Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public. http://www.nature.com/nature/current_issue/ Nature Publishing Group en © 2004 Nature Publishing Group Nature 0028-0836 1476-4679 © 2004 Nature Publishing Group permissions@nature.com http://www.nature.com/includes/rj_globnavimages/nature_logo.gif http://www.nature.com/nature/ http://dx.doi.org/10.1038/429001a Despite disagreement between governments about tackling climate change, initiatives are bubbling up from below. With help from researchers and the markets, citizens can be made more aware of how to help reduce carbon dioxide emissions. Carbon impacts made visible doi:10.1038/429001a Nature 429, 1 (2004) Nature 429 6987 Editorial 1 1 http://dx.doi.org/10.1038/429001b A moment of triumph for South Korean science appears to have been marred by doubts about lab practice. Ethics of therapeutic cloning doi:10.1038/429001b Nature 429, 1 (2004) Nature 429 6987 Editorial 1 1 http://dx.doi.org/10.1038/429003a SeoulWhen, in February, a South Korean team announced that it had derived stem cells from a cloned human embryo, its achievement was heralded as an important step on the road to ‘therapeutic cloning’. But the research is now clouded by nagging questions about the Korea's stem-cell stars dogged by suspicion of ethical breach David Cyranoski doi:10.1038/429003a Nature 429, 3 (2004) Nature 429 6987 News 3 3 http://dx.doi.org/10.1038/429004a WashingtonA US government programme to bolster public defences against bioterrorism will soon give out its first grants — despite complaints from the biotechnology industry that the programme is not working as intended.An official at the Department of Health and Human Services says it BioShield defence programme set to fund anthrax vaccine Erika Check doi:10.1038/429004a Nature 429, 4 (2004) Nature 429 6987 News 4 4 http://dx.doi.org/10.1038/429004b WashingtonA plan to use robots instead of astronauts to rescue the Hubble Space Telescope moved closer to approval last week, when NASA announced that it would solicit industry proposals for part of a salvage mission.Scientists who were initially sceptical of relying on robots NASA opens its arms to robot options for saving telescope Tony Reichhardt doi:10.1038/429004b Nature 429, 4 (2004) Nature 429 6987 News 4 4 http://dx.doi.org/10.1038/429005a San DiegoThe mysterious background of Chinese dinosaur fossils in an exhibition is posing awkward questions for North American museums, which want to ensure that only properly obtained specimens are displayed.Experts and Chinese officials are worried that some of the 34 fossils in the Feathered fossils cause a flap in museums Rex Dalton doi:10.1038/429005a Nature 429, 5 (2004) Nature 429 6987 News 5 5 http://dx.doi.org/10.1038/429005b WashingtonProspects are fading that a director for the US National Science Foundation (NSF) will be named any time this year, officials familiar with the search say.The top slot at the research agency has been filled on an interim basis by Arden Bement, head Top job at NSF on hold until after US elections Geoff Brumfiel doi:10.1038/429005b Nature 429, 5 (2004) Nature 429 6987 News 5 5 http://dx.doi.org/10.1038/429006a LondonThe creation of spin-off companies at British universities has fallen dramatically over the past six months because of a change in the tax laws, Nature has established.The country's top universities typically each launch five to ten new companies every year. But the Tax change curtails UK university spin-offs Jim Giles doi:10.1038/429006a Nature 429, 6 (2004) Nature 429 6987 News 6 6 http://dx.doi.org/10.1038/429006b WashingtonThe National Institutes of Health (NIH) has been asked to step in and halt the spiralling cost of AIDS medications in the United States.Under a 1980 technology-transfer law, the biomedical research agency can arrange for the generic production of pharmaceuticals whose invention was AIDS drug price hike prompts calls for intervention Erika Check doi:10.1038/429006b Nature 429, 6 (2004) Nature 429 6987 News 6 6 http://dx.doi.org/10.1038/429007a Quirin SchiermeierFor years, climate researchers have struggled with an apparent discrepancy in the data on global warming: temperatures in the lower atmosphere have been rising far slower than models predict, given how fast the Earth's surface is heating.The discrepancy has been central to Global warming anomaly may succumb to microwave study doi:10.1038/429007a Nature 429, 7 (2004) Nature 429 6987 News 7 7 http://dx.doi.org/10.1038/429007b Television cameras may be few and far between in rural areas of Bangladesh, south Asia's poorest nation. But killer human viruses are recurrent there, and are quietly wreaking havoc.An outbreak of the emerging Nipah virus in the Faridpur district of the country earlier this Fatal fruit bat virus sparks epidemics in southern Asia Declan Butler doi:10.1038/429007b Nature 429, 7 (2004) Nature 429 6987 News 7 7 http://dx.doi.org/10.1038/429008a Research ships firing airguns provoke Mexican stand-offSan DiegoFor the second time this year, US seismic studies in Mexico's waters have been cancelled because of concerns about harm to marine mammals.Permission for the research ship Roger Revelle to use acoustic devices to News in brief doi:10.1038/429008a