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Porcine Reproductive And Respiratory Syndrome Virus Reverse Genetics And The Major Applications, Jayeshbhai Chaudhari, Hiep Vu Jan 2020

Porcine Reproductive And Respiratory Syndrome Virus Reverse Genetics And The Major Applications, Jayeshbhai Chaudhari, Hiep Vu

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the late 1980s and became endemic in most swine producing countries, causing substantial economic losses to the swine industry. The first reverse genetics system for PRRSV was reported in 1998. Since then, several infectious cDNA clones for PRRSV have been constructed. The availability of these infectious cDNA clones has facilitated the genetic modifications of the viral genome at precise locations. Common approaches to manipulate the viral genome include site-directed mutagenesis, deletion of viral genes or …


An Evidence For Surface Expression Of An Immunogenic Epitope Of Sarcoplasmic/Endoplasmic Reticulum Calcium-Atpase2a On Antigen-Presenting Cells From Naive Mice In The Mediation Of Autoimmune Myocarditis, Rajkumar Arumugam, Bharathi Yalaka, Chandirasegara Massilamany, Ms Shihabudeen Haider Ali, Ninaad Lasrado, Sabarirajan Jayaraja, Jean-Jack Riethoven, Xinghui Sun, Jay Reddy Jan 2020

An Evidence For Surface Expression Of An Immunogenic Epitope Of Sarcoplasmic/Endoplasmic Reticulum Calcium-Atpase2a On Antigen-Presenting Cells From Naive Mice In The Mediation Of Autoimmune Myocarditis, Rajkumar Arumugam, Bharathi Yalaka, Chandirasegara Massilamany, Ms Shihabudeen Haider Ali, Ninaad Lasrado, Sabarirajan Jayaraja, Jean-Jack Riethoven, Xinghui Sun, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

We recently reported identification of sarcoplasmic/endoplasmic reticulum calcium-ATPase2a (SERCA2a) 971–990, which induces atrial myocarditis by generating autoreactive T cells in A/J mice. However, it was unknown how antigen-sensitized T cells could recognize SERCA2a 971–990, since SERCA2a-expression is confined to an intracellular compartment. In this report, we present evidence that antigen-presenting cells (APCs) from lymphoid and non-lymphoid organs in naïve animals present SERCA2a 971–990 and stimulate antigen-specific T cells. Using major histocompatibility complex (MHC) class II dextramers for SERCA2a 971–990, we created a panel of T cell hybridomas and demonstrated that splenocytes from naïve A/J mice stimulated the hybridoma cells without …


Viral Myocarditis Involves The Generation Of Autoreactive T Cells With Multiple Antigen Specificities That Localize In Lymphoid And Non-Lymphoid Organs In The Mouse Model Of Cvb3 Infection, Rakesh H. Basavalingappa, Rajkumar Arumugam, Ninaad Lasrado, Bharathi Yalaka, Chandirasegara Massilamany, Arunakumar Gangaplara, Jean-Jack Riethoven, Shi-Hua Xiang, David Steffen, Jay Reddy Jan 2020

Viral Myocarditis Involves The Generation Of Autoreactive T Cells With Multiple Antigen Specificities That Localize In Lymphoid And Non-Lymphoid Organs In The Mouse Model Of Cvb3 Infection, Rakesh H. Basavalingappa, Rajkumar Arumugam, Ninaad Lasrado, Bharathi Yalaka, Chandirasegara Massilamany, Arunakumar Gangaplara, Jean-Jack Riethoven, Shi-Hua Xiang, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Autoreactive T cells may contribute to post-viral myocarditis induced with Coxsackievirus B3 (CVB3), but the underlying mechanisms of their generation are unclear. Here, we have comprehensively analyzed the generation of antigen-specific, autoreactive T cells in the mouse model of CVB3 infection for antigens implicated in patients with myocarditis/dilated cardiomyopathy. First, comparative analysis of CVB3 proteome with five autoantigens led us to identify three mimicry epitopes, one each from adenine nucleotide translocator 1 (ANT), sarcoplasmic/ endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and cardiac troponin I. None of these induced cross-reactive T cell responses. Next, we generated major histocompatibility complex (MHC) class …


Spatial Memory And Executive Functioning In The Goto-Kakizaki Rat Model Of Diabetes, Lorielle Dietze Jan 2020

Spatial Memory And Executive Functioning In The Goto-Kakizaki Rat Model Of Diabetes, Lorielle Dietze

Theses and Dissertations (Comprehensive)

Type 2 diabetes mellitus is a disease that adversely affects cognitive function in areas extending to memory and executive functioning. The Goto-Kakizaki (GK) rat provides a model of type 2 diabetes that can illustrate the mechanisms by which this disease works. The present study compared hyperglycaemic GK rats and age-matched Wistar rats in the Morris water maze to assess spatial memory, and in a perceptual attentional set-shifting task to assess putative prefrontal-dependent executive functioning. Results showed there was no difference in path length during training trials, however, GK and Wistar rats differed in the path length travelled in the target …


Law, Structural Racism, And The Covid-19 Pandemic, Ruqaiijah Yearby, Seema Mohapatra Jan 2020

Law, Structural Racism, And The Covid-19 Pandemic, Ruqaiijah Yearby, Seema Mohapatra

All Faculty Scholarship

Racial and ethnic minorities have always been the most impacted by pandemics because of: disparities in exposure to the virus; disparities in susceptibility to contracting the virus; and disparities in treatment. This article explains how structural racism, the ways in which laws are used to advantage the majority and disadvantage racial and ethnic minorities, has caused these disparities. Specifically, this article focuses on how employment, housing, health care, and COVID-19 relief laws have been manipulated to disadvantage racial and ethnic minorities, making minorities more susceptible to COVID-19 infection and death. This article uses Blumenshine’s 2008 framework to outline how structural …


The Influence Of Polycyclic Aromatic Hydrocarbons In Fcgriib -/- Lupus Mice, Kanyarat Udompornpitak Jan 2020

The Influence Of Polycyclic Aromatic Hydrocarbons In Fcgriib -/- Lupus Mice, Kanyarat Udompornpitak

Chulalongkorn University Theses and Dissertations (Chula ETD)

The activation of aryl hydrocarbon receptor (Ahr) through polycyclic aromatic hydrocarbons (PAHs), the major components of particulate matter at 2.5 micron (PM2.5) in the polluted air, might aggravate inflammation and lupus activity. Hence, 1,4-chrysenequinone (1,4-CQ), a substance in the PAHs group, was tested in a lupus model from FcgRIIb deficiency (FcgRIIb-/-) using macrophages and mice. Although the activation by 1,4-CQ alone was unable to induce inflammation, the pre-conditioning by lipopolysaccharide (LPS), a representative inflammatory-activator, before 1,4-CQ (LPS/1,4-CQ) induced more predominant inflammation in macrophages when compared with LPS or 1,4-CQ activation alone as determined by supernatant cytokines (TNF-α, IL-6 and IL-10). …


Molecular Detection Of Viable Mycobacterium Tuberculosis Complex In Clinical Specimens, Suthidee Petsong Jan 2020

Molecular Detection Of Viable Mycobacterium Tuberculosis Complex In Clinical Specimens, Suthidee Petsong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Tuberculosis (TB) is the global health concern because of the rising incidence and mortality. TB is caused by Mycobacterium tuberculosis complex (MTBC) and transmitted via inhalation of infectious droplet nuclei circulating in the air. The World Health Organization (WHO) recommends the use of Acid-fast (AFB) smear microscopy, MTBC culture, and molecular detection of MTBC DNA for diagnosis of TB. The response to treatment should be acquired as soon as possible to reduce disease transmission and drug resistance. Although MTBC culture is a gold standard, it is laborious, expensive, and may take up to 8 weeks. The AFB staining and molecular …


ความรอบรู้ด้านอาชีวอนามัยของบุคลากรในโรงพยาบาลแห่งหนึ่งในสังกัดกรุงเทพมหานคร, วีรนุช เชาวกิจเจริญ Jan 2020

ความรอบรู้ด้านอาชีวอนามัยของบุคลากรในโรงพยาบาลแห่งหนึ่งในสังกัดกรุงเทพมหานคร, วีรนุช เชาวกิจเจริญ

Chulalongkorn University Theses and Dissertations (Chula ETD)

