Hot off the presses! Sep 17 Nature

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Latest Articles Include:

• Trust, but verify
  - Nature 461(7262):315 (2009)
  Collaborations between researchers and industry are essential to biomedical progress. But relations have to be completely open.
• Taking the NICE path
  - Nature 461(7262):315-316 (2009)
  The United States can learn from the UK body that rates the effectiveness of medical procedures.
• SETI at 50
  - Nature 461(7262):316 (2009)
  Despite the long odds against success, the search for extraterrestrial intelligence has come a long way.
• Cancer biology: Now you see it
  - Nature 461(7262):318 (2009)
  
• Technology: Lightning-fast memory
  - Nature 461(7262):318 (2009)
  
• Genetics: Yeast joins the club at last
  - Nature 461(7262):318 (2009)
  
• Chemistry: Aluminium arches
  - Nature 461(7262):318 (2009)
  
• Acoustic science: A sonic one-way street
  - Nature 461(7262):318 (2009)
  
• Atmospheric science: Alien sprites
  - Nature 461(7262):318-319 (2009)
  
• Biology: Turning tail
  - Nature 461(7262):319 (2009)
  
• Microbiology: Sussing Shewanella
  - Nature 461(7262):319 (2009)
  
• Materials science: Hard-headed theories
  - Nature 461(7262):319 (2009)
  
• Neurobiology: Teamwork rewarded
  - Nature 461(7262):319 (2009)
  
• Journal club
  - Nature 461(7262):319 (2009)
  
• News briefing: 17 September 2009
  - Nature 461(7262):320-321 (2009)
  The week in science. This article is best viewed as a pdf. Policy|Business|Awards|Research|Events|The week ahead|News maker|Number crunch may become the first major European economy to introduce a carbon tax, after President Nicolas Sarkozy announced on 10 September that he plans to implement a levy, from 2010, on activities emitting substantial amounts of carbon dioxide. Petrol, diesel, coal and natural gas would cost an extra €17 (US$25) per tonne of carbon dioxide emitted. Sarkozy also suggested that a carbon tax could be put on imports. For more, see http://tinyurl.com/lfv6th The has launched a new strategy to tackle the impacts of global warming. On 14 September department secretary Ken Salazar announced he would head a climate-change response council, which will coordinate climate science and land management in the department. Eight regional science centres of the US Geological Survey are to expand into 'response centres', providing guidance on the impacts of climate change to department bureaux such as the Fish and Wildlife Service. The European Union (EU) might have to pay developing countries up to €15 billion (US$22 billion) a year by 2020 to help them combat climate change, according to a proposal published by the on 10 September. The commission estimates that developing countries will need €100 billion annually by 2020, half of which would have to come from international public funds. The US reported on 11 September that early data from its own trials of pandemic H1N1 flu vaccines, manufactured by French company Sanofi Pasteur and by CSL Biotherapies in Pennsylvania (see Nature 562; 2009), confirmed the encouraging results of company trials. All the data suggest that one dose is enough to provoke a robust immune response in healthy adults — not two doses as widely anticipated. The latest studies showed that an adjuvant (a booster chemical) is not required for this effect. The US Securities and Exchange Commission (SEC) has accused a stem-cell biotech company, and its former chief executive and former chief scientific officer, of inflating claims about an early-stage cell therapy. based in Bothell, Washington, told investors that an experimental compound that helps stem cells migrate to specific organs of the body had been approved for human trials to treat heart damage. In reality, the company had neither formulated the compound nor attempted experiments to repair tissue, the SEC claims. For more, see http://tinyurl.com/ly75sp US pharmaceutical giant Merck and the UK's Wellcome Trust have launched a joint not-for-profit £90-million (US$150-million) medical research centre in India to develop affordable vaccines for This is the first time that a pharmaceutical company and a major medical research charity have entered into a bilateral partnership to create vaccines aimed at low-income countries. For more, see page 323. A US company announced plans on 8 September to build what could be the world's largest solar-power plant in the region of China. Backed by a feed-in tariff that will guarantee long-term electricity sales, based in Tempe, Arizona, plans to install thin-film panels that have a total generating capacity of 2,000 megawatts in Ordos City by 2019. First Solar also agreed to explore the possibility of building manufacturing sites in Ordos and expanding other operations in China. SOURCE: NASDAQ Osiris Therapeutics of Columbia, Maryland, saw its share price plummet on 8 September (see chart) after announcing that its stem-cell therapy had failed late-stage clinical trials. Prochymal, which consists of cultured mesenchymal stem cells taken from bone marrow, was no better than a placebo at subduing graft-versus-host disease — a potentially fatal complication in bone-marrow transplants in which immune cells from the donated marrow attack the recipient. "I do think it's a blow to the stem-cell community," says Edward Tenthoff, an analyst at Piper Jaffray in New York. The good news, he says, is that "it's a failed trial, not a safety concern". Last month, biopharmaceutical firm Geron, of Menlo Park, California, had to delay its trial of embryonic-stem-cell therapy for spinal-cord injury for a second time after animal data revealed microscopic cysts growing around the injury site. Researchers think that mesenchymal stem cells could still be an effective way to treat some patients. "Even though it seems to the business world to be a setback, I think [researchers] can learn and go on," says Pranela Rameshwar, a stem-cell scientist at New Jersey Medical School in Newark. Shares in various other stem-cell companies were unaffected by the Osiris trial results. The US$250,000 prize for basic medical research — which often presages a Nobel prize — has gone to British biologist at Cambridge University and at Kyoto University, Japan, for their independent work on the processes that instruct specialized adult cells to form stem cells. In 2006, Yamanaka created induced pluripotent stem cells from mouse skin cells (see Nature 962–965; 2009). The achievement was the culmination of work begun by Gurdon in the late 1950s, when he first transplanted nuclei from a tadpole's intestinal cells into frog eggs, pioneering the technique of nuclear reprogramming to clone animals. A senior scientist at RIKEN, Japan's premier research institute, was arrested last week for allegedly misappropriating research funds. Tatsuo Wada, who studies the behaviour of supramolecular assemblies of organic molecules, allegedly placed worth ¥11.7 million (US$128,000) from RIKEN to Akiba Sangyo, a Tokyo-based company that distributes scientific equipment. The company's president, Etsuo Kato, was also arrested, and RIKEN has begun legal proceedings against Wada to recover the funds. For more, see page 327. The immediate dismissal of 200 scientists from an Israeli government programme that provides jobs for high-level immigrant scientists was averted last week — but the future of the $40-million-a-year programme remains in doubt. Protests by scientists and universities led to a cabinet decision to restore 2009 funding for the , which pays the base salaries of around 500 scientists who have emigrated to Israel, mainly from the former Soviet Union. Entrance to the programme has been frozen and further changes are under consideration. For more, see http://tinyurl.com/news-2009-912 Members of the National Academy of Sciences will from July 2010 no longer be able to communicate work by a non-member for publication in the Proceedings of the National Academy of Sciences, the journal announced last week. Instead, non-members must submit papers directly to the journal for peer review, although they may ask an academy member to edit their paper first. The Darwin Centre.NATURAL HISTORY MUSEUM who won the 1970 Nobel peace prize for his role in tackling world hunger, died on 12 September aged 95. Borlaug developed high-yield, disease-resistant wheat, kick-starting the "green revolution" in the 1960s, which dramatically increased food production in the developing world. He was a distinguished professor at Texas A&M University, in College Station. A full obituary will appear in a forthcoming issue. One of three instruments on the Herschel Space Observatory, which was launched by the European Space Agency in May to study the young Universe, stopped working more than a month ago. The (HIFI), performs high-resolution infrared spectroscopy and is intended to detect elements in gas clouds swirling in star-forming regions. HIFI's project leader, Peter Roelfsema, says he is confident it will be switched on again, but doesn't yet know what caused the instrument's shutdown. For more, see http://tinyurl.com/r2l35t Click to enlarge.NASA; ESA; HUBBLE SM4 ERO TEAM This image of the ' ' (NGC 6302) was among a series of deep-space photos released by NASA from the upgraded Hubble Space Telescope last week — the first images to be published since the iconic orbiting observatory's servicing mission in May (see Nature 21; 2009), which should allow it to keep producing images until 2014. Baltimore, Maryland, hosts the 2009 World Stem Cell Summit. → http://www.worldstemcellsummit.com United Nations secretary-general Ban Ki-moon convenes a summit on climate change in New York. → http://tinyurl.com/mnjgw7 The research goals of a new international ocean drilling research programme will be set at the INVEST meeting in Bremen, Germany. → http://www.marum.de/iodp-invest.html Climate change looms large on the agenda of the G20 summit in Pittsburgh, Pennsylvania. → http://www.pittsburghg20.org The Darwin Centre.NATURAL HISTORY MUSEUM London's Natural History Museum opened a £78-million (US$130-million) Darwin Centre (pictured, right) to the public on 15 September. Its Cocoon building houses a space for visitors to peer at scientists in the lab. The loss sustained by Harvard's invested endowment assets in the fiscal year ending 30 June, a 27.3% hit. The endowment fund now sits at $26 billion. There are currently no comments.
