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Articles 13351 - 13380 of 15687

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Orphan Nuclear Receptor Nur77 Regulates Androgen Receptor Gene Expression In Mouse Ovary., Anyi Dai, Guijun Yan, Qinyuan He, Yue Jiang, Qun Zhang, Ting Fang, Lijun Ding, Jianxin Sun, Haixiang Sun, Yali Hu Jan 2012

Orphan Nuclear Receptor Nur77 Regulates Androgen Receptor Gene Expression In Mouse Ovary., Anyi Dai, Guijun Yan, Qinyuan He, Yue Jiang, Qun Zhang, Ting Fang, Lijun Ding, Jianxin Sun, Haixiang Sun, Yali Hu

Center for Translational Medicine Faculty Papers

The androgen receptor (AR) is a nuclear receptor that is expressed in growing follicles and involved in folliculogenesis and follicle growth. The orphan nuclear receptor, Nur77, also has an important role in steroid signaling and follicle maturation. We hypothesized that AR levels and androgen signaling through AR are regulated by Nur77 in the ovary. In the ovaries of Nur77 knockout mice (n = 5), real-time PCR results showed that the mRNA levels of AR and an androgen signaling target gene, Kitl, were decreased by 35% and 24%, respectively, relative to wild-type mice (n = 5), which suggested transcriptional regulation of …

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Microrna-145 Protects Cardiomyocytes Against Hydrogen Peroxide (H₂O₂)-Induced Apoptosis Through Targeting The Mitochondria Apoptotic Pathway., Ruotian Li, Guijun Yan, Qiaoling Li, Haixiang Sun, Yali Hu, Jianxin Sun, Biao Xu Jan 2012

Microrna-145 Protects Cardiomyocytes Against Hydrogen Peroxide (H₂O₂)-Induced Apoptosis Through Targeting The Mitochondria Apoptotic Pathway., Ruotian Li, Guijun Yan, Qiaoling Li, Haixiang Sun, Yali Hu, Jianxin Sun, Biao Xu

Center for Translational Medicine Faculty Papers

MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, has been implicated as critical regulatory molecules in many cardiovascular diseases, including ischemia/reperfusion induced cardiac injury. Here, we report microRNA-145, a tumor suppressor miRNA, can protect cardiomyocytes from hydrogen peroxide H₂O₂-induced apoptosis through targeting the mitochondrial pathway. Quantitative real-time PCR (qPCR) demonstrated that the expression of miR-145 in either ischemia/reperfused mice myocardial tissues or H₂O₂-treated neonatal rat ventricle myocytes (NRVMs) was markedly down-regulated. Over-expression of miR-145 significantly inhibited the H₂O₂-induced cellular apoptosis, ROS production, mitochondrial structure disruption as well as the …

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Understanding The Gender-Based Mechanism Of Mso In Als Mice: A Metabolic Characterization Of The Sod1-G93a Mouse Model, Monica Ann Bame Jan 2012

Understanding The Gender-Based Mechanism Of Mso In Als Mice: A Metabolic Characterization Of The Sod1-G93a Mouse Model, Monica Ann Bame

Wayne State University Dissertations

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron death and a corresponding loss of neuromuscular connections resulting in muscle atrophy. Patients become paralyzed shortly after symptom onset and typically die within one to five years of pulmonary complications. ALS is a relatively rare disease, with an overall incidence of approximately 2 in 100,000 people per year and a prevalence of about 5 in 100,000 people. It is typically associated with increasing age and has a slight male prevalence, with a male to female ratio of approximately 3:2. ALS is classified as either familial (the less …

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Predicting Vision Loss In Healthy Aging With Manganese-Enhanced Mri Of The Rat Eye, David Bissig Jan 2012

Predicting Vision Loss In Healthy Aging With Manganese-Enhanced Mri Of The Rat Eye, David Bissig

Wayne State University Dissertations

In healthy aging, visual function declines throughout adulthood. Age-related changes in neuronal ion homeostasis -- specifically, increased Ca2+ influx through L-type voltage gated calcium channels (L-VGCCs) -- are believed to contribute to certain functional declines, but this possibility has not yet been tested in the neural retina. In young, mid- and old adult Long-Evans rats, we compared visual function (optokinetic tracking), as well as retinal physiology and eye morphology (Mn2+-enhanced MRI (MEMRI), which uses neuronal Mn2+ uptake as a marker of Ca2+ influx). We documented significant age-related decreases in visual performance and increases in retinal ion influx. We confirmed that …

