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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 …


Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl May 2019

Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl

Electronic Theses and Dissertations

Cleft palate is a common birth defect. Etiologic mechanisms of palate cleft include defects in palate morphogenesis, mandibular growth, or spontaneous fetal mouth movement. Cleft palate linked to deficient fetal mouth movement has been demonstrated directly only in a single experimental model of loss of neurotransmission. Here, using retinoid deficient mouse embryos, we demonstrate directly for the first time that deficient fetal mouth movement and cleft palate occurs as a result of mis-patterned development of pharyngeal peripheral nerves and cartilages. Retinoid deficient embryos were generated by inactivation of retinol dehydrogenase 10 (Rdh10), which is critical for production of …


Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin May 2019

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …


Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty Dec 2018

Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty

Electronic Theses and Dissertations

This dissertation describes how poly-chlorinated biphenyls (PCBs) exacerbate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). While PCBs were banned in 1979, they still persist in contaminated biota, including food, and are detected in human plasma and adipose. The body burden of PCBs is associated with elevation of liver enzymes and necrosis markers in humans, characteristic of NAFLD. PCB exposure in high-fat diet fed mice leads to steatohepatitis that recapitulate the findings seen in exposed humans. The global estimate of people diagnosed with NAFLD is up to 1 in 4 people, unrelated to dietary or genetic factors. The hepatic mechanisms …


Cholesterol Metabolism And Statin Effects On An Fh Class Ii Ldl-Receptor Mutation., Linda Omer Dec 2018

Cholesterol Metabolism And Statin Effects On An Fh Class Ii Ldl-Receptor Mutation., Linda Omer

Electronic Theses and Dissertations

Familial hypercholesterolemia (FH) is a common genetic disease and has been studied with the aim of finding a curative measure for decades. FH is caused by mutations in the low-density lipoprotein receptor (LDLR) resulting in defects in LDL-cholesterol (LDL-C)-receptor mediated endocytosis and development of premature cardiovascular disease (CVD). Here I describe the use of a corrected and non-corrected LDLR FH cell model to investigate receptor-mediated endocytosis and statin effects. For these studies, we reprogrammed FH fibroblast cells to induced pluripotent stem cells (iPSC) and confirmed their pluripotency and ability to differentiate to hepatocyte-like cells (HLC). A clustered regularly interspaced short …


Effects Of Hydrogen Sulfide In Hyperhomocysteinemia-Mediated Skeletal Muscle Myopathy., Avisek Majumder Dec 2018

Effects Of Hydrogen Sulfide In Hyperhomocysteinemia-Mediated Skeletal Muscle Myopathy., Avisek Majumder

Electronic Theses and Dissertations

Although hyperhomocysteinemia (HHcy) occurs due to a deficiency in cystathionine-β-synthase (CBS), causing skeletal muscle myopathy, it is still unclear whether this effect is mediated through oxidative, endoplasmic reticulum (ER) stress, both or something else. Cystathionine γ-lyase (CSE) and CBS are the main H2S producing enzymes, which produce Hydrogen sulfide (H2S) from Hcy in the transsulfuration reaction. H2S is an anti-oxidant compound and patients with a CBS deficiency cannot produce enough H2S, thus rendering them vulnerable to excess Hcy-mediated damage. Both in-vitro (C2C12 cells) and in-vivo (CBS+/- mice) models were used to …


A Novel Fibroblast Growth Factor 1 Variant Reverses Nonalcoholic Fatty Liver Disease In Type 2 Diabetes., Qian Lin Aug 2018

A Novel Fibroblast Growth Factor 1 Variant Reverses Nonalcoholic Fatty Liver Disease In Type 2 Diabetes., Qian Lin

Electronic Theses and Dissertations

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with type 2 diabetes (T2D). Our recently engineered FGF1 partial agonist, carrying triple mutations (FGF1HBS) exhibits greatly reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1. This study tests the preventive and therapeutic effects of FGF1HBS on NAFLD in db/db T2D and explores potential mechanisms. The results showed that administration of FGF1HBS to 2-month-old db/db mice for 2 months constantly lowered blood glucose levels, improved insulin sensitivity, and lowered liver weight, lipid deposition, and …


Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor Aug 2018

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …


Wnt/Β-Catenin Mediated Cancer Stem Cell Activation In Hepatocellular Carcinoma., Harshulkumar M. Pandit Aug 2018

Wnt/Β-Catenin Mediated Cancer Stem Cell Activation In Hepatocellular Carcinoma., Harshulkumar M. Pandit

Electronic Theses and Dissertations

Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with variable presentation, high chemotherapy resistance and early tumor recurrence. In this dissertation, we have systematically enriched, identified and characterized HCC cancer stem cells (CSCs) from 3 different HCC cell lines (Hepa1-6, HepG2, and Hep3B) using in vitro serum-free culture method. Enriched spheroids acquired CSC properties, primarily self-renewal capability, spheroid formation ability, and drug resistance. Heterogeneous CSCs enriched from Hepa1-6 cells demonstrated higher tumor initiation and proliferation capability in vivo, compared to control HCC cells in orthotopic immunocompetent mouse model. EpCAM+ CSCs were significantly enriched within heterogeneous Hepa1-6 CSC spheroids. Consequently, …


Perinatal Nicotine With Or Without Early Life Influenza Infection Leads To Lung Dysfunction With Age., Ryan Carroll Mcallister Aug 2018

Perinatal Nicotine With Or Without Early Life Influenza Infection Leads To Lung Dysfunction With Age., Ryan Carroll Mcallister

Electronic Theses and Dissertations

Obstructive Airway Diseases (OADs) affect millions of people worldwide, and are characterized by chronic inflammation and tissue remodeling in the lung. It has been proposed that the development of OAD is greatly influenced (and perhaps pre-determined) by early life events, such as maternal smoking or a viral infection. However, direct evidence of this is limited and the mechanisms involved remain unclear. Our laboratory previously developed a murine model of perinatal nicotine exposure, and reported that nicotine leads to airway remodeling and decreased pulmonary function in the offspring. We discovered these effects were mediated through the α7 nicotinic acetylcholine receptor (nAChR). …


Maturation Of Human Induced Pluripotent Stem Cell Derived Engineered Cardiac Tissues Using Chief Transfection And Chronic Optical Pacing., Marc M. Dwenger May 2018

Maturation Of Human Induced Pluripotent Stem Cell Derived Engineered Cardiac Tissues Using Chief Transfection And Chronic Optical Pacing., Marc M. Dwenger

Electronic Theses and Dissertations

The immaturity of engineered cardiac tissues (ECTs) limits their ability to regenerate damaged myocardium and to serve as in vitro disease models and surrogates for drug toxicity testing. Several chronic biomimetic conditioning protocols, including mechanical stretch, perfusion, and electrical stimulation promote ECT maturation but have significant technical limitations. Non-contacting chronic light stimulation using heterologously expressed light-sensitive ChIEF ion channels, termed optogenetics, may be an advantageous alternative to chronic electrical stimulation. As a proof of principle, we transfected ECTs using an AAV packaged ChIEF and then verified acute optical pacing (OP) by patch clamp. We then chronically OP ECTs for 7 …


The Effects Of Polychlorinated Biphenyls Exposure On Non-Alcoholic Fatty Liver Disease : Role Of Aryl Hydrocarbon Receptor., Hongxue Shi May 2018

The Effects Of Polychlorinated Biphenyls Exposure On Non-Alcoholic Fatty Liver Disease : Role Of Aryl Hydrocarbon Receptor., Hongxue Shi

Electronic Theses and Dissertations

Polychlorinated biphenyls (PCBs) are detectable in serum of 100% of adults in US, and has been associated with fatty liver disease in epidemiological studies. PCBs are classified as either dioxin-like (DL) or non-dioxin-like (NDL) PCB based on their ability to activate the aryl hydrocarbon receptor (AhR). We used exposures that reflect human bioaccumulation patterns, which resembles Aroclor 1260 with a low level of the DL-PCB, PCB 126. Our aim was to determine if this exposure will activate the human and mouse AhR and examine if receptor activation influences these steatotic responses due to PCB exposures. DL-PCBs exposure-induced AhR activation in …


Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best May 2018

Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best

Electronic Theses and Dissertations

Legionella pneumophila is an environment organism that parasitizes a wide range of protozoa. Growth within the environmental host primes L. pneumophila for infection of human alveolar macrophages when contaminated aerosols are inhaled. Intracellular replication within either host requires the establishment a replicative niche, known as the Legionella-containing vacuole (LCV). Biogenesis of the LCV depends on the type IVb translocation system, the Dot/Icm, to translocation >320 effectors into the host cytosol. Effectors are responsible for preventing lysosome fusion to the LCV, recruitment of ER-derived vesicles to the LCV, and modulation of a plethora of host processes to promote the intracellular …


Functional And Structural Impact Of The Loss Of The Leucine-Rich Repeat Protein Lrit1 In The Mouse Retina., Catherine Ann Cobb May 2018

Functional And Structural Impact Of The Loss Of The Leucine-Rich Repeat Protein Lrit1 In The Mouse Retina., Catherine Ann Cobb

Electronic Theses and Dissertations

Mutations in genes encoding the leucine-rich repeat (LRR) proteins nyctalopin and LRIT3 lead to complete congenital stationary night blindness because they are critical to depolarizing bipolar cell function in the retina. LRIT3 has two closely related family members, LRIT1 and LRIT2. In silico analyses of publicly available RNA-Seq data showed that Lrit1 was highly expressed in the retina. Here I describe the expression pattern and impact of loss of LRIT1 on retinal function. To enable these studies, we used CRISPR/Cas9 technology to create an Lrit1-/- mouse line. Retinal morphology and morphometry analyses showed no gross changes in retinal structure …


Pcb-Associated Steatohepatitis And The Role Of Nuclear Receptors., Heather Brooke Clair Dec 2017

Pcb-Associated Steatohepatitis And The Role Of Nuclear Receptors., Heather Brooke Clair

Electronic Theses and Dissertations

Metabolic diseases, including fatty liver disease, hyperglycemia, and obesity, result when body systems responsible for managing allostasis (dynamic homeostasis across systems) are pressured beyond their collective compensatory reserve. Nutritional excess contributes to this state, the capacity of which is limited by genetic variation, and failure of one system will gradually lead to pathological overload in the others. Agents which act directly on the communication machinery linking these connected systems can also change the point at which allostatic load becomes allostatic overload. Environmental exposure to polychlorinated biphenyls (PCBs), a class of persistent organic pollutant, is associated with a specific form of …


Trunk And Respiratory Motor Control In Typically Developing Children And Its Implications In Children With Chronic Spinal Cord Injury., Goutam Singh May 2017

Trunk And Respiratory Motor Control In Typically Developing Children And Its Implications In Children With Chronic Spinal Cord Injury., Goutam Singh

Electronic Theses and Dissertations

Independent sitting is a major milestone and is also a prerequisite for optimal performance of activities of daily living (ADLs). Development of sitting posture control is a dynamic process involving control of degrees of freedom of head and trunk. Traditionally, trunk has been modeled as a single unit (segment). However, recent studies have suggested that it is made up multiple spinal units, controlled by a combination of trunk muscles. During typical development, posture control of trunk is different for different trunk segments. This motor development of trunk control is a complex process due to constant interaction between the nervous system …


The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary Dec 2016

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …


Pro-Inflammatory Cytokines Promote Viral Replication And Cell Cycle Mediators In Arenavirus-Induced Hepatitis., Gretchen E. Holz Dec 2016

Pro-Inflammatory Cytokines Promote Viral Replication And Cell Cycle Mediators In Arenavirus-Induced Hepatitis., Gretchen E. Holz

Electronic Theses and Dissertations

Lassa virus (LASV) is an arenavirus and causative agent of Lassa fever (LF), a viral hemorrhagic fever in West Africa for which there is no vaccine. Lymphocytic choriomeningitis virus (LCMV), is used as a surrogate to mimic LASV-induced liver pathology. LCMV-WE, not LCMV-ARM, causes disease in primates and mice characterized by hepatitis, high viral load, hepatocyte proliferation, and upregulated proliferative triggers (e.g. TNF-α, IL-6 ). We hypothesize LCMV-WE induces pathological hepatocyte proliferation via pro-inflammatory triggers (TNF-α, IL-6) from macrophages, leading to: increased viral replication, modulated cell cycle, and arrested cell cycle. RAW 264.7 macrophages and AML-12 hepatocytes, were used as …


