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The Obesity Prevalence Of The Students Between The Ages Of 5-19 In Kütahya, Mehmet Kaya, Ayli̇n Sayan, Mustafa Bi̇ri̇nci̇, Mevlüt Yildiz, Kami̇l Türkmen Jan 2014

The Obesity Prevalence Of The Students Between The Ages Of 5-19 In Kütahya, Mehmet Kaya, Ayli̇n Sayan, Mustafa Bi̇ri̇nci̇, Mevlüt Yildiz, Kami̇l Türkmen

Turkish Journal of Medical Sciences

To determine the prevalence of obesity among students between the ages of 5 and 19 in Kütahya, and to determine the factors associated with obesity prevalence. Materials and methods: The population in the survey was formed of students between the ages of 5 and 19 in the schools of Kütahya. Within the scope of this survey, obesity was evaluated in accordance with the percentile values indicated in a study on the body weight and height, head circumference, and body mass index reference values of Turkish children that was published in 2008. Results: It was determined that 6.5% of the students …


Epistaxis In Geriatric Patients, Alper Yüksel, Hani̇fi̇ Kurtaran, Ekrem Sai̇d Kankiliç, Nebi̇l Ark, Kadri̇ye Şeri̇fe Uğur, Mehmet Gündüz Jan 2014

Epistaxis In Geriatric Patients, Alper Yüksel, Hani̇fi̇ Kurtaran, Ekrem Sai̇d Kankiliç, Nebi̇l Ark, Kadri̇ye Şeri̇fe Uğur, Mehmet Gündüz

Turkish Journal of Medical Sciences

Epistaxis is a common emergency in otolaryngology. The aim of this study is to analyze the etiology, management, and accompanying disorders of epistaxis in geriatric patients by reviewing the literature Materials and methods: Data of 117 patients 65 years old and older who presented to the Department of Otorhinolaryngology with active epistaxis between 2004 and 2010 were retrospectively reviewed. Records were evaluated for age, sex, accompanying disorders, drug medication, detailed otorhinolaryngological findings, and management of epistaxis. Results: There were 67 women (57.26%) and 50 men (42.74%) with a mean age of 73.51 years (range: 65–90). Ninety-four (80.34%) patients had accompanying …


An Investigation Of Pulmonary Findings Of Crimean-Congo Haemorrhagic Fever Patients, Gülden Bi̇lgi̇n, Çi̇ğdem Ataman Hati̇poğlu, Şeri̇fe Altun, Cemal Bulut, Sami̇ Kinikli, Ali̇ Pekcan Demi̇röz Jan 2014

An Investigation Of Pulmonary Findings Of Crimean-Congo Haemorrhagic Fever Patients, Gülden Bi̇lgi̇n, Çi̇ğdem Ataman Hati̇poğlu, Şeri̇fe Altun, Cemal Bulut, Sami̇ Kinikli, Ali̇ Pekcan Demi̇röz

Turkish Journal of Medical Sciences

Crimean-Congo haemorrhagic fever (CCHF) generally affects many organs. In this study a retrospective evaluation of the pulmonary findings of CCHF patients was made. Materials and methods: The records of patients were retrospectively analysed. For each patient an evaluation was made of age, sex, occupation, place of residence, contact with ticks, smoking history, and pulmonary radiological and laboratory findings. A confirmed diagnosis of CCHF was made on determination by enzyme-linked immunosorbent assay or polymerase chain reaction. Results: Of the 128 patients, 48.4% were female. Symptoms of coughing were determined in 18% of patients, sputum in 4.7%, chest pain in 3.9%, dyspnoea …


Blast-Induced Tinnitus: A Combined Behavioral, Memri, And Electrophysiology Study, Jessica Pengyun Ouyang Jan 2014

Blast-Induced Tinnitus: A Combined Behavioral, Memri, And Electrophysiology Study, Jessica Pengyun Ouyang

Wayne State University Dissertations

ABSTRACT

BLAST-INDUCED TINNITUS: A COMBINED BEHAVIORAL, MEMRE, AND ELECTROPHYSIOLOGY STUDY

by

JESSICA OUYANG

May 2014 Advisor: Drs. Steve Cala & Jinsheng Zhang

Major: Physiology

Degree: Doctor of Philosophy

Tinnitus and hearing loss are the frequent auditory-related co-morbidities of blast trauma. The etiology of blast-induced tinnitus is also muddled by brain mechanisms associated with emotional and cognitive problems such as anxiety, memory loss, and depression. We set out to develop a realistic and ecologically valid model to address changes of cognitive status and psychological state that are associated with blast- induced tinnitus. In this study, 19 adult rats were randomly divided …


