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Characterization Of A Gene Encoding Two Isoforms Of A Mitochondrial Protein Upregulated By Cyclosporin A In Activated T Cells, Laurent Mascarell, Rodolphe Auger, Andres Alcover, David M. Ojcius, Thomas Jungas, Veronique Cadet-Daniel, Jean M. Kanellopoulos, Paolo Truffa-Bacchi

All Dugoni School of Dentistry Faculty Articles

Cyclosporin A (CSA) is an immunosuppressor used in organ transplantation. A recent proteomic analysis has revealed that activation of T cells in the presence of CSA induces the synthesis of hundreds of new proteins. Here we used representational difference analysis to characterize some of the corresponding induced genes. After cDNA bank screening we focused on one of these genes, which we named CSA-conditional, T cell activation-dependent (CSTAD) gene. This gene produces two mRNAs resulting from alternative splicing events. They encode two proteins of 104 and 141 amino acids, CSTADp-S and CSTADp-L, for the short and long forms, respectively. FK506 had …

Human Acyl-Coenzyme A:Cholesterol Acyltransferase Expressed In Chinese Hamster Ovary Cells: Membrane Topology And Active Site Location, Song Lin, Xiaohui Lu, Catherine C.Y. Chang, Ta-Yuan Chang

Dartmouth Scholarship

Acyl-CoA:cholesterol acyltransferase (ACAT) is a membrane-bound enzyme that produces cholesteryl esters intracellularly. Two ACAT genes (ACAT1 and ACAT2) have been identified. The expression of ACAT1 is ubiquitous, whereas that of ACAT2 is tissue restricted. Previous research indicates that ACAT1 may contain seven transmembrane domains (TMDs). To study ACAT2 topology, we inserted two different antigenic tags (hemagglutinin, monoclonal antibody Mab1) at various hydrophilic regions flanking each of its predicted TMDs, and expressed the recombinant proteins in mutant Chinese hamster ovary cells lacking endogenous ACAT. Each tagged ACAT2 was expressed in the endoplasmic reticulum as a single undegraded protein band …

Promoters Of The Murine Embryonic Β-Like Globin Genes Ey And Βh1 Do Not Compete For Interaction With The Β-Globin Locus Control Region, Xiao Hu, Michael Bulger, Julia N. Roach, Susan K. Eszterhas, Emmanuel Olivier, Eric Bouhassira, Mark Groudine, Steven Fiering

Dartmouth Scholarship

Mammalian β-globin loci contain multiple β-like genes that are expressed at different times during development. The murine β-globin locus contains two genes expressed during the embryo stage, Ey and βh1, and two genes expressed at both the fetal and postnatal stages, β-major and β-minor. Studies of transgenic human β-like globin loci in mice have suggested that expression of one gene at the locus will suppress expression of other genes at the locus. To test this hypothesis we produced mouse lines with deletions of either the Ey or βh1 promoter in the endogenous murine β-globin locus. Promoter deletion eliminated expression of …

Hierarchy Of Protein Assembly At The Vertex Ring Domain For Yeast Vacuole Docking And Fusion, Li Wang, Alexey J. Merz, Kevin M. Collins, William Wickner

Dartmouth Scholarship

Vacuole tethering, docking, and fusion proteins assemble into a “vertex ring” around the apposed membranes of tethered vacuoles before catalyzing fusion. Inhibitors of the fusion reaction selectively interrupt protein assembly into the vertex ring, establishing a causal assembly hierarchy: (a) The Rab GTPase Ypt7p mediates vacuole tethering and forms the initial vertex ring, independent of t-SNAREs or actin; (b) F-actin disassembly and GTP-bound Ypt7p direct the localization of other fusion factors; (c) The t-SNAREs Vam3p and Vam7p regulate each other’s vertex enrichment, but do not affect Ypt7p localization. The v-SNARE Vti1p is enriched at vertices by a distinct pathway that …

Detection Of Forces And Body Load In Standing And Walking In The American Cockroach, J. Adam Noah

Theses, Dissertations and Capstones

Sense organs in the legs that detect body weight are an important component in the regulation of posture and locomotion. This thesis seeks to gain an understanding of how body weight is detected by sense organs of the legs, and determine how this information influences muscle activities in standing and walking. The first study tested the ability of tibial campaniform sensilla (receptors that monitor forces in the cockroach leg) to encode variations in body load using magnets attached to the thorax. Recordings of sensory activities in freely standing animals showed that proximal tibial sensilla (oriented perpendicular to the leg long …

