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Targeting Mitochondrial Function In Diabetic Nephropathy, Colin Reily Jan 2012

Targeting Mitochondrial Function In Diabetic Nephropathy, Colin Reily

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TARGETING MITOCHONDRIAL FUNCTION IN DIABETIC NEPHROPATHY The incidence of diabetes has increased to epidemic proportions over the last 50 years, due to a complex interaction of lifestyle and dietary factors. Changes in physical activity, caloric intake, and the composition of foods consumed over the last century are thought to interact with metabolic syndrome prone subpopulations leading ultimately to diabetes. It is widely accepted that chronic hyperglycemia in the blood characterizes the diabetic condition. Since the discovery of insulin therapy in the first half of the 20th century, diabetics have extended their lifespan considerably, but at the cost of increased morbitity …

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Cystine/Glutamate Transporters As Prognostic & Therapeutic Markers Of Primary Brain Tumors, Stephanie Marie Robert Jan 2012

Cystine/Glutamate Transporters As Prognostic & Therapeutic Markers Of Primary Brain Tumors, Stephanie Marie Robert

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Glioblastoma multiforme (GBM) are the most prevalent and aggressive malignant brain tumors. Current treatment - a combination of radiation, chemotherapy and resection - has limited effectiveness and offers poor prognosis. In this study, we examined the roles of system xc- (SXC) and excitatory amino acid transporters (EAATs), which transport the amino acids cystine and glutamate, on tumor growth, neurotoxicity, and peritumoral seizure activity. Tissue micro-arrays from 45 patients were examined by immuno-histochemistry, comparing tumor-bearing tissue and adjacent normal brain. Using a novel flank tumor propagation technique, we chose 3 glioma samples with varying SXC and EAAT expression levels to study …

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Connexin 43 Remodeling Contribute To Slowed Conduction Velocity In An Irreversible Arrhythmogenic Canine Model Of Non-Ischemic Heart Failure, Jiajie Yan Jan 2012

Connexin 43 Remodeling Contribute To Slowed Conduction Velocity In An Irreversible Arrhythmogenic Canine Model Of Non-Ischemic Heart Failure, Jiajie Yan

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Heart failure is associated with a high mortality due to ventricular tachycardia leading to ventricular fibrillation that could arise from impaired conduction velocity. Myocardial conduction relies on intercellular coupling maintained primarily by the gap junction protein connexin43. The objective of this research is to assess the correlation between connexin43 remodeling and altered conduction in our novel irreversible and arrhythmogenic HF large animal model that mimics human heart failure. A novel heart failure canine model was established with combined strategy of creating aortic insufficiency and aortic constriction. We measured conduction velocity in heart failure and control left ventricular epicardium (n=5, 5) …

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Fcrl5 Exerts Binary And Compartment-Specific Influence On Innate-Like B Cell Receptor Signaling, Zilu Zhu Jan 2012

Fcrl5 Exerts Binary And Compartment-Specific Influence On Innate-Like B Cell Receptor Signaling, Zilu Zhu

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Innate-like splenic marginal zone (MZ) and peritoneal cavity (PEC)-derived B1 B lymphocytes are the major contributors to primary humoral responses and play an important role in connecting innate and adaptive immunity, but are known to significantly differ in their B cell receptor (BCR) signaling characteristics. In mice, FCRL5 is discretely expressed by innate-like MZ and B1 B cells and is furthermore equipped with cytoplasmic ITAM-like and ITIM elements, suggesting diverse signaling potential for it. Our results showed that FCRL5 markedly inhibited BCR-mediated activation in MZ B cells, but not in PEC B1 B cells. To characterize its signaling function, a …

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Clinical Evaluation Of Treatment Of White Spot Lesions With Icon, Candace A. Cronan Jan 2012

Clinical Evaluation Of Treatment Of White Spot Lesions With Icon, Candace A. Cronan

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Introduction: Despite an increased awareness by clinicians and their attempt to aid patients in the prevention of white spot lesions, enamel demineralization continues to be a problem associated with orthodontic treatment. Current treatment options for these unaesthetic scars on the teeth range from conservative options for remineralization such as the use of fluoride and CPP-ACP to more aggressive treatment involving loss of tooth structure with microabrasion or restorations. An innovative option for treatment has recently been introduced in the form of the infiltrant resin, Icon. Icon infiltration is a minimally invasive procedure performed by a dentist that is claimed to …

