Wednesday, June 2, 2010

Hot off the presses! Jun 03 Nature

The Jun 03 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:

  • Wanted: an IPCC for biodiversity
    - Nature (London) 465(7298):525 (2010)
    Nature | Editorial Wanted: an IPCC for biodiversity Journal name:NatureVolume:465,Page:525Date published:(03 June 2010)DOI:doi:10.1038/465525aPublished online02 June 2010 An independent, international science panel would coordinate and highlight research on a pressing topic. Article tools * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg The 2006 review of the economics of climate change, chaired by economist Nicholas Stern, served as a wake-up call to the need to respond to long-term climatic risks. Similarly, the final report of the Economics of Ecosystems and Biodiversity study, due this October, is touted as a 'Stern review for nature'. It will no doubt make a grim read that presents the massive price of biodiversity loss, and the destruction of ecosystems and the services they supply. Organizers of the study — an outcome of the 2007 Potsdam meeting of environment ministers of G8 countries and the five main newly industrializing countries — hope that it, too, will snap policy-makers to attention. Moves are now afoot to establish a body to review the science and anticipated effects of changes in biodiversity, reminiscent of the Intergovernmental Panel on Climate Change (IPCC). Next week in Busan, South Korea, representatives from governments around the world will decide whether to create such a panel, which currently goes by the unwieldy moniker of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES). Is the IPCC model appropriate for biodiversity? Whereas climate is driven at the global level, biodiversity change is a more local affair. Backers of the IPBES acknowledge that point; from the outset, the panel will conduct assessments on regional as well as global scales. And whereas the hugely complex challenges posed by climate change can be boiled down to a single indicator for policy-makers and the public — the question of how hot the planet will get — there is no comparably significant single question for biodiversity loss. "The IPBES will provide a much-needed focus on standards and infrastructure for biodiversity science." Despite these differences, climate change and biodiversity loss share one important attribute: they are real, economically significant phenomena that many would rather ignore. The reports of the IPCC made climate change much harder to ignore. If the IPBES can do the same for biodiversity and ecosystem change, it will be very much worth its proposed annual budget of around US$12 million. Provided it smartens up in response to recent hiccups, the IPCC remains the gold standard for independent scientific assessment on an international level. Its reports are the outputs of a formal, intergovernmental process. Representatives in Busan should do their best to reproduce those attributes to make the IPBES as strong. To ensure that it can speak to all parties that have an influence on biodiversity, the IPBES should have formal relations not just with the Convention on Biological Diversity, but also with other biodiversity treaties, agencies of the United Nations, international environmental non-governmental organizations, global scientific organizations and the private sector. So far, the panel has the backing of the UN Environment Programme, which, along with the World Meteorological Organization, oversees the IPCC. To get the input of other sectors beyond the environment ministries, the IPBES should look for additional patrons. If the UN Food and Agriculture Organization helped to run it, for example, the food-production interests of farmers and fishermen are more likely to stand behind its conclusions. The IPBES will also provide a much-needed focus on standards and infrastructure for biodiversity science. Ecologist Harold Mooney, a leading IPBES advocate at Stanford University in Palo Alto, California, argues that the panel should help to improve and harmonize predictive models of global change. A portion of its budget will no doubt be rightly allocated to scientific capacity-building in developing countries. Gap-analysis reports would provide scientists with a list of relevant information that is needed. The IPBES will undoubtedly have strong links with the Group on Earth Observations Biodiversity Observation Network (GEO BON) — a collaboration of more than 100 governmental and other organizations that already share their data and analyses of biodiversity. Fed by a stream of high-quality data from GEO BON and coordinated by the activities of the IPBES, biodiversity science should flourish. Regular assessments by the IPBES should help our planet's biota to flourish too. Additional data
  • Education ambivalence
    - Nature (London) 465(7298):525 (2010)
    Nature | Editorial Education ambivalence Journal name:NatureVolume:465,Pages:525–526Date published:(03 June 2010)DOI:doi:10.1038/465525bPublished online02 June 2010 Academic scientists value teaching as much as research — but universities apparently don't. Article tools * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Complaints about the poor quality of science education are a familiar refrain in many countries, as are national anxieties about falling behind the rest of the world. What's not so familiar is that pretty much everyone feels this way. Nature Publishing Group's educational division, Nature Education, last year conducted a survey of 450 university-level science faculty members from more than 30 countries. The first report from that survey, freely available at http://go.nature.com/5wEKij, focuses on 'postsecondary' university- and college-level education. It finds that more than half of the respondents in Europe, Asia and North America feel that the quality of undergraduate science education in their country is mediocre, poor or very poor. Despite agreeing that inadequate secondary-school science education is the major problem, respondents concurred on how they could help contribute to a solution: by having professors provide better college-level teaching. Moreover, 77% of respondents indicated that they considered their teaching responsibilities to be just as important as their research — and 16% said teaching was more important. Yet although there was general agreement about the low quality of undergraduate education, a substantial majority of the respondents felt that their own teaching was highly effective. This suggests that at least some of the respondents are fooling themselves. Certainly, that apparent complacency would help to account for the notably slow uptake of pedagogical innovations in the teaching of science to undergraduates. But there is strong evidence that talking at students isn't nearly as effective as engaging them with cooperative, hands-on learning activities. A prime example of the latter approach is Process Oriented Guided Inquiry Learning (http://pogil.org), which originated in US college chemistry departments in 1994, and which is now used in many other subject areas. But the biggest barrier to improvement is the pervasive perception that academic institutions — and the prevailing rewards structure of science — value research far more than teaching. That perception was apparent in one of the survey's most striking contradictions: despite their beliefs that teaching was at least as important as research, many respondents said that they would choose to appoint a researcher rather than a teacher to an open tenured position. To correct this misalignment of values, two things are required. The first is to establish a standardized system of teaching evaluation. This would give universities and professors alike the feedback they need to improve. Undergraduate student outcomes can already be measured in a variety of innovative ways, such as the 'concept inventory' system developed in physics. But more research is needed in this area. The second requirement is to improve the support and rewards for university-level teaching. For example, universities and professional societies could offer staff systematic training in how to teach well — something less than a two-year degree, but more than a two-hour workshop. Universities could encourage donors to endow professorships based on teaching excellence. And funding agencies could make teaching more of a financial priority, as does the private Howard Hughes Medical Institute in Chevy Chase, Maryland, which offers scientists up to US$1 million over four years to innovate in science education. Correcting the misalignment will be neither quick nor easy. But by showering so many rewards on research instead of on teaching, universities and funding agencies risk undermining the educational quality that is required for research to flourish in the long term. They need to find a more balanced way to allocate their resources — and in the process allow the majority of academic scientists to act on their conviction that teaching and research are equally important. Additional data
  • Mouse megascience
    - Nature (London) 465(7298):526 (2010)
    Nature | Editorial Mouse megascience Journal name:NatureVolume:465,Page:526Date published:(03 June 2010)DOI:doi:10.1038/465526aPublished online02 June 2010 Mouse research for human diseases has grown, and researchers must defend and promote it accordingly. Article tools * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg From cancer to cognitive disorders, the mouse has become an important biomedical model, in both academia and industry. During the past decade, the creation of mouse resources has consumed untold millions of research dollars. Large-scale efforts have contributed to the sequencing of the animal's genome; developed smart tools to make genetically modified mice in which specific genes can be switched on and off in different tissues at will; and established repositories to house and supply mouse mutant strains or genetically engineered mouse embryonic stem cells that can be developed into mice 'to order'. Within a few years, embryonic stem cells with modifications in every mouse gene will be available. But if the mouse is to fulfil its biomedical potential, that, unfortunately, is still not enough. The function of each gene must be identified through phenotyping: comprehensive screening to see what happens to the animals' organs and skeletons, and to their general physiology and behaviour, when individual genes are knocked out. This has been understood by the cognoscenti for years. The European Commission has already spent several hundred million euros pioneering large-scale systematic phenotyping, and 'mouse clinics' are starting to spring up around the world. The International Mouse Phenotyping Consortium (IMPC) has just been launched (see Nature465, 410; 2010) to focus these efforts into a single global programme, which the US National Institutes of Health, under the leadership of Francis Collins, has endorsed with an injection of US$110 million. The IMPC estimates that with 'just' $900 million it can phenotype 4,000 mutants in a five-year pilot project. To put this into perspective, the mouse has about 20,000 genes. Mouse genetics is launching itself into the league of stratospherically expensive science projects, a domain currently occupied by international physics mega-projects such as the Large Hadron Collider (LHC) and the fusion-energy project ITER. Certainly, phenotyping will become cheaper and more efficient as technologies develop, but the scope of the IMPC pilot project will also have to expand in important ways that scientists are discussing. Secondary phenotyping may be needed to investigate particularly interesting hits from primary screens in more detail. Full phenotyping under different environmental challenges — yet to be decided, but possibly including high-fat diets — will also be incorporated. The inclusion of ageing mice to model our ageing society is also likely — an expensive prospect, given the time periods over which such mice must be kept. Phenotyping is, in fact, an infinite task, as long as a piece of string. Mouse geneticists will have to prepare themselves for this new league in which they will no longer be competing for funding only within the life-sciences community, but with all scientific disciplines. First, they will need to advocate the benefits to broader audiences. A full catalogue of mouse genes and functions will be invaluable in helping to crack currently intractable diseases. Individual scientists can certainly make slow progress laboriously creating and phenotyping knockout mice from scratch to model the plethora of candidate genes weakly associated with such diseases — but would save themselves years of possibly dead-end research by simply looking in a database. Second, and most importantly, political paymasters must be reassured that the IMPC's aims are clearly ring-fenced and limited to the minimum effort that will serve all of biomedicine effectively; they will rightly fear the infinite piece of string. They face shrinking budgets, and the LHC and ITER have shown how easily — and by how much — billion-dollar budgets can overrun. They also have responsibility for competing social priorities such as climate change. The international mouse-genetics community is now as united and cohesive as the international particle-physics community was when the LHC was conceived. It just needs to be as politically coherent. Additional data
  • Geophysics: Glaciers going, going...
    - Nature (London) 465(7298):528 (2010)
  • Astronomy: Clouds with an H2 lining
    - Nature (London) 465(7298):528 (2010)
  • Ecology: What's that whale?
    - Nature (London) 465(7298):528 (2010)
  • Nanomanufacturing: Petite pottery
    - Nature (London) 465(7298):528 (2010)
  • Physiology: Marathon metabolites
    - Nature (London) 465(7298):528 (2010)
  • Genomics: Transposition trends
    - Nature (London) 465(7298):528 (2010)
  • Nanoscience: Shifted shells
    - Nature (London) 465(7298):529 (2010)
  • Geoscience: Dam that water
    - Nature (London) 465(7298):529 (2010)
  • Ecology: Mighty termite mounds
    - Nature (London) 465(7298):529 (2010)
  • Neuroscience: Sound learning
    - Nature (London) 465(7298):529 (2010)
  • Journal club
    - Nature (London) 465(7298):529 (2010)
  • News briefing: 3 June 2010
    - Nature (London) 465(7298):530 (2010)
    The week in science This article is best viewed as a PDF Policy|Events|Research|Business|Funding|Awards|Business watch|The week ahead|Number crunch|News maker An international conference in New York to review the Nuclear Non-Proliferation Treaty has reaffirmed nations' commitments to disarmament and halting the spread of weapons technology. On 28 May, after almost a month of negotiations, 189 nations, including Iran, endorsed a 28-page consensus document, which also called for a nuclear-weapons-free zone in the Middle East and global ratification of the Comprehensive Nuclear-Test-Ban Treaty. Just three days later, the International Atomic Energy Agency, based in Vienna, reported that Iran now has enough low-enriched uranium to convert into weapons-grade material for two nuclear weapons. At a climate conference in Oslo on 27 May, some 50 countries agreed to a loose framework for reducing greenhouse-gas emissions caused by deforestation. This builds on commitments made at the United Nations climate talks in Copenhagen last December. Developed countries pledged to boost funds for the framework programme from US$3.5 billion to $4 billion between now and 2012, and the deal creates a formal partnership for evaluating future efforts to tackle deforestation. The Royal Society in London, Britain's national academy of science, is reviewing its public climate-change message after receiving a complaint from 43 of its fellows. They were reportedly angered by a policy document known as 'Climate Change Controversies', which seeks to "help non-experts better understand some of the debates in this complex area of science". The fellows complained that the 2007 document was too dismissive of attacks on the understanding of climate change. The society says that a new guide will be released later this summer. BP's latest efforts to staunch the flow of oil from its wellhead in the Gulf of Mexico have failed, prompting White House energy adviser Carol Browner to admit that the leak may not be stopped before August, when drilling for relief wells will be completed. The 'top kill' operation — pumping mud into the gushing well — was followed by a 'junk shot' to block the oil leak with debris. Neither attempt worked. Robot submarines are now being deployed to cap the well. See page 532 for more. J. ROSS/NASA; INSET: A. WESLEY The Stratospheric Observatory for Infrared Astronomy has made its first airborne observations, snapping this image of Jupiter (inset, right, shown next to a visible-light image) on 25 May. The modified Boeing 747SP aircraft sports a hole in its fuselage for a 2.5-metre telescope, and can make infrared observations that would normally be obscured by water vapour in the lower atmosphere. The US$3.4-billion mission — a collaboration between NASA and the German Aerospace Center — has had its share of turmoil since development first began in 1996, almost being cancelled in 2006 when it was temporarily axed from the NASA budget. Scientific operations should begin in October, with full capacity — about 800 hours of observation time a year — expected by 2014. Two new forms of a devastating wheat fungus known as Ug99 stem rust have arisen in South Africa. Researchers at the University of the Free State in Bloemfontein found that the new variants can overcome the effects of two resistance genes in wheat that normally prevent stem rust from taking hold. There is concern that winds will help the fungus to migrate further, threatening crops in areas including the Middle East and south Asia. See go.nature.com/flSdmx for more. As many as 1,240 bird species are threatened with extinction, amounting to 12% of the 10,027 recognized bird species, says the latest update of the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. The bird count was conducted by BirdLife International, a global partnership of conservation organizations. The IUCN list also confirmed the extinction of the Alaotra grebe (Tachybaptus rufolavatus), 25 years after the last confirmed sighting. The waterfowl, found mainly in Lake Alaotra in eastern Madagascar, is thought to have been killed off by poaching and the introduction to its habitat of carnivorous fish. See go.nature.com/tSwuzE for more. On 24 May, the US Food and Drug Administration (FDA) fined Genzyme US$175 million for poor oversight at one of its manufacturing plants. Efforts by the biotechnology company, based in Cambridge, Massachusetts, to clean the plant will cause shortages of three drugs, including one used to treat thyroid cancer. But there was also good news for the beleaguered company: on 25 May, after years of struggle, Genzyme won FDA approval to market Lumizyme (alglucosidase-α) for patients with late-onset Pompe disease, a muscle-weakening illness. Amgen has secured regulatory approval from the European Commission for denosumab (Prolia), the California-based drug company's treatment for osteoporosis. The monoclonal antibody will be used to treat postmenopausal women who have an increased risk of fractures, and men experiencing the side effects of prostate-cancer treatment. Last year, a US Food and Drug Administration committee recommended that the drug be approved for certain patients, although it awaits full US approval. Analysts predict multibillion-dollar annual sales for the drug. AstraZeneca has hired Pfizer's research and development (R&D) chief, Martin Mackay, to take the helm of its own R&D programme. Pfizer and AstraZeneca are both restructuring their R&D programmes to replenish pipelines and cut costs. Mackay became head of R&D at Pfizer, the world's biggest drug maker, in 2007, but has shared the job with Mikael Dolsten since October 2009, when Pfizer completed its acquisition of rival Wyeth. Dolsten will now lead Pfizer's R&D team alone. SOURCE: BUSINESS INSIGHTS A growing need to cut pharmaceutical and biotechnology research costs is fuelling a boom in the contract research organization (CRO) industry. More than 1,000 CROs around the world provide outsourced research and clinical-trial services. According to an August 2009 report by London-based market analysts Business Insights, CROs accounted for 20% of the global pharmaceutical and biotechnology research and development budget in 2008. Revenues are expected to reach US$24 billion in 2010, doubling 2004 earnings (see chart). Much of that growth will be in emerging markets, as companies take advantage of the low costs and deep talent pools in countries such as India and China. The 300 US-based CROs still generate about half of the industry's revenue, and are predicted to grow each year by 14%. But in China, where drug development is about 20% of the cost in the United States and western Europe, the industry is expected to swell by 33% each year, reaching $791 million by 2012. Meanwhile, the proportion of global clinical trials conducted in India will grow from 2% in 2007 to 5% in 2012. These trends have been highlighted by leading US CROs such as Quintiles in Durham, North Carolina, and Charles River Laboratories in Wilmington, Massachusetts, shifting more of their operations to emerging markets. The UK Medical Research Council has called for greater investment to address the "huge mismatch" between the social and economic burden of mental illness and the relatively slow progress in research in the field. Following a six-month review, a report published last week (Lancet 375, 1854–1855; 2010) sets out a strategic plan for the next 5–10 years that would accelerate mental-health research for both prevention and treatment. Five US-based researchers will share three Shaw prizes worth US$1 million apiece. The astronomy prizewinners, announced on 27 May, are Charles Bennett of Johns Hopkins University in Baltimore, Maryland, and Lyman Page and David Spergel of Princeton University in New Jersey. The award recognizes their leadership on the Wilkinson Microwave Anisotropy Probe, which maps fluctuations in the microwave background radiation left over from the Big Bang. David Julius, a physiologist at the University of California, San Francisco, won the prize for life science and medicine for his work on molecular mechanisms of pain. The mathematics prize went to Jean Bourgain of Princeton University for his work in mathematical analysis. The prizes, first awarded in 2004, were set up by businessman Run Run Shaw. The 2010 Kavli prizes are announced in Oslo. First awarded in 2008, the biennial prizes consist of US$1 million each for nanoscience, neuroscience and astrophysics. → http://www.kavliprize.no/ Governments meet in Busan, South Korea, to decide whether to establish an Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services. → http://ipbes.net/ Oslo boasts the 'largest polar science gathering ever' at a conference on the 2007–08 International Polar Year. → http://www.ipy-osc.no/ The 2010 Millennium Technology Prize will be awarded in Helsinki. → go.nature.com/Eknzdu The number of litres per day of oil flowing from the ruptured Gulf of Mexico well, up to four times the official estimate from a month ago. Source: US National Incident Command's Flow Rate Technical Group; 27 May P. FETTERS William Bishai The tuberculosis expert will head South Africa's KwaZulu-Natal Research Institute for Tuberculosis and HIV, the first Howard Hughes Medical Institute research lab outside the United States. See go.nature.com/UhiFTr for more. There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • Financial meltdown imperils reactor
    - Nature (London) 465(7298):532 (2010)
    Faced with a huge budget shortfall, Europe rethinks future of ITER fusion project. Will the ITER reactor ever have its day in the sun?ITER ORGANIZATION It has been billed as the solution to tomorrow's energy crunch, but ITER, a massive fusion experiment by seven international partners, is under serious threat from a present-day problem: the financial crisis. In a meeting on 26 May, the cash-strapped member states of the European Union (EU) were unable to agree on how to find the additional billions needed to finance construction of the giant reactor, which is sited near St-Paul-lès-Durance, France. The EU is set to contribute 45% of the construction costs for ITER, which some estimates now put at €15 billion (US$19 billion) — three times the 2006 cost estimate (see 'The ITER rollercoaster'). Left unresolved, the impasse in Europe will, at best, delay the project further. At worst, it could cause ITER to unravel entirely. "I think the momentum of the project may be in very deep trouble," says one non-EU scientist involved with ITER who asked not to be named, citing the experiment's precarious position. "Time is pressing." ITER has been a 25-year dream for fusion advocates: a step towards turning the promise of fusion — combining hydrogen isotopes into helium — into a practical power source. Fusion releases far more energy than the fission reactions of conventional nuclear power, but it is also more difficult to achieve. The doughnut-shaped ITER reactor would use superconducting magnets to heat and squeeze hydrogen until the device ignites a fusion reaction, releasing around ten times the power it consumes. Click for a larger version.SOURCE: ITER, VARIOUS In 2006, when the EU, the United States, Russia, South Korea, China, India and Japan agreed to the project in its current form, ITER was estimated to cost around €5 billion to construct over a decade. But the rising cost of materials, gaps in the original design and the bureau­cracy needed to manage the project have caused the cost to balloon (see Nature 459, 488-489; 2009). On 5 May the European Commission, which manages the project, released a memo that put the price of Europe's share of the construction at around €7.2 billion, nearly three times the 2006 estimate. The vagaries of how the seven partners budget for the project mean a full price-tag may never be known. The most pressing problem is a €1.4-billion gap in Europe's budget for ITER in 2012–13. The commission's 5 May memo called on the 27 member states, which must ultimately pay for ITER, to "provide the additional resources necessary" for the project. The request could not have come at a worse time for Europe. Faced with an economic crisis in Greece that could spread, the EU has just approved a costly €500-billion bailout package for eurozone countries. Meanwhile, many nations are desperately trying to trim their domestic budgets in an effort to right the continent's troubled finances. The crunch is so serious that some European states have gone as far as to ask the commission to investigate the possibility of withdrawing from ITER, according to sources familiar with the negotiations. The price of such a withdrawal would probably be in the billions, as the treaty governing ITER requires heavy compensation to other partners. Mark English, a spokesman for the European Commission, declined to comment on whether member states had asked for an analysis of withdrawal. In a press conference during the most recent meeting, European officials said they remained committed to ITER. "I think that, with vision, we can overcome the difficulties," Máire Geoghegan-Quinn, the European commissioner for research, told reporters on 26 May. One temporary solution would be a loan from the European Investment Bank to cover the immediate €1.4-billion budget gap. That would work in the short term, but member states would still have to come up with a plan to cover the full €7.2-billion costs. Another possibility, floated by Annette Schavan, Germany's research minister, would be to redesign the machine, possibly building a smaller version. But scaling back ITER at this stage is unrealistic, says Stephen Dean, president of Fusion Power Associates, a non-profit advocacy group based in Gaithersburg, Maryland. The planned reactor is already half the size that scientists originally hoped it would be, and any further shrinking would risk making the machine too small to achieve its goals. Europe's member states have formed a task force to discuss how to pay for the project. The group will meet weekly in the run-up to a meeting of the full ITER council on 17 June. If the EU cannot reach an agreement in time, ITER's six other members may decide to delay the council meeting until Europe has found a way forward, insiders say. Dean says he thinks that ITER's other partners may ultimately have to provide more aid if the project is to stay on track. "If they want the [current] schedule that badly, they're going to have to come up with more money," he adds. More fundamentally, Dean says, the seemingly endless succession of cost increases and delays may cause a rethink of fusion entirely. "We're supposedly developing a power source that's going to compete with coal and nuclear," he says. But the experience so far does not bode well: "There are serious questions about the affordability of fusion as a whole as a result of ITER." There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • Researchers track path of oil from rig spill
