Digital Commons Network^™

The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka

Electronic Theses and Dissertations

Global augmentation of protein O-GlcNAcylation occurs in response to a myriad of stressors and confers a survival advantage at the cellular level. This protective phenomenon has been demonstrated to mediate cardioprotection through various in vitro and in vivo studies during ischemia-reperfusion, myocardial infarction, and oxidative stress; however, relatively little is known of the regulation of protein O-GlcNAcylation. Protein O-GlcNAcylation is regulated by two antagonistic enzymes, namely, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ablation of cardiomyocyte OGT, the enzyme that catalyzes the addition of O-GlcNAc to proteins, exacerbates cardiac dysfunction during infarct-induced heart failure (HF). However, little is known of the …

Cannabinoids Suppress The Innate Immune Response To Periodontal Pathogen Porphyromonas Gingivalis In Gingival Epithelial Cells., Rajarshi Guha Niyogi

Electronic Theses and Dissertations

Marijuana is widely used in the United States for recreational and medicinal purposes. Despite the proposed beneficial effects of cannabis on certain medical conditions, there is also a concern there is also a concern over negative health consequences of marijuana smoking. Recently, cannabis use has been established as a dose related risk factor for chronic periodontitis. Although the induction / exacerbation of chronic periodontitis in marijuana users has been established epidemiologically, the mechanisms underlying such predisposition are still unknown. It has long been suggested that marijuana has anti-inflammatory properties, while human epithelial cells are known to express cannabinoid receptor type …

Mechanisms Responsible For The Development Of Causal Perception In Infancy., Nicholas A. Holt

Electronic Theses and Dissertations

The aim of the current dissertation was to investigate the mechanisms that contribute to the emergence of causal perception in infancy. Previous research suggests that the experience of self-produced causal action may be necessary to promote the development of causal perception (Rakison & Krogh, 2012). The goal of the current study was two-fold: (1) to further explore the roles of self-produced action, haptic, proprioceptive and visual information, and parental interaction on young infants’ understanding of causality. To assess the impact of these factors on infants’ causal learning, 4½-month-olds were randomly assigned to one four conditions. Three of the conditions (Active …

Type 2 Diabetes Mellitus (T2dm) Onset And "Remission"., Srikanth Tangelloju

Electronic Theses and Dissertations

Background: Type 2 diabetes mellitus (T2DM) is a progressive disease condition. As the disease progresses the function of beta (β) cells (cells which regulate insulin) decline, thereby increasing the circulating blood glucose levels. If left unmanaged the disease progresses from onset to development of T2DM related complications and eventually death. When managed, in certain individuals, T2DM onset can be prevented and/or slowed down and in certain T2DM individuals, remission is observed. There are some known modifiable risk factors such as diet and physical activities that are associated with the speed and direction of progression, but much is still unknown. In …

Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp

Electronic Theses and Dissertations

The rapid and recent increase in the global epidemic of diabetes and cardiovascular disease suggests a strong component of the environment is contributing. Benzene is a ubiquitous volatile pollutant generated by cigarette smoke, automobile exhaust, wildfires and industrial activities. Consequently, it is found in almost all urban and rural air samples. Benzene is known to cause hematotoxicity and its metabolism generates oxidative stress. Although, benzene has been studied for many years, few investigations have probed what influence benzene exposure may have on other physiological processes. Here we hypothesize that benzene metabolism by hepatic-CYP450 2E1 generates oxidative stress and inflammation, which …

Carnosine, A Therapeutic Potential For Critical Limb Ischemic., Adjoa Agyemang Boakye

Electronic Theses and Dissertations

Critical Limb ischemia (CLI) is a serious manifestation of peripheral artery disease. Advanced CLI patients are poor candidates for vascular surgeries. Numerous studies have shown that hypoxia inducible factor 1α (HIF1-α) plays an important role in recovery from murine hindlimb ischemia (HLI). HIF1-α is regulated by oxygen dependent prolyl hydroxylases (PHDs). Previous studies have shown that inhibition of PHDs by metal quenchers and viral delivery of HIF1-α improves blood flow to the ischemic limb. However, clinical trials with these therapies are largely negative partly because they do not address the underlying chronic oxidative stress. Based on recent observations that endogenous …

