Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Effect of organic matter on the performance and N2O emission of a granular sludge anammox reactor

A continuously fed bubble column granular sludge anammox reactor was operated for 405 days to investigate the effect of organic matter on the reactor performance and N2O emission. Results showed that influent COD improved the nitrogen removal of the anammox reactor at low influent COD/TN ratios (ca. 0.1); however, a concurrent increase in N2O emission was observed. The average N2O emission increased by 2.5 times (p < 0.05) with increasing influent COD concentration, accounting for up to 0.46% of the incoming nitrogen load. A generalized method was demonstrated and applied to derive the anammox stoichiometry from experimental data for improved mass balance. Mass balance revealed that approximately 18% of the nitrate produced from anammox conversion was reduced via heterotrophic denitrification to nitrite, and 29% of this produced nitrite was further released as N2O. In addition, it was found that the experimentally measured anammox biomass yield in the overall metabolic reaction has been mistakenly used as the catabolic yield in many modelling studies. Solutions were proposed

Understanding nucleotide excision repair and its roles in cancer and ageing

Nucleotide excision repair (NER) eliminates various structurally unrelated DNA lesions by a multiwise 'cut and patch'-type reaction. The global genome NER (GG-NER) subpathway prevents mutagenesis by probing the genome for helix-distorting lesions, whereas transcription-coupled NER (TC-NER) removes transcription-blocking lesions to permit unperturbed gene expression, thereby preventing cell death. Consequently, defects in GG-NER result in cancer predisposition, whereas defects in TC-NER cause a variety of diseases ranging from ultraviolet radiation-sensitive syndrome to severe premature ageing conditions such as Cockayne syndrome. Recent studies have uncovered new aspects of DNA-damage detection by NER, how NER is regulated by extensive post-translational modifications, and the dynamic chromatin interactions that control its efficiency. Based on these findings, a mechanistic model is proposed that explains the complex genotype-phenotype correlations of transcription-coupled repair disorders