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Ca2+-Independent Phospholipase A2 Beta-Derived Lipid Signals And Osteogenesis, William Hancock Jan 2017

Ca2+-Independent Phospholipase A2 Beta-Derived Lipid Signals And Osteogenesis, William Hancock

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Bone modeling can be modulated by lipid signals and arachidonic acid (AA); its cyclo-oxygenase 2 (COX2) metabolite, prostaglandin E2 (PGE2), is an important mediator of optimal bone formation. Hydrolysis of AA from membrane glycerophospholipids is catalyzed by phospholipases A2 (PLA2s). We reported that mice deficient in the Ca2+-independent PLA2beta (iPLA2β), encoded by PLA2G6, have decreased bone formation, relative to wild type (WT) mouse bones. Here, we examined at the mechanistic and molecular levels the role of iPLA2β in bone formation using bone marrow stromal cells and calvarial osteoblasts from WT and iPLA2β-deficient mice and MC3T3-E1 osteoblast precursor cell line. Our …


Contribution Of Distinct Interneuron Subclasses To Cortical Network Activity, Andrew Scott Bohannon Jan 2017

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 …


Microenvironmental Regulation And Epigenetic Control Of Glioma Pathogenesis, Nathaniel H. Boyd Jan 2017

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 …


A Tissue Engineering Approach To The Development Of A 3d Breast Carcinoma Surrogate, Kayla Goliwas Jan 2017

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 …


Development And Assessment Of Nonsense Suppression Therapies To Ameliorate Disease Progression In A Nonsense Mouse Model Of Mps I Hurler Syndrome, Gwendolyn G. Gunn Jan 2017

Development And Assessment Of Nonsense Suppression Therapies To Ameliorate Disease Progression In A Nonsense Mouse Model Of Mps I Hurler Syndrome, Gwendolyn G. Gunn

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Nonsense mutations introduce a premature termination codon (PTC) into the open reading frame of an mRNA resulting in premature translation termination, loss of functional protein, and rapid degradation of the mutant mRNA. Approximately 11% of human genetic disorders are attributable to a nonsense mutation. Several small molecules have been identified as potential nonsense suppression compounds. These compounds increase the frequency of PTC recognition by near-cognate aminoacyl tRNAs resulting in PTC “readthrough” and restored protein production. Mucopolysaccharidosis type I-Hurler (MPS IH) is the severe form of the autosomal recessive lysosomal storage disorder caused by mutations in the iduronidase (IDUA) gene. 60-80% …


Reciprocal Regulation Of The Α2a Adrenergic Receptor And The Amyloid Precursor Protein, Mary Alana Gannon Jan 2017

Reciprocal Regulation Of The Α2a Adrenergic Receptor And The Amyloid Precursor Protein, Mary Alana Gannon

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Through widespread efferent projections, the locus coeruleus-noradrenergic (LC-NA) system supplies the cerebral cortex with norepinephrine, a key modulator of cognition. Neurodegeneration of the LC is an early hallmark of Alzheimer’s disease (AD), but despite this profound neuronal loss, there are several studies that show that NE levels actually remain stable or even elevated, especially at early stages of the disease. This indicates that the overall integrity of the NA system, rather than a loss of NE, is likely contributing to AD pathogenesis. We previously showed that activation of the α2A adrenergic receptor (α2AAR) increases amyloidogenic processing of amyloid precursor protein …


Alterations In Ubc9 Substrate Specificity Affect The Cellular Response To Dna Damage, Joshua Enyeribe Onuiri Jan 2017

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 Jan 2017

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 …


Elucidating The Physiologic And Prognostic Significance Of N-Myc And Stat Interactor Using Models Of Mammary Development And Metastasis, Hawley Christine Pruitt Jan 2017

Elucidating The Physiologic And Prognostic Significance Of N-Myc And Stat Interactor Using Models Of Mammary Development And Metastasis, Hawley Christine Pruitt