การวิจัยนี้เป็นการศึกษาเชิงพรรณนาภาคตัดขวาง วัตถุประสงค์เพื่อศึกษาความรอบรู้ด้านอาชีวอนามัย และปัจจัยที่มีความสัมพันธ์กับความรอบรู้ด้านอาชีวอนามัยของบุคลากรในโรงพยาบาลแห่งหนึ่งในสังกัดกรุงเทพมหานคร กลุ่มตัวอย่างคือบุคลากรในโรงพยาบาล จำนวน 415 คน คัดเลือกด้วยการสุ่มตัวอย่างแบบชั้นภูมิตามสัดส่วนของตำแหน่งงาน เก็บข้อมูลโดยใช้แบบประเมินความรอบรู้ด้านอาชีวอนามัยของบุคลากรในโรงพยาบาลแบบตอบด้วยตนเอง ซึ่งได้รับการตรวจสอบคุณภาพโดยการตรวจสอบความเที่ยงตรงเชิงเนื้อหาด้วยวิธีการหาค่าดัชนีความสอดคล้อง มีคะแนนอยู่ในช่วง 0.60-1.00 และการตรวจสอบความเชื่อมั่นด้วยการหาสัมประสิทธิ์แอลฟาของครอนบาค พบความเชื่อมั่นรายด้านอยู่ที่ 0.81-0.93 และทั้งฉบับอยู่ที่ 0.96 วิเคราะห์ข้อมูลด้วยสถิติเชิงพรรณนาและสถิติถดถอยพหุคูณ ผลการศึกษาพบว่ากลุ่มตัวอย่างมีความรอบรู้ด้านอาชีวอนามัยอยู่ในระดับปานกลาง โดยมีคะแนนเฉลี่ยร้อยละ 72.41 รายด้านที่มีคะแนนสูงที่สุดคือการจัดการสุขภาพของตนเองด้านอาชีวอนามัย (ร้อยละ 74.53) และรายด้านที่คะแนนน้อยที่สุดคือทักษะการสื่อสารข้อมูลด้านอาชีวอนามัย (ร้อยละ 67.27) ปัจจัยที่มีความสัมพันธ์กับความรอบรู้ด้านอาชีวอนามัยที่ดี ได้แก่ เพศหญิง (p-value=0.011) อายุไม่เกิน 45 ปี (p-value<0.001) ไม่มีการทำงานเป็นกะหรือทำงานล่วงเวลา (p-value=0.029) มีประวัติการอบรมด้านอาชีวอนามัย (p-value=0.002) มีนโยบายด้านอาชีวอนามัยและความปลอดภัย (p-value<0.001) และมีการสนับสนุนที่ดีจากหน่วยงาน (p-value=0.011) โดยสรุปการเสริมสร้างความรอบรู้ด้านอาชีวอนามัยให้กับกลุ่มบุคลากรในโรงพยาบาลควรเน้นเรื่องทักษะการสื่อสารข้อมูลด้านอาชีวอนามัย การจัดบริการด้านอาชีวอนามัยให้เหมาะสมกับกลุ่มบุคลากร การจัดอบรมการวางแผนงานนโยบายด้านอาชีวอนามัย รวมถึงให้การสนับสนุนอย่างต่อเนื่อง เพื่อให้บุคลากรสามารถพัฒนาสมรรถนะการดำเนินงานด้านอาชีวอนามัยได้อย่างปลอดภัยและมีประสิทธิภาพ


Mechanisms Of Value-Biased Prioritization In Fast Sensorimotor Decision Making, Kivilcim Afacan-Seref Jan 2020

Mechanisms Of Value-Biased Prioritization In Fast Sensorimotor Decision Making, Kivilcim Afacan-Seref

Dissertations and Theses

In dynamic environments, split-second sensorimotor decisions must be prioritized according to potential payoffs to maximize overall rewards. The impact of relative value on deliberative perceptual judgments has been examined extensively, but relatively little is known about value-biasing mechanisms in the common situation where physical evidence is strong but the time to act is severely limited. This research examines the behavioral and electrophysiological indices of how value biases split-second perceptual decisions and the possible mechanisms underlying the process. In prominent decision models, a noisy but statistically stationary representation of sensory evidence is integrated over time to an action-triggering bound, and value-biases …


Classify Multicategory Outcome In Patients With Lung Adenocarcinoma Using Clinical, Transcriptomic And Clinico-Transcriptomic Data: Machine Learning Versus Multinomial Models, Fei Deng, Lanlan Shen, He Wang, Lanjing Zhang Jan 2020

Classify Multicategory Outcome In Patients With Lung Adenocarcinoma Using Clinical, Transcriptomic And Clinico-Transcriptomic Data: Machine Learning Versus Multinomial Models, Fei Deng, Lanlan Shen, He Wang, Lanjing Zhang

Children’s Nutrition Research Center Staff Publications

Classification of multicategory survival-outcome is important for precision oncology. Machine learning (ML) algorithms have been used to accurately classify multi-category survival-outcome of some cancer-types, but not yet that of lung adenocarcinoma. Therefore, we compared the performances of 3 ML models (random forests, support vector machine [SVM], multilayer perceptron) and multinomial logistic regression (Mlogit) models for classifying 4-category survival-outcome of lung adenocarcinoma using the TCGA. Mlogit model overall performed similar to SVM and multilayer perceptron models (micro-average area under curve=0.82), while random forests model was inferior. Surprisingly, transcriptomic data alone and clinico-transcriptomic data appeared sufficient to accurately classify the 4-category survival-outcome …


Prognostic Role Of Homeostasis Model Assessment And Oral Glucose Tolerance Test Innondiabetic Patients With Bell's Palsy, Tuğba Karagöz, Ömer Bayir, Emel Çadalli Tatar, Erman Çakal, Ali̇ Özdek, Kemal Keseroğlu, Mustafa Şahi̇n, Mehmet Hakan Korkmaz Jan 2020

Prognostic Role Of Homeostasis Model Assessment And Oral Glucose Tolerance Test Innondiabetic Patients With Bell's Palsy, Tuğba Karagöz, Ömer Bayir, Emel Çadalli Tatar, Erman Çakal, Ali̇ Özdek, Kemal Keseroğlu, Mustafa Şahi̇n, Mehmet Hakan Korkmaz

Turkish Journal of Medical Sciences

Background/aim: We aimed to reveal the incidence and predictive role of insulin resistance and distorted oral glucose tolerance test in nondiabetic patients with Bell's Palsy (BP). Materials and methods: Eighty-six patients with BP and 28 control subjects; all with normal blood glucose levels and no history of diabetes, were enrolled in the study. We investigated insulin resistance (IR) in all subjects, in terms of HOMA-IR greater than 2.7. Sixtytwo of the patients also underwent an oral glucose tolerance test (OGTT). Results: The mean HOMA-IR value was significantly increased in patients, compared to the control group (3.2 vs 1.6; P < 0.01). IR was detected more in BP patients than in controls (P < 0.05). The patients with higher HOMA-IR values had more severe facial dysfunction at the initial presentation and complete recovery time took longer than the patients with normal HOMA-IR value (75 days vs 42 days; P < 0.05). Following a 2h-OGTT, impaired glucose tolerance and newly diagnosed DM were found in 60% of the patients. Recovery time was significantly longer in prediabetics and newly diagnosed diabetic patients than in patients with normal glycemia (68 days, 52 days, and 32 days, respectively; P < 0.01). Conclusion: There is a strong linkage between HOMA-IR value and BP prognosis so HOMA-IR value may have a significant role of predicting BP prognosis at presentation.


Baseline Characteristics Predicting Clinical Outcomes And Serious Adverse Events In Middle-Aged Hypertensive Women: A Subanalysis Of The Sprint In Women Aged, Volkan Aydin, Ahmet Akici, Si̇bel Sakarya, Mehmet Akman, Ali̇ Serdar Fak Jan 2020

Baseline Characteristics Predicting Clinical Outcomes And Serious Adverse Events In Middle-Aged Hypertensive Women: A Subanalysis Of The Sprint In Women Aged, Volkan Aydin, Ahmet Akici, Si̇bel Sakarya, Mehmet Akman, Ali̇ Serdar Fak

Turkish Journal of Medical Sciences

Background/aim: The predictability of clinical outcomes in hypertension in specific patient groups, especially underrepresented populations is the key to rational treatment. This study aimed to investigate the impact of baseline characteristics of


Association Between Monocyte To High-Density Lipoprotein Cholesterol Ratio And Bicuspid Aortic Valve Degeneration, Bi̇lge Duran Karaduman, Hüseyi̇n Ayhan, Telat Keleş, Engi̇n Bozkurt Jan 2020

