Nature 453, xiv (2008). doi:10.1038/7193xiva

Thousands of urine samples point to the causes of high blood pressure.

Nature 453, xiv (2008). doi:10.1038/7193xivb

Last authorThe 'progress zone' model of limb development posits that the embryonic cells that become limbs are specified in a progressive manner: first, the upper part; then the middle; and last, hand or foot. Despite there being no direct evidence for this, the model

Nature 453, xiv (2008). doi:10.1038/7193xivc

Scientific informatics programmes require massive financial investment, so it is difficult for governments to decide which ones to support. One programme that has been successful in securing funding is the iPlant Collaborative (http://iplantcollaborative.org/) — a 'cyberinfrastructure' collaborative for the plant sciences. Recently set

Nature 453, 257 (2008). doi:10.1038/453257a

Governments should work together to build the supercomputers needed for future predictions that can capture the detail required to inform policy.

Nature 453, 258 (2008). doi:10.1038/453258a

The Environmental Protection Agency must gather data on the toxicity of spreading sewage sludge.

Nature 453, 258 (2008). doi:10.1038/453258b

Retracted papers require a thorough explanation of what went wrong in the experiments.

Nature 453, 260 (2008). doi:10.1038/453260a

J. Anim. Ecol. doi:10.1111/j.1365-2656.2008.01393.x (2008)At first glance, pilot whales and cheetahs seem unlikely to have much in common, but researchers have found at least one similarity: a tendency to sprint after prey, sacrificing energy for speed. This is the

Nature 453, 260 (2008). doi:10.1038/453260b

Nature Neurosci.11, 609–616 (2008) doi:10.1038/nn.2108Neuroscientists have long thought that the brain uses different regions to locate sounds and to analyse them, as is known to be true for vision. Stephen Lomber of the University of Western

Nature 453, 260 (2008). doi:10.1038/453260c

Geology36, 315–318 (2008) doi:10.1130/G24474A.1Methane outbursts from seafloor deposits are unlikely to have been the sole cause of an extreme episode of global warming around the time of the Palaeocene–Eocene Thermal Maximum some 55 million years ago.

Nature 453, 260 (2008). doi:10.1038/453260d

Global Biogeochem. Cycles22, GB2006 (2008) doi:10.1029/2007GB002984Iron-rich dust, blown from arid lands and dropped into the oceans, is an important nutrient for phytoplankton. But according to Thibaut Wagener at the Oceanographic Laboratory of France's National Centre for Scientific Research

Nature 453, 260 (2008). doi:10.1038/453260e

Europhys. Lett.82, 30002 (2008) doi:10.1209/0295-5075/82/30002How can online gamblers be sure that the casino isn't cheating? They can't — but the quantum gambling machine devised by Yi-Sheng Zhang and colleagues at the University of Science and Technology of China

Nature 453, 260 (2008). doi:10.1038/453260f

Science doi:10.1126/science.1153651 (2008) Do humans care more about distributing goods efficiently or fairly? Is this decision rational or emotional? Steven Quartz of the California Institute of Technology in Pasadena and his colleagues used functional magnetic resonance imaging to investigate.The

Nature 453, 261 (2008). doi:10.1038/453261a

Asrophys. J.678, 647–654 (2008) doi:10.1086/533519Astronomers have spotted what seems to be the most distant galaxy ever observed.The galaxy dates to 13 billion years ago, when the Universe was less than a billion years old. Larry

Nature 453, 261 (2008). doi:10.1038/453261b

Int. Soc. Microbial Ecol.2, 510–518 (2008) doi:10.1038/ismej.2008.16Developing earthworm embryos weed out unwanted microbes, while attracting their favoured bacterial symbionts to colonize their excretory organs.Eisenia foetida bequeath their offspring a gift of Acidovorax-like bacteria,

Nature 453, 261 (2008). doi:10.1038/453261c

Science320, 800–803 (2008) doi:10.1126/science.1157174A 47-year study of British great tits (Parus major; pictured above) shows that these birds can adapt to a changing climate purely through changes in behaviour, a phenomenon known as phenotypic

