Hot off the presses! Feb 11 Nature

The Feb 11 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:

• South Africa's opportunity
  - Nature 463(7282):709 (2010)
  The nation's science enterprise still carries the scars of apartheid. But with reform — and increased funding — South Africa could become a catalyst for scientific progress throughout Africa.
• Divide and conquer
  - Nature 463(7282):709 (2010)
  NASA is taking a risk on commercial space services. But the pay-offs could be high.
• A framework for success
  - Nature 463(7282):710 (2010)
  The time is ripe for Europe's scientists to lobby for community-wide infrastructure funding.
• Ecology: Aphid deception
  - Nature 463(7282):712 (2010)
  
• Geoscience: Shocking tides
  - Nature 463(7282):712 (2010)
  
• Materials science: Small, strong and supple
  - Nature 463(7282):712 (2010)
  
• Evolution: All thumbs and toes
  - Nature 463(7282):712 (2010)
  
• Applied physics: Speedier than silicon
  - Nature 463(7282):712 (2010)
  
• Climate change: Warming boosts invasions
  - Nature 463(7282):713 (2010)
  
• Stem cells: Uneven divide
  - Nature 463(7282):713 (2010)
  
• Cardiovascular biology: Fatty foam cells
  - Nature 463(7282):713 (2010)
  
• Geoengineering: Ocean beating
  - Nature 463(7282):713 (2010)
  
• Journal club
  - Nature 463(7282):713 (2010)
  
• News briefing: 11 February 2010
  - Nature 463(7282):714 (2010)
  The week in science Download a PDF of this article. Policy|Business|People|Events|Awards|Research|Business watch|The week ahead|Number crunch|Sound bites The US National Oceanic and Atmospheric Administration (NOAA) announced plans on 8 February to create a 'climate service' charged with collecting and disseminating climate-related data and information. Thomas Karl, who is currently the director of NOAA's National Climatic Data Center, will head the programme, which will also incorporate six existing regional climate centres and a new online portal (www.climate.gov). The reorganization will require authorization from Congress, which is currently considering the 2011 budget. Legislation to establish a national climate service linking the climate programmes of all federal agencies — an idea supported by NOAA chief Jane Lubchenco — is pending in Congress. The Indian Network for Climate Change Assessment, a group of more than 200 scientists formed in October 2009, will publish its first research findings by November and feed them into the fifth report of the United Nations' Intergovernmental Panel on Climate Change (IPCC). India's Prime Minister Manmohan Singh announced the details on 5 February at a Delhi meeting on sustainable development, and also backed under-fire IPCC chairman Rajendra Pachauri. "India has full confidence in the IPCC process and its leadership and will support it in every way," he said. Fate Therapeutics, a biotech company based in San Diego, California, has been granted the first US patent for genetic reprogramming technology to create induced pluripotent stem (iPS) cells. The 4 February licence came shortly after a rival Californian company, iPierian of San Francisco, was awarded Britain's first patent for iPS cell reprogramming (see Nature 463, 592–593; 2010). The US patent covers "pretty cumbersome" technology, says David Resnick, a patent attorney with Nixon Peabody in Boston, Massachusetts, and so is unlikely to affect other researchers or companies in the field. German chemicals company BASF has received its first approval to market genetically modified seeds. Its herbicide-tolerant soya bean 'Cultivance', which was developed with Embrapa, the Brazilian Agricultural Research Cooperation, can now be sold in Brazil. Farmers will start planting the seed next year, the company expects — if China, the United States and Europe approve the variety for import. BASF is hoping to break into a market dominated by Monsanto, Syngenta, DuPont and Bayer; its 'Amflora' genetically modified starchy potato is awaiting European Union approval. London-based pharma giant GlaxoSmithKline revealed plans on 4 February to shut down early-stage research into pain and depression medications, and open a new research arm dedicated to finding treatments for rare diseases. Lay-offs related to the change in strategy would hit research centres in Harlow, UK, and Verona, Italy, although the company did not specify how many jobs would be lost. It also plans to trim £500 million (US$779 million) from its yearly budget, half of which is to come from research and development. SOURCE: USDA New biofuel standards have cleared the way for a continued expansion of maize (corn) ethanol production in the United States. The US Environmental Protection Agency (EPA) ruled on 3 February that ethanol made from maize decreases greenhouse-gas emissions by 20%, formally qualifying it as a 'renewable fuel' for a federal mandate that requires the use of 136 billion litres of biofuels in 2022. The determination went against recent studies that suggest that ethanol made from maize may increase emissions — owing in part to deforestation spurred by increased demand for the crop. More than 30% of the US maize harvest went into producing 42 billion litres of ethanol in 2008–09 (see chart), although maize production has in large part kept pace with the increased demand. The mandate requires refiners to produce nearly 57 billion litres of renewable fuels by 2015. Cellulosic ethanol and 'advanced biofuels' (which reduce emissions by more than 50%, and include ethanol made from sugarcane) must cover the remainder. But the EPA has also scaled back the 2010 requirement for cellulosic biofuels, citing slow progress in the field. The agency plans to make annual adjustments, leaving open the possibility that the production of maize ethanol could expand even further. The director of the US National Science Foundation (NSF) is departing after nearly seven years of running the agency. From 1 June, Arden Bement will lead the newly created Global Policy Research Institute at Purdue University in West Lafayette, Indiana. In 2004, Bement, previously a nuclear engineer at Purdue, was appointed by then-President George W. Bush to a six-year term at the NSF, which he already had directed on an interim basis for 10 months. His replacement has not been announced. Climate scientist Michael Mann of Pennsylvania State University, University Park, has been cleared of allegations of research misconduct by a committee at his university. The committee, convened to investigate Mann's integrity in the wake of public inquiries made after e-mails were stolen from the Climatic Research Unit of the University of East Anglia, UK, found no wrongdoing. But it said that Mann's compliance with sound academic procedures required further examination. NASA/JPL/SPACE SCIENCE INSTITUTE Cassini, the probe that has been orbiting Saturn and its moons since 2004, will get to fly until 2017, NASA announced on 3 February. The mission was originally slated to come to end in 2008, and had already been extended to 2010. The US$60-million-a-year Solstice Mission will allow Cassini to study Saturn (pictured in July 2008) when it is summer in the planet's northern hemisphere. The new schedule calls for 155 orbits around the planet, 54 fly-bys of the methane-shrouded Titan and 11 fly-bys of the icy moon Enceladus. Physicists Anton Zeilinger, John Clauser and Alain Aspect share the prestigious 2010 Wolf Prize in Physics for their work on quantum entanglement. Biologist Axel Ullrich took the medicine prize for his research in cancer (he co-developed trastuzumab, or Herceptin, used to treat breast cancer); and geneticist and plant scientist David Baulcombe got the agriculture prize for his discovery of small interfering RNA in plants, which led to the development of gene silencing. The awards, each worth US$100,000, will be presented at the Israeli parliament in Jerusalem on 13 May. Yale University in New Haven, Connecticut, will reduce its intake of graduate students by 10–15%, cut staff benefits and freeze