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Pathophysiology Of Dyt1 Dystonia: Targeted Mouse Models, Chad Christopher Cheetham Jan 2011

Pathophysiology Of Dyt1 Dystonia: Targeted Mouse Models, Chad Christopher Cheetham

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DYT1 dystonia is an inherited movement disorder caused by a trinucleotide deletion (DeltaGAG) in the DYT1 (TOR1A) gene, which codes for the torsinA protein. Dr. Yuqing Li's laboratory previously reported the characterization of a DYT1 dystonia mouse model, a knock-in carrying DeltaGAG in Dyt1 (KI), which displays a motor learning deficit of motor skill transfer. We report here that this motor learning deficit was reversed with an anticholinergic drug, trihexyphenidyl (THP), a drug commonly used to treat movement problems in dystonia patients. We further show a potential substrate for the pathophysiology, a reduction in D2 receptors in the striatum in …

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Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook Jan 2011

Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook

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Sulfation is an important Phase II drug metabolism reaction catalyzed by the cytosolic sulfotransferases (SULTs). SULT2A1 is a major SULT in liver and adrenal cortex that has been reported to sulfate a wide variety of substrates including bile acids, steroids, and drugs. The crystal structures of SULT2A1 suggest that PAPS binding causes a structural change. This study examines the kinetic changes in SULT2A1 caused by PAPS binding using computer modeling, enzyme kinetics, binding studies, and mammalian cells expressing SULT2A1. The data presented clearly demonstrate that the binding of PAPS changes the affinity of some substrates to SULT2A1 resulting in different …

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Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Jean Nick Jan 2011

Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Jean Nick

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The t(8;21) translocation, which generates an AML1-ETO fusion protein (also known as RUNX1-ETO), is one of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML). Murine studies have demonstrated that AML1-ETO promotes the accumulation of myeloid progenitor cells with self-renewal capability and impaired differentiation capacity. However, AML1-ETO+ mice do not progress to AML in the absence of additional mutations, suggesting that expression of the translocation is insufficient for leukemogenesis. This hypothesis is supported by studies demonstrating the persistence of AML1-ETO-expressing hematopoietic progenitors obtained from patients in long-term clinical remission. Mutations affecting receptor tyrosine kinases, particularly c-KIT, are commonly detected …

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Behavior Of Midbrain Vergence Cells During Stepwise Transfers Of Gaze And Oblique Tracking In Depth, Leah Corthell Jan 2011

Behavior Of Midbrain Vergence Cells During Stepwise Transfers Of Gaze And Oblique Tracking In Depth, Leah Corthell

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A long standing debate regarding the neural organization of oculomotor control began in the late 1800's with Hering and von Helmholtz proposing two opposing ideologies. Von Helmholtz proposed a monocular structure of the oculomotor circuitry in which each eye receives separate motor commands. Hering offered his law of equal innervation, which states that all eye movements are the sum of binocular vergence and conjugate commands. As a test of Hering's binocular proposal, this project compared the behavior of midbrain vergence cells during: 1) saccade-free stepwise transfers of gaze in depth; 2) combined saccade-vergence eye movements; 3) pure vergence tracking, and …

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Comparison Of Vitamin D Supplementation Regimens In Pediatric Patients With Cystic Fibrosis, Julianna Bailey Jan 2011

Comparison Of Vitamin D Supplementation Regimens In Pediatric Patients With Cystic Fibrosis, Julianna Bailey

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COMPARISON OF VITAMIN D SUPPLEMENTATION REGIMENS IN PEDIATRIC PATIENTS WITH CYSTIC FIBROSIS JULIANNA BAILEY CLINICAL NUTRITION ABSTRACT The objective of this randomized prospective study was to determine the most efficacious form of vitamin D supplementation for pediatric patients with Cystic Fibrosis (CF). We hypothesized that 50,000 IU monthly cholecalciferol would be as effective in raising serum 25-hyrdroxyvitamin D [25(OH)D] concentrations as routine daily supplementation of 1000-2000 IU cholecalciferol in pediatric patients with CF, birth to 20 years of age, over a period of 3 months. Data collected at baseline included serum 25(OH)D concentration, gender, genotype, race, age, FEV1, height, weight, …