Nature 453, 261 (2008). doi:10.1038/453261d

J. Am. Chem. Soc. doi: 10.1021/ja800180u (2008)Chemists have measured how much a bond between two atoms stretches in the transition state, which is the short-lived phase between the initial and end states in a chemical reaction.Sri Rama Koti Ainavarapu

Nature 453, 261 (2008). doi:10.1038/453261e

Author: Carl Bergstrom

An evolutionary biologist considers the virulence of emerging infectious diseases.When a pathogen — for example, HIV — emerges into the human population, it adapts to growth and transmission in human hosts. At the same time, its virulence (often measured by case mortality) typically changes

Nature 453, 280 (2008). doi:10.1038/453280a

Author: Samuel J. Spiegel

SirAs a recent policy adviser to the United Nations in a programme intended to address environmental threats in the Amazon, I would caution readers of your Special Report 'Brazil goes to war against logging' (Nature 452, 134–135; 2008). Although this analysis

Nature 453, 280 (2008). doi:10.1038/453280b

Author: André Frainer Barbosa

SirIn your Special Report 'Brazil goes to war against logging' (Nature 452, 134–135; 2008), you argue that the Brazilian government is willing to stop logging operations on the Amazon and to push down Brazil's greenhouse-gas emissions. But the Brazilian government still

Nature 453, 280 (2008). doi:10.1038/453280c

Authors: Kostas Kostarelos, Alberto Bianco & Maurizio Prato

SirIn your News story 'Stem-cell claim gets cold reception' (Nature452, 132; 10.1038/452132a2008), you report on an announcement that nanotubes have been used to reprogramme adult human cells. As you say, the result was met with scepticism because it

Nature 453, 281 (2008). doi:10.1038/453281a

Author: Myra I. Roche

SirYour recent publication of James Watson's sequenced genome (D. A. Wheeler at al. Nature452, 872–876; 2008) makes for fascinating reading — that is, for anyone who has enough knowledge of genetics and biology to interpret it. Peel

Nature 453, 281 (2008). doi:10.1038/453281b

Author: Anthony Robbins

SirYou may have been inadvertently off message about vaccination policy in your Editorial 'On message, off target' (Nature452, 128; 2008) — for what you did not say. Centuries of experience have proved the importance of societies (not doctors, parents

Nature 453, 281 (2008). doi:10.1038/453281c

Author: Neville W. Goodman

SirSadly, the implication in your Editorial 'Broken promises' (Nature452, 503; 10.1038/452503a2008), that good science depends on good ideas and not good intentions, is unlikely to make much difference to politicians anxious for public favour or to scientists anxious

Nature 453, 282 (2008). doi:10.1038/453282a

Author: Michael Sargent

Sustainable solutions to worldwide crises such as overpopulation and climate change need regulating by global bodies, but whose views should these organizations represent?

Nature 453, 284 (2008). doi:10.1038/453284a

Author: Emily Jackson

Developments in the life sciences inevitably raise complex legal questions, such as when a human life begins and ends, and how much weight should be given to individual preferences about how and when we reproduce, or die. The law cannot avoid getting involved in these

Nature 453, 285 (2008). doi:10.1038/453285a

Author: Deborah Jean Warner

Coastal margins are drawn as precise lines on maps, yet anyone who has walked on a beach knows that coastlines are unstable. Cliffs, rocks and sands change under the influence of tides, storms, tectonic movements, global climate change and other natural and artificial phenomena.Mark

Nature 453, 286 (2008). doi:10.1038/453286a

Author: Christopher Turner

The vast foyer of New York's Museum of Modern Art (MoMA) is being dive-bombed by a small electric fan. Suspended from the ceiling by wire, it propels itself on an erratic course, buzzing over the spectators like a giant insect. Rather more calming is the

Nature 453, 287 (2008). doi:10.1038/453287a

Author: Josh McDermott

In the second of a nine-part essay series, Josh McDermott explores the origins of the human urge to make and hear music.