Nature 429, 8 (2004) Nature 429 6987 News in Brief 8 9 http://dx.doi.org/10.1038/429010a A few physicists have spent decades searching for the rarest events in the Universe — and seen nothing. But their enthusiasm for the hunt is undimmed. Geoff Brumfiel asks what keeps them going. Physics: The waiting game Geoff Brumfiel doi:10.1038/429010a Nature 429, 10 (2004) Nature 429 6987 News Feature 10 11 http://dx.doi.org/10.1038/429012a A team in Seoul has stolen a march with its work towards human therapeutic cloning. The researchers have been fêted, but an ethical controversy may threaten their work. David Cyranoski investigates. Stem-cell research: Crunch time for Korea's cloners David Cyranoski doi:10.1038/429012a Nature 429, 12 (2004) Nature 429 6987 News Feature 12 14 http://dx.doi.org/10.1038/429015a No need to wait for more information: industrialized fishing is already wiping out stocks. Managing fisheries in a changing climate Boris Worm Ransom A. Myers doi:10.1038/429015a Nature 429, 15 (2004) Nature 429 6987 Correspondence 15 15 http://dx.doi.org/10.1038/429015b SirAs passionate rat researchers we were delighted to see the rat on the cover of the 1 April 2004 issue of Nature. It is little known that Japan has a long history of rat research, including studies on coat-colour inheritance that date back Colourful history of Japan's rat resources Tadao Serikawa doi:10.1038/429015b Nature 429, 15 (2004) Nature 429 6987 Correspondence 15 15 http://dx.doi.org/10.1038/429015c SirThe laboratory rat has obviously made immeasurable contributions to biomedical science and will continue to do so as long as humans conduct biological research. There are many considerations in the choice of a model organism, and rats certainly have their advantages, such as their Multiskilled mouse rivals Renaissance rat Richard A. Radcliffe doi:10.1038/429015c Nature 429, 15 (2004) Nature 429 6987 Correspondence 15 15 http://dx.doi.org/10.1038/429017a What is it that makes us different from other animals? The human factor David L. Hull doi:10.1038/429017a Nature 429, 17 (2004) Nature 429 6987 Spring Books 17 18 http://dx.doi.org/10.1038/429018a In evolutionary terms, the most remarkable discoveries of developmental biology in the 1980s and 1990s were that the molecular mechanisms of anteroposterior axis formation are shared across most of the animal kingdom, and that vertebrates form a dorsoventral axis in a similar way to insects, Walking on their ribs Nick Hopwood doi:10.1038/429018a Nature 429, 18 (2004) Nature 429 6987 Spring Books 18 19 http://dx.doi.org/10.1038/429019a Rather than being one coherent book, the narrative of Evolution's Rainbow shuttles between three interwoven agendas. The first is a passionate cry from the heart for greater understanding of sexual diversity in nature and greater tolerance for the many gay men, lesbians, bisexuals, transgenders Sexual diversity and the gender agenda Sarah Blaffer Hrdy doi:10.1038/429019a Nature 429, 19 (2004) Nature 429 6987 Spring Books 19 21 http://dx.doi.org/10.1038/429021a Devil in the Mountain is the fascinating story of geologist Simon Lamb's quest to understand how the high Andes formed. It includes a wealth of real-life, even harrowing, anecdotes of fieldwork, mixed with colourful descriptions of Bolivian culture. This engrossing and well-written book focuses High points in geology David E. James doi:10.1038/429021a Nature 429, 21 (2004) Nature 429 6987 Spring Books 21 22 http://dx.doi.org/10.1038/429022a What, you might say, yet another book from Paul and Anne Ehrlich on the environment, population and consumption, and about how humans are grossly degrading Earth's life-support systems? Can the Ehrlichs have anything new and different to offer about the crises they have been trumpeting The way or the world Norman Myers doi:10.1038/429022a Nature 429, 22 (2004) Nature 429 6987 Spring Books 22 23 http://dx.doi.org/10.1038/429023a The private life of the Verreaux's (or black) eagle, a spectacular raptor of the drier parts of Africa, does not exactly embody Victorian family values. The female nearly always lays two eggs, a few days apart, which hatch into two chicks, one a little bigger Family values H. Charles J. Godfray doi:10.1038/429023a Nature 429, 23 (2004) Nature 429 6987 Spring Books 23 25 http://dx.doi.org/10.1038/429025a Archaeology has numerous goals, which include constructing histories of peoples' cultures through space and time, offering an appreciation of the achievements of past civilizations, and providing historical contexts, both cultural and ecological, for modern events and processes. Writing about such issues for the public can Warming to a historical theme Jeremy A. Sabloff doi:10.1038/429025a Nature 429, 25 (2004) Nature 429 6987 Spring Books 25 26 http://dx.doi.org/10.1038/429026a Chang and Eng Bunker, the original (and self-styled) Siamese twins, travelled widely, married and had 22 children between them. As far as we know, they seemed happy with their conjoined state and only contemplated separation, late in their lives, to please their wives. A pair Together forever? Jonathan Cole doi:10.1038/429026a Nature 429, 26 (2004) Nature 429 6987 Spring Books 26 26 http://dx.doi.org/10.1038/429027a Dark matter and dark energy: they might be more abundant than the stuff we are made of, but are they any more interesting? Insignificance Sean Carroll doi:10.1038/429027a Nature 429, 27 (2004) Nature 429 6987 Essay 27 27 http://dx.doi.org/10.1038/429029a The first images of an extragalactic object to have been captured using infrared interferometry reveal the doughnut-shaped cloud of dust that obscures the heart of a nearby active galaxy. Astronomy: Dust-filled doughnuts in space Julian Krolik doi:10.1038/429029a Nature 429, 29 (2004) Nature 429 6987 News and Views 29 30 http://dx.doi.org/10.1038/429030a Insulin-producing β-cells in the adult pancreas were thought to derive from pancreatic stem cells. But it seems that they arise abundantly from β-cells themselves, offering a new outlook on regenerative medicine. Regenerative medicine: Self-help for insulin cells Ken Zaret doi:10.1038/429030a Nature 429, 30 (2004) Nature 429 6987 News and Views 30 31 http://dx.doi.org/10.1038/429031a Swift-swimming, open-ocean hunters such as mako sharks and tunas need a big engine. Despite their long separation in evolutionary terms, the internal drive systems adopted by these fishes are much the same. Biomechanics: Fast fish Adam P. Summers doi:10.1038/429031a Nature 429, 31 (2004) Nature 429 6987 News and Views 31 33 http://dx.doi.org/10.1038/429033a The solubility of oxygen in molten iron increases at high temperature. Could this explain why Earth's mantle is poor in iron oxide, whereas the mantle of Mars, which formed under cooler conditions, is not? Earth science: Hot metal Carl B. Agee doi:10.1038/429033a Nature 429, 33 (2004) Nature 429 6987 News and Views 33 35 http://dx.doi.org/10.1038/429034a 100 YEARS AGOIn a paper read before the American Philosophical Society Mr. Percival Lowell discusses the 375 drawings of the Martian surface made by him during the opposition of 1903. Having plotted the values allotted to the “visibility” of eighty-five canals, at different periods, 100 and 50 years ago doi:10.1038/429034a Nature 429, 34 (2004) Nature 429 6987 News and Views 34 34 http://dx.doi.org/10.1038/429035a People vary naturally in a protein called caspase-12, and hence in their susceptibility to harmful inflammation. This discovery highlights the balance between the protective and destructive effects of immunity. Human genetics: An inflammatory issue Kevin J. Tracey H. Shaw Warren doi:10.1038/429035a Nature 429, 35 (2004) Nature 429 6987 News and Views 35 37 http://dx.doi.org/10.1038/429037a Prions are clumps of misshapen proteins that can be passed between cells without the need for genetic intermediaries. The parts of the proteins that account for such infectivity are now being dissected. Cell biology: Designer prions Daniel C. Masison doi:10.1038/429037a Nature 429, 37 (2004) Nature 429 6987 News and Views 37 38 http://dx.doi.org/10.1038/429037b Alicia M. Jackson et al. have looked at nanotechnology in the round, and describe what they believe to be a promising new class of structured material (Nature Mater.3, 330–336; 2004). They have examined nanoparticles that consist of a metal centre Materials science: Variations on a golden core Tim Lincoln doi:10.1038/429037b Nature 429, 37 (2004) Nature 429 6987 News and Views 37 37 http://dx.doi.org/10.1038/429039a Cancer: Homing in on tumour metastasisCancer Cell5, 365–374 (2004)One of the deadliest hallmarks of tumour cells is their ability to spread to other organs. This process is often surprisingly specific; breast-cancer cells, for instance, frequently metastasize to the lungs and liver. News and views in brief doi:10.1038/429039a Nature 429, 39 (2004) Nature 429 6987 News and Views 39 39 http://dx.doi.org/10.1038/429040a A Cambrian fossil confirms that early arthropods shed their coats just as they do today. Moulting arthropod caught in the act Diego C. García-Bellido Desmond H. Collins doi:10.1038/429040a Nature 429, 40 (2004) Nature 429 6987 Brief Communications 40 40 http://dx.doi.org/10.1038/nature02586 Arising from: M. D. Stenner, D. J. Gauthier & M. A. Neifeld Nature425, 695–698 (2003); Stenner et al. replyThe theory of special relativity limits signal velocity to the velocity of light in a vacuum. A faster-than-light (superluminal) signal velocity would violate causality. However, there are some experimental data and theoretical arguments that a causality violation does not necessarily happen if a signal velocity becomes superluminal. Stenner et al. claim to have measured the speed of information in a fast-light optical medium by using a novel experimental set-up. The measured information (its front) travelled at a speed that did not exceed c (the velocity of light in vacuum). Their experimental result is correct but the interpretation is misleading because the information did not travel in the range of fast-light frequencies, as I explain here. Optical media: Superluminal speed of information? Günter Nimtz doi:10.1038/nature02586 Nature 429, (2004) Nature 429 6987 Brief Communications http://dx.doi.org/10.1038/nature02587 Stenner et al. reply — It was most natural to present our findings in the time domain, although there is an equivalent explanation in the frequency domain if Fourier analysis is used. Nimtz uses a frequency-domain argument to assert that