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Mir-145 Directly Targets P70s6k1 In Cancer Cells To Inhibit Tumor Growth And Angiogenesis., Qing Xu, Ling-Zhi Liu, Xu Qian, Qi Chen, Yue Jiang, Dan Li, Lihui Lai, Bing-Hua Jiang Jan 2012

Mir-145 Directly Targets P70s6k1 In Cancer Cells To Inhibit Tumor Growth And Angiogenesis., Qing Xu, Ling-Zhi Liu, Xu Qian, Qi Chen, Yue Jiang, Dan Li, Lihui Lai, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

MiR-145 can regulate cell apoptosis, proliferation, neural development and stem cell differentiation. Previous studies indicate that miR-145 is downregulated in human colon cancer cells. However, the molecular mechanisms of miR-145 used to regulate colon carcinogenesis and angiogenesis remain to be clarified. Here, we show that the expression of miR-145 is downregulated in colon and ovarian cancer tissues and cell lines. MiR-145 inhibits p70S6K1 post-transcriptional expression by binding to its 3'-UTR. The angiogenic factors hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF), which are downstream molecules of p70S6K1, are decreased by miR-145 overexpression. P70S6K1 rescues miR-145-suppressed HIF-1 and VEGF …

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The Dermatan Sulfate Proteoglycan Decorin Modulates Α2Β1 Integrin And The Vimentin Intermediate Filament System During Collagen Synthesis., Oliver Jungmann, Katerina Nikolovska, Christian Stock, Jan-Niklas Schulz, Beate Eckes, Christoph Riethmüller, Rick T Owens, Renato V Iozzo, Daniela G Seidler Jan 2012

The Dermatan Sulfate Proteoglycan Decorin Modulates Α2Β1 Integrin And The Vimentin Intermediate Filament System During Collagen Synthesis., Oliver Jungmann, Katerina Nikolovska, Christian Stock, Jan-Niklas Schulz, Beate Eckes, Christoph Riethmüller, Rick T Owens, Renato V Iozzo, Daniela G Seidler

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/-)) mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/-) mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/-) fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, …

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Limitations Of The Rhesus Macaque Draft Genome Assembly And Annotation, Xiongfei Zhang, Joel Goodsell, Robert B. Norgren Jan 2012

Limitations Of The Rhesus Macaque Draft Genome Assembly And Annotation, Xiongfei Zhang, Joel Goodsell, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

Finished genome sequences and assemblies are available for only a few vertebrates. Thus, investigators studying many species must rely on draft genomes. Using the rhesus macaque as an example, we document the effects of sequencing errors, gaps in sequence and misassemblies on one automated gene model pipeline, Gnomon. The combination of draft genome with automated gene finding software can result in spurious sequences. We estimate that approximately 50% of the rhesus gene models are missing, incomplete or incorrect. The problems identified in this work likely apply to all draft vertebrate genomes annotated with any automated gene model pipeline and thus …

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Hiv Rna Suppression And Immune Restoration: Can We Do Better?, Marilia Rita Pinzone, Michelino Di Rosa, Bruno Cacopardo, Giuseppe Nunnari Jan 2012

Hiv Rna Suppression And Immune Restoration: Can We Do Better?, Marilia Rita Pinzone, Michelino Di Rosa, Bruno Cacopardo, Giuseppe Nunnari

Department of Microbiology and Immunology Faculty Papers

HAART has significantly changed the natural history of HIV infection: patients receiving antiretrovirals are usually able to control viremia, even though not all virological responders adequately recover their CD4+ count. The reasons for poor immune restoration are only partially known and they include genetic, demographic and immunologic factors. A crucial element affecting immune recovery is immune activation, related to residual viremia; indeed, a suboptimal virological control (i.e., low levels of plasma HIV RNA) has been related with higher levels of chronic inflammation and all-cause mortality. The sources of residual viremia are not yet completely known, even though the most important …

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Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn Jan 2012

Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn

Theses and Dissertations

Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our …

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Chloroviruses: Not Your Everyday Plant Virus, James L. Van Etten, David D. Dunigan Jan 2012

Chloroviruses: Not Your Everyday Plant Virus, James L. Van Etten, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Viruses infecting higher plants are among the smallest viruses known and typically have four to ten protein-encoding genes. By contrast, many viruses that infect algae (classified in the virus family Phycodnaviridae) are among the largest viruses found to date and have up to 600 protein- encoding genes. This brief review focuses on one group of plaque-forming phycodnaviruses that infect unicellular chlorella-like green algae. The prototype chlorovirus PBCV-1 has more than 400 protein-encoding genes and 11 tRNA genes. About 40% of the PBCV-1 encoded proteins resemble proteins of known function including many that are completely unexpected for a virus. In many …

