Hot off the presses! Jul 16 Nature

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Latest Articles Include:

• Net gains
  - Nature 460(7253):307 (2009)
  The Moon landing was not the only world-changing event in the summer of '69.
• Nowhere to hide
  - Nature 460(7253):307 (2009)
  The G8 has laid down a marker by promising to restrict the rise of global temperatures.
• Animal behaviour: Smothered by a swarm
  - Nature 460(7253):308 (2009)
  
• Palaeoclimatology: Tropical ice
  - Nature 460(7253):308 (2009)
  
• Nanotechnology: Penned in protein
  - Nature 460(7253):308 (2009)
  
• Chemical biology: A glowing report
  - Nature 460(7253):308 (2009)
  
• Evolution: Nice guys finish last
  - Nature 460(7253):308 (2009)
  
• Organic chemistry: Cockroach cruncher
  - Nature 460(7253):309 (2009)
  
• Immunology: Themis in the thymus
  - Nature 460(7253):309 (2009)
  
• Developmental biology: The turtle fold
  - Nature 460(7253):309 (2009)
  
• Neurology: New neurons show the way
  - Nature 460(7253):309 (2009)
  
• Journal club
  - Nature 460(7253):309 (2009)
  
• NIH nominee draws scrutiny
  - Nature 460(7253):310-311 (2009)
  As Francis Collins prepares to take the helm of the US National Institutes of Health (NIH), opinions are divided about how the geneticist will steer the agency through its extraordinary funding boom. Following President Barack Obama's long-anticipated nomination of Collins on 8 July, Harold Varmus, NIH director from 1993 to 1999, and now president and chief executive of the Memorial Sloan-Kettering Cancer Center in New York, described him as "a terrific scientist, inspirational leader, superb manager, and adept politician.
• Malaria drug-makers ignore WHO ban
  - Nature 460(7253):310-311 (2009)
  Health agency calls for clampdown on artemisinin monotherapy. There is a growing risk that malaria parasites will develop resistance to artemisinin because almost half of both its manufacturers and malaria-affected countries are failing to comply with World Health Organization (WHO) demands to sell it only in combination with other drugs. Artemisinin and its derivatives are the leading treatments for the disease, being the only antimalarials that have not yet seen widespread resistance in malaria parasites. The full scale of the problem is revealed in a soon-to-be-published WHO briefing seen by Nature, "Stop the marketing of oral artemisinin monotherapies", which calls for governments to empower national drug-regulatory authorities to clamp down on offending companies. Treatments that use only artemisinin need to be taken for seven days to kill all parasites, but patients often stop treatment after a few days when they begin to feel much better. This leaves the remaining parasites in contact with low levels of the drug — a recipe for resistance. The WHO recommended in January 2006 that artemisinin should always be given in combination with other drugs for at least three days, because a cocktail reduces the chances of resistance. The need to move away from monotherapies has become all the more urgent with recent reports of resistance arising in Cambodia. Although artemisinin-based combination therapies (ACTs) have become the treatment of choice for malaria, with a three-day programme curing more than 95% of patients, monotherapies are cheaper to produce and sell. ADVERTISEMENT Of the 69 manufacturers of artemisinin monotherapies that the WHO has identified, 21 have withdrawn monotherapies, and 14 say they intend to comply with the WHO's recommendations. But the remaining 34 have not yet disclosed their intentions. Many have not even replied to multiple WHO e-mail and fax requests for information, says Andrea Bosman, an official at the WHO's Global Malaria Programme (see http://tinyurl.com/m4gqmn). Regulatory authorities in just 39 of the 76 countries using malaria drugs have so far complied or said they intend to comply with the WHO's recommendations (see http://tinyurl.com/m94wqk). National regulatory authorities could help by banning monotherapies, says Bosman, but many are weak, understaffed and lack expertise. "It's terrible," says Bosman, adding that every country where malaria is endemic is affected by the problem. "Who says there is no profit to be made in malaria? When you see the number of companies operating in Africa, and the diversity of products, you'd just be amazed." Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Flu furore hits Argentina
  - Nature 460(7253):311 (2009)
  Refusal to declare national emergency restricts pandemic measures. Argentines have been travelling abroad to buy flu drugs.E. Marcarian/Reuters Argentina's government has for more than two weeks ignored recommendations from a committee of influenza experts to declare a national health emergency. Such a declaration would prompt greater federal resources to combat the spread of the pandemic H1N1 2009 virus. The committee, specifically set up to advise the Ministry of Health on swine flu, issued its call just days before Argentina's national election on 28 June, which it feared could accelerate the spread of the virus. Following the committee's call for action, the health minister, Graciela Ocaña, asked for the election to be postponed, but her request was rejected. Ocaña subsequently resigned and left office on 29 June. Mirta Roses, director of the Pan American Health Organization — the Latin American and Caribbean arm of the World Health Organization (WHO) — has also criticized the decision to go ahead with the elections. "The delay was recommended because the agglomeration of people in places with little ventilation favours the transmission of the disease," says Jorge San Juan, coordinator of the expert committee and head of the intensive-care unit at Muñiz Hospital in Buenos Aires. The government now faces two lawsuits brought by individual lawyers who claim that its decision not to delay the elections recklessly endangered its citizens, who are legally required to vote. Epidemiologist Emilio Santabaya, former head of the Malbrán Institute in Buenos Aires — the country's main flu monitoring centre — adds that Argentina knew an epidemic was coming and did nothing, and that flu monitoring in the country is not adequate to track the spread of the virus. The situation contrasts with that of neighbouring country Chile, which has many more flu surveillance centres, according to Jorge Jimenez, who has worked both as Chile's health minister and as chairman of the WHO's executive committee. On 7 July, Chilean President Michelle Bachelet, who trained as an epidemiologist, signed a decree that gives health authorities in the country the power to cancel events that could spread swine flu. Meanwhile, a group of doctors, hospital workers and scientists called Médicos Sin Banderas (Doctors without Flags) has also accused the national government of deliberately hiding the full extent of the swine-flu outbreak. ADVERTISEMENT Ariel Umpierrez, a health economist who heads the group, says that its members have been sharing information about flu cases from their places of work across the country. Those data show that the government has lowered the official number of cases by excluding infected people who visit private clinics, he argues. Argentina's Ministry of Health has not responded to Nature's queries on the matter. Although scientists inside the country say they are being ignored, those outside are worried by reports of panicked Argentines travelling to Chile and Uruguay to buy flu drugs. The drugs, which are being taken without medical advice, are probably being used in a way that promotes the development of resistance, says Eric Toner, a senior associate at the University of Pittsburgh's Center for Biosecurity in Pennsylvania. Because Uruguay is heavily dependent on trade with Argentina, it is highly unlikely to prevent Argentines from entering the country — but the governments of Brazil and Bolivia are considering closing their borders to prevent the spread of infection. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Medical isotope shortage reaches crisis level