Association Between Monocyte To High-Density Lipoprotein Cholesterol Ratio And Bicuspid Aortic Valve Degeneration, Bi̇lge Duran Karaduman, Hüseyi̇n Ayhan, Telat Keleş, Engi̇n Bozkurt

Turkish Journal of Medical Sciences

Background/aim: From a pathophysiological point of view, inflammation is thought to be more dominant in bicuspid aortic valve (BAV) stenosis than tricuspid aortic valve (TAV) stenosis. Our study aimed to determine the association between monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR), a new inflammatory marker, and the speed of progression of stenosis and pathophysiology of BAV stenosis.Materials and methods: A total of 210 severe aortic stenosis patients (70 consecutive BAV patients, 140 matched TAV patients) were retrospectively enrolled in the study. Clinical and echocardiographic data and laboratory results related to our research were collected retrospectively from the patients' records. …


Structural And Biophysical Investigations Into The Mechanism Of Hiv-1 Envelope Incorporation, Richard Elliot Murphy Jan 2020

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 …


Contribution Of Adaptive Immune Responses In Chronic Lung Diseases, Thi Kim Tran-Nguyen Jan 2020

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 …


Locus Coeruleus Degeneration In Alzheimer’S Disease And Its Effect On Beta-Adrenergic Signaling In The Hippocampus, Bethany Langner Jan 2020

Locus Coeruleus Degeneration In Alzheimer’S Disease And Its Effect On Beta-Adrenergic Signaling In The Hippocampus, Bethany Langner

All ETDs from UAB

Locus coeruleus (LC) degeneration in Alzheimer’s Disease (AD) and loss of noradrenergic (NA) innervation in hippocampus contributes to learning and memory deficits. Recently, a novel rat model (TgF344-AD) has been created that allows for a more thorough investigation into these mechanisms due to its similarity to human AD pathology. The McMahon lab has recently demonstrated heightened long-term potentiation (LTP) and a ‘supersensitivity’ of -adrenergic receptors (-ARs) at excitatory synapses in the dentate gyrus (DG) in TgF344-AD rats. These mechanisms could be responsible for maintaining learning and memory during buildup of AD pathology. The first goal of this Master’s thesis was …


Molecular Regulation Of Glioblastoma Spatial Heterogeneity And Therapeutic Resistance, Soniya Bastola Jan 2020

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 …


Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk Jan 2020

Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk

All ETDs from UAB

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 …


Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen Jan 2020

Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen

All ETDs from UAB

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 …


The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman Jan 2020

The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman

All ETDs from UAB

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 …


Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang Jan 2020

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 …


Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea Jan 2020

Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea

All ETDs from UAB

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 …


Distinct Tissue Specific Functions Of Bone Marrow Regulatory T Cells, And Their Therapeudic Applications In Myeloid Neoplasms, Virginia Camacho Jan 2020

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 …


Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis Jan 2020

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 …


Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould Jan 2020

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 …


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 Jan 2020

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. …


Noninvasive Neuromodulation Using A Benchtop Approach To Mri-Guided Focused Ultrasound Blood Brain Barrier Opening, Megan Rich Jan 2020

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 Jan 2020

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 …


Cd8 T-Cell Responses To A Diverse Virus: Adaptation And Cross-Reactivity In Hiv Vaccination, Sushma Boppana Jan 2020

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 …


Investigating The Behavioral Effects Of Juvenile Stress In The Prairie Vole Model, Marigny C. Normann Jan 2020

Investigating The Behavioral Effects Of Juvenile Stress In The Prairie Vole Model, Marigny C. Normann

Graduate Research Theses & Dissertations

Early life stress during the juvenile period, such as emotional neglect, interpersonal difficulties, or other forms of non-violent maltreatment can have consequences into adulthood. Specifically, the negative effects include increased risk of psychiatric or physical illnesses, social deficits, and maladaptive behavioral responses to stress. Since these effects have far-reaching implications that can negatively alter later behavior and physiology, the present study assessed the effects of early life social stress on later social and affective behaviors in a social rodent species – the prairie vole. The prairie vole displays behavioral, cardiovascular, and neuroendocrine responses to social stress similar to those of …