salaries for some officers in order to start trimming a budget deficit of $150 million. Support for ongoing research programmes is also set to be reduced, the university's president and provost said on 3 February. Yale lost $6.6 billion of its $22.9 billion endowment between June 2008 and June 2009. The Lancet has retracted the research paper (A. J. Wakefield et al. Lancet 351, 637–641; 1998) that began the scare over a purported link between autism and the measles, mumps and rubella (MMR) vaccine. The retraction, on 2 February, said that the paper falsely claimed both that children were "consecutively referred" and that investigations were "approved" by the local ethics committee. The retraction came days after the UK General Medical Council censured the paper's lead author, Andrew Wakefield for unethical conduct (see Nature 463, 593; 2010). J. CANCALOSI/PHOTOLIBRARY.COM The US Fish and Wildlife Service has denied endangered-species protection to the American pika (Ochotona princeps). Campaigners had argued that the small herbivore (pictured) would be threatened by rising temperatures. It would have been only the second mammal other than the polar bear to be afforded such protection explicitly because of climate change. Federal biologists said that pika, which live in mountainous parts of ten western US states, would be able to migrate or adjust to warmer climes. The US National Science Foundation (NSF) announced on 4 February that selected NSF-supported researchers would be given access, via three-year agency grants, to store and analyse data using Microsoft's cloud-computing service. Two related products — developed by Google and IBM, and by HP, Intel and Yahoo — already offer some scientists access to their services (see Nature 449, 963; 2007). US Department of Energy secretary Steven Chu is questioned on his agency's proposed 2010 research and development budget by the House Committee on Science and Technology. → go.nature.com/YWJqIN NASA holds a public 'state of the agency' meeting, presenting its current and proposed programmes. → go.nature.com/DdnJf6 The American Physical Society meets in Washington DC. → go.nature.com/OTUivj The minimum global cost — by 2050 — of the melting Arctic's declining ability to cool the climate, according to a Pew Environment Group report — the first to attempt to quantify the value on the region's 'climate services'. Phil Jones, who stepped aside as director of the Climatic Research Unit (CRU), University of East Anglia, UK, following allegations that e-mails taken from CRU's computers revealed that the case for global warming was overstated. Source: Sunday Times, UK 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.
• Science lines up for seat to space
  - Nature 463(7282):716 (2010)
  Earlier this month, when US President Barack Obama cancelled NASA's Constellation programme — a system of rockets and capsules meant to return astronauts to the Moon — he cleared the field for a host of private companies eager to sell seats aboard their space vehicles. And to back it up, he offered a US$6-billion incentive, to be doled out over 5 years, to "spur the development of American commercial human spaceflight vehicles". There are currently no comments.
• Still looking for that woodpecker
  - Nature 463(7282):718 (2010)
  An expensive recovery plan to save the ivory-billed woodpecker from extinction may come decades too late. J. SARTORE/NATIONAL GEOGRAPHIC/GETTY Nearly five years after biologists thrilled the conservation world by saying that they had videotaped the elusive ivory-billed woodpecker, the US Fish and Wildlife Service (FWS) is on the verge of approving a final recovery plan to manage the species. The plan will lay out a conservation strategy, including what habitat should be preserved — all for a bird that many prominent ornithologists have given up on. In 2005, a team reported1 videotaping an ivory-billed woodpecker (Campephilus principalis) in eastern Arkansas, in what seemed to be the first documented sighting of a creature thought to have become extinct at least 50 years earlier2. Other experts have challenged the claim3, although the team members maintain that they spotted one bird4. But after five years of fruitless searching, hopes of saving the species have faded. "We don't believe a recoverable population of ivory-billed woodpeckers exists," says Ron Rohrbaugh, a conservation biologist at Cornell University in Ithaca, New York, who headed the original search team. "We don't believe a recoverable population exists." The FWS has spent $14 million trying to document and conserve the ivory-billed woodpecker throughout the southeast United States, including $8 million for habitat preservation and $2 million for search-associated costs. The hunt was suspended last October after it ran out of money. Chasing down a string of dubious and faked claims of sightings added an extra burden, undermining already-stressed wildlife programmes, experts say. Jerome Jackson, an ornithologist at Florida Gulf Coast University in Fort Myers who serves on the FWS's ivory-billed woodpecker recovery team, says that a draft recovery plan from 2007 is "incredibly biased". In his view, the plans have overemphasized evidence of the bird's existence to shore up political support for saving it. "I don't think I'm going to be happy with the final plan either," he adds. Laurie Fenwood, coordinator of the ivory-billed woodpecker project at the agency's office in Atlanta, Georgia, says that recovery plans are needed to collect the best scientific knowledge on species — even if it's not clear whether they have already gone extinct. Rohrbaugh and others have continued to publish5–7 on the likelihood of the woodpecker's existence. One study concluded that if there was just one surviving ivory-billed woodpecker in the area of Arkansas searched, the team had a 12% chance of finding it. The FWS recovery plan is meant to consider such estimates. Along the way there have been plenty of false hopes. Last spring, avian ecologist Jeff Hoover was trying to verify a photo said to be of an ivory-billed woodpecker in the Cache River State Natural Area in southern Illinois. But as Hoover, of the Illinois Natural History Survey in Champaign, was studying the photo, the person responsible for it confessed that the photo was faked. Steve Sheridan, a graphic artist in Lexington, Kentucky, says that he did see an ivory-billed woodpecker in the region, and created the photo to encourage conservation of the area. "I told him the effect could be the exact opposite, setting back restoration for years," says Hoover. Other sighting reports continue to meet with scepticism from experts. Last December, an Indiana physician named Gary Erdy told Illinois officials he had a new photograph of an ivory-billed woodpecker from the same area. They later revoked his search permit. ADVERTISEMENT Meanwhile, experts are dealing with protests by Daniel Rainsong, a landscaper based in Ames, Iowa, who says he recently photographed an ivory-billed woodpecker near the Sabine River in east Texas. Rainsong filed a formal complaint earlier this month alleging ethical and financial misconduct, because biologists he approached would not come with him to the Sabine region to confirm the sighting so that he could collect a $50,000 reward. Rohrbaugh says the Cornell team will release an analysis of Rainsong's photo in about a week. * References * Fitzpatrick, J. W.et al. Science308, 1460-1462 (2005). * Dalton, R.Nature437, 188-190 (2005). * Sibley, D. A. , Bevier, L. R. , Patten, M. A. & Elphick, C. S.Science311, 1555 (2006). * Fitzpatrick, J. W. , Lammertink, M. , Luneau, M. D. Jr , Gallagher, T. W. & Rosenberg, K. V.Science311, 1555 (2006). * Scott, J. M.et al. Avian Conserv. Ecol.3, 3 (2008). * Roberts, D. L. , Elphick, C. S. & Reed, J. M.Conserv. Biol.24, 189-196 (2010). * Elphick, C. S. , Roberts, D. L. & Reed, J. M.Biol. Conserv.doi:10.1016/j.biocon.2009.11.026 (2009). 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.
• Testing time for stem cells
  - Nature 463(7282):719 (2010)
  Industry turns to cell lines for drug screens. A deal between Roche and two academic institutions will focus on stem-cell-based drug screening.Roche The drug industry is keener on stem-cell technologies than ever before — and not just as a source of new treatments. A wave of new partnerships aims to use stem cells as a way to screen other potential drug candidates. In the latest such example, Roche last week announced a deal worth some US$20 million with Harvard University in Cambridge, Massachusetts, and Massachusetts General Hospital in Boston. Roche, based in Basel, Switzerland, will use cell lines and protocols developed by academic researchers to screen for drugs to treat cardiovascular disease and other conditions. Because relevant human cell types are often unavailable, current screens tend to use cells from rodents or human tissues other than the ones researchers want to target. The hope is that stem cells could provide exactly the type of cells relevant for an assay. The deal is the latest in a string of similar partnerships. Within the past 15 months, Pfizer of New York and GE Healthcare of Chalfont St Giles, UK, signed deals geared towards using stem cells in drug discovery with the California companies Novocell of San Diego and Geron of Menlo Park, respectively. In 2008, GlaxoSmithKline teamed up with the Harvard Stem Cell Institute for research in neuroscience, heart disease, cancer, diabetes, musculoskeletal diseases and obesity. And in 2006, AstraZeneca of London began collaborating with Cellartis of Gothenburg, Sweden, to use stem cells to make human liver and heart cells for safety tests. Although using stem cells for drug screening and early research should be easier than developing them into replacement tissues, even the most ardent advocates admit that it won't be straightforward. "At the moment it's all really early days," says Stephen Minger, who left King's College London last year to head GE Healthcare's efforts to develop drug-screening tests with cells derived from human embryonic stem cells. "What needs to be demonstrated is the actual application of the technology," adds John Walker, the chief executive of iPierian, a stem-cell company in San Francisco, California. The firm has created motor neurons using induced pluripotent stem (iPS) cells derived from people with and without spinal muscular atrophy, a neurodegenerative disease. Company scientists are investigating whether drug candidates can disrupt telltale protein clumps seen in neurons derived from affected individuals. Eventually, this work could lead to what Walker calls an "in vitro clinical trial" in which iPS cells derived from a wide variety of individuals could be used to predict patients' response to a drug. Most drug companies remain to be convinced that new screens can predict drugs' properties as well as or better than existing methods. They also don't know whether cells can be produced reliably in sufficient quantities for screening, and whether regulatory agencies will accept data derived from them. ADVERTISEMENT Roche says that it is already running screens based on stem cells to test drugs for cardiotoxicity and effects on neurogenesis. Matthias Steger, the company's global business development director for stem-cell alliances, says that under the latest deal, Harvard and Massachusetts General Hospital will work on embryonic stem cells and iPS cells derived from individuals with various forms of cardiovascular disease. The institutions will receive milestone payments as screens are validated, and the collaboration will last 3–5 years. Ruth McKernan, chief scientific officer of Pfizer's regenerative medicine unit, notes that although screens based on stem cells will be useful, they are not the main reason that Pfizer is interested in these cells. "This progress, though important, is incremental when compared to the real promise in using these cells as therapeutics," she says. 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.
• Delays prompt reshuffle at ITER fusion project
  - Nature 463(7282):721 (2010)
  In an effort to put the world's largest scientific experiment back on track after delays and cost overruns, Europe is shaking up the agency overseeing its portion of the multinational ITER reactor. On 16 February, Frank Briscoe, a British fusion scientist, will take the reins as interim director of Fusion for Energy (F4E), the agency in Barcelona, Spain, that manages Europe's ITER contribution — the largest of any partner's. There are currently no comments.
