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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 …


The Role Of Mitochondria And Plasma Membrane Ca2+ Transport Systems In Ca2+-Dependent Glutamate Release From Rat Cortical Astrocytes, Reno Cervo Reyes Jan 2009

The Role Of Mitochondria And Plasma Membrane Ca2+ Transport Systems In Ca2+-Dependent Glutamate Release From Rat Cortical Astrocytes, Reno Cervo Reyes

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Astrocytes, a type of glial cell in the central nervous system, are recognized for their support roles to neurons. They supply neurons with metabolites, maintain ion homeostasis and clear the synaptic space of neurotransmitters. However, it has been found that some astrocytes have receptors for neurotransmitter and neuroligands, exhibit Ca2+ excitability when stimulated via these receptors, and secrete gliotransmitters as an output of this Ca2+ excitability. In the Ca2+-dependent release of glutamate, it has been shown that the endoplasmic reticulum is the predominant source and the extracellular space is the auxiliary source of free Ca2+ necessary for triggering exocytosis. Because …


Mechanisms Of Growth Hormone Action In Skeletal Muscle, Mahendra Devaraj Mavalli Jan 2009

Mechanisms Of Growth Hormone Action In Skeletal Muscle, Mahendra Devaraj Mavalli

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Growth hormone (GH) and insulin like growth factor-1 (IGF-1) exert profound growth promoting actions during pre and postnatal skeletal muscle development. GH and IGF-1 seem to promote their anabolic actions by influencing skeletal muscle cell prolif-eration and fusion. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including skeletal muscle, the individual contributions of these two growth factors to anabolic responses in skeletal muscle remains poorly defined. In this dissertation research, I sought to distinguish the mechanisms responsible for growth hormone's (GH) anabolic actions in skeletal muscle. To accomplish this, I analyzed the …


The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai Jan 2009

The Essential Role Of Macrophages And Tlr Signaling In The Host Response To Mycoplasma Pneumoniae, Jen-Feng Lai

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Several reports have suggested that Mycoplasma pneumoniae (Mp) can contribute importantly to the expression of symptoms in asthmatic human subjects. As a foundation for understanding the interactions between Mp and asthma susceptibility, we first studied the mechanisms by which the host normally eliminated Mp. Mice were inoculated with 4x106 Mp intranasally. Twenty-four hours after inoculation with Mp, subpopulations of CD11b+ macrophages/monocytes had been recruited into the lungs. The clearance of Mp was impaired both in macrophage-depleted and in macrophage-deficient mice. Furthermore, mice deficient in MyD88, a major adaptor for TLR signaling, showed dramatically defective clearance of Mp, associated with reduced …


Identification And Characterization Of Virulence Factors Of Mycoplasmas, Wenyi Luo Jan 2009

Identification And Characterization Of Virulence Factors Of Mycoplasmas, Wenyi Luo

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Mycoplasmas cause a group of diseases that are characterized by their chronicity and resistance to treatment. Diseases caused by the murine pathogens Mycoplasma pulmonis and Mycoplasma arthritidis are often studied as models of human diseases caused by a variety of chronic pathogens that induce a similar pathology. Among several candidate pathogenic factors, superantigens and degradative enzymes such as glycosidases are potentially important but not well characterized. The M. arthritidis mitogen (MAM) is a superantigen secreted by M. arthritidis. Its role with respect to arthritogenicity and toxicity is unclear. To improve the efficiency of transformation and hence enhance efforts to generate …


Physical Therapy And Chiropractic Use In Survivors Of Childhood Cancer: Impact On Health-Related Quality Of Life, Michele Montgomery Jan 2009

Physical Therapy And Chiropractic Use In Survivors Of Childhood Cancer: Impact On Health-Related Quality Of Life, Michele Montgomery

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The purpose of this study to was examine prevalence of physical therapy (PT) and chiropractic use in survivors of childhood cancer and which factors are associated with the use of these services. In addition, the health-related quality of life (HRQOL) of survivors with musculoskeletal and neurological chronic conditions who reported using either PT or chiropractic was compared to those survivors with the same conditions who did not use either service. This study was a secondary analysis of the Childhood Cancer Survivor Study (CCSS) and included a subset of 9289 survivors who completed both the baseline and 2003 follow-up questionnaires. In …


Understanding The Regulatory Mechanisms Of Ubp-M And H2a Deubiquitination In Chromatin And Cellular Functions, Heui Yun Joo Jan 2009