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Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky Jan 2011

Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky

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Our laboratory reported that a combination of ionizing radiation (IR) or temozolomide (Tmz), a DNA methylating agent clinically approved against glioblastoma multiforme (GBM), a type of human brain cancer, and TRA-8, an anti-DR5 monoclonal antibody produced synergistic cytotoxicity in GBM cells in culture and in mouse xenograft models through an yet unknown mechanism. I hypothesized that understanding of the synergy phenomenon can offer an insight into the nature of GBM vulnerability. The goals of this investigation were two-fold - to elucidate the mechanism of this enhancement in cytotoxicity, and to improve understanding of DR5 mediated apoptosis toward improvement of current …

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Hierarchical And Bayesian Approaches For Estimating Prevalence Based On Pool Screening, Thomas Birkner Jan 2011

Hierarchical And Bayesian Approaches For Estimating Prevalence Based On Pool Screening, Thomas Birkner

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Pool screening is a method that combines individual items into pools. Each pool will either test positive (at least one of the items is positive) or negative (all items are negative). Pool screening is commonly applied to the study of tropical diseases where pools consist of vectors (e.g. black flies) that can transmit the disease. The goal is to estimate the proportion of infected vectors. In paper 1, we present a frequentist Bernoulli-Beta hierarchical model to relax the constant prevalence assumption underlying the traditional frequentist prevalence estimation approach. This assumption is called into question when sampling from a large geographic …

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Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland Jan 2011

Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland

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The recently characterized exopolysaccharide of Mycoplasma pulmonis, EPS-I, has been identified as modulating the susceptibility to complement-mediated lysis and binding to host mucosal epithelium. M. pulmonis produces family of size- and phase-variable lipoproteins called Vsa. Previous evidence has strongly demonstrated that the length of the tandem repeat region of the M. pulmonis Vsa protein is associated with the susceptibility to the host innate immune system through complement-mediated lysis. Mycoplasmas producing a long form of Vsa, containing about 40 repeats, are resistant complement whereas strains that produce the short form of Vsa, 5 repeats or fewer, are susceptible. Furthermore, the size …

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The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist Jan 2011

The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist

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This dissertation documents my findings in two unrelated projects. Project 1: Expansion of CAG repeats encoding glutamine in huntingtin and ataxin 3 causes the neurodegenerative diseases Huntington's disease (HD) and spinocerebellar ataxia 3 (SCA3), respectively. Both poly-glutamine (polyQ) expanded proteins misfold and ag-gregate within the cell. Preventing aggregation of polyQ proteins through molecular or pharmacological approaches provide therapeutic advantage in animal models of HD and SCA3. I hypothesized that the UL97 kinase encoded by the human cytomegalovirus (HCMV) may be able to prevent the aggregation of polyQ proteins. Initially, I showed that the UL97 kinase prevents the deposition of aggregates …

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Low And High Let Irradiation Of Human Aortic Endothelial Cells Induces Dose And Time Dependent Adhesion Of Monocytes Which Is Mediated By Chemokines Expressed By The Irradiated Endothelium., Saman Fatima Khaled Jan 2011

Low And High Let Irradiation Of Human Aortic Endothelial Cells Induces Dose And Time Dependent Adhesion Of Monocytes Which Is Mediated By Chemokines Expressed By The Irradiated Endothelium., Saman Fatima Khaled

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Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of xrays, iron (Fe56) ions, and protons on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X-rays, 0, 2, and 5 Gy Fe56 ions, and 0, 0.5, and 2 Gy protons followed by measurement of …

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An Examination Of Secondary Metabolites And Inorganic Acids As Chemical Defenses Against Predation And Fouling In Antarctic And Sub-Tropical Ascidians, Gil Koplovitz Jan 2011

An Examination Of Secondary Metabolites And Inorganic Acids As Chemical Defenses Against Predation And Fouling In Antarctic And Sub-Tropical Ascidians, Gil Koplovitz