• Vaccine venture boosts health hopes
  - Nature 461(7262):323 (2009)
  Industry and academia join forces to develop cheap jabs against diseases that afflict the poorest. Vaccines for neglected diseases are non-existent or unsuitable in poor countries.M. SWARUP/AP PHOTO US pharmaceutical giant Merck and Company and the UK Wellcome Trust will create a joint, not-for-profit £90-million (US$150-million) research centre in India to develop affordable vaccines against diseases that afflict the poor — including neglected diseases for which inadequate or no vaccines exist. The move marks the first time that a major medical-research charity and a pharmaceutical company have directly partnered to create vaccines aimed at low-income countries. "It's a tremendous development," says Adel Mahmoud, a former president of Merck Vaccines and now a professor at Princeton University in New Jersey. Unlike drugs for neglected diseases, he says, "vaccines for neglected diseases have not been given any significant attention over the years." The new research centre will be named after the late Maurice Hilleman, a Merck scientist who developed more than 40 vaccines, including against measles and hepatitis B. Its location in India has yet to be selected, but it is expected to open by the end of next year. The centre will be headed by Altaf Lal, currently health attaché at the US embassy in New Delhi and the South Asia regional representative for the US health and human services department. Lal says it will bridge the translational research gap that exists between academic scientists and clinical programmes, to help take promising leads to the proof-of-concept stage. Despite being a non-profit organization, the centre will be run as a business, and will be free beyond its £90-million seed funding to pursue partnerships with academics, companies, governments and philanthropic bodies. The centre's portfolio will include high-risk research into diseases for which no vaccines are currently available, says Ted Bianco, director of technology transfer at the Wellcome Trust in London. It will also aim for more immediate pay-offs, such as improving existing vaccines that are too expensive or poorly adapted for distribution in hot, resource-poor countries, where maintaining a chain of refrigeration is complicated. "The centre will bring the scientific and technical skills of an extremely advanced vaccine company like Merck to bear," says Marie-Paule Kieny, vaccine-research director at the World Health Organization (WHO) in Geneva, Switzerland, adding that the direct involvement of the Wellcome Trust confers considerable credibility on the venture's goals. Prospects for vaccines in low-income countries have recently improved. Public–private partnerships have been set up to develop vaccines against the big killers, such as HIV/AIDS and malaria, and the drug firm Novartis last year opened an in-house, non-profit research institute in northern Italy to develop vaccines for diarrhoeal diseases (see Nature 1037; 2008). The Geneva-based global health partnership the GAVI Alliance, created in 2000, has also greatly increased and accelerated the introduction and distribution of large volumes of vaccines. "We really want to lower a lot of the barriers that exist for developing promising products." Mark Feinberg But the crucial missing component has been bringing academic development together with industrial expertise, says Bianco. "Merck are terrific partners to have," he says. "When making vaccines, know-how is hugely significant, and vaccines are a struggle to get into developing countries without it." As well as funding the centre, Merck will offer access to its own researchers, its technologies such as adjuvants and its expertise in clinical trials, says Mark Feinberg, the company's vice-president of medical affairs and policy. The joint venture has yet to decide which diseases it will tackle, but will base the decisions on criteria such as scientific and technical feasibility, affordability and whether vaccine formulations will meet the field and other needs of the large procurement agencies such as the WHO, the United Nations Children's Fund (UNICEF) and the GAVI Alliance. One candidate being explored for vaccine suitability is the Group A Streptococcus bacterium, which causes some 400,000 deaths annually in poor countries but has attracted little research funding. To start whittling down the list of potential candidates, Wellcome and Merck organized a meeting of scientists and other stakeholders in January this year at a research centre in Kilifi, Kenya, part of the Kenya Medical Research Institute (KEMRI). The two partners have also created an advisory group of external scientists chaired by David Heymann, a former assistant director-general of the WHO and now chairman of the UK Health Protection Agency. ADVERTISEMENT The Indian centre will also collaborate with local pharmaceutical companies that can cheaply produce any vaccines it develops. That's novel, says Kieny, and may well pave the way for Western vaccine makers to allow generic versions of vaccines, such as those against human papillomavirus or pneumonia, which are available in rich countries but too expensive for poorer ones. "Affordability will be key in the technical and other choices all along the product design and development path," says Feinberg. "We really want to lower a lot of the barriers that exist for developing promising products." There are currently no comments.
• Ear to the Universe starts listening
  - Nature 461(7262):324 (2009)
  US radio array starts its search for extraterrestrial life. The Allen Telescope Array, scanning for alien radio signals.SETI INSTITUTE A large array of radio telescopes has begun its first sustained search for extraterrestrial intelligence (SETI) and at rates faster than ever before. Even so, the project has scrambled to find money to stay open and reach its planned size. "We've had a chequered time here," says Don Backer, director of the Allen Telescope Array (ATA) in Hat Creek, California. "We're skating on thin ice." The ATA has 42 six-metre dishes swivelling in the high desert, far fewer than the 350 dishes planned. In May, the array began combing the centre of our Milky Way Galaxy for alien signals across a broad slice of the radio spectrum. The effort comes 50 years after the concept of SETI was invented (see Opinion, page 345). Previous searches relied on weeks-long observing runs at facilities such as the Arecibo radio telescope in Puerto Rico. The last major search, Project Phoenix — run by the SETI Institute of Mountain View, California — ended in 2004 and required a decade to check 800 stars across a narrow frequency range. The ATA scans the sky much more quickly, allowing a million stars to be checked in just a few decades, says astronomer Seth Shostak of the SETI Institute, which operates the ATA jointly with the University of California at Berkeley. Shostak says sampling a million stars would offer a good chance of striking on one of the 10,000 intelligent civilizations that might be broadcasting in the Milky Way, according to an estimate by Frank Drake, who in 1960 developed a formula to estimate this number. Private donors, often technologists, began to support SETI in 1993, after the US Congress rescinded NASA funding for it. The family foundation of Microsoft co-founder Paul Allen provided US$25 million, beginning in 2000, to start the ATA. But in 2006, that stream of money was cut off (see Nature 9; 2006), as the SETI Institute and Berkeley struggled to find matching donations to complete the array, which to date has cost $50 million. "We've had a chequered time here — we're skating on thin ice." Last year, the National Science Foundation (NSF) turned down a proposal to support operations at the array. SETI astronomer Jill Tarter says the NSF's decision was "like a Catch-22". The array was big enough at 42 dishes to begin work — and needed money for that — but was not yet big enough to achieve the sensitivity capable of transformational science. Backer hopes that once completed, the ATA, covering vast swaths of sky rapidly, will usher in an era of transient radio astronomy — the study of things, such as supernovae, that go bump in the night rather than shine constantly like stars. Science targets could include the star-fuelling hydrogen that surrounds galaxies, and the radio afterglow of the γ-ray bursts that follow supernovae. Without the NSF money, the $1.5-million-a-year operation cost is being paid by the US Air Force, which uses the array to track satellites and orbital debris. "It's keeping our doors open right now," says Backer. The Allen Foundation has given an additional $5 million since 2006. Time at the array is split roughly equally: a third to the Air Force, a third to radio astronomy and third to SETI. Increasingly, however, SETI can piggyback on the radio astronomy work. ADVERTISEMENT The ATA is also a testbed for technologies that will be important for the rest of radio astronomy. The array has a wide view of the sky, and within that picture, multiple stars can be analysed simultaneously. This technology, known as beam forming, as well as the immense computing challenge of making a picture from many individual dishes, will be needed in future projects, such as the Square Kilometre Array, which envisions thousands of dishes. "This is where radio astronomy has to go," says Mark McKinnon, project manager for a $94-million expansion of the 27-dish Very Large Array in New Mexico. The ATA, he says, "are the only people who are actively doing this". Backer has a proposal before the NSF to double the number of dishes to 84. The request would match $6 million in NSF money with $5 million committed by five donors, including the Allen Foundation and Taiwan's Institute of Astronomy and Astrophysics. Backer says a decision is due before the end of the year. There are currently no comments.