  - Nature 460(7253):312-313 (2009)
  The worldwide shortage of medical isotopes is about to get much worse this week, as the High Flux Reactor in Petten, the Netherlands, closes for a month-long maintenance inspection. It joins the National Research Universal reactor in Chalk River, Ontario, Canada, which has been closed since 15 May because of a heavy-water leak and is unlikely to restart before late 2009, according to Atomic Energy of Canada Limited, the government-sponsored body that runs the facility.
• G8 climate target questioned
  - Nature 460(7253):313 (2009)
  The path to a meaningful deal at the Copenhagen climate summit in December seems more treacherous in the wake of last week's meeting of the G8 nations. Leaders gathered in the quake-struck Italian town of L'Aquila promised to try to prevent global temperatures from rising more than 2 °C above pre-industrial temperatures.
• Shooting for the Moon
  - Nature 460(7253):314-315 (2009)
  The Apollo programme inspired thousands of people to pursue careers in science. Today, they still support human spacefaring — but baulk at the price. Richard Monastersky reports on the results of a Nature poll. In the heady days after the Apollo 11 lunar landing on 20 July 1969, countless children travelled to the Moon by cupping their hands over their mouths and announcing: "Houston, Tranquility Base, here. The Eagle has landed." With giant strides, they bounded across the landscape just like their heroes, Neil Armstrong and Buzz Aldrin. They practised lift-off by counting backwards to zero and blasting themselves skywards. And many of them landed, decades later, in scientific careers. Humans have not walked on the Moon since the Apollo 17 mission of 1972.NASA In fact, the Moon landings deserve credit for motivating a large fraction of today's scientists, according to a survey of almost 800 researchers who have published in Nature in the past three years1. Half of the researchers who responded to an online poll last month said that the Apollo missions had inspired them to pursue science — and not just in astronomy or planetary science (see 'Survey respondents'). "I became completely space crazy," said one life scientist. "I was certain I'd be an astronaut. My interest shifted to biology, but I still believe Apollo 11 was a major influence on me." The survey, intended to capture broad impressions rather than to precisely measure attitudes, also reveals surprisingly widespread support among scientists for human space exploration. Nearly 80% of scientists polled said that there are scientific research justifications for continuing human spaceflight. More than 80% felt that the life sciences, physical sciences, engineering and human physiology all benefited to some degree from human spaceflight, and almost 90% said that it still inspires younger generations to study science (see 'Survey results'). Their impressions are not without justification. The US National Research Council concluded in 2003 that work in microgravity has had a major effect on several areas of physical sciences, including research into fluids, combustion and crystal growth2. The Neurolab experiments, which flew on NASA's space shuttle Columbia in 1998, are regarded as the high point of life-sciences research in space and resulted in 100 publications, according to Joan Vernikos, former director of life sciences at NASA. Up, up and away In principle, the scientists who participated in the poll seemed to support manned space programmes, with 62% of Americans and 83% of Europeans rating their own country's expenditures on human spaceflight as "about right" or "not enough". The stronger support in Europe perhaps reflects a vast difference in spending on either side of the Atlantic. Including money provided by the stimulus package, NASA will pour US$9.7 billion into activities related to human spaceflight in the current fiscal year, roughly half of the agency's $18.7-billion budget. The European Space Agency (ESA) allocates only €481 million ($670 million), about 13% of its €3.6-billion ($5.0 billion) budget. But support for sending people to space flagged when participants were asked to prioritize spending. Nearly 80% would welcome a shift in spending from human spaceflight to unmanned space missions, whereas 70% would prefer some of that cash to be spent on other areas of scientific research. David Southwood, director of science and robotic missions for ESA, says that the affection for shifting money rests on a false premise, because money taken from human spaceflight would not go to unmanned projects. Indeed, written responses from several of those who completed the survey revealed the opposite sentiment: some supported human spaceflight thinking it would increase spending generally on space research. Southwood says that the positive attitudes seen in the Nature poll reflect the broad impact of human spaceflight, beyond simply yielding data for science. "It gives humans a vicarious means of breaking the surly bonds of gravity," he says, borrowing a phrase from the pilot–poet John Gillespie Magee. During the lead-up to the Apollo missions, scientists had similar outlooks to those seen in the current survey. A study conducted by the American Association for the Advancement of Science in 1964 found that scientists generally supported the goal of landing humans on the Moon, but they objected to the tight timetable and the extreme costs3. At the time, the NASA budget consumed 4.3% of the total US budget; it now accounts for just 0.5%. Scientists in the public eye have generally been more sceptical about human spaceflight than those in Nature's poll, says John Logsdon, an aerospace historian at the Smithsonian Institution in Washington DC. "There have been very few scientists publicly giving this kind of support for human spaceflight," he says. ADVERTISEMENT With some scientists, the support for spaceflight was quite personal (see 'Moondreams'). About 5% have applied to be an astronaut and 14% said they would pay between $10,000 and $50,000 for a brief sub-orbital trip into space. It remains to be seen whether NASA's space programme will continue to earn their enthusiasm. Next month, a panel convened by US President Barack Obama will issue its assessment of America's plans to return to the Moon by 2020 (ref. 4), and its approval of the programme is far from certain. Yet more than 36 years after man last ventured beyond the confines of low-Earth orbit during the Apollo 17 mission, Nature's survey would suggest that many will support the next grand voyage to the Moon and beyond. * References * http://www.nature.com/nature/newspdf/apollo_results.pdf * Assessment of Directions in Microgravity and Physical Sciences Research at NASA (National Academies Press, 2003). * Abelson, P. H. Science 145, 539 (1964). * Hand, E. Nature 459, 1038-1039 (2009). Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Arms pact could boost US-Russian science
  - Nature 460(7253):316 (2009)
  Nuclear scientists in Russia and the United States say that the sputtering relationship between their weapons laboratories could be rekindled by an agreement to cut the nations' nuclear-weapons arsenals. US President Barack Obama and Russian President Dmitry Medvedev announced on 6 July that they intended to reduce their stockpile of warheads.
• Europe attacks tactics that delay generic drugs
  - Nature 460(7253):317 (2009)
  
• Obama names next head of US Geological Survey
  - Nature 460(7253):317 (2009)
  