our data with gaussian pulses (Fig. 1b in ref. 1) are consistent with the group-velocity approximation, whereas the data we used to measure the information velocity (Fig. 2 in ref. 1) are not; however, we disagree with his analysis. Optical media: Superluminal speed of information? (reply) Michael D. Stenner Daniel J. Gauthier Mark A. Neifeld doi:10.1038/nature02587 Nature 429, (2004) Nature 429 6987 Brief Communications http://dx.doi.org/10.1038/nature02520 How tissues generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation Yuval Dor Juliana Brown Olga I. Martinez Douglas A. Melton doi:10.1038/nature02520 Nature 429, 41 (2004) Nature 429 6987 Article 41 46 http://dx.doi.org/10.1038/nature02531 Active galactic nuclei (AGNs) display many energetic phenomena—broad emission lines, X-rays, relativistic jets, radio lobes—originating from matter falling onto a supermassive black hole. It is widely accepted that orientation effects play a major role in explaining the observational appearance of AGNs. Seen from certain directions, circum-nuclear dust clouds would block our view of the central powerhouse. Indirect evidence suggests that the dust clouds form a parsec-sized torus-shaped distribution. This explanation, however, remains unproved, as even the largest telescopes have not been able to resolve the dust structures. Here we report interferometric mid-infrared observations that spatially resolve these structures in the galaxy NGC 1068. The observations reveal warm (320 K) dust in a structure 2.1 parsec thick and 3.4 parsec in diameter, surrounding a smaller hot structure. As such a configuration of dust clouds would collapse in a time much shorter than the active phase of the AGN, this observation requires a continual input of kinetic energy to the cloud system from a source coexistent with the AGN. The central dusty torus in the active nucleus of NGC 1068 W. Jaffe K. Meisenheimer H. J. A. Röttgering Ch. Leinert A. Richichi O. Chesneau D. Fraix-Burnet A. Glazenborg-Kluttig G.-L. Granato U. Graser B. Heijligers R. Köhler F. Malbet G. K. Miley F. Paresce J.-W. Pel G. Perrin F. Przygodda M. Schoeller H. Sol L. B. F. M. Waters G. Weigelt J. Woillez P. T. de Zeeuw doi:10.1038/nature02531 Nature 429, 47 (2004) Nature 429 6987 Letter 47 49 http://dx.doi.org/10.1038/nature02495 Dislocations are line defects that bound plastically deformed regions in crystalline solids. Dislocations terminating on the surface of materials can strongly influence nanostructural and interfacial stability, mechanical properties, chemical reactions, transport phenomena, and other surface processes. While most theoretical and experimental studies have focused on dislocation motion in bulk solids under applied stress and step formation due to dislocations at surfaces during crystal growth, very little is known about the effects of dislocations on surface dynamics and morphological evolution. Here we investigate the near-equilibrium dynamics of surface-terminated dislocations using low-energy electron microscopy. We observe, in real time, the thermally driven nucleation and shape-preserving growth of spiral steps rotating at constant temperature-dependent angular velocities around cores of dislocations terminating on the (111) surface of TiN in the absence of applied external stress or net mass change. We attribute this phenomenon to point-defect migration from the bulk to the surface along dislocation lines. Our results demonstrate that dislocation-mediated surface roughening can occur even in the absence of deposition or evaporation, and provide fundamental insights into mechanisms controlling nanostructural stability. Dislocation-driven surface dynamics on solids S. Kodambaka S. V. Khare W. Święch K. Ohmori I. Petrov J. E. Greene doi:10.1038/nature02495 Nature 429, 49 (2004) Nature 429 6987 Letter 49 52 http://dx.doi.org/10.1038/nature02525 Enzymes efficiently synthesize biopolymers by organizing monomer units within regularly structured molecular-scale spaces and exploiting weak non-covalent interactions, such as hydrogen bonds, to control the polymerization process. This ‘template’ approach is both attractive and challenging for synthetic polymer synthesis, where structurally regulated molecular-scale spaces could in principle provide solid-phase reaction sites for precision polymerization. Previously, free-radical polymerization of methyl methacrylate in solutions containing stereoregular isotactic (it) or syndiotactic (st) poly(methyl methacrylate) (PMMA) has been shown to result in template synthesis of the opposite PMMA based on stereocomplex formation with van der Waals interactions. However, using the structure of a solid to determine the stereochemical structure of a polymer has not been satisfactorily achieved. Here we show that macromolecularly porous ultrathin films, fabricated by a single assembly step, can be used for the highly efficient stereoregular template polymerization of methacrylates through stereocomplex formation. This reaction mould accurately transfers its structural properties of stereoregularity, molecular weight and organization within the template to the new polymer. Polymerization within a molecular-scale stereoregular template Takeshi Serizawa Ken-ichi Hamada Mitsuru