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Palatability of outer tissues of 12 species of ascidians from the Western Antarctic Peninsula was evaluated using the sympatric, omnivorous predator fish Notothenia coriiceps and sea star Odontaster validus. Tissues of 100% of those tested were unpalatable to fish, while 58% were unpalatable to sea stars. Lipophilic and hydrophilic extracts of 11 species were incorporated into pellets and tested in fish and sea star bioassays. Only the lipophilic extract from Distaplia colligans caused sea star and fish feeding deterrence. Organic extracts from 10 ascidian species were also examined in food pellet assays using the sympatric, omnivorous amphipod Gondogeneia antarctica. Only …

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The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz Jan 2011

The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz

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THE ROLE OF TRIB3 IN INSULIN RESISTANCE: ITS ACTION AS NUTRIENT SENSOR AND REGULATOR OF INSULIN ACTION JIARONG LIU LAMIQUIZ PATHOLOGY ABSTRACT Insulin resistance is a hallmark of Type 2 diabetes (T2DM). A reduced capacity for insulin to stimulate increases in glucose uptake and glucose oxidation in insulin sensitive tissues, such as skeletal muscle and adipose tissue, are common defects in patients with insulin resistance, T2DM, and other related diseases. Tribbles homolog 3 (TRIB3) has been demonstrated to play a role in insulin resistance by serving as a negative regulator of Akt in mouse liver, fat, and pancreas. In a …

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Functional Imaging Of Excitable Cells: Retinal Neurons And Pancreatic Islet Beta Cells, Yichao Li Jan 2011

Functional Imaging Of Excitable Cells: Retinal Neurons And Pancreatic Islet Beta Cells, Yichao Li

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Stimulus-evoked fast intrinsic optical signals (IOSs) have time courses comparable to electrophysiological kinetics, and thus promise a sub-cellular and sub-second resolution method for functional evaluation of excitable biological tissues. The objective of my thesis research is to validate and characterize IOS imaging of stimulus-evoked activities in the retina and pancreatic islet ß-cells. In order to achieve this objective, three sets of experiments have been conducted. 1) Simultaneous measurement of retinal neurons functioning can enhance our understanding of the visual signal processing. In this stage of my study, I propose to demonstrate IOS imaging of retina slices that allows simultaneous monitoring …

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Erythropoiesis In The Absence Of Adult Hemoglobin, Shanrun Liu Jan 2011

Erythropoiesis In The Absence Of Adult Hemoglobin, Shanrun Liu

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The mammalian erythrocyte is a highly specialized blood cell that differentiates via an orderly series of committed progenitors in the bone marrow in a process termed erythropoiesis. During erythroid development, hemoglobin synthesis increases from early erythroid progenitors to mature enucleated red blood cells (RBCs). Although hemoglobin is the most extensively studied protein in history, the role, if any, that hemoglobin plays in erythroid development remains obscure. In this study, I ask the question what happens during erythropoiesis in the absence of hemoglobin. I demonstrate that my original hypothesis that excess free heme would accumulate in the absence of globin chain …

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Identification Of Putative Gene Targets Of Pgc-1alpha In The Brain: Insights Into Inhibitory Neuron Maturation, Physiology, And Behavior, Elizabeth Lucas Jan 2011

Identification Of Putative Gene Targets Of Pgc-1alpha In The Brain: Insights Into Inhibitory Neuron Maturation, Physiology, And Behavior, Elizabeth Lucas

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The transcriptional coactivator peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) is a master regulator of energy homeostasis in peripheral tissues, and it has been assumed that PGC-1α plays a similar role in the brain. Previous work has shown that PGC-1α localizes to neurons that express high levels of the enzyme glutamic acid decarboxylase of 67 kDa (GAD67) during early postnatal development, leading us to hypothesize that PGC-1α regulates gene expression primarily in GABAergic neurons. We initially investigated the distribution of inhibitory neuron markers in PGC-1α -/- mice and observed a striking reduction in expression of the Ca2+-binding protein parvalbumin …

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The Effects Of Simvastatin On Learning And Memory Mechanisms In Mice, Robert Mans Jan 2011

The Effects Of Simvastatin On Learning And Memory Mechanisms In Mice, Robert Mans

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Statins, a widely prescribed class of cholesterol-lowering drug, inhibit HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. Due to the identification of cholesterol as a risk factor for developing Alzheimer's disease (AD), a number of studies have examined whether statins are neuroprotective against developing AD or dementia. While some epidemiological studies do indicate a lower prevalence of AD in people taking statins, other reports are contradictory. A consensus has therefore not been reached regarding the neuroprotective effects of statin treatment. Aside from the well-characterized reduction in circulating cholesterol resulting from statin therapy, numerous cholesterol-independent, pleiotropic effects have been …

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Analysis Of Nphp Complex Genetic Interactions Associated With Human Cilia Disorders, Svetlana Viktorovna Masyukova Jan 2011

Analysis Of Nphp Complex Genetic Interactions Associated With Human Cilia Disorders, Svetlana Viktorovna Masyukova

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Primary cilia are antenna-like organelles that extend from the surface of almost all mammalian cell types. They regulate many signaling pathways and sense physical and chemical changes in the extracellular environment. Defects in primary cilia cause several human disorders of different severity collectively called ciliopathies, including nephronophthisis (NPHP), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). Numerous MKS, JBTS and NPHP genes have been identified but in most cases of these ciliopathies the genetic defect is unknown. Despite the fact that NPHP, JBTS and MKS patients present with distinct clinical features, they have mutations in identical genes. This can be explained …

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The Graphic Novel: A Frontier Literary Form Edges Towards The English Classroom, Malgorzata Pflueger-Pieczynska Jan 2011

The Graphic Novel: A Frontier Literary Form Edges Towards The English Classroom, Malgorzata Pflueger-Pieczynska

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Graphic novels, as not yet fully researched and examined forms under academia, suffer from their association in the public mind with the advertisement industry and cheap subject matter. This negative affiliation is especially popular in teachers' circles that use the graphic novel mostly as an instrument to improve reading skills rather than to present it as an extraordinary example of a frontier literary form. The graphic novel is one of many products that took off dynamically with the technological revolution using the visual as a communication's medium. Visual communication is not only one of the leading forms of passing information, …

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Survival Analysis With Censored Outcomes, Henry T. Robertson Jan 2011

Survival Analysis With Censored Outcomes, Henry T. Robertson

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This dissertation is arranged in the three-paper format. The unifying theme of the dissertation is estimating longevity in terms of years of life lost (YLL). The papers are presented in order of increasing methodological focus. The first paper, No compelling evidence that sibutramine prolongs life in rodents despite providing a dose-dependent reduction in body weight, was published in the International Journal of Obesity in 2010. Although sibutramine reduced food intake and body weight, it had no association with longevity. The conclusions were based on data from a 2-year toxicology trial required by the FDA. Although this paper was largely applied …

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Daoist Elements In Cai Guo-Qiang's Inopportune And Head On, Kelley Wockenfuss Jan 2011

Daoist Elements In Cai Guo-Qiang's Inopportune And Head On, Kelley Wockenfuss

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This thesis explores the Daoist elements in two of contemporary Chinese artist Cai Guo-Qiang's (1957 - ) largest installations to date, Inopportune (2004) and Head On (2006). Comprising multi-media works including gunpowder paintings, simulated animal forms, and firework displays, the two installations explore themes related to the global threat of terrorism in Inopportune and the history of the Berlin Wall in Head On. In exploring these themes, Cai attempts to create a globally accessible dialogue by emphasizing universal elements related to the forces of creation and destruction. For this reason he implements the Daoist characteristics of yin and yang in …

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High Resolution Analysis Of Clonal Pluripotent Stem Cell Lentiviral Gene Therapy In A Mouse Model Of Beta-Thalassemia, Rui Yang Jan 2011

High Resolution Analysis Of Clonal Pluripotent Stem Cell Lentiviral Gene Therapy In A Mouse Model Of Beta-Thalassemia, Rui Yang