Linking Molecular, Electrical And Anatomical Properties Of Human Epileptic Brain, Shruti Bagla Jan 2014

Linking Molecular, Electrical And Anatomical Properties Of Human Epileptic Brain, Shruti Bagla

Wayne State University Dissertations

Epilepsy is a common neurological disorder of recurrent unprovoked seizures. It affects almost 1% of the world population. Although there is a wide range of anti-epileptic drugs (AEDs) available, they only treat the seizure symptoms and do not cure the disease itself. The poor role of AEDs can be attributed to the lack of knowledge of exact mechanisms and networks that produce epileptic activities in the neocortex. At present, the best cure for epilepsy is surgical removal of electrically localized epileptic brain tissue. Surgically removed brain tissue presents an excellent opportunity to discover the molecular and cellular basis of human …


Lineage Ii Of Southeast Asian/American Denv-2 Is Associated With A Severe Dengue Outbreak In The Peruvian Amazon, Maya Williams, Sandra V. Mayer, William L. Johnson, Rubing Chen, Evgeniya Volkova, Stalin Vilcarromeor, Steven G. Widen, Thomas G. Wood, Luis Suarez-Ognio, Kanya C. Long, Katherine A. Hanley, Amy C. Morrison, Nikos Vasilakis, Eric S. Halsey Jan 2014

Lineage Ii Of Southeast Asian/American Denv-2 Is Associated With A Severe Dengue Outbreak In The Peruvian Amazon, Maya Williams, Sandra V. Mayer, William L. Johnson, Rubing Chen, Evgeniya Volkova, Stalin Vilcarromeor, Steven G. Widen, Thomas G. Wood, Luis Suarez-Ognio, Kanya C. Long, Katherine A. Hanley, Amy C. Morrison, Nikos Vasilakis, Eric S. Halsey

Faculty Publications

During 2010 and 2011, the Loreto region of Peru experienced a dengue outbreak of unprecedented magnitude and severity for the region. This outbreak coincided with the reappearance of dengue virus-2 (DENV-2) in Loreto after almost 8 years. Whole-genome sequence indicated that DENV-2 from the outbreak belonged to lineage II of the southeast Asian/American genotype and was most closely related to viruses circulating in Brazil during 2007 and 2008, whereas DENV-2 previously circulating in Loreto grouped with lineage I (DENV-2 strains circulating in South America since 1990). One amino acid substitution (NS5 A811V) in the 2010 and 2011 isolates resulted from …


Neuroprotective Effects Of Gamma-Glutamylcysteine Ethyl Ester On An In Vivo Moderate Traumatic Brain Injury-Mediated Model And In Vitro In Cortical Astrocytes And Neurons, Jooyoung Cho Jan 2014

Neuroprotective Effects Of Gamma-Glutamylcysteine Ethyl Ester On An In Vivo Moderate Traumatic Brain Injury-Mediated Model And In Vitro In Cortical Astrocytes And Neurons, Jooyoung Cho

Online Theses and Dissertations

Neurodegeneration is the loss of neuronal structures or functions, while neuroprotection is the delay or prevention of neurodegeneration. In traumatic brain injury (TBI), neurodegeneration can occur as the result of oxidative stress, the imbalance of oxidants and antioxidants levels; therefore, antioxidant approaches can be effective therapeutic methods for neuroprotection by attenuating oxidative stress. Glutathione (GSH), a naturally occurring antioxidant, plays an important role in the maintenance of intracellular redox homeostasis by scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this thesis, we attempted to evaluate the abilities of a GSH precursor, gamma-glutamylcysteine ethyl ester (GCEE), to prevent …


Regulation Of Glucose Homeostasis By The Phlpp1 Phosphatase, Kara L. Larson Jan 2014