Nature 453, 289 (2008). doi:10.1038/453289a

Author: Anthony S. Fauci

Reflecting on how far we have come scientifically since isolating HIV in 1983, Anthony S. Fauci urges a renewed commitment to the far greater challenges ahead, especially that of vaccine development.

Nature 453, 291 (2008). doi:10.1038/453291a

Authors: Ed Brook

Data laboriously extracted from an Antarctic ice core provide an unprecedented view of temperature, and levels of atmospheric carbon dioxide and methane, over the past 800,000 years of Earth's history.

Nature 453, 292 (2008). doi:10.1038/453292a

Authors: Gebhard F. X. Schertler

Determination of the architecture of an invertebrate photoreceptor protein, squid rhodopsin, is a notable event. It illuminates the mechanism of invertebrate vision and a ubiquitous intracellular signalling system.

Nature 453, 294 (2008). doi:10.1038/453294a

Authors: Paul G. Kwiat

There's a long wish list for a workable quantum computer: a viable system must be fast, compact and stable. The first integrated optical quantum logic circuits are a step in the right direction.

Nature 453, 295 (2008). doi:10.1038/453295a

Authors: Stefan H. E. Kaufmann

Many factors affect the severity of tuberculosis in infected individuals. Among these are the genetic make-up of the bacterial strain, that of the host, and the interplay between the two.

Nature 453, 296 (2008). doi:10.1038/453296a

Authors: Francis Zwiers & Gabriele Hegerl

The climate is changing, and so are aspects of the world's physical and biological systems. It is no easy matter to link cause and effect — the latest attack on the problem brings the power of meta-analysis to bear.

Nature 453, 297 (2008). doi:10.1038/453297a

Authors: Benoît Deveaud-Plédran

Polaritons are an odd cross-breed of a particle, half-matter, half-light. They could offer an abundant crop of new and improved optoelectronic devices — a promise already being fulfilled.

Nature 453, 298 (2008). doi:10.1038/453298a

Authors: Ji[rbreve]í Friml & Michael Sauer

They can't move away from shade, so plants resort to a molecular solution to find a place in the sun. The action they take is quite radical, and involves a reprogramming of their development.

Nature 453, 299 (2008). doi:10.1038/453299a

50 years agoNiels Henrik Abel: Mathematician Extraordinary — ... [Abel] was a very nineteenth-century genius. The son of a drunken Norwegian clergyman and his profligate wife, he faced poverty as a student; his subsequent rise to fame was hampered by the indifference, and

Nature 453, 300 (2008). doi:10.1038/453300a

Authors: Edward Ott

Meteorologist and father of chaos theory.

Nature 453, 301 (2008). doi:10.1038/453301a

Author: Natalie DeWitt

Life is regenerative, by definition. But by and large, humans lack the regenerative capacity of creatures such as newts and hydra. Although some of our cells have the innate ability to replenish themselves — and, by doing so, to repair ageing and injured tissues and

Nature 453, 302 (2008). doi:10.1038/nature07037

Author: Kenneth R. Chien

Recent advances in stem-cell technology are now allowing the mechanisms of human disease to be studied in human cells. A new era for regenerative medicine is arising from such disease models, extending beyond early cell-based therapies and towards evaluating genetic variation in humans and identifying

Nature 453, 306 (2008). doi:10.1038/nature07038

Author: Leonard I. Zon

When stem cells divide, they can generate progeny with the same developmental potential as the original cell, a process referred to as self-renewal. Self-renewal is driven intrinsically by gene expression in a cell-type-specific manner and is modulated through interactions with extrinsic cues from the environment,

Nature 453, 314 (2008). doi:10.1038/nature07039

Authors: Geoffrey C. Gurtner, Sabine Werner, Yann Barrandon & Michael T. Longaker

