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Medical Sciences

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2010

Doctor of Philosophy (PhD) Heersink School of Medicine

Articles 1 - 30 of 74

Full-Text Articles in Medicine and Health Sciences

The Contribution Of Different Mechanisms Of Viral Sequence Variation To The Evolution Of Positive-Sense Single-Stranded Rna Viruses, Brett Earl Pickett Jan 2010

The Contribution Of Different Mechanisms Of Viral Sequence Variation To The Evolution Of Positive-Sense Single-Stranded Rna Viruses, Brett Earl Pickett

All ETDs from UAB

The Flaviviridae family of positive-sense single-stranded RNA (+ssRNA) viruses includes viral taxa which greatly impact public health worldwide. To explore how the viruses within the Flaviviridae family evolve, we examined the extent to which these viral taxa use nucleotide covariance, spontaneous mutation, and/or homologous recombination to vary their genotype as well as the resulting phenotype. We developed and used CovarView to assist us in simultaneously viewing and inspecting the results from whole genome covariance analyses. This resulted in the identification of previously-characterized RNA functional structures in the genomes of hepatitis C virus (HCV), as well as a new RNA functional …


Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis, Dario A. Vitturi Jan 2010

Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis, Dario A. Vitturi

All ETDs from UAB

The recent discovery that red blood cells might mediate hypoxic blood flow together with accumulating evidence that suggests a role for the modulation of vascular inflammation has reshaped the way we think about the function of these cells. In this thesis we investigate the mechanisms that regulate these newly appreciated functions and focus on i) the ability of red cells to couple oxygen sensing with nitrite reduction and nitric oxide formation and ii) the role of the beta93cys, a conserved residue amongst mammalian hemoglobins and whose function remains unclear. Data will be presented that demonstrate that nitrite reduction to nitric …


Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters Jan 2010

Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters

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The ubiquitin proteasome system (UPS) is a coordinated process by which the cell can control protein distribution and abundance. Proteins are marked for turnover by the construction of a polyubiquitin chain on the protein substrate. Once engaged by the proteasome, the ubiquitin side-chain is disassembled by proteasomal deubiquitinating enzymes (DUBs), preventing entry of ubiquitin into the proteasome and recycling it for use in future reactions. One of the DUBs that resides on the proteasome is Ubiquitin Specific Protease 14 (Usp14), which is mutated in the ataxia (axJ) mice. This mutation results in pronounced physical deficits and, unexpectedly, a deficit in …


Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin Jan 2010

Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin

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DNA replication and cytokinesis are two important parts of the cell division process. Our studies address different aspects of both of these processes and potential links between them. One of the best approaches for studying DNA replication in eukaryotes has been an analysis in cell free in vitro systems. The existing cell free replication systems for Drosophila are relatively ineffective. In the first part of this work, we have developed an optimized in vitro system to study DNA replication using early egg extracts of Drosophila. Our studies indicate that this system proves to be an extremely useful tool for a …


Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley Jan 2010

Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley

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Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …


Analyzing Dna Topology And Transcription In Salmonella Enterica Serovar Typhimurium During Dichotomous Growth, Betty M. Booker Jan 2010

Analyzing Dna Topology And Transcription In Salmonella Enterica Serovar Typhimurium During Dichotomous Growth, Betty M. Booker

All ETDs from UAB

The bacterial chromosome is dynamic. The principle goal of my research is to understand how DNA topology is altered by transcription in Salmonella enterica serovar Typhimurium LT2. Gamma delta-resolution requires two direct repeat Res sites to pair a plectonemic synapse. Previous work from our lab showed that the zones of high transcription inhibited gamma delta-resolution. Using phage λ recombineering methods, we have developed Salmonella strains to study ribosomal RNA operons, which are the most highly transcribed genes in bacteria. We propose a molecular model for how supercoiling generated by high levels of transcription modifies chromosome structure.


The Role Of Toll-Like Receptors 2 And 4 In Helicobacter Felis Infections And Asthma, Carolyn Durham Jan 2010

The Role Of Toll-Like Receptors 2 And 4 In Helicobacter Felis Infections And Asthma, Carolyn Durham

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The inverse correlation between the industrialization and disease prevalence is termed the "hygiene hypothesis." Supporting this, immunological studies show Th1 cytokines modulate Th2 immune responses. Because the mucosa is essential in antigenic exposure, understanding bacterial sensing here is critical to addressing three foundations of this hypothesis: the role of bacterial exposure, relevance of noninvasive bacterial exposure, and influence of these exposures on immune responses. Key components of antigen sensing in the mucosa are toll-like receptors (TLRs) 2 and 4, which have been implicated in disease. The hypothesis of this thesis is, by globally knocking out one or both of these …


Identification And Validation Of Biodosimetry Markers In Multiple Models Of Radiation Exposure, Ashley Nicole Filiano Jan 2010

Identification And Validation Of Biodosimetry Markers In Multiple Models Of Radiation Exposure, Ashley Nicole Filiano

All ETDs from UAB

Following a radiological or nuclear disaster, radiation dose assessment is imperative to minimize morbidity and mortality through rationally directed medical intervention. Current methods of retrospective dosimetry are not amenable to mass exposure scenarios and remain limited to monitoring of clinical symptoms (nausea/vomiting and lymphocyte depletion) and cytogenetic analysis. The goal of this study was to identify radiation biomarkers capable of qualitative (non-irradiated/irradiated) and quantitative (dose) assessment of radiation exposure. Initial analyses revealed 17 radiation-responsive cytokine/chemokine genes in blood samples from 6 pediatric cancer patients undergoing fractionated total body irradiation (TBI). These 17 genes were combined with 29 additional IR-inducible genes …


Transcriptional Regulation Of The Human Heme Oxygenase-1 Via Chromatin Looping In Renal Cells, Junghyun Kim Jan 2010

Transcriptional Regulation Of The Human Heme Oxygenase-1 Via Chromatin Looping In Renal Cells, Junghyun Kim

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Heme oxygenase-1 (HO-1) is a critical enzyme catalyzing the degradation of heme and generating carbon monoxide, iron, and biliverdin. In addition to heme degradation, HO-1 expression is known to protect against various cellular insults and disease states including acute kidney injury, atherosclerosis, vascular restenosis, and others. Human HO-1 gene expression is tightly regulated at the level of transcription. The main goal of this study is to explore the transcriptional regulation of the human HO-1 gene in renal epithelial cells. Chromosome Conformation Capture (3C) demonstrates that multiple regulatory regions within the HO-1 promoter and enhancer regions are physically interacting with each …


Investigation Of Residues Of The Vesicular Stomatitis Virus Nucleocapsid Protein That Affect Transcription And Rna Replication, Djamila Harouaka Jan 2010

Investigation Of Residues Of The Vesicular Stomatitis Virus Nucleocapsid Protein That Affect Transcription And Rna Replication, Djamila Harouaka

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The template for transcription and RNA replication for vesicular stomatitis virus (VSV) and other negative-strand RNA viruses is a ribonucleoprotein (RNP) complex consisting of the viral RNA genome and associated nucleocapsid (N) protein. The structure of the RNP-like complex of VSV showed that the RNA is sequestered between two lobes of the N protein, and adjacent N monomers are linked by an extensive network of interactions. Long-range interactions mediated by the N-terminal arm and C-terminal loop of the N protein stabilize the side-to-side contacts between adjacent N monomers, and are required for RNA encapsidation. It is unclear how the polymerase …


Developing A Screen To Identify Small Molecule Inhibitors That Disrupt Protein-Protein Interactions In Mycobacteria, Deborah Mai Jan 2010

Developing A Screen To Identify Small Molecule Inhibitors That Disrupt Protein-Protein Interactions In Mycobacteria, Deborah Mai

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Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) and infects nearly one-third of the world's population. The same TB chemotherapeutic regimen has been administered for more than 50 years, and can be improved by developing innovative methods to discover new anti-TB drugs. This work describes a newly established high-throughput screen (HTS) platform technology based on Mycobacterial-Protein Fragment Complementation (M-PFC) to identify small molecule inhibitors of protein-protein interactions in mycobacteria. M-PFC HTS employs both whole cell and target-based approaches, and offers flexibility in selecting an appropriate protein interaction target for HTS. Selectable drug targets can include interactions of essential …


A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison Jan 2010

A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison

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Chronic neutrophilic inflammation is a hallmark of numerous pulmonary diseases. It is commonly associated with declining lung function, collagen turnover, and increased protease activity. Our laboratory has recently published several articles describing a biologically active collagen breakdown product, proline-glycine-proline (PGP) and its more active amino-terminus acetylated form, N-α-PGP. PGP acts via classical chemokine receptors CXCR1 and 2 to draw neutrophils (PMNs) into sites of inflammation in what is potentially a feed-forward mechanism of disease. The tri-peptide appears to be a bio-marker in certain clinical diseases like cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The present work first details …


Brms1 Coordinately Regulates Microrna To Suppress Breast, Mick D. Edmonds Jan 2010

Brms1 Coordinately Regulates Microrna To Suppress Breast, Mick D. Edmonds

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The majority of cancer related mortality is attributed to complications associated with metastatic disease. Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple cancer types in vivo and loss of nuclear BRMS1 is associated with ER-negative cancers and a high rate of proliferation. Many groups have shown BRMS1 to regulate the expression of multiple metastatic genes, yet until now no one has been able to account for how these many changes in gene expression occur. In this work, we report that BRMS1 regulates a select set of genes called microRNA (miRNA), and these miRNA themselves can regulate metastasis. Using …


Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm Jan 2010

Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm

All ETDs from UAB

Breast cancer is the second leading cause of cancer-related death in American women and metastatic breast cancer has a 5-year survival rate of only 26%. Current targeted treatments for this disease include anti-estrogen strategies for estrogen receptor positive tumors (~60%) and anti-Her2/Neu strategies for tumors overexpressing this receptor (20-25%). A percentage of breast cancer patients, however, are resistant to these therapies and are left without any effective treatment options. One of the agents currently being investigated to improve breast cancer survival is TRA-8, an agonistic monoclonal antibody to death receptor 5 (DR5), which induces apoptosis in various types of cancer …


The Role Of Wnt5a In Mammary Gland Development, Sarah Baxley Jan 2010

The Role Of Wnt5a In Mammary Gland Development, Sarah Baxley

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Transforming growth factor-beta (TGF-beta) negatively regulates mammary gland development and requires Wnt5a to exert some of these effects on mammary gland development. Wnt5a is a non-canonical signaling Wnt that is expressed in all stages of mammary gland development except lactation. Using slow release pellets containing Wnt5a, as well as Wnt5a null tissue, we previously showed that Wnt5a also acts to limit mammary development. Initial studies revealed a potential role for TGF-beta and Wnt5a in regulating mammary gland progenitor cells, indicating they may act to regulate the stem and progenitor cell population. In order to study the role of Wnt5a on …


Canonical Wnt Signaling By The Proteolytic Processing Of Lrp6, Brandon Richard Beagle Jan 2010

Canonical Wnt Signaling By The Proteolytic Processing Of Lrp6, Brandon Richard Beagle

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Low density Lipoprotein receptor Related 6 (LRP6) functions as an essential co-receptor for Wnt/Beat;-catenin signaling as pathway activation, reflected by cytosolic Beta-catenin stabilization and TCF/LEF-1 transactivation, requires Glycogen Synthase Kinase 3Beta(GSK3Beta)-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane anchored LRP6 intracellular domain. Additionally, LRP6 undergoes a proteolytic cleavage event resulting in the formation of a soluble LRP6 intracellular domain (LRP6-ICD). LRP6-ICD can function within the Wnt/Beta-catenin pathway by interacting with GSK3Beta and attenuating the phosphorylation of GSK3Beta substrates such as cytosolic Beta-catenin as well as stimulate TCF/LEF-1 activity. However, LRP6-ICD's role(s) within the Wnt/Beta-catenin pathway and the mechanism(s) that …


Cathelin-Related Antimicrobial Peptide (Cramp) Regulates B Cell Igg1 Production, Yao Chen Jan 2010

Cathelin-Related Antimicrobial Peptide (Cramp) Regulates B Cell Igg1 Production, Yao Chen

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Mammalian antimicrobial peptides, including cathelicidins and defensins, play an important role in host defense via direct antimicrobial activity as well as immune regula-tion. The cathelin-related antimicrobial peptide (mCRAMP) is the only identified mouse cathelicidin and the orthologue of human LL-37. We show that all mouse B cell subsets, including follicular, marginal zone, B1a, and B1b cells, as well as CD4+ and CD8+ T cells produce mCRAMP directly ex vivo. In addition, mCRAMP-deficient B cells produced less IgG1 antibody in vitro in response to CD40L or LPS plus IL-4 when compared to WT B cells. The addition of recombinant mCRAMP at …


Regulation Of Mucosal Innate And Adaptive Immune Responses To Commensal Microbiota, Ting Feng Jan 2010

Regulation Of Mucosal Innate And Adaptive Immune Responses To Commensal Microbiota, Ting Feng

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Host immune responses to the commensal microbiota are tightly controlled. Multiple levels of regulation reinforce intestinal homeostasis, including regulation by mucosal dendritic cells (DCs), regulatory T (Treg) cells, and the microbiota itself. However, the mechanisms involved are still largely unknown. Our current studies indicate that mucosal DCs originate and develop in the bone marrow, the latter of which is driven by retinoic acid (RA). Bone marrow cells express the RA-synthesizing enzyme ALDH, and provide RA to DC precursors in the bone marrow niche. RA induces DCs to express gut-homing CCR9 and ALDH1a2, and endows them with the ability to promote …


The Role Of Post-Translational Modifications And Valosin-Containing Protein In The Turnover And Stability Of The Microtubule-Associated Protein Tau, Philip James Dolan Jan 2010

The Role Of Post-Translational Modifications And Valosin-Containing Protein In The Turnover And Stability Of The Microtubule-Associated Protein Tau, Philip James Dolan

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Alzheimer Disease (AD) is pathologically characterized by the appearance of senile plaques composed of ß-amyloid and neurofibrillary tangles composed of the microtubule-associated protein tau. During the development of AD pathology, tau is hyperphosphorylated and aberrantly cleaved, both of which potentially contribute to its pathogenic and fibrillogenic nature. The accumulative nature of these post-translational products, and their contribution to tau pathology, has led to a great deal of study regarding mechanisms for both the maintenance of tau stability and degradation. The first part of this study reviews the developments regarding the contribution of phosphorylated tau to different physiological and pathological processes. …


Characterization Of The Oligosaccharides Of B. Anthracis Exosporium, Shengli Dong Jan 2010

Characterization Of The Oligosaccharides Of B. Anthracis Exosporium, Shengli Dong

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Fatal systemic anthrax is caused by exposure to spores of Bacillus anthracis. The outermost layer of the B. anthracis spore is called the exosporium. It consists of a paracrystalline basal layer and an external hair-like nap. The filaments of the hair-like nap are primarily composed of the glycoprotein BclA. Our previous studies showed that a 715-Da tetrasaccharide and a 324-Da disaccharide are attached to BclA through GalNAc. We named the novel nonreducing terminal sugar of the 715-Da tetrasaccharide anthrose. We subsequently proposed a plausible anthrose biosynthetic pathway and identified a gene cluster of four continuous genes that appeared to encode …


