Hot off the presses! May 07 Nature

The May 07 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:

• Between a virus and a hard place
  - Nature 459(7243):9 (2009)
  Complacency, not overreaction, is the greatest danger posed by the flu pandemic. That's a message scientists would do well to help get across.
• Keep to the vision
  - Nature 459(7243):9-10 (2009)
  The United States should not try to keep its space shuttles flying beyond 2010.
• Doing good, 50 years on
  - Nature 459(7243):10 (2009)
  Its attack on poverty and arrogance is what makes C. P. Snow's 'two cultures' lecture relevant today.
• Biology: Now hear this, or not
  - Nature 459(7243):12 (2009)
  
• Neurogenetics: Psychosis genes exposed
  - Nature 459(7243):12 (2009)
  
• Virology: HIV at the gates
  - Nature 459(7243):12 (2009)
  
• DNA repair: Chemo's modus operandi
  - Nature 459(7243):12 (2009)
  
• Conservation: Reef repair
  - Nature 459(7243):12 (2009)
  
• Materials science: Conductors with a twist
  - Nature 459(7243):13 (2009)
  
• Cosmology: No ring or reason
  - Nature 459(7243):13 (2009)
  
• Plant physiology: Gifts from grafts
  - Nature 459(7243):13 (2009)
  
• Structural biology: A virus laid bare
  - Nature 459(7243):13 (2009)
  
• Nanotechnology: The helix that delivers
  - Nature 459(7243):13 (2009)
  
• Journal club
  - Nature 459(7243):13 (2009)
  
• How severe will the flu outbreak be?
  - Nature 459(7243):14 (2009)
  
• China joins world-class synchrotron club
  - Nature 459(7243):16-17 (2009)
  
• Even big societies feel the pinch
  - Nature 459(7243):17 (2009)
  
• Neuroscientists claim growing pains
  - Nature 459(7243):19 (2009)
  
• Geologists suffer observatory glitches
  - Nature 459(7243):20 (2009)
  
• UK scientists get funding ban reprieve
  - Nature 459(7243):20 (2009)
  
• Hubble: the last hurrah
  - Nature 459(7243):21 (2009)
  
• Australia delays carbon reduction scheme
  - Nature 459(7243):23 (2009)
  
• Data 'mishandling' stalls Down's syndrome test
  - Nature 459(7243):23 (2009)
  
• Misconduct scandal hits German university
  - Nature 459(7243):23 (2009)
  
• South Korea re-enters human stem-cell research
  - Nature 459(7243):23 (2009)
  
• Biosecurity report cautious on strict researcher vetting
  - Nature 459(7243):23 (2009)
  
• Obama revokes endangered species rule
  - Nature 459(7243):23 (2009)
  
• Protein structures: Structures of desire
  - Nature 459(7243):24-27 (2009)
  
• Materials science: Enter the oxides
  - Nature 459(7243):28-30 (2009)
  
