Nature 454, x (2008). doi:10.1038/7203xa

Tracking arsenic from the Himalayas to southeast Asia's water supply.

Nature 454, x (2008). doi:10.1038/7203xb

First authorSex determination in most animals, including humans, occurs through the shuffling of sex chromosomes, but in hymenopterans — bees, ants and wasps — sex is determined by how many sets of chromosomes an individual receives. In this system, males derive from unfertilized eggs,

Nature 454, x (2008). doi:10.1038/7203xc

Blogosphere etiquette comes into question. “We seem to be at a critical juncture concerning the intersection of blogs and other Web 2.0 technologies with science,” writes associate editor Noah Gray at the Nature Neuroscience blog (http://tinyurl.com/6z7nvt).The anonymity of cyberspace provides protection

Nature 454, 367 (2008). doi:10.1038/454367a

By almost every measure, China's growth is extraordinary. But behind the astonishing statistics is a more complex reality.

Nature 454, 368 (2008). doi:10.1038/454368a

The incoming US administration can and should reverse the neglect of Earth observations.

Nature 454, 370 (2008). doi:10.1038/454370a

Proc. R. Soc. B doi:10.1098/rspb.2008.0607 (2008) Smell may be much more important to the way birds perceive their surroundings than biologists have thought. A study of nine species of bird from seven orders found, in all cases, that the majority

Nature 454, 370 (2008). doi:10.1038/454370b

Appl. Phys. Lett.92, 254102 (2008) 10.1063/1.2945893A team of researchers has made three-dimensional 'atom chips' that give unprecedented control over Bose–Einstein condensates (BECs) — clouds of extremely cold atoms that all share the same quantum state.Thorsten Schumm at Vienna

Nature 454, 370 (2008). doi:10.1038/454370c

J. Acoust. Soc. Am.124, 472–483 (2008) 10.1121/1.2932088Laughter is considered to be a reflex action, an adaptive tension-reliever with analogues in many non-human species. That congenitally deaf people laugh out loud supports this theory. But do they produce

Nature 454, 370 (2008). doi:10.1038/454370d

Proc. Natl Acad. Sci. USA doi:10.1073/pnas.0802361105 (2008)Rice is efficient, indeed disconcertingly so, at assimilating arsenic from the soils of paddy fields. But how it does this has been unclear. Now Fang-Jie Zhao at Rothamsted Research in Harpenden, UK, Jian

Nature 454, 370 (2008). doi:10.1038/454370e

Phys. Rev. D78, 022002 (2008) 10.1103/PhysRevD.78.022002Gravity is the weakest and least well understood of the four fundamental forces. It behaves well over large distances. But many theorists suspect that undiscovered particles or extra dimensions might cause its observed behaviour

Nature 454, 371 (2008). doi:10.1038/454371a

Neuron59, 125–137 (2008) 10.1016/j.neuron.2008.05.011Researchers studying anaesthetized adult gerbils fitted with earphones report that the neurotransmitter GABA calibrates the processing system that locates a sound's origin.Ursula Koch and Anna Magnusson of LMU Munich in Germany and their

Nature 454, 371 (2008). doi:10.1038/454371b

Astrophys. J.681, 1035–1045 (2008) 10.1086/588212Astronomers have found that vast stores of hot gas in the areas between clusters of gravitationally bound galaxies do form stars, though not many. The gas falls into one of the cluster's bright

Nature 454, 371 (2008). doi:10.1038/454371c

Cell Host Microbe4, 52–62 (2008) 10.1016/j.chom.2008.06.002A mutation that makes Africans resistant to a form of malaria renders them more vulnerable to HIV infection, researchers have found.The mutation halts the expression of the protein DARC in red

Nature 454, 371 (2008). doi:10.1038/454371d

Angew. Chem. Int. Edn doi:10.1002/anie.200802164 (2008) Many drugs contain compounds with fluorine–carbon bonds, as do tracers used in positron-emission tomography (PET), a medical imaging technique. Producing these compounds is tricky and involves harsh conditions. Now, Tobias Ritter and his colleagues