Regulation Of Glucose Homeostasis By The Phlpp1 Phosphatase, Kara L. Larson

Theses and Dissertations--Molecular and Cellular Biochemistry

Type 2 diabetes mellitus is a metabolic disease that affects one in ten people in the United States. It is caused by a combination of genetics and lifestyle factors. Disease progression begins with insulin resistance in peripheral tissues followed by pancreatic beta-cell failure. The mechanisms behind disease progression are not completely understood. PH domain leucine rich repeat protein phosphatase 1 (PHLPP1) is a known regulator of Akt and other members of the AGC kinase family. Akt has been established to play a role in numerous metabolic signaling pathways, including insulin action. It is hypothesized that as a regulator of Akt, …


Characterization Of A Dual-Tropic Human Immunodeficiency Virus (Hiv-1) Strain Derived From The Prototypical X4 Isolate Hxbc2, Shi-Hua Xiang, Beatriz Pacheco, Dane Bowder, Wen Yuan, Joseph Sodroski Jan 2014

Characterization Of A Dual-Tropic Human Immunodeficiency Virus (Hiv-1) Strain Derived From The Prototypical X4 Isolate Hxbc2, Shi-Hua Xiang, Beatriz Pacheco, Dane Bowder, Wen Yuan, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) coreceptor usage and tropism can be modulated by the V3 loop sequence of the gp120 exterior envelope glycoprotein. For coreceptors, R5 viruses use CCR5, X4 viruses use CXCR4, and dual-tropic (R5X4) viruses use either CCR5 or CXCR4. To understand the requirements for dual tropism, we derived and analyzed a dual-tropic variant of an X4 virus. Changes in the V3 base, which allow gp120 to interact with the tyrosine-sulfated CCR5 N-terminus, and deletion of residues 310/311 in the V3 tip were necessary for efficient CCR5 binding and utilization. Thus, both sets of V3 changes allowed …


Live Siv Vaccine Correlate Of Protection: Immune Complex-Inhibitory Fc Receptor Interactions That Reduce Target Cell Availability, Anthony J. Smith, Stephen W. Wietgrefe, Liang Shang, Cavan S. Reilly, Peter J. Southern, Katherine E. Perkey, Lijie Duan, Heinz Kohler, Sybille Muller, James Robinson, John V. Carlis, Qingsheng Li, R. Paul Johnson, Ashley T. Haase Jan 2014

Live Siv Vaccine Correlate Of Protection: Immune Complex-Inhibitory Fc Receptor Interactions That Reduce Target Cell Availability, Anthony J. Smith, Stephen W. Wietgrefe, Liang Shang, Cavan S. Reilly, Peter J. Southern, Katherine E. Perkey, Lijie Duan, Heinz Kohler, Sybille Muller, James Robinson, John V. Carlis, Qingsheng Li, R. Paul Johnson, Ashley T. Haase

Nebraska Center for Virology: Faculty Publications

Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to

protect women in the pandemic’s epicentre in Africa. We have been seeking these principles by

identifying correlates of the robust protection associated with SIVmac239Δnef vaccination in the

SIV-rhesus macaque animal model of HIV-1 transmission to women. We have identified one

correlate of SIVmac239Δnef protection against vaginal challenge as a resident mucosal system for

SIV-gp41 trimer antibody production and neonatal Fc receptor (FcRn)-mediated concentration of

these antibodies on the path of virus entry to inhibit establishment of infected founder populations

at the …


Experimental Infection Of Pregnant Goats With Bovine Viral Diarrhea Virus (Bvdv) 1 Or 2, Thomas Passler, Kay P. Riddell, Misty A. Edmondson, Manuel F. Chamorro, John D. Neill, Bruce W. Brodersen, Heather L. Walz, Patricia K. Galik, Yijing Zhang, Paul H. Walz Jan 2014

Experimental Infection Of Pregnant Goats With Bovine Viral Diarrhea Virus (Bvdv) 1 Or 2, Thomas Passler, Kay P. Riddell, Misty A. Edmondson, Manuel F. Chamorro, John D. Neill, Bruce W. Brodersen, Heather L. Walz, Patricia K. Galik, Yijing Zhang, Paul H. Walz

School of Veterinary and Biomedical Sciences: Faculty Publications

Infections with bovine viral diarrhea virus (BVDV) of the genus pestivirus, family Flaviviridae, are not limited to cattle but occur in various artiodactyls. Persistently infected (PI) cattle are the main source of BVDV. Persistent infections also occur in heterologous hosts such as sheep and deer. BVDV infections of goats commonly result in reproductive disease, but viable PI goats are rare. Using 2 BVDV isolates, previously demonstrated to cause PI cattle and white-tailed deer, this study evaluated the outcome of experimental infection of pregnant goats. Pregnant goats (5 goats/group) were intranasally inoculated with BVDV 1b AU526 (group 1) or BVDV 2 …


