Hot off the presses! Jun 11 Nature

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Latest Articles Include:

• Unjust burdens of proof
  - Nature 459(7248):751 (2009)
  English libel law adversely affects every publisher and website host whose content can be read in the United Kingdom. It must be changed.
• Watch your back
  - Nature 459(7248):751-752 (2009)
  The H1N1 flu epidemic is not the world's only disease threat.
• The sharing principle
  - Nature 459(7248):752 (2009)
  Journals and funders must insist that genetically modified mouse strains are fully available.
• Evolution: Tickle tree
  - Nature 459(7248):754 (2009)
  
• Astronomy: What's handed down
  - Nature 459(7248):754 (2009)
  
• Ecology: Evidence of emperors
  - Nature 459(7248):754 (2009)
  
• Planetary science: Pressure drop
  - Nature 459(7248):754 (2009)
  
• Oceanography: Glowing oceans
  - Nature 459(7248):754 (2009)
  
• Neurogenetics: Huntington's toxic trigger
  - Nature 459(7248):754-755 (2009)
  
• Ecology: Biomes bounce back
  - Nature 459(7248):755 (2009)
  
• High-energy physics: Muonium gets real
  - Nature 459(7248):755 (2009)
  
• Planetary science: Mercurial Mercury
  - Nature 459(7248):755 (2009)
  
• Cancer biology: Tumour clue
  - Nature 459(7248):755 (2009)
  
• Journal club
  - Nature 459(7248):755 (2009)
  