Nature 454, 371 (2008). doi:10.1038/454371e

Cell134, 148–161 (2008) 10.1016/j.cell.2008.05.032A protein called WHAMM helps shuttle other proteins between compartments in mammalian cells by interacting with two components of the cell skeleton, researchers have found.Matthew Welch, Kenneth Campellone and their colleagues at the

Nature 454, 371 (2008). doi:10.1038/454371f

Proc. Natl Acad. Sci. USA105, 9936–9941 (2008) 10.1073/pnas.0804510105In living cells, palindromes in a DNA sequence often stall the DNA replication machinery when their two halves bind, making the strand loop outwards.Such arrangements, in which similar or

Nature 454, 397 (2008). doi:10.1038/454397a

Authors: Junguo Liu, Hong Yang & H. H. G. Savenije

SirYour Editorial 'A fresh approach to water' (Nature452, 253; 2008) points out that the world's looming water crisis is driven by climate change, population growth and economic development. In China, changing food-consumption patterns are the main cause of the

Nature 454, 397 (2008). doi:10.1038/454397b

Author: Homme W. Hellinga

SirYour Editorial 'Negative results' (Nature453, 258; 10.1038/453258b2008) and News Feature 'Designer debacle' (Nature453, 275–278; 2008), on the retraction of two papers from my laboratory and the events surrounding those retractions, have provided opportunity for

Nature 454, 397 (2008). doi:10.1038/454397c

Author: J. H. Evans

SirIn your Editorial about the increasing expense of the ITER fusion reactor ('The price isn't right' Nature453, 824; 10.1038/453824a2008), you suggest that scientists might be suspected of deliberately under-quoting the price to help sell the project. Possibly. What then

Nature 454, 397 (2008). doi:10.1038/454397d

Author: Philip Strange

SirIn his Correspondence 'Fewer academics could be the answer to insufficient grants' (Nature453, 978; 10.1038/453978a2008), Andrew Doig suggests that the endemic problem of the rejection of high-quality grant proposals could be solved by cutting the number of academic

Nature 454, 398 (2008). doi:10.1038/454398a

Author: Lan Xue

Pushes to globalize science must not threaten local innovations in developing countries, argues Lan Xue.

Nature 454, 399 (2008). doi:10.1038/454399a

Researchers and businesspeople in China, expatriates and 'returnees' give their views of what it will take to make China a research and innovation powerhouse.

Nature 454, 403 (2008). doi:10.1038/454403a

Authors: Ling Chen & Gang Zhang

Scientific policy-making in China has come a long way since the 1970s, argue Ling Chen and Gang Zhang.

Nature 454, 404 (2008). doi:10.1038/454404a

Author: Jane Qiu

With up to 30,000 visitors a day, the Beijing-based China Science and Technology Museum is grossly oversubscribed. In response, China is building another one more than twice the size, costing 2 billion yuan (US$300 million). The museum (artist's impression, pictured) will open in Beijing's Olympic

Nature 454, 405 (2008). doi:10.1038/454405a

Author: Martin Kemp

A woodcut of Ferdinand Verbiest, the Kangxi Emperor's Flemish astronomer and mastermind of Beijing's Ancient Observatory, records a remarkable seventeenth-century cultural exchange. Martin Kemp explains.

Nature 454, 406 (2008). doi:10.1038/454406a

Author: Emma Marris

When Jules Verne wrote A Journey to the Centre of the Earth in 1864, science was still coming to terms with the planet's extreme age, and Verne's story of a swiss-cheese globe containing vast seas and prehistoric creatures had a satisfying ring of plausibility.

