Hot off the presses! Aug 13 Nature

The Aug 13 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:

• Lessons from Antarctica
  - Nature 460(7257):781 (2009)
  Twenty years on, the success of the Montreal Protocol can help inform plans to mitigate climate change.
• A change of tone
  - Nature 460(7257):781 (2009)
  There is every reason to be optimistic about the Obama administration's attitude towards science.
• Canine genetics: Stray genes
  - Nature 460(7257):782 (2009)
  
• Cancer biology: Suicide by nucleotide
  - Nature 460(7257):782 (2009)
  
• Atmospheric chemistry: Isoprene's fate
  - Nature 460(7257):782 (2009)
  
• Physics: Salt mined
  - Nature 460(7257):782 (2009)
  
• Speciation: Multiplying effects
  - Nature 460(7257):782-783 (2009)
  
• Neurobiology: Have guts, get nerve
  - Nature 460(7257):783 (2009)
  
• Evolution: Reinventing the egg
  - Nature 460(7257):783 (2009)
  
• Soil ecology: As different as day and night
  - Nature 460(7257):783 (2009)
  
• Molecular biology: A regulator's regulator
  - Nature 460(7257):783 (2009)
  
• Journal club
  - Nature 460(7257):783 (2009)
  
• LHC hopes for collisions by Christmas
  - Nature 460(7257):784 (2009)
  The Large Hadron Collider (LHC) should yield its first data by Christmas, smashing protons at energies high enough to begin pushing back the boundaries of particle physics. But the world's largest particle accelerator will only be operating at half the energy that it was originally designed for, and may not reach that peak until 2011 — if at all.
• Science advisers mull priorities
  - Nature 460(7257):785 (2009)
  An elite group of 21 US researchers met publicly for the first time last week as the new advisory panel to US President Barack Obama on scientific and technical matters. But despite an enthusiastic inaugural meeting, it will take time to know how effective the President's Council of Advisors on Science and Technology (PCAST) will be.
• Ice-core researchers hope to chill out
  - Nature 460(7257):786 (2009)
  Fresh freezers needed to preserve ancient gas, scientists say. Unless stored correctly, ice cores lose their value.L. Augustin/CNRS Researchers in the United States and Europe are seeking funding so that the ice cores used to study Earth's past climate can have the same luxuriously chilly storage facilities currently enjoyed by prize tuna. The cylindrical cores, drilled at multi-million-dollar expense from polar and glacial ice, can be kilometres long. They contain tiny bubbles of trapped air, allowing scientists to measure the concentration of carbon dioxide in the atmosphere from hundreds of thousands of years ago. The relative ratios of oxygen and nitrogen, and their isotopes, can also reveal temperature variations and help to date the trapped gas. But oxygen is gradually lost when ice cores are stored at −20 °C to −30 °C, the standard temperature of current cold-storage facilities in the United States and Europe (M. Bender, T. Sowers and V. Lipenkov J. Geophys. Res. 100, 18651–18660; 1995). The oxygen diffuses slowly toward the core's surface and can be lost to the air, resulting in higher ratios of nitrogen to oxygen that can distort the conclusions scientists draw from them. In 2005, Japanese researchers showed that colder storage temperatures could mitigate this gas loss (T. Ikeda-Fukazawa et al. Earth Planet. Sci. Lett. 229, 183–192; 2005), and the ice-core storage facility at the National Institute of Polar Research, Tokyo, was subsequently upgraded with technology used to maintain cold stores for high-grade tuna at −50 °C. US researchers are now seeking roughly $5 million to rebuild cold-storage facilities at the US Army Cold Regions Research and Engineering Laboratory in Hanover, New Hampshire, which would also have its storage capacity increased by about 25%. Ian Baker, a materials scientist at Dartmouth College, also in Hanover, is leading the application for funding from the National Science Foundation. If the team gets its funding, Dartmouth would then manage the refurbished facility, which could be completed by 2010. European scientists face a similar challenge. "We need a European-wide facility," says Eric Wolff at the British Antarctic Survey in Cambridge, UK. But a European Commission study in 2008 estimated that a new −50 °C facility, with associated research labs and teaching facilities, would cost €25 million (US$35 million), and is unlikely to be funded, says Frank Wilhelms of the Alfred Wegener Institute for Polar and Marine Research in Bremerhaven, Germany, which houses one of four major ice-core facilities in Europe. The International Partnerships in Ice Core Sciences (IPICS), an organization of scientists, drillers and engineers from 18 nations, has also said that urgent action is needed to prevent ice cores degrading. ADVERTISEMENT In the interim, Jeffrey Severinghaus, an IPICS steering-committee member from the Scripps Institute of Oceanography in La Jolla, California, says some institutions like his are building smaller units to keep parts of cores at −50 °C. These units can be created for about $15,000, but the necessary freezer adaptations void warranties and there are concerns that keeping sections of ice cores in many different locations may hamper researchers' access. His lab is currently studying oxygen/nitrogen ratios in ice cores drilled last year for the Western Antarctic Ice Sheet Divide Ice Core project, a collaboration of US research groups. Preliminary comparisons with the Byrd ice core, drilled in 1968 in Western Antarctica, show that oxygen has been lost in the older core during storage, he says.
• Flu database rocked by legal row
  - Nature 460(7257):786-787 (2009)
  Dispute over ownership raises concerns among flu scientists. A question mark is hanging over the future of EpiFlu, an international database created to help monitor the spread and evolution of influenza viruses. The database openly shares genetic, epidemiological and clinical data that previously had often been hoarded by countries and scientists, and is contributing to the rapid analysis of viral gene sequences from the current H1N1 pandemic. EpiFlu has become mired in a legal dispute between the Global Initiative on Sharing Avian Influenza Data (GISAID), an international group created by leading flu researchers in August 2006 to promote data sharing (see Nature 442, 981; 2006), and the Swiss Institute of Bioinformatics (SIB) in Geneva. GISAID announced a contract with the SIB in December 2006 to build the EpiFlu database. Most funding for EpiFlu came from the US Centers for Disease Control and Prevention and the Swiss government. "I hope they reach the best solution for the sake of global health." The row became public on 27 July, when visitors to the EpiFlu landing page on the GISAID website were met with a message from the SIB informing them that the database was currently unavailable on that site "due to contractual and legal issues", and instead was available only to users redirected to a SIB website. The same day, the SIB e-mailed the same message to all registered users of the database. The next day, GISAID