-terminal ubiquitin-associated domain (UBA) and STI chaperone-like regions in the middle. Alterations in UBQLN1 gene have been detected in a variety of disorders including Alzheimer’s disease, Amyotropic Lateral Sclerosis and lung cancer. UBQLN1 has been largely studied in neurodegenerative disorders in the context of protein quality control. Several studies have hypothesized that the UBA domain of UBQLN1 binds to poly-ubiquitin chains of substrate and shuttles it to the proteasome via its UBL domain for degradation. UBQLN1 …

Targeting Fas Pathway As An Effective Means Of Inducing Tolerance To Pancreatic Islets., Kyle Blake Woodward

Electronic Theses and Dissertations

Signaling through Fas/FasL is critical to immune homeostasis and tolerance to self-antigens. SA-FasL is a chimeric protein of FasL and streptavidin. SA-FasL exists as oligomers with potent apoptotic function on Fas expressing immune cells and tightly binds to biotinylated surfaces. Islet grafts engineered to transiently display SA-FasL on their surface established tolerance in allogeneic recipients with a short course of rapamycin. We hypothesized that SA-FasL on the islet allograft will induce apoptosis in alloreactive T effector (Teff) cells and phagocytes clearing apoptotic bodies will produce tolerogenic molecules, such as TGF-β, that will lead to the generation and/or expansion of Treg …

Attending To Systemic Racism : Advancing Public Health's Approach To Youth Violence Prevention., Billie Faith Castle

Electronic Theses and Dissertations

This dissertation examines how the field of public health addresses the impact of systemic racism on health and how that informs public health’s approach to youth violence prevention. Beginning with an overview of youth violence, it breaks down the concepts of race and racism and how they are addressed within the science. It also reviews concepts that contribute to risk and protective factors of youth violence. The dissertation is written from a Critical Race Theory approach, argues that the social environment contributes to why youth violence is pervasive in certain neighborhoods, and promotes action from a macro-level approach. Seven chapters …

Bdnf-Trkb Signaling Regulates Adult Taste Bud Innervation., Tao Tang

Electronic Theses and Dissertations

Taste receptor cells transduce stimuli transmitting information to gustatory neurons that carry it to the brain. They turn-over continuously in adulthood, and must be constantly reinnervated, making the maintenance of innervation to taste buds an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Taste bud innervation (40%) is lost when Bdnf is removed during adulthood, but it is unclear why remaining fibers were not lost. We found that some gustatory nerve fibers remained because they lack the TrkB receptor 55% of TrkB-labeled fibers were lost and fibers without TrkB remained following adult Bdnf gene recombination. It is …

Former Students Discuss Middle School Science Journalism : A Qualitative Study Of Personally Meaningful Disciplinary Writing., Marsha R. Buerger

Electronic Theses and Dissertations

This qualitative research study explores the experiences of six middle school students with science news writing (SciJourn) after they have transitioned to high school. The qualitative method of case study was used with the data analyzed through the method of constructivist grounded theory. SciJourn is a disciplinary approach to science literacy that allows students to choose and research their own topic, interact with experts in the field, construct their own knowledge, and have the opportunity to publish in an on-line science newspaper (Scijourner.org). Theoretically, this research draws on science as social practice where literacy learning is cognitively complex, is situated …

Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel

Electronic Theses and Dissertations

Background: An essential mitochondrial component, Mitochondrial Transcription Factor A (TFAM) is reduced within the failing heart. TFAM maintains regulatory functions of cardiomyocyte physiology and stability. Mitochondrial Transcription Factor A forms a mitochondrial nucleoid anti-oxidant structure and reduces pathophysiological abnormalities to structural and contractile proteins. Overall, this functions to physically stabilize mtDNA. Significant molecular changes such as a loss of TFAM drive pathophysiological concentrations of cytoplasmic Ca2+ and reactive oxygen species. Both of these factors induce proteolytic enzymes to degrade the physiological cardiomyocyte. In TFAMs absence, heart function deteriorates and hypertrophic expansion ensues: thereby changing the physiological myocardium to a pathological …

