Wednesday, December 9, 2009

Hot off the presses! Dec 10 Nature

The Dec 10 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:

  • A question of integrity
    - Nature 462(7274):699 (2009)
    Iran's institutions must investigate allegations of scientific plagiarism as a matter of urgency.
  • A slippery slope
    - Nature 462(7274):699 (2009)
    Animal-research policies should be guided by moral consensus, not by arbitrary decisions.
  • Animal perception: When 'wit' is not 'wet'
    - Nature 462(7274):700 (2009)
  • Climate science: Carbon sink limits
    - Nature 462(7274):700 (2009)
  • Drug delivery: Into the tumour
    - Nature 462(7274):700 (2009)
  • Immunology: Worms begone!
    - Nature 462(7274):700 (2009)
  • Physics: Electron turnstiles
    - Nature 462(7274):700 (2009)
  • Neuroscience: Hub neurons synch brain
    - Nature 462(7274):700 (2009)
  • Planetary science: Titan's tub
    - Nature 462(7274):701 (2009)
  • Microbiology: Malaria adapts to host
    - Nature 462(7274):701 (2009)
  • Chemistry: Fuel cells' future
    - Nature 462(7274):701 (2009)
  • Evolution: Bird feeder effects
    - Nature 462(7274):701 (2009)
  • Journal club
    - Nature 462(7274):701 (2009)
  • News briefing: 10 December 2009
    - Nature 462(7274):702 (2009)
    The week in science This article is best viewed as a pdf. Policy|Business|Market watch|Events|Research|The week ahead|Number crunch|Sound bites On 2 December, the US National Institutes of Health (NIH) approved 13 human embryonic stem-cell lines for use by US government-funded researchers — the first lines to be given the green light under a liberalized policy announced by President Barack Obama in March. On 4 December, a standing advisory committee to NIH director Francis Collins recommended he approve an additional 27 lines, provided he limit their use to research projects "consistent with the wording of the consent form" used to obtain the lines. This stipulates that the lines be used to study "the embryonic development of endoderm with a focus on pancreatic formation". A further 96 lines are under review. Following a similar announcement by China, India said it would cut its carbon intensity — the amount of carbon dioxide emitted relative to economic output — by 20–25% from 2005 levels by 2020. Environment minister Jairam Ramesh, announcing the commitment on 3 December, said that the target was worked out in concert with other developing countries (see Nature 462, 550; 2009). Australia's government has for the second time rejected proposed legislation to create a carbon-trading scheme. Following a fortnight of political turmoil that saw climate-change sceptic Tony Abbott elected as leader of the opposition, Prime Minister Kevin Rudd declined to call a snap election. The government said that there would be another chance to vote for the scheme when parliament resumes in February. See go.nature.com/ayfWdf for more. Carbon dioxide and other greenhouse gases are dangerous to human health, the US Environmental Protection Agency declared on 7 December. The ruling, proposed in April, allows the administration of President Barack Obama to regulate emissions under the federal Clean Air Act without going through Congress. Automobile emissions are likely to be the first to be regulated. Italian scientists have lost a final appeal against a government research call that explicitly excludes human embryonic stem cells, even though their use is legal. The researchers objected when the exclusion was added by politicians to a text agreed by a committee of scientific experts (see Nature 460, 19; 2009). They took the health ministry to court in June, arguing that the exclusion infringed a constitutional freedom of scientific research. They lost that case, and on 2 December, they lost their appeal to the supreme administrative court. On 4 December, the US Department of Energy announced $979 million for three demonstration projects to capture carbon dioxide from power plants and store it underground. Private investors would add another $2.2 billion, the agency said. Two projects involve fitting carbon-capture units to existing coal power plants (in New Haven, West Virginia and Mobile, Alabama), and a new power plant will be built near Midland, Texas. The European Union has inched closer to a system in which a single patent would cover all 27 member states, with just one, centralized appeals court. On 4 December, industry ministers agreed the principles of the plan, which would drastically cut the costs of managing patents across Europe. But they deferred agreement on crucial issues, such as the costly matter of translating a single patent into different languages. The plan awaits debate in the European parliament. The European life-sciences sector was perked up by its first large initial public offering for almost two years, after Belgian biotech firm Movetis raised €85 million (US$128 million) on its 3 December debut. Backed by venture-capital investment, Movetis has European approval to market a constipation drug, prucalopride (Resolor). Click for larger imageSOURCE: FOREST CARBON INDEX Amazonian nations will be the early winners in any market for forest carbon credits, which could grow to US$20 billion a year by 2020. The Forest Carbon Index, released by the environmental think tank Resources for the Future and consultancy firm Climate Advisers, both based in Washington DC, charts where governments should invest in preserving forests in developing countries. That is, if the Copenhagen negotiations permit rich nations to offset their emissions this way. The report says that 85% of the best places for early forest carbon returns (2013–20) are in the greater Amazon, particularly in Brazil and Peru, where there is a high rate of deforestation, cheap land, market capacity and political will to save the forests. Investment will also depend on national policies: Brazil has asked for donations — not an offset market — to help avoid deforestation, because it wants developed countries to reduce emissions at home. But it has recently said it might allow some offsets. See go.nature.com/TtU9Tm for more. M. GREENBERG/VIRGIN GALACTIC Enthusiastic space tourists got their first public viewing of the commercial passenger vehicle SpaceShipTwo (pictured, centre: mounted under its carrier aeroplane WhiteKnightTwo) on 7 December at Mojave Air and Space Port, California. The rocket ship, developed by aviation designer Burt Rutan and bankrolled by British billionaire Richard Branson, will carry passengers to the edge of outer space — for US$200,000 a ticket. Virgin Galactic, which Branson hopes will become the world's first commercial spaceline, says it has already signed up more than 300 passengers for flights from a yet-to-be-built spaceport in New Mexico. They are unlikely to get space-borne until 2011 at least — even if all flight testing goes smoothly. Details of a new £520-million (US$850-million) biomedical research centre in central London were outlined on 7 December. The UK Centre for Medical Research and Innovation will bring together four research institutes in one building. Paul Nurse, president of the Rockefeller University in New York, who is leading the development of science plans for the complex, said the budget would be "tight"; and operations could begin with fewer than the hoped-for 1,250 researchers if construction costs go over budget. See go.nature.com/uPkUlY for more. Three weeks after the theft of e-mails from the Climatic Research Unit (CRU) at the University of East Anglia in Norwich, UK, unsuccessful hacking was reported at the Canadian Centre for Climate Modelling and Analysis at the University of Victoria in British Columbia. Andrew Weaver, a climate researcher at the university, claimed that there had been a "sustained hacking attempt" in recent weeks. At CRU, Phil Jones has stepped aside as director, pending the result of a university review of the incident. G. RAMAGE/NEWSPIX/NEWS LTD Australia's national science agency has been accused of trying to alter a peer-reviewed paper that was critical of carbon-trading schemes, leading a prominent researcher to quit the agency on 2 December. Clive Spash (pictured right), an ecological economist at the Commonwealth Scientific and Industrial Research Organization in Canberra, said he had "had enough" after his paper was accepted by the journal New Political Economy earlier this year, withdrawn by the acting chief of his division, and then approved again on condition that parts were reworded. See go.nature.com/OoYXwX for more. Tuberculosis research has seen funding jump in each of the past few years, but the rate of increase is dropping off. So says a report released on 3 December by the Treatment Action Group, an AIDS research and policy think tank based in New York. Tuberculosis funding increased by 8% last year to US$510 million, compared with annual increases of 13% in 2007 and 17% in 2006. The balance of funding is also shifting, from government agencies to philanthropic organizations such as the Bill & Melinda Gates Foundation. A panel of anthropologists has again criticized the Human Terrain System, a controversial US Department of Defense project to embed social scientists in military units in Iraq and Afghanistan to gain cultural understanding (see Nature 455, 583–588; 2008). In a report presented by the American Anthropological Association at its annual meeting on 3 December, an internal committee said the programme had uneasy ethical tensions — such as being too closely aligned with military intelligence gathering — and could "no longer be considered a legitimate professional exercise of anthropology". New Zealand hosts the Antarctic Treaty Meeting of Experts, which will recommend ways to manage ship-borne tourism to Antarctica. → go.nature.com/cUJGwI This year's Nobel science laureates receive their awards in Stockholm, Sweden. → go.nature.com/PUfasn NASA's orbiting infrared telescope, the Wide-Field Infrared Survey Explorer, is scheduled to launch. → http://wise.ssl.berkeley.edu The American Geophysical Union meets in San Francisco, California. → www.agu.org/meetings/fm09 The number of days unmanned underwater glider Scarlet Knight took to cross the Atlantic Ocean, gathering water data. It is the first craft of its kind to make the crossing. Source: Rutgers, the State University of New Jersey Michael Sohlman, executive director of the Nobel Foundation, thinks that the Nobel prizes might have to be shrunk as a result of the economic downturn. Source: Reuters There are currently no comments.
  • Plagiarism scandal grows in Iran
    - Nature 462(7274):704 (2009)
    Investigation finds more cases of duplication in publications co-authored by ministers and senior officials. Nature has uncovered further instances of apparent plagiarism in papers co-authored by government ministers and senior officials in Iran. The spate of new examples raises questions about whether such incidents are symptomatic of conditions also common in other developing countries — such as difficulties with English or pressure to acquire academic credentials as a prerequisite for promotion — or whether they are also linked specifically to the Iranian regime, where growth of a merit-based university culture has been undermined by political appointments and purges of reform-minded scientists (see page 699). Research papers co-authored by Hamid Behbahani contain text from other works.A. KENARE/AFP/GETTY An earlier probe1,2 revealed extensive plagiarism in a paper co-authored by transport minster Hamid Behbahani and four papers co-authored by science minister Kamran Daneshjou. The revelations received wide coverage in the Iranian media and blogosphere. Scientists inside and outside the country have called for investigations, as well as for stronger ethical oversight in Iran's research institutions. Daneshjou, a mechanical engineer at the Iran University of Science & Technology (IUST) in Tehran, was head of the interior-ministry office that oversaw this year's disputed election that kept President Mahmoud Ahmadinejad in power. In October, the Iranian parliament's commission for science and education held an informal inquiry into the four Daneshjou papers. Although it made no official conclusion, it effectively cleared Daneshjou after his co-author, IUST colleague Majid Shahravi, took responsibility for the papers' contents in the Iranian media — although both Shahravi and some members of the commission also maintain that the papers contained originality. Three of the four papers have now been retracted by the journals in question — the fourth was in an Iranian journal. The paper3 by Behbahani, an IUST researcher who supervised Ahmadinejad's PhD, has not been investigated, although it seems to be almost entirely put together from three earlier articles by different authors2. It was retracted by the journal Transport in October. Behbahani has publicly said that the paper did not constitute plagiarism because only parts of the article were identical to earlier work. He challenged the allegations of plagiarism, calling them a "media attack, far from fairness and integrity" and "an illegitimate accusation". Nature has now uncovered yet more instances of apparent plagiarism in papers from Behbahani and some of his co-authors. One paper4 on asphalt-road resistance — by Behbahani's Transport co-authors Hassan Ziari, a deputy minister of roads and transportation whom Daneshjou recently appointed as head of Payame Noor University in Tehran, and Mohammed Khabiri, then a PhD student at the IUST — contains many sections that are identical to a 2005 paper5 by scientists in Pakistan. And two 2008 papers6,7 on strengthening asphalt roads, co-authored by Behbahani and Ziari with PhD student Shams Noubakhat, also contain duplicated material. The first6 includes multiple passages from three earlier papers8,9,10 and the second7 is also largely taken from three other papers10,11,12. One scientist familiar with the field, who asked to remain anonymous, says that he has difficulty making sense of the first paper's results, and that some data in it6 are identical to those in one of the earlier papers by different researchers8. "That the two sets of results could be identical is improbable," he says. Behbahani and Ziari did not respond to requests for comment. Muhammad Atif Ramay, managing editor of the Journal of Applied Sciences Research in which both papers were published, says that the journal has withdrawn the articles from its website pending further investigation. Also in question is a 2008 paper on modelling pollution in Iran13, which is co-authored by one of the 37 members of the Iranian Supreme Council of Cultural Revolution, Mohammad Ali Kaynejad, an environmental engineer at Sahand University of Technology in Tabriz, Iran. The paper almost entirely duplicates a 2001 conference paper14 on modelling pollution in Hungary. The Iranian paper acknowledges the original source of the model, although the authors wrote that it was "tested via the simulation of a photochemical oxidant episode that took place in Tabriz, Iran in 2007". But Alison Tomlin, an environmental modeller at the University of Leeds, UK, and a co-author on the Hungary model, says that the Iranian paper contains "no new results" and "is definitely a copy". It includes computer simulations purportedly of Iranian data, but they match the Hungary figures — and the background map outlines Hungary, not Iran. The first author of the Iranian paper, Esmaeil Fatehifar, an environmental engineer at Sahand University of Technology, places the responsibility on another member of the team. "He said these are measured data about Tabriz Petrochemical Complex," he says. "I thought he was right and accepted it." Fatehifar says he intends to cancel the team member's PhD plans. He adds that Kaynejad had "not seen that paper" even though his name is on it. Kaynejad did not respond to Nature's interview requests. Questions have also been raised over work co-authored by Ali Reza Ali-Ahmadi, education minister in the previous government of Ahmadinejad. A 2006 paper15 on supply networks co-authored by him includes many sentences and paragraphs that are identical to those in three earlier papers16,17,18. Mika Ojala at Tampere University of Technology in Finland, a co-author on one of the earlier studies, says that in his opinion this is not coincidence. Ali-Ahmadi could not be reached for comment. Babak Amiri, an IUST researcher and a co-author on the paper, says that a draft version of the paper was accidentally submitted before it was checked by himself or Ali-Ahmadi. "I apologize for this big mistake," he says. ADVERTISEMENT Nature has also learned that the US National Academy of Sciences earlier this year removed a chapter from a 2003 book19 on a US–Iranian workshop. Ironically, the chapter, authored by Hassan Zohoor, secretary of the Academy of Sciences of the Islamic Republic of Iran, was called 'The impact of moral values on the promotion of science'. It was withdrawn because it substantially duplicated a 1999 paper20 by Douglas Allchin, a historian and philosopher now at the University of Minnesota in Minneapolis. Zohoor says that he never saw Allchin's paper, and that he only prepared a draft of the paper, leaving others in his office to "develop it and add the literature review". Zohoor says that the explanation of the staff member involved — that the copying happened "quite accidentally and as a mere negligence" — is inadequate, and that he intends to write to Allchin to apologize. "In my entire life I've never copied anyone else's work," says Zohoor. * References * Butler, D.Nature doi:10.1038/news.2009.945 (2009). * Butler, D.Nature461, 578-579 (2009). * Ziari, H. , Behbahani, H. & Khabiri, M. M.TransportXXI, 207-212 (2006). * Ziari, H. & Khabiri, M. M.J. Eng. Appl. Sci.2, 33-37 (2007). * Kamal, M. A. , Shazib, F. & Yasin, B.J. East. Asia Soc. Transport. Stud.6, 1329-1343 (2005). * Behbahani, H. , Ziari, H. & Noubakhat, S.J. Appl. Sci. Res.4, 96-102 (2008). * Behbahani, H. , Ziari, H. & Noubakhat, S.J. Appl. Sci. Res.4, 282-286 (2008). * Awwad, M. T. & Shbeeb, L.Am. J. Appl. Sci.4, 390-396 (2007). * Lucena, M. C. C. , Soares, S. A. & Soares, J. B.Mater. Res.7, 529-534 (2004). * Emery, S. J. & O'Connell, J. in Proc. 7th Conf. Asphalt Pavements for Southern Africa 29 August–2 September 1999, Victoria Falls, Zimbabwe (CAPSA, 1999). * Hofsink, W. , Kong Kam Wa, N. Y. & Dickinson, M. N. in Proc. 8th Conf. on Asphalt Pavements for Southern Africa 12–16 September 2004, Sun City, South Africa (CAPSA, 2004). * Hanyu, A. , Ueno, S. , Kasahara, A. & Saito, K.J. East. Asia Soc. Transport. Stud.6, 1153-1167 (2005). * Fatehifar, E. , Alizadeh Osalu, A. , Kaynejad, M. A. & Elkamel, A. in Proc. 3rd IASME/WSEAS Int. Conf. Energy & Environment 23–25 February 2008, Univ. Cambridge, 330-335 (2008). * Lagzi, A. S.et al. in Air Pollution Modelling and Simulation (ed. Sportisse, B.) 264-273 (Springer, 2002). * Aliahmadi, A. R. , Jafari, M. & Amiri, B. in Proc. 2nd National Conf. Logistics & Supply Chain 20–21 November 2006, Tehran (2006). * Hallikas, J. , Karvonen, I. , Pulkkinen, U. , Virolainen, V.-M. & Tuominen, M.Int. J. Prod. Econ.90, 47-58 (2004). * Ojala, M. & Hallikas, J.Int. J. Prod. Econ.104, 201-213 (2006). * Harland, C. , Brenchley, R. & Walker, H.J. Purchasing Supply Management9, 51-62 (2003). * The Experiences and Challenges of Science and Ethics: Proceedings of an American-Iranian Workshop (NAS, 2003). * Allchin, D.Sci. Educ.8, 1-12 (1999). There are currently no comments.