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Analysis Of Ergothioneine Production In Mycobacterium Tuberculosis, Loni Ann Guidry Jan 2012

Analysis Of Ergothioneine Production In Mycobacterium Tuberculosis, Loni Ann Guidry

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Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, currently infects more than two billion people worldwide. Mtb is a highly adaptable pathogen, capable of modifying its metabolism in response to its environment. We previously showed that Mtb WhiB3 is a redox-responsive regulator of core intermediary metabolism and lipid anabolism through which it maintains redox homeostasis. In this work, through the use of metabolomic analysis and a novel radioactive thin layer chromatography assay, we discovered that WhiB3 regulates the production of the intracellular thiol ergothioneine (ergo) when using immunomodulatory lipid precursors as the major carbon source. Our results suggest that this …

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The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta Jan 2012

The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta

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Several studies have established the importance of epigenetic regulation of gene transcription in the brain during memory consolidation. Epigenetic mechanisms involve modifying the DNA or the associated histone proteins to determine the transcriptional outcome of a gene. The work encompassed in this dissertation serves as an initial investigation for the role of histone lysine methylation mechanisms in regulating gene activation and suppression in the medial temporal lobe that includes entorhinal cortex (EC), hippocampus, and amygdala during memory consolidation. To this end, we found that di-methylation of histone H3 at lysine 9 (H3K9me2) which promotes gene suppression was specific to associative …

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The Role Of Vpr-1 Msp Signaling In C. Elegans, Sung Min Han Jan 2012

The Role Of Vpr-1 Msp Signaling In C. Elegans, Sung Min Han

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In C. elegans, the major sperm protein (MSP) is the most abundant protein in sperm and functions as an intracellular cytoskeleton protein and a secreted extracellular signal that induces oocyte maturation and sheath contraction. Evolutionarily, MSP domain-containing proteins originate from the VAPs (VAMP/synaptobrevin-associated proteins), which comprise a highly conserved protein family with an MSP domain at the N-terminus and a transmembrane domain at the C-terminus. I have been studying the signaling role of VAP MSP domains using the C. elegans model system. In collaboration with Hugo Bellen's lab at Baylor College of Medicine, we have shown that C. elegans, Drosophila, …

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Effect Of Childhood Obesity On Risk Of Pelvic Bone Fracture In Simulated Sideways Fall, Min-Heng Hsieh Jan 2012

Effect Of Childhood Obesity On Risk Of Pelvic Bone Fracture In Simulated Sideways Fall, Min-Heng Hsieh

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Since the number of obese children in the U.S. has been increasing, the question arises whether obese children could be at higher or lower risk compared to nonobese children. The objective of this research was to investigate the risk of pediatric pelvic bone fracture in sideways falls using computational modeling and simulation considering various levels of obesity. Two sets of models were developed and tested. The first set was body component models. Several 10-year-old pelvis-femur complex models were developed. The models included biological soft tissue layers to reflect various levels of obesity, and they were validated against published experimental data. …

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Model System Using Controlled Receptor Expression For Molecular Ultrasound Imaging Applications, Reshu Saini Jan 2012

Model System Using Controlled Receptor Expression For Molecular Ultrasound Imaging Applications, Reshu Saini

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Ultrasound is a noninvasive, inexpensive imaging modality used to characterize biological tissues. Targeted contrast-enhanced ultrasound imaging is an emerging preclinical strategy which uses contrast agents for characterization of biological processes on a molecular level. These microbubble agents are lipid shelled micron-sized particles that have the capability to be coated with ligands such as antibodies or small peptides in order to bind to their target receptors. Molecular ultrasound imaging, using these targeted contrast agents, allows for a quantitative assessment of molecular targets with a high sensitivity. Although this technique is in preclinical research, further advances in contrast agent design and potential …

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Innate Immune Mechanisms Against The Atypical Fungal Pathogen Pneumocystis Murina, Michael Paul Nelson Jan 2012

