Dynamic protein methylation in chromatin biology

Post-translational modification of chromatin is emerging as an increasingly important regulator of chromosomal processes. In particular, histone lysine and arginine methylation play important roles in regulating transcription, maintaining genomic integrity, and contributing to epigenetic memory. Recently, the use of new approaches to analyse histone methylation, the generation of genetic model systems, and the ability to interrogate genome wide histone modification profiles has aided in defining how histone methylation contributes to these processes. Here we focus on the recent advances in our understanding of the histone methylation system and examine how dynamic histone methylation contributes to normal cellular function in mammals

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Swell impact on reef sedimentary processes: A case study of the La Reunion fringing reef

Two surface-sediment sampling campaigns were carried out in November and December 2003, before and after a strong swell event, in the back-reef area of a microtidal fringing reef on the western coast of La Reunion, Indian Ocean. The spatial distributions of the mean grain size, sorting and skewness parameters are determined, and grain-size trend analysis is performed to estimate the main sediment transport pathways in the reef. The results of this analysis are compared with hydrodynamic records obtained in the same reef area during fair weather conditions and during swell events. Sediment dynamics inferred from the hydrodynamic records show that significant sediment erosion and transport occur only during swell events and under strongly agitated sea states. Under normal wave conditions, there is a potential for onshore sediment transport from the reef-flat to the back-reef, but this transport is episodic and occurs principally during high-tide stages. Sediment transport trends revealed by the grain-size trend analysis method show onshore and alongshore low-energy transport processes that are in agreement with the hydrodynamic records. The grain-size trend analysis method also provides evidence of an offshore high-energy transport trend that could be interpreted as a real physical process associated with return flow from the shore to the reef. The impact of swell on the reef sediment dynamics is clearly demonstrated by onshore and alongshore transport. Considering different combinations of the vector transport trends computed through the grain-size trend analysis approach, more realistic and pertinent results can be obtained by applying an exclusive OR operation (XOR case) on the vectors. The main results presented here highlight a trend towards the accumulation of carbonate sands in the back-reef area of the fringing reef. These sediments can only be resuspended during extreme events such as storms or tropical cyclones

No advantage of Aβ 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies

10.1212/01.wnl.0000313933.17796.f6Neurology70242291-2298NEUR