also e-mailed users to assert that the SIB "had no right [to cut off the access to the EpiFlu Database via GISAID] or to operate the EpiFlu Database on its own". Both SIB and GISAID officials declined to discuss the details because of the ongoing legal dispute. But the SIB alleges that GISAID has breached its contract by failing to pay its bills on time. GISAID officials say that although there had been a hiatus in its funding, they had acted in good faith and had subsequently obtained additional funds to meet some of the bills. "GISAID continues to work with the SIB to resolve their monetary dispute," says Cheryl Bennett, an official at the GISAID Foundation's Washington DC office. "However, before the monetary dispute can fairly be resolved, GISAID must receive an accurate accounting from the SIB, which GISAID has requested but the SIB has thus far not provided." She asserts that the SIB's continued operation of the database, including GISAID's trademark logos and data-access agreement, amounts to "misappropriation" of the database, and claims that under the terms of the contract, all EpiFlu data remain GISAID's property, giving the SIB no right to operate the database independently. However, the SIB had written to GISAID in September 2008 declaring that it was terminating their contract. The SIB argues that GISAID has not settled its bills in full and that, under Swiss law, a default on payment renders a contract null and void, giving the SIB the rights to the database it built. Since then, the SIB claims that it has operated the database without asking for more money from GISAID, and has taken fund-raising for the database into its own hands. Although researchers can still access the database, public-health officials are worried by the longer-term implications of the row. Before the creation of GISAID, several countries — including Indonesia, an avian flu hotspot — had refused to share sequence data on the grounds that they got little in return. But they were persuaded to share by GISAID's terms of access, similar to those of open-source software, in which all users agree to share their own data and give due credit to the originators. ADVERTISEMENT "Indonesia has been supportive of GISAID from the outset," says Widjaja Lukito, a senior policy adviser at the country's ministry of health. He adds that he is watching "with great concern the problems faced by the GISAID Initiative during this pandemic phase". He says that he strongly hopes that "the parties involved will reach the best solution for the sake of global public health". One flu scientist, who is a member of GISAID's scientific council, adds that EpiFlu is more than just the database computing infrastructure built by the SIB. Considerable effort has been invested by GSAID and its partners in "building trust" between the scientific community and countries who have sequence data to deposit, and in contributing influenza expertise. Lawyers for both the SIB and GISAID have in the past weeks made confidential settlement offers to each other, and both say they are keen to reach a peaceful settlement. "The SIB is 100% committed to the EpiFlu database as part of the GISAID initiative. We are working very hard to find the best possible solution for all concerned," says Ron Appel, head of the SIB.
• Climate data spat intensifies
  - Nature 460(7257):787 (2009)
  A leading UK climatologist is being inundated by freedom-of-information-act requests to make raw climate data publicly available, leading to a renewed row over data access. Since 2002, Steve McIntyre, the editor of Climate Audit, a blog that investigates the statistical methods used in climate science, has repeatedly asked Phil Jones, director of the Climatic Research Unit (CRU) at the University of East Anglia, UK, for access to monthly global surface temperature data held by the institute.
• Return of the rat
  - Nature 460(7257):788 (2009)
  The European Commission has approved the world's first major systems-biology programme to study the rat. Known as EURATRANS — for European large-scale functional genomics in the rat for translational research — the multimillion-euro project includes collaborators in the United States and Japan.
• Satellite data show Indian water stocks shrinking
  - Nature 460(7257):789 (2009)
  Groundwater depletion raises spectre of shortages. Unsustainable water use in India is threatening agricultural production and raising the spectre of a major water crisis. Matthew Rodell of NASA's Goddard Space Flight Center in Greenbelt, Maryland, and colleagues used data from the Gravity Recovery and Climate Experiment (GRACE) satellites — operated by NASA and the German Aerospace Center (DLR) — to determine how groundwater levels are changing in the Indian states of Rajasthan, Punjab and Haryana, which includes the national capital of New Delhi. "If farmers could shift away from water-intensive crops and implement more efficient irrigation methods, that would help." Their research, published online in Nature this week (M. Rodell et al. Nature doi:10.1038/nature08238; 2009), found gravity anomalies suggesting a net loss of 109 cubic kilometres of water — equivalent to a mass of 109 billion tonnes — from August 2002 to October 2008. The amount lost is double the capacity of India's largest surface-water reservoir, the Upper Wainganga, and almost three times the capacity of Lake Mead in Nevada, the largest reservoir in the United States. A second study using GRACE data, by scientists at the University of Colorado and the National Center for Atmospheric Research in Boulder, has found that the most intensively irrigated areas in northern India, eastern Pakistan and parts of Bangladesh are losing groundwater at an overall rate of 54 cubic kilometres per year, consistent with Rodell's results (V. M. Tiwari et al. Geophys. Res. Lett. doi:10.1029/2009GL039401; in the press). Groundwater depletion in northwest India is a known problem, but Rodell's data suggest that the loss rate is around 20% higher than the Indian authorities have previously estimated. Rodell notes that rainfall during the study period was close to the long-term climatic mean, and says that the observed groundwater depletion is unlikely to be the result of unusual dryness or variability. ADVERTISEMENT The regions of Rajasthan, Punjab and Haryana have a combined population of 114 million people, and receive an average of 500 millimetres of rainfall per year — just slightly less than that of London — but with pronounced seasonal and regional differences. Although less than a third of agricultural land there is irrigated, crop irrigation accounts for up to 95% of groundwater consumption. "If farmers could shift away from water-intensive crops, such as rice, and implement more efficient irrigation methods, that would help," says Rodell. Meanwhile, the Indian government is looking into framing regulations to reduce groundwater consumption. "Hopefully," says Rodell, "our research will give them the evidence they need to carry through."
• Europe prepares for drugs from GM plants
  - Nature 460(7257):791 (2009)
  
