Hot off the presses! Jul 30 Nature

The Jul 30 issue of the Nature is now up on Pubget (About Nature): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Information overload
  - Nature 460(7255):551 (2009)
  A report released last week by the US National Academies makes recommendations for tackling the issues surrounding the era of petabyte science.
• The shale revolution
  - Nature 460(7255):551-552 (2009)
  The vast reserves of US natural gas must be used judiciously to ease the transition to clean energy.
• Inspiring non-scientists
  - Nature 460(7255):552 (2009)
  Those wishing to reveal scientific ideas should learn from the engaging style of TED conference talks.
• Biology: Chill bill
  - Nature 460(7255):554 (2009)
  
• Phytology: Tree carbon recalibrated?
  - Nature 460(7255):554 (2009)
  
• Nanochemistry: Protein fondue
  - Nature 460(7255):554 (2009)
  
• Cancer biology: Cancer's metabolic roots
  - Nature 460(7255):554 (2009)
  
• Microfluidics: The sounds of science
  - Nature 460(7255):554 (2009)
  
• Earth monitoring: Tsunamis from space
  - Nature 460(7255):555 (2009)
  
• Chemistry: A one-pot shot
  - Nature 460(7255):555 (2009)
  
• Behaviour: Why 'there's never just one'
  - Nature 460(7255):555 (2009)
  
• Physics: A cold shake
  - Nature 460(7255):555 (2009)
  
• Development: Starting from scratch
  - Nature 460(7255):555 (2009)
  
• Journal club
  - Nature 460(7255):555 (2009)
  
• Biodefence lab criticized
  - Nature 460(7255):556-557 (2009)
  The US government's decision to locate a new national biosecurity lab in Manhattan, Kansas, has been called into question by a congressional watchdog. The Government Accountability Office (GAO) concluded that the Department of Homeland Security (DHS) relied on a flawed risk assessment when deciding the location of the US$650-million National Bio and Agro-Defense Facility.
• Physicians fight back against disclosure rules
  - Nature 460(7255):556-557 (2009)
  Even as US legislators work to limit ties between academic physicians and industry, a small group of doctors is calling for greater industry collaboration. On 23 July, they gathered at Brigham and Women's Hospital in Boston to launch a new organization opposed to strict conflict-of-interest rules.
• European body told to cut free
  - Nature 460(7255):557 (2009)
  The European Commission must make "immediate corrections" to the running of the European Research Council (ERC) or risk the body suffering a "deadly blow", an expert review has found. On 23 July, a panel led by the former president of Latvia, Vaira Vike-Freiberga, published a review of the ERC — the first pan-European initiative to fund frontier research solely on the basis of excellence.
• LHC students face data drought
  - Nature 460(7255):558 (2009)
  Computer simulations are the only option when the world's largest particle accelerator isn't working. Last November, Sara Bolognesi stood before a committee at the University of Turin in Italy and defended her PhD thesis in experimental high-energy physics. The 180-page document is a treatise on finding the Higgs boson, part of the mechanism believed to endow all other matter with mass. The pages are crammed with dozens of figures and tables, but something is missing: real data. Sara Bolognesi hopes to move from simulated experiments to real data collection at CERN. That's because the Large Hadron Collider (LHC), the world's largest particle accelerator at CERN, outside Geneva in Switzerland, is broken. The 4.6-billion Swiss franc (US$4.3-billion) collider is designed to accelerate protons to near the speed of light and smash them together in four giant detectors spread around its 27-kilometre circumference. Physicists once hoped that the LHC would start its collisions in late 2006, but last September, after a series of delays and soon after the machine was switched on, an electrical short caused extensive damage along a sector of the machine. Repairs have taken longer than expected, and, as of last week, the LHC was not scheduled to restart before mid-November. The long delays have ended the dreams of a generation of graduate students hoping to use fresh data for their theses. With no machine to deliver results, "people are doing experimental PhDs and effectively doing very little experimenting", says Will Reece, a graduate student at Imperial College London working on a detector known as LHCb. "It's a strange situation." "People are doing experimental PhDs and effectively doing very little experimenting." Strange but not unprecedented, says Rolf-Dieter Heuer, CERN's director-general. During the mid-1980s, physicists were focused on building the Large Electron–Positron collider, the predecessor to the LHC. Over that period, Heuer says, graduate students sometimes wrote theses based on data from detector tests. Today, many of the same physicists work on the LHC project. But although the electron collider took a few years to build, construction of the LHC took more than a decade, and most testing for the current detectors ended years ago. Aside from a trickle of data created by stray cosmic rays hitting the detectors, there will be no data to be analysed until the collider restarts. "It's a mess," says Burton Richter, a Nobel-prizewinning physicist at the SLAC National Accelerator Laboratory in Menlo Park, California. European graduate students such as Bolognesi face strict time constraints for completing their PhDs. Most universities require a thesis to be submitted within three to four years, and that means that students cannot wait for their data. Instead, their analyses are being done with data from 'Monte Carlo' simulations — computer programs that replicate what might come out of real collisions. Not everybody thinks that the simulated data are a problem. "I don't feel that bad about not having data in my thesis," says Carsten Hof, a graduate student at Aachen University in Germany, who is finishing his PhD on software that will automatically analyse real collisions. "All the bugs we found and fixed now will also be fixed for real data." Hof adds that the data drought may actually be an advantage. "You look at everything with no bias," he says. Heuer says that the situation reflects the growing size and sophistication of high-energy physics experiments. Whereas early experiments could be done in days by a handful of people, machines such as the LHC take thousands of researchers years to complete. The current generation of students may not be familiar with real data, he says, but they have extensive experience in building the huge detectors needed to capture them. Future PhD students will work on software without touching the innards of the detectors, he points out. As long as students get a taste of what's involved with each stage of the project, he says, "I don't think that people are losing anything." Others are more worried. Although Monte Carlo simulations can reproduce the uncertainties seen in real data, they will never contain a big surprise. That means simulated data can never be as good as the real thing, says Gustaaf Brooijmans, a physicist at Columbia University in New York. "It's like a badly written murder mystery," he says. "In the first chapter you're given enough information that you know who did it, and then you read the rest of the book, and, lo and behold, you get the right answer." For this reason, Columbia and other US institutions require students to use real data in their PhD theses. That solves the data dilemma, but creates a new problem: US students working on the LHC must move to finish their theses. For students such as Ketino Kaadze of Kansas State University in Manhattan, this meant travelling from Geneva to Batavia, Illinois, the home of the world's other major particle collider, the Tevatron. ADVERTISEMENT Kaadze says that she was initially nervous about the move from one experiment to the other, but she has found it valuable. Although it will take her longer to complete her PhD, she is glad to have made the switch. "I think it's very important to have this experience," she says. Now at CERN for a postdoctoral fellowship, Bolognesi worries that she will be at a disadvantage compared with students like Kaadze. "Two years from now, I will have to search for work," she says. "I hope they will not discriminate against me." By the time she is looking for a job, the LHC should have completed its first run, and Bolognesi will hopefully have completed a first of her own — an analysis of real collisions. 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
• Italy introduces performance-related funding
  - Nature 460(7255):559 (2009)