Cost Of Care For Hospitalized Patients With Pulmonary Mycobacterial Diseases In The United States., Mary Beth Wells Allen Dec 2016

Cost Of Care For Hospitalized Patients With Pulmonary Mycobacterial Diseases In The United States., Mary Beth Wells Allen

Electronic Theses and Dissertations

Background: Pulmonary mycobacterial diseases describe both tuberculosis (TB) and nontuberculous mycobacteria (NTM). Few data are available measuring the cost burden of mycobacterial diseases on the national level. The purpose of this study was to evaluate the cost burden and measure emerging trends in hospitalization of pulmonary TB and NTM in the US from 2001 through 2012. Methods: This study was a retrospective community based cost analysis of hospitalized patients with a principal diagnosis of pulmonary mycobacterial diseases from 2001 through 2012. Data for pulmonary TB and NTM were retrieved from the Healthcare Cost and Utilization Project (HCUP), US Department of …


Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve Dec 2016

Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a highly heterogeneous clonal disorder characterized by an accumulation of malignant immature myeloid progenitors in the bone marrow (BM) that hinder normal hematopoiesis. Patient AML exhibits a dramatic heterogeneity in terms of cytogenetics, disease morphology, and associated prognoses and/or chemotherapeutic sensitivity. Thus it becomes clearly evident that the investigation of novel therapeutics for AML will require model systems that are capable of recapitulating this stark heterogeneity in a patient specific manner. Furthermore, it is now understood that the surrounding bone marrow (BM) microenvironment and supporting cells play a critical role in leukemic progression as well …


Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo Aug 2016

Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo

Electronic Theses and Dissertations

Sexually transmitted infections affect hundreds of millions of worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir …


Air Pollution, Pulmonary Oxidative Stress, And The Endothelin System In The Development Of Cardiovascular Injury., Jordan B. Finch Aug 2016

Air Pollution, Pulmonary Oxidative Stress, And The Endothelin System In The Development Of Cardiovascular Injury., Jordan B. Finch

Electronic Theses and Dissertations

The goal of this project was to examine the role of endothelin-1 (ET-1) as a mediator in the pathway between air pollution exposure and the development of vascular injury. A human cohort and male mice (C57BL/6 and ecSOD-Tg) were used to evaluate changes in the ET-1 system in response to exposures of fine particulate matter (PM2.5). Human ET-1 levels were significantly associated with environmental factors and markers of vascular change, but were decreased with increased PM2.5. No association was seen between ET-1 and endothelial progenitor cells (EPCs) except for EPC-4, possibly indicating a regulatory relationship with this specific population. In …


Vinyl Chloride-Diet Interactions In Liver Disease : Potential Roles Of Autophagy And Energy Management., Anna L. Lang Aug 2016

Vinyl Chloride-Diet Interactions In Liver Disease : Potential Roles Of Autophagy And Energy Management., Anna L. Lang

Electronic Theses and Dissertations

Vinyl chloride (VC) is a prevalent environmental toxicant that has been shown to cause liver injury at high, occupational exposures. However, most studies have not addressed interactions of low doses with risk-modifying factors. This study aims to explore low-level VC metabolite exposure interactions with other potential risk-modifying factors and their effect on underlying liver disease. We examined sub-hepatotoxic effects of a VC metabolite (chloroethanol, CE) in two murine models of liver injury using ethanol and lipopolysaccharide (LPS). In both, CE significantly enhanced liver injury when compared to either ethanol or LPS alone. Previous studies have shown an increase in mTOR …