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Distant metastasis of breast carcinoma reduces the five year survival rate of patients from 90% to a dismal 25%. Although the metastatic cascade has been extensively studied for decades, players that influence the progression of metastatic disease remain elusive. N-MYC and STAT Interactor (NMI) is a gene previously demonstrated by Devine et. al. to be downregulated with metastatic progression of breast cancer. However, due to the lack of a relevant genetic model, details of biological consequence of the loss of expression of this gene were unknown. We have constructed and characterized a mammary specific Nmi knock out mouse to elucidate …


Uncovering The Role Of Common Gamma-Chain Cytokines In Aspergillus Fumigatus Associated Diseases, Kristen Marie Reeder Jan 2017

Uncovering The Role Of Common Gamma-Chain Cytokines In Aspergillus Fumigatus Associated Diseases, Kristen Marie Reeder

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Fungal pathogens contribute to a wide range of diseases that are largely dependent on the host’s immune state. In the case of immune suppression, Aspergillus fumigatus is the causative agent of invasive aspergillosis. Furthermore, asthmatics sensitized to fungi such as Aspergillus fumigatus are reported to have more severe asthma. We have previously described a role for IL-22 in mouse models of invasive aspergillosis and fungal asthma. IL-22 was found to play a protective role in invasive aspergillosis, while it was found to play an immunopathogenic role in asthma. Here we describe the cell sources of IL-22 in both models. We …


Relationship Between Walking Speed And Kinematic Trajectory Complexity In People With Poststroke Hemiparesis, Deanna Delayne Rumble Jan 2017

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 Hur In Astrocytes In Spinal Cord Injury, Thaddaeus Kwan Jan 2017

The Role Of Hur In Astrocytes In Spinal Cord Injury, Thaddaeus Kwan

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Neuroinflammation is a defining event during the acute phase of spinal cord injury (SCI). The inflammatory cascade is initiated by activated glial cells such as astrocytes and microglia in the milieu of the injured tissue through release of pro-inflammatory cytokines, matrix metalloproteinases, and reactive oxygen species. These soluble factors produce cytotoxicity to neurons and other cells either directly or indirectly by promoting permeabilization of the blood-spinal cord barrier, edema and subsequent ischemia. These factors also serve to recruit and activate additional glia and peripheral immune cells. The mRNAs of many of these soluble factors such as TNFα, IL-1β, CXCL1, and …


Post-Transcriptional Regulation Of Autophagy By The 5’-3’ Mrna Decay Pathway In Saccharomyces Cerevisiae, Matthew Weaver Jan 2017

Post-Transcriptional Regulation Of Autophagy By The 5’-3’ Mrna Decay Pathway In Saccharomyces Cerevisiae, Matthew Weaver

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The process of bulk degradation of cytoplasmic contents, called macroautophagy or simply autophagy, is a heavily conserved cellular process from yeast to humans. In yeast, it involves more than 30 different autophagy related genes (ATG) that coordinate the process of building a double membrane vesicle, called the autophagosome, that fuses with the vacuole to allow degradation and recycling of its contents. This process can also be selective, involving the recruitment of the autophagic machinery to specific organelles. In this work, we used RNA sequencing (RNA-seq) to identify a subset of ATG genes that are heavily upregulated in response to nitrogen …


The Role Of Adipocytes And Osteocytes In Multiple Myeloma Progression, Timothy Nathan Trotter Jan 2017

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 …


Characterization Of Molecular Pathways Involved In The Production Of Class-Switched Antibodies, Arthur James Vanvalkenburg Jan 2017

Characterization Of Molecular Pathways Involved In The Production Of Class-Switched Antibodies, Arthur James Vanvalkenburg