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 …

Effects Of Invasive Shrub Honeysuckle (Lonicera Maackii) And Forest Composition On Bird Communities In Woodland Stands., Katie Rae Lynch

Electronic Theses and Dissertations

Invasive species pose a threat to aquatic and terrestrial ecosystems by decreasing biodiversity (Didham et al. 2005). Amur bush honeysuckle (Lonicera maackii) has typically reduced native plant diversity and altered animal communities by influencing animal abundance and activity (Collier and Vankat 2002). This study was intended to determine whether honeysuckle density or other characteristics of forested stands influence avian diversity, whether impacts are seasonally dependent, and whether correlations exist between attributes of forested stands and honeysuckle density. In order to test the hypotheses, thirteen forest stands within the Louisville Metropolitan Area were selected. They had similar tree composition …

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 …

Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva

Electronic Theses and Dissertations

Background: Hyperhomocysteinemia (HHcy) has been observed to promote hypertension, but the mechanisms are unclear. Toll-like receptor 4 (TLR-4) is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. TLR-4 activation has been shown to promote inflammation that has been associated with pathogenesis of hypertension. In this study, we hypothesize that HHcy induces hypertension by TLR-4 activation that promotes inflammatory cytokine up-regulation (IL-1β, IL-6, TNF-α) and initiation of mitochondrial dysfunction leading to cell death and chronic vascular inflammation. Methods: To test this hypothesis, we used C57BL/6J mice (WT); Cystathionine-β-synthase deficient mice (CBS+/-) with genetic mild …

Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp

Electronic Theses and Dissertations

Cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury (AKI) in 30% of patients. Although recovery can occur after one episode of cisplatin-induced AKI, studies have indicated multiple episodes may lead to the development of chronic kidney disease (CKD), an irreversible disease with no current treatments. The standard mouse model of cisplatin-induced AKI consists of one, high dose of cisplatin (> 20 mg/kg) that is lethal to the animal three days later. This model doesn’t accurately reflect the repeated dosing regimen patients receive, and doesn’t allow for long-term outcome studies of pathologies associated with CKD. We have developed a …

Impact Of Luminance And Spatial Parameters On The Generation Of The Human Pattern Electroretinogram., Kate A. Godwin

Electronic Theses and Dissertations

The current work assessed some of the key hypotheses behind the generation of the pattern electroretinogram (PERG) response. The first of these hypotheses states that the PERG response is the result of linear cancellation of simultaneous increment and decrement retinal responses, as generated by the retinal ON- and OFF-pathways. Experiment 1 evaluated the possibility of simulating the PERG by summing the ERG responses elicited by increment and decrement flashes, and found that it was indeed possible to simulate the PERG from these responses. However, only the steady-state PERG could be modeled consistently. The second hypothesis evaluated a theory that the …

Effects Of Neonatal Capsaicin On Formalin-Induced Atf3 Expression In The Adult Rat., Sarah Krupp

Electronic Theses and Dissertations

Acute and chronic pain can be extremely debilitating conditions, and a better understanding of their underlying pathology is necessary to provide effective treatment. C-Fibers are responsible for transmission of the majority of nociceptive signals, with TRPV1+ C-Fibers being specific to noxious heat. Formalin, an inflammatory agent, acts through TRPA1+ C-Fibers, which have a high degree of co-localization with TRPV1. Using a neonatal capsaicin preparation, which irreversibly ablates the majority of TRPV1+ C-Fibers, formalin- induced inflammation and subsequent ATF3 expression was investigated. Results provide evidence that in addition to a lack of thermal nociception, animals treated with neonatal capsaicin had a …

The Discovery Of A Novel, Ras-Mediated Nore1a/Pmliv Tumor Suppressor Complex., Jessica Mezzanotte Sharpe

