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Comparisons Between Behavioral And Electrophysiological Measures Of Visual Function In Rodent Models Of Retinal Degeneration, Glen R. Rubin Jan 2009

Comparisons Between Behavioral And Electrophysiological Measures Of Visual Function In Rodent Models Of Retinal Degeneration, Glen R. Rubin

All ETDs from UAB

The critical flicker frequency (CFF) is the lowest frequency for which a flickering light appears steady. Measuring CFF indicates rod- and cone-driven function relative to light intensity. CFF can be measured by both electroretinogram (ERG) and behavior. We measured CFF in several rodent models of retinal degeneration in order to better characterize retinal degeneration and understand the functional implications of electrophysiological changes. We measured ERG CFF in RCS dystrophic (RCS-p+) and wild type (WT) rats at PN23, PN44, and PN64. ERG CFF data in RCS rats show significant early degeneration of the rods followed by cones. CFF was significantly lower …


Oxidative Stress-Stimulated Vascular Calcification, Chang Hyun Byon Jan 2009

Oxidative Stress-Stimulated Vascular Calcification, Chang Hyun Byon

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Oxidative stress plays a critical role in pathogenesis of atherosclerosis. However, the effect of oxidative stress-induced molecular signaling in development of vascular calcification, a feature of advanced atherosclerosis, has not been defined. Osteogenic differentiation of vascular smooth muscle cells (VSMC) is critical in development of vascular calcification. We determined hydrogen peroxide (H2O2)-induced oxidative stress promoted a phenotypic switch of mouse primary VSMC from contractile to osteogenic phenotype. This effect was associated with increased expression and transactivity of Runx2, a key transcription factor for osteogenic differentiation. Inhibition of Runx2 using short hairpin RNA blocked oxidative stress-induced VSMC calcification. By contrast, adenovirus-mediated …


Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang Jan 2009

Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang

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Embryonic stem (ES) cells are pluripotent and, therefore, can differentiate into most if not all somatic cell types. Because of this characteristic, ES cells have great potential for medical therapies. Since the first cloned mammal, Dolly the sheep, was published in 1996 (1), several groups have successfully cloned other animals by the same nuclear transfer method (2). Isogenic ES cell lines can also be established from donor cells by the same technique (3). However, to date there has been no report of successful derivation of human ES cells by nuclear transfer. Based on the cell fusion (4) and nuclear transfer …


The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng Jan 2009

The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng

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Zinc is an essential cation for life that is involved in numerous physiology and pathophysiology processes. Despite its wide use as a cytoprotective agent in medications, its cellular and molecular mechanisms of action have not been well established. In order to define the potential therapeutic benefit of zinc, I used several Cystic Fibrosis (CF) and non-CF human airway epithelial cell lines as models in my studies. Extracellular zinc caused release calcium from the endoplasmic reticulum though zinc-sensitive Gq-coupled receptor(s) that may subsequently modulate ion channels. In addition, zinc also exhibited anti-inflammatory effects. Zinc inhibited pro-inflammatory molecular TNFα-induced cytokine and chemokine …


Parental Attitudes Of Human Papillomavirus Vaccination Of Adolescent Girls In Alabama, Allison G. Litton Jan 2009

Parental Attitudes Of Human Papillomavirus Vaccination Of Adolescent Girls In Alabama, Allison G. Litton

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Human papillomavirus is the most common sexually transmitted infection in the United States. This study examined racial and socio-demographic differences between African Americans and non-Hispanic Whites in Alabama regarding HPV vaccine acceptability. This cross sectional study employed a statewide survey of Alabama parents using a random digit dial phone method conducted through the Survey Research Unit at UAB. Participants were female caregivers of adolescent girls between the ages of 10-14 years. The final sample size was 403. Analyses included descriptive statistics, cross tabulations and odds ratios to assess race/ethnicity and other subgroup differences and logistic regression of intention to vaccinate …


Development And Implementation Of Knock-In And Bac-In Il-2 Reporter Mouse Models To Characterize Il2 Gene Regulation In Cd4 T Cells, Rita Jeanne Luther Jan 2009