• Presidential panel lays out options for NASA's future
  - Nature 460(7257):791 (2009)
  
• Batteries feel the benefit of green car money
  - Nature 460(7257):791 (2009)
  
• Stalled science buildings restart in California
  - Nature 460(7257):791 (2009)
  
• German scientists found guilty of negligence
  - Nature 460(7257):791 (2009)
  An independent investigation committee has found four scientists at the elite University of Göttingen, Germany, guilty of gross negligence because they included three unfinished manuscripts in publication lists supporting an application for research funding. But the researchers did not invent or falsify data, the committee says. The application was for the continuation of a collaborative research centre (SFB): a highly prized award funded by the DFG, Germany's major national research agency. The collaboration was set up to study the stability of the Indonesian rainforest and had received €16.6 million (US$22.3 million) from 2000 to June 2009 (see Nature 459, 23; 2009). Investigations by the university and local public prosecutors into possible financial irregularities continue.
• Novartis targeted by animal-rights extremists
  - Nature 460(7257):791 (2009)
  E. Leanza/PA Militant animal-rights activists were responsible for the torching of the Alpine holiday home (pictured) of Daniel Vasella, head of the Swiss pharmaceutical company Novartis, in the early hours of 3 August, Swiss authorities assume. The chalet was destroyed but no one was hurt. Novartis has reported at least ten other recent attacks on its employees. These include the desecration of graves of Vasella's family and the theft of his mother's ashes at the end of last month, as well as the placing of incendiary devices under the cars of Novartis's administrative chief, Ulrich Lehner, in May. Swiss police say they expect further attacks. The Stop Huntingdon Animal Cruelty (SHAC) group has called an Action Week for 24–30 August against major customers of Huntingdon Life Sciences, a contract animal-testing company near Cambridge, UK, that has faced a sustained campaign of attacks. Novartis denies being a Huntingdon Life Sciences customer, as the SHAC website claims.
• Atmospheric science: Fixing the sky
  - Nature 460(7257):792-795 (2009)
  Later this month, something sinister will start to take shape above Antarctica. As sunlight reappears in the polar skies after the long winter, chlorine and bromine compounds in the stratosphere will begin destroying part of the ozone layer that shelters Earth's surface from harmful ultraviolet radiation.
• Ape and human similarities can be deceptive
  - Nature 460(7257):796 (2009)
  In his Essay 'Darwin's last laugh' (Nature 460, 175; 2009), Frans de Waal suggests that ape vocalizations are homologous to human laughter, which they could be — but that does not necessarily imply that apes have a sense of humour. Adaptive divergence could be at play, making humans the ones who get the jokes.
• Speed of reporting isn't the issue when your work is scooped
  - Nature 460(7257):796 (2009)
  In your Editorial 'How to stop blogging' (Nature 460, 152; 2009), you urge the conference community to be clear from the outset about whether their meetings are 'open' or 'closed' with respect to the informal dissemination of their content.
• European bodies can help to tackle TB worldwide
  - Nature 460(7257):796 (2009)
  We welcome your Editorial plea ('Orphan giant' Nature 459, 1034; 2009) for stronger advocacy for tackling tuberculosis (TB), a shared global strategy and increased commitment to research and innovation. The emerging threat of drug-resistant TB in Europe, highlighted in a recent report from the European Academies Science Advisory Council (EASAC; http://www.easac.eu
• Africa's biotechnology battle
  - Nature 460(7257):797-798 (2009)
  An influential book accuses Europe of keeping genetically modified crops out of Africa, but, by polarizing the debate, it undermines efforts to improve the continent's agriculture, warn Ian Scoones and Dominic Glover.
• The world in a grain of sand
  - Nature 460(7257):798-799 (2009)
  On an island off the southwestern coast of Turkey, called Sedir Adasi, lies a stunning stretch of white sand known as Cleopatra's Beach. According to legend, Cleopatra's lover Mark Antony made the beach for her as a lavish gift by shipping bargeloads of sand from Egypt to the island some 2,000 years ago.
• D-Day forecast fictionalized
  - Nature 460(7257):799-800 (2009)
  Fluid dynamics and weather prediction seem unpromising material for a gripping story. But Giles Foden has ingeniously dramatized what is perhaps the most important weather forecast ever made: that for the D-Day landings, the invasion of continental Europe at Normandy by the Allied forces towards the end of the Second World War.
• Bling of the Bactrians
  - Nature 460(7257):800 (2009)
  Desire for gold has driven people out of their homes and out of their minds. So Soviet archaeologist Viktor Sarianidi cannot have been surprised when a crowd gathered to gawk at a mound he was excavating in northern Afghanistan in 1978.
• Mathematical physics: A tight squeeze
  - Nature 460(7257):801-802 (2009)
  How can identical particles be crammed together as densely as possible? A combination of theory and computer simulations shows how the answer to this intricate problem depends on the shape of the particles.
• Stem cells: Escaping fates with open states
  - Nature 460(7257):802-803 (2009)
  The ability of embryonic stem cells to give rise to any cell type relies on a remodelling protein that maintains open chromatin. But the chromatin landscape of these cells may be more complex than previously thought.
• Ecology: Elementary factors
  - Nature 460(7257):803-804 (2009)
  The identification of a general connection between biogeochemistry and the structure of food webs would constitute a considerable advance in understanding ecosystems. Ecologists are on the case.
• Cancer: More than kin and less than kind
  - Nature 460(7257):804-807 (2009)
  A gene that is found to be mutated in a type of blood cancer exhibits properties of both a growth-suppressing tumour suppressor and a growth-promoting oncogene.
• Chemical biology: Protein picker
  - Nature 460(7257):805 (2009)
  Abstract
• 50 & 100 years ago
  - Nature 460(7257):807 (2009)
  Most areas where there is a high prevalence of multiple sclerosis coincide in a highly suggestive fashion with areas where glaciation has played an important part in providing parent material for soils. However, the converse is certainly not true: all glacial soils cannot be correlated with areas where the prevalence of multiple sclerosis is high.
• Microbial genetics: Love the one you're with
  - Nature 460(7257):807-808 (2009)
  Candida albicans is notorious as an opportunistic microbe that causes thrush and serious systemic disease. For geneticists, however, it offers continuing revelations into the wondrously varied sex lives of fungi.
• Technology: Hydrogen-fuelled vehicles
  - Nature 460(7257):809-811 (2009)
  Hydrogen is hailed as a non-polluting synthetic fuel that could replace oil, especially for transport applications. The technology to make this a reality — particularly hydrogen-storage materials — has been a long time coming, but the first commercial vehicles might now be only a few years away.
• Metalloproteins
  - Nature 460(7257):814-822 (2009)
  Reactions involving H2, N2, CO, CO2 and CH4 are likely to have been central to the origin of life. This is indicated by the active-site structures of the enzymes involved, which are often reminiscent of minerals. Through the combined efforts of protein crystallography, various types of spectroscopy, theoretical calculations and model chemistry, it has been possible to put forward plausible mechanisms for gas-based metabolism by extant microorganisms. Although the reactions are based on metal centres, the protein matrix regulates reactivity and substrate and product trafficking through internal pathways, specific ligation and dielectricity.
• Structure–function relationships of anaerobic gas-processing metalloenzymes
  - Nature 460(7257):814-822 (2009)
  Reactions involving H2, N2, CO, CO2 and CH4 are likely to have been central to the origin of life. This is indicated by the active-site structures of the enzymes involved, which are often reminiscent of minerals. Through the combined efforts of protein crystallography, various types of spectroscopy, theoretical calculations and model chemistry, it has been possible to put forward plausible mechanisms for gas-based metabolism by extant microorganisms. Although the reactions are based on metal centres, the protein matrix regulates reactivity and substrate and product trafficking through internal pathways, specific ligation and dielectricity.
• Metalloproteins and metal sensing
  - Nature 460(7257):823-830 (2009)
  Almost half of all enzymes must associate with a particular metal to function. An ambition is to understand why each metal–protein partnership arose and how it is maintained. Metal availability provides part of the explanation, and has changed over geological time and varies between habitats but is held within vital limits in cells. Such homeostasis needs metal sensors, and there is an ongoing search to discover the metal-sensing mechanisms. For metalloproteins to acquire the right metals, metal sensors must correctly distinguish between the inorganic elements.
• Function and biogenesis of iron–sulphur proteins
  - Nature 460(7257):831-838 (2009)
  Iron–sulphur (Fe–S) clusters have long been recognized as essential and versatile cofactors of proteins involved in catalysis, electron transport and sensing of ambient conditions. Despite the relative simplicity of Fe–S clusters in terms of structure and composition, their synthesis and assembly into apoproteins is a highly complex and coordinated process in living cells. Different biogenesis machineries in both bacteria and eukaryotes have been discovered that assist Fe–S-protein maturation according to uniform biosynthetic principles. The importance of Fe–S proteins for life is documented by an increasing number of diseases linked to these components and their biogenesis.
• Molybdenum cofactors, enzymes and pathways
  - Nature 460(7257):839-847 (2009)
  The trace element molybdenum is essential for nearly all organisms and forms the catalytic centre of a large variety of enzymes such as nitrogenase, nitrate reductases, sulphite oxidase and xanthine oxidoreductases. Nature has developed two scaffolds holding molybdenum in place, the iron–molybdenum cofactor and pterin-based molybdenum cofactors. Despite the different structures and functions of molybdenum-dependent enzymes, there are important similarities, which we highlight here. The biosynthetic pathways leading to both types of cofactor have common mechanistic aspects relating to scaffold formation, metal activation and cofactor insertion into apoenzymes, and have served as an evolutionary 'toolbox' to mediate additional cellular functions in eukaryotic metabolism.