• The potential for water conflict is on the increase
  - Nature 459(7243):31 (2009)
  Wendy Barnaby dispels the myth of future water wars, arguing that countries "solve their water shortages through trade and international agreements" (see Nature 458, 282–283; 2009).
• Increasing inequality is already making shortages worse
  - Nature 459(7243):31 (2009)
  Wendy Barnaby is hasty in her conclusion that water shortages can and will be resolved through international trade and economic development (see Nature 458, 282–283; 2009).
• Water is a source of cooperation rather than war
  - Nature 459(7243):31 (2009)
  Water, like any scarce common resource, creates competition that can lead to conflict, but, as Wendy Barnaby concludes in her Essay, wars are not waged over water (see Nature 458, 282–283; 2009).
• Dissecting The Two Cultures
  - Nature 459(7243):32-33 (2009)
  Fifty years ago today, Charles Percy Snow argued in an influential lecture that the failure of science and the humanities to converse, and the lack of scientists in positions of power, was disastrous for society. In the first of three essays marking this anniversary, Martin Kemp contends that the real enemy of understanding is not these 'Two Cultures' but specialization in all disciplines.
• Science's new battle lines
  - Nature 459(7243):34-35 (2009)
  In the second of three essays on the 'Two Cultures', Georgina Ferry detects that today's division lies between optimists and pessimists rather than between scientific and literary intellectuals.
• Snow's portrait of science in politics
  - Nature 459(7243):36-39 (2009)
  BOOK REVIEWED-Extract from Science and Government by C. P. Snow Harvard University Press: 1961. Charles Percy Snow ignited controversy around science and policy-making in a series of lectures at Harvard University a year after his 'Two Cultures' debate. Below we reproduce an extract from the resulting book, Science and Government. It gives a remarkable insight into how science feeds into political decision-making. Snow was one of Britain's leading science civil servants. He capitalized on his experience at the heart of the government machinery to analyse the role of science and scientists in the United Kingdom during the Second World War. He wanted to disentangle how political decisions were made during the war and, importantly, how scientific advice was used to make them. Snow's portrait of science in politics POPPERFOTO/GETTY; CENTRAL PRESS/HULTON ARCHIVE/GETTY Frederick Lindemann (right) vehemently disagreed with Henry Tizard (left) over the development of radar as Britain's method of air defence. In the extract, Snow gives a colourful account of the decision to invest in the development of radar — an unproven technology in the mid-1930s that would prove to be key to the success of the allied war effort. In the years leading up to the war, the British government did not know how to handle the rise of Adolf Hitler and his military build-up in Germany. Snow homes in on two men, both scientists. One is the chemist Henry Tizard — rector of Imperial College, London, and chairman of an influential committee that advised the Labour government to invest in radar technology. The other is Tizard's one-time friend and later rival, Frederick Lindemann, a close adviser to Winston Churchill, who was then part of the Conservative opposition. Such an account could have been dry and factual, but this is not what we get from Snow's pen. Instead, his readers are treated to a page-turner. Snow the novelist is not afraid to tell us what his characters might be thinking. He is indiscreet about their personal lives, social connections and professional backgrounds. He guesses their motives and provides his own verdict on their judgements. Snow was attacked for not being detached enough in his analysis. Yet the book's accessibility ensured it was widely read. Five decades later, Science and Government remains a rare inside view of the relationship between science and political authority. Extract from Science and Government by C. P. Snow, pages 23-38. In 1934 both Tizard and Lindemann were nearly fifty. Of the two, Tizard had been by a long way the more successful, though even he, judged by the standard he set himself, had not lived up to his promise. He was a trusted man of affairs, he had been knighted, he was head of a university institution, but in his own eyes he had not done much. As for Lindemann, he had done much less. The professional physicists did not take him seriously as a scientist, and dismissed him as a cranky society pet. Scientifically his name was worth little. He was the intimate friend of [Churchill] a politician whose name was scarcely worth as much. Then, quite suddenly, Tizard was given the chance for which he was made. England was strategically in a desperately vulnerable position, for reasons — the tiny size of the country, the density of the population — which apply more harshly today. In 1934 [Stanley] Baldwin was the main figure in the government, and it was only two years since he had said lugubriously: "The bomber will always get through." In public, rebellious politicians like Churchill were attacking the whole of the government's defence policy. In secret, the government scientists, the military staffs, the high officials, were beating round for some sort of defence. There was nothing accidental about this. It was predictable that England, more vulnerable to air attack than any major country, would spend more effort trying to keep bombers off. But there was something accidental and unpredictable in Tizard being given his head. The Air Ministry, under the influence of their scientific adviser, H. E. Wimperis, himself prodded by a bright young government scientist called A. P. Rowe,1 set up a Committee for the Scientific Study of Air Defence. Its terms of reference were as flat as usual: "To consider how far advances in scientific and technical knowledge can be used to strengthen the present methods of defence against hostile aircraft." The committee was nothing very important to start with. No one took much notice when its membership was announced. There may have been slight curiosity about the appointment, which was entirely due to Wimperis,2 of Tizard as chairman. The appointment would not and could not have happened, though, if Tizard had not been so well connected in official life. Well, that committee was called the Tizard Committee almost from its first meeting. It is slightly touching that in his diary Tizard, who could not use that title, never seems to have been quite certain what its official title really was. From the first meeting on January 28th, 1935 he gripped the problems. This was the job for which he was born. Quite soon, by the summer of that year, small ripples of confidence oozed under the secret doors and penetrated Whitehall, almost