A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease

With an overall prevalence of 10-20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries. We performed an association scan of >500,000 SNPs in 280 individuals with gallstones and 360 controls. A follow-up study of the 235 most significant SNPs in 1,105 affected individuals and 873 controls replicated the disease association of SNP A-1791411 in ABCG8 (allelic P value P(CCA) = 4.1 x 10(-9)), which was subsequently attributed to coding variant rs11887534 (D19H). Additional replication was achieved in 728 German (P = 2.8 x 10(-7)) and 167 Chilean subjects (P = 0.02). The overall odds ratio for D19H carriership was 2.2 (95% confidence interval: 1.8-2.6, P = 1.4 x 10(-14)) in the full German sample. Association was stronger in subjects with cholesterol gallstones (odds ratio = 3.3), suggesting that His19 might be associated with a more efficient transport of cholesterol into the bile.     

基于先验知识与模块性的网络社区结构探测算法

在分析模块性指标和Newman有关网络社区结构探测算法的基础上，提出了一种基于先验知识与模块性的社区结构探测算法．利用节点度等社会网络结构先验知识，获得一个社区结构的基本划分，然后进行社区的合并，以此获得一个清晰的社区结构．经计算机模拟网络、Ucinet软件网络和中国农民工社会网络的社区结构探测，结果表明所提算法比Newman的迭代次数减少近50％，并且可以获得更好的模块性指标．     

Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration

Influenza viruses account for significant morbidity worldwide. Inflammatory responses, including excessive generation of reactive oxygen and nitrogen species (RONS), mediate lung injury in severe influenza infections. However, the molecular basis of inflammation-induced lung damage is not fully understood. Here, we studied influenza H1N1 infected cells in vitro, as well as H1N1 infected mice, and we monitored molecular and cellular responses over the course of 2 weeks in vivo. We show that influenza induces DNA damage to both, when cells are directly exposed to virus in vitro (measured using the comet assay) and also when cells are exposed to virus in vivo (estimated via γH2AX foci). We show that DNA damage, as well as responses to DNA damage persist in vivo until long after virus has been cleared, at times when there are inflammation associated RONS (measured by xanthine oxidase activity and oxidative products). The frequency of lung epithelial and immune cells with increased γH2AX foci is elevated in vivo, especially for dividing cells (Ki-67-positive) exposed to oxidative stress during tissue regeneration. Additionally, we observed a significant increase in apoptotic cells as well as increased levels of DNA double strand break (DSB) repair proteins Ku70, Ku86 and Rad51 during the regenerative phase. In conclusion, results show that influenza induces DNA damage both in vitro and in vivo, and that DNA damage responses are activated, raising the possibility that DNA repair capacity may be a determining factor for tissue recovery and disease outcome.     

Interannual atmospheric variability forced by the deep equatorial Atlantic Ocean

Climate variability in the tropical Atlantic Ocean is determined by large-scale ocean-atmosphere interactions, which particularly affect deep atmospheric convection over the ocean and surrounding continents. Apart from influences from the Pacific El Ni?o/Southern Oscillation and the North Atlantic Oscillation, the tropical Atlantic variability is thought to be dominated by two distinct ocean-atmosphere coupled modes of variability that are characterized by meridional and zonal sea-surface-temperature gradients and are mainly active on decadal and interannual timescales, respectively. Here we report evidence that the intrinsic ocean dynamics of the deep equatorial Atlantic can also affect sea surface temperature, wind and rainfall in the tropical Atlantic region and constitutes a 4.5-yr climate cycle. Specifically, vertically alternating deep zonal jets of short vertical wavelength with a period of about 4.5?yr and amplitudes of more than 10?cm?s(-1) are observed, in the deep Atlantic, to propagate their energy upwards, towards the surface. They are linked, at the sea surface, to equatorial zonal current anomalies and eastern Atlantic temperature anomalies that have amplitudes of about 6?cm?s(-1) and 0.4?°C, respectively, and are associated with distinct wind and rainfall patterns. Although deep jets are also observed in the Pacific and Indian oceans, only the Atlantic deep jets seem to oscillate on interannual timescales. Our knowledge of the persistence and regularity of these jets is limited by the availability of high-quality data. Despite this caveat, the oscillatory behaviour can still be used to improve predictions of sea surface temperature in the tropical Atlantic. Deep-jet generation and upward energy transmission through the Equatorial Undercurrent warrant further theoretical study.     

Improved business planning through an awareness of political cycles

Can business planning be improved if more attention is paid to underlying political cycles? This paper compares practitioner and researcher perspectives on this issue. While practioners stand to gain useful insights from a careful examination of past political cycles, these insights may be disconfirmed by rigorous tests carried out by researchers. In this paper we isolate and examine five hypotheses from the literature on the political-economic cycle.     

The anchor and adjustment heuristic in time-series forecasting

This paper explores the relevance of the anchor and adjustment heuristic in judgmental time-series extrapolation. Using a database of real time series it examines the proposition that people anchor on the last history value of the series and make insufficient adjustments from it in making their forecast. In contrast to studies in behavioral decision making, analysis shows that the anchor and adjustment heuristic does not describe the behavior of time-series forecasters. Adjustments from the anchor are often excessive, not insufficient. A number of possible explanations for this exceptional finding are explored.     

Conceptual Barriers to Progress Within Evolutionary Biology

In spite of its success, Neo-Darwinism is faced with major conceptual barriers to further progress, deriving directly from its metaphysical foundations. Most importantly, neo-Darwinism fails to recognize a fundamental cause of evolutionary change, “niche construction”. This failure restricts the generality of evolutionary theory, and introduces inaccuracies. It also hinders the integration of evolutionary biology with neighbouring disciplines, including ecosystem ecology, developmental biology, and the human sciences. Ecology is forced to become a divided discipline, developmental biology is stubbornly difficult to reconcile with evolutionary theory, and the majority of biologists and social scientists are still unhappy with evolutionary accounts of human behaviour. The incorporation of niche construction as both a cause and a product of evolution removes these disciplinary boundaries while greatly generalizing the explanatory power of evolutionary theory.

Triplet-singlet spin relaxation via nuclei in a double quantum dot

The spin of a confined electron, when oriented originally in some direction, will lose memory of that orientation after some time. Physical mechanisms leading to this relaxation of spin memory typically involve either coupling of the electron spin to its orbital motion or to nuclear spins. Relaxation of confined electron spin has been previously measured only for Zeeman or exchange split spin states, where spin-orbit effects dominate relaxation; spin flips due to nuclei have been observed in optical spectroscopy studies. Using an isolated GaAs double quantum dot defined by electrostatic gates and direct time domain measurements, we investigate in detail spin relaxation for arbitrary splitting of spin states. Here we show that electron spin flips are dominated by nuclear interactions and are slowed by several orders of magnitude when a magnetic field of a few millitesla is applied. These results have significant implications for spin-based information processing.