  Agency to evaluate research is launched. The Italian government has finally given the go-ahead to a national research evaluation agency, ANVUR. But at the same time it published Italy's first university ranking and said performance-related funding would begin immediately. The 24 July announcement of ANVUR was welcomed by many scientists who say that the country has not adequately rewarded best-performing research institutions. A law creating the agency was passed two years ago, but not put into practice until now. ANVUR should start work in about a year, says Mariastella Gelmini, the minister of universities and research. Her ranking of universities caused political outcry however. Up to 7% of the approximately €7-billion (US$10-billion) national university budget will be allocated according to the list. Universities in the centre and north of the country generally did well, but most universities in the poorer south ranked at the bottom. The ranking was based on an internal research evaluation carried out several years ago, combined with other criteria intended to assess teaching quality. Raffaele Lombardo, president of Sicily, denounced the ranking criteria as discriminatory. Poor infrastructure in many southern universities prevents them from attracting independent research funds, he said in newspaper interviews, and high unemployment rates make it hard for graduates to find jobs, a criterion used to measure effectiveness of teaching. Lombardo and others also criticized the use of old bibliometric data. ADVERTISEMENT All universities are concerned that performance-related funding is being introduced in a year when the government plans a 10% cut in the university budget. Davide Bassi, rector of the top-ranking University of Trento, says that this will be a "disaster for all universities, including our own". Details of ANVUR's operation have yet to be set, but it is likely to be responsible for fine-tuning the criteria used in ranking exercises. 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
• Forest growth studies begin to turn up the heat
  - Nature 460(7255):559 (2009)
  Across the United States, researchers are firing up experiments to determine how rising temperatures could reshape the nation's forests. The studies encompass the pines and maples of eastern forests in Massachusetts and North Carolina, the spruce and fir of northern Minnesota, and the alpine tundra ecosystem above the treeline in the Rocky Mountains in Colorado.
• Mice made from induced stem cells
  - Nature 460(7255):560 (2009)
  Two teams of Chinese researchers have created live mice from induced pluripotent stem (iPS) cells, answering a lingering question about the developmental potential of the cells. Since Shinya Yamanaka of Kyoto University in Japan created the first iPS cells1 in 2006, researchers have wondered whether they could generate an entire mammalian body from iPS cells, as they have from true embryonic stem cells.
• Legal battle may reshape nanotechnology firm
  - Nature 460(7255):561 (2009)
  Oxonica, one of the United Kingdom's leading nanotechnology companies (see Nature 446, 963; 2007.
• US puts flu vaccines on trial
  - Nature 460(7255):562 (2009)
  NIAID director Anthony Fauci explains testing strategy. Anthony Fauci.J. Reed/Reuters The US National Institute of Allergy and Infectious Diseases (NIAID) announced last week that it will begin five clinical trials for two pandemic H1N1 influenza vaccines in early August. These trials will help inform a likely US mass-vaccination campaign beginning in September. NIAID director Anthony Fauci talks about what vaccines were chosen, and why. We have planned seven priority trials. The five I announced on 22 July are for non-adjuvanted vaccines, but we also plan two more: testing GlaxoSmithKline's AS03 adjuvant with vaccine from Sanofi Pasteur and from CSL Biotherapies. We prioritized non-adjuvanted vaccines as the US government seems likely to recommend using these for vaccinating the first tier of priority groups — expected to include children and groups at higher risk of severe disease, such as those with certain underlying illnesses and pregnant women. We fully intend to proceed with trials of adjuvanted vaccines. The Europeans have lots of data on the use of adjuvanted flu vaccine in the elderly, but I don't think anybody has really good data on adjuvants in children. The Department of Health and Human Services (DHHS) has therefore decided that we are not going to take the chance, and has made a policy decision that we are not going to give adjuvanted flu vaccines to kids. We don't have the time to collect substantial data. Yes. But, as in other countries, there are many ethical constraints. We are working with both principal investigators and institutional review boards to draw up protocols for such groups. Even if the Food and Drug Administration (FDA) is considering the initial non-adjuvanted vaccines as simply a strain substitution of seasonal vaccine, it's still a new vaccine, so we want to get data from healthy adults before launching into risk groups. We are asking questions that will inform policy decisions likely to affect how we use vaccines, whereas the focus of vaccine makers is generally directed towards studies needed to get a licence for their vaccine. The sort of information that the FDA, DHHS and the vaccine makers told us they needed most included what levels of antigen per dose are essential to getting an adequate immune response, and whether one or two shots of vaccine will be needed. So two trials will test both single and double shots of both 15-microgram [the amount in seasonal H1N1 vaccine] or 30-µg doses of antigen, using antigen from Sanofi Pasteur and from CSL Biotherapies. We will give the first doses in the first week or so of August, and the second dose 21 days later. We will learn very quickly after 21 days, when we draw blood, if one dose of 15 µg is enough. And if it isn't, if 30 µg is any better. And if 15 µg is enough, does 30 µg give an even better response? Shortly after 42 days, we will have data on the second doses. Novartis has quite a sophisticated clinical-trials apparatus. The United States will purchase 45% from Novartis, 26% from Sanofi Pasteur and a little bit less than 19% from CSL Biotherapies. Novartis is able to carry the ball itself, so we made a reasonably well-based decision to fill in the gaps and get information on CSL and Sanofi Pasteur. We don't know. Testing two vaccines against different H1N1s at the same time has never been done. We'll look at three test regimes: giving the pandemic 2009 vaccine before, at the same time as, or after seasonal H1N1 vaccine. ADVERTISEMENT If you give the pandemic H1N1 vaccine first, will subsequently giving the seasonal H1N1 enhance the response to the original dose, or will there be antigenic competition or interference? If you give both at same time, is the body going to have a response that is enhanced against seasonal flu and not do a very good job against the pandemic vaccine, or will it actually amplify the response? And if you give pandemic vaccine after [seasonal vaccine], is that going to have an enhancing or suppressing effect? Immunologically, you can't predict the outcome. You never can predict that, but things look encouraging to me from a molecular-virological standpoint. If you look at the molecular and genetic make-up of the virus from the very first isolates in early April compared to what we are seeing now in late July, it's virtually an identical virus everywhere. So it doesn't look like it is under pressure to mutate to a significant degree. We hope it stays that way for the autumn and winter season. www.nature.com/swineflu 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 research bodies draft synthetic-biology plan
  - Nature 460(7255):563 (2009)
  
