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Full-Text Articles in Medicine and Health Sciences
Mechanism Of Cytomegalovirus-Induced Mucosal Inflammation, Evida Adiko Dennis
Mechanism Of Cytomegalovirus-Induced Mucosal Inflammation, Evida Adiko Dennis
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Cytomegalovirus (CMV) is an opportunistic β-herpesvirus that causes severe mucosal inflammation in recipients of organ and stem cell transplants, HIV-1-infected subjects, and persons with inflammatory bowel disease. The gastrointestinal mucosa is among the most common sites of CMV inflammatory disease, and the inflammatory lesions associated with CMV mucosal infection contain infected macrophages and increased levels of macrophage-derived cytokines, implicating mucosal macrophages in the inflammatory process. Paradoxically, in healthy human intestinal mucosa, macrophages are profoundly down-regulated for pro-inflammatory responses (inflammation anergy) due to stromal TGF-β-induction of Smad signaling and inactivation of NF-κB. To elucidate the mechanism whereby CMV promotes macrophage-mediated mucosal …
The Function Of Protein Kinase Ck2 In Cd4 T Cell Differentiation And Autoimmunity, Sara Ann Gibson
The Function Of Protein Kinase Ck2 In Cd4 T Cell Differentiation And Autoimmunity, Sara Ann Gibson
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Protein kinase CK2 is a highly conserved serine/threonine kinase essential for cell viability. CK2 exhibits immense pleiotropy and has well characterized interactions with canonical cytosolic signaling pathways such as PI3K/Akt/mTOR and JAK/STAT. These pathways are critical for CD4+ T cell function, and further are known to be aberrantly active in the T cell-driven autoimmune disease Multiple Sclerosis, but little is known as to how CK2 functions in CD4+ T cells or in the context of autoimmune diseases. The current dissertation examines the understudied T cell-specific functions of CK2 utilizing two approaches, pharmacologic inhibition and genetic deletion. We discovered CK2 to …
The G Protein-Coupled Estrogen Receptor (Gper) Mediates Estrogen-Induced Regulation Of Heart Rate By Modulating Thyroid Hormone Levels In Zebrafish Embryos, Shannon Nicole Romano
The G Protein-Coupled Estrogen Receptor (Gper) Mediates Estrogen-Induced Regulation Of Heart Rate By Modulating Thyroid Hormone Levels In Zebrafish Embryos, Shannon Nicole Romano
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Estrogens regulate cell signaling and gene expression by binding to nuclear estrogen receptors (ERs) alpha and beta (ERα, ERβ), ligand-dependent transcription factors. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. In the cardiovascular system, estrogens regulate vessel pressure and exert cardioprotective effects on the vasculature. However, whether estrogens act directly to modulate heart function, and the mechanism by which this occurs is not well understood. Therefore, the overall goals of this dissertation were to (1) determine if estrogen receptor ligands modulate heart rate and to (2) determine the …
Extrasynaptic Signaling To Interneuron Networks, Angela Nietz
Extrasynaptic Signaling To Interneuron Networks, Angela Nietz
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In recent years, a form of extrasynaptic signaling through fast neurotransmitters, termed spillover, has been shown in multiple brain regions. This discovery suggests that spillover is more ubiquitous than previously thought. The circuitry within the cerebellar cortex has been well mapped. However, glutamate from cerebellar climbing fibers (CF) has been shown to spill over to nearby interneurons and alter their tonic activity. Cerebellar Golgi cells are spontaneously active interneurons at the input stage to the cerebellar cortex re-sponsible for regulating influx of cortical information. Previous research has shown an in vivo connection between CFs and Golgi cells (GoC), with CF …
Evaluation Of Peripheral And Mucosal T Cell Phenotypes Of Chlamydia-Infected Women, Brian Makori Omwena Ogendi
Evaluation Of Peripheral And Mucosal T Cell Phenotypes Of Chlamydia-Infected Women, Brian Makori Omwena Ogendi
