Variation in FTO contributes to childhood obesity and severe adult obesity

We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.     

PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.     

Poly(ADP-ribose) is required for spindle assembly and structure

The mitotic spindle is typically thought of as an array of microtubules, microtubule-associated proteins and motors that self-organizes to align and segregate chromosomes. The major spindle components consist of proteins and DNA, the primary structural elements of the spindle. Other macromolecules including RNA and lipids also associate with spindles, but their spindle function, if any, is unknown. Poly(ADP-ribose) (PAR) is a large, branched, negatively charged polymeric macromolecule whose polymerization onto acceptor proteins is catalysed by a family of poly(ADP-ribose) polymerases (PARPs). Several PARPs localize to the spindle in vertebrate cells, suggesting that PARPs and/or PAR have a role in spindle function. Here we show that PAR is enriched in the spindle and is required for spindle function--PAR hydrolysis or perturbation leads to rapid disruption of spindle structure, and hydrolysis during spindle assembly blocks the formation of bipolar spindles. PAR exhibits localization dynamics that differ from known spindle proteins and are consistent with a low rate of turnover in the spindle. Thus, PAR is a non-proteinaceous, non-chromosomal component of the spindle required for bipolar spindle assembly and function.     

Perceived luminance depends on temporal context

Brightness--the perception of an object's luminance--arises from complex and poorly understood interactions at several levels of processing. It is well known that the brightness of an object depends on its spatial context, which can include perceptual organization, scene interpretation, three-dimensional interpretation, shadows, and other high-level percepts. Here we present a new class of illusion in which temporal relations with spatially neighbouring objects can modulate a target object's brightness. When compared with a nearby patch of constant luminance, a brief flash appears brighter with increasing onset asynchrony. Simultaneous contrast, retinal effects, masking, apparent motion and attentional effects cannot account for this illusory enhancement of brightness. This temporal context effect indicates that two parallel streams--one adapting and one non-adapting--encode brightness in the visual cortex.     

Interhemispheric climate links revealed by late-glacial cooling episode in southern Chile

Understanding the relative timings of climate events in the Northern and Southern hemispheres is a prerequisite for determining the causes of abrupt climate changes. But climate records from the Patagonian Andes and New Zealand for the period of transition from glacial to interglacial conditions--about 14.6-10 kyr before present, as determined by radiocarbon dating--show varying degrees of correlation with similar records from the Northern Hemisphere. It is necessary to resolve these apparent discrepancies in order to be able to assess the relative roles of Northern Hemisphere ice sheets and oceanic, atmospheric and astronomical influences in initiating climate change in the late-glacial period. Here we report pollen records from three sites in the Lake District of southern Chile (41 degrees S) from which we infer conditions similar to modern climate between about 13 and 12.2 14C kyr before present (BP), followed by cooling events at about 12.2 and 11.4 14C kyr BP, and then by a warming at about 9.8 14C kyr BP. These events were nearly synchronous with important palaeoclimate changes recorded in the North Atlantic region, supporting the idea that interhemispheric linkage through the atmosphere was the primary control on climate during the last deglaciation. In other regions of the Southern Hemisphere, where climate events are not in phase with those in the Northern Hemisphere, local oceanic influences may have counteracted the effects that propagated through the atmosphere.     

2-Phenylethanol, a presumed sexual stimulant produced by the male cabbage looper moth, Trichoplusia ni.

A sex pheromone produced by male cabbage looper moths, Trichoplusia ni (Hübner), has been isolated from the genital scent brushes and identified as 2-phenylethanol. It is shown conclusively to elicit specific behavioural responses in the female (such as wing vibration and abdominal elevation), as determined by a novel behavioural laboratory bioassay. This is taken as further evidence that the male pheromone of T. ni acts as a sexual stimulant (aphrodisiac) prior to mating. 2-Phenylethanol represents the first identification of a genital scent brush pheromone in the family Noctuidae, and of a male pheromone in the subfamily Plusiinae.