The repair of wounds is one of the most complex biological processes that occur during human life. After an injury, multiple biological pathways immediately become activated and are synchronized to respond. In human adults, the wound repair process commonly leads to a non-functioning mass of

Nature 453, 322 (2008). doi:10.1038/nature07040

Authors: Robert Passier, Linda W. van Laake & Christine L. Mummery

The potential usefulness of human embryonic stem cells for therapy derives from their ability to form any cell in the body. This potential has been used to justify intensive research despite some ethical concerns. In parallel, scientists have searched for adult stem cells that can

Nature 453, 330 (2008). doi:10.1038/nature07041

Authors: Ann P. Chidgey, Daniel Layton, Alan Trounson & Richard L. Boyd

There is much interest in using embryonic stem cells to regenerate tissues and organs. For this approach to succeed, these stem cells or their derivatives must engraft in patients over the long term. Unless a cell transplant is derived from the patient's own cells, however,

Nature 453, 338 (2008). doi:10.1038/nature07042

Authors: Yue Xu, Yan Shi & Sheng Ding

An improved understanding of stem-cell and regenerative biology, as well as a better control of stem-cell fate, is likely to produce treatments for many devastating diseases and injuries. Chemical approaches are starting to have an increasingly important role in this young field. Attention has focused

Nature 453, 345 (2008). doi:10.1038/nature07043

Author: Timm Schroeder

The ability to observe biological processes continuously, instead of at discrete time points, holds great promise for the study of tissue regeneration. Ideally, single cells would be followed continuously within large tissue volumes (such as organs) over long periods of time. Technical limitations, however, preclude

Nature 453, 353 (2008). doi:10.1038/nature06937

Authors: Cynthia Rosenzweig, David Karoly, Marta Vicarelli, Peter Neofotis, Qigang Wu, Gino Casassa, Annette Menzel, Terry L. Root, Nicole Estrella, Bernard Seguin, Piotr Tryjanowski, Chunzhen Liu, Samuel Rawlins & Anton Imeson

Significant changes in physical and biological systems are occurring on all continents and in most oceans, with a concentration of available data in Europe and North America. Most of these changes are in the direction expected with warming temperature. Here we show that these changes

Nature 453, 358 (2008). doi:10.1038/nature06929

Authors: Travis N. Mavrich, Cizhong Jiang, Ilya P. Ioshikhes, Xiaoyong Li, Bryan J. Venters, Sara J. Zanton, Lynn P. Tomsho, Ji Qi, Robert L. Glaser, Stephan C. Schuster, David S. Gilmour, Istvan Albert & B. Franklin Pugh

Comparative genomics of nucleosome positions provides a powerful means for understanding how the organization of chromatin and the transcription machinery co-evolve. Here we produce a high-resolution reference map of H2A.Z and bulk nucleosome locations across the genome of the fly Drosophila melanogaster and compare

Nature 453, 363 (2008). doi:10.1038/nature06925

Authors: Midori Murakami & Tsutomu Kouyama

Invertebrate phototransduction uses an inositol-1,4,5-trisphosphate signalling cascade in which photoactivated rhodopsin stimulates a Gq-type G protein, that is, a class of G protein that stimulates membrane-bound phospholipase Cβ. The same cascade is used by many G-protein-coupled receptors, indicating that invertebrate rhodopsin is a

Nature 453, 368 (2008). doi:10.1038/nature06911

Authors: Paul Schenk, Isamu Matsuyama & Francis Nimmo

The tectonic patterns and stress history of Europa are exceedingly complex and many large-scale features remain unexplained. True polar wander, involving reorientation of Europa’s floating outer ice shell about the tidal axis with Jupiter, has been proposed as a possible explanation for some of the features. This mechanism is possible if the icy shell is latitudinally variable in thickness and decoupled from the rocky interior. It would impose high stress levels on the shell, leading to predictable fracture patterns. No satisfactory match to global-scale features has hitherto been found for polar wander stress patterns. Here we describe broad arcuate troughs and depressions on Europa that do not fit other proposed stress mechanisms in their current position. Using imaging from three spacecraft, we have mapped two global-scale organized concentric antipodal sets of arcuate troughs up to hundreds of kilometres long and 300 m to ∼1.5 km deep. An excellent match to these features is found with stresses caused by an episode of ∼80° true polar wander. These depressions also appear to be geographically related to other large-scale bright and dark lineaments, suggesting that many of Europa’s tectonic patterns may also be related to true polar wander.

