Hot off the presses! Aug 20 Nature

The Aug 20 issue of the Nature is now up on Pubget (About Nature): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Common consent
  - Nature 460(7258):933 (2009)
  The distribution of human cell lines used in research should not be hindered by restrictions from donors.
• A question of control
  - Nature 460(7258):933 (2009)
  Scientists must address the ethics of using neuroactive compounds to quash domestic crises.
• Biomaterials: Pearly pedigree
  - Nature 460(7258):934 (2009)
  
• Animal behaviour: Ties that bind
  - Nature 460(7258):934 (2009)
  
• Physics: Close heat
  - Nature 460(7258):934 (2009)
  
• Bioelectronics: It's electrifying
  - Nature 460(7258):934 (2009)
  
• Population ecology: Evolution to the rescue
  - Nature 460(7258):934 (2009)
  
• Neuroscience: Categorically hard-wired
  - Nature 460(7258):934-935 (2009)
  
• Cancer: From the source
  - Nature 460(7258):935 (2009)
  
• Biophysics: Protein friction
  - Nature 460(7258):935 (2009)
  
• Immunology: Helping the helpers
  - Nature 460(7258):935 (2009)
  
• Planetary science: What an atmosphere
  - Nature 460(7258):935 (2009)
  
• Journal club
  - Nature 460(7258):935 (2009)
  
• Paying to save the rainforests
  - Nature 460(7258):936-937 (2009)
  In Brazil, details are emerging for plans to stop deforestation. Can it serve as a model for other nations? Cash incentives could be part of a multi-pronged approach to stopping slash-and-burn deforestation.G. GILABERT/CORBIS SABA Along the Trans-Amazonian Highway in the Brazilian state of Pará, many landowners try to boost their income by clearing a hectare or two each year for farms or cattle grazing. This year, however, may be different: if all goes to plan, around 350 families will receive payments to put rainforest preservation first. If approved by the Brazilian Development Bank within the coming weeks, the project would be one of the first to stem from the Amazon Fund, a major initiative created by Brazil last year to attract international aid. It is the largest forest-conservation initiative in the world, and the only national programme that could demonstrate how tropical-forest protection might be folded into the global-warming treaty that international leaders hope to sign in Copenhagen in December. "The Amazon Fund could be interpreted as the fundamental test case for the rest of the world," says Paulo Moutinho, who heads research at the Amazon Institute for Environmental Research (IPAM) in Brasília. "The international community is watching Brazil and how we will deal with this experiment." With a total price tag of about US$17 million, the Pará project is just one example of how the Amazon Fund could distribute its money. Landowners who sign up to preserve their forest would begin receiving monthly cheques, starting at around $16 and increasing to $350 in the tenth and final year. Other investments would help to modernize local agriculture in an effort to increase income from land that is already cleared, so that landowners don't need to begin cutting down trees again when the payments stop. Moutinho says the programme could be scaled up to 10,000 families in the Pará region alone. All told, the project would reduce the otherwise expected greenhouse-gas emissions by 3.1 million tonnes of carbon dioxide — equivalent to taking more than half a million vehicles off the road for one year — at a cost of just more than $5 per tonne. That is 75% less than the going price on the European carbon market. Backed by a satellite monitoring system and an increasingly focused enforcement programme, Brazil thus has an opportunity to show whether this way of reducing emissions from deforestation and degradation (REDD) works. "I would call the Amazon Fund the biggest experiment in tropical conservation history," says Dan Nepstad, a researcher at the Woods Hole Research Center in Massachusetts. "If it works, REDD will survive. If it fails, there's a chance REDD will fail." "The Amazon Fund is the biggest experiment in tropical conservation history." The Amazon River basin covers some 7 million square kilometres and nearly half of Brazil. By some estimates 15% of the basin has been cleared in recent decades. Worldwide, deforestation accounts for as much as 20% of greenhouse-gas emissions, and up to 70% of Brazil's emissions. Climate negotiators in the United Nations talks are looking at various ways to link international carbon markets to forest conservation, but Brazil has long opposed the idea of allowing US or European companies to offset their emissions by paying for forest conservation projects in the tropics. The Amazon Fund was designed as an alternative, allowing Brazil to deploy direct international aid as part of a comprehensive national strategy. Last year Brazil pledged to reduce deforestation by 70% by the end of 2017; the government has since extended that commitment to 80% by 2020. Source: Instituto de Pesquisa Ambiental da Amazônia Achieving those goals won't be easy, given poverty levels, enforcement difficulties and ongoing questions about who holds title to what land. Even within the federal government, policies promoting agricultural growth are often at loggerheads with those intended to protect rainforest. Deforestation rates fell for three years after peaking in 2004 (see graphic), but then increased in the 2008 season when prices spiked for commodities such as soya and beef. Deforestation rates seem to have dropped again in the most recent season; experts credit better enforcement and new policies but also the economic crisis, which cut demand for many commodities. The Amazon Fund got off the ground with a pledge from Norway, which committed up to $1 billion until 2015. Brazil will receive around $114 million this year, but must continue reducing emissions in order to receive future payments. Climate negotiators are increasingly focusing on national baselines such as this, instead of on particular projects that might save one patch of forest while pushing loggers, developers and landowners down the road to another patch. Getting REDD right in Brazil and beyond is "totally possible and essential", says Lars Løvold, director of the Rainforest Foundation Norway in Oslo, which, along with Friends of the Earth Norway, proposed to the Norwegian government that it invest in a big forest conservation initiative. "But you need some projects to show that it works." Eyes in the sky In the coming weeks, the Brazilian Development Bank, which manages the Amazon Fund, is expected to announce the first such project awards. Several dozen applications have been submitted, ranging from community initiatives like the project in Pará to land registry programmes and a proposal from Brazil's National Institute for Space Research for a new satellite to monitor deforestation. Within Brazil, the money coming from abroad has whetted local appetites for more. And in June, the nine governors of the Brazilian states in the Amazon region penned a letter to Brazilian President Luiz Inácio Lula da Silva urging the country to reconsider its opposition to directly tapping carbon markets for forest conservation. The governors called the Copenhagen talks "a golden opportunity", suggesting that carbon markets could surpass $2 trillion annually by 2020 and $15 trillion in 2050. ADVERTISEMENT Paulo Adario, Amazon campaign director for the Brazilian arm of environmental organization Greenpeace, is wary of governors opening their states directly to international investments; such a deal, he says, could undermine the idea of a national baseline, without which there is no way to protect the forest as a whole. "The federal government needs to have a national vision about the problems and the solutions for the country," he says, "and then performance will be evaluated against results." The official deforestation data for the 2009 season, which ended in July, will be available in December. Preliminary results suggest that total deforestation will hit a two-decade low of less than 10,000 square kilometres — low enough to secure another payment from Norway in 2010. There are currently no comments.