the only ripples of confidence that touched the official world during those years. Tizard insisted on a very small committee which he chose himself. Wimperis had to be there, Rowe was brought in as secretary, but at the beginning there were only two members of independent standing, A. V. Hill and P. M. S. Blackett. Both of these were eminent scientists, of a quite different order of accomplishment from Tizard or Lindemann. Hill was one of the most distinguished physiologists in the world and had won a Nobel prize in 1922. Blackett, who was only thirty-seven at this time, was one of [Ernest] Rutherford's most brilliant pupils, and later himself won a Nobel prize.3 ... The committee made up its mind about [radar] before the device really existed. Watson Watt, who was the pioneer of radar in England, ... , had done some preliminary experiments. This device might, not certainly but possibly, work in real war in three or four years. Nothing else possibly could. Tizard, Hill, Blackett had faith in their own reasoning. Without fuss, and without backward glances, the choice was made. That was only a resolution on paper, and they had to make it actual. The administrative mechanism by which this was done is itself interesting. In form the Air Minister, Lord Swinton,4 arranged for a new high-level committee ... . Over this new body he himself presided, and on to it was brought the government's chief military critic, Winston Churchill. In fact, however, one has got to imagine a great deal of that apparently casual to-ing and fro-ing by which high English business gets done. As soon as the Tizard committee thought there was something in radar, one can take it that Tizard would lunch with Hankey5 at the Athenaeum; Hankey, the secretary of the Cabinet, would find it convenient to have a cup of tea with Swinton and Baldwin. If the Establishment had not trusted Tizard as one of their own, there might have been a waste of months or years. In fact, everything went through with the smoothness, the lack of friction, and the effortless speed which can only happen in England when the Establishment is behind one. Within a very short time! the Tizard Committee were asking for millions of pounds, and getting it without a blink of an eye. Two successive secretaries of the Cabinet, Hankey and Bridges,6 did much more than their official duties in pushing the project through. The second active job was, in particular, to persuade the serving officers of the Air Staff that radar was their one hope and, in general, to make scientists and military people understand each other. Here again this might have been impossible. In fact, with the exception of those concerned with bombing policy, the senior officers were ready to be convinced as soon as Tizard started to talk.7 They often thought of putting him in uniform: but that would have defeated his whole virtue as an interpreter between the two sides. "I utterly refuse to wear a busby," he used to say. Fairly soon he had not only got radar stations in principle accepted and hoped for, but also succeeded, with the help of Blackett's exceptional drive and insight, in beginning to teach one lesson each to the scientists and the military, lessons that Tizard and Blackett went on teaching for twenty years. The lesson to the military was that you cannot run wars on gusts of emotion. You have to think scientifically about your own operations. This was the start of operational research,8 the development of which was Blackett's major personal feat in the 1939–45 war.9 The lesson to the scientists was that the prerequisite of sound military advice is that the giver must convince himself that, if he were responsible for action, he would himself act so. It is a difficult lesson to learn. If it were learnt, the number of theoretical treatises on the future of war would be drastically reduced. The committee met for the first time, as I said, in January 1935. By the end of 1935 its important decisions were in effect taken. By the end of 1936 most of those decisions were translated into action. It was one of the most effective small committees in history. But before it clinched its choices, there was a most picturesque row. The committee had been set up, as we saw, from inside the Air Ministry. One of the reasons was, no doubt, to forestall criticism from outside, which came most loudly and effectively from Churchill. In 1934 he had publicly challenged the government's underestimate of the size of Hitler's air force. His figures, which had been produced by Lindemann, were much nearer the truth than the government's. Thus, simultaneously, there were going on the secret deliberations and discussions of the Tizard Committee, and an acrimonious military argument in full light in the House of Commons and the press, with Churchill the antigovernment spokesman. Snow's portrait of science in politics V. WEISZ/SOLO SYNDICATION/ASSOCIATED NEWSPAPERS LTD/BRITISH CARTOON ARCHIVE, UNIV. KENT, WWW.CARTOONS.AC.UK "But the trouble is when you get on to any kind of moral escalator, to know whether you're ever going to be able to get off." – C. P. Snow (1961). It is one of the classical cases of "closed" politics coexisting with "open" politics. Passing from one to the other, an observer would not have known that he was dealing with the same set of facts. By the middle of 1935 Baldwin, who had just in form as well as fact become Prime Minister, wanted to reduce the temperature of the "open" military argument. He used the orthodox manoeuvre of asking Churchill in. Not into the Cabinet: the personal rifts were too deep for that, but onto the new Swinton Committee, [a] political committee ..., which was to keep a supervisory eye on air defence. The history is very tangled at this point. No minutes have ever been published, but if I know Hankey and his colleagues at all — and I had the good luck to work under them a short time later — I have not much doubt that on the one hand they felt confident that they could give the Tizard Committee its head (Tizard sat himself on the political committee and made his requests for money to it), and that on the other hand it could not do harm, and might do good, if Churchill were given exact information of what was actually being done, rather than inexact. Roughly that was what happened, but there were other consequences. Churchill entered the political committee, retaining the right to criticise in public and insisting that Lindemann, as his personal scientific adviser, be given a place on the Tizard Committee. Both these conditions were reasonable enough: but then the private war began. Almost from the moment that Lindemann took his seat in the committee room, the meetings did not know half an hour's harmony or work undisturbed. I must say, as one with a taste for certain aspects of human behaviour, I should have dearly liked to