  • Exoplanet claim bites the dust
    - Nature 462(7274):705 (2009)
    Ground-based astrometry dealt a blow as planet found not to exist. Is there really a planet orbiting VB10 (red star)?NASA/JPL-Caltech Strike one planet from the list of 400-odd found around stars in other solar systems: a proposed planet near a star some 6 parsecs from Earth may not exist after all. The finding is also a strike against a planet-seeking strategy called astrometry, which measures the side-to-side motion of a star on the sky to see whether any unseen bodies might be orbiting it. Ground-based astrometry has been used for more than a century, but none of the extrasolar planets it has detected has been verified in subsequent studies. In May, Steven Pravdo of the Jet Propulsion Laboratory in Pasadena, California, and his colleagues raised fresh hopes for the technique when they announced an exoplanet, six times more massive than Jupiter, orbiting VB10, a star about one-thirteenth the mass of the Sun, using a telescope at the Palomar Observatory in southern California (S. Pravdo and S. Shaklan Astrophys. J. 700, 623–632; 2009). But now a group led by Jacob Bean at the Georg-August University in Gottingen, Germany, has used a different approach, and found nothing. "The planet is not there," says Bean. Bean and his colleagues used a well-honed technique called radial velocity, which has found most of the extrasolar planets detected so far. The method looks for shifts in the lines of a star's absorption spectrum to track its motion towards and away from Earth, which would be caused by the influence of a planet. Radial-velocity measurements typically exploit the visible bands of the electromagnetic spectrum. But VB10 is a very dim star and gives off most of its light as infrared radiation. At the Very Large Telescope in Chile, Bean placed a gas cell filled with ammonia in the path of the starlight, enabling him to calibrate the instrument for the infrared. "We would definitely have seen a significant amount of variation in our data if [the planet] was there," says Bean, who has submitted the work to the Astrophysical Journal (J. L. Bean et al. Astrophys. J. preprint at http://fr.arxiv.org/abs/0912.0003; 2009). Pravdo says that Bean and his colleagues "may be correct, but there is hyperbole in their rejection of our candidate planet". Bean's paper, for instance, only rules out the presence of any planet that is at least three times more massive than Jupiter, says Pravdo, adding that the work "limits certain orbits for possible planets but not all planets". "Unfortunately, astrometry is a very difficult business," counters Bean, explaining that Earth's atmosphere can introduce distortions that affect the measurements. Astrometrists rely on watching a field of stars about the same distance away as the target star to calibrate their measurements, and that can be tricky, says Alessandro Sozzetti, an astrometry expert at the Turin Observatory in Italy. "Even if we think we have selected a good set of reference stars," he says, "we may still be limited by atmospheric effects that cause an extra jitter" in the motion of those stars. Alan Boss, an exoplanet expert at the Carnegie Institution of Washington, agrees. He points to the well-known 'detection' of 1963, when Dutch astronomer Piet van de Kamp used astrometry to claim that two planets were orbiting Barnard's Star — a finding disproved a decade later. The dispute over the VB10 planet, says Boss, "is another example of how hard it is to detect extrasolar planets using astrometry from the ground". ADVERTISEMENT Astronomers expect astrometry to work much better above the distorting effects of the atmosphere. Two space missions in the works — the European Space Agency's GAIA, due to launch in 2012, and NASA's Space Interferometry Mission, the launch date for which is yet to be set — will use the technique to search for planets as small as Earth around Sun-like stars, says Sozzetti. More significantly, astrometry can yield the mass of a planet, whereas radial velocity only puts a lower limit on it. Bean admits that astronomers might one day find a planet around VB10 if they scrutinize the star long and hard enough. "The main lesson from VB10," says Boss, is that a lot of high-quality data are needed to be sure that an exoplanet is present.
  • Primate study halted by US university
    - Nature 462(7274):706 (2009)
    Administrators at Oklahoma State University (OSU) in Stillwater have abruptly cancelled an anthrax vaccine study that would have killed dozens of baboons. The project, funded by the US National Institutes of Health (NIH) and led by Shinichiro Kurosawa of Boston University School of Medicine in Massachusetts, had been approved by the OSU animal-care committee in September and was awaiting review by the biosafety committee when OSU president Burns Hargis vetoed it in October, calling the study "controversial".
  • Culture clash at Australian synchrotron
    - Nature 462(7274):706 (2009)
    The future of Australia's biggest scientific facility, the Australian Synchrotron in Melbourne, is in question. After its director was fired and its staff went on strike in recent weeks, relations between the board that oversees the facility and the scientists who use it have broken down.
  • 'Killer application' for protein synthesis is retracted
    - Nature 462(7274):707 (2009)
    Lost lab notes hamper attempts to repeat crucial experiment. The retraction of two papers from the lab of prominent US chemist Peter Schultz is a setback for researchers trying to synthesize and study glycoproteins — proteins with sugar chains attached. The papers, published in Science1 and the Journal of the American Chemical Society2 (JACS), seemed to show that technology enabling the bacterium Escherichia coli to make proteins from many non-natural amino acids could also incorporate sugars at specific sites. Schultz, of the Scripps Research Institute in La Jolla, California, says that while attempting to replicate the work in the two papers, members of his lab discovered that non-natural glycosylated amino acids — ones with attached sugars — behave differently from all other non-natural amino acids his lab has studied. The researchers were unable to get the specific amino acids described in the two papers to integrate into proteins, although they did manage to get the bacteria to make proteins incorporating other glycosylated amino acids, Schultz says. He and his colleagues retracted the JACS paper on 4 September3 and the Science paper on 27 November4. "This takes away one of the benchmarks people would cite to show how far the method could go." In August, a paper co-authored by Eric Tippmann, a former postdoc of Schultz's who is now at Cardiff University, UK, argued that the method described in the papers could not have worked anyway5. E. coli, he reported, has insufficient levels of the relevant enzymes necessary to process the glycosylated amino acids that were used in the experiment. He and his colleagues suggest5 that the proteins reported in the retracted papers contained natural rather than non-natural glycosylated amino acids. Schultz says it could be true that the proteins incorporated natural rather than non-natural amino acids, but adds that there are other possible explanations for his results. He says that the conditions of the original experiments may have allowed the E. coli to process the glycosylated amino acids, which had been modified to allow them to enter the bacteria easily. However, the lab no longer has the notebooks detailing the original experiments, so the team can't replicate those conditions, Schultz explains. Schultz says that he had members of his lab try to replicate the papers for more than two years. "We worked hard on it, and there are real peculiarities associated with the glycosylated amino acids that we still don't understand," Schultz says. "We couldn't get it to work." Only then did the team decide to retract the papers. "I think we did the right thing," says Schultz. Glycoproteins are ubiquitous in biology and pharmacology, but difficult to make artificially in living cell systems, so the ability to direct bacteria to make specific glycoproteins would have been a boon. Chemist David Tirrell of the California Institute of Technology in Pasadena, who also studies methods for incorporating non-natural amino acids into proteins, says the retractions will be a blow for glycobiologists. But because the glycobiology work was often seen as proof of principle, it is also a disappointment for anyone working on making proteins from non-natural amino acids, he says. "This takes away one of the benchmarks people would cite to show how far the method could go," says Tirrell. Another former postdoc of Schultz's, Ryan Mehl, who is now at Franklin & Marshall College in Lancaster, Pennsylvania, agrees. "[Glycobiologists] went from something where they had the potential for great tools to zero, so it's a big deal for that field." ADVERTISEMENT Schultz's underlying method for incorporating non-natural amino acids into proteins has been reproduced by other labs, note Tirrell, Mehl and other scientists. But the ability to incorporate glycoproteins "would have been a killer application", says Steven Benner of the Foundation for Applied Molecular Evolution in Gainesville, Florida. "I'm disappointed that it didn't work." * References * Zhang, Z.et al. Science303, 371-373 (2004). * Xu, R.et al. J. Am. Chem. Soc.126, 15654-15655 (2004). * Xu, R.et al. J. Am. Chem. Soc.131, 13883 (2009). * Zhang, Z.et al. Science326, 1187 (2009). * Antonczak, A. K. , Simova, Z. & Tippmann, E. M.J. Biol. Chem.284, 28795-28800 (2009). There are currently no comments.