• Nanoparticle safety in doubt
  - Nature 460(7258):937 (2009)
  Lung damage in Chinese factory workers sparks health fears. Could nanoparticles cause some lung damage?C. Juste/Miami Herald/Newscom Claims that seven Chinese factory workers developed severe lung damage from inhaling nanoparticles are stoking the debate over the environmental-health effects of nanotechnology. A paper published in the European Respiratory Journal claims to be the first to document cases of ill health caused by nanoparticles in humans (Y. Song, X. Li and X. Du Eur. Respir. J. 34, 559–567; 2009). Other experts are sceptical as to whether nanoparticles are actually to blame, but the paper has triggered lively discussions. "The study raises the bar for doing appropriate research as fast as possible to find out where the dangers might lie when working with nanomaterials," says Andrew Maynard, a nanotechnology expert at the Woodrow Wilson International Center for Scholars in Washington DC. The study describes seven women, aged 18–47 years, who worked in an unidentified printing factory in China; two of them later died. They all had pleural granulomas — ball-like collections of immune cells in the lining of the lung that form when the immune system is unable to remove a foreign body. They also had excessive, discoloured fluid in the lung lining. Particles around 30 nanometres in diameter were found in lung fluid and tissue. The study says that the symptoms were caused by inhaling fumes produced when the workers heated polystyrene boards to 75–100 °C. The boards had previously been sprayed with a 'paste material' made from a plastic identified as a polyacrylate ester. "We can't say what the link is or if there are other exacerbating circumstances." The workroom, of around 70 square metres, had one door and no windows. The ventilation unit had broken down five months before symptoms started to manifest, and the door had been kept closed to keep the room warm. The workers wore cotton gauze masks only on an "occasional basis". Electron microscopy found nanoparticles around 30 nanometres in diameter in the paste and in dust particles that had collected at the inlet of the broken ventilation unit. Lead author Yuguo Song, a clinical toxicologist at Beijing Chaoyang Hospital, says "it is obvious the disease is not due to microparticles or vapours, because the pulmonary epithelial cells are full of nanoparticles". Maynard says the symptoms seen in the patients are "similar" to those seen in animals exposed to nanoparticles. He adds that damage to the areas surrounding the lungs suggests that larger particles are not to blame, as these tend to be constrained within the lungs. But because the study does not identify what nanoparticles were involved or their concentration, he says, "we can't say what the link is or if there are other exacerbating circumstances". Ken Donaldson, a respiratory toxicologist at the University of Edinburgh, UK, doubts that nanoparticles are to blame. He says the symptoms are more typical of chemical exposure. "I don't doubt that nanoparticles were present, but that does not mean they were the main arbiters," he says. ADVERTISEMENT Donaldson says that the plastic material the patients worked with is the more likely culprit — as it would have been highly toxic at the levels they were probably exposed to given the size of the room they worked in and its lack of ventilation. Anthony Seaton, an emeritus professor in environmental and occupational medicine at the University of Aberdeen, UK, agrees that the study does not pin down nanoparticles as the cause of the ill health. Rather than an insight into the toxicology of nanoparticles, he says, the study is an example of a "total failure in health and safety procedures".
• Japan election sparks science pledges
  - Nature 460(7258):938 (2009)
  Both parties make vague promises about research, but differ in their climate targets. Yukio Hatoyama, president of the opposition DPJ.K. SASAHARA/AP Japan's upcoming elections, on 30 August, could see the party that has ruled almost continuously for more than half a century lose its grip on power. As Nature went to press, polls suggested that the Democratic Party of Japan (DPJ) would take a majority in the lower house of parliament, giving it the right to appoint a prime minister to replace Taro Aso of the Liberal Democratic Party (LDP). Some researchers have expressed concern that the DPJ, with its emphasis on the responsible use of taxes, might cut basic-research budgets. Last week at a press conference, DPJ president Yukio Hatoyama tried to dispel such rumours. "Japan should be a leading country in basic science," he said in response to a question from Nature. "If anything, I think overall scientific funding should be expanded." The DPJ has been throwing out similar promises to voters concerned about Japan's struggling economy. For example, the party's manifesto includes a new annual allowance of ¥312,000 (US$3,300) for every child until they finish junior high school. The party says that it can pay for this and other big programmes by reducing spending elsewhere, such as on road and dam projects, and shifting decision-making power towards elected officials and away from government bureaucrats. SOURCE: MEXT But Japan last week officially pulled out of recession, and many scientists have been happy with the way bureaucrats have fought to maintain or even increase the science budget during slow economic growth (see chart) when most other sectors of government were seeing budgets cut. Major projects include the Japan Proton Accelerator Research Complex in Tokaimura and the X-ray free-electron laser scheduled to be completed next year at the SPring-8 synchrotron in western Japan. Biophysicist Akiyoshi Wada, former director of RIKEN's Genomic Sciences Center in Yokohama, speculates that the DPJ's declared drive to get rid of waste might affect research. "They say they want to stop listening to the bureaucrats, but how much will they be able to do without?" Wada asks. "Large-scale 'challenging' projects might get drastically cut." Indeed, the party's manifesto promises to re-evaluate the "independent administrative organizations" that include many of Japan's largest research bodies, among them RIKEN. In response to a Nature questionnaire, Hatoyama's office pledged support for big projects: "Japan is already a top runner in some fields that require huge budgets, like particle physics," it said, "and we will actively aim to maintain that position by building world-class research bases and deepening research ties with Europe, the United States and Asian countries." The statement also said that the DPJ would take (unspecified) measures to increase the science budget. It noted that although Japan overall invests a high percentage of its gross domestic product (GDP) in research — 3.67% in 2007 — the percentage of government investment is low compared with investment by industry. "Cultivating researchers needs to be part of our central policies," the statement said. Hatoyama received a doctorate in engineering from Stanford University in California and was a professor at the Tokyo Institute of Technology. He plays down his scientific background, saying "what matters for politicians is having principles and convictions, and a broad perspective". Naoto Kan, the former DPJ head and one of its two acting presidents, got a doctorate in applied physics before becoming a patent lawyer; some say he might bring more attention to issues that have plagued Japanese patent law, such as the need for broader patents to compete with the United States and streamlining the lengthy patent application procedure. Hatoyama says that the DPJ will create a 'science and technology strategy office' to replace the Council for Science and Technology Policy (CSTP), the country's highest science-policy body. Like the CSTP, the new office would coordinate science-related budget requests, but it would also, in ways unspecified, take a more active role in "promoting basic and applied sciences in a unified manner". If the DPJ does create a top-level scientific body, this might find itself in the thick of an ongoing debate over the role of big science projects. Tadamitsu Kishimoto, an immunologist at Osaka University and a former CSTP member, says money has been wasted on big biology projects, and he complains that the ¥270 billion earmarked for 30 new projects by the CSTP could be more of the same. "Right now young PIs don't get enough to work with," he says, "and using that money to give ¥10-million grants to many young researchers would produce a lot more good science." The LDP platform acknowledges the many Nobel prizes garnered by Japanese scientists, and vows to "educate and send out into the world more researchers than ever before", and to create 30 "world-class research facilities". ADVERTISEMENT On climate change, the DPJ calls for a cut in greenhouse-gas emissions to more than 25% below 1990 levels by 2020. The LDP's proposal of an 8% target has been criticized by developing countries and environmental groups as not going far enough. But Japan has consistently missed targets for its original Kyoto Protocol pledge to cut emissions to 6% below 1990 levels during 2008–12, and many in the business community in particular are sceptical about the DPJ's emissions targets. "If we follow the DPJ's targets, we will end up with a 3.2% drop in the GDP" based on government estimates, LDP secretary-general Hiroyuki Hosoda said last week. "The party that presents the more dramatic figure is more attractive, but it is not feasible," he said. There are currently no comments.