Innate Immune Mechanisms Against The Atypical Fungal Pathogen Pneumocystis Murina, Michael Paul Nelson

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Pneumonia caused by the fungal pathogen Pneumocystis continues to be the leading cause of morbidity and mortality in AIDS patients. In addition, there are a number of other non-HIV-associated diseases that render an individual susceptible to Pneumocystis infection, including chronic obstructive pulmonary disease. Innate immune mechanisms are important for controlling Pneumocystis lung infection. As alveolar macrophages serve the front lines of lung host defense, our goal was to elucidate their responses during lung Pneumocystis infection. Here, we established a role for Src family kinases in the lung immune response to Pneumocystis, which uncovered a role for alternatively activated alveolar macrophages. …

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Electrophysiological Investigation Of Rabbit Retinal Ganglion Cells, Przemyslaw Nowak Jan 2012

Electrophysiological Investigation Of Rabbit Retinal Ganglion Cells, Przemyslaw Nowak

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The retina is the first stage of the visual system, responsible for transducing light into the neural signal and for subsequent processing of this signal before sending it to the higher visual centers in the brain. The output to the higher visual centers is mediated by retinal ganglion cells, which not only relay the signal, but also substantially contribute to its processing. Depending on what computations they perform, they are subdivided into different types. These cells have been extensively studied in various spices, one prominent example being the rabbit. In rabbits, one characteristic type comprises On-Off directionally selective retinal ganglion …

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Association Between Cc Chemokine Ligand 3-Like-1 (Ccl3l1) Gene Copy Number And Rheumatoid Arthritis In African Americans, Mawuli Kwame Nyaku Jan 2012

Association Between Cc Chemokine Ligand 3-Like-1 (Ccl3l1) Gene Copy Number And Rheumatoid Arthritis In African Americans, Mawuli Kwame Nyaku

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Gene copy number of the CC Chemokine ligand 3-Like-1 (CCL3L1) located on chromosome 17 position q12 varies between ethnicities. Previously, gene copy number of CCL3L1 greater than the ethnic median copy has been associated with an increased risk of Rheumatoid Arthritis. Three later studies found no association between CCL3L1 and RA. All studies were conducted in non-African Americans and an objective of this study was to determine this association in an African American cohort. CCL3L1 shares significant homology with three other genes within the same cluster; CC Chemokine ligand 3 (CCL3), CC Chemokine ligand 3-Like-2 (CCL3L2) and CC Chemokine ligand …

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Post-Transcriptional Control Of Type I Interferon Genes By Ksrp In The Innate Immune Response Against Viral Infection, Wei-Jye Lin Jan 2011

Post-Transcriptional Control Of Type I Interferon Genes By Ksrp In The Innate Immune Response Against Viral Infection, Wei-Jye Lin

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Several strategies are used in eukaryotic cells in order to determine the gene expression level, including the transcriptional and post-transcriptional mechanisms. One of the post-transcriptional mechanisms is the regulation of mRNA stability, which varies considerably from one mRNA species to another. Previous studies have shown that inherently unstable mRNAs encoding cytokines and proto-oncogenes contain the AU-rich elements (AREs) in the 3' untranslated regions (UTRs). Their decay requires decay-promoting RNA-binding proteins that recognize the AREs and recruit mRNA decay machineries to facilitate the rapid decay of targeting mRNA. KH-type splicing regulatory protein (KSRP) was previously identified as an ARE decay promoting …

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Statistical Methods In The Analysis Of Copy Number Variation Data, Nathan Wineinger Jan 2011

Statistical Methods In The Analysis Of Copy Number Variation Data, Nathan Wineinger

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Copy number variation is a significant form of genetic variation that has been shown to influence many traits. However, current methods used to estimate copy number variation are imprecise and prone to errors. This property is demonstrated in a study examining copy number variation in African Americans recruited into the Hypertensive Genetic Epidemiology Network study, and who were genotyped on the Affymetrix 6.0 array. The effect this has on downstream association analyses is explored, an alternative methods are proposed. Finally, a method is proposed that uses linkage disequilibrium between copy number variants and single nucleotide polymorphisms to improve the accuracy …

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Mechanisms And Consequences Of Thy-1 Shedding, John Edwin Bradley Jan 2011

Mechanisms And Consequences Of Thy-1 Shedding, John Edwin Bradley

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Idiopathic Pulmonary Fibrosis (IPF) is characterized by chronic fibrosis in the lung interstitium of unknown etiology, and causes death within 2 to 4 years after diagnosis. There are no clinical interventions save for lung transplantation that give any survival benefit. Aberrant collagen deposition and aggregates of proliferating fibroblasts and myofibroblasts called fibroblastic foci (FF) are the classic features of IPF. Therefore, the cell type most often implicated as pathogenic in IPF is the fibroblast, especially its differentiated phenotype, the myofibroblast. Fibroblasts are a remarkably heterogeneous cell type. Expression of the cell surface glycoprotein Thy-1 (Thymocyte differentiation antigen 1) delineates a …

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The Relationship Between Sunlight And Cerebrovascular Health, Shia T. Kent Jan 2011

The Relationship Between Sunlight And Cerebrovascular Health, Shia T. Kent

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Sunlight radiation may be related to stroke risk through increased vitamin D production. The latter has been associated with a number of conditions including stroke, cognitive function and cardiovascular disease. We performed three sets of analyses to determine whether higher levels of sunlight radiation were associated with lower rates of stroke incidence, all-cause mortality, and cognitive decline. We explored these relationships using the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national longitudinal cohort of 30,239 participants. We merged the participants' residential histories with a ground and satellite-derived NASA dataset to characterize 15-year average sunlight radiation and …

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Sox2/Parylated Parp1 Complexes Regulate Pluripotency, Yi-Shin Lai Jan 2011

Sox2/Parylated Parp1 Complexes Regulate Pluripotency, Yi-Shin Lai

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Embryonic stem cells (ESCs) were first derived from the inner cell mass (ICM) of blastocyst-stage embryos. ESCs are distinguished from other cell types by their pluripotency and unlimited self-replication. ESCs are able to differentiate into multiple cell types that represent all three primary germ layers (ectoderm, mesoderm and endoderm) and can form an entire adult organism. Under defined conditions, ESCs are self-renewable and have an extended life-span without compromising pluripotency. The plasticity of ESCs provides opportunities for regenerative medicine. The recent production of induced pluripotent stem cells (iPSC) offers an ideal "personalized" substitute for ESCs. Overexpression of four transcription factors, …

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A Study Of The Relationships Among Maternal Caregiver Family Management Behaviors, Childhood Asthma Morbidity, And Asthma Control, Linda M. Gibson Jan 2011

A Study Of The Relationships Among Maternal Caregiver Family Management Behaviors, Childhood Asthma Morbidity, And Asthma Control, Linda M. Gibson

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A STUDY OF THE RELATIONSHIPS AMONG MATERNAL CAREGIVER FAMILY MANAGEMENT BEHAVIORS, CHILDHOOD ASTHMA MORBIDITY, AND ASTHMA CONTROL ABSTRACT LINDA GIBSON NURSING Childhood asthma, the most common chronic childhood condition, is associated with high rates of asthma morbidity (emergency department visits, hospitalizations, and school days missed due to asthma). Inadequate asthma control accounts for $1.9 billion annual health expenditures. Numerous studies have identified the relationship of the family caregiver's perception regarding asthma management and the child's asthma outcomes; though few have examined family caregiver asthma management behaviors. Knafl and colleagues (2003) defined family management behaviors as accommodations that family members use …

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Biology And Conservation Of The Diamondback Terrapin, Malaclemys Terrapin Pileata, In Alabama, Andy Coleman Jan 2011

Biology And Conservation Of The Diamondback Terrapin, Malaclemys Terrapin Pileata, In Alabama, Andy Coleman

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The diamondback terrapin is the only obligate estuarine turtle in North America and is considered an integral member of the salt marsh ecosystem. Unfortunately, many populations throughout the terrapin's range have experienced size declines due to past overexploitation and have been unable to rebound due to current threats including crab trap mortality, habitat degradation, nest predation, and road mortality. The current study was the first comprehensive study examining various population and conservation parameters of Mississippi diamondback terrapins in Alabama. Through various field survey methods conducted in numerous salt marshes along the Gulf Coast of Alabama, it was concluded that Cedar …