  • Cattle disease faces total wipeout
    - Nature 462(7274):709 (2009)
    Rinderpest goes the way of smallpox. Vaccines developed in the 1980s have helped to control outbreaks of rinderpest around the world.F. PALADINI/FAO What does it take to wipe a scourge off the face of the Earth? A massive global push to hunt down and eradicate the last few stubborn pockets of disease — whether the problem is in people or cattle. World health bodies say that within 18 months they will celebrate the eradication of rinderpest, the world's most devastating cattle disease. It would become only the second disease that humans have wiped from the globe — after smallpox, which was declared vanquished in 1980 — and will mark a "massive achievement for the veterinary community", says Chris Oura, head of the Non-Vesicular Disease Reference Laboratory Group at the Institute for Animal Health in Pirbright, UK. "Rinderpest tops the list of killer [animal] diseases," says Juan Lubroth, chief veterinary officer for the Food and Agricultural Organization of the United Nations (FAO) in Rome. Just as smallpox ripped through human populations for centuries, so too has rinderpest drastically reduced animal populations. Also known as cattle plague, rinderpest can lead to famine when people lose the beasts they need to plough their fields. It first spread from Asia to Europe in the herds of invading tribes, causing outbreaks in the Roman Empire in 376–386, and since then it has killed millions of cattle and other wildlife throughout Europe, Africa, the Middle East and the Indian sub-continent. The world's first veterinary science school was established in France in 1762 to train specialists to deal with rinderpest. The disease, which can kill 80–90% of infected cattle within ten days, is caused by a morbillivirus — a group of viruses that also includes measles. Clinical signs include fever, discharges from the eyes and nose, diarrhoea and dehydration. In the 1980s, outbreaks in Nigeria cost around US$2 billion. But that decade also saw a breakthrough in controlling the disease: a vaccine containing the attenuated virus that was heat-stable and could be stored and transported over long distances. Going global SOURCE: FAO In 1994, a global effort to eradicate rinderpest was launched, headed by the FAO and the World Organisation for Animal Health (OIE), based in Paris. It incorporated several earlier, regional efforts and focused on widespread vaccination programmes and on long-term monitoring of cattle and wildlife. The last known outbreak was in Kenya in 2001, with the last remaining pockets of the disease in Pakistan, Sudan and the Somali Ecosystem (parts of Somalia, Ethiopia and Kenya) thought to have been eradicated by 2007 (see map). Oura says that the biggest scientific challenge in eradicating the virus is the large-scale monitoring and surveillance needed to ensure that the virus is gone. "It's a huge task when you have the virus in developing countries and war zones, such as Somalia, to carry out monitoring and surveillance," he says. By the 1970s, smallpox, too, was found only in the war-torn Horn of Africa, where the last case was isolated in Somalia in 1977. Although the rinderpest vaccine can provide life-long protection, it also poses a challenge. Because it contains the live virus, diagnostic tests can't differentiate between infected and vaccinated animals, as both will test positive for antibodies against the virus. Cows also pass on antibodies to their offspring through their milk. So, to confirm whether the virus has been eradicated, vaccinations must stop for a period of two years and calves younger than two years old then need to be tested. "It is a difficult, long process to make sure nothing is there," says Oura. ADVERTISEMENT Lubroth says he is "confident" that the world is already free of the disease but that the FAO and the OIE expect to make an official declaration that it has been eradicated in 18 months. Bernard Vallat, director-general of the OIE, says that the hold-up is because 12 countries are yet to submit their final test and surveillance results to the organization. Even after the disease is declared extinct in the wild, it will live on in the lab. Over the next year and a half, the OIE will be drawing up an inventory of which governments and laboratories around the world are keeping a stock of the virus for research purposes. There are currently no comments.
  • Centre turns away from healing herbs
    - Nature 462(7274):711 (2009)
    A decade ago, US National Institutes of Health (NIH) director Harold Varmus was invited to quit when he opposed a senator's plans to elevate a small NIH office into a research centre for testing the validity of alternative therapies. Having grown from those modest beginnings, the National Center for Complementary and Alternative Medicine (NCCAM) in Bethesda, Maryland, celebrates its tenth anniversary this week.
  • Israel weighs up new funding agency
    - Nature 462(7274):712 (2009)
    Israel is a research powerhouse, sustained by a per-capita level of spending that, by some counts, is the highest in the world. But most of that money is spent by industry; in basic research, which is mostly conducted in higher-education institutions, Israel lags behind many other developed countries (see graph), with biomedical research bringing up the rear. There are currently no comments.
  • Copenhagen: the scientists' view
    - Nature 462(7274):714 (2009)
    The United Nations Climate Change Conference is mainly a political affair but it has drawn hundreds of scientists to the Danish capital. Jeff Tollefson finds out what they hope to gain. Download a PDF of this story As the United Nations summit on global warming kicks into gear in Copenhagen this week, upwards of 15,000 people are converging on the city. The official negotiators from 193 countries will spend much of their time behind closed doors at the Bella conference centre, but they will be a minority of the visitors. Orbiting around the negotiators will be representatives of almost every segment of society, including hundreds of scientists. The researchers will attend scheduled science sessions and gather for countless impromptu discussions in corridors and cafeterias. Many are presenting their latest work — on a vast array of topics including forest carbon, emissions scenarios and green technologies. Some hope to influence policy-makers and provide technical advice on issues that emerge during the negotiations. Others are coming to educate themselves about the treaty process and to network. A climate summit is a flurry of activity, with the central negotiations surrounded by side shows that last from early in the morning until late at night. When the formal sessions finally wind down (if, in fact, they do, as negotiations have been known to go all night), discussions often continue over dinner and drinks. The Copenhagen meeting, which runs from 7 to 18 December, is officially the 15th Conference of the Parties (COP) to the United Nations Framework Convention on Climate Change, which was signed at the Earth Summit in Rio de Janeiro in 1992. Negotiators have been meeting each year for a COP since 1995, but the expectations and the stakes for this summit are orders of magnitude higher than for any previous one. Twelve years after taking their first tentative steps with the Kyoto Protocol, countries are now aiming to restructure the global economy and to lock in deep cuts in greenhouse-gas emissions for decades to come. In advance of the summit, Nature talked to researchers from around the world about how they plan to take part. M. URBAN/PIK "I wouldn't say that I am depressed, but I feel very sad about the negotiation process as it stands now. But I don't see that this can be changed substantially by scientists." Edenhofer is wearing two hats in Copenhagen. As co-chair of the Intergovernmental Panel on Climate Change (IPCC) working group on mitigation, he is presenting results from the group's 2007 assessment at several side events and briefings for policy-makers. But those events frequently lead to additional contacts, requests and conversations in which, as an independent scientist, he can offer his own thoughts on the latest research and what it means for policy-makers. Edenhofer says that the negotiations are falling short of what is needed to address global warming and that scientists are unlikely to change that now. However, he argues it would be wrong to downplay the role of science in the process. Scientists were the first to raise concerns about climate change, and the IPCC's fourth assessment has served as the foundation for the negotiations. He sums up the IPCC's findings this way: humans cause climate change; climate change has severe impacts; and it is not too costly to reduce emissions. "These three messages have already changed the mindset of the negotiators," he says. P. RICE/SUSTAINABILITY INST. "We have this philosophy that if science is going to be helpful, it has to show up, wanting to serve. What can we do to our model to make it more useful to somebody who is incredibly busy, overwhelmed, with not enough time and a huge responsibility?" The Sustainability Institute has developed user-friendly climate-modelling software that can be run on a laptop computer to help negotiators assess the ultimate impact of any given emissions scenario. Negotiators can manually adjust the emissions and other parameters to analyse their own proposals as well as those of other countries; the model spits out forecasts for variables such as future temperatures and sea-level rise. In Copenhagen, Sawin says, the team is providing a "widget" that can be installed on computers to get the latest climate readings whenever Sawin's group updates its model with any new commitments announced by countries. The application has generally received positive feedback from negotiators, but Sawin acknowledges the sobering reality that some delegates are less interested in detailed climate projections than in the next election in their home country. Nonetheless, she finds the whole affair touching. "I see that there are warts, and there is unfairness, and there are flaws in this process, but at least it's happening," she says. "So when I come home and talk to my kids, that's what I emphasize: that we happen to be alive at a time when people are trying to make common decisions about how to protect our common planet." M. BASCOMBE "I never had the slightest notion in my mind that one day I would be the guy telling everybody that the [target of] 2 °C the majority of the world wants is absolutely crazy. 