Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Inflammation (4)
- Autophagy (3)
- Cognition (3)
- Mitochondria (3)
- Aging (2)
-
- Aspergillus fumigatus (2)
- Bioenergetics (2)
- Hippocampus (2)
- IL-22 (2)
- Macrophage (2)
- Metastasis (2)
- Neuroinflammation (2)
- Pneumococcus (2)
- Post-transcriptional regulation (2)
- ARDS (1)
- Adipocyte (1)
- Adrenergic receptors (1)
- Adult neurogenesis (1)
- Alpha-synuclein (1)
- Alphavirus (1)
- Alzheimer’s disease (1)
- Aminolgycosides (1)
- Amygdala (1)
- Amyloid precursor protein (1)
- Antibody secreting cells (1)
- Antiviral response (1)
- Anxiety (1)
- Astrocyte (1)
- Atherosclerosis (1)
Articles 1 - 30 of 54
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 …
Contribution Of Distinct Interneuron Subclasses To Cortical Network Activity, Andrew Scott Bohannon
Contribution Of Distinct Interneuron Subclasses To Cortical Network Activity, Andrew Scott Bohannon
All ETDs from UAB
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
Microenvironmental Regulation And Epigenetic Control Of Glioma Pathogenesis, Nathaniel H. Boyd
All ETDs from UAB
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
All ETDs from UAB
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 …
Immunoregulation During Acute And Chronic Exposure To Aspergillus Fumigatus, Jaleesa M. Garth
Immunoregulation During Acute And Chronic Exposure To Aspergillus Fumigatus, Jaleesa M. Garth
All ETDs from UAB
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
All ETDs from UAB
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 …
Evaluating The Genotype Phenotype Correlations In Cleidocranial Dysplasia, Stephen Lamar Greene
Evaluating The Genotype Phenotype Correlations In Cleidocranial Dysplasia, Stephen Lamar Greene
All ETDs from UAB
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 Hur In Astrocytes In Spinal Cord Injury, Thaddaeus Kwan
The Role Of Hur In Astrocytes In Spinal Cord Injury, Thaddaeus Kwan
All ETDs from UAB
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 …
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
All ETDs from UAB
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
Reciprocal Regulation Of The Α2a Adrenergic Receptor And The Amyloid Precursor Protein, Mary Alana Gannon
All ETDs from UAB
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
Alterations In Ubc9 Substrate Specificity Affect The Cellular Response To Dna Damage, Joshua Enyeribe Onuiri
All ETDs from UAB
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
All ETDs from UAB
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
Cd8+ T Lymphocyte Responses To Persistent Murine Cytomegalovirus Infection Of The Central Nervous System, Kristine Valenteros
All ETDs from UAB
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
All ETDs from UAB
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
The Use Of Web Computing To Solve Modern Data Problems In Science And Medicine, Alex M. Dussaq
All ETDs from UAB
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
A Delicate Balancing Act: Curing Humanized Mouse Models Of Cooley’S Anemia By Reducing The Globin Chain Imbalance, Suean D. Fontenard
All ETDs from UAB
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
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 …
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
All ETDs from UAB
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 …
Elucidating The Physiologic And Prognostic Significance Of N-Myc And Stat Interactor Using Models Of Mammary Development And Metastasis, Hawley Christine Pruitt
Elucidating The Physiologic And Prognostic Significance Of N-Myc And Stat Interactor Using Models Of Mammary Development And Metastasis, Hawley Christine Pruitt
All ETDs from UAB
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 …
Structure/Function Studies Of Yersinia Pestis Metal Transport Systems, Christopher David Radka
Structure/Function Studies Of Yersinia Pestis Metal Transport Systems, Christopher David Radka
All ETDs from UAB
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 …
Autophagy In Mitochondrial Quality Control And Proteotoxicity In Neurons, Matthew Redmann
Autophagy In Mitochondrial Quality Control And Proteotoxicity In Neurons, Matthew Redmann
All ETDs from UAB
Parkinson’s disease (PD) is the 2nd most common neurodegenerative disorder with aging as a significant risk factor. Sharing with aging brains, postmortem PD brains exhibit cellular deficits including autophagic dysfunction, mitochondrial dysfunction, and intracellular protein aggregates of alpha-synuclein. This dissertation will focus on the interplay between these key disease features. To that end, we coupled primary cortical neuronal cultures from either rats or mice with Seahorse extracellular flux, metabolomics and biochemical techniques. Autophagy is an important cell recycling program responsible for the clearance of damaged proteins and organelles. Bafilomycin A1 and chloroquine are compounds that inhibit autophagy by targeting the …
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
All ETDs from UAB
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 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
All ETDs from UAB
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
All ETDs from UAB
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 …
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 …
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
All ETDs from UAB
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 …
Advances In The Creation And Use Of Genetically Modified Rodent Models, Laura Lambert
Advances In The Creation And Use Of Genetically Modified Rodent Models, Laura Lambert
All ETDs from UAB
Rodents have been the model of choice for decades in biomedical research due to their relatively high physiological similarity to humans and amenability to genomic modification. While transgenic constructs were first used in mouse blastocysts in 1974 and the first mouse embryonic stem (ES) cell line created in 1981, the lack of reliable methods to produce ES cells or culture embryos from the rat led to the limitation of its use in spite of several advantages such as larger size and higher genetic homology with humans. Use of genetic modification has recently expanded due to the advent of tailored nucleases …
The Role Of Klotho In Adult Neurogenesis, Ann Laszczyk
The Role Of Klotho In Adult Neurogenesis, Ann Laszczyk
All ETDs from UAB
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 …
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
All ETDs from UAB
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 …
Activation Of Ampk To Diminish Sepsis-Induced Lung Injury, Nathaniel Bone
Activation Of Ampk To Diminish Sepsis-Induced Lung Injury, Nathaniel Bone
All ETDs from UAB
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 …