Akashi doi:10.1038/nature02525 Nature 429, 52 (2004) Nature 429 6987 Letter 52 55 http://dx.doi.org/10.1038/nature02524 From 1979 to 2001, temperatures observed globally by the mid-tropospheric channel of the satellite-borne Microwave Sounding Unit (MSU channel 2), as well as the inferred temperatures in the lower troposphere, show only small warming trends of less than 0.1 K per decade (refs 1–3). Surface temperatures based on in situ observations however, exhibit a larger warming of ∼0.17 K per decade (refs 4, 5), and global climate models forced by combined anthropogenic and natural factors project an increase in tropospheric temperatures that is somewhat larger than the surface temperature increase. Here we show that trends in MSU channel 2 temperatures are weak because the instrument partly records stratospheric temperatures whose large cooling trend offsets the contributions of tropospheric warming. We quantify the stratospheric contribution to MSU channel 2 temperatures using MSU channel 4, which records only stratospheric temperatures. The resulting trend of reconstructed tropospheric temperatures from satellite data is physically consistent with the observed surface temperature trend. For the tropics, the tropospheric warming is ∼1.6 times the surface warming, as expected for a moist adiabatic lapse rate. Contribution of stratospheric cooling to satellite-inferred tropospheric temperature trends Qiang Fu Celeste M. Johanson Stephen G. Warren Dian J. Seidel doi:10.1038/nature02524 Nature 429, 55 (2004) Nature 429 6987 Letter 55 58 http://dx.doi.org/10.1038/nature02473 Core formation on the Earth and Mars involved the physical separation of metal and silicate, most probably in deep magma oceans. Although core-formation models explain many aspects of mantle geochemistry, they have not accounted for the large differences observed between the compositions of the mantles of the Earth (∼8 wt% FeO) and Mars (∼18 wt% FeO) or the smaller mass fraction of the martian core. Here we explain these differences as a consequence of the solubility of oxygen in liquid iron-alloy increasing with increasing temperature. We assume that the Earth and Mars both accreted from oxidized chondritic material. In a terrestrial magma ocean, 1,200–2,000 km deep, high temperatures resulted in the extraction of FeO from the silicate magma ocean owing to high solubility of oxygen in the metal. Lower temperatures of a martian magma ocean resulted in little or no extraction of FeO from the mantle, which thus remains FeO-rich. The FeO extracted from the Earth's magma ocean may have contributed to chemical heterogeneities in the lowermost mantle, a FeO-rich D″ layer and the light element budget of the core. Partitioning of oxygen during core formation on the Earth and Mars David C. Rubie Christine K. Gessmann Daniel J. Frost doi:10.1038/nature02473 Nature 429, 58 (2004) Nature 429 6987 Letter 58 61 http://dx.doi.org/10.1038/nature02435 The evolution of ‘thunniform’ body shapes in several different groups of vertebrates, including whales, ichthyosaurs and several species of large pelagic fishes supports the view that physical and hydromechanical demands provided important selection pressures to optimize body design for locomotion during vertebrate evolution. Recognition of morphological similarities between lamnid sharks (the most well known being the great white and the mako) and tunas has led to a general expectation that they also have converged in their functional design; however, no quantitative data exist on the mechanical performance of the locomotor system in lamnid sharks. Here we examine the swimming kinematics, in vivo muscle dynamics and functional morphology of the force-transmission system in a lamnid shark, and show that the evolutionary convergence in body shape and mechanical design between the distantly related lamnids and tunas is much more than skin deep; it extends to the depths of the myotendinous architecture and the mechanical basis for propulsive movements. We demonstrate that not only have lamnids and tunas converged to a much greater extent than previously known, but they have also developed morphological and functional adaptations in their locomotor systems that are unlike virtually all other fishes. Convergent evolution in mechanical design of lamnid sharks and tunas Jeanine M. Donley Chugey A. Sepulveda Peter Konstantinidis Sven Gemballa Robert E. Shadwick doi:10.1038/nature02435 Nature 429, 61 (2004) Nature 429 6987 Letter 61 65 http://dx.doi.org/10.1038/nature02492 Indirect-benefit models of sexual selection assert that females gain heritable offspring advantages through a mating bias for males of superior genetic quality. This has generally been tested by associating a simple morphological quality indicator (for example, bird tail length) with offspring viability. However, selection acts simultaneously on many characters, limiting the ability to detect significant associations, especially if the simple indicator is weakly correlated to male fitness. Furthermore, recent conceptual developments suggest that the benefits gained from such mating biases may be sex-specific because of sexually antagonistic genes that differentially influence male and female reproductive ability. A