Nature contents: 18 July 2013

Can't view this email? Click here to view in your browser.     Volume 499 Number 7458      nature •Visit Nature homepage •Subscribe to Nature •View Table of Contents The science that matters. Every week.               See what nature is hiding BD Horizon™ Brilliant Violet™ polymer conjugates are brighter than traditional dyes and can help identify cell populations with lower receptor density than previously possible. Learn how to resolve rare and dim cell populations with our expanded set of tools and information and request a free sample at bdbiosciences.com/go/brilliant.        Jump to the content that matters to you View Table of Contents ▶ ▼ News & Comment   ▼ Biological Sciences   ▼ Chemical Sciences   ▼ Physical Sciences   ▼ Earth & Environmental Sciences   ▼ Careers & Jobs       This week's highlights     Special - Learning in a digital age     From massive open online courses (MOOCs) that are delivered to tens of thousands around the globe to adaptive digital tools that can improve outcomes by providing tailored learning experiences as well as mapping a student's individual progress at every juncture, technology is transforming the 21st century student. Through feature articles and commentaries from experts in the field, this special collaboration between the editors of Scientific American and Nature probes the revolution underway in education and what it means for learning and research. ▼ more       Physical Sciences More Physical sciences ▼   Sequential deposition as a route to high-performance perovskite-sensitized solar cells   Practical applications of a promising type of solar cell are brought closer by work published in Nature this week. Solution-processable solid-state solar cells using organic–inorganic perovskites to harvest light can in principle show impressive power conversion efficiencies, but their performance is unpredictable because of the uncontrolled way in which the pigment is usually deposited. Julian Burschka and colleagues report a two-step deposition process that minimizes variations in the pigment, resulting in power conversion efficiencies of 15% - a new record.       Earth & Environmental Sciences More Earth & Environmental sciences ▼   Increase in forest water-use efficiency as atmospheric carbon dioxide concentrations rise   Rising atmospheric carbon dioxide concentrations are expected to increase the efficiency with which plants use water, but the magnitude of this effect in natural forests has been difficult to establish. A two-decade analysis of carbon and water fluxes from forest research sites across the Northern Hemisphere now confirms that water-use efficiency - the ratio of water loss to carbon gain - has increased in these forests and rising carbon dioxide levels are the most plausible driver. This trend, which cannot be fully explained by current theory and terrestrial biosphere models, may have important implications for forest productivity and responses to drought.       Biological Sciences More Biological sciences ▼   High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat   Naked mole rats combine extreme longevity with virtually complete resistance to cancer. Now a novel glycosaminoglycan variant that may have evolved to provide the creatures with skin suited to a subterranean lifestyle has been identified as a key contributor to their cancer resistance. The mole rat has a high-molecular-mass hyaluronan (HMM-HA), more than five times larger than mouse and human equivalents. HMM-HA acts through the CD44 receptor and its removal makes naked mole-rat cells susceptible to transformation.       Podcast & Video     In this week's podcast: switching off the extra chromosome in Down's syndrome, using endless waves to explore quantum systems, and how massive open online courses are transforming learning.           Special - Learning in a digital age ▲top               Feature                   Education online: The virtual lab ▶     Confronted with the explosive popularity of online learning, researchers are seeking new ways to teach the practical skills of science.             Comment                   Digital learning: Look, then leap ▶     Massive open online courses can make higher education more accessible, immersive and comprehensive — if they are deployed with due caution, says Michael M. Crow.             Education: Online on-ramps ▶     Giving scientists greater access to conceptual and technical tuition through massive open online courses will aid interdisciplinary research, say Hazel Sive and Sanjay Sarma.             Naturejobs                   Online learning: How to make a MOOC ▶     With forethought and support, science instructors can design effective massive open online courses.               