• El Niño arrives in the Pacific Ocean
  - Nature 460(7253):317 (2009)
  US climate scientists last week announced the arrival of El Niño, a cyclical rise in sea-surface temperatures in the central and eastern Pacific Ocean. The event is known to influence fisheries and global weather patterns. El Niños, which are associated with a weakening in the easterly trade wind, occur every two to five years and typically last for about a year. The current one is expected to continue developing over the next several months and to last through the winter, according to the National Oceanic and Atmospheric Administration in Washington DC. Previous El Niños have seen more rainfall over the central tropical Pacific, drought in Indonesia and powerful winter storms in California as well as flooding and mudslides in Central and South America. The phenomenon has also been linked to less hurricane activity in the Atlantic Ocean and additional winter precipitation in the arid southwestern United States. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• German molecular biologist to head EMBO
  - Nature 460(7253):317 (2009)
  
• US renewable energy gets cash boost
  - Nature 460(7253):317 (2009)
  
• Mars Science Laboratory devours budgets
  - Nature 460(7253):317 (2009)
  NASA/JPL-CALTECH A further budget overrun for NASA's Mars Science Laboratory rover (pictured), due to launch in 2011, could for the first time delay other missions in the agency's cash-strapped planetary-science division. In a report due to be handed to Congress by the end of July, NASA will announce that the mission needs between $15 million and $115 million more than its estimated price tag — which, at $2.28 billion, is already 40% above an official $1.63-billion estimate made in 2006. The agency has so far raided technology-development funds within the Mars programme, but if additional costs rise too much, it may have to delay two planned Moon missions. "The time for some tough decisions is here," said NASA science chief Ed Weiler, breaking the news to planetary scientists at an advisory-committee meeting on 9 July at NASA headquarters in Washington DC. Weiler also confirmed, as expected, that NASA would work in partnership with the European Space Agency on all future major Mars missions. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Correction
  - Nature 460(7253):317 (2009)
  The News Feature 'One gene, twenty years' (Nature 460, 164–169; 2009) incorrectly stated Robert Beall's current title. He is, in fact, president and chief executive of the Cystic Fibrosis Foundation. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Cell biology: Ahead of the curve
  - Nature 460(7253):318-320 (2009)
  To view the innards of a cell is to view architecture reminiscent of Antoni Gaudi: the gentle arc of the cell membrane, the contortions of internal tubing, the tight bubbles of vesicles. But for biologists, this architecture is an intellectual puzzle as well as a beautiful structure.
• Earth science: A lakeful of trouble
  - Nature 460(7253):321-323 (2009)
  Africa's Lake Kivu contains vast quantities of gas, which makes it both dangerous and valuable. Anjali Nayar asks whether it is possible to tap the gas without causing a disaster. Download a PDF of this story In late 2001, Mount Nyiragongo in the Democratic Republic of the Congo (DRC) was growing restless. Plumes of smoke issued from the central crater, alarming volcanologists in the nearby city of Goma. Then, on 17 January 2002, lava fountained from a fracture on Nyiragongo's southern flank. The molten rock snaked down the sides of the volcano and razed the centre of Goma, engulfing houses and setting off a string of explosions at fuel stations and power plants. That evening, the lava streamed into nearby Lake Kivu, generating a plume of water vapour that clouded the area for days1. More than 100 people were killed and nearly 300,000 people fled their homes. The only obvious refuge for the displaced people was along the shores of the lake. But Kivu poses its own threats. Beneath its placid surface, the lake contains 300 cubic kilometres of carbon dioxide and 60 cubic kilometres of methane. A disruption to the lake — such as a bigger, closer eruption — could cause a gas burst, with potentially deadly consequences for the roughly 2 million people who live along Kivu's shores. The risks are hard to quantify, however. Although scientists have studied the lake for decades, basic details about Kivu and its gases are still relatively scarce, and there is now debate about how hazardous the situation is. The issue is complicated by the lake's economic potential. The valuable methane dissolved in the water has started a feeding frenzy among energy companies working with the DRC and Rwanda, the other nation bordering the lake. In deals worth hundreds of millions of dollars, companies have started to siphon off the methane, in some cases working with the very scientists who have been assessing the lake's hazards. Proponents say that those degassing efforts will reduce the risk of gas eruption, but some researchers are worried that schemes to extract methane could make the situation more dangerous if they upset the lake's equilibrium. "It could be one of the great remediation projects of all time." George Kling "It could be one of the great remediation projects of all time: mitigating a lethal natural hazard and at the same time bringing power to people who desperately need it," says George Kling, a biogeochemist from the University of Michigan in Ann Arbor. "If it is done right." An expanding problem Lake Kivu lies in the Great Rift Valley, where tectonic forces are slowly ripping Africa apart. That movement brings up molten rock, which releases carbon dioxide that seeps into the bottom of Lake Kivu. Bacteria convert some of the carbon dioxide into methane, and other bacteria produce methane by breaking down organic matter in the deep waters (see graphic). Kivu is permanently stratified, with layers of dense salt-rich water below fresh water at the surface. Deeper than about 50–80 metres, the lake is anoxic and the concentrations of dissolved carbon dioxide and methane increase with depth2. The differences in density prevent the layers of water from vertically mixing, and so trap the gases at the bottom of the lake. Residents around the lake have known about the dissolved gases for many decades, but it wasn't generally thought to be a hazard. Then, in 1984, carbon dioxide erupted from Lake Monoun in Cameroon, killing 37 people. Two years later, another Cameroonian lake, Lake Nyos, spat up 0.3–1 cubic kilometres of carbon dioxide, asphyxiating more than 1,700 people. Kling was part of a team that visited Lake Nyos in the weeks following the eruption. "The animals were all dead, thousands of cattle just lying about," he says. Kling had been to Nyos the year before, but had only sampled surface waters. "We knew nothing about the gas bomb in the bottom of the lake," he says. It turned out that the deep waters of Lake Nyos were nearly saturated with carbon dioxide and, like in Lake Kivu, the gases were kept in solution by the pressure of the overlying water. Kling postulates that a landslide disturbed the lake's stratification, forcing gas-rich waters to move upwards3. That started a chain reaction. The reduction in pressure caused carbon dioxide to come out of solution and form bubbles, much like what happens when a bottle of champagne is uncorked. The rising bubbles dragged up the surrounding water, which also degassed, leading to a violent gas burst — a limnic eruption. Carbon dioxide is denser than air so, when it emerged, it hugged the ground, smothering everything as it spread up to 26 kilometres from the lake. The scale of the disaster compelled scientists to assess the risk at Kivu, the other lake known for its dissolved gases. Click to see a larger version. Latent threat There are no historic records of limnic eruptions in Lake Kivu. But gaps in layers of plankton fossils at the bottom of the lake suggest