2 °C is too much for too many people." Raised in the mountains of Jamaica, Binger did a brief stint as a chemical engineer in the petroleum industry before earning a doctorate in agronomy at the University of Georgia. Today he is an official delegate advising island nations that are seeking to limit average global warming to 1.5 °C — or preferably less. Regularly oscillating between anger and a healthy island humour, he says. "Everybody needs to clean up their own goddamn mess." Although Binger has full access to the talks, he leaves negotiating to the negotiators. His job is to harness scientific evidence in the push for more stringent greenhouse-gas targets. In practice, this means helping to answer questions that arise during the talks and providing scientific evidence for use in speeches and debates. As an islander who stands to lose everything to ocean acidification and sea-level rise, Binger takes the issue personally. "We want 1.5 °C or less, and we don't really ask it selfishly. Every person on this planet is better off at 1.5 °C than they are at 2 °C. I can sleep very easily with that." C. CALVIN/UCAR "To a certain degree, the physical modellers have a much easier job than these politicians. Our molecules don't think for themselves and start doing different things midstream." At COP 14 in Poland in 2008, Buja gave a briefing on NCAR's climate-modelling results for the fourth assessment of the IPCC, issued in 2007. He headed the modelling team at the time but is now directing a new group that is developing integrated climate models that include social and economic forces. His career change reflects a larger shift — Buja goes so far as to call it a "sea change" — for NCAR as an institution. Physical modelling will remain a core activity as scientists seek to clarify and provide more detail about the potential impacts of greenhouse gases, he says, but NCAR recognizes that it needs to provide policy-makers with more information about potential solutions. In Copenhagen, one of his colleagues is presenting modelling results analysing the level and timing of emission-reduction targets, focusing on the 2050–2100 time frame. Buja is on hand to talk about these issues as well as to answer questions about the physical modelling, which is now being ramped up for the IPCC's fifth assessment, due out in 2014. But information flows both ways at these meetings, he says. "What this exposes the scientists to is how these negotiations and agreements are developed and what our role in informing them might be." "For individual scientists like me, frankly, many would say there's not much point in going. But I think it's a chance to meet those at the fringes of the political system who potentially do have quite a lot of leverage." Were you to bump into him in Copenhagen and ask how the negotiations are going, Parry says he wouldn't have a clue. He has minimal or no contact with negotiators but says he finds value in exchanging ideas with scientists and activists. Those discussions can be particularly important, Parry says, because advocacy groups such as the WWF can then inject the latest scientific thinking into the political process as they lobby negotiators and government officials. In Copenhagen, he is expecting to participate in two side events, one on development issues and a second on agriculture. Parry is also thinking about how to assess a major hole in how the world intends to respond to climate change. Some impacts can be avoided by reducing greenhouse-gas emissions. Others can be managed with enough money; in the vulnerable developing world, that means financial aid from wealthier nations. But the current proposals for emissions cuts and monetary support are not enough to avoid major impacts. "We're trying to close a gap here, coming at it from both ends," he says. Parry hopes that framing the issue this way — and quantifying the impacts — in Copenhagen will clarify where the policy-makers are coming up short, both in terms of emissions reductions and money for adaptation. C. AZEVEDO-RAMOS "I believe that [the forest-protection strategy called] REDD could make a difference in COP 15, not just as a way to address emissions from tropical deforestation, but also to create a new kind of synergy among nations. I believe that. That's exactly why I am going." Moutinho started his career studying ants but has spent most of his time in recent years looking at ways to use carbon markets to stem emissions from deforestation while protecting biodiversity and the rights of indigenous people. Hopes have faded for a complete treaty in Copenhagen, but he is holding out for a significant decision on the forest-carbon component known as Reducing Emissions from Deforestation and Forest Degradation (REDD). Through REDD, wealthier nations seeking to 'reduce' their emissions would provide money for developing nations to protect their forests. In Copenhagen, Moutinho is presenting his organization's latest work on REDD in the Amazon and discussing Brazil's national greenhouse-gas commitments. ADVERTISEMENT For him, Copenhagen is a perfect fit. Spending time in the field and publishing papers in Nature or Science is one thing, he says, but the goal must be to translate results into a digestible form for policy-makers. "Science is a tool to reach sustainable development. That's my view about science, and that's exactly what I'm doing." And when it comes to REDD, Moutinho says, the science is evolving rapidly and still plays an important part in the negotiations.
  • Emerging disease: Looking for trouble
    - Nature 462(7274):717 (2009)
    Every day, more than 100 patients line up for treatment outside the bare cement walls of a rural health clinic in the Niete forest of southern Cameroon. Most of them suffer from what virologist Nathan Wolfe calls "the usual suspects": malaria and typhoid. There are currently no comments.
  • Emissions: Canada should not be isolating itself
    - Nature 462(7274):720 (2009)
    It should be possible to draw up a fair, ambitious and legally binding treaty on climate change after this week's United Nations summit in Copenhagen (see http://go.nature.com/sRCuKV
  • Emissions: taking a collaborative lead will work better
    - Nature 462(7274):720 (2009)
    The developing world is urging rich countries to take the lead in tackling climate change, as Jiahua Pan points out in his Opinion article (Nature 461, 1055; 2009). However, in doing so, they should not overlook opportunities for technological collaboration as a means to work towards achieving a global low-carbon economy.
  • Need for religions to promote values of conservation
    - Nature 462(7274):720 (2009)
    Boris Hillmann and Jan Barkmann suggest in their Correspondence that the world's religions could make a positive contribution to biodiversity conservation (Nature 461, 37; 2009).
  • Time to future-proof plants in storage
    - Nature 462(7274):721 (2009)
    Seed banks must collect and condition their holdings of wild species so that they can thrive in landscapes transformed by climate change, say Jeffrey Walck and Kingsley Dixon.
  • A guide to the day of big data
    - Nature 462(7274):722 (2009)
    Michael Nielsen enjoys a rich and stimulating collection of essays on the way in which massive computing power is changing science, from astronomy to zoology.
  • How to get your message across
    - Nature 462(7274):723 (2009)
    The gulf between science and the rest of the world seems to be widening. If you think that keeping your head down, doing your research and not attempting to bridge that gap is enough, two books might convince you that science needs your voice — now.
  • Third physics opera for Philip Glass
    - Nature 462(7274):724 (2009)
    As a baritone in the role of astronomer Johannes Kepler sings of his thought processes when discovering that the orbits of planets are ellipses rather than egg-shaped, Philip Glass's music becomes almost lyrical. The renowned minimalist composer uses a rather tuneful set of pieces for the hybrid of science and the arts that is his latest opera, Kepler.
  • In Retrospect: Kepler's Astronomia Nova
    - Nature 462(7274):725 (2009)
    Jack J. Lissauer explains how the great astronomer's insight into planetary orbits is still revealing new views of the Universe four centuries on — from extrasolar Earths to black holes.
  • Developmental biology: Asymmetry with a twist
    - Nature 462(7274):727 (2009)
    In snails, manipulating the orientation of cells in the early embryo alters the left–right asymmetry of the shell and body. These findings refine the search for the symmetry-breaking event in this and other animals.