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This dissertation research describes two independent characterizations of molecular pathways involved in the manufacture of class-switched antibodies and differentiation of B cells involving the adaptor protein Hematopoietic SRC Homology 2 Domain-containing protein (HSH2) and the surface molecule CD19. HSH2 is dynamically expressed in different subsets of B cells, showing high expression in B1 and MZ B cells and low expression in GC B cells. Experiments involving HSH2 transgenic mice have determined that HSH2 may act as a rheostat regulating the production of class-switched antibodies. Various factors that stimulate B cell activation and differentiation induce HSH2 expression, although regulation of HSH2 …


The Impact Of Mitochondrial Genetic Background On Development Of Complex Multifactorial Diseases, Alexander Wendell Bray Jan 2017

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 …


Evaluating The Genotype Phenotype Correlations In Cleidocranial Dysplasia, Stephen Lamar Greene Jan 2017

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 Jan 2017

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 …


Immunoregulation During Acute And Chronic Exposure To Aspergillus Fumigatus, Jaleesa M. Garth Jan 2017

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 …


Identification Of The Microrna Mir-101a And Its Target Ezh2 As Contributors To Rodent Anxiety-Like Behavior, Joshua Cohen Jan 2017

Identification Of The Microrna Mir-101a And Its Target Ezh2 As Contributors To Rodent Anxiety-Like Behavior, Joshua Cohen

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Anxiety disorders are the most commonly diagnosed mental illness in the United States. Yet current treatment options are of limited efficacy, resulting in chronic disability for many patients. A greater mechanistic understanding of the neural states that cause anxiety behavior is necessary to develop better treatments for anxiety disorders. Since rodent models provide greater opportunity for investigating cellular and molecular under-pinnings of anxiety-like behavior, the present studies utilized rats bred for High Response to novelty (High Responders, HRs) and Low Response to novelty (Low Responders, LRs) which naturally exhibit low and high levels of anxiety respectively. Because the HR/LR anxiety …


Tgf-Β Regulates The Stability Of Sox9 In Cartilage, George Coricor Jan 2017

Tgf-Β Regulates The Stability Of Sox9 In Cartilage, George Coricor

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One out of two people in the U.S. will experience some form of Osteoarthritis (OA) in their lifetime. Members of the Transforming Growth Factor-β (TGF-β) superfamily are important factors that stimulate chondrocyte matrix biosynthesis. Mice with a dominant-negative mutation of the TGF-βIIR develop a degenerative joint disease resembling OA. Another key chondrogenic factor, SOX9, is important for maintaining chondrocyte function. SOX9 and TGF-β receptors are decreased in OA patients. Our overall hypothesis is that TGF-β regulates SOX9 to maintain articular cartilage. We utilized two cell culture models for these experiments, ATDC5 cells, and primary bovine articular chondrocytes. We showed that …


Attachment Of Streptococcus Pneumoniae Capsular Polysaccharide To The Cell, Thomas Robbin Larson Jan 2017

Attachment Of Streptococcus Pneumoniae Capsular Polysaccharide To The Cell, Thomas Robbin Larson

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Streptococcus pneumoniae is an important human pathogen. The major virulence factor for S. pneumoniae is the capsular polysaccharide (CPS). Proper expression and localization of the CPS is essential for pathogenesis. Despite the importance of the proper transfer to the cell surface of this virulence factor, no studies have shown the exact structure and attachment to either the cell wall or membrane. Using the S. pneumoniae serotype 2 CPS as a model, which is synthesized by the widespread Wzy mechanism, we found that the CPS attaches to the cell wall β-D-N-acetylglucosamine (GlcNAc) of peptidoglycan (PG) via a direct glycosidic linkage. This …


A Novel Role For T-Bet And Ifng In Directing B Cell Differentiation, Sara Stone Stone Jan 2017

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 …


Cd8+ T Lymphocyte Responses To Persistent Murine Cytomegalovirus Infection Of The Central Nervous System, Kristine Valenteros Jan 2017

Cd8+ T Lymphocyte Responses To Persistent Murine Cytomegalovirus Infection Of The Central Nervous System, Kristine Valenteros