News & Comment Read daily news coverage▶ ▲top               THIS WEEK           Editorials                   The benefits of brain mapping ▶     Two huge projects have the potential to revolutionize neuroscience, as long as they don't drain money from other work and are monitored to keep them on target.             Active protection ▶     Parents should vaccinate their children against human papillomavirus.             Light show ▶     Lasers will one day improve data transfer from spacecraft, but hurdles must still be overcome.             World View                   Don't market stem-cell products ahead of proof ▶     The controversy over an unproven stem-cell therapy in Italy highlights the dangers of doing translational medicine in reverse, argues Paolo Bianco.             Seven Days                   Seven days: 12–18 July 2013 ▶     The week in science: Antarctic glacier sheds massive iceberg, Indian nuclear reactor moves forward, and Hubble reveals blue-hued exoplanet.             NEWS IN FOCUS           Asteroid plan looks rocky ▶     NASA mission to retrieve a small space rock could be tripped up by lack of candidates.             Hunt for mystery GM wheat hots up ▶     Investigators hope to track origins of the transgenic crop.             NIH gambles on recycled drugs ▶     Early success could bolster congressional support for agency's translational science centre.             Rinderpest research restarts ▶     As moratorium lifts, oversight is put in place to assess studies on eradicated cattle virus.             Fukushima offers real-time ecolab ▶     But ecologists say they need more funding.             Lasers boost space communications ▶     Optical systems set to handle planetary science's big data.             Feature                   Neuroscience: Solving the brain ▶     The United States and Europe are both planning billion-dollar investments to understand how the brain works. But the technological challenges are vast.             COMMENT           Books and Arts                   In retrospect: The Prince ▶     John Whitfield finds resonance with today's behavioural sciences in Niccolò Machiavelli's great Renaissance political treatise, begun five centuries ago this month.             Neurophilosophy: My brain and I ▶     Chris Frith reflects on a book that probes the knotty nexus between brain and mind.             Genomics: Art of the hypothetical ▶     Elie Dolgin gets the inside story on the data displays rendered as abstract visualizations at a renowned genomics institute.             Correspondence                   Russian science: Academy reform needs a reality check Sergey V. Razin, Yegor S. Vassetzky | Reproducibility: Two more red flags for suspect work Jason E. McDermott | Science and the public: Promotional tactics corrupt research Michael Kelly | Analysis: Don't do big-data science backwards David B. Lindenmayer, Gene E. Likens             Correction                   Correction ▶                     Biological Sciences ▲top             RESEARCH           Latest Online                   Cell biology: Tumour stem cells in bone ▶     Mone Zaidi, Simón Méndez-Ferrer             Structural biology: Meet the B family ▶     Patrick M. Sexton, Denise Wootten             Influenza: Pathways to human adaptation ▶     David A. Steinhauer             Insights into the phylogeny and coding potential of microbial dark matter OPEN ▶     Christian Rinke, Patrick Schwientek, Alexander Sczyrba et al.     Uncultivated archaeal and bacterial cells of major uncharted branches of the tree of life are targeted and sequenced using single-cell genomics; this enables resolution of many intra- and inter-phylum-level relationships, uncovers unexpected metabolic features that challenge established boundaries between the three domains of life, and leads to the proposal of two new superphyla.             Structure of class B GPCR corticotropin-releasing factor receptor 1 ▶     Kaspar Hollenstein, James Kean, Andrea Bortolato et al.     Approximately 30% of known drugs target G protein-coupled receptors (GPCRs), but all the published structures of GPCRs to date are from the class A family of GPCRs; here the first X-ray crystal structure of a member of the class B family of GPCRs, the human corticotropin-releasing factor receptor 1, is determined.             Structure of the human glucagon class B G-protein-coupled receptor ▶     Fai Yiu Siu, Min He, Chris de Graaf et al.     The X-ray crystal structure of the human glucagon receptor, a potential drug target for type 2 diabetes, offers a structural basis for molecular recognition by class B G-protein-coupled receptors.             Translating dosage compensation to trisomy 21 ▶     Jun Jiang, Yuanchun Jing, Gregory J. Cost et al.     This study uses zinc-finger nucleases to target an inducible XIST transgene into chromosome 21 from trisomic Down's syndrome pluripotent stem cells; the XIST RNA coats one copy of chromosome 21 and triggers whole chromosome silencing, suggesting the potential of this approach for studying chromosomal disorders such as Down's syndrome and for research into gene therapies.             A latent capacity for evolutionary innovation through exaptation in metabolic systems ▶     Aditya Barve, Andreas Wagner     A computational analysis of the ability of a metabolic reaction network to synthesize all biomass from a single source of carbon and energy shows that when such networks are required to be viable on one particular carbon source, they are typically also viable on multiple other carbon sources that were not targets of selection.             Maternal imprinting at the H19–Igf2 locus maintains adult haematopoietic stem cell quiescence ▶     Aparna Venkatraman, Xi C. He, Joanne L. Thorvaldsen et al.     Maternal genomic imprinting is crucial for the maintenance of adult stem cells, which is accomplished by maintaining long-term haematopoietic stem cell quiescence.             The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy ▶     Jens Füllgrabe, Melinda A. Lynch-Day, Nina Heldring et al.     Induction of autophagy is coupled to reduction of histone H4 lysine 16 acetylation through downregulation of the histone acetyltransferase hMOF, showing that histone modifications regulate the outcome of autophagy.             Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle ▶     Jeremy B. Chang, James E. Ferrell Jr     In an in vitro Xenopus extract system that can undergo cell cycles, mitosis spreads through the cytoplasm in 'trigger waves' of Cdk1 activation, which may reflect a more general biological mechanism related to action potentials and calcium waves.             Structural basis for molecular recognition of folic acid by folate receptors ▶     Chen Chen, Jiyuan Ke, X. Edward Zhou et al.     Folate receptor-α (FRα) is overexpressed in many cancer cells and is therefore an important therapeutic target: here the X-ray crystal structure of folate-bound FRα is presented, revealing details of the ligand-binding pocket that may be useful in the development of small-molecule inhibitors for anticancer therapy.             An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways ▶     Takashi Hirose, H. Robert Horvitz     Removal of cells during development in Caenorhabditis elegans requires the precise execution of cell-death programs, which can include both caspase-dependent and -independent pathways; here it is shown that a single upstream transcription factor can drive both, in parallel, to destroy a single cell.             Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids ▶     Dhirendra K. Simanshu, Ravi Kanth Kamlekar, Dayanjan S. Wijesinghe et al.     A human lipid transfer protein (GLTPD1, named here CPTP) is shown to regulate eicosanoid production by mediating the intermembrane transfer of the phosphorylated sphingolipid ceramide-1-phosphate through a non-vesicular transport mechanism elucidated by structural, functional and biological data.             DNA unwinding heterogeneity by RecBCD results from static molecules able to equilibrate ▶     Bian Liu, Ronald J. Baskin, Stephen C. Kowalczykowski     The bacterial RecBCD helicase/nuclease shows broad, and apparently static, heterogeneity in the unwinding rate manifest by individual molecules: here it is shown that transiently halting an enzyme during processive translocation allows for a change, most likely conformational, such that the velocity of the molecule after pausing can fall anywhere within the spectrum of rates seen for a population.             Ptpn11 deletion in a novel progenitor causes metachondromatosis by inducing hedgehog signalling ▶     Wentian Yang, Jianguo Wang, Douglas C. Moore et al.     Deletion of Ptpn11 in a newly defined mesenchymal progenitor population in the perichondral groove of Ranvier leads to metachondromatosis by increasing Indian hedgehog expression and activating hedgehog signalling, a process that can be reversed with the use of hedgehog pathway inhibitors.             Articles and Letters                   Ultrasensitive fluorescent proteins for imaging neuronal activity ▶     Tsai-Wen Chen, Trevor J. Wardill, Yi Sun et al.     Sensitive protein sensors of calcium have been created; these new tools are shown to report neural activity in cultured neurons, flies and zebrafish and can detect single action potentials and synaptic activation in the mouse visual cortex in vivo.             Myomaker is a membrane activator of myoblast fusion and muscle formation ▶     Douglas P. Millay, Jason R. O'Rourke, Lillian B. Sutherland et al.     A muscle-specific membrane protein called myomaker is transiently expressed during myogenesis and is both necessary and sufficient to drive myoblast fusion in vivo and in vitro.             LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling ▶     Xiaomeng Wang, Sabu Abraham, Jenny A. G. McKenzie et al.     LRG1 is identified as a new regulator of TGF-β signalling that promotes angiogenesis via a TβRII–ALK1–ENG–Smad1/5/8 signalling pathway; antibody-mediated inhibition of LRG1 reduces pathogenic neovascularization in a mouse model of retinal injury.             Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2 ▶     Shaun D. Wong, Martin Srnec, Megan L. Matthews et al.     Synchrotron-based nuclear resonance vibrational spectroscopy is used to characterize the reactive Fe(iv)=O intermediate of the halogenase SyrB2; the substrate directs the orientation of this intermediate, presenting specific frontier molecular orbitals that can activate the selective halogenation.             Increase in forest water-use efficiency as atmospheric carbon dioxide concentrations rise ▶     Trevor F. Keenan, David Y. Hollinger, Gil Bohrer et al.     Present-day forests use water more efficiently, probably owing to the effect of increased atmospheric carbon dioxide on leaf stomata, which partially close to maintain a near-constant level of carbon dioxide inside the leaves despite increasing atmospheric levels.             Reversal of an ancient sex chromosome to an autosome in Drosophila  ▶     Beatriz Vicoso, Doris Bachtrog     An autosomal chromosome pair in Drosophila, the dot chromosome, is shown to have evolved from an ancestral X chromosome: these findings explain several previously puzzling aspects of dot chromosome biology and challenge the view that differentiated sex chromosomes represent a terminal evolutionary stage.             Behaviour-dependent recruitment of long-range projection neurons in somatosensory cortex ▶     Jerry L. Chen, Stefano Carta, Joana Soldado-Magraner et al.     In the mouse whisker region of primary somatosensory cortex (S1), neurons projecting to secondary somatosensory cortex (S2) and primary motor cortex (M1), respectively, are differentially activated during distinct whisker-based behavioural tasks; sensory stimulus features alone do not elicit these differences, suggesting that selective transmission of S1 information to S2 and M1 is driven by behaviour.             Activity-dependent phosphorylation of MeCP2 threonine 308 regulates interaction with NCoR ▶     Daniel H. Ebert, Harrison W. Gabel, Nathaniel D. Robinson et al.     Rett syndrome is caused by mutations in MeCP2, and this study identifies a site on MeCP2, T308, whose phosphorylation is regulated by neuronal activity: phosphorylation of T308 blocks the interaction of MeCP2 with the NCoR co-repressor complex, suppressing MeCP2's ability to repress transcription, and mice carrying mutations of MeCP2 T308 show Rett-syndrome-related symptoms.             High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat ▶     Xiao Tian, Jorge Azpurua, Christopher Hine et al.     Naked mole rats seem almost entirely protected from developing cancer, and this can now, at least in part, be explained by the production of a unique high-molecular-mass form of hyaluronan, a component of the extracellular matrix; together with an increased sensitivity of naked mole-rat cells to hyaluronan signalling, this form protects its cells from oncogenic transformation.             Structure and function of the Salmonella Typhi chimaeric A2B5 typhoid toxin ▶     Jeongmin Song, Xiang Gao, Jorge E. Galán     Unlike most salmonellae, Salmonella enterica serovar Typhi causes life-threatening systemic infections known as typhoid fever, for which the molecular basis is unknown; here administration of typhoid toxin produced by S. Typhi reproduces many of the acute symptoms of typhoid fever, carbohydrates on cell surface glycoproteins are identified as receptors for typhoid toxin and the toxin's crystal structure is determined, providing insights into these interactions.             Three-state mechanism couples ligand and temperature sensing in riboswitches ▶     Anke Reining, Senada Nozinovic, Kai Schlepckow et al.     In the human pathogen Vibrio vulnificus, the riboswitch regulating gene expression of the adenosine deaminase is shown to exist in three distinct stable conformational states; this three-state mechanism allows control of gene expression over a broad temperature range, which is essential for Vibrio adaptation.             Promoter directionality is controlled by U1 snRNP and polyadenylation signals ▶     Albert E. Almada, Xuebing Wu, Andrea J. Kriz et al.     Asymmetric sequence determinants flanking gene transcription start sites are shown to control directionality of transcription elongation in mammalian cells by regulating promoter-proximal cleavage and polyadenylation.             Carbon catabolite repression of the maltose transporter revealed by X-ray crystallography ▶     Shanshuang Chen, Michael L. Oldham, Amy L. Davidson et al.     The X-ray crystal structure of a member of the glucose-specific phosphotransferase system (EIIAGlc) bound to the MalFGK2 maltose transporter is presented, revealing that two EIIAGlc proteins bind to the cytoplasmic ATPase subunits of the maltose transporter to stabilize it in an inward-facing conformation that prevents ATP hydrolysis.             