Development And Implementation Of Knock-In And Bac-In Il-2 Reporter Mouse Models To Characterize Il2 Gene Regulation In Cd4 T Cells, Rita Jeanne Luther

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Maintenance of immune homeostasis involves a balance between T cell effector responses to antigen stimulus and reciprocal downregulation of this response through peripheral tolerance mechanisms. Upon exposure to pathogen, cytokine production and signaling serve to tightly coordinate cell-mediated clearance of antigen followed by contraction of the immune response. Interkeukin-2 (IL-2) is a type I family cytokine critical for expansion of activated T cells in vitro and enhancement of T cell memory responses in vivo. Deficiency of IL-2 in vivo also revealed a critical role for IL-2 in immune tolerance through the maintenance of T regulatory cell populations (Treg) in peripheral …


The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud Jan 2009

The Significance Of Heavy Chain Cdr3 Diversity In The Antibody Response To Polysaccharides, Tamer Mahmoud

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An understanding of the molecular mechanisms involved in the generation of protective antibody responses to polysaccharides associated with pathogenic microorganisms is of importance for improving vaccine design. The heavy chain third complementarity-determining region (HCDR3) of an antibody molecule is at the center of its antigen-binding site and plays a determinative role in antigen recognition. The goal of this dissertation was to investigate the role of HCDR3 diversity and composition on the antibody response to the polysaccharide α 1→3 Dextran (DEX). In the first study, we investigated the role of TdT, a DNA polymerase that plays a major role in generating …


Localization And Function Of Electrogenic Na/Bicarbonate Cotransporter Nbce1 In Rat Brain, Debeshi Majumdar Jan 2009

Localization And Function Of Electrogenic Na/Bicarbonate Cotransporter Nbce1 In Rat Brain, Debeshi Majumdar

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Na-Coupled Bicarbonate Transporters (NCBTs) are members of the bicarbonate transporter superfamily that play important roles in regulating intracellular pH (pHi) and extracellular pH (pHo) in the central nervous system. Electrogenic Na/bicarbonate Cotransporter 1 (NBCe1) is an NCBT that is expressed in different mammalian tissues including the brain. NBCe1 has three splice variants - NBCe1-A, -B and -C - that differ in the amino and carboxy termini. We have first performed a systematic characterization of the localization profiles of the three NBCe1 splice variants at mRNA and protein levels in rat brain. In these studies, we have used anti-sense probes and …


The Distinction Between First And Higher-Order Pregnancies Among Low-Income Adolescents, Ann Elizabeth Montgomery Jan 2009

The Distinction Between First And Higher-Order Pregnancies Among Low-Income Adolescents, Ann Elizabeth Montgomery

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Rapid repeat pregnancy is defined as having a subsequent pregnancy within 2 years of the first. In the United States, approximately 30-50% of adolescent mothers will experience a repeat pregnancy within 12 to 24 months of the first birth (Sangalang, Barth, & Painter, 2006; Coard, Nitz, & Felice, 2000). The negative implications of adolescents having a first birth--most notably in the areas of "health, career, and economic conditions" (Khalili, 2005, p. 19)--are compounded when a second pregnancy occurs (Key, Barbosa, & Owens, 2001). This exploratory study addressed one of the primary gaps in the literature related to rapid repeat adolescent …


Parenting Behaviors And Adolescent Obesity, Kathy Lynne Newman Jan 2009

Parenting Behaviors And Adolescent Obesity, Kathy Lynne Newman

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PARENTING BEHAVIORS AND EARLY ADOLESCENT OBESITY KATHY NEWMAN SCHOOL OF NURSING ABSTRACT The incidence of adolescent obesity has more than tripled in the past 30 years with the rate increasing from 5% to 17%. Approximately 17.0% of adolescents in the United States are obese with 4% being categorized as morbidly obese. Obesity disproportionately affects minority adolescent groups. Previous studies have examined relationships between parental behaviors and adolescent health risk behaviors, but few studies have compared these relationships across different racial/ethnic groups. The purpose of this study was to examine the relationships between parental nurturance, parental involvement, family cohesion, and early …


Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros Jan 2009

Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros

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Old World and New World hantaviruses, family Bunyaviridae, mature intracellularly within cellular compartments. Although it is generally accepted they assemble and bud in the Golgi apparatus the site remains controversial for New World hantaviruses, because some studies have raised the possibility of their maturation at the plasma membrane. Furthermore, the site of assembly hantaviruses still remains undetermined. The nucleocapsid (N) protein has been proposed to play a key role in facilitating assembly. To gain insight into the assembly pathways of Old World hantaviruses, we examine the intracellular trafficking of the Hantaan (HTN) virus N protein. We show progressive redistribution of …


Design Of The Predictive Power Method With Two Endpoints, Kiya R. Hamilton Jan 2009

Design Of The Predictive Power Method With Two Endpoints, Kiya R. Hamilton

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Three reasons to review accumulating data in clinical trials include: ethical issues, financial concerns and administrative concerns. Interim analysis is a good way to monitor accumulating data in clinical trials. Interim analysis allows for the possibility that a study may be terminated early; that is, if the currently observed data convincingly favor the null or the alternative hypothesis then the study ends early. In addition, many clinical trials are conducted to compare a treatment group to a standard group on multiple endpoints. Combining interim analyses with multiple endpoints allows for more information to be provided from the trial than either …


Insulin Signaling And Function In Osteoblasts, Keertik S. Fulzele Jan 2009

Insulin Signaling And Function In Osteoblasts, Keertik S. Fulzele

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Insulin and insulin-like growth factor-1 (IGF-1) are evolutionarily conserved hormonal signaling pathways with structurally similar ligands and receptors. Recent stu-dies suggest that that insulin and IGF-1 exert distinct as well as overlapping functions to regulate different aspects of skeletal development. A major problem in distinguishing the actions of insulin and IGF-1 is the fact that the receptors are co-expressed in many cell types and each ligand is able to cross-activate the other ligands' receptor. To distinguish direct skeletal actions of insulin from that of IGF-1, we have conditionally disrupted each receptor in vitro and in vivo specifically in osteoblasts. Studies …


Patterns Of Differential Mrna And Protein Expression During Minus Lens Compensation And Recovery In Tree Shrew Sclera, Hong Gao Jan 2009

Patterns Of Differential Mrna And Protein Expression During Minus Lens Compensation And Recovery In Tree Shrew Sclera, Hong Gao

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During the juvenile period of human development, an emmetropization mechanism uses visual signals to precisely guide the axial length elongation rate of the eyes to the optical power to keep the images in sharp focus. However, almost a third of the U.S. population develops axial myopia, in which the eye is elongated relative to the focal plane. The aims of the study were to examine 27 genes and 6 proteins in tree shrew sclera for potential differential expression patterns during minus lens compensation and dur-ing recovery. The study hypothesized that, in response to hyperopia produced by a -5 D lens, …


Theoretical Context Of A Common Reproductive Health Behavior: Vaginal Douching Among A National Sample Of Young Adult Women, Disa Cornish Jan 2009

Theoretical Context Of A Common Reproductive Health Behavior: Vaginal Douching Among A National Sample Of Young Adult Women, Disa Cornish

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Current research suggests that up to 75% of American women have engaged in vaginal douching during their lives. Prevalence of the behavior is disproportionately high among minority women (especially African American) and women of low SES. Two bodies of research present conflicting results regarding the benefits or risks to reproductive health that are posed by vaginal douching, although the majority of research on this topic suggests that douching is associated with negative health outcomes. Although studies have suggested prevalence rates, behavioral correlates, and biological associations of vaginal douching, very few studies have used behavioral theory when examining the practice. The …