• Avian influenza aided readiness for swine flu
  - Nature 459(7248):756-757 (2009)
  Despite gains from threat of bird flu, pandemic preparedness is patchy. With the World Health Organization discussing whether to declare, as Nature went to press, that a swine influenza pandemic has arrived, doctors, scientists and government officials say the enormous preparedness efforts of recent years have aided the world's response to the virus. Britain has sufficient stockpiles of antiviral drugs to protect 50%; of its population.Britain has sufficient stockpiles of antiviral drugs to protect 50% of its population.K. COLLINS/REUTERS "Clearly, the global preparedness for dealing with an influenza outbreak is much better now than it was five or six years ago," says virologist Malik Peiris of the University of Hong Kong. But there have been some hiccups, due largely to the mismatch between the pandemic scenarios envisaged and the one that has arrived. Most nations had prepared for a pandemic sparked by the deadly A(H5N1) avian influenza virus, which kills up to 60% of those infected, but the A(H1N1) swine flu virus epidemic has been much less severe so far. "Many nations built their plans around the idea that a pandemic strain would evolve in southeast Asia, that we would recognize it early, and that we would be able to contain it," says Eric Toner, a physician and preparedness analyst with the University of Pittsburgh Medical Center's Center for Biosecurity in Pennsylvania. "None of that turned out to be true." "The idea that one could trap it at the early stages was certainly not successful." Global pandemic planning efforts were ramped up after severe acute respiratory syndrome (SARS) swept through Asia in 2003, and the deadly H5N1 strain emerged in the same year. Local, national and international entities involved in flu response are now better coordinated, observers say. That was evident with regard to the current situation, as officials — for instance, at the US Centers for Disease Control and Prevention in Atlanta, Georgia — delivered open and consistent public messages about the seriousness and uncertainty of swine flu infections, says Georges Benjamin, executive director of the American Public Health Association in Washington DC. That's in contrast to 2001, when some conflicting messages were delivered during the anthrax attacks. In some countries, pandemic planning has led to stockpiled antiviral medication (see 'Preparedness by the numbers') being distributed to treat people with swine flu and their contacts. And the boost in research spending on epidemiological modelling and laboratory studies has enabled scientists to understand the H1N1 virus in record time, prepare to manufacture more vaccine faster, make more informed decisions on how to intervene in the virus's spread, and understand and share information on its genetic characteristics. "We got an extraordinary laboratory understanding of this virus in a very short period of time, and that is the scientific 'wow' of what really happened in this outbreak," says Benjamin. But the divergence between the anticipated pandemic and the one that has actually arrived has caused some glitches. For instance, the swine flu virus was not detected in time to contain it, as had been envisaged in some scenarios involving avian flu. "By the time the surveillance systems picked [the virus] up, it was already spreading way out of control, so the idea that one could trap it at the early stages was certainly not successful," says Peiris. As swine flu began to spread throughout North America, which had hoped to have weeks of warning before a virus arrived from Asia, officials were initially confused about how to implement response plans. For instance, swine flu symptoms were milder and less severe than anticipated — impossible to distinguish from seasonal flu — and hospitals and health departments were swamped with people seeking tests for swine flu. A report issued on 4 June by the non-profit group Trust for America's Health, based in Washington DC, also noted that budget cuts at health departments at all levels slowed the US response, for instance by delaying testing. "We have to consider what happened in the month of May as maybe a warning of what's coming, and we're working very hard this summer to have countermeasures available if the need for those arises" in the autumn, says Robin Robinson, principal deputy director of the Biomedical Advanced Research and Development Authority within the US Health and Human Services department. By contrast, Asia had expected an avian pandemic virus to arise in its backyard and was not fully prepared for swine flu from overseas. Most of the flu plans for the members of the Association of Southeast Asian Nations "focus on how to cull chickens", says Hitoshi Oshitani, a virologist with the Tohoku University Graduate School of Medicine in Sendai, Japan. "They may have some rapid containment plan, but containment is not possible for this current virus," he says. Some Asian countries have applied containment measures that had little chance of working. China, for example, quarantined foreign travellers with fever symptoms and symptomless travellers in contact with those, a move not backed by scientific evidence, Toner says. When the virus spread to Europe, some nations found they were not as ready as their thorough plans had led them to believe they were. For instance, Britain's Health Protection Agency, which was responsible for investigating the initial swine flu cases, did not at first have enough staff available to carry out the investigations, says Sandra Mounier-Jack, a health-policy analyst at the London School of Hygiene and Tropical Medicine. And a planned telephone line that was to have been used to help distribute antivirals had not been set up when swine flu appeared. These are common problems, says Mounier-Jack. "The major gaps are about making the plans operational — making sure that people at local levels know their roles and responsibilities, even in countries which have very good plans and are rich." And some long-standing challenges for Europe have still not been addressed, such as the piecemeal nature of the response. "We have 27 pandemic preparedness plans in different states of maturity, and now individual ministries of health are all lining up to buy up vaccines," says Albert Osterhaus of the University of Rotterdam in the Netherlands. ADVERTISEMENT Advertisement But perhaps the biggest global challenge is arriving now, as the Southern Hemisphere enters its flu season and swine flu threatens many of the least-ready countries. "In general, the developing countries are not prepared," Oshitani says. The World Bank has released billions of dollars for preparedness in these regions, but many developing nations still do not have plans for dealing with a pandemic — and some that do have simply cut and pasted versions of plans from developed countries, which do not apply to poorer nations unable to afford vaccines and antivirals. People in poor nations already suffer from a higher incidence of conditions, such as malnutrition and HIV, that make them more vulnerable to the new virus. In addition, they are likely to be left out of the global scramble for a vaccine, which has already started as nations such as the United States and Britain rush to tie up vaccine contracts. On the whole, Oshitani says, "this pandemic came too early. If we had had two more years, we would have been better prepared." 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
• UK science shuffled again
  - Nature 459(7248):757 (2009)
  British prime minister Gordon Brown has scrapped the government department in charge of science and higher education, just two years after it was created. As part of a cabinet reshuffle on 5 June, responsibilities for research and universities were absorbed into a newly inflated business department that will "build Britain's capabilities to compete in the global economy", says a government statement.
• Moon mission tackles water question
  - Nature 459(7248):758-759 (2009)
  NASA's Lunar Reconnaissance Orbiter (LRO), scheduled for launch on 17 June, should end a long-standing debate on whether the Moon has water ice. For nearly half a century, scientists have argued over the idea that bits of ice hide within the frigid darkness of permanently shadowed craters at the Moon's poles.
• Last weather ship faces closure
  - Nature 459(7248):759 (2009)