more suitable test of the indirect-benefit model would examine associations between an aggregate quality indicator (such as male mating success) and gender-specific adult fitness components, under the expectation that these components may trade off. Here, we show that a father's mating success in the cricket, Allonemobius socius, is positively genetically correlated with his son's mating success but negatively with his daughter's reproductive success. This provides empirical evidence that a female mating bias can result in sexually antagonistic offspring fitness. Female mating bias results in conflicting sex-specific offspring fitness Kenneth M. Fedorka Timothy A. Mousseau doi:10.1038/nature02492 Nature 429, 65 (2004) Nature 429 6987 Letter 65 67 http://dx.doi.org/10.1038/nature02469 Much of what is known about the functional organization and plasticity of adult sensory cortex is derived from animals housed in standard laboratory cages. Here we report that the transfer of adult rats reared in standard laboratory cages to a naturalistic habitat modifies the functional and morphological organization of the facial whisker representation in the somatosensory ‘barrel’ cortex. Cortical whisker representations, visualized with repeated intrinsic signal optical imaging in the same animals, contracted by 46% after four to six weeks of exposure to the naturalistic habitat. Acute, multi-site extracellular recordings demonstrated suppressed evoked neuronal responses and smaller, sharper constituent receptive fields in the upper cortical layers (II/III), but not in the thalamic recipient layer (IV), of rats with naturalistic experience. Morphological plasticity of the layer IV barrel field was observed, but on a substantially smaller scale than the functional plasticity. Thus, transferring animals to an environment that promotes the expression of natural, innate behaviours induces a large-scale functional refinement of cortical sensory maps. Naturalistic experience transforms sensory maps in the adult cortex of caged animals Daniel B. Polley Eugen Kvašňák Ron D. Frostig doi:10.1038/nature02469 Nature 429, 67 (2004) Nature 429 6987 Letter 67 71 http://dx.doi.org/10.1038/nature02502 Myocardial infarction (MI) has become one of the leading causes of death in the world. Its pathogenesis includes chronic formation of plaque inside the vessel wall of the coronary artery and acute rupture of the artery, implicating a number of inflammation-mediating molecules, such as the cytokine lymphotoxin-α (LTA). Functional variations in LTA are associated with susceptibility to MI. Here we show that LTA protein binds to galectin-2, a member of the galactose-binding lectin family. Our case–control association study in a Japanese population showed that a single nucleotide polymorphism in LGALS2 encoding galectin-2 is significantly associated with susceptibility to MI. This genetic substitution affects the transcriptional level of galectin-2 in vitro, potentially leading to altered secretion of LTA, which would then affect the degree of inflammation; however, its relevance to other populations remains to be clarified. Smooth muscle cells and macrophages in the human atherosclerotic lesions expressed both galectin-2 and LTA. Our findings thus suggest a link between the LTA cascade and the pathogenesis of MI. Functional variation in LGALS2 confers risk of myocardial infarction and regulates lymphotoxin-α secretion in vitro Kouichi Ozaki Katsumi Inoue Hiroshi Sato Aritoshi Iida Yozo Ohnishi Akihiro Sekine Hideyuki Sato Keita Odashiro Masakiyo Nobuyoshi Masatsugu Hori Yusuke Nakamura Toshihiro Tanaka doi:10.1038/nature02502 Nature 429, 72 (2004) Nature 429 6987 Letter 72 75 http://dx.doi.org/10.1038/nature02451 Caspases mediate essential key proteolytic events in inflammatory cascades and the apoptotic cell death pathway. Human caspases functionally segregate into two distinct subfamilies: those involved in cytokine maturation (caspase-1, -4 and -5) and those involved in cellular apoptosis (caspase-2, -3, -6, -7, -8, -9 and -10). Although caspase-12 is phylogenetically related to the cytokine maturation caspases, in mice it has been proposed as a mediator of apoptosis induced by endoplasmic reticulum stress including amyloid-β cytotoxicity, suggesting that it might contribute to the pathogenesis of Alzheimer's disease. Here we show that a single nucleotide polymorphism in caspase-12 in humans results in the synthesis of either a truncated protein (Csp12-S) or a full-length caspase proenzyme (Csp12-L). The read-through single nucleotide polymorphism encoding Csp12-L is confined to populations of African descent and confers hypo-responsiveness to lipopolysaccharide-stimulated cytokine production in ex vivo whole blood, but has no significant effect on apoptotic sensitivity. In a preliminary study, we find that the frequency of the Csp12-L allele is increased in African American individuals with severe sepsis. Thus, Csp12-L attenuates the inflammatory and innate immune response to endotoxins and in doing so may constitute a risk factor for developing sepsis. Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms Maya Saleh John P. Vaillancourt Rona K. Graham Matthew Huyck Srinivasa M. Srinivasula Emad S. Alnemri Martin H. Steinberg Vikki Nolan Clinton T. Baldwin Richard S. Hotchkiss Timothy G. Buchman Barbara A. Zehnbauer Michael R. Hayden Lindsay A. Farrer Sophie Roy Donald W. Nicholson doi:10.1038/nature02451 Nature 429, 75 (2004) Nature 429 6987 Letter 75 79 http://dx.doi.org/10.1038/nature02504 Nitric oxide (NO) is a potent intercellular signal in mammals that mediates key aspects of blood pressure, hormone release, nerve transmission and the immune response of higher organisms. Proteins homologous to full-length mammalian nitric oxide synthases (NOSs) are found in lower multicellular organisms. Recently, genome sequencing has shown that some bacteria contain genes coding for truncated NOS proteins; this is consistent with reports of NOS-like activities in bacterial extracts. Biological functions for bacterial NOSs are unknown, but have been presumed to be analogous to their role in mammals. Here we describe a gene in the plant pathogen Streptomyces turgidiscabies that encodes a NOS homologue, and we reveal its role in nitrating a dipeptide phytotoxin required for plant pathogenicity. High similarity between bacterial NOSs indicates a general function in biosynthetic nitration; thus, bacterial NOSs constitute a new class of enzymes. Here we show that the primary function of Streptomyces NOS is radically different from that of mammalian NOS. Surprisingly, mammalian NO signalling and bacterial biosynthetic nitration share an evolutionary origin. Nitration of a peptide phytotoxin by bacterial nitric oxide synthase Johan A. Kers Michael J. Wach Stuart B. Krasnoff Joanne Widom Kimberly D. Cameron Raghida A. Bukhalid Donna M. Gibson Brian R. Crane Rosemary Loria doi:10.1038/nature02504 Nature 429, 79 (2004) Nature 429 6987 Letter 79 82 http://dx.doi.org/10.1038/nature02543 Physical forces elicit biochemical signalling in a diverse array of cells, tissues and organisms, helping to govern fundamental biological processes. Several hypotheses have been advanced that link physical forces to intracellular signalling pathways, but in many cases the molecular mechanisms of mechanotransduction remain elusive. Here we find that compressive stress shrinks the lateral intercellular space surrounding epithelial cells, and triggers cellular signalling via autocrine binding of epidermal growth factor family ligands to the epidermal growth factor receptor. Mathematical analysis predicts that constant rate shedding of autocrine ligands into a collapsing lateral intercellular space leads to increased local ligand concentrations that are sufficient to account for the observed receptor signalling; direct experimental comparison of signalling stimulated by compressive stress versus exogenous soluble ligand supports this prediction. These findings establish a mechanism by which mechanotransduction arises from an autocrine ligand–receptor circuit operating in a dynamically regulated extracellular volume, not requiring induction of force-dependent biochemical processes within the cell or cell membrane. Mechanotransduction through growth-factor shedding into the extracellular space Daniel J. Tschumperlin Guohao Dai Ivan V. Maly Tadashi Kikuchi Lily H. Laiho Anna K. McVittie Kathleen J. Haley Craig M. Lilly Peter T. C. So Douglas A. Lauffenburger Roger D. Kamm Jeffrey M. Drazen doi:10.1038/nature02543 Nature 429, 83 (2004) 2004-04-21 Nature 2004-04-21 429 6987 Letter 83 86 http://dx.doi.org/10.1038/nature02514 COP1 (constitutively photomorphogenic 1) is a RING-finger-containing protein that functions to repress plant photomorphogenesis, the light-mediated programme of plant development. Mutants of COP1 are constitutively photomorphogenic, and this has been attributed to their inability to negatively regulate the proteins LAF1 (ref. 1) and HY5 (ref. 2). The role of COP1 in mammalian cells is less well characterized. Here we identify the tumour-suppressor protein p53 as a COP1-interacting protein. COP1 increases p53 turnover by targeting it for degradation by the proteasome in a ubiquitin-dependent fashion, independently of MDM2 or Pirh2, which are known to interact with and negatively regulate p53. Moreover, COP1 serves as an E3 ubiquitin ligase for p53 in vitro and in vivo, and inhibits p53-dependent transcription and apoptosis. Depletion of COP1 by short interfering RNA (siRNA) stabilizes p53 and arrests cells in the G1 phase of the cell cycle. Furthermore, we identify COP1 as a p53-inducible gene, and show that the depletion of COP1 and MDM2 by siRNA cooperatively sensitizes U2-OS cells to ionizing-radiation-induced cell death. Overall, these results indicate that COP1 is a critical negative regulator of p53 and represents a new pathway for maintaining p53 at low levels in unstressed cells. The ubiquitin ligase COP1 is a critical negative regulator of p53 David Dornan Ingrid Wertz Harumi Shimizu David Arnott Gretchen D. Frantz Patrick Dowd Karen O' Rourke Hartmut Koeppen Vishva M. Dixit doi:10.1038/nature02514 Nature 429, 86 (2004) 2004-04-21 Nature 2004-04-21 429 6987 Letter 86 92 http://dx.doi.org/10.1038/nature02456 The flood of high-throughput biological data has led to the expectation that computational (or in silico) models can be used to direct biological discovery, enabling biologists to reconcile heterogeneous