• Step-by-step rating system set to improve African labs
  - Nature 460(7255):563 (2009)
  The number of accredited labs in Africa may rise.AM. SOC. CLIN. PATHOL. An accreditation system that aims to raise the standard of disease diagnosis in African medical laboratories was launched on 27 July in Kigali, Rwanda. The process, developed by the World Health Organization in collaboration with the US government, will mark African pathology labs on an incremental scale, upping the rating as their quality improves rather than using the 'pass or fail' system of many developed countries. The scheme was launched alongside a training programme for African lab workers. The US Centers for Disease Control and Prevention in Atlanta, Georgia, which will implement the step-by-step system, estimates that it could see 60 currently unaccredited African laboratories attain ratings verging on the standard of an average lab in the developed world over the next two years. 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 government urged to disclose evidence base
  - Nature 460(7255):563 (2009)
  
• Mauna Kea adds to its family of telescopes
  - Nature 460(7255):563 (2009)
  Mauna Kea in Hawaii has beaten off competition from Cerro Armazones, in Chile's Atacama desert, to host the Thirty Meter Telescope. Henry Yang, chancellor of the University of California, Santa Barbara, and chair of the telescope's board of directors, announced the winning site on 21 July. The decision has been two years in the making, he said. Mauna Kea, which already hosts many other telescopes, was picked over its Chilean rival for its superior observing climate. It is higher and drier, has less atmospheric turbulence, and its average temperature fluctuates less through the year and over a day, notes board member Richard Ellis of the California Institute of Technology in Pasadena. Construction of the telescope, which will cost around US$1 billion, is scheduled to begin in 2011 and end in 2018. 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
• Genetic barcode for plants close to agreement
  - Nature 460(7255):563 (2009)
  