  Oceanographers rally to try to save Norwegian vessel. Leading climate scientists and oceanographers are urging the Norwegian government to revise or postpone the decommissioning of the world's last stationary weather ship. Without funding from elsewhere, the M/V Polarfront will be decommissioned.Without funding from elsewhere, the M/V Polarfront will be decommissioned.M. Yelland Located at 66 ° N in the Norwegian Sea, some 450 kilometres off the coast, the M/V Polarfront maintains Station M (Mike), the last of what was a network of 13 weather stations in the North Atlantic. The International Civil Aviation Organization set them up in 1948 to support air traffic, but by 1974 only four were left, and the penultimate station closed in the 1990s. Now, as satellites, buoys and reports from moving ships have eclipsed the stationary station for weather-forecasting purposes, the Norwegian government says it cannot justify the expense and intends to decommission the ship by 31 December. Annual operational costs are €2.5 million (US$3.5 million), most of which is paid for by the Norwegian Meteorological Institute in Oslo. The station constitutes more than half of the institute's running expenses for all meteorological observations in the country, including weather radars. "I have received no further offers to share the expenses." Researchers protest that the shutdown will harm crucial observational programmes in the climate and ocean sciences. "It's a blow," says Ingunn Skjelvan, a chemical oceanographer at the Bjerknes Centre for Climate Research in Bergen, Norway. "Equally reliable ocean time series are just not available from satellites, buoys or drifting vessels," says Margaret Yelland, a physical oceanographer at the National Oceanography Centre in Southampton, UK. In more than 60 years of observations, Station Mike has collected measurements of temperature and salinity down to 2,500 metres five times a week — the world's longest time series of its kind. Among other things, the station has provided key information on the long-term variability of the Nordic seas and on changes in Atlantic Ocean circulation. "These are not oceanographic curiosities," says Tom Rossby, an oceanographer at the University of Rhode Island in Narragansett. "They are of fundamental importance." Shutting down the Polarfront "will have dramatic negative consequences for climate change research, as irreplaceable long-term measurements will come to an end", wrote Howard Cattle of the World Climate Research Program in a letter to Norwegian research authorities. "Other weather ships were withdrawn from service by the mid-1990s, before the importance of such sustained observations for understanding climate was fully realized." ADVERTISEMENT Advertisement Deploying and calibrating hydrographic moorings to replace the Polarfront for climate-quality measuring will require at least a couple of years, experts say. Norway's research minister, Tora Aasland, has acknowledged the urgent need for new monitoring infrastructure. In a response last month to letters from worried scientists, she said that the Research Council of Norway is prepared to consider scientific proposals for work at Station Mike, and that a decision on funding those could be made this summer. Even so, the days of the Polarfront seem to be numbered. "I have received an overwhelming number of statements stressing the importance of continuing the operation of the ship, but no further offers to share the expenses," says Anton Eliassen, director of the Norwegian Meteorological Institute. 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
• Quantum dots go large
  - Nature 459(7248):760-761 (2009)
  Nanocrystals called quantum dots have promised to revolutionize display technologies, solar power and biological imaging for more than a decade. Yet the quantum-dot market has remained small, with a handful of companies selling dots directly to researchers, using the particles to develop their own products or licensing their technologies to partners.
• Grant applications swamp agency
  - Nature 459(7248):763 (2009)
  Peer-review system for National Institutes of Health grants is stretched to its limits. The US National Institutes of Health, already groaning under the weight of grant applications brought on by a $10.4-billion economic stimulus package, is likely to be inundated with a second tidal wave of applications this autumn that would send success rates plummeting, agency officials predict. Mary-Claire KingMary-Claire King: problems ahead.Newscom The flood of applications for Challenge Grants, a new category created by the stimulus funds, means that the success rate will probably be less than 1%. If scientists rejected for Challenge Grants this summer resubmit their applications for standard investigator-initiated 'R01' grants in the autumn, paylines — the percentage of fundable applications — will also bottom out, officials said at an 8 June meeting of the NIH's peer-review advisory committee. "The NIH budget for 2010, unless there's another miracle, is a very small increase," said Story Landis, director of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. "So if in fact all those grants come in, the payline will go to nothing." "To the low single digits," interjected Antonio Scarpa, director of the agency's Center for Scientific Review. His back-of-the-envelope calculations project that the agency would receive 30,000 R01 proposals this autumn, many of them reincarnated Challenge Grants. Furthermore, he calculated that when the unsuccessful applications from that round are resubmitted yet again, the agency will face 25,000 review decisions in October 2010. Reviewing at this magnitude "is not sustainable," Scarpa said. The agency is already reviewing more than 40,000 investigator-initiated applications; in a typical June review round, that figure would be 16,000. The NIH normally uses around 8,000 reviewers; it is now up to about 30,000. More than 21,000 applications have been submitted for Challenge Grants (see table). Others at the advisory meeting said that the serial wave of applications is being unwisely encouraged by university deans of research. "We have been hearing that deans are telling people: 'If you don't get a Challenge Grant, you turn around and submit another research project grant.' This is a really serious problem," said Louise Ramm, deputy director of NIH's National Center for Research Resources. "It's frightening." Garret FitzGerald, chair of pharmacology at the University of Pennsylvania in Philadelphia, added: "Deans have been told they will be rewarded by the number of grants that go out the door. This is irresponsible behaviour." At universities, "the sponsored-projects offices have been flooded by the number of grants going in. That flood is now becoming a tsunami," Mary-Claire King, a human geneticist at the University of Washington in Seattle, said last week. "They need an early-warning system." The NIH is in the process of modelling the likely downstream impact of the stimulus spending. That is difficult to gauge at this point, acting NIH director Raynard Kington said last week, in part because it also depends on how much money Congress gives the agency in 2011 and beyond. Its budget for fiscal year 2009 is $30.3 billion; last month, President Barack Obama proposed a $443-million, or 1.4%, increase for fiscal year 2010. The NIH, which is already in the middle of implementing changes to its peer-review system, has responded to the Challenge Grant flood by recruiting thousands of extra reviewers and adopting 'editorial board' reviews, which involve initial reviews by e-mail and final assessments by boards of highly accomplished scientists. Among concerns voiced by Kington's advisers at a 4 June meeting is the potential burden imposed by new quarterly reporting requirements for the stimulus money. These have not come into effect yet, but are expected to do so by late summer. The Office of Management and Budget is setting up a reporting system to track the overall $787 billion in stimulus money; reporting will be consistent across all federal agencies. ADVERTISEMENT Advertisement "All of us in the extramural world are concerned about what this reporting requirement is going to be and how we are going to manage it," said King. She implored Kington and his staff to adjust the government's template, once finalized, so that "an ordinary mortal scientist" can fill it out. Kington said it is highly unlikely that the NIH would be able to modify a reporting template signed off by top administration officials as a universal requirement. But, he said, the stimulus money has launched a discussion about how the United States tracks the impact of its science funding. "That's going to be here to stay." 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
• Sweden finally picks nuclear-waste burial site
  - Nature 459(7248):764 (2009)
  
