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2010

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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

All ETDs from UAB

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 …

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Visualizing The Productive Program Of Hpv In Differentiating Squamous Epithelial Tissue, Aaron A. Duffy Jan 2010

Visualizing The Productive Program Of Hpv In Differentiating Squamous Epithelial Tissue, Aaron A. Duffy

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The human papillomavirus (HPV) establishes persistent infections in the basal stratum of squamous epithelia, while productive amplification of viral DNA occurs in differentiated keratinocytes prior to virion assembly in the superficial strata. Until recently, only in situ hybridization (ISH) of low-grade HPV lesions could be used to reveal a snap shot of the viral life cycle. There has been a critical need to reproducibly propagate HPV infections in culture for consistent genetic analyses. Organotypic raft cultures recapitulate a differentiated squamous epithelium. Our lab utilized in vivo Cre-mediated recombination to reconstitute the entire HPV-18 genome in primary human keratinocytes (PHKs). My …

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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 …

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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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and Davidson and MacKinnon’s HC3 perform reasonably well in terms of Type I error

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Generation And Analysis Of The Oncolytic Efficacy Of A Conditionally Replicating Adenovirus Bearing Rgd Modifications On Pix And Fiber Capsid Proteins, Lena Jeanelle Gamble Jan 2010

Generation And Analysis Of The Oncolytic Efficacy Of A Conditionally Replicating Adenovirus Bearing Rgd Modifications On Pix And Fiber Capsid Proteins, Lena Jeanelle Gamble

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Ovarian cancer is the leading cause of gynecological disease death in women. For the past two decades, scientists have attempted to perfect the use of adenovirus as an anti-cancer therapeutic agent. One major impediment to ovarian tumor infection with adenovirus has been dearth of adenovirus native receptor, Coxsackie and Adenovirus receptor, (CAR), on the surface of tumor cells. To address this problem, scientists have engineered CAR-independent adenoviruses which target the AlphavBeta3 and AlphavBeta5 by adding an arginine-glycine-aspartate (RGD) motif to the fiber knob of a conditionally replicating adenovirus (CRAd) Delta24FiberRGD CRAd. We hypothesize that incorporation of RGD into the pIX …

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A Multiresolution Approach To The Detection Of Image Discrepancies For Improved Quality Control Of Oligonucleotide Microarray Images, Vetria L. Byrd Jan 2010

A Multiresolution Approach To The Detection Of Image Discrepancies For Improved Quality Control Of Oligonucleotide Microarray Images, Vetria L. Byrd

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The impact of microarrays on biological research has been phenomenal. By enabling scientists to assess the expression levels of thousands of genes simultaneously this high-throughput technology significantly reduces the time spent per experiment and allows for more complicated experiments. The microarray process is a complex series of steps that yields enormous amounts of data in microarray images. The Affymetrix GeneChip® system pioneered microarray technology, creating an image file format that has become standard for microarray image processing. During a microarray experiment, a microarray chip is scanned using a confocal laser scanner that captures the raw data (.DAT). A summary of …

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Hpv Dna Partitioning During Mitosis As Followed By Fluorescence Microscopy, Robert J. Carter Jan 2010

Hpv Dna Partitioning During Mitosis As Followed By Fluorescence Microscopy, Robert J. Carter

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Human papillomaviruses (HPVs) are small, double-stranded deoxyribonucleic acid (DNA) tumor viruses capable of establishing persistent infections in the epithelia. After infecting actively-dividing basal cells, the papillomavirus (PV) genome is main-tained as extrachromosomal nuclear plasmids. It is largely unknown how the viral ge-nome is maintained in actively-dividing cells. Our lab demonstrated that several HPV genotypes appear to employ a distinct strategy to facilitate partitioning of HPV DNA into daughter cells during mitosis. Association of the HPV-11 origin of replication (ori)-binding protein E2 with the mitotic apparatus via cellular adapter proteins is thought to mediate equal partitioning of HPV genomes into daughter …

