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Full-Text Articles in Medicine and Health Sciences
Ca2+-Independent Phospholipase A2 Beta-Derived Lipid Signals And Osteogenesis, William Hancock
Ca2+-Independent Phospholipase A2 Beta-Derived Lipid Signals And Osteogenesis, William Hancock
All ETDs from UAB
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 …
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 …
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 …
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 …
Cd8+ T Lymphocyte Responses To Persistent Murine Cytomegalovirus Infection Of The Central Nervous System, Kristine Valenteros
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
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 …
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
All ETDs from UAB
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 …
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 …
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 …
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 …
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 …
Development And Assessment Of Nonsense Suppression Therapies To Ameliorate Disease Progression In A Nonsense Mouse Model Of Mps I Hurler Syndrome, Gwendolyn G. Gunn
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% …
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 …
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 …
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 …
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 …
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 …
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 …
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 …
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 …
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. …
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 …
The Role Of Klotho In Adult Neurogenesis, Ann Laszczyk
The Role Of Klotho In Adult Neurogenesis, Ann Laszczyk
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Klotho is an anti-aging protein that when upregulated, extends lifespan and enhances cognition. Klotho knockout mice age prematurely and die by ~8 weeks of life after developing cognitive impairment. Klotho function outside of the brain is well established but the protein’s action within the brain remains unknown. As klotho regulates peripheral stem cell populations, I sought to determine whether klotho contributes to cognition through a role in the maintenance of the adult hippocampal neurogenic niche. I examined adult mouse neurogenesis using global klotho-deficiency or global klotho overexpression models. Klotho knockout brains show reduced progenitor proliferation and granule cell production while …
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 …
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 …
The Role Of Ribosomal Protein S25 In Non-Canonical Translation Initiation, Beth Angela Walters
The Role Of Ribosomal Protein S25 In Non-Canonical Translation Initiation, Beth Angela Walters
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Most messenger RNA (mRNA) are translated in a cap-dependent manner, requir-ing the recognition of a 5’ cap structure by a set of eukaryotic initiation factors (eIFs) in-cluding the 40S ribosomal subunit. The subunit scans the mRNA until the start codon is recognized, triggering the release of eIFs and recruitment of the 60S subunit. Cellular stress and viral infection down-regulate cap-dependent translation, therefore, cellular and viral messages rely on a cap-independent mechanism. One mechanism requires an inter-nal ribosome entry site (IRES). Viral IRESs were discovered over 25 years ago, with cellular IRESs to follow. The study of viral IRESs has brought …
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 …
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 …