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The Role Of Inter-Enlargement Propriospinal Neurons In Locomotion Following Spinal Cord Injury., Courtney Therese Shepard

Electronic Theses and Dissertations

The focus of this dissertation is to explore the functional role of two anatomically-defined pathways in the adult rat spinal cord before and after spinal cord injury (SCI). To do this, a Tet^On dual virus system was used to selectively and reversibly silence neurons with cell bodies at spinal segment L2 and projections to spinal segment C6 (long ascending propriospinal neurons, LAPNs) and neurons that originate in the C6 spinal segment and terminate at L2 spinal segment (long descending propriospinal neurons, LDPNs). This dissertation is divided into five chapters. Chapter One provides background information regarding spinal cord injury, locomotion, …

Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch

Electronic Theses and Dissertations

Cardiovascular disease (CVD) is the leading cause of death worldwide. Tobacco smoke is the most significant modifiable risk factor in CVD development and contains numerous toxic compounds, including aldehydes, which have been linked to CVD. Formaldehyde, acetaldehyde, acrolein, and crotonaldehyde have been identified as significant contributors to cigarette-induced health effects, but the mechanism of these effects is not well understood. These aldehydes are also found in aerosols produced by e-cigarettes (e-cigs). The goal of this dissertation was to explore the systemic, hematological, and endothelium-related effects of exposure to tobacco products and constituent aldehydes and to identify potential mechanisms of injury. …

Development Of Rationally Designed Live Attenuated Vaccines For Lassa Fever And Venezuelan Equine Encephalitis., Dylan Macgregor Johnson

Electronic Theses and Dissertations

Lassa Virus (LASV) and Venezuelan Equine Encephalitis Virus (VEEV) are two single stranded RNA viruses belonging to the Arenavirus and Alphavirus families, respectively. Both are emerging pathogens without approved vaccines or treatments. VEEV is an important biothreat pathogen because it has been weaponized and is extremely infectious as an aerosol. VEEV causes biphasic febrile illness that can progress to a viral encephalitis with low mortality, but high morbidity. LASV causes a viral hemorrhagic fever, Lassa Fever (LF), which is endemic in West Africa, and responsible for between 100-500k annual infections with a 1-2% overall mortality rate. ML29 and VEEV TC-83 …

Mechanistic Insight Of The Role Of Nherf1 In Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle

Electronic Theses and Dissertations

Background. Acute kidney injury (AKI) develops in 30% of patients who receive cisplatin, a widely used chemotherapeutic agent. We previously showed that NHERF1 loss resulted in increased susceptibility to cisplatin nephrotoxicity. The overarching goal of this dissertation was to elucidate mechanisms of susceptibility to cisplatin-induced AKI, specifically the effects of NHERF1 loss on tubule cell metabolism, tubule cell mitochondrial function, and alterations in oxidative state and/or renal handling of cisplatin. Methods. 2-4 month male wild type (WT) and NHERF1 knock out (KO) mice were treated with either vehicle control or cisplatin (20 mg/kg dose IP) for 4, 24, and 72 …

The Retinoblastoma Protein Mediates Metabolic Reprogramming In Lung Cancer., Lindsey R. Conroy

Electronic Theses and Dissertations

Lung cancer is among the most frequently diagnosed cancers and is the leading cause of cancer-related deaths worldwide. One of the hallmark events in lung cancer pathogenesis is deregulation of the cell cycle. The retinoblastoma protein (pRb) is a tumor suppressor that is deleted, mutated, or inactivated in most lung cancer cases. Canonically, pRb functions to regulate cell cycle progression by repressing the transcriptional activity of the E2F family of transcription factors, inhibiting S phase entry. Although the cell cycle functions of pRb have been well established, recent studies have highlighted a functional role for pRb in controlling cellular metabolism. …

Examining Corporate Blameworthiness In Relation To Federal Organizational Sentencing For Probation And Corporate Monitors., Emily M. Homer

Electronic Theses and Dissertations

Organizations that have benefitted from the commission of federal crimes committed by their employees may be sentenced to federal criminal penalties. Two of these potential penalties include probation and the requirement to implement a corporate monitor. The federal guidelines provide suggestions for sentencing probation that echo the theoretical focal concern of blameworthiness. This research used eight years of United States Sentencing Commission data covering 2011 to 2018 (n= 1,224) to examine if organizations were being sentenced to probation and monitoring consistent with the federal guidelines and focal concern of blameworthiness. The study examined nine potential measures of blameworthiness …

Black Middle-Class Neighborhoods In Louisville Through Multiple Lenses., Jamar M. Wheeler

Electronic Theses and Dissertations

This dissertation is an articles-based, mixed methods study that analyzes Black middle-class neighborhood attainment in Louisville. Racialized social structure theory is the theoretical framework that is employed to make sense of the adverse positionality of Black middle-class neighborhoods. Racialized social structure theory posits that individuals are placed in racial categories that are hierarchically arranged, which, at the neighborhood level, translates to White and Black householders advancing their material interests in competing ways. These competing interests are asymmetrical in terms of power relations, which means that the neighborhood choices of the Black middle-class are constrained by the routinized ways that the …

Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li

Electronic Theses and Dissertations

Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …

Hotel De Vagabundos: Reviewing African American Theatre Journey., Manuel Francisco Viveros

Electronic Theses and Dissertations

This analysis examines how Hotel de Vagabundos, a play written by a black playwright from Colombia, fits into the core of definitions of Black Theatre in the United States. I will examine six documents I consider relevant to shape the idea of Black Theatre in the US from 1900 through 2005. The author's experience in New York during the 1940s inspires Hotel de Vagabundos. The author navigates the globalized ethos idea unleashing clashes about identity to criticize aspects of American culture about immigrants, poor people, and internalized racism within African American and Black diasporic communities. The play “like a …

Modulation Of Host Innate Immune Cells By Yersinia Pestis To Create A Permissive Environment For Replication., Amanda Rose Pulsifer

Electronic Theses and Dissertations

Yersinia pestis has gained widespread infamy due to the historic outbreak during the middle ages, referred to as The Black Death. Infection with Y. pestis typically begins with deposition of Y. pestis into the dermis (bubonic plague) or respiratory tract (pneumonic plague). Tissue resident macrophages are the first innate immune cell encountered by Y. pestis. Macrophages are likely a way for Y. pestis to avoid neutrophils early in infection when the neutrophil neutralizing Type Three Secretion System is not expressed. This work focuses on which Rab host proteins are manipulated by Y. pestis, and how neutrophils are forced to …

Tobacco Smoke Exposures And Fertility-Related Outcomes Among Females Seeking Fertility Care, And The Interaction With N-Acetyltransferase 2 (Nat2).., T'Shura S. A. Ali

Electronic Theses and Dissertations

Cigarette smoke contains thousands of harmful substances and is one of the leading preventable causes of mortality and morbidity in the United States. Past studies examining tobacco smoke exposures on fecundability and pregnancy outcomes are inconsistent. NAT2 is an important enzyme in the metabolism of xenobiotic substances found within tobacco smoke. This preconception cohort study examines associations between active smoking and secondhand smoke exposure (SHSe) on fecundability and spontaneous abortion (SA), and explores a possible interaction with NAT2 acetylator status. A total of 223 women seeking fertility care were followed for up to 2.3 years. Preconception tobacco smoke exposures were …

Evaluation Of Metal Concentration In Water And Soil In The Southern Region Of Lake Nacogdoches, Olawunmi Taiwo

Electronic Theses and Dissertations

The concentrations of metals (Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sr, V, Zn) were investigated in soil and water samples collected over four different sites in the southern part of Lake Nacogdoches over one year from August 2018 through June 2019. Water samples were analyzed using the USEPA method 200.8 part 11.2 for total recoverable metals. Soil samples were analyzed using the USEPA method 3050B for total recoverable metals. Although the total concentration gives some indication of the level of contamination, it is not enough to give information on the bioavailability or mobility of the element. A modified …

Quality Of Life Of Adults Who Have Attempted Suicide, Karen Hoefer

Electronic Theses and Dissertations

This study focuses on the quality of life of suicide attempt survivors and the trajectories of their lives after their last attempt in the past two to ten years. Employing both a quantitative and qualitative approach but focusing largely on the qualitative data, I collected demographic data, gathered responses on an abbreviated Reasons for Living Inventory, and conducted open-ended phone interviews with 26 participants. The primary life course finding is that participants’ suicide attempts are often built on years of dealing with mental illness. The analysis also dispels many stereotypes associated with people who have attempted suicide. I explore patterns …