  • Gamma-ray bursts: Magnetism in a cosmic blast
    - Nature 462(7274):728 (2009)
    Astronomers know little about γ-ray bursts other than that they are the most energetic explosions in the Universe. The latest observations indicate that large-scale magnetism contributes to their power.
  • 50 & 100 years ago
    - Nature 462(7274):729 (2009)
    Wisdom of the West. By Bertrand Russell — This is Lord Russell's second brilliant venture into a comprehensive history of Western (mainly philosophical) thought ... Of course, despite the brilliance and apparent novelty of presentation, it should be realized that on the whole this is old wine poured into new bottles ... There are still the rough and ready divisions into the Continental rationalists (who are rather wicked) and the more virtuous British empiricists, supported arbitrarily by the quite unproved suggestion that the diagrams representing these two types of philosophical systems are, respectively, a pyramid standing on its head, as against the other, standing on its feet ... But these are minor criticisms.
  • Neuroscience: Excitatory view of a receptor
    - Nature 462(7274):729 (2009)
    Ion channels opened by glutamate mediate fast cell-to-cell information transfer in the nervous system. The structure of a full-length tetrameric glutamate receptor is both confirmatory and revelatory.
  • Earth science: The enigma of D′′
    - Nature 462(7274):731 (2009)
    A phase transition of Earth's most abundant mineral occurs at pressures and temperatures corresponding to those thought to exist just above Earth's core. New experiments shed light on this enigmatic D′′ region.
  • Immunology: Dendritic-cell genealogy
    - Nature 462(7274):732 (2009)
    The differing origins of gut dendritic cells — white blood cells that modulate immune responses — may explain how the intestinal immune system manages to destroy harmful pathogens while tolerating beneficial bacteria.
  • Structural biology: Molecular coin slots for urea
    - Nature 462(7274):733 (2009)
    Membrane-bound protein channels that allow only urea to pass through are vital to the kidney's ability to conserve water. Crystal structures show that the channels select urea molecules by passing them through thin slots.
  • Obituary: Qian Xuesen (1911–2009)
    - Nature 462(7274):735 (2009)
    Founder of China's missile and space programme.
  • Systems chemistry: Molecular networks come of age
    - Nature 462(7274):736 (2009)
    The advent of sophisticated analytical tools enables the collective behaviour of networks of interacting molecules to be studied. The emerging field of systems chemistry promises to allow such networks to be designed to perform complex functions, and might even shed light on the origins of life.
  • Evidence for escape from adaptive conflict?
    - Nature 462(7274):E1 (2009)
    Arising from: D. L. Des Marais & M. D. Rausher Nature 454, 762–765 (2008); Des Marais & Rausher reply Gene duplication is the primary source of new genes1, but the molecular evolutionary mechanisms underlying functional divergence of duplicate genes are not well understood2. Des Marais and Rausher3 argued that data from plant dihydroflavonol-4-reductase (DFR) genes support the model that gene duplication allows the escape from adaptive conflict (EAC) among several functions of a single-copy progenitor gene4. As the authors indicated, the key predictions of EAC, in comparison to other models1, 5, 6, are that (i) adaptive changes occur in both daughter genes after duplication, and (ii) these adaptive changes must improve ancestral functions. Furthermore, EAC indicates that (iii) the improvement of several ancestral functions is constrained before duplication, although this last point was not explicitly stated. Here we show that contrary to the predictions of EAC, only one of the duplicated DFR lineages exhibited adaptive sequence changes. Owing to the lack of information on en! zyme concentrations3 we question the accuracy of enzyme activity comparisons, and it is thus not clear that any ancestral function has been improved in either lineage.
  • Des Marais & Rausher reply
    - Nature 462(7274):E2 (2009)
    Replying to: T. Barkman & J. Zhang Nature 462, 10.1038/nature08663 (2009) Barkman and Zhang1 level two criticisms at our report of escape from adaptive conflict (EAC)2. The first criticism is that our evidence of repeated adaptive substitution in the DFR-A/C lineage is consistent with either EAC or neofunctionalization in that lineage. As indicated in our original report2, we do not disagree with this claim, but believe it misses the point that the hallmark of EAC is the adaptive improvement of function in both duplicate lineages. The repeated positive selection in the DFR-A/C lineage simply demonstrates improvement of some as yet unspecified function in that lineage.
  • Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
    Dang L White DW Gross S Bennett BD Bittinger MA Driggers EM Fantin VR Jang HG Jin S Keenan MC Marks KM Prins RM Ward PS Yen KE Liau LM Rabinowitz JD Cantley LC Thompson CB Vander Heiden MG Su SM - Nature 462(7274):739 (2009)
    Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature of a major subset of primary human brain cancers. These mutations occur at a single amino acid residue of the IDH1 active site, resulting in loss of the enzyme's ability to catalyse conversion of isocitrate to α-ketoglutarate. However, only a single copy of the gene is mutated in tumours, raising the possibility that the mutations do not result in a simple loss of function. Here we show that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of α-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). Structural studies demonstrate that when arginine 132 is mutated to histidine, residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert α-ketoglutarate to 2HG. Excess accumulation of 2HG has been shown to lead! to an elevated risk of malignant brain tumours in patients with inborn errors of 2HG metabolism. Similarly, in human malignant gliomas harbouring IDH1 mutations, we find markedly elevated levels of 2HG. These data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.
  • X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor
    Sobolevsky AI Rosconi MP Gouaux E - Nature 462(7274):745 (2009)
    Ionotropic glutamate receptors mediate most excitatory neurotransmission in the central nervous system and function by opening a transmembrane ion channel upon binding of glutamate. Despite their crucial role in neurobiology, the architecture and atomic structure of an intact ionotropic glutamate receptor are unknown. Here we report the crystal structure of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-sensitive, homotetrameric, rat GluA2 receptor at 3.6 Å resolution in complex with a competitive antagonist. The receptor harbours an overall axis of two-fold symmetry with the extracellular domains organized as pairs of local dimers and with the ion channel domain exhibiting four-fold symmetry. A symmetry mismatch between the extracellular and ion channel domains is mediated by two pairs of conformationally distinct subunits, A/C and B/D. Therefore, the stereochemical manner in which the A/C subunits are coupled to the ion channel gate is different! from the B/D subunits. Guided by the GluA2 structure and site-directed cysteine mutagenesis, we suggest that GluN1 and GluN2A NMDA (N-methyl-d-aspartate) receptors have a similar architecture, with subunits arranged in a 1-2-1-2 pattern. We exploit the GluA2 structure to develop mechanisms of ion channel activation, desensitization and inhibition by non-competitive antagonists and pore blockers.
  • Crystal structure of a bacterial homologue of the kidney urea transporter
    Levin EJ Quick M Zhou M - Nature 462(7274):757 (2009)
    Urea is highly concentrated in the mammalian kidney to produce the osmotic gradient necessary for water re-absorption. Free diffusion of urea across cell membranes is slow owing to its high polarity, and specialized urea transporters have evolved to achieve rapid and selective urea permeation. Here we present the 2.3 Å structure of a functional urea transporter from the bacterium Desulfovibrio vulgaris. The transporter is a homotrimer, and each subunit contains a continuous membrane-spanning pore formed by the two homologous halves of the protein. The pore contains a constricted selectivity filter that can accommodate several dehydrated urea molecules in single file. Backbone and side-chain oxygen atoms provide continuous coordination of urea as it progresses through the filter, and well-placed α-helix dipoles provide further compensation for dehydration energy. These results establish that the urea transporter operates by a channel-like mechanism and reveal the ph! ysical and chemical basis of urea selectivity.
  • Encounter and extrusion of an intrahelical lesion by a DNA repair enzyme
    - Nature 462(7274):762 (2009)
    How living systems detect the presence of genotoxic damage embedded in a million-fold excess of undamaged DNA is an unresolved question in biology. Here we have captured and structurally elucidated a base-excision DNA repair enzyme, MutM, at the stage of initial encounter with a damaged nucleobase, 8-oxoguanine (oxoG), nested within a DNA duplex. Three structures of intrahelical oxoG-encounter complexes are compared with sequence-matched structures containing a normal G base in place of an oxoG lesion. Although the protein–DNA interfaces in the matched complexes differ by only two atoms—those that distinguish oxoG from G—their pronounced structural differences indicate that MutM can detect a lesion in DNA even at the earliest stages of encounter. All-atom computer simulations show the pathway by which encounter of the enzyme with the lesion causes extrusion from the DNA duplex, and they elucidate the critical free energy difference between oxoG and G along the ex! trusion pathway.