that such paroxysms have struck several times in the past 5,000 years4. If Kivu were to undergo a limnic eruption soon, it would dwarf the Nyos disaster. Kivu is more than 3,000 times larger and contains more than 350 times as much gas as was released by Lake Nyos. Kivu's shores are also densely populated. "Kivu is basically the nasty big brother of Nyos," says Kling. But there is no scientific consensus on the current risks of that kind of a disaster. "I'm not afraid of swimming in Lake Kivu." Martin Schmid Gas concentrations measured in 1974 and a limited study conducted in 2004 (ref. 5) show that there has been a 15–20% increase in methane and a 10% increase in carbon dioxide levels in the lake in the past 30 years, says Martin Schmid, a researcher at the Swiss Federal Institute of Aquatic Science and Technology in Kastanienbaum. If this trend continues, the lake will be saturated within the century and, like Lake Nyos, it could erupt with even the slightest disturbance. At the moment, however, the closest Kivu comes to gas overload is at a depth of 330 metres, where the water is 55% saturated — 10% with carbon dioxide and 45% with methane — says Schmid, so an eruption is less likely. (Methane contributes most of the gas pressure and the risk of eruption because it is less soluble than carbon dioxide.) According to modelling work, only an intense eruption in the gas-rich depths would be powerful enough to overturn the lake6. The 2002 eruption barely affected its stabili! ty because the magma did not reach those depths7. "The probability is low," says Schmid. "At least I am not afraid of swimming in Lake Kivu." But Dario Tedesco, a volcanologist from the Second University of Naples in Caserta, Italy, who is writing the DRC's Mount Nyiragongo eruption contingency plan for the United Nations, says an eruption at the bottom of Lake Kivu is a possibility. Tedesco has studied bathymetric surveys of the lake and found cone-like structures that are probably volcanic in origin, he says. That evidence matches some other signs. During the 2002 Nyiragongo eruption, new fractures opened on the south side of the volcano, just a few kilometres from the lake. The lava from the fractures was also compositionally different from the volcano's crater lake1, suggesting that there are separate reservoirs of magma in the region, some of which could extend under the lake. "Nyiragongo is going to erupt again," says Tedesco. "The only real question is where." Tedesco's research at Kivu highlights its complexity. The lake contains at least five basins, with different characteristics and different probabilities of turnover2. The Kabuno basin, in the lake's northwest corner, has high gas concentrations only 12 metres below the surface. An eruption in Kabuno could release at least three times more gas than Lake Nyos did. Researchers agree that it is important to relieve gas pressure at Lake Kivu to avoid a natural disaster — and the economic incentives are pushing that work forwards. The 60 cubic kilometres of methane equals roughly ten times the combined annual commercial energy needs of both the DRC and Rwanda. Tapping that reserve is particularly attractive to energy-starved Rwanda, and Lake Kivu has become the centrepiece of the country's plans to expand electricity production. Extracting methane from Kivu is not a new idea. A brewery in Rwanda burned the lake's methane to heat its boilers for 40 years before it shifted to electricity. But commercial interest in using methane to generate electricity only burgeoned in recent years, in part because of growing political stability in Rwanda. Around 60 companies, most of them from foreign countries, have approached the government for access to the lake since 2005, says Albert Butare, Rwanda's minister responsible for energy, water and sanitation. Rwanda has already handed out methane concessions totalling hundreds of megawatts to five consortia, including a US$325 million, 100-megawatt deal with ContourGlobal, an energy company based in New York. And in June, Rwanda and the DRC announced a new joint plan to develop an additional 200 megawatts from the lake. The growing interest in Kivu has kept scientists busy discussing best practices for methane removal. Most of the proposed models use a floating platform to suspend a vertical pipe down into the gas-rich layers. A small pump initially pulls up some of the bottom water to lower pressures, until it becomes saturated with gas and starts forming bubbles. After this priming, the bubbling drives water up the pipe without additional pumping. The extraction works like a controlled limnic eruption. The methane, being less soluble than the carbon dioxide, comes out of solution first. It is then piped onshore where it is burned to generate electricity. The problem is what to do with the carbon-dioxide-laden water. From the standpoint of safety, it would be ideal to extract the carbon dioxide and reinsert the degassed water into the deep parts of the lake, where it wouldn't disturb the equilibrium, says Kling. But removing the carbon dioxide makes the water lighter, hence less stable at depth. "We don't want to generate any sinking or rising of water masses that will cause mixing," he says. Only water from the very bottom of the lake would still be dense enough to be reinserted in the deepest layers once it was degassed, but that would be prohibitively expensive. So Kling suggests keeping the carbon dioxide in the water. "Every solution is a compromise," he says. Close call: lava from Mount Nyiragongo didn't go deep enough into lake Kivu in January 2002 to set off a limnic eruption, but next time it could.G. MULALA/REUTERS Conflict of interests? Klaus Tietze, a geophysicist and the director of Physik-Design-Technology, a consulting company based in Celle, Germany, argues that with carbon dioxide concentrations in the lake increasing at a rate of more than 3% a decade, "leaving the carbon dioxide in the lake is a very bad solution". He is pushing for removing both methane and carbon dioxide as quickly as possible and reinserting the water above the main gas accumulations in the lake, so that it doesn't dilute the methane resource. "This is pure business. This has nothing to do with the hazard of the situation." Dario Tedesco Schmid discounts that plan, however, because the nutrients in the degassed deep water would overload the lake's upper layers. With so much disagreement among scientists, the best way forwards for developers is unclear, especially because the extraction technology has been problematic. So far only one 4-megawatt platform, called KP, is sporadically generating electricity for Rwanda's national grid. Another, a 3.6-megawatt project funded by the Rwandan Investment Group, sank last year a week before it was scheduled to begin production. Some have attributed the loss to sabotage but others have blamed bad engineering. Complicating the situation is the potential for conflicts of interest; some of the scientists who studied the lake and identified its hazard are now involved in the methane extraction projects. For example, Michel Halbwachs, a recently retired physicist from University of Savoie in France, has spent two decades studying Nyos and Kivu and now spearheads the Rwandan Investment Group's project. He says that the engineering of the sunken platform was sound and the company is now rebuilding it. Halbwachs says that his previous work on the lake is not a conflict of interest, but rather makes him uniquely knowledgeable about how to extract gases safely. Tietze agrees that only the few scientists who "know the whole lake" through decades of experience are qualified to run the methane projects. He is also trying to get into the extraction game and is now looking for investors. But other scientists worry that the safety of the lake could be compromised if the researchers who are assessing the gas hazard are also working on commercial methane extraction. The best interests of the lake's two million inhabitants could get