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Full-Text Articles in Medicine and Health Sciences
Dopamine-Dependent Transcriptional Dynamics In Striatal Physiology And Cocaine Reward, Morgan Elizabeth Zipperly
Dopamine-Dependent Transcriptional Dynamics In Striatal Physiology And Cocaine Reward, Morgan Elizabeth Zipperly
All ETDs from UAB
Exposure to drugs of abuse alters transcriptional programs and neuronal activity, leading to long-lasting cellular and behavioral adaptations that may contribute to addiction. The nucleus accumbens (NAc), part of the mesocorticolimbic dopamine pathway, plays a central role in motivation, reward, and reward-related learning, and this brain region is highly implicated in the development and maintenance of addiction. However, the specific contributions of defined cell populations in the NAc to drug reward processes is still poorly understood. Here, we used electrophysiological, optogenetic, and single-nucleus RNA-sequencing (snRNA-seq) approaches in a rodent model system to define the acute physiological and transcriptional responses of …
Noninvasive Neuromodulation Using A Benchtop Approach To Mri-Guided Focused Ultrasound Blood Brain Barrier Opening, Megan Rich
All ETDs from UAB
Fundamental neuroscience research has provided a deeper understanding of the genes, molecules and cellular circuitry involved in neurological disorders, however translating discovery into clinical application remains a major challenge. This bench to bedside gap is in part due to the discrepancy in techniques used in the laboratory vs. the clinic for targeting the mechanisms that underlie disease. Ideally this discrepancy would be resolved not only by implementing novel clinical techniques to provide more precise targeting of disease foci, but also by using the same techniques in the clinic that are used at the lab bench to provide a direct bench …
Structural And Biophysical Investigations Into The Mechanism Of Hiv-1 Envelope Incorporation, Richard Elliot Murphy
Structural And Biophysical Investigations Into The Mechanism Of Hiv-1 Envelope Incorporation, Richard Elliot Murphy
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Recent advancements in drug therapies and patient care have drastically improved upon the mortality rates of HIV-1 infected individuals. Many of these therapies were developed or improved upon using structure-based techniques, which underscores the importance of obtaining atomic level structural data critical to the understanding of essential mechanisms in the replication cycle of HIV-1. One such process which remains poorly understood on the structural level is the incorporation of the envelope glycoprotein (Env) into budding virus particles. The Env protein mediates viral infection of host cells, and there is strong evidence suggesting that incorporation of Env is mediated by an …
Molecular Regulation Of Glioblastoma Spatial Heterogeneity And Therapeutic Resistance, Soniya Bastola
Molecular Regulation Of Glioblastoma Spatial Heterogeneity And Therapeutic Resistance, Soniya Bastola
All ETDs from UAB
Glioblastoma multiforme (GBM) is a highly invasive, highly vascularized, and heterogeneous malignant tumor of the brain. Due to the highly infiltrative phenotype of GBM, surgery often leaves behind residual tumor cells. In many cases, recurrence occurs close to the surgical margin suggesting the role of these remaining cells in promoting tumor aggressiveness. Rapidly growing tumor creates subsequent hypoxic, and hypovascular core due to limited nutrients, whereas tumor cells in the leading edge have access to nutrients from vasculature enriched microenvironment. Studies have identified the cellular and molecular heterogeneity between the tumors in core and edge. Still, their mechanisms of intercellular …
Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen
Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen
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GENE–ENVIRONMENT INTERACTION IN PARKINSON DISEASE: THE GUT MICROBIOME ZACHARY D. WALLEN GENETICS, GENOMICS, AND BIOINFORMATICS ABSTRACTParkinson disease (PD) is a progressive neurodegenerative disease with no cure. Majority of cases are idiopathic, and the cause is unknown. Studies have been conducted in human and animals to identify PD risk factors, resulting in a list of genetic and environmental factors that modestly increases risk of PD. Still, no individual risk factor fully explains the cause of PD, and neither has the combination of these factors. Additional avenues of research are being investigated to find potential triggers of PD, and factors that might …
Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue
Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue
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With rapidly increasing novel discoveries of associations between genomic data and complex disease phenotypes, the translation of those associations into knowledge and the identification of critical molecular mechanisms are essential to guild clinical decisions such as the diagnosis of symptomatic individuals, the prediction of disease risk, reproductive genetic counseling, and determining pharmacogenetic profiles for treatment. To decipher the genome of complex diseases, gene-centric analyses focus on detecting molecular mechanisms lead by driver genetics variants, abnormally expressed genes and high-abundance proteins through gene module construction. Additionally, the gene module construction approaches implement systems biology analysis to reveal the causative co-expressed gene …
Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea
Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea
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The Ldb1:Isl1 LIM transcriptional complex is critical for endocrine pancreas development as well as b-cell terminal differentiation. These complexes have been shown to interact with various proteins to elicit transcriptional regulation in other tissues, yet few interactors have been identified in b-cells. Therefore, the objective of this dissertation was to identify interactors of Ldb1 and Isl1 and assess their contributions to endocrine pancreas development and function. Using a reversible crosslink immunoprecipitation (ReCLIP) and mass spectrometry (MS) strategy to isolate endogenous Ldb1 and/or Isl1 interacting protiens, SSBP3, Rnf20, and Rnf40 (E3 ubiquitin ligases) coregulators were identified. SSBP3 was found to interact …
Dna Methylation: A Mechanism For Sustained Alteration Of Kir4.1 Expression Following Central Nervous System Insult, Jessica Boni
Dna Methylation: A Mechanism For Sustained Alteration Of Kir4.1 Expression Following Central Nervous System Insult, Jessica Boni
All ETDs from UAB
Astrocytes are the most numerous cells in the brain and play a critical role in maintaining homeostatic extracellular potassium ([K+]e). Maintaining low [K+]e is essential for many cellular functions including maintenance of intensely negative resting membrane potentials in the central nervous system. This process is mediated, in part, by a glial-specific, inwardly rectifying potassium channel, Kir4.1. Underscoring the role of Kir4.1 in CNS functioning, genetic mutations in Kcnj10, the gene which encodes Kir4.1, causes seizures, ataxia and developmental disability in humans. Notably, loss of Kir4.1 protein and mRNA are consistently observed after CNS injury, and in a number of neurological …
Distinct Tissue Specific Functions Of Bone Marrow Regulatory T Cells, And Their Therapeudic Applications In Myeloid Neoplasms, Virginia Camacho
Distinct Tissue Specific Functions Of Bone Marrow Regulatory T Cells, And Their Therapeudic Applications In Myeloid Neoplasms, Virginia Camacho
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In the bone marrow, Regulatory T cells (Tregs) constitute nearly 30% of CD4+ T cells, a significantly higher ratio than other tissues. Although a few of the mechanisms by which Tregs regulate normal hematopoiesis have been elucidated, our understanding of this process during leukemogenesis is ex-tremely limited. In this work, we define how Tregs maintain and support the bone marrow microenvironment. We propose that the role of Tregs extends be-yond their canonical immuno-suppressive function and that these cells are re-quired to maintain healthy hematopoiesis. We have defined tissue-specific roles for Tregs in the bone marrow including the maintenance of hematopoietic …
Disease Specific Dysregulation Of Stat1 And Stat5 Activation In Mature Cd4+ And Cd8+ T Cells Influences Enhanced Kinetic Responses And Inflammation In Patients With Treatment-Naïve Relapsing Remitting Multiple Sclerosis (Rrms), Brandon Jay Pope
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Autoimmunity is propagated through the lack of effective mechanisms of central and peripheral tolerance. In relapsing remitting multiple sclerosis (RRMS), dysregulated adaptive immune cells have been shown to contribute to disease morbidity through the influence of immune-modulating cytokines in the peripheral blood. Interleukin-2 (IL-2) is a cytokine with several key functions in regulating homeostatic mechanisms within the human immune system. Interferon gamma (IFNγ) is a type II interferon that is needed for an effective response to intracellular bacteria infection through the actions of Th1 cells. IL-2 and IFNγ signaling occurs primarily through signal transducer and activator of transcription (STAT) activation. …
Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke
Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke
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Drug addiction is a chronic relapsing condition inflicting tremendous harm to individuals and society with ineffective treatment options available to most people. Drugs of abuse elevate dopamine levels in a brain region known as the nucleus accumbens (NAc), and activate gene programs considered essential for producing lasting synaptic and cell state changes which underlie the generation of addictive behavior. These gene expression changes remain poorly understood due to a complex heterogenous cellular architecture, and the rapidly fluctuating nature of the transcriptional processes themselves which make investigation difficult. Recent technical advances increase access to both profiling and manipulating these transcriptional changes …
Exploring The Roles Of Long Non-Coding Rnas In Glioblastoma Tumor Recurrence And Therapy Resistance, Christian Tyler Stackhouse
Exploring The Roles Of Long Non-Coding Rnas In Glioblastoma Tumor Recurrence And Therapy Resistance, Christian Tyler Stackhouse
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ABSTRACT Glioblastoma (GBM) is the most common and devastating primary CNS brain tumor with a median survival time of around 14 months. Most patients succumb to re-current disease which is often more malignant than the primary tumor and is frequently therapy resistant. There have not been significant advances in the treatment of GBM despite decades of research. This is partly due to the lack of accurate preclinical models and of the focus on primary rather than recurrent tumors. We created a 350 gene custom GBM-specific panel which contains 16 molecular signatures including molecular sub-typing signatures. We have demonstrated concordance of …
Exploring The Mechanism Of Cleavage And Secretion Of The Major Sperm Protein (Msp) Domain Of The Vapb/Vpr-1 Protein, Hala Zein-Sabatto
Exploring The Mechanism Of Cleavage And Secretion Of The Major Sperm Protein (Msp) Domain Of The Vapb/Vpr-1 Protein, Hala Zein-Sabatto
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VAPB is one of three mammalian VAP proteins. It is a type-II ER transmembrane protein whose N-terminal major sperm protein domain (MSPd) is cleaved and secreted. Since the MSPd faces the cytosol, rather than the ER lumen, how it is cleaved and secreted is not yet known. In humans, P56S is a substitution mutation within the VAPB protein that segregates with cases of familial Amyotrophic Lateral Sclerosis (ALS) and prevents the secretion of VAPB MSPd. The work described in this thesis uses C. elegans to study how the N-terminal MSPd of VAPB is proteolytically processed, secreted, and regulated. C. elegans …
From Pathology To Circuits: Loss Of Pink1 Function In Parkinson’S Disease, Rose Berthe Creed
From Pathology To Circuits: Loss Of Pink1 Function In Parkinson’S Disease, Rose Berthe Creed
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Parkinson’s disease (PD) is the most common neurogenerative motor disorder, affecting over 10 million people worldwide. Clinically, PD is diagnosed by presentation of hypokinetic movements such as bradykinesia, rigidity, and resting tremor. Additionally, PD patients have non-motor symptoms that include anosmia, constipation, and hypophonia. Current therapeutics have been successful in treating many of the locomotor symptoms, however no therapies stop or slow disease progression and the effectiveness of current medications diminishes as the symptoms invariably become more severe over the course of many years. Histopathologically, PD diagnosis is confirmed postmortem by two pathological hallmarks: 1. loss of dopaminergic neurons in …
Cd8 T-Cell Responses To A Diverse Virus: Adaptation And Cross-Reactivity In Hiv Vaccination, Sushma Boppana
Cd8 T-Cell Responses To A Diverse Virus: Adaptation And Cross-Reactivity In Hiv Vaccination, Sushma Boppana
All ETDs from UAB