Circuits For Active Vision : Parallel Tectothalamocortical Visual Pathways In The Mouse., Na Zhou

Electronic Theses and Dissertations

Vision is a critical sensation for the interaction between humans and their surrounding environment. The eyes connect with the brain via retinal ganglion cell axons, which transmit visual sensory information from the periphery into the central nervous system for further processing, eventually leading to visual perception and the visual guidance of movement. Two main targets of retinal axons are the superior colliculus (SC) and the dorsal thalamus. From the SC, visual information is conveyed to the dorsal thalamus, and from the dorsal thalamus visual information is conveyed to the cortex, striatum and amygdala. This dissertation is focused on the functional …

Stretching Adversely Modulates Locomotor Capacity Following Spinal Cord Injury Via Activation Of Nociceptive Afferents., Anastasia V. Keller

Electronic Theses and Dissertations

Spinal cord injury (SCI) is the second leading cause of paralysis in the United States, affecting around 282,000 people with 17,000 new cases each year. Initial and secondary damage to the spinal cord disrupts multiple descending pathways that modulate the function of sympathetic preganglionic neurons and central pattern generating circuitry. Resulting loss of autonomic and locomotor functions, as well as decreased levels of physical activity, lead to a myriad of complications that affect multiple organ systems and significantly reduce both quality of life and life expectancy in individuals with SCI. Spasticity and muscle contractures are two common secondary conditions that …

Novel Insight Into The Liver-Lung Axis In Alcohol-Enhanced Acute Lung Injury., Lauren G. Poole

Electronic Theses and Dissertations

Background. Individuals who chronically abuse alcohol are almost 4 times more likely to develop Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), but the mechanisms by which alcohol abuse sensitizes the lung to injury are poorly understood. However, the lung appears to share many parallel mechanisms of injury with the liver- a primary target of alcohol abuse. The overarching goal of this dissertation was therefore to expand on established mechanisms of alcohol-induced liver injury to ask innovative questions about mechanisms of alcohol-enhanced acute lung injury, as well as to develop new tools that may …

How Muslims Help : An Ethnography Of Muslim Voluntary Assistance For Syrian Refugees In Louisville, Ky., Irene Levy Yates

Electronic Theses and Dissertations

This thesis examines Islamic faith-based organizations’ involvement in Syrian refugee resettlement in Louisville, KY with special attention to the impact of an Islamic Relief USA community engagement grant awarded to Kentucky Refugee Ministries in 2014. A description of local Muslim community support for newly arrived refugees was constructed via participant observation and semi-structured interviews with former and current resettlement agency employees, a diverse set of Muslim community volunteers, and refugees who participate in and/or are supported by Islamic faith-based organizations. Muslim communities in Louisville approach refugee resettlement in ways that are significantly different from both resettlement agency staff and past …

Advances In Tumor-Targeted Therapy Using Nanomedicine., Divya Karukonda

Electronic Theses and Dissertations

Despite continuous improvement and significant progress made in diagnostic and therapeutic approaches for cancer, it is still the leading cause of death worldwide. Although conventional chemotherapy has made significant advances in improving patient survival the indiscriminate destruction of normal cells leads to severe side effects and poor clinical outcomes. Thus, there is a need for effective delivery of drugs to the tumor site avoiding normal tissues to reduce toxicity in the rest of the body. For this reason, a novel multidisciplinary field called Nanotechnology has evolved in recent years and advances in this field have contributed to the development of …

Prevention And Treatment Of Familial Adenomatous Polyposis And Colorectal Cancer By Bilberry-Derived Anthocyanidins., Ashley M. Mudd

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths within the United States. Familial adenomatous polyposis (FAP) is an inherited disorder which if left untreated will develop into colon cancer. The family of plant-derived compounds, anthocyanins, show significant therapeutic potential against a variety of diseases, however, they are limited by their instability and poor bioavailability. The goal of my Master’s research project was to determine whether anthocyanidins (non-glycosylated anthocyanins) are more effective than the native anthocyanins, and whether exosomal formulation of anthocyanidins (ExoAnthos) can enhance therapeutic potency compared with free Anthos against both FAP and CRC. The antiproliferative …