• German science secures historic windfall
  - Nature 459(7248):764 (2009)
  
• Rotavirus vaccines win global recommendation
  - Nature 459(7248):764 (2009)
  The World Health Organization (WHO) has recommended that health authorities in all nations routinely vaccinate young children against rotavirus, which causes 2 million hospitalizations and 500,000 deaths from severe diarrhoeal dehydration every year. Rotavirus vaccines are already recommended for use in the Americas and Europe. But more than 85% of deaths caused by rotavirus occur in developing countries in Asia and Africa, says the WHO. The recommendation was made by the WHO's Strategic Advisory Group of Experts, which reviewed a clinical trial of GlaxoSmithKline's Rotarix vaccine in South Africa and Malawi that cut the occurrence of severe diarrhoeal episodes. RotaTeq, a rotavirus vaccine developed by Merck, is being tested in clinical trials in Japan, India, Mali, Ghana, Kenya, Bangladesh and Vietnam. 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
• Californian universities hit by state's budget woes
  - Nature 459(7248):764 (2009)
  
• Legal accord eases path to Europe's research facilities
  - Nature 459(7248):764 (2009)
  
• Submersible plumbs the depths
  - Nature 459(7248):764 (2009)
  
• Media research: The black box
  - Nature 459(7248):765-768 (2009)
  Assessing the effects of television on young children is far from easy. But, as researchers tell Jim Schnabel, that is no reason not to try. Download a PDF of this story Download a PDF of this story In 1998, Dimitri Christakis took time off from work to care for his two-month-old son. At home he found himself watching television to pass the time — "more TV than I had ever watched in my life", he remembers. Soon he noticed that his infant son was watching too. Even CNN kept the boy glued to the screen. "Obviously he wasn't following the news," says Christakis, a professor of paediatrics at the University of Washington in Seattle. Christakis realized that the jumpy images on the screen were engaging the child's 'orienting response', a basic attentional reflex that directs the senses towards a sudden change in the environment. He wondered about the long-term effect of this on a brain that was at such a sensitive developmental stage. Could it alter the brain to 'expect' overstimulation, so that ordinary reality would thereafter seem dull by comparison? And could such a mechanism help to explain the ongoing tsunami of attention deficit hyperactivity disorder (ADHD) diagnoses, whose rise had roughly coincided with the dramatic increase in media consumption in Western societies? Christakis decided to try to address these questions with research. Together with several colleagues, he examined a database called the National Longitudinal Survey of Youth. After analysing some 1,300 children for whom the appropriate data were available, they found that on average, a child who had watched two hours of television per day before the age of three was 20% more likely to have attentional problems at the age of seven, compared with a child who had watched none. Christakis and his colleagues published their results in 2004 (ref. 1). Then, working with public-health expert Fred Zimmerman, who is now at the University of California, Los Angeles, Christakis did a follow-up study2 with a different longitudinal sample, showing that the link to later attentional problems was particularly strong for cartoons and other entertainment programmes watched before the age of three. For educational programmes, such as the gently paced US series Mister Rogers' Neighborhood, they found no such link. These studies were among the largest and most persuasive ever to have linked TV to reduced attention and, as such, they made splashes in the media and the research community. But as observational studies, they had their limitations. An association between TV watching and later attention problems did not prove that one had caused the other. A host of other factors, such as the socio-economic status of a household, could also have contributed to the association, and although researchers typically try to take those other factors into account, they can't always do so accurately. So, like other scientists who had addressed this issue, Zimmerman and Christakis concluded that more research was needed. In particular, Christakis believed that what was needed was a large-scale intervention study, a clinical-trial-type experiment in which one randomly selected group of children would be assigned to watch only a small amount of educational TV, whereas the other group would watch whatever their parents normally allowed. However, Christakis's 2006 proposal — which would have enrolled 900 children, reduced TV exposure in half of them in the first two years of life and assessed attention and related cognitive functions until the age of four — was turned down by reviewers for the US National Institutes of Health (NIH). Even now, the NIH does not have an interventional study under way or planned in this area — nor does Christakis know of one under way or planned anywhere else in the world. This apparent lack of follow-through seems to be part of a broader phenomenon. On the one hand, there is fairly convincing evidence that some TV content, such as the widely aired Sesame Street, can benefit children in a certain age range. On the other, a great deal of research suggests that some TV content can be harmful — yet despite the ominous public-health implications, little seems to be done about it. "Media are arguably the most ubiquitous environmental influence on kids' health and development," says Michael Rich, a paediatrician and media-effects researcher at Harvard Medical School in Boston, Massachusetts. "The problem is that as a society we have not seen this as enough of a health concern that we've decided to invest in it." Because work on the potential effects of media is seldom distinguished from other kinds of developmental and public-health research, it is difficult to know how much is spent on it. But Christakis estimates that the worldwide total is "below US$10 million per year". Tuned out Some major funding agencies just "don't think that media are as important as other factors in children's lives," says Ellen Wartella, a developmental psychologist at the University of California, Riverside. She notes that at a recent meeting of the Society for Research in Child Development, part of the US National Academy of Sciences, "out of hundreds of sessions on children, only three sessions were devoted to media effects". Even when media-effects research is done, and its conclusions seem compelling, it appears to have little influence. For example, in at least two recent studies3,4, researchers have tried but failed to find evidence that popular DVDs targeting infants have cognitive benefits, and one of these studies, co-authored by Christakis3, hinted that they might even impair children's language development. Because of research like this, the American Academy of Pediatrics (AAP) discourages parents from letting infants watch TV at all. But apart from France, which last year banned infant-targeted programmes from its broadcast channels, few, if any, countries have policies that restrict infant TV. And Wartella notes that according to surveys, mothers frequently ignore the AAP's advice and don't tell their paediatricians. "They don't want to hear that they shouldn't put their child in front of the screen," she says. Science's slight impact on media consumption extends beyond issues relating to infants. In the past two decades, researchers have found strong and consistent links between older children's exposure to certain media content and, for example, obesity, eating disorders, aggression, desensitization to violence, sexual promiscuity and the use of alcohol and cigarettes. Brian Primack, a paediatrician at the University of Pittsburgh School of Medicine in Pennsylvania who researches media effects on adolescents, says that for some of these outcomes, "I think we do have enough data [to justify] warning labels". Studies of adolescents and younger children, meanwhile, show that their media exposure continues to expand rapidly, creating what media-effects researchers have begun to call a 'digital childhood'. Is this happening because the evidence for media's harmful effects remains sparse? Or have researchers such as Christakis found themselves up against cultural forces that they cannot defeat with evidence alone? Researchers argue that a host of factors, both scientific and societal, are to blame. For one thing, researchers such as Christakis, Rich and Primack are paediatricians, yet their proposals for epidemiological-type research on the effects of childhood media are usually reviewed by developmental psychologists. Developmental research traditionally hasn't placed great emphasis on media effects amid the complexities of childhood development, says Kevin Durkin, a developmental psychologist at the University of Strathclyde, UK. Among his colleagues, he adds, "there's still a bit of a reluctance to engage with the real world and with things that [children] are actually doing on a daily basis" — and a corresponding preference for theory-driven, laboratory-based research. Media-effects research, by contrast, has often been considered methodologically messy. Virtually all studies of potential health effects, for example, have been observational studies of real-world populations — populations before and after media exposure, or populations in which different people have different exposures. Because the groups being compared in these cases are not randomly assigned to 'watch' or 'not watch', it is at least conceivable that their differing outcomes are the result of other, perhaps hidden, factors not directly related to media exposure. "There's always going to be that question, because it's not like a randomized clinical trial," says Primack. As he and other researchers note, the same problem once plagued researchers who wanted to show that cigarette smoking harmed people's lungs. A 'clinical trial' of smoking's health effects, in which groups of people were randomized to smoke or not smoke, would have been grossly unethical. Over time, however, researchers were able to build a case against tobacco with well-designed observational studies, for example showing a 'dose–response effect' in which heavier smoking was linked to higher cancer risk. But although cigarette smoke is a relatively simple kind of exposure, media exposure is much harder to track. Typically, researchers have lacked the means to monitor precisely what their subjects are watching from day to day for study periods that may last months or even years. They have often relied on self-reporting or parental reports, both of which are considered unreliable. "If you ask the parents about how much TV their kid watches, they tend to overestimate, whereas the kid tends to underestimate," says Rich. "One way or another the report tends to be biased." In the past few years, Rich, Primack and others have been experimenting with other monitoring methods such as ecological momentary assessment, in which subjects or their parents report real-time data of their media exposures to researchers using cellphones, personal organizers and even camcorders. Information overload "How do you measure screen exposure if the kid is clicking through 72 web pages a minute?" Susan Newcomer On the whole, though, technological evolution may be making it harder to study media's effects. "It's no longer the box in the middle of the living room that everybody gathers around," notes Rich. "We have screens everywhere — in our pockets, you know? I was in a hotel recently and I realized that from where I sat I could see seven screens with seven different things on them. And I wasn't even actively watching media." Similarly, notes Susan Newcomer, a programme officer who oversees some media-effects research at the National Institute of Child Health and Human Development (NICHD) in