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Chlamydia trachomatis (CT) infection is the most prevalent bacterial sexually transmitted infection worldwide and women are disproportionately affected due to its reproductive complications. T cell phenotypes present during CT infection have been well characterized in the murine model, but remain to be elucidated in humans. Therefore, studies aimed at increasing our understanding of T cell phenotypes in CT-infected humans were the focus of this dissertation. The first chapter of this dissertation reviews various aspects of chlamydial infection while in the second chapter aims to address the influence of CT infection on T cell phenotypes. We first compared differences in peripheral …
Alterations In Ubc9 Substrate Specificity Affect The Cellular Response To Dna Damage, Joshua Enyeribe Onuiri
Alterations In Ubc9 Substrate Specificity Affect The Cellular Response To Dna Damage, Joshua Enyeribe Onuiri
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This dissertation seeks to uncover the impact of a post-translational modification, the small ubiquitin-related modifier (SUMO), on the cell response to DNA damage. Covalent modification of cellular proteins by SUMO occurs through an enzymatic cascade involving an E1 activating enzyme, an E2 conjugating enzyme, and a ligase (E3). Eukaryotic cells possess a single E1 and a single E2 for SUMO conjugation. The E2 for SUMO, Ubc9, is able to recognize and modify substrates on its own, although substrate recognition and modification are enhanced in the presence of the E3. Two independent genetic screens carried out in the budding yeast Saccharomyces …
N-Acetyl-D-Glucosamine-Reactive Natural Antibodies: Roles In Suppression Of Autoimmune Diabetes And Environmental Factors Influencing Their Development, James Stewart New
N-Acetyl-D-Glucosamine-Reactive Natural Antibodies: Roles In Suppression Of Autoimmune Diabetes And Environmental Factors Influencing Their Development, James Stewart New
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Type 1 Diabetes suppression in diabetes prone mice following immunization with Group A Streptococcus correlates with the B lymphocyte response to N-acetyl-D-glucosamine (GlcNAc) present in the Group A Carbohydrate cell wall polysaccharide. GlcNAc-specific B cells recognize cryptic GlcNAc-epitopes in beta cells. Following exposure of GlcNAc-modified antigens on beta cells during cellular apoptosis, GlcNAc-specific IgM antibodies opsonize these epitopes and mediate classical complement pathway activation. In vitro, opsonization of apoptotic beta cells with GlcNAc-specific IgM increases their uptake by dendritic cells, while suppressing the subsequent presentation of beta cell-derived antigens to diabetogenic T lymphocytes. Passive administration of Group A Streptococcus antisera …
Relationship Between Walking Speed And Kinematic Trajectory Complexity In People With Poststroke Hemiparesis, Deanna Delayne Rumble
Relationship Between Walking Speed And Kinematic Trajectory Complexity In People With Poststroke Hemiparesis, Deanna Delayne Rumble
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Individuals with chronic poststroke hemiparesis (PS) exhibit increased variability in spatiotemporal kinematic variables related to endpoint control during walking. For nonimpaired individuals, walking faster or slower than a preferred walking speed, results in less consistent stepping behavior. In three studies I investigated variability in swing phase foot trajectory area on a step-by-step basis (SBS-FTA) in nonimpaired individuals and people with PS. The primary aims of these studies were to 1) validate SBS-FTA in nonimpaired individuals, 2) observe if there was a difference in SBS-FTA variability between nonimpaired individual’s limb, the PS paretic, and nonparetic limbs, and across a wide range …
The Role Of Adipocytes And Osteocytes In Multiple Myeloma Progression, Timothy Nathan Trotter
The Role Of Adipocytes And Osteocytes In Multiple Myeloma Progression, Timothy Nathan Trotter