• The future of European research
  - Nature 463(7282):722 (2010)
  With a new research commissioner arriving in Brussels, and big policy changes on the cards, Nature explains how scientists could be affected. Máire Geoghegan-Quinn (pronounced Moira Gey-gan-Quinn) is an unknown quantity in European research affairs. She held ministerial positions in several Irish governments in the 1980s and 90s before moving to the European Court of Auditors in 1999. She has also been a columnist for the Irish Times, and in 1996 published a novel, The Green Diamond, set in Dublin.J. THYS/AFP/Getty Despite having no background in science, Máire Geoghegan-Quinn is about to become one of the most powerful people in European research. This week, she begins work as Europe's research commissioner, replacing Janez Potočnik, and faces the mammoth task of revamping the programmes that fund scientists across the European Union (EU). She arrives at the European Commission at the beginning of a major rethink on science policy that will affect almost every scientist in the union, and their collaborations with partners around the world. One of her immediate challenges will be to preside over the design of the Eighth Framework Programme of Research (FP8), due to launch in 2014. The framework programmes are the EU's main science-funding mechanism, and FP8 is expected to spend €50 billion–100 billion (US$68 billion–137 billion) over seven years. European researchers flock to the framework programmes, but are appalled by their convoluted bureaucracy. Scientists from other countries, including the United States, can also win funding from some areas of the programmes. It is already clear that FP8 will be markedly different from its predecessor: Geoghegan-Quinn wants to create a less bureaucratic framework that supports EU goals, including the creation of a European Research Area. She also becomes Europe's innovation tsar, coordinating with all research programmes in other directorates such as energy, environment and agriculture. Here, Nature looks at some of the issues that will confront Geoghegan-Quinn as she gets to grips with her brief. European Research Area Enabling the free movement of researchers and funding across national borders became a formal goal of the EU in 2000, when the union created the European Research Area (ERA). A functional ERA, with no barrier to researchers moving between EU countries, would open up opportunities for funding and make it easier to hire the best talent regardless of nationality. But ERA has proved difficult to implement, and still requires numerous legal changes by national governments. Most national funding agencies cannot transfer their money to other countries, and it remains almost impossible to transfer pensions. And money is tight. When the European Council of Ministers created ERA, they pledged to support the scheme by raising national research budgets to 3% of gross domestic product (GDP) by 2010. But the EU's investment in research rose from 1.82% of GDP in 2000 to only 1.9% in 2008. Ministers are now working on a ten-year strategy called EU 2020 that will make ERA more achievable. European Research Council Launched in 2007 as an investigator-driven research agency along the lines of the US National Science Foundation, the European Research Council is popular with scientists and policy-makers alike. "Because the grants are given purely on scientific merit it really shows grant winners the degree of recognition they have from their peers," says cell biologist Wieland Huttner of the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, who was last month awarded a €2.5-million ERC Advanced Investigator Grant. "It is such a substantial amount of money, it will allow me to do an intensity of research that I wouldn't have otherwise been able to afford, even at a Max Planck Institute." The ERC has distributed about €1.7 billion in individual grants, and is likely to receive continued support in FP8. But the council, despite an annual budget of more than €1 billion, is underfunded for its mission of strengthening and shaping European research through competitive funding. And increasing the budget might prove tough — new EU members, particularly from the former communist bloc, have done poorly out of the ERC and may seek to cap funding. Cooperation programmes Scientists have a love–hate relationship with the cooperation programmes, which were meant to pave the way for ERA by creating Europe-wide consortia of academic and industry scientists to tackle problems relevant to EU policies, from health to energy. The programmes take up two-thirds of FP7's cash, and each consortium can involve up to 30 principal investigators in different countries, with up to €12 million at their disposal. Every aspect of cooperation projects must be documented. Every cent and every research hour must be justified and accounted for, both before and after it has been spent, and plans updated annually with explanations of why estimates may have slipped. "It's a world of administration, order, liability, accountability — it's unforgiving, and clashes with the culture of science," says immunologist Maria Masucci from the Karolinska Institute in Stockholm, who has participated in several of these programmes. Yet she hopes they will continue. "Our networks have had a very positive scientific impact on our fields and have sparked collaborations we may not otherwise have had," she says. The commission has managed to reduce the number of audits required in some five-year programmes, but this is a minor improvement. The European Court of Auditors last year suggested the more radical idea that cooperation programmes should be managed by external agencies, rather than the commission itself. Some influential commission personnel would, however, be glad to see this element of the framework programme disappear. They argue that a new mechanism called joint programming, whereby programmes are funded by member states instead of the commission, could replace it entirely. "It would be a terrible mistake to go in this direction," says biochemist and Nobel prizewinner Aaron Ciechanover of the Technion Institute of Technology in Haifa, Israel. "It's the only programme that brings together people speaking so many different languages and gets them to work productively." Joint programming Joint programming was proposed by the commission in 2008 to promote ERA. Themes for programmes are selected politically — the first to enter the planning stage is on neurodegenerative diseases — and national research agencies choose whether to buy in. Many member states like this idea because it allows them to follow their national interests. But some scientists worry that countries will prefer to team up with only a small set of partners, further fragmenting the European research effort. "Countries such as Italy, which are considered unreliable research partners, would be at a disadvantage in joint programming," points out cell biologist Pier Paolo di Fiore of the University of Milan, Italy, who has participated in large cooperation programmes. Infrastructure Deciding how to fund research infrastructure such as genomics databases, will be one of the trickiest parts of the FP8 negotiations. These facilities are usually beyond national budgets, and need long-term international funding. ADVERTISEMENT Member states have refused to let the commission commit to this funding, but some politicians will argue for a dedicated budget line in FP8 for infrastructure. There is also €10.2 billion set aside to fund infrastructure projects within the EU's massive structural funds for poor regions — most of which remains unspent, and must be used by 2013. Although Geoghegan-Quinn has not given details about how she will tackle these issues, at her confirmation hearing last month she billed herself as a woman of action. "This is a politician who is in charge of doing things, who wants results and who wants delivery," she told MEPs. "I won't be a mouse, I won't be quiet." For an interview with Spain's science minister on her European policy plans, see go.nature.com/1igQ1J 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.
• Palaeogenetics: Icy resolve
  - Nature 463(7282):724 (2010)
  All Eske Willerslev wanted was a scrap of something human: some hair, a bone, a tooth. For this, the Danish evolutionary biologist flew to Greenland's most remote northern tundra in 2006. There are currently no comments.
• South African science: black, white and grey
  - Nature 463(7282):726 (2010)
  When Nelson Mandela was released from prison on 11 February 1990, Carolyn Williamson watched the events on her television in the Canadian province of Newfoundland. Having completed her doctorate a year previously, she was seven months pregnant and being supported by her husband. There are currently no comments.
• Still a way to go for South Africa's science revolution
  - Nature 463(7282):729 (2010)
  In the two decades that have passed since Nelson Mandela's release from prison, everything in South Africa has been revolutionized, including science. The country has hosted big science projects.
• Iranian physics society striving to prevent misconduct
  - Nature 463(7282):729 (2010)
  Allegations of unethical behaviour by a few Iranian scientists have recently been highlighted in the media, and notably in Nature (Nature 461, 578–579; 2009; Nature 462, 699; 2009; Nature462, 704–705; 2009).