Protective Humoral Immune Response Induced By An Inactivated Porcine Reproductive And Respiratory Syndrome Virus Expressing The Hypo-Glycosylated Glycoprotein 5, Jung-Ah Lee, Byungjoon Kim, Fernando A. Osorio, Asit K. Pattnaik, Nak-Hyung Lee, Sang-Won Lee, Seung-Yong Park, Chang-Seon Song, In-Soo Choi, Joong-Bok Lee Jan 2014

Protective Humoral Immune Response Induced By An Inactivated Porcine Reproductive And Respiratory Syndrome Virus Expressing The Hypo-Glycosylated Glycoprotein 5, Jung-Ah Lee, Byungjoon Kim, Fernando A. Osorio, Asit K. Pattnaik, Nak-Hyung Lee, Sang-Won Lee, Seung-Yong Park, Chang-Seon Song, In-Soo Choi, Joong-Bok Lee

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses to the swine industry worldwide. Although inactivated and live vaccines are commercially available for the control of PRRS, both types of vaccine have not always proven successful in terms of generating a protective immune response, particularly in the case of inactivated vaccines. In this study, we tested whether an inactivated vaccine could induce a humoral immune response to PRRS during a homologous challenge. Amino acid substitutions were introduced into glycoprotein (GP) 5 of the FL12 strain of the PRRS virus (PRRSV) using site-directed mutagenesis with a pFL12 infectious clone. The …


Moraxella Spp. Isolated From Field Outbreaks Of Infectious Bovine Keratoconjunctivitis: A Retrospective Study Of Case Submissions From 2010 To 2013, John Dustin Loy, Bruce W. Brodersen Jan 2014

Moraxella Spp. Isolated From Field Outbreaks Of Infectious Bovine Keratoconjunctivitis: A Retrospective Study Of Case Submissions From 2010 To 2013, John Dustin Loy, Bruce W. Brodersen

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious bovine keratoconjunctivitis (IBK), also known as pinkeye, is the most costly eye disease of cattle. The principal etiologic agent of IBK is the Gram-negative bacterium Moraxella bovis. However, there have been reports of IBK outbreaks associated with Moraxella bovoculi. A retrospective study of IBK diagnostic cases submitted from July 1, 2010, through October 31, 2013, was conducted. Included in the study were 1,042 Moraxella isolates from 1,538 swabs of lacrimal secretions collected from 282 herds from 30 U.S. states. Moraxella isolates were identified to the species level and were composed of M. bovoculi (701 isolates), M. bovis …


Generation And Screening Of A Comprehensive Mycobacterium Avium Subsp. Paratuberculosis Transposon Mutant Bank, Govardhan Rathnaiah, Elise A. Lamont, N. Beth Harris, Robert J. Fenton, Denise K. Zinniel, Xiaofei Liu, Josh Sotos, Zhengyu Feng, Ayala Livneh-Kol, Nahum Y. Shpigel, Charles J. Czuprynski, Srinand Sreevatsan, Raul G. Barletta Jan 2014

Generation And Screening Of A Comprehensive Mycobacterium Avium Subsp. Paratuberculosis Transposon Mutant Bank, Govardhan Rathnaiah, Elise A. Lamont, N. Beth Harris, Robert J. Fenton, Denise K. Zinniel, Xiaofei Liu, Josh Sotos, Zhengyu Feng, Ayala Livneh-Kol, Nahum Y. Shpigel, Charles J. Czuprynski, Srinand Sreevatsan, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne’s Disease in ruminants. This enteritis has significant economic impact and world wide distribution. Vaccination is one of the most cost effective infectious disease control measures. Unfortunately, current vaccines reduce clinical disease and shedding, but are of limited efficacy and do not provide long-term protective immunity. Several strategies have been followed to mine the MAP genome for virulence determinants that could be applied to vaccine and diagnostic assay developent. In this study, a comprehensive mutant bank of 13,536 MAP K-10 Tn5367 mutants (P>95% )was constructed and screened in …


Influence Of Iron And Aeration On Staphylococcus Aureus Growth, Metabolism, And Transcription, Nagender Ledala, Bo Zhang, Javier Seravalli, Robert Powers, Greg Somerville Jan 2014