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Multiple myeloma (MM) is a hematological malignancy of plasma cells that is intrinsically tied to the bone marrow (BM). Many cells in the BM microenvironment have been studied in MM, yet there is still much progress to be made. Recent work has revealed two new potential cellular targets in MM: adipocytes and osteocytes. Both are endocrine cells and secrete many molecules that regulate other cells proximally and systemically. Our lab previously showed that MM cells shift osteoblast precursor cells towards adipogenesis through soluble molecules alone. Recent findings also revealed that osteocyte apoptosis is enhanced in MM patients compared to healthy …
Immunoregulation During Acute And Chronic Exposure To Aspergillus Fumigatus, Jaleesa M. Garth
Immunoregulation During Acute And Chronic Exposure To Aspergillus Fumigatus, Jaleesa M. Garth
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A. fumigatus is one of the most common fungal isolates with clinical disorders ranging from mild to severe. The development of Aspergillus-induced allergic and invasive fungal infections is a major health concern in several patient populations. IL-1 family members have been shown to play critical roles in host defense against A. fumigatus. IL-33, an IL-1 family member widely study in allergic and inflammatory diseases, was induced upon acute exposure to A. fumigatus. IL-33 receptor knockout mice, (Il1rl1-/-), demonstrated lower lung fungal burden in the presence of enhanced IL-1α, IL-1β, IL-6, IL-17A, IL-22, and PGE2 production. Administration of IL-33 to normal …
Streptococcus Pneumoniae In The Heart Subvert The Host Response Through Biofilm-Mediated Resident Macrophage Killing, Anukul T. Shenoy
Streptococcus Pneumoniae In The Heart Subvert The Host Response Through Biofilm-Mediated Resident Macrophage Killing, Anukul T. Shenoy
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During invasive disease, blood circulating Streptococcus pneumoniae are capable of invading the heart and forming bacteria filled cardiac microlesions. These microlesions are devoid of immune cells and disruptive of cardiac functionality. While the mechanisms underlying pneumococcal invasion of the myocardium are well-described, how the heart-invaded pneumococci evade immune detection and clearance is unknown. Since its discovery in 1881, invasive pneumococcal disease has been associated with the presence of extracellular diplococci or short chains in affected tissues. Herein, we show that heart-invaded pneumococci replicate within cellular vesicles and transition into biofilms. Although the host cell permissible for intracellular replication is yet …
O-Acetyltransferase Functionality Mediates Pneumococcal Capsular Diversity, Brady Spencer
O-Acetyltransferase Functionality Mediates Pneumococcal Capsular Diversity, Brady Spencer
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Streptococcus pneumoniae (pneumococcus) is an important human pathogen that asymptomatically colonizes the nasopharynx but can disseminate opportunistically to cause diseases such as otitis media, pneumonia, septicemia, or meningitis. The pneumo-coccal capsular polysaccharide is necessary to prevent opsonophagocytosis as nonencap-sulated pneumococci are largely avirulent. Currently, 98 antigenically distinct capsule types (serotypes) have been identified, which vary in virulence. O-acetylation, a subtle capsular modification, contributes to pneumococcal capsular diversity and modulates capsular physicochemical properties and interaction with innate or vaccine immunity. Replacement serotypes (and future vaccine types) 33F and 15B have O-acetylated capsules due to membrane-bound O-acetyltransferases (MOATs). We hypothesize that future …
A Novel Role For T-Bet And Ifng In Directing B Cell Differentiation, Sara Stone Stone
A Novel Role For T-Bet And Ifng In Directing B Cell Differentiation, Sara Stone Stone
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The transcription factor T-bet regulates the epigenetic programming and differentiation of cytotoxic and helper T (Th) cells. Several studies recently identified T-bet expression in B cells after stimulation with TLR7 or interferon alpha or gamma. T-bet controls isotype switching to IgG2a in B cells; however, the mechanism by which T-bet exerts this effect and whether T-bet regulates fate decision beyond isotype choice is not clear. When activated by interferon gamma-producing Th cells, B cells rapidly upregulate T-bet and undergo T-bet dependent changes in chromatin accessibility and wide-scale transcriptional reprogramming. T-bet controls expression of the core transcription factors required for antibody …