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Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Polan, Michael A. Barry, Karl A. Nath, Andrew D. Badley Jan 2012

Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Polan, Michael A. Barry, Karl A. Nath, Andrew D. Badley

Nebraska Center for Virology: Faculty Publications

Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median …

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Copper–Zinc Superoxide Dismutase-Deficient Mice Show Increased Susceptibility To Experimental Autoimmune Encephalomyelitis Induced With Myelin Oligodendrocyte Glycoprotein 35–55, Chandirasegara Massilamany, Arunakumar Gangaplara, Heejeong Kim, Charlotte Standord, Govardhan Rathnaiah, David Steffen, Jaekwon Lee, Jay Reddy Jan 2012

Copper–Zinc Superoxide Dismutase-Deficient Mice Show Increased Susceptibility To Experimental Autoimmune Encephalomyelitis Induced With Myelin Oligodendrocyte Glycoprotein 35–55, Chandirasegara Massilamany, Arunakumar Gangaplara, Heejeong Kim, Charlotte Standord, Govardhan Rathnaiah, David Steffen, Jaekwon Lee, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

In this report, we have addressed the role of copper–zinc superoxide dismutase (SOD1) deficiency in the mediation of central nervous system autoimmunity. We demonstrate that SOD1-deficient C57Bl/6 mice develop more severe autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein (MOG) 35–55, compared with wild type mice. This alteration in the disease phenotype was not due to aberrant expansion of MOG-specific T cells nor their ability to produce inflammatory cytokines; rather lymphocytes generated in SOD1-deficient mice were more prone to spontaneous cell death when compared with their wild type littermate controls. The data point to a role for SOD1 in the maintenance …

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Rhodotorula Minuta Fungemia In A Ewe Lamb, C G. Chitko-Mckown, K A. Leymaster, M. P. Heaton, D D. Griffin, J K. Veatch, S A. Jones, M. L. Clawson Jan 2012

Rhodotorula Minuta Fungemia In A Ewe Lamb, C G. Chitko-Mckown, K A. Leymaster, M. P. Heaton, D D. Griffin, J K. Veatch, S A. Jones, M. L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

An 8-month-old crossbred ewe, normal upon physical examination, was humanely euthanized for tissue collection. After approximately 3 weeks in tissue culture, fungi began budding out of cells obtained from the choroid plexus. After an additional 3 weeks, budding was observed in kidney cell cultures and eventually in monocyte cultures as well. Serum from the lamb was submitted to the Veterinary Diagnostic Laboratory at Colorado State University for fungal diagnosis and was found negative for Aspergillus, Blastomyces, Coccidioidomycosis and Histoplasmosis. DNA was isolated from fungi collected from tissue culture supernatants and used in a set of pan-fungal PCR assays with DNA …

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Identification Of Amino Acid Residues Important For Anti-Ifn Activity Of Porcine Reproductive And Respiratory Syndrome Virus Non-Structural Protein 1, Lalit Beura, Sakthivel Subramaniam, Hiep Vu, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio Jan 2012

Identification Of Amino Acid Residues Important For Anti-Ifn Activity Of Porcine Reproductive And Respiratory Syndrome Virus Non-Structural Protein 1, Lalit Beura, Sakthivel Subramaniam, Hiep Vu, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

The non-structural protein 1 (nsp1) of porcine reproductive and respiratory syndrome virus is partly responsible for inhibition of type I interferon (IFN) response by the infected host. By performing alanine-scanning mutagenesis, we have identified amino acid residues in nsp1α and nsp1β~ (the proteolytic products of nsp1) that when substituted with alanine(s) exhibited significant relief of IFNsuppression. A mutant virus (16-SA, in which residues 16-20 of nsp1β were substituted with alanines) encoding mutant nsp1β recovered from infectious cDNA clone was shown to be attenuated for growth in vitro and induced significantly higher amount of type I IFN transcripts in infected macrophages. …

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Glycosyl-Phosphatidylinositol (Gpi)-Anchored Membrane Association Of The Porcine Reproductive And Respiratory Syndrome Virus Gp4 Glycoprotein And Its Co-Localization With Cd163 In Lipid Rafts, Yijun Du, Asit K. Pattnaik, Cheng Song, Dongwan Yoo, Gang Li Jan 2012

