Epigenomic Convergence of Neural-Immune Risk Factors in Neurodevelopmental Disorder Cortex.

Neurodevelopmental disorders (NDDs) affect 7-14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into NDD etiology. Whole-genome bisulfite sequencing was used to examine DNA cytosine methylation in 49 human cortex samples from 3 different NDDs (autism spectrum disorder, Rett syndrome, and Dup15q syndrome) and matched controls. Integration of methylation changes across NDDs with relevant genomic and genetic datasets revealed differentially methylated regions (DMRs) unique to each type of NDD but with shared regulatory functions in neurons and microglia. NDD DMRs were enriched within promoter regions and for transcription factor binding sites with identified methylation sensitivity. DMRs from all 3 disorders were enriched for ontologies related to nervous system development and genes with disrupted expression in brain from neurodevelopmental or neuropsychiatric disorders. Genes associated with NDD DMRs showed expression patterns indicating an important role for altered microglial function during brain development. These findings demonstrate an NDD epigenomic signature in human cortex that will aid in defining therapeutic targets and early biomarkers at the interface of genetic and environmental NDD risk factors

Investigation of modifier genes within copy number variations in Rett syndrome.

MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). We investigated whether copy number variants (CNVs) may modulate the phenotype by comparison of array-CGH data from two discordant pairs of sisters and four additional discordant pairs of unrelated girls matched by mutation type. We also searched for potential MeCP2 targets within CNVs by chromatin immunopreceipitation microarray (ChIP-chip) analysis. We did not identify one major common gene/region, suggesting that modifiers may be complex and variable between cases. However, we detected CNVs correlating with disease severity that contain candidate modifiers. CROCC (1p36.13) is a potential MeCP2 target, in which a duplication in a Z-RTT and a deletion in a classic patient were observed. CROCC encodes a structural component of ciliary motility that is required for correct brain development. CFHR1 and CFHR3, on 1q31.3, may be involved in the regulation of complement during synapse elimination, and were found to be deleted in a Z-RTT but duplicated in two classic patients. The duplication of 10q11.22, present in two Z-RTT patients, includes GPRIN2, a regulator of neurite outgrowth and PPYR1, involved in energy homeostasis. Functional analyses are necessary to confirm candidates and to define targets for future therapies. Journal of Human Genetics (2011) 56, 508-515; doi: 10.1038/jhg.2011.50; published online 19 May 201

Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex

Many genes have oscillating gene expression pattern in circadian centers of the brain. This study shows cortical diurnal DNA methylation oscillation in a mouse model of Prader-Willi syndrome, and describes corresponding changes in gene expression and chromatin compaction

Rheology of Lignocellulose Suspensions and Impact of Hydrolysis: A Review

White biotechnologies have several challenges to overcome in order to become a viable industrial process. Achieving highly concentrated lignocellulose materials and releasing fermentable substrates, with controlled kinetics in order to regulate micro-organism activity, present major technical and scientific bottlenecks. The degradation of the main polymeric fractions of lignocellulose into simpler molecules is a prerequisite for an integrated utilisation of this resource in a biorefinery concept. The characterisation methods and the observations developed for rheology, morphology, etc., that are reviewed here are strongly dependent on the fibrous nature of lignocellulose, are thus similar or constitute a good approach to filamentous culture broths. This review focuses on scientific works related to the study of the rheological behaviour of lignocellulose suspensions and their evolution during biocatalysis. In order to produce the targeted molecules (synthon), the lignocellulose substrates are converted by enzymatic degradation and are then metabolised by micro-organisms. The dynamics of the mechanisms is limited by coupled phenomena between flow, heat and mass transfers in regard to diffusion (within solid and liquid phases), convection (mixing, transfer coefficients, homogeneity) and specific inhibitors (concentration gradients). As lignocellulose suspensions consist of long entangled fibres for the matrix of industrial interest, they exhibit diverse and complex properties linked to this fibrous character (rheological, morphological, thermal, mechanical and biochemical parameters). Among the main variables to be studied, the rheological behaviour of such suspensions appears to be determinant for process efficiency. It is this behaviour that will determine the equipment to be used and the strategies applied (substrate and biocatalysis feed, mixing, etc.). This review provides an overview of (i) the rheological behaviour of fibrous materials in suspension, (ii) the methods and experimental conditions for their measurements, (iii) the main models used and (iv) their evolution during biocatalytic reactions with a focus on enzymatic hydrolysis