• Lucky find of undersea methane bubbles
  - Nature 460(7255):563 (2009)
  NOAA While testing equipment off the Californian coast last month, a newly refitted research vessel stumbled across plumes of methane gas rising 1,400 metres from the sea floor. The Okeanos Explorer, commissioned last year by the US National Oceanic and Atmospheric Administration (NOAA) after a US$20-million refit, was testing a new multi-beam sonar system in the Mendocino fracture zone (see sonar image, above). On 15 July the ship returned to the site to capture plume material for analysis in the coming weeks. The plumes, which measure up to 1 kilometre across, typically dissipate about 600 metres below the surface. Cruise scientist Stephen Hammond of the NOAA office in Newport, Oregon, suspects this is because ice with methane gas trapped in its crystal structure melts at the combination of pressure and temperature at that depth. Similar methane plumes have been discovered from the Oregon coast to the Black Sea, but not this large or numerous. 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
• Wind power: High hopes
  - Nature 460(7255):564-566 (2009)
  A ride on a kite boat might just kill you from fright — if it doesn't crush you first. The vessel is essentially an 8-metre catamaran dragged behind a kite the size of a movie screen — a lot of horsepower for such a small craft.
• Immunology: Lights, camera, infection
  - Nature 460(7255):568-570 (2009)
  Behind the heavy black curtains of his microscopy room, Mark Miller is shooting an action movie. He gives the settings on the multiphoton microscope a once-over while his senior scientist Vjollca Konjufca checks the sedated mouse on the warmed stage.
• Flu: vaccinate to cut risk of chimaeric virus emerging
  - Nature 460(7255):571 (2009)
  The international scientific community and decision-makers on public health are debating how best to manage the anticipated vaccine shortage for the new pandemic strain of influenza A virus, recently emerged from the animal reservoir. Priority distribution of the first product batches must be to individuals at high risk and to crucial employees.
• Flu: weighing up conflicting expert information
  - Nature 460(7255):571 (2009)
  In his Essay 'Pandemics: avoiding the mistakes of 1918' (Nature 459, 324–325; 2009), John M. Barry writes that during an influenza pandemic "telling the public the truth is ... paramount".
• Where will we find the tritium to fuel hybrid reactors?
  - Nature 460(7255):571 (2009)
  In your News Feature 'The hybrid returns' (Nature460, 25–28; 2009), you discuss the feasibility of creating a fusion–fission hybrid reactor to generate greenhouse-gas-free and waste-free nuclear energy. However, there is another challenge to add to the factors to be considered: where would the hundreds of grams of tritium needed daily to fuel the deuterium–tritium fusion reaction be produced?
• The invention of heroes
  - Nature 460(7255):572-573 (2009)
  The Western public's misapprehension that genius in science is always male and caucasian is partly a legacy of Victorian politics, says Christine MacLeod.
• A break from the bench
  - Nature 460(7255):574-577 (2009)
  Nature regulars give their recommendations for relaxed, inspiring holiday reading and viewing — from climate-change history to Isaac Newton the detective.
• Optics: All smoke and metamaterials
  - Nature 460(7255):579-580 (2009)
  An illusion device, placed near but not enclosing an object of arbitrary shape, manipulates and transforms light scattered off the object so as to give it the appearance of a completely different object.
• Structural biology: Trimeric ion-channel design
  - Nature 460(7255):580-581 (2009)
  Cavernous chambers, intricate passages, a gate with a curious lock — the structure of an ATP-activated ion channel reveals its architecture. And this intriguing interior design is found in another type of ion channel too.
• Oceanography: A fishy mix
  - Nature 460(7255):581-582 (2009)
  Ocean life is in almost constant motion, and such activity must surely stir things up. Innovative investigations into this concept of 'biogenic mixing' show a role for jellyfish and their brethren.
• Planetary science: Windy clues to Saturn's spin
  - Nature 460(7255):582-583 (2009)
  Saturn's rotation period has been a mystery. An estimate based on its meteorology comes with implications for our understanding of the planet's atmospheric jet streams and interior structure.
• Earth science: Trickle-down geodynamics
  - Nature 460(7255):583-584 (2009)
  Analysis of the platinum-group elements in a particular type of ancient volcanic rock provides clues about Earth's early history as well as a fresh approach to understanding mantle dynamics.
• Developmental biology: Skeletal muscle comes of age
  - Nature 460(7255):584-585 (2009)
  A regulatory protein thought to be crucial for maintaining the muscle stem-cell pool throughout life is shown to be dispensable in the adult. Muscle biologists are left wondering what fundamental things apply as time goes by.
• Supramolecular chemistry: Phosphorus caged
  - Nature 460(7255):585-586 (2009)
  Violent criminals are imprisoned to keep them under control. Similarly, incarceration in a molecular jail stops white phosphorus from bursting into flames — but on release, it regains its fiery character.
• Recent progress in the biology and physiology of sirtuins
  - Nature 460(7255):587-591 (2009)
  The sirtuins are a highly conserved family of NAD+-dependent enzymes that regulate lifespan in lower organisms. Recently, the mammalian sirtuins have been connected to an ever widening circle of activities that encompass cellular stress resistance, genomic stability, tumorigenesis and energy metabolism. Here we review the recent progress in sirtuin biology, the role these proteins have in various age-related diseases and the tantalizing notion that the activity of this family of enzymes somehow regulates how long we live.
• Biased reptilian palaeothermometer?
  - Nature 460(7255):E1 (2009)
  Arising from: J. J. Head et al.Nature 457, 715–717 (2009); Head et al.reply Palaeotemperatures can be estimated from characteristics of fossils if their living relatives represent the full evolutionary potential of the larger taxon to which the fossil belongs. By drawing on observations1, 2 that the body size of poikilotherms decreases globally with ambient temperature, Head et al.3 used the 13 m length of the newly described fossil boid Titanoboa cerrejonensis to estimate that the Palaeocene neotropical mean annual temperature (MAT) was 30–34 °C. I question the validity of this palaeotemperature estimate by using the same data and approach as Head et al.3 to show that Varanus (Megalania) prisca4, a large extinct lizard that lived in eastern Australia during the Late Pleistocene, was 3–4 times longer than predicted by the largest lizard species in the tropics today. This suggests that the scarcity of large predatory reptiles today may primarily be a function of competition with mammalian carnivores, rather than a function of modern temperatures.
• Re-calibrating the snake palaeothermometer
  - Nature 460(7255):E2 (2009)
  Arising from: J. J. Head et al.Nature 457, 715–717 (2009); Head et al.reply In a recent study1 a new proxy for palaeoclimate reconstructions was proposed on the basis of a theoretical approach linking the largest body sizes to ambient temperature in extant taxa of air-breathing poikilotherms2, 3. The value of the largest fossil snake's body length was used to estimate the mean annual temperature (MAT) for the Palaeocene neotropics of T = 3.8–7.2 °C above the modern value1. Here we argue that the reported temperature difference is a twofold overestimate and obtain a corrected estimate of T = 1.9–3.7 °C using the taxon-specific metabolic scaling exponent = 0.17 for boid snakes. The importance of using relevant taxon-specific information in case of one-taxon-based temperature reconstructions1 while leaving the theoretically derived generic values (such as = 0.33 used by Head et al.1) for broad inter-taxonomic analyses2, 3 is emphasized.