Influence Of Iron And Aeration On Staphylococcus Aureus Growth, Metabolism, And Transcription, Nagender Ledala, Bo Zhang, Javier Seravalli, Robert Powers, Greg Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

Staphylococcus aureus is a prominent nosocomial pathogen and a major cause of biomaterial-associated infections. The success of S. aureus as a pathogen is due in part to its ability to adapt to stressful environments. As an example, the transition from residing in the nares to residing in the blood or deeper tissues is accompanied by changes in the availability of nutrients and elements such as oxygen and iron. As such, nutrients, oxygen, and iron are important determinants of virulence factor synthesis in S. aureus. In addition to influencing virulence factor synthesis, oxygen and iron are critical cofactors in enzymatic and …


Francisella Tularensis Lvs Invasion Of Primary Murine Macrophages And Mtor Signaling, Michael Warren Edwards Jan 2014

Francisella Tularensis Lvs Invasion Of Primary Murine Macrophages And Mtor Signaling, Michael Warren Edwards

All ETDs from UAB

Francisella tularensis is an intracellular pathogen and the etiologic agent of tularemia. Because virulent strains cause morbidity and lethality in human, the attenuated live vaccine strain (LVS) has been used to study F. tularensis pathogenesis in murine models, since the disease in mice resembles human tularemia. Despite growing knowledge about host responses to Francisella infection, there is scarce information on the cell signaling events involved in Francisella host cell entry and in early immune re-sponses. Therefore, the purpose of this dissertation was to assess the involvement of the mammalian target of rapamycin (mTOR) in these processes. First, we evaluated the …


The Role Of Wnt5a In Tumor Suppression And Differentiation, Stephanie Easter Jan 2014

The Role Of Wnt5a In Tumor Suppression And Differentiation, Stephanie Easter

All ETDs from UAB

TGF-beta and the Wnt signaling pathways play key roles in regulating ductal growth and branching morphogenesis in the mammary gland. Disruption to this signaling can cause deregulation of the normal mammary stem cell population and foster an environment favorable for tumorigenesis and recurrence. Recent studies show that TGF-beta up-regulates expression of the non-canonical Wnt, Wnt5a, in the mammary gland and that Wnt5a antagonizes canonical Wnt/beta-catenin signaling in mammary epithelial cells. Canonical Wnt/beta-catenin signaling has been strongly implicated in expanding the mammary stem/progenitor cell pool. Here, we test the hypothesis that Wnt5a suppresses the expansion of the mammary stem and progenitor …


Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano Jan 2014

Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano

All ETDs from UAB

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Two major factors in both familial and sporadic PD are mitochondrial dysfunction and insufficient autophagy. My thesis research focuses on the interplay between these activities in PD. To investigate the common and differential effects of PD-inducing neurotoxins on mitochondrial bioenergetics and their relationships to cell survival, we used an in vitro culture system, differentiated dopaminergic SH-SY5Y neuroblastoma cells. We found that the neurotoxins rotenone, 1-methyl-4- phenylyridinium (MPP+) and 6-hydroxydopamine (6-OHDA), decreased mitochondrial respiration and induced cell death in these cells. The extent and characteristics of mitochondrial dysfunction in response to …


Regulation Of Skeletal Muscle Plasticity Using Engineered Configurations Of The Transcription Factors Myod And E12, Vladimir Grubisic Jan 2014

Regulation Of Skeletal Muscle Plasticity Using Engineered Configurations Of The Transcription Factors Myod And E12, Vladimir Grubisic

All ETDs from UAB

Skeletal muscle fibers, although terminally differentiated, can change their features, such as contraction speed and endurance, and throughout adult life in response to variety of stimuli, like exercise. This process is called plasticity and is mainly regulated by the type of nerve activity. Over the past several decades, research has shown that the properties of myofibers are also determined during muscle development. Ultimately, the change in phenotype requires a change in gene expression which is, in turn, regulated by transcription factors (TFs). Basic helix-loop-helix (bHLH) TFs regulate myogenesis and the central role belongs to the myogenic differentiation 1 (MyoD), often …


Recognition Of Hiv-1 Cryptic Epitopes During Infection And Following Vaccination, Anne Bet Jan 2014

Recognition Of Hiv-1 Cryptic Epitopes During Infection And Following Vaccination, Anne Bet

