The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Additive effects of lupin protein and phytic acid on aortic calcification in ApoE deficient mice

Lupin proteins have repeatedly been shown to exhibit lipid lowering properties and reduce aortic calcification in atherosclerosis models. Despite many efforts on its identification, the component which is responsible for the observed effects is still under debate. Phytic acid which is generally associated with lupin protein isolates has currently been described as bioactive plant compound. The objective of the study was to determine the role of associated phytic acid for the described lupin protein effects. A two-factorial study with ApoE knockout mice was conducted in which mice received lupin protein isolate or casein with or without phytase. Phytic acid was added to the casein diets to a final concentration identical to the lupin protein diets. Here we show that the serum concentrations of cholesterol, lathosterol and desmosterol were lower and the faecal bile acid excretion was higher in the groups fed lupin proteins than in the groups fed casein (p < 0.05). Mice that received the lupin protein diet containing phytic acid were characterized by a lower aortic calcification than mice of the other three groups (p < 0.05). In conclusion, our results show that the cholesterol lowering properties of lupin protein isolate were not caused by phytic acid. However, the hypocalcific action of lupin proteins appears to depend on the combination of lupin proteins and phytic acid

EURO-CORDEX: new high-resolution climate change projections for European impact research

A new high-resolution regional climate change ensemble has been established for Europe within the World Climate Research Program Coordinated Regional Downscaling Experiment (EURO-CORDEX) initiative. The first set of simulations with a horizontal resolution of 12.5 km was completed for the new emission scenarios RCP4.5 and RCP8.5 with more simulations expected to follow. The aim of this paper is to present this data set to the different communities active in regional climate modelling, impact assessment and adaptation. The EURO-CORDEX ensemble results have been compared to the SRES A1B simulation results achieved within the ENSEMBLES project. The large-scale patterns of changes in mean temperature and precipitation are similar in all three scenarios, but they differ in regional details, which can partly be related to the higher resolution in EURO-CORDEX. The results strengthen those obtained in ENSEMBLES, but need further investigations. The analysis of impact indices shows that for RCP8.5, there is a substantially larger change projected for temperature-based indices than for RCP4.5. The difference is less pronounced for precipitation-based indices. Two effects of the increased resolution can be regarded as an added value of regional climate simulations. Regional climate model simulations provide higher daily precipitation intensities, which are completely missing in the global climate model simulations, and they provide a significantly different climate change of daily precipitation intensities resulting in a smoother shift from weak to moderate and high intensities

Erratum to: EURO-CORDEX: new high-resolution climate change projections for European impact research

International audienceThe author would like to correct the errors in the publication of the original article. The corrected details are given below for your reading.In result section, third sentence of the fourth paragraph should read as:“The zone between regions in which precipitation increases in the north and decreases in the south shifts northwards in summer and southwards in winter”The ranges in Table 3 should be:Cold spell duration index, Max, Continental, RCP8.5 from −6 to −8.Annual total precipitation, Min, Southern, RCP4.5 from −11 to 2.Annual total precipitation, Max, Southern, RCP4.5 from 2 to −11.The correct Table 3 is given in the following page

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation