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Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood Jan 2010

Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood

Nebraska Center for Virology: Faculty Publications

Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi’s sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, …

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Method For Identification Of Virulence Determinants, Raul G. Barletta, Beth Harris Jan 2010

Method For Identification Of Virulence Determinants, Raul G. Barletta, Beth Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

Disclosed are methods for the determination of virulence determinants in bacteria and in particular bacteria of the genus Mycobacterium. Also disclosed are compositions and methods for stimulating an immune response in an animal using bacteria and virulence determinants identified by the methods of the present invention.

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Effect Of Telmisartan On Vascular Endothelium In Hypertensive And Type 2 Diabetic Hypertensive Patients, Burcu Barutçuoğlu, Zuhal Parildar, M. Işil Mutaf, Di̇lek Özmen, Emi̇n Ali̇oğlu, Sara Habi̇f, Oya Bayindir Jan 2010

Effect Of Telmisartan On Vascular Endothelium In Hypertensive And Type 2 Diabetic Hypertensive Patients, Burcu Barutçuoğlu, Zuhal Parildar, M. Işil Mutaf, Di̇lek Özmen, Emi̇n Ali̇oğlu, Sara Habi̇f, Oya Bayindir

Turkish Journal of Medical Sciences

Hypertension and type 2 diabetes mellitus (DM) cause endothelial dysfunction and may result in cardiovascular disease. The aim of this study was to assess endothelial dysfunction in essential hypertensives, and normotensive and hypertensive type 2 diabetics and to evaluate the effect of telmisartan on endothelium in hypertensives. Materials and methods: Eighteen essential hypertensives (group 1), 16 type 2 diabetic hypertensives (group 2), 10 type 2 diabetic normotensives (group 3), and 10 control subjects (group 4) were included in this study. Groups 1 and 2 received 40 mg/day telmisartan for 12 weeks and were evaluated at the beginning and end. Groups …

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Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley Jan 2010

Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley

All ETDs from UAB

Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …

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Small Molecule Inhibitors Of Acid Sensing Ion Channel-1, Yawar J. Qadri Jan 2010

Small Molecule Inhibitors Of Acid Sensing Ion Channel-1, Yawar J. Qadri

All ETDs from UAB

Acid Sensing Ion Channel 1 is one of the many proteins in the Epithelial Sodium Channel/Degenerin family. The proteins in this family interact to form cation channels with unique biophysical properties and can all be inhibited by the small molecule amiloride. Their expression in many different cell types underlies their involvement in a large variety of physiological and pathophysiological processes. ASIC-1 containing channels, specifically, are an important therapeutic target for ischemic stroke, nociception, the invasiveness of glioblastoma cells, and many other processes including anxiety and memory formation. Of the members of the ENaC/Deg family, chicken ASIC-1 is the only protein …

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O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho Jan 2010

O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho

All ETDs from UAB

O-GlcNAcylation is an abundant and dynamic post-translational modification on serine and threonine residues of nuclear and cytoplasmic proteins. O-GlcNAc Transferase (OGT) and Nuclear Cytoplasmic O-GlcNAcase and Acetyltransferase (NCOAT) are the only two enzymes and major regulators in this process. In the past two decades, many studies have demonstrated its important modulation roles in nutrient sensing, protein turnover, cell cycle progression, transcription, translation as well as stress resistance. Among these biological functions, the understanding of O-GlcNAcylation dependent oxidative stress is relatively unknown. This study aims to examine the effects of O-GlcNAcylation on JNK1 and FOXO4 transcription factors under acute oxidative stress …

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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

All ETDs from UAB

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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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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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

All ETDs from UAB

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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Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher Jan 2010

Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher

All ETDs from UAB

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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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 …

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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

All ETDs from UAB

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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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 …

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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

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 …

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Roles Of Nr4a3 In Insulin Sensitivity In Skeletal Muscle, Xiaolin Zhu Jan 2010

Roles Of Nr4a3 In Insulin Sensitivity In Skeletal Muscle, Xiaolin Zhu

All ETDs from UAB

For the past several decades, the prevalence of Type 2 Diabetes and the metabolic syndrome has been increasing. Insulin resistance is the central pathogenic event for these diseases. We previously reported that the NR4A family of orphan nuclear receptors augments insulin sensitivity in adipocytes. We now found that lentiviral mediated NR4A3 hyper-expression increased insulin stimulated glucose transport (ISGT) in C2C12 myocytes while NR4A3 knock-down exhibited opposite effect. We also examined the effects of prostaglandin A2 (PGA2) on insulin action and NR4A3 trans-activation in C2C12 myocytes. PGA2 augmented ISGT and insulin stimulated AKT phosphorylation in C2C12 myocytes. Importantly, PGA2 treatment led …

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Evolution And Genetic Diversity In Streptococcus Pneumoniae, Diana Lee Dupraw Jan 2010

Evolution And Genetic Diversity In Streptococcus Pneumoniae, Diana Lee Dupraw

All ETDs from UAB

The relative contributions of point mutations and intergenomic recombination via lateral gene transfer (LGT) determine the population structure and evolutionary style for a given bacterial species. Streptococcus pneumoniae has a weakly clonal population structure; adaptive clonal complexes can be detected; however, these can also be rapidly lost due to the high rate of recombination. To characterize the diversity of pneumococcal isolates in clonal complex, and to elucidate possible mechanisms for the long-term stability of such complexes, 35 serotype 6B strains belonging to a previously identified clonal complex, CC14, were assayed by Comparative Genome Hybridization (CGH) and Multi Locus Sequence Typing …

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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 …

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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 …

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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 …

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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

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 …

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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

