Extracellular ATP plays a role in nociceptive signalling and sensory regulation of visceral function through ionotropic receptors variably composed of P2X 2 and P2X 3 subunits. P2X 2 and P2X 3 subunits can form homomultimeric P2X 2 , homomultimeric P2X 3 , or heteromultimeric P2X 2/3 receptors. However, the relative contribution of these receptor subtypes to afferent functions of ATP in vivo is poorly understood. Here we describe null mutant mice lacking the P2X 2 receptor subunit (P2X 2 −/− ) and double mutant mice lacking both P2X 2 and P2X 3 subunits (P2X 2 /P2X 3 Dbl−/− ), and compare these with previously characterized P2X 3 −/− mice. In patch-clamp studies, nodose, coeliac and superior cervical ganglia (SCG) neurones from wild-type mice responded to ATP with sustained inward currents, while dorsal root ganglia (DRG) neurones gave predominantly transient currents. Sensory neurones from P2X 2 −/− mice responded to ATP with only transient inward currents, while sympathetic neurones had barely detectable responses. Neurones from P2X 2 /P2X 3 Dbl−/− mice had minimal to no response to ATP. These data indicate that P2X receptors on sensory and sympathetic ganglion neurones involve almost exclusively P2X 2 and P2X 3 subunits. P2X 2 −/− and P2X 2 /P2X 3 Dbl−/− mice had reduced pain-related behaviours in response to intraplantar injection of formalin. Significantly, P2X 3 −/− , P2X 2 −/− , and P2X 2 /P2X 3 Dbl−/− mice had reduced urinary bladder reflexes and decreased pelvic afferent nerve activity in response to bladder distension. No deficits in a wide variety of CNS behavioural tests were observed in P2X 2 −/− mice. Taken together, these data extend our findings for P2X 3 −/− mice, and reveal an important contribution of heteromeric P2X 2/3 receptors to nociceptive responses and mechanosensory transduction within the urinary bladder.

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Verruculogen is a tremorgenic mycotoxin and contains an endoperoxide bond. In this study, we describe the cloning, overexpression and purification of a non-heme Fe(ii) and alpha-ketoglutarate-dependent dioxygenase FtmOx1 from Aspergillus fumigatus, which catalyses the conversion of fumitremorgin B to verruculogen by inserting an endoperoxide bond between two prenyl moieties. Incubation with (18)O(2)-enriched atmosphere demonstrated that both oxygen atoms of the endoperoxide bond are derived from one molecule of O(2). FtmOx1 is the first endoperoxide-forming non-heme Fe(ii) and alpha-ketoglutarate-dependent dioxygenase reported so far. A mechanism of FtmOx1-catalysed verruculogen formation is postulated and discussed.

A meta-analysis of cross-sectional studies found that shorter-time sleep was correlated with increased risk of obesity in children. However, findings from prospective cohort studies were inconsistent. PubMed and other data resources were searched through May 2015. Twenty-five eligible studies were identified including 56,584 children and adolescents with an average 3.4-year follow-up. Compared with children having the longest sleep duration (~12.2 hours), kids with the shortest sleep duration (~10.0 hours) were 76% more likely to be overweight/obese (pooled odds ratio [OR]: 1.76; 95% confidence interval [CI]: 1.39, 2.23); and had relatively larger annual BMI gain (pooled β coefficient: 0.13; 95% CI: 0.01, 0.25 kg/m2). With every 1 hour/day increment in sleep duration, the risk of overweight/obesity was reduced by 21% (OR: 0.79; 95% CI: 0.70, 0.89); and the annual BMI gain declined by 0.05 kg/m2 (β = −0.05; 95% CI: −0.09, −0.01). The observed associations were not appreciably modified by region, baseline age or the length of follow-up. Accumulated literature indicates a modest inverse association between sleep duration and the risk of childhood overweight/obesity. Further research is needed to determine the age and gender specified optimal hours of sleep and ideal sleep pattern with respect to obesity prevention in children.