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.     

Prions and their partners in crime

Prions, the infectious agents of transmissible spongiform encephalopathies (TSEs), have defied full characterization for decades. The dogma has been that prions lack nucleic acids and are composed of a pathological, self-inducing form of the host's prion protein (PrP). Recent progress in propagating TSE infectivity in cell-free systems has effectively ruled out the involvement of foreign nucleic acids. However, host-derived nucleic acids or other non-PrP molecules seem to be crucial. Interactions between TSE-associated PrP and its normal counterpart are also pathologically important, so the physiological functions of normal PrP and how they might be corrupted by TSE infections have been the subject of recent research.     

The twentieth century was the wettest period in northern Pakistan over the past millennium

Twentieth-century warming could lead to increases in the moisture-holding capacity of the atmosphere, altering the hydrological cycle and the characteristics of precipitation. Such changes in the global rate and distribution of precipitation may have a greater direct effect on human well-being and ecosystem dynamics than changes in temperature itself. Despite the co-variability of both of these climate variables, attention in long-term climate reconstruction has mainly concentrated on temperature changes. Here we present an annually resolved oxygen isotope record from tree-rings, providing a millennial-scale reconstruction of precipitation variability in the high mountains of northern Pakistan. The climatic signal originates mainly from winter precipitation, and is robust over ecologically different sites. Centennial-scale variations reveal dry conditions at the beginning of the past millennium and through the eighteenth and early nineteenth centuries, with precipitation increasing during the late nineteenth and the twentieth centuries to yield the wettest conditions of the past 1,000 years. Comparison with other long-term precipitation reconstructions indicates a large-scale intensification of the hydrological cycle coincident with the onset of industrialization and global warming, and the unprecedented amplitude argues for a human role.     

Vigorous exchange between the Indian and Atlantic oceans at the end of the past five glacial periods

The magnitude of heat and salt transfer between the Indian and Atlantic oceans through 'Agulhas leakage' is considered important for balancing the global thermohaline circulation. Increases or reductions of this leakage lead to strengthening or weakening of the Atlantic meridional overturning and associated variation of North Atlantic Deep Water formation. Here we show that modern Agulhas waters, which migrate into the south Atlantic Ocean in the form of an Agulhas ring, contain a characteristic assemblage of planktic foraminifera. We use this assemblage as a modern analogue to investigate the Agulhas leakage history over the past 550,000 years from a sediment record in the Cape basin. Our reconstruction indicates that Indian-Atlantic water exchange was highly variable: enhanced during present and past interglacials and largely reduced during glacial intervals. Coherent variability of Agulhas leakage with northern summer insolation suggests a teleconnection to the monsoon system. The onset of increased Agulhas leakage during late glacial conditions took place when glacial ice volume was maximal, suggesting a crucial role for Agulhas leakage in glacial terminations, timing of interhemispheric climate change and the resulting resumption of the Atlantic meridional overturning circulation.     

Decline of surface temperature and salinity in the western tropical Pacific Ocean in the Holocene epoch

In the present-day climate, surface water salinities are low in the western tropical Pacific Ocean and increase towards the eastern part of the basin. The salinity of surface waters in the tropical Pacific Ocean is thought to be controlled by a combination of atmospheric convection, precipitation, evaporation and ocean dynamics, and on interannual timescales significant variability is associated with the El Ni?o/Southern Oscillation cycles. However, little is known about the variability of the coupled ocean-atmosphere system on timescales of centuries to millennia. Here we combine oxygen isotope and Mg/Ca data from foraminifers retrieved from three sediment cores in the western tropical Pacific Ocean to reconstruct Holocene sea surface temperatures and salinities in the region. We find a decrease in sea surface temperatures of approximately 0.5 degrees C over the past 10,000 yr, whereas sea surface salinities decreased by approximately 1.5 practical salinity units. Our data imply either that the Pacific basin as a whole has become progressively less salty or that the present salinity gradient along the Equator has developed relatively recently.     

Systems Practice in China: New Developments and Cross-Cultural Collaborations

This short paper introduces a special issue of Systemic Practice and Action Research on new developments in Chinese systems practice. It focuses on the recent history of systems thinking in China, describing a paradigm shift that is currently taking place from an "objectivist" to a more pluralistic stance. Details are provided of the Hull–Beijing research program, which has contributed to this paradigm shift. In one way or another, all the papers in this special issue can be seen as having a connection with this research program.