The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Michael J Holtzman - One of the best experts on this subject based on the ideXlab platform.
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selective interaction of a subset of interferon gamma response element binding proteins with the intercellular adhesion molecule 1 icam 1 gene promoter controls the pattern of expression on epithelial cells
Journal of Biological Chemistry, 1994Co-Authors: Dwight C Look, Mark R Pelletier, Michael J HoltzmanAbstract:Abstract Intercellular adhesion molecule-1 (ICAM-1) modulates epithelial and endothelial leukocyte adherence, but epithelial cell ICAM-1 levels (unlike endothelial cell levels) are selectively sensitive to interferon-gamma (IFN-gamma). Nuclear run-off assays indicated that IFN-gamma regulation of epithelial ICAM-1 levels occurs at a transcriptional level, so the basis for selective cytokine control of ICAM-1 expression was investigated using the ICAM-1 gene promoter region. A plasmid construct containing 5.0 kilobases of ICAM-1 gene 5'-flanking region fused to a reporter gene was selectively responsive to IFN-gamma in (human tracheal) epithelial cells but not in (human umbilical vein) endothelial cells, indicating that this region is sufficient to mediate proper cell-specific expression. An IFN-gamma response element (IRE) was localized to a DNA segment (nucleotides -130 to -94) in the ICAM-1 gene by comparisons of nested 5'-deletional constructs and by demonstrating that this segment confers IFN-gamma responsiveness on heterologous promoters. This same IRE formed a single major binding complex (IRE-BC) in gel retardation assays with nuclear proteins from IFN-gamma-stimulated but not unstimulated epithelial cells, and mutation of the IRE consensus motif (TTTCCGGGAAA at -116 to -106) resulted in loss of IRE-protein binding and abolished IFN-gamma responsiveness, indicating that this sequence is required for ICAM-1 IRE function. Comparison of the ICAM-1 IRE to DNA elements that confer IFN responsiveness in other human genes indicated similarity only to response regions in the Fc gamma RI and IRF-1 genes. The findings provide evidence for a distinct IRE subset that combines a DNA element common to all IFN-responsive genes (GAAA) with a distinct flanking sequence (the inverted repeat GAAA) in order to fine-tune IFN responses and activate a subset of immune response genes (ICAM-1, Fc gamma RI, and IRF-1).
Avril V. Somlyo - One of the best experts on this subject based on the ideXlab platform.
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g protein mediated inhibition of myosin light chain phosphatase in vascular smooth muscle
Proceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: Toshio Kitazawa, Masatoshi Masuo, Avril V. SomlyoAbstract:Abstract The mechanism of G protein-mediated sensitization of the contractile apparatus of smooth muscle to Ca2+ was studied in receptor-coupled alpha-toxin-permeabilized rabbit portal vein smooth muscle. To test the hypothesis that Ca2+ sensitization is due to inhibition of myosin light-chain (MLC) phosphatase activity, we measured the effect of guanosine 5'-[gamma-thio]triphosphate and phenylephrine on the rate of MLC dephosphorylation in muscles preactivated with Ca2+ and incubated in Ca(2+)- and ATP-free solution containing 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9) to block MLC kinase activity. Guanosine 5'-[gamma-thio]triphosphate alone (300 microM) or in combination (3 microM) with phenylephrine decreased the rates of relaxation and dephosphorylation of MLC to about half of control values; this inhibition is sufficient to account for maximal G protein-mediated Ca2+ sensitization of MLC phosphorylation. The rate of thiophosphorylation of MLC with adenosine 5'-[gamma-thio]-triphosphate was not affected by guanosine 5'-[gamma-thio]triphosphate. We suggest that inhibition of protein phosphatase(s) by G protein(s) may have important regulatory functions.
