An unusually brilliant transient in the galaxy M85

Historically, variable and transient sources have both surprised astronomers and provided new views of the heavens. Here we report the discovery of an optical transient in the outskirts of the lenticular galaxy Messier 85 in the Virgo cluster. With a peak absolute R magnitude of -12, this event is distinctly brighter than novae, but fainter than type Ia supernovae (which are expected in a population of old stars in lenticular galaxies). Archival images of the field do not show a luminous star at that position with an upper limit in the g filter of about -4.1 mag, so it is unlikely to be a giant eruption from a luminous blue variable star. Over a two-month period, the transient source emitted radiation energy of almost 10(47) erg and subsequently faded in the optical sky. It is similar to, but six times more luminous at peak than, an enigmatic transient in the galaxy M31 (ref. 1). A possible origin of M85 OT2006-1 is a stellar merger. If so, searches for similar events in nearby galaxies will not only allow study of the physics of hyper-Eddington sources, but also probe an important phase in the evolution of stellar binary systems.     

Temporal dissociation of parallel processing in the human subcortical outputs.

Many tasks require rapid and fine-tuned adjustment of motor performance based on incoming sensory information. This process of sensorimotor adaptation engages two parallel subcorticocortical neural circuits, involving the cerebellum and basal ganglia, respectively. How these distributed circuits are functionally coordinated has not been shown in humans. The cerebellum and basal ganglia show very similar convergence of input-output organization, which presents an ideal neuroimaging model for the study of parallel processing at a systems level. Here we used functional magnetic resonance imaging to measure the temporal coherence of brain activity during a tactile discrimination task. We found that, whereas the prefrontal cortex maintained a high level of activation, output activities in the cerebellum and basal ganglia showed different phasic patterns. Moreover, cerebellar activity significantly correlated with the activity of the supplementary motor area but not with that of the primary motor cortex; in contrast, basal ganglia activity was more strongly associated with the activity of the primary motor cortex than with that of the supplementary motor area. These results demonstrate temporally partitioned activity in the cerebellum and basal ganglia, implicating functional independence in the parallel subcortical outputs. This further supports the idea of task-related dynamic reconfiguration of large-scale neural networks.     

Rapid responses of British butterflies to opposing forces of climate and habitat change.

Habitat degradation and climate change are thought to be altering the distributions and abundances of animals and plants throughout the world, but their combined impacts have not been assessed for any species assemblage. Here we evaluated changes in the distribution sizes and abundances of 46 species of butterflies that approach their northern climatic range margins in Britain-where changes in climate and habitat are opposing forces. These insects might be expected to have responded positively to climate warming over the past 30 years, yet three-quarters of them declined: negative responses to habitat loss have outweighed positive responses to climate warming. Half of the species that were mobile and habitat generalists increased their distribution sites over this period (consistent with a climate explanation), whereas the other generalists and 89% of the habitat specialists declined in distribution size (consistent with habitat limitation). Changes in population abundances closely matched changes in distributions. The dual forces of habitat modification and climate change are likely to cause specialists to decline, leaving biological communities with reduced numbers of species and dominated by mobile and widespread habitat generalists.     

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.     

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.     

Genome-wide association study identifies a common variant associated with risk of endometrial cancer

Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.     

A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk

To identify risk variants for colorectal cancer (CRC), we conducted a genome-wide association study, genotyping 550,163 tag SNPs in 940 individuals with familial colorectal tumor (627 CRC, 313 advanced adenomas) and 965 controls. We evaluated selected SNPs in three replication sample sets (7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 (involved in TGF-beta and Wnt signaling) associated with CRC. Across the four sample sets, the association between rs4939827 and CRC was highly statistically significant (P(trend) = 1.0 x 10(-12)).     

The clinical potential of sphingolipid-based therapeutics

The era of sphingolipid-based therapeutics is upon us. A large body of work has been accumulating that demonstrates the distinct biological roles of sphingolipids in maintaining a homeostatic environment and in responding to environmental stimuli to regulate cellular processes. It is thus necessary to further investigate alterations in sphingolipid-metabolism in pathological conditions and, in turn, try to exploit altered sphingolipid-metabolizing enzymes and their metabolites as therapeutic targets. This review will examine how advances in the fields of drug delivery, drug discovery, synthetic chemistry, enzyme replacement therapy, immunobiology, infectious disease and nanotechnology have delivered the potential and promise of utilizing and/or targeting sphingolipid metabolites as therapies for diverse diseases.     

Genetic contributions to stability and change in intelligence from childhood to old age

Understanding the determinants of healthy mental ageing is a priority for society today. So far, we know that intelligence differences show high stability from childhood to old age and there are estimates of the genetic contribution to intelligence at different ages. However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative. Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years). We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals. We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change.