Role Of Heme Oxygenase-1 In Acute Kidney Injury, Subhashini Bolisetty Jan 2010

Role Of Heme Oxygenase-1 In Acute Kidney Injury, Subhashini Bolisetty

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Acute kidney injury (AKI), defined as the rapid loss of kidney function, is often seen in the setting of multiple organ failure in critically ill patients. Lack of established therapeutic approaches to overcome AKI has lead to unacceptably high incidence of morbidity and mortality in these patients. The molecular mechanisms that lead to AKI often have oxidative stress as a common pathogenic event. The kidney responds by prompt induction of its own anti-oxidant machinery including the highly inducible, anti-inflammatory and anti-apoptotic gene-heme oxygenase-1 (HO-1). This microsomal enzyme degrades pro-oxidant heme, which is released from heme proteins. The cytoprotective properties of …


The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang Jan 2010

The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang

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Exposure to air pollutants are known to induce airway inflammation, decrease lung function, and worsen existing pulmonary conditions such as asthma. Additionally, air pollutant exposure has also been shown to impact cardiovascular health. Although these pollutant-induced cardiovascular effects were considered to be mediated by the direct action of pollutants upon the cardiovascular tissue and/or the indirect release of pro-inflammatory factors into the circulation, the relative contribution of the two pathways remained equivocal. Recently, several epidemiology studies associated ozone exposure with cardiovascular mortalities. However, relatively few studies to date have examined ozone in this context. In order to address our hypothesis …


Translocation And Function Of Akt In The Mitochondria, Keri A. Mans Jan 2010

Translocation And Function Of Akt In The Mitochondria, Keri A. Mans

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The ubiquitously expressed kinase Akt is a known survival protein, and is involved in multiple cell signaling cascades, notably the phosphatidylinositol 3-kinase (PI3K) pathway. Active Akt translocates from the plasma membrane to different subcellular compartments, including mitochondria, where it phosphorylates compartment-specific substrates. The mechanism of this translocation and the specific function of Akt within the mitochondria remains a mystery. The goals of this study were to elucidate the mechanism by which Akt enters the mitochondria and examine the role of Akt in mitochondrial function. Finally, the possibilities of using post-mortem human brain tissue to study mitochondrial function in normal and …


Translation Initiation Signaling Components Altered By Mechanical Load Dictate Skeletal Muscle Hypertrophy, David Lawrence Mayhew Jan 2010

Translation Initiation Signaling Components Altered By Mechanical Load Dictate Skeletal Muscle Hypertrophy, David Lawrence Mayhew

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The regulation of protein synthesis (i.e., mRNA translation) is an energetically costly and extensively regulated process, which is primarily regulated at the initiation step. Mechanical load is a potent stimulus of translation in skeletal muscle, and thus this tissue provides an excellent model system to study the plasticity of the translational apparatus. We investigated the effects of alterations in translation initiation cell signaling pathways in skeletal muscle using a variety of in vitro and in vivo mouse and human model systems. Collectively, our results suggest that, although many proteins in translational signaling pathways are responsive to mechanical load, the response …


Roles Of Nr4a3 In Insulin Sensitivity In Skeletal Muscle, Xiaolin Zhu Jan 2010

Roles Of Nr4a3 In Insulin Sensitivity In Skeletal Muscle, Xiaolin Zhu

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For the past several decades, the prevalence of Type 2 Diabetes and the metabolic syndrome has been increasing. Insulin resistance is the central pathogenic event for these diseases. We previously reported that the NR4A family of orphan nuclear receptors augments insulin sensitivity in adipocytes. We now found that lentiviral mediated NR4A3 hyper-expression increased insulin stimulated glucose transport (ISGT) in C2C12 myocytes while NR4A3 knock-down exhibited opposite effect. We also examined the effects of prostaglandin A2 (PGA2) on insulin action and NR4A3 trans-activation in C2C12 myocytes. PGA2 augmented ISGT and insulin stimulated AKT phosphorylation in C2C12 myocytes. Importantly, PGA2 treatment led …