The Ca2+ Dynamics Of Isolated Mouse Β-Cells And Islets: Implications For Mathematical Models, Min Zhang, Paula Goforth, Richard Bertram, Arthur Sherman, Leslie S. Satin

Pharmacology and Toxicology Publications

ABSTRACT

[Ca²⁺]_i and electrical activity were compared in isolated β-cells and islets using standard techniques. In islets, raising glucose caused a decrease in [Ca²⁺]_i followed by a plateau and then fast (2–3 min⁻¹), slow (0.2–0.8 min⁻¹), or a mixture of fast and slow [Ca²⁺]_i oscillations. In β-cells, glucose transiently decreased and then increased [Ca²⁺]_i, but no islet-like oscillations occurred. Simultaneous recordings of [Ca²⁺]_i and electrical activity suggested that differences in [Ca²⁺]_i signaling are due to …

Analysis Of Gene × Environment Interactions In Sibships Using Mixed Models, Jill S. Barnholtz-Sloan, Laila M. Poisson, Steven W. Coon, Gary A. Chase, Benjamin A. Rybicki

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Gene × environment models are widely used to assess genetic and environmental risks and their association with a phenotype of interest for many complex diseases. Mixed generalized linear models were used to assess gene × environment interactions with respect to systolic blood pressure on sibships adjusting for repeated measures and hierarchical nesting structures. A data set containing 410 sibships from the Framingham Heart Study offspring cohort (part of the Genetic Analysis Workshop 13 data) was used for all analyses. Three mixed gene × environment models, all adjusting for repeated measurement and varying levels of nesting, were compared for …

The Role Of Ap-1 Transcription Complex In Retinoic Acid-Dependent B16 Melanoma Cell Growth Arrest And Differentiation, Ying Huang

Theses, Dissertations and Capstones

Our laboratory has been studying the effects of all-trans retinoic acid (atRA) on the growth and differentiation of the B16 mouse melanoma cells. RA inhibits both anchorage-dependent and –independent growth and stimulates melanin production in B16 cells, which are accompanied by an increase in AP-1 activity. To further investigate the RA-induced AP-1 activity, I established clones of B16 stably expressing an AP-1-luciferase reporter gene. Treatment of these clones with phorbol dibutyrate (PDB), a known activator of AP-1, rapidly increased AP-1 activity which reached its maximum level at 2-4 h and returned to baseline level by 24 h. In contrast, RA …

Structural Analyses Of Phycodnaviridae And Iridoviridae, Alan A. Simpson, Narayanasamy Nandhagopal, James L. Van Etten, Michael G. Rossmann

Nebraska Center for Virology: Faculty Publications

The Phycodnaviridae, Iridoviridae and related viruses, with diameters of 1500±2000 A Ê , are formed from large trigonal arrays of hexagonally close-packed capsomers forming the faces of icosahedra [Yan et al. (2000), Nature Struct. Biol. 7, 101-103; Nandhagopal et al. (2002), Proc. Natl Acad. Sci. USA, 99, 14758-14763]. Caspar and Klug predicted that such structures could be assembled from hexameric capsomers [Caspar & Klug (1962), Cold Spring Harbor. Symp. Quant. Biol. 27, 1-24], as was subsequently found in numerous icosahedral viruses. During the course of evolution, some viruses, including the virus families …

Nucleotide Excision Repair- And Polymerase Eta-Mediated Error-Prone Removal Of Mitomycin C Interstrand Cross-Links, H. Zheng, X. Wang, A. J. Warren, R. J. Legerski, Rodney S. Nairn, Joshua W. Hamilton, Lei Li

Dartmouth Scholarship

Interstrand cross-links (ICLs) make up a unique class of DNA lesions in which both strands of the double helix are covalently joined, precluding strand opening during replication and transcription. The repair of DNA ICLs has become a focus of study since ICLs are recognized as the main cytotoxic lesion inflicted by an array of alkylating compounds used in cancer treatment. As is the case for double-strand breaks, a damage-free homologous copy is essential for the removal of ICLs in an error-free manner. However, recombination-independent mechanisms may exist to remove ICLs in an error-prone fashion. We have developed an in vivo …

Par Mediation Of Thrombin-Induced Effects On Motoneurons, Nadim Salman, Drew Watkins, Kate Hamel, Lakisha Gadsden, Sarah Funderburk, Victoria Turgeon

Journal of the South Carolina Academy of Science

No abstract provided.

