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Mechanisms Of Major Outer Membrane Protein (Momp)-Vaccine Induced Protective Immunity Against Chlamydia Muridarum Genital Infection, Christina M. Farris Jan 2010

Mechanisms Of Major Outer Membrane Protein (Momp)-Vaccine Induced Protective Immunity Against Chlamydia Muridarum Genital Infection, Christina M. Farris

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Urogenital infection with Chlamydia trachomatis is the most common bacterial sexually transmit-ted disease with an estimated 90 million new infections occurring each year worldwide. In women infection with C. trachomatis can result in serious complications including ectopic pregnancy, pelvic inflammatory disease and tubal factor infertility. Despite very effective antimicrobial chemotherapy, control of the infection will likely require an effective vaccine. We have assessed the protective effect of an outer membrane based vaccine using a murine model of chlamydial genital tract infection. Female mice were vaccinated with C. muridarum major outer membrane protein (MOMP) plus the immunostimulatory adjuvants CpG-1826 and Montanide …

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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 …

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Chronic Alcohol Consumption Promotes Opening Of The Mitochondrial Permeability Transition Pore And Increases Mitochondrial Injury In Liver, Adrienne Lester King Jan 2010

Chronic Alcohol Consumption Promotes Opening Of The Mitochondrial Permeability Transition Pore And Increases Mitochondrial Injury In Liver, Adrienne Lester King

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Alcoholic liver disease is a serious public health concern. In particular, the mitochondrion is a specific target of ethanol toxicity and much of the damage can be related to unregulated Ca2+ homeostasis and oxidative stress which are key players in the induction of the mitochondrial permeability transition pore (MPTP) within the organelle. The mechanism behind the induction of the MPTP remains elusive. Therefore, this body of work will provide insight on what effects chronic alcohol consumption has on mitochondrial dysfunction with an emphasis on the MPTP. Chapter 2: Assessment of mitochondrial dysfunction arising from treatment with hepatotoxicants provides a description …

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The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon Jan 2010

The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon

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Glioma-associated oncogene homolog 1 (Gli1) is a well-known oncogene and a transcription factor that mediates several signaling pathways important for tumor progression, such as hedgehog, TGFß, Ras, and EGFR. Although Gli1 is known to play an important role in cancers of brain, skin, prostate, and the pancreas, the role of Gli1 in breast cancer was not previously well-defined. Therefore, this dissertation focuses on defining the role of Gli1 and the mechanism underlying Gli1-mediated transcription in breast cancer. Interestingly, the major findings of the dissertation clearly indicate that Gli1 promotes cell survival and is predictive of a poor outcome in Estrogen …

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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 …

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Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher Jan 2010

Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher

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Serogroup 6 of Streptococcus pneumoniae has been known to contain three serotypes, named 6A, 6B and 6C, with highly homologous capsule gene loci. The 6A and 6B capsule gene loci consistently differ from each other by only one nucleotide in the wciP gene. The 6A capsule gene locus has a galactosyltransferase (wciNα), which has been replaced with a glucosyltransferase (wciNß) in the 6C capsule gene locus. We considered that a new serotype, 6D, would be possible if the glucosyltransferase found in 6C strains was combined with the wciP gene from a 6B strain. We demonstrate that this gene combination yields …

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Chemically Mediated Macroalgal-Mesograzer Interactions Along The Western Antarctic Peninsula, Craig Farrar Aumack Jan 2010

Chemically Mediated Macroalgal-Mesograzer Interactions Along The Western Antarctic Peninsula, Craig Farrar Aumack

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In the following dissertation, we explore benthic communities along the Western Antarctic Peninsula, specifically, interactions between the immense macroalgal and mesograzer assemblages and how these relationships are chemically mediated. Despite the widespread production of various chemical feeding deterrents throughout the macroalgal community, the system supports an abundant and diverse array of crustacean amphipods. Gut content analysis and stable isotopic signatures indicate that filamentous macroalgae and epiphytic diatoms probably play an important role as dietary constituents, despite their visible absence in the sub-tidal zones. Subsequent palatability and extract feeding assays revealed that none of the filamentous macroalgal material found in amphipod …

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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

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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 …

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A Novel Approach To Dual Excitation Ratiometric Optical Mapping Of Cardiac Action Potentials With Di-4-Anepps Using Pulsed Led Excitation, Andrew Dennison Bachtel Jan 2010

A Novel Approach To Dual Excitation Ratiometric Optical Mapping Of Cardiac Action Potentials With Di-4-Anepps Using Pulsed Led Excitation, Andrew Dennison Bachtel

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We developed a new method for ratiometric optical mapping of transmembrane potential (Vm) in cardiac preparations stained with di-4-ANEPPS (DI-4). The method uses pulsed light emitting diode (LED) excitation. Vm-dependent shifts of excitation and emission spectra establish two excitation bands (<481 nm and >481 nm) that produce positive and negative changes in fluorescence within a single emission band (570-615 nm). The ratio of these positive and negative fluorescence signals (excitation ratiometry) increases Vm sensitivity and removes artifacts common to both signals. We pulsed blue (460±20 nm) and cyan (505±20 nm) LEDs at 500 Hz in alternating phase synchronized to a photodetector (1 …

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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 …

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Host Preference Profile In An Area Of Eastern Equine Encephalitis (Eee) Virus Transmission In Alabama, Ana Lucia Oliveira Jan 2010

Host Preference Profile In An Area Of Eastern Equine Encephalitis (Eee) Virus Transmission In Alabama, Ana Lucia Oliveira

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osteoporosis susceptibility, perceived osteoporosis severity, perceived barriers to

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

Pneumococcal Vaccine Response And Aging In Human, Saeyoung Park

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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 …

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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 …

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Structural Studies Of The Ligand Binding Domain Of The Human Retinoid X Receptor Bound To Retinoids And The Coactivator Peptide Grip-1, Gang Xia Jan 2010

Structural Studies Of The Ligand Binding Domain Of The Human Retinoid X Receptor Bound To Retinoids And The Coactivator Peptide Grip-1, Gang Xia

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Retinoid X receptors (RXRs) are ligand-dependent transcription factors which belong to the nuclear receptor (NR) superfamily. When a ligand binds to RXRs, it activates the protein allosterically for the recruitment of coactivator proteins and enhancement of gene transcription. RXRs form either homodimers or heterodimers with numerous other NRs. Thus, RXRs are involved in many signaling pathways in vivo. 9cRA, Targretin and UAB retinoids are RXR agonists and found to be effective agents to prevent and treat cancers. The structures of retinoid-bound RXRs will be helpful in designing new retinoids. This dissertation focuses on structural studies of the human retinoid X …

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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

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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. …

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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

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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 …

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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

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

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Microhardness And Caries Resistance Of An Infiltrant Resin In A Novel Artificial Mouth, Ian Saad Mugisa Jan 2010

Microhardness And Caries Resistance Of An Infiltrant Resin In A Novel Artificial Mouth, Ian Saad Mugisa

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No abstract provided.

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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

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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 …

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The Effectiveness Of Advanced Oxidation Techniques In Degrading Steroids In Wastewater, Bryan Stuart Arwood Jan 2010

The Effectiveness Of Advanced Oxidation Techniques In Degrading Steroids In Wastewater, Bryan Stuart Arwood

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No abstract provided.

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Cystic Fibrosis And Vitamin D Supplementation, Lindsay Clare Ball Jan 2010

Cystic Fibrosis And Vitamin D Supplementation, Lindsay Clare Ball

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No abstract provided.

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Effect Of Dietary Protein An D Carbohydrate Levels On Weight Gain And Organ Production In The Sea Urchin Lytechinus Variegatus, Laura E Wright Heflin Jan 2010

Effect Of Dietary Protein An D Carbohydrate Levels On Weight Gain And Organ Production In The Sea Urchin Lytechinus Variegatus, Laura E Wright Heflin

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No abstract provided.

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Gastric Th17 Response To Helicobacter Pylori Infection In Children, Shelton W. Wright Jan 2010

Gastric Th17 Response To Helicobacter Pylori Infection In Children, Shelton W. Wright

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No abstract provided.

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A Missionary's Journey, Denise Turner Jan 2010

A Missionary's Journey, Denise Turner

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No abstract provided.

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Debunking The Myth Of Victorian Medievalism In George Eliot's Adam Bede, Patricia A. Rippetoe Jan 2010

Debunking The Myth Of Victorian Medievalism In George Eliot's Adam Bede, Patricia A. Rippetoe

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No abstract provided.

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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

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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 …

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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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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

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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 …

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