The Mark Of The Devil : Medical Proof In Witchcraft Trials., Sarah Dunn

Electronic Theses and Dissertations

This thesis examines the use of physical evidence to prove the identity of witches in witchcraft trials from approximately 1300 to 1650 in Western Europe. Throughout this period, trial records for accused witches and witchcraft texts include references to Devil marks. According to contemporary texts, these were physical marks on witches, which were visible to the human eye. Doctors and midwives verified these marks upon examination of the accused witch’s body. In this instance, medical proof in the courtroom verified supernatural powers. This thesis will analyze the intersection between medical and religious beliefs in the fourteenth through seventeenth centuries to …

Traces Of The (Un)Familiar : Family, Identity, And The Return Of The Repressed In The Photographs Of Ralph Eugene Meatyard., Hunter Martin Kissel

Electronic Theses and Dissertations

This thesis explores the ways in which photographs by Ralph Eugene Meatyard provoke the uncanny—or Das unheimlich as Freud originally wrote in 1919—by breaking from conventions of mid-twentieth century family photography often utilized to establish and maintain genealogical unity. Meatyard’s photographs of his family and friends are accentuated by blurring techniques, prolonged exposures, and the incorporation of dime-store masks, and as a result depict moments when reality is disrupted by the return of repressed material from childhood. For a multitude of reasons, Meatyard’s photographs elicit comparisons to Surrealist photography as well as certain American modernists who also explored the notion …

The Role Of Hif-1Α In Intestinal Epithelial Barrier Function In Alcoholic Liver Disease., Tuo Shao

Electronic Theses and Dissertations

Hypoxia inducible factor 1 α (HIF1α) is an oxygen-responsive subunit. HIF-1α plays a pivotal role in many pathophysiological processes. In addition to oxygen availability, HIF-1α can be regulated by multiple other factors in response to various pathophysiological processes. Previous studies showed that hepatic HIF-1α could be beneficial or harmful in experimental alcoholic liver disease (ALD). However, the role of intestinal HIF-1α in ALD has not yet been studied. Given the critical role of the gut-liver axis in ALD, it is important to elucidate the role of intestinal epithelial HIF-1α in ALD. In the first chapter, we used wide type (WT) …

Characterization Of Porphyromonas Gingivalis Mfa1 Fimbriae., Jae Yong Lee

Electronic Theses and Dissertations

Porphyromonas gingivalis, an obligate anaerobic bacterium associated with chronic periodontitis, utilizes various virulence factors to achieve pathogenicity, one of which is the Mfa1 fimbriae. As a surface structure comprising Mfa1 major subunit along with accessory fimbrial proteins Mfa2-5, the Mfa1 fimbriae has been shown to mediate the adherence of P. gingivalis to antecedent bacterial colonizers of the oral cavity to cause increased virulence. However, the spatial relationships amongst the individual subunits and their assembly mechanism have remained unclear. Through immuno-electron microscopy, Mfa1-4 were localized on the surface of P. gingivalis with Mfa1 localizing throughout the fimbriae and Mfa2 in …

Gene Expression Of Ammonium Transporters In Ustilago Maydis And Their Role In Pathogenicity And Virulence., Kirsten Richardson

Electronic Theses and Dissertations

The fungus, Ustilago maydis, a plant pathogen of Zea mays, is capable of a dimorphic switch, e.g., a transition between a yeast-like form and a filamentous form. This switch is activated when U. maydis cells are starved for their preferred nitrogen source - ammonium. U. maydis has two important genes that play a role in this switch, ump1 and ump2. Each gene is responsible for the uptake of ammonium and the latter is responsible for the filamentous response in the absence of ammonium. Ump2 deletion mutants are unable to filament in response to low ammonium while ump1 deletion …

Biomechanical Testing Of An Exercise For Strengthening The Proximal Femur., Alyssa Osbourne

Electronic Theses and Dissertations

Based on the principles of cutting edge bone remodeling research, a unique therapeutic exercise device was designed specifically to improve bone quality at the most critical location of the proximal femur prone to fracture: the superior-lateral femoral neck where the fracture first initiates during a fall. The exercise/device is intended to work by inducing enough strain in the bone to stimulate the body’s natural bone remodeling mechanisms to increase bone density in the proximal femur and consequently prevent a fracture from arising if a fall to the side does occur.