be there. The faces themselves would have been a nice picture. Lindemann, Hill, and Blackett were all very tall men of distinguished physical presence — Blackett sculptured and handsome, Hill ruddy and English, Lindemann pallid, heavy, Central European. Blackett and Hill would be dressed casually, like academics. Tizard and Lindemann, who were both conventional in such things, would be wearing black coats and striped trousers, and both would come to the meetings in bowler hats. At the table Blackett and Hill, neither of them especially patient men nor overfond of listening to nonsense, sat with incredulity through diatribes by Lindemann, scornful, contemptuous, barely audible, directed against any decision that Tizard had made, wa! s making, or ever would make. Tizard sat it out for some time. He could be irritable, but he had great resources of temperament, and he knew that this was too serious a time to let the irritability flash. He also knew, from the first speech that Lindemann made in committee, that the friendship of years was smashed. There must have been hidden resentments and rancours, which we are now never likely to know and which had been latent long before this. No doubt Lindemann, who was a passionate man, with the canalised passion of the repressed, felt that he ought to have been doing Tizard's job. No doubt he felt, because no one ever had more absolute belief in his own conclusions, that he would have done Tizard's job much better, and that his specifics for air defence were the right ones, and the only right ones. No doubt he felt, with his fanatical patriotism, that Tizard and his accomplices, these Blacketts, these Hills, were a menace to the country and ought to be swept away. It may have been — there are some who were close to these events who have told me so — that all his judgments at these meetings were due to his hatred of Tizard, which had burst out as uncontrollably as love. That is, whatever Tizard wanted and supported, Lindemann would have felt unshakably was certain to be wrong and would have opposed. The other view is that Lindemann's scientific, as well as his emotional, temperament came in: it was not only hatred for Tizard, it was also his habit of getting self-blindingly attached to his own gadgety ideas that led him on. Whatever the motive was, he kept making his case to the committee in his own characteristic tone of grinding certainty. It was an unjustifiable case. The issue in principle was very simple. Radar was not yet proved to work: but Tizard and the others, as I have said, were certain that it was the only hope. None of them was committed to any special gadget. That was not the cast of their minds. There was only a limited amount of time, of people, of resources. Therefore the first priority must be given to radar — not only to making the equipment, but to making arrangements, well in advance even of the first tests, for its operational use. (It was in fact in the operational use of radar, rather than in the equipment, that England got a slight tactical lead.) Lindemann would not have any of this. Radar was not proved. He demanded that it should be put much lower on the priority list and research on other devices given the highest priority. He had two pet devices of his own. One was the use of infra-red detection. This seemed wildly impracticable then, to any of the others and to anyone who heard the idea. It seems even more wildly impracticable now. The other putative device was the dropping, in front of hostile aircraft, of parachute bombs and parachute mines. Mines in various forms had a singular fascination for Lindemann. Snow's portrait of science in politics HULTON-DEUTSCH COLLECTION/CORBIS C. P. Snow championed openness but recognized that radar would not have been developed without 'closed' decision-making. For twelve months Lindemann ground on with his feud on the committee. He was tireless. He was ready at each meeting to begin again from the beginning. He was quite unsoftened, quite impregnable to doubt. Only a very unusual man, and one of abnormal emotional resistance and energy, could sit with men so able and not be affected in the slightest regard. They themselves were not affected so far as choice was concerned. Tizard went ahead with the radar decisions and let Lindemann register his disagreement. But gradually they got worn down. Neither Blackett nor Hill was phlegmatic enough to endure this monomaniac tension for ever. In July 1936,10 when the committee were preparing a report, Lindemann abused Tizard in his usual form, over the invariable issue of too much priority for radar, but in terms so savage that the secretaries had to be sent out of the room.11 At that point Blackett and Hill had had enough of it. They resigned and did not try to give an emollient excuse for doing so. Whether this was done after discussion with Tizard is not clear. No discussion was really necessary. They all believed that this friction was doing too much harm. They were all experienced enough to know that, with Churchill still out of office, they could make their own terms. Within a short time the committee was reappointed. Tizard was still chairman, Blackett and Hill were still members. Lindemann, however, was not. He was replaced by E. V. Appleton, the greatest living English expert on the propagation of radio waves. Radar itself was an application of Appleton's fundamental work. The announcement of his name meant, in the taciturn eloquence of official statements, a clear victory for radar and for Tizard. The radar stations and the radar organisation were ready, not perfect but working, in time for the Battle of Britain. This had a major, and a perhaps decisive, effect. This cautionary story of the first Lindemann–Tizard collision seems to me to contain a number of lessons, some of them not obvious. But there is one, at the same time so obvious and so ironic that I shall mention it now. It is simply that the results of closed politics can run precisely contrary to the results of open politics. That is an occupational feature of the way in which closed politics works and the way in which secret choices are made. Probably not more than a hundred people had any information whatever about Tizard's first radar decision; not more than twenty people took any effective part in it, and at the point of choice not more than five or six. While that was going on, so also was violent open politics, the open politics of the thirties, the most ferocious and deeply felt open politics of my lifetime. Nearly everyone I knew of my own age who was politically committed, that is, who had decided that fascism had at all costs to be stopped, wanted Churchill brought into government. Partly for his own gifts, partly as a symbol of a country which was not going to let the Nazis win by default. We signed collective letters