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University of Alabama at Birmingham

Doctor of Philosophy (PhD) Heersink School of Medicine

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Full-Text Articles in Medicine and Health Sciences

Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle Jan 2024

Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle

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This thesis focuses on two key questions: 1) how are bone development and regeneration regulated by the CREB3L1 transcription factor; and 2) what is the mechanism of action of the endoplasmic reticulum resident protein JAGN1, which when dysregulated, causes severe congenital neutropenia (SCN)? CREB3L1 regulates bone development and regeneration in mammalian models by facilitating the expression of COL1A1 and components of the secretory pathway required for collagen secretion. We generated two zebrafish models of Creb3l1 dysfunction (creb3l1ΔbZIP/ΔbZIP and creb3l1TA+/TA+). Both models showed that Creb3l1 functions in regulating col1a1a transcription and overall regenerate size are conserved in zebrafish. However, we also …


Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose Jan 2024

Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose

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Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a channel responsible for the transport of chloride and bicarbonate ions across the apical cell surface. In the respiratory tract, defective CFTR results in viscous and adherent mucus that becomes static within the airway, which leads to chronic infections, progressive lung damage, and early mortality. Historically, CF mucus stasis has been attributed to significant airway dehydration; however, growing evidence has demonstrated that aberrant electrostatic properties of mucins also contribute to mucus stasis in CF. Mucins are large, polymeric glycoproteins …


The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter Jan 2024

The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter

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Chronic inflammation plays a role in the development and progression of airway diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). COPD is caused primarily by chronic cigarette smoke exposure. Conversely, CF is a single gene disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Although the causes of COPD and CF are different, there are common pathological features. Studies show that chronic inflammation plays a significant role in the pathogenesis of both COPD and CF. Moreover, chronic inflammation induces ageing-associated pathomechanisms like cellular senescence, which exacerbates chronic inflammation. Previous work demonstrates that …


Phosphate Drives Pulmonary Inflammation Through Fgfr1, Erk, And Akt Signaling, Seth Bollenbecker Jan 2024

Phosphate Drives Pulmonary Inflammation Through Fgfr1, Erk, And Akt Signaling, Seth Bollenbecker

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Chronic kidney disease (CKD) is characterized as irreversible progressive loss of renal function and affects over one tenth of the global population. Although CKD-associated comorbidities contribute significantly to its mortality, the lungs are often not considered. Lung diseases make up three of the top six leading causes of death worldwide and share many comorbidities with CKD. Clinical reports show that CKD patients are more likely to develop obstructive and restrictive lung diseases, but the mechanisms underlying this propensity for CKD-associated pulmonary complications are unknown. Hyperphosphatemia and associated elevations of fibroblast growth factor (FGF) 23, two of many consequences of reduced …


Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar Jan 2024

Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar

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Around 39 million people globally are currently infected with Human immunodeficiency virus 1 (HIV-1), more than half of whom are women. HIV-1 is a retrovirus that infects and depletes an individual’s immune cells, culminating in the development of acquired immunodeficiency syndrome (AIDS) if not managed with anti-retroviral therapies (ART). Most women acquire HIV-1 through heterosexual intercourse. However, the early mechanisms and virologic determinants of HIV-1 transmission to women remain unclear. Herein, we demonstrate transmitted/founder (TF) HIV-1 representing two genetically and pathogenically distinct subtypes (A and D) in vivo have distinct replication phenotypes in an ex vivo cervical explant tissue (CET) …


Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman Jan 2024

Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman

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As the largest and most dynamic family of GTPases within the mammalian cell, Rabs play an essential role as molecular switches in regulating intracellular vesicular trafficking and serve as significant signaling transducers. Over the last few decades, Rabs have been identified to regulate endocytic, transcytosis, and exocytotic pathways, and mutations in Rabs, or alterations in downstream effectors lead to embryonic lethality and diseases such as cancer and ciliopathies. Ciliopathies are a class of pathologies that result from defects in structure or function of the primary cilia. Primary cilia, found on virtually all mammalian cells, is a microtubule-derived appendage that relies …


Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome, Robert Follett Rosencrans Jan 2024

Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome, Robert Follett Rosencrans

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The sympathetic nervous system is a key regulator of energy homeostasis, in part, through the control of white adipose tissue lipolysis. Sympathetic nerves modulate adipose tissue physiology through the release of catecholamines, particularly norepinephrine, onto alpha- and beta-adrenergic receptors (a-AR; B-AR). Lipolysis refers to the breakdown of triglycerides into glycerol and free fatty acids, often in response to activation of B2/3-AR. Beta adrenergic activation of lipolysis is widely known to be impaired in patients with metabolic syndrome and animal models thereof (catecholamine resistance). Recent studies have demonstrated that catecholamine regulation of adipokine release is also disrupted, suggesting that catecholamine resistance …


The Influence Of Proximity On Patient Outcomes For Differently Structured Ambulatory Surgery Centers, Wendy Michelle Smith Jan 2023

The Influence Of Proximity On Patient Outcomes For Differently Structured Ambulatory Surgery Centers, Wendy Michelle Smith

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THE INFLUENCE OF PROXIMITY ON PATIENT OUTCOMES FOR DIFFERENTLY STRUCTURED AMBULATORY SURGERY CENTERSWENDY SMITH HEALTH SERVICES ADMINISTRATION ABSTRACT This study examines the complication rates and patient-reported outcome measures (PROMs) for total hip and knee replacement surgeries conducted in one of two differently structured ambulatory surgical centers (ASCs) with varying interprofessional surgical teams. There is an ongoing shift from in-hospital total joint replacement surgeries to ASCs. Additionally, there is specialization occurring within ASCs. In this study, we compare single specialty ASCs designed to perform solely TJR surgeries with one orthopedic group and interprofessional team, with multi-specialty ASCs that perform an array …


Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman Jan 2023

Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman

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In the United States, acute kidney injury (AKI) affects nearly 20% of all intensive care unit patients. Additionally, over a third of Americans aged 50 or older suffer from stage 3 chronic kidney disease (CKD) or higher. AKI and CKD are encompassing terms for many etiologies and pathological processes that affect different regions of the kidney but converge at tissue inflammation and fibrosis. Macrophages perform vital homeostatic functions and can initiate or ameliorate inflammation and fibrosis. As the largest component of the kidney immune system, kidney resident macrophages (KRMs) have been implicated in both disease propagation and mitigation, yet the …


Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen Jan 2023

Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen

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Autoimmune diseases are a classification of more than eighty diseases where the immune system recognizes a self-antigen and mistakenly attacks the body’s own tissue, inducing inflammation a nd p otentially l eading t o d amage. Autoimmune diseases disproportionately affect women and develop at any age depending on the disease. The prevalence of some autoimmune diseases is increased in minority populations. Despite this, research into higher-risk populations is lacking. This highlights the need to contribute research into understanding autoimmune disease pathogenesis in diverse studies to understand why disease is more severe in these populations. We analyzed transcriptomes and methylomes of …


Manipulation And Dependence On Host Cell Cycle By Human Rna And Dna Viruses: Human Coronavirus Oc43 And Bk Polyomavirus, Jason M. Needham Jan 2023

Manipulation And Dependence On Host Cell Cycle By Human Rna And Dna Viruses: Human Coronavirus Oc43 And Bk Polyomavirus, Jason M. Needham

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Cell cycle is a universal necessity of cellular life and impacts nearly every process within the cell. However, despite over one hundred years of research, there still remain questions concerning the mechanisms and regulation of eukaryotic cell cycle. From the beginning, viruses have informed our knowledge of cell cycle. Many key regulators such as the E2F transcription factors, Src kinase, and p53 were originally discovered while studying the interactions between viruses and the cell. Herein, we continue the investigation of viral interactions with cell cycle machinery by researching an RNA virus and a DNA virus. These viruses, human coronavirus OC43 …


The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma Jan 2023

The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma

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Epilepsy affects over 70 million people worldwide with a global incidence of 2.4 million new cases per year. In many of these patients, neuroinflammation (NI) is a key pathological contributor to focal seizure generation and maintenance. Sustained NI degrades the blood–brain barrier, leads to neuronal death, and ultimately decreases seizure threshold. Finding ways to image and treat NI is especially important for the >30% of patients with treatment-resistant epilepsy (TRE) who cannot achieve seizure freedom with standard antiseizure medications. Cannabidiol (CBD) effectively reduces seizure frequency and severity in many TRE patients, although its antiepileptic effects remain poorly understood. Atypically high …


Application Of Machine Learning And Network Approaches To Prioritize Safe And Efficacious Drug Repurposing Candidates, Jennifer L. Fisher Jan 2023

Application Of Machine Learning And Network Approaches To Prioritize Safe And Efficacious Drug Repurposing Candidates, Jennifer L. Fisher