Elucidating The Cellular Function Of The N-Terminal Domain Of Tyrosyl-Dna Phosphodiesterase I, Selma Marcela Cuya
Elucidating The Cellular Function Of The N-Terminal Domain Of Tyrosyl-Dna Phosphodiesterase I, Selma Marcela Cuya
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Tyrosyl-DNA phosphodiesterase I (Tdp1) is a conserved eukaryotic DNA repair enzyme that removes adducts from DNA-ends. This includes DNA topoisomerase I (Top1)-DNA covalent complexes reversibly stabilized by camptothecins (CPTs). Tdp1s two-step catalytic cycle requires the action of its nucleophilic histidine (Hisnuc) that detaches the adduct by forming a Tdp1-DNA adduct, and its general acid/base histidine (Hisgab) to activate water, thereby releasing Tdp1 from the DNA-end. Tdp1 expression is associated with genomic instability, cancer etiology, chemotherapeutic resistance, and SCAN1-neurodegeneration, via Tdp1HisgabArg catalytic mutant. Our lab has characterized substitutions of the catalytic histidines in both yeast and human cell models. These substitutions …
A Delicate Balancing Act: Curing Humanized Mouse Models Of Cooley’S Anemia By Reducing The Globin Chain Imbalance, Suean D. Fontenard
A Delicate Balancing Act: Curing Humanized Mouse Models Of Cooley’S Anemia By Reducing The Globin Chain Imbalance, Suean D. Fontenard
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Cooley’s Anemia (CA) is a hereditary disease which occurs when an individual inherits two null β-globin alleles. CA presents during the latter part of the first year of life due to the high levels of fetal hemoglobin (HbF) in the circulating red blood cells (RBCs) at birth. The absence of β-globin chains, to dimerize with α-globin chains in the newly formed bone marrow derived erythroblasts, results in premature destruction of the erythroid cells in the marrow and ineffective erythropoiesis. I hypothesized that increas-ing the amount of β-like globin chains for hemoglobin assembly in erythroblasts would lessen disease severity or even …
Optimizing The Non-Ablative Conditioning Regimen For Bone Marrow Transplantation Using A Murine Model Of Sickle Cell Disease, Divya Devadasan
Optimizing The Non-Ablative Conditioning Regimen For Bone Marrow Transplantation Using A Murine Model Of Sickle Cell Disease, Divya Devadasan
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In this dissertation, we sought to determine if a sub-myeloablative conditioning regimen followed by bone marrow transplantation/hematopoietic stem cell transplantation (HSCT) using syngeneic donor cells could facilitate donor chimerism using a clinically relevant mouse model of sickle cell disease (SCD). This pre-clinical study determined the feasibility of using sub-myeloablative conditioning in the context of autologous HSCT. The prospect of using less-intense conditioning is particularly appealing in the era of modern gene-editing technologies since its extension to use in humans will allow for HSCT to be less toxic and hence be applicable in all patients. We showed that using a sub-myeloablative …
A Tissue Engineering Approach To The Development Of A 3d Breast Carcinoma Surrogate, Kayla Goliwas
A Tissue Engineering Approach To The Development Of A 3d Breast Carcinoma Surrogate, Kayla Goliwas
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Tumors are three dimensional tissues consisting of malignant cells and various stromal cell populations within a volume of extracellular matrix. These components form an intricate network that influences many facets of tumor biology. Paracrine interactions between tumor cells and the surrounding microenvironment can alter drug response and impact therapeutic efficacy in vivo, yet most current in vitro models do not accurately recapitulate the stromal microenvironment or associated dimensionality of human tumors. In vitro models that are more representative of the human tumor microenvironment, including a more recapitulative dimensionality and cellular composition, have broad utility in the evaluation of mechanisms driving …
Characterization Of Spinal Cord Injury And Spinal Cord Injury Induced Neuropathic Pain, Amanda Mohaimany-Aponte