    - Nature (London) 465(7298):532 (2010)
    Officials desperately seek answers on where the slick will head. An ocean-monitoring sensor package is about to be dropped from a plane.M. Schrope With no end in sight for the oil gushing from the explosion site at the Deepwater Horizon drilling rig, anxious US officials are looking to researchers who study the Gulf of Mexico and its idiosyncratic currents to help determine where all the oil is and where it might be heading. Long-term efforts to understand the movement of Gulf waters because of their effect on hurricanes are now being used to address the more immediate question of which regions and ecosystems outside the immediate spill zone are most likely to bear the brunt of a non-stop river of oil. "This is where a lot of the action is," says Lynn 'Nick' Shay, a physical oceanographer at the University of Miami in Florida. Shay is referring to an expanse of open water visible from the window of the National Oceanic and Atmospheric Administration (NOAA) 'hurricane hunter' research plane that routinely carries him on 9-hour-long sweeps of the Gulf. At this particular spot, some 460 kilometres southeast of the spill, the Gulf's hairpin-shaped Loop Current is pinching off to form a circular eddy about the size of Ireland. The eddy, a temporary detour from the current's normal path, could well be a lucky break. As the oil spreads, it is gradually becoming entrained in the Loop Current, an offshoot of the Gulf Stream that flows south and east of the spill site off the Louisiana coast towards the opening between Cuba and Florida. The prospect of large amounts of oil moving towards coastlines in that region is a dire one for communities and fisheries, as well as for the sensitive coral reefs. By contrast, oil pulled into the eddy could be sequestered there for months as the vortex drifts westward at "about the speed of Miami traffic", says Shay. Although it would still threaten marine life, the effects on coastal ecosystems would be lessened, because there would be more time for evaporation and microbes to help break down the oil. "The question is how much goes each way," says Shay. Shay's team is helping to answer the question by gathering detailed information on the state of the Loop Current and eddy on its research flights. Every few minutes during a flight, a sensor package about the size of a poster tube is dropped through a hole in the floor of the plane. Depending on which sensor is used, the tube will radio back information on temperature, salinity or current movement as it plunges into the depths. The deep-water data are important because so little is known about what the currents are doing below the surface — and that's exactly where much of the oil may be hiding, in the form of vast underwater plumes (see Nature 465, 274–275; 2010). As Shay and his team criss-cross the Gulf by air, scientists aboard the F. G. Walton Smith research ship are tracking the subsurface spread of layers of what seems to be an oil plume at multiple depths west of ground zero. And two other research groups have just returned from studying other areas of apparent deep oil. James Cowan, a fisheries biologist at Louisiana State University in Baton Rouge, has been aboard a small charter fishing boat about 120 kilometres northwest of the main spill deploying a remotely operated vehicle to examine water down to about 120 metres. In one large area beneath visible surface oil, says Cowan, "we saw oil all the way down as far as we could go. It was thick enough so that it pretty much covered our camera globe and the lights." The challenge now is to predict where all that oil will go. Ruoying He, an oceanographer with the ocean observing and modelling group at North Carolina State University in Raleigh, works with an ocean-circulation model that takes data such as temperature and wind measurements and tries to forecast the behaviour of the currents in the Gulf and the adjacent portion of the Atlantic. Having built up expertise over years, He's ocean modelling group is one of several teams running ocean-circulation forecast models used by NOAA's Emergency Response Division. NOAA, the lead agency for scientific issues relating to the spill, is using these modelling results to generate its prediction of the oil's movement and so guide local, state and federal responses. ADVERTISEMENT But He acknowledges that lack of data from the deep water makes the entire situation murky. The stricken oil well lies 1,500 metres down, and no one really knows how the oil is distributed at such depths or how well the numerical models of ocean circulation can perform there. "Information from only the surface might be misleading," He says. Yonggang Liu, a physical oceanographer at the University of South Florida in St Petersburg, agrees that the observations are sparse. "We need more data," he says. "Without it, our models are very limited." In the coming weeks, some of those data will start to trickle in. They will do nothing to stop the oil, but they will be essential in revealing what happens next. There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • Model stars set to explode
    - Nature (London) 465(7298):534 (2010)
    Realistic computational models of supernovae might soon solve a long-standing mystery. Giant, mushroom-shaped blobs of nickel speed out from the blistering core of the supernova at 4,000 kilometres per second, piercing the smooth, ballooning sphere of hydrogen. The effect looks something like a cosmic hernia, but astrophysicist Hans-Thomas Janka couldn't be more pleased with what his computer model is showing. This three-dimensional model shows the evolution of a supernova in its first half-second. The explosion has a 200 km radius in the first frame; in the last frame, it is 1,900 km.H-TH. JANKA, MAX PLANCK INST. FOR ASTROPHYSICS In a paper published in the 10 May issue of the Astrophysical Journal1, Janka and his colleagues from the Max Planck Institute for Astrophysics in Garching, Germany, used their model to address a long-standing puzzle: how do heavier elements, synthesized in the core of the massive, dying star, get out of the explosion before the lighter stuff that sits in the star's outer shells? But the simulated explosion, with its colourful protrusions, is significant for another reason. It marks the first published, nearly complete, three-dimensional (3D) model of a supernova. Simpler one-dimensional (1D) and two-dimensional (2D) models, which assume that an explosion unfolds symmetrically, fail to get ticking star bombs to blow. So a handful of computational astrophysics groups, including Janka's, are moving up to the third dimension. The computational demands of tracking a complex and rapidly evolving explosion in which densities, temperatures and velocities are all at physical extremes are themselves astronomical. And the researchers have yet to tackle the toughest challenge: modelling the first milliseconds of the explosion in the innermost core of a supernova. But when they do, astrophysicists hope their models will finally reveal the root mechanism that triggers supernovae, a problem that has eluded their profession since modelling began 40 years ago. "I think there's overwhelming evidence that going to 3D calculations makes the explosions easier," says Eliot Quataert, who has been following progress in the field as director of the Theoretical Astrophysics Center at the University of California, Berkeley. "That's what everyone is rushing after now." Supernovae are among the most energetic events in the Universe, briefly outshining entire galaxies as they synthesize and spread the heavy elements that are essential to biological life. One type of supernova detonates when a dense white-dwarf star sucks in enough additional mass for a fusion explosion. The second, and more mysterious, type occurs when a star a few times more massive than the Sun runs out of nuclear fuel. As the star's internal pressure plummets, its massive core collapses into a neutron star just a few tens of kilometres across. At this point the neutrons can be compressed no further, and the core rebounds, sending a shock wave out against the crushing weight of the star's outer layers. But the shock wave by itself isn't enough to blow the star apart, and for a fraction of a second it stalls. The question is what 'revives' the shock, causing the explosion to proceed. "For a fraction of a second a supernova stalls. The question is, what revives it?" Some have suggested that energy locked up in the tightly coiled magnetic fields of a spinning core might provide the extra nudge. But many theorists favour a trigger from neutrinos, which are produced in unimaginably large numbers when the neutron star is born. Because of their weak coupling with other forms of matter, the vast majority of the neutrinos simply fly straight through the dying star. But if enough impart their energy to the infalling matter, they could provide the extra kick needed to restart the shock wave and blow up the outer shells of matter. "We're at the point now where we believe the final threshold is being crossed for the neutrino model," says astrophysicist Stan Woosley at the University of California, Santa Cruz, who is leading a 3D modelling effort. "A lot of us think it's going to work when we take this next step." Multi-dimensional models But modelling the interactions of the neutrinos with the infalling matter is the most computationally difficult part of the problem; until now, modellers have had to use lower-dimensional short cuts. Not only have these models generally failed to ignite the supernova, but they also preserve unrealistic symmetries, with the progenitor star maintaining its onion layering as it blows up: hydrogen and helium first, followed by heavier elements. The spectacular 1987 supernova in the Large Magellanic Cloud was heralded by a burst of X-rays and γ-rays coming from radioactive heavy elements such as nickel — meaning that the heavy material had somehow punched through the lighter layers. "That was the point when theorists realized that 1D models cannot explain the physics that was observed in the explosion," says Janka. The rapid increase in available computer power now allows the modellers to run more-ambitious and realistic simulations in a manageable time — currently, Janka needs two to three months to run one supernova in 3D. At some point, researchers say, a digital cataclysm will attain a level of detail adequate to reproduce what occurs in the real Universe. "That is what the big competition is about," says Janka. Optimistic outlook ADVERTISEMENT Adam Burrows, an astrophysicist at Princeton University in New Jersey, who is working with Woosley, has already analysed the benefits of 3D models. In 2008, he showed that going to 2D made a simulated supernova of a given luminosity blow up 1.4 times as often as the 1D version2. Repeating the analysis, he found that 3D models should make supernovae go off twice as easily as in 1D models. The reason, he says, is that 3D allows the infalling matter to take random walks in all directions — which means that it spends slightly more time interacting with neutrinos and absorbing their energy. Ultimately, the aim is to construct a 3D explosion that is faithful enough to generate a supernova without fail. In the process, the physical forces that govern it should become apparent. That's why Janka is rushing to fill out the rest of his 3D model to include the neutrino mechanics in the first second of the explosion. He also has to find a computer that can handle the job. He estimates that he needs a computer to perform about 1021 floating point operations, or flops — roughly 50,000 times the computing power behind his latest simulations. This would mean several months of devoted time from a major supercomputer that can perform a petaflop, or 1015 operations, per second. With the growth in worldwide computing infrastructure, Quataert says, that is now not a completely outrageous request. "That's part of the reason for optimism that there will be a breakthrough in this problem," he says. * References * Hammer, N. J. , Janka, H.-Th. & Müller, E.Astrophys. J.714, 1371 (2010). * Murphy, J. W. & Burrows, A.Astrophys. J.688, 1159 (2008). There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • US prepares for climate burden
    - Nature (London) 465(7298):535 (2010)
    National summit paves way for concerted action on global warming. It hasn't always been easy to get the White House to lead on climate change, so for years the question of how to incorporate global warming into long-range planning and public infrastructure in the United States has fallen to cities, states and individual federal agencies. Now, the Obama administration is looking to fold these independent efforts into a comprehensive adaptation strategy for the entire country. Last week, about 150 experts gathered in Washington DC to swap ideas and information about exisiting adpatation plans across the country and to consider how the federal government should coordinate and encourage further steps. Ordered last year by John Holdren, Obama's chief science adviser, the three-day National Climate Adaptation Summit served as a brainstorming session where users and providers of 'climate services' could talk about their needs and capabilities. The gathering took place just a week after the National Research Council called on the government to develop a national strategy for dealing with the impacts of a changing climate. "There's a sense that this is a moment to put everything together and figure out what we are going to do to prepare," says Richard Moss, a senior scientist at the Joint Global Change Research Institute in College Park, Maryland, and former director of the US Global Change Research Program. "And I give the administration credit for holding this meeting and asking for ideas, rather than just rolling out an answer." "I give the administration credit for holding this meeting and asking for ideas, rather than just rolling out an answer." Increased drought, heatwaves, forest fires, severe storms and rising sea levels in coastal cities are among the challenges that climate change could pose for the United States. A National Climate Service, modelled on the National Weather Service at the National Oceanic and Atmospheric Administration (NOAA) in Silver Spring, Maryland, could help local authorities to anticipate such stresses and provide a one-stop clearinghouse for information designed to reduce susceptibility to climate-related disasters. While seeking congressional approval for the service, NOAA is pushing forwards with a reorganization that would essentially make the approach a reality. The plan includes a series of regional climate centres to help provide guidance for local governments and businesses. The goal, says Thomas Karl, interim director of NOAA's Climatic Service, is to provide useful information about environmental impacts so that planners can assess water supplies, update flood-plain maps or decide how high to build levies. But the first step, he says, is to establish "good communication with those who will want to use the data". To be effective, the centres will need to be adept at translating hard data into metrics and standards to guide public and private infrastucture projects, says Anne Choate, vice-president of the business consultancy ICF International. "There's this gap between what the engineers say they need and what climate scientists can provide," she says. Some scientists have already begun closing that gap. In 2008, a team led by Don Wuebbles, an atmospheric scientists at the University of Illinois at Urbana-Champaign, analysed global climate models to produce more detailed climate projections for the city of Chicago. The results suggest that the city could be significantly warmer in 2100, with implications for everything from power generation to the kinds of tree that the city is planting today. "We're going to look more like New Orleans than Chicago," says Joyce Coffee, who handles the city's adaptation planning. "We need to be planting species that will survive current cold snaps and thrive in a much warmer climate in the future." ADVERTISEMENT Other federal initiatives are focusing on environmental planning at the regional level. For instance, the Interior Department is setting up 'Landscape Conservation Cooperatives' to bring federal agencies together with state and local governments to collaborate on planning for issues ranging from wildfires and water supplies to invasive species and energy development. "I think this is going to be the new model for environmental adaptation strategies," says Deputy Interior Secretary David Hayes. An adaptation task force formed by the White House last year will incorporate the results of the summit into a white paper scheduled for release this autumn. There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • Biologists tackle cells' identity crisis
    - Nature (London) 465(7298):537 (2010)
    DNA fingerprinting scheme aims to make sure researchers are working on the right cells. Breast cancer cells: not always what they're supposed to be.S. GSCHMEISSNER/SPL Ever since biologists learned how to grow human cells in culture half a century ago, the cells have been plagued by a problem of identity: many commonly used cell lines are not actually what researchers think they are. Cell-line misidentification has led to mistakes in the literature, misguided research based on those results and millions wasted in grant money. Last year, Nature described the situation as a scandal1. But a universal system for determining the identity of cell lines may now be in view. Next month, a working group led by the American Type Culture Collection (ATCC), a nonprofit biological repository based in Manassas, Virginia, that stores 3,600 cell lines from more than 150 species, plans to unveil standardized protocols for verifying the identity of cultured cells using DNA fingerprinting. Labs worldwide — including repositories such as the ATCC itself — would use the protocols to determine whether a breast-cancer line, for instance, did come from breast tissue. The group also plans to create a public database, which the National Center for Biotechnology Information in Bethesda, Maryland, has agreed to host, to store DNA profiles of validated lines, allowing researchers to compare their own cell cultures with the ATCC's reference lines. "I really think it's fantastic progress," says Rolf König, director of the Tissue Culture Core Facility at the University of Texas Medical Branch in Galveston. Misidentification can happen when faster-growing cells contaminate cultures of slower-growing cells in the same lab, or when researchers simply mislabel a specimen. One particularly robust cell line called HeLa, the first human cell line grown in the lab, has contaminated dozens of other lines without researchers' knowledge2, and there are many other examples where melanoma cells and ovarian cells, for example, have been mistaken for breast cells. In this month's Nature Reviews Cancer3, the ATCC consortium notes that one group has published around 20 papers since 1988 in which they incorrectly use a line called Int-407 as a model of normal intestinal cells. The working group, composed of representatives from academia, government and industry, as well as from other cell repositories, advocates verifying cells' identities by comparing their DNA in regions where short stretches of three to five bases are repeated. Closely related cells are likely to have the same number of repeats; comparing these snippets at several different positions in the DNA sequence provides an overall estimate of relatedness. Forensics applications, such as paternity testing and identifying crime victims, already use the technique. But cell lines often come from tumour tissue, in which DNA mutates at a higher rate than normal, making a 100% match between cells unlikely. Instead, the consortium suggests, cells that match at 75% or above can be considered to be the same. The group has now developed and tested a standardized procedure for extracting DNA from cells, doing the fingerprinting and interpreting the results. "Without policing, many investigators may not be motivated to do the necessary tests." Many researchers already use DNA fingerprinting to test their cell lines, notes Steve Oglesbee, director of the tissue-culture facility at the Lineberger Comprehensive Cancer Center of the University of North Carolina in Chapel Hill. The ATCC and other repositories have already established fingerprints for some of the most commonly used lines. "We're recommending that investigators authenticate from the beginning, and do it at least at the very end, and if they feel the need even during the work process," he says. Having a universally accepted approach will allow different facilities to compare their cell lines with each other, he adds. Fingerprinting has its limits, cautions Michael Johnson, a cancer researcher at Georgetown University in Washington DC. "Just because a cell fingerprints out as the same [as another cell] doesn't mean they will behave the same," he says, noting that a cell's properties can also be affected by the way it has been grown, the number of times it has been cultured anew and small genetic changes that wouldn't show up in a fingerprint test. One classic example, he notes, is an immortalized breast cell line called MCF10A, which can form organized hollow structures similar to those found in mammary tissue; MCF10A cells currently distributed by ATCC do not do this nearly as efficiently. Cell solution ADVERTISEMENT He worries that, useful though it would be, a database such as the one ATCC proposes "in some sense creates a false sense of security" about the "official version" of a cell line. Being able to keep track of a cell line's lineage — where it was derived — could be as important as ascertaining its DNA fingerprint, he adds. Others note that researchers will probably need an extra push to embrace the ATCC protocols. About half a dozen journals, including Wiley's International Journal of Cancer and journals published by the American Association for Cancer Research, have begun demanding that researchers authenticate their cell lines before they publish their work. And Nature has endorsed efforts to make verification easier and cheaper for researchers, pledging to require it once funders acknowledge the need and provide the necessary financial support1. "Without the policing by journal editors and granting agencies," says Gertrude Buehring, a virologist at the University of California, Berkeley, "many investigators may not be motivated to do the necessary tests to authenticate the cell lines used for their research." * References * Nature457, 935-936 (2009). * Lucey, B. P.et al. Arch. Pathol. Lab. Med.133, 1463-1467 (2009). * ATCC Standards Development Organization Workgroup AN-0002Nature Rev. Cancer10, 441-448 (2010). There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • Acupuncture for mice
    - Nature (London) 465(7298):538 (2010)
    Study hints at biological mechanism for alternative therapy. Is acupuncture more than mere placebo?Z. Kaluzny/Getty Images Long derided by much of the mainstream medical community, acupuncture seems to have just got a little bit less alternative. Despite anecdotal evidence claiming benefits in treating ailments from allergies to pain, acupuncture faces two big challenges to acceptance in mainstream medicine. Many reviews of clinical trials have concluded that there is no evidence of efficacy for most conditions beyond the placebo effect1, and there is no scientifically accepted mechanism for how the treatment works. Research in mice has now provided a biochemical explanation that some experts are finding more persuasive2, although it might account for only some of the treatment's supposed benefits. "Our study shows there is a clear biological mechanism behind acupuncture," says Maiken Nedergaard, a neuroscientist at the University of Rochester in New York, who led the research. Nedergaard's team wanted to find out whether the neuromodulator adenosine, which is produced when tissue is injured and has pain-dulling effects, was involved in the purported pain-relieving effects of acupuncture. After inducing pain in the right hind paws of their mice, the researchers inserted and rotated an acupuncture needle just below the 'knee', at a place known in humans as the 'Zusanli point'. For about an hour after the treatment the mice took longer to respond to touch or heat on the paw, indicating that their pain had been dulled. The team found that adenosine levels had increased at the acupuncture site, and that mice lacking a key cell receptor for adenosine did not show the same response. "One thing that's really nice about this is they approach this question with a specific and firm hypothesis," says Vitaly Napadow, a neuroscientist who studies acupuncture at Harvard Medical School in Boston, Massachusetts. Although sceptical that the mechanism could explain, for example, how acupuncture could relieve headaches, he says that "in conditions such as carpal tunnel syndrome, a mechanism such as that described in this paper might very well be important". Dominik Irnich, head of the Multidisciplinary Pain Centre at the University of Munich in Germany, and a doctor who uses acupuncture, notes that other studies have proposed mechanisms such as the release of endorphins or other neurotransmitters3,4. But Nedergaard says that these would act on the whole nervous system — her study found no effect when acupuncture was applied to the rodents' pain-free left legs, suggesting that there is not a central mechanism. Edzard Ernst, who studies the effectiveness of alternative therapies at the Peninsula Medical School in Exeter, UK, says that the mechanism is credible, but that the work does not address whether acupuncture is an effective treatment. "If the clinical effect is not beyond placebo, which most of the well-controlled clinical trials seem to suggest, the mechanism is irrelevant and the true mechanism is placebo," he says. ADVERTISEMENT Jana Sawynok, a pharmacologist who studies the pain-modulating effects of adenosine at Dalhousie University in Halifax, Canada, notes that caffeine blocks the adenosine receptor pinpointed in this study. Given the caffeine intake of many countries where acupuncture trials are carried out, this could be a serious confounding issue in trials, she suggests. Nedergaard says her work may open the way to making acupuncture more effective. Her study also treated the mice with a drug called deoxycoformycin, which suppresses the breakdown of adenosine and is approved in the United States for treating some types of leukaemia. The drug prolonged the pain-relieving effects of the acupuncture treatment by more than an hour; Nedergaard is now trying to organize a trial of this strategy in humans. * References * Ernst, E. J. Pain Symptom Manage.37, 709-714 (2009). | Article * Goldman, N. et al. Nature Neurosci.doi:10.1038/nn.2562 (2010). * Clement-Jones, V. et al. Lancet316, 946-949 (1980). | Article * Bing, Z. et al. Pain47, 71-77 (1991). | Article | PubMed | ChemPort | There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • Fisheries: What's the catch?