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Gene therapy for hematopoietic disorders using viral vectors has achieved significant clinical benefit. However this approach has been held back by adverse genotoxic events due to random viral integration into the genome. A better understanding of viral transgene chromosomal position effects is critical for the design of safer viral vectors and clinical protocols. However, detailed analysis of viral transgenes is hampered by the heterogeneity of the viral-transduced bone marrow cell populations. I hypothesized that viral transduction of pluripotent stem cells would enable the clonal analysis of viral transgene expression, safety, and efficacy both in vitro and in vivo. Here I …

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Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang Jan 2011

Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang

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The most common genetic diseases worldwide, £] thalassemia and Sickle Cell Anemia (SCA) result from mutations in the adult £] globin gene. One promising therapeutic method to ameliorate these diseases is to reactivate the endogenous fetal f× globin gene. I hypothesize that an erythroid mutagenic transposon system can be used to activate f× globin gene expression. To test this hypothesis three lines of genetically modified mice were generated and bred together. The first is a transgenic mouse line that contains a multicopy array of erythroid mutagenic PiggyBac (PB) transposons. The second transgenic mouse line expresses the PB transposase (TPase) from …

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Determining The Functional Role Of Trem-Like Transcript 2 In The Innate Immune Response, Matthew Martin Halpert Jan 2011

Determining The Functional Role Of Trem-Like Transcript 2 In The Innate Immune Response, Matthew Martin Halpert

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TLT2 is one of four receptors conserved between mouse and human within the TREM locus, and is expressed on B cells, macrophages, and neutrophils. TLT2 ligation on murine macrophages induces the production of chemokines and growth factors, as evidenced by ex vivo treatment with anti-TLT2 mAbs. This treatment did not lead to the upregulation of activation markers such as CD69 or costimulatory molecules such as CD80 and CD86, indicating a specific response following TLT2 ligation. This is recapitulated in vivo following injection of anti-TLT2 mAbs resulting in the production of chemokines and growth factors, which ultimately lead to enhanced neutrophil …

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Ampa Receptor Trafficking In Schizophrenia, John Hammond Jan 2011

Ampa Receptor Trafficking In Schizophrenia, John Hammond

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The glutamate hypothesis of schizophrenia is based primarily on NMDA receptor dysfunction. Recent studies have led to an expansion of this hypothesis to include AMPA receptors which are essential for neurotransmission through NMDA receptors. Examination of total AMPA receptor protein expression in schizophrenia has been inconsistent and led to examination of AMPA receptor interacting proteins and trafficking and subcellular localization of the receptors. AMPA receptors are highly trafficked from the endoplasmic reticulum to the synapse and in a complex system of endosomes. Alterations in the subcellular localization of these receptors may be a part of the underlying pathophysiology of schizophrenia. …

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Bone Morphogenetic Protein Signaling Pathways During Mouse Heart Development: Roles For Chd7 And Mycn, Cristina Harmelink Jan 2011

Bone Morphogenetic Protein Signaling Pathways During Mouse Heart Development: Roles For Chd7 And Mycn, Cristina Harmelink

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Bone Morphogenetic Protein (BMP) signaling pathways are imperative for proper heart development. BMP ligands bind serine threonine kinase receptors, which activate intracellular receptor-regulated SMAD proteins. SMAD1, SMAD5, and SMAD8 transduce BMP signals from the cytoplasm to the nucleus, where they regulate transcription. We have investigated two aspects of BMP signaling during mouse cardiogenesis: identifying SMAD1-interacting proteins and exploring the roles of a known BMP target, Mycn, in the developing myocardium. Chromodomain helicase DNA binding protein 7 (CHD7) is a highly conserved transcription factor that promotes protein synthesis, proliferation, and differentiation. Haploinsufficiency for CHD7 causes CHARGE syndrome, a developmental disorder characterized …

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The Role Of Mitochondrial Oxidative Stress In Cardiovascular Disease Development, Corey Michael Harrison Jan 2011