Characterization Of Spinal Cord Injury And Spinal Cord Injury Induced Neuropathic Pain, Amanda Mohaimany-Aponte
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Spinal cord injury (SCI) affects between 40 and 80 million people globally. Within the United States over 400,000 individuals live with SCI, and annually over 17,000 individu-als are added to this population. SCI patients are afflicted with a myriad of issues, one of which being SCI induced neuropathic pain (SCI-NP). Up to 80% of SCI patients go on to develop SCI-NP, which has been shown to last chronically and present itself as evoked pain, spontaneous pain, or a combination of both. SCI-NP is a top concern for SCI pa-tients, often listed before functional recovery. SCI-NP has been shown to greatly …
Modeling Mild And Repeated Mild Traumatic Brain Injury Induced Functional And Pathophysiological Alterations, Jessica Nicole Nichols
Modeling Mild And Repeated Mild Traumatic Brain Injury Induced Functional And Pathophysiological Alterations, Jessica Nicole Nichols
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Mild traumatic brain injury (mTBI) is a major health concern and accounts for over 75% of the 2.5 million brain injuries reported annually in the United States. Afflicted individuals typically experience a broad spectrum of physical, cognitive, and neuropsychological symptoms. Repeated mTBIs (rmTBIs) can further exacerbate these physiological alterations and negatively impact patient quality of life. Currently, there are no therapeutic agents that have successfully navigated clinical trials to be shown efficacious despite mounds of preclinical evidence suggesting to the contrary. This lack of translation exposes the dire need to design, characterize, and implement better and more relevant model systems …
Investigating Phenotypic Severity Associated With Sister Chromatid Cohesion Defects In Human Disease, Stefanie Marie Percival
Investigating Phenotypic Severity Associated With Sister Chromatid Cohesion Defects In Human Disease, Stefanie Marie Percival
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INVESTIGATING PHENOTYPIC SEVERITY ASSOCIATED WITH SISTER CHROMATID COHESION DEFECTS IN HUMAN DISEASE STEFANIE M. PERCIVAL GRADUATE BIOMEDICAL SCIENCES ABSTRACT Sister chromatid cohesion (SCC) is a process that utilizes a proteinaceous ring, cohesin, for accurate chromosome segregation. An essential process in S phase termed cohesion establishment is necessary to stabilize cohesin rings around sister chromatids. Mutations in establishment of cohesion homolog 2 (ESCO2), a protein essential for cohesion establishment, cause a developmental disorder called Roberts Syndrome (RBS). Cytogenetic analysis in patients reveals heterochromatic repulsion (HR), a centromeric puffing, indicative of cohesion defects. The severity of phenotypes varies from preterm lethal to …
Interplay Of The Circadian Clock And Growth Hormone Signaling In The Heart, Ryan Darrell Berry
Interplay Of The Circadian Clock And Growth Hormone Signaling In The Heart, Ryan Darrell Berry
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Growth hormone (GH) signaling plays a critical role in postnatal development and the details of its release, regulation, and influence on the development of a number of organs has been well studied. GH is released from the anterior pituitary in a pulsatile fashion with pulse amplitude being greater at night than during the day in a number of species, including humans. Once in circulation, GH binds to the GH receptor (GHR) on target tissues throughout the body altering gene expression and stimulating the local production of insulin-like growth factor 1 (IGF-1). IGF-1 primarily acts in an autocrine and paracrine fashion. …
Contribution Of Distinct Interneuron Subclasses To Cortical Network Activity, Andrew Scott Bohannon
Contribution Of Distinct Interneuron Subclasses To Cortical Network Activity, Andrew Scott Bohannon
