Female mice are less susceptible to the negative metabolic consequences of high-fat diet feeding than male mice, for reasons that are incompletely understood. Here we identify sex-specific differences in hypothalamic microglial activation via the CX3CL1-CX3CR1 pathway that mediate the resistance of female mice to diet-induced obesity. Female mice fed a high-fat diet maintain CX3CL1-CX3CR1 levels while male mice show reductions in both ligand and receptor expression. Female Cx3cr1 knockout mice develop ‘male-like' hypothalamic microglial accumulation and activation, accompanied by a marked increase in their susceptibility to diet-induced obesity. Conversely, increasing brain CX3CL1 levels in male mice through central pharmacological administration or virally mediated hypothalamic overexpression converts them to a ‘female-like' metabolic phenotype with reduced microglial activation and body-weight gain. These data implicate sex differences in microglial activation in the modulation of energy homeostasis and identify CX3CR1 signalling as a potential therapeutic target for the treatment of obesity.

Hydrologic model calibration is usually a central element of streamflow forecasting based on the ensemble streamflow prediction (ESP) method. Evaluation measures of forecast errors such as root-meansquare error (RMSE) are heavily influenced by bias, which in turn is readily reduced by calibration. On the other hand, bias can also be reduced by postprocessing (e.g., "training" bias correction schemes based on retrospective simulation error statistics). This observation invites the question: How much is forecast error reduced by calibration, beyond what can be accomplished by postprocessing to remove bias? The authors address this question through retrospective evaluation of forecast errors at eight streamflow forecast locations distributed across the western United States. Forecast periods of length ranging from 1 to 6 months are investigated, for forecasts initiated from 1 December to 1 June, which span the period when most runoff occurs from snowmelt-dominated western U.S. rivers. ESP forecast errors are evaluated both for uncalibrated forecasts to which a percentile mapping bias correction approach is applied, and for forecasts from an objectively calibrated model without explicit bias correction. Using the coefficient of prediction (C p ), which essentially is a measure of the fraction of variance explained by the forecast, the authors find that the reduction in forecast error as measured by C p that is achieved by bias correction alone is nearly as great as that resulting from hydrologic model calibration.

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With its headwaters in the water towers of the western Cordillera of North America, the Fraser River is one of the continent’s mightiest rivers by annual flows, supplies vital freshwater resources to populous downstream locations, and sustains the world’s largest stocks of sockeye salmon along with four other salmon species. Here we show the Variable Infiltration Capacity (VIC) model’s ability to reproduce accurately observed trends in daily streamflow for the Fraser River’s main stem and six of its major tributaries over 1949-2006 when air temperatures rose by 1.4 °C while annual precipitation amounts remained stable. Rapidly declining mountain snowpacks and earlier melt onsets result in a 10-day advance of the Fraser River’s spring freshet with subsequent reductions in summer flows when up-river salmon migrations occur. Identification of the sub-basins driving the Fraser River’s most significant changes provides a measure of seasonal predictability of future floods or droughts in a changing climate.

Attributing variations of temporal and spatial groundwater recharge: a statistical analysis of climatic and non-climatic factors Guobin Fu,