Nature 454, 406 (2008). doi:10.1038/454406b

Author: Victor R. Baker

Geologists study Earth by applying principles borrowed from more fundamental sciences. Yet geology also has its own set of attitudes that have accrued during the discipline's long history. The nature of geological inquiry, involving a synthesis of historical and philosophical reasoning, lies at the heart

Nature 454, 407 (2008). doi:10.1038/454407a

Author: Andrew H. Knoll

A few years ago, at the Massachusetts Institute of Technology's artificial intelligence lab, I met an android. Her conversation was perfunctory, mostly simple responses to my equally simple words, but her eyes, widening, narrowing and subtly changing angle, made a genuine emotional connection. That robot

Nature 454, 408 (2008). doi:10.1038/454408a

Author: John Kirkland

Higher education is increasingly market driven, but its most expensive product — the doctorate — is more popular than ever. Doctoral student numbers continue to rise as funding bodies support them with new initiatives.Doctorates are expensive. For sponsors, spending around US$200,000 on a single

Nature 454, 409 (2008). doi:10.1038/454409a

Author: Simon Winchester

An English biochemist single-handedly changed the West's perception of China, revealing its past scientific glories and predicting more to come. Simon Winchester investigates the ongoing legacy of Joseph Needham.

Nature 454, 412 (2008). doi:10.1038/454412a

Authors: J. Rogers Hollingsworth, Karl H. Müller & Ellen Jane Hollingsworth

Could the end of US world dominance over research mark the passing of national science giants, ask J. Rogers Hollingsworth, Karl H. Müller and Ellen Jane Hollingsworth.

Nature 454, 415 (2008). doi:10.1038/454415a

Authors: Charles F. Harvey

South Asia's well-water is widely polluted with arsenic, but no one has located the source. A study on the Mekong River finds that contamination begins in pond sediments, and is spread by groundwater flow to wells.

Nature 454, 416 (2008). doi:10.1038/454416a

Authors: Andrew Cossins & Michael Berenbrink

Nitric oxide generated from the nitrite ion limits the tissue damage caused by restricted blood flow. Gene knockout experiments in mice now reveal that myoglobin is the mediator of this effect.

Nature 454, 417 (2008). doi:10.1038/454417a

Authors: A. Prasanna de Silva

Silicon chips have thousands of electronic logic gates etched on them. But there are other ways to decorate monolithic surfaces with logic gates, as a system using metal complexes secured to glass slides shows.

Nature 454, 418 (2008). doi:10.1038/454418a

Authors: David M. Holtzman

An agent that clears disease-associated amyloid aggregates from the brains of patients with Alzheimer's disease does not alleviate disease progression. Yet this disappointing news should not rule out such potential therapies.

Nature 454, 419 (2008). doi:10.1038/454419a

50 years agoAs from June 1, 1958, the Clean Air Act, 1956 ... is fully in force, and it will be an offence punishable by fine to emit 'dark smoke' (defined as as dark as or darker than shade 2 on the Ringelmann Chart)

Nature 454, 420 (2008). doi:10.1038/454420a

Authors: Sharon C. Glotzer & Aaron S. Keys

What do you get when you cross a crystal with a quasicrystal? The answer is a structure that links the ancient tiles of Archimedes, the iconic Fibonacci sequence of numbers and a book from the seventeenth century.

Nature 454, 421 (2008). doi:10.1038/454421a

Authors: Michael Lichten

Meiotic recombination shuffles the genome, so each generation inherits a new combination of parental traits. Combining traditional and modern approaches, new work pinpoints where recombination occurs genome-wide.

Nature 454, 422 (2008). doi:10.1038/454422a

Authors: F. I. Woodward

During the growing season, with photosynthesis at its peak, leaf temperatures remain constant over a wide latitudinal range. This is a finding that overturns a common assumption and has various ramifications.

Nature 454, 424 (2008). doi:10.1038/454424a

Author: Paul Nurse

Focusing on information flow will help us to understand better how cells and organisms work.