    - Nature (London) 465(7298):540 (2010)
    New England fishermen have mixed feelings about a programme designed to allow overfished species to recover. Mark Schrope reports on how catch shares have scientists fishing for answers. Download a PDF of this story. Dave Marciano first started working on commercial fishing boats when he was ten. Unlike many from his hometown in Gloucester, Massachusetts, Marciano didn't have deep generational ties to the sea. His father sold insurance. He nevertheless saved up the money to buy his first boat in 1993 — the Angelica Joseph, an 11-metre, Maine-built lobster rig. But in May, things changed dramatically for Marciano, 45, when regional fisheries managers instituted a new system to regulate the harvesting of 'groundfish' — cod, haddock and other predators that live on or near the sea floor. Convinced that he could no longer survive financially, he sold his fishing permit. He doubts he'll find a buyer for his current boat. The changes in New England — the region containing Massachusetts, as well as Connecticut, Maine, New Hampshire, Rhode Island and Vermont — portend what is likely to be the main thrust of US fisheries management for years, if not decades, to come. Under pressure from stiff new legal mandates, managers have had to slash the size of allowable catches for overfished species. To do this, they've chosen to implement catch shares, a radical departure from past management. Where previous systems enforced seasonal, area-based and other limits to reduce catches, catch shares give set quotas to individual fishermen, who are then free to decide how and when to fill them. They can also lease quotas to others or, as in Marciano's case, sell them off. In theory, catch shares have economic and ecological benefits, making for steadier income streams for fishermen and improving incentives for environmentally friendly practices. Many researchers, conservationists and even some fishermen have grown increasingly enamoured of catch shares and hail an emerging policy at the National Oceanic and Atmospheric Administration (NOAA) encouraging their widespread use as part of the solution for ailing oceans. These supporters are not insensitive to the social and economic costs associated with major management shifts, but they say the long-term benefits will be worth it. Still, some fishermen, legislators and scientists question whether the policy will work to replenish stocks and whether it is fair to fishermen. Scientists are struggling with the fact that catch shares have had different effects in different places. "Catch shares are an effective tool for addressing a lot of economic problems," says Roy Crabtree, southeast regional administrator for NOAA's Fisheries Service, "But I think the benefits from a biological perspective really have to be looked at case by case." Catch-share programmes have been used! to a limited degree in the United States, but the New England groundfish programme, because it is particularly challenging, will provide a unique test case for NOAA's new catch-shares policy, with lessons for other US fisheries and beyond. In the early seventeenth century, the English privateer Bartholomew Gosnold named the crooked finger of land extending from the Massachusetts coast Cape Cod, after the fish then so abundant in its surrounding waters that they "vexed" his crew. But as early as the 1800s, it was the lack of cod that became vexing, with fishermen travelling ever farther offshore for their quarry1. Eventually, cod became an infamous cautionary tale of ocean exploitation, and a key target of restoration. The situation varies within New England waters, but one of the most troubled cod stocks, on the Georges Bank, a 29,000-square-kilometre shallow located 100 kilometres off the Cape (see map), stands at just 12% of restoration goals, which in turn are probably a fraction of historic levels2. Click for a larger version. For decades, fisheries managers have tried increasingly restrictive methods to rebuild fish populations. In the 1990s, the New England Fisheries Management Council settled on the Days at Sea system. This is a complex series of fishing curbs including limitations on the number of days a fisherman can fish and how much fish can be caught per day, along with various fishing-ground closures. It essentially mandated inefficiency to limit catches and was restrictive enough to slash the number of active fishing boats from about 1,200 in 2001 to roughly 600 by 2009. Disaster management Some fish populations increased under the Days at Sea policy. However, most people agree that the system didn't work economically. "Days at Sea has been a disaster," says Robert Steneck, a marine ecologist at the University of Maine in Walpole. Jackie Odell, executive director of the Northeast Seafood Coalition, an industry group based in Gloucester, agrees. "People were very frustrated," she says — fishermen and scientists alike. An even greater incentive to seek a new management system came in 2007, with the reauthorization and revision of the Magnuson–Stevens Fishery Conservation and Management Act, wide-ranging national legislation passed in 1976 to regulate fisheries. New provisions included two ambitious mandates. First, managers had to eliminate overfishing — the practice of taking more than a sustainable level of fish — by 2010, by setting a total allowable catch for each stressed population each year. Second, if a stock is officially overfished — a distinct designation meaning the population is too low to be stable — total allowable catches need to be low enough to allow stocks to rebuild within a decade. Catch shares began looking more attractive than traditional management structures. One group of fishermen in 2004 got the management council to approve such a programme for cod caught on hook and line on the Georges Bank. In 2006, the pilot programme expanded to include net fishing in the area. In June 2009, the council decided to adopt the scheme as its primary management tool. Some countries have been adopting and modifying catch-share programmes since the 1970s. Considered a market-based solution, the idea is to minimize the competition for a limited resource by giving individual fishers the right to catch a certain amount of fish. Among the potential benefits, quotas can stabilize fishermen's income and allow them to fill their quotas whenever they like, spreading out fishing efforts. Doing away with season restrictions reduces 'derby' conditions, in which fishermen race out, even in dangerous weather, to catch as much as possible. It also eliminates seasonal market gluts, potentially increasing the prices fishermen can command for their catch. On the ecological side, catch shares can be designed to limit the catch of non-target fish, increase populations of regulated fish and possibly encourage better resource stewardship. Although many catch-share systems are based on giving fishermen individual quotas, the New England council opted for collec! tive sectors in which groups of fishing operations are allotted a quota and can determine what portion of it goes to each sector member. For the quota system in New England, a major contention is not so much the catch shares themselves, but how the quotas are set. And here, say many, the science is lacking. The Magnuson–Stevens reauthorization dictates that NOAA scientists conduct annual assessments for each managed population. In some cases, assessments were being done about once every five years. And it's doubtful that NOAA currently has the resources to scale up the effort. "That's big science," says Steve Cadrin, a biologist with NOAA's National Marine Fisheries Service based in Woods Hole, Massachusetts and chair of the scientific committee that advises the New England management council. Cadrin says that the agency has proposed relying on multiyear surveys that would set catch limits for a similar amount of time. Cod once dominated the waters off New England.NORTH WIND PICTURE ARCHIVES/ALAMY Stock growth Some have also questioned the accuracy of certain current surveys. In New England, the best available data show that overfishing is going on for 11 species or regionally distinct populations. Even more populations are already low enough to qualify as officially overfished. The New England Fishery Management Council is therefore required by law to drastically lower catch rates in 2010. Marciano says that the measures being taken don't align with his experience on the water. "If you set the technical definitions of overfishing aside for a minute and look at the stocks overall, you'll see nothing but upward trajectory for the past 15 to 20 years," he says. "There are more fish now than I've seen my entire life." But fishermen have a different perspective from scientists, says Cadrin. "They're out there every day and they know their fishing grounds very well, but they probably don't have as broad a view of all the different areas and different species." For instance, they may not appreciate the importance of rebuilding a variety of stocks if at least some stocks are doing very well. Recent research even suggests that genetic variety within a species is necessary to ensure a secure fishery3 (see page 609). Fisherman Dave Marciano in 1998 (left) and with family in 2007, says that the implementation of catch shares has forced him out of business.MARCIANO FAMILY Other scientists, however, find fault with the targets. Brian Rothschild, who oversaw implementation of the original Magnuson–Stevens act for NOAA is now a professor at the University of Massachusetts in Dartmouth. He says that the restoration targets for some troubled species are too high and that the ecosystem isn't equipped to handle maximum levels of all species all the time. "The carrying capacities of ecosystems don't really work that way," he says. Another question is whether catch shares are the best way to achieve mandated population restorations and increased biodiversity. A study4 published in 2008 analysed a database of more than 11,000 fisheries, 121 of which were managed using some form of catch shares. The study focused mainly on landings data, and looked for drops in catch as a sign of fishery collapse. The authors concluded that those under catch shares were less prone to collapse and that catch shares can halt or even reverse collapse. Other studies, using different methods, have suggested a more complicated picture. Timothy Essington, a fisheries ecologist at the University of Washington in Seattle, for instance, looked in more detail at 15 catch-share programmes in North America, analysing their effect on fish numbers, the use of habitat-damaging gear and commercial landings5. He found that results varied widely between systems, with continued population declines for some fisheries even under catch share management. "It totally depends on the baseline you're looking at," says Essington. Rise of the crustaceans Steneck, who was part of a task force that examined the catch-share concept for NOAA, says that the scheme could address the loss of diversity in New England's fisheries, which he has studied for more than 20 years. Initially focused on lobsters, he noticed early on that fish such as cod that feed on lobster young were suspiciously scarce. His work has convinced him that the ecosystem may well have shifted into a new state dominated by crustaceans. Even efforts to substantially limit fishing for cod on Georges Bank failed to revive the stocks. Although he has some reservations, Steneck says that catch shares could be a step in the right direction for fisheries management. "We really have to work on breathing more life into the biodiversity of the marine ecosystem for the good and stability of the populations and also for economic diversity," he says. "We really have to work on breathing more life into the biodiversity of the marine ecosystem." One way catch shares may do this is by reducing by-catch — the non-target fish caught and often discarded. Under the Days at Sea system, and most traditional management schemes, the incentive is to catch a lot of fish quickly and there is no individual penalty for by-catch. Under the catch-share system, fishermen get very small annual quotas for the most troubled species — choke species — and throwing fish overboard becomes illegal. Once the choke species quotas are met, all fishing by the sector has to end, providing a strong incentive for avoiding them, for instance by working with other fishers to identify and avoid areas where choke species are most plentiful. In theory, overexploited species will have a better chance of recovery. Another oft-touted benefit of catch shares, and one more difficult to prove, is that the system inspires better resource stewardship, including of the habitat on which a fishery depends as nursery and spawning ground. Fishermen might, for example, call for or acquiesce to new protected areas or fishing-gear limitations if they think it will improve the resources they share. "I've seen fishermen argue for closed areas and no-trawl zones because of the longer-term perspective that catch shares allow," says Rod Fujita, a senior scientist with the Environmental Defense Fund, a non-profit organization, based in San Francisco, California. But Les Watling, a deep-sea ecologist at the University of Hawaii at Manoa, says that anecdote isn't enough. "I haven't seen anything that demonstrates that the industry will protect bottom habitat as a result of catch shares," he says. ADVERTISEMENT Beyond such disputes lies the question of how the catch shares should be distributed. In New England's catch-share system, like most, quotas are determined on the basis of fishing history, but this can cause fairness issues. "The allocation issue really is the tough nut," says Essington. "Chances are there will be winners and losers." Marciano definitely considers himself a loser. Last year he landed almost 36 tonnes of cod, but his quota allocation for this year under catch shares was only 16.8 tonnes. He couldn't afford to buy quotas from others. There are no solid estimates of how many fishermen like Marciano will go out of business, but catch-share opponents say it could be 50% or more, a number many managers and scientists question. Have to be in it to win it "If you're in it, you think it's great. If you don't have any quota, you think it's terrible." Discontent with catch shares isn't universal among independent fishermen. "If you're in it, you think it's great. If you don't have any quota, you think it's terrible," says Larry Huntley, a commercial fisherman based in Pensacola, Florida, where several fledgling catch-share systems are in place. Tom Dempsey, policy coordinator for the Cape Cod Commercial Hook Fishermen's Association in North Chatham, Massachusetts, which has helped to organize some catch-share sectors, says that because of past problems with Days at Sea, many fishermen he works with are optimistic. "The thinking in town largely is that this is going to help them be more efficient and profitable," he says. He adds, however, that his group still has problems with some of the underlying economics of the system, including a lack of measures to protect against consolidation and monopolies. His group has already started a trust fund to purchase quotas that can then be leased to fishermen who might not otherwise ! be able to stay in the system. Many fishermen and scientists are hoping that the catch-share system will be changed to correct perceived economic inequities and other problems. But politicians aren't always willing to wait. US Representative Barney Frank (Democrat, Massachusetts) is proposing legislation to ease the requirements and timetables of the Magnuson–Stevens reauthorization. Huntley says he fears that such whims may be the greatest threat to the long-term success of rebuilding efforts. In the Gulf of Mexico, for example, in addition to commercial pressure, managers also have to address the concerns of powerful recreational fishing lobbies that have been generally displeased with their allocations under catch-share systems. "What worries me is that politics may outplay the science," says Huntley, "and I don't want to see that." Mark Schrope is a freelance writer in Melbourne, Florida. * References * Steneck, R. S. , Vavrinec, J. & Leland, A. V.Ecosystems7, 323-332 (2004). * Rosenberg, A. A.et al. Front. Ecol. Environ.3, 78-84 (2005). * Schindler, D. E.et al. Nature465, 609-612 (2010). * Costello, C. , Gaines, S. D. & Lynham, J.Science321, 1678-1681 (2008). * Essington, T. E.Proc. Natl Acad. Sci. USA107, 754-759 (2010). There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • Volcanology: Out of the ashes
    - Nature (London) 465(7298):544 (2010)
    The Icelandic eruption has given researchers the opportunity of a lifetime. Katharine Sanderson talks to scientists working around the clock to study the volcano and its effects. Download a PDF of this story On the evening of 14 April, Gelsomina Pappalardo sent a rushed message to her colleagues across Europe, asking them to switch on their lasers and point them skywards. The volcano Eyjafjallajökull in Iceland had just erupted, and an unusual wind pattern was sending the ash cloud into Europe's crowded airspace. Pappalardo, who works at the Institute of Methodologies for Environmental Analysis outside Potenza, Italy, wanted to use the network of laser-based instruments, known as lidars, to measure the ash as it spread over the continent. It would be a chance for the lidar collaboration to shine. Pappalardo, who coordinates the European Aerosol Research Lidar Network (EARLINET), wasn't the only scientist on high alert. As Eyjafjallajökull sullied the skies, dozens of researchers across Europe started scrambling to gather data. Atmospheric modellers, remote-sensing researchers, air-sampling experts, geologists and volcanologists are all taking advantage of this rare opportunity to measure a volcano in their own backyard. Researchers in Iceland are probing the volcano's plumbing beneath the surface, whereas scientists farther afield are trying to assess the evolution of the ash cloud. All are hoping to fulfil their own scientific curiosity about a rare and dramatic phenomenon, but they must first answer to national governments and civil-aviation authorities, who are demanding data on the eruption as soon as possible to forecast potential problems. That means putting aside normal practices. Working virtually non-stop since the eruption, researchers are quickly gathering data and releasing them, instead of keeping the information to themselves until it is ready for publication. "It's hard work for us," says Pappalardo, who has relied on the goodwill of her team to put in the extra hours for free to address government requests. "Since the 15th of April, I've been sleeping two or three hours a night, maximum." Pappalardo is faced with a problem: her data are highly valued by aviation authorities and atmospheric modellers, who want them instantly. But the measurements are not useful until they are analysed, and that takes time. The data are normally used in long-term studies of clouds, Saharan dust and other atmospheric components that affect the climate. "This is not a simple technique," she says. Pappalardo wants to ensure that the information she gives to others is accurate, so that forecasts made with those data are correct. So she stays up late, collating and analysing data from the 26 lidar stations across Europe, and then making the results available to aviation authorities. In the future, she says she would like governments to support the infrastructure for real-time monitoring and automated analysis. Faster access to such data would help atmospheric modellers improve their projections of ash concentrations at various altitudes. Aviation officials need that information when deciding whether to close airspaces (see Nature 464, 1253; 2010). An eye on Eyjafjallajökull Icelandic scientists are at the centre of the action and have been the busiest of all. For them, Eyjafjallajökull is more than just a recent air-traffic nuisance. "I've been keeping a close watch on this volcano for 18 years," says Freysteinn Sigmundsson, a volcanologist from the Institute of Earth Sciences at the University of Iceland in Reykjavík, who is interested in how Earth's crust deforms during seismic events. The volcano has been seismically jumpy for the entire time that Sigmundsson has studied it. But the earthquake activity intensified in December 2009, and came to a head with a lava-spewing eruption on the volcano's flank on 20 March. The spike in seismic unrest led authorities to evacuate people from the volcano's immediate vicinity before its summit started shooting ash on 14 April. This eruption seems to be similar to the volcano's previous one in 1821, which pulsed on and off for more than a year. Although the nineteenth-century pattern might indicate that the present eruption will be prolonged, the magmatic plumbing under Eyjafjallajökull is complicated says Sigmundsson, making predictions difficult. "There is no way of knowing how long this will last," he says. "There is no way of knowing how long this will last." Sigmundsson and his colleagues want to trace the magma conduits that feed the volcano. To do this, they track ground movement using Global Positioning System receivers around Iceland and satellite-borne radar interferometers, while seismic recordings provide information about underground structures. Such data are useful for the Icelandic Meteorological Office and the government, which must assess whether the volcanic activity is likely to increase. Magnús Tumi Gudmundsson, head of the faculty of Earth sciences at the University of Iceland, is watching the eruption itself using a variety of means, including radar instruments that can see through the ash cloud into the crater. His research group is studying the composition and amount of ash and rock discharged from the volcano, as well as water generated from the melting of glacial ice on top of Eyjafjallajökull. These data can help to predict whether the volcano will produce ash or lava, as well as whether floods are likely. Fire and water The meltwater produced by the initial stages of the eruption had far-reaching consequences. Researchers suspect that the interaction between water and magma produced exceptionally fine-grained ash. Between 50% and 70% of the ash grains were less than 100 micrometres in diameter, and some were smaller than 10 micrometres, says Gudmundsson. Such minute particles stay airborne longer than heavy particles, and they can get into jet engines and then melt, causing damage. Because the eruption quickly melted all ice near the summit, the ash grew coarser after the first four days. As they gather their data, Gudmundsson and his colleagues upload much of it to the university's website and send it to the Icelandic Meteorological Office. Gudmundsson says that 20 people from his institute are working "flat out" to monitor the volcano — putting aside regular research projects to do so. Eventually, Gudmundsson hopes to make geological sense of the data, and use them to investigate the magma chambers beneath the volcano and what controls the changes in magma behaviour, particularly when it interacts with water. At the moment all ideas are "highly speculative", he says. "I haven't had a chance to get a handle on changes that are happening." While Pappalardo, Sigmundsson and Gudmunsson's teams rushed to measure the eruption, Urs Baltensperger just had to bide his time. Baltensperger runs an atmospheric chemistry lab at the Paul Scherrer Institute in Villigen, Switzerland, which has instruments atop Jungfraujoch, a 3,500-metre-high Swiss mountain. Once Baltensperger realized that the ash cloud was on its way, he knew that this was a data-collection opportunity too good to miss. "We just had nothing to do but sit back, relax and wait for the plume to arrive," he says. Baltensperger's team, and his colleagues at Empa, the Swiss federal laboratories for materials science and technology, used filters and other instruments to determine the ash's mass concentration — the mass per volume of air. His group also measured how much light the ash cloud was blocking. From those two values, the researchers could calculate a parameter needed to turn lidar information into measures of how much ash is in the sky, of what type, and at what altitude. Such data complement the information provided to aviation authorities by Pappalardo's lidar network. Baltensperger was happy to pass his results on to the Swiss aviation authority. But, like Pappalardo, he says that to monitor future eruptions properly, real-time analysis and an automated data-transmission system are required. ADVERTISEMENT The eruption and the crisis it created in Europe are uniting researchers in unusual ways. Thor Thordarsson, a volcanologist from the University of Edinburgh, UK, who was in Iceland when the eruption began, says that because the ash blew over northern Europe, with its dense research network, it presents a unique opportunity to reconstruct the entire eruption and work out what happened within the volcano. But, as he told a group of UK-based scientists in Oxford at the end of April, "It can only work if everyone works together." Sigmundsson has taken a strategic approach to the release of data. His group posts updates on the seismicity, meltwater and the nature of the plume, such as its height, colour and heading. But it doesn't put up raw information. "We are expecting other scientists to allow us time to fully analyse those data for scientific publications," he says. Pappalardo says she hopes that her team's efforts to get lidar data out to the people who need them will bring something in return. The EARLINET lidar network has been running for a decade, at times on a completely voluntary basis. In a brief break from her work, she says the eruption might help to secure long-term funding for the network. "Now everybody wants to have these data." Katharine Sanderson is a freelance writer in London. There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • World view: Defending democracy
    - Nature (London) 465(7298):546 (2010)
    Government surveillance technology programmes must aim to protect privacy and civil rights from the start, says Daniel Sarewitz. Notwithstanding the incompetence of last month's New York City would-be bomber, the terrorist threat is real. One way governments try to meet this threat is with improved security technologies that keep track of terrorists' movements and communications. But these same devices will also be monitoring innocent people, and so can threaten privacy and civil rights. Will less freedom be an unavoidable side effect of powerful new surveillance technologies? Not necessarily — but the time to start thinking about the impact of security technologies on democratic rights is during research and development (R&D), not after the devices have been introduced into society. Ji Sun Lee, a lawyer at the US Department of Homeland Security (DHS) in Washington DC, is trying to do just this. Up to four times a year, Lee convenes a 15-person 'community acceptance of technology panel' to gather feedback on the social implications of one of the DHS's 140 technology projects. Panellists include experts in the social aspects of security and surveillance, as well as representatives of interest groups who might be particularly affected. Not exactly reassuring Some projects are pretty spooky — perhaps none more so than Future Attributes Screening Technology (FAST, see Nature 465, 412–415; 2010). Using physiological indicators such as heart rate and breathing, these devices would screen individuals at stadiums, airports and other possible terrorism sites for what the DHS inelegantly calls "malintent". Lee rejects my suggestion that FAST is leading the DHS into the territory of Minority Report, a movie in which authorities monitor citizens to predict crimes before they happen. But when I ask her about political and ethical concerns raised by her FAST panel, the DHS public-affairs officer monitoring our interview interrupts, saying: "We're not going into that level of detail." Such interdictions do not relieve one's paranoia. Hardly less worrisome are 'mobile biometrics' devices. These portable technologies will gather information, such as fingerprints, iris scans and facial images, and feed them into national databases to make rapid identifications and threat assessments. "The potential for abuse is massive," says Nihad Awad, executive director of the Council on American–Islamic Relations in Washington DC, and a participant in Lee's 2008 mobile-biometrics panel. "How are the data stored, who gets access to them, what sources of oversight exist?" "The time to start thinking about the impact of security technologies on democratic rights is during R&D." Similar questions emerged when Lee convened a panel on detecting terrorists at the US–Canada border. Panellists considered the implications of video surveillance along remote, unfenced parts of the border. They also discussed a DHS proposal to embed radio-frequency identification chips in the registration cards of vehicles and boats owned by Americans living near the border. The chip programme would allow more efficient monitoring of border-area security threats because US authorities could focus surveillance on vehicles without chips — but this would also turn every vehicle owned by a Canadian into a target of suspicion. Not surprisingly, Canadian panellists didn't want "the US government to be spying on Canadians doing whatever it was they wanted to do in the backwoods" and border towns, recalls panellist David Mutimer, a political scientist at York University in Toronto, Ontario. To make matters worse, the DHS gave no assurances about how the data would be used and privacy protected. Have the panels had any effect? Lee says that the panels provide recommendations to programme managers, but they don't have authority to terminate a project or dictate how technologies are developed. Awad and Mutimer feel that the process could be valuable, but neither has heard anything from the DHS since their panels, and they have no idea if their deliberations made a difference. Lee's boss, Sharla Rausch, head of the Human Factors/Behavioral Sciences Division, does say that one DHS project was substantially changed as a result of panel recommendations, but she will not provide specifics. In any case, one-off panels are not enough. Ongoing and interactive partnerships between panellists and technical teams are necessary. Awad, an engineer by training, is sympathetic to the idea that more-inclusive discussions could reduce some negative aspects of security technologies. But he emphasizes that panellists need to see the effects of their involvement so that they can develop trust in the process. For example, the American–Islamic council was strongly opposed to body scanners at airports because they violated Islamic rules on modesty. "If we had been involved in discussing the technologies from the beginning," Awad says, "we would have suggested that the software be designed to blur the images, and this would have avoided much controversy". Privacy by design The idea of R&D programmes that simultaneously consider technical prospects and social implications is hardly novel. In 1947, Detlev Bronk, head of the National Research Council, made this point in testimony to Congress: "Social scientists should work hand in hand with natural scientists, so that problems may be solved as they arise, and so that many of them may not arise in the first instance." In reality, the problem is less one of social-science research than of opening up the innovation process to a variety of informed perspectives. But the important point is that unless R&D programmes include consideration of social impacts at an early stage, scientists and engineers will miss opportunities to develop more socially desirable technologies. More than 60 years later, Lee's programme is a modest but hopeful step in this direction. Despite the DHS's self-defeating fear of transparency, Lee is working to figure out how to identify, discuss and address complex social dangers before they get locked into the new technologies. But to really make a difference, her programme — among the smallest in the DHS's billion-dollar science and technology directorate — would need to be ramped up to become a full partner in all of the agency's technology development. It would need to consider many more technologies, and do so in an open, integrated and persistent manner, rather than through single panels. Such a mainstreaming process might go a long way towards relieving the irony of technologies that protect citizens' lives even as they threaten their rights. Daniel Sarewitz, co-director of the Consortium for Science, Policy and Outcomes at Arizona State University, is based in Washington DC. e-mail: dsarewitz@gmail.com There are currently no comments. This is a public forum. Please keep to our Community Guidelines. You can be controversial, but please don't get personal or offensive and do keep it brief. Remember our threads are for feedback and discussion - not for publishing papers, press releases or advertisements.
  • Budget cuts: funding needed for startling new discoveries too
    - Nature (London) 465(7298):547 (2010)
    UK research-funding bodies have reacted to paucity in their budgets with plans to focus on supporting just a handful of scientists (see, for example, Nature465, 16–17; 2010); translational research; or research in areas of monetary importance, such as ageing. However, these strategies leave little room for surprising and groundbreaking discoveries.
  • Budget cuts: leaven the curriculum with a pinch of research
    - Nature (London) 465(7298):547 (2010)
    Diane Auer Jones suggests that cash-strapped US universities should reserve some faculty positions just for teaching (Opinion, Nature 465, 32–33; 2010). But a university's power and efficiency comes from combining research and teaching.
  • Budget cuts: company investment could help offset the shortfall
    - Nature (London) 465(7298):547 (2010)
    Research should not be left just to the elite universities (Opinion, Nature 465, 32–33; 2010).Take the public university where I teach, where research is important and cost-effective.
  • Protection needed for international species collections
    - Nature (London) 465(7298):547 (2010)
    The destruction of most of the zoological collection of the Butantan Institute in São Paulo, Brazil, by a fire on 15 May, will affect zoology worldwide (see Nature465, 272; 2010). Safeguarding and financing such important collections, including those housed in facilities in developing countries, should be an international concern.
  • Environment groups are not to blame for public complacency
    - Nature (London) 465(7298):547 (2010)
    It is an oversimplification to suggest that environmental groups have distanced themselves from the ordinary people whose interests they seek to serve (Column, Nature465, 287; 2010). Environmental groups continue to work as hard as ever, but face an increasing challenge because environmental problems are beyond the scale of direct perception by individuals.
  • Strategic body needed to beat food crises
    - Nature (London) 465(7298):548 (2010)
    The system that oversees global agriculture and food security needs an overhaul, says Joachim von Braun.
  • Empowerment is key
    - Nature (London) 465(7298):550 (2010)
    A plan to pull millions out of poverty while addressing climate change fails to acknowledge the importance of dispersing power to the people, explains Iqbal Quadir.
  • Excavating the puzzle of the Paris zodiac
    - Nature (London) 465(7298):551 (2010)
    Compared with other ancient astronomical artefacts, the Egyptian carving known as the Dendera zodiac has been largely forgotten. Yet, two centuries ago, it was as celebrated as the just-discovered Rosetta Stone.
  • More lab in the library
    - Nature (London) 465(7298):552 (2010)
    Jennifer Rohn, editor of the webzine LabLit.com, asks why so many novels with scientists as central characters have been published this year.
  • Condensed-matter physics: The emergent and hidden unveiled
    - Nature (London) 465(7298):553 (2010)
    The appearance of an unexplained electronic state in the uranium metal URu2Si2 at low temperatures has long puzzled condensed-matter physicists. The latest experiment on the material sheds light on the process.
  • Apoptosis: Lack of oxygen aids cell survival
    - Nature (London) 465(7298):554 (2010)
    In worms, neurons respond to low levels of environmental oxygen in a way that protects distant tissues from stress-induced cell death. The molecules that mediate this cell-cell signalling may be targets for cancer treatment.
  • Quantum physics: Frustrated trio mimicked
    - Nature (London) 465(7298):555 (2010)
    Quantum simulation is a promising tool for navigating the complex world of many-body physics. The technique has now been employed to simulate a frustrated network of three quantum magnets by using trapped ions.
  • Cell biology: How to don a coat
    - Nature (London) 465(7298):556 (2010)
    Cargo-carrying vesicles can assemble from hundreds of locations on the cell membrane, but how these sites are selected has been unclear. A small family of membrane-sculpting proteins may select the perfect location.
  • Geoscience: Driving Earth's surface motions
    - Nature (London) 465(7298):559 (2010)
    Density variations within Earth's mantle may be a significant driver of both horizontal and vertical surface movements. The fingerprints of such mantle processes have been found in the Mediterranean region.
  • Astrophysics: Young stars in young galaxies
    - Nature (London) 465(7298):559 (2010)
    A fine marriage between galaxy data and theoretical simulations offers an explanation for two apparently conflicting sets of observations on the rate at which stars formed at early cosmic times.
  • Organic chemistry: Symmetrizing the unsymmetrical
    - Nature (London) 465(7298):560 (2010)
    You might think that the partial symmetry of the molecule complanadine A makes it easy to prepare, but the reverse is true. Two syntheses of this compound offer insight into how to make partly symmetrical molecules.
  • Correction
    - Nature (London) 465(7298):561 (2010)
    Nature | Correction Correction Journal name:NatureVolume:465,Page:561Date published:(03 June 2010)DOI:doi:10.1038/465561aPublished online02 June 2010 Article tools * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg The News & Views article "Nuclear physics: Doubly magic tin" by Paul Cottle (Nature465, 430–431; 2010) gave the isotope of lead as lead-28 (28Pb), when the correct notation is of course lead-208 (208Pb). Additional data
  • Q&A: Cancer: Clues from cell metabolism
    - Nature (London) 465(7298):562 (2010)
    Interest in the abnormal metabolism exhibited by cancer cells has been reawakened by the discovery of oncogenic mutations in metabolic enzymes, and by tools that monitor metabolism in living cells. Existing and emerging therapies aim to target this abnormal metabolism in various ways.