  • Ten per cent polarized optical emission from GRB 090102
    - Nature 462(7274):767 (2009)
    The nature of the jets and the role of magnetic fields in gamma-ray bursts (GRBs) remains unclear1, 2. In a baryon-dominated jet only weak, tangled fields generated in situ through shocks would be present3. In an alternative model, jets are threaded with large-scale magnetic fields that originate at the central engine and that accelerate and collimate the material4. To distinguish between the models the degree of polarization in early-time emission must be measured; however, previous claims of gamma-ray polarization have been controversial5, 6, 7, 8. Here we report that the early optical emission from GRB 090102 was polarized at 10 ± 1 per cent, indicating the presence of large-scale fields originating in the expanding fireball. If the degree of polarization and its position angle were variable on timescales shorter than our 60-second exposure, then the peak polarization may have been larger than ten per cent.
  • A connection between star formation activity and cosmic rays in the starburst galaxy M82
    The VERITAS Collaboration Acciari VA Aliu E Arlen T Aune T Bautista M Beilicke M Benbow W Boltuch D Bradbury SM Buckley JH Bugaev V Byrum K Cannon A Celik O Cesarini A Chow YC Ciupik L Cogan P Colin P Cui W Dickherber R Duke C Fegan SJ Finley JP Finnegan G Fortin P Fortson L Furniss A Galante N Gall D Gibbs K Gillanders GH Godambe S Grube J Guenette R Gyuk G Hanna D Holder J Horan D Hui CM Humensky TB Imran A Kaaret P Karlsson N Kertzman M Kieda D Kildea J Konopelko A Krawczynski H Krennrich F Lang MJ Lebohec S Maier G McArthur S McCann A McCutcheon M Millis J Moriarty P Mukherjee R Nagai T Ong RA Otte AN Pandel D Perkins JS Pizlo F Pohl M Quinn J Ragan K Reyes LC Reynolds PT Roache E Rose HJ Schroedter M Sembroski GH Smith AW Steele D Swordy SP Theiling M Thibadeau S Varlotta A Vassiliev VV Vincent S Wagner RG Wakely SP Ward JE Weekes TC Weinstein A Weisgarber T Williams DA Wissel S Wood M Zitzer B - Nature 462(7274):770 (2009)
    Although Galactic cosmic rays (protons and nuclei) are widely believed to be mainly accelerated by the winds and supernovae of massive stars, definitive evidence of this origin remains elusive nearly a century after their discovery1. The active regions of starburst galaxies have exceptionally high rates of star formation, and their large size—more than 50 times the diameter of similar Galactic regions—uniquely enables reliable calorimetric measurements of their potentially high cosmic-ray density2. The cosmic rays produced in the formation, life and death of massive stars in these regions are expected to produce diffuse γ-ray emission through interactions with interstellar gas and radiation. M82, the prototype small starburst galaxy, is predicted3, 4 to be the brightest starburst galaxy in terms of γ-ray emission. Here we report the detection of >700-GeV γ-rays from M82. From these data we determine a cosmic-ray density of 250 eV cm-3 in the starburst core, ! which is about 500 times the average Galactic density. This links cosmic-ray acceleration to star formation activity, and suggests that supernovae and massive-star winds are the dominant accelerators.
  • Disordered, quasicrystalline and crystalline phases of densely packed tetrahedra
    - Nature 462(7274):773 (2009)
    All hard, convex shapes are conjectured by Ulam to pack more densely than spheres1, which have a maximum packing fraction of φ = π/√18 ≈ 0.7405. Simple lattice packings of many shapes easily surpass this packing fraction2, 3. For regular tetrahedra, this conjecture was shown to be true only very recently; an ordered arrangement was obtained via geometric construction with φ = 0.7786 (ref. 4), which was subsequently compressed numerically to φ = 0.7820 (ref. 5), while compressing with different initial conditions led to φ = 0.8230 (ref. 6). Here we show that tetrahedra pack even more densely, and in a completely unexpected way. Following a conceptually different approach, using thermodynamic computer simulations that allow the system to evolve naturally towards high-density states, we observe that a fluid of hard tetrahedra undergoes a first-order phase transition to a dodecagonal quasicrystal7, 8, 9, 10, which can be compressed to a packing fraction of φ ! = 0.8324. By compressing a crystalline approximant of the quasicrystal, the highest packing fraction we obtain is φ = 0.8503. If quasicrystal formation is suppressed, the system remains disordered, jams and compresses to φ = 0.7858. Jamming and crystallization are both preceded by an entropy-driven transition from a simple fluid of independent tetrahedra to a complex fluid characterized by tetrahedra arranged in densely packed local motifs of pentagonal dipyramids that form a percolating network at the transition. The quasicrystal that we report represents the first example of a quasicrystal formed from hard or non-spherical particles. Our results demonstrate that particle shape and entropy can produce highly complex, ordered structures.
  • Catastrophic flood of the Mediterranean after the Messinian salinity crisis
    - Nature 462(7274):778 (2009)
    The Mediterranean Sea became disconnected from the world's oceans and mostly desiccated by evaporation about 5.6 million years ago during the Messinian salinity crisis1, 2, 3. The Atlantic waters found a way through the present Gibraltar Strait and rapidly refilled the Mediterranean 5.33 million years ago in an event known as the Zanclean flood4. The nature, abruptness and evolution of this flood remain poorly constrained4, 5, 6. Borehole and seismic data show incisions over 250 m deep on both sides of the Gibraltar Strait that have previously been attributed to fluvial erosion during the desiccation4, 7. Here we show the continuity of this 200-km-long channel across the strait and explain its morphology as the result of erosion by the flooding waters, adopting an incision model validated in mountain rivers. This model in turn allows us to estimate the duration of the flood. Although the available data are limited, our findings suggest that the feedback between! water flow and incision in the early stages of flooding imply discharges of about 108 m3 s-1 (three orders of magnitude larger than the present Amazon River) and incision rates above 0.4 m per day. Although the flood started at low water discharges that may have lasted for up to several thousand years, our results suggest that 90 per cent of the water was transferred in a short period ranging from a few months to two years. This extremely abrupt flood may have involved peak rates of sea level rise in the Mediterranean of more than ten metres per day.
  • Thickness and Clapeyron slope of the post-perovskite boundary
    - Nature 462(7274):782 (2009)
    The thicknesses and Clapeyron slopes of mantle phase boundaries strongly influence the seismic detectability of the boundaries and convection in the mantle. The unusually large positive Clapeyron slope found for the boundary between perovskite (Pv) and post-perovskite (pPv)1, 2, 3 (the 'pPv boundary') would destabilize high-temperature anomalies in the lowermost mantle4, in disagreement with the seismic observations5. Here we report the thickness of the pPv boundary in (Mg0.91Fe2+0.09)SiO3 and (Mg0.9Fe3+0.1)(Al0.1Si0.9)O3 as determined in a laser-heated diamond-anvil cell under in situ high-pressure (up to 145 GPa), high-temperature (up to 3,000 K) conditions. The measured Clapeyron slope is consistent with the D′′ discontinuity6. In both systems, however, the pPv boundary thickness increases to 400–600 ± 100 km, which is substantially greater than the thickness of the D′′ discontinuity (<30 km)7. Although the Fe2+ buffering effect of ferrope! riclase8, 9, 10 could decrease the pPv boundary thickness, the boundary may remain thick in a pyrolitic composition because of the effects of Al and the rapid temperature increase in the D′′ layer. The pPv boundary would be particularly thick in regions with an elevated Al content and/or a low Mg/Si ratio, reducing the effects of the large positive Clapeyron slope on the buoyancy of thermal anomalies and stabilizing compositional heterogeneities in the lowermost mantle. If the pPv transition is the source of the D′′ discontinuity, regions with sharp discontinuities may require distinct compositions, such as a higher Mg/Si ratio or a lower Al content.
