In this review, we discuss several reproducible methods by which hESCs or iPS cells are efficiently Bioactive Compound Library screening isolated and differentiated into functional motor neurons, and possible clinical applications.”
“Essential hypertension is a multifactorial disease, considered to be one of the world’s greatest public health problems. Despite recent, major, technical advances aiming to elucidate its genetic component, the discovered biomarkers up to now were reported to have only small effects, explaining consequently a tiny fraction of its phenotypic variance and resulting in a large proportion of missing heritability. Likewise, little evidence is available with regard
to the epigenetic regulation of essential hypertension, since no robust biomarkers have yet been reported.\n\nIn the current review, we discuss the main approaches used exclusively to study the genetics and epigenetics of essential hypertension, the HDAC inhibitor biomarkers
identified, their clinical utility and the difficulties to be overcome. Furthermore, we propose a new category of functional genetic-epigenetic biomarkers, eMethSNPs, and we provide their hypothetical gene expression profiles for a genetic functional regulation of hypertension via DNA methylation. Though believed to be infrequent, eMethSNPs could constitute a new category of mechanistically-based genetic biomarkers predisposing to essential hypertension. (C) 2012 Elsevier B.V. All rights reserved.”
“The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR gamma) has important roles in adipogenesis and immune response as well as roles in both lipid and carbohydrate metabolism. Although synthetic agonists for PPAR gamma
are widely used as insulin sensitizers, the identity of the natural ligand(s) for PPAR gamma is still not clear. Suggested natural ligands include 15-deoxy-Delta(12,14)-prostaglandin GM6001 J2 and oxidized fatty acids such as 9-HODE and 13-HODE. Crystal structures of PPAR gamma have revealed the mode of recognition for synthetic compounds. Here we report structures of PPAR gamma bound to oxidized fatty acids that are likely to be natural ligands for this receptor. These structures reveal that the receptor can (i) simultaneously bind two fatty acids and (ii) couple covalently with conjugated oxo fatty acids. Thermal stability and gene expression analyses suggest that such covalent ligands are particularly effective activators of PPAR gamma and thus may serve as potent and biologically relevant ligands.”
“External climate forcings-such as long-term changes in solar insolation-generate different climate responses in tropical and high latitude regions(1). Documenting the spatial and temporal variability of past climates is therefore critical for understanding how such forcings are translated into regional climate variability.