lost along the way, says Tedesco, who calls the plans for tapping methane "pure business". "This has nothing to do with the hazard of the situation," he adds. "It's a little bit like someone has dropped free money on the street and everyone's running around trying to gather it up," says Kling. He is part of an international team that is working with the World Bank and the involved nations to create rules for methane extraction in the lake. The team wants every project to be monitored through a local institute, which then reports to an international group of experts. "There has to be a separation between who is doing the work and who is checking the work," he says. In mid-June, the team came out with its first draft of legislation, which will now have to get parliamentary backing both in Rwanda and in the DRC. Although, in theory, removing the methane should make the lake safer, it remains unclear whether the hazard will be reduced. The plans for degassing are preliminary, and no one knows how they will affect the lake's stability. ADVERTISEMENT The chances of avoiding a disaster depend on many factors, some well beyond the control of the scientists or even the governments in that region. Armed militias in the DRC recently took over four of the area's seven seismic monitoring stations, hampering the ability of volcanologists to predict when Nyiragongo will erupt. And in the past few months, renewed fighting in rural areas has displaced hundreds of thousands of people. Goma's population has almost tripled since the 2002 Nyiragongo eruption, to an estimated 1.2 million people. There are shanties crammed into every usable piece of land, many constructed from lava blocks from the volcano's last eruption. So as scientists and developers fight over Lake Kivu's methane resource, the displaced people remain pinned between a volcano, the militias and an explosive lake. Anjali Nayar is an International Development Research Centre fellow at Nature. * References * Tedesco, D. et al. J. Geophys. Res. 112, B09202 (2007). * Tassi, F. et al. Geochem. Geophys. Geosyst. 10, Q02005 (2009). * Kling, G. W. et al. Science 236, 169-175 (1987). * Haberyan, K. A. & Hecky, R. E. Palaeogeogr. Palaeoclimatol. Palaeoecol. 61, 169-197 (1987). * Schmid, M. , Halbwachs, M. , Wehrli, B. & Wüest, A. Geochem. Geophys. Geosyst. 6, Q07009 (2005). * Schmid, M. et al. Acta Vulcanologica 14/15, 115-122 (2003). * Lorke, A. , Tietze, K. , Halbwachs, M. & Wuest, A. Limnol. Oceanogr. 49, 778-783 (2004). Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Sharing different mouse strains is not always so simple
  - Nature 460(7253):324 (2009)
  I was disappointed by the view expressed in your Editorial 'The sharing principle' (Nature 459, 752; 2009) that the mouse community does not share its strains. This is untrue.
• Invasion biology is a discipline that's too young to die
  - Nature 460(7253):324 (2009)
  Mark Davis suggests in his book Invasion Biology that the discipline should be reabsorbed into general community ecology, as Emma Marris reports in her Review 'The end of the invasion?' (Nature 459, 327–328; 2009).
• For cancer, seek and destroy or live and let live?
  - Nature 460(7253):324 (2009)
  In his Essay 'A change of strategy in the war on cancer' (Nature 459, 508–509; 2009), Robert Gatenby proposes that controlling a tumour's growth may be more efficient in the long term than trying to eradicate it. However, it could be some time before we can establish whether such a switch in treatment strategy is clinically beneficial.
• Why we need space travel
  - Nature 460(7253):325 (2009)
  Giovanni Bignami reflects on the people who persuaded him that we must send humans beyond Earth's orbit to inspire public and political support for science.
• The slow slide towards a new battlefield?
  - Nature 460(7253):326-327 (2009)
  The cold war saw governments develop international policies to regulate outer space for military and civil uses. Loopholes in those policies must now be closed, writes Roald Sagdeev.
• The return path to the Moon
  - Nature 460(7253):327-328 (2009)
  In The Seventh Landing, Michael Carroll adeptly lays out NASA's strategy for returning to the Moon, establishing a permanent outpost there, and, if all goes well, pushing on to Mars. It is a complex and ambitious undertaking, requiring a new fleet of launch vehicles, an updated crew module, a more versatile lunar lander, sophisticated all-terrain vehicles, souped-up spacesuits, lunar habitats and enough acronyms to make your head explode.
• Apollo books
  - Nature 460(7253):328 (2009)
  The anniversary of the first footstep on the Moon is being celebrated in an array of new books. Drawing on NASA's archive of oral histories, and declassified Central Intelligence Agency material on the space race, historian Craig Nelson tells in Rocket Men (Viking) the full story of the Apollo programme from the crews' training to the first moonwalkers' return as media stars.
• In Retrospect: Calvino's Cosmicomics
  - Nature 460(7253):329 (2009)
  The soaring imagination of the Italian author abounds in a new compilation of his cosmic fables. Mostly written in the age of the space race, they are heavily informed by science, finds Alan Lightman.
• Ageing: A midlife longevity drug?
  - Nature 460(7253):331-332 (2009)
  The small molecule rapamycin, already approved for clinical use for various human disorders, has been found to significantly increase lifespan in mice. Is this a step towards an anti-ageing drug for people?
• Atmospheric physics: Cosmic rays, clouds and climate
  - Nature 460(7253):332-333 (2009)
  Galactic cosmic rays could influence Earth's cloudiness by creating aerosol particles that prompt cloud formation. That possible effect looks to be smaller than thought, but the story won't end there.
• Galaxy formation: Anatomy of elliptical galaxies
  - Nature 460(7253):333-334 (2009)
  The family of elliptical galaxies is remarkable for the structural regularity of its members. Inspecting irregularities in this regularity could help in understanding how these galaxies form.
• Ecology: Towards a theory of biodiversity
  - Nature 460(7253):334-335 (2009)
  Models of ecological communities that incorporate mutation and spatial dispersal can yield results that go some way to explaining observations. A further step is to add sexual reproduction to the mix.
• Climate change: Beyond the CO2 connection
  - Nature 460(7253):335-336 (2009)
  At times in the past, mobile ocean fronts in the subtropics have exercised an influence on the magnitude of climate change by decoupling temperature from levels of carbon dioxide in the atmosphere.
• Photonics: Light control at will
  - Nature 460(7253):337 (2009)
  Microchips that make use of light instead of electrons could outperform their electronic counterparts if light flow can be controlled at will. Photonic crystals are instrumental in achieving such a manoeuvre.
• Obituary: Jean Dausset (1916–2009)
  - Nature 460(7253):338 (2009)
  'Father' of the human leukocyte antigen system.
• Primate archaeology
  - Nature 460(7253):339-344 (2009)
  All modern humans use tools to overcome limitations of our anatomy and to make difficult tasks easier. However, if tool use is such an advantage, we may ask why it is not evolved to the same degree in other species. To answer this question, we need to bring a long-term perspective to the material record of other members of our own order, the Primates.
• The Schistosoma japonicum genome reveals features of host–parasite interplay
  - Nature 460(7253):345-351 (2009)
  Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signalling pathways for growth, development and maturation. Having a complex nervous system and a well-developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis co! ntrol.
• The genome of the blood fluke Schistosoma mansoni
  - Nature 460(7253):352-358 (2009)
  Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have! identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