• Italy's stem-cell challenge gaining momentum
  - Nature 463(7282):729 (2010)
  Last summer we unsuccessfully challenged the Italian government in the courts, over its decision to exclude human embryonic stem cells from a ministerial research-funding call for projects studying the biology and therapeutic use of stem cells (see Nature460, 19; 2009; Nature460, 449; 2009). As scientists concerned about inappropriate political interference in scientific affairs, we intend to continue the fight through the courts, even if it takes years.
• Did the bunny sell or sully the story on toxicity testing?
  - Nature 463(7282):729 (2010)
  I question your use of the photograph of a rabbit to illustrate a News story about the European Chemicals Agency (Nature463, 142–143; 2010). Rats, not rabbits, are mainly used in the reproductive-toxicity tests currently required over two generations of animals.
• IPCC: cherish it, tweak it or scrap it?
  - Nature 463(7282):730 (2010)
  As calls for reform intensify following recent furores about e-mails, conflicts of interest, glaciers and extreme weather, five climatologists propose ways forward for the Intergovernmental Panel on Climate Change. Their suggestions range from reaffirming the panel' governing principles to increasing the number and speed of its publications to replacing the volunteer organization with a permanently staffed structure.
• AIDS research must link to local policy
  - Nature 463(7282):733 (2010)
  HIV research in South Africa is world class. To halt the country's epidemic, scientists need to shift focus from global problems to priorities at home, say Salim Abdool Karim and Quarraisha Abdool Karim.
• Why we cannot predict earthquakes
  - Nature 463(7282):735 (2010)
  Roger Bilham enjoys a history of a potentially useful field in which spectacular failures can win accolades.
• The virtue of vagueness
  - Nature 463(7282):736 (2010)
  Although scientists strive for increasing clarity in their measurements and concepts, it is often uncertainty that spurs new thinking. The haziness of the species notion set the young Charles Darwin pondering evolution.
• Date and create
  - Nature 463(7282):736 (2010)
  The offspring of a speed-dating mixer between young scientists and designers is exhibited at London's Dana Centre this week. On display are prototypes of three designs that communicate the broad themes of energy and recycling, synthetic and systems biology and imaging.
• Q&A: Carl Zimmer on writing popular-science books
  - Nature 463(7282):737 (2010)
  Acclaimed essayist Carl Zimmer has eight popular-science books to his name, on topics from parasites and Escherichia coli to evolution. In the second in a series of five interviews with authors who each write science books for a different audience, Zimmer describes how passion breeds popular success.
• Evolutionary biology: Face of the past reconstructed
  - Nature 463(7282):739 (2010)
  DNA is particularly well preserved in hair — enabling the genome of a human to be sequenced, and his ancestry and appearance to be determined, from 4,000-year-old remains.
• 50 & 100 years ago
  - Nature 463(7282):740 (2010)
  In his first lecture, Prof. Medawar had emphasized the fallibility and limitations of our efforts to predict the future. Nevertheless, he maintained in his second lecture that it is not true to say that advances in medicine and hygiene must cause a genetical deterioration of mankind; there is more to be feared from a slow decline of human intelligence.
• Nuclear physics: Weighing up the superheavies
  - Nature 463(7282):740 (2010)
  To discover superheavy elements and study their properties, we need to know the masses of the isotopes of elements heavier than uranium. Weighing these isotopes in an electromagnetic trap has now become possible.
• Palaeontology: Decay distorts ancestry
  - Nature 463(7282):741 (2010)
  Experiments with simple chordate animals show how decay may make the resulting fossils seem less evolved. The consequence is to distort evidence of the evolution of the earliest vertebrates and their precursors.
• Cosmology: Census at a distance
  - Nature 463(7282):742 (2010)
  Abstract
• Neuroscience: Lack of inhibition leads to abuse
  - Nature 463(7282):743 (2010)
  Chronic drug use can lead to addiction, which is initiated by specific brain circuits. The mystery of how one class of drugs, the benzodiazepines, affects activity in this circuitry has finally been solved.
• Parkinson's disease: Mitochondrial damage control
  - Nature 463(7282):744 (2010)
  Defects in mitochondria are implicated in Parkinson's disease. Study of a quality-control pathway involving the proteins PINK1 and Parkin provides further clues about the mechanism involved.
• Astrophysics: Less greedy galaxies gulp gas
  - Nature 463(7282):745 (2010)
  The cool molecular gas from which stars form has been detected in relatively ordinary faraway galaxies. The results point to a continuous fuelling of gas into the star-forming guts of assembling galaxies.
• Chronic DLL4 blockade induces vascular neoplasms
  - Nature 463(7282):E6 (2010)
  Arising from: J. Ridgway et al.Nature 444, 1083–1087 (2006) Delta-like 4 (DLL4)-mediated Notch signalling has emerged as an attractive target for cancer therapy1, 2. However, the potential side effects of blocking this pathway remain uncertain. Here we show that chronic DLL4 blockade causes pathological activation of endothelial cells, disrupts normal organ homeostasis and induces vascular tumours, raising important safety concerns.
• The next generation of scenarios for climate change research and assessment
  - Nature 463(7282):747 (2010)
  Advances in the science and observation of climate change are providing a clearer understanding of the inherent variability of Earth's climate system and its likely response to human and natural influences. The implications of climate change for the environment and society will depend not only on the response of the Earth system to changes in radiative forcings, but also on how humankind responds through changes in technology, economies, lifestyle and policy. Extensive uncertainties exist in future forcings of and responses to climate change, necessitating the use of scenarios of the future to explore the potential consequences of different response options. To date, such scenarios have not adequately examined crucial possibilities, such as climate change mitigation and adaptation, and have relied on research processes that slowed the exchange of information among physical, biological and social scientists. Here we describe a new process for creating plausible scenar! ios to investigate some of the most challenging and important questions about climate change confronting the global community.
• Ancient human genome sequence of an extinct Palaeo-Eskimo
  - Nature 463(7282):757 (2010)
  We report here the genome sequence of an ancient human. Obtained from ~4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20×, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise! to the modern Native Americans and Inuit.