Nature 453, 372 (2008). doi:10.1038/nature06979

Authors: S. I. Tsintzos, N. T. Pelekanos, G. Konstantinidis, Z. Hatzopoulos & P. G. Savvidis

The increasing ability to control light–matter interactions at the nanometre scale has improved the performance of semiconductor lasers in the past decade. The ultimate optimization is realized in semiconductor microcavities, in which strong coupling between quantum-well excitons and cavity photons gives rise to hybrid half-light/half-matter polariton quasiparticles. The unique properties of polaritons—such as stimulated scattering, parametric amplification, lasing, condensation and superfluidity—are believed to provide the basis for a new generation of polariton emitters and semiconductor lasers. Until now, polariton lasing and nonlinearities have only been demonstrated in optical experiments, which have shown the potential to reduce lasing thresholds by two orders of magnitude compared to conventional semiconductor lasers. Here we report an experimental realization of an electrically pumped semiconductor polariton light-emitting device, which emits directly from polariton states at a temperature of 235 K. Polariton electroluminescence data reveal characteristic anticrossing between exciton and cavity modes, a clear signature of the strong coupling regime. These findings represent a substantial step towards the realization of ultra-efficient polaritonic devices with unprecedented characteristics.

Nature 453, 376 (2008). doi:10.1038/nature06972

Authors: Hiroki Takahashi, Kazumi Igawa, Kazunobu Arii, Yoichi Kamihara, Masahiro Hirano & Hideo Hosono

The iron- and nickel-based layered compounds LaOFeP (refs 1, 2) and LaONiP (ref. 3) have recently been reported to exhibit low-temperature superconducting phases with transition temperatures Tc of 3 and 5 K, respectively. Furthermore, a large increase in the midpoint Tc of up to ∼26 K has been realized in the isocrystalline compound LaOFeAs on doping of fluoride ions at the O2- sites (LaO1-xFxFeAs). Experimental observations and theoretical studies suggest that these transitions are related to a magnetic instability, as is the case for most superconductors based on transition metals. In the copper-based high-temperature superconductors, as well as in LaOFeAs, an increase in Tc is often observed as a result of carrier doping in the two-dimensional electronic structure through ion substitution in the surrounding insulating layers, suggesting that the application of external pressure should further increase Tc by enhancing charge transfer between the insulating and conducting layers. The effects of pressure on these iron oxypnictide superconductors may be more prominent than those in the copper-based systems, because the As ion has a greater electronic polarizability, owing to the covalency of the Fe–As chemical bond, and, thus, is more compressible than the divalent O2- ion. Here we report that increasing the pressure causes a steep increase in the onset Tc of F-doped LaOFeAs, to a maximum of ∼43 K at ∼4 GPa. With the exception of the copper-based high-Tc superconductors, this is the highest Tc reported to date. The present result, together with the great freedom available in selecting the constituents of isocrystalline materials with the general formula LnOTMPn (Ln, Y or rare-earth metal; TM, transition metal; Pn, group-V, ‘pnicogen’, element), indicates that the layered iron oxypnictides are promising as a new material platform for further exploration of high-temperature superconductivity.

