546 research outputs found

    Platinum-group elements, S, Se and Cu in highly depleted abyssal peridotites from the Mid-Atlantic Ocean Ridge (ODP Hole 1274A): Influence of hydrothermal and magmatic processes

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    Highly depleted harzburgites and dunites were recovered from ODP Hole 1274A, near the intersection between the Mid-Atlantic Ocean Ridge and the 15°20′N Fracture Zone. In addition to high degrees of partial melting, these peridotites underwent multiple episodes of melt-rock reaction and intense serpentinization and seawater alteration close to the seafloor. Low concentrations of Se, Cu and platinum-group elements (PGE) in harzburgites drilled at around 35-85 m below seafloor are consistent with the consumption of mantle sulfides after high degrees (>15-20 %) of partial melting and redistribution of chalcophile and siderophile elements into PGE-rich residual microphases. Higher concentrations of Cu, Se, Ru, Rh and Pd in harzburgites from the uppermost and lowest cores testify to late reaction with a sulfide melt. Dunites were formed by percolation of silica- and sulfur-undersaturated melts into low-Se harzburgites. Platinum-group and chalcophile elements were not mobilized during dunite formation and mostly preserve the signature of precursor harzburgites, except for higher Ru and lower Pt contents caused by precipitation and removal of platinum-group minerals. During serpentinization at low temperature (<250 °C) and reducing conditions, mantle sulfides experienced desulfurization to S-poor sulfides (mainly heazlewoodite) and awaruite. Contrary to Se and Cu, sulfur does not record the magmatic evolution of peridotites but was mostly added in hydrothermal sulfides and sulfate from seawater. Platinum-group elements were unaffected by post-magmatic low-temperature processes, except Pt and Pd that may have been slightly remobilized during oxidative seawater alteration

    Substrate specificity of microbial transglutaminase as revealed by three-dimensional docking simulation and mutagenesis

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    Transglutaminases (TGases) are used in fields such as food and pharmaceuticals. Unlike other TGases, microbial transglutaminase (MTG) activity is Ca2+-independent, broadening its application. Here, a three-dimensional docking model of MTG binding to a peptide substrate, CBZ-Gln-Gly, was simulated. The data reveal CBZ-Gln-Gly to be stretched along the MTG active site cleft with hydrophobic and/or aromatic residues interacting directly with the substrate. Moreover, an oxyanion binding site for TGase activity may be constructed from the amide groups of Cys64 and/or Val65. Alanine mutagenesis verified the simulated binding region and indicated that large molecules can be widely recognized on the MTG cleft

    On the Location of the Gamma-ray Emission in the 2008 Outburst in the BL Lacertae Object AO 0235+164 through Observations across the Electromagnetic Spectrum

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    We present observations of a major outburst at centimeter, millimeter, optical, X-ray, and gamma-ray wavelengths of the BL Lacertae object AO 0235+164. We analyze the timing of multi-waveband variations in the flux and linear polarization, as well as changes in Very Long Baseline Array (VLBA) images at 7mm with 0.15 milliarcsecond resolution. The association of the events at different wavebands is confirmed at high statistical significance by probability arguments and Monte-Carlo simulations. A series of sharp peaks in optical linear polarization, as well as a pronounced maximum in the 7 mm polarization of a superluminal jet knot, indicate rapid fluctuations in the degree of ordering of the magnetic field. These results lead us to conclude that the outburst occurred in the jet both in the quasi-stationary "core" and in the superluminal knot, both parsecs downstream of the supermassive black hole. We interpret the outburst as a consequence of the propagation of a disturbance, elongated along the line of sight by light-travel time delays, that passes through a standing recollimation shock in the core and propagates down the jet to create the superluminal knot. The multi-wavelength light curves vary together on long time-scales (months/years), but the correspondence is poorer on shorter time-scales. This, as well as the variability of the polarization and the dual location of the outburst, agrees with the expectations of a multi-zone emission model in which turbulence plays a major role in modulating the synchrotron and inverse Compton fluxes.Comment: Accepted for Publication in the Astrophysical Journal Letters. 7 pages (including 5 figures). Minor corrections with regard to previous version, as proposed by the refere

    Stimuli-Responsive Membrane Anchor Peptide Nanofoils for Tunable Membrane Association and Lipid Bilayer Fusion

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    Self-assembled peptide nanostructures with stimuli-responsive features are promising as functional materials. Despite extensive research efforts, water-soluble supramolecular constructs that can interact with lipid membranes in a controllable way are still challenging to achieve. Here, we have employed a short membrane anchor protein motif (GLFD) and coupled it to a spiropyran photoswitch. Under physiological conditions, these conjugates assemble into ∼3.5 nm thick, foil-like peptide bilayer morphologies. Photoisomerization from the closed spiro (SP) form to the open merocyanine (MC) form of the photoswitch triggers rearrangements within the foils. This results in substantial changes in their membrane-binding properties, which also varies sensitively to lipid composition, ranging from reversible nanofoil reformation to stepwise membrane adsorption. The formed peptide layers in the assembly are also able to attach to various liposomes with different surface charges, enabling the fusion of their lipid bilayers. Here, SP-to-MC conversion can be used both to trigger and to modulate the liposome fusion efficiency

    Irs2 Silencing Increases Apoptosis And Potentiates The Effects Of Ruxolitinib In Jak2v617f-positive Myeloproliferative Neoplasms.