Understanding The Regulatory Mechanisms Of Ubp-M And H2a Deubiquitination In Chromatin And Cellular Functions, Heui Yun Joo

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Posttranslational modifications of histones regulate important chromatin and cellular functions. Among them, ubiquitination of histone H2A is correlated to transcriptional repression, such as HOX gene silencing and X chromosome inactiviation. Little was known about the removal of ubiquitin from histones, the enzyme(s) involved and its function in chromatin dynamics. We have identified the protein Ubp-M (USP16) to be the H2A- and nucleosome-specific deubiquitinase. We also demonstrated that Ubp-M-mediated H2A deubiquitination is involved in cell cycle progression to M-phase, HOX gene expression, and posterior development in Xenopus laevis. Furthermore, we have also purified USP12 and USP46 which contain an Ubp-M independent …


The Antecedents And Consequences Of The Niche Approach To Healthcare Delivery, Lejon Poole Jan 2009

The Antecedents And Consequences Of The Niche Approach To Healthcare Delivery, Lejon Poole

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ABSTRACT OBJECTIVE: Niche hospitals represent a growing segment in the health care industry. A niche strategy is an approach that focuses on a narrow market segment that its resources and capabilities can exploit (Porter, 1980; Powers and Khan, 2004). The purpose of the proposed study was to provide an understanding of the antecedents and consequences of the niche approach to healthcare delivery. The interaction of the niche strategy and the physician-owner as a unique bundle of resources was also examined. The subsequent model tested the relationships among generic strategies, market effects, firm effects, and financial performance. RESEARCH DESIGN AND METHODS: …


Sustained Pupil Constriction Following Brief Light Exposure: Relation To Retinal Health, Laxmikanth Kankipati Jan 2009

Sustained Pupil Constriction Following Brief Light Exposure: Relation To Retinal Health, Laxmikanth Kankipati

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The pupillary light reflex (PLR) is an indispensable clinical measure of visual, neurological and autonomic function which, until recently, was thought to be driven by only rods and cones. In 2000, a novel subset of retinal ganglion cells (RGCs) was discovered that express melanopsin and are intrinsically photosensitive (ipRGC). These ipRGCs contribute to the PLR and are responsible for the sustained pupilloconstriction observed following light offset (the post-illumination pupil response (PIPR)). The primary goal of this project was to examine the PIPR in a broad sample of the general human population. Using a newly-developed, wide-field optical system, we demonstrate that …


Characterization Of The Induction And Regulation Of Early B Cell Development, Melissa Ann Thal Jan 2009

Characterization Of The Induction And Regulation Of Early B Cell Development, Melissa Ann Thal

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Hematopoiesis is a highly regulated process directed by the microenvironment or niche in the bone marrow and the transcription factors those signals activate. Gene knockout experiments have identified critical cytokine signals and transcription factors required for promoting the differentiation of a hematopoietic stem cell to a B cell, but the regulatory mechanisms have yet to be fully elucidated. In early B cell development, a transcriptional hierarchy exists wherein E2A proteins activate early B-cell factor (Ebf1), which in turn activates expression of the B cell commitment factor, Pax5. In our studies, we use IL-7 receptor alpha chain (IL-7Rα) knockout animals that …


Genetic Complexity And Population Diversity Of Plasmodium Falciparum In The Peruvian Amazon, Patrick Lee Sutton Jan 2009

Genetic Complexity And Population Diversity Of Plasmodium Falciparum In The Peruvian Amazon, Patrick Lee Sutton

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GENETIC COMPLEXITY AND POPULATION DIVERSITY OF PLASMODIUM FALCIPARUM IN THE PERUVIAN AMAZON PATRICK LEE SUTTON MICROBIOLOGY GRADUATE PROGRAM ABSTRACT Characterizing the genetic complexity of immunologically relevant proteins, expressed during the life cycle of P. falciparum, is essential for identifying and advancing potential vaccine candidates. The current malaria immunity paradigm is rooted in high transmission studies which have investigated the impact of high genetic diversity on the development of humoral responses. Given the dynamic nature of malaria parasites, especially their ability to acclimate to change, it is likely that regions of low transmission do not share the same malaria immunity paradigm …


Regulation Of Tissue Remodeling Through The Calreticulin Binding Domain Of Thrombospondin-1, Mariya Ts'ana Sweetwyne Jan 2009

Regulation Of Tissue Remodeling Through The Calreticulin Binding Domain Of Thrombospondin-1, Mariya Ts'ana Sweetwyne

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Thrombospondin-1 (TSP1) is a multifunctional matricellular protein released by platelets in response to injury and secreted by cells under stress. TSP1 is cleaved into functional N- and C-terminal domain fragments, which have paradoxical actions with respect to angiogenesis, cell survival, and cell adhesion. Wound healing studies by others demonstrated that TSP1 knockout mice have delayed rates of wound closure, which was attributed to actions of the C-terminal domain. We wished to investigate the specific role of the N-terminal domain in tissue remodeling. Previously, we established that a sequence (aa 17-35) in the N-terminal domain of TSP1 induces focal adhesion disassembly, …


The Role Of Gbf1 In Golgi Biogenesis And Secretory Traffic., Tomasz Szul Jan 2009

The Role Of Gbf1 In Golgi Biogenesis And Secretory Traffic., Tomasz Szul

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The secretory pathway within a cell consists of series of membrane compartments connected by shuttling secretory vesicles containing cargo that travel from endoplasmic reticulum (ER) though ER-to-Golgi intermediate compartment (ERGIC), the Golgi apparatus, and endosomal compartment to the plasma membrane (PM). The Golgi specific brefeldin A (BFA)-resistant factor 1 GBF1 has been identified as an important factor involved in traffic between ER and Golgi and within the Golgi apparatus. GBF1 belongs to a family of guanine nucleotide exchange factors (GEFs) that stimulate the exchange of GDP for GTP on small GTPases, ADP-ribosylation factors (ARFs). The exchange of the nucleotide activates …


The Effects Of P-Glycoprotein Deficiency On Intestinal Integrity And Homeostasis, Elizabeth Marie Staley Jan 2009

The Effects Of P-Glycoprotein Deficiency On Intestinal Integrity And Homeostasis, Elizabeth Marie Staley

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THE EFFECTS OF P-GLYCOPROTEIN DEFICIENCY ON INTESTINAL INTEGRITY AND HOMEOSTASIS ELIZABETH M. STALEY MICROBIOLOGY ABSTRACT P-glycoprotein (P-gp) is an ATP-binding transmembrane pump associated with substrate extrusion in cells of epithelial and hematopoietic lineage. Polymorphisms in multidrug resistance genes (MDR), which encode this protein, are associated with development of inflammatory bowel disease in patient subsets. Furthermore, FVB/N animals deficient in P-gp expression develop spontaneous colitis. Disease in FVB.mdr1a-/- animals is reported to be the result of P-gp deficiencies in intestinal epithelial cells. We developed a neonatal model of bone marrow reconstitution to accurately evaluate the contribution of P-gp deficiencies in either …


The Potential Role Of Vh Replacement In Editing And Generating Autoreactive Antibodies, Run Fan Jan 2009

The Potential Role Of Vh Replacement In Editing And Generating Autoreactive Antibodies, Run Fan

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VH replacement occurs through RAG-mediated secondary recombination between an upstream VH gene and an existing VHDJH joint. In the first part of this dissertation, we focused on the potential regulation of VH replacement in the human B lineage EU12 cells muHC+ population, which underwent spontaneous VH replacement during in vitro culture. We cloned one of the dominant IgH genes, A19H, expressed in the EU12 muHC+ cells, and generated recombinant antibodies. We found that these recombinant antibodies recognize SM antigens. The anti-SM reactivity of A19H can not be efficiently neutralized by a randomly selected group of fourteen IgL chains from healthy …


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 …


Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck Jan 2009

Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck

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Capsule has been associated with virulence in numerous bacterial pathogens. The Mollicutes are a host-specific group of pathogens that cause a variety of economically relevant diseases important to man. Mycoplasma pneumoniae is responsible for 2 million cases of atypical pneumonia and 100,000 hospitalizations every year in the United States (Atkinson et al., 2008) (Krause and Taylor-Robinson, 1992). There was a toxic galactan molecule described as early as 1958 in Mycoplasma mycoides subsp. mycoides (Plackett and Buttery, 1958), although no evidence was presented that it was produced by the bacteria. Over the intervening fifty years the evidence to support the production …


Parenting Practices And Desire For A Child Among Mothers Living With Hiv, Natalie De La Cruz Jan 2009

Parenting Practices And Desire For A Child Among Mothers Living With Hiv, Natalie De La Cruz

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One-quarter of adults living with HIV/AIDS in the US are women, most of whom are facing decisions regarding their reproductive future. Despite clear challenges and complexities facing HIV-positive women, most research suggests that they maintain strong desires and intentions for motherhood. This research explores the correlates of desire for another child, with a specific emphasis on examining the relationship between current parenting experiences and future childbearing desires, among a predominantly black sample of HIV-positive women (n=96) participating in the Making Our Mothers Stronger (MOMS) Project. Predictors of contraceptive use and consistency between contraceptive practices and fertility desires are also explored …


Regulation Of Redox Signaling By Lipid Electrophiles In Breast Cancer, Anne R. Diers Jan 2009

Regulation Of Redox Signaling By Lipid Electrophiles In Breast Cancer, Anne R. Diers

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A number of steps in breast cancer progression and metastasis are regulated by redox signaling pathways. Electrophilic lipids such as 15-deoxy-delta12,14-Prostaglandin J2 (15d-PGJ2) are mediators of redox signaling pathways because of their ability to modify critical cysteine residues (thiols) in redox-sensitive proteins. In this thesis, we examine the effect of lipid electrophiles such as 15d-PGJ2 and others on redox signaling pathways in breast cancer. Furthermore, we develop new strategies to regulate cancer cell behavior in response to lipid electrophiles using three strategies: 1) through organelle-specific targeting of electrophiles 2) by exploiting the concentration-dependence of effects of electrophiles, and 3) utilizing …


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 …


Regulation Of Vh Replacement In Human Immature B Cells By B Cell Receptor (Bcr) - Mediated Signaling, Jing Liu Jan 2009

Regulation Of Vh Replacement In Human Immature B Cells By B Cell Receptor (Bcr) - Mediated Signaling, Jing Liu

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VH replacement occurs through RAG-mediated secondary recombination to change unwanted IgH genes. In this dissertation, I focused on studying the molecular mechanism that regulates VH replacement in human immature B cells. In part I, our results show that VH replacement is regulated by B cell antigen receptor (BCR) mediated signaling. Using the human EU12 mHC+ cells as an experimental model system, crosslinking BCR with F(ab')2 anti-IgM antibodies results in BCR internalization, cell proliferation arrest, and induction of VH replacement. Pretreatment of human EU12 mHC+ cells with the protein tyrosine kinase inhibitor Genistein, Syk kinase inhibitors, and a Src kinase inhibitor …


Counterregulatory Roles Of Transforming Growth Factor (Tgf)-Beta And Atrial Natriuretic Peptide (Anp) In Pressure Overload-Induced Cardiac Remodeling And Fibrosis, Jason Anthony Lucas Jan 2009

Counterregulatory Roles Of Transforming Growth Factor (Tgf)-Beta And Atrial Natriuretic Peptide (Anp) In Pressure Overload-Induced Cardiac Remodeling And Fibrosis, Jason Anthony Lucas

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Pressure overload stress (eg. hypertension or aortic stenosis) results in excessive cardiac fibrosis, changes in left ventricular (LV) geometry, and disruption of LV contractility, ultimately leading to heart failure. We hypothesize that transforming growth factor-beta (TGF-beta), a pro fibrogenic factor, and atrial natriuretic peptide (ANP), an anti fibrogenic factor, interact directly in a counterregulatory manner to balance the production of extracellular matrix (ECM) under pressure overload induced cardiac stress or hypoxia-induced pulmonary vascular adaptation. In this report, we examine structural and functional responses of the intact heart to pressure overload stress in vivo. We then utilize isolated rat pulmonary artery …


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

All ETDs from UAB

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 …


A Functional Analysis Of The Human Immunodeficiency Virus, Sushma Jyotika Bhakta Jan 2009

A Functional Analysis Of The Human Immunodeficiency Virus, Sushma Jyotika Bhakta

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The retroviral life cycle is separated into two distinct phases of infection. In the first phase, viral enzymes and proteins allow the virus to establish infection. The virus usurps host machinery in the second stage to produce infectious virus. In both phases of the replication cycle, the envelope (Env) glycoprotein (gp) is a key component of infectivity. Env plays a pivotal role in viral entry, by mediating attachment and facilitating fusion of the viral and cellular membranes, and during assembly, where Env must be incorporated into budding virions in order to produce infectious virions. The Env cytoplasmic domain (CD) interacts …


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 …