In the four decades since human immunodeficiency virus (HIV) was discovered, significant progress has been made in treating HIV infection and in understanding the viral and immune dynamics underlying disease pathogenesis. However, in spite of scientific advances, HIV remains a significant global health issue, and an effective preventative vaccine has yet to be created. Many groups have demonstrated the importance of CD8 T cells in viral control during natural HIV infection and believe that CD8 T cells could contribute to vaccine efficacy by alleviating disease course in individuals who became infected despite vaccination. One major obstacle to inducing potent CD8 …
Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford
Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford
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The effective antibiotic pool is shrinking with antibiotic resistance a constant problem that threatens to make our current therapies obsolete. To combat this, new drug screening methodologies are required since the traditional drug screens are offering limited results or only improvements upon current treatments. This work expands upon the idea that transition metal toxicity can be preferentially targeted towards bacteria. Specifically, the focus is on copper dependent inhibitors that quickly work to eliminate Staphylococcus aureus. S. aureus is a particularly threatening bacteria with high strain variability, a litany of survival and virulence factors, and multiple drug resistance mechanisms that are …
Protective Effects Of Thioredoxin Reductase Inhibition In The Murine Lung: The Regulation And Contribution Of Heme Oxygenase-1, Katelyn Louise Dunigan
Protective Effects Of Thioredoxin Reductase Inhibition In The Murine Lung: The Regulation And Contribution Of Heme Oxygenase-1, Katelyn Louise Dunigan
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Endogenous antioxidant responses defend the lung against oxygen toxicity. In premature neonates, oxygen toxicity and impaired antioxidant defenses contribute to the development of bronchopulmonary dysplasia (BPD), the leading cause of long-term morbidity among premature infants. In adults, oxygen toxicity and impaired antioxidant defense contributes to the pathogenesis of acute lung injury (ALI). Acute Respiratory Distress Syndrome (ARDS), a severe form of ALI, can cause permeant lung damage and mortality. Our lab has established that pharmacologic thioredoxin reductase-1 (TXNRD1) inhibition attenuates lung injury in murine BPD and ALI models. The protective effects of TXNRD1 inhibition are mediated by the activation of …
Rna Polymerase I Elongation Kinetics: A Biochemical And Global Study Of A Cancer Therapeutic Target, Catherine Elizabeth Scull
Rna Polymerase I Elongation Kinetics: A Biochemical And Global Study Of A Cancer Therapeutic Target, Catherine Elizabeth Scull
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My graduate research has focused on understanding the elongation kinetics of RNA polymerase I (Pol I), the enzyme responsible for synthesizing ribosomal RNA (rRNA), and defining how inhibition of ribosome biogenesis may be used as a cancer therapeutic strategy. Here, I have defined key biophysical features of Pol I and I have expanded the field’s understanding of Pol I elongation by: 1) characterizing the enzymatic properties of Pol I by mutational analysis of the polymerase itself, and by 2) elucidating the role of DNA sequence on Pol I arrest and nucleolytic cleavage activity. In recent years, Pol I has become …
Contribution Of Adaptive Immune Responses In Chronic Lung Diseases, Thi Kim Tran-Nguyen
Contribution Of Adaptive Immune Responses In Chronic Lung Diseases, Thi Kim Tran-Nguyen
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Immune dysregulation is a hallmark of various chronic lung diseases such as Chronic Obstructive Pulmonary Diseases (COPD) and Idiopathic Pulmonary Fibrosis (IPF). Previous studies in our lab have shown evidences of autoimmunity such as increases in autoantibodies, abnormal T cell profile, immune complex deposition and the presence of ectopic lymphoid structures in the lung of these patients. This thesis consolidates two separate projects about various aberrant immune responses in these diseases. The first project identified Glucose-Regulated-Protein 78 (GRP78) as the common autoantigen in COPD and characterized how GRP78 autoantibodies may increase COPD mortality via its atherogenic effects. I demonstrated that …
C-Reactive Protein Subverts The Myeloid Lineage: Implications For Renal Injury, Rachel Jimenez
C-Reactive Protein Subverts The Myeloid Lineage: Implications For Renal Injury, Rachel Jimenez