  • Nearby galaxies as pointers to a better theory of cosmic evolution
    - Nature (London) 465(7298):565 (2010)
    Nature | Review Nearby galaxies as pointers to a better theory of cosmic evolution * P. J. E. Peebles1 Search for this author in: * NPG journals * PubMed * Google Scholar * Adi Nusser2 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Corresponding authorJournal name:NatureVolume:465,Pages:565–569Date published:(03 June 2010)DOI:doi:10.1038/nature09101 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg The great advances in the network of cosmological tests show that the relativistic Big Bang theory is a good description of our expanding Universe. However, the properties of nearby galaxies that can be observed in greatest detail suggest that a better theory would describe a mechanism by which matter is more rapidly gathered into galaxies and groups of galaxies. This more rapid growth occurs in some theoretical ideas now under discussion. View full text Subject terms: * Astronomy * Astrophysics Figures at a glance * Figure 1: Galaxies at radial distances 1 < D < 8 Mpc from the centre of the Local Group of galaxies. The Local Sheet is the concentration along the centre plane, and the Local Void is the region on the upper left in the left-hand projection. The ten most luminous galaxies (including M31 and the Milky Way at D < 1 Mpc) are indicated by the open circles. The orthogonal projections are plotted in supergalactic coordinates63. Black filled circles: 337 galaxies largely discovered on photographic plates and with well-measured distances64. Red triangles: 172 galaxies added by the Sloan Digital Sky Survey65 (SDSS), with redshift errors of less than 50 km s−1. Blue squares: 53 galaxies discovered by the H i Parkes All Sky Survey (HIPASS) from 21-cm emission by atomic hydrogen50. SDSS and HIPASS have less secure redshift distances and cover only the parts of the sky roughly indicated by the red and blue curves, respectively. There are many more dwarf galaxies to be discovered at this distance. * Figure 2: A galaxy typical of those found in low-density regions. The contours trace the extended, rotationally supported disk of atomic hydrogen. The central grey patch is a negative image of the more concentrated starlight. The circle at the bottom left indicates the telescope angular resolution. * Figure 3: Ongoing rearrangement of matter in the central luminous regions of galaxies. In this pure dark matter simulation, the haloes are suitable homes for spiral galaxies similar to the Milky Way. The figure was produced by J. Wang, Durham University, using the Aquarius66 simulation. The haloes are identified by letter code as in the first column of the simulation parameters at level 2 in table 1 in ref. 66. Dark matter particles at distances D < 2.9 kpc from the halo centre at the present epoch are plotted in yellow in all panels, particles now at 2.9 kpc < D < 7 kpc are plotted in black, particles now at D > 7 kpc but within the part of the halo that is now nominally close to statistical equilibrium are plotted in grey tones representing their surface number density, and particles now farther away are not plotted in any of the panels. The stars in a galaxy like the Milky Way are largely within ~7 kpc of the centre, the outer radius at the present epoch for the particles plotted in black. The box width, 830 kpc, is constant in p! hysical units. Present positions (redshift z = 0) are shown in the bottom row, positions when the universe was half its present size (z = 1) are shown in the middle row, and positions when the universe was one-quarter its present size (z = 3) are shown in the top row. The matter falling into the central regions that are largely occupied by the stars in a real galaxy tends to be balanced by matter flowing out47. The infalling matter does not so much add mass to the central parts of a galaxy as rearrange it. The parameter h is a measure of the present value of the Hubble constant. * Figure 4: Measures of early-type galaxies in more and less crowded environments. The vertical axis shows the galaxy radius, R. The horizontal axis shows a product of the galaxy radius, luminosity, L, and line-of-sight star velocity dispersion, σ, where μr is proportional to the logarithm of the surface brightness (∝L/R2). If the distributions of mass and star velocities were similar in these galaxies, the condition that gravity balance the pressure of the star velocities would require that the mass varies as M ∝ Rσ2, and if the mass were proportional to the luminosity, the variables would follow the red line. The contours showing the distributions of measurements, which follow the trend of the black line, are tilted from the red line such that M/L ∝ R0.3; larger galaxies have larger apparent mass-to-light ratios. The contours represent galaxies in more dense (dashed) and less dense (dotted) environments. Inset, histograms showing the distributions of departures from the trend indicated by the black line, expressed as departures, μ −!  μFP, of surface brightness from the mean, for galaxies in more dense (dashed) and less dense (dotted) environments. The differences between the histograms show that there is a systematic difference between mass-to-light ratios at given radius in galaxies in more and less crowded regions, but the difference is small. Author information * Author information * Comments Affiliations * Joseph Henry Laboratories, Princeton University, Princeton, New Jersey 08544, USA * P. J. E. Peebles * Physics Department, Technion, Haifa 32000, Israel * Adi Nusser Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * P. J. E. Peebles (pjep@princeton.edu) Additional data
  • Imaging the Fano lattice to 'hidden order' transition in URu2Si2
    - Nature (London) 465(7298):570 (2010)
    Nature | Article Imaging the Fano lattice to 'hidden order' transition in URu2Si2 * A. R. Schmidt1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * M. H. Hamidian1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * P. Wahl1, 3 Search for this author in: * NPG journals * PubMed * Google Scholar * F. Meier1 Search for this author in: * NPG journals * PubMed * Google Scholar * A. V. Balatsky4 Search for this author in: * NPG journals * PubMed * Google Scholar * J. D. Garrett5 Search for this author in: * NPG journals * PubMed * Google Scholar * T. J. Williams6 Search for this author in: * NPG journals * PubMed * Google Scholar * G. M. Luke6, 7 Search for this author in: * NPG journals * PubMed * Google Scholar * J. C. Davis1, 2, 8, 9 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:570–576Date published:(03 June 2010)DOI:doi:10.1038/nature09073Received09 December 2009Accepted30 March 2010 Abstract * Abstract * Author information * Supplementary information * Comments Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Within a Kondo lattice, the strong hybridization between electrons localized in real space (-space) and those delocalized in momentum-space (-space) generates exotic electronic states called 'heavy fermions'. In URu2Si2 these effects begin at temperatures around 55 K but they are suddenly altered by an unidentified electronic phase transition at To = 17.5 K. Whether this is conventional ordering of the -space states, or a change in the hybridization of the -space states at each U atom, is unknown. Here we use spectroscopic imaging scanning tunnelling microscopy (SI-STM) to image the evolution of URu2Si2 electronic structure simultaneously in -space and -space. Above To, the 'Fano lattice' electronic structure predicted for Kondo screening of a magnetic lattice is revealed. Below To, a partial energy gap without any associated density-wave signatures emerges from this Fano lattice. Heavy-quasiparticle interference imaging within this gap reveals its cause as the r! apid splitting below To of a light -space band into two new heavy fermion bands. Thus, the URu2Si2 'hidden order' state emerges directly from the Fano lattice electronic structure and exhibits characteristics, not of a conventional density wave, but of sudden alterations in both the hybridization at each U atom and the associated heavy fermion states. View full text Subject terms: * Materials * Materials science * Methods Figures at a glance * Figure 1: A Kondo lattice model and its resulting band structure. , A schematic representation of the screening of a localized spin-half state (red) by delocalized -space electrons (green) caused by the Kondo effect1, 2, 3, 4, 5. , A typical Fano tunnelling-conductance spectrum5 expected near the electronic many-body state depicted in . , A schematic representation of the T ≈ 0 band structure expected of a Kondo lattice as in equation (2), with the light hole-like band at high temperature depicted by a dashed line. The approximate hybridization energy range is shown by horizontal arrows. * Figure 2: Imaging the Fano lattice in URu2Si2. , A typical topographic image of the Si-terminated surface of URu2Si2. The Si site is marked with a cross and the U site with an X. Data were acquired at −60 mV and 2 GΩ junction resistance. , A typical spatially averaged Fano-like spectrum detected on all Si-terminated surfaces of URu2Si2 at T < 20 K. The inset shows the layered structure of the crystal with the U-terminated surface; the Si-terminated surface is two atomic layers below with each Si at the middle site between four U atoms. , Image of the many-body state energy ε0() extracted from fitting the spatially resolved Fano spectrum according to equation (1); the FOV is indicated by the yellow box in . U atoms are designated by an X and the maximum in ε0 always occurs at these sites. , Image of the hybridization width Γ() extracted from fitting the spatially resolved Fano spectrum according to equation (1); the FOV is the same as in . The minimum in Γ occurs at the U sites. , Image of the rati! o of electron tunnelling probability ζ() extracted from fitting the spatially resolved Fano spectrum according to equation (1); the FOV is the same as in and . The maximum in ζ occurs at the U sites. * Figure 3: Evolution of DOS(E) upon entering the hidden-order phase. , Topographic image of U-terminated surface with the temperature dependence of its spatially averaged spectra in the inset. Each of these spectra is shifted vertically by 5 nS for clarity. Blue data are within 1 K of To for 1% Th-doped samples. The image was taken at −10 mV and 2.5 MΩ junction resistance. , Temperature dependence of DOS(E) modifications due to the appearance of the hidden order at the U-terminated surfaces. Each spectrum is derived by subtracting the spectrum for T > To (and shifted vertically for clarity). The DOS(E) changes are limited to approximately ±5 meV. , Topographic image of Si-terminated surface with the temperature dependence of its spatially averaged spectra in the inset. Each of these spectra is shifted vertically by 5 nS for clarity. The image was taken at 150 mV and 3 GΩ junction resistance. , Temperature dependence of DOS(E) modifications due to the appearance of the hidden order at the Si-terminated su! rfaces. Each spectrum is derived by subtracting the fit to a Fano spectrum (equation (1)), which excludes data points in the range −7.75 mV to 6.75 mV. The DOS(E) changes are again limited to approximately ±5 meV. * Figure 4: Energy dependence of heavy f-electron quasiparticle interference. –, Atomically resolved g(, E) for six energies measured at the U-terminated surface. Extremely rapid changes in the interference patterns occur within an energy range of only a few millielectronvolts. Data were acquired at –6 mV and 25 MΩ setpoint junction resistance. –, Fourier transforms g(, E) of the g(, E) in –. The associated g(, E) movie is shown in the Supplementary Information. The length of half-reciprocal unit-cell vectors are shown as dots at the edge of each image. Starting at energies below EF (), the predominant QPI wavevectors diminish very rapidly until ; upon crossing a few millielectronvolts above EF, they jump to a significantly larger value and rotate through 45°. Then they again diminish in radius with increasing energy in , and . This evolution is not consistent with a fixed * conventional density wave state but is consistent with an avoided crossing between a light band and a very heavy band. * Figure 5: Emergence of the two new heavy bands below the hidden-order transition. , Dispersion of the primary QPI wavevector for T > To along the (0, 1) direction (see Fig. 4g). A single light hole-like band crosses EF. , Dispersion of the primary QPI wavevector for T > To along the (1, 1) direction (see Fig. 4g). A single light hole-like band crosses EF. , Dispersion of the primary QPI wavevector for T ≈ 5.9 K along the (0, 1) direction (see Fig. 4g). Two heavy bands have evolved from the light band and become well segregated in -space within the hybridization gap. , Dispersion of the primary QPI wavevector for T ≈ 5.9 K along the (1, 1) direction (see Fig. 4g). Two heavy bands have evolved from the light band and are again segregated in -space within the hybridization gap. Author information * Abstract * Author information * Supplementary information * Comments Affiliations * Laboratory for Atomic and Solid State Physics, Department of Physics, Cornell University, Ithaca, New York 14853, USA * A. R. Schmidt, * M. H. Hamidian, * P. Wahl, * F. Meier & * J. C. Davis * Condensed Matter Physics and Materials Science Department, Brookhaven National Laboratory, Upton, New York 11973, USA * A. R. Schmidt, * M. H. Hamidian & * J. C. Davis * Max-Planck-Institut für Festkörperforschung, Heisenbergstraße1, D-70569 Stuttgart, Germany * P. Wahl * Theory Division and Center for Integrated Nanotechnology, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA * A. V. Balatsky * Brockhouse Institute for Materials Research, McMaster University, Hamilton, Ontario, L85 4M1, Canada * J. D. Garrett * Department of Physics and Astronomy, McMaster University, Hamilton, Ontario, L8S 4M1, Canada * T. J. Williams & * G. M. Luke * Canadian Institute for Advanced Research, Toronto, Ontario, M5G 1Z8, Canada * G. M. Luke * School of Physics and Astronomy, University of St Andrews, St Andrews, Fife KY16 9SS, UK * J. C. Davis * Department of Physics and Astronomy, University of British Columbia, Vancouver, V6T 1Z1, Canada * J. C. Davis Contributions A.R.S., M.H.H., P.W. and F.M. performed the SI-STM measurements and data analysis. J.D.G, T.J.W. and G.M.L. synthesized and characterized the materials. A.V.B. provided the theoretical framework. J.C.D. wrote the manuscript and supervised the project. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * J. C. Davis (jcdavis@ccmr.cornell.edu) Supplementary information * Abstract * Author information * Supplementary information * Comments Movies * Supplementary Video 1 (2.3M) This movie shows the Fourier transform of the real space conductance maps of Th-doped URu2Si2 in the heavy fermion paramagnetic phase at a temperature of 19K. The patterns are due to quasiparticle interference. The red diamonds in the corners mark the locations of the U atom reciprocal lattice vectors. * Supplementary Video 2 (4.8M) This movie shows the Fourier transform of the real space conductance maps of Th-doped URu2Si2 in the hidden order phase at a temperature of 1.9K. The red diamonds in the corners mark the locations of the U atom reciprocal lattice vectors. The patterns are due to quasiparticle interference. The two dimensional patterns are seen to become highly separated from the patterns seen at 19K for biases -3mV to 3mV. PDF files * Supplementary Information (1.8M) This file contains Supplementary Notes (I)-(IX), Supplementary Figures S1-S9 with legends and References. Additional data
  • HIF-1 antagonizes p53-mediated apoptosis through a secreted neuronal tyrosinase
    - Nature (London) 465(7298):577 (2010)
    Nature | Article HIF-1 antagonizes p53-mediated apoptosis through a secreted neuronal tyrosinase * Ataman Sendoel1, 2, 3 Search for this author in: * NPG journals * PubMed * Google Scholar * Ines Kohler1, 7 Search for this author in: * NPG journals * PubMed * Google Scholar * Christof Fellmann1, 4, 5 Search for this author in: * NPG journals * PubMed * Google Scholar * Scott W. Lowe4, 6 Search for this author in: * NPG journals * PubMed * Google Scholar * Michael O. Hengartner1 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:577–583Date published:(03 June 2010)DOI:doi:10.1038/nature09141Received08 February 2010Accepted28 April 2010 Abstract * Abstract * Author information * Supplementary information * Comments Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Hypoxia-inducible factor (HIF) is a transcription factor that regulates fundamental cellular processes in response to changes in oxygen concentration. HIFα protein levels are increased in most solid tumours and correlate with patient prognosis. The link between HIF and apoptosis, a major determinant of cancer progression and treatment outcome, is poorly understood. Here we show that Caenorhabditis elegans HIF-1 protects against DNA-damage-induced germ cell apoptosis by antagonizing the function of CEP-1, the homologue of the tumour suppressor p53. The antiapoptotic property of HIF-1 is mediated by means of transcriptional upregulation of the tyrosinase family member TYR-2 in the ASJ sensory neurons. TYR-2 is secreted by ASJ sensory neurons to antagonize CEP-1-dependent germline apoptosis. Knock down of the TYR-2 homologue TRP2 (also called DCT) in human melanoma cells similarly increases apoptosis, indicating an evolutionarily conserved function. Our findings identify a nov! el link between hypoxia and programmed cell death, and provide a paradigm for HIF-1 dictating apoptotic cell fate at a distance. View full text Subject terms: * Cancer Figures at a glance * Figure 1: HIF-1 antagonizes DNA-damage-induced apoptosis. , HIF-1 western blot analysis of synchronized young adult hermaphrodites. All alleles used in this study are defined in Methods. –, Synchronized young adult hermaphrodites were exposed to ionizing radiation (IR) and germline apoptosis was analysed by DIC microscopy 12 h after treatment. Arrows indicate germ cell corpses. Scale bars, 10 μm. –, Quantification of germline apoptosis. Synchronized young adult hermaphrodites were exposed to IR and germline apoptosis was quantified at the indicated time points. Data shown represent the average of three to six independent experiments ± s.d. (n > 20 animals for each experiment and time point). * Figure 2: HIF-1 impedes DNA-damage-induced apoptosis by inhibiting CEP-1. , Wild-type or vhl-1(ok161) worms were grown on bacteria containing either an empty control RNAi vector or ced-9(RNAi). Germline apoptosis was quantified at the indicated time points beginning at the fourth larval (L4) stage. Data shown represent the average of three independent experiments ± s.d. (n > 20). , CEP-1 western blot analysis of synchronized young adult animals. pCEP-1, phosphorylated CEP-1. β-actin was used as loading control. * Figure 3: The antiapoptotic function of HIF-1 is mediated by a concerted action of TYR-2 and TYR-3. , Wild-type or vhl-1(ok161) worms were grown on bacteria containing either an empty control RNAi vector or the HIF-1β homologue aha-1(RNAi) beginning at the third larval stage (L3). Synchronized young adult animals were irradiated and germline apoptosis was quantified at the indicated time points. Data shown represent the average of three independent experiments ± s.d. (n > 20 per time point and experiment). –, Time-course analysis of germ cell apoptosis in synchronized control or irradiated young adult animals. Data shown represent the average of three to six independent experiments ± s.d. (n > 20). , Western blot analysis of CEP-1 in synchronized young adult worms. β-actin was used as loading control. , Analysis of germ cell apoptosis in unirradiated synchronized animals 48 h after L4 stage. Data shown represent the average of three independent experiments ± s.d. (n > 20). * Figure 4: HIF-1 drives tyr-2 expression in ASJ neurons. , Transcriptional tyr-2 GFP-reporter opIs216[Ptyr-2::gfp] in a vhl-1(ok161) mutant background reveals HIF-1-dependent expression in two neurons in the head. Arrowheads indicate the dendritic extensions to the anterior end of the worm. Arrows indicate axons that are associated with the nerve ring. Scale bar, 20 μm. –, DiD staining in opIs216[Ptyr-2::gfp]; vhl-1(ok161) reveals that the GFP signal co-localizes with the most ventro-posterior amphid neurons, the ASJL and ASJR sensory neurons. Scale bars, 10 μm. * Figure 5: TYR-2 is a l-dopachrome tautomerase secreted by the ASJ neurons to inhibit apoptosis. , Laser microbeam ablation of ASJ neurons. Germline apoptosis of laser-ablated and mock-ablated animals was quantified 24 h after irradiation and the presence of GFP-positive ASJ neurons was determined subsequently. The number of intact ASJ neurons is indicated. Representative head and appendant germ lines are shown on the right; mock-ablated animals in the top row, ASJ-ablated animals are shown in the bottom row. Arrows indicate ASJ neurons; arrowheads apoptotic germ cells. Scale bars, 10 μm. , Germline endocytosis was inhibited by rme-2(RNAi) and germ cell apoptosis quantified. Data shown represent the average of three independent experiments ± s.d. (n > 20 animals). , , DIC microscopy section and TYR-2::GFP nuclear localization in the germ line of Phus-1::tyr-2-SP::gfp::tyr-2(3′region) animals, which express TYR-2 lacking the signal peptide (amino acids 1–22). Scale bars, 5 μm. , Nuclear localization of TYR-2::GFP in Ptyr-2::tyr-2-SP::gfp::tyr-2(3′r! egion) animals. Hypodermal nuclei are depicted. Scale bar, 5 μm. , l-dopachrome tautomerase activity of GST::TYR-2, GST::GFP and mushroom tyrosinase. , Model for HIF-1-mediated inhibition of germline apoptosis. –, Loss of human tyrosinase-related protein 2 (TRP2; also called DCT) results in increased cisplatin-induced apoptosis in WM266-4 metastatic melanoma cells. Melanoma cells were treated with 50 μM cisplatin, stained with Annexin-V/propidium iodide (PI) 24 h after treatment and analysed by flow cytometry. TRP2 knock down (shDCT374) increases Annexin-V positive/PI negative fractions (early apoptotic cells) compared to control shRNA (Luciferase) in WM266-4 melanoma cells (, ). The shDCT374 (targeting endogenous TRP2 5′ UTR) phenotype is rescued by expression of wild-type TRP2 (MSCV-DCT) (), but not of the catalytically inactive point mutant TRP2(H189A/R194A) (MSCV-DCT)(). Data shown are representative of four experiments. APC-A, allophycocyanin conjugate-Anne! xin-V. , TRP2 and p53 western blot analysis in WM266-4 melanom! a cells. Author information * Abstract * Author information * Supplementary information * Comments Affiliations * Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland * Ataman Sendoel, * Ines Kohler, * Christof Fellmann & * Michael O. Hengartner * PhD program in Cancer Biology, University of Zurich, Winterthurerstrassse 190, CH-8057 Zurich, Switzerland * Ataman Sendoel * MD-PhD program, University of Zurich, 8057 Zurich, Switzerland * Ataman Sendoel * Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA * Christof Fellmann & * Scott W. Lowe * PhD program in Molecular Life Sciences, University of Zurich, Winterthurerstrassse 190, CH-8057 Zurich, Switzerland * Christof Fellmann * Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA * Scott W. Lowe * Present address: Institute of Medical Virology, University of Zurich, Winterthurerstrassse 190, CH-8057 Zurich, Switzerland. * Ines Kohler Contributions A.S. designed experiments, performed most of the experiments and analysed data; I.K. generated opIs425 transgenic animals and performed experiments; C.F. established shRNA melanoma cell lines and helped to perform melanoma experiments; S.W.L. contributed to the design of melanoma experiments and analysed data; M.O.H. designed experiments and analysed the data. A.S. and M.O.H. wrote the paper. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Michael O. Hengartner (michael.hengartner@imls.uzh.ch) Supplementary information * Abstract * Author information * Supplementary information * Comments PDF files * Supplementary Information (4.7M) This file contains Supplementary Figures 1-21 with legends, Supplementary Tables 1-2 and References. Additional data
  • A dicer-independent miRNA biogenesis pathway that requires Ago catalysis
    Cheloufi S Dos Santos CO Chong MM Hannon GJ - Nature (London) 465(7298):584 (2010)
    Nature | Article A dicer-independent miRNA biogenesis pathway that requires Ago catalysis * Sihem Cheloufi1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Camila O. Dos Santos1 Search for this author in: * NPG journals * PubMed * Google Scholar * Mark M. W. Chong3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * Gregory J. Hannon1 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Corresponding authorJournal name:NatureVolume:465,Pages:584–589Date published:(03 June 2010)DOI:doi:10.1038/nature09092Received26 February 2010Accepted19 April 2010Published online27 April 2010 Abstract * Abstract * Accession codes * Author information * Supplementary information * Comments Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg The nucleolytic activity of animal Argonaute proteins is deeply conserved, despite its having no obvious role in microRNA-directed gene regulation. In mice, Ago2 (also known as Eif2c2) is uniquely required for viability, and only this family member retains catalytic competence. To investigate the evolutionary pressure to conserve Argonaute enzymatic activity, we engineered a mouse with catalytically inactive Ago2 alleles. Homozygous mutants died shortly after birth with an obvious anaemia. Examination of microRNAs and their potential targets revealed a loss of miR-451, a small RNA important for erythropoiesis. Though this microRNA is processed by Drosha (also known as Rnasen), its maturation does not require Dicer. Instead, the pre-miRNA becomes loaded into Ago and is cleaved by the Ago catalytic centre to generate an intermediate 3′ end, which is then further trimmed. Our findings link the conservation of Argonaute catalysis to a conserved mechanism of microRNA biogenesis! that is important for vertebrate development. View full text Subject terms: * Biochemistry * Genetics * Genomics * Developmental biology Figures at a glance * Figure 1: Ago2 is essential for extra-embryonic development , LacZ whole-mount staining of embryonic day 9.5 embryos bearing the Ago2gt or Ago1gt gene trap beta-galactosidase reporter alleles and wild-type controls (WT ctrl). , Allelic combination in Ago2 insertional mutant embryos, with the structure of each allele shown. HPRT, Hypoxanthine-guanine phosphoribosyl transferase gene; NEO, neomycin resistance gene; PURO, puromycin resistance gene. , Example wild type (WT) and mutant (Ago2mmc/gt) embryos from heterozygous intercrosses. Left panel: embryonic day 10.5 embryos within their embryonic yolk sac and placentas. Right panel: embryos dissected from their extra-embryonic components. , Representative embryonic day 12.5 chimaeric embryo developed from Ago2 null ES cells aggregated with wild-type tetraploid embryos. From left to right: whole chimaeric embryonic conceptus (Ago2mc/gt:WT), beta-galactosidase staining of the whole embryo showing contribution of Ago2 null ES cells (Ago2 mc/gt), beta-galactosidase staining of the placenta s! howing contribution of the ES cells to the vasculature invading the placental labyrinth (Ago2mc/gt:WT). * Figure 2: Ago2 catalysis is essential for development , Representative neonates from Ago2ADH heterozygous inter-crosses. WT, wild type; Mut, Ago2 homozygous mutant. , Peripheral blood count of litter mates from WT and Mut. Data are the mean ± s.d. *t-test (unequal variance for embryonic day 18.5 time point P = 0.035, equal variance for the birth time point P = 1.95 × 10-7). , Representative FACS analysis using CD71/Ter-119 erythroid populations marking of individual bone marrow samples of mutant versus wild-type litter mates. Three independent pairs from three different litters showed virtually identical profiles. APC, Allophycocyanin; FITC, fluorescein isothiocyanate * Figure 3: Mature miR-451 expression depends on Ago2 catalysis , Scatter plot of miRNA reads in wild-type versus mutant fetal liver. , Quantitative RT–PCR of primary transcript levels of miR-144 and miR-451 in wild-type and mutant liver samples. Data are the mean of three biological replicates ± s.d. *t-test with equal variance P > 0.05. , The unique structure of the miR-451 hairpin compared to miR-144 with the miRBase annotation of mature miR-451 and miR-144 mapped to the predicted secondary hairpin structure shown. Guide strand in red and passenger strand in blue. * Figure 4: Non-canonical biogenesis of miR-451. , Effect on mature miRNA levels of Drosha conditional ablation in Drosha flox/flox Cre-ER MEFs. , In vitro processing of miR-451 and miR-144 primary transcripts by Drosha immunoprecipitates (IP). Pre-miR-144 and pre-miR-451 are indicated with their corresponding expected sizes. Additional fragments released by possible Drosha processing of the 5′ miR-451 flank are indicated with asterisks. Flanks are indicated with arrowheads. , Northern blots for confirmation of in vitro Drosha processing assays. , Effect on mature miRNA levels of Dicer conditional ablation in Dicer flox/flox Cre-ER ES cells. , Effect on mature miRNA levels in Dicer null stable ES cells. , Northern blot of mature miR-451 expression in Dicer null stable ES cells. U6 is used as a loading control. * Figure 5: Ago2 catalysis is required for miR-451 biogenesis , Left panels, northern blot on total RNA from WT and mutant livers probing for the miR-451 guide strand and the passenger arm of the hairpin (indicated). Let-7 is used as a loading control. Right panels, northern blots of Ago2 and IgG control immunoprecipitates from WT and mutant liver extracts with the indicated probes. , miRNA read length distribution for the indicated miRNA from deep sequencing of WT and mutant livers. , prediction of a miR-451 Ago2 cleavage site. Top, miR-451 3′ end heterogeneity. Bottom, predicted cleavage site at the thirtieth phosphodiester bond of pre-miR-451. , Left gel, in vitro cleavage assay of pre-miR-451 by an Ago2 immunoprecipitate. Right gel, confirmation of the 3′ end character of the Ago2 cleavage product using beta elimination and 3′ end ligation reactions. β, beta-eliminated; UT, untreated. , Immunoprecipitation-northern blot indicating presence of the mature form of miR-451 in Ago2 complexes and loading of pre-miR-451 without pro! cessing in Ago1 complexes. , Left, schematic depictions of the pre-let-7-miR-451 mimic hairpin compared to the native pre-let-7. Guide strand in red and passenger strand in blue. Right, FACS analysis for GFP in the indicated samples. Cells were co-transfected with phycoerythrin (PE)–siRNA control. PE-positive cells (105) were gated and analysed for GFP expression. Accession codes * Abstract * Accession codes * Author information * Supplementary information * Comments Primary accessions Gene Expression Omnibus * GSE21370 Author information * Abstract * Accession codes * Author information * Supplementary information * Comments Affiliations * Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA * Sihem Cheloufi, * Camila O. Dos Santos & * Gregory J. Hannon * Graduate Program in Genetics, Stony Brook University, Stony Brook, New York 11794, USA * Sihem Cheloufi * The Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA * Mark M. W. Chong * The Walter and Eliza Hall Institute of Medical Research Parkville, Victoria 3052, Australia * Mark M. W. Chong Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Gregory J. Hannon (Correspondence and requests for materials should be addressed to G.J.H. (hannon@cshl.edu).) Sequencing data has been deposited in GEO and assigned accession number GSE21370. Supplementary information * Abstract * Accession codes * Author information * Supplementary information * Comments PDF files * Supplementary Information (5.9M) This file contains Supplementary Table 1 and Supplementary Figures S1-S8 with legends. An earlier version of this paper was published online on 27 April 2010 Additional data
