Nature contents: 24 April 2014

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Volume 508 Number 7497      nature •Visit Nature homepage •Subscribe to Nature •View Table of Contents The science that matters. Every week.               Starting a CRISPR/CAS9 project for genome editing? Come to OriGene for a wide selection of tools:  • All-in-one pCAS-Guide vectors, • gRNA and donor vector cloning services • Genome-wide gene knockout kit Learn about CRISPR technology from a Youtube video Go to http://www.origene.com/CRISPR-CAS9/ to learn more.       Jump to the content that matters to you View Table of Contents ▶ ▼ News & Comment   ▼ Biological Sciences   ▼ Health Sciences   ▼ Physical Sciences   ▼ Earth & Environmental Sciences   ▼ Careers & Jobs       This week's highlights     Biological Sciences More Biological sciences ▼   Guidelines for investigating causality of sequence variants in human disease   The wide-scale availability of high-throughput DNA sequencing technologies means that data on genetic variation in human diseases are accumulating rapidly. Here Daniel MacArthur and colleagues sound a note of caution, pointing out that up to a quarter of reported disease-linked mutations have been found to have little clinical relevance. The authors propose a two-step process for assessing whether genetic variants are implicated in a disease, with the goal of facilitating translation of genomic research findings into the clinical diagnostic setting.       Physical Sciences More Physical sciences ▼   Superconducting quantum circuits at the surface code threshold for fault tolerance   Practical implementation of quantum computers will require them to be fault-tolerant, like conventional computers. This requires a system that detects any errors and corrects them. Rami Barends and colleagues have now constructed a logic gate that performs code quantum error-correction through a row of five qubits made from superconducting devices. Such systems could be used in integrated circuit quantum processors with a view to developing large-scale, fault-tolerant quantum circuits.       Earth & Environmental Sciences More Earth & Environmental sciences ▼   Plate tectonics, damage and inheritance   Plate tectonics – the division of the Earth's surface into rigid plates separated by linear zones of concentrated deformation – is unique among known terrestrial bodies. As yet there is no consensus view on how the phenomenon arose. David Bercovici and Yanick Ricard have arrived at an explanation that starts with the microscopic properties of deforming minerals. When sufficient lithospheric damage accumulates, the theory states, shear-localization occurs and long-lived weak zones develop. Transient mantle flow and migrating proto-subduction then lead to the accumulation of plate boundaries and eventually tectonic plates.           Podcast & Video     In this week's podcast: the function of the Y chromosome, helping corals breed in the face of climate change, and the scientific life of author Beatrix Potter.         News & Comment Read daily news coverage▶ ▲top               THIS WEEK           Editorials                   A toxic legacy ▶     Illegal dumping of toxic waste in the Italian Campania has been blamed for high rates of ill health in the region. The suspected link needs to be investigated using the most modern methods.             A question of trust ▶     NASA’s decision to renege on SOFIA project casts doubts over its reliability as a partner.             Take care ▶     The United States must tread carefully when building a health-data system.             World View                   Iran needs to present a united front on science ▶     Iranian scientists must be allowed to interact abroad without fear of persecution, says Elise Auerbach.             Seven Days                   Seven days: 18–24 April 2014 ▶     The week in science: NIH allows reuse of rejected grant ideas; China’s land pollution revealed; and NASA’s LADEE probe crashes into the Moon.             NEWS IN FOCUS           Tamiflu report comes under fire ▶     Conclusions on stockpiling of antiviral drugs challenged.             Chile quake defies expectations ▶     Smaller-than-expected tremor has scientists scrambling to redefine rules for areas of extreme seismic stress.             Quantum communications leap out of the lab ▶     China begins work on super-secure network as ‘real-world’ trial successfully sends quantum keys and data.             RNA interference rebooted ▶     Gene-silencing technique yields promising treatments for liver-linked disorders.             Features                   Climate-change adaptation: Designer reefs ▶     Biologists are directing the evolution of corals to prepare them to fight climate change.             Renewable energy: Biofuels heat up ▶     A new generation of industrial plants can make liquid fuels from almost any organic scraps — from corn stalks and wood chips to urban rubbish.             