• Collins sets out his vision for the NIH
  - Nature 460(7258):939 (2009)
  Translational research and neglected diseases are on the agenda for incoming director. On his first day in the job, the new director of the US National Institutes of Health (NIH) laid out a five-point road map for the agency — which includes focusing greater attention on translational research, neglected diseases and health-care reform. But Francis Collins's top priority will be tackling budget constraints after the $10.4-billion boost from the economic stimulus package runs out in 2010. "I don't want you to think that all it's going to take is a few speeches or maybe a little playing the guitar for this to be successful," he said at a 17 August town-hall meeting at NIH headquarters in Bethesda. For example, he estimated that only around 3% of applicants for the stimulus-backed 'challenge grants' will be funded, although some have predicted success rates of below 1%. Collins has raised red flags about losing a generation of young scientists if the NIH budget drops or flatlines. The budget for fiscal year 2010 has not yet been finalized, but the administration of President Barack Obama has requested a 1.4% increase over the 2009 budget of $30.6 billion. Collins, who headed the National Human Genome Research Institute in Bethesda from 1993 to 2008, made the case that investment in biomedical research creates jobs and offers quick economic returns. Looking ahead, he said that the agency should devote more money to "five areas of special opportunity". First, to applying high-throughput technologies in genomics and nanotechnology to discover the genetic bases of diseases including cancer, autism, diabetes and neurodegenerative disorders. Second, to developing diagnostics, preventative strategies and therapeutic tools through more public–private partnerships. Third, to reining in the costs of health care with comparative-effectiveness research and personalized medicine. Fourth, to expanding research into diseases affecting the developing world. Finally, to increasing budgets and investing in training and peer review to achieve a predictable funding trajectory for the research community. "He presented a vision that was very much tailored to the times — scientifically and in terms of our public-health challenges, of where the nation is now, and where the mission of the NIH lies ahead," says Raynard Kington, who has served as acting director since last October and will return to his role of deputy director. Collins stressed that he plans to devote all his energy to his new position, although he will maintain an active research lab. His latest book (on personalized medicine) is slated for a January 2010 release, he said, and he has resigned from the Washington DC-based BioLogos Foundation, an organization he founded earlier this year aimed at bridging the gap between science and religion. "I don't want anyone at NIH or outside of NIH to think that I have a religious agenda in coming to this role," said Collins, a devout Christian. "I will not. I'm here as your scientific director and I will keep that focus." However, Collins's wife, genetic counsellor Diane Baker, will stay on the BioLogos board and will probably have a significant advisory role at the NIH, he said. There are currently no comments.
• Environmental concerns delay seismic testing
  - Nature 460(7258):939 (2009)
  Lawsuit puts research voyage on hold. US research vessel Marcus Langseth was scheduled to work in Canadian waters.Lamont–Doherty Earth Observatory An environmental lawsuit is threatening the departure of a long-planned, US$4.7-million research cruise to image sea-floor structures off the coast of western Canada. The RV Marcus Langseth, a vessel operated by Columbia University in New York for the US National Science Foundation, had acquired all its permits to depart on 21 August for the Endeavour hydrothermal vents, 250 kilometres southwest of Vancouver Island. But on 10 August, the Canadian activist legal group Ecojustice, in Vancouver, British Columbia, sued the university, the Canadian department of fisheries and oceans and the minister of foreign affairs, alleging among other things that proper procedures were not followed in assessing how the seismic air bursts set off during the cruise would affect marine life. Cruise co-leader Douglas Toomey, a geophysicist at the University of Oregon in Eugene, says the ship was specifically scheduled and routed to avoid whales, and that marine-mammal observers would be on hand when airguns were fired. As Nature went to press, a hearing on the lawsuit was being scheduled for this week. The cruise plans to sink 64 portable seismometers near the Endeavour vent field, fire airguns into the water for 10 days, then retrieve the data-laden seismometers that pop to the surface. Toomey hopes that the analysis will answer important questions about the flow of Earth's mantle, as well as about earthquakes in the region. ADVERTISEMENT Ecojustice officials didn't respond to interview requests, but a statement on its website attributed to group lawyer Lara Tessaro says that the Canadian government should "refuse to sanction the harassment of endangered whales". The lawsuit was filed on behalf of the Living Oceans Society and the Canadian Parks and Wilderness Society, and argues that the minister of foreign affairs should not grant the vessel clearance. The use of airguns for seismic studies in western Canada has stirred environmental anger before. In 2008, a joint US–Canadian study of granite structures underlying British Columbia was halted (see Nature 451, 3; 2008). Since then, the region has seen growing environmental activism, including a recent sabotage (see Nature doi:10.1038/news.2009.715; 2009) of an onshore explosive charge that was part of a seismic test. There are currently no comments.
• Cardiovascular disease gets personal
  - Nature 460(7258):940-941 (2009)
  Gene-association studies hint at better ways of treating the leading cause of death, but capitalizing on them is proving to be a slow and difficult process. Erika Check Hayden reports. Cardiovascular conditions are the leading cause of death worldwide.A. MASSEE/SPL As personalized cancer treatment edges into the clinic, doctors and scientists are hoping that cardiovascular disease — the world's top killer — will be next to benefit from genomics. An avalanche of studies has linked genetic variants to various cardiovascular conditions and to patients' responses to commonly prescribed drugs. First up could be genetic guidance for the anti-clotting agents warfarin and clopidogrel, followed by testing for genetic variants responsible for conditions such as atrial fibrillation, a heart-rhythm abnormality that is a leading cause of stroke. Doctors caution that there is a long way to go before the hints raised by gene-association studies translate into solid evidence that genetic variants can improve clinical practice. "I would hope that cardiovascular disease would be one of the next leading areas of personalized medicine, because it has such an enormous impact on public health," says Christopher Granger, a cardiologist at Duke University Medical Center in Durham, North Carolina. But "we're at a primitive stage right now", he says. Warfarin exemplifies some of the promise and pitfalls of personalized medicine. The drug is commonly used to prevent clotting in patients who have atrial fibrillation and other conditions, yet the dose needed varies from patient to patient; if it's not precisely right, it can trigger fatal haemorrhaging. In 2007, after studies found that variants in two genes, CYP2C9 and VKORC1, account for up to half of the reason why patient response differed, the US Food and Drug Administration (FDA) changed the labelling to suggest that doctors consider using genetic tests to guide dosing. Yet studies have failed to show that such tests help improve patient outcomes. In 2007, for instance, a trial of 206 people reported that using information about a patient's genetic variants to guide their dosing regimens didn't lessen the risk that patients on warfarin would develop unsafe levels of clotting proteins1. And this January, another group reported that genetic testing wouldn't save money if done in all patients prescribed the drug, partly because it still costs hundreds of dollars to determine the genetic variants of each patient2. The US National Heart, Lung and Blood Institute in Bethesda, Maryland, is now sponsoring a larger clinical trial to test the usefulness of genetically guided warfarin dosing. But as Eric Topol, director of the Scripps Translational Science Institute in La Jolla, California, says: "Warfarin was kind of the poster adult