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Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi Dec 2023

Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi

Electronic Theses and Dissertations

Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation …


Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson Dec 2023

Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson

Electronic Theses and Dissertations

Alcohol-associated liver disease (ALD) is a broad spectrum of diseases ranging from steatosis to severe hepatic cirrhosis, none of which have any FDA approved therapies. Downregulation of hepatic Sirtuin 1 (Sirt1) activity by ethanol has been shown to lead to an upregulation of the pro-lipogenic gene targets under its jurisdiction, resulting in increased lipogenesis and triglyceride accumulation. It was hypothesized that ethanol acts on α4*-nicotinic acetylcholine receptors (α4*-nAChRs) in hepatocytes to decrease Sirt1 expression, which ultimately dysregulates lipid metabolic homeostasis. Ethanol’s effects were investigated in cultured AML12 hepatocytes and in WT primary mouse hepatocytes acutely exposed to ethanol. Consistent with …


Clinical And Environmental Factors Affecting The Survival Outcomes Among Stage 1a Tn0m0 First Primary Non-Small Cell Lung Carcinoma Patients In The United States., Naiya Patel Aug 2023

Clinical And Environmental Factors Affecting The Survival Outcomes Among Stage 1a Tn0m0 First Primary Non-Small Cell Lung Carcinoma Patients In The United States., Naiya Patel

Electronic Theses and Dissertations

Background: Lung cancer is the second leading cause of death in the United States (U.S.). The most prevalent histological type of lung cancer is Non-Small Cell Lung Cancer (NSCLC), which has an overall five years survival of 5% if left untreated. Therefore, early treatment of NSCLC is vital to improve overall survival (OS) outcomes. Several factors affect survival outcomes, which can be categorized as modifiable or non-modifiable. The difference in timely receipt of guideline-concordant treatment affects the survival outcomes of patients with stage 1A NSCLC. This dissertation explored factors that affect treatment and survival outcomes among stage 1A NSCLC patients …


Aurka Inhibition-Based Combination Therapy Approaches In Glioblastoma., Muge Sak Aug 2023

Aurka Inhibition-Based Combination Therapy Approaches In Glioblastoma., Muge Sak

Electronic Theses and Dissertations

Glioblastoma is the most common and aggressive central nervous system tumor in adults with a 6% survival rate. Decades of research for improving life expectancy and quality of life have been ineffective. The discovery of better treatment strategies is urgent to improve the survival rates for glioblastoma patients. Aurora Kinase A is a regulator of tumor progression and is overexpressed in glioblastoma. We used a specific Aurora Kinase A inhibitor alisertib in combination with DNA-damaging platinum agent carboplatin or brain-penetrating taxane TPI 287. We investigated the efficacy of these combinations in treating in vitro and in vivo tissue culture models …


The Impact Of Volatile Organic Compound Exposure On Subclinical Biomarkers Of Cardiovascular Injury., Breandon Taylor Dec 2022

The Impact Of Volatile Organic Compound Exposure On Subclinical Biomarkers Of Cardiovascular Injury., Breandon Taylor

Electronic Theses and Dissertations

Pollution has been identified as the leading environmental cause of non-communicable disease and premature deaths globally. Volatile organic compounds (VOCs) are gaseous chemical constituents of pollution derived from a variety of sources, including industrial solvents and byproducts, automobile exhaust, tobacco smoke, cleaning supplies, and personal care products. VOCs are also abundant at various Superfund and Hazardous Waste Sites. Emerging data suggest that VOC exposure is associated with several adverse health outcomes, including cardiovascular disease (CVD). VOCs and their metabolites can potentially damage the endothelial lining of blood vessels, resulting in perturbed vascular function and vascular inflammation. We hypothesize that VOC …


Defining The Impact Of Clinically Modeled Hindlimb Stretching, Exercise, & Inactivity On Functional Recovery After Spinal Cord Injury., Greta Cesarz Dec 2022

Defining The Impact Of Clinically Modeled Hindlimb Stretching, Exercise, & Inactivity On Functional Recovery After Spinal Cord Injury., Greta Cesarz

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life altering event that affects approximately 282,000 Americans. The most obvious side effect of SCI is paralysis due to damage to the spinal cord that disrupts ascending and descending pathways as well as central pattern generating circuitry. In addition to paralysis, patients suffer from other debilitating side effects including altered cardiovascular function, autonomic dysreflexia, neuropathic pain, spasticity, and contractures. In contrast to humans, rodents display spontaneous locomotor recovery following incomplete SCI due to in-cage activity/training. Previously, our laboratory has studied the effect of lack of in-cage training by utilizing custom designed rodent wheelchairs. …