Nature 453, 379 (2008). doi:10.1038/nature06949

Authors: Dieter Lüthi, Martine Le Floch, Bernhard Bereiter, Thomas Blunier, Jean-Marc Barnola, Urs Siegenthaler, Dominique Raynaud, Jean Jouzel, Hubertus Fischer, Kenji Kawamura & Thomas F. Stocker

Changes in past atmospheric carbon dioxide concentrations can be determined by measuring the composition of air trapped in ice cores from Antarctica. So far, the Antarctic Vostok and EPICA Dome C ice cores have provided a composite record of atmospheric carbon dioxide levels over the past 650,000 years. Here we present results of the lowest 200 m of the Dome C ice core, extending the record of atmospheric carbon dioxide concentration by two complete glacial cycles to 800,000 yr before present. From previously published data and the present work, we find that atmospheric carbon dioxide is strongly correlated with Antarctic temperature throughout eight glacial cycles but with significantly lower concentrations between 650,000 and 750,000 yr before present. Carbon dioxide levels are below 180 parts per million by volume (p.p.m.v.) for a period of 3,000 yr during Marine Isotope Stage 16, possibly reflecting more pronounced oceanic carbon storage. We report the lowest carbon dioxide concentration measured in an ice core, which extends the pre-industrial range of carbon dioxide concentrations during the late Quaternary by about 10 p.p.m.v. to 172–300 p.p.m.v.

Nature 453, 383 (2008). doi:10.1038/nature06950

Authors: Laetitia Loulergue, Adrian Schilt, Renato Spahni, Valérie Masson-Delmotte, Thomas Blunier, Bénédicte Lemieux, Jean-Marc Barnola, Dominique Raynaud, Thomas F. Stocker & Jérôme Chappellaz

Atmospheric methane is an important greenhouse gas and a sensitive indicator of climate change and millennial-scale temperature variability. Its concentrations over the past 650,000 years have varied between ∼350 and ∼800 parts per 109 by volume (p.p.b.v.) during glacial and interglacial periods, respectively. In comparison, present-day methane levels of ∼1,770 p.p.b.v. have been reported. Insights into the external forcing factors and internal feedbacks controlling atmospheric methane are essential for predicting the methane budget in a warmer world. Here we present a detailed atmospheric methane record from the EPICA Dome C ice core that extends the history of this greenhouse gas to 800,000 yr before present. The average time resolution of the new data is ∼380 yr and permits the identification of orbital and millennial-scale features. Spectral analyses indicate that the long-term variability in atmospheric methane levels is dominated by ∼100,000 yr glacial–interglacial cycles up to ∼400,000 yr ago with an increasing contribution of the precessional component during the four more recent climatic cycles. We suggest that changes in the strength of tropical methane sources and sinks (wetlands, atmospheric oxidation), possibly influenced by changes in monsoon systems and the position of the intertropical convergence zone, controlled the atmospheric methane budget, with an additional source input during major terminations as the retreat of the northern ice sheet allowed higher methane emissions from extending periglacial wetlands. Millennial-scale changes in methane levels identified in our record as being associated with Antarctic isotope maxima events are indicative of ubiquitous millennial-scale temperature variability during the past eight glacial cycles.

Nature 453, 387 (2008). doi:10.1038/nature06834

Authors: Kiminori Maeda, Kevin B. Henbest, Filippo Cintolesi, Ilya Kuprov, Christopher T. Rodgers, Paul A. Liddell, Devens Gust, Christiane R. Timmel & P. J. Hore

Approximately 50 species, including birds, mammals, reptiles, amphibians, fish, crustaceans and insects, are known to use the Earth’s magnetic field for orientation and navigation. Birds in particular have been intensively studied, but the biophysical mechanisms that underlie the avian magnetic compass are still poorly understood. One proposal, based on magnetically sensitive free radical reactions, is gaining support despite the fact that no chemical reaction in vitro has been shown to respond to magnetic fields as weak as the Earth’s (∼50 μT) or to be sensitive to the direction of such a field. Here we use spectroscopic observation of a carotenoid–porphyrin–fullerene model system to demonstrate that the lifetime of a photochemically formed radical pair is changed by application of ≤50 μT magnetic fields, and to measure the anisotropic chemical response that is essential for its operation as a chemical compass sensor. These experiments establish the feasibility of chemical magnetoreception and give insight into the structural and dynamic design features required for optimal detection of the direction of the Earth’s magnetic field.