• Ghosts still present in the medical machine
  - Nature 461(7262):325 (2009)
  Unattributed authors remain an issue for journals. A paper's authors are not always apparent from the author list.FOTOPIC/MONSOON/PHOTOLIBRARY/CORBIS The medical literature continues to be haunted by ghostwriting — a practice that, in its most extreme form, involves pharmaceutical companies designing and paying for studies or reviews, then seeking a guest author to be credited while the company goes unacknowledged. The problem persists, said experts last week, despite recent drug-company policy changes and efforts by journals to cut down on the practice (see 'Spectre of industry bias'). A new survey attempting to quantify the phenomenon looked at more than 600 authors who had published papers in six major medical journals in 2008. Of them, 7.8% indicated there was a 'ghost' lurking behind the paper — someone who contributed significantly, perhaps as a writer or statistician, but who wasn't credited as an author or elsewhere. In a similar 1996 survey, the percentage that identified ghosts was 11%. "It is still a problem," says Josef Wislar, a research analyst for the Journal of the American Medical Association (JAMA) in Chicago, Illinois, who presented the work in Vancouver, Canada, at the 10–12 September Sixth International Congress on Peer Review and Biomedical Publication. Recent media reports have described how pharmaceutical giant Merck sponsored work about its painkiller Vioxx (rofecoxib), and Wyeth did the same for its hormone-replacement therapy Prempro, without being fully acknowledged in some resulting papers. And GlaxoSmithKline ran a programme in which employees approached doctors to help them write up their experiences with the depression medicine Paxil (paroxetine). Three published case studies resulted, none acknowledging the assistant writer, says company spokesman Kevin Colgin. These high-profile cases involve papers published largely in the late 1990s or early 2000s, and Merck, Wyeth and GlaxoSmithKline have all since changed their policies to strengthen rules on disclosure. Yet medical-journal editors say the issue continues. "We receive several manuscripts a month that are suspicious," says William Tierney, co-editor-in-chief of the Journal of General Internal Medicine in Indianapolis, Indiana. These include, for example, favourable reviews for new drugs apparently penned by authors who had not previously published on that topic. Whether such ghostwriting has an adverse effect is hard to pin down. The aim of sponsoring and writing papers is simply to "broaden knowledge about the latest science", says Wyeth spokesman Doug Petkus. But Drummond Rennie, deputy editor at JAMA, says that ghostwritten papers tend to have more positive conclusions and can be used to market off-label uses of drugs. Journal editors can fight the practice by having strict rules on disclosure and by publishing the specific contributions of each author, says Jenny White, a research analyst at the University of California, San Francisco. In work presented at the Vancouver meeting, White found that among journals targeted by a ghostwriting campaign by Parke-Davis — a subsidiary of Pfizer — for Neurontin (gabapentin), used to relieve neuropathic pain, the journals that published the work were less likely to have strong rules about authorship and disclosure than those that did not. Still, only 4 of 26 journals she studied explicitly mention ghostwriting in their policies today. ADVERTISEMENT The World Association for Medical Editors recommends that journal editors "publish a notice that a manuscript has been ghost written, along with the names of the responsible companies and the submitting author", alert the academic institution involved and provide the media with details if contacted about the case. Many journal editors do this. "We name and shame constantly," says Rennie. But, says Christine Laine, editor of the Annals of Internal Medicine in Philadelphia, Pennsylvania, the only way to stop the ghostwriting is if "respected names in academia" stop being "willing to put their names on papers they have not been fully involved in, or without proper acknowledgements". "I work regularly with scientists employed by drug companies, and to a person they are honest, ethical and interested in the truth," says Tierney. "These ghostwriting misadventures are the product of the drug companies' marketing offices, and they are maddening."
• Q&A: Choon Fong Shih
  - Nature 461(7262):326 (2009)
  The first president of Saudia Arabia's King Abdullah University of Science and Technology talks. KAUST On 23 September, King Abdullah of Saudi Arabia will open the new King Abdullah University of Science and Technology (KAUST), an endeavour to build an internationally competitive university from scratch. Officials say they have recruited some 70 professors, mainly in chemistry, physics, mathematics and engineering; fewer than 10% of them, however, are women. KAUST has furnished laboratories with cutting-edge equipment, including a 222-teraflop Shaheen supercomputer from IBM. But questions remain over whether KAUST can become a true player on the international stage and whether academic freedom can flourish there. Nature spoke to Choon Fong Shih, its first president. King Abdullah's vision captured my imagination. The king spoke of KAUST as rekindling the Islamic spirit of learning and scientific inquiry, of inspiring a new age of scientific achievement for the region. In fact, the king spoke of KAUST as the new House of Wisdom. The Islamic House of Wisdom was a centre of learning; it drew the very best minds from the known world to discover knowledge, to share knowledge and to apply knowledge. He sees KAUST as a catalyst to bring about a new age of scientific achievement. Western countries have invested in their universities for centuries. Today we see the fruits of that investment. The investment in higher education and in research is a recent investment for this part of the world, and I believe in time we will see the fruit and the benefit. I see KAUST as a new paradigm in academia, advancing the frontiers of science, harnessing science and technology to address some of the global challenges of our time. So that means discovery and the creation of results, and also applying those results to the problems that face humanity. We want to stand with the leading research universities around the world. In a generation or so, we will stand among them. We hope in ten years that our publications per academic will be equal to those of the very best research universities. We are looking at the metrics, both qualitative and quantitative, to be comparable to the top research universities around the world. But, more than that, we will encourage partnerships with major corporations. The endowment is in good hands; it is intact and we are doing well. Besides the endowment, we have other sources of revenue to support KAUST: we have sponsored research that brings in revenue from working with companies, we are sending proposals to government funding agencies and other funding agencies around the world, and we have benefactors who are contributing because KAUST has captured the imagination. We also have tuition income. We see this as an opportunity. We work harder to recruit the best academics from regions affected by the economic downturn. KAUST recruits by global standards. We will not be taking our own students as faculty members because they graduated from KAUST. They will be subject to the same standards we apply to candidates around the world. I believe that our PhD graduates will be very competitive for faculty positions at KAUST and around the world. We have many women on campus. This is a research environment. Our people here — men and women — enjoy the same opportunities, the same resources, as they would find in America, in Europe and in Asia. We have a very active programme in renewable energy. We have a programme to turn sea water into clean, potable water. We are doing plant biology so we can grow plants in arid conditions and green the desert land into arable land. We are looking at some of the most pressing challenges of our time. There is no shortage of exciting problems. Our plate is full. I spent 30 years in the East, I spent 30 years in North America, and with some luck I hope to spend 30 years at the confluence of East and West. There are currently no comments.