Glycosyl-Phosphatidylinositol (Gpi)-Anchored Membrane Association Of The Porcine Reproductive And Respiratory Syndrome Virus Gp4 Glycoprotein And Its Co-Localization With Cd163 In Lipid Rafts, Yijun Du, Asit K. Pattnaik, Cheng Song, Dongwan Yoo, Gang Li

School of Veterinary and Biomedical Sciences: Faculty Publications

The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that …

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Amino Acid Residues In The Non-Structural Protein 1 Of Porcine Reproductive And Respiratory Syndrome Virus Involved In Down-Regulation Of Tnf-Cx Expression In Vitro And Attenuation In Vivo, Sakthivel Subramaniam, Lalit Beura, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio Jan 2012

Amino Acid Residues In The Non-Structural Protein 1 Of Porcine Reproductive And Respiratory Syndrome Virus Involved In Down-Regulation Of Tnf-Cx Expression In Vitro And Attenuation In Vivo, Sakthivel Subramaniam, Lalit Beura, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses tumor necrosis factor-alpha (TNF-α) production at both transcriptional and post-transcriptional levels by its non-structural proteins 1α and 1β (Nsp1α and Nsp1β). To identifY the amino acid residues responsible for this activity, we generated several alanine substitution mutants of Nsp1α and Nsp1β. Examination of the mutant proteins revealed that Nsp1α residues Gly90, Asn91 , Arg97, Argl 00 and Arg124 were necessary for TNF-α promoter suppression, whereas several amino acids spanning the entire Nsp1β ~ were found to be required for this activity. Two mutant viruses, with mutations at Nsp1α Gly90 or Nsp1β residues …

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Staphylococcal Response To Oxidative Stress, Rosmarie Gaupp, Nagender Ledala, Greg A. Somerville Jan 2012

Staphylococcal Response To Oxidative Stress, Rosmarie Gaupp, Nagender Ledala, Greg A. Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous osidative and nitrosative stress are often due to the bacteria's interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, …

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An Epidemiological Model Of Rift Valley Fever With Spatial Dynamics, Tianchan Niu, Holly D. Gaff, Yiannis E. Papelis, David M. Hartley Jan 2012

An Epidemiological Model Of Rift Valley Fever With Spatial Dynamics, Tianchan Niu, Holly D. Gaff, Yiannis E. Papelis, David M. Hartley

Biological Sciences Faculty Publications

As a category A agent in the Center for Disease Control bioterrorism list, Rift Valley fever (RVF) is considered a major threat to the United States (USA). Should the pathogen be intentionally or unintentionally introduced to the continental USA, there is tremendous potential for economic damages due to loss of livestock, trade restrictions, and subsequent food supply chain disruptions. We have incorporated the effects of space into a mathematical model of RVF in order to study the dynamics of the pathogen spread as affected by the movement of humans, livestock, and mosquitoes. The model accounts for the horizontal transmission of …

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Hyperactivation Of The Hypothalamo-Pituitary-Adrenocortical Axis In Streptozotocin Diabetic Rats: Effect Of Tinospora Cordifolia (Willd.) And Insulin Therapy, Nagaraja Puranik, Sheela Devi Devi, Kararshaha Kammar Jan 2012

Hyperactivation Of The Hypothalamo-Pituitary-Adrenocortical Axis In Streptozotocin Diabetic Rats: Effect Of Tinospora Cordifolia (Willd.) And Insulin Therapy, Nagaraja Puranik, Sheela Devi Devi, Kararshaha Kammar

Turkish Journal of Medical Sciences

In the present study, we investigated the extent to which changes in corticosterone level and food and water intake behavior occur in diabetes and explored the effect of Tinospora cordifolia extracts and insulin therapy in streptozotocin-induced diabetic rats. Materials and methods: Female albino rats of the inbred Wistar strain (body weight: 180-210 g) were used in this study. Experimental diabetes was induced by injecting freshly prepared streptozotocin once at the dose of 55 mg/kg body weight intravenously in 0.1 M citrate buffer, pH 4.5. The drug was administered orally for 10 days and 30 days in different groups containing 6 …

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Cytotoxic Effect Of Cigarette Smoke Condensate On Mice And Rat Mesenchymal Stem Cells And Hela Cells, Aftab Ahmad, Abdul Rauf Shakoori Jan 2012