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The Effects Of Runx2 Deficiency In Cartilaginous And Mineralized Craniofacial Element, David Summerford Jan 2011

The Effects Of Runx2 Deficiency In Cartilaginous And Mineralized Craniofacial Element, David Summerford

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The development of the orofacial structure in mammals is a highly ordered process that is coordinated activity of epithelial and mesenchymal cells. Chondrocytes and osteoblasts work in close association for development of many cartilaginous skeletal structures and cartilaginous orofacial structures. Two major orofacial structures are the palate and the temporomandibular joint (TMJ). The transcription factor, Runx2, is obligatory for differentiation of mesenchymal cells into chondrocytes and osteoblasts. However, specific contributions of chondrocyte in cartilaginous and mineralized structures of the craniofacial skeleton are not known. Thus, the objective of this study was to discover the regulatory role of Runx2 in chondrocyte …

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An Investigation Of The Effects Of Ocean Acidification On Larval Development, Juvenile Settlement And Mortality, Growth, Onset Of Egg Production, Shell Integrity And Feeding Activity In The Common Barnacle Amphibalanus Amphitrite, Michelle R. Mcdonald Jan 2011

An Investigation Of The Effects Of Ocean Acidification On Larval Development, Juvenile Settlement And Mortality, Growth, Onset Of Egg Production, Shell Integrity And Feeding Activity In The Common Barnacle Amphibalanus Amphitrite, Michelle R. Mcdonald

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ABSTRACT Ocean acidification is of great concern among the scientific community and is caused by the anthropogenic release of CO2 from the burning of fossil fuels. Higher levels of atmospheric CO2 are anticipated to cause a decrease in oceanic pH. Recent studies have shown that this can have adverse effects on a variety of marine organisms; calcified organisms are predicted to be the most heavily affected and of these types of organisms, barnacles have received little attention. The barnacle Amphibalanus amphitrite was utilized to examine the effects of Ocean acidification across various life history stages. No adverse effects of reduced …

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Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin Jan 2011

Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin

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The most common and most malignant gliomas are the Grade IV Glioblastoma Multiforme (GBM), characterized by a highly proliferative tumor mass and extremely invasive phenotype that allows for profuse dispersal of tumor cells throughout the brain. GBM cells must specifically regulate their cell volume to thrive within the edematous tumor mass and infiltrate throughout the tortuous extracellular spaces of the brain. These rapid and directed volume changes are governed by the controlled flux of potassium and chloride ions across the cell membrane, which move osmotically obliged water. The goal of this dissertation was to investigate the role of calcium-activated potassium …

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Killer Immunoglobulin-Like Receptors And Human Leukocyte Polymorphisms In Hiv-1 Pathogenesis, Aimee Marie Merino Jan 2011

Killer Immunoglobulin-Like Receptors And Human Leukocyte Polymorphisms In Hiv-1 Pathogenesis, Aimee Marie Merino

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Human leukocyte antigen (HLA) molecules influence the adaptive and innate immune responses through interactions with cytotoxic T lymphocytes and natural killer cells (NK). HLA influence the activation state of NK through direct binding to killer immunoglobulin-like receptors (KIR) and presentation of HLA-derived peptides to NKG2 receptors. Activated NK can kill HIV-infected cells through direct cytolysis and release cytokines that influence other aspects of the immune system. Variations in KIR gene content and allelic variants have been associated with autoimmunity, transplantation success, and infectious diseases such as hepatitis C and HIV/AIDS. We investigated the impact of KIR genes and potential KIR-HLA …

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The Cut, Robert Ben Henry Moffatt Jan 2011

The Cut, Robert Ben Henry Moffatt

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The Cut is a novella centered on Kyle Gordon. He works as a Cutter for a government program that has been tasked with weighing one citizen against another. The dangerous rise in global temperature has unleashed a pandemic that seems unstoppable. In an attempt to preserve civilization people like Gordon are deciding who is worth saving and who isn't. Those that pass the Cut are then taken into orbit where they will stay safely out of reach from the catastrophes on Earth. Gordon's task becomes even more difficult when he realizes that one of the citizens he failed was actually …

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Supporting Autonomy In Early Childhood: A Case Study Of Educators Offering Choice, Jann Montgomery Jan 2011

Supporting Autonomy In Early Childhood: A Case Study Of Educators Offering Choice, Jann Montgomery

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The purpose of this study was to explore the behaviors of early childhood educators that support their students' autonomy. Researchers have shown that the most prevalent style of teaching is an autonomy-suppressive style that has been determined to undermine student functioning and achievement (Assor, Kaplan, & Roth, 2002; Reeve, 2009). Teachers are often unaware of the atmosphere they create in their classroom (DeVries & Zan, 1994) and this can result in learning environments that are coercive which has been found to impede children's autonomous thinking (Reeve, 2009). This study sought to explore autonomy-supportive teacher behaviors in the early childhood classroom. …

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Syntheses Of Marine Natural Products And Their Analogs As Potential Anticancer Agents, Dwayaja H. Nadkarni Jan 2011

Syntheses Of Marine Natural Products And Their Analogs As Potential Anticancer Agents, Dwayaja H. Nadkarni

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Cancer is an abnormal and uncontrolled growth of cells and is one of the most common causes of millions of deaths worldwide. Currently used chemotherapeutic drugs have severe side effects. Hence, there is a need to develop new cancer therapeutic drugs that can offer higher survival rates and fewer limitations. About 60 % of the known anticancer drugs are either natural products or are derived from natural products. Development of marine natural products into drugs has received increasing attention as a part of humanity's quest for newer sources of cancer drugs. Marine natural products are isolated only in small quantities …

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Structural And Mechanistic Studies On Er Upr Sensor Perk And Mitochondrial Translocon Element Tim44, Wenjun Cui Jan 2011

Structural And Mechanistic Studies On Er Upr Sensor Perk And Mitochondrial Translocon Element Tim44, Wenjun Cui

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The unfolded protein response is one mechanism utilized by endoplasmic reticulum (ER) to maintain the homeostasis between ER protein folding machinery and ER proteins. UPR is induced by three ER transmembrane sensors: IRE1, ATF6 and PERK. PKR-like ER kinase (PERK) can sense the ER stress signal through its luminal domain to activate its cytoplasmic kinase domain catalytic activity. PERK kinase domain belongs to the eIF2α family. Members in this family are activated after being autophosphorylated at their activation loops and then specifically phosphorylate eIF2α at its Ser51 position. Phosphorylation of eIF2α can shutdown the cytosol protein translation from the initiation …

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Osteogenic Differentiation Of Human Mesenchymal Stem Cells Enhanced By Bone Ecm Analogous Nanomatrix Composites, Jeremy Benton Vines Jan 2011

Osteogenic Differentiation Of Human Mesenchymal Stem Cells Enhanced By Bone Ecm Analogous Nanomatrix Composites, Jeremy Benton Vines

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A growing trend in the area of bone tissue engineering is the development of materials that mimic the native bone extracellular matrix (ECM). This need is typically met through the creation of composites, which attempt to recapitulate both the organic and inorganic components of the native bone ECM. However, few composites have been created with organic ECM analogous components that are functionalized to direct cellular behaviors. Furthermore, a majority of these studies do not investigate how the ratio of the inorganic and organic components affects cellular behaviors. To address this issue, hydroxyapatite nanoparticles (HANPs) were dispersed within peptide amphiphile (PA) …

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Strategies For Combined Screening And Imaging Of Breast Cancer, Jason Morgan Warram Jan 2011

Strategies For Combined Screening And Imaging Of Breast Cancer, Jason Morgan Warram

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Successful treatment of breast cancer directly correlates with tumor stage and grade at diagnosis. Early diagnosis leads to a five-year relative survival rate of 96.8% as opposed to only a 22.5% five-year survival rate when diagnosed at late stage. Cancer-specific mechanisms need to be extended to enable cancer detection in an individual patient, in particular, the metastatic burden that currently cannot be assessed by conventional imaging. This approach for cancer detection would remove the biases of patient characteristics, permit immediate diagnostic feedback, improve sensitivity for early detection of small metastatic lesions, and be cost effective. Toward this goal, the cancer-specific …

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