for pharmacogenomics, but it's really lost favour." He and other doctors now see greater potential instead for clopidogrel, marketed by Bristol-Myers Squibb of New York and Sanofi-Aventis of Paris as Plavix. Clopidogrel is given to fight clotting, including in patients who have already had a stroke or heart attack. The drug, second in the world in global sales, is converted in the body into an active form that inhibits the pro-clotting protein P2Y12. But it, too, can cause haemorrhages. In December, three groups reported that variations in the CYP2C19 gene were associated with an increased risk of cardiovascular events in patients on clopidogrel3,4,5, and a poor ability to convert clopidogrel into its active form4. And last month, the FDA approved a new drug, prasugrel, which is a more potent inhibitor of P2Y12 but also carries a higher risk of bleeding. It is conceivable that patients who have the genetic variants associated with poor response to clopidogrel might instead be treated with prasugrel, says Matthew Price, an interventional cardiologist at Scripps Clinic/Green Hospital in La Jolla. Misunderstood Predicting the overall risk of cardiovascular diseases is proving even more complicated than treating them with genetically targeted drugs. Many genome-wide association studies have been done, but few have uncovered variants that, on their own, boost the risk of cardiovascular disease very much. And taken together, the variants discovered so far still don't explain most of the genetic risk of various diseases. For instance, last January, US researchers aimed to improve risk prediction of cardiovascular disease by adding information about a genetic variant associated with coronary artery disease and diabetes to other risk factors, such as smoking, cholesterol levels and family history of heart attack.The variant, found on chromosome 9, had formed the basis of a genetic test sold by deCODE Genetics in Reykjavik, Iceland. The team found that genotyping the variant did not improve the ability to predict whether the 22,129 women in the study would develop heart disease6. "Our study didn't show very much change [in risk-prediction ability], especially over the risk score that had family history in it already," says Nina Paynter, team leader and an epidemiologist at Brigham and Women's. "I was a little bit disappointed." Since Paynter's study began, however, many more genetic associations with cardiac risk have been reported, and companies such as deCode, Navigenics of Foster City, California, and 23andMe of Mountain View, California, now sell tests that purport to assess heart-disease risk using combinations of these variants. Paynter's group is evaluating multi-variant genomic tests, as is the independent Evaluation of Genomic Applications in Practice and Prevention initiative set up by the US Centers for Disease Control and Prevention in 2004, which is expected to issue recommendations on their use this autumn. "I would hope that cardiovascular disease would be one of the next leading areas of personalized medicine." Other groups have already examined genomic tests for diabetes, which greatly increases the risk of heart disease and stroke. Last year, for instance, three groups published studies examining whether a number of variants associated with diabetes could predict a person's risk of developing this disease7,8,9. All found that the variants added little to the predictive value of known diabetes risk factors, such as obesity, smoking and family history. In addition, the way these genomics tests are reported can be confusing to consumers. Companies update consumers' risk profiles as new variants are discovered, but because each new variant changes a person's risk so little, variants added to a risk profile can cancel out previous ones. A team led by Cecile Janssens of Erasmus Medical College in Rotterdam, the Netherlands, showed this by studying the same diabetes-associated variants analysed in the 2008 risk-prediction studies10. When genotypes of 17 of these variants were added to an existing risk profile based on variants of TCF7L2 — a gene whose variants confer a substantial increase in risk of common forms of diabetes — 34% of the patients' risk profiles changed, for example, from high to low or low to high. When data about patients' age, sex and body mass index were added to the profiles, 29% changed risk categories, and 11% of the participants reverted to their initial risk category. Patients hoping to use their genotyping results to motivate healthy lifestyle changes might thus be confused when their disease risk changes multiple times without any action on their part, Janssens says: "Our studies show that these products are not ready for prime time." Cardiologists hope that will change, and see some promise on the horizon in specific cardiovascular diseases. Last month, for instance, two research teams published studies that linked variants in the ZFHX3 gene to atrial fibrillation11,12. Two years ago one of the same groups published variants adjacent to a separate gene, PITX2, that almost doubles the risk of atrial fibrillation13. Drugs and monitoring can be used to treat the condition, and might help prevent the roughly one-third of strokes that have no known cause. So atrial fibrillation could serve as an early example of genomic risk prediction, Topol says. "To be able to zoom in on the probable cause of a stroke by genomics, and then institute a much more intensive heart-rhythm monitoring programme, would be a whole new path that we didn't have months or even a year ago," he says. ADVERTISEMENT But even if the tests are proven useful, they may still have a limited impact on patient care — at least at first. Granger says that doctors already have various risk-prediction tools that work, but don't use them effectively. For instance, patients with higher levels of the protein complex troponin, an indicator of heart-muscle damage, do better on certain treatment strategies. But, Granger says, they are no more likely to get those drugs for various reasons, including that family doctors are not as familiar with the cardiac literature. "Part of our challenge is that we've already got some information that could help us better customize medicine to patient risk, and we tend not to be doing that in practice." Remedying that problem will require more physician education — and some knockout examples of genetic profiling aiding medicine, as seems to be happening in cancer. "Maybe we need a couple of major success stories of the benefit of using genetic variants for treatment of disease, and I think we're getting some of those," Granger says. Cancer drugs may be blazing the trail for personalized medicine, but cardiovascular drugs may not be far behind. * References * Anderson, J. L.et al. Circulation116, 2563-2570 (2007). * Eckman, M. H. , Rosand, J. , Greenberg, S. M. & Gage, B. F.Ann. Intern. Med.150, 73-83 (2009). * Collet, J.-P.et al. Lancet373, 309-317 (2009). * Mega, J. L.et al. N. Engl. J. Med.360, 354-362 (2009). * Simon, T.et al. N. Engl. J. Med.360, 363-375 (2009). * Paynter, N. P.et al. Ann. Intern. Med.150, 65-72 (2009). * Lango, H.et al. Diabetes57, 3129-3135 (2008). * van Hoek, M.et al. Diabetes57, 3122-3128 (2008). * Lyssenko, V.et al. N. Engl. J. Med.359, 2220-2232 (2008). * Mihaescu, R.et al. Genet. Med. advance online publication doi:10.1097/GIM.0b013e3181b13a4f (2009). * Benjamin, E. J.et al. Nature Genet.41, 879-881 (2009). * Gudbjartsson, D. F.et al. Nature Genet.41, 876-878 (2009). * Gudbjartsson, D. F.et al. Nature448, 353-357 (2007). There are currently no comments.
• NASA needs more money to track asteroid threats
  - Nature 460(7258):943 (2009)
  NASA won't reach its mandated goal of tracking nearly all potentially hazardous near-Earth asteroids by 2020 with its current funding, according to an interim report published by the US National Research Council last week. In 2005, the US Congress gave NASA a deadline of 2020 to detect, track and characterize 90% of near-Earth objects bigger than 140 metres. This is the size of objects thought to pose a significant risk if striking in urban areas, and at least twice the size of the object that levelled 2,000 square kilometres of Siberian forest in the 1908 Tunguska explosion. The report, the final version of which is expected at the end of the year, says that the goal could be reached if more funding is found for future facilities, such as the Large Synoptic Survey Telescope or the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS). It also cites the importance of the large Arecibo radar telescope in Puerto Rico, which is well suited to characterizing asteroids once they are found. There are currently no comments.