data types, find inconsistencies and systematically generate hypotheses. Such a process is fundamentally iterative, where each iteration involves making model predictions, obtaining experimental data, reconciling the predicted outcomes with experimental ones, and using discrepancies to update the in silico model. Here we have reconstructed, on the basis of information derived from literature and databases, the first integrated genome-scale computational model of a transcriptional regulatory and metabolic network. The model accounts for 1,010 genes in Escherichia coli, including 104 regulatory genes whose products together with other stimuli regulate the expression of 479 of the 906 genes in the reconstructed metabolic network. This model is able not only to predict the outcomes of high-throughput growth phenotyping and gene expression experiments, but also to indicate knowledge gaps and identify previously unknown components and interactions in the regulatory and metabolic networks. We find that a systems biology approach that combines genome-scale experimentation and computation can systematically generate hypotheses on the basis of disparate data sources. Integrating high-throughput and computational data elucidates bacterial networks Markus W. Covert Eric M. Knight Jennifer L. Reed Markus J. Herrgard Bernhard O. Palsson doi:10.1038/nature02456 Nature 429, 92 (2004) Nature 429 6987 Letter 92 96 http://dx.doi.org/10.1038/429101a Protein arrays and protein assays in parallel are enabling researchers to look at protein interactions and activity on a large scale, as Lisa Melton finds out. Protein arrays: Proteomics in multiplex Lisa Melton doi:10.1038/429101a Nature 429, 101 (2004) Nature 429 6987 Technology Feature 101 107 http://dx.doi.org/10.1038/429101b For those who want to spot their own arrays, a number of companies provide standard-sized 25 × 76 mm coated slides especially formulated for protein arrays. Proteins arrayed on the nitrocellulose-coated FASTSlide from Schleicher and Schuell Bioscience in Cologne, Germany, are stable for up to Do-it-yourself arrays doi:10.1038/429101b Nature 429, 101 (2004) Nature 429 6987 Technology Feature 101 101 http://dx.doi.org/10.1038/429103a How proteins interact with each other has become a key issue in drug discovery and development. Once a target for a drug is identified, it is also important to define how strongly it binds to other biomolecules to obtain information about selectivity. Biacore of Uppsala, A natural affinity doi:10.1038/429103a Nature 429, 103 (2004) Nature 429 6987 Technology Feature 103 103 http://dx.doi.org/10.1038/429105a “Suppose you could develop a chemical tool so powerful that you could go into a cell and identify all the members of one family — all the protein kinases, or all the hydrolases or the phosphatases,” proposes John Kozarich, president and chief scientific officer at Family business doi:10.1038/429105a Nature 429, 105 (2004) Nature 429 6987 Technology Feature 105 105 http://dx.doi.org/10.1038/429107a A number of companies have developed peptide arrays for detecting protein interactions, such as the interaction of protein kinases with their substrates. Using high-throughput peptide synthesis, they manufacture an entire potential protein target as overlapping peptides and array them on a chip or a membrane. Breaking down the problem doi:10.1038/429107a Nature 429, 107 (2004) Nature 429 6987 Technology Feature 107 107 http://dx.doi.org/10.1038/429109a Table of suppliers doi:10.1038/429109a Nature 429, 109 (2004) Nature 429 6987 Technology Feature 109 110 http://dx.doi.org/10.1038/nj6987-111a It is five years since the National Academy of Sciences issued its seminal report on employment conditions for US postdocs. Last month, at a convocation in Washington, postdocs and policy-makers gathered to assess the progress being made over the issues identified by the academy's Committee Swatting flies Paul Smaglik doi:10.1038/nj6987-111a Nature 429, 111 (2004) Nature 429 6987 Naturejobs 111 111 http://dx.doi.org/10.1038/nj6987-112a The English countryside flew by as I sat on my train heading for Cambridge, the university where I spent four years as an undergraduate. This time I was going there as a postgrad to take part in a multidisciplinary retreat.Once there, I found myself Graduate Journal: Through the looking glass Amber Jenkins doi:10.1038/nj6987-112a Nature 429, 112 (2004) Nature 429 6987 Naturejobs 112 112 http://dx.doi.org/10.1038/nj6987-112b Passing the interviewSo, you've done your homework on the organization, applied for a job and landed an interview. How can you give yourself the best possible chance of success? The key is preparation.Before you go, pick three to five points that you believe Nuts & Bolts Deb Koen doi:10.1038/nj6987-112b Nature 429, 112 (2004) Nature 429 6987 Naturejobs 112 112 http://dx.doi.org/10.1038/nj6987-112c Alistair Walker, director, Cerro Tololo Inter-American Observatory, La Serena, ChileTo follow a waxing interest in astronomy, Alistair Walker had to leave his native New Zealand. He chose South Africa as a place to do his PhD, partly because the University of Cape Town's astronomy Movers doi:10.1038/nj6987-112c Nature 429, 112 (2004) Nature 429 6987 Naturejobs 112 112