• RIKEN scientist arrested
  - Nature 461(7262):327 (2009)
  Japanese researcher allegedly misused institutional funds. "He has made some very highly functional and original materials." Hachiro Nakanishi Tohoku University, Sendai A Japanese researcher, well known for his work on 'supramolecules', was arrested last week for allegedly misappropriating research funds. The scientist, Tatsuo Wada, is based at the Advanced Science Institute in Wako, part of Japan's network of research labs known as RIKEN. The case is an embarrassment for RIKEN, which has an annual budget of ¥100 billion (US$1 billion) and whose researchers are often looked at enviously for their generous funding. "We expect to get strong criticism for this," says Haruhiko Maekawa, director of RIKEN's general-affairs division. "We will have to show that our operations are sound." RIKEN president Ryoji Noyori says: "We will put in place thorough protective measures and redouble awareness of these matters throughout the institute so we can meet the public's expectations." It is the first time in RIKEN's 92-year history that a researcher is alleged to have misappropriated research funds. Wada is known for creating organic supramolecular systems — assemblies of organic molecules whose shape, size and orientation can be manipulated to convey information. He focuses on designing supramolecules that react to light in a way that would allow them to be used in sensors or solar cells. These 'soft optoelectronic' materials could replace semiconductors and other materials that are costly to process. He has also been working on supramolecules that could go into Japan's ubiquitous touch-and-go train passes. An international review of Wada's work last year said he had "an original approach and the laboratory is to be highly commended for its accomplishments in this area". "He has made some very highly functional and original materials," says Hachiro Nakanishi, a materials scientist at Tohoku University in Sendai who was on the review committee. But on 3 August, Wada called RIKEN's head of research affairs, Yoshiharu Doi, and apologized for "causing trouble for RIKEN through his transactions with the supplier". He gave no details, says Maekawa. On 8 September, Tokyo's police department arrested Wada for allegedly transferring payments with RIKEN money of approximately ¥11 million on more than 20 fictitious orders. The orders were to the account with Akiba Sangyo, a Tokyo-based company that distributes scientific equipment. The police also arrested Akiba Sangyo's president Etsuo Kato, on charges of breach of trust. Both Wada and Kato are being detained. Neither could be reached for comment while in custody. A person who picked up the phone at Akiba Sangyo said that the company, which could not contact its president, was not prepared to make an official statement. A decision as to whether to proceed to trial is expected by 18 September. As RIKEN waits for a full tally of the allegedly misappropriated money, it has started legal proceedings against Wada to recover the funds. It has also put together an eight-person committee, composed of a lawyer and accountant from outside the institute, two RIKEN scientists and four other RIKEN staff, to investigate. Maekawa says he expects to have a preliminary report within two months. The timing is making RIKEN researchers nervous because the recently elected Democratic Party of Japan, which takes the reins this week, has already promised to pare down the "independent administrative institutions", of which RIKEN is one, in an attempt to cut down on corruption and waste. Three years ago, a misappropriation scandal at Waseda University in Tokyo put a funding programme there temporarily on ice (see Nature 442, 121; 2006). Wada has been replaced as head of his group. Maekawa says it is unlikely that Wada will be able to retain his position as a RIKEN scientist. Nakanishi says that researchers in Japan suffer from overly strict rules about how grants are used and argues that they should be given more discretion as to how to use their funds. "The government talks on and on about internationalizing research, but if you try … to invite a foreign researcher or take one out to eat, you can't use the funding," he says. "I've had to use my own money for such work-related expenses." "But the numbers in this case go far beyond the kind of money I'm talking about," he adds. Criminal proceedings against Wada and Kato could carry a jail term of 5 years or a ¥500,000 fine. There are currently no comments.
• Wonder weed plans fail to flourish
  - Nature 461(7262):328-329 (2009)
  The first of four weekly articles on biofuels looks at how investment in jatropha is slowing, as investors realize that basic research is needed. The promise of green gold is fading from Jatropha curcus, a shrub that thrives in arid conditions and whose seeds yield a diesel-like oil. Many had seen it as a potential saviour for marginal lands, a plant that could lift developing countries out of poverty and into a sustainable oily future. Billion-dollar investment plans for large-scale farming of the jatropha biofuel crop are on hold.K. SIA/AFP/GETTY IMAGES Just last year, some analysts were predicting that the area planted with jatropha worldwide — at the time, 721,000 hectares — would rise as high as 22 million hectares by 2014. The Jatropha Alliance, an advocacy group based in Berlin, was estimating that investments of up to US$1 billion could be expected annually. More than 130 companies were in the race, dominated by D1 Oils of London, which in 2007 had landed a $160-million deal with oil giant BP. But this July, BP and D1 announced that their deal was off. And of 140 investments made in biofuels so far this year, says analyst Harry Boyle of London-based New Energy Finance, only four or five have been in jatropha projects. "Jatropha has gone very quiet," he says. What happened? It's difficult to untangle the impacts of the global financial downturn from disappointment with jatropha in particular, says Rob Bailis, an environmental scientist at Yale University. But "over the past three years, the investment got way ahead of the plant science", he says. "Over the past three years, the investment got way ahead of the plant science." Early investors are now realizing the plant's limitations. Jatropha can live in very dry conditions, but doesn't necessarily yield a lot of seeds. The plant takes three years or more to reach maturity, requiring care along the way. And jatropha seedlings are often not well-suited to the climate in which they are planted. Even supporters acknowledge that the allure of jatropha is fading somewhat. "This year, a lot of projects did not continue," admits Thilo Zelt, director of the Jatropha Alliance. One blow came with the publication of a controversial paper in June, in which a team led by Arjen Hoekstra at the University of Twente in the Netherlands suggested that jatropha needs more water than other bioenergy crops, such as maize (corn), to produce the same amount of oil (W. Gerbens-Leenes et al. Proc. Natl Acad. Sci. USA 10219–10223; 2009). Jatropha had nearly four times the water footprint of sugar-cane ethanol, for instance. Critics point out what they see as flaws in that analysis, including the fact that it is difficult to compare jatropha, which is wild, with crops such as maize that were domesticated for optimal use thousands of years ago. In addition, the analysis looked at a small number of plantations, all of which had young trees, which could skew the conclusions, says Bart Muys, a forest ecologist at the University of Leuven in Belgium. But Hoekstra says that more thought needs to be given to variables such as where jatropha is planted and how it is harvested. "Jatropha was the hallelujah crop," he says, but in reality "it is just another crop with its own characteristics". The split between D1 Oils and BP has hurt jatropha's reputation as a good business investment, says Boyle. In a statement, BP spokeswoman Sheila Williams said that "the decision to pull out of this is purely based on economics and a decision to focus on key strategic areas", such as sugar-cane ethanol from Brazil, cellulosic ethanol from the United States and biobutanol. In the meantime, D1 Oils has shifted from planting jatropha to focusing on basic research — including starting a breeding programme to develop seeds with high oil yields, says Henk Joos, the company's head of plant science. Another company concentrating on basic science is SG Biofuels, based in Encinitas, California. It has collected samples from jatropha plants growing wild in different