The Role Of Mitochondrial Oxidative Stress In Cardiovascular Disease Development, Corey Michael Harrison

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An estimated 70 million Americans have one or more types of cardiovascular disease (CVD). Although the sequence of events leading to CVD are still controversial, there is a general consensus that atherosclerotic lesions result from oxidative stress associated with risk factor. For this study, it was hypothesized that endogenous mitochondrial oxidative stress would influence susceptibility to atherogenesis and mitochondrial damage mediated by CVD risk factor exposure. To test this hypothesis, atherosclerotic lesion formation, oxidant stress, and mitochondrial DNA damage were assessed in hypercholestoremic mice (apolipoprotein E null - apoE -/- SOD2 +/+) and mice with significantly decreased levels of the …

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The Role Of Ll-37 In Prostate Cancer And Its Potential As A Therapeutic Target, Jonathan Adam Hensel Jan 2011

The Role Of Ll-37 In Prostate Cancer And Its Potential As A Therapeutic Target, Jonathan Adam Hensel

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LL-37 is the only cathelicidin-derived anti-microbial peptide in humans and has been shown to stimulate proliferation, angiogenesis, cellular migration and inhibit apoptosis, in addition to serving as a chemoattractant for leukocytes. It is produced primarily by epithelial cells and leukocytes, and has recently been discovered to be over-expressed in breast, ovarian and lung cancers. Based on these findings, we compared levels of LL-37 expression in benign and cancerous human prostate tissues. Results of this investigation demonstrated that LL-37 is increasingly over-expressed in primary prostate tumors in a grade dependent manner and in metastatic lesions. Since the physiological mechanisms of LL-37 …

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Protein Modifications And The Response To Oxidized Lipids In Cardiovascular Cells, Ashlee Higdon Jan 2011

Protein Modifications And The Response To Oxidized Lipids In Cardiovascular Cells, Ashlee Higdon

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Free radical catalyzed oxidation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid is increased in cardiovascular disease states, including atherosclerosis and heart failure. Oxidized lipids have been extensively studied and found to recapitulate several key steps in atherogenesis. However, clinical trials with antioxidants such as alpha-tocopherol have been less promising than originally predicted. Now appreciated as more than just biomarkers of disease, lipid peroxidation products have been shown to have roles in pathogenesis as well as physiology. Of particular interest are reactive lipid species that possess electrophilic carbonyls enabling them to act in a receptor-independent manner. To date, the …

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The Role Of Cd19 In Follicular Dendritic Cell Activation, Riley Croom Myers Jan 2011

The Role Of Cd19 In Follicular Dendritic Cell Activation, Riley Croom Myers

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Germinal Centers (GC) are organized foci in secondary lymphoid organs of birds and mammals and are the principle sites of memory B cell generation and plasma cell formation. GC concentrate antigen within follicles to facilitate recognition by responding B cells to promote somatic hypermutation and affinity maturation. Follicular dendritic cells (FDC) reside within the light zones of GC and serve to facilitate B cell interactions with antigen, as well as B cell selection, proliferation, and survival. The work contained within this dissertation addresses the collaborative interactions between B cells and FDC. FDC within an active, GC-containing follicle express an array …

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Developing A Screen To Identify Small Molecule Inhibitors That Disrupt Protein-Protein Interactions In Mycobacteria, Deborah Mai Jan 2010

Developing A Screen To Identify Small Molecule Inhibitors That Disrupt Protein-Protein Interactions In Mycobacteria, Deborah Mai

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Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) and infects nearly one-third of the world's population. The same TB chemotherapeutic regimen has been administered for more than 50 years, and can be improved by developing innovative methods to discover new anti-TB drugs. This work describes a newly established high-throughput screen (HTS) platform technology based on Mycobacterial-Protein Fragment Complementation (M-PFC) to identify small molecule inhibitors of protein-protein interactions in mycobacteria. M-PFC HTS employs both whole cell and target-based approaches, and offers flexibility in selecting an appropriate protein interaction target for HTS. Selectable drug targets can include interactions of essential …

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