Development Of An Automated Thiopurine Methyltransferase (Tpmt) Genotyping Assay, Mary Corcoran

Theses

Thiopurine methyltransferase (TPMT) is a cytosolic enzyme that catalyses the S- methylation of aromatic and sulphydryl compounds known as the thiopurines. These therapeutic agents are used in the treatment of acute lymphoblastic leukemia, autoimmune disorders, inflammatory bowel disease and organ transplant recipients.

Erythrocyte TPMT activity is polymorphic and patients with intermediate or deficient TPMT are at significant risk for excessive toxicity after receiving ‘standard’ doses of thiopurine medications. The activity of TPMT is inherited as an autosomal co-dominant trait. Several mutations in the TPMT gene have been described that correlate with a low activity phenotype. Three mutations G238C, G460A and …

Animal Anti-Apoptotic Genes Ameliorate The Loss Of Turgor In Water-Stressed Transgenic Tobacco, Tala Awada, D. D. Dunigan, M. B. Dickman

Nebraska Center for Virology: Faculty Publications

Nicotiana tabacum L. ‘Glurk’ plants were transformed with antiapoptotic animal genes [chicken Bcl-xl; nematode CED-9; chicken Bcl-xl(GA) a mutant of Bcl-xl; and a 3’ non-coding region of human Bcl-2, referred to as 161-1]. Our objectives were to determine whether plant transformation with anti-apoptotic genes ameliorates drought tolerance in tobacco plants by subjecting the plants to a dry-down period. The non-transformed Glurk and the transgenic Glurk harboring G115, which expresses β-glucuronidase, served as controls. Transformation of tobacco plants with animal anti-apoptotic genes significantly impacted the rates of photosynthesis (A) and stomatal conductance (g_s), but not to the same extent …

Method To Detect The Presence Of A Microorganism Or Agent In An Animal, David R. Smith, Laura L. Hungerford, Rodney A. Moxley, Susanne Hinkley, Terry Klopfenstein, Jeff Gray

School of Veterinary and Biomedical Sciences: Faculty Publications

The present invention provides a method to detect the presence of a microorganism or agent in an animal. The method encompasses placement of devices at various locations where the animal resides so as to induce the animal to initiate contact with the device. As a result of this contact, the animal deposits various microorganisms and agents on the device. The device is then tested for the presence of the particular microorganism or agent of interest.

Saru, A Sara Homolog, Is Repressed By Sart And Regulates Virulence Genes In Staphylococcus Aureus, Adhar C. Manna, Ambrose L. Cheung

Dartmouth Scholarship

In searching the Staphylococcus aureus genome, we previously identified sarT, a homolog of sarA, which encodes a repressor for alpha-hemolysin synthesis. Adjacent but transcribed divergently to sarT is sarU, which encodes a 247-residue polypeptide, almost twice the length of SarA. Sequence alignment disclosed that SarU, like SarS, which is another SarA homolog, could be envisioned as a molecule with two halves, with each half being homologous to SarA. SarU, as a member of the SarA family proteins, disclosed conservation of basic residues within the helix-turn-helix motif and within the beta hairpin loop, two putative DNA binding domains within this protein …

Faculty Publications 2002, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 876 publications.

Myosin Heavy Chain And Physiological Adaptation Of The Rat Diaphragm In Elastase-Induced Emphysema., Dong Kwan Kim, Jianliang Zhu, Benjamin W Kozyak, James M Burkman, Neal A Rubinstein, Edward B Lankford, Hansell H Stedman, Taitan Nguyen, Sanford Levine, Joseph B Shrager

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. METHODS: We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform …

Good Life In The Balance: A Cross-National Study Of Dutch And Australian Disability Perspectives On Euthanasia And Physician-Assisted Suicide, Erik A. Leipoldt

