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Articles 1 - 30 of 971
Full-Text Articles in Medicine and Health Sciences
Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle
Non-Catalytic Regulators Of The Secretory Pathway, Peyton Vanwinkle
All ETDs from UAB
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
Investigating The Electrostatics Of Mucins As Key Contributors To Mucus Stasis In Cystic Fibrosis, Elex Skylar Rose
All ETDs from UAB
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 …
Associations Between Grit, Life Satisfaction, And Academic Outcomes In Elementary And Middle School Students, Charles Jaylon Williams
Associations Between Grit, Life Satisfaction, And Academic Outcomes In Elementary And Middle School Students, Charles Jaylon Williams
All ETDs from UAB
Grit is used to predict various positive benefits within students. Grit is trying to get back up to attempt another try at one’s goal after failure. Recently, grit has been seen as a potential candidate in improving the life satisfaction and academic performance of individuals. Grit is conceptualized as having two components, perseverance of effort and consistency of interest. Perseverance of effort is trying again until you finally accomplish your goal, while consistency of interest is a constant drive to complete one’s goals over a long-time span. This study measured the effects that grit has on elementary and middle school …
Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar
Investigating Hiv-1 Transmission To Human Cervix Using Reporter Virus Technologies, Dana Frances Indihar
All ETDs from UAB
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) …
The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter
The Role Of Fibroblast Growth Factor Receptors In Inflammatory Airway Diseases, Molly Easter
All ETDs from UAB
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
Phosphate Drives Pulmonary Inflammation Through Fgfr1, Erk, And Akt Signaling, Seth Bollenbecker
All ETDs from UAB
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 …
Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman
Novel Roles Of Rab35 In Development And Disease, Kelsey Ruth Clearman
All ETDs from UAB
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
Catecholamines And Catecholamine Resistance In Animal Models Of Metabolic Syndrome, Robert Follett Rosencrans
All ETDs from UAB
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 …
Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen
Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen
All ETDs from UAB
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 …
Chronic Hiv Infection Influences The Immune Response To Sars-Cov-2, Skye Opsteen
Chronic Hiv Infection Influences The Immune Response To Sars-Cov-2, Skye Opsteen
All ETDs from UAB
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global morbidity and mortality since late 2019. Many infections result in self-limited disease and recovery in 1-2 weeks. However, a subset of individuals experience more severe illness, associated with hospitalization, ventilation, and potential mortality. HIV infection is a proposed risk factor for more severe illness due to people living with HIV (PLWH) experiencing chronic immune activation and inflammation despite effective antiretroviral therapy. While there is supporting evidence showing worsened clinical outcomes in PLWH experiencing acute COVID-19, the immune response driving these outcomes is less explored. We analyzed markers of immune activation …
Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman
Spatial/Temporal Zonation, Diversification, And Evolutionary Conservation Of Kidney Resident Macrophage Subpopulations In Mice And Humans After Kidney Injury, Elise Nicole Erman
All ETDs from UAB
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 …
Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine I Benjamin
Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine I Benjamin
All ETDs from UAB
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. …
Neuropeptide Y Overexpression In The Presence Of P23h Rhodopsin Mutation, Jean Sun
Neuropeptide Y Overexpression In The Presence Of P23h Rhodopsin Mutation, Jean Sun
All ETDs from UAB
Neuropeptide Y (NPY), a 36-amino acid peptide, has been found to be the most abundant neuropeptide in the central nervous system, and it is widespread across mammalian species. NPY plays a dual role as a neurotransmitter and neuromodulator in the nervous system. NPY functions as a multifaceted neuromodulator through binding NPY receptors (NPYRs). NYP interacts with NPYRs and regulates various activities, such as cell growth, neurogenesis, neuroprotection, mitochondrial behaviors, food intake, anxiety, and addiction formation. In terms of NPY’s neuroprotective potential, NPY inhibits neuronal death signaling, thus preventing apoptosis, and displays anti-inflammatory and anti-oxidative effects. Additionally, it influences metabolism by …
Aberrant Signal Transduction Of Neuronal Injury: Trauma And Toxicology, Alan Umfress
Aberrant Signal Transduction Of Neuronal Injury: Trauma And Toxicology, Alan Umfress
All ETDs from UAB
Neurological injuries occur in epidemic proportions worldwide. Neuronal injuries are events resulting in damage to the central nervous system (CNS) that impair neurological function. Subsequent impairments in neuronal function can be rapid, existing immediately after injury, or progressive and chronic impairments that persist for the lifetime of the survivor. CNS injury constitutes a broad class of environmental and pathophysiological insults ranging from blunt-force trauma to the brain or spinal cord, to acute ischemic and hemorrhagic strokes, and insults resultant from neurotoxic agents. While divergent in initial cause, many of these insults share underlying pathophysiological outcomes including excitotoxic cell signaling, neuroinflammation, …