In order to test the proposed exercise, experiments simulating the …

Custom Software For The 3d Printing Of Patient Specific Plate Bending Templates In Pelvic Fracture Repair., Gordon B Lents

Electronic Theses and Dissertations

The purpose of this work is to reduce the operative time and blood loss incurred during open reduction and internal fixation (ORIF) of traumatic pelvic injuries through the creation of patient specific bending templates for reconstruction plates. These templates are 3D printed in a resin capable of being sterilized and taken into the operating room so that bending may be performed by the surgeon before the patient is opened or by another team member in parallel with the surgeon.

A novel software extension was created in 3D modeling software to allow a surgeon to individually position screws on a pelvic …

Effects Of Acute Sepsis On Renal Structure And Sympathetic Innervation In Mice, Tuqa Alkhateeb

Electronic Theses and Dissertations

Sympathetic nerves are important for renal physiology and sepsis pathophysiology. A recent study showed sprouting of sympathetic nerves in spleen of septic mice. This study was done to test if renal sprouting of sympathetic nerves also happens and to investigate renal morphology in septic mice. Cecal ligation and puncture (CLP) was used to induce sepsis and kidneys were removed for evaluation. Bowman’s space was diminished with cortical bubble cells present suggestive of acute renal pathology, however, renal function was unchanged. Acute sepsis did not affect either renal sympathetic innervation or non-neuronal cholinergic cells. Mouse kidneys had more epinephrine (EPI) than …

Ecological Informatics: An Agent Based Model On Coexistence Dynamics, Shiva Thapa

Electronic Theses and Dissertations

The coexistence of species is probably one of the most interesting and complex phenomenon in nature. We constructed an agent based model to study the coexistence dynamics of prey - predator populations by varying productivity levels of producers in fragmented and connected habitats along with different levels of quality of predators. Our results indicated that productivity levels of producers in fragmented and connected habitats along with levels of predator quality are significantly responsible for overall predator - prey population size and survivorship. In the absence of predation, competition between identical prey populations is more probable in connected habitats than in …

Mirna Expression Changes In Arsenic-Induced Skin Cancer In Vitro And In Vivo., Laila Al-Eryani

Electronic Theses and Dissertations

Arsenic is a naturally prevalent metalloid. Chronic arsenic ingestion through drinking water causes skin cancer. Arsenic-induced cancer mechanisms are not well defined. Epigenetic changes, including microRNA expression changes, might be playing a role. This dissertation investigates the impact of miRNA expression changes in arsenic-induced skin cancer. MiRNA expression was measure and compared using 3 different techniques, RTq-PCR, hybridization arrays and RNA-sequencing. MiRNAs differential expression in skin lesions was phenotype- and stage-related. Immortalized human keratinocytes (HaCaT) were transformed by chronic low arsenite exposure serving as a model for arsenic-induced skin carcinogenesis. Early changes in miRNAs and target mRNAs contribute to arsenic-induced …

A Novel Method For Synthesis Of Hydroxytyrosol, Emmanuel Onobun

Electronic Theses and Dissertations

Hydroxytyrosol, 3,4-dihydroxyphenolethanol, a naturally occurring polyphenol most common in olive tree (Olea europaea), is one of the most effective member of the polyphenols family, because of its remarkable antioxidant activity, its ability to inhibit oxidation of low density lipids (LDL), and its protection against DNA oxidative damage. Hydroxytyrosol, which is widely used in cosmetics and food supplements industries, can be purchased as an olive oil extract that contains low concentration of hydroxytyrosol besides other polyphenols. The price and low natural abundance of hydroxytyrosol make alternative synthetic sources very attractive. In this research, a novel method for the synthesis of pure …

