Significance of a highly refractory source during subduction initiation to form the Izu-Bonin-Mariana Arc

The ascendent theory that unifies the Earth Sciences is Plate Tectonics,a regime which is unique to Earth.Other convectively active,solid silicate bodies of our...     

RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease

Receptor for AGE (RAGE) is a member of the immunoglobulin superfamily that engages distinct classes of ligands. The biology of RAGE is driven by the settings in which these ligands accumulate, such as diabetes, inflammation, neurodegenerative disorders and tumors. In this review, we discuss the context of each of these classes of ligands, including advance glycation end-products, amyloid beta peptide and the family of beta sheet fibrils, S100/calgranulins and amphoterin. Implications for the role of these ligands interacting with RAGE in homeostasis and disease will be considered.     

Calcineurin/NFAT signalling regulates pancreatic beta-cell growth and function

The growth and function of organs such as pancreatic islets adapt to meet physiological challenges and maintain metabolic balance, but the mechanisms controlling these facultative responses are unclear. Diabetes in patients treated with calcineurin inhibitors such as cyclosporin A indicates that calcineurin/nuclear factor of activated T-cells (NFAT) signalling might control adaptive islet responses, but the roles of this pathway in beta-cells in vivo are not understood. Here we show that mice with a beta-cell-specific deletion of the calcineurin phosphatase regulatory subunit, calcineurin b1 (Cnb1), develop age-dependent diabetes characterized by decreased beta-cell proliferation and mass, reduced pancreatic insulin content and hypoinsulinaemia. Moreover, beta-cells lacking Cnb1 have a reduced expression of established regulators of beta-cell proliferation. Conditional expression of active NFATc1 in Cnb1-deficient beta-cells rescues these defects and prevents diabetes. In normal adult beta-cells, conditional NFAT activation promotes the expression of cell-cycle regulators and increases beta-cell proliferation and mass, resulting in hyperinsulinaemia. Conditional NFAT activation also induces the expression of genes critical for beta-cell endocrine function, including all six genes mutated in hereditary forms of monogenic type 2 diabetes. Thus, calcineurin/NFAT signalling regulates multiple factors that control growth and hallmark beta-cell functions, revealing unique models for the pathogenesis and therapy of diabetes.     

Discovery of two new satellites of Pluto

Pluto's first known satellite, Charon, was discovered in 1978. It has a diameter (approximately 1,200 km) about half that of Pluto, which makes it larger, relative to its primary, than any other moon in the Solar System. Previous searches for other satellites around Pluto have been unsuccessful, but they were not sensitive to objects less, similar150 km in diameter and there are no fundamental reasons why Pluto should not have more satellites. Here we report the discovery of two additional moons around Pluto, provisionally designated S/2005 P 1 (hereafter P1) and S/2005 P 2 (hereafter P2), which makes Pluto the first Kuiper belt object known to have multiple satellites. These new satellites are much smaller than Charon, with estimates of P1's diameter ranging from 60 km to 165 km, depending on the surface reflectivity; P2 is about 20 per cent smaller than P1. Although definitive orbits cannot be derived, both new satellites appear to be moving in circular orbits in the same orbital plane as Charon, with orbital periods of approximately 38 days (P1) and approximately 25 days (P2).