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Articles 1 - 30 of 53
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 …
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
All ETDs from UAB
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
All ETDs from UAB
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
All ETDs from UAB
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 …
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 …
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
All ETDs from UAB
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 …
Role Of Endogenous Tau In Lewy-Like Pathology, Lindsay Stoyka
Role Of Endogenous Tau In Lewy-Like Pathology, Lindsay Stoyka
All ETDs from UAB
Lewy Body Diseases (LBDs) are a group of disorders characterized by intracellular inclusions of misfolded alpha-synuclein (α-synuclein). Of these, Parkinson’s Disease (PD) is the most common neurodegenerative movement disorder, and Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative dementia. PD is characterized clinically by bradykinesia, resting tremor, rigidity, and postural instability. In addition, up to 80% of patients eventually develop dementia, termed Parkinson’s Disease Dementia (PDD). DLB is characterized by onset of dementia before or concurrently with parkinsonism. Currently, no disease-modifying therapies exist for either of these diseases. Lewy pathology is found in regions important for cognition …
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
All ETDs from UAB
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 …
Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould
Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould
All ETDs from UAB
Vesicular stomatitis virus (VSV) is a member of the order Mononegavirales, which is comprised of viruses with genomes of non-segmented negative sense RNA. Many fundamental insights into the molecular biology of mononegaviruses were first made in VSV, such as the unique viral RNA synthesis template comprised of the nucleocapsid (N) protein and genomic RNA and the distinctive large (L) protein which contributes all enzymatic activities of RNA synthesis and transcript maturation. The L protein performs its enzymatic functions in concert with the phosphoprotein (P), a flexible, charged, and phosphorylated cofactor. The goal of the research presented in this dissertation was …
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
All ETDs from UAB
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 …
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
All ETDs from UAB
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 …
The Role Of Neutrophils In Chronic Heart Failure, Sergey Antipenko
The Role Of Neutrophils In Chronic Heart Failure, Sergey Antipenko
All ETDs from UAB
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 …
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, …
Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang
Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang
All ETDs from UAB
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 …
Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel
Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel
All ETDs from UAB
Aspergillus fumigatus is an environmental airborne fungus that acts as both an opportunistic pathogen and an allergen. In immunocompromised hosts, A. fumigatus can germinate in the lung, cause tissue damage and pneumonia, and disseminate to other organs, causing a disease termed invasive aspergillosis (IA). In severe asthma, sensitization to fungi such as A. fumigatus is associated with more severe disease. Determination of host and fungal factors that drive immunoprotection versus immunopathogenesis in both of these settings will ultimately enable therapeutic modulation of immune responses to improve disease outcomes. In this body of work, we build on recent findings that implicate …
Diurnal Dysfunction In Control Of Sodium Excretion In Diet-Induced Obesity, Reham Soliman
Diurnal Dysfunction In Control Of Sodium Excretion In Diet-Induced Obesity, Reham Soliman
All ETDs from UAB
The renal endothelin system plays a key role in sodium excretion, particularly under high salt (HS) diet. HS stimulates renal endothelin-1 (ET-1), which binds and activates the endothelin receptor B (ETB) to excrete the excess salt. Loss of ETB receptor is linked to the development of hypertension under HS. Central clock genes are important in maintaining rhythmic patterns of sodium excretion and ET-1 is identified as a target for clock genes, including Period and Bmal1. ET-1 excretion follows a diurnal rhythm along with sodium excretion. Sexual dimorphism is evident in the diurnal regulation of endothelin-mediated natriuresis and its downstream targets. …
Mitochondrial Priming Of Tumor Initiating Cells Involves Repression Of Mitochondrial Fission Activity Towards Redox Regulation Of The Cell Cycle Regulator Cyclin E, Brian Spurlock
All ETDs from UAB
Mitochondrial dynamics primarily refers to the opposing fission or fusion events between individual mitochondria, which maintains steady-state mitochondrial morphology in cells. Fission and fusion activities maintain the energetics of normal and neoplastic stem cells. We developed the novel approach mito-SinCe2 to study the bidirectional relationship between mitochondrial dynamics and energetics. Application of this method led to the hypothesis that mitochondria-dependent ovarian tumor initiating cells interconvert between 3 states with distinct mitochondrial energetics/dynamics relationships. Cells in one state, characterized by high mitochondrial ROS and low fission activity, appear to be primed for self-renewal by mitochondria. We call these cells mitochondria-primed stem …
Toxin Secretion By Mycobacterium Tuberculosis, Uday Tak
Toxin Secretion By Mycobacterium Tuberculosis, Uday Tak
All ETDs from UAB
Mycobacterium tuberculosis (Mtb) is a highly infectious airborne bacterial pathogen, and the causative agent of human tuberculosis. Mtb infects approximately one-third of the human population, and is responsible for more deaths than any other infectious disease in the history of mankind. Mtb is an intracellular pathogen and primarily infects myeloid cells, such as macrophages in the human lung. In macrophages, Mtb establishes a replication niche within membrane-bound vacuoles named phagosomes, while subverting immunity. The intracellular survival of Mtb depends on manipulation of host cellular processes through secreted effector proteins. Ultimately, this intracellular vacuole is ruptured by the type VII secretion …
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
All ETDs from UAB
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 …
Abnormalities In The Akt-Mtor Signaling Pathway In The Dorsolateral Prefrontal Cortex In Schizophrenia, Radhika Chadha
Abnormalities In The Akt-Mtor Signaling Pathway In The Dorsolateral Prefrontal Cortex In Schizophrenia, Radhika Chadha
All ETDs from UAB
Schizophrenia (SZ) is a complex and heterogeneous mental illness in which myriad changes across multiple neurotransmitter systems (dopamine, serotonin, GABA, glutamate, and others) have been reported. Numerous regulatory mechanisms have been explored in SZ research and rather than being a disorder of one specific neurotransmitter pathway, SZ may instead be a disturbance of intracellular signaling processes that underlie the regulation of these systems. The AKT-mTOR signaling cascade plays an important role in core cellular processes of cell growth, metabolism and survival and is one such potential candidate. Abnormalities in AKT expression and activity have been consistently implicated in SZ pathophysiology …
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby
All ETDs from UAB
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 …
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 …
Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis
Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis
All ETDs from UAB
Circadian rhythms are biological processes that cycle every ~24 hours and have allowed life to adapt for optimal function across the day. These rhythms are present in all tissues in the body and are coordinated to the light/dark cycle by the suprachiasmatic nucleus (SCN) in the hypothalamus. Along with active-rest cycles, cognitive performance fluctuates across the course of the day, peaking during the active phase. In addition to the light cycle, food and meal timing can provide signaling cues to extra-SCN tissues. Food access only during the inactive phase results in weight gain and memory impairment. High fat diet protocols …
Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo
Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo
All ETDs from UAB
Genomic enhancers are cis-regulatory elements in the DNA that exhibit spatial and temporal control over intricate gene expression programs shaping fate and function of heterogeneous cell populations in the developing and adult brain. In addition to their role in cellular development and maintenance, enhancer activity drives transcriptional changes in response to stimulation. Active enhancers are subject to bidirectional transcription that yields non-coding enhancer RNAs (eR-NAs). However, the functional role of eRNAs in transcriptional regulation remains controversial. Therefore, we used primary neuronal cultures to investigate en-hancers and eRNAs in the rat genome. We identified and verified enhancer-gene pairs, characterized their response …
Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly
Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly
All ETDs from UAB
Parkinson’s disease (PD) is an age-related, progressive, movement disorder pathologically characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of proteinaceous aggregates, termed Lewy bodies, that are largely comprised of αSynuclein (αSyn). Missense mutations in the leucine-rich repeat kinase (LRRK2) gene are the most common genetic cause of PD and lead to gain-of-function increases in kinase activity. The G2019S-LRRK2 mutation is the most frequent mutation and elevates kinase activity by ~2-3 fold. Genetic and biochemical evidence suggest elevated LRRK2 kinase activity plays a pathogenic role in the development of PD, implicating LRRK2 …
Deficiency Of Tumor Suppressor Merlin Induces Metabolic Reprogramming In Breast Cancer, Mateus Mota
Deficiency Of Tumor Suppressor Merlin Induces Metabolic Reprogramming In Breast Cancer, Mateus Mota
All ETDs from UAB
The tumor suppressor Merlin is encoded by Neurofibromin 2 (NF2) gene. Merlin is predominantly located in the cell cortex where regulates cell proliferation by mediating cell contact-dependent growth inhibition. Metastatic breast cancer tissues presented with a remarkable loss of Merlin protein, revealing clinical relevance of Merlin. In order to examine the cellular effect of Merlin deficiency, breast cancer cell lines were silenced for NF2. Additionally, to assess the impact of Merlin loss at the organismal level, a mammary-specific NF2 knockout mouse mammary tumor model was engineered. Merlin deficiency induced a metabolic shift from mitochondrial oxidative phosphorylation to aerobic glycolysis. Furthermore, …
Understanding The Impact Of Diet And Obesity On Anti-Tumor Immunity And Therapeutic Efficacy In Kidney Cancer, Rachael Miller Orlandella
Understanding The Impact Of Diet And Obesity On Anti-Tumor Immunity And Therapeutic Efficacy In Kidney Cancer, Rachael Miller Orlandella
All ETDs from UAB
Obesity is regarded as a major risk factor for developing renal cell carcinoma (RCC). Advanced-stage RCC exhibits chemotherapeutic resistance, but is responsive to immunotherapies such as the immune checkpoint inhibitor anti-programmed cell death-1 (anti-PD-1). Despite some clinical successes, response rates remain low for anti-PD-1 monotherapy (20-30%). Preclinical evaluations of immunotherapeutic strategies typically use lean mice and do not account for patient comorbidities. This may explain the underwhelming success rates following clinical translation of new cancer treatments. Recent studies found that obesity was associated with favorable outcomes and responses to immunotherapy in melanoma. However, the effects of obesity on anti-tumor immunity …
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
All ETDs from UAB
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. …
Novel Mechanisms Of Nitric Oxide Activation In The Kidney, Randee Sedaka
Novel Mechanisms Of Nitric Oxide Activation In The Kidney, Randee Sedaka
All ETDs from UAB
Globally, adult sodium consumption has far exceeded daily intake recommendations, leading to one in ten cardiovascular deaths. Given the rise in hypertension prevalence, uncontrolled hypertension with antihypertensive medication use, and significant associations between high salt intake and high blood pressure, there is a need to better understand the mechanisms involved in hypertension. Nitric oxide synthase 1 (NOS1) is a well-established regulator of fluid and electrolyte balance in the renal collecting duct (CD) with highest activity in the inner medulla (IM). We previously reported that high salt (HS) intake stimulates CD endothelin B receptor (ETBR)/NOS1-dependent generation of NO, thereby inhibiting the …