• World population will grow fastest in poorest areas
  - Nature 460(7258):943 (2009)
  SOURCES: POPULATION REF. BUREAU, UN POPULATION DIV. The world's least-developed regions will double in population between now and 2050, from 828 million to 1.66 billion, predicts the non-profit Population Reference Bureau, based in Washington DC, in data published last week. These 49 countries, 33 of which are in Africa, have the lowest incomes, highest economic vulnerability and poorest human-development indicators according to United Nations definitions. The bureau's projections show that, over the same time period, the population of the world's more developed countries will creep up 7%, from 1.23 billion to 1.32 billion — fuelled mainly by immigration from less-developed regions. In the United States, however, more than half of the expected growth will be due to births there; it has one of the highest fertility rates in the developed world. Worldwide, the population could hit 9.4 billion in 2050, up from 6.8 billion today and topping 7 billion in the latter half of 2011. By 2050, India will overtake China as the world's most populous country. There are currently no comments.
• Australia seeks carbon-reduction compromise
  - Nature 460(7258):943 (2009)
  Following last week's defeat in the Senate of his proposed scheme for reducing carbon emissions, Australian Prime Minister Kevin Rudd was this week hoping at least to spur billions of dollars of renewable-energy investment. As Nature went to press, a law requiring 20% of Australia's energy to come from renewable sources by 2020 was expected to make its way through parliament. The energy bill was delinked from a much broader legislative package that would use a cap-and-trade scheme to limit greenhouse-gas emissions from industry (see Nature 458, 554–555; 2009). But that was voted down by opposition politicians on 12 August. Rudd intends to re-submit the contentious emissions-trading scheme to Senate for voting before the end of the year. There are currently no comments.
• Innovation urged for water management in Asia
  - Nature 460(7258):943 (2009)
  Asian irrigation systems require urgent reform, according to a report published on 18 August by the International Water Management Institute in Battaramulla, Sri Lanka, together with the Food and Agriculture Organization of the United Nations and other partner groups. Canals in many Asian regions are in dire need of maintenance.INT. WATER MANAGEMENT INST. Asia contains 70% of the world's irrigated land, much of it watered by state-funded canal systems that were installed in the 1970s. But the systems are poorly maintained. If Asia is to meet the needs of its growing population, the report says, it needs more efficient, better-regulated irrigation systems; more involvement by the private sector in managing them; and more education about, and investment in, watering programmes. The report also suggests that governments should support and regulate extraction from groundwater aquifers by individual farmers, rather than condemn the practice. There are currently no comments.
• Conflict of interest and resignation at drug agency
  - Nature 460(7258):943 (2009)
  The upper echelons of the US Food and Drug Administration (FDA) received unwanted attention last week. Daniel Schultz, head of the FDA's medical device division, resigned after allegations from employees that products were approved despite the concerns of agency scientists. And it emerged that California-based Amphastar Pharmaceuticals had in April asked the FDA that Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, be removed from judging drug approvals of a generic blood-thinner because of her interactions with a competing firm, Momenta Pharmaceuticals, based in Cambridge, Massachusetts. Woodcock asked Momenta's co-founder, Ram Sasisekharan, to lead an FDA task force investigating tainted Chinese-made heparin last year, and she and Momenta scientists then co-authored medical journal articles on the topic. The FDA is looking into the complaints. There are currently no comments.
• Climate gloom
  - Nature 460(7258):943 (2009)
  "If we don't have more movement and more consensus than we saw here, we won't have an agreement." Jonathan Pershing, US lead climate negotiator. "The best likely outcome in Copenhagen may be an interim agreement nailing down the basic architecture." Elliot Diringer, vice-president of the Pew Center on Global Climate Change in Arlington, Virginia. "My fear is that we sign another agreement that doesn't have any teeth." Kevin Conrad, delegate from Papua New Guinea. "It would be incomprehensible if this opportunity were lost." Yvo de Boer, executive secretary of the United Nations Framework Convention on Climate Change. Sources: New York Times, AP, Bloomberg, AFP There are currently no comments.
• Biodiversity: Rack and field
  - Nature 460(7258):944-946 (2009)
  More than 100 streams run through Bradley Cardinale's laboratory. Some trickle, others gush. There are currently no comments.
• Mouse genetics: The check-up
  - Nature 460(7258):947-948 (2009)
  Each and every Thursday it is the same. At 10 a.m., the conference room at the Helmholtz Centre Munich starts to fill with top consultants and clinical researchers from the university hospitals in Munich, Bonn and Heidelberg. There are currently no comments.
• International peer review improved Irish research rankings
  - Nature 460(7258):949 (2009)
  Your News story 'Italy outsources peer review to NIH' (Nature459, 900; 2009) highlights a problem common to many countries with a small population of research scientists. Ireland can be held up as a successful model in addressing this problem because, over the past eight years, funding agencies have moved to fully international peer review.
• Hispanic people start leaping over barriers to better jobs
  - Nature 460(7258):949 (2009)
  Earlier this month, Sonia Sotomayor was confirmed as a member of the US Supreme Court, the first judge of Puerto Rican descent to be appointed. It is an encouraging result for both women and Hispanic people in the United States.
• Whistleblowers at risk as science fails to correct itself
  - Nature 460(7258):949 (2009)
  In his review of my book about Jan Hendrik Schön's fraud at Bell Laboratories, Plastic Fantastic: How the Biggest Fraud in Physics Shook the Scientific World, Martin Blume argues that the vigilance of whistleblowers is part of the natural corrective process of science ('Keeping up scientific standards' Nature 459, 645–646; 2009). I disagree.
• South Dakota school replies to sexual harassment claims
  - Nature 460(7258):949 (2009)
  Your News story 'Sex scandal allegations surface at South Dakota school' (Nature459, 148; 2009) questions how the South Dakota School of Mines and Technology "will handle human-resource issues under its ... subcontract for the Deep Underground Science and Engineering Laboratory" in the light of alleged issues of sexual harassment. Your implication is unfair.
• Biologists napping while work militarized
  - Nature 460(7258):950-951 (2009)
  As researchers discover more agents that alter mental states, the Chemical Weapons Convention needs modification to help ensure that the life sciences are not used for hostile purposes, says Malcolm Dando.
• Misadventures in the Burgess Shale
  - Nature 460(7258):952-953 (2009)
  One hundred years after Charles Doolittle Walcott found a wealth of Cambrian fossils in the Rocky Mountains of British Columbia, Desmond Collins reflects on the bumpy road of their classification.
• Leading the fight against smallpox
  - Nature 460(7258):954-955 (2009)
  Donald Henderson directed the World Health Organization's effort to eradicate the variola virus. His memoir is a lesson in managing complex projects and personalities, says John Carmody.
• Space for improvement at NASA
  - Nature 460(7258):955 (2009)
  Mark Twain once said that "History doesn't repeat itself, but it does rhyme." Julianne Mahler, a political scientist at George Mason University in Fairfax, Virginia, makes a case for this observation in her examination of NASA's organizational responses to the losses of the space shuttles Challenger in 1986 and Columbia in 2003.
• No more fish in the sea
  - Nature 460(7258):956 (2009)
  So Long, and Thanks for All the Fish: the quirky title of Douglas Adams's novel could turn out to be visionary. Our rampant exploitation of the oceans is such that by 2048 we may be facing a future with no fish.
• An eye for evidence
  - Nature 460(7258):956-957 (2009)
  To mark its centenary, the Institute of Scientific Police at the University of Lausanne, Switzerland, has released from its archives 120 crime-related photographs taken by its founder, a pioneer of forensic photography called Rodolphe Archibald Reiss. Now on show in Lausanne's Elysée Museum (Musée de l'Elysée), the exhibition comes with a warning: it is not suitable for sensitive people or children under 14.
• Earliest sketches of the Moon
  - Nature 460(7258):957 (2009)
  Amid the commemoration of the Apollo landings, another lunar anniversary has just passed quietly. Four centuries ago, on 26 July 1609, the English scholar Thomas Harriot pointed his recently acquired 'Dutch trunke' at the Moon and drew what he saw.
• Correction
  - Nature 460(7258):957 (2009)
  In the book review 'Keeping up scientific standards' by Martin Blume (Nature 459, 645–646; 2009), we inadvertently omitted the author's declaration of competing interests, submitted before he was engaged to write the review. This has been restored online at http://tinyurl.com/mwserz
• Plant biology: Genetics of high-rise rice
  - Nature 460(7258):959-960 (2009)
  When subject to flooding, deepwater rice survives by shooting up in height. Knowledge of the genetic context of this and other responses to inundation will be a boon in enhancing rice productivity.
• Chemical physics: Electronic movies
  - Nature 460(7258):960-961 (2009)
  Strong laser fields can tear an electron away from a molecule, leaving a hole in the electronic wavefunction that races through the molecule. The ultrafast motion of such a hole has been traced at last.
• Neuroscience: Activity acts locally
  - Nature 460(7258):961-963 (2009)
  How does neuronal activity affect the development of neural circuits? Work on the retina shows that blocking activity at the synapses between neurons reduces local synapse assembly without affecting global cellular structure.
• Planetary science: Archaeology of the asteroid belt
  - Nature 460(7258):963-964 (2009)
  The size of asteroids in the Solar System's main asteroid belt may help constrain one of the least-understood aspects of planet formation — the transition from pebble-sized dust balls to mountain-sized planetesimals.
• Astrophysics: Gravity ripples chased
  - Nature 460(7258):964-965 (2009)
  Discovering gravitational waves would not only validate Einstein's theory of gravitation but also reveal aspects of the Universe's earliest moments. The hunt for these elusive ripples is now well under way.
• Evidence for an early prokaryotic endosymbiosis
  - Nature 460(7258):967-971 (2009)
  Endosymbioses have dramatically altered eukaryotic life, but are thought to have negligibly affected prokaryotic evolution. Here, by analysing the flows of protein families, I present evidence that the double-membrane, Gram-negative prokaryotes were formed as the result of a symbiosis between an ancient actinobacterium and an ancient clostridium. The resulting taxon has been extraordinarily successful, and has profoundly altered the evolution of life by providing endosymbionts necessary for the emergence of eukaryotes and by generating Earth's oxygen atmosphere. Their double-membrane architecture and the observed genome flows into them suggest a common evolutionary mechanism for their origin: an endosymbiosis between a clostridium and actinobacterium.
• High harmonic interferometry of multi-electron dynamics in molecules
  Smirnova O Mairesse Y Patchkovskii S Dudovich N Villeneuve D Corkum P Ivanov MY - Nature 460(7258):972-977 (2009)
  High harmonic emission occurs when an electron, liberated from a molecule by an incident intense laser field, gains energy from the field and recombines with the parent molecular ion. The emission provides a snapshot of the structure and dynamics of the recombining system, encoded in the amplitudes, phases and polarization of the harmonic light. Here we show with CO2 molecules that high harmonic interferometry can retrieve this structural and dynamic information: by measuring the phases and amplitudes of the harmonic emission, we reveal 'fingerprints' of multiple molecular orbitals participating in the process and decode the underlying attosecond multi-electron dynamics, including the dynamics of electron rearrangement upon ionization. These findings establish high harmonic interferometry as an effective approach to resolving multi-electron dynamics with sub-Ångström spatial resolution arising from the de Broglie wavelength of the recombining electron, and attosecond! temporal resolution arising from the timescale of the recombination event.
• Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin
  Orso G Pendin D Liu S Tosetto J Moss TJ Faust JE Micaroni M Egorova A Martinuzzi A McNew JA Daga A - Nature 460(7258):978-983 (2009)
  Establishment and maintenance of proper architecture is essential for endoplasmic reticulum (ER) function. Homotypic membrane fusion is required for ER biogenesis and maintenance, and has been shown to depend on GTP hydrolysis. Here we demonstrate that Drosophila Atlastin—the fly homologue of the mammalian GTPase atlastin 1 involved in hereditary spastic paraplegia—localizes on ER membranes and that its loss causes ER fragmentation. Drosophila Atlastin embedded in distinct membranes has the ability to form trans-oligomeric complexes and its overexpression induces enlargement of ER profiles, consistent with excessive fusion of ER membranes. In vitro experiments confirm that Atlastin autonomously drives membrane fusion in a GTP-dependent fashion. In contrast, GTPase-deficient Atlastin is inactive, unable to form trans-oligomeric complexes owing to failure to self-associate, and incapable of promoting fusion in vitro. These results demonstrate that Atlastin mediates m! embrane tethering and fusion and strongly suggest that it is the GTPase activity that is required for ER homotypic fusion.
• Specific pathways prevent duplication-mediated genome rearrangements
  Putnam CD Hayes TK Kolodner RD - Nature 460(7258):984-989 (2009)
  We have investigated the ability of different regions of the left arm of Saccharomyces cerevisiae chromosome V to participate in the formation of gross chromosomal rearrangements (GCRs). We found that the 4.2-kilobase HXT13-DSF1 region sharing divergent homology with chromosomes IV, X and XIV, similar to mammalian segmental duplications, was 'at risk' for participating in duplication-mediated GCRs generated by homologous recombination. Numerous genes and pathways, including SGS1, TOP3, RMI1, SRS2, RAD6, SLX1, SLX4, SLX5, MSH2, MSH6, RAD10 and the DNA replication stress checkpoint requiring MRC1 and TOF1, were highly specific for suppressing these GCRs compared to GCRs mediated by single-copy sequences. These results indicate that the mechanisms for formation and suppression of rearrangements occurring in regions containing at-risk sequences differ from those occurring in regions of single-copy sequence. This explains how extensive genome instability is prevented in euk! aryotic cells whose genomes contain numerous divergent repeated sequences.
• An upper limit on the stochastic gravitational-wave background of cosmological origin
  - Nature 460(7258):990-994 (2009)
  A stochastic background of gravitational waves is expected to arise from a superposition of a large number of unresolved gravitational-wave sources of astrophysical and cosmological origin. It should carry unique signatures from the earliest epochs in the evolution of the Universe, inaccessible to standard astrophysical observations1. Direct measurements of the amplitude of this background are therefore of fundamental importance for understanding the evolution of the Universe when it was younger than one minute. Here we report limits on the amplitude of the stochastic gravitational-wave background using the data from a two-year science run of the Laser Interferometer Gravitational-wave Observatory2 (LIGO). Our result constrains the energy density of the stochastic gravitational-wave background normalized by the critical energy density of the Universe, in the frequency band around 100 Hz, to be <6.9 10-6 at 95% confidence. The data rule out models of early Universe evo! lution with relatively large equation-of-state parameter3, as well as cosmic (super)string models with relatively small string tension4 that are favoured in some string theory models5. This search for the stochastic background improves on the indirect limits from Big Bang nucleosynthesis1, 6 and cosmic microwave background7 at 100 Hz.