Cytotoxic Effect Of Cigarette Smoke Condensate On Mice And Rat Mesenchymal Stem Cells And Hela Cells, Aftab Ahmad, Abdul Rauf Shakoori

Turkish Journal of Medical Sciences

Aim: To study the effect of cigarette smoke condensate (CSC) on HeLa cells and mesenchymal stem cells (MSCs) of mice (mMSC) and rats (rMSC). Cigarette smoking results in the deaths of millions of people annually. The constituents of cigarette smoke produce oxidants in the cells that result in inflammation, carcinogenesis, and apoptosis. Materials and methods: CSC was collected on filter paper and dissolved in dimethyl sulfoxide, and 10-100 µg/mL was added to HeLa cells, mMSCs, and rMSCs in a 96-well plate. The cytotoxic effect of CSC was measured after 48 h using a neutral red uptake assay. Images of the …

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The Role Of Primary Cilia In Articular Cartilage And Growth Plate, Ching-Fang Chang Jan 2012

The Role Of Primary Cilia In Articular Cartilage And Growth Plate, Ching-Fang Chang

All ETDs from UAB

Primary cilia are now considered an important organelle required for many key steps during developmental processes including skeletal development. Articular cartilage and growth plate are two cartilage compartments whose functions are important postnatally. Articular cartilage is a think cartilage layer which serves as a cushion to protect the joint space, whereas growth plate is important for postnatal long bone growth. Both articular cartilage and growth plate need to be developed properly to ensure the normal bone function. Here, we show an important role of primary cilia in development of both articular cartilage and growth plate using genetic modified mouse model …

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Neuropharmacology Of The Α2a Adrenergic Receptor In Disorders Of Mood And Cognition, Christopher Cottingham Jan 2012

Neuropharmacology Of The Α2a Adrenergic Receptor In Disorders Of Mood And Cognition, Christopher Cottingham

All ETDs from UAB

Depressive disorders carry relatively high lifetime risks of greater than 10%, and the antidepressant drugs used in the pharmacotherapy of these mood/cognitive disorders are among the most-prescribed pharmacological agents. However, a detailed understanding of both depressive etiology and the pharmacological mechanisms of action for antidepressant drugs remain elusive. The overall goal of this dissertation research is to provide novel in-sights through a detailed study of the neuropharmacology of the α2A adrenergic receptor (AR). α2ARs, as key regulators of noradrenergic neurotransmission, have been broadly understood to have some ill-defined role in both the neurobiology and neuropharmacology of depressive disorders. The studies …

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Adhesion Molecule Interactions Influence The Implementation Of Immune Responses To Infection, Maureen Ann Cox Jan 2012

Adhesion Molecule Interactions Influence The Implementation Of Immune Responses To Infection, Maureen Ann Cox

All ETDs from UAB

Interactions mediated by intercellular adhesion molecule-1 (ICAM-1) enhance both the antigenic and cytokine signals that CD8 T cells perceive, and these interactions have been suggested to be required for the formation of memory CD8 T cells. Following acute lymphocytic choriomeningitis virus (LCMV) infection of ICAM-1-/- mice, we observe elevated numbers of "effector-phenotype" (CD127lo KLRG-1hi IL-2-) virus-specific CD8 T cells well into the memory phase, while the development of memory-phenotype CD8 T cells (CD127hi KLRG-1lo IL-2 producing) is not impaired. The enhanced maintenance of effector-phenotype cells is due to ICAM-1 deficiency on non-T cell subsets, suggesting a role for ICAM-1 mediated …

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Modulation Of Alpha-Synuclein Metabolism And Toxicity By Cathepsin D, Donna Marlana Crabtree Jan 2012

Modulation Of Alpha-Synuclein Metabolism And Toxicity By Cathepsin D, Donna Marlana Crabtree

All ETDs from UAB

Parkinson's disease (PD) is the most commonly occurring neurodegenerative movement disorder, and aberrant accumulation of the protein α-synuclein is thought to be a major contributing factor in disease development. Dysfunction of the autophagy lysosome pathway (ALP) has been implicated in PD pathogenesis. Our lab and others have shown that the lysosomal enzyme cathepsin D (CD) is an important regulator of α-synuclein degradation. The primary focus of this thesis is probing the structure/function dynamic that exists between α-synuclein and CD. We have found that lentiviral-mediated over expression of wild type CD (wtCD) leads to subtle alterations in the ALP in a …

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Regulation Of Clc-3 In Human Malignant Glioma, Vishnu Anand Cuddapah Jan 2012