• Genome sequencing and analysis of the model grass Brachypodium distachyon
  - Nature 463(7282):763 (2010)
  Three subfamilies of grasses, the Ehrhartoideae, Panicoideae and Pooideae, provide the bulk of human nutrition and are poised to become major sources of renewable energy. Here we describe the genome sequence of the wild grass Brachypodium distachyon (Brachypodium), which is, to our knowledge, the first member of the Pooideae subfamily to be sequenced. Comparison of the Brachypodium, rice and sorghum genomes shows a precise history of genome evolution across a broad diversity of the grasses, and establishes a template for analysis of the large genomes of economically important pooid grasses such as wheat. The high-quality genome sequence, coupled with ease of cultivation and transformation, small size and rapid life cycle, will help Brachypodium reach its potential as an important model system for developing new energy and food crops.
• Neural bases for addictive properties of benzodiazepines
  - Nature 463(7282):769 (2010)
  Benzodiazepines are widely used in clinics and for recreational purposes, but will lead to addiction in vulnerable individuals. Addictive drugs increase the levels of dopamine and also trigger long-lasting synaptic adaptations in the mesolimbic reward system that ultimately may induce the pathological behaviour. The neural basis for the addictive nature of benzodiazepines, however, remains elusive. Here we show that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABAA (γ-aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition, which relies on α1-containing GABAA receptors expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement. Taken together, our data provide evidence that benzodiazepines share defining pharmacological features of addictive drugs through cell-type-specific expression of! α1-containing GABAA receptors in the ventral tegmental area. The data also indicate that subunit-selective benzodiazepines sparing α1 may be devoid of addiction liability.
• Rfx6 directs islet formation and insulin production in mice and humans
  - Nature 463(7282):775 (2010)
  Insulin from the β-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor neurogenin 3 (Neurog3) initiates the differentiation of the β-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurog3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and huma! ns. Rfx6 could prove useful in efforts to generate β-cells for patients with diabetes.
• High molecular gas fractions in normal massive star-forming galaxies in the young Universe
  - Nature 463(7282):781 (2010)
  Stars form from cold molecular interstellar gas. As this is relatively rare in the local Universe, galaxies like the Milky Way form only a few new stars per year. Typical massive galaxies in the distant Universe formed stars an order of magnitude more rapidly1, 2. Unless star formation was significantly more efficient, this difference suggests that young galaxies were much more molecular-gas rich. Molecular gas observations in the distant Universe have so far largely been restricted to very luminous, rare objects, including mergers and quasars3, 4, 5, and accordingly we do not yet have a clear idea about the gas content of more normal (albeit massive) galaxies. Here we report the results of a survey of molecular gas in samples of typical massive-star-forming galaxies at mean redshifts of about 1.2 and 2.3, when the Universe was respectively 40% and 24% of its current age. Our measurements reveal that distant star forming galaxies were indeed gas rich, and that the ! star formation efficiency is not strongly dependent on cosmic epoch. The average fraction of cold gas relative to total galaxy baryonic mass at z = 2.3 and z = 1.2 is respectively about 44% and 34%, three to ten times higher than in today's massive spiral galaxies6. The slow decrease between z ≈ 2 and z ≈ 1 probably requires a mechanism of semi-continuous replenishment of fresh gas to the young galaxies.
• Direct mass measurements above uranium bridge the gap to the island of stability
  - Nature 463(7282):785 (2010)
  The mass of an atom incorporates all its constituents and their interactions1. The difference between the mass of an atom and the sum of its building blocks (the binding energy) is a manifestation of Einstein's famous relation E = mc2. The binding energy determines the energy available for nuclear reactions and decays (and thus the creation of elements by stellar nucleosynthesis), and holds the key to the fundamental question of how heavy the elements can be. Superheavy elements have been observed in challenging production experiments2, 3, 4, but our present knowledge of the binding energy of these nuclides is based only on the detection of their decay products. The reconstruction from extended decay chains introduces uncertainties that render the interpretation difficult. Here we report direct mass measurements of trans-uranium nuclides. Located at the farthest tip of the actinide species on the proton number–neutron number diagram, these nuclides represent the ga! teway to the predicted island of stability. In particular, we have determined the mass values of 252-254No (atomic number 102) with the Penning trap mass spectrometer SHIPTRAP5. The uncertainties are of the order of 10 keV/c2 (representing a relative precision of 0.05 p.p.m.), despite minute production rates of less than one atom per second. Our experiments advance direct mass measurements by ten atomic numbers with no loss in accuracy, and provide reliable anchor points en route to the island of stability.
• Above-room-temperature ferroelectricity in a single-component molecular crystal
  - Nature 463(7282):789 (2010)
  Ferroelectrics are electro-active materials that can store and switch their polarity (ferroelectricity), sense temperature changes (pyroelectricity), interchange electric and mechanical functions (piezoelectricity), and manipulate light (through optical nonlinearities and the electro-optic effect): all of these functions have practical applications. Topological switching of π-conjugation in organic molecules, such as the keto-enol transformation, has long been anticipated as a means of realizing these phenomena in molecular assemblies and crystals1. Croconic acid, an ingredient of black dyes2, was recently found to have a hydrogen-bonded polar structure in a crystalline state3. Here we demonstrate that application of an electric field can coherently align the molecular polarities in crystalline croconic acid, as indicated by an increase of optical second harmonic generation, and produce a well-defined polarization hysteresis at room temperature. To make this simple pe! ntagonal molecule ferroelectric, we switched the π-bond topology using synchronized proton transfer instead of rigid-body rotation. Of the organic ferroelectrics, this molecular crystal exhibits the highest spontaneous polarization (~20 μC cm-2) in spite of its small molecular size, which is in accord with first-principles electronic-structure calculations. Such high polarization, which persists up to 400 K, may find application in active capacitor and nonlinear optics elements in future organic electronics.
• Zonal flow formation in the Earth's core
  - Nature 463(7282):793 (2010)
  Zonal jets are very common in nature. Well-known examples are those in the atmospheres of giant planets and the alternating jet streams found in the Earth's world ocean1. Zonal flow formation in nuclear fusion devices is also well studied2. A common feature of these zonal flows is that they are spontaneously generated in turbulent systems. Because the Earth's outer core is believed to be in a turbulent state, it is possible that there is zonal flow in the liquid iron of the outer core. Here we report an investigation at the current low-viscosity limit of numerical simulations of the geodynamo. We find a previously unknown convection regime of the outer core that has a dual structure comprising inner, sheet-like radial plumes and an outer, westward cylindrical zonal flow. We numerically confirm that the dual-convection structure with such a zonal flow is stable under a strong, self-generated dipole magnetic field.