• Mechanistic considerations of halogenating enzymes
  - Nature 460(7257):848-854 (2009)
  In nature, halogenation is a strategy used to increase the biological activity of secondary metabolites, compounds that are often effective as drugs. However, halides are not particularly reactive unless they are activated, typically by oxidation. The pace of discovery of new enzymes for halogenation is increasing, revealing new metalloenzymes, flavoenzymes, S-adenosyl-L-methionine (SAM)-dependent enzymes and others that catalyse halide oxidation using dioxygen, hydrogen peroxide and hydroperoxides, or that promote nucleophilic halide addition reactions.
• Design of functional metalloproteins
  - Nature 460(7257):855-862 (2009)
  Metalloproteins catalyse some of the most complex and important processes in nature, such as photosynthesis and water oxidation. An ultimate test of our knowledge of how metalloproteins work is to design new metalloproteins. Doing so not only can reveal hidden structural features that may be missing from studies of native metalloproteins and their variants, but also can result in new metalloenzymes for biotechnological and pharmaceutical applications. Although it is much more challenging to design metalloproteins than non-metalloproteins, much progress has been made in this area, particularly in functional design, owing to recent advances in areas such as computational and structural biology.
• Chd1 regulates open chromatin and pluripotency of embryonic stem cells
  - Nature 460(7257):863-868 (2009)
  An open chromatin largely devoid of heterochromatin is a hallmark of stem cells. It remains unknown whether an open chromatin is necessary for the differentiation potential of stem cells, and which molecules are needed to maintain open chromatin. Here we show that the chromatin remodelling factor Chd1 is required to maintain the open chromatin of pluripotent mouse embryonic stem cells. Chd1 is a euchromatin protein that associates with the promoters of active genes, and downregulation of Chd1 leads to accumulation of heterochromatin. Chd1-deficient embryonic stem cells are no longer pluripotent, because they are incapable of giving rise to primitive endoderm and have a high propensity for neural differentiation. Furthermore, Chd1 is required for efficient reprogramming of fibroblasts to the pluripotent stem cell state. Our results indicate that Chd1 is essential for open chromatin and pluripotency of embryonic stem cells, and for somatic cell reprogramming to the pluri! potent state.
• The diversity of type Ia supernovae from broken symmetries
  - Nature 460(7257):869-872 (2009)
  Type Ia supernovae result when carbon-oxygen white dwarfs in binary systems accrete mass from companion stars, reach a critical mass and explode. The near uniformity of their light curves makes these supernovae good 'standard candles' for measuring cosmic expansion1, 2, 3, 4, but a correction must be applied to account for the fact that the brighter ones have broader light curves5. One-dimensional modelling, with a certain choice of parameters, can reproduce this general trend in the width–luminosity relation6, 7, 8; but the processes of ignition and detonation have recently been shown to be intrinsically asymmetric9, 10, 11, 12, 13, so parameterization must have its limits. Here we report multi-dimensional modelling of the explosion physics and radiative transfer, which reveals that the breaking of spherical symmetry is a critical factor in determining both the width–luminosity relation and the observed scatter about it. The deviation from spherical symmetry can a! lso explain the finite polarization detected in the light from some supernovae14. The slope and normalization of the width–luminosity relation has a weak dependence on certain properties of the white dwarf progenitor, in particular the trace abundances of elements other than carbon and oxygen. Failing to correct for this effect could lead to systematic overestimates of up to 2 per cent in the distance to remote supernovae.
• Storms in the tropics of Titan
  - Nature 460(7257):873-875 (2009)
  Methane clouds, lakes and most fluvial features on Saturn's moon Titan have been observed in the moist high latitudes1, 2, 3, 4, 5, 6, while the tropics have been nearly devoid of convective clouds and have shown an abundance of wind-carved surface features like dunes7, 8. The presence of small-scale channels and dry riverbeds near the equator observed by the Huygens probe9 at latitudes thought incapable of supporting convection10, 11, 12 (and thus strong rain) has been suggested to be due to geological seepage or other mechanisms not related to precipitation13. Here we report the presence of bright, transient, tropospheric clouds in tropical latitudes. We find that the initial pulse of cloud activity generated planetary waves that instigated cloud activity at other latitudes across Titan that had been cloud-free for at least several years. These observations show that convective pulses at one latitude can trigger short-term convection at other latitudes, even those no! t generally considered capable of supporting convection, and may also explain the presence of methane-carved rivers and channels near the Huygens landing site.
• Dense packings of the Platonic and Archimedean solids
  - Nature 460(7257):876-879 (2009)