Electronic Theses and Dissertations

Ras is the most commonly activated oncogene in human cancer. Activated Ras drives cell growth and proliferation by activating multiple mitogenic signaling pathways. However, Ras also has the paradoxical ability to promote anti-growth, pro-apoptotic, and pro-senescent signaling. The signaling pathways of many of these biological effectors remain poorly defined. One group of proteins capable of promoting Ras-induced apoptosis and cell cycle arrest is the RASSF family of tumor suppressors. Novel Ras Effector 1A, or NORE1A, was the first member of this family discovered and is a bona fide tumor suppressor that is lost or inactivated in a number of different …

In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah

Electronic Theses and Dissertations

Klebsiella pneumoniae causes an acute respiratory infection in human with severe outcomes and high mortality rates even with antibiotic treatment. Even with its critical clinical importance, few virulence systems have been identified for K. pneumoniae limiting the development of new therapeutic strategies. Accordingly, we performed Next Generation sequencing for the strain ATCC 43816, a virulent strain in mouse respiratory disease models, and compared its genomic data with two previously sequenced strains NTUH-K2044 and MGH 78578 for the purpose of identifying genes required for colonizing host lungs. Furthermore, the virulence potential of the three K. pneumoniae strains were tested in a …

Microfluidic Platform For Impedance Characterization Of Endothelial Cells Under Fluid Shear Stress., Vanessa Velasco

Electronic Theses and Dissertations

Endothelium dysfunction has been associated with many pathophysiological processes leading to cardiovascular diseases. Studying endothelium behavior is vital to understand the onset, prevention, and treatment of such diseases. Electrical impedance spectroscopy has been shown to provide a real-time in vitro evaluation of cell behavior including cell monolayer permeability. However, the majority of published work has been primarily with static cell culture models or macro-scale models that do not properly represent the physiological sizes, structures, and environmental conditions of human blood vessels. Within this dissertation, the design, fabrication, characterization, and application of a microfluidic impedance platform is presented for the in …

The Role Of The Nucleolus In Neurodegeneration., Justin Lauren Hallgren

Electronic Theses and Dissertations

The overarching goal of my studies was to determine the role of the nucleolus in neurodegenerative disease. Numerous studies suggest the impairment of ribosomal biogenesis in neurodegenerative disease and such a condition may contribute to neuronal dysfunction in two ways, loss of function and stress response. Ribosomal biogenesis has been demonstrated to play an essential role in both neuronal growth and maintenance. Therefore insufficient levels of ribosomal biogenesis would be expected to produce atrophy and synapse loss. Moreover, the fidelity of ribosomal biogenesis is monitored by nucleolar and ribosomal stress responses which induce apoptosis and/or cell cycle arrest. Therefore, I …

A Systems Biology Approach Identifies A Gene Regulatory Network In Parotid Acinar Cell Differentiation., Melissa Ann Metzler

Electronic Theses and Dissertations

Objective: This project sought to understand the gene regulatory networks that drive parotid salivary gland acinar cells to terminally differentiate, and drive expression of terminal differentiation genes in dedifferentiated ParC5 cells. Methodology: Laser capture microdissection was used to isolate acinar cells at multiple time points during differentiation. This important step allowed us to measure gene expression in a single and important cell type. A systems biology approach was taken to measure global mRNA and microRNA expression across acinar cell terminal differentiation in the rat parotid salivary gland. In ParC5 cells, the ER stress activator tunicamycin was used to stimulate Xbp1 …

Putting Christians On The Map : Topographic Mosaics From Late Antique Jordan As Representations Of Authority And Status., Tracey Elizabeth Eckersley

Electronic Theses and Dissertations

In this dissertation, I examine nine ecclesiastic floor mosaics from Late Antique Palaestina and Arabia that contain topographic motifs ­­˗ images of cities set in realistic or stylized landscapes. Previous interpretations of the pavements have been limited by two assumptions: that artists or bishops were solely responsible for determining the compositions, and that only religious interpretations were intended for church pavements. Inscriptions indicating that patrons were generally lay people and iconography that encourages secular interpretations complicates both assumptions. This study investigates the mosaics in light of Late Antique euergetism in order to determine why donors included architectonic elements in the …