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Only ten percent of drugs in clinical trials are ultimately approved by the Food and Drug Administration (FDA). With many diseases and disorders needing therapeutic options, computational drug repurposing methodologies are great alternatives to some drug discovery methods due to quicker FDA approval and lower cost. We sought to gain insights to improve the identification of drug repurposing candidates that will be safe and effective to increase the success of computational drug repurposing approaches. In regards to identifying safe drug candidates, pharmacovigilance studies of adverse event case reports identified that women are more likely to experience an adverse event, and …


Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer Jan 2023

Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer

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During the process of malignant transformation, cells have striking changes in their cell surface glycosylation. One of these changes is an enrichment for α2,6 sialic acid which is added by the sialyltransferase, ST6GAL1. ST6GAL1 is upregulated in numerous malignancies and acts by adding an α2,6 sialic acid onto receptors bound for the plasma membrane. This sialic acid, in turn, modulates the activity of the receptor by regulating conformation, clustering, and cell surface retention. The work presented in this dissertation focuses on how ST6GAL1-mediated sialylation of a specific cell surface receptor, epidermal growth factor receptor (EGFR), regulates many of its properties. …


Strategies For Her2 Targeted Pet Imaging, Maxwell Adams Ducharme Jan 2023

Strategies For Her2 Targeted Pet Imaging, Maxwell Adams Ducharme

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Breast cancer is one of the most common and deadly cancers diagnosed in women each year. The HER2-positive subtype of breast cancer is associated with poor prognosis and lower progression-free survival. Early identification of HER2 expression is extremely important for the effective treatment of the disease. Current methods to diagnose HER2-positive breast cancer involve invasive biopsies to semi-quantitatively determine the amount of HER2 expression. However, many lesions are often unavailable for biopsy due to their location and there may be variable HER2 expression between the primary tumor and metastasis. Positron emission tomography (PET) can give a full-body, non-invasive evaluation of …


Neutrophil Heterogeneity And Alternative Granulopoiesis In Chronic Inflammatory Conditions, Ashley N. Connelly Jan 2023

Neutrophil Heterogeneity And Alternative Granulopoiesis In Chronic Inflammatory Conditions, Ashley N. Connelly

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Neutrophils, the most abundant type of circulating leukocyte, represent a heterogeneous population with distinct roles in immune regulation and disease pathogenesis. A major obstacle to our understanding of neutrophil biology is that neutrophils are readily activated during preparation. The lack of standardized methodology for neutrophil characterization makes the comparison of results across studies challenging. Here we provide a careful comparison of eight characterization methods and present a novel, optimized protocol for the characterization of whole blood neutrophils minimizing activationinduced phenotypic alterations during processing. Despite successful virological control, HIV-1-infected individuals maintain an increased risk of life-threatening comorbidities including liver, cardiovascular, and …


Impact Of Exercise On Antioxidative-Stress Induced Endoplasmic Reticulum Dysfunction And Cardiac Remodelling, Arun Jyothidasan Jan 2023

Impact Of Exercise On Antioxidative-Stress Induced Endoplasmic Reticulum Dysfunction And Cardiac Remodelling, Arun Jyothidasan

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The gain of function of nuclear factor erythroid 2 like 2 (Nrf2), in the absence of oxidative stress (or toxic insults), its pathophysiology arising from the endoplasmic reticulum and exercise intervention to mitigate the pathology are the focal point of this dissertation. Nrf2, when constitutively expressed, has been previously associated with cardiomyopathy. Chapter II investigated the hypothesis that cardiac-specific expression of Nrf2 (mNrf2-TG) would establish a pro-reductive state and trigger adaptive cardiac remodeling by enhancing the basal antioxidant defense. Through RNA profiling and imaging techniques, the study underscored that while acute preconditioning might prove advantageous against oxidative stress, prolonged pro-reductive …


Dact1, The “Super-Crosslinker”: Regulation Of Non-Canonical Wnt Signaling During Vertebrate Convergent Extension By Modulating Dishevelled Oligomerization, Allyson Angermeier Jan 2023

Dact1, The “Super-Crosslinker”: Regulation Of Non-Canonical Wnt Signaling During Vertebrate Convergent Extension By Modulating Dishevelled Oligomerization, Allyson Angermeier

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A broad spectrum of human birth defects arise from the disruption of morphogenesis, the critical process through which tissues and organs acquire their proper shape. Convergent extension (CE) is a universal morphogenetic engine that promotes polarized extension of diverse tissues and organs by regulating directional cell behavior, such as oriented cell intercalation. In vertebrates, CE is regulated by non-canonical Wnt/Planar Cell Polarity (PCP) pathway, an ancient signaling pathway that was originally discovered to coordinate the cellular polarity in the plane of the epithelium. Non-canonical Wnt/PCP signaling shares the Frizzled (Fz) receptor and cytoplasmic signal transducer Dishevelled (Dvl) with the canonical …


Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses, Nicole Michelle Arroyo-Diaz Jan 2023

Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses, Nicole Michelle Arroyo-Diaz

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T follicular helper (Tfh) cells constitute a distinct subset of CD4 T cells that reside within B cell follicles, playing an indispensable role in orchestrating the Germinal Center (GC) response. In response to polarizing environments, such as Influenza A virus infection (IAV), Tfh cells secrete effector cytokines, including IFN-γ and IL-4. Nevertheless, the specific functions of cytokine-producing Tfh cell subsets, beyond their involvement in driving class switch recombination (CSR), remain largely unexplored. Here, we demonstrate that, following IAV infection, Tfh cell cytokine production undergoes a dynamic shift, transitioning from early IFN-γ dominance to later predominance of IL-4. The initial IFN-γ …


Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine I Benjamin Jan 2023

Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine I Benjamin

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Circadian disruption is a disturbance in biological timing which can occur within or between different organizational levels, ranging from molecular rhythms within specific cells to misalignment of behavioral and environmental cycles. Previous work has shown that changing the timing of food availability is sufficient to lower blood pressure and improve insulin sensitivity in prediabetic males, demonstrating the importance of timing of food intake for cardiovascular health. Findings from our group demonstrated that less than one week of mistimed feeding is sufficient to invert diurnal blood pressure rhythms, although kidney excretory rhythms and kidney function remained aligned with the light-dark cycle. …


Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin Jan 2023

Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin

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Polyphosphate (polyP) is an ancient, conserved, inorganic biomolecule. Biological systems have adapted many functions for this high-energy molecule, ranging from immune regulation in mammals to gene regulation in prokaryotes. Of particular interest is its use in bacterial stress responses. Bacteria use polyP to resist hazardous environmental elements like toxic molecules or nutrient starvation. In many bacterial species, polyP is synthesized by polyphosphate kinases (PPKs). PPK – discovered in Escherica coli (E. coli) – hydrolyzes adenosine-5’-triphosphate (ATP) to synthesize polyP. Species that use PPK develop multiple pathogenic defects when PPK activity is impaired, including, among others, antibiotic susceptibility. There is no …


Challenges And Opportunities In Glioblastoma And Immunovirotherapy With Oncolytic Herpes Simplex Virus Type 1, Dagoberto Estevez-Ordonez Jan 2023

Challenges And Opportunities In Glioblastoma And Immunovirotherapy With Oncolytic Herpes Simplex Virus Type 1, Dagoberto Estevez-Ordonez

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This dissertation covers data from published and pre-published studies exploring challenges and opportunities in the treatment of malignant glioma with emphasis in glioblastoma and oncolytic immunovirotherapy with an oncolytic herpes simplex virus type 1 (HSV-1) designed to induce expression of IL-12, M002 (murine IL-12) and M032 (human IL-12).It starts with the report of a study that uncovered important racial and socioeconomic disparities experienced by patients with glioblastoma treated in Alabama. Notable results also include the unexpected finding of increased survival in African American patients with glioblastoma even after controlling for factors associated with survival and socioeconomic disparities. The implications of …


Time-Restricted Feeding Attenuates Obesity-Induced Muscle Dysfunction Through Energy Metabolism And Microbiota Modulation, Chris Livelo Jan 2023

Time-Restricted Feeding Attenuates Obesity-Induced Muscle Dysfunction Through Energy Metabolism And Microbiota Modulation, Chris Livelo

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Obesity is a global epidemic that affects countless numbers of people caused by genetic and environmental factors including circadian disruption, which poses significant health risks to skeletal muscle physiology and other tissues. While a feeding fasting intervention known as time-restricted feeding (TRF) has been shown to mitigate obesity-related muscle dysfunction, the underlying mechanisms remain a subject of investigation. In this study, we delve into potential mechanisms underlying TRF's protective effects on muscle physiology in the context of diet- and genetic-induced obesity using Drosophila models. Our findings reveal that TRF triggers the upregulation of key genes involved in glycine production (Sardh …


Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White Jan 2023

Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White

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We reported that Ca2+-independent phospholipase A2β (iPLA2) contributes to type 1 diabetes (T1D) development; however, the impact of lipid signaling from T-cells is unknown. To address this, we first administered splenocytes from NOD, NOD.iPLA2+/- (NOD.HET), or NOD.iPLA2-/- (NOD.KO) mice to 4-week-old NOD.scid recipients. As expected, T1D onset was rapid in NOD cell recipients and 100% by 12 weeks. However, onset was delayed by 1-3 weeks in NOD.HET or NOD.KO cell recipients and only 60% became diabetic, suggesting a role for T-cell iPLA2. Next, to establish importance of iPLA2 in CD4 or CD8 cells, purified cells were administered to NOD.scid mice. …