about Churchill; we used what influence we had, which in those years was not much. We wanted a government which would resist, the kind of government we finally got in 1940. That was the position, I think, of Blackett and most of my liberal friends. It was certainly my own. Looking back, I think we were right, and if put back in those years again I should do what I did then. The ifs of history are not very profitable — but if Churchill had been brought back to office, if open politics had gone the way my friends and I clamoured and implored that it should? We should, without any question, have been morally better prepared for war when it came. We should have been better prepared in the amount of war material. But, studying the story I have just told, I find it hard to resist the possibility that, in some essential technical respects, we might have been worse prepared. If Churchill had come into office, Lindemann would have come with him, as happened later. It is then very hard to imagine Lindemann not getting charge of the Tizard Committee. As I have said, I take a pretty Tolstoyan view of history in the large. In a broad sense I cannot easily accept that these small personal accidents could affect major destinies. And yet ... without getting the radar in time we should not have stood a good chance in the war that finally arrived. With Lindemann instead of Tizard, it seems at least likely that different technical choices would have been made. If that had been so, I still cannot for the life of me see how the radar system would have been ready in time. These retrospective fears are not profitable. But I do not know of a clearer case where open and closed politics appear to tell such different stories and point to such different fates. Reprinted by permission of the publisher from Science and Government by C. P. Snow, pp. 23–38, Harvard University Press, Cambridge, Mass. © 1960, 1961 by the President and Fellows of Harvard College. © renewed by Charles Percy Snow.
• Palaeoanthropology: Homo floresiensis from head to toe
  - Nature 459(7243):41-42 (2009)
  Fossils of tiny ancient humans, found on the island of Flores, have provoked much debate and speculation. Evidence that they are a real species comes from analyses of the foot and also — more surprisingly — of dwarf hippos.
• 50 & 100 years ago
  - Nature 459(7243):43 (2009)
  According to the present model, the solar corona consists of a gas of electrons and protons with a small mixture of heavy elements which is isothermal at a temperature of approximately a million degrees and which is in hydrostatic equilibrium in the gravitational field of the Sun. The alternative model which we propose is that the solar corona consists of trapped charged particles moving in the magnetic field of the Sun, very like the charged-particle cloud surrounding the Earth which has been recently discovered by Van Allen and his ollaborators.
• Astrophysics: Galaxy connections
  - Nature 459(7243):43-44 (2009)
  A combined millimetre- and visible-light view of a forming cluster of galaxies in the young Universe adds yet another piece to the puzzle of how today's Universe of galaxies formed and evolved.
• Translation: Till termination us do part
  - Nature 459(7243):44-45 (2009)
  Translation of messenger RNA into protein is a complex and intricate process involving several steps and many step-specific protein factors. But one factor — eIF5A — seems to have a hand in every step.
• Mechanochemistry: Polymers react to stress
  - Nature 459(7243):45-46 (2009)
  The latest polymers are chameleon-like: they change colour on deformation. The transduction mechanism underpinning this effect could be used to make polymers that respond in many other ways to mechanical stress.
• Cell biology: Arrest by ribosome
  - Nature 459(7243):46-47 (2009)
  Impaired assembly of cells' protein-synthesis factories, the ribosomes, can cause cell-cycle arrest and disease. This finding emphasizes the close link between cell proliferation and ribosome formation.
• The formation of the first stars and galaxies
  - Nature 459(7243):49-54 (2009)
  Observations made using large ground-based and space-borne telescopes have probed cosmic history from the present day to a time when the Universe was less than one-tenth of its present age. Earlier still lies the remaining frontier, where the first stars, galaxies and massive black holes formed. They fundamentally transformed the early Universe by endowing it with the first sources of light and chemical elements beyond the primordial hydrogen and helium produced in the Big Bang. The interplay of theory and upcoming observations promises to answer the key open questions in this emerging field.
• HDAC2 negatively regulates memory formation and synaptic plasticity
  - Nature 459(7243):55-60 (2009)
  Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficie! nt mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment.
• Spatial correlation between submillimetre and Lyman-alpha galaxies in the SSA 22 protocluster
  - Nature 459(7243):61-63 (2009)
  Lyman-alpha emitters are thought to be young, low-mass galaxies with ages of approx108 yr (refs 1, 2). An overdensity of them in one region of the sky (the SSA 22 field) traces out a filamentary structure in the early Universe at a redshift of z approximately 3.1 (equivalent to 15 per cent of the age of the Universe) and is believed to mark a forming protocluster3, 4. Galaxies that are bright at (sub)millimetre wavelengths are undergoing violent episodes of star formation5, 6, 7, 8, and there is evidence that they are preferentially associated with high-redshift radio galaxies9, so the question of whether they are also associated with the most significant large-scale structure growing at high redshift (as outlined by Lyman-alpha emitters) naturally arises. Here we report an imaging survey of 1,100-mum emission in the SSA 22 region. We find an enhancement of submillimetre galaxies near the core of the protocluster, and a large-scale correlation between the submillimetre! galaxies and the low-mass Lyman-alpha emitters, suggesting synchronous formation of the two very different types of star-forming galaxy within the same structure at high redshift. These results are in general agreement with our understanding of the formation of cosmic structure.
• A large iron isotope effect in SmFeAsO1 - xFx and Ba1 - xKxFe2As2
  - Nature 459(7243):64-67 (2009)