environments and is creating a library of genetic material from which it intends to develop enhanced seed strains to test, says chief executive Kirk Haney. Eventually, jatropha might prove more useful on a local scale. For instance, Diligent Energy Systems, a company based in Eindhoven, the Netherlands, has set up small-scale operations in Tanzania, where it provides jatropha seeds for farmers to plant among other crops or on spare land that is unsuitable for food crops. The farmers are guaranteed a price for the oil seeds they produce, and so have an incentive to tend the crop and harvest it carefully, says company founder Ruud van Eck. Some 5,000 farmers are involved, he says, with a total of 3,500 hectares of jatropha planted between them. "The idea is to grow to 10,000 by the end of this year," he says. In other countries, jatropha has yet to capture local support. In the Lao People's Democratic Republic, farmers have been bombarded with seeds and promotional material from companies but received little to no support, says Jakob Rietzler of the Lao Institute for Renewable Energy in Vientiane. As a result, he says, the jatropha they planted reached harvest at the same time as the rice crops. "Farmers neglect their jatropha seeds because they have to harvest their rice," he says. More oil per seed is the goal.T. SANTIKO BUDI/JIWAFOTO/ZUMA PRESS In India, where much of the jatropha hype originated, success will come only if a conservative, realistic approach is adopted at the beginning, says Pushpito Ghosh, director of the Central Salt and Marine Chemicals Research Institute in Bhavnagar. Biodiesel from his institute's jatropha project (see Nature 652–655; 2007) has been used in test cars belonging to the project and in collaboration with General Motors. Ghosh's team has been working to improve the genetic stock of their jatropha, and is about to embark on a life-cycle analysis of how much biodiesel jatropha can generate from a 50-hectare plot. Even so, "it would be premature to call [jatropha] a success in India", says Ghosh. "It is still in the take-off stage." He sees the hype and subsequent disappointment surrounding jatropha as a weeding-out process, leaving behind smaller, more professional players. These include the Australia-based Jatoil, which in August announced a memorandum of understanding with the European biofuel producer PT Waterland. The deal is expected to give Jatoil between 1,000 and 2,000 hectares of established jatropha-bearing land in Java. And China, one of the world's leading biofuel manufacturers, is also taking an interest in jatropha, with 105,000 hectares planted in the country by 2008 and a total of 700,000 predicted by 2015. ADVERTISEMENT The next year is likely to see more basic research into the crop. Muys and his team, for instance, have analysed global land suitability and developed a high-resolution map to show where jatropha might grow best; Madagascar, Tanzania and Ethiopia are likely candidates. Meanwhile, Bailis is conducting jatropha life-cycle analyses to account for land-use change in India and Brazil. Zelt says that seeds optimized to produce more oil will be entering the market in the coming months, and the first real second-generation plants will be planted next year. So although jatropha may not be a saviour plant, transforming vast quantities of desert land into biofuel-producing moneymakers, it is likely to find its niche as a local alternative in certain developing countries. "We need to find ways to use local business resources more efficiently," says Jeremy Woods from Imperial College London's Centre for Environmental Policy. "And jatropha can play a big part in that." There are currently no comments.
• Money in biomedicine: The senator's sleuth
  - Nature 461(7262):330-334 (2009)
  In February 1991, a US Army specialist, one month past his 21st birthday, was busy driving huge supply trucks bearing tank ammunition through the Saudi Arabian desert as part of the US First Infantry Division in the Gulf War. At night, he would watch the vast desert sky, lit by the bombs of US warplanes pounding Saddam Hussein's Iraqi troops. There are currently no comments.
• Health economics: Life in the balance
  - Nature 461(7262):336-339 (2009)
  In May 2008, a research report concluded that it would be too expensive to keep some British people with kidney cancer alive. The 290-page review and economic evaluation had been put together to assess the effectiveness of four new treatments — bevacizumab, sorafenib, sunitinib and temsirolimus — for renal-cell carcinoma. There are currently no comments.
• Non-lethal weapons and the civilian death toll in war time
  - Nature 461(7262):340 (2009)
  The scientific community should think twice before it turns its back on non-lethal weapons, as Malcolm Dando suggests in his Opinion piece 'Biologists napping while work militarized' (Nature 460, 950–951; 2009).It is true that fentanyl killed scores of civilians when it was used to end the Moscow theatre seige in 2002.
• Don't overlook the rigorously reviewed novel work in patents
  - Nature 461(7262):340 (2009)
  Why are patent citations so conspicuously absent across academic journals, with most even omitting formatting instructions for these in their author guidelines? Patents present novel, rigorously reviewed unpublished work, as well as providing an unmatched resource for detail.
• Keeping track of the Earth's carbon-cycle components
  - Nature 461(7262):340 (2009)
  In a recent Editorial (Nature 460, 436; 2009), you call for improved Earth-monitoring tools to verify whether climate policies are effective. I am pleased to report that the global carbon-monitoring activities of the Group on Earth Observations (GEO) are well on the way to meeting your recommended course of action and should make a useful contribution to climate discussions in Copenhagen at the end of the year.
• Were crocodiles responsible for the stones we call tools?
  - Nature 461(7262):341 (2009)
  Could Nature have been unknowingly publishing papers for the past 80 years about crocodilian gastroliths (stomach stones) instead of stones concluded to be 2.5-million-year-old hominid tools?
• Ethical concerns over use of new cloning technique in humans
  - Nature 461(7262):341 (2009)
  The announcement that induced pluripotent stem (iPS) cells have been used successfully to produce viable mice (X. Y. Zhao et al. Nature 461, 86–90; 2009 and M. J. Boland et al. Nature 461, 91–94; 2009
• The need for a fresh symbol to designate copernicium
  - Nature 461(7262):341 (2009)
  There could be a question mark hanging over the symbol proposed for the newly recognized element 112, copernicium (Nature460, 449; 2009).According to the current recommendations of the International Union of Pure and Applied Chemistry on naming new elements, a candidate name cannot be reused on another element (W. H. Koppenol Pure Appl. Chem. 74, 787–791; 2002
• Plan B for Copenhagen
  - Nature 461(7262):342-344 (2009)
  In 11 days the curtain will rise in Bangkok for the penultimate round of negotiations before the climate change conference in Copenhagen. David Victor warns of the dangers of a rushed, stapled-together deal.
• An alien concept
  - Nature 461(7262):345-346 (2009)
  Fifty years ago this week, a Nature paper legitimized the idea that there could be civilizations elsewhere, able to communicate and wanting to contact us. Fred Kaplan reflects on its origins, impacts and legacy.
• Ocean fertilization: time to move on
  - Nature 461(7262):347-348 (2009)
  Adding iron to the ocean is not an effective way to fight climate change, and we don't need further research to establish that, say Aaron Strong, Sallie Chisholm, Charles Miller and John Cullen.
• On the origin of technology
  - Nature 461(7262):349 (2009)
  An overdue theory of how machines and tools evolve downplays human creativity, argues Jon Agar.
• Sound for the masses
  - Nature 461(7262):350-351 (2009)
  The first person to make a reproducible recording of sound was not Thomas Edison. As Greg Milner explains in Perfecting Sound Forever, it was a French printer, Edouard-Léon Scott de Martinville, who etched sound waves on to a thin film of soot in 1857, some two decades before Edison.
• Q&A: The inventor with an ear for the past
  - Nature 461(7262):351 (2009)
  Engineer Duncan Miller has spent decades reviving the lost art of acoustic recording to wax cylinders, a technique pioneered by Thomas Edison. Nature finds out how his Vulcan Cylinder Record Company, based in Sheffield, UK, has combined sleuthing and modern chemistry to craft a new repertoire for the hand-cranked phonograph.