COMMENT           Medical genomics: Gather and use genetic data in health care ▶     Research into how genetic variants can guide successful treatments must become part of routine medical practice and records, says Geoffrey Ginsburg.             Books and Arts                   Natural history: A scientist's eye ▶     Beatrix Potter's meticulous artistry served mycology and entomology as well as children's fiction, reveals Linda Lear.             Medicine: The commodified body ▶     Scott Carney assesses a study of banked human blood, sperm and milk.             Climate science: Stratospheric folly ▶     Tim Kruger examines an argument against injecting aerosols into the atmosphere to counter climate change.             Correspondence                   Russian science: US sanctions put research at risk Konstantin Severinov | Research strategy: Ecology must seek universal principles John Harte | Mental health: More than neurobiology Eiko Fried, Francis Tuerlinckx, Denny Borsboom | Mental health: Drug search on risky path Douglas Kell | Health database: Restore public trust in care.data project Colin Mitchell, Linda Briceno Moraia, Jane Kaye                 Biological Sciences ▲top             RESEARCH           Latest Online                   Ecology: Drought in the Congo Basin ▶     Jeffrey Q. Chambers, Dar A. Roberts             Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation ▶     Lorena Riol-Blanco, Jose Ordovas-Montanes, Mario Perro et al.     In mice, it is possible to induce a psoriasis-like condition by applying imiquimod; here, the production of interleukin-23 that is stimulated by such skin inflammation is shown to depend on the interaction of nociceptors expressing the Nav1.8 and TRPV1 channels with skin-resident dendritic cells.             Structure of the AcrAB–TolC multidrug efflux pump ▶     Dijun Du, Zhao Wang, Nathan R. James et al.     Many bacteria are able to survive in the presence of antibiotics in part because they possess pumps that can remove a broad range of small molecules; here, the structure of one such pump, AcrAB–TolC, is determined using X-ray crystallography and cryo-electron microscopy.             Elevated CO2 further lengthens growing season under warming conditions ▶     Melissa Reyes-Fox, Heidi Steltzer, M. J. Trlica et al.     A grassland warming and CO2 enrichment experiment shows that temperature increase brings forward the growing season of early leafing species, but does not affect or delays senescence in late species, the latter enhanced by elevated CO2.             Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer ▶     Irfan A. Asangani, Vijaya L. Dommeti, Xiaoju Wang et al.     Small-molecule compounds that target the BET domain in proteins such as BRD4 have recently been identified as potential anticancer agents; here, the efficacy of the BRD4-targeting compound JQ1 is demonstrated in castration-resistant prostate cancer driven by deregulated androgen receptor action.             Dichloroacetate prevents restenosis in preclinical animal models of vessel injury ▶     Tobias Deuse, Xiaoqin Hua, Dong Wang et al.     During development of myointimal hyperplasia in human arteries, smooth muscle cells have hyperpolarized mitochondrial membrane potential (ΔΨm), high proliferation and apoptosis resistance; PDK2 is a key regulatory protein whose activation is necessary for myointima formation, and its blockade with dichloroacetate prevents Δψm hyperpolarization, facilitates apoptosis and reduces myointima formation in injured arteries, without preventing vessel re-endothelialization, possibly representing a novel strategy to prevent proliferative vascular diseases.             Articles and Letters                   Juno is the egg Izumo receptor and is essential for mammalian fertilization ▶     Enrica Bianchi, Brendan Doe, David Goulding et al.     The egg receptor for Izumo, a sperm cell-surface protein required for male fertility, is identified here and renamed Juno; these findings show that the Izumo–Juno interaction is conserved within mammals, and open new opportunities for the development of fertility treatments and contraceptives.             Origins and functional evolution of Y chromosomes across mammals ▶     Diego Cortez, Ray Marin, Deborah Toledo-Flores et al.     Using high-throughput genome and transcriptome sequencing, Y chromosome evolution across 15 representative mammals is explored, with results providing evidence for three independent sex chromosome originations in mammals and birds.             Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators ▶     Daniel W. Bellott, Jennifer F. Hughes, Helen Skaletsky et al.     A study comparing the Y chromosome across mammalian species reveals that selection to maintain the ancestral dosage of homologous X–Y gene pairs preserved a handful of genes on the Y chromosome while the rest were lost; the survival of broadly expressed dosage-sensitive regulators of gene expression suggest that the human Y chromosome is essential for male viability.             Herbivores and nutrients control grassland plant diversity via light limitation ▶     Elizabeth T. Borer, Eric W. Seabloom, Daniel S. Gruner et al.     Experimental data collected from 40 grasslands on 6 continents show that nutrients and herbivores can serve as counteracting forces to control local plant diversity; nutrient addition reduces local diversity through light limitation, and herbivory rescues diversity at sites where it alleviates light limitation.             Eutrophication weakens stabilizing effects of diversity in natural grasslands ▶     Yann Hautier, Eric W. Seabloom, Elizabeth T. Borer et al.     Experimental eutrophication weakens the stabilizing effects of plant diversity on the productivity of natural grasslands.             Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion ▶     Katherine S. Ralston, Michael D. Solga, Nicole M. Mackey-Lawrence et al.     Entamoeba histolytica, the causative agent of fatal diarrhoeal disease in children in the developing world, is shown here to kill human cells by biting off and ingesting pieces of cells, in a process reminiscent of the trogocytosis seen between immune cells; ingestion of bites is required for killing and this mechanism is used both in tissue culture and during invasion of intestinal explants.             Inhibition of miR-25 improves cardiac contractility in the failing heart ▶     Christine Wahlquist, Dongtak Jeong, Agustin Rojas-Muñoz et al.     Reduced activity of the calcium-transporting ATPase SERCA2a is a hallmark of heart failure; here, microRNAs that downregulate SERCA2a function are identified, and antagonism of one, miR-25, is shown to halt heart failure in mice.             Foxc1 is a critical regulator of haematopoietic stem/progenitor cell niche formation ▶     Yoshiki Omatsu, Masanari Seike, Tatsuki Sugiyama et al.     Transcription factor Foxc1 is a key regulator of haematopoietic stem/progenitor cell niche formation.             Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus ▶     Pengda Liu, Michael Begley, Wojciech Michowski et al.     Phosphorylation of Akt at its carboxy-terminal tail is an essential layer of Akt activation to regulate its physiological functions.             Nectar secretion requires sucrose phosphate synthases and the sugar transporter SWEET9 ▶     I Winnie Lin, Davide Sosso, Li-Qing Chen et al.     Although nectar is known to be important, for example in plant–insect interactions, little has been known about the mechanism of its secretion; sucrose phosphate synthases are now reported to be essential for the synthesis of the sucrose component of nectar and the transporter protein SWEET9 is shown to mediate sucrose export into the extracellular space of the nectary.             Structure of a type IV secretion system ▶     Harry H. Low, Francesca Gubellini, Angel Rivera-Calzada et al.     The three-dimensional structure of the type IV secretion system encoded by the Escherichia coli R388 conjugative plasmid.             Reviews and Perspectives                   Guidelines for investigating causality of sequence variants in human disease ▶     D. G. MacArthur, T. A. Manolio, D. P. Dimmock et al.     Acceleration in discovery of rare genetic variants possibly linked with disease may mean an increased risk of false-positive reports of causality; this Perspective proposes guidelines to distinguish disease-causing sequence variants from the many potentially functional variants in a human genome, and to assess confidence in their pathogenicity, and highlights priority areas for development.             News & Views                   Sensory systems: Do you hear what I see? ▶     Ione Fine             Infection biology: Nibbled to death ▶     Nancy Guillén             Genetics: The vital Y chromosome ▶     Andrew G. Clark             50 & 100 Years Ago ▶             Reproductive biology: Sperm protein finds its mate ▶     Paul M. Wassarman             Ecology: Drought in the Congo Basin ▶     Jeffrey Q. Chambers, Dar A. Roberts             Corrigendum                   Corrigendum: C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma ▶     Matthew Parker, Kumarasamypet M. Mohankumar, Chandanamali Punchihewa et al.             Research Highlights                   Antimicrobials: Biocide boosts bacterial binding | Organismal biology: 'Extinct' plankton found in Pacific | Animal behaviour: Fruit-fly microbes draw more flies | Microbial evolution: How a flesh-eater evolved | Microbiology: Bacteria elbow out the competition | Zoology: Sex changed in Brazilian insect | Illegal fishing reels in online chatter         NEWS & COMMENT           Take care | Medical genomics: Gather and use genetic data in health care | A toxic legacy | Natural history: A scientist's eye | Medicine: The commodified body | Research strategy: Ecology must seek universal principles | Mental health: More than neurobiology | Mental health: Drug search on risky path | Health database: Restore public trust in care.data project | Tamiflu report comes under fire | RNA interference rebooted             More Biological Sciences ▶                 Nature Outlook Schizophrenia Putting the pieces together.   Access the Outlook free online for six months.   Produced with support from Otsuka Pharmaceutical Development and Commercialization, Inc.          Health Sciences ▲top             RESEARCH           Latest Online                   Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer ▶     Irfan A. Asangani, Vijaya L. Dommeti, Xiaoju Wang et al.     Small-molecule compounds that target the BET domain in proteins such as BRD4 have recently been identified as potential anticancer agents; here, the efficacy of the BRD4-targeting compound JQ1 is demonstrated in castration-resistant prostate cancer driven by deregulated androgen receptor action.             Dichloroacetate prevents restenosis in preclinical animal models of vessel injury ▶     Tobias Deuse, Xiaoqin Hua, Dong Wang et al.     During development of myointimal hyperplasia in human arteries, smooth muscle cells have hyperpolarized mitochondrial membrane potential (ΔΨm), high proliferation and apoptosis resistance; PDK2 is a key regulatory protein whose activation is necessary for myointima formation, and its blockade with dichloroacetate prevents Δψm hyperpolarization, facilitates apoptosis and reduces myointima formation in injured arteries, without preventing vessel re-endothelialization, possibly representing a novel strategy to prevent proliferative vascular diseases.             Articles and Letters                   Inhibition of miR-25 improves cardiac contractility in the failing heart ▶     Christine Wahlquist, Dongtak Jeong, Agustin Rojas-Muñoz et al.     Reduced activity of the calcium-transporting ATPase SERCA2a is a hallmark of heart failure; here, microRNAs that downregulate SERCA2a function are identified, and antagonism of one, miR-25, is shown to halt heart failure in mice.             Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus ▶     Pengda Liu, Michael Begley, Wojciech Michowski et al.     Phosphorylation of Akt at its carboxy-terminal tail is an essential layer of Akt activation to regulate its physiological functions.             News & Views                   Sensory systems: Do you hear what I see? ▶     Ione Fine             Corrigendum                   Corrigendum: C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma ▶     Matthew Parker, Kumarasamypet M. Mohankumar, Chandanamali Punchihewa et al.           NEWS & COMMENT           Take care | Medical genomics: Gather and use genetic data in health care | A toxic legacy | Medicine: The commodified body | Mental health: More than neurobiology | Health database: Restore public trust in care.data project | Tamiflu report comes under fire | RNA interference rebooted             More Health Sciences ▶               Physical Sciences ▲top             RESEARCH           Latest Online                   Spontaneous transfer of chirality in an atropisomerically enriched two-axis system ▶     Kimberly T. Barrett, Anthony J. Metrano, Paul R. Rablen et al.     An enantioselective reaction involving a molecule with two axes of stereochemical consequence produces four stereoisomers, and rather than racemizing as the system approaches equilibrium, one of the diastereomeric pairs drifts spontaneously to a higher enantiomeric ratio.             Articles and Letters                   Superconducting quantum circuits at the surface code threshold for fault tolerance ▶     R. Barends, J. Kelly, A. Megrant et al.     A universal set of logic gates in a superconducting quantum circuit is shown to have gate fidelities at the threshold for fault-tolerant quantum computing by the surface code approach, in which the quantum bits are distributed in an array of planar topology and have only nearest-neighbour couplings.             Electroreduction of carbon monoxide to liquid fuel on oxide-derived nanocrystalline copper ▶     Christina W. Li, Jim Ciston, Matthew W. Kanan     The electrochemical conversion of CO and H2O into liquid fuel is made feasible at modest potentials with the use of oxide-derived nanocystalline Cu as the catalyst.             Hybrid shallow on-axis and deep off-axis hydrothermal circulation at fast-spreading ridges ▶     Jörg Hasenclever, Sonja Theissen-Krah, Lars H. Rüpke et al.     High-resolution three-dimensional simulations of hydrothermal flow beneath fast-spreading ridges predict two interacting flow components — shallow on-axis flow and deeper off-axis flow — that merge to feed axial vent sites, reconciling previously incompatible models favouring only one flow component.             