Regulation Of Clc-3 In Human Malignant Glioma, Vishnu Anand Cuddapah

All ETDs from UAB

Malignant gliomas are the most common and deadly form of primary brain cancer afflicting adults. Current treatment regimens, including surgical debulking, radiotherapy, and chemotherapy, have limited efficacy, and median patient survival remains only 14 months. Therefore, novel therapies must target different aspects of glioma biology. Two of the most striking features of this cancer are the unusual ability of glioma cells to robustly proliferate and migrate in the brain, and recent evidence suggests that ClC-3, a voltage-gated Cl- channel/transporter is implicated in both of these processes. We hypothesize that ClC-3 may facilitate proliferation and migration by promoting hydrodynamic shape and …

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Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai Jan 2012

Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai

All ETDs from UAB

Glutamate mediates excitatory synaptic transmission in the central nervous system (CNS). Regulation of glutamate release and uptake shapes the spatiotemporal dynamics of glutamate at and around synapses to influence information transfer between neural cells. This dissertation focuses on the modulation of glutamate release and uptake at excitatory synapses of cerebellar Purkinje cells (PC). In the first project we show that differential expression of PC glutamate transporters controls the amount of glutamate entering the extrasynaptic space, thereby influencing the excitatory responses in surrounding Bergmann glia. This work provides the first evidence that neuronal glutamate uptake affects glial glutamatergic signaling. In the …

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Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac, Jason Derek Whitt Jan 2012

Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac, Jason Derek Whitt

All ETDs from UAB

ABSTRACT The nonsteroidal anti-inflammatory drug (NSAID) sulindac has displayed the ability to inhibit the proliferation of colorectal cancer (CRC) cells and to increase the sensitivity of multidrug resistant (MDR) cancer cells to a wide variety of chemotherapeutic agents. The antineoplastic activity of sulindac has been attributed to inhibition of the prostaglandin producing enzyme COX-2, but the exact mechanism remains elusive and the inhibition of prostaglandin synthesis can result in gastrointestinal, hepatic, and cardiovascular toxicities. Enzymatic, cellular, and imaging assays were used to identify mechanisms that could contribute to the antiproliferative and apoptotic activity of sulindac. Screening of more than 500 …

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Development Of Electrospun Bone-Mimetic Matrices For Bone Regenerative Applications, Matthew Christopher Phipps Jan 2012

Development Of Electrospun Bone-Mimetic Matrices For Bone Regenerative Applications, Matthew Christopher Phipps

All ETDs from UAB

Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein …

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Antiphagocytic Factors Of Mycoplasma Pulmonis, Brandon Michael Shaw Jan 2012

Antiphagocytic Factors Of Mycoplasma Pulmonis, Brandon Michael Shaw

All ETDs from UAB

Mycoplasma pulmonis is a murine respiratory pathogen and is used as a model for studying chronic mycoplasmal respiratory disease. This organism has been used by many in vivo and in vitro studies to gain a better understanding of host-pathogen interactions in chronic respiratory infection. Studies have shown that alveolar macrophages play an important role in the removal of this pathogen from the host. Given that M. pulmonis is able to produce a chronic disease state, this organism should produce antiphagocytic factors that aid in avoidance of killing by alveolar macrophages. The Vsa proteins are involved in the avoidance of killing …

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Evaluating The Efficacy Of Radiofrequency Amplitude-Modulated Electromagnetic Fields As A Novel Treatment For Hepatocellular Carcinoma, Jacquelyn Winifred Zimmerman Jan 2012

Evaluating The Efficacy Of Radiofrequency Amplitude-Modulated Electromagnetic Fields As A Novel Treatment For Hepatocellular Carcinoma, Jacquelyn Winifred Zimmerman

All ETDs from UAB

Hepatocellular carcinoma (HCC) incidence in the US is dramatically increasing. Five-year survival has remained 3-5% for the past several decades, demonstrating urgent need for additional therapies. Intrabuccal administration of amplitude-modulated radiofrequency electromagnetic fields (RF EMF) is a novel, minimally invasive treatment modality. Clinical evidence demonstrates this treatment approach elicits therapeutic responses in cancer patients. In vitro we have described a phenotype in HCC cells following RF EMF exposure that included proliferative inhibition, modulation of gene expression, and disruption of the mitotic spindle. This phenotype was specific for HCC cells exposed to HCC-specific RF EMF. We have demonstrated similar efficacy in …

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