• The active form of DNA polymerase V is UmuD'2C–RecA–ATP
  - Nature 460(7253):359-363 (2009)
  DNA-damage-induced SOS mutations arise when Escherichia coli DNA polymerase (pol) V, activated by a RecA nucleoprotein filament (RecA*), catalyses translesion DNA synthesis. Here we address two longstanding enigmatic aspects of SOS mutagenesis, the molecular composition of mutagenically active pol V and the role of RecA*. We show that RecA* transfers a single RecA–ATP stoichiometrically from its DNA 3'-end to free pol V (UmuD'2C) to form an active mutasome (pol V Mut) with the composition UmuD'2C–RecA–ATP. Pol V Mut catalyses TLS in the absence of RecA* and deactivates rapidly upon dissociation from DNA. Deactivation occurs more slowly in the absence of DNA synthesis, while retaining RecA–ATP in the complex. Reactivation of pol V Mut is triggered by replacement of RecA–ATP from RecA*. Thus, the principal role of RecA* in SOS mutagenesis is to transfer RecA–ATP to pol V, and thus generate active mutasomal complex for translesion synthesis.
• Contamination of the asteroid belt by primordial trans-Neptunian objects
  - Nature 460(7253):364-366 (2009)
  The main asteroid belt, which inhabits a relatively narrow annulus 2.1–3.3 au from the Sun, contains a surprising diversity of objects ranging from primitive ice–rock mixtures to igneous rocks. The standard model used to explain this assumes that most asteroids formed in situ from a primordial disk that experienced radical chemical changes within this zone1. Here we show that the violent dynamical evolution of the giant-planet orbits required by the so-called Nice model2, 3, 4 leads to the insertion of primitive trans-Neptunian objects into the outer belt. This result implies that the observed diversity of the asteroid belt is not a direct reflection of the intrinsic compositional variation of the proto-planetary disk. The dark captured bodies, composed of organic-rich materials, would have been more susceptible to collisional evolution than typical main-belt asteroids. Their weak nature makes them a prodigious source of micrometeorites—sufficient to explain why ! most are primitive in composition and are isotopically different from most macroscopic meteorites5, 6.
• Manipulation of photons at the surface of three-dimensional photonic crystals
  - Nature 460(7253):367-370 (2009)
  In three-dimensional (3D) photonic crystals1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, refractive-index variations with a periodicity comparable to the wavelength of the light passing through the crystal give rise to so-called photonic bandgaps, which are analogous to electronic bandgaps for electrons moving in the periodic electrostatic potential of a material's crystal structure. Such 3D photonic bandgap crystals are envisioned to become fundamental building blocks for the control and manipulation of photons in optical circuits. So far, such schemes have been pursued by embedding artificial defects3, 4, 5, 8, 9, 10, 11, 12 and light emitters4, 5, 6, 7, 8, 9 inside the crystals, making use of 3D bandgap directional effects. Here we show experimentally that photons can be controlled and manipulated even at the 'surface' of 3D photonic crystals, where 3D periodicity is terminated, establishing a new and versatile route for photon manipulation. By making use of an evanescent-! mode coupling technique, we demonstrate that 3D photonic crystals possess two-dimensional surface states, and we map their band structure. We show that photons can be confined and propagate through these two-dimensional surface states, and we realize their localization at arbitrary surface points by designing artificial surface-defect structures through the formation of a surface-mode gap. Surprisingly, the quality factors of the surface-defect mode are the largest reported for 3D photonic crystal nanocavities (Q up to 9,000). In addition to providing a new approach for photon manipulation by photonic crystals, our findings are relevant for the generation and control of plasmon-polaritons in metals and the related surface photon physics. The absorption-free nature of the 3D photonic crystal surface may enable new sensing applications and provide routes for the realization of efficient light–matter interactions.
• Photoconductance and inverse photoconductance in films of functionalized metal nanoparticles
  - Nature 460(7253):371-375 (2009)
  In traditional photoconductors1, 2, 3, the impinging light generates mobile charge carriers in the valence and/or conduction bands, causing the material's conductivity to increase4. Such positive photoconductance is observed in both bulk and nanostructured5, 6 photoconductors. Here we describe a class of nanoparticle-based materials whose conductivity can either increase or decrease on irradiation with visible light of wavelengths close to the particles' surface plasmon resonance. The remarkable feature of these plasmonic materials is that the sign of the conductivity change and the nature of the electron transport between the nanoparticles depend on the molecules comprising the self-assembled monolayers (SAMs)7, 8 stabilizing the nanoparticles. For SAMs made of electrically neutral (polar and non-polar) molecules, conductivity increases on irradiation. If, however, the SAMs contain electrically charged (either negatively or positively) groups, conductivity decreases. ! The optical and electrical characteristics of these previously undescribed inverse photoconductors can be engineered flexibly by adjusting the material properties of the nanoparticles and of the coating SAMs. In particular, in films comprising mixtures of different nanoparticles or nanoparticles coated with mixed SAMs, the overall photoconductance is a weighted average of the changes induced by the individual components. These and other observations can be rationalized in terms of light-induced creation of mobile charge carriers whose transport through the charged SAMs is inhibited by carrier trapping in transient polaron-like states9, 10. The nanoparticle-based photoconductors we describe could have uses in chemical sensors and/or in conjunction with flexible substrates.
• Evidence for middle Eocene Arctic sea ice from diatoms and ice-rafted debris
  - Nature 460(7253):376-379 (2009)
  Oceanic sediments from long cores drilled on the Lomonosov ridge, in the central Arctic1, contain ice-rafted debris (IRD) back to the middle Eocene epoch, prompting recent suggestions that ice appeared in the Arctic about 46 million years (Myr) ago2, 3. However, because IRD can be transported by icebergs (derived from land-based ice) and also by sea ice4, IRD records2, 3 are restricted to providing a history of general ice-rafting only. It is critical to differentiate sea ice from glacial (land-based) ice as climate feedback mechanisms vary and global impacts differ between these systems: sea ice directly affects ocean–atmosphere exchanges5, whereas land-based ice affects sea level and consequently ocean acidity6. An earlier report3 assumed that sea ice was prevalent in the middle Eocene Arctic on the basis of IRD, and although somewhat preliminary supportive evidence exists2, these data are neither comprehensive nor quantified. Here we show the presence of middle Eo! cene Arctic sea ice from an extraordinary abundance of a group of sea-ice-dependent fossil diatoms (Synedropsis spp.). Analysis of quartz grain textural characteristics further supports sea ice as the dominant transporter of IRD at this time. Together with new information on cosmopolitan diatoms and existing IRD records2, our data strongly suggest a two-phase establishment of sea ice: initial episodic formation in marginal shelf areas 47.5 Myr ago, followed 0.5 Myr later by the onset of seasonally paced sea-ice formation in offshore areas of the central Arctic. Our data establish a 2-Myr record of sea ice, documenting the transition from a warm, ice-free3 environment to one dominated by winter sea ice at the start of the middle Eocene climatic cooling phase7.