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The excitatory glutamatergic output of the cerebral neocortex is tightly regulated by the release of the inhibitory neurotransmitter GABA from cortical interneurons (INs). Once viewed as a largely homogenous population, recent studies have revealed that cortical INs display a diverse range of biochemical, anatomical and physiological properties. In this work we sought to determine if differences in the physiology and connectivity patterns of identified cortical IN populations enable them to differentially contribute to network activity. Specifically, we investigated the contribution of discrete L2/3 IN groups to the generation of aberrant cortical synchrony, and the influence of HCN channels on information …
Activation Of Ampk To Diminish Sepsis-Induced Lung Injury, Nathaniel Bone
Activation Of Ampk To Diminish Sepsis-Induced Lung Injury, Nathaniel Bone
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Sepsis is the most frequent cause of death of hospitalized patients in modern ICUs. Severe infection, trauma, hemorrhage, burns, and surgery are significant causes of multi-organ injury and immune dysfunction that in turn primes for a high risk of secondary lung infections. In addition to detrimental inflammation, sepsis is linked to loss of metabolic plasticity due to mitochondrial dysfunction in immune cells and lung tissue. In particular, mitochondrial failure in lungs of critically ill septic patients is correlated with high mortality rates. We proposed that AMP-activated protein kinase (AMPK) activation, a major bioenergetic sensor and metabolic regulator, is a plausible …
Transcriptional Dysregulation In Interneurons Causes Altered Modulation Of Hippocampal Synaptic Transmission And Circuit Function By The Dopamine System, Lillian J. Brady
Transcriptional Dysregulation In Interneurons Causes Altered Modulation Of Hippocampal Synaptic Transmission And Circuit Function By The Dopamine System, Lillian J. Brady
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Genetic deletion of the transcriptional coactivator PGC-1α leads to transcriptional dysregulation in interneurons, and transcriptional dysregulation in interneurons lead to changes in hippocampal synaptic transmission and circuit function. Hippocampal circuit activity and synaptic transmission alterations have implications for symptoms of cognitive impairment in neurological disorders like schizophrenia. Modulation of dopamine receptor activity through pharmacologic application of haloperidol and the specific dopamine D4 receptor antagonist L-745,870 in PGC-1α-/- mice leads to altered effects on inhibitory/excitatory synaptic transmission balance, circuit function, and innate hippocampal dependent nesting behavior. These are key aspects underlying hippocampus dependent cognitive impairment. Specifically, bath application of haloperidol restores …
Immunobiology Of The Mucosal Response To Helicobacter Pylori In Children, Kyle Brawner
Immunobiology Of The Mucosal Response To Helicobacter Pylori In Children, Kyle Brawner
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Helicobacter pylori colonizes the stomach of approximately one half of the world’s population. However, the vast majority of infected persons remain asymptomatic. The degree of H. pylori-induced gastric inflammation depends on a complex interaction of several factors. In this dissertation, we focus on age as a determinant of gastritis severity. Children are known to respond to H. pylori infection with a stronger T regulatory cell profile compared with infected adults, yet the reason remains unknown. The influence of the microbiota on, and the communication among, cells of the innate immune system shape the nature of the adaptive immune response to …
The Impact Of Mitochondrial Genetic Background On Development Of Complex Multifactorial Diseases, Alexander Wendell Bray
The Impact Of Mitochondrial Genetic Background On Development Of Complex Multifactorial Diseases, Alexander Wendell Bray
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Complex multifactorial diseases such as cardiovascular disease (CVD) and cancer are a pervasive and inescapable component of modern society. However, the genetic elements that modulate individual susceptibility to these diseases remain poorly defined. Excessive mitochondrial oxidant production has been implicated in the initiation and progression of both CVD and cancer. Moreover, polymorphisms inherited on the mitochondria genome appear to influence mammalian mitochondrial function and oxidant generation. In the present study, mitochondrial-nuclear-eXchange (MNX) mice were used to directly assess the contribution of mitochondrial DNA (mtDNA) polymorphisms to atherosclerosis in the apoE deficient (apoE-/-) mouse model of hypercholesterolemia induced atherogenesis. ApoE-/- mice …
Microenvironmental Regulation And Epigenetic Control Of Glioma Pathogenesis, Nathaniel H. Boyd
Microenvironmental Regulation And Epigenetic Control Of Glioma Pathogenesis, Nathaniel H. Boyd
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Tumor microenvironments can promote stem cell maintenance, tumor growth, and therapeutic resistance, findings linked by the tumor initiating cell hypothesis. The ischemic microenvironment characterized by low oxygen and glucose, and acidic stress occurs in both solid tumors and non-neoplastic tissue injury. Standard of care for glioblastoma (GBM) includes the chemotherapy temozolomide, which is not curative due, in part, to residual therapy-resistant brain tumor initiating cells (BTICs). Temozolomide efficacy may be increased by targeting carbonic anhydrase 9 (CAIX), a hypoxia and acidic stress responsive gene important for maintaining the altered pH gradient of tumor cells. Using patient-derived GBM xenograft cells, we …
Nadph Oxidase-Derived Superoxide Production During Coxsackie B Virus Infection Fuels Macrophage Activation To Accelerate Type 1 Diabetes, Ashley R. Burg
Nadph Oxidase-Derived Superoxide Production During Coxsackie B Virus Infection Fuels Macrophage Activation To Accelerate Type 1 Diabetes, Ashley R. Burg
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Type 1 diabetes (T1D) is a chronic inflammatory autoimmune disease in which autoreactive T cells selectively destroy insulin-producing pancreatic β-cells. While genetic predisposition underlies susceptibility, environmental factors are proposed to play the important role of triggering the activation of autoimmunity in T1D individuals. Viral infections, particularly by Coxsackie B viruses, are highly suspected as a precipitating event. However, the exact molecular mechanism for how viral infections elicit β-cell-specific autoimmunity remains unclear. Rodent models of virus-induced T1D suggest it is through bystander activation, during which innate antiviral responses to pancreas-tropic viral infections create an inflammatory milieu that breaks the peripheral tolerance …
Evaluating The Genotype Phenotype Correlations In Cleidocranial Dysplasia, Stephen Lamar Greene
Evaluating The Genotype Phenotype Correlations In Cleidocranial Dysplasia, Stephen Lamar Greene
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Cleidocranial dysplasia (CCD, OMIM 119600) is a rare (1 in 1,000,000) human autosomal dominant skeletal disorder with unique craniofacial and dental features caused by mutations the gene coding for transcription factor RUNX2. RUNX2 is a key master regulator of osteoblast differentiation, chondrocyte maturation and tooth formation. CCD is commonly diagnosed based on bone defects with ~90% of cases presenting with supernumerary teeth or a “third dentition”. Mouse Runx2 null models (Runx2+/-), although having similar CCD skeletal defects, do not mimic the human dental phenotype of supernumerary teeth. Instead, Runx2-/- mouse have arrested tooth formation at the cap stage. Furthermore, based …
Purification, Characterization, And Enzymatic Activity Of Human Cytosolic Sulfotransferase 1c4, Amber Lynn Guidry
Purification, Characterization, And Enzymatic Activity Of Human Cytosolic Sulfotransferase 1c4, Amber Lynn Guidry
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Human cytosolic sulfotransferase 1C4 (hSULT1C4) is a dimeric Phase II drug-metabolizing enzyme primarily expressed in the developing fetus. SULTs facilitate the transfer of a hydrophilic sulfonate moiety from 3’-phosphoadenosine-5’-phosphosulfate (PAPS) onto an acceptor substrate altering the substrate’s biological activity and increasing the compound’s water solubility. While several of the hSULTs’ endogenous and xenobiotic substrates have been identified, the physiological function of hSULT1C4 remains unknown. The fetal expression of hSULT1C4 leads to the hypothesis that the function of this enzyme may be to regulate metabolic and hormonal signaling molecules, such as estrogenic compounds, that may be generated or consumed by the …