378 research outputs found

    Myosin II Light Chain Phosphorylation Regulates Membrane Localization and Apoptotic Signaling of Tumor Necrosis Factor Receptor-1

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    Activation of myosin II by myosin light chain kinase (MLCK) produces the force for many cellular processes including muscle contraction, mitosis, migration, and other cellular shape changes. The results of this study show that inhibition or potentiation of myosin II activation via over-expression of a dominant negative or wild type MLCK can delay or accelerate tumor necrosis factor-α (TNF)-induced apoptotic cell death in cells. Changes in the activation of caspase-8 that parallel changes in regulatory light chain phosphorylation levels reveal that myosin II motor activities regulate TNF receptor-1 (TNFR-1) signaling at an early step in the TNF death signaling pathway. Treatment of cells with either ionomycin or endotoxin (lipopolysaccharide) leads to activation of myosin II and increased translocation of TNFR-1 to the plasma membrane independent of TNF signaling. The results of these studies establish a new role for myosin II motor activity in regulating TNFR-1-mediated apoptosis through the translocation of TNFR-1 to or within the plasma membrane

    Prenatal Exposure to Tetrachloroethylene-Contaminated Drinking Water and the Risk of Congenital Anomalies: A Retrospective Cohort Study

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    BACKGROUND: Prior animal and human studies of prenatal exposure to solvents including tetrachloroethylene (PCE) have shown increases in the risk of certain congenital anomalies among exposed offspring. OBJECTIVES: This retrospective cohort study examined whether PCE contamination of public drinking water supplies in Massachusetts influenced the occurrence of congenital anomalies among children whose mothers were exposed around the time of conception. METHODS: The study included 1,658 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 2,999 children of unexposed mothers. Mothers completed a self-administered questionnaire to gather information on all of their prior births, including the presence of anomalies, residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model. RESULTS: Children whose mothers had high exposure levels around the time of conception had an increased risk of congenital anomalies. The adjusted odds ratio of all anomalies combined among children with prenatal exposure in the uppermost quartile was 1.5 (95% CI: 0.9, 2.5). No meaningful increases in the risk were seen for lower exposure levels. Increases were also observed in the risk of neural tube defects (OR: 3.5, 95% CI: 0.8, 14.0) and oral clefts (OR 3.2, 95% CI: 0.7, 15.0) among offspring with any prenatal exposure. CONCLUSION: The results of this study suggest that the risk of certain congenital anomalies is increased among the offspring of women who were exposed to PCE-contaminated drinking water around the time of conception. Because these results are limited by the small number of children with congenital anomalies that were based on maternal reports, a follow-up investigation should be conducted with a larger number of affected children who are identified by independent records.National Institute of Environmental Health (5 P42 ES007381); National Institutes of Healt

    Differential Gene Expression in Liver, Gill, and Olfactory Rosettes of Coho Salmon (Oncorhynchus kisutch) After Acclimation to Salinity.

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    Most Pacific salmonids undergo smoltification and transition from freshwater to saltwater, making various adjustments in metabolism, catabolism, osmotic, and ion regulation. The molecular mechanisms underlying this transition are largely unknown. In the present study, we acclimated coho salmon (Oncorhynchus kisutch) to four different salinities and assessed gene expression through microarray analysis of gills, liver, and olfactory rosettes. Gills are involved in osmotic regulation, liver plays a role in energetics, and olfactory rosettes are involved in behavior. Between all salinity treatments, liver had the highest number of differentially expressed genes at 1616, gills had 1074, and olfactory rosettes had 924, using a 1.5-fold cutoff and a false discovery rate of 0.5. Higher responsiveness of liver to metabolic changes after salinity acclimation to provide energy for other osmoregulatory tissues such as the gills may explain the differences in number of differentially expressed genes. Differentially expressed genes were tissue- and salinity-dependent. There were no known genes differentially expressed that were common to all salinity treatments and all tissues. Gene ontology term analysis revealed biological processes, molecular functions, and cellular components that were significantly affected by salinity, a majority of which were tissue-dependent. For liver, oxygen binding and transport terms were highlighted. For gills, muscle, and cytoskeleton-related terms predominated and for olfactory rosettes, immune response-related genes were accentuated. Interaction networks were examined in combination with GO terms and determined similarities between tissues for potential osmosensors, signal transduction cascades, and transcription factors

    Gestion de la douleur chronique par les infirmières des Groupes de médecine de famille

