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Full-Text Articles in Medicine and Health Sciences
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
All ETDs from UAB
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 …
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 …
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 …
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 …
The Role Of Macrophages In Pressure-Overload Induced Cardiac Remodeling, Bindiya Dinesh Patel
The Role Of Macrophages In Pressure-Overload Induced Cardiac Remodeling, Bindiya Dinesh Patel
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Cardiac pressure-overload is a state of increased hemodynamic load and is initially characterized by concentric left ventricular (LV) hypertrophy, but can transition to eccentric hypertrophy and adverse LV remodeling leading to heart failure (HF). Cardiac remodeling during pressure-overload is accompanied by dysregulated collagen deposition, cardiomyocyte hypertrophy, and increased inflammatory signaling. Both clinical and preclinical studies have documented increased expression of inflammatory cytokines and leukocyte infiltration in the pressure-overloaded heart, indicating inflammatory mechanisms are active during cardiac remodeling. Despite the well-known link between leukocyte infiltration and exacerbated tissue injury, the role of innate immune cells, particularly monocytes, macrophages and dendritic cells, …
Endogenous Interferon-Β Regulates Survival And Development Of Transitional B Cells, Jennie Ann Hamilton
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 …
Ca2+-Independent Phospholipase A2 Beta-Derived Lipid Signals And Osteogenesis, William Hancock
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 …
The Use Of Web Computing To Solve Modern Data Problems In Science And Medicine, Alex M. Dussaq
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 …
Attachment Of Streptococcus Pneumoniae Capsular Polysaccharide To The Cell, Thomas Robbin Larson
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 …
Phenomic And Metabolomic Analysis Of Chronological Aging In Saccharomyces Cerevisiae, Haley Albright
Phenomic And Metabolomic Analysis Of Chronological Aging In Saccharomyces Cerevisiae, Haley Albright
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Systematic investigation of chronological lifespan (CLS) in the Saccharomyces cerevisiae yeast gene knockout and knockdown (YKO/KD) strains reveals genes, path-ways, and interactions of potential relevance for aging of all eukaryotic cell types. Growth curves obtained by quantitative high-throughput cell array phenotyping (Q-HTCP) of the entire YKO/KD strain collection provide comprehensive snapshots of the influence of each individual gene on CLS. Yeast CLS is also influenced by media com-position, auxotrophic background, and media buffering. We used Q-HTCP to analyze CLS of the YKO/KD libraries, focusing on the interaction between gene networks and media buffering, with respect to their influence on CLS. …
Structure/Function Studies Of Yersinia Pestis Metal Transport Systems, Christopher David Radka
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 …
Uncovering The Role Of Common Gamma-Chain Cytokines In Aspergillus Fumigatus Associated Diseases, Kristen Marie Reeder
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 …
The Role Of Rig-I And Mda5 In Alphavirus Replication, Ivan Viachaslavavich Akhrymuk
The Role Of Rig-I And Mda5 In Alphavirus Replication, Ivan Viachaslavavich Akhrymuk
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Evolution of vertebrates has resulted in the development of a wide range of cellular pattern recognition receptors (PRRs), which detect the presence of virus-specific molecules termed pathogen-associated molecular patterns (PAMPs). Sensing of the incoming viruses and/or their replication by PRRs activates the cascade of cellular pathways that ultimately result in activation of antiviral response. Such response is determined by hundreds of cellular genes, whose products either directly interfere with virus replication or are released from the cells and activate antiviral state in yet uninfected cells. Consequently, the latter cell signaling prevents development of the next rounds of infection both in …
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 …
Post-Transcriptional Regulation Of Autophagy By The 5’-3’ Mrna Decay Pathway In Saccharomyces Cerevisiae, Matthew Weaver
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 …
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 …
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. …
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 …
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 …
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 …
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 …
The Role Of Hur In Astrocytes In Spinal Cord Injury, Thaddaeus Kwan
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 …
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 …
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 …
Identification Of The Microrna Mir-101a And Its Target Ezh2 As Contributors To Rodent Anxiety-Like Behavior, Joshua Cohen
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 …
Reciprocal Regulation Of The Α2a Adrenergic Receptor And The Amyloid Precursor Protein, Mary Alana Gannon
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 …
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 …
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 …
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 …