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Development Of A Mucosal Vaccine Protective Against Francisella Tularensis Infection, Amit R. Ashtekar Jan 2010

Development Of A Mucosal Vaccine Protective Against Francisella Tularensis Infection, Amit R. Ashtekar

All ETDs from UAB

Francisella tularensis, a facultative intracellular, gram-negative coccobacillus, is the causative agent of tularemia and has been classified as a category A biological agent. Since there currently is no licensed vaccine available, in this study, we assessed the potential of a bivalent subunit vaccine comprising of DnaK and Tul4 to protect against respiratory tularemia. Intranasal immunization of C57BL/6 mice with DnaK, Tul4, and the adjuvant GPI-0100 resulted in mucosal and systemic antibody responses to DnaK and Tul4. In addition to antibody responses, this immunization regimen also induced both Th1 and Th2 cell-mediated immune responses specific for DnaK and Tul4. Finally, more …


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

The Role Of Wnt5a In Mammary Gland Development, Sarah Baxley

All ETDs from UAB

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 …


Pneumococcal Vaccine Response And Aging In Human, Saeyoung Park Jan 2010

Pneumococcal Vaccine Response And Aging In Human, Saeyoung Park

All ETDs from UAB

Streptococcus pneumoniae is a major human pathogen, especially for young children and older adults. To protect from pneumococcal diseases, 23-valent pneumococcal polysaccharide vaccine (PPV23) has been used clinically since 1983. However, PPV23 is not so effective among old adults with its protective efficacy diminishing with age. We confirmed that young and old adults, who were immunized with PPV23, have comparable pneumococcal polysaccharide (PS) specific IgG levels. Interestingly, we found that old adults had lower IgA and IgM antibody levels than young adults for three serotypes (serotype 14, 18C and 23F). Consistent with the previous results, opsonic capacities of immune sera …


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

Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin

All ETDs from UAB

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 …


The Structural And Functional Studies Of Yeast Nucleotide Exchange Factor Sil1p And Its Complex With Bip, Ming Yan Jan 2010

The Structural And Functional Studies Of Yeast Nucleotide Exchange Factor Sil1p And Its Complex With Bip, Ming Yan

All ETDs from UAB

Sil1 is an Endoplasmic Reticulum (ER) localized protein. SIL1 was initially identified as a UPR-regulated gene. Later studies show Sil1 functions as the nucleotide exchange factor of ER lumenal Hsp70--Bip by directly interacting with the ATPase domain of Bip. Currently, the molecular mechanism how Sil1 catalyzes nucleotide exchange of Bip is still elusive. In this study we determine the complex structure of yeast S.cerevisia Sil1 and Bip (also called Kar2) ATPase domain at 2.3Å resolution by Single-anomalous dispersion (SAD) methods. The Sil1-Bip complex structure reveals that one sil1 molecule interacts with one Bip ATPase domain molecule to form the complex. …


A Timp2-Armed Conditionally-Replicating Adenovirus For The Treatment Of Ovarian Cancer, Sherry Wei Yang Jan 2010

A Timp2-Armed Conditionally-Replicating Adenovirus For The Treatment Of Ovarian Cancer, Sherry Wei Yang

All ETDs from UAB

Ovarian cancer remains the most lethal gynecological malignancy in the U.S. Conventional therapies have limited therapeutic value due to advanced stage of the disease at diagnosis. Conditionally-replicating adenoviruses (CRAds) are promising, novel anti-cancer agents that are designed to selectively replicate in and lyse tumor cells. In clinical trials, CRAds exhibited limited efficacy thus far. Second generation CRAds are being developed to express a therapeutic protein to further enhance antitumor efficacy. One attractive target in ovarian tumor microenvironment is the matrix metalloproteinases (MMPs) that degrade the extracellular matrix. Thus, tissue inhibitor of metalloproteinase 2 (TIMP2), an endogenous inhibitor of MMPs, is …


Cross-Talk Between Marginal Zone B Cells And Marginal Zone Macrophages, Yuying You Jan 2010

Cross-Talk Between Marginal Zone B Cells And Marginal Zone Macrophages, Yuying You

All ETDs from UAB

the test of group differences and the test of covariate. When we force the predictors in the


Faculty Publications 2009, Lsu Health Sciences Center New Orleans Jan 2010

Faculty Publications 2009, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 806 publications.


The Cytokine, Interleukin-7, Transcriptionally Regulates The Gene Expression Of The Hexokinase Ii To Mediate Glucose Utilization, Mounir Chehtane Jan 2010

The Cytokine, Interleukin-7, Transcriptionally Regulates The Gene Expression Of The Hexokinase Ii To Mediate Glucose Utilization, Mounir Chehtane

Electronic Theses and Dissertations

The cytokine, interleukin-7 (IL-7), has essential growth activities that maintain the homeostatic balance of the immune system. Little is known of the mechanism by which IL-7 signaling regulates metabolic activity in support of its vital function in lymphocytes. We observed that IL-7 deprivation caused a rapid decline in ATP levels that were attributable to loss of intracellular glucose retention. To identify the transducer of the IL-7 metabolic signal, we examined the expression of three important regulators of glucose metabolism, the glucose transporter, GLUT-1, and two glycolytic enzymes, Hexokinase II (HXKII) and phosphofructokinase-1 (PFK1), using an IL-7-dependent T-cell line and primary …


Interleukin-7 Differentially Regulates The Activation, Proliferation, And Homing Of T-Cells: Implications For Immunotherapy, Christina Kittipatarin Jan 2010

Interleukin-7 Differentially Regulates The Activation, Proliferation, And Homing Of T-Cells: Implications For Immunotherapy, Christina Kittipatarin

Electronic Theses and Dissertations

Interleukin-7 (IL-7) is an essential lymphocyte growth factor required for the survival and proliferation of mature T-cells. As a therapeutic agent, IL-7 has the potential to restore T-cell numbers following immune depletion and to promote immunity against cancers. While the survival function of IL-7 is well established, less is known about how it supports T-cell expansion, a critical feature of the immune response. To study the biological effects of IL-7 on T-cell growth, we developed an in vitro culture technique to expand T-cells ex vivo. A significant finding from our studies is that IL-7 did not induce the expansion of …


Magnetic Nanosensors For Multiplexed Bacterial Pathogenesis Identification, Charalambos Kaittanis Jan 2010

Magnetic Nanosensors For Multiplexed Bacterial Pathogenesis Identification, Charalambos Kaittanis

Electronic Theses and Dissertations

Developing diagnostic modalities that utilize nanomaterials and miniaturized detectors can have an impact in point-of-care diagnostics. Diagnostic systems that (i) are sensitive, robust, and portable, (ii) allow detection in clinical samples, (iii) require minimal sample preparation yielding results quickly, and (iv) can simultaneously quantify multiple targets, would have a great potential in biomedical research and public healthcare. Bacterial infections still cause pathogenesis throughout the world (Chapter I). The emergence of multi-drug resistant strains, the potential appearance of bacterial pandemics, the increased occurrence of bacterial nosocomial infections, the wide-scale food poisoning incidents and the use of bacteria in biowarfare highlight the …


Electroconvulsive Shock Ameliorates Disease Processes And Extends Survival In Huntington Mutant Mice, Akanksha Baharani Jan 2010

Electroconvulsive Shock Ameliorates Disease Processes And Extends Survival In Huntington Mutant Mice, Akanksha Baharani

Electronic Theses and Dissertations

Huntington's disease (HD) is a devastating autosomal dominantly inherited neurological disorder caused by an abnormal expansion of CAG trinucleotide repeats in the gene coding for the Nterminal region of the huntingtin (Htt) protein, which leads to the formation of a polyglutamine stretch. The greater the CAG repeats, the earlier the onset of the disease. The polyglutamine stretch destabilizes the Htt protein leading to misfolding, abnormal processing, aggregation, and inclusion formation. Mutant Htt protein is believed to damage and kill neurons in the striatum by a mechanism involving increased oxidative and metabolic stress, and impaired adaptive cellular stress responses. A large …


Transplantation Of Ips Cells Reduces Apoptosis And Fibrosis And Improves Cardiac Function In Streptozotocin-Induced Diabetic Rats, Sarah Elizabeth Neel Jan 2010

Transplantation Of Ips Cells Reduces Apoptosis And Fibrosis And Improves Cardiac Function In Streptozotocin-Induced Diabetic Rats, Sarah Elizabeth Neel

