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Development Of An Axonal Outgrowth Assessment Methodology For Dorsal Root Ganglia Explants And Demonstration Of Method Efficacy On Electrospun Polymer Scaffolds, Sarah Margaret Kezar Jan 2014

Development Of An Axonal Outgrowth Assessment Methodology For Dorsal Root Ganglia Explants And Demonstration Of Method Efficacy On Electrospun Polymer Scaffolds, Sarah Margaret Kezar

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In chronic spinal cord injury (SCI), a glial encapsulated cyst develops at the injury site and acts as a physical and biochemical barrier to regeneration. Discussion has suggested that filling the cyst with a growth promoting scaffold is a promising approach to cure chronic SCI, though the research to date lacks a systematic approach. Dorsal root ganglia (DRG) explants are an extremely common tissue culture model of neural regeneration employed in this field, however there is no uniform method for objectively quantifying substrate biocompatibility and neurite outgrowth. Therefore, we aimed to develop a novel DRG growth assessment methodology and to …

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Contribution Of Hyperactive Glycogen Synthase Kinase-3 (Gsk3) To Impaired Neurogenesis And Cognition In Mice, Margaret Kimbrough King Jan 2014

Contribution Of Hyperactive Glycogen Synthase Kinase-3 (Gsk3) To Impaired Neurogenesis And Cognition In Mice, Margaret Kimbrough King

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The overall goals of this research were to examine the regulatory actions of glycogen synthase kinase-3 (GSK3) in adult mouse hippocampal neurogenesis and in mouse cognitive functions in order to gain further insight regarding the function of GSK3 in the healthy and diseased central nervous system. Focusing on differences between male and female mice, we found that hippocampal neurogenesis was impaired by hyperactive GSK3 in both sexes, but was improved by environmental enrichment in male, but not female, mice. Chronic stress reduced neurogenesis in male mice, but not in female mice. Environmental enrichment and chronic stress inhibited, and activated, respectively, …

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The Direct Effects And Vertical Transfer Of Carbonaceous And Metal-Loaded Hydrochars In Aquatic Organisms, Katie Lauren Kohlenberg Jan 2014

The Direct Effects And Vertical Transfer Of Carbonaceous And Metal-Loaded Hydrochars In Aquatic Organisms, Katie Lauren Kohlenberg

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Industrial use of reactive micro- and nano-sized carbonaceous hydrochar (CH) is expanding rapidly. These carbonaceous particulates are synthesized by the pyrolysis of biomass in an industrial process called hydrothermal carbonization (HTC) and have gained attention as a soil conditioner. Additionally, the HTC process is being expanded to coat heavy-metal nanoparticles, such as nano-copper and nano-iron, to prevent surface oxidation of these metals. These carbonaceous particles are likely to undergo secondary reactions with metals, toxicants, or other compounds. There is potential for these carbonaceous particulates to enter watersheds and have deleterious effects on aquatic food web dynamics. In this study, we …

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Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li Jan 2014

Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li

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Alzheimer disease (AD) is a devastating neurological condition that slowly destroys memory and thinking skills of the affected patients. No disease-modifying medications are available. While all the treatment against Aߒ (major component of one hallmark pathology of AD) failed in clinical trials, tau (major component of the other hallmark pathology of AD) is emerging as a better alternative. Germline knockout of tau does not cause overt abnormalities in young mice and prevents AD-like deficits in mouse models of AD. Germline knockout of tau also confers resistance to epileptiform activity in models of both AD and epilepsy. Therefore tau is proposed …

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Type I Interferons-Induced Follicular Translocation Of Lymphotoxin-Expressing Marginal Zone B Cells Initiates Lupus, Hao Li Jan 2014

Type I Interferons-Induced Follicular Translocation Of Lymphotoxin-Expressing Marginal Zone B Cells Initiates Lupus, Hao Li

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Systemic lupus erythematosus (SLE) is characterized by elevation of type I interferon (IFN) signature genes and production of autoantibodies against apoptotic self-antigens. The complex nature of SLE, however, suggests that multiple immune dysregulations must integrate to initiate the disease. Here, we provided evidence that lupus can be initiated via type I IFNs-induced follicular translocation of membrane lymphotoxin (mLT)-expressing marginal zone (MZ) B cells in the spleen of lupus prone BXD2 mice. The mislocation of mLT+ MZ B cells induces two important pathogenic effects including deteriorations of marginal zone macrophages (MZMs) in the MZ, leading to defective clearance of apoptotic debris, …

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Anatomical And Neurochemical Investigation Of The Brain In Autism, Lauren E. Libero Jan 2014

Anatomical And Neurochemical Investigation Of The Brain In Autism, Lauren E. Libero

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with widespread behavioral symptoms and a strong neurobiological origin. Neuroimaging studies of ASD have uncovered evidence for widespread abnormalities in brain anatomy and functioning. Abnormalities reported by structural brain imaging, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) studies have aided in characterizing ASD as a complex, systems-wide disorder. The overarching goal of this project was to use multiple modalities of neuroimaging to investigate the underlying neural mechanisms of ASD. The following techniques were used to collect and analyze multimodal neuroimaging data from a relatively large number of participants …

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Ksrp Ablation Enhances Lipolysis In White Adipose Tissue Through Reduced Mir-145 Expression, Yi-Yu Lin Jan 2014

Ksrp Ablation Enhances Lipolysis In White Adipose Tissue Through Reduced Mir-145 Expression, Yi-Yu Lin

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White adipose tissue (WAT) releases fatty acids from stored triacylglycerol (TAG) for energy source. Here, we report that null mice for KH-type splicing regulatory protein (KSRP), an RNA-binding protein, resisted high fat diet (HFD) induced obesity. Target of deletion of KSRP regulates gene expression at multiple levels and enhances lipolysis in epididymal WAT (eWAT) due to up-regulation of genes promoting lipolytic activity. Expression of miR-145 is decreased due to impaired pri-miR-145 processing in Ksrp-/- eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals …

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Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker Jan 2014

Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker

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Vitally important to HIV-1 vaccine and prevention studies is a well-characterized animal model that recapitulates the salient features of HIV infection in humans. SIVmac and SIVsmm infection of rhesus macaques share key virological and pathological parallels with HIV-1 infection of humans including target cell entry via CD4 and CCR5 (Edinger et al., 1997), progressive T cell loss (Swanstrom & Coffin, 2012), generalized immune activation and preferential loss of mucosal Th17 cells (Brenchley et al., 2008; Klatt & Brenchley, 2010), and a vigorous but ultimately ineffective adaptive immune response. Though commonly used as a vaccine challenge strain in the macaque model, …

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Exploring Intrinsic Biomarkers For Optical Assessment Of Outer Retina, Rongwen Lu Jan 2014

Exploring Intrinsic Biomarkers For Optical Assessment Of Outer Retina, Rongwen Lu

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The retina suffers pathological changes after attacked by eye diseases. The objective of my PhD dissertation is to explore intrinsic biomarkers for noninvasive assessment of retinal morphological structure and physiological function. Fundus autofluorescence (FAF), optical coherence tomography (OCT), etc. have provided indispensable information for eye disease detection. However, better understanding of the intrinsic biomarkers in FAF and OCT is desirable for quantitative interpretation of clinical outcomes. The first specific aim of the dissertation research was to characterize FAF signals across the whole retinal depth using two-photon excitation. FAF signals are usually attributable to fluorophores from the choroidal vessel and the …

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The Role Of The Autophagy-Lysosome Pathway In In Vitro Models Of Neurodegeneration, Burton Mader Jan 2014

The Role Of The Autophagy-Lysosome Pathway In In Vitro Models Of Neurodegeneration, Burton Mader

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Recent studies have provided strong evidence that alterations in protein degradation pathways, such as the autophagy-lysosome pathway (ALP), may contribute to neuronal dysfunction and death which lead to clinical symptoms diagnosed with various neurodegenerative diseases. Parkinson's disease (PD) is characterized by neuromuscular abnormalities resulting from the pathological loss of substantia nigra dopaminergic neurons and widespread detection of Lewy bodies, intracellular protein inclusions composed primarily of α-synuclein. Additionally, altered gene function regulating the expression of α-synuclein has been directly linked to the PD pathogenesis. Autophagy is an intracellular degradation process that when altered can lead to the accumulation neurotoxic proteins such …

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Night Comes Early To The Valley, Caitlin Murphree Miller Jan 2014

Night Comes Early To The Valley, Caitlin Murphree Miller

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Night Comes Early to the Valley is a collection of short stories about vulnerable, flawed people trying to discover the best way to live their lives. They are well-meaning mothers, fathers, children, and lovers, yet all struggle to balance the fulfillment of their personal responsibilities with the realization of their deepest individual desires. The collection highlights characters who are desperate to atone for their mistakes, build brighter futures, and live up to the expectations of their loved ones--only to realize, over time, that the most formidable judge they'll ever face is their own conscience.

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Glial Fibrillary Acidic Protein And Gliosis: Is Gfap More Than A Marker?, Heather Renee Minkel Jan 2014

Glial Fibrillary Acidic Protein And Gliosis: Is Gfap More Than A Marker?, Heather Renee Minkel

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Alexander Disease (AxD) is a `gliopathy' caused by toxic, dominant gain-of-function mutations in the gene encoding glial fibrillary acidic protein (GFAP). Two distinct types of AxD exist. Type I AxD affected individuals develop cerebral symptoms by four years of age and generally suffer from macrocephaly, seizures, and physical and mental delays. As detection and diagnosis have improved, a larger portion, now about half of all AxD patients diagnosed, have onset >4 years and brainstem/spinal cord involvement. These type II AxD patients typically experience ataxia, palatal myoclonus, dysphagia and dysphonia. To date no study has examined a mechanistic link between the …

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The Role Of Ih In 4-Aminopyridine Induced Epileptiform Activity, Steven Patrick Palladino Jan 2014

The Role Of Ih In 4-Aminopyridine Induced Epileptiform Activity, Steven Patrick Palladino

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significantly different from sex ratios of control groups produced at constant incubation

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Altered Dna Methylation Contributes To Temporal Lobe Epilepsy And Associated Memory Deficits, Robert Ryley Parrish Jan 2014

Altered Dna Methylation Contributes To Temporal Lobe Epilepsy And Associated Memory Deficits, Robert Ryley Parrish

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Status epilepticus (SE) triggers molecular mechanisms that underlie the cellular and network changes that occur during the development of temporal lobe epilepsy (TLE). Additionally, gene expression alterations occur during epileptogenesis and in the epileptic brain that contribute to the persistence of the phenotype. However, the underlying epigenetic mechanisms responsible for aberrant gene expression that occur with epilepsy require further investigation. This dissertation investigates how DNA methylation in the hippocampus affects epilepsy and contributes to the memory impairments associated with the disorder. We found that DNA methylation was altered in a hippocampal subregion specific manner in the epileptic brain, displaying altered …

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Bio-Hybrid Tubular Electrospun Scaffold For Vascular Tissue Engineering Application, Harsh Narendrakumar Patel Jan 2014

Bio-Hybrid Tubular Electrospun Scaffold For Vascular Tissue Engineering Application, Harsh Narendrakumar Patel

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Atherosclerosis is an asymmetric thickening of the intima (innermost layer) of the artery due to plaque (a combination of lipids, debris, connective tissue elements and cells) build up causing the artery to become narrower and stiffer, resulting in a major hemodynamic disturbance[1, 2]. When atherosclerosis affects coronary arteries and prevents blood flow to the heart muscles posing a threat of, or a actual myocardial infarction, that condition is identified as coronary artery disease (CAD). To treat severely blocked coronary arteries,coronary artery bypass grafts (CABG) have became the gold standard for when angioplasty and stent placement has failed to unclog the …

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Biology, Ecology, And Conservation Of Hatchling And Post-Hatchling Diamondback Terrapin (Malaclemys Terrapin Pileata), Tandy Dolin Petrov Jan 2014