• Non-random decay of chordate characters causes bias in fossil interpretation
  - Nature 463(7282):797 (2010)
  Exceptional preservation of soft-bodied Cambrian chordates provides our only direct information on the origin of vertebrates1, 2. Fossil chordates from this interval offer crucial insights into how the distinctive body plan of vertebrates evolved, but reading this pre-biomineralization fossil record is fraught with difficulties, leading to controversial and contradictory interpretations3, 4. The cause of these difficulties is taphonomic: we lack data on when and how important characters change as they decompose, resulting in a lack of constraint on anatomical interpretation and a failure to distinguish phylogenetic absence of characters from loss through decay3. Here we show, from experimental decay of amphioxus and ammocoetes, that loss of chordate characters during decay is non-random: the more phylogenetically informative are the most labile, whereas plesiomorphic characters are decay resistant. The taphonomic loss of synapomorphies and relatively higher preservatio! n potential of chordate plesiomorphies will thus result in bias towards wrongly placing fossils on the chordate stem. Application of these data to Cathaymyrus (Cambrian period of China) and Metaspriggina (Cambrian period of Canada) highlights the difficulties: these fossils cannot be placed reliably in the chordate or vertebrate stem because they could represent the decayed remains of any non-biomineralized, total-group chordate. Preliminary data suggest that this decay filter also affects other groups of organisms and that 'stem-ward slippage' may be a widespread but currently unrecognized bias in our understanding of the early evolution of a number of phyla.
• Competition drives cooperation among closely related sperm of deer mice
  - Nature 463(7282):801 (2010)
  Among the extraordinary adaptations driven by sperm competition is the cooperative behaviour of spermatozoa1. By forming cooperative groups, sperm can increase their swimming velocity and thereby gain an advantage in intermale sperm competition1, 2. Accordingly, selection should favour cooperation of the most closely related sperm to maximize fitness3. Here we show that sperm of deer mice (genus Peromyscus) form motile aggregations, then we use this system to test predictions of sperm cooperation. We find that sperm aggregate more often with conspecific than heterospecific sperm, suggesting that individual sperm can discriminate on the basis of genetic relatedness. Next, we provide evidence that the cooperative behaviour of closely related sperm is driven by sperm competition. In a monogamous species lacking sperm competition, Peromyscus polionotus, sperm indiscriminately group with unrelated conspecific sperm. In contrast, in the highly promiscuous deer mouse, Peromys! cus maniculatus, sperm are significantly more likely to aggregate with those obtained from the same male than with sperm from an unrelated conspecific donor. Even when we test sperm from sibling males, we continue to see preferential aggregations of related sperm in P. maniculatus. These results suggest that sperm from promiscuous deer mice discriminate among relatives and thereby cooperate with the most closely related sperm, an adaptation likely to have been driven by sperm competition.
• Animal cryptochromes mediate magnetoreception by an unconventional photochemical mechanism
  - Nature 463(7282):804 (2010)
  Understanding the biophysical basis of animal magnetoreception has been one of the greatest challenges in sensory biology. Recently it was discovered that the light-dependent magnetic sense of Drosophila melanogaster is mediated by the ultraviolet (UV)-A/blue light photoreceptor cryptochrome (Cry)1. Here we show, using a transgenic approach, that the photoreceptive, Drosophila-like type 1 Cry and the transcriptionally repressive, vertebrate-like type 2 Cry of the monarch butterfly (Danaus plexippus) can both function in the magnetoreception system of Drosophila and require UV-A/blue light (wavelength below 420 nm) to do so. The lack of magnetic responses for both Cry types at wavelengths above 420 nm does not fit the widely held view that tryptophan triad-generated radical pairs mediate the ability of Cry to sense a magnetic field. We bolster this assessment by using a mutant form of Drosophila and monarch type 1 Cry and confirm that the tryptophan triad path! way is not crucial in magnetic transduction. Together, these results suggest that animal Crys mediate light-dependent magnetoreception through an unconventional photochemical mechanism. This work emphasizes the utility of Drosophila transgenesis for elucidating the precise mechanisms of Cry-mediated magnetosensitivity in insects and also in vertebrates such as migrating birds.
• Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
  - Nature 463(7282):808 (2010)
  Immune homeostasis is dependent on tight control over the size of a population of regulatory T (Treg) cells capable of suppressing over-exuberant immune responses. The Treg cell subset is comprised of cells that commit to the Treg lineage by upregulating the transcription factor Foxp3 either in the thymus (tTreg) or in the periphery (iTreg)1, 2. Considering a central role for Foxp3 in Treg cell differentiation and function3, 4, we proposed that conserved non-coding DNA sequence (CNS) elements at the Foxp3 locus encode information defining the size, composition and stability of the Treg cell population. Here we describe the function of three Foxp3 CNS elements (CNS1–3) in Treg cell fate determination in mice. The pioneer element CNS3, which acts to potently increase the frequency of Treg cells generated in the thymus and the periphery, binds c-Rel in in vitro assays. In contrast, CNS1, which contains a TGF-β–NFAT response element, is superfluous for tTreg cell diff! erentiation, but has a prominent role in iTreg cell generation in gut-associated lymphoid tissues. CNS2, although dispensable for Foxp3 induction, is required for Foxp3 expression in the progeny of dividing Treg cells. Foxp3 binds to CNS2 in a Cbf-β–Runx1 and CpG DNA demethylation-dependent manner, suggesting that Foxp3 recruitment to this 'cellular memory module' facilitates the heritable maintenance of the active state of the Foxp3 locus and, therefore, Treg lineage stability. Together, our studies demonstrate that the composition, size and maintenance of the Treg cell population are controlled by Foxp3 CNS elements engaged in response to distinct cell-extrinsic or -intrinsic cues.