Murakami-Ego : Collective Culpability And Selective Retention., Yun Kweon Jeong

Electronic Theses and Dissertations

The purpose of this thesis is to argue that Murakami’s art expresses the Japanese’s psychological suffering by showing their struggle between remembering themselves as victims but forgetting themselves as aggressors. I apply the Mitscherlichs’ psychoanalisys of the Germans’s psyche to the Japanese because their people have had similar experiences. The first section examines the history of Japan surrounding WWII in order to demonstrate its effects on the Japanese people’s psyche. The second section introduces Otaku to better understand Murakami’s art. The third section examines how selective retention works on the Japanese’s psyche. The fourth section analyzes how Murakami’s art represents …

Care, Constraint, And Collaboration : Situating Gender And Power Among Multidisciplinary Human Service Organizations., Christa Jane Moore

Electronic Theses and Dissertations

This study incorporated a feminist approach to the use of multiple qualitative methods by conducting participant observation, focus group interviewing, and in-depth interviewing of women and men affiliated with a diverse representation of human service organizations. An applied research partnership with a multi-county human service organization provided entrée to the study population. Through analytic induction using a grounded theoretical approach the study explored perceptions of power, authority, gender, inequality, and bureaucratic constraints that emerged during organizational processes of interagency collaboration among multidisciplinary human service organizations (Charmaz 2014; Corbin and Strauss 2014). Findings indicate that establishing relationships is critical for interagency …

Effects Of Glyceollin On Mrna Expression In The Female Mouse Brain., Sanaya Firdaus Bamji

Electronic Theses and Dissertations

Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Glys exhibit mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Glys on brain physiology and function are unknown. The purpose of the experiments summarized in this dissertation was to gain an understanding of the effects of Gly on brain-related functions in the female mouse brain through the observation of changes in gene expression. For our initial studies, we treated ovariectomized Swiss Webster (CFW) …

Learning Styles Of Physical Therapy And Physical Therapist Assistant Students In Accredited Physical Therapy Programs, Margaret A. Lowdermilk

Electronic Theses and Dissertations

The purpose of this study was to determine the learning styles of Doctor of Physical Therapy (DPT) students and associate degree Physical Therapist Assistant (PTA) students and identify any association between their learning styles and examine the association between gender and age by learning style.

Participants included 337 DPT and PTA students attending CAPTE accredited institutions with doctoral DPT or associate PTA programs in Tennessee and southwest Virginia. The Felder (1996) and Soloman Index of Learning Styles (ILS) was used to determine learning style preferences within 4 learning style dimensions (active-reflective, sensing-intuitive, visual-verbal, and sequential-global).

Demographics included program of study, …

Improving The P300-Based Brain-Computer Interface By Examining The Role Of Psychological Factors On Performance, Samantha A. Sprague

Electronic Theses and Dissertations

The effects of neurodegenerative diseases such as amyotrophic-lateral sclerosis (ALS) eventually render those suffering from the illness unable to communicate, leaving their cognitive function relatively unharmed and causing them to be “locked-in” to their own body. With this primary function compromised there has been an increased need for assistive communication methods such as brain-computer interfaces (BCIs). Unlike several augmentative or alternative communication methods (AACs), BCIs do not require any muscular control, which makes this method ideal for people with ALS. The wealth of BCI research focuses mainly on increasing BCI performance through improving stimulus processing and manipulating paradigms. Recent research …

Imagining The Nigerian Nation Through The West African Pilot 1960-1966., David Zintak

Electronic Theses and Dissertations

The independence era in Nigeria, ushered in after 1960 and ending in 1966 with the fall of the civilian-elected government in a military coup, was a pivotal juncture in the construction and imagining of the nation and the citizen. Ideas of what a citizen should act like, dress like, and what mindsets were proper to hold were discussed frequently in the media. One critically important media outlet during the independence era was the West African Pilot. The Pilot is generally considered an influential nationalist publication during and prior to this era. This thesis explores how Nigeria was imagined through the …

Molecular Docking, Synthesis And Evaluation Of Pyrrolo[2,1-C][1,4]Benzodiazepines Derivatives As Non-Β-Lactam Β-Lactamases Inhibitors, Joseph Osamudiamen Osazee

Electronic Theses and Dissertations

Our research aim was to design, synthesize, and study the competitive enzyme inhibition kinetics of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) derivatives as potential non-²-lactam ²-lactamase inhibitors. All compounds (1-13) passed the Lipinski’s rule of 5 test and were docked into the active site of TEM-1 ²-lactamase. PBD derivatives 1-7 were synthesized in high yields and tested for their potency against TEM-1 and P99 ²-lactamases. Kinetic data showed that compounds 1, 4, 5, and 7 possessed inhibitory activity against TEM-1 ranging from 4-34 %. Docking results revealed significant interactive spanning of the active site of TEM-1 by PBDs. …

Synthesis, Characterization And Biological Evaluation Of Pyrrolo[2,1-C][1,4]Benzodiazepines For Cytotoxicity And Serine Β-Lactamases Inhibition, Joel K. Annor-Gyamfi

Electronic Theses and Dissertations

Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) derivatives possess cancerostatic and anti-infective properties thus making them candidates of possible antibacterial agents. ²-lactam antibiotics are vital weapons for the treatment of bacterial infections, but their existence and effectiveness has been faced with resistance from ²-lactamases. Therefore, the need for new effective antimicrobial drugs is very crucial. In this work, we synthesized in high yields, PBD analogs 1−3, 5 and 7−9 in three to four synthetic steps from commercially available L-proline and isatoic anhydride. MTT Assay was employed to test the in vitro cytotoxicity of PBD analogs 1, 2, 5 …

The Effects Of Environmental Modifications And Visual Supports In The Home On Engagement And Challenging Behaviors In Children With Autism, Teresa L. Boggs

Electronic Theses and Dissertations

The purpose of this study was to determine the impact on engagement and challenging behaviors in young children with autism spectrum disorder (ASD) under two treatment conditions: 1) physical modifications to the home environment, and 2) physical modifications plus visual supports in the home environment. Treatment conditions were implemented in the child's home environment with parents serving as interventionist.

A single-subject nonconcurrent baseline design was used across three male participants: ages 3 years, 2 months; 4 years, 4 months; and 4 years, 11 months. The study included four to five baseline sessions, six to nine sessions in Treatment 1, six …

Synthesis And Characterization Of Imidazolo 3,1- Tetrakis (N-Phenylacetamidato) Dirhodium (Ii) And A Crystallographic Study Of A Copper And Two Molybdenum Model Cofactors, Gabriel I.G. Thompson

Electronic Theses and Dissertations

Imidazole was reacted with 3,1-tetrakis (N-phenlyacetamidato) dirhodium (II) to explore the chemistry of asymmetric dirhodium catalysts. The imidazolo 3,1-tetrakis (Nphenlyacetamidato) dirhodium (II) complex was synthesized and then characterized by Nuclear Magnetic Resonance and Ultraviolet-Visible spectroscopies as well as by single crystal X-ray Diffraction. Additionally, one copper and two molybdenum model cofactors were characterized by XRD to better understand their structure/function relationships. NMR results gave evidence of the formation of the 3,1-imidazole complex, and UV-Vis indicated that even in large excess imidazole was coordinated only to one axial site. The structure of the 3,1-imidazole complex was confirmed by XRD with the …

Aaaneurysm Outreach Screening Data And Emergency Healthcare Accessibility In Louisiana: Identifying High-Risk Populations For Targeted Interventions, Amy M. Poole

Electronic Theses and Dissertations

Abdominal aortic aneurysms are the third leading cause of sudden death in men 60 years and over. AAAneurysm Outreach provides free screenings to residents of Louisiana and beyond. Service areas were calculated for each AAAneurysm Outreach screening event location and stroke center. Data provided by the 2010 U.S. Census, the American Community Survey, and the Behavioral Risk Factor Surveillance System were used to describe demographics of the underserved populations and to identify high-risk areas for targeted interventions. Twenty-five percent of age-eligible Louisianans reside outside optimal drive-time-to-screening-event zones but within spatially clustered areas of increased prevalence rates. The maximum drive-time-to-treatment zones …