Nature 453, 391 (2008). doi:10.1038/nature06877

Authors: Marc Hanikenne, Ina N. Talke, Michael J. Haydon, Christa Lanz, Andrea Nolte, Patrick Motte, Juergen Kroymann, Detlef Weigel & Ute Krämer

Little is known about the types of mutations underlying the evolution of species-specific traits. The metal hyperaccumulator Arabidopsis halleri has the rare ability to colonize heavy-metal-polluted soils, and, as an extremophile sister species of Arabidopsis thaliana, it is a powerful model for research on adaptation. A. halleri naturally accumulates and tolerates leaf concentrations as high as 2.2% zinc and 0.28% cadmium in dry biomass. On the basis of transcriptomics studies, metal hyperaccumulation in A. halleri has been associated with more than 30 candidate genes that are expressed at higher levels in A. halleri than in A. thaliana. Some of these genes have been genetically mapped to broad chromosomal segments of between 4 and 24 cM co-segregating with Zn and Cd hypertolerance. However, the in planta loss-of-function approaches required to demonstrate the contribution of a given candidate gene to metal hyperaccumulation or hypertolerance have not been pursued to date. Using RNA interference to downregulate HMA4 (HEAVY METAL ATPASE 4) expression, we show here that Zn hyperaccumulation and full hypertolerance to Cd and Zn in A. halleri depend on the metal pump HMA4. Contrary to a postulated global trans regulatory factor governing high expression of numerous metal hyperaccumulation genes, we demonstrate that enhanced expression of HMA4 in A. halleri is attributable to a combination of modified cis-regulatory sequences and copy number expansion, in comparison to A. thaliana. Transfer of an A. halleri HMA4 gene to A. thaliana recapitulates Zn partitioning into xylem vessels and the constitutive transcriptional upregulation of Zn deficiency response genes characteristic of Zn hyperaccumulators. Our results demonstrate the importance of cis-regulatory mutations and gene copy number expansion in the evolution of a complex naturally selected extreme trait. The elucidation of a natural strategy for metal hyperaccumulation enables the rational design of technologies for the clean-up of metal-contaminated soils and for bio-fortification.

Nature 453, 396 (2008). doi:10.1038/nature06882

Authors: Elaine Holmes, Ruey Leng Loo, Jeremiah Stamler, Magda Bictash, Ivan K. S. Yap, Queenie Chan, Tim Ebbels, Maria De Iorio, Ian J. Brown, Kirill A. Veselkov, Martha L. Daviglus, Hugo Kesteloot, Hirotsugu Ueshima, Liancheng Zhao, Jeremy K. Nicholson & Paul Elliott

Metabolic phenotypes are the products of interactions among a variety of factors—dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40–59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10-16), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.

Nature 453, 401 (2008). doi:10.1038/nature06876

Authors: Francesca V. Mariani, Christina P. Ahn & Gail R. Martin

Half a century ago, the apical ectodermal ridge (AER) at the distal tip of the tetrapod limb bud was shown to produce signals necessary for development along the proximal–distal (P–D) axis, but how these signals influence limb patterning is still much debated. Fibroblast growth factor (FGF) gene family members are key AER-derived signals, with Fgf4, Fgf8, Fgf9 and Fgf17 expressed specifically in the mouse AER. Here we demonstrate that mouse limbs lacking Fgf4, Fgf9 and Fgf17 have normal skeletal pattern, indicating that Fgf8 is sufficient among AER-FGFs to sustain normal limb formation. Inactivation of Fgf8 alone causes a mild skeletal phenotype; however, when we also removed different combinations of the other AER-FGF genes, we obtained unexpected skeletal phenotypes of increasing severity, reflecting the contribution that each FGF can make to the total AER-FGF signal. Analysis of the compound mutant limb buds revealed that, in addition to sustaining cell survival, AER-FGFs regulate P–D-patterning gene expression during early limb bud development, providing genetic evidence that AER-FGFs function to specify a distal domain and challenging the long-standing hypothesis that AER-FGF signalling is permissive rather than instructive for limb patterning. We discuss how a two-signal model for P–D patterning can be integrated with the concept of early specification to explain the genetic data presented here.

