66 research outputs found

    Barium isotopes in mid-ocean ridge hydrothermal vent fluids: A source of isotopically heavy Ba to the ocean

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    Mid-ocean ridge (MOR) hydrothermal vent fluids are enriched with dissolved barium, but due to barite (BaSO4) precipitation during mixing between Ba-bearing vent fluids and SO4-bearing seawater, the magnitude of hydrothermal Ba input to the ocean remains uncertain. Deep-ocean Ba isotopes show evidence for non-conservative behavior, which might be explained by input of isotopically heavy hydrothermal Ba. In this study we present the first Ba isotope data in mid-ocean ridge hydrothermal vent fluids and particles from systems on the Mid-Atlantic Ridge (Rainbow 36oN and TAG 26oN), the East Pacific Rise (EPR9-10oN and 13oN) and the Juan de Fuca Ridge (MEF and ASHES). The vent fluids display a wide range of dissolved Ba concentrations from 0.43 to 97.9 μmol/kg and δ138/134Ba values from -0.26 to +0.91 ‰, but are modified relative to initial composition due to precipitation of barite. Calculated endmember vent fluid δ138/134Ba values, prior to barite precipitation, are between -0.17 and +0.09 ‰, consistent with the values observed in oceanic basalts and pelagic sediments. Water-rock interaction inside the hydrothermal system appears to occur without isotope fractionation. During subsequent venting and mixing with seawater, barite precipitation preferentially removes isotopically light Ba from vent fluids with a fractionation factor of Δ138/134Bahyd-barite-fluid = -0.35 ± 0.10 ‰ (2SE, n=2). Based on knowledge of barite saturation and isotope fractionation during precipitation, the effective hydrothermal Ba component that mixes with seawater after all barite precipitation has taken place can be calculated: δ138/134Bahyd = +1.7 ± 0.7 ‰ (2SD). This value is isotopically heavier than deep ocean waters and may explain the observed non-conservative of Ba isotopes. These new constraints on hydrothermal Ba compositions enable the hydrothermal input of Ba to Atlantic deep waters to be assessed at ≈ 3 – 9 % of the observed Ba. Barium isotopes might be used as a tracer to reconstruct the history of hydrothermal Ba inputs and seawater SO4 concentrations in the past.US NSF grants: 0549547, 0751771, 0813861, 0961188 and 173667

    A new era for understanding amyloid structures and disease

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    The aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions is the hallmark of amyloid disease. The accumulation and deposition of amyloid fibrils, collectively known as amyloidosis, is associated with many pathological conditions that can be associated with ageing, such as Alzheimer disease, Parkinson disease, type II diabetes and dialysis-related amyloidosis. However, elucidation of the atomic structure of amyloid fibrils formed from their intact protein precursors and how fibril formation relates to disease has remained elusive. Recent advances in structural biology techniques, including cryo-electron microscopy and solid-state NMR spectroscopy, have finally broken this impasse. The first near-atomic-resolution structures of amyloid fibrils formed in vitro, seeded from plaque material and analysed directly ex vivo are now available. The results reveal cross-β structures that are far more intricate than anticipated. Here, we describe these structures, highlighting their similarities and differences, and the basis for their toxicity. We discuss how amyloid structure may affect the ability of fibrils to spread to different sites in the cell and between organisms in a prion-like manner, along with their roles in disease. These molecular insights will aid in understanding the development and spread of amyloid diseases and are inspiring new strategies for therapeutic intervention

    Protein Dynamics of the HIF-2α PAS-B Domain upon Heterodimerization and Ligand Binding

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    Hypoxia-Inducible Factor (HIF) transcription factors are heterodimeric proteins involved in the regulation of oxygen homeostatis. Their upregulation has been related to several tumors with a remarkably poor clinical outcome. The recent discovery of a druggable cavity in the HIF-2α PAS-B domain has opened an unprecedented opportunity for targeting the HIF-2α transcription factor in view of pharmaceutical strategies. Coincidentally, a novel compound able to selectively disrupt the HIF heterodimerization with a submicromolar activity has been reported. In this work, we investigated the molecular mechanisms responsible for the inhibition by comparing the dynamical features of the HIF-2α PAS-B monomer and the HIF-2α PAS-B/HIF-1β PAS-B complex, in the ligand-bound and -unbound states. Plain and biased Molecular Dynamics were used to characterize the differential conformational changes both structurally and energetically
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