Bethesda, Maryland, "How do you measure screen exposure if the kid is clicking through 72 web pages a minute? And not just clicking through the web but also texting a friend, listening to music, all at the same time?" Compounding this problem is the fact that even for a single, uncomplicated medium — such as one television channel — a viewer faces multiple potential influences that may be difficult, if not impossible, to tease apart. There is the stream of content within a television programme, for example, and then there are the contents of interleaved advertisements. Viewers may be affected, too, by the 'formal', non-conceptual properties of TV watching, such as the rapid image-shifts meant to trigger viewers' orienting responses. There is also the likelihood that in watching TV, a viewer will be inert on a sofa instead of exercising, sitting alone instead of socializing, and staying awake instead of sleeping — and all of these behavioural displacements have their own potential health effects. "You're about to go to bed and you turn on the television to wind down, but then three hours have passed and you've seen Dracula again," says Primack, pointing out that a lack of sleep is now believed by some to contribute to obesity as well as mental-health problems. According to James Griffin, a programme officer whose NICHD branch oversees research on infants and young children, the institute now generally prefers studies that can identify specific cognitive mechanisms of a child's interaction with media. "We are focusing more on looking at what infants and toddlers are capable of learning [from media]," he says. In theory, interventional studies would get around many of these problems because the source and content of media could be controlled and monitored. So why not do them? "Good luck getting that past either an NIH review panel or an institutional review board," says Newcomer. Over the time needed for any effect to appear, she explains, it would be "both ethically and pragmatically a real challenge to constrain people not to look at television, for example, or to look at only certain kinds of television". Yet Christakis argues that such intervention studies are still feasible, particularly when it comes to the effects of TV on very young children. In principle, for such children, TV watching can be more easily controlled by parents, and more easily monitored by researchers. The early developmental stage of these children also means that TV's effects may show up more quickly, thus requiring shorter studies. Without such investigations, Christakis says, "it's going to be very difficult for us to satisfactorily prove to the critics and the cynics that a particular content is harmful". Media-effects researchers are not just fighting resistance in the scientific community. They say they face a broad cultural resistance too, one rooted in core Western beliefs — that humans have 'free will'; that they choose autonomously and rationally from the information put before them; that a free market in information is better than a restricted one. "Questioning TV has been viewed as an assault on the First Amendment." Dimitri Christakis "In the United States, questioning any aspect of television has been viewed as a direct assault on the First Amendment," says Christakis. "Tobacco researchers didn't have to deal with that issue." And the issue isn't confined to the United States. In 2005, India's government banned film images of actors using cigarettes — a known motivator for adolescents to start smoking — yet the country's High Court reversed the ban earlier this year, on free-speech grounds. Researchers say that they confront a related problem called the 'third-person effect'. "Most people will acknowledge that TV is on balance a bad thing; they just don't think it's bad for their kids," explains Christakis. "Somehow they think that their kids are immune, or that the way they use TV is different." But the conceit isn't justified, Rich says, because "epidemiologic data [showing a harmful influence] are generated on our kids, not on somebody else's kids". Media-effects researchers also say that their arguments are apt to be treated, by the public and even by other scientists, as old-fashioned arguments about the immorality of popular-media content, now dressed up as modern health issues. Yet Rich insists that the difference between moral issues and health issues is real and may be crucial in convincing people to change their media-consumption habits. "The moral issue has helped to stalemate this," he says. "People have different value systems. But if you present them clear data that show what the effect of this media content is on that health outcome, you can get them to agree." "Parents tend to say I'm sorry I need to put the kids in front of the tube so I can get the house vacuumed." Michael Rich Even if people can agree such things on a rational level, in practice their media-consumption behaviours are deeply entrenched, as even Rich admits. "Parents do tend to say I'm sorry I need to put the kids in front of the tube so I can get the house vacuumed. Sometimes, governments step in to break cultural stalemates, and in the United States — where the majority of media-effects research takes place — that almost happened. In 2004, Senator Joseph Lieberman (Democrat, Connecticut) introduced a bill called the Children and Media Research Advancement Act (CAMRA). Designed to remedy "the paucity of research" in this area, and enthusiastically backed by researchers including Rich and Wartella, it would have dedicated an NIH budget for media-effects studies during 2005–09, starting at $10 million per year and ending at $25 million per year — figures that would have dramatically increased the activity in this field. The bill never made it past the committee stage. Indeed, a group called Citizens Against Government Waste criticized Lieberman, stating in a press release that his proposed effort "belittles the ability of parents to use common sense in deciding what entertainment is appropriate for their own child's consumption". CAMRA has been reintroduced several times since then, with funding levels left unspecified. But it still has not made it into law. According to a Senate staffer who didn't want her name used, some senators have objected to the legislative determination of where NIH funds should be applied — which they say the agency has had enough of already. (A 2006 version would have placed the programme with the Centers for Disease Control and Prevention in Atlanta, Georgia.) Other legislators simply have not wanted to spend the money, although on an annual basis that money would have amounted only to the cost of a few episodes of a hit TV show. "That in a nutshell is our societal ambivalence towards this subject," says Rich. Accentuate the positive Last year, Christakis was able to get a media-effects study funded by the NICHD. Just starting now, the project will look at the effects on pre-school children of changing TV content rather than eliminating it. "We're trying to get them to watch less aggression and more prosocial programming," says Christakis. "But we're not telling them to watch less; we just want them to watch better TV." The pro-TV message, he adds, is "something that everybody gets behind". Rich, too, notes that "the problem with coming at it from a totally negative standpoint is that people just check out". He urges a greatly expanded research base "that tells us how to live with media, because we're going to have to one way or another". He also foresees that media use will change, albeit 'generationally', as it did with cigarettes. As evidence accumulates that TV can cause health or behavioural problems, he predicts, certain kinds of media use may start to be seen by youngsters and their parents not as forbidden pleasures but as "just dumb". Christakis is less sanguine. He stopped his own kids from watching TV until the age of two and now places modest restrictions on their Internet use. He worries that, in addition to its functional entrenchment in people's daily lives, a lot of media content might be physiologically addictive — perhaps less so than nicotine-laden cigarettes, but with a much larger susceptible population. "I think there's a biochemical response to that kind of stimulation, that instant gratification, that rush, which isn't very well understood," he says. "And I think there's a sense in which some people are very reluctant to acknowledge that there's a problem, because they also suffer from it." ADVERTISEMENT Advertisement Although the concept of behavioural as opposed to drug-induced addiction is still somewhat controversial in Western countries, it is less so in South Korea and Japan. The exposure to electronic media, especially the Internet, seems to be greater there, and the reported prevalence of related addiction behaviours is remarkably high5. Christakis suspects that those societies may be "the canary in the coal mine" when it comes to media addiction. One advantage researchers had in studying the effects of cigarette smoking was that, even if they couldn't experiment directly on humans, they could do so on animals. Christakis now hopes to remove that advantage. This summer he will begin tests on a rodent model of media exposure, comparing rats raised in a 'hyperstimulating' environment of fast-changing sounds and lights, with those raised in a quiet setting, and looking at outcomes relating to attention and addiction. "Animal studies have their limitations," he says. "But they have their strengths too, because you can totally control the animal. You can drill down, so to speak, to a level you could never do in humans." * References * Christakis, D. A. , Zimmerman, F. J. , DiGiuseppe, D. L. & McCarty, C. A. Pediatrics 113, 708– 713 (2004). * Zimmerman, F. J. & Christakis, D. A. Pediatrics 120, 986– 992 (2007). * Zimmerman, F. J. , Christakis, D. A. & Meltzoff, A. N. J. Pediatr. 151, 364– 368 (2007). * Robb, M. B. , Richert, R. A. & Wartella, E. A. Br. J. Dev. Psychol. 27, 27– 45 (2009). * Block, J. J. Am. J. Psychiatry 165, 306– 307(2008). 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
• Geomicrobiology: Low life
  - Nature 459(7248):770-773 (2009)
  In February, a team of American and German oceanographers set out on a ship for a little-known destination in the middle of the Atlantic Ocean called North Pond. This patch of sea floor lies on the western flank of the Mid-Atlantic Ridge — the longest mountain range in the world — where the topography of the ocean bottom drops to form a 10-kilometre-long basin rimmed by underwater peaks.
• Gene data for endangered species have limitations
  - Nature 459(7248):774 (2009)
  Your News story 'Time to sequence the "red and the dead"' (Nature 458, 812–813; 2009) reports on plans to sequence the genomes of endangered and extinct species. Supporters claim that these sequences could help us learn why some species became extinct and provide a scientific argument to warn politicians and the public about which species are endangered, resulting in improved policies.
• How science upholds civilization, human rights and democracy
  - Nature 459(7248):774 (2009)
  I would like to add two important points to the discussions of C. P.
• Stick as well as carrot needed to solve age-old gender bias
  - Nature 459(7248):774 (2009)
  Your Editorial 'The female underclass' highlights the problems faced by women scientists in many European countries (Nature 459, 299; 2009).
• The future of saving our past
  - Nature 459(7248):775-776 (2009)
  As letters and diaries give way to e-mails and laptops, fresh challenges and opportunities have emerged for archivists. Jeremy Leighton John explores the digital wilderness for the British Library.
• Looking for planets like ours
  - Nature 459(7248):777-778 (2009)
  The hunt for habitable worlds near other stars brings home the realization that our own Solar System might not be as special as we think, says Michael Brown.
• Charting the heavens from China
  - Nature 459(7248):778-779 (2009)
  