  • Quantum simulation of frustrated Ising spins with trapped ions
    - Nature (London) 465(7298):590 (2010)
    Nature | Letter Quantum simulation of frustrated Ising spins with trapped ions * K. Kim1 Search for this author in: * NPG journals * PubMed * Google Scholar * M.-S. Chang1 Search for this author in: * NPG journals * PubMed * Google Scholar * S. Korenblit1 Search for this author in: * NPG journals * PubMed * Google Scholar * R. Islam1 Search for this author in: * NPG journals * PubMed * Google Scholar * E. E. Edwards1 Search for this author in: * NPG journals * PubMed * Google Scholar * J. K. Freericks2 Search for this author in: * NPG journals * PubMed * Google Scholar * G.-D. Lin3 Search for this author in: * NPG journals * PubMed * Google Scholar * L.-M. Duan3 Search for this author in: * NPG journals * PubMed * Google Scholar * C. Monroe1 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:590–593Date published:(03 June 2010)DOI:doi:10.1038/nature09071Received10 January 2010Accepted31 March 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg A network is frustrated when competing interactions between nodes prevent each bond from being satisfied. This compromise is central to the behaviour of many complex systems, from social1 and neural2 networks to protein folding3 and magnetism4, 5. Frustrated networks have highly degenerate ground states, with excess entropy and disorder even at zero temperature. In the case of quantum networks, frustration can lead to massively entangled ground states, underpinning exotic materials such as quantum spin liquids and spin glasses6, 7, 8, 9. Here we realize a quantum simulation of frustrated Ising spins in a system of three trapped atomic ions10, 11, 12, whose interactions are precisely controlled using optical forces13. We study the ground state of this system as it adiabatically evolves from a transverse polarized state, and observe that frustration induces extra degeneracy. We also measure the entanglement in the system, finding a link between frustration and ground-state ent! anglement. This experimental system can be scaled to simulate larger numbers of spins, the ground states of which (for frustrated interactions) cannot be simulated on a classical computer. View full text Subject terms: * Applied physics * Engineering * Materials science * Information technology Figures at a glance * Figure 1: Frustrated Ising spins. , Simplest case of spin frustration, with three antiferromagnetic spins on a triangle. , Image of three trapped atomic 171Yb+ ions in the experiment, taken with an intensified charge-coupled-device camera, with nearest-neighbour (J1) and next-nearest-neighbour (J2) interactions. , Expected form of the Ising interactions J1 and J2, controlled through the detuning, μ, of an optical spin-dependent force, scaled to the axial (νz) and transverse (ν1) centre-of-mass (CM) normal-mode frequencies of motion such that the CM, tilt and zigzag modes of transverse motion occur at = 0, −1 and −2.4, respectively13. * Figure 2: Quantum simulation of the three-spin Ising model with a transverse field. , Theoretical phase diagram of ferromagnetic order of the Ising model with a transverse field, characterized by P↓↓↓ + P↑↑↑ plotted as a function of the final value of By/Jrms and the scaled laser beat-note detuning, . –, Evolution of each of the eight spin states, measured with a charge-coupled-device camera, plotted as By/Jrms is ramped down in time, with each plot corresponding to a different form of the Ising couplings through the laser detuning (trajectories denoted by vertical dashed lines in ). The green circles are the two ferromagnetic states, the blue diamonds are the two symmetric antiferromagnetic states and the red squares are the remaining four asymmetric antiferromagnetic states. The dotted lines correspond to the populations in the exact ground state and the solid lines represent the theoretical evolution expected from the actual ramp, including non-adiabaticity from the initial sudden switch-on of the Ising Hamiltonian. The probability of i! nelastic spontaneous scattering is not included in the theoretical curves. , All interactions are antiferromagnetic (region I of Fig. 1c). The ferromagnetic-ordered states vanish and the six antiferromagnetic states are all populated as By → 0. Because J2 ≈ 0.8J1 for this data, a population imbalance also develops between symmetric and asymmetric antiferromagnetic states. , All interactions are ferromagnetic (region II of Fig. 1c), with evolution to the two ferromagnetic states as By → 0. , Strong antiferromagnetic interactions between next-nearest neighbours and weak ferromagnetic interactions between nearest neighbours. Here the four asymmetric antiferromagnetic states |↓↓↑, |↑↓↓, |↓↑↑ and |↑↑↓ emerge with roughly equal probabilities. , Next-nearest-neighbour antiferromagnetic interactions balance nearest-neighbour ferromagnetic interactions, with six states emerging. , Nearest-neighbour antiferromagnetic interactions and next-nea! rest-neighbour ferromagnetic interactions, with states |↓↑! ↓ and |↑↓↑ emerging. * Figure 3: Entanglement generation through the quantum simulation. Comparison of entanglement witness-operator measurements, using a photomultiplier tube for detection (see Methods for the error budgets), for ferromagnetic () and antiferromagnetic () situations as |By|/Jrms is ramped down, with a negative value of the witness operator indicating entanglement. For this data, |J2/J1| ≈ 0.85. Angle brackets indicate expectation values. , In the ferromagnetic regime, we measure a GHZ witness operator with φ = y (filled circles) and find that entanglement occurs for |By|/Jrms < 1.25. The GHZ fidelity, F (open circles), or the overlap probability with the ideal GHZ state, is also extracted from this measurement, where F > 0.5 indicates entanglement24. , For the frustrated antiferromagnetic case, we measure a W-state witness operator (filled circles) and find that entanglement emerges for By/Jrms < 1.1. In both and , the dashed lines are theoretical witness-operator values for the exact ground states, and the solid lines theoret! ically describe the expected witness-operator values given the actual ramps, not including detection errors or errors due to spontaneous scattering or fluctuations in control parameters. The error bars represent the spread over the observed witness-operator expectations following various global rotation directions of the spins, and indicate the uncertainty due to parasitic effective magnetic fields not appearing in equation (1) as well as possible drifts in the control parameters. * Figure 4: Entanglement and frustration. The effect of symmetry breaking on the ferromagnetic and antiferromagnetic cases of the Ising model, using a photomultiplier tube for detection. , Measured x-basis populations of ferromagnetic Ising model (J1, J2 < 0; By/Jrms = 0.42), expressed in terms of the probability, PM, of there being M spins in state |↑. , Measured populations of the ferromagnetic Ising model with By/Jrms = 0.34, where a symmetry-breaking field is added during the ramp and increases linearly to Bx/Jrms = 0.87, showing the emergence of the single state, |↑↑↑. , Measurement of the GHZ witness operator without (filled circles) and with (open squares) a symmetry-breaking field, showing a quenching of entanglement. In the presence of a symmetry-breaking field, the direction φ in the GHZ witness operator is coordinated with the time-dependent phase of the GHZ state. , Measured x-basis populations of the antiferromagnetic Ising model (J1, J2 > 0; By/Jrms = 0.36). , Measured populations of t! he antiferromagnetic Ising model with By/Jrms = 0.34, where a symmetry-breaking field is added during the ramp and increases linearly to Bx/Jrms = 1.19, showing the emergence of the three states, |↑↑↓, |↑↓↑ and |↓↑↑. , Measurement of the bipartite spin-squeezing entanglement witness operator in the antiferromagnetic case, showing that entanglement remains even after symmetry is broken. As in Fig. 3, the error bars in and represent the uncertainty due to parasitic effective magnetic fields and drifts not appearing in equation (1). Author information * Author information * Supplementary information * Comments Affiliations * Joint Quantum Institute, University of Maryland Department of Physics and National Institute of Standards and Technology, College Park, Maryland 20742, USA * K. Kim, * M.-S. Chang, * S. Korenblit, * R. Islam, * E. E. Edwards & * C. Monroe * Department of Physics, Georgetown University, Washington DC 20057, USA * J. K. Freericks * MCTP and Department of Physics, University of Michigan, Ann Arbor, Michigan 48109, USA * G.-D. Lin & * L.-M. Duan Contributions All of the authors contributed equally to this work: experimental work was performed by K.K., M.-S.C., S.K., R.I., E.E.E. and C.M.; and theoretical work was performed by J.K.F., G.-D.L. and L.-M.D. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * K. Kim (khkim@umd.edu) Supplementary information * Author information * Supplementary information * Comments PDF files * Supplementary Information (123K) This file contains a Supplementary Discussion and References. Additional data
  • An entangled-light-emitting diode
    - Nature (London) 465(7298):594 (2010)
    Nature | Letter An entangled-light-emitting diode * C. L. Salter1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * R. M. Stevenson1 Search for this author in: * NPG journals * PubMed * Google Scholar * I. Farrer2 Search for this author in: * NPG journals * PubMed * Google Scholar * C. A. Nicoll2 Search for this author in: * NPG journals * PubMed * Google Scholar * D. A. Ritchie2 Search for this author in: * NPG journals * PubMed * Google Scholar * A. J. Shields1 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorsJournal name:NatureVolume:465,Pages:594–597Date published:(03 June 2010)DOI:doi:10.1038/nature09078Received22 December 2009Accepted13 April 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg An optical quantum computer, powerful enough to solve problems so far intractable using conventional digital logic, requires a large number of entangled photons1, 2. At present, entangled-light sources are optically driven with lasers3, 4, 5, 6, 7, which are impractical for quantum computing owing to the bulk and complexity of the optics required for large-scale applications. Parametric down-conversion is the most widely used source of entangled light, and has been used to implement non-destructive quantum logic gates8, 9. However, these sources are Poissonian4, 5 and probabilistically emit zero or multiple entangled photon pairs in most cycles, fundamentally limiting the success probability of quantum computational operations. These complications can be overcome by using an electrically driven on-demand source of entangled photon pairs10, but so far such a source has not been produced. Here we report the realization of an electrically driven source of entangled photon pairs! , consisting of a quantum dot embedded in a semiconductor light-emitting diode (LED) structure. We show that the device emits entangled photon pairs under d.c. and a.c. injection, the latter achieving an entanglement fidelity of up to 0.82. Entangled light with such high fidelity is sufficient for application in quantum relays11, in core components of quantum computing such as teleportation12, 13, 14, and in entanglement swapping15, 16. The a.c. operation of the entangled-light-emitting diode (ELED) indicates its potential function as an on-demand source without the need for a complicated laser driving system; consequently, the ELED is at present the best source on which to base future scalable quantum information applications17. View full text Subject terms: * Applied physics * Engineering Figures at a glance * Figure 1: Device design and operation. , Schematic of the active region of the ELED, showing the emission of a polarization entangled photon pair through the biexciton cascade. The different regions of the heterostructure are labelled. Here the diode is in its 'off' state, just after non-resonant electrical injection of two electrons (blue circles) and two holes (grey circles) into the quantum dot (QD). The orange arrows represent recombination of the carriers and the blue and green arrows represent the subsequent entangled photon pair. , Electroluminescence spectrum of the quantum dot investigated in this report using d.c. electrical injection with a current density of 31 nA μm−2. a.u., arbitrary units. * Figure 2: Polarized pair-correlation results from d.c. electrical injection into the ELED. The current density is 31 nA μm−2. –, and measured in the rectilinear (), diagonal () and circular () bases with a time resolution of 0.2 ns. Labels denote the polarizations of the first (XX) and second (X) photons (in that order) as vertical (V), horizontal (H), diagonal (D), anti-diagonal (A), right-handed circular (R) and left-handed circular (L). Correlations measured for photons of the same polarization ( ) are shown in black and those measured for photons of orthogonal polarizations ( ) are shown in red. , Fidelity, f+, measured as a function of time delay, τ. The dashed lines represent the classical threshold fidelity, of 0.5, and the uncorrelated-light fidelity, of 0.25. * Figure 3: Polarized pair-correlation results from a.c. electrical injection into the ELED. –, and measured in the rectilinear (), diagonal () and circular () polarization bases with a time resolution of 0.2 ns. , Corresponding fidelity about zero time delay. The dashed lines represent the classical threshold fidelity, of 0.5, and the uncorrelated-light fidelity, of 0.25. Error bars, 1 s.d. , Fidelity as a function of gate width for the 11 central pulse periods. , Fidelity at τ = 0 (filled squares) and the Bell parameters (open circles: black, SRD; blue, SDC; red, SRC) as functions of the proportion of the total biphoton intensity that is analysed. The biphoton intensity is varied by changing the gate width (top axis). Solid lines indicate 1-s.d. error envelopes. Reduced biphoton intensity () and non-zero delay () diminish the measured coincidences and thus increase error due to Poissonian counting statistics. This also explains the fluctuations in fidelity about 0.25 for the non-zero periods in at very low gate widths. Author information * Author information * Comments Affiliations * Toshiba Research Europe Limited, 208 Cambridge Science Park, Cambridge CB4 0GZ, UK * C. L. Salter, * R. M. Stevenson & * A. J. Shields * Cavendish Laboratory, University of Cambridge, J. J. Thomson Avenue, Cambridge CB3 0HE, UK * C. L. Salter, * I. Farrer, * C. A. Nicoll & * D. A. Ritchie Contributions C.L.S. and R.M.S. performed measurements and analysis with support from other authors. All authors contributed to the heterostructure design. The heterostructures were grown by I.F., C.A.N. and D.A.R. LEDs were processed by C.L.S. This work was directed by A.J.S. All authors contributed to writing the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding authors Correspondence to: * R. M. Stevenson (mark.stevenson@crl.toshiba.co.uk) or * A. J. Shields (andrew.shields@crl.toshiba.co.uk) Additional data
  • Ligand exchanges and selective catalytic hydrogenation in molecular single crystals
    - Nature (London) 465(7298):598 (2010)
    Nature | Letter Ligand exchanges and selective catalytic hydrogenation in molecular single crystals * Zheng Huang1 Search for this author in: * NPG journals * PubMed * Google Scholar * Peter S. White1 Search for this author in: * NPG journals * PubMed * Google Scholar * Maurice Brookhart1 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:598–601Date published:(03 June 2010)DOI:doi:10.1038/nature09085Received07 January 2010Accepted15 April 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Chemical reactions inside single crystals are likely to be highly selective, but examples of single crystal to single crystal (SC–SC) transformations are uncommon, because crystallinity is difficult to retain following the rearrangement of atoms in the solid state1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19. The most widely studied SC–SC transformations involve solvent exchange reactions in porous coordination polymers or metal–organic frameworks, which take advantage of the robust polymeric networks of the hosts2, 8, 9, 10, 11. Examples of reactions occurring within molecular organic crystals generally involve photo-induced reactions, such as the coupling of alkenes or alkynes within the crystal1, 2, 12, 13, 14, 15. For nonporous molecular inorganic or organometallic crystals, single-crystal transformations involving the formation or cleavage of metal–ligand bonds are rare17, 18, 19, 20, 21; known examples usually involve ligand loss from the si! ngle crystal and reversible religation, a process sometimes accompanied by decay of the single crystal to a microcrystalline powder20, 21. Here we report a series of SC–SC transformations that involve the interchange of multiple small gaseous ligands (N2, CO, NH3, C2H4, H2 and O2) at an iridium centre in molecular single crystals of a pincer Ir(I) complex. The single crystal remains intact during these ligand-exchange reactions, which occur within the crystal and do not require prior ligand extrusion. We reveal a selective catalytic transformation within a nonporous molecular crystal: pincer iridium single crystals ligated with nitrogen, ethylene or hydrogen show selective hydrogenation of ethylene relative to propylene (25:1) when surface sites are passified by CO. View full text Subject terms: * Methods * Materials Figures at a glance * Figure 1: Single-crystal structures of [Ir]-N2, [Ir]-CO, [Ir]-NH3, [Ir]-C2H4, [Ir]-(H)2(H2), and [Ir]-O2. Iridium, dark green; phosphorus, pink; fluorine, light green; oxygen, red; nitrogen, dark blue; carbon, grey; hydrogen, light blue. Hydrogen atoms are omitted for clarity, except for those in C2H4, NH3 and H2 ligands. All SC–SC transformations occur at 25 °C in the presence of 1 atm of gas, except for the transformation of [Ir]-N2 to [Ir]-(H)2(H2), for which 1.5 atm of H2 was used. * Figure 2: Unit-cell and stacking diagrams of single-crystal [Ir]-N2. Colours as in Fig. 1. , Unit-cell of single-crystal [Ir]-N2 along a direction. , Stacking diagram of single-crystal [Ir]-N2 along a direction, showing the disordered toluene (light blue). , Stacking diagram along b direction (hydrogen atoms are omitted for clarity). * Figure 3: Superposition of crystal structures. [Ir]-N2, purple; [Ir]-CO, dark blue); [Ir]-NH3, light blue; [Ir]-C2H4, green; [Ir]-(H)2(H2), red. Author information * Author information * Supplementary information * Comments Affiliations * Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA * Zheng Huang, * Peter S. White & * Maurice Brookhart Contributions M.B. directed the project. Z.H. carried out all complex syntheses, crystallizations and reactions. P.S.W. carried out single crystal X-ray diffraction experiments and crystal structure determinations. M.B. and Z.H. analysed the data and wrote the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Maurice Brookhart (mbrookhart@unc.edu) Supplementary crystallographic data for this paper has been deposited at the Cambridge Crystallographic Data Centre under deposition numbers CCDC 728556 to 728561, 729323, 729324 and 759994 to 759996. These data can be obtained free of charge from http://www.ccdc.cam.ac.uk/data_request/cif. Supplementary information * Author information * Supplementary information * Comments PDF files * Supplementary Information (537K) This file contains Supplementary Experiments, Methods and Synthesis, Supplementary Tables 1- 6, Supplementary Figures 1-7 with legends and References. Additional data
  • Shaping mobile belts by small-scale convection
    - Nature (London) 465(7298):602 (2010)
    Nature | Letter Shaping mobile belts by small-scale convection * Claudio Faccenna1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Thorsten W. Becker3 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:602–605Date published:(03 June 2010)DOI:doi:10.1038/nature09064Received11 October 2009Accepted26 March 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Mobile belts are long-lived deformation zones composed of an ensemble of crustal fragments, distributed over hundreds of kilometres inside continental convergent margins1, 2. The Mediterranean represents a remarkable example of this tectonic setting3: the region hosts a diffuse boundary between the Nubia and Eurasia plates comprised of a mosaic of microplates that move and deform independently from the overall plate convergence4. Surface expressions of Mediterranean tectonics include deep, subsiding backarc basins, intraplate plateaux and uplifting orogenic belts. Although the kinematics of the area are now fairly well defined, the dynamical origins of many of these active features are controversial and usually attributed to crustal and lithospheric interactions. However, the effects of mantle convection, well established for continental interiors5, 6, 7, should be particularly relevant in a mobile belt, and modelling may constrain important parameters such as slab coherence! and lithospheric strength. Here we compute global mantle flow on the basis of recent, high-resolution seismic tomography to investigate the role of buoyancy-driven and plate-motion-induced mantle circulation for the Mediterranean. We show that mantle flow provides an explanation for much of the observed dynamic topography and microplate motion in the region. More generally, vigorous small-scale convection in the uppermost mantle may also underpin other complex mobile belts such as the North American Cordillera or the Himalayan–Tibetan collision zone. View full text Subject terms: * Geophysics * Earth sciences * Geology Figures at a glance * Figure 1: Topography and deformation indicators for the Mediterranean. , GPS measurements (yellow arrows, Eurasia fixed reference frame24) and seismicity (dots, colour-coded by depth) with magnitude M > 5 (ref. 8), colour-coded by depth. z, Elevation. , Residual topography relative to a regional mean, estimated by correcting for isostatic adjustment using the CRUST2.0 model30; with plus and minus symbols showing uplift and subsidence, respectively (see text for references). * Figure 2: Reference flow model for the Mediterranean region. The model is based on the tomography model of ref. 11. , Layer viscosity η and predicted surface velocities of Adria and Anatolia–Aegea (white vectors). Geodetic velocities (orange vectors) and prescribed velocities (grey vectors, from NUVEL-1A) are in the Eurasia fixed reference frame. Plate boundaries are treated as weak narrow belts, with a simplified geometry merging the eastern Alps with the Dinarides. , Predicted dynamic topography (zdyn is dynamic elevation, boundary in green). , , Horizontal (white vectors) and vertical flow (background colour shading) field at 250 km () and 600 km depth (). , Cross-sections from Massif Central to Calabria and to Anatolia (marked in ), with temperature (normalized by a reference temperature) in the background. * Figure 3: Additional flow models for the Mediterranean. Surface velocities (as in Fig. 2a) are superimposed on dynamic topography (as in Fig. 2b). , Flow (white vectors) generated by density anomalies only (that is, surface held fixed outside the microplates). , Reference model with Bitlis and Alps collisional zones coupled (weak zones removed within dashed regions). Geodetic velocities (orange vectors) and prescribed velocities (grey vectors, from NUVEL-1A) are in the Eurasia fixed reference frame. * Figure 4: Cartoon illustrating the architecture of the subduction zones and the related pattern of mantle convection in the Mediterranean region. Vigorous convection (red arrows) is mainly confined to the uppermost portion of the upper mantle and related to subduction (white arrows) within the Africa–Eurasia convergence (black arrows) . We note also the large-scale toroidal flow beneath the Middle East. Author information * Author information * Supplementary information * Comments Affiliations * Dipartimento Scienze Geologiche, University Roma TRE, 00146 Rome Italy * Claudio Faccenna * Consiglio Nazionale Ricerche—IGAG 00016, Rome, Italy * Claudio Faccenna * Department of Earth Sciences, University of Southern California, Los Angeles, California 90089-0740, USA * Thorsten W. Becker Contributions T.W.B. performed numerical modelling, C.F. designed the modelling strategy. Both authors contributed equally to interpreting and analysing the data and to writing the paper. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Claudio Faccenna (faccenna@uniroma3.it) Supplementary information * Author information * Supplementary information * Comments PDF files * Supplementary Information (5.4M) This file contains Supplementary Information, References, and Supplementary Figures S1-S4 with legends. Additional data
  • The key nickel enzyme of methanogenesis catalyses the anaerobic oxidation of methane
    - Nature (London) 465(7298):606 (2010)