An Investigation Of Anxiety- And Depression-Like Behavior After Head Trauma In Mice, Sean K. Payne

Electronic Theses and Dissertations

Every year around 2 million people in the United States (US) suffer a traumatic brain injury. Those people are often at a higher risk of post-TBI psychiatric illness, like anxiety and depression. Animal models of TBI are a useful way to measure such psychiatric illnesses in a pre-clinical setting. There were two purposes of this study: the first being to test the modified Marmarou TBI model, and second to investigate anxiety- and depression-like symptoms in C57Bl6/J mice following a TBI. The modified Marmarou model used different weights (95g, 30g, & sham) to see how severity affected the manifestation of anxiety-like …

A Novel Mathematical Model Of The Trojan Y-Chromosome Strategy With Optimal Control, Christopher Turner

Electronic Theses and Dissertations

Invasive species are a prevalent problem all over the world. Controlling and eradicating an invasive species is an even more diffcult problem. The Trojan Y Chromosome (TYC) eradication strategy is one control method. This method alters the female to male sex ratio by introducing sex reversed males called supermales. These sex reversed males can only produce male progeny. Mathematical models of this strategy have shown that a population can be driven to extinction with a continuous supply of these sex reversed males. There are many different mathematical models of this strategy, but most have serious flaws, such as negative solutions …

Depressive Symptoms And Survival Among Lung Cancer Patients: Biomarkers And Potential Benefits Of An Ipod- And Mindfulness-Based Intervention., Chelsea J. Siwik

Electronic Theses and Dissertations

Lung cancer patients experience high levels of distress, which commonly manifests as depressive symptoms. Importantly, depressive symptoms have demonstrated prognostic significance in cancer contexts, although the biological pathways by which depressive symptoms lead to poorer survival remain unclear and warrant greater attention. In addition to understanding the biological pathways by which depressive symptoms accelerate disease, identification of efficacious and effective psychological treatments for depressive symptoms are needed to improve both quality and quantity of life for cancer patients. Interventions that reduce depressive symptoms and improve downstream clinical outcomes are certainty needed; however, because many cancer patients face considerable burden, interventions …

Medusa For Three Sopranos And Chamber Orchestra., Joshua Baerwald

Electronic Theses and Dissertations

Many people know the story of Medusa as she relates to Hercules' adventures. Most think of her as the monster who turns anyone who looks into her eyes into stone. Few people know, however, why Medusa was that way. One of the first written versions of Medusa's story comes from Ovid's Metamorphoses, written in 8 AD. Ovid says that Medusa's beauty invited jealous aspirations from many suitors. One of those suitors was Poseidon, God of the Sea. As was often the case in Greek myth, Poseidon did whatever it would take to have Medusa, and raped her in Athena's Temple. …

Tobacco Enhances Bacterial-Induced Periodontal Bone Loss In Mice., Mina Iskander

Electronic Theses and Dissertations

Background: Tobacco smoking is the leading environmental risk factor for periodontal diseases. Delineation of the mechanisms underlying tobacco-induced or exacerbated periodontitis is hampered by the lack of an appropriate and reliable animal model. Hypothesis: We hypothesized that Porphyromonas-gingivalis-infected, cigarette smoke-exposed mice would represent reproducible models of acute (ligature model) and chronic (oral gavage model) tobacco-enhanced periodontitis that reflect multiple aspects of the disease noted in human smokers. Methods: In a chronic oral gavage disease model, Balb/c mice (6-8 weeks, 4 groups of n = 6 per group) were exposed to smoke produced by a Teague-10 smoking machine from 1R6F research …

Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle

Electronic Theses and Dissertations

BACKGROUND: The relative importance of environmental exposures such as volatile organic compounds (VOCs) is one of the paramount public health priorities of our time, yet is presently unstudied. VOCs are ubiquitous in the environment and have been associated with numerous adverse health effects, including a number of cardiovascular and metabolic effects that are components of Cardiometabolic Syndrome (CMS). OBJECTIVES: To examine the relationship between CMS and individual-level exposures to VOCs, measured as urinary metabolites of VOCs (UM-VOCs), in a nationally representative sample. METHODS: Associations between urinary biomarkers of exposure to 19 parent VOCs and CMS were assessed using the National …