The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock Jan 2023

The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock

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SET binding protein 1 (SETBP1) encodes a transcription factor (TF) participating in diverse cellular processes. SETBP1 is an epigenetic hub associated with variants linked to three distinct diseases. Germline variants cause rare pediatric Schinzel Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disorder (SETBP1-HD), featuring multisystemic abnormalities and neurodegeneration or milder brain issues with hypotonia, respectively. On the other hand, somatic variants contribute to hematological malignancies and adult cancer. To understand tissue-specific SETBP1 mechanisms, public RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project were analyzed. SETBP1 and targets were broadly expressed across 31 adult human tissues, revealing three distinct expression patterns: transcription …


Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter Jan 2023

Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter

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Gout is a common inflammatory arthritis that is increasing in prevalence globally. It has clear sex differences, being more common among men, though comorbidities appear to be more common among women. It also varies in prevalence between populations, driven by a combination of genetic and socioeconomic factors. Genetic studies have identified gout-associated genetic variants, several of which are shared between different populations. Here, I combined gout-associated genetic variants into a gout polygenic risk score. This score was then used to elucidate the genetic underpinning of gout severity and presence of comorbidities, comparing its effects in different sexes and populations. I …


Biochemical Characterization Of Rna Polymerases I, Ii, And Iii And Its Therapeutic Implications, Ruth Qian Jacobs Jan 2023

Biochemical Characterization Of Rna Polymerases I, Ii, And Iii And Its Therapeutic Implications, Ruth Qian Jacobs

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In contrast to Bacteria and Archaea that express a single DNA-dependent RNA polymerase (RNAP), eukaryotes express at least three structurally distinct, nuclear, DNA-dependent RNA polymerases (Pols I, II, and III) that are responsible for synthesizing all the genome-encoded RNA required by the cell. Despite the discovery of the Pols over 50 years ago, there remains a knowledge gap concerning their enzymatic properties. Over the course of evolution, we know that Pols I, II, and III have diverged in structure and function. They share a 10-subunit core and are each responsible for transcribing unique genetic loci. What remains to be understood …


Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos Jan 2023

Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos

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The overall risk of infection after total knee arthroplasty (TKA) has not improved over the past 20 years, remaining 10-40 times greater than the risk of infection of a native knee. Despite extensive research into periprosthetic joint infection (PJI), little is known about the synovial fluid immune homeostasis of the native knee joint and how TKA surgery itself impacts the local immune composition. While many postulate a role for cartilage in maintaining this immune homeostasis, the exact method in which it contributes remains elusive. Therefore, in this dissertation I have investigated the synovial fluid changes occurring in the knee joint …


Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing Jan 2023

Regulating Cancer Cell Metabolism During Hypoxia-Reoxygenation: Examing The Interplay Of Gasotransmitters And Glutaminolysis, Dianna L. Xing

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Oxidative phosphorylation is an oxygen-dependent metabolic process that provides the majority of ATP used to support essential cellular functions. However, in cancer, limitations in oxygen availability occur during the development and metastasis of tumors. To compensate for the demands of rapidly proliferating cells, many cancers exhibit an increased demand for glycolysis, the TCA cycle, and glutaminolysis. In this thesis, extracellular flux technology and metabolomics were applied in a hypoxia-reoxygenation model to investigate the metabolic adaptations that occur in dynamic changes in oxygen and nutrient availability in cancer cells. We show the significance of glutaminolysis and its substrates in regulating cancer …


Interactions Between Pseudomonas Aeruginosa And The Oral Commensal Streptococcus Salivarius, Sara Noelle Stoner Jan 2023

Interactions Between Pseudomonas Aeruginosa And The Oral Commensal Streptococcus Salivarius, Sara Noelle Stoner

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The cystic fibrosis airway is a polymicrobial environment often dominated by opportunistic pathogens such as Pseudomonas aeruginosa, a leading cause of lung function decline and mortality in persons with CF. Commensal streptococcal colonization has been associated with stable CF lung function in multiple studies. However, few studies have examined interactions between P. aeruginosa and commensals as well as their impact on P. aeruginosa airway infections. In the first half of this work, we studied interactions between P. aeruginosa and the oral commensal Streptococcus salivarius within a biofilm setting. We found that S. salivarius biofilm formation is promoted by the non-mucoid …