Stromal Vascular Fraction Restores Vasodilatory Function By Reversing Mitochondrial Dysfunction And Oxidative Stress In Aging-Induced Coronary Microvascular Disease., Evan Paul Tracy Aug 2022

Stromal Vascular Fraction Restores Vasodilatory Function By Reversing Mitochondrial Dysfunction And Oxidative Stress In Aging-Induced Coronary Microvascular Disease., Evan Paul Tracy

Electronic Theses and Dissertations

Background: Coronary Microvascular Disease (CMD) presents in aging post-menopausal women with chronic angina due to microvascular hyperconstriction. The objective was to identify mechanisms of adipose stromal vascular fraction’s (SVF) restorative effects on vasodilation. We hypothesize aging-induced CMD is caused by a) abrogated flow-mediated dilation (FMD) due to loss of nitric oxide signaling and b) ROS-dependent βADR desensitization & internalization, reversible by ameliorating mitochondrial dysfunction and oxidative stress with SVF. Methods: Coronary microvessels were isolated from female rats either young, old, or old with SVF tail-vein injection (OSVF). Pressure myography, RNA-sequencing, immunofluorescence, Western blotting, and morphological analysis were performed to …


Porphyromonas Gingivalis, Ethanol, And Chronic Diseases., Nicholas Alan Short May 2022

Porphyromonas Gingivalis, Ethanol, And Chronic Diseases., Nicholas Alan Short

Electronic Theses and Dissertations

This dissertation is an investigation into the relationships among Porphyromonas gingivalis, ethanol, and a series of chronic diseases, focusing primarily on atherosclerosis. It uses evolutionary theory to understand clinical parameters related to chronic disease biology. The initial research question was, "If people who drink a glass of wine each day have a lower risk for atherosclerosis, could one explanation involve antibacterial effects on pathogens associated with causing atherosclerosis, namely, Porphyromonas gingivalis?". This dissertation is divided into four chapters. Chapter One provides the foundational information pertinent to the dissertation. Chapter Two describes an in- vitro experiment aimed at understanding …


Protest-Related Tear Gas Exposure And Menstrual Function, Emily Kathleen (Steinmetz) Reece May 2022

Protest-Related Tear Gas Exposure And Menstrual Function, Emily Kathleen (Steinmetz) Reece

Electronic Theses and Dissertations

During the racial justice protests of 2020 and 2021, crowd control chemical irritants (referred to as “tear gas”) were deployed against protesters, after which there were anecdotal reports of altered menstrual cycles among exposed individuals. There is only one peer reviewed published study on tear gas exposure and menstrual health. This study examined whether tear gas exposure was associated with menstrual cycle outcomes among women attending the 2020-2021 protests. Data from 103 women who attended racial justice protests in 2020 and 2021 were collected through an online questionnaire. Data included protest attendance, acute symptoms of tear gas exposure, whether medical …


Spectroscopic Measurements Of Meibum Compositional, Structural, And Functional Relationships To Elucidate The Role Of Meibum In Dry Eye., Anthony Chigozie Ewurum May 2022

Spectroscopic Measurements Of Meibum Compositional, Structural, And Functional Relationships To Elucidate The Role Of Meibum In Dry Eye., Anthony Chigozie Ewurum

Electronic Theses and Dissertations

The major aim of my dissertation was to investigate the etiology of dry eye disease which affects about 7 million people in the United States, causing symptoms that can lead to visual disturbance. Correlation between dry eye and an abnormal lipid layer of the tear film has been found. Tear film lipids originate mostly from the meibomian glands. Cholesteryl ester (CE) and Wax ester (WE) lipids make up most of the human meibum lipidome and the CE/WE ratio has been shown to decrease in patients with meibomian gland dysfunction. Model studies using synthetic CE and WE, although providing some insight, …


The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen May 2022

The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen

Electronic Theses and Dissertations

Early-onset colon cancer (EOCC) is a leading cause of cancer death among people younger than 50 years of age in the United States and is associated with metabolic dysfunction and obesity. Anti-inflammatory tumor-associated macrophages (TAM) and low Peroxisome Proliferator Activated Receptor Gamma (PPARγ) gene expression in colon cancer (CC) tissue promote tumor progression and decreased patient survival. Obesity-related hormones, such as leptin and adiponectin, have the potential to affect gene expression in TAM to promote CC progression and thereby link obesity and EOCC. The aim of this project was to identify target genes in human CC and to investigate the …