  The recent discovery of superconductivity in oxypnictides with a critical transition temperature (T C) higher than the McMillan limit of 39 K (the theoretical maximum predicted by Bardeen–Cooper–Schrieffer theory) has generated great excitement1, 2, 3, 4, 5. Theoretical calculations indicate that the electron–phonon interaction is not strong enough to give rise to such high transition temperatures6, but strong ferromagnetic/antiferromagnetic fluctuations have been proposed to be responsible7, 8, 9. Superconductivity and magnetism in pnictide superconductors, however, show a strong sensitivity to the crystal lattice, suggesting the possibility of unconventional electron–phonon coupling. Here we report the effect of oxygen and iron isotope substitution on T C and the spin-density wave (SDW) transition temperature (T SDW) in the SmFeAsO1 - xFx and Ba1 - xKxFe2As2 systems. The oxygen isotope effect on T C and T SDW is very small, while the iron isotope exponent alp! ha C = -dlnT C/dlnM is about 0.35 (0.5 corresponds to the full isotope effect). Surprisingly, the iron isotope exchange shows the same effect on T SDW as T C. This indicates that electron–phonon interaction plays some role in the superconducting mechanism, but a simple electron–phonon coupling mechanism seems unlikely because a strong magnon–phonon coupling is included.
• Force-induced activation of covalent bonds in mechanoresponsive polymeric materials
  - Nature 459(7243):68-72 (2009)
  Mechanochemical transduction enables an extraordinary range of physiological processes such as the sense of touch, hearing, balance, muscle contraction, and the growth and remodelling of tissue and bone1, 2, 3, 4, 5, 6. Although biology is replete with materials systems that actively and functionally respond to mechanical stimuli, the default mechanochemical reaction of bulk polymers to large external stress is the unselective scission of covalent bonds, resulting in damage or failure7. An alternative to this degradation process is the rational molecular design of synthetic materials such that mechanical stress favourably alters material properties. A few mechanosensitive polymers with this property have been developed8, 9, 10, 11, 12, 13, 14; but their active response is mediated through non-covalent processes, which may limit the extent to which properties can be modified and the long-term stability in structural materials. Previously, we have shown with dissolved po! lymer strands incorporating mechanically sensitive chemical groups—so-called mechanophores—that the directional nature of mechanical forces can selectively break and re-form covalent bonds15, 16. We now demonstrate that such force-induced covalent-bond activation can also be realized with mechanophore-linked elastomeric and glassy polymers, by using a mechanophore that changes colour as it undergoes a reversible electrocyclic ring-opening reaction under tensile stress and thus allows us to directly and locally visualize the mechanochemical reaction. We find that pronounced changes in colour and fluorescence emerge with the accumulation of plastic deformation, indicating that in these polymeric materials the transduction of mechanical force into the ring-opening reaction is an activated process. We anticipate that force activation of covalent bonds can serve as a general strategy for the development of new mechanophore building blocks that impart polymeric materials with! desirable functionalities ranging from damage sensing to full! y regenerative self-healing.
• Self-assembly of a nanoscale DNA box with a controllable lid
  - Nature 459(7243):73-76 (2009)
  The unique structural motifs and self-recognition properties of DNA can be exploited to generate self-assembling DNA nanostructures of specific shapes using a 'bottom-up' approach1. Several assembly strategies have been developed for building complex three-dimensional (3D) DNA nanostructures2, 3, 4, 5, 6, 7, 8. Recently, the DNA 'origami' method was used to build two-dimensional addressable DNA structures of arbitrary shape9 that can be used as platforms to arrange nanomaterials with high precision and specificity9, 10, 11, 12, 13. A long-term goal of this field has been to construct fully addressable 3D DNA nanostructures14, 15. Here we extend the DNA origami method into three dimensions by creating an addressable DNA box 42 times 36 times 36 nm3 in size that can be opened in the presence of externally supplied DNA 'keys'. We thoroughly characterize the structure of this DNA box using cryogenic transmission electron microscopy, small-angle X-ray scattering and atomic ! force microscopy, and use fluorescence resonance energy transfer to optically monitor the opening of the lid. Controlled access to the interior compartment of this DNA nanocontainer could yield several interesting applications, for example as a logic sensor for multiple-sequence signals or for the controlled release of nanocargos.
• Upper-mantle volatile chemistry at Oldoinyo Lengai volcano and the origin of carbonatites
  - Nature 459(7243):77-80 (2009)
  Carbonatite lavas are highly unusual in that they contain almost no SiO2 and are >50 per cent carbonate minerals. Although carbonatite magmatism has occurred throughout Earth's history, Oldoinyo Lengai, in Tanzania, is the only currently active volcano producing these exotic rocks1. Here we show that volcanic gases captured during an eruptive episode at Oldoinyo Lengai are indistinguishable from those emitted along mid-ocean ridges, despite the fact that Oldoinyo Lengai carbonatites occur in a setting far removed from oceanic spreading centres. In contrast to lithophile trace elements, which are highly fractionated by the immiscible phase separation that produces these carbonatites, volatiles (CO2, He, N2 and Ar) are little affected by this process. Our results demonstrate that a globally homogenous reservoir exists in the upper mantle and supplies volatiles to both mid-ocean ridges and continental rifts. This argues against an unusually C-rich mantle being responsible! for the genesis of Na-rich carbonatite and its nephelinite source magma at Oldoinyo Lengai. Rather, these carbonatites are formed in the shallow crust by immiscibility from silicate magmas (nephelinite), and are stable under eruption conditions as a result of their high Na contents.
• The foot of Homo floresiensis
  - Nature 459(7243):81-84 (2009)
  Homo floresiensis is an endemic hominin species that occupied Liang Bua, a limestone cave on Flores in eastern Indonesia, during the Late Pleistocene epoch1, 2. The skeleton of the type specimen (LB1) of H. floresiensis includes a relatively complete left foot and parts of the right foot3. These feet provide insights into the evolution of bipedalism and, together with the rest of the skeleton, have implications for hominin dispersal events into Asia. Here we show that LB1's foot is exceptionally long relative to the femur and tibia, proportions never before documented in hominins but seen in some African apes. Although the metatarsal robusticity sequence is human-like and the hallux is fully adducted, other intrinsic proportions and pedal features are more ape-like. The postcranial anatomy of H. floresiensis is that of a biped1, 2, 3, but the unique lower-limb proportions and surprising combination of derived and primitive pedal morphologies suggest kinematic and biome! chanical differences from modern human gait. Therefore, LB1 offers the most complete glimpse of a bipedal hominin foot that lacks the full suite of derived features characteristic of modern humans and whose mosaic design may be primitive for the genus Homo. These new findings raise the possibility that the ancestor of H. floresiensis was not Homo erectus but instead some other, more primitive, hominin whose dispersal into southeast Asia is still undocumented.
