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2010

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Role Of Epithelial Sodium Channel And Acid Sensing Ion Channel In Glioblastoma Multiforme, Niren Kapoor Jan 2010

Role Of Epithelial Sodium Channel And Acid Sensing Ion Channel In Glioblastoma Multiforme, Niren Kapoor

All ETDs from UAB

Glioblastoma Multifrome is the most common and aggressive of the primary brain tumors. These tumors express multiple members of the Epithelial Sodium Channel (ENaC)/Degenerin (Deg) family, associated with a basally active amiloride sensitive cation current. We hypothesize that this glioma current is mediated by a hybrid channel composed of a mixture of Epithelial Sodium Channel (ENaC) and Acid Sensing Ion Channel (ASIC) subunits. To test this hypothesis we made dominant negative cDNAs for ASIC1, αENaC, and γENaC. D54-MG glioma cells transfected with the dominant negative constructs for ASIC1, αENaC, or γENaC showed reduced protein expression for each of the specific …

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An Investigation Of The Molecular Mechanisms Involved In The Generation Of Breast Cancer, Joseph Tyson Deangelis Jan 2010

An Investigation Of The Molecular Mechanisms Involved In The Generation Of Breast Cancer, Joseph Tyson Deangelis

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Cell culture models of oncogenesis that use cellular reprogramming to generate a neoplastic cell from a normal cell provide one of the few opportunities to study the early stages of breast cancer development. Human mammary epithelial cells (HMECs) were induced to undergo a neoplastic transformation using defined genetic elements to generate transformed HMECs (THMECs). We conducted proteomic and transcriptomic analysis of three points in the neoplastic progression of breast cancer. First we monitored alterations in the proteome that revealed a progressive trend towards a metastatic state. Next, we identified a set of genes from transcriptomic analysis that displayed this same …

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The Mechanism Of Human Papillomavirus E7 Protein Mediated S-Phase Reentry In The Squamous Epithelium, Nicholas John Genovese Jan 2010

The Mechanism Of Human Papillomavirus E7 Protein Mediated S-Phase Reentry In The Squamous Epithelium, Nicholas John Genovese

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different heteroskedasticity consistent covariance matrix estimators (HCCM) under

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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

All ETDs from UAB

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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Determination Of The Effects Of University Building Usage On Energy Efficiency And Recommendations For Improvement, Dana Aaron Lackey Jan 2010

Determination Of The Effects Of University Building Usage On Energy Efficiency And Recommendations For Improvement, Dana Aaron Lackey

All ETDs from UAB

Energy costs are increasing at an alarming rate, and electricity use can contribute to carbon emissions and, therefore, to global warming. With this in mind and under direction of the University of Alabama at Birmingham (UAB) Facilities Management Department, researchers conducted building occupancy surveys of UAB buildings after working hours and on weekends to evaluate occupancy by day and time and by lighting condition of unoccupied rooms. The goals of this research consisted of identifying situations in which measures such as motion sensor installation or heating and/or air conditioning shutdown or setback could result in energy and cost savings and …

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The Effects Of Paternal Absence On The Sexual Behaviors Of African-American Adolescents Living In Impoverished Neighborhoods, Cheri Nicolette Langley Jan 2010

The Effects Of Paternal Absence On The Sexual Behaviors Of African-American Adolescents Living In Impoverished Neighborhoods, Cheri Nicolette Langley

All ETDs from UAB

According to the 2005 Youth Risk Behavior Survey (YRBS), 47% of the surveyed high school students reported ever having sexual intercourse, with 6% reporting having initiated their first sexual intercourse before the age of 13 (Eaton et al., 2006). Using the Mobile Youth Survey (1998-2008), the purpose of this study is four-fold: (a) to describe the MYS sample (1998-2008) in terms of its primary independent variable (the absence of a father figure) and its primary outcomes (sexual debut, sexual frequency, number of sex partners, condom use, pregnancy in the last year, and pregnancy intention); (b) to determine the impact of …

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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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Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben Jan 2010

Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben

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ROLE OF TRANSIENT RECEPTOR POTENTIAL CANONICAL CHANNELS IN GLIOMA CELL BIOLOGY VALERIE C. BOMBEN DEPARTMENT OF NEUROBIOLOGY ABSTRACT Gliomas, primary brain tumors derived from glial cells, constitute the majority of malignant tumors within the central nervous system. The most malignant of these tumors, grade IV Glioblastoma multiforme, are characterized by extensive proliferation, cellular and nuclear atypia, angiogenesis, areas of necrosis, and widespread invasion into the brain parenchyma. Data from our lab and others have implicated ion channels in the invasion and proliferation of glioma cells. Moreover, calcium signaling in gliomas and other cells has been implicated in both migration and …

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Membranes For Periodontal Regeneration: From Commercially Available To Spatially Designed And Functionally Graded Materials, Marco Cicero Bottino Jan 2010

Membranes For Periodontal Regeneration: From Commercially Available To Spatially Designed And Functionally Graded Materials, Marco Cicero Bottino

All ETDs from UAB

The aging of the global population will lead to a considerable increase in the number of surgical and restorative procedures related to oral rehabilitation or periodontal regeneration. Periodontitis is one of the most aggressive pathologies that concern the integrity of the periodontal system that can lead to the destruction of the periodontium. Guided tissue and guided bone regeneration (GTR/GBR) have been used for the repair and regeneration of periodontal tissues by utilizing an occlusive membrane.The goal of this dissertation is to advance the knowledge in the area of periodontal regeneration by investigating the properties of a commercially available freeze-dried collagen-based …

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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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Project-Induced Displacement, Secondary Stressors, And Health, Yue Cao Jan 2010

Project-Induced Displacement, Secondary Stressors, And Health, Yue Cao

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It is estimated that 15 million migrants displaced by development projects every year in the world. However, research on health impacts of project-induced displacement is insufficient. The existing literature concerning the causal effect of migration on health is inconclusive due to the selective nature of migration and other methodological problems. This study employs the stress process model as the major theoretical framework, components from Cernea's IRR model as well as Scudder and Colson's framework are also incorporated to examine the short-term health impact of the displacement resulting from China's Three Gorges Dam Project. I also explore whether the displacement's effect …

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Fraspa: A Framework For Synthesizing Parallel Applications, Ritu Arora Jan 2010

Fraspa: A Framework For Synthesizing Parallel Applications, Ritu Arora

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Scientists, engineers and other domain-experts have computational problems that are growing in size and complexity, thereby, increasing the demand for High Performance Computing (HPC). The demand for reduced time-to-solution is also increasing and simulations on high performance computers are being preferred over physical prototype development. Though HPC is gradually becoming indispensible for business growth, the programming challenges associated with HPC application development are a key bottleneck to embracing it on a massive scale. Current high-level approaches for generating HPC applications are either domain-dependent or do not leverage from existing applications. Message Passing Interface (MPI) is the most popular standard for …

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Determinants Of Self-Efficacy To Seek Care For Tuberculosis And Complete Tuberculosis Treatment Among Hiv-Positive Patients Attending Government Hiv/Aids Clincis In Honduras, Mayra Silvana Arias Jan 2010

Determinants Of Self-Efficacy To Seek Care For Tuberculosis And Complete Tuberculosis Treatment Among Hiv-Positive Patients Attending Government Hiv/Aids Clincis In Honduras, Mayra Silvana Arias

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control

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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

All ETDs from UAB

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

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 …

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Age Bias In Physicians' Recommendation For Physical Activity, Adherence, And Health Related Quality Of Life Among Individuals With Arthritis, Shamly Austin Jan 2010

Age Bias In Physicians' Recommendation For Physical Activity, Adherence, And Health Related Quality Of Life Among Individuals With Arthritis, Shamly Austin

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The association between individuals' ages, physicians' recommendations for physical activity, adherence, and health related quality of life among individuals with arthritis was examined using the 2007 Behavioral Risk Factor Surveillance System. The sample included 33,071 individuals with self-reported, physician-diagnosed arthritis who were 45 years or older. To answer the research questions, three sets of data were created: a whole sample (n=33,071), those 45-64 years old (n=17,607), and those 65 years or older (n=15,464). The conceptual framework for the study was based on the Behavioral Model of Health Services Utilization. The variables of interests were physicians' recommendations for physical activity, adherence …

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

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

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

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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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A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik Jan 2010

A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik

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The E2F family of transcription factors are important regulators of cell proliferation, and are often dysregulated in cancers. One member of the E2F family, E2F1, also has the ability to induce apoptosis; therefore, uncovering how E2F1-induced apoptosis is controlled is of interest in understanding tumorigenesis. To this end, we identified RRP1B as a novel target specifically induced by E2F1. RRP1B expression is specifically upregulated by E2F1 overexpression, but not other E2F family members. RRP1B expression is correlated with E2F1 expression during the cell cycle, and is significantly induced after DNA damage. The minimal RRP1B promoter region responsive to E2F1 was …

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

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

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

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Challenge Difficulty And Cardiovascular Responses In Mild Cognitive Impairment, Christopher Conley Stewart Jan 2010

Challenge Difficulty And Cardiovascular Responses In Mild Cognitive Impairment, Christopher Conley Stewart

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This study examined the effect of challenge difficulty on cardiovascular responses in patients with Alzheimer's disease and amnestic mild cognitive impairment. It extended from a model characterizing the determinants and cardiovascular consequences of effort in people confronted with performance challenges. One component of this model holds that ability has the potential to accentuate, attenuate, or have no effect on cardiovascular responses. Specifically, lower ability should accentuate cardiovascular responses so long as performers' view a challenge possible and worthwhile. However, lower ability should attenuate cardiovascular responses when it leads to the perception that a challenge is excessively difficult or impossible. The …

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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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