Adipose-Derived Stromal Vascular Fraction Therapy Improves Age-Related Adrenergic Mediated Microvascular Dysfunction And Increases Revascularization Potential Following Injury., Gabrielle Brown May 2022

Adipose-Derived Stromal Vascular Fraction Therapy Improves Age-Related Adrenergic Mediated Microvascular Dysfunction And Increases Revascularization Potential Following Injury., Gabrielle Brown

Electronic Theses and Dissertations

The role of the microcirculation is to balance blood flow and oxygen delivery to meet local metabolic and oxygen demands. With advancing age, the health of the endothelium declines leading to improper augmentation of the microcirculation; decreasing vasoreactivity and angiogenic potential which can further increase the risk of ischemia. The multiple contributing factors that drive the decline in endothelial health with age make traditional pharmacological interventions challenging whereas cell-based therapies can exert multifactorial gains. Adipose-derived stromal vascular fraction (SVF) is an emerging therapeutic for its easily accessible, autologous, anti-inflammatory, and angiogenic properties. It is a heterogenous population comprised of leukocyte …


Etracellular Vesicles From Lactobacillus Rhamnosus Gg Protect Against Alcohol-Induced Liver Injury Through Suppression Of Intestinal Mir 194 And Subsequent Activation Of Fxr In Mice., Mengwei Jiang May 2022

Etracellular Vesicles From Lactobacillus Rhamnosus Gg Protect Against Alcohol-Induced Liver Injury Through Suppression Of Intestinal Mir 194 And Subsequent Activation Of Fxr In Mice., Mengwei Jiang

Electronic Theses and Dissertations

Numerous studies have reported the efficacy of probiotics for alcohol-associated liver disease (ALD). These studies indicate a strong interest among the scientific and medical communities in identifying alternative or adjunctive approaches for ALD, for which there is no effective or widely accepted therapeutic option. However, in-depth molecular knowledge on how probiotics render their effects is lacking. Patients with ALD often have increased hepatic bile acids (BAs), which can be toxic and are an important causative factor in liver injury and hepatocyte death. BAs are released into the intestines and serve not only as a “detergent” to promote fat absorption, but …


Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan May 2022

Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan

Electronic Theses and Dissertations

Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction …


Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam Dec 2021

Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam

Electronic Theses and Dissertations

Recent studies have associated elevated protein acetylation levels with heart failure in humans. Although mechanisms promoting elevated acetylation levels are not fully known, excess acetyl-CoA may drive enzyme-independent acetylation of cardiac proteins. Accumulation of acetyl-CoA depends on the availability of sufficient CoA, whose production is regulated by pantothenate kinases in the CoA biosynthetic pathway. We show that cardiac proteins are hyperacetylated during heart failure in humans and tested in mice whether limiting CoA abundance would improve ventricular remodeling during pressure overload-induced hypertrophy. We limited cardiac CoA levels by deleting the rate-limiting enzyme in CoA biosynthesis, Pank1 (one of three PANK-encoding …


Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge Dec 2021

Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge

Electronic Theses and Dissertations

It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …


Genetic And Functional Analysis Of Rat Mammary Cancer Susceptibility., Emily L Duderstadt May 2021

Genetic And Functional Analysis Of Rat Mammary Cancer Susceptibility., Emily L Duderstadt

Electronic Theses and Dissertations

Breast cancer genetic susceptibility is modulated by high to low penetrance risk alleles. Population frequencies of high and moderate penetrant predisposing mutations are rare and responsible for a small percentage of population cases. Most genetic variation in breast cancer susceptibility is low penetrance common variants where causal genes and risk-associated mechanisms are largely unknown. Comparative genetics uses animal models to isolate and mechanistically evaluate genetic susceptibility to human disease. Rat strains have different susceptibility phenotypes to chemical-induced carcinogenesis. Selective breeding and genetic linkage analysis using a 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis model have identified Mammary carcinoma susceptibilityquantitative trait loci …


Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller May 2021

Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller

Electronic Theses and Dissertations

Despite the success of immunotherapy in many types of cancer, pancreatic adenocarcinoma (PDAC) has yet to benefit. Innate immune cells are critical to antitumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Though trained innate immunity has mostly been investigated in the context of infection, the induction of trained innate immunity could also protect against tumors, and specifically pancreatic tumors. Here, we demonstrate that yeast-derived particulate β-glucan, a known inducer of trained immunity, traffics to the pancreas following IP administration. This causes …


Pde4 Inhibition: A Novel Therapeutic Strategy In Liver Fibrosis., Mohamed Elnagdy May 2021

Pde4 Inhibition: A Novel Therapeutic Strategy In Liver Fibrosis., Mohamed Elnagdy