Transient Display Of Chimeric Proteins On Biological Surfaces As An Effective Strategy For Modulations Of Innate And Adaptive Immune Responses., Pradeep Shrestha

Electronic Theses and Dissertations

The major premise of this dissertation was to transiently display novel immunological ligands on biological membranes as a localized means of modulating innate and adaptive immune responses with applications to bone marrow and pancreatic islet transplantation. In Chapter two, we engineered donor allogeneic bone marrow cells to transiently display a novel form of FasL, SA-FasL, to efficiently purge out alloreactive donor T cells to prevent acute GVHD. In Chapter three, we engineered pancreatic islets with a novel form of CD47, SA-CD47, to modulate instant blood mediated inflammatory reaction (IBMIR) to prevent immediate islet graft loss following intraportal transplantation. GVHD is …

Sulforaphane Protects Against Ethanol-Induced Apoptosis And Teratogenesis Through Epigenetic Modulation Of Anti-Apoptotic Genes., Yihong Li

Electronic Theses and Dissertations

Background. Ethanol-induced excessive apoptosis in neural crest cells (NCCs), a multipotent progenitor cell population, is one of the major mechanisms underlying the pathogenesis of Fetal Alcohol Spectrum Disorders (FASD). However, the molecular mechanisms underlying FASD that results from maternal alcohol exposure during pregnancy are poorly understood. The overall goals of this study are to examine the mechanisms by which ethanol induces apoptosis and malformations in vitro and in vivo, and to develop a nutritional-based approach by using SFN and SFN-rich BSE to prevent FASD through epigenetic modulation. Results. This study demonstrates that ethanol exposure resulted in a significant increase …

Anxiety And How To Control It: The Functional Role Of The Bed Nucleus Of The Stria Terminalis., Lindsay K. Knight

Electronic Theses and Dissertations

Anxiety disorders afflict up to one third of the population. Research to date has primarily focused on the amygdala, however, new perspectives suggest that a tiny basal forebrain region known as the bed nucleus of the stria terminalis (BNST) may hold key insights into understanding and treating anxiety disorders. Therefore, my first aim was to empirically investigate the importance and influence of the BNST in anxiety processing. Using fearful faces and human screams as aversive stimuli, two threat conditions were created: one in which threats were certain and predictable (fear) and another in which threats were uncertain and unpredictable (anxiety). …

Invocation., Shae Taylor Goodlett

Electronic Theses and Dissertations

The research of this thesis is concerned with the investigation of various approaches to religious theory; specifically, the observable analysis of performed ritualistic procedures and their theoretical anticipated effects. Through the examination of the illusory characteristics of the interaction of color and light I am able to draw analogous correlations between art making and ritualistic action. By enacting optical illusion as metaphor for ritual presence, I compare rational and empirical methods of observation. This analysis examines the discrepancy of physical fact and physic effect in that illusion employs physically observable means to render an intangible (non-material) physic effect. Such observances …

Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson

Electronic Theses and Dissertations

Cigarette smoking is the single largest risk factor for cardiovascular disease (CVD) pathophysiology. Numerous researchers have shown potential associations between aldehydes in tobacco-derived aerosols from mainstream cigarette smoke (MCS) or electronic cigarettes (e-cigs) and their cardiotoxicity by damaging blood vessel endothelium. The severity of exposure to these toxicants can furthermore lead to adverse cardiovascular outcomes such as myocardial infarctions, stroke, coronary and peripheral artery disease, or atherosclerosis due to blood clots, a pro-thrombotic event. However, the mechanisms by which levels of harmful and potentially harmful constituents (HPHCs) such as aldehydes induce thrombosis are not well-known. Of specific interest, evidence has …

The Role Of Slc7a11 In Controlling Extracellular And Intracellular Redox Environments Of Lung Fibroblasts - Potential Targets For Intervention In Aging And Idiopathic Pulmonary Fibrosis., Yuxuan Zheng