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 …

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

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

All ETDs from UAB

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

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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 …

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

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

All ETDs from UAB

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

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The Role Of Fc Receptor-Like 2 In B Cell Signaling, Tanisha Anne Jackson Jan 2010

The Role Of Fc Receptor-Like 2 In B Cell Signaling, Tanisha Anne Jackson

All ETDs from UAB

Fc receptor-like 2 (FCRL2) is a transmembrane protein with immunomodulatory potential that is preferentially expressed by memory B cells in humans. It has two consensus immunoreceptor tyrosine-based inhibitory motifs (ITIM) in addition to a putative immunoreceptor tyrosine-based activation motif (ITAM) sequence in its cytoplasmic domain. We have confirmed the cellular distribution of FCRL2 and ana-lyzed its functional potential to show that coligation with the B cell receptor (BCR) leads to tyrosine phosphorylation of its ITIM motifs and subsequent SHP-1 recruitment to facilitate inhibition of BCR signaling. Mutational analysis indicates that the tyrosine residues in both inhibitory motifs of FCRL2 are …

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Translocation And Function Of Akt In The Mitochondria, Keri A. Mans Jan 2010

Translocation And Function Of Akt In The Mitochondria, Keri A. Mans

All ETDs from UAB

The ubiquitously expressed kinase Akt is a known survival protein, and is involved in multiple cell signaling cascades, notably the phosphatidylinositol 3-kinase (PI3K) pathway. Active Akt translocates from the plasma membrane to different subcellular compartments, including mitochondria, where it phosphorylates compartment-specific substrates. The mechanism of this translocation and the specific function of Akt within the mitochondria remains a mystery. The goals of this study were to elucidate the mechanism by which Akt enters the mitochondria and examine the role of Akt in mitochondrial function. Finally, the possibilities of using post-mortem human brain tissue to study mitochondrial function in normal and …

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A Ck2-Dependent Mechanism For Activation Of The Jak-Stat Signaling Pathway: Implications For Cancer Biology, Ying Zheng Jan 2010

A Ck2-Dependent Mechanism For Activation Of The Jak-Stat Signaling Pathway: Implications For Cancer Biology, Ying Zheng

All ETDs from UAB

Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) signaling is involved in regulation of cell survival, proliferation and differentiation. JAK tyrosine kinases can be transiently activated by cytokines or growth factors in normal cells, while they become constitutively activated as a result of mutations that affect their function in tumors. Specifically, the JAK2V617F mutation is present in the majority of patients with myeloproliferative disorders (MPDs) and is implicated in the pathogenesis of these diseases. In this dissertation, we report the identification of the serine/threonine kinase CK2 as a novel interactor and important regulator of activation of the JAK-STAT signaling …

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Effect Of Overexpressing Apolipoprotein A-I In An Animal Model Of Alzheimer's Disease, Terry L. Lewis Jan 2010

Effect Of Overexpressing Apolipoprotein A-I In An Animal Model Of Alzheimer's Disease, Terry L. Lewis

All ETDs from UAB

Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoprotein (HDL) in circulation and is expressed mainly by the liver and intestine. The levels of apoA-I/HDL are inversely related to the incidence of cardiovascular disease. Because of the connections between heart disease and Alzheimer's disease (AD), it is conceivable that high levels of apoA-I/HDL may be protective against AD. However, the limited literature shows mixed results on the role of apoA-I/HDL in the development of AD. It is hypothesized that increased expression of human apoA-I will ameliorate the behavioral deficits and characteristic amyloid-ß (Aß) plaque formation in a …

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Protective Antibodies To The Proline-Rich And Alpha Helical Regions Of Pneumococcal Surface Protein A And Their Detection In An In Vitro Surrogate Assay, Calvin Clay Daniels Jan 2010

Protective Antibodies To The Proline-Rich And Alpha Helical Regions Of Pneumococcal Surface Protein A And Their Detection In An In Vitro Surrogate Assay, Calvin Clay Daniels

All ETDs from UAB

Current pneumococcal vaccines containing pneumococcal capsular polysaccharide antigens protect against infection by pneumococci. However, this protection is limited to strains expressing the capsule types included in the vaccine. Since the introduction of these vaccines, the increase in incidence of infection by serotypes not targeted by the vaccine, a process called "serotype replacement," and the growing antibiotic resistance of replacement strains both stress the need for vaccines with broader protection. The alpha-helical region of a protein present on all clinical isolates of pneumococci, Pneumococcal Surface Protein A (PspA), elicits protective immunity. Downstream of the alpha-helical region is a highly conserved region …

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Identification Of A Novel Cytokine Inducible Stat5 Phosphoserine Site (Ps193) That Positively Regulates Its Transcriptional Activity And Is Found Constitutively Activated In Certain Hematopoietic Cancers, Abhisek Mitra Jan 2010

Identification Of A Novel Cytokine Inducible Stat5 Phosphoserine Site (Ps193) That Positively Regulates Its Transcriptional Activity And Is Found Constitutively Activated In Certain Hematopoietic Cancers, Abhisek Mitra

Open Access Theses & Dissertations

Hematological malignancies such as leukemia and lymphoma, can develop from aberrant changes in the cell signaling molecules to drive their uncontrolled cellular proliferation and differentiation. Activation, maturation, expansion and differentiation of T cells are critically regulated by the dynamics of various transcription factors activated by a variety of cytokines. Additionally, multiple effector molecules that mediate these T cells dependent signals include the JAK (Janus Kinase)-STAT (Signal transducer and activator of transcription) cascade. These signaling proteins are activated in response to a broad array of cytokines. Constitutively activated JAKs and STATs have been described in several T cell malignancies. A growing …

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