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C-reactive protein (CRP) is an evolutionarily conserved pattern recognition molecule that was first characterized for its participation in the acute phase response to bacterial infection. In the last 90 years, knowledge of CRP biology in innate immunity has expanded significantly. CRP is known to bind and activate the classical pathway of complement, to opsonize bacteria and inflamed tissue, and to modulate myeloid cell functions. CRP is normally present in the blood at low levels with its biosynthesis and serum concentration rapidly rises upon systemic inflammation. For example, high levels of serum CRP are found following acute kidney injury (AKI) in …
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
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Glioblastoma (GBM) is the most common adult primary malignant brain tumor with a median survival of about 15 months, even after aggressive treatment. Treatment of GBM is difficult for multiple reasons including the location of the tumor, tumor invasiveness, and the high degree of both inter-and intra-tumoral heterogeneity. Contributing to intratumoral heterogeneity are highly tumorigenic, stem-like tumor cells, with the capacity to self-renew and propagate the tumor, termed brain tumor initiating cells (BTICs). BTICs are also commonly therapy resistant, highly invasive, and metabolically plastic with elevated expression of glucose transporter 3 (GLUT3) allowing them to preferentially survive in low nutrient …
The Role Of Neutrophils In Chronic Heart Failure, Sergey Antipenko
The Role Of Neutrophils In Chronic Heart Failure, Sergey Antipenko
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Acute myocardial infarction (MI) produces massive, sudden cardiomyocyte death, triggering an inflammatory and healing response that initially leads to scar formation and ultimately may induce progressive ischemic cardiomyopathy and heart failure (HF). Scar formation and left ventricular (LV) hypertrophy occur in response to MI to stabilize injury compensating for lost myocardial function. Over time, heart function can become decompensated due to neuroendocrine dysfunction and adverse LV remodeling, ultimately leading to HF. Adverse remodeling is characterized by continued dysregulated collagen deposition, cardiomyocyte hypertrophy, and increased inflammation. Studies have documented a resurgence in inflammatory cytokines and infiltrating leukocytes after resolution of the …
Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood
Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood
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Alpha-synuclein (αsyn) is the key component of proteinaceous aggregates termed Lewy Bodies (LBs) that pathologically define a group of disorders known as synucleinopathies, including Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn is thought to misfold and spread throughout the brain in a prion-like fashion. Transmission of αsyn necessitates the release of misfolded αsyn from one cell and the uptake of that αsyn by another, in which it templates the misfolding of endogenous αsyn. Identifying regulators of this process is essential to understanding how αsyn propagates and furthers disease progression. In this study, we investigated Rab27 and 14-3-3θ …
Circadian Clock And Lipid Metabolism Disruption In Fatty Liver Disease, Jennifer Valcin
Circadian Clock And Lipid Metabolism Disruption In Fatty Liver Disease, Jennifer Valcin
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Hepatic Steatosis, characterized by the accumulation of triglyceride (TG) in the liver is the first stage of Alcoholic Liver Disease (ALD) and Nonalcoholic Fatty Liver Disease (NAFLD). Many metabolic pathways, including lipid metabolism, are regulated by the molecular circadian clock. Importantly, alcohol consumption and obesity induce circadian clock disruption, a risk factor for many diseases, including liver disease. In our first study, we investigated the combined effect of clock disruption and alcohol feeding on liver pathology, and diurnal rhythms in the liver molecular clock and lipid metabolism. Male liver-specific Bmal1 knockout (LKO) mice and control littermates were fed a control …
Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk
Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk
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Alzheimer’s disease (AD) is the leading neurodegenerative disorder that affects an astonishing 5.8 million Americans, a number projected to reach 14 million by the year 2050. While only about 1% of all AD cases are caused by mutations in APP, PSEN1, and PSEN2, the cause of sporadic AD remains unknown. Variations in several risk genes have been proposed to contribute to the development of sporadic AD cases. Since, currently, there are no disease-modifying therapies for families affected by AD and multiple anti-amyloid-beta therapies failed in clinical trials, determining how these risk genes contribute to the development of AD is crucial …
The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman
The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman
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Differentiation of pre-osteoblasts is critical to controlling in-vivo development and growth of bone. Recent studies highlight the importance of epigenetic regulation in directing osteoblast commitment and function. Here we show that the microRNA-23a cluster (miR-23a, 27a, and 24-2) controls bone mass in-vivo through a previously unknown epigenetic mechanism. MiR-23a cluster knockdown increased the intensity of Alkaline Phosphatase staining in MC3T3-E1 cells. Additionally, it upregulated mRNA expression of osteogenic marker genes such as Runx2 and Osteocalcin. Micro-CT analysis of 2-month and 6-month femurs showed that trabecular bone volume and trabecular number significantly increased in miR-23aClZIP mice as compared to controls. Histological …
T Cells In Synucleinopathies, Gregory Paul Williams
T Cells In Synucleinopathies, Gregory Paul Williams
All ETDs from UAB
Synucleinopathies, which include Parkinson disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA), are a collection of neurodegenerative diseases that are in major part defined by the presence of alpha-synuclein (α-syn) rich protein aggregates in the brain. Increasing evidence has highlighted a neuroinflammatory phenotype also associated with these synucleinopathies. This neuroinflammatory phenotype includes the activation of central nervous system (CNS) microglia, increased pro-inflammatory cytokines, and the infiltration of peripheral T cells into the CNS. We sought to further explore the T cell responses associated with PD and MSA. Using two preclinical mouse models of PD and MSA, …
The Role Of The Viral Envelope Protein Gpul132 In Assembly Compartment Formation And Virion Production: Intracellular Lipids And/Or Cholesterol, Hui Wu
All ETDs from UAB
Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects over 50% of the world’s population. HCMV infection is asymptomatic in healthy individuals, however can cause severe morbidity and mortality in individuals with compromised innate or adaptive immunity. As a complex virus that has been known for about 70 years, we are still in search of vaccines or effective treatments against it. HCMV genome encodes over 175 open reading frames with the function of majority proteins remains to be defined. A unique feature of HCMV among herpesvirus is the reorganization of cellular secretory pathway and membranes to form assembly compartment (AC). …
Co-Factors In Fgf Signaling, Christopher Yanucil
Co-Factors In Fgf Signaling, Christopher Yanucil
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The fibroblast growth factor (FGF) family consists of a group of proteins whose diverse biological functions are mediated by receptor tyrosine kinases, termed FGF receptors (FGFR) 1-4. While paracrine FGFs require heparin sulfate as a co-factor for FGFR bind-ing and signaling, it has been assumed that endocrine FGFs, such as FGF23, do not bind heparin but instead require klotho, a family of transmembrane proteins, as a co-receptor on specific target cells. FGF23 acts as bone-derived hormone that targets tubular epitheli-al cells in the kidney via FGFR1 and α-klotho to reduce renal phosphate uptake. In chron-ic kidney disease (CKD), the kidney …
Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang
Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang
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Many physiological processes, including blood pressure (BP) regulation, follow specific rhythms tied to a 24-h cycle. This is largely because circadian genes operate in virtually every cell type in the body. In healthy individuals, BP during nighttime is 10-20% lower compared to daytime, a phenomenon known as “nocturnal dipping”. It is acknowledged that the dipping of BP is essential in maintaining normal cardiovascular and renal function. However, it remains unclear as to what factors contribute to nocturnal dipping. The purpose of this dissertation is to elucidate mechanisms underlying the circadian rhythm of BP. Bmal1 is one of the core circadian …