Theses: Doctorates and Masters

This is a cross-national qualitative study with the purpose of obtaining perspectives held by people with quadriplegia and leading figures in disability movements in the Netherlands and Australia on the issues of euthanasia and physician-assisted suicide (EPAS). A disability voice is not prominent in public debate on EPAS in Australia or the Netherlands, even though people with disabilities are often thought to be vulnerable in relation to EPAS policies. Disability perspectives are potentially valuable in illuminating issues in relation to euthanasia and physician-assisted suicide, because issues of dependence, independence, and individual autonomy play important roles in relation to both EPAS …

Dose-Response Effects Of Lithium On Spatial Memory In The Black Molly Fish., Thomas Kyle Creson

Electronic Theses and Dissertations

Lithium continues to be widely prescribed for the management of bipolar disease, yet cognitive impairment-related side effects promote noncompliance of the treatment regimen. We have introduced a novel animal model, the black molly fish, to study dose-response effects of lithium on short-term (STM) and long-term (LTM) memories. We developed a method utilizing capillary ion analysis (CIA), to measure plasma and brain lithium levels employed in our behavioral studies. We then developed an appropriate testing environment to ascertain learning capacities of these fish. We established that black mollies could adequately perform a forced-choice spontaneous alternation (SA) task used extensively in rodents …

Review Of "The Human Embryonic Stem Cell Debate: Science, Ethics, And Public Policy (Basic Bioethics)," Edited By Suzanne Holland, Karen Lebacqz, And Laurie Zoloth, James Steele

The University of New Hampshire Law Review

[Excerpt] "Perhaps like others, I started "The Human Embryonic Stem Cell Debate" not knowing many of the finer points of embryonic stem cell research, but I certainly had an opinion. This issue is far more complex than I had initially imagined. The editors do a commendable effort of compiling a sample of the innumerable arguments surrounding the debate."

Executive Functions In Preschool Children Born Preterm: Application Of Cognitive Neuroscience Paradigms, K. A. Espy, M. M. Stalets, M. D. Mcdiarmid, T. E. Senn, M. F. Cwik, A. Hamby

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Although children born preterm are at risk for neuropsychological impairments at school age and adolescence, including difficulties with visual motor integration, spatial/constructional skills, attention, arithmetic, and nonverbal executive functions, specific neuropsychological outcome has not been investigated adequately in preschoolers. Application of cognitive neuroscience tasks offers the opportunity to characterize early executive functions in young children born preterm. In a preliminary sample of 29 preschool children born preterm (M birth gestational age=32.4 weeks), executive function outcome was compared to that of fullterm controls by contrasting performance on two prototypic delayed-response-type paradigms, Delayed Alternation and Spatial Reversal. Preschoolers born preterm correctly retrieved …

Topical Micronutrient Delivery System And Uses Of Thereof, Elaine L. Jacobson, Myron Jacobson, Jaber G. Qasem, Hyuntae Kim, Moonsun Kim

Graduate Center for Nutritional Sciences Faculty Patents

The invention involves methods and compositions useful in delivering micronutrients to cells. By formulating the micronutrient in the form of an ester that is convertible to the active form of the micronutrient, one can combine it with a co-ester that inhibits esterases, so that the micronutrient can reach the targeted cells prior to degradation. Both methods and compositions are described.

The Influence Of Warning Label Presentation In Memory Recognition Of Aging Adults, Brian J. Call

Master's Theses - Daytona Beach

Research indicates that hundreds of thousands of people are injured each year as a result of poor communication between medical personnel, warning label information, and consumers when taking over the counter or prescription medication. Typically, as adults age, they are increasingly responsible for remembering the hazards of taking medications. If inadequate information exists in memory in regards to side effects, dosage, and other warnings, the likelihood of improper usage will increase. Because aging adults typically have a reduction in cognitive resources, it was hypothesized that older adults would require the aid of additional warning information to assist in the retrieval …

Current Issues In Forensic Dna Profiling, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Defective Cd19-Dependent Signaling In B-1a And B-1b B Lymphocyte Subpopulations., Goutam Sen, Hsin-Jung Wu, Gabriel Bikah, Chandrasekar Venkataraman, Darrell A Robertson, E Charles Snow, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Peritoneal and pleural cavities in mice and humans contain a unique population of B-lymphocytes called B-1 cells that are defective in B cell antigen receptor (BCR) signaling but have an increased propensity to produce autoantibodies. Several molecules such as Btk, Vav, and CD19 known to be important for BCR signaling have been shown to be critical for the development of B-1 cells from undefined precursors. Here we demonstrate that B-1 cell unresponsiveness to BCR cross-linking is in part due to defective signaling through CD19, a molecule known to modulate signaling thresholds in B cells. The defective CD19 signaling is manifested …