• Can the giant snake predict palaeoclimate?
  - Nature 460(7255):E3 (2009)
  Arising from: J. J. Head et al.Nature 457, 715–717 (2009); Head et al.reply In their report on Titanoboa cerrejonensis, Head et al.1 propose that the great size of this 58 to 60 million-year-old snake (estimated length = 13 m, mass = 1,135 kg) indicates a mean annual neotropical temperature (MAT) of 30–34 °C, substantially higher than previous estimates for that period. They argue that the high MAT was necessary to compensate for the decreased mass-specific metabolic rate intrinsic to a snake of this size. However, the relationship on which Head et al.1 base their conclusion does not account for the scope of behavioural control over body temperature available to Titanoboa due to its huge mass. Our calculations suggest that because of its ability to behaviourally control its body temperature, Titanoboa cannot serve as an accurate palaeothermometer.
• Head et al. reply
  - Nature 460(7255):E4 (2009)
  Replying to: J. M. K. Sniderman Nature 460, 10.1038/nature08222 (2009); A. M. Makarieva, V. G. Gorshkov & B.-L. Li Nature 460, 10.1038/nature08223 (2009); M. W. Denny, B. L. Lockwood & G. N. Somero Nature 460, 10.1038/nature08224 (2009) Denny et al.1 and Sniderman2 question our use of body size in Titanoboa cerrejonensis as an equatorial temperature proxy during the Palaeocene3, and Makarieva et al.4 suggest an adjustment to our temperature estimates. Denny et al.1 misinterpret the physiological model of our study5, 6 and the implications of their body temperature (Tb) estimates relative to the thermal ecology of extant snakes. They assert that our model is inappropriate for large-bodied animals because the relationship between Tb and air temperature (mean annual temperature; MAT3) is not constant across different body sizes in poikilotherms. In fact, the model does not assume constancy of Tb relative to MAT. Changes in Tb (and thus body size) relative to MAT resulting from increasing thermal inertia with size are inherent in the model, as evidenced by the scaling of body length and MAT (see Fig. 3 in ref. 3). The model is accurate for the longest extant snake, Python reticulatus6, with a maximum body lengt! h 70% that of Titanoboa3, indicating that it is appropriate to use with animals approximating the sizes of the largest known snakes.
• Crystal structure of the ATP-gated P2X4 ion channel in the closed state
  - Nature 460(7255):592-598 (2009)
  P2X receptors are cation-selective ion channels gated by extracellular ATP, and are implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Because P2X receptors are not related to other ion channel proteins of known structure, there is at present no molecular foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation. Here we present crystal structures of the zebrafish P2X4 receptor in its closed, resting state. The chalice-shaped, trimeric receptor is knit together by subunit–subunit contacts implicated in ion channel gating and receptor assembly. Extracellular domains, rich in -strands, have large acidic patches that may attract cations, through fenestrations, to vestibules near the ion channel. In the transmembrane pore, the 'gate' is defined by an 8 Å slab of protein. We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP bi! nding promotes subunit rearrangement and ion channel opening.
• Pore architecture and ion sites in acid-sensing ion channels and P2X receptors
  - Nature 460(7255):599-604 (2009)
  Acid-sensing ion channels are proton-activated, sodium-selective channels composed of three subunits, and are members of the superfamily of epithelial sodium channels, mechanosensitive and FMRF-amide peptide-gated ion channels. These ubiquitous eukaryotic ion channels have essential roles in biological activities as diverse as sodium homeostasis, taste and pain. Despite their crucial roles in biology and their unusual trimeric subunit stoichiometry, there is little knowledge of the structural and chemical principles underlying their ion channel architecture and ion-binding sites. Here we present the structure of a functional acid-sensing ion channel in a desensitized state at 3 Å resolution, the location and composition of the 8 Å 'thick' desensitization gate, and the trigonal antiprism coordination of caesium ions bound in the extracellular vestibule. Comparison of the acid-sensing ion channel structure with the ATP-gated P2X4 receptor reveals similarity in pore arc! hitecture and aqueous vestibules, suggesting that there are unanticipated yet common structural and mechanistic principles.
• Resonant stripping as the origin of dwarf spheroidal galaxies
  - Nature 460(7255):605-607 (2009)
  Dwarf spheroidal galaxies are the most dark-matter-dominated systems in the nearby Universe1, 2, 3 and their origin is one of the outstanding puzzles of how galaxies form. Dwarf spheroidals are poor in gas and stars, making them unusually faint4, 5, 6, and those known as ultra-faint dwarfs7, 8 have by far the lowest measured stellar content of any galaxy9, 10. Previous theories11 require that dwarf spheroidals orbit near giant galaxies like the Milky Way, but some dwarfs have been observed in the outskirts of the Local Group12. Here we report simulations of encounters between dwarf disk galaxies and somewhat larger objects. We find that the encounters excite a process, which we term 'resonant stripping', that transforms them into dwarf spheroidals. This effect is distinct from other mechanisms proposed to form dwarf spheroidals, including mergers13, galaxy–galaxy harassment14, or tidal and ram pressure stripping, because it is driven by gravitational resonances. It m! ay account for some of the observed properties of dwarf spheroidals in the Local Group. Within this framework, dwarf spheroidals should form and interact in pairs, leaving detectable long stellar streams and tails.
• Saturn's rotation period from its atmospheric planetary-wave configuration
  - Nature 460(7255):608-610 (2009)
  The rotation period of a gas giant's magnetic field (called the System III reference frame) is commonly used to infer its bulk rotation1. Saturn's dipole magnetic field is not tilted relative to its rotation axis (unlike Jupiter, Uranus and Neptune), so the surrogate measure of its long-wavelength (kilometric) radiation is currently used to fix the System III rotation period2. The period as measured now by the Cassini spacecraft is up to 7 min longer3 than the value of 10 h 39 min 24 s measured 28 years ago by Voyager2. Here we report a determination of Saturn's rotation period based on an analysis of potential vorticity. The resulting reference frame (which we call System IIIw) rotates with a period of 10 h 34 min 13 20 s. This shifted reference frame is consistent with a pattern of alternating jets on Saturn that is more symmetrical between eastward and westward flow. This suggests that Saturn's winds are much more like those of Jupiter than hitherto believed4.
• A 'granocentric' model for random packing of jammed emulsions
  - Nature 460(7255):611-615 (2009)
  Packing problems are ubiquitous1, 2, ranging from oil extraction through porous rocks to grain storage in silos and the compaction of pharmaceutical powders into tablets. At a given density, particulate systems pack into a mechanically stable and amorphous jammed state3, 4. Previous theoretical studies have explored a connection between this jammed state and the glass transition4, 5, 6, 7, 8, the thermodynamics of jamming9, 10, 11, 12 and geometric modelling of random packings13, 14, 15. Nevertheless, a simple underlying mechanism for the random assembly of athermal particles, analogous to crystalline ordering, remains unknown. Here we use three-dimensional measurements of packings of polydisperse emulsion droplets to build a simple statistical model in which the complexity of the global packing is distilled into a local stochastic process. From the perspective of a single particle, the packing problem is reduced to the random formation of nearest neighbours, followed ! by a choice of contacts among them. The two key parameters in the model—the available space around a particle and the ratio of contacts to neighbours—are directly obtained from experiments. We demonstrate that this 'granocentric' view captures the properties of the polydisperse emulsion packing—ranging from the microscopic distributions of nearest neighbours and contacts, to local density fluctuations, to the global packing density. Application of our results to monodisperse and bidisperse systems produces quantitative agreement with previously measured trends in global density16. Our model therefore reveals a general principle of organization for random packing and may provide the foundations for a theory of jammed matter.
• Carbon respiration from subsurface peat accelerated by climate warming in the subarctic
  - Nature 460(7255):616-619 (2009)
  Among the largest uncertainties in current projections of future climate is the feedback between the terrestrial carbon cycle and climate1. Northern peatlands contain one-third of the world's soil organic carbon, equivalent to more than half the amount of carbon in the atmosphere2. Climate-warming-induced acceleration of carbon dioxide (CO2) emissions through enhanced respiration of thick peat deposits, centuries to millennia old, may form a strong positive carbon cycle–climate feedback. The long-term temperature sensitivity of carbon in peatlands, especially at depth, remains uncertain, however, because of the short duration or correlative nature of field studies3, 4, 5 and the disturbance associated with respiration measurements below the surface in situ or during laboratory incubations6, 7. Here we combine non-disturbing in situ measurements of CO2 respiration rates and isotopic (13C) composition of respired CO2 in two whole-ecosystem climate-manipulation experime! nts in a subarctic peatland. We show that approximately 1 °C warming accelerated total ecosystem respiration rates on average by 60% in spring and by 52% in summer and that this effect was sustained for at least eight years. While warming stimulated both short-term (plant-related) and longer-term (peat soil-related) carbon respiration processes, we find that at least 69% of the increase in respiration rate originated from carbon in peat towards the bottom (25–50 cm) of the active layer above the permafrost. Climate warming therefore accelerates respiration of the extensive, subsurface carbon reservoirs in peatlands to a much larger extent than was previously thought6, 7. Assuming that our data from a single site are indicative of the direct response to warming of northern peatland soils on a global scale, we estimate that climate warming of about 1 °C over the next few decades could induce a global increase in heterotrophic respiration of 38–100 megatonnes of C per ye! ar. Our findings suggest a large, long-lasting, positive feedb! ack of carbon stored in northern peatlands to the global climate system.
• Progressive mixing of meteoritic veneer into the early Earth's deep mantle
  - Nature 460(7255):620-623 (2009)
  Komatiites are ancient volcanic rocks, mostly over 2.7 billion years old (from the Archaean era), that formed through high degrees of partial melting of the mantle and therefore provide reliable information on bulk mantle compositions1. In particular, the platinum group element (PGE) contents of komatiites provide a unique source of information on core formation, mantle differentiation and possibly core–mantle interaction2, 3, 4, 5, 6, 7, 8. Most of the available PGE data on komatiites are from late Archaean (2.7–2.9 Gyr old) or early Proterozoic (2.0–2.5 Gyr old) samples. Here we show that most early Archaean (3.5–3.2 Gyr old) komatiites from the Barberton greenstone belt of South Africa and the Pilbara craton of Western Australia are depleted in PGE relative to late Archaean and younger komatiites. Early Archaean komatiites record a signal of PGE depletion in the lower mantle, resulting from core formation. This signal diminishes with time owing to progressiv! e mixing-in to the deep mantle of PGE-enriched cosmic material that the Earth accreted as the 'late veneer' during the Early Archaean (4.5–3.8 Gyr ago) meteorite bombardment.
• A viscosity-enhanced mechanism for biogenic ocean mixing
  - Nature 460(7255):624-626 (2009)
  Recent observations of biologically generated turbulence in the ocean have led to conflicting conclusions regarding the significance of the contribution of animal swimming to ocean mixing. Measurements indicate elevated turbulent dissipation—comparable with levels caused by winds and tides—in the vicinity of large populations of planktonic animals swimming together1. However, it has also been noted that elevated turbulent dissipation is by itself insufficient proof of substantial biogenic mixing, because much of the turbulent kinetic energy of small animals is injected below the Ozmidov buoyancy length scale, where it is primarily dissipated as heat by the fluid viscosity before it can affect ocean mixing2. Ongoing debate regarding biogenic mixing has focused on comparisons between animal wake turbulence and ocean turbulence3, 4. Here, we show that a second, previously neglected mechanism of fluid mixing—first described over 50 years ago by Charles Darwin5— is ! the dominant mechanism of mixing by swimming animals. The efficiency of mixing by Darwin's mechanism is dependent on animal shape rather than fluid length scale and, unlike turbulent wake mixing, is enhanced by fluid viscosity. Therefore, it provides a means of biogenic mixing that can be equally effective in small zooplankton and large mammals. A theoretical model for the relative contributions of Darwinian mixing and turbulent wake mixing is created and validated by in situ field measurements of swimming jellyfish using a newly developed scuba-based laser velocimetry device6. Extrapolation of these results to other animals is straightforward given knowledge of the animal shape and orientation during vertical migration. On the basis of calculations of a broad range of aquatic animal species, we conclude that biogenic mixing via Darwin's mechanism can be a significant contributor to ocean mixing and nutrient transport.
• Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements
  - Nature 460(7255):627-631 (2009)
  Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically1, and Pax7 alone perinatally2, 3, 4, 5. Several in vitro studies support the critical role of Pax7 in these functions of adult muscle stem cells5, 6, 7, 8 (satellite cells), but a formal demonstration has been lacking in vivo. Here we show, through the application of inducible Cre/loxP lineage tracing9 and conditional gene inactivation to the tibialis anterior muscle regeneration paradigm, that, unexpectedly, when Pax7 is inactivated in adult mice, mutant satellite cells are not compromised in muscle regeneration, they can proliferate and reoccupy the sublaminal satellite niche, and they are able to support further regenerative processes. Dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal that Pax7 is only required up to the juvenile period when proge! nitor cells make the transition into quiescence. Furthermore, we demonstrate a cell-intrinsic difference between neonatal progenitor and adult satellite cells in their Pax7-dependency. Our finding of an age-dependent change in the genetic requirement for muscle stem cells cautions against inferring adult stem-cell biology from embryonic studies, and has direct implications for the use of stem cells from hosts of different ages in transplantation-based therapy.
• Presenilins are essential for regulating neurotransmitter release
  - Nature 460(7255):632-636 (2009)
  Mutations in the presenilin genes are the main cause of familial Alzheimer's disease. Loss of presenilin activity and/or accumulation of amyloid- peptides have been proposed to mediate the pathogenesis of Alzheimer's disease by impairing synaptic function1, 2, 3, 4, 5. However, the precise site and nature of the synaptic dysfunction remain unknown. Here we use a genetic approach to inactivate presenilins conditionally in either presynaptic (CA3) or postsynaptic (CA1) neurons of the hippocampal Schaeffer-collateral pathway. We show that long-term potentiation induced by theta-burst stimulation is decreased after presynaptic but not postsynaptic deletion of presenilins. Moreover, we found that presynaptic but not postsynaptic inactivation of presenilins alters short-term plasticity and synaptic facilitation. The probability of evoked glutamate release, measured with the open-channel NMDA (N-methyl-d-aspartate) receptor antagonist MK-801, is reduced by presynaptic inactiv! ation of presenilins. Notably, depletion of endoplasmic reticulum Ca2+ stores by thapsigargin, or blockade of Ca2+ release from these stores by ryanodine receptor inhibitors, mimics and occludes the effects of presynaptic presenilin inactivation. Collectively, these results indicate a selective role for presenilins in the activity-dependent regulation of neurotransmitter release and long-term potentiation induction by modulation of intracellular Ca2+ release in presynaptic terminals, and further suggest that presynaptic dysfunction might be an early pathogenic event leading to dementia and neurodegeneration in Alzheimer's disease.
• Macrophage elastase kills bacteria within murine macrophages
  - Nature 460(7255):637-641 (2009)
  Macrophages are aptly positioned to function as the primary line of defence against invading pathogens in many organs, including the lung and peritoneum. Their ability to phagocytose and clear microorganisms has been well documented1, 2. Macrophages possess several substances with which they can kill bacteria, including reactive oxygen species, nitric oxide, and antimicrobial proteins3, 4, 5, 6, 7, 8, 9. We proposed that macrophage-derived proteinases may contribute to the antimicrobial properties of macrophages. Macrophage elastase (also known as matrix metalloproteinase 12 or MMP12) is an enzyme predominantly expressed in mature tissue macrophages10 and is implicated in several disease processes, including emphysema11. Physiological functions for MMP12 have not been described. Here we show that Mmp12-/- mice exhibit impaired bacterial clearance and increased mortality when challenged with both Gram-negative and Gram-positive bacteria at macrophage-rich portals of ent! ry, such as the peritoneum and lung. Intracellular stores of MMP12 are mobilized to macrophage phagolysosomes after the ingestion of bacterial pathogens. Once inside phagolysosomes, MMP12 adheres to bacterial cell walls where it disrupts cellular membranes resulting in bacterial death. The antimicrobial properties of MMP12 do not reside within its catalytic domain, but rather within the carboxy-terminal domain. This domain contains a unique four amino acid sequence on an exposed loop of the protein that is required for the observed antimicrobial activity. The present study represents, to our knowledge, the first report of direct antimicrobial activity by a matrix metallopeptidase, and describes a new antimicrobial peptide that is sequentially and structurally unique in nature.
• MicroRNA-mediated switching of chromatin-remodelling complexes in neural development
  - Nature 460(7255):642-646 (2009)
  One of the most distinctive steps in the development of the vertebrate nervous system occurs at mitotic exit when cells lose multipotency and begin to develop stable connections that will persist for a lifetime1, 2. This transition is accompanied by a switch in ATP-dependent chromatin-remodelling mechanisms that appears to coincide with the final mitotic division of neurons. This switch involves the exchange of the BAF53a (also known as ACTL6a) and BAF45a (PHF10) subunits within Swi/Snf-like neural-progenitor-specific BAF (npBAF) complexes for the homologous BAF53b (ACTL6b) and BAF45b (DPF1) subunits within neuron-specific BAF (nBAF) complexes in post-mitotic neurons. The subunits of the npBAF complex are essential for neural-progenitor proliferation, and mice with reduced dosage for the genes encoding its subunits have defects in neural-tube closure similar to those in human spina bifida3, one of the most serious congenital birth defects. In contrast, BAF53b and the n! BAF complex are essential for an evolutionarily conserved program of post-mitotic neural development and dendritic morphogenesis4, 5. Here we show that this essential transition is mediated by repression of BAF53a by miR-9* and miR-124. We find that BAF53a repression is mediated by sequences in the 3' untranslated region corresponding to the recognition sites for miR-9* and miR-124, which are selectively expressed in post-mitotic neurons. Mutation of these sites led to persistent expression of BAF53a and defective activity-dependent dendritic outgrowth in neurons. In addition, overexpression of miR-9* and miR-124 in neural progenitors caused reduced proliferation. Previous studies have indicated that miR-9* and miR-124 are repressed by the repressor-element-1-silencing transcription factor (REST, also known as NRSF)6. Indeed, expression of REST in post-mitotic neurons led to derepression of BAF53a, indicating that REST-mediated repression of microRNAs directs the essential ! switch of chromatin regulatory complexes.
• Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation
  Kalantry S Purushothaman S Bowen RB Starmer J Magnuson T - Nature 460(7255):647-651 (2009)
  XX female mammals undergo transcriptional silencing of most genes on one of their two X chromosomes to equalize X-linked gene dosage with XY males in a process referred to as X-chromosome inactivation (XCI). XCI is an example of epigenetic regulation1. Once enacted in individual cells of the early female embryo, XCI is stably transmitted such that most descendant cells maintain silencing of that X chromosome2. In eutherian mammals, XCI is thought to be triggered by the expression of the non-coding Xist RNA from the future inactive X chromosome (Xi)3, 4, 5; Xist RNA in turn is proposed to recruit protein complexes that bring about heterochromatinization of the Xi6, 7. Here we test whether imprinted XCI, which results in preferential inactivation of the paternal X chromosome (Xp), occurs in mouse embryos inheriting an Xp lacking Xist. We find that silencing of Xp-linked genes can initiate in the absence of paternal Xist; Xist is, however, required to stabilize silencing ! along the Xp. Xp-linked gene silencing associated with mouse imprinted XCI, therefore, can initiate in the embryo independently of Xist RNA.
• Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia
  - Nature 460(7255):652 (2009)
  Nature 458, 776–779 (2009) During resubmission of this work, another paper linking CML and Hedgehog signalling was published1. The studies use distinct approaches but come to similar conclusions.
• Hard man to surprise
  - Nature 460(7255):658 (2009)
  A birthday treat.