Nature 454, 427 (2008). doi:10.1038/454427a

Author: Ursula Weiss

Inflammation is the body's immediate response to damage to its tissues and cells by pathogens, noxious stimuli such as chemicals, or physical injury. Acute inflammation is a short-term response that usually results in healing: leukocytes infiltrate the damaged region, removing the stimulus and repairing the

Nature 454, 428 (2008). doi:10.1038/nature07201

Author: Ruslan Medzhitov

Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation — infection and tissue injury — are at one end of a

Nature 454, 436 (2008). doi:10.1038/nature07205

Authors: Alberto Mantovani, Paola Allavena, Antonio Sica & Frances Balkwill

The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes

Nature 454, 445 (2008). doi:10.1038/nature07204

Authors: Stephen J. Galli, Mindy Tsai & Adrian M. Piliponsky

Allergic disorders, such as anaphylaxis, hay fever, eczema and asthma, now afflict roughly 25% of people in the developed world. In allergic subjects, persistent or repetitive exposure to allergens, which typically are intrinsically innocuous substances common in the environment, results in chronic allergic inflammation. This

Nature 454, 455 (2008). doi:10.1038/nature07203

Authors: Kezhong Zhang & Randal J. Kaufman

The endoplasmic reticulum is responsible for much of a cell's protein synthesis and folding, but it also has an important role in sensing cellular stress. Recently, it has been shown that the endoplasmic reticulum mediates a specific set of intracellular signalling pathways in response to

Nature 454, 463 (2008). doi:10.1038/nature07206

Authors: Christoph Handschin & Bruce M. Spiegelman

Inadequate physical activity is linked to many chronic diseases. But the mechanisms that tie muscle activity to health are unclear. The transcriptional coactivator PGC1α has recently been shown to regulate several exercise-associated aspects of muscle function. We propose that this protein controls muscle plasticity, suppresses

Nature 454, 470 (2008). doi:10.1038/nature07202

Authors: Steven J. Bensinger & Peter Tontonoz

The nuclear receptors known as PPARs and LXRs are lipid-activated transcription factors that have emerged as key regulators of lipid metabolism and inflammation. PPARs and LXRs are activated by non-esterified fatty acids and cholesterol metabolites, respectively, and both exert positive and negative control over the

Nature 454, 479 (2008). doi:10.1038/nature07135

Authors: Eugenio Mancera, Richard Bourgon, Alessandro Brozzi, Wolfgang Huber & Lars M. Steinmetz

Meiotic recombination has a central role in the evolution of sexually reproducing organisms. The two recombination outcomes, crossover and non-crossover, increase genetic diversity, but have the potential to homogenize alleles by gene conversion. Whereas crossover rates vary considerably across the genome, non-crossovers and gene conversions

Nature 454, 486 (2008). doi:10.1038/nature07101

Authors: Tony Warne, Maria J. Serrano-Vega, Jillian G. Baker, Rouslan Moukhametzianov, Patricia C. Edwards, Richard Henderson, Andrew G. W. Leslie, Christopher G. Tate & Gebhard F. X. Schertler

G-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 Å resolution crystal structure of a β1-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey (Meleagris gallopavo

Nature 454, 492 (2008). doi:10.1038/nature07114

Authors: Makoto Kishimoto, Robert Antonucci, Omer Blaes, Andy Lawrence, Catherine Boisson, Marcus Albrecht & Christian Leipski

Quasars are thought to be powered by supermassive black holes accreting surrounding gas. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output. It is well known, however, that the most extensively studied disk model—an optically thick disk which is heated locally by the dissipation of gravitational binding energy—is apparently contradicted by observations in a few major respects. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared, but this is not generally seen in the visible wavelength region where the disk spectrum is observable. A crucial difficulty has been that, towards the infrared, the disk spectrum starts to be hidden under strong, hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emitting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct.

Nature 454, 495 (2008). doi:10.1038/nature07110

Authors: Qing Cao, Hoon-sik Kim, Ninad Pimparkar, Jaydeep P. Kulkarni, Congjun Wang, Moonsub Shim, Kaushik Roy, Muhammad A. Alam & John A. Rogers