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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 …

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Diversity, Commonality, And Stability Of Mutans Streptococci In High Caries Risk Children, Kyounga Cheon Jan 2010

Diversity, Commonality, And Stability Of Mutans Streptococci In High Caries Risk Children, Kyounga Cheon

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Mutans streptococci (MS), Streptococcus mutans and Streptococcus sobrinus are associated with the initiation of dental caries in humans. Initially, a single S. mutans genotype has been shown to colonize primary molars soon after eruption. More genotypes can be acquired with age and further dental development. Current methods used to genotype isolates from an individual have not systematically determined the minimum number required to demonstrate an individual's genetic diversity. The purpose of this study was to determine the optimum number of oral isolates of MS (i.e., from plaque samples) to genotype in order to demonstrate diversity. This study also initiated a …

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The Effects Of Weight Reduction On Obesity-Related Cancer Biomarkers And In Vitro Cancer Cell Growth, Maria Azrad Jan 2010

The Effects Of Weight Reduction On Obesity-Related Cancer Biomarkers And In Vitro Cancer Cell Growth, Maria Azrad

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Obesity increases the risk for breast and endometrial cancers while weight loss reduces the risk for these cancers. One aim of this dissertation was to determine the effects of weight loss from an overweight state [body mass index (BMI) 27-30] to a normal weight state on several obesity-related cancer biomarkers in African-American (AA) and European-American (EA) premenopausal women. We also sought to determine whether the method of weight loss, caloric restriction alone (CR) or combined with exercise resulted in similar changes in cancer biomarkers. The biomarkers of interest were urinary estrogen metabolites, and serum adiponectin, leptin, insulin-like growth factor (IGF)-1, …

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Study Of The Role Of The Amygdala In The Effects Of Stress On Sensory Processing Of The Urinary Bladder, Jennifer Deberry Jan 2010

Study Of The Role Of The Amygdala In The Effects Of Stress On Sensory Processing Of The Urinary Bladder, Jennifer Deberry

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Interstitial cystitis (IC) is a chronic visceral condition of the urinary bladder characterized by pelvic/suprapubic pain, and urinary frequency and urgency. There is no documented cause for IC, but a prominent role for stress in its pathophysiology and presentation are well-documented. In the clinical setting, IC pain-related symptomatology is exacerbated during periods of stress. Numerous laboratory studies of humans and animals have similarly demonstrated stress-induced visceral hypersensitivity. The amygdala is highly connected with physiological stress response systems and pain modulatory pathways, and its connectivity with these systems places it in a unique anatomical position for mediating the reciprocal relationship between …

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Parental Well-Being And Child Outcomes Among School-Aged, Prematurely-Born Children., Desiree Maria De Jong Jan 2010

Parental Well-Being And Child Outcomes Among School-Aged, Prematurely-Born Children., Desiree Maria De Jong

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Children born prematurely are at a significantly higher risk than their full-term peers for developing cognitive, behavioral, attention, and executive functioning difficulties by the time they reach school-age. Parents of children born prematurely are also at greater risk for developing symptoms of depression and stress compared to parents of full-term children. However, the literature is conflicting with respect to whether or not parental well-being remains compromised by the time the preterm child reaches school-age. Additionally, much of the research examining this relationship is conducted prior to school-age, with little research beyond these years. A primary purpose of the current study …

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Regulation Of Redox Signaling By Lipid Electrophiles In Breast Cancer, Anne R. Diers Jan 2010

Regulation Of Redox Signaling By Lipid Electrophiles In Breast Cancer, Anne R. Diers

