WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature

Macrophages have a critical role in inflammatory and immune responses through their ability to recognize and engulf apoptotic cells. Here we show that macrophages initiate a cell-death programme in target cells by activating the canonical WNT pathway. We show in mice that macrophage WNT7b is a short-range paracrine signal required for WNT-pathway responses and programmed cell death in the vascular endothelial cells of the temporary hyaloid vessels of the developing eye. These findings indicate that macrophages can use WNT ligands to influence cell-fate decisions--including cell death--in adjacent cells, and raise the possibility that they do so in many different cellular contexts.     

Long-term decline of global atmospheric ethane concentrations and implications for methane

After methane, ethane is the most abundant hydrocarbon in the remote atmosphere. It is a precursor to tropospheric ozone and it influences the atmosphere's oxidative capacity through its reaction with the hydroxyl radical, ethane's primary atmospheric sink. Here we present the longest continuous record of global atmospheric ethane levels. We show that global ethane emission rates decreased from 14.3 to 11.3 teragrams per year, or by 21 per cent, from 1984 to 2010. We attribute this to decreasing fugitive emissions from ethane's fossil fuel source--most probably decreased venting and flaring of natural gas in oil fields--rather than a decline in its other major sources, biofuel use and biomass burning. Ethane's major emission sources are shared with methane, and recent studies have disagreed on whether reduced fossil fuel or microbial emissions have caused methane's atmospheric growth rate to slow. Our findings suggest that reduced fugitive fossil fuel emissions account for at least 10-21 teragrams per year (30-70 per cent) of the decrease in methane's global emissions, significantly contributing to methane's slowing atmospheric growth rate since the mid-1980s.     

Global variation in copy number in the human genome

Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.     

Strategies for mitigating an influenza pandemic

Development of strategies for mitigating the severity of a new influenza pandemic is now a top global public health priority. Influenza prevention and containment strategies can be considered under the broad categories of antiviral, vaccine and non-pharmaceutical (case isolation, household quarantine, school or workplace closure, restrictions on travel) measures. Mathematical models are powerful tools for exploring this complex landscape of intervention strategies and quantifying the potential costs and benefits of different options. Here we use a large-scale epidemic simulation to examine intervention options should initial containment of a novel influenza outbreak fail, using Great Britain and the United States as examples. We find that border restrictions and/or internal travel restrictions are unlikely to delay spread by more than 2-3 weeks unless more than 99% effective. School closure during the peak of a pandemic can reduce peak attack rates by up to 40%, but has little impact on overall attack rates, whereas case isolation or household quarantine could have a significant impact, if feasible. Treatment of clinical cases can reduce transmission, but only if antivirals are given within a day of symptoms starting. Given enough drugs for 50% of the population, household-based prophylaxis coupled with reactive school closure could reduce clinical attack rates by 40-50%. More widespread prophylaxis would be even more logistically challenging but might reduce attack rates by over 75%. Vaccine stockpiled in advance of a pandemic could significantly reduce attack rates even if of low efficacy. Estimates of policy effectiveness will change if the characteristics of a future pandemic strain differ substantially from those seen in past pandemics.     

Assessment of the uncertainties in temperature change in China during the last century

We have used the China Homogenized Historic Temperature dataset and some long-term station series of the neighbor countries from CRUTEM3, a 5°×5° gridded dataset of monthly mean temperature since 1900, to provide a 107-year record of surface tem-perature trends and variability. We derived a comprehensive set of uncertainty estimates to accompany the data: measurement and sampling errors, uncertainties in temperature bias estimates, and uncertainties arising from limited observational coverage on large-scale averages have all been estimated. We reanalysed the temperature changes during the period of record. The best estimates of trends for 1900–2006 with uncertainties at 95% confidence range are about 0.09±0.017°C/decade for the year as a whole, and 0.14±0.021°C/decade, 0.11±0.021°C/decade, 0.04±0.017°C/decade, and 0.07±0.017°C/decade for winter, spring, summer and autumn respectively. For 1954–2006, the trends for annual, winter, spring, summer and autumn are: 0.26±0.032°C/decade, 0.35±0.046°C/decade, 0.25±0.051°C/decade, 0.16±0.037°C/decade and 0.22±0.055°C/decade. Winter saw the most significant warming trend in both 1900–2006 and 1954–2006, while during the most recent period (the satellite era, 1979–2006), all the seasons show similar warming trends: 0.45±0.13°C/decade, 0.51±0.11°C/decade, 0.52±0.16°C/decade, 0.37±0.10°C/decade and 0.50±0.16°C/decade for annual, winter, spring, summer and autumn. Trends arising from urbanization have been evaluated as less than 5% of the total warming trend for 1951–2001, so this bias was not removed.