• Human host factors required for influenza virus replication
  König R Stertz S Zhou Y Inoue A -Heinrich Hoffmann H Bhattacharyya S Alamares JG Tscherne DM Ortigoza MB Liang Y Gao Q Andrews SE Bandyopadhyay S De Jesus P Tu BP Pache L Shih C Orth A Bonamy G Miraglia L Ideker T García-Sastre A Young JA Palese P Shaw ML Chanda SK - Nature 463(7282):813 (2010)
  Influenza A virus is an RNA virus that encodes up to 11 proteins and this small coding capacity demands that the virus use the host cellular machinery for many aspects of its life cycle1. Knowledge of these host cell requirements not only informs us of the molecular pathways exploited by the virus but also provides further targets that could be pursued for antiviral drug development. Here we use an integrative systems approach, based on genome-wide RNA interference screening, to identify 295 cellular cofactors required for early-stage influenza virus replication. Within this group, those involved in kinase-regulated signalling, ubiquitination and phosphatase activity are the most highly enriched, and 181 factors assemble into a highly significant host–pathogen interaction network. Moreover, 219 of the 295 factors were confirmed to be required for efficient wild-type influenza virus growth, and further analysis of a subset of genes showed 23 factors necessary for vira! l entry, including members of the vacuolar ATPase (vATPase) and COPI-protein families, fibroblast growth factor receptor (FGFR) proteins, and glycogen synthase kinase 3 (GSK3)-β. Furthermore, 10 proteins were confirmed to be involved in post-entry steps of influenza virus replication. These include nuclear import components, proteases, and the calcium/calmodulin-dependent protein kinase (CaM kinase) IIβ (CAMK2B). Notably, growth of swine-origin H1N1 influenza virus is also dependent on the identified host factors, and we show that small molecule inhibitors of several factors, including vATPase and CAMK2B, antagonize influenza virus replication.
• Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication
  - Nature 463(7282):818 (2010)
  Influenza A virus, being responsible for seasonal epidemics and reoccurring pandemics, represents a worldwide threat to public health1. High mutation rates facilitate the generation of viral escape mutants, rendering vaccines and drugs directed against virus-encoded targets potentially ineffective2. In contrast, targeting host cell determinants temporarily dispensable for the host but crucial for virus replication could prevent viral escape. Here we report the discovery of 287 human host cell genes influencing influenza A virus replication in a genome-wide RNA interference (RNAi) screen. Using an independent assay we confirmed 168 hits (59%) inhibiting either the endemic H1N1 (119 hits) or the current pandemic swine-origin (121 hits) influenza A virus strains, with an overlap of 60%. Notably, a subset of these common hits was also essential for replication of a highly pathogenic avian H5N1 strain. In-depth analyses of several factors provided insights into their infect! ion stage relevance. Notably, SON DNA binding protein (SON)3 was found to be important for normal trafficking of influenza virions to late endosomes early in infection. We also show that a small molecule inhibitor of CDC-like kinase 1 (CLK1)4 reduces influenza virus replication by more than two orders of magnitude, an effect connected with impaired splicing of the viral M2 messenger RNA. Furthermore, influenza-virus-infected p27-/- (cyclin-dependent kinase inhibitor 1B; Cdkn1b) mice accumulated significantly lower viral titres in the lung, providing in vivo evidence for the importance of this gene. Thus, our results highlight the potency of genome-wide RNAi screening for the dissection of virus–host interactions and the identification of drug targets for a broad range of influenza viruses.
• Mical links semaphorins to F-actin disassembly
  - Nature 463(7282):823 (2010)
  How instructive cues present on the cell surface have their precise effects on the actin cytoskeleton is poorly understood. Semaphorins are one of the largest families of these instructive cues and are widely studied for their effects on cell movement, navigation, angiogenesis, immunology and cancer1. Semaphorins/collapsins were characterized in part on the basis of their ability to drastically alter actin cytoskeletal dynamics in neuronal processes2, but despite considerable progress in the identification of semaphorin receptors and their signalling pathways3, the molecules linking them to the precise control of cytoskeletal elements remain unknown. Recently, highly unusual proteins of the Mical family of enzymes have been found to associate with the cytoplasmic portion of plexins, which are large cell-surface semaphorin receptors, and to mediate axon guidance, synaptogenesis, dendritic pruning and other cell morphological changes4, 5, 6, 7. Mical enzymes perform redu! ction–oxidation (redox) enzymatic reactions4, 5, 8, 9, 10 and also contain domains found in proteins that regulate cell morphology4, 11. However, nothing is known of the role of Mical or its redox activity in mediating morphological changes. Here we report that Mical directly links semaphorins and their plexin receptors to the precise control of actin filament (F-actin) dynamics. We found that Mical is both necessary and sufficient for semaphorin–plexin-mediated F-actin reorganization in vivo. Likewise, we purified Mical protein and found that it directly binds F-actin and disassembles both individual and bundled actin filaments. We also found that Mical utilizes its redox activity to alter F-actin dynamics in vivo and in vitro, indicating a previously unknown role for specific redox signalling events in actin cytoskeletal regulation. Mical therefore is a novel F-actin-disassembly factor that provides a molecular conduit through which actin reorganization—a hallmark o! f cell morphological changes including axon navigation—can b! e precisely achieved spatiotemporally in response to semaphorins.
• Mechanism of substrate recognition and transport by an amino acid antiporter
  - Nature 463(7282):828 (2010)
  In extremely acidic environments, enteric bacteria such as Escherichia coli rely on the amino acid antiporter AdiC to expel protons by exchanging intracellular agmatine (Agm2+) for extracellular arginine (Arg+)1, 2, 3. AdiC is a representative member of the amino acid-polyamine-organocation (APC) superfamily of membrane transporters4, 5. The structure of substrate-free AdiC revealed a homodimeric assembly, with each protomer containing 12 transmembrane segments and existing in an outward-open conformation6, 7. The overall folding of AdiC is similar to that of the Na+-coupled symporters8, 9, 10, 11. Despite these advances, it remains unclear how the substrate (arginine or agmatine) is recognized and transported by AdiC. Here we report the crystal structure of an E. coli AdiC variant bound to Arg at 3.0 Å resolution. The positively charged Arg is enclosed in an acidic binding chamber, with the head groups of Arg hydrogen-bonded to main chain atoms of AdiC and the alip! hatic portion of Arg stacked by hydrophobic side chains of highly conserved residues. Arg binding induces pronounced structural rearrangement in transmembrane helix 6 (TM6) and, to a lesser extent, TM2 and TM10, resulting in an occluded conformation. Structural analysis identified three potential gates, involving four aromatic residues and Glu 208, which may work in concert to differentially regulate the upload and release of Arg and Agm.
• Fashion victim
  - Nature 463(7282):840 (2010)
  It's all sewn up.