Mitochondrial Bioenergetics And Cellular Stress, Brian Dranka Jan 2009

Mitochondrial Bioenergetics And Cellular Stress, Brian Dranka

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Mitochondria are responsible for most of the energy produced in human tissues, and this is dependent on the reduction of oxygen (O2) to water by the mitochondrial respiratory chain. Defects in mitochondrial energy production are now recognized to be involved in diabetes, cancer, cardiovascular disease, and other pathologies. To date, studies of these defects have employed quantification of O2 consumption in isolated, purified mitochondria. By using this strategy however, the cellular context, role of glycolysis, and normal regulation of mitochondrial function by metabolite availability are lost. Thus, an understanding of how mitochondria function and respond to stimuli in an intact …


Analysis Of The Malaria Vaccine Potential Of Plasmodium Falciparum Merozoite Surface Protein-3, Stephen James Jordan Jan 2009

Analysis Of The Malaria Vaccine Potential Of Plasmodium Falciparum Merozoite Surface Protein-3, Stephen James Jordan

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Malaria causes an estimated 1-3 million deaths each year, with the majority of deaths being a result of infection with Plasmodium falciparum. No commercially available vaccine currently exists, but multiple subunit-based vaccines are in development including one based on the promising vaccine candidate P. falciparum Merozoite Surface Protein-3 (PfMSP3). PfMSP3 varies in sequence between P. falciparum isolates, but all variation is restricted to the N-terminal domain. This observation has lead to the development of a PfMSP3-based vaccine comprised solely of the highly conserved, yet poorly immunogenic, C-terminal domain. The rationale for supporting the C-terminal domain relies entirely on its conserved …


A System Genetics Analysis Of Energy Metabolism Traits In Drosophila Melanogaster, Patricia Paola Jumbo-Lucioni Jan 2009

A System Genetics Analysis Of Energy Metabolism Traits In Drosophila Melanogaster, Patricia Paola Jumbo-Lucioni

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Obesity is emerging as a global public health problem and it has shown to precede and predict the development of type 2 diabetes, a complex disease that has also reached epidemic proportions in the US and worldwide. Despite that obesity-related traits are highly heritable, the genetic basis underlying their natural variation and the loci playing pleiotropic roles among organismal traits have not been fully elucidated. The overall goals of these present studies were: to shed light on the architecture of the genetic co-expression networks regulating variations in obesity-related traits, elucidate the extent to which they are regulated by pleiotropic loci, …


Effects Of Daily Versus 30-Day Continuous Contact Lens Wear On Tear Cytokine Levels, Lucy Ebunoluwa Kehinde Jan 2009

Effects Of Daily Versus 30-Day Continuous Contact Lens Wear On Tear Cytokine Levels, Lucy Ebunoluwa Kehinde

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The purpose of this investigation was to determine if 30 days of continuous contact lens wear produces a different ocular inflammatory response compared to 30 days of daily wear of Bausch & Lomb® PureVisionTM silicone hydrogel contact lenses. Eighty-five individuals wore these lenses for 30 days continuously in one eye and daily in the contralateral eye. Relative concentrations of 27 cytokines were measured in tear samples collected from the subjects using cytometric bead-based assays. Clinical tests were also conducted to correlate changes in cytokine levels to changes in clinical profiles. This study contributes to a greater understanding of the impact …


Impact Of Genetic And Epigenetic Variability In Response To Two Test Drugs 5-Fluorouracil And Lansoprazole, Adam Michael Lee Jan 2009

Impact Of Genetic And Epigenetic Variability In Response To Two Test Drugs 5-Fluorouracil And Lansoprazole, Adam Michael Lee

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Pharmacogenetics has proven to be an invaluable tool in predicting variability in drug response; however, there are numerous incidences where genetics cannot fully explain interindividual drug variability. Other factors, such as the epigenetic mechanism of DNA methylation, may offer an alternate explanation. Therefore, this dissertation focuses on both genetic and epigenetic regulation in order to gain a better understanding of the molecular basis behind drug response variability. Initial investigations focused on the antineoplastic agent 5-Fluorouracil (5-FU), which can produce severe toxicity in patients with deficiency in dihydropyrimidine dehydrogenase (DPD). Genotypic studies have identified >32 sequence variants in the DPYD gene; …


The Peptidyl-Prolyl Isomerase Pin1 Promotes Nf-Kappab And Stat3 Signaling In Glioblastoma, George Prescott Atkinson Jan 2009

The Peptidyl-Prolyl Isomerase Pin1 Promotes Nf-Kappab And Stat3 Signaling In Glioblastoma, George Prescott Atkinson

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Glioblastoma (GBM) is an incurable tumor of the central nervous system (CNS). Over the past 50 years, little progress has made in improving the quality of life and median lifespans of patients who are diagnosed with this devastating disease. However, new insights into the aberrant signaling pathways at the root of GBM pathology are providing new targets for next generation cancer therapies. Two signaling pathways that are commonly upregulated in GBM are NF-kappaB and STAT3. Importantly, tumor models in which NF-kappaB and STAT3 signaling are inhibited have demonstrated the importance of these pathways to GBM growth and proliferation. Therefore, better …


Non-Shared Familial Environment As A Determinant Of Discordant Patterns Of Disordered Eating Behaviors Among Sibling Pairs In A Family, Suparna Bagchi Jan 2009

Non-Shared Familial Environment As A Determinant Of Discordant Patterns Of Disordered Eating Behaviors Among Sibling Pairs In A Family, Suparna Bagchi

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Worldwide 15-40% of adolescents practice Disordered Eating Behavior (DEB). This study examined DEB development and the role of 1) shared familial factors among sibling pairs; and 2) non-shared familial experiences among discordant sibling pairs adjusted for individual and shared familial factors. The "National Longitudinal Study of Adolescent Health" data on 3274 adolescents were analyzed. The sample contained: twins (n=952), full siblings (n=1434), half siblings (n=418), and biologically not-related siblings (n=470). Multivariable regression analysis examined familial factors associated with DEB in the overall sample and sibling pair types. Adolescents engaging in DEB (~16%) were more likely to be white females with …


Small Molecule Inhibitors Of Acid Sensing Ion Channel-1, Yawar J. Qadri Jan 2009

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

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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 …


Oncostatin M-Induced Gene Expression And Regulation In Astrocytes And Microglia, Brandi Janece Baker Jan 2009

Oncostatin M-Induced Gene Expression And Regulation In Astrocytes And Microglia, Brandi Janece Baker

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Astrocytes and microglia are specialized glial cells of the Central Nervous System (CNS) that modulate neural activity and regulate immunological and inflammatory events. These cells perform their functions, in part, through the secretion of soluble mediators such as cytokines and chemokines. However, in response to the same neurological insult or inflammatory stimuli, the responses of these cells can vary greatly. This notion of differential responses was examined in our studies using Oncostatin M (OSM). OSM is a member of the IL-6 family of cytokines, which can be produced by microglia, astrocytes, neurons, and infiltrating leukocytes in the CNS, and is …


Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya Jan 2009

Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya

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Syndecan-1 (CD138), a transmembrane heparan sulfate-bearing proteoglycan, is expressed at high levels on most myeloma cells and is shed into the microenvironment. In patients, high levels of serum syndecan-1 are indicative of poor prognosis and elevation of shed syndecan-1 in animal models dramatically enhances tumor growth, angiogenesis and metastasis. Because syndecan-1 is a key regulator of myeloma pathogenesis, we hypothesized that reduction of syndecan-1 levels expressed by the myeloma cells will block their growth and dissemination. Syndecan-1 knockout and knockdown variants of two human myeloma cell lines, CAG and RPMI-8226, were developed using short hairpin RNA (shRNA) technology. In vitro, …


Factors Associated With Sleep Disruption Among Community-Dwelling Older Adults In The Health And Retirement Study, Laura L. Williams Jan 2009

Factors Associated With Sleep Disruption Among Community-Dwelling Older Adults In The Health And Retirement Study, Laura L. Williams