• Migration of the subtropical front as a modulator of glacial climate
  - Nature 460(7253):380-383 (2009)
  Ice cores extracted from the Antarctic ice sheet suggest that glacial conditions, and the relationship between isotopically derived temperatures and atmospheric have been constant over the last 800,000 years of the Late Pleistocene epoch1. But independent lines of evidence, such as the extent of Northern Hemisphere ice sheets2, sea level3 and other temperature records4, point towards a fluctuating severity of glacial periods, particularly during the more extreme glacial stadials centred around 340,000 and 420,000 years ago (marine isotope stages 10 and 12). Previously unidentified mechanisms therefore appear to have mediated the relationship between insolation, CO2 and climate. Here we test whether northward migration of the subtropical front (STF) off the southeastern coast of South Africa acts as a gatekeeper for the Agulhas current5, 6, which controls the transport of heat and salt from the Indo-Pacific Ocean to the Atlantic Ocean. Using a new 800,000-year record o! f sea surface temperature and ocean productivity from ocean sediment core MD962077, we demonstrate that during cold stadials (particularly marine isotope stages 10 and 12), productivity peaked and sea surface temperature was up to 6 °C cooler than modern temperatures. This suggests that during these cooler stadials, the STF moved northward by up to 7° latitude, nearly shutting off the Agulhas current. Our results, combined with faunal assemblages from the south Atlantic7, 8 show that variable northwards migration of the Southern Hemisphere STF can modulate the severity of each glacial period by altering the strength of the Agulhas current carrying heat and salt to the Atlantic meridional overturning circulation. We show hence that the degree of northwards migration of the STF can partially decouple global climate from atmospheric partial pressure of carbon dioxide, , and help to resolve the long-standing puzzle of differing glacial amplitudes within a consistent range of ! atmospheric .
• Global patterns of speciation and diversity
  - Nature 460(7253):384-387 (2009)
  In recent years, strikingly consistent patterns of biodiversity have been identified over space, time, organism type and geographical region1, 2. A neutral theory (assuming no environmental selection or organismal interactions) has been shown to predict many patterns of ecological biodiversity2, 3. This theory is based on a mechanism by which new species arise similarly to point mutations in a population without sexual reproduction. Here we report the simulation of populations with sexual reproduction, mutation and dispersal. We found simulated time dependence of speciation rates, species–area relationships and species abundance distributions consistent with the behaviours found in nature1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. From our results, we predict steady speciation rates, more species in one-dimensional environments than two-dimensional environments, three scaling regimes of species–area relationships and lognormal distributions of species abundance with! an excess of rare species and a tail that may be approximated by Fisher's logarithmic series. These are consistent with dependences reported for, among others, global birds4 and flowering plants5, marine invertebrate fossils6, ray-finned fishes7, British birds8, 9 and moths10, North American songbirds11, mammal fossils from Kansas12 and Panamanian shrubs13. Quantitative comparisons of specific cases are remarkably successful. Our biodiversity results provide additional evidence that species diversity arises without specific physical barriers6, 11, 14. This is similar to heavy traffic flows, where traffic jams can form even without accidents or barriers15.
• Evolution of a malaria resistance gene in wild primates
  - Nature 460(7253):388-391 (2009)
  The ecology, behaviour and genetics of our closest living relatives, the nonhuman primates, should help us to understand the evolution of our own lineage. Although a large amount of data has been amassed on primate ecology and behaviour, much less is known about the functional and evolutionary genetic aspects of primate biology, especially in wild primates. As a result, even in well-studied populations in which nongenetic factors that influence adaptively important characteristics have been identified, we have almost no understanding of the underlying genetic basis for such traits. Here, we report on the functional consequences of genetic variation at the malaria-related FY (DARC) gene in a well-studied population of yellow baboons (Papio cynocephalus) living in Amboseli National Park in Kenya. FY codes for a chemokine receptor normally expressed on the erythrocyte surface that is the known entry point for the malarial parasite Plasmodium vivax 1, 2, 3. We identified v! ariation in the cis-regulatory region of the baboon FY gene that was associated with phenotypic variation in susceptibility to Hepatocystis, a malaria-like pathogen that is common in baboons4, 5. Genetic variation in this region also influenced gene expression in vivo in wild individuals, a result we confirmed using in vitro reporter gene assays. The patterns of genetic variation in and around this locus were also suggestive of non-neutral evolution, raising the possibility that the evolution of the FY cis-regulatory region in baboons has exhibited both mechanistic and selective parallels with the homologous region in humans6, 7, 8. Together, our results represent the first reported association and functional characterization linking genetic variation and a complex trait in a natural population of nonhuman primates.
• Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
  - Nature 460(7253):392-395 (2009)
  Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies1, 2, 3, 4, 5; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival poi! nt. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.
• A conserved ubiquitination pathway determines longevity in response to diet restriction
  - Nature 460(7253):396-399 (2009)
  Dietary restriction extends longevity in diverse species, suggesting that there is a conserved mechanism for nutrient regulation and prosurvival responses1. Here we show a role for the HECT (homologous to E6AP carboxy terminus) E3 ubiquitin ligase WWP-1 as a positive regulator of lifespan in Caenorhabditis elegans in response to dietary restriction. We find that overexpression of wwp-1 in worms extends lifespan by up to 20% under conditions of ad libitum feeding. This extension is dependent on the FOXA transcription factor pha-4, and independent of the FOXO transcription factor daf-16. Reduction of wwp-1 completely suppresses the extended longevity of diet-restricted animals. However, the loss of wwp-1 does not affect the long lifespan of animals with compromised mitochondrial function or reduced insulin/IGF-1 signalling. Overexpression of a mutant form of WWP-1 lacking catalytic activity suppresses the increased lifespan of diet-restricted animals, indicating that WWP! -1 ubiquitin ligase activity is essential for longevity. Furthermore, we find that the E2 ubiquitin conjugating enzyme, UBC-18, is essential and specific for diet-restriction-induced longevity. UBC-18 interacts with WWP-1 and is required for the ubiquitin ligase activity of WWP-1 and the extended longevity of worms overexpressing wwp-1. Taken together, our results indicate that WWP-1 and UBC-18 function to ubiquitinate substrates that regulate diet-restriction-induced longevity.
• A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning
  - Nature 460(7253):400-404 (2009)
  Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a marked increase in incidence in the early 1960s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative1, 2. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation3, 4, 5. Both X-irradiation5 and thalidomide-induced phocomelia5, 6 have been interpreted as patterning defects in the context of the progress zone model, which states that a cell's proximodistal identity is determined by the length of time spent in a distal limb region termed the 'progress zone'7. In! deed, studies of X-irradiation-induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the progress zone model. Here, using a combination of molecular analysis and lineage tracing in chick, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. Because skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the aetiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that proximodistal patterning is unaffected after X-irradiation does not support t! he predictions of the progress zone model.
• The AP-1 transcription factor Batf controls TH17 differentiation
  - Nature 460(7253):405-409 (2009)
  Activator protein 1 (AP-1, also known as JUN) transcription factors are dimers of JUN, FOS, MAF and activating transcription factor (ATF) family proteins characterized by basic region and leucine zipper domains1. Many AP-1 proteins contain defined transcriptional activation domains, but BATF and the closely related BATF3 (refs 2, 3) contain only a basic region and leucine zipper, and are considered to be inhibitors of AP-1 activity3, 4, 5, 6, 7, 8. Here we show that Batf is required for the differentiation of IL17-producing T helper (TH17) cells9. TH17 cells comprise a CD4+ T-cell subset that coordinates inflammatory responses in host defence but is pathogenic in autoimmunity10, 11, 12, 13. Batf-/- mice have normal TH1 and TH2 differentiation, but show a defect in TH17 differentiation, and are resistant to experimental autoimmune encephalomyelitis. Batf-/- T cells fail to induce known factors required for TH17 differentiation, such as RORt11 (encoded by Rorc) and the c! ytokine IL21 (refs 14–17). Neither the addition of IL21 nor the overexpression of RORt fully restores IL17 production in Batf-/- T cells. The Il17 promoter is BATF-responsive, and after TH17 differentiation, BATF binds conserved intergenic elements in the Il17a–Il17f locus and to the Il17, Il21 and Il22 (ref. 18) promoters. These results demonstrate that the AP-1 protein BATF has a critical role in TH17 differentiation.
• Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus
  - Nature 460(7253):410-413 (2009)
  Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair1, 2. In addition, evidence from model organisms3, 4, 5, 6 and from human genetics7 suggests that cohesin is involved in the control of gene expression8, 9. This non-canonical role has recently been rationalized by the findings that mammalian cohesin complexes are recruited to a subset of DNase I hypersensitive sites and to conserved noncoding sequences by the DNA-binding protein CTCF10, 11, 12, 13. CTCF functions at insulators (which control interactions between enhancers and promoters) and at boundary elements (which demarcate regions of distinct chromatin structure)14, and cohesin contributes to its enhancer-blocking activity10, 11. The underlying mechanisms remain unknown, and the full spectrum of cohesin functions remains to be determined. Here we show that cohesin forms the topological and mechanistic basis for cell-type-specific long-range chromosoma! l interactions in cis at the developmentally regulated cytokine locus IFNG. Hence, the ability of cohesin to constrain chromosome topology is used not only for the purpose of sister chromatid cohesion1, 2, but also to dynamically define the spatial conformation of specific loci. This new aspect of cohesin function is probably important for normal development3, 4, 5, 6 and disease7.
• Systems biology: Untangling the protein web
  - Nature 460(7253):415-418 (2009)
  Researchers have identified thousands of macromolecular interactions within cells. But, as Nathan Blow finds out, joining them up in networks and figuring out how they work still poses a big challenge.
• Systems biology: Playing by the rules
  - Nature 460(7253):417 (2009)
  M. TYERS Graphical representation of the current budding-yeast interaction network. When researchers at Plectix BioSystems in Somerville, Massachusetts, began to use their new Cellucidate software to model the epidermal growth factor receptor pathway, they calculated that there were 1033 potential states — including all protein complexes and phosphorylation states — for the system. "This is the kind of complexity that scientists have to grapple with when it comes to cell-signalling networks," says Gordon Webster, vice-president of biology at Plectix. Although not all these potential states necessarily occur in that pathway, when it comes to creating more manageable models for understanding cell signalling researchers face a difficult question: what interaction data do they use in their models? Although many commercial and public databases still rely heavily on the small-scale protein–protein-interaction studies that appear in peer-reviewed literature, the emergence of high-throughput experimental approaches that generate very large interaction data sets is creating the need for a new set of rules. "In practice, what comes out of these high-throughput studies is not a yes/no thing — 'these interact, and these don't' — but in fact they generate a list of interactions and associated probabilities," says Jack Greenblatt from the University of Toronto in Canada. To generate such probabilities for his mass-spectrometry studies, Greenblatt applied a 'gold standard' for protein interactions — a set of protein complexes or interactions in which there is a strong amount of confidence according to the literature — as well as a set of proteins not known to interact with one another as a negative standard. He then tackled the question of whether or not data sets generated by mass spectrometry stacked up against protein-interaction reports seen in peer-reviewed literature. "What we did in the end was to use the same gold standard to look at the molecular-biology literature," says Greenblatt. After adjusting the cut-off point so that the average confidence score from a high-throughput study matched the confidence score of interactions reported in the literature, he says the interaction data from such studies are no better or worse than what is in the literature. Marc Vidal, a geneticist at the Dana–Farber Cancer Institute in Boston, Massachusetts, wants to see a similar approach taken with yeast two-hybrid and other binary screens. "Let's roll up our sleeves and decide on a positive and negative gold standard," he says. "But let's also use orthogonal assays to give confidence scores to the interactions." In January, Vidal and his colleagues published a series of papers6–9 suggesting the use of new binary interaction assays to build confidence in basic networks produced using yeast two-hybrid data sets. "You say 'OK, this is basic network' and then push that into a framework where all interactions are going to be tested by two or three orthogonal assays. And not only that, but do that under conditions where you have a positive and negative gold standard," says Vidal, adding that the high-scoring interactions can then serve as hypotheses for researchers to test. Whether or not these efforts and standards will lead researchers to rely more on large-scale data sets and mine them more deeply will only be known in time. For some, even with confidence measures, large-scale data sets lack information often found in smaller studies. "This is one of the paradoxes that we find when people talk about systems biology. With technology it is very easy to generate spreadsheets of interaction data, but that alone does not represent any knowledge," says Webster. But for Greenblatt and others, large-scale data sets represent a starting point for further research efforts. "To me, high-throughput studies are just like the conventional literature," he says, "providing a gold mine for people to dig into." N.B.
• Systems biology: Table of suppliers
  - Nature 460(7253):419-420 (2009)
  Table 1
• Makeover
  - Nature 460(7253):428 (2009)
  Off on the wrong track.