Electronic Theses and Dissertations

Background: Streptozotocin (STZ) induced diabetes leads to various complications including cardiomyopathy. Recent data suggests transplanted bone marrow stem cells improve cardiac function in diabetic cardiomyopathy. However, whether modified ES, iPS cells, or factors released from these cells can inhibit apoptosis and fibrosis remains completely unknown. The present study was designed to determine the effects of transplanted ES cells overexpressing pancreatic transcription factor 1 a (Ptf1a), a propancreatic endodermal transcription factor, iPS cells, or their respective conditioned media (CM) on diabetic cardiomyopathy. Methods: Experimental diabetes was induced in male Sprague Dawley rats (8-10 weeks old) by intraperitoneal STZ injections (65 mg/kg …


Imaging Spontaneous Mmtvneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products., Mathew L Thakur, Devakumar Devadhas, Kaijun Zhang, Richard G Pestell, Chenguang Wang, Peter Mccue, Eric Wickstrom Jan 2010

Imaging Spontaneous Mmtvneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products., Mathew L Thakur, Devakumar Devadhas, Kaijun Zhang, Richard G Pestell, Chenguang Wang, Peter Mccue, Eric Wickstrom

Department of Radiology Faculty Papers

INTRODUCTION: Despite the great strides made in imaging breast cancer (BC) in humans, the current imaging modalities miss up to 30% of BC, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. Annually in the United States, approximately 5.6 million biopsies find benign lesions. More than 50% of human BCs overexpress cyclin D1, and all BCs exhibit VPAC1 oncogene products. Together, these gene products may provide an excellent biomarker for the early and accurate detection of BC. We have evaluated 4 biologically active peptide analogs that have high affinity for …


The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar Jan 2010

The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar

All ETDs from UAB

Upon human immunodeficiency virus (HIV) infection the host mounts a robust and multifaceted immune response. To achieve successful replication, HIV must possess a powerful arsenal of immune evasion weapons. While a complex strategy for HIV immune evasion has been described in the periphery, little is known about the mechanism allowing HIV to overcome the simple interferon (IFN)-ß-mediated innate immune defenses of the central nervous system (CNS). In light of the devastating cognitive dysfunction that is caused by HIV replication within the CNS, a better understanding of this mechanism is critical. Recent studies have shown that viral pathogens can induce the …


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 …


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

All ETDs from UAB

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 …


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

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

All ETDs from UAB

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 …


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

All ETDs from UAB

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


Cellular Mechanisms Involved In Host Responses To Porphyromonas Gingivalis And Its Virulence Factor Hemagglutinin B, Dalia Emil Gaddis Jan 2010

Cellular Mechanisms Involved In Host Responses To Porphyromonas Gingivalis And Its Virulence Factor Hemagglutinin B, Dalia Emil Gaddis

All ETDs from UAB

Porphyromonas gingivalis is a main causative agent for adult chronic periodontitis and immunization with its virulence factor Hemagglutinin B (HagB) provides protection against infection. Toll-like receptors (TLRs) recognize various microbial products and are crucial in eliciting and regulating the innate and adaptive immune responses to infections. The objective of this dissertation was to investigate the cellular mechanisms that influence the innate and adaptive immune response to HagB and P. gingivalis, focusing on the role of TLR signaling in the response. We started with investigating the ability of HagB to activate dendritic cells (DC), the most efficient antigen-presenting cell in priming …


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

All ETDs from UAB

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 …


The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen Jan 2010

The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen

All ETDs from UAB

The ubiquitin proteasome system (UPS) plays critical roles in regulating multiple cellular functions, including protein abundance, trafficking, and cell signaling. In the nervous system, the UPS has been implicated in controlling a wide diversity of cellular process such as synaptic transmission, axon outgrowth, axon targeting, and synapse development. Although impairment of the UPS is observed in both neurodegenerative and developmental diseases, the mechanisms underlying how UPS dysregulation contributes to disease pathogenesis are not known. The proteasome, an approximate 2.5 megadaltons protein complex composed of 19S and 20S assemblies, is the site of ubiquitin-dependent protein degradation. Recent studies have demonstrated dysfunction …


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

All ETDs from UAB

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 …


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

All ETDs from UAB

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

All ETDs from UAB

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 …


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

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

All ETDs from UAB

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 …


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

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

All ETDs from UAB

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 …


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

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

All ETDs from UAB

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 …


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

All ETDs from UAB

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 …


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 …