Biology, Ecology, And Conservation Of Hatchling And Post-Hatchling Diamondback Terrapin (Malaclemys Terrapin Pileata), Tandy Dolin Petrov

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The diamondback terrapin has been considered a keystone species along its range in the coastal, brackish estuaries bordering the Atlantic Coast and Gulf of Mexico. Historically, diamondback terrapin populations have been numerous; however, in Alabama; the population has dramatically declined over the past century due to a variety of threats. The threats in Alabama include predation by raccoons, incidental drowning in crab traps, as well as road mitigated mortality. Because of these threats, collaboration efforts between UAB, USA, DISL, and the Alabama Department of Conservation and Natural Resources, a head-start program has been initiated to mitigate the predation of hatchlings. …

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The Impact Of Interleukin-21 On Intestinal Inflammation During Health And Disease, Catherine Poholek Jan 2014

The Impact Of Interleukin-21 On Intestinal Inflammation During Health And Disease, Catherine Poholek

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The intestinal environment is extremely complex due to the dynamic interactions between host cells and luminal contents. The immune cells located in the intestine are responsible for sensing and responding to intestinal pathogens as well as maintaining tolerance to non-pathogenic organisms and environmental antigens. Disruption in this delicate balance results in chronic intestinal inflammation. Particularly important to the maintenance of intestinal homeostasis are CD4 T cells and innate lymphoid cells (ILCs). These cells produce cytokines in an antigen-specific and antigen-independent manner, respectively, and have analogous subsets with similar cytokine profiles. CD4 T cells and ILCs expressing ROR gamma t (Th17 …

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Molecular And Functional Interaction Of Runx2 And Sp7 For Development Of The Osteoblast Phenotype, Harunur Rashid Jan 2014

Molecular And Functional Interaction Of Runx2 And Sp7 For Development Of The Osteoblast Phenotype, Harunur Rashid

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Runx2 and Sp7 transcription factors are essential for skeletogenesis. Deletion of either gene in mice results in failure of bone tissue development. However, underlying mechanisms responsible for a surprisingly similar phenotype by two distinctly unrelated proteins remain unknown. Sp7 is a Runx2 downstream target gene and is not expressed in Runx2 null mice. Thus, the Runx2 null model represents a compound phenotype of loss of both proteins. In contrast, normal levels of Runx2 mRNA are noted in Sp7 null mice. The failure of Runx2 to promote bone formation in Sp7 null mice suggests that Sp7 is required for Runx2 function …

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Neuropathology Of Dopamine Systems In Schizophrenia: Regional Dopamine Pathologies In The Substantia Nigra/Ventral Tegmental Area Complex, Matthew Warner Rice Jan 2014

Neuropathology Of Dopamine Systems In Schizophrenia: Regional Dopamine Pathologies In The Substantia Nigra/Ventral Tegmental Area Complex, Matthew Warner Rice

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Dopaminergic neurotransmission anomalies are a well-established aspect of schizophrenia, a devastating mental disorder that affects approximately 1% of the world population. The substantia nigra/ventral tegmental area (SN/VTA), which extends from diencephalic to mesencephalic territories, provides the largest dopaminergic input to the brain. The SN/VTA contains subpopulations of dopaminergic neurons that project preferentially through different pathways, providing dopamine input to brain regions where dopaminergic anomalies have been reported in schizophrenia. We hypothesized that anomalies in the synthesis of tyrosine hydroxylase (TH), the rate-limiting enzyme for the production of dopamine, could contribute to the dopaminergic anomalies observed in this disorder. We first …

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White Matter Integrity In Adults With Hemiparetic Multiple Sclerosis Given Constraint-Induced Movement Therapy, Tyler Rickards Jan 2014

White Matter Integrity In Adults With Hemiparetic Multiple Sclerosis Given Constraint-Induced Movement Therapy, Tyler Rickards

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In adults with chronic stroke and children with cerebral palsy, structural changes in grey matter correlate with clinical improvements due to an efficacious upper-extremity (UE) rehabilitation therapy, Constraint-Induced Movement (CI) Therapy. Changes in white matter following CI therapy have not been observed, but damage to white matter tracts has not been found to decrease motor improvement resulting from this treatment. The objectives of this project were to: 1) evaluate the efficacy of CI therapy compared to complementary and alternative medicine (CAM) treatments on improving impaired UE function in participants with the progressive form of multiple sclerosis (MS), 2) investigate whether …

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Combined Effects Of Corexit Ec 9500a With Secondary Abiotic And Biotic Stressors In The Rotifer Brachionus Plicatilis, Michael Britt Williams Jan 2014

Combined Effects Of Corexit Ec 9500a With Secondary Abiotic And Biotic Stressors In The Rotifer Brachionus Plicatilis, Michael Britt Williams

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Following the Deepwater Horizon oil spill the dispersant Corexit EC 9500A (C-9500) was applied to facilitate rapid oil degradation. C-9500 toxicity has been evaluated on a number of marine species; however, many of these studies do not account for environmental conditions that may increase negative outcomes related to dispersant exposure in the wild. We examined lethality and behavioral effects of C-9500 exposure on the model marine zooplankton Brachionus plicatilis. We also evaluated interactions of abiotic and biotic stressors that may alter outcomes of exposure. C-9500 exposure at standard husbandry conditions (17.5ppt, 24°C, 200 rotifer*ml-1 density) produced a 24 hr median …

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Targeting Reactive Oxygen Species Production To Prevent Left Ventricle Remodeling In Volume Overload, Danielle Marie Yancey Jan 2014

Targeting Reactive Oxygen Species Production To Prevent Left Ventricle Remodeling In Volume Overload, Danielle Marie Yancey

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Mechanisms of left ventricular dysfunction in cardiac volume overload (VO) are not well understood and currently, no medical therapy exists to treat this condition. Cardiac VO is marked by eccentric remodeling and contractile dysfunction ultimately resulting in cardiac failure. Oxidative stress is implicated in the pathophysiology of heart failure and recent evidence suggests mitochondrially- produced reactive oxygen species play a role in VO. To study VO, we used a rat model of aortocaval fistula (ACF). ACF results in early diastolic stress on the left ventricle (LV) and recapitulates the progressive nature of heart failure with contractile function being initially maintained …

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Gut Microbiome And Its Role In Obesity And Aging In C57bl/6j Mice, Yongbin Yang Jan 2014

Gut Microbiome And Its Role In Obesity And Aging In C57bl/6j Mice, Yongbin Yang

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turtles and its’ ecological and evolutionary significance regarding certain aspects of

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High Spatiotemporal Resolution Mapping Of Retinal Physiology, Qiuxiang Zhang Jan 2014

High Spatiotemporal Resolution Mapping Of Retinal Physiology, Qiuxiang Zhang

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The objective of my PhD dissertation research is to explore high resolution imaging of retinal function using transient intrinsic optical signals (IOSs) correlated with retinal physiological activation. The retina is responsible for capturing photons and preliminary visual information processing. Functional examination of retinal neural cells is important for eye disease detection and treatment evaluation. It is known that different diseases can target different retinal cell types, and thus high resolution imaging of retinal function is desirable. Fast IOSs with time courses comparable to retinal electroretinogram (ERG) kinetics can act as a unique biomarker to map physiological distortions correlated with eye …

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Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman Jan 2014

Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman

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Calreticulin (CRT) is an ER chaperone and regulator of Ca2+ signaling which is increased following ER stress and in fibrotic and vascular fibroproliferative disorders. Previously, we demonstrated that ER CRT regulates type I collagen transcript, trafficking, secretion, and processing into the extracellular matrix (ECM). These studies investigated the role of CRT in regulating ECM production through control TGF-ß dependent signaling pathways. Our studies show that CRT -/- mouse embryonic fibroblasts (MEFs), rat lung fibroblasts, and human IPF lung fibroblasts with siRNA knockdown of CRT had impaired production of type I collagen and fibronectin when stimulated with TGF-ß. Similarly, knockdown of …

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Gene Expression Signatures In Tree Shrew Sclera In Different Visual Conditions, Lin Guo Jan 2014

Gene Expression Signatures In Tree Shrew Sclera In Different Visual Conditions, Lin Guo

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The sclera is a target tissue that receives signals that are initiated in the retina, cascade through retinal pigment epithelium (RPE) and choroid, and cause scleral extra cellular matrix remodeling. Biomechanical alterations of the sclera are produced by these biochemical changes, and in turn control the axial length of the eye. This dissertation project examined scleral gene expression changes in mRNA level of juvenile tree shrews. Three specific aims were investigated: specific aim one tested the hypothesis that three different GO visual conditions that all produce axial elongation and myopia: minus-lens wear, form deprivation, and continuous darkness, will produce similar …

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Risk Assessment And Staging Of Cardiometabolic Diseases, Fangjian Guo Jan 2014

Risk Assessment And Staging Of Cardiometabolic Diseases, Fangjian Guo

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Obesity is associated with elevated risk for morbidity and mortality and has become an epidemic both in the United States and around the world. Insulin resistance is essentially involved in the pathogenic process of cardiometabolic diseases in obese people, which involves defects in glucose production by the liver and insulin-stimulated glucose uptake and utilization by peripheral tissues. Insulin resistance appears at an early stage of life and is the first step in the development of cardiometabolic diseases. Long-term insulin resistance will induce metabolic syndrome and prediabetes and eventually will cause type 2 diabetes and cardiovascular diseases. Obesity may exacerbate insulin …

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Evaluation Of Municipal Wastewater In The Vicinity Of Birmingham, Alabama For Estrogens Using Vitellogenin Gene Expression In Largescale Stonerollers (Campostoma Oligolepis), Shara Blackwell Legg Jan 2014

Evaluation Of Municipal Wastewater In The Vicinity Of Birmingham, Alabama For Estrogens Using Vitellogenin Gene Expression In Largescale Stonerollers (Campostoma Oligolepis), Shara Blackwell Legg

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Environmental endocrine disrupting compounds (EDCs) have become a growing threat to the health of humans and wildlife. Numerous studies have demonstrated the presence of EDCs in freshwater aquatic environments. Environmental estrogens, both natural and synthetic, appear to be posing a threat to the reproductive fitness of aquatic organisms. Wastewater treatment plants (WWTPs) have been identified as significant routes by which the EDCs enter waterways. The egg yolk precursor protein vitellogenin (VTG) has proven to be a useful biomarker that can be used to identify organisms that have been exposed to environmental estrogens. In this study, a quantitative RT-PCR assay for …

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Examining The Role Of G Protein-Coupled Estrogen Receptor 1 (Gper) Activation In 17beta-Estradiol-Mediated Protection In Traumatic Brain Injury, Nicole Day Jan 2014

Examining The Role Of G Protein-Coupled Estrogen Receptor 1 (Gper) Activation In 17beta-Estradiol-Mediated Protection In Traumatic Brain Injury, Nicole Day

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Traumatic brain injury (TBI) affects millions of persons per year, potentially leading to permanent disability or death, and exacts a staggering financial toll. Despite the severity of this public health problem, there are no clinically proven pharmacotherapeutics available that effectively attenuate the secondary neurochemically-mediated damage that follows the initial biomechanical insult. In addition, the heterogeneous nature of TBI and complexity of secondary injury cascades suggest that a polytherapeutic approach could be a powerful strategy with which to simultaneously target more than one deleterious pathway. Recently, sex steroid hormones have sparked interest as possible neuroprotective agents after traumatic injury. One of …

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Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft Jan 2014

Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft

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Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in OS treatment, more specific molecular targets are needed. One target of interest is alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation. Here, we show that α-CaMKII is highly expressed in primary OS tissue, and α-CaMKII deletion in human OS cell lines significantly reduces tumor burden in vivo. This inhibition of α-CaMKII results in decreased vascular endothelial growth factor (VEGF) protein secretion. Highly aggressive OS cells express VEGF receptor …

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