• Atmospheric chemistry: Thwarting the seeds of clouds
  - Nature 461(7262):353-354 (2009)
  Atmospheric oxidation of hydrocarbons emitted from plants leads to the formation of aerosol particles that affect cloud properties. Contrary to what was thought, this process might add to global warming.
• Developmental biology: Asexual healing
  - Nature 461(7262):354-355 (2009)
  The development of healthy monkeys from embryos in which the egg contains nuclear DNA from one donor and mitochondrial DNA from another suggests a method to prevent inheritance of certain human diseases.
• 50 & 100 years ago
  - Nature 461(7262):355 (2009)
  More science means more information, in the form of books, journals and conferences. No scientist needs to be reminded of this.
• Fluid dynamics: To merge or not to merge ...
  - Nature 461(7262):356 (2009)
  ... that is the dilemma addressed in a study of oppositely charged liquid drops controlled by an electric field. Contrary to conventional wisdom, beyond a critical charge, the drops fail to merge.
• Genomics: Hepatitis C virus gets personal
  - Nature 461(7262):357-358 (2009)
  Many people infected with the hepatitis C virus are not cured despite gruelling therapy. A human genetic variant that predicts successful treatment has been identified. So is personalized therapy now a possibility?
• Biological chemistry: Beyond radical thinking
  - Nature 461(7262):358-359 (2009)
  Radiation-induced DNA damage has been attributed to hydroxyl radicals, which form when water absorbs high-energy photons or charged particles. But another product of water's radiolysis might be the real culprit.
• Epigenetics: Ready for the marks
  - Nature 461(7262):359-360 (2009)
  Genomic imprinting, in which genes are expressed from either the maternal or paternal genome, involves the addition of methyl marks to DNA. Paradoxically, demethylation of histone proteins is an essential first step.
• Microbiology: Showering with bacteria
  - Nature 461(7262):360 (2009)
  Abstract
• VEGFR1-activity-independent metastasis formation
  - Nature 461(7262):E4 (2009)
  Arising from: R. N. Kaplan et al.Nature 438, 820–827 (2005); Kaplan et al.reply Molecules such as vascular endothelial growth factor (VEGF) or placental growth factor—critical regulators of tumour angiogenesis—are also thought to mobilize into blood circulation bone marrow-derived cells (BMDCs)1, which may subsequently be recruited to tumours and facilitate tumour growth and metastasis2, 3. A study4 has suggested that BMDCs form 'metastatic niches' in lungs before arrival of cancer cells, and showed that pharmacological inhibition of VEGF receptor 1 (VEGFR1, also known as Flt1)—cognate receptor for VEGF and placental growth factor—prevented BMDC infiltration in lungs and 'metastatic niche' formation. Here we report that blockade of VEGFR1 activity does not affect the rate of spontaneous metastasis formation in a clinically relevant and widely used preclinical model5, 6, 7, 8. Therefore, alternative pathways probably mediate the priming of tissues for metastasis.
• Kaplan et al. reply
  - Nature 461(7262):E5 (2009)
  Replying to: M. R. Dawson et al.Nature 461, 10.1038/nature08254 (2009) Commenting on ref. 1, Dawson et al.2 claim that metastasis formation is independent of VEGFR1 activity, contradicting work by us and many others, including the original description of flt1TK-/- (VEGFR1-TK-/-) mice in the metastatic setting3. Contrasting the findings by Dawson et al.2, here we show that VEGFR1 knockdown in myelomonocytic cells eradicates micro- and macrometastases in a non-amputation/resection tumour model.
• The structural basis of tail-anchored membrane protein recognition by Get3
  - Nature 461(7262):361-366 (2009)
  Targeting of newly synthesized membrane proteins to the endoplasmic reticulum is an essential cellular process. Most membrane proteins are recognized and targeted co-translationally by the signal recognition particle. However, nearly 5% of membrane proteins are 'tail-anchored' by a single carboxy-terminal transmembrane domain that cannot access the co-translational pathway. Instead, tail-anchored proteins are targeted post-translationally by a conserved ATPase termed Get3. The mechanistic basis for tail-anchored protein recognition or targeting by Get3 is not known. Here we present crystal structures of yeast Get3 in 'open' (nucleotide-free) and 'closed' (ADPAlF4--bound) dimer states. In the closed state, the dimer interface of Get3 contains an enormous hydrophobic groove implicated by mutational analyses in tail-anchored protein binding. In the open state, Get3 undergoes a striking rearrangement that disrupts the groove and shields its hydrophobic surfaces. These data! provide a molecular mechanism for nucleotide-regulated binding and release of tail-anchored proteins during their membrane targeting by Get3.
• Mitochondrial gene replacement in primate offspring and embryonic stem cells
  - Nature 461(7262):367-372 (2009)
  Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle–chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA ! came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.
• Misaligned spin and orbital axes cause the anomalous precession of DI Herculis
  - Nature 461(7262):373-376 (2009)
  The orbits of binary stars precess as a result of general relativistic effects, forces arising from the asphericity of the stars, and forces from any additional stars or planets in the system. For most binaries, the theoretical and observed precession rates are in agreement1. One system, however—DI Herculis—has resisted explanation for 30 years2, 3, 4. The observed precession rate is a factor of four slower than the theoretical rate, a disagreement that once was interpreted as evidence for a failure of general relativity5. Among the contemporary explanations are the existence of a circumbinary planet6 and a large tilt of the stellar spin axes with respect to the orbit7, 8. Here we report that both stars of DI Herculis rotate with their spin axes nearly perpendicular to the orbital axis (contrary to the usual assumption for close binary stars). The rotationally induced stellar oblateness causes precession in the direction opposite to that of relativistic precession,! thereby reconciling the theoretical and observed rates.
• Non-coalescence of oppositely charged drops
  - Nature 461(7262):377-380 (2009)
  Electric fields induce motion in many fluid systems, including polymer melts1, surfactant micelles2 and colloidal suspensions3. Likewise, electric fields can be used to move liquid drops4. Electrically induced droplet motion manifests itself in processes as diverse as storm cloud formation5, commercial ink-jet printing6, petroleum and vegetable oil dehydration7, electrospray ionization for use in mass spectrometry8, electrowetting9 and lab-on-a-chip manipulations10. An important issue in practical applications is the tendency for adjacent drops to coalesce, and oppositely charged drops have long been assumed to experience an attractive force that favours their coalescence11, 12, 13. Here we report the existence of a critical field strength above which oppositely charged drops do not coalesce. We observe that appropriately positioned and oppositely charged drops migrate towards one another in an applied electric field; but whereas the drops coalesce as expected at low f! ield strengths, they are repelled from one another after contact at higher field strengths. Qualitatively, the drops appear to 'bounce' off one another. We directly image the transient formation of a meniscus bridge between the bouncing drops, and propose that this temporary bridge is unstable with respect to capillary pressure when it forms in an electric field exceeding a critical strength. The observation of oppositely charged drops bouncing rather than coalescing in strong electric fields should affect our understanding of any process involving charged liquid drops, including de-emulsification, electrospray ionization and atmospheric conduction.