Microrna-186 And Metastatic Prostate Cancer., Dominique Zilpha Jones May 2016

Microrna-186 And Metastatic Prostate Cancer., Dominique Zilpha Jones

Electronic Theses and Dissertations

MicroRNA (miR) dysregulation alters cancer-associated gene expression, which contributes to cancer pathogenesis. For example, miR-186 over expression lead to enhanced proliferation and migration in pancreatic cancer cell models. However, the role of miR-186 in prostate cancer (PCa) remains controversial. Previously, miR-186-5p was up-regulated in PCa patient serum (stage III/IV) compared to controls. Furthermore, miR-186-5p was up-regulated in metastatic PCa (PC-3, MDA PCa 2b, LNCaP) relative to normal prostate epithelial cells (RWPE1). We hypothesized miR-186 inhibition will reduce aggressive PCa using metastatic cell models. To test this, we evaluated whether miR-186-5p inhibition would reduce aggressive PCa behavior and overexpression induce malignant …


The Influence Of Mir-99a On Mtor Signaling Regulation In Colorectal Cancer Cell Lines., Jonathan Rice May 2016

The Influence Of Mir-99a On Mtor Signaling Regulation In Colorectal Cancer Cell Lines., Jonathan Rice

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. These are staggering statistics for a disease that can essentially be cured if caught early and the pathology is favorable to therapeutic intervention. There is currently a drastic decrease in five year survival as the cancer stage increases from locally confined disease to metastatic disease. These statistics suggest that although some strides have been made with colon cancer screening and early intervention, there is still much room for improvement in both screening and treatment of CRC. One of the pathways that have …


Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen May 2016

Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen

Electronic Theses and Dissertations

Alcohol consumption can cause alcoholic liver disease (ALD), which remains a major cause of morbidity and mortality in the United States. Chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Acrolein forms protein adducts and triggers endoplasmic reticulum (ER) stress and hepatocyte apoptosis, which are recognized etiologic factors in ALD. Several studies have established the critical role of the gut-liver axis in ALD pathogenesis, wherein alcohol-induced gut barrier dysfunction contributes to liver injury. This study investigates, in vitro and in vivo, the …


Pathogenic Role Of Acrolein In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen Dec 2014

Pathogenic Role Of Acrolein In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen

Electronic Theses and Dissertations

Alcohol is the most socially accepted addictive drug, and it can cause alcoholic liver disease (ALD), which is a major cause of morbidity and mortality in the United States and worldwide. Animal and human studies demonstrate that chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation and the accumulation of by-products such as acrolein and 4-hydroxynonenal. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Also, acrolein is a major component of cigarette smoke, and there is increasing evidence that smoking negatively impacts the incidence, severity, and clinical course of chronic …


Development Of Models For The Study Of The Molecular Mechanisms Of Host Restriction And Adaptation Of Hantaviruses., Ryan Carroll Mcallister 1988- Dec 2014

Development Of Models For The Study Of The Molecular Mechanisms Of Host Restriction And Adaptation Of Hantaviruses., Ryan Carroll Mcallister 1988-

Electronic Theses and Dissertations

Hantaviruses, family Bunyaviridae, are present throughout the globe in a variety of mouse, rat, mole, vole, shrew, or bat species. Hantaviruses persist for the lifetime of the animal reservoir, while causing no signs or symptoms of disease. Only the rodent-borne hantaviruses cause disease in humans. In contrast, a “spillover” infection of a hantavirus into a nonreservoir rodent species results in an asymptomatic acute infection. We and others in the field are interested in understanding the biology of these virus-host interactions and mechanisms that underlie these three very different outcomes. The second chapter of my thesis focused on probing the intrahost …


The Epidemiological Phase Of Syphilis Control In Louisville., Gradie Raymond Rowntree 1903-1993 Jan 1940

The Epidemiological Phase Of Syphilis Control In Louisville., Gradie Raymond Rowntree 1903-1993

Electronic Theses and Dissertations

No abstract provided.


The Influence Of Temperature On The Internal Secretory Activity Of Transplanted Ovaries In The Rat., Arthur K. Lampton 1915-1978 Jan 1939

The Influence Of Temperature On The Internal Secretory Activity Of Transplanted Ovaries In The Rat., Arthur K. Lampton 1915-1978

Electronic Theses and Dissertations

No abstract provided.