  Dense particle packings have served as useful models of the structures of liquid, glassy and crystalline states of matter1, 2, 3, 4, granular media3, 5, heterogeneous materials3 and biological systems6, 7, 8. Probing the symmetries and other mathematical properties of the densest packings is a problem of interest in discrete geometry and number theory9, 10, 11. Previous work has focused mainly on spherical particles—very little is known about dense polyhedral packings. Here we formulate the generation of dense packings of polyhedra as an optimization problem, using an adaptive fundamental cell subject to periodic boundary conditions (we term this the 'adaptive shrinking cell' scheme). Using a variety of multi-particle initial configurations, we find the densest known packings of the four non-tiling Platonic solids (the tetrahedron, octahedron, dodecahedron and icosahedron) in three-dimensional Euclidean space. The densities are 0.782, 0.947, 0.904... and 0.836..., re! spectively. Unlike the densest tetrahedral packing, which must not be a Bravais lattice packing, the densest packings of the other non-tiling Platonic solids that we obtain are their previously known optimal (Bravais) lattice packings. Combining our simulation results with derived rigorous upper bounds and theoretical arguments leads us to the conjecture that the densest packings of the Platonic and Archimedean solids with central symmetry are given by their corresponding densest lattice packings. This is the analogue of Kepler's sphere conjecture for these solids.
• Atlantic hurricanes and climate over the past 1,500 years
  - Nature 460(7257):880-883 (2009)
  Atlantic tropical cyclone activity, as measured by annual storm counts, reached anomalous levels over the past decade1. The short nature of the historical record and potential issues with its reliability in earlier decades, however, has prompted an ongoing debate regarding the reality and significance of the recent rise2, 3, 4, 5. Here we place recent activity in a longer-term context by comparing two independent estimates of tropical cyclone activity over the past 1,500 years. The first estimate is based on a composite of regional sedimentary evidence of landfalling hurricanes, while the second estimate uses a previously published statistical model of Atlantic tropical cyclone activity driven by proxy reconstructions of past climate changes. Both approaches yield consistent evidence of a peak in Atlantic tropical cyclone activity during medieval times (around ad 1000) followed by a subsequent lull in activity. The statistical model indicates that the medieval peak, wh! ich rivals or even exceeds (within uncertainties) recent levels of activity, results from the reinforcing effects of La-Niña-like climate conditions and relative tropical Atlantic warmth.
• Glacial effects limiting mountain height
  - Nature 460(7257):884-887 (2009)
  The height of mountain ranges reflects the balance between tectonic rock uplift, crustal strength and surface denudation. Tectonic deformation and surface denudation are interdependent, however, and feedback mechanisms—in particular, the potential link to climate—are subjects of intense debate1, 2. Spatial variations in fluvial denudation rate caused by precipitation gradients are known to provide first-order controls on mountain range width, crustal deformation rates and rock uplift3, 4. Moreover, limits to crustal strength5 are thought to constrain the maximum elevation of large continental plateaus, such as those in Tibet and the central Andes. There are indications that the general height of mountain ranges is also directly influenced by the extent of glaciation through an efficient denudation mechanism known as the glacial buzzsaw6, 7, 8, 9. Here we use a global analysis of topography and show that variations in maximum mountain height correlate closely with c! limate-controlled gradients in snowline altitude for many high mountain ranges across orogenic ages and tectonic styles. With the aid of a numerical model, we further demonstrate how a combination of erosional destruction of topography above the snowline by glacier-sliding and commensurate isostatic landscape uplift caused by erosional unloading can explain observations of maximum mountain height by driving elevations towards an altitude window just below the snowline. The model thereby self-consistently produces the hypsometric signature of the glacial buzzsaw, and suggests that differences in the height of mountain ranges mainly reflect variations in local climate rather than tectonic forces.
• Pelvic claspers confirm chondrichthyan-like internal fertilization in arthrodires
  Ahlberg P Trinajstic K Johanson Z Long J - Nature 460(7257):888-889 (2009)
  Recent finds1, 2 demonstrate that internal fertilization and viviparity (live birth) were more widespread in the Placodermi, an extinct group of armoured fishes, than was previously realized. Placoderms represent the sister group of the crown group jawed vertebrates (Gnathostomata)3, 4, making their mode(s) of reproduction potentially informative about primitive gnathostome conditions. An ossified pelvic fin basipterygium discovered in the arthrodire Incisoscutum ritchiei was hypothesized to be identical in males and females, with males presumed to have an additional cartilaginous element or series forming a clasper. Here we report the discovery of a completely ossified pelvic clasper in Incisoscutum ritchiei (WAM 03.3.28) which shows that this interpretation was incorrect: the basipterygium described previously1 is in fact unique to females. The male clasper is a slender rod attached to a square basal plate that articulates directly with the pelvis. It carries a small! cap of dermal bone covered in denticles and small hooks that may be homologous with the much larger dermal component of the ptyctodont clasper.
• Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans
  - Nature 460(7257):890-893 (2009)
  Candida albicans is the most common fungal pathogen in humans, causing both debilitating mucosal infections and potentially life-threatening systemic infections1, 2. Until recently, C. albicans was thought to be strictly asexual, existing only as an obligate diploid. A cryptic mating cycle has since been uncovered in which diploid a and cells undergo efficient cell and nuclear fusion, resulting in tetraploid a/ mating products3, 4, 5, 6. Whereas mating between a and cells has been established (heterothallism), we report here two pathways for same-sex mating (homothallism) in C. albicans. First, unisexual populations of a cells were found to undergo autocrine pheromone signalling and same-sex mating in the absence of the Bar1 protease. In both C. albicans and Saccharomyces cerevisiae, Bar1 is produced by a cells and inactivates mating pheromone , typically secreted by cells7, 8, 9, 10. C. albicansbar1a cells were shown to secrete both a and mating pheromones; -phero! mone activated self-mating in these cells in a process dependent on Ste2, the receptor for -pheromone. In addition, pheromone production by cells was found to promote same-sex mating between wild-type a cells. These results establish that homothallic mating can occur in C. albicans, revealing the potential for genetic exchange even within unisexual populations of the organism. Furthermore, Bar1 protease has an unexpected but pivotal role in determining whether sexual reproduction can potentially be homothallic or is exclusively heterothallic. These findings also have implications for the mode of sexual reproduction in related species that propagate unisexually, and indicate a role for specialized sexual cycles in the survival and adaptation of pathogenic fungi.
• Programming cells by multiplex genome engineering and accelerated evolution
  Wang HH Isaacs FJ Carr PA Sun ZZ Xu G Forest CR Church GM - Nature 460(7257):894-898 (2009)
  The breadth of genomic diversity found among organisms in nature allows populations to adapt to diverse environments1, 2. However, genomic diversity is difficult to generate in the laboratory and new phenotypes do not easily arise on practical timescales3. Although in vitro and directed evolution methods4, 5, 6, 7, 8, 9 have created genetic variants with usefully altered phenotypes, these methods are limited to laborious and serial manipulation of single genes and are not used for parallel and continuous directed evolution of gene networks or genomes. Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid ! and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-d-xylulose-5-phosphate (DXP) biosynthesis pathway in Escherichia coli to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day. We isolated variants with more than fivefold increase in lycopene production within 3 days, a significant improvement over existing metabolic engineering techniques. Our multiplex approach embraces engineering in the context of evolution by expediting the design and evolution of organisms with new and improved properties.
• Intrinsic light response of retinal horizontal cells of teleosts
  Cheng N Tsunenari T Yau KW - Nature 460(7257):899-903 (2009)
  The discovery of intrinsically photosensitive retinal ganglion cells has overthrown the long-held belief that rods and cones are the exclusive retinal photoreceptors1, 2. Intrinsically photosensitive retinal ganglion cells use melanopsin3 as the photopigment, and mediate non-image-forming visual functions such as circadian photoentrainment. In fish, in situ hybridization studies indicated that melanopsin is present in retinal horizontal cells4, 5, 6—lateral association neurons critical for creating the centre-surround receptive fields of visual neurons. This raises the question of whether fish horizontal cells are intrinsically photosensitive. This notion was examined previously in flat-mount roach retina, but all horizontal-cell light response disappeared after synaptic transmission was blocked6, making any conclusion difficult to reach. To examine this question directly, we have now recorded from single, acutely dissociated horizontal cells from catfish and goldfis! h. We found that light induced a response in catfish cone horizontal cells, but not rod horizontal cells, consisting of a modulation of the nifedipine-sensitive, voltage-gated calcium current. The light response was extremely slow, lasting for many minutes. Similar light responses were observed in a high percentage of goldfish horizontal cells. We have cloned two melanopsin genes and one vertebrate ancient (VA) opsin gene from catfish. In situ hybridization indicated that melanopsin, but less likely VA opsin, was expressed in the horizontal-cell layer of catfish retina. This intrinsic light response may serve to modulate, over a long timescale, lateral inhibition mediated by these cells. Thus, at least in some vertebrates, there are retinal non-rod/non-cone photoreceptors involved primarily in image-forming vision.
• Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms
  Sanada M Suzuki T Shih LY Otsu M Kato M Yamazaki S Tamura A Honda H Sakata-Yanagimoto M Kumano K Oda H Yamagata T Takita J Gotoh N Nakazaki K Kawamata N Onodera M Nobuyoshi M Hayashi Y Harada H Kurokawa M Chiba S Mori H Ozawa K Omine M Hirai H Nakauchi H Koeffler HP Ogawa S - Nature 460(7257):904-908 (2009)
  Acquired uniparental disomy (aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes1, but also with gain-of-function mutations of proto-oncogenes2. Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features. The C-CBL proto-oncogene, a cellular homologue of v-Cbl, encodes an E3 ubiquitin ligase and negatively regulates signal transduction of tyrosine kinases3, 4, 5, 6. Homozygous C-CBL mutations were found in most 11q-aUPD-positive myeloid malignancies. Although the C-CBL mutations were oncogenic in NIH3T3 cells, c-Cbl was shown to functionally and genetically act as a tumour suppressor. C-CBL mutants did not have E3 ubiquitin ligase activity, but inhibited that of wild-type C-CBL and CBL-B (also known as CBLB), ! leading to prolonged activation of tyrosine kinases after cytokine stimulation. c-Cbl-/- haematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines compared to c-Cbl+/+ HSPCs, and transduction of C-CBL mutants into c-Cbl-/- HSPCs further augmented their sensitivities to a broader spectrum of cytokines, including stem-cell factor (SCF, also known as KITLG), thrombopoietin (TPO, also known as THPO), IL3 and FLT3 ligand (FLT3LG), indicating the presence of a gain-of-function that could not be attributed to a simple loss-of-function. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in a c-Cbl+/+ background or by co-transduction of wild-type C-CBL, which suggests the pathogenic importance of loss of wild-type C-CBL alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a new insight into a role of gain-of-function mutations of a tumour suppressor associated wit! h aUPD in the pathogenesis of some myeloid cancer subsets.
• A role for Lin28 in primordial germ-cell development and germ-cell malignancy
  West JA Viswanathan SR Yabuuchi A Cunniff K Takeuchi A Park IH Sero JE Zhu H Perez-Atayde A Frazier AL Surani MA Daley GQ - Nature 460(7257):909-913 (2009)
  The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwart efforts to investigate molecular mechanisms of germ-cell specification. stella (also called Dppa3) marks the rare founder population of the germ lineage1, 2. Here we differentiate mouse embryonic stem cells carrying a stella transgenic reporter into putative PGCs in vitro. The Stella+ cells possess a transcriptional profile similar to embryo-derived PGCs, and like their counterparts in vivo, lose imprints in a time-dependent manner. Using inhibitory RNAs to screen candidate genes for effects on the development of Stella+ cells in vitro, we discovered that Lin28, a negative regulator of let-7 microRNA processing3, 4, 5, 6, is essential for proper PGC development. Furthermore, we show that Blimp1 (also called Prdm1), a let-7 target and a master regulator of PGC specification7, 8, 9, can rescue the effect of Lin28 deficiency during PGC development, thereby establishing a! mechanism of action for Lin28 during PGC specification. Overexpression of Lin28 promotes formation of Stella+ cells in vitro and PGCs in chimaeric embryos, and is associated with human germ-cell tumours. The differentiation of putative PGCs from embryonic stem cells in vitro recapitulates the early stages of gamete development in vivo, and provides an accessible system for discovering novel genes involved in germ-cell development and malignancy.
• Multiple roles for MRE11 at uncapped telomeres
  Deng Y Guo X Ferguson DO Chang S - Nature 460(7257):914-918 (2009)
  Progressive telomere attrition or uncapping of the shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks1. Telomere deprotection activates both ataxia telangiectasia mutated (ATM) and telangiectasia and Rad3-related (ATR) kinase-dependent DNA damage response pathways, and promotes efficient non-homologous end-joining (NHEJ) of dysfunctional telomeres2, 3, 4, 5. The mammalian MRE11–RAD50–NBS1 (MRN; NBS1 is also known as NBN) complex interacts with ATM to sense chromosomal double-strand breaks and coordinate global DNA damage responses6, 7. Although the MRN complex accumulates at dysfunctional telomeres, it is not known whether mammalian MRN promotes repair at these sites. Here we address this question by using mouse alleles that either inactivate the entire MRN complex or eliminate only the nuclease activities of MRE11 (ref. 8). We show that cells lacking MRN do not! activate ATM when telomeric repeat binding factor 2 (TRF2) is removed from telomeres, and ligase 4 (LIG4)-dependent chromosome end-to-end fusions are markedly reduced. Residual chromatid fusions involve only telomeres generated by leading strand synthesis. Notably, although cells deficient for MRE11 nuclease activity efficiently activate ATM and recruit 53BP1 (also known as TP53BP1) to deprotected telomeres, the 3' telomeric overhang persists to prevent NHEJ-mediated chromosomal fusions. Removal of shelterin proteins that protect the 3' overhang in the setting of MRE11 nuclease deficiency restores LIG4-dependent chromosome fusions. Our data indicate a critical role for the MRN complex in sensing dysfunctional telomeres, and show that in the absence of TRF2, MRE11 nuclease activity removes the 3' telomeric overhang to promote chromosome fusions. MRE11 can also protect newly replicated leading strand telomeres from NHEJ by promoting 5' strand resection to generate POT1a–TP! P1-bound 3' overhangs.
• Bombs away!
  - Nature 460(7257):924 (2009)
  Happy landings.