• Superstition challenged
  - Nature 459(7248):779-780 (2009)
  
• The technology of illusion
  - Nature 459(7248):780 (2009)
  
• Planetary science: The Solar System's extended shelf life
  - Nature 459(7248):781-782 (2009)
  Simulations show that orbital chaos can lead to collisions between Earth and the inner planets. But Einstein's tweaks to Newton's theory of gravity render these ruinous outcomes unlikely in the next few billion years.
• Cell cycle: Cell division brought down to size
  - Nature 459(7248):782-783 (2009)
  Cells normally divide on reaching a fairly specific size, but how cell size dictates the timing of cell division remains obscure. In fission yeast, a spatial gradient of a cell-tip protein may provide an answer.
• Ecology: Traits of plant invaders
  - Nature 459(7248):783-784 (2009)
  Many plants introduced to new habitats have fewer microbial pathogens than when in their home range, and have the ability to grow rapidly. Such a combination may make for especially troublesome immigrants.
• Immunology: Immunity's ancient arms
  - Nature 459(7248):784-786 (2009)
  Diverse receptors on two types of cell mediate adaptive immunity in jawed vertebrates. In the lamprey, a jawless vertebrate, immunity is likewise compartmentalized but the molecular mechanics are very different.
• 50 & 100 years ago
  - Nature 459(7248):785 (2009)
  A general investigation has been in progress for some time in this Department into certain aspects of the chemistry of Ulex europaeus. This common furze has a local reputation as a supplementary animal foodstuff ... No previous results are available on the carotene content of the green matter (spines) of furze and its seasonal variation, which are now reported ... From October to February or March — when furze is fed to stock — the average carotene content is 126 mgm.
• Organic chemistry: Synthetic lessons from nature
  - Nature 459(7248):786-787 (2009)
  Most syntheses in organic chemistry target one molecule, or a few closely related analogues at most. But by taking a leaf from nature's book, the latest synthetic strategy opens the door to a whole family of compounds.
• Cell biology: The proteasome assembly line
  - Nature 459(7248):787-788 (2009)
  The assembly of the proteasome — the cellular machine that eliminates unwanted proteins — is a carefully choreographed affair, involving a complex sequence of steps overseen by dedicated protein chaperones.
• Solar eclipses as an astrophysical laboratory
  - Nature 459(7248):789-795 (2009)
  Observations of the Sun during total eclipses have led to major discoveries, such as the existence of helium (from its spectrum), the high temperature of the corona (though the reason for the high temperature remains controversial), and the role of magnetic fields in injecting energy into—and trapping ionized gases within—stellar atmospheres. A new generation of ground-based eclipse observations reaches spatial, temporal and spectral-resolution domains that are inaccessible from space and therefore complement satellite studies.
• Early Cambrian ocean anoxia in South China
  - Nature 459(7248):E5 (2009)
  Arising from: M. Wille, T. F. Nägler, B. Lehmann, S. Schröder & J. D. Kramers Nature 453, 767–769 (2008); Wille et al. reply The cause of the most marked changes in the evolution of life, which define the first-order stratigraphic boundary between the Precambrian and the Phanerozoic eon, remains enigmatic and a highly topical subject of debate. A global ocean anoxic event, triggered by large-scale hydrogen sulphide (H2S) release to surface waters, has been suggested by Wille et al. 1, on the basis of two data sets from South China and Oman, to explain the fundamental biological changes across the Precambrian/Cambrian (PC/C) boundary. Here we report a new precise SHRIMP U–Pb zircon age of 532.3 plusminus 0.7 million years (Myr) ago (Fig. 1) for a volcanic ash bed in the critical unit that reflects the ocean anoxic event, the lowermost black shale sequence of the Niutitang Formation in the Guizhou Province, South China. This age is significantly younger than the precise PC/C boundary age of 542.0 plusminus 0.3 Myr ago2, approximately 10 Myr younger than the extinction of the Ediacaran fauna, and th us challenging the view of a major ocean anoxic event having been responsible for the major changes in the direction of evolution at the PC/C boundary.
• Wille et al. reply
  - Nature 459(7248):E6 (2009)
  Replying to: S.-Y. Jiang et al. Nature 459, 10.1038/nature08048 (2009) Jiang et al. 1 present a new SHRIMP U–Pb zircon age of 532.3 plusminus 0.7 million years (Myr) ago for an ash bed in the lowermost black shale sequence of the Niutitang Formation, China, and claim that the data presented in our recent paper2 do not firmly support the idea that the biological and environmental changes at the Precambrian/Cambrian transition can be explained by a single global hydrogen sulphide (H2S) release event. Their new age seems to be supported by another recent SHRIMP investigation3 which indeed suggests that the Chinese metal-enriched sulphide layer does not represent the Precambrian/Cambrian boundary and shows that the redox history of both basins (Oman and South China) was much more complex.
• Dual nature of the adaptive immune system in lampreys
  Guo P Hirano M Herrin BR Li J Yu C Sadlonova A Cooper MD - Nature 459(7248):796-801 (2009)
  Jawless vertebrates use variable lymphocyte receptors (VLR) comprised of leucine-rich-repeat (LRR) segments as counterparts of the immunoglobulin-based receptors that jawed vertebrates use for antigen recognition. Highly diverse VLR genes are somatically assembled by the insertion of variable LRR sequences into incomplete germline VLRA and VLRB genes. Here we show that in sea lampreys (Petromyzon marinus) VLRA and VLRB anticipatory receptors are expressed by separate lymphocyte populations by monoallelic VLRA or VLRB assembly, together with expression of cytosine deaminase 1 (CDA1) or 2 (CDA2), respectively. Distinctive gene expression profiles for VLRA+ and VLRB+ lymphocytes resemble those of mammalian T and B cells. Although both the VLRA and the VLRB cells proliferate in response to antigenic stimulation, only the VLRB lymphocytes bind native antigens and differentiate into VLR antibody-secreting cells. Conversely, VLRA lymphocytes respond preferentially to a classic al T-cell mitogen and upregulate the expression of the pro-inflammatory cytokine genes interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF). The finding of T-like and B-like lymphocytes in lampreys offers new insight into the evolution of adaptive immunity.
• Histone H4 lysine 16 acetylation regulates cellular lifespan
  - Nature 459(7248):802-807 (2009)
  Cells undergoing developmental processes are characterized by persistent non-genetic alterations in chromatin, termed epigenetic changes, represented by distinct patterns of DNA methylation and histone post-translational modifications. Sirtuins, a group of conserved NAD+-dependent deacetylases or ADP-ribosyltransferases, promote longevity in diverse organisms; however, their molecular mechanisms in ageing regulation remain poorly understood. Yeast Sir2, the first member of the family to be found, establishes and maintains chromatin silencing by removing histone H4 lysine 16 acetylation and bringing in other silencing proteins. Here we report an age-associated decrease in Sir2 protein abundance accompanied by an increase in H4 lysine 16 acetylation and loss of histones at specific subtelomeric regions in replicatively old yeast cells, which results in compromised transcriptional silencing at these loci. Antagonizing activities of Sir2 and Sas2, a histone acetyltransferas e, regulate the replicative lifespan through histone H4 lysine 16 at subtelomeric regions. This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin.
• Flipping of alkylated DNA damage bridges base and nucleotide excision repair
  - Nature 459(7248):808-813 (2009)
  Alkyltransferase-like proteins (ATLs) share functional motifs with the cancer chemotherapy target O 6-alkylguanine-DNA alkyltransferase (AGT) and paradoxically protect cells from the biological effects of DNA alkylation damage, despite lacking the reactive cysteine and alkyltransferase activity of AGT. Here we determine Schizosaccharomyces pombe ATL structures without and with damaged DNA containing the endogenous lesion O 6-methylguanine or cigarette-smoke-derived O 6-4-(3-pyridyl)-4-oxobutylguanine. These results reveal non-enzymatic DNA nucleotide flipping plus increased DNA distortion and binding pocket size compared to AGT. Our analysis of lesion-binding site conservation identifies new ATLs in sea anemone and ancestral archaea, indicating that ATL interactions are ancestral to present-day repair pathways in all domains of life. Genetic connections to mammalian XPG (also known as ERCC5) and ERCC1 in S. pombe homologues Rad13 and Swi10 and biochemical interactions w ith Escherichia coli UvrA and UvrC combined with structural results reveal that ATLs sculpt alkylated DNA to create a genetic and structural intersection of base damage processing with nucleotide excision repair.
• Earth's transmission spectrum from lunar eclipse observations
  - Nature 459(7248):814-816 (2009)
  Of the 342 planets so far discovered1 orbiting other stars, 58 'transit' the stellar disk, meaning that they can be detected through a periodic decrease in the flux of starlight2. The light from the star passes through the atmosphere of the planet, and in a few cases the basic atmospheric composition of the planet can be estimated3, 4, 5. As we get closer to finding analogues of Earth6, 7, 8, an important consideration for the characterization of extrasolar planetary atmospheres is what the transmission spectrum of our planet looks like. Here we report the optical and near-infrared transmission spectrum of the Earth, obtained during a lunar eclipse. Some biologically relevant atmospheric features that are weak in the reflection spectrum9 (such as ozone, molecular oxygen, water, carbon dioxide and methane) are much stronger in the transmission spectrum, and indeed stronger than predicted by modelling10, 11. We also find the 'fingerprints' of the Earth's ionosphere and of the major atmospheric constituent, molecular nitrogen (N2), which are missing in the reflection spectrum.
• Existence of collisional trajectories of Mercury, Mars and Venus with the Earth
  - Nature 459(7248):817-819 (2009)
  It has been established that, owing to the proximity of a resonance with Jupiter, Mercury's eccentricity can be pumped to values large enough to allow collision with Venus within 5 Gyr (refs 1–3). This conclusion, however, was established either with averaged equations1, 2 that are not appropriate near the collisions or with non-relativistic models in which the resonance effect is greatly enhanced by a decrease of the perihelion velocity of Mercury2, 3. In these previous studies, the Earth's orbit was essentially unaffected. Here we report numerical simulations of the evolution of the Solar System over 5 Gyr, including contributions from the Moon and general relativity. In a set of 2,501 orbits with initial conditions that are in agreement with our present knowledge of the parameters of the Solar System, we found, as in previous studies2, that one per cent of the solutions lead to a large increase in Mercury's eccentricity—an increase large enough to allow collision s with Venus or the Sun. More surprisingly, in one of these high-eccentricity solutions, a subsequent decrease in Mercury's eccentricity induces a transfer of angular momentum from the giant planets that destabilizes all the terrestrial planets approx3.34 Gyr from now, with possible collisions of Mercury, Mars or Venus with the Earth.
• Direct observation of a widely tunable bandgap in bilayer graphene
  - Nature 459(7248):820-823 (2009)
  The electronic bandgap is an intrinsic property of semiconductors and insulators that largely determines their transport and optical properties. As such, it has a central role in modern device physics and technology and governs the operation of semiconductor devices such as p–n junctions, transistors, photodiodes and lasers1. A tunable bandgap would be highly desirable because it would allow great flexibility in design and optimization of such devices, in particular if it could be tuned by applying a variable external electric field. However, in conventional materials, the bandgap is fixed by their crystalline structure, preventing such bandgap control. Here we demonstrate the realization of a widely tunable electronic bandgap in electrically gated bilayer graphene. Using a dual-gate bilayer graphene field-effect transistor (FET)2 and infrared microspectroscopy3, 4, 5, we demonstrate a gate-controlled, continuously tunable bandgap of up to 250 meV. Our technique avoid s uncontrolled chemical doping6, 7, 8 and provides direct evidence of a widely tunable bandgap—spanning a spectral range from zero to mid-infrared—that has eluded previous attempts2, 9. Combined with the remarkable electrical transport properties of such systems, this electrostatic bandgap control suggests novel nanoelectronic and nanophotonic device applications based on graphene.
• Total synthesis of eudesmane terpenes by site-selective C–H oxidations
  - Nature 459(7248):824-828 (2009)
  From menthol to cholesterol to Taxol, terpenes are a ubiquitous group of molecules (over 55,000 members isolated so far) that have long provided humans with flavours, fragrances, hormones, medicines and even commercial products such as rubber1. Although they possess a seemingly endless variety of architectural complexities, the biosynthesis of terpenes often occurs in a unified fashion as a 'two-phase' process2, 3. In the first phase (the cyclase phase), simple linear hydrocarbon phosphate building blocks are stitched together by means of 'prenyl coupling', followed by enzymatically controlled molecular cyclizations and rearrangements. In the second phase (the oxidase phase), oxidation of alkenes and carbon–hydrogen bonds results in a large array of structural diversity. Although organic chemists have made great progress in developing the logic3, 4, 5 needed for the cyclase phase of terpene synthesis, particularly in the area of polyene cyclizations6, much remains to be learned if the oxidase phase is to be mimicked in the laboratory. Here we show how the logic of terpene biosynthesis has inspired the highly efficient and stereocontrolled syntheses of five oxidized members of the eudesmane family of terpenes in a modicum of steps by a series of simple carbocycle-forming reactions followed by multiple site-selective inter- and intramolecular carbon–hydrogen oxidations. This work establishes an intellectual framework in which to conceive the laboratory synthesis of other complex terpenes using a 'two-phase' approach.
• The proportionality of global warming to cumulative carbon emissions
  - Nature 459(7248):829-832 (2009)
  The global temperature response to increasing atmospheric CO2 is often quantified by metrics such as equilibrium climate sensitivity and transient climate response1. These approaches, however, do not account for carbon cycle feedbacks and therefore do not fully represent the net response of the Earth system to anthropogenic CO2 emissions. Climate–carbon modelling experiments have shown that: (1) the warming per unit CO2 emitted does not depend on the background CO2 concentration2; (2) the total allowable emissions for climate stabilization do not depend on the timing of those emissions3, 4, 5; and (3) the temperature response to a pulse of CO2 is approximately constant on timescales of decades to centuries3, 6, 7, 8. Here we generalize these results and show that the carbon–climate response (CCR), defined as the ratio of temperature change to cumulative carbon emissions, is approximately independent of both the atmospheric CO2 concentration and its rate of change on these timescales. From observational constraints, we estimate CCR to be in the range 1.0–2.1 °C per trillion tonnes of carbon (Tt C) emitted (5th to 95th percentiles), consistent with twenty-first-century CCR values simulated by climate–carbon models. Uncertainty in land-use CO2 emissions and aerosol forcing, however, means that higher observationally constrained values cannot be excluded. The CCR, when evaluated from climate–carbon models under idealized conditions, represents a simple yet robust metric for comparing models, which aggregates both climate feedbacks and carbon cycle feedbacks. CCR is also likely to be a useful concept for climate change mitigation and policy; by combining the uncertainties associated with climate sensitivity, carbon sinks and climate–carbon feedbacks into a single quantity, the CCR allows CO2-induced global mean temperature change to be inferred directly from cumulative carbon emissions.
• Slow earthquakes triggered by typhoons
  - Nature 459(7248):833-836 (2009)
  The first reports1, 2 on a slow earthquake were for an event in the Izu peninsula, Japan, on an intraplate, seismically active fault. Since then, many slow earthquakes have been detected3, 4, 5, 6, 7, 8. It has been suggested9 that the slow events may trigger ordinary earthquakes (in a context supported by numerical modelling10), but their broader significance in terms of earthquake occurrence remains unclear. Triggering of earthquakes has received much attention: strain diffusion from large regional earthquakes has been shown to influence large earthquake activity11, 12, and earthquakes may be triggered during the passage of teleseismic waves13, a phenomenon now recognized as being common14, 15, 16, 17. Here we show that, in eastern Taiwan, slow earthquakes can be triggered by typhoons. We model the largest of these earthquakes as repeated episodes of slow slip on a reverse fault just under land and dipping to the west; the characteristics of all events are sufficientl y similar that they can be modelled with minor variations of the model parameters. Lower pressure results in a very small unclamping of the fault that must be close to the failure condition for the typhoon to act as a trigger. This area experiences very high compressional deformation but has a paucity of large earthquakes; repeating slow events may be segmenting the stressed area and thus inhibiting large earthquakes, which require a long, continuous seismic rupture.
• Two types of dopamine neuron distinctly convey positive and negative motivational signals
  - Nature 459(7248):837-841 (2009)
  Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward1, 2, 3, 4. These excitatory responses increase as the reward value increases5. This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is true only for a subset of dopamine neurons. We recorded the activity of dopamine neurons in monkeys (Macaca mulatta) during a Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face, respectively). We found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value hypothesis predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the hypothesis. Some dopamine neurons were also excited by both rewards and airpuffs themselves, especially when they were unpredictable. Neurons excited by the airpuff-predicting stimuli were located more dorsolaterally in the substantia nigra pars compacta, whereas neurons inhibited by the stimuli were located more ventromedially, some in the ventral tegmental area. A similar anatomical difference was observed for their responses to actual airpuffs. These findings suggest that different groups of dopamine neurons convey motivational signals in distinct manners.