    Nature | Letter The key nickel enzyme of methanogenesis catalyses the anaerobic oxidation of methane * Silvan Scheller1 Search for this author in: * NPG journals * PubMed * Google Scholar * Meike Goenrich2 Search for this author in: * NPG journals * PubMed * Google Scholar * Reinhard Boecher2 Search for this author in: * NPG journals * PubMed * Google Scholar * Rudolf K. Thauer2 Search for this author in: * NPG journals * PubMed * Google Scholar * Bernhard Jaun1 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:606–608Date published:(03 June 2010)DOI:doi:10.1038/nature09015Received21 November 2009Accepted17 March 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Large amounts (estimates range from 70 Tg per year to 300 Tg per year) of the potent greenhouse gas methane are oxidized to carbon dioxide in marine sediments by communities of methanotrophic archaea and sulphate-reducing bacteria1, 2, 3, and thus are prevented from escaping into the atmosphere. Indirect evidence indicates that the anaerobic oxidation of methane might proceed as the reverse of archaeal methanogenesis from carbon dioxide with the nickel-containing methyl-coenzyme M reductase (MCR) as the methane-activating enzyme4, 5. However, experiments showing that MCR can catalyse the endergonic back reaction have been lacking. Here we report that purified MCR from Methanothermobacter marburgensis converts methane into methyl-coenzyme M under equilibrium conditions with apparent Vmax (maximum rate) and Km (Michaelis constant) values consistent with the observed in vivo kinetics of the anaerobic oxidation of methane with sulphate6, 7, 8. This result supports the hypoth! esis of 'reverse methanogenesis'4, 9 and is paramount to understanding the still-unknown mechanism of the last step of methanogenesis. The ability of MCR to cleave the particularly strong C–H bond of methane without the involvement of highly reactive oxygen-derived intermediates is directly relevant to catalytic C–H activation, currently an area of great interest in chemistry10, 11, 12, 13. View full text Subject terms: * Biochemistry * Environmental science * Chemical biology Figures at a glance * Figure 1: Reverse methanogenesis. In methanogenic archaea, MCR with its prosthetic group coenzyme F430 () converts a methyl thioether (methyl-coenzyme M) and a thiol (coenzyme B) into methane and the heterodisulphide of coenzymes M and B14, 15 (black arrow). The hypothesis of 'reverse methanogenesis'4, 9 postulates that ANME-type archaea found in microbial communities oxidizing methane anaerobically to HCO3– with sulphate1, 2, 3 use a very similar enzyme to functionalize methane (red arrow). Proteins closely homologous to MCR found in ANME-I and ANME-II archaea5 contain the nickel hydroporphins (ref. 25) and (refs 16–18), respectively. * Figure 2: Incorporation of 13C from 13CH4 into the methyl group of CH3-S-CoM as catalysed by purified MCR-I from M. marburgensis at 60 °C. 600 MHz 1H-NMR spectra of the assay solution in the region of the CH3S signal of CH3-S-CoM. , Before the start of the reaction with enzyme: 12CH3-S-CoM = 4 mM; –, After 8, 15, 30, 60 min incubation with the enzyme at 60 °C: 12/13CH3-S-CoM = 2 mM (50 ± 2% conversion to 12CH4 and CoM-S-S-CoB). For numeric data see Supplementary Table 1. The spectra are scaled to the same absolute intensity for an internal standard (dioxane). Assay conditions: 1.6 ml 50 mM potassium phosphate buffer, pH 7.6, 4 mM 12CH3-S-CH2CH2SO3–, 2 mM coenzyme B and 1 bar of 13CH4 in the headspace (5 ml), 60 °C. Start with 4.06 mg (80 U) of purified MCR-I. * Figure 3: Formation of 13CH3-S-CoM (in μmol) after 30 min at 60 °C. , As a function of the concentration of purified MCR-I from M. marburgensis. , As a function of the partial pressure of 13CH4. The points at (0, 0) in are control experiments showing that no 13C incorporation occurs in the absence of the enzyme. Two independent experimental series (black and red dots) are shown. Assay conditions as in Fig. 2. Author information * Author information * Supplementary information * Comments Affiliations * Laboratory of Organic Chemistry, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093 Zurich, Switzerland * Silvan Scheller & * Bernhard Jaun * Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Str. 10, 35043 Marburg, Germany * Meike Goenrich, * Reinhard Boecher & * Rudolf K. Thauer Contributions B.J., R.K.T. and S.S. conceived and planned the experiments. S.S. carried out the synthesis of substrates, the NMR measurements and data analysis. M.G. and R.B. purified the enzyme, and S.S., M.G. and R.B. carried out the assays for the reverse reaction. B.J., R.K.T. and S.S. wrote the manuscript. All authors discussed and edited the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Bernhard Jaun (jaun@org.chem.ethz.ch) Supplementary information * Author information * Supplementary information * Comments PDF files * Supplementary Information (926K) This file contains Supplementary Figures S1-S5 with legends, Supplementary Tables 1-3, Supplementary Notes, a Supplementary Discussion and References. Additional data
  • Population diversity and the portfolio effect in an exploited species
    - Nature (London) 465(7298):609 (2010)
    Nature | Letter Population diversity and the portfolio effect in an exploited species * Daniel E. Schindler1 Search for this author in: * NPG journals * PubMed * Google Scholar * Ray Hilborn1 Search for this author in: * NPG journals * PubMed * Google Scholar * Brandon Chasco1 Search for this author in: * NPG journals * PubMed * Google Scholar * Christopher P. Boatright1 Search for this author in: * NPG journals * PubMed * Google Scholar * Thomas P. Quinn1 Search for this author in: * NPG journals * PubMed * Google Scholar * Lauren A. Rogers1 Search for this author in: * NPG journals * PubMed * Google Scholar * Michael S. Webster2 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:609–612Date published:(03 June 2010)DOI:doi:10.1038/nature09060Received21 October 2009Accepted24 March 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg One of the most pervasive themes in ecology is that biological diversity stabilizes ecosystem processes and the services they provide to society1, 2, 3, 4, a concept that has become a common argument for biodiversity conservation5. Species-rich communities are thought to produce more temporally stable ecosystem services because of the complementary or independent dynamics among species that perform similar ecosystem functions6. Such variance dampening within communities is referred to as a portfolio effect7 and is analogous to the effects of asset diversity on the stability of financial portfolios8. In ecology, these arguments have focused on the effects of species diversity on ecosystem stability but have not considered the importance of biologically relevant diversity within individual species9. Current rates of population extirpation are probably at least three orders of magnitude higher than species extinction rates10, so there is a pressing need to clarify how populatio! n and life history diversity affect the performance of individual species in providing important ecosystem services. Here we use five decades of data from Oncorhynchus nerka (sockeye salmon) in Bristol Bay, Alaska, to provide the first quantification of portfolio effects that derive from population and life history diversity in an important and heavily exploited species. Variability in annual Bristol Bay salmon returns is 2.2 times lower than it would be if the system consisted of a single homogenous population rather than the several hundred discrete populations it currently consists of. Furthermore, if it were a single homogeneous population, such increased variability would lead to ten times more frequent fisheries closures. Portfolio effects are also evident in watershed food webs, where they stabilize and extend predator access to salmon resources. Our results demonstrate the critical importance of maintaining population diversity for stabilizing ecosystem services and! securing the economies and livelihoods that depend on them. T! he reliability of ecosystem services will erode faster than indicated by species loss alone. View full text Subject terms: * Environmental science Figures at a glance * Figure 1: Bristol Bay sockeye habitat and associated change in variability of returns at different spatial scales and levels of life history aggregation. , Map of Bristol Bay, southwest Alaska. Sockeye salmon nursery lakes are shown in solid black. Fishing districts associated with major rivers are highlighted as striped areas. , Map of the Wood River system showing streams supporting anadromous salmon populations. , Interannual variability in total returns to sockeye populations and stocks at three spatial scales and two levels of life history aggregation. Grey symbols are for the Wood River, highlighting the watershed for which continuous long-term data on stream populations (1962–2007, n = 8) exist. Black symbols are for rivers (including the Wood River, n = 8) and the Bristol Bay aggregate (1958–2008). Circles show average variabilities for populations and stocks with their observed age composition, and triangles show average variabilities for the dominant age classes at each spatial scale. Error bars, 1 s.e. , Three age classes of reproductively mature male sockeye salmon from the Wood River that have spent one, tw! o or three years at sea, as indicated. * Figure 2: Effect of interannual variability on the probability of fishery closures or capacity-swamping returns. Probability of total annual return being less than 10,000,000 (solid line) or greater than 60,000,000 (dotted line) as a function of the coefficient of variation in the overall distribution of returns. No fishing is allowed when total returns are less than about 10,000,000. Returns in excess of 60,000,000 swamp the capacity of the fishing fleet and processing industry to capture their allocation of the resource. Stock abundances were assumed to be characterized by log-normal distributions. Current Bristol Bay returns have a CV of about 0.55 and the simplest component of the stock dynamics is about 1.2. * Figure 3: Annual run timing to fishing districts and streams. , Cumulative returns (catch plus escapement) to each of the major fishing districts in Bristol Bay for 2000–2007. The Bristol Bay fishery can currently process about 2,000,000 fish per day; on days with total returns above this level, the industry cannot capture their allocation of the resource. Between 1978 and 2007, the daily catch plus escapement was >2,000,000 fish on about seven days per season, on average. However, if all the fish had arrived at the fishing grounds with exactly the same timing, as determined by the distribution observed in any single fishing district in a given year, the length of the peak fishing season would have been reduced on average by 20% (range, 8–34%). , Comparison of the dates of occupancy (dot, peak; line, occupancy period) in spawning habitats where sockeye salmon are available to predators and scavengers for 30 populations in the Wood River system (Supplementary Fig. 1). Author information * Author information * Supplementary information * Comments Affiliations * School of Aquatic and Fishery Sciences, University of Washington, Box 355020, Seattle, Washington 98195-5020, USA * Daniel E. Schindler, * Ray Hilborn, * Brandon Chasco, * Christopher P. Boatright, * Thomas P. Quinn & * Lauren A. Rogers * The Gordon and Betty Moore Foundation, 1661 Page Mill Road, Palo Alto, California 94304, USA * Michael S. Webster Contributions D.E.S. designed and coordinated the project; R.H., B.C. and L.A.R contributed to the analyses; M.S.W. helped design the project; and all authors contributed to the writing. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Daniel E. Schindler (deschind@u.washington.edu) Supplementary information * Author information * Supplementary information * Comments PDF files * Supplementary Information (273K) This file contains Supplementary Information comprising: Value of sockeye salmon resources in Bristol Bay and Variance scaling in data, Supplementary Figures 1-3 with legends and References. Additional data
  • Experimentally assessing the relative importance of predation and competition as agents of selection
    Calsbeek R Cox RM - Nature (London) 465(7298):613 (2010)
    Nature | Letter Experimentally assessing the relative importance of predation and competition as agents of selection * Ryan Calsbeek1 Search for this author in: * NPG journals * PubMed * Google Scholar * Robert M. Cox1 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:613–616Date published:(03 June 2010)DOI:doi:10.1038/nature09020Received09 December 2009Accepted17 March 2010Published online09 May 2010Corrected online03 June 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Field experiments that measure natural selection in response to manipulations of the selective regime are extremely rare1, even in systems where the ecological basis of adaptation has been studied extensively. The adaptive radiation of Caribbean Anolis lizards has been studied for decades2, 3, 4, 5, leading to precise predictions about the influence of alternative agents of selection in the wild. Here we present experimental evidence for the relative importance of two putative agents of selection in shaping the adaptive landscape for a classic island radiation. We manipulated whole-island populations of the brown anole lizard, Anolis sagrei, to measure the relative importance of predation versus competition as agents of natural selection. We excluded or included bird and snake predators across six islands that ranged from low to high population densities of lizards, then measured subsequent differences in behaviour and natural selection in each population. Predators altered ! the lizards' perching behaviour and increased mortality, but predation treatments did not alter selection on phenotypic traits. By contrast, experimentally increasing population density dramatically increased the strength of viability selection favouring large body size, long relative limb length and high running stamina. Our results from A. sagrei are consistent with the hypothesis6 that intraspecific competition is more important than predation in shaping the selective landscape for traits central to the adaptive radiation of Anolis ecomorphs. View full text Subject terms: * Evolution * Animal behaviour * Zoology * Environmental science Figures at a glance * Figure 1: Differences in survival (open circles) and perching behaviour (filled circles) as a function of predator treatment. Survival was lowest on experimental islands exposed both to bird and snake predators. Lizards on these six islands were also perched significantly higher in the canopy when recaptured. Letters indicate significant post-hoc differences among treatment groups for survival (a, b) and perch height (α, β). Error bars show variance (± 1 s.e.m.) in survival across experimental replicates and variance (± 1 s.e.m.) in perching behaviour across individual lizards. Illustrations depict experimental treatments. * Figure 2: Left panels show mean values (± 1 s.e.m.) of selection gradients measured in two replicates across each of three predation treatments. Right panels show mean values (±1 s.e.m.) of selection gradients measured at low and high population densities (Supplementary Fig. 2 shows regressions of gradients against continuous variation in density). High and low densities were greater or less than 0.2 lizards per square metre, respectively (ref. 28).Differentials were measured within each island and then corrected for year effects. Illustrations above each panel depict treatments. Change history * Change history * Author information * Supplementary information * CommentsCorrected online 03 June 2010The penultimate sentence in the Fig. 2 legend was changed. Author information * Change history * Author information * Supplementary information * Comments Affiliations * Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA * Ryan Calsbeek & * Robert M. Cox Contributions Both authors contributed equally to study design, fieldwork and data analysis. R.C. prepared the manuscript with assistance from R.M.C. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Ryan Calsbeek (ryan.calsbeek@dartmouth.edu) Supplementary information * Change history * Author information * Supplementary information * Comments PDF files * Supplementary Information (536K) This file contains Supplementary Methods, Supplementary Tables S1-S2 and Supplementary Figures S1-S2 with legends. Supplementary Table 1 was amended on 3 June 2010. Additional data
  • The Ectocarpus genome and the independent evolution of multicellularity in brown algae
    - Nature (London) 465(7298):617 (2010)
    Nature | Letter Open The Ectocarpus genome and the independent evolution of multicellularity in brown algae * J. Mark Cock1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Lieven Sterck3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * Pierre Rouzé3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * Delphine Scornet1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Andrew E. Allen5 Search for this author in: * NPG journals * PubMed * Google Scholar * Grigoris Amoutzias3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * Veronique Anthouard6 Search for this author in: * NPG journals * PubMed * Google Scholar * François Artiguenave6 Search for this author in: * NPG journals * PubMed * Google Scholar * Jean-Marc Aury6 Search for this author in: * NPG journals * PubMed * Google Scholar * Jonathan H. Badger5 Search for this author in: * NPG journals * PubMed * Google Scholar * Bank Beszteri7, 35 Search for this author in: * NPG journals * PubMed * Google Scholar * Kenny Billiau3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * Eric Bonnet3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * John H. Bothwell8, 9, 10 Search for this author in: * NPG journals * PubMed * Google Scholar * Chris Bowler11, 12 Search for this author in: * NPG journals * PubMed * Google Scholar * Catherine Boyen1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Colin Brownlee10 Search for this author in: * NPG journals * PubMed * Google Scholar * Carl J. Carrano13 Search for this author in: * NPG journals * PubMed * Google Scholar * Bénédicte Charrier1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Ga Youn Cho1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Susana M. Coelho1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Jonas Collén1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Erwan Corre14 Search for this author in: * NPG journals * PubMed * Google Scholar * Corinne Da Silva6 Search for this author in: * NPG journals * PubMed * Google Scholar * Ludovic Delage1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Nicolas Delaroque15 Search for this author in: * NPG journals * PubMed * Google Scholar * Simon M. Dittami1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Sylvie Doulbeau16 Search for this author in: * NPG journals * PubMed * Google Scholar * Marek Elias17 Search for this author in: * NPG journals * PubMed * Google Scholar * Garry Farnham10 Search for this author in: * NPG journals * PubMed * Google Scholar * Claire M. M. Gachon18 Search for this author in: * NPG journals * PubMed * Google Scholar * Bernhard Gschloessl1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Svenja Heesch1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Kamel Jabbari6, 11 Search for this author in: * NPG journals * PubMed * Google Scholar * Claire Jubin6 Search for this author in: * NPG journals * PubMed * Google Scholar * Hiroshi Kawai19 Search for this author in: * NPG journals * PubMed * Google Scholar * Kei Kimura20 Search for this author in: * NPG journals * PubMed * Google Scholar * Bernard Kloareg1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Frithjof C. Küpper18 Search for this author in: * NPG journals * PubMed * Google Scholar * Daniel Lang21 Search for this author in: * NPG journals * PubMed * Google Scholar * Aude Le Bail1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Catherine Leblanc1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Patrice Lerouge22 Search for this author in: * NPG journals * PubMed * Google Scholar * Martin Lohr23 Search for this author in: * NPG journals * PubMed * Google Scholar * Pascal J. Lopez11 Search for this author in: * NPG journals * PubMed * Google Scholar * Cindy Martens3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * Florian Maumus11 Search for this author in: * NPG journals * PubMed * Google Scholar * Gurvan Michel1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Diego Miranda-Saavedra24, 35 Search for this author in: * NPG journals * PubMed * Google Scholar * Julia Morales25, 26 Search for this author in: * NPG journals * PubMed * Google Scholar * Hervé Moreau27 Search for this author in: * NPG journals * PubMed * Google Scholar * Taizo Motomura20 Search for this author in: * NPG journals * PubMed * Google Scholar * Chikako Nagasato20 Search for this author in: * NPG journals * PubMed * Google Scholar * Carolyn A. Napoli28 Search for this author in: * NPG journals * PubMed * Google Scholar * David R. Nelson29 Search for this author in: * NPG journals * PubMed * Google Scholar * Pi Nyvall-Collén1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Akira F. Peters1, 2, 35 Search for this author in: * NPG journals * PubMed * Google Scholar * Cyril Pommier30 Search for this author in: * NPG journals * PubMed * Google Scholar * Philippe Potin1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Julie Poulain6 Search for this author in: * NPG journals * PubMed * Google Scholar * Hadi Quesneville30 Search for this author in: * NPG journals * PubMed * Google Scholar * Betsy Read31 Search for this author in: * NPG journals * PubMed * Google Scholar * Stefan A. Rensing21 Search for this author in: * NPG journals * PubMed * Google Scholar * Andrés Ritter1, 2, 32 Search for this author in: * NPG journals * PubMed * Google Scholar * Sylvie Rousvoal1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Manoj Samanta33 Search for this author in: * NPG journals * PubMed * Google Scholar * Gaelle Samson6 Search for this author in: * NPG journals * PubMed * Google Scholar * Declan C. Schroeder10 Search for this author in: * NPG journals * PubMed * Google Scholar * Béatrice Ségurens6 Search for this author in: * NPG journals * PubMed * Google Scholar * Martina Strittmatter18 Search for this author in: * NPG journals * PubMed * Google Scholar * Thierry Tonon1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * James W. Tregear16 Search for this author in: * NPG journals * PubMed * Google Scholar * Klaus Valentin7 Search for this author in: * NPG journals * PubMed * Google Scholar * Peter von Dassow34 Search for this author in: * NPG journals * PubMed * Google Scholar * Takahiro Yamagishi19 Search for this author in: * NPG journals * PubMed * Google Scholar * Yves Van de Peer3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * Patrick Wincker6 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:617–621Date published:(03 June 2010)DOI:doi:10.1038/nature09016Received09 November 2009Accepted15 March 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related1. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae2, 3, 4, 5, closely related to the kelps6, 7 (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the pre! sence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic2 approaches to explore these and other4, 5 aspects of brown algal biology further. View full text Subject terms: * Evolution * Developmental biology Figures at a glance * Figure 1: Simplified representation of the evolutionary tree of the eukaryotes showing the five major groups that have evolved complex multicellularity (indicated in colour). Here we define groups showing complex multicellularity as those that include macroscopic organisms with defined, recognizable morphologies and composed of multiple cell types. Coloured bars indicate the approximate, relative times of emergence of complex multicellularity in each lineage. The inset tree to the right indicates the relationship of Ectocarpus to selected brown algal genera. Kelps are represented in the tree by the genus Laminaria. * Figure 2: An integrated viral sequence in the Ectocarpus genome. , Representation of the linear and circular forms of the EsV-1 genome compared to the inserted viral genome. Genes on the upper and lower strands are above and below the line, respectively. A short region of the viral genome containing the putative integrase gene has been transposed to supercontig 0371. Gray parallelograms connect regions of high gene density that are also found in other phaeoviruses. These regions contain many of the genes that are thought to be important for the viral life cycle. Percent nucleotide identities between cognate regions in EsV-1 and in the integrated viral genome are indicated. Dashed line, algal DNA. ITRA and ITRA', inverted terminal repeats. , Mean expression levels of the inserted viral genes: the graph shows the mean of the normalized expression values (4 replicates) ± s.d. of the genes that were included in the microarray experiments carried out in ref. 29. Expression data are shown for the control condition, but gene expression profil! es were highly similar under stress conditions (not shown). Each bar represents the expression value for one coding sequence, the bars are in the same order as the corresponding genes along the supercontigs. Red bars correspond to virus genes, blue bars to host genes. Supercontigs 0062, 0052 and 0028 are adjacent on the genetic map, supercontig 0371 is part of another linkage group. The hybridization signals for 95% of the negative controls (median of four random probes on the same array) were between 19 and 59 (indicated by the two dotted lines). * Figure 3: Predicted pattern of loss and gain of gene families during the evolution of a broad range of eukaryotes. The number of gene families that were acquired (black) or lost (red) at each time point (grey circles) in the tree (Supplementary Information 1.15) was estimated using the Dollo parsimony principle. For each species, the number of orphans (genes that lacked homologues in the eukaryotic data set), the total number of gene families gained or lost and the overall gain (that is, total gain minus total loss) is indicated. * Figure 4: Phylogenetic analysis showing the independent evolution of eukaryotic receptor kinases from the opisthokont, green plant and stramenopile lineages. Protein maximum-likelihood tree generated using a multiple alignment of kinase domains from eukaryotic receptor kinases and related cytosolic kinases. Bootstrap values, when above 65%, are provided at the nodes for maximum-likelihood (first value) and neighbour-joining (second value) analyses. Accession codes * Accession codes * Author information * Supplementary information * Comments Primary accessions EMBL Nucleotide Sequence Database * CABU01000001–CABU01013533 * FN647682–FN649242 * FN649726–FN649760 * FP245546–FP312611 Gene Expression Omnibus * ERA000209 * GSE19912 Author information * Accession codes * Author information * Supplementary information * Comments Affiliations * UPMC Université Paris 6, The Marine Plants and Biomolecules Laboratory, UMR 7139, Station Biologique de Roscoff, Place Georges Teissier, BP74, 29682 Roscoff Cedex, France * J. Mark Cock, * Delphine Scornet, * Catherine Boyen, * Bénédicte Charrier, * Ga Youn Cho, * Susana M. Coelho, * Jonas Collén, * Ludovic Delage, * Simon M. Dittami, * Bernhard Gschloessl, * Svenja Heesch, * Bernard Kloareg, * Aude Le Bail, * Catherine Leblanc, * Gurvan Michel, * Pi Nyvall-Collén, * Akira F. Peters, * Philippe Potin, * Andrés Ritter, * Sylvie Rousvoal & * Thierry Tonon * CNRS, UMR 7139, Laboratoire International Associé Dispersal and Adaptation in Marine Species, Station Biologique de Roscoff, Place Georges Teissier, BP74, 29682 Roscoff Cedex, France * J. Mark Cock, * Delphine Scornet, * Catherine Boyen, * Bénédicte Charrier, * Ga Youn Cho, * Susana M. Coelho, * Jonas Collén, * Ludovic Delage, * Simon M. Dittami, * Bernhard Gschloessl, * Svenja Heesch, * Bernard Kloareg, * Aude Le Bail, * Catherine Leblanc, * Gurvan Michel, * Pi Nyvall-Collén, * Akira F. Peters, * Philippe Potin, * Andrés Ritter, * Sylvie Rousvoal & * Thierry Tonon * Department of Plant Systems Biology, VIB, B-9052 Ghent, Belgium * Lieven Sterck, * Pierre Rouzé, * Grigoris Amoutzias, * Kenny Billiau, * Eric Bonnet, * Cindy Martens & * Yves Van de Peer * Department of Plant Biotechnology and Genetics, Ghent University, B-9052 Ghent, Belgium * Lieven Sterck, * Pierre Rouzé, * Grigoris Amoutzias, * Kenny Billiau, * Eric Bonnet, * Cindy Martens & * Yves Van de Peer * J. Craig Venter Institute, San Diego, California 92121, USA * Andrew E. Allen & * Jonathan H. Badger * CEA, DSV, Institut de Génomique, Génoscope, 2 rue Gaston Crémieux, CP5706, 91057 Evry, France * Veronique Anthouard, * François Artiguenave, * Jean-Marc Aury, * Corinne Da Silva, * Kamel Jabbari, * Claire Jubin, * Julie Poulain, * Gaelle Samson, * Béatrice Ségurens & * Patrick Wincker * Alfred Wegener Institute for Polar and Marine Research, Am Handelshafen 12, 27570 Bremerhaven, Germany * Bank Beszteri & * Klaus Valentin * Queen's University Belfast, School of Biological Sciences, 97 Lisburn Road, Belfast, BT9 7BL, UK * John H. Bothwell * Queen's University Marine Laboratory, Portaferry, Co. Down, BT22 1PF, UK * John H. Bothwell * Marine Biological Association of the UK, The Laboratory, Citadel Hill, Plymouth, PL1 2PB, UK * John H. Bothwell, * Colin Brownlee, * Garry Farnham & * Declan C. Schroeder * Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Centre National de la Recherche Scientifique UMR8197, Ecole Normale Supérieure, 75005 Paris, France * Chris Bowler, * Kamel Jabbari, * Pascal J. Lopez & * Florian Maumus * Stazione Zoologica, Villa Comunale, I 80121 Naples, Italy * Chris Bowler * San Diego State University, 5500 Campanile Drive, San Diego, California 92182-1030, USA * Carl J. Carrano * Computer and Genomics Resource Centre, FR 2424, Station Biologique de Roscoff, Place Georges Teissier, BP74, 29682 Roscoff Cedex, France * Erwan Corre * Fraunhofer Institute for Cell Therapy and Immunology IZI, Perlickstrasse 1, 04103 Leipzig, Germany * Nicolas Delaroque * IRD, IRD/CIRAD Palm Developmental Biology Group, UMR 1097 DIAPC, 911 avenue Agropolis, 34394 Montpellier, France * Sylvie Doulbeau & * James W. Tregear * Charles University in Prague, Faculty of Science, Department of Botany and Department of Parasitology, Benatska 2, 128 01 Prague 2, Czech Republic * Marek Elias * Scottish Association for Marine Science, Department of Microbial and Molecular Biology, Scottish Marine Institute, Oban, Argyll PA37 1QA, UK * Claire M. M. Gachon, * Frithjof C. Küpper & * Martina Strittmatter * Kobe University Research Center for Inland Seas, 1-1, Rokkodai, Nadaku, Kobe 657-8501, Japan * Hiroshi Kawai & * Takahiro Yamagishi * Muroran Marine Station, Field Science Center for Northern Biosphere, Hokkaido University, Muroran 051-0003, Hokkaido, Japan * Kei Kimura, * Taizo Motomura & * Chikako Nagasato * University of Freiburg, Faculty of Biology, Hauptstr. 