  • Reproductive skew and selection on female ornamentation in social species
    - Nature 462(7274):786 (2009)
    Male animals are typically more elaborately ornamented than females1. Classic sexual selection theory notes that because sperm are cheaper to produce than eggs2, and because males generally compete more intensely for reproductive opportunities and invest less in parental care than females3, males can obtain greater fitness benefits from mating multiply2, 4. Therefore, sexual selection typically results in male-biased sex differences in secondary sexual characters1, 4. This generality has recently been questioned, because in cooperatively breeding vertebrates, the strength of selection on traits used in intrasexual competition for access to mates (sexual selection1, 4) or other resources linked to reproduction (social selection5, 6) is similar in males and females7, 8. Because selection is acting with comparable intensity in both sexes in cooperatively breeding species, the degree of sexual dimorphism in traits used in intrasexual competition should be reduced in cooper! ative breeders6. Here we use the socially diverse African starlings (Sturnidae) to demonstrate that the degree of sexual dimorphism in plumage and body size is reduced in cooperatively breeding species as a result of increased selection on females for traits that increase access to reproductive opportunities, other resources, or higher social status. In cooperative breeders such as these, where there is unequal sharing of reproduction (reproductive skew) among females, and where female dominance rank influences access to mates and other resources, intrasexual competition among females may be intense7 and ultimately select for female trait elaboration9. Selection is thereby acting with different intensities on males and females in cooperatively versus non-cooperatively breeding species, and female–female interactions in group-living vertebrates will have important consequences for the evolution of female morphological, physiological and behavioural traits.
  • Chiral blastomere arrangement dictates zygotic left–right asymmetry pathway in snails
    Kuroda R Endo B Abe M Shimizu M - Nature 462(7274):790 (2009)
    Most animals display internal and/or external left–right asymmetry. Several mechanisms for left–right asymmetry determination have been proposed for vertebrates1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and invertebrates1, 2, 4, 9, 11, 12, 13, 14 but they are still not well characterized, particularly at the early developmental stage. The gastropods Lymnaeastagnalis and the closely related Lymnaea peregra have both the sinistral (recessive) and the dextral (dominant) snails within a species and the chirality is hereditary, determined by a single locus that functions maternally15, 16, 17, 18. Intriguingly, the handedness-determining gene(s) and the mechanisms are not yet identified. Here we show that in L. stagnalis, the chiral blastomere arrangement at the eight-cell stage (but not the two- or four-cell stage) determines the left–right asymmetry throughout the developmental programme, and acts upstream of the Nodal signalling pathway. Thus, we could demonstrate that mechanica! l micromanipulation of the third cleavage chirality (from the four- to the eight-cell stage) leads to reversal of embryonic handedness. These manipulated embryos grew to 'dextralized' sinistral and 'sinistralized' dextral snails—that is, normal healthy fertile organisms with all the usual left–right asymmetries reversed to that encoded by the mothers' genetic information. Moreover, manipulation reversed the embryonic nodal expression patterns. Using backcrossed F7 congenic animals, we could demonstrate a strong genetic linkage between the handedness-determining gene(s) and the chiral cytoskeletal dynamics at the third cleavage that promotes the dominant-type blastomere arrangement. These results establish the crucial importance of the maternally determined blastomere arrangement at the eight-cell stage in dictating zygotic signalling pathways in the organismal chiromorphogenesis. Similar chiral blastomere configuration mechanisms may also operate upstream of t! he Nodal pathway in left–right patterning of deuterostomes/v! ertebrates.
  • Ecoenzymatic stoichiometry of microbial organic nutrient acquisition in soil and sediment
    - Nature 462(7274):795 (2009)
    Biota can be described in terms of elemental composition, expressed as an atomic ratio of carbon:nitrogen:phosphorus (refs 1–3). The elemental stoichiometry of microoorganisms is fundamental for understanding the production dynamics and biogeochemical cycles of ecosystems because microbial biomass is the trophic base of detrital food webs4, 5, 6. Here we show that heterotrophic microbial communities of diverse composition from terrestrial soils and freshwater sediments share a common functional stoichiometry in relation to organic nutrient acquisition. The activities of four enzymes that catalyse the hydrolysis of assimilable products from the principal environmental sources of C, N and P show similar scaling relationships over several orders of magnitude, with a mean ratio for C:N:P activities near 1:1:1 in all habitats. We suggest that these ecoenzymatic ratios reflect the equilibria between the elemental composition of microbial biomass and detrital organic matter! and the efficiencies of microbial nutrient assimilation and growth. Because ecoenzymatic activities intersect the stoichiometric and metabolic theories of ecology7, 8, 9, they provide a functional measure of the threshold at which control of community metabolism shifts from nutrient to energy flow.
  • Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target
    - Nature 462(7274):799 (2009)
    Transcription in eukaryotic genomes generates an extensive array of non-protein-coding RNA, the functional significance of which is mostly unknown1. We are investigating the link between non-coding RNA and chromatin regulation through analysis of FLC — a regulator of flowering time in Arabidopsis and a target of several chromatin pathways. Here we use an unbiased strategy to characterize non-coding transcripts of FLC and show that sense/antisense transcript levels correlate in a range of mutants and treatments, but change independently in cold-treated plants. Prolonged cold epigenetically silences FLC in a Polycomb-mediated process called vernalization2. Our data indicate that upregulation of long non-coding antisense transcripts covering the entire FLC locus may be part of the cold-sensing mechanism. Induction of these antisense transcripts occurs earlier than, and is independent of, other vernalization markers3 and coincides with a reduction in sense transcript! ion. We show that addition of the FLC antisense promoter sequences to a reporter gene is sufficient to confer cold-induced silencing of the reporter. Our data indicate that cold-induced FLC antisense transcripts have an early role in the epigenetic silencing of FLC, acting to silence FLC transcription transiently. Recruitment of the Polycomb machinery then confers the epigenetic memory. Antisense transcription events originating from 3′ ends of genes might be a general mechanism to regulate the corresponding sense transcription in a condition/stage-dependent manner.
  • Long-range oncogenic activation of Igh–c-myc translocations by the Igh 3′ regulatory region
    - Nature 462(7274):803 (2009)
    B-cell malignancies, such as human Burkitt's lymphoma, often contain translocations that link c-myc or other proto-oncogenes to the immunoglobulin heavy chain locus (IgH, encoded by Igh)1. The nature of elements that activate oncogenes within such translocations has been a long-standing question. Translocations within Igh involve DNA double-strand breaks initiated either by the RAG1/2 endonuclease during variable, diversity and joining gene segment (V(D)J) recombination, or by activation-induced cytidine deaminase (AID, also known as AICDA) during class switch recombination (CSR)2, 3, 4. V(D)J recombination in progenitor B (pro-B) cells assembles Igh variable region exons upstream of μ constant region (Cμ) exons, which are the first of several sets of CH exons ('CH genes') within a CH locus that span several hundred kilobases (kb)5, 6. In mature B cells, CSR deletes Cμ and replaces it with a downstream CH gene6. An intronic enhancer (iEμ) between the variable! region exons and Cμ promotes V(D)J recombination in developing B cells7. Furthermore, the Igh 3′ regulatory region (Igh3′RR) lies downstream of the CH locus and modulates CSR by long-range transcriptional enhancement of CH genes8, 9, 10. Transgenic mice bearing iEμ or Igh3′RR sequences fused to c-myc are predisposed to B lymphomas, demonstrating that such elements can confer oncogenic c-myc expression11, 12, 13, 14, 15, 16. However, in many B-cell lymphomas, Igh–c-myc translocations delete iEμ and place c-myc up to 200 kb upstream of the Igh3′RR1. Here we address the oncogenic role of the Igh3′RR by inactivating it in two distinct mouse models for B-cell lymphoma with Igh–c-myc translocations. We show that the Igh3′RR is dispensable for pro-B-cell lymphomas with V(D)J recombination-initiated translocations, but is required for peripheral B-cell lymphomas with CSR-associated translocations. As the Igh3′RR is not required for CSR-associated Igh breaks ! or Igh–c-myc translocations in peripheral B-cell lymphoma pr! ogenitors, we conclude that this regulatory region confers oncogenic activity by long-range and developmental stage-specific activation of translocated c-myc genes.
  • Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma
    - Nature 462(7274):808 (2009)
    Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences1, 2, 3. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly1, 2. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps—free-standing, genome-encoded editing proteins that clear Ser-tRNAAla. The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the α-amino group of the bound amino ! acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.
  • In the recovery room
    - Nature 462(7274):818 (2009)
    The advance of science.

No comments: