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Volume 468 Issue 7324, 2 December 2010

Alphaviruses are significant animal and human pathogens - as demonstrated in recent outbreaks of infection with the mosquito-borne Chikungunya virus in India and southeast Asia. The E1 and E2 glycoproteins of alphaviruses are central to the way the virus infects host cells. The E1/E2 heterodimers that form spikes on the virus surface dissociate in the acidic conditions found in the internal vesicles of host cells, and E1 triggers infection by fusing with the endosomal membrane. Flix Rey and colleagues present the structure of Chikungunya virus envelope glycoprotein at neutral pH, and Michael Rossmann and colleagues reveal the structure of the envelope proteins of Sindbis virus at low pH. Sindbis virus can cause fever in humans and is the most extensively studied alphavirus. Comparison of the two structures provides insight into how fusion activation is controlled and points to possible vaccine targets. On the cover, surface structures of Chikungunya virus (right) and Sindbis virus.

Editorial

  • Europe says it is embarking on an unprecedented overhaul of its electricity system. But it must do more to convince the private sector that it is serious.

    Editorial

    Advertisement

  • Overpriced and underused, the International Space Station could still be a research asset.

    Editorial
  • Republican opposition to the US–Russia arms-control treaty is based on politics, not science.

    Editorial
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World View

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Research Highlights

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Seven Days

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News

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News Feature

  • Bob Klein founded the California Institute for Regenerative Medicine, the biggest state-run research project in US history. What legacy will he leave behind?

    • Elie Dolgin
    News Feature
  • Is a vast undersea grid bringing wind-generated electricity from the North Sea to Europe a feasible proposition or an overpriced fantasy?

    • Colin Macilwain
    News Feature
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Comment

  • What was the impact of the nanotechnology funding boom of the past ten years? Philip Shapira and Jue Wang have scrutinized the literature to find out.

    • Philip Shapira
    • Jue Wang
    Comment
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Books & Arts

  • A balanced biography brings out the many contradictions of nuclear physicist Edward Teller, finds Robert P. Crease.

    • Robert P. Crease
    Books & Arts
  • Instructions for the afterlife from Ancient Egypt reveal a step change in moral psychology, discovers Andrew Robinson.

    • Andrew Robinson
    Books & Arts
  • A hands-on exhibition shows how online tools are shaping the way we use knowledge, says Aleks Krotoski.

    • Aleks Krotoski
    Books & Arts
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Correspondence

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News & Views

  • The lack of absorption features in the transmission spectrum of exoplanet GJ 1214b rules out a hydrogen-rich atmosphere for the planet. It is consistent with an atmosphere rich in water vapour or abundant in clouds. See Letter p.669

    • Drake Deming
    News & Views
  • Resistance of tumour cells to chemotherapy can severely affect the efficacy of this anticancer treatment. The non-tumour cells of the organ in which the tumour resides may aid the emergence of such resistance.

    • Urban Emmenegger
    • Robert S. Kerbel
    News & Views
  • As in humans, the actions and reactions of male and female fruitflies during courtship are quite distinct. The differences seem to lie in gender-specific neural interpretations of the same sensory signals. See Letter p.686

    • Richard Benton
    News & Views
  • Labelling molecules by fast oxidation allows mass spectrometry to study protein folding at submillisecond time resolution. The method also brings a wealth of structural information about protein folding within reach.

    • Martin Gruebele
    News & Views
  • The transition by certain nematode worms to plant parasitism, and possibly more generally to herbivory, is illuminated by an investigation into how nematodes acquired the protein weapons to penetrate the plant cell wall.

    • Noah K. Whiteman
    • Andrew D. Gloss
    News & Views
  • Extensive mapping of local electronic structure in copper oxide superconductors reveals fluctuating stripe-like electron patterns that appear as a high-temperature precursor to superconductivity. See Letter p.677

    • Kathryn A. Moler
    News & Views
  • Blood cells are generated from haematopoietic stem cells on demand. The protein Lkb1, which lies at the crossroad of energy metabolism and cell growth, seems to regulate these stem cells' dynamics. See Articles p.653, p.659 & Letter p.701

    • Ellen M. Durand
    • Leonard I. Zon
    News & Views
  • Alphaviruses infect their host by binding to cellular receptors and fusing with cell membranes. New studies define the receptor-binding protein of these viruses and its regulation of the membrane-fusion reaction. See Letters p.705 & p.709

    • Margaret Kielian
    News & Views
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Review Article

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Article

  • Haematopoietic stem cells (HSCs) are very sensitive to energetic and oxidative stress, and modulation of the balance between their quiescence and proliferation is needed to respond to metabolic stress while preserving HSCs' long-term regenerative capacity. Here the tumour suppressor Lkb1 is shown to promote stem-cell maintenance and tissue regeneration by regulating energy metabolism and by preventing aneuploidy.

    • Daisuke Nakada
    • Thomas L. Saunders
    • Sean J. Morrison
    Article
  • Haematopoietic stem cells (HSCs) are very sensitive to energetic and oxidative stress, and modulation of the balance between their quiescence and proliferation is needed to respond to metabolic stress while preserving HSCs' long term regenerative capacity. Here the tumour suppressor Lkb1 is shown to have a crucial role in maintaining energy homeostasis in haematopoietic cells — an effect largely independent of AMPK and mTOR signalling.

    • Sushma Gurumurthy
    • Stephanie Z. Xie
    • Nabeel Bardeesy
    Article
  • Splicing is carried out by a collection of protein–RNA complexes known as snRNPs. The spliceosome contains equal quantities of the U1, U2, U4, U5 and U6 snRNPs, but the U1 snRNP is made in levels excess to the amounts needed to form spliceosomes, leading to the idea that excess U1s might have splicing independent functions. Here it is shown that the U1 snRNA interacts with some pre mRNAs whose introns have cryptic polyadenylation sites. This interaction prevents premature termination and polyadenylation of the pre mRNA.

    • Daisuke Kaida
    • Michael G. Berg
    • Gideon Dreyfuss
    Article
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Letter

  • Three distinct models for the recently discovered super-Earth (masses 2–10 times that of Earth) planet GJ 1214b that are consistent with its mass and radius have been suggested. Breaking the degeneracy between these models requires obtaining constraints on the planet's atmospheric composition. Here, a ground based measurement of the transmission spectrum of GJ 1214b between 780 and 1,000 nm is reported. The lack of features in this spectrum rules out cloud free atmospheres composed primarily of hydrogen. If the planet's atmosphere is hydrogen-dominated, then it must contain clouds or hazes that are optically thick at pressures <200 mbar. Alternatively, the data are also consistent with the presence of a dense water vapour atmosphere.

    • Jacob L. Bean
    • Eliza Miller-Ricci Kempton
    • Derek Homeier
    Letter
  • Antihydrogen, the bound state of an antiproton and a positron, has been produced at low energies at CERN since 2002. It is of fundamental interest for testing the standard model of elementary particles and interactions. However, experiments so far have produced antihydrogen that is not confined, precluding detailed study of its structure. Here, trapping of antihydrogen atoms is demonstrated, opening the door to precision measurements on anti atoms.

    • G. B. Andresen
    • M. D. Ashkezari
    • Y. Yamazaki
    Letter
  • A long-standing question has been the interplay between pseudogap, which is generic to all hole doped copper oxide superconductors, and stripes, whose static form occurs in only one family of copper oxides over a narrow range of the phase diagram. This study reports observations of the spatial reorganization of electronic states with the onset of the pseudogap state at T* in the high temperature superconductor Bi2Sr2CaCu2O8+x using scanning tunnelling microscopy. The onset of the pseudogap phase coincides with the appearance of electronic patterns that have the predicted characteristics of fluctuating stripes. The experiments indicate that stripes are a consequence of pseudogap behaviour rather than its cause.

    • Colin V. Parker
    • Pegor Aynajian
    • Ali Yazdani
    Letter
  • Here it is shown that the ratio of zinc to total iron content constrains the valence state of iron in primary arc basalts and their mantle sources. Primitive arc magmas have identical Zn/FeT ratios (FeT = Fe2+ + Fe3+) as mid-ocean-ridge basalts, indicating a similar iron oxidation state of primary mantle melts in arcs and ridges and that the subduction of oxidized crustal material may not significantly alter the redox state of the mantle wedge. It is concluded that the observed higher oxidation states of arc lavas must therefore be, in part, a consequence of shallow-level differentiation processes.

    • Cin-Ty A. Lee
    • Peter Luffi
    • William P. Leeman
    Letter
  • Innate differences between male and female behaviours must be inscribed in their respective genomes, but how these encode distinct neuronal circuits remains largely unclear. Focusing on sex specific responses to the cVA pheromone in fruitflies, a chain of four successive neurons carrying olfactory signals down to motor centres has been identified, with all male to female anatomical differences lying downstream of a conserved sensory cell. The techniques developed should help others in the task of neuronal circuit mapping, which remains daunting even for the relatively simple fly brain.

    • Vanessa Ruta
    • Sandeep Robert Datta
    • Richard Axel
    Letter
  • Acid sensing has so far been demonstrated in the gustatory system only. Now, fruitfly olfactory sensory neurons selectively activated by acidic compounds have been identified. Acid sensing also requires the transmembrane protein IR64a, expressed in those neurons as well as neurons involved in the detection of non acidic odorants. Although the IR64a protein isn't sufficient by itself to determine acid recognition, the requirement for IR64a in acid recognition is the first function for a member of this recently discovered family of putative odorant receptors — the ionotropic receptor family.

    • Minrong Ai
    • Soohong Min
    • Greg S. B. Suh
    Letter
  • Haematopoietic stem cells (HSCs) are very sensitive to energetic and oxidative stress, and modulation of the balance between their quiescence and proliferation is needed to respond to metabolic stress while preserving HSCs' long-term regenerative capacity. Here, and in two accompanying studies, it is shown that the tumour suppressor Lkb1 has a crucial role in maintaining energy homeostasis in haematopoietic cells.

    • Boyi Gan
    • Jian Hu
    • Ronald A. DePinho
    Letter
  • The E1 and E2 glycoproteins of alphaviruses form heterodimers and assemble into spikes on the virus surface, which mediate receptor binding and endocytosis. When the virion encounters acidic pH in the endosome E1 and E2 dissociate and E1 triggers fusion with the endosomal membrane. Two papers now provide the first crystal structures for glycoprotein complexes incorporating E2 at acidic and neutral pH, respectively. Together they provide insight into how fusion activation is controlled in alphaviruses.

    • Long Li
    • Joyce Jose
    • Michael G. Rossmann
    Letter
  • The E1 and E2 glycoproteins of alphaviruses form heterodimers and assemble into spikes on the virus surface, which mediate receptor binding and endocytosis. When the virion encounters acidic pH in the endosome E1 and E2 dissociate and E1 triggers fusion with the endosomal membrane. Two papers now provide the first crystal structures for glycoprotein complexes incorporating E2 at acidic and neutral pH, respectively. Together they provide insight into how fusion activation is controlled in alphaviruses.

    • James E. Voss
    • Marie-Christine Vaney
    • Félix A. Rey
    Letter
  • During translation, tRNAs enter the ribosome and then move sequentially through three sites, known as A, P and E, as they transfer their attached amino acids onto the growing peptide chain. How the ribosome facilitates tRNA translocation between the sites remains largely unknown. Now a study uses multiparticle cryoelectron microscopy of a ribosome bound to the translation elongation factor, EF-G, to get information about tRNA movement. It identifies two new substates and sees that translocation is linked to unratcheting of the 30S ribosomal subunit.

    • Andreas H. Ratje
    • Justus Loerke
    • Christian M. T. Spahn
    Letter
  • The energy-coupling factor transporters are responsible for vitamin uptake in prokaryotes. Here, the X-ray crystal structure of the membrane-embedded, substrate-binding domain of a riboflavin transporter from Staphylococcus aureus is reported. The transporter adopts a previously unreported fold and contains a riboflavin molecule bound to a loop and the periplasmic portion of several transmembrane segments.

    • Peng Zhang
    • Jiawei Wang
    • Yigong Shi
    Letter
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Feature

  • Manuscript-editing services are growing. Can they turn a mediocre paper into a publishable one? And at what cost?

    • Karen Kaplan

    Collection:

    Feature
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Career Brief

  • Canadian postdocs seek better working conditions.

    Career Brief
  • Scottish universities try to preserve research posts in the face of cuts.

    Career Brief
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Futures

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