• Specificity of sensory–motor connections encoded by Sema3e–Plxnd1 recognition
  - Nature 459(7248):842-846 (2009)
  Spinal reflexes are mediated by synaptic connections between sensory afferents and motor neurons1, 2, 3. The organization of these circuits shows several levels of specificity. Only certain classes of proprioceptive sensory neurons make direct, monosynaptic connections with motor neurons4. Those that do are bound by rules of motor pool specificity: they form strong connections with motor neurons supplying the same muscle, but avoid motor pools supplying antagonistic muscles1, 5, 6, 7. This pattern of connectivity is initially accurate and is maintained in the absence of activity8, implying that wiring specificity relies on the matching of recognition molecules on the surface of sensory and motor neurons. However, determinants of fine synaptic specificity here, as in most regions of the central nervous system, have yet to be defined. To address the origins of synaptic specificity in these reflex circuits we have used molecular genetic methods to manipulate recognition pr oteins expressed by subsets of sensory and motor neurons. We show here that a recognition system involving expression of the class 3 semaphorin Sema3e by selected motor neuron pools, and its high-affinity receptor plexin D1 (Plxnd1) by proprioceptive sensory neurons, is a critical determinant of synaptic specificity in sensory–motor circuits in mice. Changing the profile of Sema3e–Plxnd1 signalling in sensory or motor neurons results in functional and anatomical rewiring of monosynaptic connections, but does not alter motor pool specificity. Our findings indicate that patterns of monosynaptic connectivity in this prototypic central nervous system circuit are constructed through a recognition program based on repellent signalling.
• Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger
  - Nature 459(7248):847-851 (2009)
  Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities1. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states1, 2. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders3. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias4, 5, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abr ogated H3K4me3 binding also abolished leukaemic transformation. NUP98–PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98–PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.
• Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle
  - Nature 459(7248):852-856 (2009)
  Cells normally grow to a certain size before they enter mitosis and divide. Entry into mitosis depends on the activity of Cdk1, which is inhibited by the Wee1 kinase and activated by the Cdc25 phosphatase1. However, how cells sense their size for mitotic commitment remains unknown. Here we show that an intracellular gradient of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) Pom1, which emanates from the ends of rod-shaped Schizosaccharomyces pombe cells, serves to measure cell length and control mitotic entry. Pom1 provides positional information both for polarized growth and to inhibit cell division at cell ends2, 3, 4, 5. We discovered that Pom1 is also a dose-dependent G2–M inhibitor. Genetic analyses indicate that Pom1 negatively regulates Cdr1 and Cdr2, two previously described Wee1 inhibitors of the SAD kinase family6, 7, 8, 9, 10. This inhibition may be direct, because in vivo and in vitro evidence suggest that Pom1 phosphorylates Cdr2. W hereas Cdr1 and Cdr2 localize to a medial cortical region, Pom1 forms concentration gradients from cell tips that overlap with Cdr1 and Cdr2 in short cells, but not in long cells. Disturbing these Pom1 gradients leads to Cdr2 phosphorylation and imposes a G2 delay. In short cells, Pom1 prevents precocious M-phase entry, suggesting that the higher medial Pom1 levels inhibit Cdr2 and promote a G2 delay. Thus, gradients of Pom1 from cell ends provide a measure of cell length to regulate M-phase entry.
• A spatial gradient coordinates cell size and mitotic entry in fission yeast
  - Nature 459(7248):857-860 (2009)
  Many eukaryotic cell types undergo size-dependent cell cycle transitions controlled by the ubiquitous cyclin-dependent kinase Cdk1 (refs 1–4). The proteins that control Cdk1 activity are well described but their links with mechanisms monitoring cell size remain elusive. In the fission yeast Schizosaccharomyces pombe, cells enter mitosis and divide at a defined and reproducible size owing to the regulated activity of Cdk1 (refs 2, 3). Here we show that the cell polarity protein kinase Pom1, which localizes to cell ends5, regulates a signalling network that contributes to the control of mitotic entry. This network is located at cortical nodes in the middle of interphase cells, and these nodes contain the Cdk1 inhibitor Wee1, the Wee1-inhibitory kinases Cdr1 (also known as Nim1) and Cdr2, and the anillin-like protein Mid1. Cdr2 establishes the hierarchical localization of other proteins in the nodes, and receives negative regulatory signals from Pom1. Pom1 forms a polar gradient extending from the cell ends towards the cell middle and acts as a dose-dependent inhibitor of mitotic entry, working through the Cdr2 pathway. As cells elongate, Pom1 levels decrease at the cell middle, leading to mitotic entry. We propose that the Pom1 polar gradient and the medial cortical nodes generate information about cell size and coordinate this with mitotic entry by regulating Cdk1 through Pom1, Cdr2, Cdr1 and Wee1.
• Chaperone-mediated pathway of proteasome regulatory particle assembly
  - Nature 459(7248):861-865 (2009)
  The proteasome is a protease that controls diverse processes in eukaryotic cells. Its regulatory particle (RP) initiates the degradation of ubiquitin–protein conjugates by unfolding the substrate and translocating it into the proteasome core particle (CP) to be degraded1. The RP has 19 subunits, and their pathway of assembly is not understood. Here we show that in the yeast Saccharomyces cerevisiae three proteins are found associated with RP but not with the RP–CP holoenzyme: Nas6, Rpn14 and Hsm3. Mutations in the corresponding genes confer proteasome loss-of-function phenotypes, despite their virtual absence from the holoenzyme. These effects result from deficient RP assembly. Thus, Nas6, Rpn14 and Hsm3 are RP chaperones. The RP contains six ATPases–the Rpt proteins–and each RP chaperone binds to the carboxy-terminal domain of a specific Rpt. We show in an accompanying study2 that RP assembly is templated through the Rpt C termini, apparently by their insertion into binding pockets in the CP. Thus, RP chaperones may regulate proteasome assembly by directly restricting the accessibility of Rpt C termini to the CP. In addition, competition between the RP chaperones and the CP for Rpt engagement may explain the release of RP chaperones as proteasomes mature.
• Hexameric assembly of the proteasomal ATPases is templated through their C termini
  - Nature 459(7248):866-870 (2009)
  Substrates of the proteasome are recognized and unfolded by the regulatory particle, and then translocated into the core particle (CP) to be degraded1. A hetero-hexameric ATPase ring, containing subunits Rpt1-6, is situated within the base subassembly of the regulatory particle1. The ATPase ring sits atop the CP, with the Rpt carboxy termini inserted into pockets in the CP2, 3, 4, 5, 6. Here we identify a previously unknown function of the Rpt proteins in proteasome biogenesis through deleting the C-terminal residue from each Rpt in the yeast Saccharomyces cerevisiae. Our results indicate that assembly of the hexameric ATPase ring is templated on the CP. We have also identified an apparent intermediate in base assembly, BP1, which contains Rpn1, three Rpts and Hsm3, a chaperone for base assembly. The Rpt proteins with the strongest assembly phenotypes, Rpt4 and Rpt6, were absent from BP1. We propose that Rpt4 and Rpt6 form a nucleating complex to initiate base assembly, and that this complex is subsequently joined by BP1 to complete the Rpt ring. Our studies show that assembly of the proteasome base is a rapid yet highly orchestrated process.
• An unusual carbon–carbon bond cleavage reaction during phosphinothricin biosynthesis
  - Nature 459(7248):871-874 (2009)
  Natural products containing phosphorus–carbon bonds have found widespread use in medicine and agriculture1. One such compound, phosphinothricin tripeptide, contains the unusual amino acid phosphinothricin attached to two alanine residues. Synthetic phosphinothricin (glufosinate) is a component of two top-selling herbicides (Basta and Liberty), and is widely used with resistant transgenic crops including corn, cotton and canola. Recent genetic and biochemical studies showed that during phosphinothricin tripeptide biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP)2. Here we report the in vitro reconstitution of this unprecedented C(sp 3)–C(sp 3) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-haem iron(ii)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members of this family, the oxidative consumption of HEP does not require additional co factors or the input of exogenous electrons. The current study expands the scope of reactions catalysed by the 2-His–1-carboxylate mononuclear non-haem iron family of enzymes.
• Timed release
  - Nature 459(7248):880 (2009)
  Clean thoughts.