News & Views                   Electrochemistry: Catalysis at the boundaries ▶     Aaron M. Appel             Research Highlights                   Astronomy: Earth twin spotted in habitable zone | Physics: Liquid bubbles stop sound         NEWS & COMMENT           A question of trust | Quantum communications leap out of the lab | Renewable energy: Biofuels heat up             More Physical Sciences ▶               Earth & Environmental Sciences ▲top             RESEARCH           Latest Online                   Ecology: Drought in the Congo Basin ▶     Jeffrey Q. Chambers, Dar A. Roberts             Widespread decline of Congo rainforest greenness in the past decade ▶     Liming Zhou, Yuhong Tian, Ranga B. Myneni et al.     The long-term drying trend in central African rainforests might help to explain satellite-detected large-scale vegetation browning in the Congolese forests.             Articles and Letters                   Sea-level and deep-sea-temperature variability over the past 5.3 million years ▶     E. J. Rohling, G. L. Foster, K. M. Grant et al.     A novel approach to the estimation of sea level and deep-sea temperature has been used to determine these quantities over the past 5.3 million years; this approach, based on oxygen isotope records from the eastern Mediterranean, shows that temperature and sea-level histories are broadly correlated but also show intriguing temporal offsets.             Hybrid shallow on-axis and deep off-axis hydrothermal circulation at fast-spreading ridges ▶     Jörg Hasenclever, Sonja Theissen-Krah, Lars H. Rüpke et al.     High-resolution three-dimensional simulations of hydrothermal flow beneath fast-spreading ridges predict two interacting flow components — shallow on-axis flow and deeper off-axis flow — that merge to feed axial vent sites, reconciling previously incompatible models favouring only one flow component.             Plate tectonics, damage and inheritance ▶     David Bercovici, Yanick Ricard     Lithospheric damage, combined with transient mantle flow and migrating proto-subduction, is proposed to explain the apparent emergence of plate tectonics three billion years ago; modelling confirms that tectonic plate boundaries and fully formed tectonic plates can arise under conditions characteristic of Earth but not of Venus.             News & Views                   Climate science: Sea levels from ancient seashells ▶     Ralph Schneider             Ecology: Drought in the Congo Basin ▶     Jeffrey Q. Chambers, Dar A. Roberts             Corrigendum                   Corrigendum: Rapid remobilization of magmatic crystals kept in cold storage ▶     Kari M. Cooper, Adam J. R. Kent             Research Highlights                   Geology: Ancient impact recorded in rock | Illegal fishing reels in online chatter         NEWS & COMMENT           Climate-change adaptation: Designer reefs | A toxic legacy | Climate science: Stratospheric folly | Chile quake defies expectations             More Earth & Environmental Sciences ▶                   nature.com webcasts   Macmillan Science Communication presents a custom webcast: Using digital PCR for next generation sequencing.   Wednesday April 30th at 8am PDT / 11am EDT / 4pm BST / 5pm CEST   Register for the free webcast followed by a live Q & A session    Sponsored by: Life Technologies         Careers & Jobs ▲top               Grants: Funder storm ▶     A confluence of budget disappointments has confounded US scientists and left many uncertain about their future.                   Turning point: Andrew Zwicker ▶     Plasma physicist-turned-educator turns his sights on public office.                   Burnout predictors ▶     A greater total workload makes women more vulnerable to burnout, finds study.                   UK visa fast-track ▶     Agencies collaborate to hasten foreign scientists' admission.                   Science 2.0 ▶     Study concludes that more scientists should use social media in their work.             Careers related news & comment                   Iran needs to present a united front on science Elise Auerbach | Seven days: 18–24 April 2014 | Medicine: The commodified body Scott Carney | Russian science: US sanctions put research at risk Konstantin Severinov | RNA interference rebooted Erika Check Hayden               naturejobs.com Science jobs of the week       PhD position     Ulm University            Postdoctoral Research Fellow     Duke University            Postdoctoral Research Assistant     Queen Mary University of London          No matter what your career stage, student, postdoc or senior scientist, you will find articles on naturejobs.com to help guide you in your science career. 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