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Introduction: The purpose of this study was to examine behavioral outcomes and sleep disruption in aging adults using data from the 2004 wave of the longitudinal Health and Retirement Study (HRS). It was hypothesized that sleep disruption is associated with behavioral outcomes and sociodemographic variables in a population-based sample. Methods: The 2004 HRS data (N=20,129) represents a cross-sectional analysis of community dwelling aging adults born in the US at or before 1923 through 1953. Data are stratified by date of birth to provide five cohorts of aging elderly. The HRS Psychosocial Leave-Behind Participant Lifestyle Questionnaire (PLBQ) was given to a …


The Acute Onset Of Insulin Resistance In Adipose Tissue Following Trauma And Hemorrhage, Vanessa L. Williams Jan 2009

The Acute Onset Of Insulin Resistance In Adipose Tissue Following Trauma And Hemorrhage, Vanessa L. Williams

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Insulin resistance and hyperglycemia are common findings in patients following acute illnesses or injuries, such as surgical trauma, thermal injury, infection, hemorrhage, and sepsis. Insulin has three main target tissues: liver, skeletal muscle, and adipose tissue. Insulin resistance in the liver results in an increase in gluconeogenesis. In skeletal muscle, insulin resistance causes a decrease in insulin-stimulated glucose uptake. However, little is known about the contribution that adipose tissue makes to the insulin resistant state. The goals of the research presented in this dissertation were to: 1) determine whether insulin resistance developed in adipose tissue following acute trauma and hemorrhage; …


Modification Of Adenovirus Capsid Proteins For Gene Therapy Applications, Yizhe Tang Jan 2009

Modification Of Adenovirus Capsid Proteins For Gene Therapy Applications, Yizhe Tang

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Adenovirus (Ad) is the most commonly used viral vector in gene therapy applications to date for a broad range of diseases. Although Ad-based viral vectors have many advantages in a variety of gene therapy designs, the commonly used adenoviral vectors have several key shortcomings. Those shortcomings include (1) inefficient transduction in cell types devoid of Ad’s native receptors and the incapability of gene delivery to targets behind physical barriers; (2) restricted accessibility to the central nerve system due to the existence of the blood-brain barrier (BBB); (3) lack of a useful strategy and platform to generate multi-functionality displaying Ad vectors …


Targeting Angiogenesis With Plasminogen Kringle 5, Braden Cox Mcfarland Jan 2009

Targeting Angiogenesis With Plasminogen Kringle 5, Braden Cox Mcfarland

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The recombinant fifth kringle domain of plasminogen (rK5) has been shown to induce apoptosis of dermal microvessel endothelial cells (MvEC), and this pro-apoptotic effect required rK5 binding to cell surface glucose-regulated protein 78 (GRP78). GRP78 is a member of the heat shock protein family and under certain conditions is expressed on the cell surface. I am interested in identifying new anti-angiogenic therapy for glioblastoma tumors. The efficacy of certain anti-angiogenic therapy can be improved when combined with radiation, and radiation is a standard therapy for glioblastoma tumors; therefore, I investigated the pro-apoptotic effect of rK5 combined with radiation on primary …


Regulation Of Neural Precursor Cell Apoptosis And Proliferation By Glycogen Synthase Kinase-3, Tae-Yeon Eom Jan 2009

Regulation Of Neural Precursor Cell Apoptosis And Proliferation By Glycogen Synthase Kinase-3, Tae-Yeon Eom

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Neurogenesis is a crucial process for development, plasticity, and regenerative capacity of the developing and adult brain. Impairment of neurogenesis has been implicated in the etiology of psychiatric disorders. Although substantial studies have shown that therapeutic interventions enhance neurogenesis, much less is known about what factors impair neurogenesis. Thus, the present work examined if glycogen synthase kinase-3 (GSK3) has a role in impaired neurogenesis, focusing on apoptosis and proliferation of neural precursor cells (NPCs). This investigation found that GSK3 promotes apoptotic signaling in cultured NPCs subjected to two insults, trophic factor withdrawal and genotoxic stress. Both stimuli activated GSK3, Bax, …