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g protein mediated ca2 sensitization of smooth muscle contraction through myosin light chain phosphorylation
Journal of Biological Chemistry, 1991Co-Authors: Toshio Kitazawa, Bruce D Gaylinn, Gerald H Denney, Avril V. SomlyoAbstract:Abstract The Ca2+ sensitivities of tonic (pulmonary and femoral artery) and phasic (portal vein and ileum) smooth muscles and the effects of guanosine 5'-O-(gamma-thiotriphosphate) (GTP gamma S) and norepinephrine on Ca2+ sensitivity of force development and myosin light chain (MLC20) phosphorylation were determined in permeabilized preparations that retained coupled receptors and endogenous calmodulin. The Ca2+ sensitivity of force was higher (approximately 3-fold) in the tonic than in the phasic smooth muscles. The nucleotide specificity of Ca2+ sensitization was: GTP gamma S much greater than GTP greater than ITP much greater than CTP = UTP. Baseline phosphorylation (7% at pCa greater than 8) and maximal phosphorylation (58% at pCa 5.0) were both lower in portal vein than in femoral artery (20 and 97%). Norepinephrine and GTP gamma S increased phosphorylation at constant [Ca2+] (pCa 7.0-6.5). MLC20 phosphorylation induced by norepinephrine was completely inhibited by guanosine 5'-O-(beta-thiodiphosphate) (GDP beta S). In portal vein at pCa 5, GTP gamma S increased phosphorylation from 58%, the maximal Ca2(+)-activated value, to 75%, and at pCa greater than 8, from 7 to 13%. In femoral artery at pCa 5, neither phosphorylation (97%) nor force was affected by GTP gamma S, while at pCa greater than 8, GTP gamma S caused an increase in force (16% of maximum) with a borderline increase in MLC20 phosphorylation (from 20 to 27%). MLC20 phosphorylation (up to 100%) was positively correlated with force. The major results support the hypothesis that the G-protein coupled Ca2(+)-sensitizing effect of agonists on force development is secondary to increased MLC20 phosphorylation.
Peter C Weber - One of the best experts on this subject based on the ideXlab platform.
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docosahexaenoic acid selectively attenuates induction of vascular cell adhesion molecule 1 and subsequent monocytic cell adhesion to human endothelial cells stimulated by tumor necrosis factor α
Arteriosclerosis Thrombosis and Vascular Biology, 1995Co-Authors: Christian Weber, Wolfgang Erl, Angelika Pietsch, Ulrich Danesch, Peter C WeberAbstract:Abstract Incorporation of the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) but not eicosapentaenoic acid or n-6 arachidonic acid into human umbilical vein endothelial cell (HUVEC) phospholipids dose-dependently reduced tumor necrosis factor–α (TNF-α)–induced surface expression of vascular cell adhesion molecule–1 (VCAM-1). In parallel, DHA inhibited TNF-α–stimulated monocytic U937 cell adhesion to HUVECs but did not affect TNF-α– or interferon gamma–induced expression of intercellular adhesion molecule–1 and endothelial leukocyte adhesion molecule–1 or VCAM-1 induction by interleukin-1β. DHA appeared to attenuate VCAM-1 transcription, as it reduced induction of VCAM-1 mRNA by TNF-α. VCAM-1 induction is regulated by activation of nuclear factor–kB, which can be mediated by a TNF-α–responsive phosphatidylcholine-specific phospholipase C (PC-PLC). Gel-shift analysis showed inhibition of TNF-α–induced nuclear factor–kB mobilization by DHA. While the PC-PLC inhibitor D609 dose-dependently prevente...
Christoph Hilgers - One of the best experts on this subject based on the ideXlab platform.