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A number of steps in breast cancer progression and metastasis are regulated by redox signaling pathways. Electrophilic lipids such as 15-deoxy-delta12,14-Prostaglandin J2 (15d-PGJ2) are mediators of redox signaling pathways because of their ability to modify critical cysteine residues (thiols) in redox-sensitive proteins. In this thesis, we examine the effect of lipid electrophiles such as 15d-PGJ2 and others on redox signaling pathways in breast cancer. Furthermore, we develop new strategies to regulate cancer cell behavior in response to lipid electrophiles using three strategies: 1) through organelle-specific targeting of electrophiles 2) by exploiting the concentration-dependence of effects of electrophiles, and 3) utilizing …

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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. …

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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 …

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Lens Cataract: Biochemical Analysis Of The Alpha Crystallins, David Ray Stella Jan 2010

Lens Cataract: Biochemical Analysis Of The Alpha Crystallins, David Ray Stella

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The cataract is a common ailment affecting the aged population. It appears over time and affects the quality of one’s life by the eventual loss of vision. Currently, there is no effective strategy to prevent or treatment to reverse the development of a cataract. As well, there is no consensus on one particular mechanism or sequence of events that contributes to its formation. In order to better understand the possible etiology of the cataract, it is necessary to define the biochemical changes that occur to lens proteins as one ages, as these are the key players in the prevention of …

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Methods For Estimating Mediation Effect In Survival Analysis: Does Weight Loss Mediate The Undernutrition-Mortality Relationship In The Older Adults?, Yanhui Sun Jan 2010

Methods For Estimating Mediation Effect In Survival Analysis: Does Weight Loss Mediate The Undernutrition-Mortality Relationship In The Older Adults?, Yanhui Sun

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The influence of undernutrition on mortality and other adverse outcomes through the mechanism of unintentional weight loss in older adults is often assumed, but the analytic methods to test these mediation mechanisms are not well-developed, and the need for methodological advances in this area motivated this program of research. We first examined the test-retest reliability and predictive validity of self-reported caloric intake as a measure of undernutrition. Acceptable reliability was observed, consistent with previous reports, but the evidence for predictive validity was inconsistent and self-reported caloric intake deficiency was not found to be related to observed weight loss. We then …

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Exosomal Curcumin: Its Bioavailability And Potential Anti-Inflammation Activity, Dongmei Sun Jan 2010

Exosomal Curcumin: Its Bioavailability And Potential Anti-Inflammation Activity, Dongmei Sun

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Curcumin, a pleiotropic polyphenol derived from turmeric plants Curcuma Longa with rhizome, exhibits strong evidence as an anti-inflammation, anti-oxidant and anti-cancer reagent both in vitro and in vivo. Due to its low stability and systemic bioavailability, a large amount of curcumin has to be administrated to achieve therapeutic effects both in animal and in human. The major effort to overcome this barrier is making by encapsulation of curcumin into nanoparticles such as polymers and liposomes; some promising data have demonstrated the effectiveness of such method. Exosomes are vesicle-like nanoparticles secreted by living cells. Exosomes contain both cell surface molecules and …

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Representation, Analysis, And Refactoring Techniques To Support Code Clone Maintenance, Robert Ambrosius Tairas Jan 2010

Representation, Analysis, And Refactoring Techniques To Support Code Clone Maintenance, Robert Ambrosius Tairas

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The existence of code cloning, which represents identical or near identical sections of code, has been documented to occur frequently in software systems. The main purpose of cloning is the reuse of a code fragment that performs some functionality by copying and pasting it to a new location in the source code. Code clones embody a unique form of coupling, because their similarity inadvertently connects their representative sections of code together. This inherent duplication requires attention to be given to all related duplicates, even if just one of these duplicates is being evaluated or changed. Failure to consider all related …

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Structural And Functional Study Of P58(Ipk), Jiahui Tao Jan 2010

Structural And Functional Study Of P58(Ipk), Jiahui Tao

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P58(IPK) is an endoplasmic reticulum (ER)-resident protein which is upregulated during unfolded protein response (UPR). In stressed cells, P58(IPK) functions to restore protein folding equilibrium in ER by suppressing protein aggregation and promoting protein folding. P58(IPK) associates with the unfolded protein via its N-terminal TPR domain and presents it to BiP (binding immunoglobulin protein) for subsequent folding. P58(IPK) belongs to the Hsp40 family. Collectively, P58(IPK) is a stress-inducible ER-resident molecular chaperone. In this dissertation, we report the crystal structure of P58(IPK) TPR domain to 2.5 Å resolution. In the crystal structure, the 43-kDa TPR domain consists of nine tandemly linked …

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Roles Of Adiponectin And Its Receptors In Foam Cell Transformation, Ling Tian Jan 2010

Roles Of Adiponectin And Its Receptors In Foam Cell Transformation, Ling Tian

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Macrophages play a critical role in the initiation and progression of atherosclerosis by producing pro-inflammatory mediators and transforming into lipid-laden foam cells. The prevention of lipid accumulation and inflammation in macrophage foam cells, therefore, represents a promising target for effective therapy for atherosclerosis. Adiponectin is a circulating cytokine primarily expressed and secreted by adipocytes, and is downregulated in obesity-linked diseases including type 2 diabetes, coronary artery disease and hypertension. In oxidized low-density lipoprotein (oxLDL)-induced human THP-1 macrophage foam cells, adiponectin suppresses lipid accumulation through decreasing lipid uptake and increasing high-density lipoprotein (HDL)-mediated lipid efflux. The potential mechanisms that adiponectin utilizes …

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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

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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 …

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Biophysical Studies On Human Telomeric G-Quadruplex Dna: Characterization Of Ligand And Protein Interactions, Jason Scott Hudson Jan 2010

Biophysical Studies On Human Telomeric G-Quadruplex Dna: Characterization Of Ligand And Protein Interactions, Jason Scott Hudson

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G-quadruplex DNAs are higher order nucleic acid structures that have been implicated in the regulation of a number of vital biological processes, including gene transcription and telomeric extension. Guanine rich sequences that are capable of forming G-quadruplex structure are found in the telomeres of chromosomes. The presence of the G-quadruplex structure prevents the binding of telomerase and inhibits the telomeric extension that would result in the immortality of cancer cells. This dissertation describes research that is focused on the biophysical characterization of the G-quadruplex and interactions with a ligand and protein. The anticancer compound, actinomycin D, is demonstrated to bind …

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Functional Determinants Of The Porin Mspa And Its Role In Permeabilizing Mycobacterial Outer Membranes, Jason Huff Jan 2010

Functional Determinants Of The Porin Mspa And Its Role In Permeabilizing Mycobacterial Outer Membranes, Jason Huff

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Mycobacterium tuberculosis (Mtb) infects one third of the global population and causes approximately 2,000,000 Tuberculosis-related deaths annually. Mycobacteria are Gram positive organisms but contain a unique outer membrane (OM) which is functionally similar but structurally different from those of Gram negative bacteria. The mycobacterial OM presents an efficient permeability barrier towards hydrophilic solutes. Slow permeation kinetics of hydrophilic molecules through membranes and several discoveries of cell wall channel-forming proteins indicate that mycobacterial OMs are functionalized by proteins. MspA is the primary porin of M. smegmatis and mediates diffusion of small, hydrophilic nutrients and antibiotics across the OM. Unlike porins of …

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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, …

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Molecular Mechanisms Of Hepatic Insulin Resistance Following Injury, Shaoning Jiang Jan 2010

Molecular Mechanisms Of Hepatic Insulin Resistance Following Injury, Shaoning Jiang

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Insulin resistance commonly occurs following injuries or critical illness independent of previous diabetic status. The development of insulin resistance and hyperglycemia is associated with increased mortality and morbidity in critically ill patients. However, the molecular mechanisms underlying the acute insulin resistance following injuries remain poorly understood. With an animal model of trauma and hemorrhage, we have previously demonstrated the rapid development of insulin resistance in liver, and a critical role of TNFα in hemorrhage-induced defects in insulin signaling following resuscitation. However, hepat-ic insulin signaling is impaired prior to a significant increase in plasma TNFα, suggesting the initial development of hemorrhage-induced …

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In Vitro Elucidation Of The Role And Mechanism Of Rankl In Tnf-And Il-1-Mediated Osteoclast Formation And Function, Joel Jules Jan 2010

In Vitro Elucidation Of The Role And Mechanism Of Rankl In Tnf-And Il-1-Mediated Osteoclast Formation And Function, Joel Jules

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The receptor activator of NF-қB (RANK) ligand (RANKL) and its receptor RANK play a critical role in osteoclast biology. RANK has three tumor necrosis factor receptor associated factor (TRAF)-binding motifs [PFQEP369-373 (Motif 1), PVQEET559-564 (Motif 2), and PVQEQG604-609 (Motif 3)] that regulate osteoclast formation and function. RANK also contains a TRAF-independent motif (IVVY535-538) that commits bone marrow macrophages (BMMs), which are osteoclast precursors, to the osteoclast lineage for osteoclastogenesis. Notably, tumor necrosis factor-α (TNF) and interlukin-1 (IL-1) utilize TRAFs to initiate most of the signaling pathways known to be activated by RANKL but fail to form osteoclasts unless attended by …

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The Role Of The Intracellular Signaling Pathway In Ehrlichia Canis Infection In Vitro, Chang-Hyun Kim Jan 2010

The Role Of The Intracellular Signaling Pathway In Ehrlichia Canis Infection In Vitro, Chang-Hyun Kim

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Ehrlichia canis is a pleomorphic obligatory intracellular gram-negative bacterium that causes tick-borne canine ehrlichiosis. A systematic investigation on the pathogenesis of the disease has been hindered largely by lack of a reliable quantitative assay. Using quantitative real time PCR (qPCR), a quantitative assay for E. canis was developed and validated. Using the qPCR, the intracellular proliferation kinetics of E. canis in the canine 030F cell-line was studied for the first time. Many intracellular bacterial pathogens have been shown to use Ca2+ signaling in the host cells to induce their own internalization and proliferation. However, it is not clear how Ca2+ …

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Identification And Characterization Of Downstream Target Genes Of The Bmp Signaling Pathway, Nam Chul Kim Jan 2010

Identification And Characterization Of Downstream Target Genes Of The Bmp Signaling Pathway, Nam Chul Kim

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During nervous system development, neurons proliferate, differentiate, project their axons to their targets and make synapses with them. At the neuromuscular junction of Drosophila, these functional synapses enlarge as the body grows to maintain physiologically effective synaptic transmission with the muscles. Drosophila Bone Morphogenetic Protein (BMP) type II receptor, Wishful thinking (Wit), is important in this proper synaptic growth and function. To identify transcriptional targets of Wit signaling, we performed microarray experiments comparing normal controls to wit mutants. Through this study, we found that some of the verified target genes showed isoform-specific regulation in wit mutants, and that several neuropeptide …

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Development Of A Multiscale Material Model For Brain Tissue And Its Application To The Impact Response Of The Human Head, Sandeep Kulathu Jan 2010

Development Of A Multiscale Material Model For Brain Tissue And Its Application To The Impact Response Of The Human Head, Sandeep Kulathu

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The development of a finite element model capable of predicting brain injury sustained as a result of an impact load to the head is of considerable importance not only for the development of adequate protection systems but also in deciding an appropriate mode of treatment for an individual. With advancements in imaging technologies, it is now possible to visualize the neuron fiber structures in the brain. In the first half of this project, an analytical micro-mechanical model was developed from the individual isotropic behaviors of the Cerebro-Spinal Fluid (CSF) and brain tissue present in the brain, such that the resultant …

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