Recent advances in understanding Cushing disease: resistance to glucocorticoid negative feedback and somatic USP8 mutations

Cushing’s disease is a rare disease with a characteristic phenotype due to significant hypercortisolism driven by over-secretion of adrenocorticotropic hormone and to high morbidity and mortality if untreated. It is caused by a corticotroph adenoma of the pituitary, but the exact mechanisms leading to tumorigenesis are not clear. Recent advances in molecular biology such as the discovery of somatic mutations of the ubiquitin-specific peptidase 8 (USP8) gene allow new insights into the pathogenesis, which could be translated into exciting and much-needed therapeutic applications

The Oxytocin Receptor (OXTR) Contributes to Prosocial Fund Allocations in the Dictator Game and the Social Value Orientations Task

Background: Economic games observe social decision making in the laboratory that involves real money payoffs. Previously we have shown that allocation of funds in the Dictator Game (DG), a paradigm that illustrates costly altruistic behavior, is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a receptor gene (AVPR1a). In the current investigation, the gene encoding the related oxytocin receptor (OXTR) was tested for association with the DG and a related paradigm, the Social Values Orientation (SVO) task. Methodology/Principal Findings: Association (101 male and 102 female students) using a robust-family based test between 15 single tagging SNPs (htSNPs) across the OXTR was demonstrated with both the DG and SVO. Three htSNPs across the gene region showed significant association with both of the two games. The most significant association was observed with rs1042778 (p = 0.001). Haplotype analysis also showed significant associations for both DG and SVO. Following permutation test adjustment, significance was observed for 2–5 locus haplotypes (p,0.05). A second sample of 98 female subjects was subsequently and independently recruited to play the dictator game and was genotyped for the three significant SNPs found in the first sample. The rs1042778 SNP was shown to be significant for the second sample as well (p = 0.004, Fisher’s exact test). Conclusions: The demonstration that genetic polymorphisms for the OXTR are associated with human prosocial decisio

Constraints on simulated past Arctic amplification and lapse rate feedback from observations

The Arctic has warmed more rapidly than the global mean during the past few decades. The lapse rate feedback (LRF) has been identified as being a large contributor to the Arctic amplification (AA) of climate change. This particular feedback arises from the vertically non-uniform warming of the troposphere, which in the Arctic emerges as strong near-surface and muted free-tropospheric warming. Stable stratification and meridional energy transport are two characteristic processes that are evoked as causes for this vertical warming structure. Our aim is to constrain these governing processes by making use of detailed observations in combination with the large climate model ensemble of the sixth Coupled Model Intercomparison Project (CMIP6). We build on the result that CMIP6 models show a large spread in AA and Arctic LRF, which are positively correlated for the historical period of 1951–2014. Thus, we present process-oriented constraints by linking characteristics of the current climate to historical climate simulations. In particular, we compare a large consortium of present-day observations to co-located model data from subsets that show a weak and strong simulated AA and Arctic LRF in the past. Our analyses suggest that the vertical temperature structure of the Arctic boundary layer is more realistically depicted in climate models with weak (w) AA and Arctic LRF (CMIP6/w) in the past. In particular, CMIP6/w models show stronger inversions in the present climate for boreal autumn and winter and over sea ice, which is more consistent with the observations. These results are based on observations from the year-long Multidisciplinary Drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition in the central Arctic, long-term measurements at the Utqiaġvik site in Alaska, USA, and dropsonde temperature profiling from aircraft campaigns in the Fram Strait. In addition, the atmospheric energy transport from lower latitudes that can further mediate the warming structure in the free troposphere is more realistically represented by CMIP6/w models. In particular, CMIP6/w models systemically simulate a weaker Arctic atmospheric energy transport convergence in the present climate for boreal autumn and winter, which is more consistent with fifth generation reanalysis of the European Centre for Medium-Range Weather Forecasts (ERA5). We further show a positive relationship between the magnitude of the present-day transport convergence and the strength of past AA. With respect to the Arctic LRF, we find links between the changes in transport pathways that drive vertical warming structures and local differences in the LRF. This highlights the mediating influence of advection on the Arctic LRF and motivates deeper studies to explicitly link spatial patterns of Arctic feedbacks to changes in the large-scale circulation

The extremely hot and dry 2018 summer in central and northern Europe from a multi-faceted weather and climate perspective

The summer of 2018 was an extraordinary season in climatological terms for northern and central Europe, bringing simultaneous, widespread, and concurrent heat and drought extremes in large parts of the continent with extensive impacts on agriculture, forests, water supply, and the socio-economic sector. Here, we present a comprehensive, multi-faceted analysis of the 2018 extreme summer in terms of heat and drought in central and northern Europe, with a particular focus on Germany. The heatwave first affected Scandinavia in mid-July and shifted towards central Europe in late July, while Iberia was primarily affected in early August. The atmospheric circulation was characterized by strongly positive blocking anomalies over Europe, in combination with a positive summer North Atlantic Oscillation and a double jet stream configuration before the initiation of the heatwave. In terms of possible precursors common to previous European heatwaves, the Eurasian double-jet structure and a tripolar sea surface temperature anomaly over the North Atlantic were already identified in spring. While in the early stages over Scandinavia the air masses at mid and upper levels were often of a remote, maritime origin, at later stages over Iberia the air masses primarily had a local-to-regional origin. The drought affected Germany the most, starting with warmer than average conditions in spring, associated with enhanced latent heat release that initiated a severe depletion of soil moisture. During summer, a continued precipitation deficit exacerbated the problem, leading to hydrological and agricultural drought. A probabilistic attribution assessment of the heatwave in Germany showed that such events of prolonged heat have become more likely due to anthropogenic global warming. Regarding future projections, an extreme summer such as that of 2018 is expected to occur every 2 out of 3 years in Europe in a +1.5 ∘C warmer world and virtually every single year in a +2 ∘C warmer world. With such large-scale and impactful extreme events becoming more frequent and intense under anthropogenic climate change, comprehensive and multi-faceted studies like the one presented here quantify the multitude of their effects and provide valuable information as a basis for adaptation and mitigation strategies

The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the Dictator Game and the social value orientations task

10.1371/journal.pone.0005535PLoS ONE45e553