Differential Mechanisms Of Intestinal Inflammation Drive Pathogenesis Of Diabetic Retinopathy In Type 1 And Type 2 Diabetes, Jason Levi Floyd
Differential Mechanisms Of Intestinal Inflammation Drive Pathogenesis Of Diabetic Retinopathy In Type 1 And Type 2 Diabetes, Jason Levi Floyd
All ETDs from UAB
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and, along with diabetic macular edema (DME), accounts for the greatest source of vision-threatening eye disease in the working-age community. DR is caused by weakening of the retinal vasculature, the blood-retinal barrier (BRB), by high levels of blood glucose (hyperglycemia), exacerbations of oxidative stress, and systemic inflammatory factors. Many of these inflammatory factors are metabolic by-products and cell membrane constituents of the gut microbiota, the resident community of microbial species which inhabit the lumen of the gastrointestinal tract. These factors are collectively termed gut microbial antigens (GMAs). In diabetes, …
Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos
Impact Of Arthroplasty Surgery On The Local Immune Composition Of The Knee Joint And Implications For The Periprosthetic Joint Infection, Kyle H. Cichos
All ETDs from UAB
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 …
The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma
The Effects Of Cannabidiol On Brain Temperature In Treatment-Resistant Epilepsy, Ayushe A. Sharma
All ETDs from UAB
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 …
Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer
Sialylation Of Epidermal Growth Factor Receptor By The Sialyltransferase St6gal1 Modulates Receptor Activity And Downstream Signaling, Katherine Ankenbauer
All ETDs from UAB
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
Strategies For Her2 Targeted Pet Imaging, Maxwell Adams Ducharme
All ETDs from UAB
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
Neutrophil Heterogeneity And Alternative Granulopoiesis In Chronic Inflammatory Conditions, Ashley N. Connelly
All ETDs from UAB
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 …
Uncovering The Role Of Spt5 In Rna Polymerase I Transcription Through Targeted Protein Degradation Via The Auxin Inducible Degron System In Saccharomyces Cerevisiae, Nathan Bellis
All ETDs from UAB
RNA Polymerases are the molecular machines responsible for the synthesis of RNA from the DNA template. The presence of these machines is an absolute requirement for the function and replication of all cellular organisms. In eukaryotic organisms, there are a minimum of three RNA polymerases (Pols I, II, II). Despite shared subunits and homology, these three protein complexes are functionally distinct, with many unique sub-units and additional trans-acting factors. Pol I is responsible for the synthesis of three of the four ribosomal RNA species which is the first and rate limiting step of ribosome biogenesis. Pol I synthesizes the majority …
Impact Of Exercise On Antioxidative-Stress Induced Endoplasmic Reticulum Dysfunction And Cardiac Remodelling, Arun Jyothidasan
Impact Of Exercise On Antioxidative-Stress Induced Endoplasmic Reticulum Dysfunction And Cardiac Remodelling, Arun Jyothidasan
All ETDs from UAB
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
Dact1, The “Super-Crosslinker”: Regulation Of Non-Canonical Wnt Signaling During Vertebrate Convergent Extension By Modulating Dishevelled Oligomerization, Allyson Angermeier
All ETDs from UAB
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
Crucial Role Of T Follicular Helper Cell-Derived Ifn-Γ In Lung Resident Memory B Cell Responses, Nicole Michelle Arroyo-Diaz
All ETDs from UAB
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 …
Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin
Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin
All ETDs from UAB
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 …
Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White
Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White
All ETDs from UAB
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
The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock
All ETDs from UAB
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
Sex-Stratified Genetic Analysis Of Gout And Comorbidities, Nicholas Andrew Sumpter
All ETDs from UAB
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
Biochemical Characterization Of Rna Polymerases I, Ii, And Iii And Its Therapeutic Implications, Ruth Qian Jacobs
All ETDs from UAB
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 …
Characterizing A Unique Oprm1 Expressing Neuronal Population In The Rat Nucleus Accumbens, Emma Andraka
Characterizing A Unique Oprm1 Expressing Neuronal Population In The Rat Nucleus Accumbens, Emma Andraka
All ETDs from UAB
Opioid-related overdose deaths have increased drastically in the past three decades, and especially since the beginning of the COVID-19 pandemic, due to the addictive, analgesic, and euphoric properties of the drugs. To produce these effects, opioids bind to the mu opioid receptor (MOR) in GABAergic neurons. The MOR is encoded by the Oprm1 gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc). Previous studies of Oprm1 knockdown in medium spiny neurons (MSNs) of the mouse NAc have shown that these neuronal populations are involved in reinforcing reward-context pairing as well …