Heparanase Drives The Aggressive Myeloma Phenotype: Preclinical Development Of A Heparanase Inhibitor For The Treatment Of Multiple Myeloma, Joe Ritchie Jan 2010

Heparanase Drives The Aggressive Myeloma Phenotype: Preclinical Development Of A Heparanase Inhibitor For The Treatment Of Multiple Myeloma, Joe Ritchie

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Heparanase, an endoglycosidase which cleaves heparan sulfate chains at specific sites, is rarely expressed in normal tissues but becomes evident in many human cancers. We have previously shown that heparanase promotes myeloma growth and angiogenesis through modulation of the tumor microenvironment. Recognition that heparanase drives the aggressive myeloma phenotype has led to new strategies designed to therapeutically target this enzyme. SST0001, a non-anticoagulant heparin that is 100% N-acetylated and 25% glycol split, was previously described as a potent inhibitor of heparanase activity in vitro, and, in limited in vivo experiments, SST0001 was identified to have efficacy as an anti-tumor agent …


Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke Jan 2010

Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke

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Apoptosis, or programmed cell death, is essential for the development and maintenance of mammalian tissues. Activation of cysteinyl aspartate specific proteases, called caspases, is crucial to the implementation apoptosis. During apoptosis, the second mito-chondrial derived activator of caspase (Smac), augments caspase activity by antagonizing the inhibitor of apoptosis proteins (IAPs) down-regulation of caspase function. Smac protein synthesis occurs in the cytosol from a nuclear gene. Mitochondrial import of Smac leads to proteolytic removal of the first 55 amino acids, exposing a novel amino-terminus composed Ala56-Val-Pro-Ile59, which is an inhibitor of apoptosis binding motif (IBM). The IBM facilitates the interactions with …


O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho Jan 2010

O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho

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O-GlcNAcylation is an abundant and dynamic post-translational modification on serine and threonine residues of nuclear and cytoplasmic proteins. O-GlcNAc Transferase (OGT) and Nuclear Cytoplasmic O-GlcNAcase and Acetyltransferase (NCOAT) are the only two enzymes and major regulators in this process. In the past two decades, many studies have demonstrated its important modulation roles in nutrient sensing, protein turnover, cell cycle progression, transcription, translation as well as stress resistance. Among these biological functions, the understanding of O-GlcNAcylation dependent oxidative stress is relatively unknown. This study aims to examine the effects of O-GlcNAcylation on JNK1 and FOXO4 transcription factors under acute oxidative stress …


Role Of The Human Cytomegalovirus Tegument Protein Pp150 In The Trafficking And Assembly Of Infectious Virions, Sabarish Vellatheri Indran Jan 2010

Role Of The Human Cytomegalovirus Tegument Protein Pp150 In The Trafficking And Assembly Of Infectious Virions, Sabarish Vellatheri Indran

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Human cytomegalovirus, a ubiquitous human pathogen, establishes a persistent infection in the infected host. HCMV assembly takes place in the nucleus and cytoplasm of infected cells by a complex and incompletely defined process. The viral DNA is enclosed by the capsid, which is surrounded by a proteinaceous tegument, which is covered by a cell-derived envelope studded with viral glycoproteins. The assembly pathway and protein interactions required for formation of the tegument layer and the function of most of the proteins in the tegument remain poorly understood. In this study, we investigated the functions of an essential abundant tegument protein, pp150, …


Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez Jan 2010

Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez

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Growth factors are important inducers of vascular cell growth whose regulation is altered during the pathogenesis of atherosclerosis. An increase in growth factor and cytokine production, as well as lipid oxidation is observed in cardiovascular disease (CVD) and contributes to altered vascular cell signaling, exacerbated atherosclerotic lesions and heart failure. A change in cellular bioenergetic status due to mitochondrial dysfunction or damage has also been noted in CVD. In this thesis, we first examine cell signaling pathways in vascular smooth muscle cells (VSMC) which are activated in response to platelet-derived growth factor (PDGF) and regulate the cell cycle protein changes …