Synaptic potentiation onto habenula neurons in the learned helplessness model of depression

The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.     

Turbidite deposition in the southern South China Sea during the last glacial: Evidence from grain-size and major elements records

High-resolution grain size and major element geochemical measurements were performed on the marine sediments of Core MD05-2895 to help understand the formation of turbidite sequences. Grain-size results show that these turbidite sediments contain more coarse sediment grains than normal marls. The coarse sediment grains are mostly derived from relict sediments on the Sunda Shelf. Relict sediments are composed mainly of quartz, feldspar, tephra and a few titaniferous or ferruginous heavy minerals. Corresponding to the concentration of these minerals, increases in Si/Al, K/Al, Ti/Al and Fe/Al ratios are observed in the turbidite layers. As all the observed turbidite sequences were deposited during the last glacial, the occurrence of these turbidity events is implied to be closely related to instabilities in sea-level-induced sediment supply. We suggest that deposition of sediment particles from a single turbidity current is usually controlled by a counterbalance between gravity and buoyancy, with the interaction of individual grains being of minor importance.     

Robust forecasting with exponential and Holt–Winters smoothing

Robust versions of the exponential and Holt–Winters smoothing method for forecasting are presented. They are suitable for forecasting univariate time series in the presence of outliers. The robust exponential and Holt–Winters smoothing methods are presented as recursive updating schemes that apply the standard technique to pre‐cleaned data. Both the update equation and the selection of the smoothing parameters are robustified. A simulation study compares the robust and classical forecasts. The presented method is found to have good forecast performance for time series with and without outliers, as well as for fat‐tailed time series and under model misspecification. The method is illustrated using real data incorporating trend and seasonal effects. Copyright © 2009 John Wiley & Sons, Ltd.     

More extreme swings of the South Pacific convergence zone due to greenhouse warming

The South Pacific convergence zone (SPCZ) is the Southern Hemisphere's most expansive and persistent rain band, extending from the equatorial western Pacific Ocean southeastward towards French Polynesia. Owing to its strong rainfall gradient, a small displacement in the position of the SPCZ causes drastic changes to hydroclimatic conditions and the frequency of extreme weather events--such as droughts, floods and tropical cyclones--experienced by vulnerable island countries in the region. The SPCZ position varies from its climatological mean location with the El Ni?o/Southern Oscillation (ENSO), moving a few degrees northward during moderate El Ni?o events and southward during La Ni?a events. During strong El Ni?o events, however, the SPCZ undergoes an extreme swing--by up to ten degrees of latitude toward the Equator--and collapses to a more zonally oriented structure with commensurately severe weather impacts. Understanding changes in the characteristics of the SPCZ in a changing climate is therefore of broad scientific and socioeconomic interest. Here we present climate modelling evidence for a near doubling in the occurrences of zonal SPCZ events between the periods 1891-1990 and 1991-2090 in response to greenhouse warming, even in the absence of a consensus on how ENSO will change. We estimate the increase in zonal SPCZ events from an aggregation of the climate models in the Coupled Model Intercomparison Project phases 3 and 5 (CMIP3 and CMIP5) multi-model database that are able to simulate such events. The change is caused by a projected enhanced equatorial warming in the Pacific and may lead to more frequent occurrences of extreme events across the Pacific island nations most affected by zonal SPCZ events.     

PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells

Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T (Treg) cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity. Here we identify peroxisome proliferator-activated receptor (PPAR)-γ, the 'master regulator' of adipocyte differentiation, as a crucial molecular orchestrator of VAT Treg cell accumulation, phenotype and function. Unexpectedly, PPAR-γ expression by VAT Treg cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of Treg cells with unique functions can be precisely targeted to therapeutic ends.     

Mechanisms linking obesity with cardiovascular disease

Obesity increases the risk of cardiovascular disease and premature death. Adipose tissue releases a large number of bioactive mediators that influence not only body weight homeostasis but also insulin resistance - the core feature of type 2 diabetes - as well as alterations in lipids, blood pressure, coagulation, fibrinolysis and inflammation, leading to endothelial dysfunction and atherosclerosis. We are now beginning to understand the underlying mechanisms as well as the ways in which smoking and dyslipidaemia increase, and physical activity attenuates, the adverse effects of obesity on cardiovascular health.     

WNT11 acts as a directional cue to organize the elongation of early muscle fibres

The early vertebrate skeletal muscle is a well-organized tissue in which the primitive muscle fibres, the myocytes, are all parallel and aligned along the antero-posterior axis of the embryo. How myofibres acquire their orientation during development is unknown. Here we show that during early chick myogenesis WNT11 has an essential role in the oriented elongation of the myocytes. We find that the neural tube, known to drive WNT11 expression in the medial border of somites, is necessary and sufficient to orient myocyte elongation. We then show that the specific inhibition of WNT11 function in somites leads to the disorganization of myocytes. We establish that WNT11 mediates this effect through the evolutionary conserved planar cell polarity (PCP) pathway, downstream of the WNT/beta-catenin-dependent pathway, required to initiate the myogenic program of myocytes and WNT11 expression. Finally, we demonstrate that a localized ectopic source of WNT11 can markedly change the orientation of myocytes, indicating that WNT11 acts as a directional cue in this process. All together, these data show that the sequential action of the WNT/PCP and the WNT/beta-catenin pathways is necessary for the formation of fully functional embryonic muscle fibres. This study also provides evidence that WNTs can act as instructive cues to regulate the PCP pathway in vertebrates.     

Contact time of a bouncing drop

When a liquid drop lands on a solid surface without wetting it, it bounces with remarkable elasticity. Here we measure how long the drop remains in contact with the solid during the shock, a problem that was considered by Hertz for a bouncing ball. Our findings could help to quantify the efficiency of water-repellent surfaces (super-hydrophobic solids) and to improve water-cooling of hot solids, which is limited by the rebounding of drops as well as by temperature effects.     

Strategies for containing an emerging influenza pandemic in Southeast Asia

Highly pathogenic H5N1 influenza A viruses are now endemic in avian populations in Southeast Asia, and human cases continue to accumulate. Although currently incapable of sustained human-to-human transmission, H5N1 represents a serious pandemic threat owing to the risk of a mutation or reassortment generating a virus with increased transmissibility. Identifying public health interventions that might be able to halt a pandemic in its earliest stages is therefore a priority. Here we use a simulation model of influenza transmission in Southeast Asia to evaluate the potential effectiveness of targeted mass prophylactic use of antiviral drugs as a containment strategy. Other interventions aimed at reducing population contact rates are also examined as reinforcements to an antiviral-based containment policy. We show that elimination of a nascent pandemic may be feasible using a combination of geographically targeted prophylaxis and social distancing measures, if the basic reproduction number of the new virus is below 1.8. We predict that a stockpile of 3 million courses of antiviral drugs should be sufficient for elimination. Policy effectiveness depends critically on how quickly clinical cases are diagnosed and the speed with which antiviral drugs can be distributed.