• New particle formation in forests inhibited by isoprene emissions
  - Nature 461(7262):381-384 (2009)
  It has been suggested that volatile organic compounds (VOCs) are involved in organic aerosol formation, which in turn affects radiative forcing and climate1. The most abundant VOCs emitted by terrestrial vegetation are isoprene and its derivatives, such as monoterpenes and sesquiterpenes2. New particle formation in boreal regions is related to monoterpene emissions3 and causes an estimated negative radiative forcing4 of about -0.2 to -0.9 W m-2. The annual variation in aerosol growth rates during particle nucleation events correlates with the seasonality of monoterpene emissions of the local vegetation, with a maximum during summer5. The frequency of nucleation events peaks, however, in spring and autumn5. Here we present evidence from simulation experiments conducted in a plant chamber that isoprene can significantly inhibit new particle formation. The process leading to the observed decrease in particle number concentration is linked to the high reactivity of isopren! e with the hydroxyl radical (OH). The suppression is stronger with higher concentrations of isoprene, but with little dependence on the specific VOC mixture emitted by trees. A parameterization of the observed suppression factor as a function of isoprene concentration suggests that the number of new particles produced depends on the OH concentration and VOCs involved in the production of new particles undergo three to four steps of oxidation by OH. Our measurements simulate conditions that are typical for forested regions and may explain the observed seasonality in the frequency of aerosol nucleation events, with a lower number of nucleation events during summer compared to autumn and spring5. Biogenic emissions of isoprene are controlled by temperature and light2, and if the relative isoprene abundance of biogenic VOC emissions increases in response to climate change or land use change, the new particle formation potential may decrease, thus damping the aerosol negative ra! diative forcing effect.
• Holocene thinning of the Greenland ice sheet
  - Nature 461(7262):385-388 (2009)
  On entering an era of global warming, the stability of the Greenland ice sheet (GIS) is an important concern1, especially in the light of new evidence of rapidly changing flow and melt conditions at the GIS margins2. Studying the response of the GIS to past climatic change may help to advance our understanding of GIS dynamics. The previous interpretation of evidence from stable isotopes (18O) in water from GIS ice cores was that Holocene climate variability on the GIS differed spatially3 and that a consistent Holocene climate optimum—the unusually warm period from about 9,000 to 6,000 years ago found in many northern-latitude palaeoclimate records4—did not exist. Here we extract both the Greenland Holocene temperature history and the evolution of GIS surface elevation at four GIS locations. We achieve this by comparing 18O from GIS ice cores3, 5 with 18O from ice cores from small marginal icecaps. Contrary to the earlier interpretation of 18O evidence from ice core! s3, 6, our new temperature history reveals a pronounced Holocene climatic optimum in Greenland coinciding with maximum thinning near the GIS margins. Our 18O-based results are corroborated by the air content of ice cores, a proxy for surface elevation7. State-of-the-art ice sheet models are generally found to be underestimating the extent and changes in GIS elevation and area; our findings may help to improve the ability of models to reproduce the GIS response to Holocene climate.
• Genotypic sex determination enabled adaptive radiations of extinct marine reptiles
  - Nature 461(7262):389-392 (2009)
  Adaptive radiations often follow the evolution of key traits, such as the origin of the amniotic egg and the subsequent radiation of terrestrial vertebrates. The mechanism by which a species determines the sex of its offspring has been linked to critical ecological and life-history traits1, 2, 3 but not to major adaptive radiations, in part because sex-determining mechanisms do not fossilize. Here we establish a previously unknown coevolutionary relationship in 94 amniote species between sex-determining mechanism and whether a species bears live young or lays eggs. We use that relationship to predict the sex-determining mechanism in three independent lineages of extinct Mesozoic marine reptiles (mosasaurs, sauropterygians and ichthyosaurs), each of which is known from fossils to have evolved live birth4, 5, 6, 7. Our results indicate that each lineage evolved genotypic sex determination before acquiring live birth. This enabled their pelagic radiations, where the relat! ively stable temperatures of the open ocean constrain temperature-dependent sex determination in amniote species. Freed from the need to move and nest on land4, 5, 8, extreme physical adaptations to a pelagic lifestyle evolved in each group, such as the fluked tails, dorsal fins and wing-shaped limbs of ichthyosaurs. With the inclusion of ichthyosaurs, mosasaurs and sauropterygians, genotypic sex determination is present in all known fully pelagic amniote groups (sea snakes, sirenians and cetaceans), suggesting that this mode of sex determination and the subsequent evolution of live birth are key traits required for marine adaptive radiations in amniote lineages.
• Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
  - Nature 461(7262):393-398 (2009)
  Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement1. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population1. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion2. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars3, 4. Here we report the sequence of the P. infestans genome, which at 240 megabases (Mb) is by far the largest an! d most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
• Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance
  - Nature 461(7262):399-401 (2009)
  Chronic infection with hepatitis C virus (HCV) affects 170 million people worldwide and is the leading cause of cirrhosis in North America1. Although the recommended treatment for chronic infection involves a 48-week course of peginterferon--2b (PegIFN--2b) or --2a (PegIFN--2a) combined with ribavirin (RBV), it is well known that many patients will not be cured by treatment, and that patients of European ancestry have a significantly higher probability of being cured than patients of African ancestry. In addition to limited efficacy, treatment is often poorly tolerated because of side effects that prevent some patients from completing therapy. For these reasons, identification of the determinants of response to treatment is a high priority. Here we report that a genetic polymorphism near the IL28B gene, encoding interferon--3 (IFN--3), is associated with an approximately twofold change in response to treatment, both among patients of European ancestry (P = 1.06 10-25)! and African-Americans (P = 2.06 10-3). Because the genotype leading to better response is in substantially greater frequency in European than African populations, this genetic polymorphism also explains approximately half of the difference in response rates between African-Americans and patients of European ancestry.
• Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs
  - Nature 461(7262):402-406 (2009)
  The isolation of human induced pluripotent stem cells (iPSCs)1, 2, 3 offers a new strategy for modelling human disease. Recent studies have reported the derivation and differentiation of disease-specific human iPSCs4, 5, 6, 7. However, a key challenge in the field is the demonstration of disease-related phenotypes and the ability to model pathogenesis and treatment of disease in iPSCs. Familial dysautonomia (FD) is a rare but fatal peripheral neuropathy, caused by a point mutation in the IKBKAP8 gene involved in transcriptional elongation9. The disease is characterized by the depletion of autonomic and sensory neurons. The specificity to the peripheral nervous system and the mechanism of neuron loss in FD are poorly understood owing to the lack of an appropriate model system. Here we report the derivation of patient-specific FD-iPSCs and the directed differentiation into cells of all three germ layers including peripheral neurons. Gene expression analysis in purified F! D-iPSC-derived lineages demonstrates tissue-specific mis-splicing of IKBKAP in vitro. Patient-specific neural crest precursors express particularly low levels of normal IKBKAP transcript, suggesting a mechanism for disease specificity. FD pathogenesis is further characterized by transcriptome analysis and cell-based assays revealing marked defects in neurogenic differentiation and migration behaviour. Furthermore, we use FD-iPSCs for validating the potency of candidate drugs in reversing aberrant splicing and ameliorating neuronal differentiation and migration. Our study illustrates the promise of iPSC technology for gaining new insights into human disease pathogenesis and treatment.
• Optogenetic dissection of a behavioural module in the vertebrate spinal cord
  - Nature 461(7262):407-410 (2009)
  Locomotion relies on neural networks called central pattern generators (CPGs) that generate periodic motor commands for rhythmic movements1. In vertebrates, the excitatory synaptic drive for inducing the spinal CPG can originate from either supraspinal glutamatergic inputs or from within the spinal cord2, 3. Here we identify a spinal input to the CPG that drives spontaneous locomotion using a combination of intersectional gene expression and optogenetics4 in zebrafish larvae. The photo-stimulation of one specific cell type was sufficient to induce a symmetrical tail beating sequence that mimics spontaneous slow forward swimming. This neuron is the Kolmer–Agduhr cell5, which extends cilia into the central cerebrospinal-fluid-containing canal of the spinal cord and has an ipsilateral ascending axon that terminates in a series of consecutive segments6. Genetically silencing Kolmer–Agduhr cells reduced the frequency of spontaneous free swimming, indicating that activit! y of Kolmer–Agduhr cells provides necessary tone for spontaneous forward swimming. Kolmer–Agduhr cells have been known for over 75 years, but their function has been mysterious. Our results reveal that during early development in zebrafish these cells provide a positive drive to the spinal CPG for spontaneous locomotion.
• Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras
  - Nature 461(7262):411-414 (2009)
  The cascade comprising Raf, mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) is a therapeutic target in human cancers with deregulated Ras signalling, which includes tumours that have inactivated the Nf1 tumour suppressor1, 2. Nf1 encodes neurofibromin, a GTPase-activating protein that terminates Ras signalling by stimulating hydrolysis of Ras–GTP. We compared the effects of inhibitors of MEK in a myeloproliferative disorder (MPD) initiated by inactivating Nf1 in mouse bone marrow and in acute myeloid leukaemias (AMLs) in which cooperating mutations were induced by retroviral insertional mutagenesis. Here we show that MEK inhibitors are ineffective in MPD, but induce objective regression of many Nf1-deficient AMLs. Drug resistance developed because of outgrowth of AML clones that were present before treatment. We cloned clone-specific retroviral integrations to identify candidate resistance genes including Rasgrp1, Rasgrp4! and Mapk14, which encodes p38. Functional analysis implicated increased RasGRP1 levels and reduced p38 kinase activity in resistance to MEK inhibitors. This approach represents a robust strategy for identifying genes and pathways that modulate how primary cancer cells respond to targeted therapeutics and for probing mechanisms of de novo and acquired resistance.
• KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints
  - Nature 461(7262):415-418 (2009)
  Differential DNA methylation of the paternal and maternal alleles regulates the parental origin-specific expression of imprinted genes in mammals1, 2. The methylation imprints are established in male and female germ cells during gametogenesis, and the de novo DNA methyltransferase DNMT3A and its cofactor DNMT3L are required in this process3, 4, 5. However, the mechanisms underlying locus- and parental-specific targeting of the de novo DNA methylation machinery in germline imprinting are poorly understood. Here we show that amine oxidase (flavin-containing) domain 1 (AOF1), a protein related to the lysine demethylase KDM1 (also known as LSD1)6, functions as a histone H3 lysine 4 (H3K4) demethylase and is required for de novo DNA methylation of some imprinted genes in oocytes. AOF1, now renamed lysine demethylase 1B (KDM1B) following a new nomenclature7, is highly expressed in growing oocytes where genomic imprints are established. Targeted disruption of the gene encodin! g KDM1B had no effect on mouse development and oogenesis. However, oocytes from KDM1B-deficient females showed a substantial increase in H3K4 methylation and failed to set up the DNA methylation marks at four out of seven imprinted genes examined. Embryos derived from these oocytes showed biallelic expression or biallelic suppression of the affected genes and died before mid-gestation. Our results suggest that demethylation of H3K4 is critical for establishing the DNA methylation imprints during oogenesis.
• Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress antisense RNAs
  - Nature 461(7262):419-422 (2009)
  Eukaryotic transcriptomes are characterized by widespread transcription of noncoding and antisense RNAs1, 2, 3, which is linked to key chromosomal processes, such as chromatin remodelling, gene regulation and heterochromatin assembly4, 5, 6, 7. However, these transcripts can be deleterious, and their accumulation is suppressed by several mechanisms including degradation by the nuclear exosome8, 9. The mechanisms by which cells differentiate coding RNAs from transcripts targeted for degradation are not clear. Here we show that the variant histone H2A.Z, which is loaded preferentially at the 5' ends of genes by the Swr1 complex containing a JmjC domain protein, mediates suppression of antisense transcripts in the fission yeast Schizosaccharomyces pombe genome. H2A.Z is partially redundant in this regard with the Clr4 (known as SUV39H in mammals)-containing heterochromatin silencing complex that is also distributed at euchromatic loci, and with RNA interference component ! Argonaute (Ago1). Loss of Clr4 or Ago1 alone has little effect on antisense transcript levels, but cells lacking either of these factors and H2A.Z show markedly increased levels of antisense RNAs that are normally degraded by the exosome. These analyses suggest that as well as performing other functions, H2A.Z is a component of a genome indexing mechanism that cooperates with heterochromatin and RNAi factors to suppress read-through antisense transcripts.
• Bursts of retrotransposition reproduced in Arabidopsis
  - Nature 461(7262):423-426 (2009)
  Retrotransposons, which proliferate by reverse transcription of RNA intermediates, comprise a major portion of plant genomes1, 2. Plants often change the genome size and organization during evolution by rapid proliferation and deletion of long terminal repeat (LTR) retrotransposons3, 4. Precise transposon sequences throughout the Arabidopsis thaliana genome and the trans-acting mutations affecting epigenetic states make it an ideal model organism with which to study transposon dynamics5, 6, 7, 8, 9. Here we report the mobilization of various families of endogenous A. thaliana LTR retrotransposons identified through genetic and genomic approaches with high-resolution genomic tiling arrays and mutants in the chromatin-remodelling gene DDM1 (DECREASE IN DNA METHYLATION 1)10, 11. Using multiple lines of self-pollinated ddm1 mutant, we detected an increase in copy number, and verified this for various retrotransposons in a gypsy family (ATGP3) and copia families (ATCOPIA13,! ATCOPIA21, ATCOPIA93), and also for a DNA transposon of a Mutator family, VANDAL21. A burst of retrotransposition occurred stochastically and independently for each element, suggesting an additional autocatalytic process. Furthermore, comparison of the identified LTR retrotransposons in related Arabidopsis species revealed that a lineage-specific burst of retrotransposition of these elements did indeed occur in natural Arabidopsis populations. The recent burst of retrotransposition in natural population is targeted to centromeric repeats, which is presumably less harmful than insertion into genes. The ddm1-induced retrotransposon proliferations and genome rearrangements mimic the transposon-mediated genome dynamics during evolution and provide experimental systems with which to investigate the controlling molecular factors directly.
• Selective epigenetic control of retrotransposition in Arabidopsis
  - Nature 461(7262):427-430 (2009)
  Retrotransposons are mobile genetic elements that populate chromosomes, where the host largely controls their activities1, 2, 3. In plants and mammals, retrotransposons are transcriptionally silenced by DNA methylation1, 4, which in Arabidopsis is propagated at CG dinucleotides by METHYLTRANSFERASE 1 (MET1)5. In met1 mutants, however, mobilization of retrotransposons is not observed, despite their transcriptional activation4, 5, 6. A post-transcriptional mechanism therefore seems to be preventing retrotransposition. Here we show that a copia-type retrotransposon (Évadé, French for 'fugitive') evaded suppression of its movement during inbreeding of hybrid epigenomes consisting of met1- and wild-type-derived chromosomes. Évadé (EVD) reinsertions caused a series of developmental mutations that allowed its identification. Genetic testing of host control of the EVD life cycle showed that transcriptional suppression occurred by CG methylation supported by RNA-directed DN! A methylation. On transcriptional reactivation, subsequent steps of the EVD cycle were inhibited by plant-specific RNA polymerase IV/V7, 8 and the histone methyltransferase KRYPTONITE (KYP). Moreover, genome resequencing demonstrated retrotransposition of EVD but no other potentially active retroelements when this combination of epigenetic mechanisms was compromised. Our results demonstrate that epigenetic control of retrotransposons extends beyond transcriptional suppression and can be individualized for particular elements.
• Answers from the event horizon
  - Nature 461(7262):438 (2009)
  The secrets of the Universe.