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ORIGINAL PAPER Solution-precipitation creep and fluid flow in halite: a case study of Zechstein (Z1) rocksalt from Neuhof salt mine (Germany)
2016Co-Authors: Christoph HilgersAbstract:Abstract Zechstein (Z1) rocksalt from the Fulda basin, from the immediate vicinity of the Hessen potash bed is folded into tight to isoclinal folds which are cut by an undeformed, 1 cm thick, coarse-grained halite vein. Microstructures were investigated in etched, gamma-irra-diated thin sections from both the wall rock and the vein. The lack of synsedimentary dissolution structures and the widespread occurrence of plate-shaped and hopper grains in the wall-rock suggests that the sedimentary environment was perennial lake. Deformation microstructures are in good agreement with solution-precipitation creep process, and salt flow under very low differential stress. Strength contrast between anhydrite-rich and anhydrite-poor layers caused the small scale folding in the halite beds. The vein is completely sealed and composed mainly of euhedral to subhedral halite grains, which often overgrow the wall-rock grains. Those microstructures, together with the presence of occasional fluid inclusion bands, suggest that the crystals grew into a solution-filled open space. Based on consider-ations on the maximum value of in-situ differential stress, the dilatancy criteria, the amount of released fluids from the potash bed during metamorphism and the volume change, it is proposed that the crack was generated by hydrofracturing of the rocksalt due to the presence of the salt-metamorphic fluid at near-lithostatic pressure
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solution precipitation creep and fluid flow in halite a case study of zechstein z1 rocksalt from neuhof salt mine germany
International Journal of Earth Sciences, 2008Co-Authors: Zsolt Schleder, Janos Urai, Sofie Nollet, Christoph HilgersAbstract:Zechstein (Z1) rocksalt from the Fulda basin, from the immediate vicinity of the Hessen potash bed is folded into tight to isoclinal folds which are cut by an undeformed, 1 cm thick, coarse-grained halite vein. Microstructures were investigated in etched, gamma-irradiated thin sections from both the wall rock and the vein. The lack of synsedimentary dissolution structures and the widespread occurrence of plate-shaped and hopper grains in the wall-rock suggests that the sedimentary environment was perennial lake. Deformation microstructures are in good agreement with solution-precipitation creep process, and salt flow under very low differential stress. Strength contrast between anhydrite-rich and anhydrite-poor layers caused the small scale folding in the halite beds. The vein is completely sealed and composed mainly of euhedral to subhedral halite grains, which often overgrow the wall-rock grains. Those microstructures, together with the presence of occasional fluid inclusion bands, suggest that the crystals grew into a solution-filled open space. Based on considerations on the maximum value of in-situ differential stress, the dilatancy criteria, the amount of released fluids from the potash bed during metamorphism and the volume change, it is proposed that the crack was generated by hydrofracturing of the rocksalt due to the presence of the salt-metamorphic fluid at near-lithostatic pressure.
Dwight C Look - One of the best experts on this subject based on the ideXlab platform.
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selective interaction of a subset of interferon gamma response element binding proteins with the intercellular adhesion molecule 1 icam 1 gene promoter controls the pattern of expression on epithelial cells
Journal of Biological Chemistry, 1994Co-Authors: Dwight C Look, Mark R Pelletier, Michael J HoltzmanAbstract:Abstract Intercellular adhesion molecule-1 (ICAM-1) modulates epithelial and endothelial leukocyte adherence, but epithelial cell ICAM-1 levels (unlike endothelial cell levels) are selectively sensitive to interferon-gamma (IFN-gamma). Nuclear run-off assays indicated that IFN-gamma regulation of epithelial ICAM-1 levels occurs at a transcriptional level, so the basis for selective cytokine control of ICAM-1 expression was investigated using the ICAM-1 gene promoter region. A plasmid construct containing 5.0 kilobases of ICAM-1 gene 5'-flanking region fused to a reporter gene was selectively responsive to IFN-gamma in (human tracheal) epithelial cells but not in (human umbilical vein) endothelial cells, indicating that this region is sufficient to mediate proper cell-specific expression. An IFN-gamma response element (IRE) was localized to a DNA segment (nucleotides -130 to -94) in the ICAM-1 gene by comparisons of nested 5'-deletional constructs and by demonstrating that this segment confers IFN-gamma responsiveness on heterologous promoters. This same IRE formed a single major binding complex (IRE-BC) in gel retardation assays with nuclear proteins from IFN-gamma-stimulated but not unstimulated epithelial cells, and mutation of the IRE consensus motif (TTTCCGGGAAA at -116 to -106) resulted in loss of IRE-protein binding and abolished IFN-gamma responsiveness, indicating that this sequence is required for ICAM-1 IRE function. Comparison of the ICAM-1 IRE to DNA elements that confer IFN responsiveness in other human genes indicated similarity only to response regions in the Fc gamma RI and IRF-1 genes. The findings provide evidence for a distinct IRE subset that combines a DNA element common to all IFN-responsive genes (GAAA) with a distinct flanking sequence (the inverted repeat GAAA) in order to fine-tune IFN responses and activate a subset of immune response genes (ICAM-1, Fc gamma RI, and IRF-1).