Nature 453, 406 (2008). doi:10.1038/nature06849

Authors: Bijan Pesaran, Matthew J. Nelson & Richard A. Andersen

We often face alternatives that we are free to choose between. Planning movements to select an alternative involves several areas in frontal and parietal cortex that are anatomically connected into long-range circuits. These areas must coordinate their activity to select a common movement goal, but how neural circuits make decisions remains poorly understood. Here we simultaneously record from the dorsal premotor area (PMd) in frontal cortex and the parietal reach region (PRR) in parietal cortex to investigate neural circuit mechanisms for decision making. We find that correlations in spike and local field potential (LFP) activity between these areas are greater when monkeys are freely making choices than when they are following instructions. We propose that a decision circuit featuring a sub-population of cells in frontal and parietal cortex may exchange information to coordinate activity between these areas. Cells participating in this decision circuit may influence movement choices by providing a common bias to the selection of movement goals.

Nature 453, 410 (2008). doi:10.1038/nature06868

Authors: Juliana Hamzah, Manfred Jugold, Fabian Kiessling, Paul Rigby, Mitali Manzur, Hugo H. Marti, Tamer Rabie, Sylvia Kaden, Hermann-Josef Gröne, Günter J. Hämmerling, Bernd Arnold & Ruth Ganss

The vasculature of solid tumours is morphologically aberrant and characterized by dilated and fragile vessels, intensive vessel sprouting and loss of hierarchical architecture. Constant vessel remodelling leads to spontaneous haemorrhages and increased interstitial fluid pressure in the tumour environment. Tumour-related angiogenesis supports tumour growth and is also a major obstacle for successful immune therapy as it prevents migration of immune effector cells into established tumour parenchyma. The molecular mechanisms for these angiogenic alterations are largely unknown. Here we identify regulator of G-protein signalling 5 (Rgs5) as a master gene responsible for the abnormal tumour vascular morphology in mice. Loss of Rgs5 results in pericyte maturation, vascular normalization and consequent marked reductions in tumour hypoxia and vessel leakiness. These vascular and intratumoral changes enhance influx of immune effector cells into tumour parenchyma and markedly prolong survival of tumour-bearing mice. This is the first demonstration, to our knowledge, of reduced tumour angiogenesis and improved immune therapeutic outcome on loss of a vascular gene function and establishes a previously unrecognized role of G-protein signalling in tumour angiogenesis.

Nature 453, 415 (2008). doi:10.1038/nature06893

Authors: Xuekui Yu, Lei Jin & Z. Hong Zhou

Cytoplasmic polyhedrosis virus (CPV) is unique within the Reoviridae family in having a turreted single-layer capsid contained within polyhedrin inclusion bodies, yet being fully capable of cell entry and endogenous RNA transcription. Biochemical data have shown that the amino-terminal 79 residues of the CPV turret protein (TP) is sufficient to bring CPV or engineered proteins into the polyhedrin matrix for micro-encapsulation. Here we report the three-dimensional structure of CPV at 3.88 Å resolution using single-particle cryo-electron microscopy. Our map clearly shows the turns and deep grooves of α-helices, the strand separation in β-sheets, and densities for loops and many bulky side chains; thus permitting atomic model-building effort from cryo-electron microscopy maps. We observed a helix-to-β-hairpin conformational change between the two conformational states of the capsid shell protein in the region directly interacting with genomic RNA. We have also discovered a messenger RNA release hole coupled with the mRNA capping machinery unique to CPV. Furthermore, we have identified the polyhedrin-binding domain, a structure that has potential in nanobiotechnology applications.