Matter Under Mind, John F. Lause

Electronic Theses and Dissertations

The artist discusses the work for his Masters of Fine Arts exhibition, Mind under Matter, held at the Tipton Gallery in downtown Johnson City, Tennessee. Exhibition dates are from March 27th through April 5th 2017. ‘Matter under Mind’ explores the balance of control and non-control within the art-making process. This technique creates an automatic dialogue resulting in abstraction guided by the subconscious. The title ‘Matter under Mind’ is a slight play on the phrase ‘mind over matter’ emphasizing how matter/material is manipulated by the mind through the making of artwork, and within the mind’s eye or imagination.

The video installation …

Exploring The Relationship Between Physical Activity And Executive Function In Early Childhood Populations: An Investigation Of Maternal Encouragement Of Activity, Lauren P. Driggers-Jones

Electronic Theses and Dissertations

Researchers have found positive associations between physical activity and executive function in adolescence and adulthood. However, research in early childhood has revealed only negative relationships. In the present study, I explored whether maternal encouragement of physical activity might moderate this relationship in very young children. Using video recordings from an archival dataset, eight maternal encouragement measures were derived from mother-child free play sessions. Although it was expected that maternal encouragement of child activity would broadly play a moderating role in the relationship between children’s physical activity and their executive function, only maternal questions seemed to moderate this relationship. One explanation …

Role Of Tlrs, Hippo-Yap1 Signaling, And Micrornas In Cardiac Repair And Regeneration Of Damaged Myocardium During Ischemic Injury, Xiaohui Wang

Electronic Theses and Dissertations

Cardiovascular disease is a leading cause of death in the United States. Toll-like receptor (TLR)-mediated pathways have been demonstrated to play a role in myocardial ischemia/reperfusion (I/R) injury. We and others have shown that PI3K/Akt signaling is involved in regulating cellular survival and protecting the myocardium from I/R induced injury. In this dissertation, we provide compelling evidence that miR-125b serves to “fine tune” TLR mediated NF-kB responses by repressing TNF-a and TRAF6 expression. We constructed lentiviral expressing miR-125b, delivered it into the myocardium. The data showed that delivery of lentivirus expressing miR-125b significantly reduces myocardial infarct size and improves cardiac …

Enemy Exacerbation: Effects Of Predator Stress On Sulfate Lethality In Freshwater Amphipods (Gammarus Minus), Trevor Chapman

Electronic Theses and Dissertations

Predator cues can influence how aquatic organisms respond to anthropogenic contaminants. This study examined the effects of predator cues on behavior, metabolic rate, and sulfate (as Na₂SO₄) toxicity in amphipods (Gammarus minus). Predator cues included alarm cue (macerated conspecifics) and kairomone from mosquitofish (Gambusia affinis). Amphipods decreased activity and increased time in refuge when exposed to alarm cue, and increased time in refuge when exposed to kairomone. While median lethal concentrations (96-h LC₅₀) were not influenced by predator cues, analysis of dose response curves indicated that kairomone exposure increased amphipod …

Vulnerability Assessment Of Groundwater To No3 Contamination Using Gis, Drastic Model And Geostatistical Analysis, Adela Beauty Adu Agyemang

Electronic Theses and Dissertations

The study employed Geographical Information System (GIS) technology to investigate the vulnerability of groundwater to NO₃ content in Buncombe County, North Carolina in two different approaches. In the first study, the spatial distribution of NO₃ contamination was analyzed in a GIS environment using Kriging Interpolation. Cokriging interpolation was used to establish how NO₃ relates to land cover types and depth to water table of wells in the county. The second study used DRASTIC model to assess the vulnerability of groundwater in Buncombe County to NO₃ contamination. To get an accurate vulnerability index, the DRASTIC parameters were …