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    INTRODUCTION : Des milliers de personnes souffrent actuellement de douleur chronique (DC) pour laquelle la prise en charge s’avère souvent inadéquate. Au Québec, les infirmières qui oeuvrent dans les Groupes de médecine de famille (GMF) jouent un rôle clé dans le suivi des personnes aux prises avec des problèmes de santé chroniques dont la DC. OBJECTIFS : Cette étude a pour objectifs de décrire les activités réalisées par les infirmières œuvrant en GMF en lien avec la gestion de la douleur chez la clientèle souffrant de DC, ainsi que les barrières à ces activités. MÉTHODE : Un dispositif descriptif corrélationnel transversal de type enquête postale a été utilisé. La population accessible à l’étude comprend les infirmières qui figurent sur la liste des membres de l’Ordre des infirmières et infirmiers du Québec travaillant en GMF. L’ensemble des infirmières figurant sur cette liste ayant consenti à être contactées à leur domicile pour des fins de recherche ont été contactées. Un questionnaire postal auto-administré (Pain Management Activities Questionnaire) a été complété par 53 infirmières travaillant en GMF. RÉSULTATS : Les trois activités le plus souvent réalisées par les infirmières sont d’établir une relation thérapeutique avec le client; de discuter avec le médecin de l’efficacité des mesures thérapeutiques et de faire un enseignement personnalisé au client. Les infirmières ont la perception qu’elles rencontrent en moyenne 2,68 personnes par semaine qui souffrent de DC. La méconnaissance des interventions possibles en douleur (71,7%) et la non-disponibilité de l’information sur la gestion de la douleur (52,8%) constituent les principales barrières selon les infirmières sondées. CONCLUSION : Les infirmières au sein des GMF font actuellement peu d’activités en gestion de la DC probablement en raison du manque de reconnaissance de la DC. -- Mots-clés : Douleur chronique ; Soins infirmiers ; Soins primaires

    A fluorescent resonant energy transfer–based biosensor reveals transient and regional myosin light chain kinase activation in lamella and cleavage furrows

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    Approaches with high spatial and temporal resolution are required to understand the regulation of nonmuscle myosin II in vivo. Using fluorescence resonance energy transfer we have produced a novel biosensor allowing simultaneous determination of myosin light chain kinase (MLCK) localization and its [Ca2+]4/calmodulin-binding state in living cells. We observe transient recruitment of diffuse MLCK to stress fibers and its in situ activation before contraction. MLCK is highly active in the lamella of migrating cells, but not at the retracting tail. This unexpected result highlights a potential role for MLCK-mediated myosin contractility in the lamella as a driving force for migration. During cytokinesis, MLCK was enriched at the spindle equator during late metaphase, and was maximally activated just before cleavage furrow constriction. As furrow contraction was completed, active MLCK was redistributed to the poles of the daughter cells. These results show MLCK is a myosin regulator in the lamella and contractile ring, and pinpoints sites where myosin function may be mediated by other kinases

    Evolutionary Status of Dwarf ``Transition'' Galaxies

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    We present deep B, R and Halpha imaging of 3 dwarf galaxies: NGC3377A, NGC4286, and IC3475. Based on previous broadband imaging and HI studies, these mixed-morphology galaxies were proposed by Sandage & Hoffman (1991) to be, respectively, a gas-rich low surface brightness Im dwarf, a nucleated dwarf that has lost most of its gas and is in transition from Im to dS0,N, and the prototypical example of a gas-poor ``huge low surface brightness'' early-type galaxy. From the combination of our broadband and Halpha imaging with the published information on the neutral gas content of these three galaxies, we find that (1) NGC3377A is a dwarf spiral; (2) NGC3377A and NGC4286 have comparable amounts of ongoing star formation, as indicated by their Halpha emission, while IC3475 has no detected HII regions to a very low limit; (3) the global star formation rates are at least a factor of 20 below that of 30 Doradus for NGC3377A and NGC4286; (4) while the amount of star formation is comparable, the distribution of star forming regions is very different between NGC3377A and NGC4286; (5) given their current star formation rates and gas contents, both NGC3377A and NGC4286 can continue to form stars for more than a Hubble time; (6) both NGC3377A and NGC4286 have integrated total B-R colors that are redder than the integrated total B-R color for IC3475, and thus it is unlikely that either galaxy will ever evolve into an IC3475 counterpart; and (7) IC3475 is too blue to be a dE. We thus conclude that we have not identified potential precursors to galaxies such as IC3475, and unless signifcant changes occur in the star formation rates, neither NGC3377A nor NGC4286 will evolve into a dwarf elliptical or dwarf spheroidal within a Hubble time.Comment: 34 pages, 6 jpg figures, 3 postscript figures, and 4 tables, uses AASTeX, ApJ, in pres
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