• Insular dwarfism in hippos and a model for brain size reduction in Homo floresiensis
  - Nature 459(7243):85-88 (2009)
  Body size reduction in mammals is usually associated with only moderate brain size reduction, because the brain and sensory organs complete their growth before the rest of the body during ontogeny1, 2. On this basis, 'phyletic dwarfs' are predicted to have a greater relative brain size than 'phyletic giants'1, 3. However, this trend has been questioned in the special case of dwarfism of mammals on islands4. Here we show that the endocranial capacities of extinct dwarf species of hippopotamus from Madagascar are up to 30% smaller than those of a mainland African ancestor scaled to equivalent body mass. These results show that brain size reduction is much greater than predicted from an intraspecific 'late ontogenetic' model of dwarfism in which brain size scales to body size with an exponent of 0.35. The nature of the proportional change or grade shift2, 5 observed here indicates that selective pressures on brain size are potentially independent of those on body size. Th! is study demonstrates empirically that it is mechanistically possible for dwarf mammals on islands to evolve significantly smaller brains than would be predicted from a model of dwarfing based on the intraspecific scaling of the mainland ancestor. Our findings challenge current understanding of brain–body allometric relationships in mammals and suggest that the process of dwarfism could in principle explain small brain size, a factor relevant to the interpretation of the small-brained hominin found on the Island of Flores, Indonesia6.
• Decision-related activity in sensory neurons reflects more than a neuron's causal effect
  - Nature 459(7243):89-92 (2009)
  During perceptual decisions, the activity of sensory neurons correlates with a subject's percept, even when the physical stimulus is identical1, 2, 3, 4, 5, 6, 7, 8, 9. The origin of this correlation is unknown. Current theory proposes a causal effect of noise in sensory neurons on perceptual decisions10, 11, 12, but the correlation could result from different brain states associated with the perceptual choice13 (a top-down explanation). These two schemes have very different implications for the role of sensory neurons in forming decisions14. Here we use white-noise analysis15 to measure tuning functions of V2 neurons associated with choice and simultaneously measure how the variation in the stimulus affects the subjects' (two macaques) perceptual decisions16, 17, 18. In causal models, stronger effects of the stimulus upon decisions, mediated by sensory neurons, are associated with stronger choice-related activity. However, we find that over the time course of the tria! l these measures change in different directions—at odds with causal models. An analysis of the effect of reward size also supports this conclusion. Finally, we find that choice is associated with changes in neuronal gain that are incompatible with causal models. All three results are readily explained if choice is associated with changes in neuronal gain caused by top-down phenomena that closely resemble attention19. We conclude that top-down processes contribute to choice-related activity. Thus, even forming simple sensory decisions involves complex interactions between cognitive processes and sensory neurons.
• Compound vesicle fusion increases quantal size and potentiates synaptic transmission
  - Nature 459(7243):93-97 (2009)
  Exocytosis at synapses involves fusion between vesicles and the plasma membrane1. Although compound fusion between vesicles2, 3 was proposed to occur at ribbon-type synapses4, 5, whether it exists, how it is mediated, and what role it plays at conventional synapses remain unclear. Here we report the existence of compound fusion, its underlying mechanism, and its role at a nerve terminal containing conventional active zones in rats and mice. We found that high potassium application and high frequency firing induced giant capacitance up-steps, reflecting exocytosis of vesicles larger than regular ones, followed by giant down-steps, reflecting bulk endocytosis. These intense stimuli also induced giant vesicle-like structures, as observed with electron microscopy, and giant miniature excitatory postsynaptic currents (mEPSCs), reflecting more transmitter release. Calcium and its sensor for vesicle fusion, synaptotagmin, were required for these giant events. After high frequ! ency firing, calcium/synaptotagmin-dependent mEPSC size increase was paralleled by calcium/synaptotagmin-dependent post-tetanic potentiation. These results suggest a new route of exocytosis and endocytosis composed of three steps. First, calcium/synaptotagmin mediates compound fusion between vesicles. Second, exocytosis of compound vesicles increases quantal size, which increases synaptic strength and contributes to the generation of post-tetanic potentiation. Third, exocytosed compound vesicles are retrieved via bulk endocytosis. We suggest that this vesicle cycling route be included in models of synapses in which only vesicle fusion with the plasma membrane is considered1.
• Fused has evolved divergent roles in vertebrate Hedgehog signalling and motile ciliogenesis
  Wilson CW Nguyen CT Chen MH Yang JH Gacayan R Huang J Chen JN Chuang PT - Nature 459(7243):98-102 (2009)
  Hedgehog (Hh) signalling is essential for several aspects of embryogenesis1, 2. In Drosophila, Hh transduction is mediated by a cytoplasmic signalling complex3, 4, 5 that includes the putative serine-threonine kinase Fused (Fu) and the kinesin Costal 2 (Cos2, also known as Cos), yet Fu does not have a conserved role in Hh signalling in mammals6, 7. Mouse Fu (also known as Stk36) mutants are viable and seem to respond normally to Hh signalling. Here we show that mouse Fu is essential for construction of the central pair apparatus of motile, 9+2 cilia and offers a new model of human primary ciliary dyskinesia. We found that mouse Fu physically interacts with Kif27, a mammalian Cos2 orthologue8, and linked Fu to known structural components of the central pair apparatus, providing evidence for the first regulatory component involved in central pair construction. We also demonstrated that zebrafish Fu is required both for Hh signalling and cilia biogenesis in Kupffer's vesi! cle. Mouse Fu rescued both Hh-dependent and -independent defects in zebrafish. Our results delineate a new pathway for central pair apparatus assembly, identify common regulators of Hh signalling and motile ciliogenesis, and provide insights into the evolution of the Hh cascade.