All ETDs from UAB

Cryptic epitopes (CE) are a unique set of human leukocyte antigen class I (HLA-I)-restricted peptides that are encoded by alternative reading frames (ARFs) of genes. During human immunodeficiency virus-1 (HIV-1) infection, CE translated from either sense or antisense transcripts elicit epitope-specific CD8 T cell responses. Previous studies using simian immunodeficiency virus (SIV)-vaccinated animals have shown that an increased breadth of CD8 T cell responses is correlated with controlling viral replication, therefore stressing the potential clinical benefit of vaccine-induced T cell responses to a diverse set of viral epitopes. Yet, the genetic profiles and immunological significance of CE remain poorly understood. …


The Modulation Of High Density Lipoprotein Metabolism In Systemic Lupus Erythematosus, Leland Latham Black Jan 2014

The Modulation Of High Density Lipoprotein Metabolism In Systemic Lupus Erythematosus, Leland Latham Black

All ETDs from UAB

Apolipoprotein A-I (ApoA-I), the major lipid-binding protein of high-density lipoprotein (HDL), can suppress inflammation and autoimmunity in hypercholesterolemic mice by modulating cellular cholesterol homeostasis and lipid oxidation. However, the cellular and molecular mechanisms involved are poorly understood, and whether ApoA-I or ApoA-I mimetic peptides can similarly exert immunosuppressive effects or improve inflammatory organ disease in SLE under normolipidemic conditions remains unresolved. We therefore first took a genetic approach in which bone marrow from SLE-prone Sle123 mice was transferred into wild-type, ApoA-I knockout (ApoA-I-/-) and ApoA-I transgenic (ApoA-Itg) mice. Transgenic expression of ApoA-I suppressed CD4+ T and B lymphocyte activation, reduced …


Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker Jan 2014

Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker

All ETDs from UAB

Vitally important to HIV-1 vaccine and prevention studies is a well-characterized animal model that recapitulates the salient features of HIV infection in humans. SIVmac and SIVsmm infection of rhesus macaques share key virological and pathological parallels with HIV-1 infection of humans including target cell entry via CD4 and CCR5 (Edinger et al., 1997), progressive T cell loss (Swanstrom & Coffin, 2012), generalized immune activation and preferential loss of mucosal Th17 cells (Brenchley et al., 2008; Klatt & Brenchley, 2010), and a vigorous but ultimately ineffective adaptive immune response. Though commonly used as a vaccine challenge strain in the macaque model, …


The Role Of The Autophagy-Lysosome Pathway In In Vitro Models Of Neurodegeneration, Burton Mader Jan 2014

The Role Of The Autophagy-Lysosome Pathway In In Vitro Models Of Neurodegeneration, Burton Mader

All ETDs from UAB

Recent studies have provided strong evidence that alterations in protein degradation pathways, such as the autophagy-lysosome pathway (ALP), may contribute to neuronal dysfunction and death which lead to clinical symptoms diagnosed with various neurodegenerative diseases. Parkinson's disease (PD) is characterized by neuromuscular abnormalities resulting from the pathological loss of substantia nigra dopaminergic neurons and widespread detection of Lewy bodies, intracellular protein inclusions composed primarily of α-synuclein. Additionally, altered gene function regulating the expression of α-synuclein has been directly linked to the PD pathogenesis. Autophagy is an intracellular degradation process that when altered can lead to the accumulation neurotoxic proteins such …


Glial Fibrillary Acidic Protein And Gliosis: Is Gfap More Than A Marker?, Heather Renee Minkel Jan 2014

Glial Fibrillary Acidic Protein And Gliosis: Is Gfap More Than A Marker?, Heather Renee Minkel

All ETDs from UAB

Alexander Disease (AxD) is a `gliopathy' caused by toxic, dominant gain-of-function mutations in the gene encoding glial fibrillary acidic protein (GFAP). Two distinct types of AxD exist. Type I AxD affected individuals develop cerebral symptoms by four years of age and generally suffer from macrocephaly, seizures, and physical and mental delays. As detection and diagnosis have improved, a larger portion, now about half of all AxD patients diagnosed, have onset >4 years and brainstem/spinal cord involvement. These type II AxD patients typically experience ataxia, palatal myoclonus, dysphagia and dysphonia. To date no study has examined a mechanistic link between the …