Electronic Theses and Dissertations

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by extracellular matrix deposition by fibroblasts. Aging and oxidative stress increase the susceptibility to IPF. Redox couples, cysteine/cystine (Cys/CySS) and glutathione/glutathione disulfide (GSH/GSSG), and their redox potentials (E_h) quantify oxidative stress. Fibroblasts from old mice maintain more oxidized extracellular E_h(Cys/CySS) than young mice. Microarray shows down-regulation of Slc7a11 potentially mediates this age-related oxidation. Slc7a11 is the key component of system X_c^-, an antiporter that imports CySS and exports glutamate. The first aim of this dissertation is to investigate the mechanistic link between Slc7a11 …

The Cardiovascular Effects Of Tobacco Product-Derived Aldehydes: Contribution Of Transient Receptor Potential Ankyrin-1., Lexiao Jin

Electronic Theses and Dissertations

Cardiovascular diseases (CVD) are the leading cause of death in most countries and are significant health and financial burden worldwide. Smoking contributes to more than 480,000 premature deaths annually -- accounting for one of every five deaths in the United States each year. Numerous studies have shown that smoking increases the risk of factors including endothelial dysfunction, thrombosis, and atherosclerosis, which may lead to an incidence of myocardial infarction, coronary artery disease, and stroke. Electronic cigarettes (e-cigarettes) are a new kind of tobacco product, and some studies show that e-cigarettes also could induce CVD since both e-cigarettes and conventional tobacco …

Exosomes From Embryonic Stem Cells As A Prophylactic Vaccine Against Lung Cancer., Shuhan Meng

Electronic Theses and Dissertations

The antigenic similarity between embryos and tumors has raised the idea of using embryonic materials as a preventative vaccine against neoplastic disease. Indeed, a previous study reported that a vaccine comprised of allogeneic murine embryonic stem cells (ESCs) and murine fibroblasts expressing immune-stimulatory granulocyte macrophage-colony stimulating factor (GM-CSF) successfully blocked the outgrowth of an implantable lung cancer (Lewis lung carcinoma; LLC) and lung tumors caused by a combination of a mutagen followed by chronic pulmonary inflammation. However, such a vaccine is obviously impractical for application to humans. The use of fibroblasts to produce GM-CSF is needlessly complicated, and intact live …

Development Of In Vitro Models To Study The Rapid Extraintestinal Dissemination Of Salmonella., Adarsh Gopinath

Electronic Theses and Dissertations

Salmonella appears in the bloodstream of mice in as little as 15 minutes after oral inoculation and establishes persistent colonies in the spleen and liver. While its pathway to blood is undetermined, this phenomenon is dependent on the activity of Salmonella pathogenicity island 2 (SPI-2) coded type III secretion system (T3SS) and CD18+ phagocytes. We hypothesize that dendritic cells associated with the basal face of the gut epithelium, that are naturally migratory and known to sample for luminal antigens directly transport Salmonella to the bloodstream. This process comprises of at least two phases, dissociation and reverse transmigration. We define dissociation …

Evaluation Of Tracing Techniques In The Rat Spinal Cord Using A Custom Matlab Application., Rachel M. Zalla

Electronic Theses and Dissertations

The objective of this research project is to evaluate the efficiency of traditional chemical tracing compared to dual-viral tracing for labeling long ascending propriospinal neurons (LAPNs) in the uninjured rat spinal cord, and to develop a MATLAB program which will accurately quantify this labeling.

To evaluate chemical tracing, Fluoro-Ruby (FR) was injected at the level of the axon terminals, and the number of ipsilateral labeled cell bodies at lumbar level was quantified. Similarly, two dual-viral systems were evaluated, by either injecting retro-AAV-Cre or HiRet-Lenti-Cre unilaterally in combination with a Cre-dependent adeno-associated virus. The HiRet-Lenti and FR groups labeled significantly greater …

Neonatal Abstinence Syndrome And The Relationship Between Respiration And Feeding, Paul Rice

Electronic Theses and Dissertations

Objective: The primary purpose of this study was to determine the relationship between respiratory status and feeding difficulties in infants with NAS in comparison to full-term infants with no exposure to opioids.

Methods: A group of infants with NAS (262) were compared to a group of full-term infants with no exposure to opioids (279). These groups were further divided into feeding and respiratory groups based on severity. These groups were analyzed for differences in behavior and outcomes.

Results: Infants with NAS are 34.23 times more likely to develop respiratory distress and 111.03 times more likely to develop severe feeding difficulty. …