The ability to form integrated circuits on flexible sheets of plastic enables attributes (for example conformal and flexible formats and lightweight and shock resistant construction) in electronic devices that are difficult or impossible to achieve with technologies that use semiconductor wafers or glass plates as substrates. Organic small-molecule and polymer-based materials represent the most widely explored types of semiconductors for such flexible circuitry. Although these materials and those that use films or nanostructures of inorganics have promise for certain applications, existing demonstrations of them in circuits on plastic indicate modest performance characteristics that might restrict the application possibilities. Here we report implementations of a comparatively high-performance carbon-based semiconductor consisting of sub-monolayer, random networks of single-walled carbon nanotubes to yield small- to medium-scale integrated digital circuits, composed of up to nearly 100 transistors on plastic substrates. Transistors in these integrated circuits have excellent properties: mobilities as high as 80 cm2 V-1 s-1, subthreshold slopes as low as 140 m V dec-1, operating voltages less than 5 V together with deterministic control over the threshold voltages, on/off ratios as high as 105, switching speeds in the kilohertz range even for coarse (∼100-μm) device geometries, and good mechanical flexibility—all with levels of uniformity and reproducibility that enable high-yield fabrication of integrated circuits. Theoretical calculations, in contexts ranging from heterogeneous percolative transport through the networks to compact models for the transistors to circuit level simulations, provide quantitative and predictive understanding of these systems. Taken together, these results suggest that sub-monolayer films of single-walled carbon nanotubes are attractive materials for flexible integrated circuits, with many potential areas of application in consumer and other areas of electronics.

Nature 454, 501 (2008). doi:10.1038/nature07074

Authors: Jules Mikhael, Johannes Roth, Laurent Helden & Clemens Bechinger

Monolayers on crystalline surfaces often form complex structures with physical and chemical properties that differ strongly from those of their bulk phases. Such hetero-epitactic overlayers are currently used in nanotechnology and understanding their growth mechanism is important for the development of new materials and devices. In comparison with crystals, quasicrystalline surfaces exhibit much larger structural and chemical complexity leading, for example, to unusual frictional, catalytical or optical properties. Deposition of thin films on such substrates can lead to structures that may have typical quasicrystalline properties. Recent experiments have indeed showed 5-fold symmetries in the diffraction pattern of metallic layers adsorbed on quasicrystals. Here we report a real-space investigation of the phase behaviour of a colloidal monolayer interacting with a quasicrystalline decagonal substrate created by interfering five laser beams. We find a pseudomorphic phase that shows both crystalline and quasicrystalline structural properties. It can be described by an archimedean-like tiling consisting of alternating rows of square and triangular tiles. The calculated diffraction pattern of this phase is in agreement with recent observations of copper adsorbed on icosahedral Al70Pd21Mn9 surfaces. In addition to establishing a link between archimedean tilings and quasicrystals, our experiments allow us to investigate in real space how single-element monolayers can form commensurate structures on quasicrystalline surfaces.

Nature 454, 505 (2008). doi:10.1038/nature07093

Authors: Matthew L. Polizzotto, Benjamin D. Kocar, Shawn G. Benner, Michael Sampson & Scott Fendorf

Tens of millions of people in south and southeast Asia routinely consume ground water that has unsafe arsenic levels. Arsenic is naturally derived from eroded Himalayan sediments, and is believed to enter solution following reductive release from solid phases under anaerobic conditions. However, the processes governing aqueous concentrations and locations of arsenic release to pore water remain unresolved, limiting our ability to predict arsenic concentrations spatially (between wells) and temporally (future concentrations) and to assess the impact of human activities on the arsenic problem. This uncertainty is partly attributed to a poor understanding of groundwater flow paths altered by extensive irrigation pumping in the Ganges-Brahmaputra delta, where most research has focused. Here, using hydrologic and (bio)geochemical measurements, we show that on the minimally disturbed Mekong delta of Cambodia, arsenic is released from near-surface, river-derived sediments and transported, on a centennial timescale, through the underlying aquifer back to the river. Owing to similarities in geologic deposition, aquifer source rock and regional hydrologic gradients, our results represent a model for understanding pre-disturbance conditions for other major deltas in Asia. Furthermore, the observation of strong hydrologic influence on arsenic behaviour indicates that release and transport of arsenic are sensitive to continuing and impending anthropogenic disturbances. In particular, groundwater pumping for irrigation, changes in agricultural practices, sediment excavation, levee construction and upstream dam installations will alter the hydraulic regime and/or arsenic source material and, by extension, influence groundwater arsenic concentrations and the future of this health problem.

Nature 454, 509 (2008). doi:10.1038/nature07177

Authors: Tom Parsons, Chen Ji & Eric Kirby

On 12 May 2008, the devastating magnitude 7.9 (Wenchuan) earthquake struck the eastern edge of the Tibetan plateau, collapsing buildings and killing thousands in major cities aligned along the western Sichuan basin in China. After such a large-magnitude earthquake, rearrangement of stresses in the crust commonly leads to subsequent damaging earthquakes. The mainshock of the 12 May earthquake ruptured with as much as 9 m of slip along the boundary between the Longmen Shan and Sichuan basin, and demonstrated the complex strike–slip and thrust motion that characterizes the region. The Sichuan basin and surroundings are also crossed by other active strike–slip and thrust faults. Here we present calculations of the coseismic stress changes that resulted from the 12 May event using models of those faults, and show that many indicate significant stress increases. Rapid mapping of such stress changes can help to locate fault sections with relatively higher odds of producing large aftershocks.

Nature 454, 511 (2008). doi:10.1038/nature07031

Authors: Brent R. Helliker & Suzanna L. Richter

The oxygen isotope ratio (δ18O) of cellulose is thought to provide a record of ambient temperature and relative humidity during periods of carbon assimilation. Here we introduce a method to resolve tree-canopy leaf temperature with the use of δ18O of cellulose in 39 tree species. We show a remarkably constant leaf temperature of 21.4 ± 2.2 °C across 50° of latitude, from subtropical to boreal biomes. This means that when carbon assimilation is maximal, the physiological and morphological properties of tree branches serve to raise leaf temperature above air temperature to a much greater extent in more northern latitudes. A main assumption underlying the use of δ18O to reconstruct climate history is that the temperature and relative humidity of an actively photosynthesizing leaf are the same as those of the surrounding air. Our data are contrary to that assumption and show that plant physiological ecology must be considered when reconstructing climate through isotope analysis. Furthermore, our results may explain why climate has only a modest effect on leaf economic traits in general.

Nature 454, 515 (2008). doi:10.1038/nature06970

Authors: Armand M. Kuris, Ryan F. Hechinger, Jenny C. Shaw, Kathleen L. Whitney, Leopoldina Aguirre-Macedo, Charlie A. Boch, Andrew P. Dobson, Eleca J. Dunham, Brian L. Fredensborg, Todd C. Huspeni, Julio Lorda, Luzviminda Mababa, Frank T. Mancini, Adrienne B. Mora, Maria Pickering, Nadia L. Talhouk, Mark E. Torchin & Kevin D. Lafferty

Parasites can have strong impacts but are thought to contribute little biomass to ecosystems. We quantified the biomass of free-living and parasitic species in three estuaries on the Pacific coast of California and Baja California. Here we show that parasites have substantial biomass in these ecosystems. We found that parasite biomass exceeded that of top predators. The biomass of trematodes was particularly high, being comparable to that of the abundant birds, fishes, burrowing shrimps and polychaetes. Trophically transmitted parasites and parasitic castrators subsumed more biomass than did other parasitic functional groups. The extended phenotype biomass controlled by parasitic castrators sometimes exceeded that of their uninfected hosts. The annual production of free-swimming trematode transmission stages was greater than the combined biomass of all quantified parasites and was also greater than bird biomass. This biomass and productivity of parasites implies a profound role for infectious processes in these estuaries.

Nature 454, 519 (2008). doi:10.1038/nature07052

Authors: Martin Hasselmann, Tanja Gempe, Morten Schiøtt, Carlos Gustavo Nunes-Silva, Marianne Otte & Martin Beye

Sex determination in honeybees (Apis mellifera) is governed by heterozygosity at a single locus harbouring the complementary sex determiner (csd) gene, in contrast to the well-studied sex chromosome system of Drosophila melanogaster. Bees heterozygous at csd are females, whereas homozygotes and hemizygotes (haploid individuals) are males. Although at least 15 different csd alleles are known among natural bee populations, the mechanisms linking allelic interactions to switching of the sexual development programme are still obscure. Here we report a new component of the sex-determining pathway in honeybees, encoded 12 kilobases upstream of csd. The gene feminizer (fem) is the ancestrally conserved progenitor gene from which csd arose and encodes an SR-type protein, harbouring an Arg/Ser-rich domain. Fem shares the same arrangement of Arg/Ser- and proline-rich-domain with the Drosophila principal sex-determining gene transformer (tra), but lacks conserved motifs except for a 30-amino-acid motif that Fem shares only with Tra of another fly, Ceratitis capitata. Like tra, the fem transcript is alternatively spliced. The male-specific splice variant contains a premature stop codon and yields no functional product, whereas the female-specific splice variant encodes the functional protein. We show that RNA interference (RNAi)-induced knockdowns of the female-specific fem splice variant result in male bees, indicating that the fem product is required for entire female development. Furthermore, RNAi-induced knockdowns of female allelic csd transcripts result in the male-specific fem splice variant, suggesting that the fem gene implements the switch of developmental pathways controlled by heterozygosity at csd. Comparative analysis of fem and csd coding sequences from five bee species indicates a recent origin of csd in the honeybee lineage from the fem progenitor and provides evidence for positive selection at csd accompanied by purifying selection at fem. The fem locus in bees uncovers gene duplication and positive selection as evolutionary mechanisms underlying the origin of a novel sex determination pathway.

Nature 454, 523 (2008). doi:10.1038/nature07106

Authors: Takeshi Saito, David M. Owen, Fuguo Jiang, Joseph Marcotrigiano & Michael Gale Jr.

Innate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated molecular patterns (PAMPs). Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide. Infection is regulated by hepatic immune defences triggered by the cellular RIG-I helicase. RIG-I binds PAMP RNA and signals interferon regulatory factor 3 activation to induce the expression of interferon-α/β and antiviral/interferon-stimulated genes (ISGs) that limit infection. Here we identify the polyuridine motif of the HCV genome 3′ non-translated region and its replication intermediate as the PAMP substrate of RIG-I, and show that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of RIG-I recognition and immune triggering in human and murine cells. 5′ terminal triphosphate on the PAMP RNA was necessary but not sufficient for RIG-I binding, which was primarily dependent on homopolymeric ribonucleotide composition, linear structure and length. The HCV PAMP RNA stimulated RIG-I-dependent signalling to induce a hepatic innate immune response in vivo, and triggered interferon and ISG expression to suppress HCV infection in vitro. These results provide a conceptual advance by defining specific homopolymeric RNA motifs within the genome of HCV and other RNA viruses as the PAMP substrate of RIG-I, and demonstrate immunogenic features of the PAMP–RIG-I interaction that could be used as an immune adjuvant for vaccine and immunotherapy approaches.

Nature 454, 528 (2008). doi:10.1038/nature07034

Authors: Morgan E. Carlson, Michael Hsu & Irina M. Conboy

Adult skeletal muscle robustly regenerates throughout an organism’s life, but as the muscle ages, its ability to repair diminishes and eventually fails. Previous work suggests that the regenerative potential of muscle stem cells (satellite cells) is not triggered in the old muscle because of a decline in Notch activation, and that it can be rejuvenated by forced local activation of Notch. Here we report that, in addition to the loss of Notch activation, old muscle produces excessive transforming growth factor (TGF)-β (but not myostatin), which induces unusually high levels of TGF-β pSmad3 in resident satellite cells and interferes with their regenerative capacity. Importantly, endogenous Notch and pSmad3 antagonize each other in the control of satellite-cell proliferation, such that activation of Notch blocks the TGF-β-dependent upregulation of the cyclin-dependent kinase (CDK) inhibitors p15, p16, p21 and p27, whereas inhibition of Notch induces them. Furthermore, in muscle stem cells, Notch activity determines the binding of pSmad3 to the promoters of these negative regulators of cell-cycle progression. Attenuation of TGF-β/pSmad3 in old, injured muscle restores regeneration to satellite cells in vivo. Thus a balance between endogenous pSmad3 and active Notch controls the regenerative competence of muscle stem cells, and deregulation of this balance in the old muscle microniche interferes with regeneration.

Nature 454, 533 (2008). doi:10.1038/nature07062

Authors: Simon G. Sprecher & Claude Desplan

Specificity of sensory neurons requires restricted expression of one sensory receptor gene and the exclusion of all others within a given cell. In the Drosophila retina, functional identity of photoreceptors depends on light-sensitive Rhodopsins (Rhs). The much simpler larval eye (Bolwig organ) is composed of about 12 photoreceptors, eight of which are green-sensitive (Rh6) and four blue-sensitive (Rh5). The larval eye becomes the adult extraretinal ‘eyelet’ composed of four green-sensitive (Rh6) photoreceptors. Here we show that, during metamorphosis, all Rh6 photoreceptors die, whereas the Rh5 photoreceptors switch fate by turning off Rh5 and then turning on Rh6 expression. This switch occurs without apparent changes in the programme of transcription factors that specify larval photoreceptor subtypes. We also show that the transcription factor Senseless (Sens) mediates the very different cellular behaviours of Rh5 and Rh6 photoreceptors. Sens is restricted to Rh5 photoreceptors and must be excluded from Rh6 photoreceptors to allow them to die at metamorphosis. Finally, we show that Ecdysone receptor (EcR) functions autonomously both for the death of larval Rh6 photoreceptors and for the sensory switch of Rh5 photoreceptors to express Rh6. This fate switch of functioning, terminally differentiated neurons provides a novel, unexpected example of hard-wired sensory plasticity.

Nature 454, 538 (2008). doi:10.1038/nature07065

Authors: Riina M. Luik, Bin Wang, Murali Prakriya, Minnie M. Wu & Richard S. Lewis

Ca2+-release-activated Ca2+ (CRAC) channels generate sustained Ca2+ signals that are essential for a range of cell functions, including antigen-stimulated T lymphocyte activation and proliferation. Recent studies have revealed that the depletion of Ca2+ from the endoplasmic reticulum (ER) triggers the oligomerization of stromal interaction molecule 1 (STIM1), the ER Ca2+ sensor, and its redistribution to ER–plasma membrane (ER–PM) junctions where the CRAC channel subunit ORAI1 accumulates in the plasma membrane and CRAC channels open. However, how the loss of ER Ca2+ sets into motion these coordinated molecular rearrangements remains unclear. Here we define the relationships among [Ca2+]ER, STIM1 redistribution and CRAC channel activation and identify STIM1 oligomerization as the critical [Ca2+]ER-dependent event that drives store-operated Ca2+ entry. In human Jurkat leukaemic T cells expressing an ER-targeted Ca2+ indicator, CRAC channel activation and STIM1 redistribution follow the same function of [Ca2+]ER, reaching half-maximum at ∼200 µM with a Hill coefficient of ∼4. Because STIM1 binds only a single Ca2+ ion, the high apparent cooperativity suggests that STIM1 must first oligomerize to enable its accumulation at ER–PM junctions. To assess directly the causal role of STIM1 oligomerization in store-operated Ca2+ entry, we replaced the luminal Ca2+-sensing domain of STIM1 with the 12-kDa FK506- and rapamycin-binding protein (FKBP12, also known as FKBP1A) or the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR, also known as FRAP1). A rapamycin analogue oligomerizes the fusion proteins and causes them to accumulate at ER–PM junctions and activate CRAC channels without depleting Ca2+ from the ER. Thus, STIM1 oligomerization is the critical transduction event through which Ca2+ store depletion controls store-operated Ca2+ entry, acting as a switch that triggers the self-organization and activation of STIM1–ORAI1 clusters at ER–PM junctions.