Electronic Theses and Dissertations

Background: Liver fibrosis is accumulation of extracellular matrix (ECM) proteins due to chronic liver injury. Chronic hepatic damage can occur due to multiple causes including, alcohol, non-alcoholic steatohepatitis and chronic viral hepatitis. Liver fibrosis is a critical problem worldwide due to the extremely high incidence of alcohol associated liver damage and chronic viral hepatitis. Moreover, there is no FDA approved therapy for liver fibrosis. Activation and transdifferentiation of quiecent hepatic stellate cells (HSCs) to myofibroblasts (MFBs) is the main event contributing to liver fibrosis. This process involves two phases, the initiation and the perpetuation phases. Hepatocyte injury and inflammatory response …


Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar) Dec 2020

Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)

Electronic Theses and Dissertations

The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …


Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding Aug 2020

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …


Modulation Of Inflammatory Pathway By Inflammatory Inhibitor Jsh-23 Mitigates Diabetic Retinopathy., Rubens Petit Homme Aug 2020

Modulation Of Inflammatory Pathway By Inflammatory Inhibitor Jsh-23 Mitigates Diabetic Retinopathy., Rubens Petit Homme

Electronic Theses and Dissertations

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). Its pathology is consisted of the breakdown of the blood-retinal barrier (BRB), particularly the inner blood-retinal barrier (iBRB). The exact mechanism that leads to the iBRB impairment and the development of DR has not been elucidated yet. However, chronic inflammation that is hallmark of the type I DM has recently become a key focus in DR study. Hyperglycemia causes dysregulation of nuclear factor-kappa B (NF-kB); and its constant activation increases the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular adhesion molecule-1 (ICAM-1) in the …


Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle May 2020

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 …


Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch May 2020

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. …


Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li May 2020

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 …


The Emerging Oral Pathogen, Filifactor Alocis, Disrupts Neutrophil Functions To Enhance Survival And Dysregulate Inflammation., Irina Miralda Molina May 2020

The Emerging Oral Pathogen, Filifactor Alocis, Disrupts Neutrophil Functions To Enhance Survival And Dysregulate Inflammation., Irina Miralda Molina

Electronic Theses and Dissertations

Periodontitis is an irreversible, chronic inflammatory disease where pathogenic microbial communities accumulate in the gingival crevice. Advances in culture-independent techniques have facilitated the identification of new bacterial species in periodontal lesions, such as the Gram-positive anaerobe, Filifactor alocis. Neutrophils are a major component of the innate host response, and the outcome of their interaction with F. alocis may be a determinant of oral health status. While neutrophil functions typically protect the host against periodontal disease, oral pathogens have adapted to evade or disarm neutrophil microbicidal functions while promoting mechanisms that drive inflammation, which also provides a source of nutrients …


Development Of Rationally Designed Live Attenuated Vaccines For Lassa Fever And Venezuelan Equine Encephalitis., Dylan Macgregor Johnson May 2020

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 …


Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson May 2020

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 Manipulation Of Host Transcription By The Ankh Effector Of Legionella., Juanita E. Von Dwingelo Dec 2019

The Manipulation Of Host Transcription By The Ankh Effector Of Legionella., Juanita E. Von Dwingelo

Electronic Theses and Dissertations

Legionella pneumophila is a Gram-negative facultative intracellular bacterium that can be found dispersed throughout freshwater environments, where it primarily parasitizes amoebae and other protozoan species. Humans are an accidental host for L. pneumophila, and infection occurs upon inhalation of aerosolized water droplets that contain the bacteria. L. pneumophila is the causative agent of Legionnaires’ Disease, which is the result of intracellular proliferation within alveolar macrophages. Pathogenesis of L. pneumophila is dependent on the Dot/Icm type 4 secretion system (T4SS) apparatus, which is comprised of 27 proteins and is responsible for translocating over 330 effector proteins into the host cell. Many …


The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan Dec 2019

The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan

Electronic Theses and Dissertations

Cigarette smoking is a leading cause of preventable disease and premature death worldwide. The adverse effects of cigarette smoking, including proarrhythmia, are related to the mixture of chemicals, including nicotine (which sustains tobacco addiction). However, it remains unclear which individual tobacco smoke constituents and biological pathways mediate this increased risk. The purpose of this research was to explore the chronic effects of cigarette smoking, as well as compare the acute effects of nicotine and cigarette smoking, and the possible role of β-adrenoreceptors, on human cardiac electrophysiology. Chapter 1 is a comprehensive literature review of (a) the ex vivo and in …