• Haematopoietic stem cells depend on Galphas-mediated signalling to engraft bone marrow
  Adams GB Alley IR Chung UI Chabner KT Jeanson NT Celso CL Marsters ES Chen M Weinstein LS Lin CP Kronenberg HM Scadden DT - Nature 459(7243):103-107 (2009)
  Haematopoietic stem and progenitor cells (HSPCs) change location during development1 and circulate in mammals throughout life2, moving into and out of the bloodstream to engage bone marrow niches in sequential steps of homing, engraftment and retention3, 4, 5. Here we show that HSPC engraftment of bone marrow in fetal development is dependent on the guanine-nucleotide-binding protein stimulatory alpha subunit (Galphas). HSPCs from adult mice deficient in Galphas (Galphas -/-) differentiate and undergo chemotaxis, but also do not home to or engraft in the bone marrow in adult mice and demonstrate a marked inability to engage the marrow microvasculature. If deleted after engraftment, Galphas deficiency did not lead to lack of retention in the marrow, rather cytokine-induced mobilization into the blood was impaired. Testing whether activation of Galphas affects HSPCs, pharmacological activators enhanced homing and engraftment in vivo. Galphas governs specific aspects of H! SPC localization under physiological conditions in vivo and may be pharmacologically targeted to improve transplantation efficiency.
• Histone modifications at human enhancers reflect global cell-type-specific gene expression
  Heintzman ND Hon GC Hawkins RD Kheradpour P Stark A Harp LF Ye Z Lee LK Stuart RK Ching CW Ching KA Antosiewicz-Bourget JE Liu H Zhang X Green RD Lobanenkov VV Stewart R Thomson JA Crawford GE Kellis M Ren B - Nature 459(7243):108-112 (2009)
  The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene1, 2, 3, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome4, 5, 6. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a globa! l scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.
• CBP/p300-mediated acetylation of histone H3 on lysine 56
  Das C Lucia MS Hansen KC Tyler JK - Nature 459(7243):113-117 (2009)
  Acetylation within the globular core domain of histone H3 on lysine 56 (H3K56) has recently been shown to have a critical role in packaging DNA into chromatin following DNA replication and repair in budding yeast1, 2. However, the function or occurrence of this specific histone mark has not been studied in multicellular eukaryotes, mainly because the Rtt109 enzyme that is known to mediate acetylation of H3K56 (H3K56ac) is fungal-specific3, 4. Here we demonstrate that the histone acetyl transferase CBP (also known as Nejire) in flies and CBP and p300 (Ep300) in humans acetylate H3K56, whereas Drosophila Sir2 and human SIRT1 and SIRT2 deacetylate H3K56ac. The histone chaperones ASF1A in humans and Asf1 in Drosophila are required for acetylation of H3K56 in vivo, whereas the histone chaperone CAF-1 (chromatin assembly factor 1) in humans and Caf1 in Drosophila are required for the incorporation of histones bearing this mark into chromatin. We show that, in response to DNA! damage, histones bearing acetylated K56 are assembled into chromatin in Drosophila and human cells, forming foci that colocalize with sites of DNA repair. Furthermore, acetylation of H3K56 is increased in multiple types of cancer, correlating with increased levels of ASF1A in these tumours. Our identification of multiple proteins regulating the levels of H3K56 acetylation in metazoans will allow future studies of this critical and unique histone modification that couples chromatin assembly to DNA synthesis, cell proliferation and cancer.
• Hypusine-containing protein eIF5A promotes translation elongation
  - Nature 459(7243):118-121 (2009)
  Translation elongation factors facilitate protein synthesis by the ribosome. Previous studies identified two universally conserved translation elongation factors, EF-Tu in bacteria (known as eEF1A in eukaryotes) and EF-G (eEF2), which deliver aminoacyl-tRNAs to the ribosome and promote ribosomal translocation, respectively1. The factor eIF5A (encoded by HYP2 and ANB1 in Saccharomyces cerevisiae), the sole protein in eukaryotes and archaea to contain the unusual amino acid hypusine (N epsilon-(4-amino-2-hydroxybutyl)lysine)2, was originally identified based on its ability to stimulate the yield (endpoint) of methionyl-puromycin synthesis—a model assay for first peptide bond synthesis thought to report on certain aspects of translation initiation3, 4. Hypusine is required for eIF5A to associate with ribosomes5, 6 and to stimulate methionyl-puromycin synthesis7. Because eIF5A did not stimulate earlier steps of translation initiation8, and depletion of eIF5A in yeast onl! y modestly impaired protein synthesis9, it was proposed that eIF5A function was limited to stimulating synthesis of the first peptide bond or that eIF5A functioned on only a subset of cellular messenger RNAs. However, the precise cellular role of eIF5A is unknown, and the protein has also been linked to mRNA decay, including the nonsense-mediated mRNA decay pathway10, 11, and to nucleocytoplasmic transport12, 13. Here we use molecular genetic and biochemical studies to show that eIF5A promotes translation elongation. Depletion or inactivation of eIF5A in the yeast S. cerevisiae resulted in the accumulation of polysomes and an increase in ribosomal transit times. Addition of recombinant eIF5A from yeast, but not a derivative lacking hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover, inactivation of eIF5A mimicked the effects of the eEF2 inhibitor sordarin, indicating that eIF5A might function together with eEF2 to promote ribosomal translocation. Because! eIF5A is a structural homologue of the bacterial protein EF-P! 14, 15, we propose that eIF5A/EF-P is a universally conserved translation elongation factor.
• Temperature-dependent thermal diffusivity of the Earth's crust and implications for magmatism
  - Nature 459(7243):122 (2009)
  Nature 458, 319–321 (2009) In equation (3) of this Letter, 10-6 should be 106. The corrected equation is: Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com.
• New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure
  - Nature 459(7243):122 (2009)
  Nature 454, 1000–1004 (2008) In the Methods Summary of this Letter, the concentrations of IBMX and dexamethasone were incorrectly listed as 0.5 muM and 5 mM, respectively. The correct concentrations are 0.5 mM IBMX and 5 muM dexamethasone.
• Ice blue
  - Nature 459(7243):128 (2009)
  Escape from your cells.