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    The recurrent V617F mutation in JAK2 (JAK2V617F) has emerged as the primary contributor to the pathogenesis of myeloproliferative neoplasms (MPN). However, the lack of complete response in most patients treated with the JAK1/2 inhibitor, ruxolitinib, indicates the need for identifying pathways that cooperate with JAK2. Activated JAK2 was found to be associated with the insulin receptor substrate 2 (IRS2) in non-hematological cells. We identified JAK2/IRS2 binding in JAK2V617F HEL cells, but not in the JAK2WT U937 cell line. In HEL cells, IRS2 silencing decreased STAT5 phosphorylation, reduced cell viability and increased apoptosis; these effects were enhanced when IRS2 silencing was combined with ruxolitinib. In U937 cells, IRS2 silencing neither reduced cell viability nor induced apoptosis. IRS1/2 pharmacological inhibition in primary MPN samples reduced cell viability in JAK2V617F-positive but not JAK2WT specimens; combination with ruxolitinib had additive effects. IRS2 expression was significantly higher in CD34+ cells from essential thrombocythemia patients compared to healthy donors, and in JAK2V617F MPN patients when compared to JAK2WT. Our data indicate that IRS2 is a binding partner of JAK2V617F in MPN. IRS2 contributes to increased cell viability and reduced apoptosis in JAK2-mutated cells. Combined pharmacological inhibition of IRS2 and JAK2 may have a potential clinical application in MPN.

    Protein Crosslinking by Transglutaminase Controls Cuticle Morphogenesis in Drosophila

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    Transglutaminase (TG) plays important and diverse roles in mammals, such as blood coagulation and formation of the skin barrier, by catalyzing protein crosslinking. In invertebrates, TG is known to be involved in immobilization of invading pathogens at sites of injury. Here we demonstrate that Drosophila TG is an important enzyme for cuticle morphogenesis. Although TG activity was undetectable before the second instar larval stage, it dramatically increased in the third instar larval stage. RNA interference (RNAi) of the TG gene caused a pupal semi-lethal phenotype and abnormal morphology. Furthermore, TG-RNAi flies showed a significantly shorter life span than their counterparts, and approximately 90% of flies died within 30 days after eclosion. Stage-specific TG-RNAi before the third instar larval stage resulted in cuticle abnormality, but the TG-RNAi after the late pupal stage did not, indicating that TG plays a key role at or before the early pupal stage. Immediately following eclosion, acid-extractable protein from wild-type wings was nearly all converted to non-extractable protein due to wing maturation, whereas several proteins remained acid-extractable in the mature wings of TG-RNAi flies. We identified four proteins—two cuticular chitin-binding proteins, larval serum protein 2, and a putative C-type lectin—as TG substrates. RNAi of their corresponding genes caused a lethal phenotype or cuticle abnormality. Our results indicate that TG-dependent protein crosslinking in Drosophila plays a key role in cuticle morphogenesis and sclerotization

    Cytosolic Guanine Nucledotide Binding Deficient Form of Transglutaminase 2 (R580a) Potentiates Cell Death in Oxygen Glucose Deprivation

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    Transglutaminase 2 (TG2) is a hypoxia-responsive protein that is a calcium-activated transamidating enzyme, a GTPase and a scaffolding/linker protein. Upon activation TG2 undergoes a large conformational change, which likely affects not only its enzymatic activities but its non-catalytic functions as well. The focus of this study was on the role of transamidating activity, conformation and localization of TG2 in ischemic cell death. Cells expressing a GTP binding deficient form of TG2 (TG2-R580A) with high basal transamidation activity and a more extended conformation showed significantly increased cell death in response to oxygen-glucose deprivation; however, targeting TG2-R580A to the nucleus abrogated its detrimental role in oxygen-glucose deprivation. Treatment of cells expressing wild type TG2, TG2-C277S (a transamidating inactive mutant) and TG2-R580A with Cp4d, a reversible TG2 inhibitor, did not affect cell death in response to oxygen-glucose deprivation. These findings indicate that the pro-cell death effects of TG2 are dependent on its localization to the cytosol and independent of its transamidation activity. Further, the conformational state of TG2 is likely an important determinant in cell survival and the prominent function of TG2 in ischemic cell death is as a scaffold to modulate cellular processes

    Novel interactions of transglutaminase-2 with heparan sulphate proteoglycans: reflection on physiological implications

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    This mini-review brings together information from publications and recent conference proceedings that have shed light on the biological interaction between transglutaminase-2 and heparan sulphate proteoglycans. We subsequently draw hypothesis of possible implications in the wound healing process. There is a substantial overlap in the action of transglutaminase-2 and the heparan sulphate proteoglycan syndecan-4 in normal and abnormal wound repair. Our latest findings have identified syndecan-4 as a possible binding and signalling partner of fibronectinbound TG2 and support the idea that transglutaminase-2 and syndecan-4 acts in synergy
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