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Protease Dysregulation: Role In Neutrophilic Inflammation In Cystic Fibrosis, Amit Gaggar Jan 2007

Protease Dysregulation: Role In Neutrophilic Inflammation In Cystic Fibrosis, Amit Gaggar

All ETDs from UAB

Cystic fibrosis (CF) is a lethal disorder characterized by abnormal epithelial ion transport; this disorder is characterized by an ongoing airway remodeling and neutrophilic inflammation. Much of the airway remodeling is due to activation of a group of enzymes known as proteases; human neutrophil elastase (HNE) is a prominent protease found in the CF airway. While specific cytokines/chemokines are well-known for their role in the inflammation seen in CF, it is unknown how the protease-rich environment in CF lung disease influences airway inflammation. Recently, our group has characterized a novel collagen-derived fragment, proline-glycine-proline (PGP), which causes neutrophil influx through mechanisms …

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Protein Interaction And Cell Surface Trafficking Differences Between Wild-Type And Δf508 Cystic Fibrosis Transmembrane Conductance Regulator, Rebecca F. Goldstein Jan 2007

Protein Interaction And Cell Surface Trafficking Differences Between Wild-Type And Δf508 Cystic Fibrosis Transmembrane Conductance Regulator, Rebecca F. Goldstein

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Cystic fibrosis (CF) is caused by mutation of one protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which normally functions as a chloride channel at the apical surface of epithelial cells. The most common CFTR mutation results in the deletion of a single amino acid (phenylalanine) at position 508, which causes the protein to fold improperly. The ΔF508 CFTR is a temperature-sensitive (TS) processing mutant: At the restrictive temperature, 37°C, ΔF508 CFTR misfolds in the endoplasmic reticulum (ER) and is degraded, but at the permissive temperature, 27°C, it is “rescued” from degradation (rΔF508). In particular, rΔF508 CFTR folds correctly enough …

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Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han Jan 2007

Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han

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The replication of Human immunodeficiency virus type 1 (HIV-1) is characterized by the process of reverse transcription, which converts the viral RNA genome into a DNA intermediate prior to integration into the host cell chromosome. The initiation of reverse transcription needs a cellular tRNA primer, which binds to a region in the viral RNA genome, designated as the primer binding site (PBS). The 18-nucleotide PBS region of HIV-1, which is complementary to the 3′ terminal 18 nucleotides of tRNALys,3, is absolutely conserved among all HIV-1. The highly conserved PBS is a very good target for HIV-1 therapy. My dissertation research …

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Regulation Of The Human Heme Oxygenase-1 Gene, Thomas D. Hock Jan 2007

Regulation Of The Human Heme Oxygenase-1 Gene, Thomas D. Hock

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The heme oxygenase-1 (HO-1) gene encodes a microsomal enzyme that catalyzes the conversion of heme to carbon monoxide, Iron, and biliverdin. HO-1 transcription is induced upon a plethora of cellular stresses including heme, heavy metal exposure, hy-poxia, oxidative stress and many others. The goal of this work was to explore the molecu-lar regulation of HO-1 transcription. Four DNase 1 hypersensitive sites are detected within the HO-1 promoter extending from ~-40bp to ~-9.2kb relative to the transcription start site. Dimethylsulfate (DMS) in vivo footprinting is shown for two regulatory re-gions and reveals nine protected guanines in all. Mutational analyses indicates that …

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Quantitation Of Antiretrovirals In Alternative Matrices, Chantelle Bennetto Hood Jan 2007

Quantitation Of Antiretrovirals In Alternative Matrices, Chantelle Bennetto Hood

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The human immunodeficiency virus (HIV) pandemic is a growing concern, affecting almost 40 million people worldwide. Treatment for HIV infection consists of highly active antiretroviral therapy (HAART) to block different steps in the viral lifecycle, ultimately reducing HIV RNA to undetectable levels in the plasma. However, HIV RNA can be detected in numerous reservoirs outside of the blood despite the use of HAART. Therefore, measurement of antiretroviral (ARV) drugs in other biological matrices is important to broaden our understanding of HIV transmission, the development of viral resistance with sub-optimal ARV exposure, and fetal and neonatal drug exposure. This work describes …

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The Educational And Psychological Experiences Of Children Orphaned By Aids In Western Kenya, Grace Jepkemboi Jan 2007

The Educational And Psychological Experiences Of Children Orphaned By Aids In Western Kenya, Grace Jepkemboi