High-Resolution Physical Map For Chromosome 16q12.1-Q13, The Blau Syndrome Locus., Xiaoju Wang, Helena Kuivaniemi, Gina Bonavita, Charlene J Williams, Gerard Tromp

Department of Medicine Faculty Papers

BACKGROUND: The Blau syndrome (MIM 186580), an autosomal dominant granulomatous disease, was previously mapped to chromosome 16p12-q21. However, inconsistent physical maps of the region and consequently an unknown order of microsatellite markers, hampered us from further refining the genetic locus for the Blau syndrome. To address this problem, we constructed our own high-resolution physical map for the Blau susceptibility region. RESULTS: We generated a high-resolution physical map that provides more than 90% coverage of a refined Blau susceptibility region. The map consists of four contigs of sequence tagged site-based bacterial artificial chromosomes with a total of 124 bacterial artificial chromosomes, …

Hiv Tat Protein Activates Endothelial Cells Through Nfκb And Map Kinase Pathways., Jason L. Henry

Electronic Theses and Dissertations

HIV infection has been shown to predispose patients to accelerated development of heart disease. One mechanism for this pathology may involve endothelial activation either by HIV itself or by its secreted proteins, gp120 (a viral envelope protein) and tat (a protein that upregulates transcription of viral genes). We have studied the effects of gp120 and tat on signaling and production of inflammatory cytokines by Human Pulmonary Artery Endothelial Cells (HPAEC). HPAEC were stimulated at varying time points with combinations of gp120, tat, and monokines (IL-1β and TNFα). Cell lysate fractions were analyzed for MAP Kinase activity and NFκB activation, and …

Glutathione Levels And Bax Activation During Apoptosis Due To Oxidative Stress In Cells Expressing Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator, Thomas Jungas, Iris Motta, Francis Duffieux, Pascale Fanen, Veronique Stoven, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Cystic fibrosis is characterized by chronic inflammation and an imbalance in the concentrations of alveolar and lung oxidants and antioxidants, which result in cell damage. Modifications in lung glutathione concentrations are recognized as a salient feature of inflammatory lung diseases such as cystic fibrosis, and glutathione plays a major role in protection against oxidative stress and is important in modulation of apoptosis. The cystic fibrosis transmembrane conductance regulator (CFTR) is permeable to Cl−, larger organic ions, and reduced and oxidized forms of glutathione, and the ΔF508 CFTR mutation found in cystic fibrosis patients has been correlated with impaired glutathione transport …

Distinct Properties Of Crac And Mic Channels In Rbl Cells, J. Ashot Kozak, Hubert H. Kerschbaum, Michael D. Cahalan

Neuroscience, Cell Biology & Physiology Faculty Publications

In rat basophilic leukemia (RBL) cells and Jurkat T cells, Ca²⁺ release–activated Ca²⁺ (CRAC) channels open in response to passive Ca²⁺ store depletion. Inwardly rectifying CRAC channels admit monovalent cations when external divalent ions are removed. Removal of internal Mg²⁺ exposes an outwardly rectifying current (Mg²⁺-inhibited cation [MIC]) that also admits monovalent cations when external divalent ions are removed. Here we demonstrate that CRAC and MIC currents are separable by ion selectivity and rectification properties: by kinetics of activation and susceptibility to run-down and by pharmacological sensitivity to external Mg²⁺, spermine, and …

Estimating Population Numbers Of Black Bears (Ursus Americanus) In Eastern Kentucky Using Microsatellite Analysis, Kelly Vowels

Masters Theses & Specialist Projects

Black bears (Ursus americanus) occur sporadically in eastern Kentucky, and there is some evidence that a breeding population exists. In order to establish management practices to enhance the black bear population in Kentucky, information about this population is needed. However, until recently, no population size estimate has been available. Gathering information on black bears is difficult because black bears are elusive animals. The development of new molecular methods has made it easier to track and gather information on black bear populations, including estimates of population size. Molecular markers are particularly useful in that they do not require physical contact with …