• In situ observation of incompressible Mott-insulating domains in ultracold atomic gases
  - Nature 460(7258):995-998 (2009)
  The observation of the superfluid to Mott insulator phase transition of ultracold atoms in optical lattices1 was an enabling discovery in experimental many-body physics, providing the first tangible example of a quantum phase transition (one that occurs even at zero temperature) in an ultracold atomic gas. For a trapped gas, the spatially varying local chemical potential gives rise to multiple quantum phases within a single sample, complicating the interpretation of bulk measurements1, 2, 3, 4, 5. Here we report spatially resolved, in-situ imaging of a two-dimensional ultracold atomic gas as it crosses the superfluid to Mott insulator transition, providing direct access to individual characteristics of the insulating, superfluid and normal phases. We present results for the local compressibility in all phases, observing a strong suppression in the insulator domain and suppressed density fluctuations for the Mott insulator, in accordance with the fluctuation–dissipati! on theorem. Furthermore, we obtain a direct measure of the finite temperature of the system. Taken together, these methods enable a complete characterization of multiple phases in a strongly correlated Bose gas, and of the interplay between quantum and thermal fluctuations in the quantum critical regime.
• Satellite-based estimates of groundwater depletion in India
  - Nature 460(7258):999-1002 (2009)
  Groundwater is a primary source of fresh water in many parts of the world. Some regions are becoming overly dependent on it, consuming groundwater faster than it is naturally replenished and causing water tables to decline unremittingly1. Indirect evidence suggests that this is the case in northwest India2, but there has been no regional assessment of the rate of groundwater depletion. Here we use terrestrial water storage-change observations from the NASA Gravity Recovery and Climate Experiment satellites3 and simulated soil-water variations from a data-integrating hydrological modelling system4 to show that groundwater is being depleted at a mean rate of 4.0 1.0 cm yr-1 equivalent height of water (17.7 4.5 km3 yr-1) over the Indian states of Rajasthan, Punjab and Haryana (including Delhi). During our study period of August 2002 to October 2008, groundwater depletion was equivalent to a net loss of 109 km3 of water, which is double the capacity of India's largest su! rface-water reservoir. Annual rainfall was close to normal throughout the period and we demonstrate that the other terrestrial water storage components (soil moisture, surface waters, snow, glaciers and biomass) did not contribute significantly to the observed decline in total water levels. Although our observational record is brief, the available evidence suggests that unsustainable consumption of groundwater for irrigation and other anthropogenic uses is likely to be the cause. If measures are not taken soon to ensure sustainable groundwater usage, the consequences for the 114,000,000 residents of the region may include a reduction of agricultural output and shortages of potable water, leading to extensive socioeconomic stresses.
• Global electromagnetic induction constraints on transition-zone water content variations
  - Nature 460(7258):1003-1006 (2009)
  Small amounts of water can significantly affect the physical properties of mantle materials, including lowering of the solidus1, and reducing effective viscosity2 and seismic velocity3. The amount and distribution of water within the mantle thus has profound implications for the dynamics and geochemical evolution of the Earth4, 5. Electrical conductivity is also highly sensitive to the presence of hydrogen in mantle minerals6. The mantle transition zone minerals wadsleyite and ringwoodite in particular have high water solubility4, and recent high pressure experiments show that the electrical conductivity of these minerals is very sensitive to water content7, 8, 9. Thus estimates of the electrical conductivity of the mantle transition zone derived from electromagnetic induction studies have the potential to constrain the water content of this region. Here we invert long period geomagnetic response functions to derive a global-scale three-dimensional model of electrical ! conductivity variations in the Earth's mantle, revealing variations in the electrical conductivity of the transition zone of approximately one order of magnitude. Conductivities are high in cold, seismically fast, areas where slabs have subducted into or through the transition zone. Significant variations in water content throughout the transition zone provide a plausible explanation for the observed patterns. Our results support the view10, 11 that at least some of the water in the transition zone has been carried into that region by cold subducting slabs.
• Phase-locking and environmental fluctuations generate synchrony in a predator–prey community
  Vasseur DA Fox JW - Nature 460(7258):1007-1010 (2009)
  Spatially synchronized fluctuations in system state are common in physical and biological systems ranging from individual atoms1 to species as diverse as viruses, insects and mammals2, 3, 4, 5, 6, 7, 8, 9, 10. Although the causal factors are well known for many synchronized phenomena, several processes concurrently have an impact on spatial synchrony of species, making their separate effects and interactions difficult to quantify. Here we develop a general stochastic model of predator–prey spatial dynamics to predict the outcome of a laboratory microcosm experiment testing for interactions among all known synchronizing factors: (1) dispersal of individuals between populations; (2) spatially synchronous fluctuations in exogenous environmental factors (the Moran effect); and (3) interactions with other species (for example, predators) that are themselves spatially synchronized. The Moran effect synchronized populations of the ciliate protist Tetrahymena pyriformis; how! ever, dispersal only synchronized prey populations in the presence of the predator Euplotes patella. Both model and data indicate that synchrony depends on cyclic dynamics generated by the predator. Dispersal, but not the Moran effect, 'phase-locks' cycles, which otherwise become 'decoherent' and drift out of phase. In the absence of cycles, phase-locking is not possible and the synchronizing effect of dispersal is negligible. Interspecific interactions determine population synchrony, not by providing an additional source of synchronized fluctuations, but by altering population dynamics and thereby enhancing the action of dispersal. Our results are robust to wide variation in model parameters representative of many natural predator–prey or host–pathogen systems. This explains why cyclic systems provide many of the most dramatic examples of spatial synchrony in nature.
• A highly annotated whole-genome sequence of a Korean individual
  - Nature 460(7258):1011-1015 (2009)
  Recent advances in sequencing technologies have initiated an era of personal genome sequences. To date, human genome sequences have been reported for individuals with ancestry in three distinct geographical regions: a Yoruba African, two individuals of northwest European origin, and a person from China1, 2, 3, 4. Here we provide a highly annotated, whole-genome sequence for a Korean individual, known as AK1. The genome of AK1 was determined by an exacting, combined approach that included whole-genome shotgun sequencing (27.8 coverage), targeted bacterial artificial chromosome sequencing, and high-resolution comparative genomic hybridization using custom microarrays featuring more than 24 million probes. Alignment to the NCBI reference, a composite of several ethnic clades5, 6, disclosed nearly 3.45 million single nucleotide polymorphisms (SNPs), including 10,162 non-synonymous SNPs, and 170,202 deletion or insertion polymorphisms (indels). SNP and indel densities were ! strongly correlated genome-wide. Applying very conservative criteria yielded highly reliable copy number variants for clinical considerations. Potential medical phenotypes were annotated for non-synonymous SNPs, coding domain indels, and structural variants. The integration of several human whole-genome sequences derived from several ethnic groups will assist in understanding genetic ancestry, migration patterns and population bottlenecks.