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The purpose of this study was to describe the perceptions of teachers and caregivers concerning the psychological and educational experiences of children orphaned by AIDS in Western Kenya. On the basis of qualitative inquiry, the design of the study focused on phenomenology inquiry. Audio-taped interviews were used as the primary source to gather data for this study. The questions that guided the study were "What are the psychological characteristics of children orphaned by AIDS in Kenya?" "What are the educational experiences of children orphaned by AIDS?" and "What strategies do the teachers and caregivers at the orphanages use to help …

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Synthesis And Control Of Microstructure, Mechanical Properties, And Bioactivity In Biphasic And Preferentially Oriented Calcium Phosphate Bioceramics, Hyunbin Kim Jan 2007

Synthesis And Control Of Microstructure, Mechanical Properties, And Bioactivity In Biphasic And Preferentially Oriented Calcium Phosphate Bioceramics, Hyunbin Kim

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Calcium phosphate bioceramics are recognized as one of the most biocompatible materials and are widely used in systems for bone repair and regeneration. In this work, the pulsed laser deposition technique was chosen to produce calcium phosphate materials with different crystallographic texture and chemical composition for investigation of their structural, mechanical, as well as biological properties. Various calcium phosphate coatings were obtained on Ti6Al4V substrates using a KrF excimer laser (248 nm) with an energy density of 4−8 J/cm2 and substrate temperature of 625−730 °C. A method was developed that enables the deposition of highly textured hydroxyapatite by controlling the …

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On The Immunological Roles Of Tlt2 And Hsh2, R Glenn King Jan 2007

On The Immunological Roles Of Tlt2 And Hsh2, R Glenn King

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The evolution of multicellular organisms necessitated the ability to detect and remove harmful parasitic microorganisms from the host. This simple requirement for self non-self discrimination has evolved in vertebrates into an elaborate system consisting of a variety of effector mechanisms to perform this process. The immune system is often described as consisting of two distinct yet complimentary components, the innate and adaptive immune systems. It is now recognized that the immune system relies on the highly coordinated interplay between a variety of cell types which cooperate to maintain the health of the organism. The work outlined in this dissertation addresses …

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The Effect Of The Aml1-Eto Translocation On Cell Cycle Tumor Suppressor Gene Function, Rose Marie Ko Jan 2007

The Effect Of The Aml1-Eto Translocation On Cell Cycle Tumor Suppressor Gene Function, Rose Marie Ko

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The t(8;21)(q22;q22) AML1-ETO translocation is one of the most frequent translocations in acute myeloid leukemia (AML), occurring in approximately 12% of cases. Our laboratory has generated a mouse model in which AML1-ETO is expressed in hematopoietic progenitor cells using a retroviral vector and assayed using bone marrow transplantation. Animals transplanted with AML1-ETO-expressing cells failed to develop leukemia. However, AML1-ETO promoted significant expansion of immature myeloid cells suggesting a “pre-leukemic” state that requires secondary mutations for disease progression. In addition, analysis of cell cycle kinetics in AML1-ETOexpressing myeloid progenitor cells showed that AML1- ETO slowed G1 to S phase progression compared …

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Cytoplasmic Assembly Of Human Cytomegalovirus., Jun-Young Seo Jan 2007

Cytoplasmic Assembly Of Human Cytomegalovirus., Jun-Young Seo

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No abstract provided.

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The Scales Are Still Unbalanced:A Phenomenological Study Of Parental Involvement Of Lower Socioeconomic Students Attending School In An Affluent Southeastern Educational Community, Debra Walker Smith Jan 2007

The Scales Are Still Unbalanced:A Phenomenological Study Of Parental Involvement Of Lower Socioeconomic Students Attending School In An Affluent Southeastern Educational Community, Debra Walker Smith

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With the pressures of No Child Left Behind, and many schools being identified as failing, parents are willing to make major sacrifices in order to provide what they believe is a quality education. The research addressed what it meant for twelve low socioeconomic parents to be involved in their children’s education in an affluent educational environment. The researcher defined low socioeconomics as students participating in the National School Lunch Program, as this was one of the identifiers used to determine this subgroup for the State Department of Education’s Adequate Yearly Progress. A phenomenological study was conducted to answer the following …

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Stability Of Clones Over Two Decades And The Role Of Murm In Penicillin Resistance And Evolution Of Streptococcus Pneumoniae, Dorothy Broughton Payne Jan 2007

Stability Of Clones Over Two Decades And The Role Of Murm In Penicillin Resistance And Evolution Of Streptococcus Pneumoniae, Dorothy Broughton Payne

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No abstract provided.

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Breast Cancer Chemoprevention With The Natural Polyphenols Resveratrol And Genistein, Alone And In Combination, Timothy Glynn Whitsett Jan 2007

Breast Cancer Chemoprevention With The Natural Polyphenols Resveratrol And Genistein, Alone And In Combination, Timothy Glynn Whitsett

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No abstract provided.

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Prenatal Lead Exposure In Karachi: Magnitude, Determinants And Effect On Birth Weight, Naveed Zafar Janjua Jan 2007

Prenatal Lead Exposure In Karachi: Magnitude, Determinants And Effect On Birth Weight, Naveed Zafar Janjua

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No abstract provided.

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The Recovery Experience For Persons With A Myocardial Infarction And Their Spouses/Partners, Vicki Lynnette Bingham Jan 2007

The Recovery Experience For Persons With A Myocardial Infarction And Their Spouses/Partners, Vicki Lynnette Bingham

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Coronary heart disease, the leading cause of death in Americans today, affects both genders in numerous ethnic populations. This life-threatening event causes both physical and emotional distress for persons with a myocardial infarction (MI), as well as for their spouses or partners and thus possibly forces them on a spiritual journey. The purpose of this study was to increase the understanding of the ways in which spirituality is defined and experienced by both persons with an MI and their spouses/partners during the recovery process. The method utilized in this study was a qualitative approach using interpretative phenomenology from a Heideggerian …

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Localization And Function Of G2e3, William Samuel Brooks Jan 2007

Localization And Function Of G2e3, William Samuel Brooks

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A microarray study was performed which identified G2E3 as a novel, putative ubiquitin ligase that was both G2/M-specific in expression and down regulated at the transcriptional level following DNA damage by γ-irradiation. The initial characterization of this protein is described herein. G2E3 is composed of three PHD/RING (plant homoedomain/really interesting new gene) domains within its amino-terminal half and a carboxy-terminal HECT (homologous to E6AP carboxy-terminus) domain. G2E3 is regulated in part by its subcellular localization. The protein normally resides within the nucleoplasm of cultured cells and distinctly within the nucleolus of HeLa cells. G2E3 is a nucleo-cytoplasmic shuttling protein with …

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Loss Of Pias3 Expression In Glioblastoma Multiforme Tumors:Implications For Stat-3 Activation And Gene Expression, Emily Claire Brantley Jan 2007

Loss Of Pias3 Expression In Glioblastoma Multiforme Tumors:Implications For Stat-3 Activation And Gene Expression, Emily Claire Brantley

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Glioblastoma multiforme (GBM) is the most common form of cancer in the central nervous system in adults. Because of the infiltrative and aggressive nature of GBM, current treatments including surgical resection, radiation and chemotherapy provide little benefit to patients diagnosed with this tumor. Median survival, after treatment, is less than one year. Despite advances in the basic understanding of cancer biology, this poor prognosis has remained virtually unchanged for several decades. Given the continuing difficulty of clinical treatment of GBMs, a molecular appreciation of relevant signaling pathways has grown. Signal Transducers and Activators of Transcription (STATs) function to activate gene …

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Characterization Of A Novel Acetyltransferase Found Only In Pathogenic Strains Of Mycobacterium Tuberculosis, David K. Crossman Jan 2007

Characterization Of A Novel Acetyltransferase Found Only In Pathogenic Strains Of Mycobacterium Tuberculosis, David K. Crossman

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Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is still a major threat to the human population. Roughly one third of the world population is asymptomatically infected and two million people die each year of TB. Effective treatments are available as a multi-drug regimen, but there is an ever increasing problem with the rise of multi-drug resistant strains that newer drug targets and a better understanding of how M. tuberculosis affects the host need to be elucidated. The primary target of M. tuberculosis in the human host is the macrophage where M. tuberculosis secretes virulence factors that inhibit various signal …

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A Study Into The Protein/Protein Interactions Involved In Hiv-1 Capsid Assembly, Chanel Catherine Douglas Jan 2007

A Study Into The Protein/Protein Interactions Involved In Hiv-1 Capsid Assembly, Chanel Catherine Douglas

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The aim of this work was to build an understanding of the protein/protein interactions involved in HIV-1 capsid assembly as it relates to the condensation of capsid within the virion. This was undertaken in an attempt to (i) understand how capsid subunits recognize and interact with each other, (ii) gain insight into the protein-protein interactions involved in the process, and (iii) determine if the protein-protein interactions involved in virus cap-sid assembly can be used as a target for viral inhibition. Within this dissertation you will find two approaches to this investigation. The first examines the role of electrostatics in the …

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The Molecular Biology Of Temperature-Dependent Sex Determination In Reptiles, Keela Dodd Jan 2007

The Molecular Biology Of Temperature-Dependent Sex Determination In Reptiles, Keela Dodd

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Temperature-dependent sex determination (TSD) is a type of environmental sex determination in which the egg’s incubation temperature determines the sex of the embryo. The exact physiology of TSD is not yet understood. Hormones and temperaturetriggered genes have been hypothesized to play a role. This study evaluates putative male and female factors that may play a role in TSD. Regarding female factors, this study evaluates clutch sensitivity to estradiol-17β and an aromatase inhibitor, and estradiol- 17β’s potential role in müllerian duct differentiation. Regarding male factors, this study also quantifies SOX9 mRNA during TSD in untreated and estradiol-17β treated embryos. In the …

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Factors Associated With Sexual Debut And Depression Among Adolescents In Rural Jamaica, Olaniyi J. Ekundayo Jan 2007

Factors Associated With Sexual Debut And Depression Among Adolescents In Rural Jamaica, Olaniyi J. Ekundayo

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Individual and family factors have been hypothesized to influence adolescent sexual behavior and depression, but the extent to which this is true for adolescents in Jamaica as a whole and for those in rural areas in particular, has not been well studied. The objective of this dissertation was to identify individual and family factors associated with sexual debut and depression among rural Jamaican adolescents. To elucidate these factors and to provide information to guide future interventions, we analyzed data on 748 adolescents attending public high schools in the rural parish of Hanover, Jamaica. Multivariate logistic regression was used to predict …

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Sexual Violence And Correlates Among Women In Hiv Discordant Union, Uganda, Donath Emusu Jan 2007

Sexual Violence And Correlates Among Women In Hiv Discordant Union, Uganda, Donath Emusu

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We sought to estimate the prevalence of sexual violence and sexually transmitted diseases (STDs), identify risk factors for sexual violence and STDs among women in Human Immunodeficiency Virus (HIV) discordant unions, and investigate the lived experiences of sexual violence among women in HIV discordant unions attending post-test club services at AIDS Information Centers (AICs) in Uganda. We carried out a prospective cohort study of women in HIV discordant and HIV negative concordant unions after disclosure of their HIV serostatus. We estimated prevalence of STDs in the two study cohorts and compared them for occurrence of risk factors for sexual violence …

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Characterization, Community Structure And Ecological Importance Of Sponge-Associated Bacteria, Patrick M. Erwin Jan 2007

Characterization, Community Structure And Ecological Importance Of Sponge-Associated Bacteria, Patrick M. Erwin

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The study of sponge-bacteria symbioses is emerging as a prominent field in marine biology and biotechnology, with implications ranging from a fundamental understanding of sponge ecology and insight into the evolution of prokaryote-eukaryote symbiotic interactions to natural products prospecting and bioactive metabolite synthesis. The research conducted herein integrates molecular genetic techniques with ecological methodologies to address fundamental issues of sponge-microbe associations. Bacterial communities associated with the marine sponges Hymeniacidon heliophila and Xestospongia sp. were compared to microbial assemblages from ambient seawater and the sympatric tunicate, Didemnum sp, using replicated clone libraries of 16S ribosomal RNA (rRNA) genes and terminal restriction …

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Pneumococcal Choline-Binding Protein A: Its Role In Virulence And Its Utility As A Streptococcus Pneumoniae Vaccine Antigen, David Tawayne Glover Jan 2007

Pneumococcal Choline-Binding Protein A: Its Role In Virulence And Its Utility As A Streptococcus Pneumoniae Vaccine Antigen, David Tawayne Glover

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Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. S. pneumoniae is a leading cause of pneumonia, meningitis, septicemia, and otitis media. Although all age groups can be affected, children and the elderly are espccially susceptible to infection. Currently there is a conjugate vaccine available for use, but this vaccine only contains capsular polysaccahride antigens from the seven most prevelant S. pneumoniae serotypes. The use of the conjugate vaccine has led to serotype shift, with more disease being caused by non-vaccine serotype bacteria. The studies presented in this dissertation identify and characterize a novel S. penumoniae vaccine candidate …

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A Role For P63 In The Regulati On Of Cell Cycle Progression And Cell Death, Eric Scott Helton Jan 2007

A Role For P63 In The Regulati On Of Cell Cycle Progression And Cell Death, Eric Scott Helton

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p63 is a member of the p53 family of transcription factors that is a critical regulator of epithelial development. Studies have shown that p63 does not appear to function as a classical tumor suppressor like p53. Instead, the expression pattern of p63 in cancers suggests that p63 retains the potential to function as either a tumor suppressor or an onco-protein. Here, we provide evidence describing the transcriptional activity of the p63 isoforms and provide mechanisms whereby p63 function is regulated in a context dependent manner. Our data shows that both the ΔNp63 and TAp63 variants retain the potential to regulate …

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Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer, Curt E. Harper Jan 2007

Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer, Curt E. Harper

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Prostate cancer is the second leading cause of cancer-related death among men in the United States. The goal of this research was to investigate the potential of three nutriceutical polyphenols, genistein, resveratrol, and epigallocatechin-3-gallate (EGCG), to suppress prostate cancer. Cancer chemoprevention and mechanism of action studies were carried out in transgenic models of prostate cancer. In TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, resveratrol suppressed poorly differentiated tumors by 86%, whereas EGCG suppressed precancerous lesions, but failed to prevent late-stage prostate cancer. Agents that were chemopreventive in the TRAMP model were subsequently evaluated alone, and in combination, in the …

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Teaching Reading Using Informational Texts In Third Grade Classrooms: A Case Study In An Urban School District, Dimple J. Martin Jan 2007

Teaching Reading Using Informational Texts In Third Grade Classrooms: A Case Study In An Urban School District, Dimple J. Martin

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The purpose of these multiple descriptive case studies was to describe and analyze the perspectives of three third grade classroom teachers and two third grade reading coaches regarding the use of informational texts and their influence on reading instruction. The research design involved interviews, and observations using a sample composed of three third grade classroom teachers and two third grade reading coaches in five urban, public elementary schools in the Southeastern United States. The aim of this research was to portray a vivid description of the reading episodes in third grade classrooms. The key findings from the study were that …

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Primer Selection Of E. Coli Trna Lys,3 By Human Immunodeficiency Virus Type-1, Anna Mcculley Jan 2007

Primer Selection Of E. Coli Trna Lys,3 By Human Immunodeficiency Virus Type-1, Anna Mcculley

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Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS). HIV replication includes the notable process of reverse transcription, a conversion of RNA to DNA. Reverse transcription is initiated from a primer by a viral enzyme, reverse transcriptase. The primer, tRNALys,3, is selected from the cytoplasm of an infected cell, annealed via the 3’ terminal 18-nucleotides to the viral primer binding site (PBS), and used in a subsequent infection. The mechanism of primer selection has not been determined although numerous studies have been performed. This has been hampered by the challenge of tRNALys,3 manipulation in the cell and …

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Sperm Production And Vitellogenesis As Biomarkers Of Endocrine Disruption In The Male Western Mosquitofish, Gambusia Affinis, Paul D. Melvin Jan 2007

Sperm Production And Vitellogenesis As Biomarkers Of Endocrine Disruption In The Male Western Mosquitofish, Gambusia Affinis, Paul D. Melvin

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Estrogenic compounds of anthropogenic origin enter the environment from several different sources, including domestic wastewater and agricultural runoff. Natural estrogens, synthetic estrogens, and estrogen breakdown products have been identified in wastewater treatment plant (WWTP) effluents. These compounds have direct and indirect effects on the endocrine systems of organisms living in the receiving waters. Male mosquitofish (Gambusia affinis) have been suggested as model bioindicator organisms for endocrine disruption by estrogenic compounds for a variety of reasons, including their hardiness, broad environmental tolerances (including temperature, salinity, and dissolved oxygen), widespread geographical distribution, and ease of use in the laboratory. We examined two …

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Directing Akt And Gsk3ss: Molecular Insights Into Cell Signaling And Survival, Gordon P. Meares Jan 2007

Directing Akt And Gsk3ss: Molecular Insights Into Cell Signaling And Survival, Gordon P. Meares

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Proper regulation of survival signaling is critical for all organisms. One important signaling cascade involved in the coordinated effort to control signals influencing cell fate is the phosphatidylinositol 3-kinase (PI3K)-Akt-glycogen synthase kinase 3β (GSK3β) signaling cascade. Following activation by growth factors the PI3K-Akt pathway promotes cell survival and, cell death is facilitated following inhibition of Akt. Many factors influence the function of the Akt-GSK3β signaling dyad, including phosphorylation, protein complex formation and subcellular localization. Previous work had demonstrated that the 90kDa heat shock protein, HSP90, directly binds and stabilizes Akt. Furthermore, several heat shock proteins including HSP90 and HSP105 can …

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