Beschreibung: The European CORDEX (EURO-CORDEX) initiative is a large voluntary effort that seeks to advance regional climate and Earth system science in Europe. As part of the World Climate Research Programme (WCRP) - Coordinated Regional Downscaling Experiment (CORDEX), it shares the broader goals of providing a model evaluation and climate projection framework and improving communication with both the General Circulation Model (GCM) and climate data user communities. EURO-CORDEX oversees the design and coordination of ongoing ensembles of regional climate projections of unprecedented size and resolution (0.11° EUR-11 and 0.44° EUR-44 domains). Additionally, the inclusion of empirical-statistical downscaling allows investigation of much larger multi-model ensembles. These complementary approaches provide a foundation for scientific studies within the climate research community and others. The value of the EURO-CORDEX ensemble is shown via numerous peer-reviewed studies and its use in the development of climate services. Evaluations of the EUR-44 and EUR-11 ensembles also show the benefits of higher resolution. However, significant challenges remain. To further advance scientific understanding, two flagship pilot studies (FPS) were initiated. The first investigates local-regional phenomena at convection-permitting scales over central Europe and the Mediterranean in collaboration with the Med-CORDEX community. The second investigates the impacts of land cover changes on European climate across spatial and temporal scales. Over the coming years, the EURO-CORDEX community looks forward to closer collaboration with other communities, new advances, supporting international initiatives such as the IPCC reports, and continuing to provide the basis for research on regional climate impacts and adaptation in Europe.

Beschreibung: Medicanes are cyclones over the Mediterranean Sea having a tropical-like structure but a rather small size, that can produce significant damage due to the combination of intense winds and heavy precipitation. Future climate projections, performed generally with individual atmospheric climate models, indicate that the intensity of the medicanes could increase under climate change conditions. The availability of large ensembles of high resolution and ocean–atmosphere coupled regional climate model (RCM) simulations, performed in MedCORDEX and EURO-CORDEX projects, represents an opportunity to improve the assessment of the impact of climate change on medicanes. As a first step towards such an improved assessment, we analyze the ability of the RCMs used in these projects to reproduce the observed characteristics of medicanes, and the impact of increased resolution and air-sea coupling on their simulation. In these storms, air-sea interaction plays a fundamental role in their formation and intensification, a different mechanism from that of extra-tropical cyclones, where the baroclinic instability mechanism prevails. An observational database, based on satellite images combined with high resolution simulations (Miglietta et al. in Geophys Res Lett 40:2400–2405, 2013), is used as a reference for evaluating the simulations. In general, the simulated medicanes do not coincide on a case-by-case basis with the observed medicanes. However, observed medicanes with a high intensity and relatively long duration of tropical characteristics are better replicated in simulations. The observed spatial distribution of medicanes is generally well simulated, while the monthly distribution reveals the difficulty of simulating the medicanes that first appear in September after the summer minimum in occurrence. Increasing the horizontal resolution has a systematic and generally positive impact on the frequency of simulated medicanes, while the general underestimation of their intensity is not corrected in most cases. The capacity of a few models to better simulate the medicane intensity suggests that the model formulation is more important than reducing the grid spacing alone. A negative intensity feedback is frequently the result of air-sea interaction for tropical cyclones in other basins. The introduction of air-sea coupling in the present simulations has an overall limited impact on medicane frequency and intensity, but it produces an interesting seasonal shift of the simulated medicanes from autumn to winter. This fact, together with the analysis of two contrasting particular cases, indicates that the negative feedback could be limited or even absent in certain situations. We suggest that the effects of air-sea interaction on medicanes may depend on the oceanic mixed layer depth, thus increasing the applicability of ocean–atmosphere coupled RCMs for climate change analysis of this kind of cyclones.

Beschreibung: Nature Genetics 45, 1464 (2013). doi:10.1038/ng.2799 Authors: Cristina Balbás-Martínez, Ana Sagrera, Enrique Carrillo-de-Santa-Pau, Julie Earl, Mirari Márquez, Miguel Vazquez, Eleonora Lapi, Francesc Castro-Giner, Sergi Beltran, Mònica Bayés, Alfredo Carrato, Juan C Cigudosa, Orlando Domínguez, Marta Gut, Jesús Herranz, Núria Juanpere, Manolis Kogevinas, Xavier Langa, Elena López-Knowles, José A Lorente, Josep Lloreta, David G Pisano, Laia Richart, Daniel Rico, Rocío N Salgado, Adonina Tardón, Stephen Chanock, Simon Heath, Alfonso Valencia, Ana Losada, Ivo Gut, Núria Malats & Francisco X Real Urothelial bladder cancer (UBC) is heterogeneous at the clinical, pathological and genetic levels. Tumor invasiveness (T) and grade (G) are the main factors associated with outcome and determine patient management. A discovery exome sequencing screen (n = 17), followed by a prevalence screen (n = 60), identified new genes mutated in this tumor coding for proteins involved in chromatin modification (MLL2, ASXL2 and BPTF), cell division (STAG2, SMC1A and SMC1B) and DNA repair (ATM, ERCC2 and FANCA). STAG2, a subunit of cohesin, was significantly and commonly mutated or lost in UBC, mainly in tumors of low stage or grade, and its loss was associated with improved outcome. Loss of expression was often observed in chromosomally stable tumors, and STAG2 knockdown in bladder cancer cells did not increase aneuploidy. STAG2 reintroduction in non-expressing cells led to reduced colony formation. Our findings indicate that STAG2 is a new UBC tumor suppressor acting through mechanisms that are different from its role in preventing aneuploidy.

Beschreibung: NANOG is a key pluripotency factor in embryonic stem cells that is frequently expressed in squamous cell carcinomas (SCCs). However, a direct link between NANOG and SCCs remains to be established. Here, we show that inducible overexpression of NANOG in mouse skin epithelia favours the malignant conversion of skin papillomas induced by chemical carcinogenesis, leading to increased SCC formation. Gene expression analyses in pre-malignant skin indicate that NANOG induces genes associated to epithelial-mesenchymal transition (EMT). Some of these genes are directly activated by NANOG, including EMT-associated genes Zeb1, Zeb2, Twist1, Prrx1 and miR-21. Finally, endogenous NANOG binds to the promoters of theses genes in human SCC cells and, moreover, NANOG induces EMT features in primary keratinocytes. These results provide in vivo evidence for the oncogenic role of NANOG in squamous cell carcinomas. Scientific Reports 5 doi: 10.1038/srep10205