1, 79104 Freiburg, Germany * Daniel Lang & * Stefan A. Rensing * Laboratoire Glyco-MEV EA 4358, IFRMP 23, Université de Rouen, 76821 Mont-Saint-Aignan, France * Patrice Lerouge * Institut für Allgemeine Botanik, Johannes Gutenberg-Universität Mainz, 55099 Mainz, Germany * Martin Lohr * Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK * Diego Miranda-Saavedra * UPMC Université Paris 6, UMR 7150 Mer & Santé, Equipe Traduction Cycle Cellulaire et Développement, Station Biologique de Roscoff, 29680 Roscoff, France * Julia Morales * CNRS, UMR 7150 Mer & Santé, Station Biologique de Roscoff, 29680 Roscoff, France * Julia Morales * Laboratoire ARAGO, BP44, 66651 Banyuls-sur-mer, France * Hervé Moreau * Bio5 Institute and Department of Plant Sciences, University of Arizona, Tucson, Arizona 85719, USA * Carolyn A. Napoli * University of Tennessee Health Science Center, Department of Molecular Sciences, 858 Madison Ave, Suite G01, Memphis, Tennessee 38163, USA * David R. Nelson * Unité de Recherches en Génomique-Info (UR INRA 1164), INRA, Centre de recherche de Versailles, bat.18, RD10, Route de Saint Cyr, 78026 Versailles Cedex, France * Cyril Pommier & * Hadi Quesneville * Biological Sciences, Cal State University, San Marcos, California 92096-0001, USA * Betsy Read * Departamento de Ecología, Center for Advanced Studies in Ecology and Biodiversity, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile * Andrés Ritter * Systemix Institute, Redmond, Washington 98053, USA * Manoj Samanta * CNRS, UMR 7144, Evolution du Plancton et PaleOceans, Station Biologique de Roscoff, Place Georges Teissier, BP74, 29682 Roscoff Cedex, France * Peter von Dassow * Present addresses: Department of Microbiology, Oregon State University, Corvallis, Oregon 97331, USA (B.B.); WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, 565-0871, Osaka, Japan (D.M-S.); Bezhin Rosko, 28 route de Perharidy, 29680 Roscoff, France (A.F.P.). * Bank Beszteri, * Diego Miranda-Saavedra & * Akira F. Peters Contributions J.M.C. coordinated genome analysis and manuscript preparation. P.W. and Y.V.d.P. coordinated genome assembly and centralized and enabled the annotation process, respectively. P.W. and Y.V.d.P. should be considered joint last authors. L.S. and P.R. implemented the automated annotation of the genome and made substantial contributions to genome annotation and analysis. D.S. developed and implemented protocols for library construction. L.S., P.R and D.S. should be considered joint second authors. All other authors are members of the genome sequencing consortium and contributed annotation, analyses or data to the genome project. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * J. Mark Cock (cock@sb-roscoff.fr) The annotated Ectocarpus genome sequence can be obtained through the EMBL Nucleotide Sequence Database (accession numbers CABU01000001–CABU01013533, FN647682–FN649242, FN649726–FN649760) and can be browsed at the Bogas website (http://bioinformatics.psb.ugent.be/webtools/bogas/). cDNA sequence data are available through accession numbers FP245546–FP312611 and small RNA sequences and tiling array data have been submitted to the GEO database (accession numbers ERA000209 and GSE19912, respectively). The Ectocarpus microRNAs have been submitted to miRBase (accession numbers esi-MIR3450–esi-MIR3469). Supplementary information * Accession codes * Author information * Supplementary information * Comments Excel files * Supplementary Table 43 (1.5M) This table shows genes predicted to be derived from an endosymbiotic event involving a red alga. * Supplementary Table 44 (677K) This table shows genes predicted to be derived from an endosymbiotic event involving a green alga. PDF files * Supplementary Information (1.4M) This file contains Supplementary Methods (1.1-1.21), Supplementary Notes comprising: Genome Structure and organization (2.1-2.18); Metabolism (2.2.1-2.2.13); Signalling and cell biology (2.3.1-2.3.16) and References. * Supplementary Figures (9.1M) This file contains Supplementary Figures 1-55 with legends. * Supplementary Tables (1.1M) This file contains Supplementary Tables 1-42. Creative Commons Attribution-Non-Commercial-Share Alike licence This article is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence (http://creativecommons.org/licenses/by-nc-sa/3.0/), which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation, and derivative works must be licensed under the same or similar licence. Additional data
  • The role of mentorship in protégé performance
    - Nature (London) 465(7298):622 (2010)
    Nature | Letter The role of mentorship in protégé performance * R. Dean Malmgren1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Julio M. Ottino1, 3 Search for this author in: * NPG journals * PubMed * Google Scholar * Luís A. Nunes Amaral1, 3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorsJournal name:NatureVolume:465,Pages:622–626Date published:(03 June 2010)DOI:doi:10.1038/nature09040Received21 December 2009Accepted19 March 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg The role of mentorship in protégé performance is a matter of importance to academic, business and governmental organizations. Although the benefits of mentorship for protégés, mentors and their organizations are apparent1, 2, 3, 4, 5, 6, 7, 8, 9, the extent to which protégés mimic their mentors' career choices and acquire their mentorship skills is unclear10, 11, 12, 13, 14, 15, 16. The importance of a science, technology, engineering and mathematics workforce to economic growth and the role of effective mentorship in maintaining a 'healthy' such workforce demand the study of the role of mentorship in academia. Here we investigate one aspect of mentor emulation by studying mentorship fecundity—the number of protégés a mentor trains—using data from the Mathematics Genealogy Project17, which tracks the mentorship record of thousands of mathematicians over several centuries. We demonstrate that fecundity among academic mathematicians is correlated with other m! easures of academic success. We also find that the average fecundity of mentors remains stable over 60 years of recorded mentorship. We further discover three significant correlations in mentorship fecundity. First, mentors with low mentorship fecundities train protégés that go on to have mentorship fecundities 37% higher than expected. Second, in the first third of their careers, mentors with high fecundities train protégés that go on to have fecundities 29% higher than expected. Finally, in the last third of their careers, mentors with high fecundities train protégés that go on to have fecundities 31% lower than expected. View full text Subject terms: * Research management * Mathematics * Statistics * Sociology * Applied physics * Engineering Figures at a glance * Figure 1: Relationship between mentorship fecundity and other performance metrics. , Cumulative distribution of the mentorship fecundity for NAS members (red) and non-NAS members (black). NAS members have an average fecundity of kNAS = 14, which is far greater than the average fecundity of non-NAS members, knon-NAS = 3.1, indicating that fecundity is closely related to academic recognition. Not all mathematicians in the non-NAS group were eligible for NAS membership, owing to citizenship and other circumstances. This fact makes the result in the figure all the more striking. , Average number of publications as a function of the mentorship fecundity, for NAS members (red) and non-NAS members (black). NAS members have nearly twice as many publications on average as non-NAS members for all fecundity levels. Error bars, 1 s.e. * Figure 2: Evolution of the fecundity distribution. –, Cumulative distribution of the fecundity of mathematicians that graduated during 1910 (), 1930 () and 1950 () (symbols), compared with the best-estimate predictions of a mixture of two discrete exponentials (lines). Monte Carlo hypothesis testing confirms that this model can not be rejected as a model of the fecundity distribution during every year from 1900–1960, as denoted by the P values above the α = 0.05 significance level (Methods). –, Best-estimate parameters as functions of time, calculated by maximum likelihood for a mixture of two discrete exponentials. Dashed lines denote average parameter values between 1900 and 1960 and coloured circles indicate the years displayed in panels –. The probability, πh, of being a 'have' changes over time, generally in relation to historic events (hashed grey shading indicates the First and Second World Wars). In contrast, the average fecundities remain stable, with time-average values of = 9.8 ± 0.4 and = 0.47�! ��± 0.03, until 1960, the time at which mentorship records become incomplete (Methods), and then steadily decrease (grey shaded region). * Figure 3: Branching process null models. , Subset of the mathematician genealogy network. Mentors/parents (black circles) are connected to each of their protégés/children (white circles). The horizontal positions of mathematicians represent their graduation/birth dates, t. The bottom two parents were born in 1924, the top two parents were born in 1937, and all four parents have a child born in 1958. From a parent's perspective, three essential features of the empirical network must be preserved in random networks generated from the two branching process null models: the birth date, tp, the fecundity, kp, and the chronology of child births, {tc}. , Random networks from ensemble I preserve these three essential features. Solid red lines highlight the links in the empirical network whose end points can be randomized. Dashed red lines illustrate one of the possible randomization moves after switching the corresponding pair of links. We note that the age difference between parent and child is not preserved. , Random! networks from ensemble II preserve the three essential features as well as the age difference between parent and child. Solid blue lines of the same colour highlight the links in the empirical network whose end points can be randomized. Dashed blue lines illustrate one of the possible randomization moves after switching the corresponding pair of links. Random networks for each ensemble are generated by attempting 100 switches per link (Methods). * Figure 4: Effect of age difference between mentor and protégé, tc − tp, on protégé fecundity. , Fecundity distribution of children born during the 1910s (for which the average fecundity was 1.4) to parents with kp < 3, 3 ≤ kp < 10 and kp ≥ 10, compared with the expectation from ensemble I (grey line). We separate children into terciles (early, middle, late) according to tc − tp, and denote the average fecundities of the children born early, middle and late in their parents' lives as kE, kM and kL, respectively. The average fecundity of children born to parents with kp < 3 is higher than expected, regardless of whether they were born during the early, middle or later part of their parents' lives. We also note that the average fecundity of children born to parents with kp ≥ 10 decreases throughout their parents' lives. , We quantify the significance of these trends during each decade (coloured symbols) by computing the z-score of the average child fecundity, kc, compared with the average child fecundity in networks from ensembl! e I. This information is summarized by identifying the linear regression (solid black line; slope and intercept as shown). The regression lines for networks from our null model (grey lines) vary around the expectation of our null model (dashed black line). , Significance of linear regressions in . We compare the slope and intercept of the empirical regression (black circle) with the distribution of the slope and intercept of the same quantities computed from the null model. Because these quantities are approximately distributed as a multivariate Gaussian, we compute the equivalent of a two-tailed P value by finding the fraction of synthetically generated slope–intercept pairs that lie outside the equiprobability surface of the multivariate Gaussian (dashed ellipse). The slopes and intercepts of the regressions for children of parents with low (P = 0.009) and high (P < 0.001) fecundities are significantly different from the expectations for the null model, consistent w! ith the data displayed in . Comparisons with expectations from! random networks from ensemble II yield the same conclusions (Supplementary Fig. 4). Author information * Author information * Supplementary information * Comments Affiliations * Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA * R. Dean Malmgren, * Julio M. Ottino & * Luís A. Nunes Amaral * Datascope Analytics, Evanston, Illinois 60201, USA * R. Dean Malmgren * Northwestern Institute on Complex Systems, Northwestern University, Evanston, Illinois 60208, USA * Julio M. Ottino & * Luís A. Nunes Amaral * Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois 60208, USA * Luís A. Nunes Amaral Contributions R.D.M. analyzed data, designed the study and wrote the paper. J.M.O. and L.A.N.A. designed the study and wrote the paper. Competing financial interests The authors declare no competing financial interests. Corresponding authors Correspondence to: * Julio M. Ottino (jm-ottino@northwestern.edu) or * Luís A. Nunes Amaral (amaral@northwestern.edu) Supplementary information * Author information * Supplementary information * Comments PDF files * Supplementary Information (527K) This file contains Supplementary Figures 1-4 with legends and a Supplementary Discussion. Additional data
  • Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines
    Atwell S Huang YS Vilhjálmsson BJ Willems G Horton M Li Y Meng D Platt A Tarone AM Hu TT Jiang R Muliyati NW Zhang X Amer MA Baxter I Brachi B Chory J Dean C Debieu M de Meaux J Ecker JR Faure N Kniskern JM Jones JD Michael T Nemri A Roux F Salt DE Tang C Todesco M Traw MB Weigel D Marjoram P Borevitz JO Bergelson J Nordborg M - Nature (London) 465(7298):627 (2010)
    Nature | Letter Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines * Susanna Atwell1, 14 Search for this author in: * NPG journals * PubMed * Google Scholar * Yu S. Huang1, 14 Search for this author in: * NPG journals * PubMed * Google Scholar * Bjarni J. Vilhjálmsson1, 14 Search for this author in: * NPG journals * PubMed * Google Scholar * Glenda Willems1, 14 Search for this author in: * NPG journals * PubMed * Google Scholar * Matthew Horton3 Search for this author in: * NPG journals * PubMed * Google Scholar * Yan Li3 Search for this author in: * NPG journals * PubMed * Google Scholar * Dazhe Meng1 Search for this author in: * NPG journals * PubMed * Google Scholar * Alexander Platt1 Search for this author in: * NPG journals * PubMed * Google Scholar * Aaron M. Tarone1 Search for this author in: * NPG journals * PubMed * Google Scholar * Tina T. Hu1 Search for this author in: * NPG journals * PubMed * Google Scholar * Rong Jiang1 Search for this author in: * NPG journals * PubMed * Google Scholar * N. Wayan Muliyati3 Search for this author in: * NPG journals * PubMed * Google Scholar * Xu Zhang3 Search for this author in: * NPG journals * PubMed * Google Scholar * Muhammad Ali Amer1 Search for this author in: * NPG journals * PubMed * Google Scholar * Ivan Baxter4 Search for this author in: * NPG journals * PubMed * Google Scholar * Benjamin Brachi6 Search for this author in: * NPG journals * PubMed * Google Scholar * Joanne Chory7, 8 Search for this author in: * NPG journals * PubMed * Google Scholar * Caroline Dean9 Search for this author in: * NPG journals * PubMed * Google Scholar * Marilyne Debieu10 Search for this author in: * NPG journals * PubMed * Google Scholar * Juliette de Meaux10 Search for this author in: * NPG journals * PubMed * Google Scholar * Joseph R. Ecker8 Search for this author in: * NPG journals * PubMed * Google Scholar * Nathalie Faure6 Search for this author in: * NPG journals * PubMed * Google Scholar * Joel M. Kniskern3 Search for this author in: * NPG journals * PubMed * Google Scholar * Jonathan D. G. Jones11 Search for this author in: * NPG journals * PubMed * Google Scholar * Todd Michael8 Search for this author in: * NPG journals * PubMed * Google Scholar * Adnane Nemri11 Search for this author in: * NPG journals * PubMed * Google Scholar * Fabrice Roux3, 6 Search for this author in: * NPG journals * PubMed * Google Scholar * David E. Salt5 Search for this author in: * NPG journals * PubMed * Google Scholar * Chunlao Tang1 Search for this author in: * NPG journals * PubMed * Google Scholar * Marco Todesco12 Search for this author in: * NPG journals * PubMed * Google Scholar * M. Brian Traw3 Search for this author in: * NPG journals * PubMed * Google Scholar * Detlef Weigel12 Search for this author in: * NPG journals * PubMed * Google Scholar * Paul Marjoram2 Search for this author in: * NPG journals * PubMed * Google Scholar * Justin O. Borevitz3 Search for this author in: * NPG journals * PubMed * Google Scholar * Joy Bergelson3 Search for this author in: * NPG journals * PubMed * Google Scholar * Magnus Nordborg1, 13 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:627–631Date published:(03 June 2010)DOI:doi:10.1038/nature08800Received23 June 2009Accepted30 December 2009Published online24 March 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Although pioneered by human geneticists as a potential solution to the challenging problem of finding the genetic basis of common human diseases1, 2, genome-wide association (GWA) studies have, owing to advances in genotyping and sequencing technology, become an obvious general approach for studying the genetics of natural variation and traits of agricultural importance. They are particularly useful when inbred lines are available, because once these lines have been genotyped they can be phenotyped multiple times, making it possible (as well as extremely cost effective) to study many different traits in many different environments, while replicating the phenotypic measurements to reduce environmental noise. Here we demonstrate the power of this approach by carrying out a GWA study of 107 phenotypes in Arabidopsis thaliana, a widely distributed, predominantly self-fertilizing model plant known to harbour considerable genetic variation for many adaptively important traits3. Ou! r results are dramatically different from those of human GWA studies, in that we identify many common alleles of major effect, but they are also, in many cases, harder to interpret because confounding by complex genetics and population structure make it difficult to distinguish true associations from false. However, a-priori candidates are significantly over-represented among these associations as well, making many of them excellent candidates for follow-up experiments. Our study demonstrates the feasibility of GWA studies in A. thaliana and suggests that the approach will be appropriate for many other organisms. View full text Subject terms: * Evolution * Plant sciences * Genetics * Genomics Figures at a glance * Figure 1: The number of associations identified using different P-value thresholds for each phenotype. For each phenotype, the numbers of distinct peaks of association significant at nominal P-value thresholds (colour scale) are shown. The number of SNPs (out of 250,000) that would be expected to exceed each threshold is shown for comparison. , No correction for population structure (non-parametric Wilcoxon rank-sum test). , Correction for population structure (parametric mixed model (EMMA)). * Figure 2: GWA analysis of hypersensitive response to the bacterial elicitor AvrRpm1. , Genome-wide P values from Fisher's exact test. The horizontal dash–dot line corresponds to a nominal 5% significance threshold with Bonferroni correction for 250,000 tests. , Magnification of the genomic region surrounding RPM1, the position (and extent) of which is indicated by the vertical blue line. Mb, megabase. * Figure 3: Candidate SNPs are over-represented among strong associations. GWA analysis of the phenotype of flowering time at 10 °C: P values from the Wilcoxon rank-sum test are plotted against those from EMMA. Points corresponding to SNPs within 20 kb of a candidate gene are shown in red; the rest are shown in blue. The enrichment of the former over the latter in different parts of the distribution is as indicated. * Figure 4: Association with FLC expression at the top of chromosome 4 near FRI. The P values are from EMMA and the position of FRI is indicated by a vertical yellow line. The blue and red dots correspond to the Columbia and Landsberg erecta alleles of FRI, respectively. The horizontal dash–dot lines correspond to a nominal 5% significance threshold with Bonferroni correction for 250,000 tests. , Single-SNP tests. , Test with the Columbia allele included as a cofactor in the model. , Test with the Landsberg erecta allele included as a cofactor in the model. , Test with both alleles included as cofactors in the model. Author information * Author information * Supplementary information * Comments Primary authors * These authors contributed equally to this work. * Susanna Atwell, * Yu S. Huang, * Bjarni J. Vilhjálmsson & * Glenda Willems Affiliations * Molecular and Computational Biology, * Susanna Atwell, * Yu S. Huang, * Bjarni J. Vilhjálmsson, * Glenda Willems, * Dazhe Meng, * Alexander Platt, * Aaron M. Tarone, * Tina T. Hu, * Rong Jiang, * Muhammad Ali Amer, * Chunlao Tang & * Magnus Nordborg * Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA * Paul Marjoram * Department of Ecology & Evolution, University of Chicago, Chicago, Illinois 60637, USA * Matthew Horton, * Yan Li, * N. Wayan Muliyati, * Xu Zhang, * Joel M. Kniskern, * Fabrice Roux, * M. Brian Traw, * Justin O. Borevitz & * Joy Bergelson * Bindley Bioscience Center, * Ivan Baxter * Purdue University, West Lafayette, Indiana 47907, USA * David E. Salt * Laboratoire de Génétique et Evolution des Populations Végétales, UMR CNRS 8016, Université des Sciences et Technologies de Lille 1, F-59655 Villeneuve d'Ascq Cedex, France * Benjamin Brachi, * Nathalie Faure & * Fabrice Roux * Howard Hughes Medical Institute, La Jolla, California 92037, USA * Joanne Chory * Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA * Joanne Chory, * Joseph R. Ecker & * Todd Michael * Department of Cell and Development Biology, John Innes Centre, Norwich NR4 7UH, UK * Caroline Dean * Max Planck Institute for Plant Breeding Research, D-50829 Cologne, Germany * Marilyne Debieu & * Juliette de Meaux * Sainsbury Laboratory, Norwich NR4 7UH, UK * Jonathan D. G. Jones & * Adnane Nemri * Department of Molecular Biology, Max Planck Institute for Developmental Biology, D-72076 Tübingen, Germany * Marco Todesco & * Detlef Weigel * Gregor Mendel Institute, A-1030 Vienna, Austria * Magnus Nordborg Contributions J.O.B., J.B. and M.N. are equal senior authors. J.R.E. and D.W. generated the SNPs used in this project. S.A., M.H., Y.L., N.W.M., X.Z., J.O.B. and J.B. were responsible for the experimental aspects of genotyping. Y.S.H., B.J.V., M.H., T.T.H., R.J., X.Z., M.A.A., P.M., J.O.B., J.B. and M.N. were responsible for data management and the bioinformatics pipeline. S.A., I.B., B.B., J.C., C.D., M.D., J.d.M., N.F., J.M.K., J.D.G.J., T.M., A.N., F.R., D.E.S., C.T., M.T., M.B.T., D.W., J.B. and M.N. were responsible for phenotyping. S.A., Y.S.H., B.J.V., G.W., D.M., A.P., A.M.T., P.M. and M.N carried out the GWA analyses. Y.S.H. and D.M. developed the project website. M.N. wrote the paper with significant contributions from S.A., Y.S.H., B.J.V., G.W., A.P. and J.B. J.O.B., J.B. and M.N. designed and supervised the project. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Magnus Nordborg (magnus.nordborg@gmi.oeaw.ac.at) Supplementary information * Author information * Supplementary information * Comments PDF files * Supplementary Information (34.4M) This file contains Supplementary Information which comprises: 1 Genotyping; 2 Association Mapping Methods; 3 Enrichment for a priori candidates, Supplementary Figures 1-152 with legends, Supplementary References and Supplementary Tables 1-7. Additional data
  • Natural allelic variation underlying a major fitness trade-off in Arabidopsis thaliana
    - Nature (London) 465(7298):632 (2010)
    Nature | Letter Natural allelic variation underlying a major fitness trade-off in Arabidopsis thaliana * Marco Todesco1, 13 Search for this author in: * NPG journals * PubMed * Google Scholar * Sureshkumar Balasubramanian1, 13, 14 Search for this author in: * NPG journals * PubMed * Google Scholar * Tina T. Hu2, 14 Search for this author in: * NPG journals * PubMed * Google Scholar * M. Brian Traw3 Search for this author in: * NPG journals * PubMed * Google Scholar * Matthew Horton4 Search for this author in: * NPG journals * PubMed * Google Scholar * Petra Epple5 Search for this author in: * NPG journals * PubMed * Google Scholar * Christine Kuhns6, 7 Search for this author in: * NPG journals * PubMed * Google Scholar * Sridevi Sureshkumar1, 14 Search for this author in: * NPG journals * PubMed * Google Scholar * Christopher Schwartz8, 9 Search for this author in: * NPG journals * PubMed * Google Scholar * Christa Lanz1 Search for this author in: * NPG journals * PubMed * Google Scholar * Roosa A. E. Laitinen1 Search for this author in: * NPG journals * PubMed * Google Scholar * Yu Huang2 Search for this author in: * NPG journals * PubMed * Google Scholar * Joanne Chory8, 10 Search for this author in: * NPG journals * PubMed * Google Scholar * Volker Lipka6, 7 Search for this author in: * NPG journals * PubMed * Google Scholar * Justin O. Borevitz4 Search for this author in: * NPG journals * PubMed * Google Scholar * Jeffery L. Dangl5, 11 Search for this author in: * NPG journals * PubMed * Google Scholar * Joy Bergelson4 Search for this author in: * NPG journals * PubMed * Google Scholar * Magnus Nordborg2, 12 Search for this author in: * NPG journals * PubMed * Google Scholar * Detlef Weigel1 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:632–636Date published:(03 June 2010)DOI:doi:10.1038/nature09083Received10 July 2009Accepted14 April 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Plants can defend themselves against a wide array of enemies, from microbes to large animals, yet there is great variability in the effectiveness of such defences, both within and between species. Some of this variation can be explained by conflicting pressures from pathogens with different modes of attack1. A second explanation comes from an evolutionary 'tug of war', in which pathogens adapt to evade detection, until the plant has evolved new recognition capabilities for pathogen invasion2, 3, 4, 5. If selection is, however, sufficiently strong, susceptible hosts should remain rare. That this is not the case is best explained by costs incurred from constitutive defences in a pest-free environment6, 7, 8, 9, 10, 11. Using a combination of forward genetics and genome-wide association analyses, we demonstrate that allelic diversity at a single locus, ACCELERATED CELL DEATH 6 (ACD6)12, 13, underpins marked pleiotropic differences in both vegetative growth and resistance to! microbial infection and herbivory among natural Arabidopsis thaliana strains. A hyperactive ACD6 allele, compared to the reference allele, strongly enhances resistance to a broad range of pathogens from different phyla, but at the same time slows the production of new leaves and greatly reduces the biomass of mature leaves. This allele segregates at intermediate frequency both throughout the worldwide range of A. thaliana and within local populations, consistent with this allele providing substantial fitness benefits despite its marked impact on growth. View full text Subject terms: * Plant sciences * Evolution * Genetics * Genomics Figures at a glance * Figure 1: Identification of a natural ACD6 allele affecting growth and defence traits. , Top: rosettes of 6-week-old plants. Bottom: close-up of twelfth leaf, stained with Trypan blue for dead cells. gACD6.Est is an acd6-2 mutant in Col-0 (which is morphologically normal; Supplementary Fig. 3) transformed with an Est-1 genomic fragment. Scale bars: 1 cm (top); 1 mm (bottom). , Leaf initiation rates. , QTL maps. The dashed black line indicates significance threshold; ticks indicate positions of genetic markers14. LOD, logarithm of odds. , PR1 expression in the sixth leaf (two biological replicates each), normalized to those in 12-day-old Est-1 plants. , PR1 expression in different genotypes. , Leaf initiation rates. , SA content in the sixth leaf of 35-day-old plants. Only wild-type Est-1 was significantly different from any of the other lines (P < 0.005). The 35S::amiR-ACD6 construct had no effect on SA levels in Col-0. FW, fresh weight. Standard errors are indicated in panels , –. * Figure 2: Effects of a natural ACD6 allele on leaf biomass, pathogen susceptibility and metabolite content. , Leaf biomass. The difference between wild-type and transgenic lines was significant for all accessions but Col-0 (P < 0.001). , G. orontii T1 conidiophores on 4-week-old plants, 5 days post inoculation (d.p.i.). , H. arabidopsidis Noco2 sporangiophores on 2-week-old seedlings (5 d.p.i.). cot., cotyledon. , P. syringae DC3000 growth. 35S::amiR-ACD6 did not affect susceptibility of Col-0. , Camalexin and jasmonate concentrations. The difference between Est-1 and the other genotypes was significant (P < 0.005). Standard errors are indicated in panels , , , . * Figure 3: Effects of a natural ACD6 allele on pathogen susceptibility. , Infection of 4-week-old plants by G. orontii T1 (5 d.p.i.). Arrows indicate fungal growth. , Trypan blue staining of inoculated leaves. Dead plant cells (dc), hyphae (hy) and mature conidiophores (cp) are indicated. , Infection of 6-week-old plants with G. cichoracearum UCSC1 (10 d.p.i.). Note the increasing severity of infection symptoms from left to right. , Five-week-old plants inoculated with H. arabidopsidis Noco2. Trypan blue staining of the fourth leaf (7 d.p.i.) is shown. Hyphal growth (hy), which was seldom observed in Est-1, as well as oosporangia (os) were common in 35S::amiR-ACD6 Est-1 plants. See Supplementary Fig. 7 for adult leaves. In Col-0, many sporangiophores (sp) were seen. For both powdery and downy mildews, pathogen susceptibility and ACD6 expression levels in 35S::amiR-ACD6 lines were correlated (see Supplementary Fig. 2a). Scale bars: 1 cm in and ; 1 mm in and . * Figure 4: ACD6 sequence diversity in Arabidopsis. , Hierarchical clustering of ACD6 alleles. Col-0 and Est-1 are indicated with arrows, and Est-1-like sequences are highlighted. Yellow indicates mild, orange intermediate and red severe late-onset necrosis. KZ-10-like alleles are grey. , Pair-wise identity of ACD6 alleles. , Whole-genome scan of 216,130 SNPs for association with necrosis across 96 accessions shown in 24. , Genomic region containing 9 of 15 SNPs with lowest P-values. , Polymorphism and divergence levels at ACD6 (see also Supplementary Figs 8 and 10 and Supplementary Table 6). Blue lines indicate non-synonymous SNPs shared among Est-1-like alleles, and Fab-2 and Fab-4 (Supplementary Fig. 5). The two causal SNPs (see ) are indicated by asterisks, as is the acd6-1 mutation. dN, rate of non-synonymous substitutions; dS, rate of synonymous substitutions. , Six-week-old acd6-2 plants transformed with modified genomic clones of ACD6, in which two codons were swapped between Est-1 and Col-0. See also Supplementary Fi! g. 6. Compare to Fig. 1a and Supplementary Fig. 3a for unmutated versions. Scale bars: 1 cm. * Figure 5: Correlation between late-onset necrosis, growth and defence traits. , Late-onset necrosis in accessions with an Est-1-like ACD6 allele is suppressed by 35S::amiR-ACD6, or by nahG-mediated SA depletion. See Supplementary Fig. 9 for additional accessions. Scale bars: 2 cm for rosettes; 1 mm for micrographs. , Correlation between late-onset necrosis and different traits across 96 accessions used for genome-wide association studies24. Lesioning scores reflect the range of symptoms indicated in Fig. 4a. Accession codes * Accession codes * Author information * Supplementary information * Comments Primary accessions GenBank * HM053468 * HM053469 * HM214805 * HM214897 Author information * Accession codes * Author information * Supplementary information * Comments Primary authors * These authors contributed equally to this work. * Marco Todesco & * Sureshkumar Balasubramanian Affiliations * Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany * Marco Todesco, * Sureshkumar Balasubramanian, * Sridevi Sureshkumar, * Christa Lanz, * Roosa A. E. Laitinen & * Detlef Weigel * Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089, USA * Tina T. Hu, * Yu Huang & * Magnus Nordborg * Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15238, USA * M. Brian Traw * Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA * Matthew Horton, * Justin O. Borevitz & * Joy Bergelson * Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA * Petra Epple & * Jeffery L. Dangl * The Sainsbury Laboratory, John Innes Centre, Colney, Norwich NR4 7UH, UK * Christine Kuhns & * Volker Lipka * Albrecht von Haller Institute for Plant Sciences, Georg August University Göttingen, 37073 Göttingen, Germany * Christine Kuhns & * Volker Lipka * Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA * Christopher Schwartz & * Joanne Chory * Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA * Christopher Schwartz * Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA * Joanne Chory * Department of Microbiology and Immunology, Curriculum in Genetics and Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599, USA * Jeffery L. Dangl * Gregor Mendel Institute, 1030 Vienna, Austria * Magnus Nordborg * Present addresses: School of Biological Sciences, University of Queensland, St Lucia, Queensland 4072, Australia (S.B., S.S.); Lewis-Sigler Institute, Princeton University, Princeton, New Jersey 08544, USA (T.T.H.). * Sureshkumar Balasubramanian, * Tina T. Hu & * Sridevi Sureshkumar Contributions M.T., S.B., J.C., V.L., J.O.B., J.L.D., J.B., M.N. and D.W. conceived the study; M.T., S.B., M.B.T., M.H., P.E., C.K., S.S., C.S., C.L. and R.A.E.L. performed the experiments; M.T., S.B., T.T.H., M.B.T., Y.H., J.B., M.N. and D.W. analysed the data; and M.T., S.B. and D.W. wrote the paper with contributions from all authors. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * Detlef Weigel (weigel@weigelworld.org) DNA sequences have been deposited in GenBank under accession numbers HM053468 and HM053469 and HM214805 to HM214897. Supplementary information * Accession codes * Author information * Supplementary information * Comments PDF files * Supplementary Information (1.7M) This file contains Supplementary Methods, References, Supplementary Tables 1-9 and Supplementary Figures 1-13 with legends. Additional data
  • The folding cooperativity of a protein is controlled by its chain topology
    - Nature (London) 465(7298):637 (2010)
    Nature | Letter The folding cooperativity of a protein is controlled by its chain topology * Elizabeth A. Shank1, 2, 7, 8 Search for this author in: * NPG journals * PubMed * Google Scholar * Ciro Cecconi1, 2, 7, 8 Search for this author in: * NPG journals * PubMed * Google Scholar * Jesse W. Dill2, 3, 7 Search for this author in: * NPG journals * PubMed * Google Scholar * Susan Marqusee1, 2 Search for this author in: * NPG journals * PubMed * Google Scholar * Carlos Bustamante1, 2, 4, 5, 6 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorsJournal name:NatureVolume:465,Pages:637–640Date published:(03 June 2010)DOI:doi:10.1038/nature09021Received30 June 2009Accepted18 March 2010Published online23 May 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg The three-dimensional structures of proteins often show a modular architecture comprised of discrete structural regions or domains. Cooperative communication between these regions is important for catalysis, regulation and efficient folding; lack of coupling has been implicated in the formation of fibrils and other misfolding pathologies1. How different structural regions of a protein communicate and contribute to a protein's overall energetics and folding, however, is still poorly understood. Here we use a single-molecule optical tweezers approach to induce the selective unfolding of particular regions of T4 lysozyme and monitor the effect on other regions not directly acted on by force. We investigate how the topological organization of a protein (the order of structural elements along the sequence) affects the coupling and folding cooperativity between its domains. To probe the status of the regions not directly subjected to force, we determine the free energy changes d! uring mechanical unfolding using Crooks' fluctuation theorem. We pull on topological variants (circular permutants) and find that the topological organization of the polypeptide chain critically determines the folding cooperativity between domains and thus what parts of the folding/unfolding landscape are explored. We speculate that proteins may have evolved to select certain topologies that increase coupling between regions to avoid areas of the landscape that lead to kinetic trapping and misfolding. View full text Subject terms: * Biochemistry * Molecular biology * Biophysics * Structural biology Figures at a glance * Figure 1: Experimental set-up and structure of *T4L variants. , Schematic of the optical tweezer experimental set-up. The protein is tethered between two polystyrene beads, one held by suction to a micropipette and the other trapped in an optical trap. The protein contains cysteines that permit covalent attachment to two ~500 base pair dsDNA molecular handles through disulphide linkages. The dsDNA is attached to the micropipette bead via biotin/streptavidin and to the optical trap bead through a digoxigenin/anti-digoxigenin antibody association. By moving the two beads relative to each other, force and extension can be applied to the protein. , Three-dimensional protein structure of T4L coloured blue and green to distinguish the two energetically distinct C- and N-domains, respectively14. The sites of DNA attachment (residues 16, 61 and 159) are coloured red. , Schematic of WT*T4L and CP13*T4L variants coloured as in . * Figure 2: Unfolding and refolding force-extension curves of WT*T4L and CP13*T4L variants. Representative force-extension curves from , 16,159 WT*T4L, , 16,61 WT*T4L, , 16,159 CP13*T4L and , 16,61 CP13*T4L (red, unfolding; blue, refolding). All data shown were collected using a 50 Hz sampling rate and a pulling speed of 180 nm s-1 (except for 16,61 WT*T4L, which were collected using a pulling speed of 60 nm s-1). The insert in shows the curves for 16,159 CP13*T4L in finer detail, illustrating the diverse unfolding and refolding behaviour. These curves were analysed as described previously17. * Figure 3: The dynamic force spectrum of *T4L variants. The protein unfolding force dependence on experimental pulling speed. All points represent the average unfolding force measured at each pulling speed and the error bars are the standard error of the mean of the measured unfolding forces; the regression lines are included to guide the eye. 16,61 WT*T4L (pink circles, 460 total unfolding events from 48 individual proteins); 16,159 WT*T4L (maroon triangles, 1,189 total unfolding events from 47 proteins); 16,61 CP13*T4L (orange diamonds, 877 total unfolding events from 30 proteins); and 16,159 CP13*T4L full protein (yellow squares), C-domain (green squares) and N-domain (blue squares) (1,869 total unfolding events from 38 proteins). * Figure 4: The normalized probability curves of unfolding and refolding work of 16,61 WT*T4L and CP13*T4L. The normalized probability curves of the work required for the unfolding (in red) and refolding (in blue) measured as described in the main and Supplementary texts. The CFT was used to calculate the free energy from the single molecule experiments. , The calculated free energy for 16,61 WT*T4L (ΔG = 12.3 ± 0.6 kcal mol-1) agrees well with the free energy measured in bulk solution unfolding experiments (ΔG = 14.1 ± 0.6 kcal mol-1) (ref. 15). , The calculated free energy of 16,61 13CP*T4L (ΔG = 3.6 ± 0.2 kcal mol-1) corresponds to the free energy of the N-domain measured in bulk solution using native state hydrogen exchange (ΔG = 6.1 ± 1.0 kcal mol-1) (ref. 14). Author information * Author information * Supplementary information * Comments Primary authors * These authors contributed equally to this work. * Elizabeth A. Shank, * Ciro Cecconi & * Jesse W. Dill Affiliations * Department of Molecular & Cell Biology, University of California, Berkeley, California 94720, USA * Elizabeth A. Shank, * Ciro Cecconi, * Susan Marqusee & * Carlos Bustamante * Jason L. Choy Laboratory of Single Molecule Biophysics, Institute for Quantitative Biosciences, University of California, Berkeley, California 94720, USA * Elizabeth A. Shank, * Ciro Cecconi, * Jesse W. Dill, * Susan Marqusee & * Carlos Bustamante * Biophysics Graduate Group, University of California, Berkeley, California 94720, USA * Jesse W. Dill * Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA * Carlos Bustamante * Department of Physics, University of California, Berkeley, California 94720, USA * Carlos Bustamante * Department of Chemistry, University of California, Berkeley, California 94720, USA * Carlos Bustamante * Present addresses: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA (E.A.S.); Department of Physics, University of Modena and Reggio Emilia, Via Campi 213/A 4100 Modena, Italy (C.C.). * Elizabeth A. Shank & * Ciro Cecconi Contributions E.A.S., C.C., J.W.D. conducted the experiments and analysed the data. J.W.D. carried out the Crooks fluctuation analysis. E.A.S., J.W.D., S.M. and C.B. wrote the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding authors Correspondence to: * Susan Marqusee (Marqusee@berkeley.edu) or * Carlos Bustamante (Carlos@alice.berkeley.edu) Supplementary information * Author information * Supplementary information * Comments PDF files * Supplementary Information (836K) This file contains Supplementary Figures 1-6 with legends, Supplementary Tables 1-2 and References. Additional data
  • A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases
    Schmidt BH Burgin AB Deweese JE Osheroff N Berger JM - Nature (London) 465(7298):641 (2010)
    Nature | Letter A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases * Bryan H. Schmidt1 Search for this author in: * NPG journals * PubMed * Google Scholar * Alex B. Burgin2 Search for this author in: * NPG journals * PubMed * Google Scholar * Joseph E. Deweese3 Search for this author in: * NPG journals * PubMed * Google Scholar * Neil Osheroff3, 4 Search for this author in: * NPG journals * PubMed * Google Scholar * James M. Berger1 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorJournal name:NatureVolume:465,Pages:641–644Date published:(03 June 2010)DOI:doi:10.1038/nature08974Received24 November 2009Accepted01 March 2010Published online19 May 2010Corrected online03 June 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Type II topoisomerases are required for the management of DNA tangles and supercoils1, and are targets of clinical antibiotics and anti-cancer agents2. These enzymes catalyse the ATP-dependent passage of one DNA duplex (the transport or T-segment) through a transient, double-stranded break in another (the gate or G-segment), navigating DNA through the protein using a set of dissociable internal interfaces, or 'gates'3, 4. For more than 20 years, it has been established that a pair of dimer-related tyrosines, together with divalent cations, catalyse G-segment cleavage5, 6, 7. Recent efforts have proposed that strand scission relies on a 'two-metal mechanism'8, 9, 10, a ubiquitous biochemical strategy that supports vital cellular processes ranging from DNA synthesis to RNA self-splicing11, 12. Here we present the structure of the DNA-binding and cleavage core of Saccharomyces cerevisiae topoisomerase II covalently linked to DNA through its active-site tyrosine at 2.5�! �Å resolution, revealing for the first time the organization of a cleavage-competent type II topoisomerase configuration. Unexpectedly, metal-soaking experiments indicate that cleavage is catalysed by a novel variation of the classic two-metal approach. Comparative analyses extend this scheme to explain how distantly-related type IA topoisomerases cleave single-stranded DNA, unifying the cleavage mechanisms for these two essential enzyme families. The structure also highlights a hitherto undiscovered allosteric relay that actuates a molecular 'trapdoor' to prevent subunit dissociation during cleavage. This connection illustrates how an indispensable chromosome-disentangling machine auto-regulates DNA breakage to prevent the aberrant formation of mutagenic and cytotoxic genomic lesions. View full text Subject terms: * Biochemistry * Structural biology Figures at a glance * Figure 1: Structure of a topo II–DNA cleavage complex. , S. cerevisiae topo II domain arrangement. Functional regions are coloured and labelled. Active-site residues are red; 'trapdoor' residues green. , DNA substrate. One strand (top) contains a 3′-bridging phosphorothiolate between the -1/+1 positions (red, boxed). Two complementary strands (bottom) adjoin at a nick (red arrowhead). Blue diamonds indicate DNA bend points. The terminal two base pairs (grey) are disordered. , The cleavage complex. One topo II monomer is coloured as in (). 2Fo-Fc density (1σ contour, orange) is shown around the DNA. , The 5′-phosphotyrosine link modelled into a composite simulated-annealing omit map (1σ contour). * Figure 2: A cleavage-competent active site. Close-up showing DNA (yellow), catalytic amino acids (cyan, TOPRIM; green, winged helix domain) and metal coordination (black spheres). A Zn-anomalous difference map is shown as purple mesh (5σ contour). The two modelled zinc ions are spaced 3.5 Å apart. Hydrogen bonds and metal interactions are displayed as dashed lines. Both non-bridging phosphotyrosyl oxygens are liganded, one by metal A and the other by R781. Mg2+ ions seen in a non-covalent topo II–DNA complex13 and in the DNA-free topo VI A-subunit21 are shown as blue and red spheres, respectively. * Figure 3: DNA cleavage by type IA and II topoisomerases. , Proposed cleavage mechanism. The general base (B:) and acid (HA) are unknown, but may be metal-associated waters. Metal A and R781 stabilize the transition state; metal B and H736 anchor the (-1) phosphate. Amino acids (blue, TOPRIM; green, winged helix domain) are labelled on the basis of positions in yeast topo II, except for a lysine residue present in type IA (but not type II) topoisomerases (grey, E. coli topo I/III numbering). , Type IA/II topoisomerase active site superposition. A DNA-bound (and uncleaved) topo III structure24 (grey) is overlaid on topo II complex (cyan/green). Catalytic residues are labelled (yeast topo II/E. coli topo III numbering). * Figure 4: Cleavage-dependent control of C-gate dynamics. , Superposition of non-covalent (grey)13 and cleavage (orange) complexes between topo II and DNA reveal how C-gate opening and closure is linked to active site status. The connection from the active-site tyrosines to the coiled–coil arms is coloured green/magenta. For clarity, the TOPRIM domains are hidden. , Close-up of positional shifts. Upper panel, upward movement of the active-site tyrosine upon becoming attached to the DNA. Lower panel, concomitant inward movement of the coiled–coil joint through a conserved salt bridge network. Accession codes * Accession codes * Change history * Author information * Supplementary information * Comments Primary accessions Protein Data Bank * 3L4J * 3L4K * 3L4J * 3L4K Change history * Accession codes * Change history * Author information * Supplementary information * CommentsCorrected online 03 June 2010A correction was made to Fig. 1a. Author information * Accession codes * Change history * Author information * Supplementary information * Comments Affiliations * Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA * Bryan H. Schmidt & * James M. Berger * Emerald BioStructures, Bainbridge Island, Washington 98110, USA * Alex B. Burgin * Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA * Joseph E. Deweese & * Neil Osheroff * Department of Medicine (Hematology/Oncology), Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA * Neil Osheroff Contributions B.H.S. purified the complex, grew the crystals, and solved the structures. J.M.B. assisted with refinement and inspection of the molecular models. A.B.B. synthesized the phosphorothiolate reagent. J.E.D. assisted the design of the DNA substrate and optimizing cleavage conditions. N.O. and J.M.B. designed the experiments. All authors contributed to the manuscript. Competing financial interests The authors declare no competing financial interests. Corresponding author Correspondence to: * James M. Berger (jmberger@berkeley.edu) Coordinates for the apo and Zn-bound complexes have been deposited in the RSCB PDB under the accession numbers 3L4J and 3L4K. Supplementary information * Accession codes * Change history * Author information * Supplementary information * Comments Movies * Supplementary Movie SM1 (18.6M) The movie shows that the transition between cleaved and uncleaved DNA states permits C-gate opening (see Supplementary Information file for full legend). PDF files * Supplementary Information (929K) This file contains Supplementary Table S1, Supplementary Figures S1-S6 with legends, Supplementary Movie SM1 legend and References. Additional data
  • Affinity gradients drive copper to cellular destinations
    Banci L Bertini I Ciofi-Baffoni S Kozyreva T Zovo K Palumaa P - Nature (London) 465(7298):645 (2010)
    Nature | Letter Affinity gradients drive copper to cellular destinations * Lucia Banci1 Search for this author in: * NPG journals * PubMed * Google Scholar * Ivano Bertini1 Search for this author in: * NPG journals * PubMed * Google Scholar * Simone Ciofi-Baffoni1 Search for this author in: * NPG journals * PubMed * Google Scholar * Tatiana Kozyreva1 Search for this author in: * NPG journals * PubMed * Google Scholar * Kairit Zovo2 Search for this author in: * NPG journals * PubMed * Google Scholar * Peep Palumaa2 Search for this author in: * NPG journals * PubMed * Google Scholar * Affiliations * Contributions * Corresponding authorsJournal name:NatureVolume:465,Pages:645–648Date published:(03 June 2010)DOI:doi:10.1038/nature09018Received25 August 2009Accepted17 March 2010Published online12 May 2010 Article tools * Full text * 日本語要約 * Print * Email * Download PDF * Download citation * Order reprints * Rights and permissions * Share/bookmark * Connotea * CiteULike * Facebook * Twitter * Delicious * Digg Copper is an essential trace element for eukaryotes and most prokaryotes1. However, intracellular free copper must be strictly limited because of its toxic side effects. Complex systems for copper trafficking evolved to satisfy cellular requirements while minimizing toxicity2. The factors driving the copper transfer between protein partners along cellular copper routes are, however, not fully rationalized. Until now, inconsistent, scattered and incomparable data on the copper-binding affinities of copper proteins have been reported. Here we determine, through a unified electrospray ionization mass spectrometry (ESI-MS)-based strategy, in an environment that mimics the cellular redox milieu, the apparent Cu(I)-binding affinities for a representative set of intracellular copper proteins involved in enzymatic redox catalysis, in copper trafficking to and within various cellular compartments, and in copper storage. The resulting thermodynamic data show that copper is drawn to th! e enzymes that require it by passing from one copper protein site to another, exploiting gradients of increasing copper-binding affinity. This result complements the finding that fast copper-transfer pathways require metal-mediated protein–protein interactions and therefore protein–protein specific recognition3. Together with Cu,Zn-SOD1, metallothioneins have the highest affinity for copper(I), and may play special roles in the regulation of cellular copper distribution; however, for kinetic reasons they cannot demetallate copper enzymes. Our study provides the thermodynamic basis for the kinetic processes that lead to the distribution of cellular copper. View full text Subject terms: * Chemical biology * Biochemistry Figures at a glance * Figure 1: Determination of the relative Cu(I)-binding affinity of GSH and DETC. , , Fractional content of metallated proteins (Y = ICuProt/(IProt + ICuProt) for HAH1 () and Cox17 () at increasing concentrations of DTT (open circles) and GSH (filled circles). , Fractional content of metallated Sco2 (Y = ICuSco2/(ISco2 + ICuSco2) at increasing concentrations of DTT (left) and DETC (right). Conditions: proteins 3 μM; 20 mM ammonium acetate, Cu(I)–DTT 5 μM, pH 7.5; T = 25 °C. Solid lines, fitting curves. * Figure 2: Demetallation of Cu1Sco1 and the CuA site of CcO by apo-MT-2 as followed by ESI-MS. , ESI-MS spectra of Cu1Sco1 (2.5 μM) in the absence () and presence of 0.5 μM (), 1.0 μM () and 2 μM () apo-MT-2. , ESI-MS spectra of Cu2Cox2 (2.5 μM) after addition of apo-MT-2 (2.5 μM), at 2 min (), 5 min (), 10 min () and 20 min (). The charge state ions +9 (for Sco1) and +10 (for Cox2) are presented and the numbers on the peaks denote the metal stoichiometry of the complex. * Figure 3: Free-energy gradients of cellular Cu(I) delivery pathways. Values for ΔG0 were calculated from the apparent values of KCu for Cu(I)-binding proteins and GSH (Table 1) by using the relation ΔG0 = -RT × ln(KCu) (R, gas constant (8.314 J K-1 mol-1); T, absolute temperature in kelvins (298 K)). Metallothioneins can participate in buffering of copper(I) and regulation of its distribution. Author information * Author information * Supplementary information * Comments Affiliations * Magnetic Resonance Center CERM and Department of Chemistry, University of Florence, Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Florence, Italy * Lucia Banci, * Ivano Bertini, * Simone Ciofi-Baffoni & * Tatiana Kozyreva * Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia * Kairit Zovo & * Peep Palumaa Contributions L.B., I.B., S.C.-B., K.Z., P.P. designed the research; K.Z., T.K. and P.P. performed the research. All authors analysed the data and contributed to the writing of the paper. Competing financial interests The authors declare no competing financial interests. Corresponding authors Correspondence to: * Ivano Bertini (ivanobertini@cerm.unifi.it) or * Peep Palumaa (peepp@staff.ttu.ee) Supplementary information * Author information * Supplementary information * Comments PDF files * Supplementary Information (3.3M) This file contains Supplementary Figures S1-S18 with legends. Figure S1 is a simple schematic summarizing the main findings in the paper. Figures S2-18 report ESI-MS spectra performed on the copper proteins, the fittings of the ESI-MS data to obtain the apparent dissociation constants and kinetics data on demetallation processes of copper enzymes. Additional data
  • Sense of wonder
    - Nature (London) 465(7298):656 (2010)
    Memories are made of this.

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