Epithelial Sodium Channel Purification And X-Ray Crystallographic Studies, Bharat G. Reddy Jan 2014

Epithelial Sodium Channel Purification And X-Ray Crystallographic Studies, Bharat G. Reddy

All ETDs from UAB

Epithelial sodium channels (ENaC) play a critical role in maintaining Na+ homeostasis in various tissues throughout our body. Understanding of ENaC structure is mediated from studies of the homologous acid sensing ion channel 1 (ASIC1). However, ENaC has sev-eral notable functional differences compared to ASIC1, thereby providing justification for determination of its three-dimensional structure. Unfortunately, this goal remains elu-sive due to several experimental challenges. Of the subunits that comprise a physiological hetero-trimeric ENaC (α, ß, and γ), the α-subunit alone is of significant interest. αENaC is unique in that it is capable of forming a homo-trimeric structure capable of conducting …


Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman Jan 2014

Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman

All ETDs from UAB

Calreticulin (CRT) is an ER chaperone and regulator of Ca2+ signaling which is increased following ER stress and in fibrotic and vascular fibroproliferative disorders. Previously, we demonstrated that ER CRT regulates type I collagen transcript, trafficking, secretion, and processing into the extracellular matrix (ECM). These studies investigated the role of CRT in regulating ECM production through control TGF-ß dependent signaling pathways. Our studies show that CRT -/- mouse embryonic fibroblasts (MEFs), rat lung fibroblasts, and human IPF lung fibroblasts with siRNA knockdown of CRT had impaired production of type I collagen and fibronectin when stimulated with TGF-ß. Similarly, knockdown of …


Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft Jan 2014

Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft

All ETDs from UAB

Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in OS treatment, more specific molecular targets are needed. One target of interest is alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation. Here, we show that α-CaMKII is highly expressed in primary OS tissue, and α-CaMKII deletion in human OS cell lines significantly reduces tumor burden in vivo. This inhibition of α-CaMKII results in decreased vascular endothelial growth factor (VEGF) protein secretion. Highly aggressive OS cells express VEGF receptor …


The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers Jan 2014

The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers

All ETDs from UAB

In recent years, a new appreciation of the role of neutrophils in regulating the immune system has emerged. Neutrophils are the most abundant leukocyte population and are traditionally recognized as essential effector cells of the innate immune system in the host defense against invading organisms. Neutrophils play a critical role in controlling bacterial and fungal infections by multiple mechanisms including phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Neutrophils have been shown to play important roles in viral pathogenesis, a knowledge gap exists in our understanding of the function of neutrophils in individuals infected with human immunodeficiency virus-1 (HIV-1). …


Sialic Acid: A Signal For Pneumococcal Egress From The Nasal Mucosa Into The Central Nervous System, Brandon L. Hatcher Jan 2014

Sialic Acid: A Signal For Pneumococcal Egress From The Nasal Mucosa Into The Central Nervous System, Brandon L. Hatcher

All ETDs from UAB

Streptococcus pneumoniae (pneumococcus) is one of the leading causes of bacterial meningitis world-wide. The classic paradigm in the establishment of bacterial meningitis is that in the absence of physical trauma, infection in the peripheral blood is needed to cause invasion of the central nervous system (CNS). Our previous studies have shown that pneumococci, a frequent colonizer of the nasopharynx, can cause bacterial meningitis through a nonhematogenous route by which bacteria appear to travel along the olfactory nerves, through the cribriform plate to the olfactory bulbs and into the rest of the CNS. However, with the frequency of nasopharyngeal colonization and …


Proteomic Analysis Of Rosenthal Fibers And The Development Of Software For Proteomics, Michael Raymond Heaven Jan 2014

Proteomic Analysis Of Rosenthal Fibers And The Development Of Software For Proteomics, Michael Raymond Heaven

All ETDs from UAB

The first aim of my thesis was to identify the protein composition of the protein aggregates, called Rosenthal fibers, which are the defining feature of Alexander disease (AxD). AxD is a rare neurodegenerative disease caused by mutations in the astrocyte specific protein, glial fibrillary acidic protein (GFAP). GFAP is a type III intermediate filament protein that is overexpressed in AxD. A guiding hypothesis of this project was that sequestration of vital cell proteins in the aggregates contributed to disease. The results of my research do not support this hypothesis, but do provide an in depth characterization of the protein composition …