• Neurotransmission selectively regulates synapse formation in parallel circuits in vivo
  - Nature 460(7258):1016-1020 (2009)
  Activity is thought to guide the patterning of synaptic connections in the developing nervous system. Specifically, differences in the activity of converging inputs are thought to cause the elimination of synapses from less active inputs and increase connectivity with more active inputs1, 2. Here we present findings that challenge the generality of this notion and offer a new view of the role of activity in synapse development. To imbalance neurotransmission from different sets of inputs in vivo, we generated transgenic mice in which ON but not OFF types of bipolar cells in the retina express tetanus toxin (TeNT). During development, retinal ganglion cells (RGCs) select between ON and OFF bipolar cell inputs (ON or OFF RGCs) or establish a similar number of synapses with both on separate dendritic arborizations (ON-OFF RGCs). In TeNT retinas, ON RGCs correctly selected the silenced ON bipolar cell inputs over the transmitting OFF bipolar cells, but were connected with ! them through fewer synapses at maturity. Time-lapse imaging revealed that this was caused by a reduced rate of synapse formation rather than an increase in synapse elimination. Similarly, TeNT-expressing ON bipolar cell axons generated fewer presynaptic active zones. The remaining active zones often recruited multiple, instead of single, synaptic ribbons. ON-OFF RGCs in TeNT mice maintained convergence of ON and OFF bipolar cells inputs and had fewer synapses on their ON arbor without changes to OFF arbor synapses. Our results reveal an unexpected and remarkably selective role for activity in circuit development in vivo, regulating synapse formation but not elimination, affecting synapse number but not dendritic or axonal patterning, and mediating independently the refinement of connections from parallel (ON and OFF) processing streams even where they converge onto the same postsynaptic cell.
• In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses
  - Nature 460(7258):1021-1025 (2009)
  Influenza A viruses cause recurrent outbreaks at local or global scale with potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. On 11 June 2009 the World Health Organization declared that the infections caused by the new strain had reached pandemic proportion. Characterized as an influenza A virus of the H1N1 subtype, the genomic segments of the new strain were most closely related to swine viruses1. Most human infections with swine-origin H1N1 influenza viruses (S-OIVs) seem to be mild; however, a substantial number of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To achieve a better assessment of the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1! ; hereafter referred to as CA04), as well as several other S-OIV isolates, in vitro and in vivo. In mice and ferrets, CA04 and other S-OIV isolates tested replicate more efficiently than a currently circulating human H1N1 virus. In addition, CA04 replicates efficiently in non-human primates, causes more severe pathological lesions in the lungs of infected mice, ferrets and non-human primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific-pathogen-free miniature pigs, CA04 replicates without clinical symptoms. The assessment of human sera from different age groups suggests that infection with human H1N1 viruses antigenically closely related to viruses circulating in 1918 confers neutralizing antibody activity to CA04. Finally, we show that CA04 is sensitive to approved and experimental antiviral drugs, suggesting that these compounds could function as a first line of defence against the recently declared S-OIV pandemic.
• The ethylene response factors SNORKEL1 and SNORKEL2 allow rice to adapt to deep water
  - Nature 460(7258):1026-1030 (2009)
  Living organisms must acquire new biological functions to adapt to changing and hostile environments. Deepwater rice has evolved and adapted to flooding by acquiring the ability to significantly elongate its internodes, which have hollow structures and function as snorkels to allow gas exchange with the atmosphere, and thus prevent drowning1, 2, 3. Many physiological studies have shown that the phytohormones ethylene, gibberellin and abscisic acid are involved in this response4, 5, 6, 7, 8, but the gene(s) responsible for this trait has not been identified. Here we show the molecular mechanism of deepwater response through the identification of the genes SNORKEL1 and SNORKEL2, which trigger deepwater response by encoding ethylene response factors involved in ethylene signalling. Under deepwater conditions, ethylene accumulates in the plant and induces expression of these two genes. The products of SNORKEL1 and SNORKEL2 then trigger remarkable internode elongation via g! ibberellin. We also demonstrate that the introduction of three quantitative trait loci from deepwater rice into non-deepwater rice enabled the latter to become deepwater rice. This discovery will contribute to rice breeding in lowland areas that are frequently flooded during the rainy season.
• Characterization of two classes of small molecule inhibitors of Arp2/3 complex
  Nolen BJ Tomasevic N Russell A Pierce DW Jia Z McCormick CD Hartman J Sakowicz R Pollard TD - Nature 460(7258):1031-1034 (2009)
  Polymerization of actin filaments directed by the actin-related protein (Arp)2/3 complex supports many types of cellular movements1. However, questions remain regarding the relative contributions of Arp2/3 complex versus other mechanisms of actin filament nucleation to processes such as path finding by neuronal growth cones; this is because of the lack of simple methods to inhibit Arp2/3 complex reversibly in living cells. Here we describe two classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where it appears to block movement of Arp2 and Arp3 into their active conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and alters its conformation. Both classes of compounds inhibit formation of actin filament comet tails by Listeria and podosomes by monocytes. Two inhibitors with different mechanisms of action provide a powerful approach for s! tudying the Arp2/3 complex in living cells.
• XIAP discriminates between type I and type II FAS-induced apoptosis
  Jost PJ Grabow S Gray D McKenzie MD Nachbur U Huang DC Bouillet P Thomas HE Borner C Silke J Strasser A Kaufmann T - Nature 460(7258):1035-1039 (2009)
  FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development1, 2, 3, 4. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis1, 2, 3, 4. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic -cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist)5 is essential6, 7, 8. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein)9, 10 function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC11, also called DIABLO12; direct IAP-binding protein with low pI) mimetic drug in mice render! ed hepatocytes and -cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.
• Structure of a prokaryotic virtual proton pump at 3.2 Å resolution
  - Nature 460(7258):1040-1043 (2009)
  To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5–4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry1, 2, 3, 4, 5, 6, 7. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump'8 in the inner membrane, called AdiC3, 4, that imports l-arginine from the gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins6, 7, 9, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis10, facil! itation of insulin release from pancreatic -cells11, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids12, 13. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 Å resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.
• Kinematic variables and water transport control the formation and location of arc volcanoes
  - Nature 460(7258):1044 (2009)
  Nature 459, 694–697 (2009) In this Letter, two of the Table 1 headings were incorrectly reversed. The Central Aleutians in ref. 13 and Western Aleutian in ref. 14 are comparable geographic regions. This discrepancy was not noted in the original Table 1. The corrected Table is printed below.
• Generation of pluripotent stem cells from adult human testis
  - Nature 460(7258):1044 (2009)
  Nature 456, 344–349 (2008) In this Letter, we omitted to disclose that the original patient consent forms to collect the material used to derive the pluripotent stem cells precluded distribution to third parties, as ruled on 8 December 2008, by the Ethics Commission of the School of Medicine and University Hospital Tübingen. Moreover, the Commission also ruled that the materials used to generate the lines were obtained from individuals who had signed consent forms that did not allow retention of the cells in culture for more than 3 years. We have now received broader consent of a few individuals permitting distribution of cells. These cells will be cultivated, and after quality tests they will be distributed to other scientists. The other individuals whose tissues were used in the study have opted for the terms of the initial consent, and thus their cell lines will be destroyed when the 3-year period runs out. We are now using the described protocols to generate new cell lines from individuals who ha! ve given explicit consent for distribution of lines to scientists. Editor's note: See associated Nature Editorial doi:10.1038/nature460933a (http://www.nature.com/nature/journal/v460/n7258/full/460933a.html)
• Dual nature of the adaptive immune system in lampreys
  - Nature 460(7258):1044 (2009)
  Nature 459, 796–801 (2009) In this Letter, the scale bars in Fig. 5c are incorrectly listed as 1 mm, the correct size of the scale bars is 1 m.
• The Piltdown angel
  - Nature 460(7258):1050 (2009)
  Dig for victory.