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Cytomegalovirus (CMV) is the most frequent cause of congenital brain abnormalities and can lead to lifelong neurological sequalae. Although the brain is a major target in congenital CMV infection, little is known about the long-term effects of infection of the central nervous system (CNS) following acute infection and the resulting neuroimmune responses involved. Due to species-specificity of HCMV, we use a mouse model to study the pathogenesis of HCMV infection of the developing CNS. Newborn mice peripherally infected with murine CMV (MCMV) develop high levels of viremia and subsequent productive infection in the brain parenchyma. CD8+ T lymphocytes are essential …


The Functional Role Of Toll-Like Receptor 4 In The Renal Microcirculation., Justin Pieter Van Beusecum Jan 2017

The Functional Role Of Toll-Like Receptor 4 In The Renal Microcirculation., Justin Pieter Van Beusecum

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Renal autoregulation is an intrinsic property of afferent arterioles that maintains a stable RBF, glomerular capillary pressure, and GFR, while protecting the glomeruli against fluctuations in arterial pressure. Recently it has been reported that immune system activation and inflammation have been linked to impairment of renal autoregulatory behavior. Evidence suggests that activation of toll-like receptor 4 (TLR4) plays an important role in the progression of AKI and CKD. The contributions of innate immune system activation, TLR4 and renal autoregulatory dysfunction remain unknown. This dissertation explores the novel concept that both acute and chronic TLR4 activation leads to the attenuation of …


The Use Of Web Computing To Solve Modern Data Problems In Science And Medicine, Alex M. Dussaq Jan 2017

The Use Of Web Computing To Solve Modern Data Problems In Science And Medicine, Alex M. Dussaq

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Modern day research in science and medicine has become dominated by the ideas of 'Big Data'. Life science data have become progressively more complex and the rate at which it is generated continues to accelerate. This combination of complexity and genera- tion speed creates a multitude of informatics problems to solve. We believe that among the many issues facing modern data scientists, there exists a substantial subset that can only be satisfactorily solved utilizing web computing. Of these web specific issues, we have chosen to focus primarily on data storage and retrieval, data privacy, and data visualization. We present here …


A Delicate Balancing Act: Curing Humanized Mouse Models Of Cooley’S Anemia By Reducing The Globin Chain Imbalance, Suean D. Fontenard Jan 2017

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 …


The Function Of Protein Kinase Ck2 In Cd4 T Cell Differentiation And Autoimmunity, Sara Ann Gibson Jan 2017

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 …


Endogenous Interferon-Β Regulates Survival And Development Of Transitional B Cells, Jennie Ann Hamilton Jan 2017

Endogenous Interferon-Β Regulates Survival And Development Of Transitional B Cells, Jennie Ann Hamilton

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The survival responses of transitional B cells play a key role in shaping the development of mature, antibody producing B cells. Abnormal transitional T1 B cell survival responses are associated with the generation of polyreactive self-antigen-reactive mature B cells in systemic lupus erythematosus (SLE). Type I interferon (IFN) dysregulation is strongly associated with autoantibodies (autoAbs) and disease flares, particularly in African American (AA) patients. B cells produce a variety of immune-modulatory cytokines, but B cell production of high affinity IFNβ in SLE has not been investigated. In the present study, analysis of PBMCs from SLE patients (n=34) and healthy controls …


Structure/Function Studies Of Yersinia Pestis Metal Transport Systems, Christopher David Radka Jan 2017

Structure/Function Studies Of Yersinia Pestis Metal Transport Systems, Christopher David Radka

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The largest market sector of the global antibiotics industry is on the verge of becoming obsolete because the incidence of β-lactam antibiotic resistance in the clinic continues to rise. Therefore, we are in dire need of new therapeutics to address the increasing threat of antibiotic resistance. Novel targets that could lead to a new drug class are ABC (ATP-binding cassette) importers, which are only found in bacteria. The substrate-binding protein (SBP) components of these transporters present an intriguing subject of study because of their abundance in the cell and potential roles in infection. As a contribution to the scholarship of …