News & Views                   Biogeochemistry: Carbon dioxide and water use in forests ▶     Belinda Medlyn & Martin De Kauwe             50 & 100 Years Ago ▶             RNA biophysics: A three-state balancing act ▶     Ronald Micura             Cancer: Calculated treatment ▶     Natalia L. Komarova, C. Richard Boland             Bacteriology: Toxins in tandem ▶     C. Erec Stebbins             Cell biology: Tumour stem cells in bone ▶     Mone Zaidi, Simón Méndez-Ferrer             Structural biology: Meet the B family ▶     Patrick M. Sexton, Denise Wootten             Influenza: Pathways to human adaptation ▶     David A. Steinhauer             Research Highlights                   Medical microbiology: HIV disrupts gut bacteria | Genetics: Old origins for New World dogs | Physiology: Bulging muscles gain strength | Cancer biology: Nerves spur prostate cancer | Symbiosis: Citrus pest's little helper | Molecular biology: Designer gene knockdowns | Animal behaviour: Cricket winners show off | Biophysics: Sounds of red blood cells         NEWS & COMMENT           The benefits of brain mapping | Active protection | Don't market stem-cell products ahead of proof | Hunt for mystery GM wheat hots up | NIH gambles on recycled drugs | Neuroscience: Solving the brain | In retrospect: The Prince | Neurophilosophy: My brain and I | Genomics: Art of the hypothetical | Analysis: Don't do big-data science backwards | Rinderpest research restarts | Fukushima offers real-time ecolab             More Biological Sciences ▶                   Nature Reprint Collection  MicroRNAs from bench to clinic This Nature Reprint Collection presents some of the recent advances in moving microRNAs from basic research into the clinic both as diagnostic biomarkers and therapeutic targets.   Click here to access the Collection for free!   Produced with support from:         Chemical Sciences ▲top             RESEARCH           Articles and Letters                   Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2 ▶     Shaun D. Wong, Martin Srnec, Megan L. Matthews et al.     Synchrotron-based nuclear resonance vibrational spectroscopy is used to characterize the reactive Fe(iv)=O intermediate of the halogenase SyrB2; the substrate directs the orientation of this intermediate, presenting specific frontier molecular orbitals that can activate the selective halogenation.             News & Views                   RNA biophysics: A three-state balancing act ▶     Ronald Micura             Bacteriology: Toxins in tandem ▶     C. Erec Stebbins             More Chemical Sciences ▶               Physical Sciences ▲top             RESEARCH           Latest Online                   Condensed-matter physics: Dark and heavy ▶     Christoph Becker             Heavy solitons in a fermionic superfluid ▶     Tarik Yefsah, Ariel T. Sommer, Mark J. H. Ku et al.     Solitons — solitary waves that maintain their shape as they propagate — in a strongly interacting superfluid of fermionic lithium atoms are found to have an effective mass more than 50 times larger than the theoretically predicted value, a sign of strong quantum fluctuations.             Stretchable nanoparticle conductors with self-organized conductive pathways ▶     Yoonseob Kim, Jian Zhu, Bongjun Yeom et al.     Stretchable conductors have many applications, from flexible electronics to medical implants; here polyurethane is filled with gold nanoparticles to give a composite with tunable viscoelastic properties arising from the dynamic self-organization of the nanoparticles under stress.             Articles and Letters                   Exciting Andreev pairs in a superconducting atomic contact ▶     L. Bretheau, Ç. Ö. Girit, H. Pothier et al.     A fundamental and previously unobserved aspect of the Josephson effect is revealed through spectroscopic measurements of the excited Andreev states in superconducting atomic contacts.             Sequential deposition as a route to high-performance perovskite-sensitized solar cells ▶     Julian Burschka, Norman Pellet, Soo-Jin Moon et al.     A method of producing perovskite-sensitized solar cells by sequential — as opposed to single-step — deposition of the perovskite's components onto a nanoporous titanium oxide film allows for greater reproducibility of device performance and a record power conversion efficiency of 15 per cent.             Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2 ▶     Shaun D. Wong, Martin Srnec, Megan L. Matthews et al.     Synchrotron-based nuclear resonance vibrational spectroscopy is used to characterize the reactive Fe(iv)=O intermediate of the halogenase SyrB2; the substrate directs the orientation of this intermediate, presenting specific frontier molecular orbitals that can activate the selective halogenation.             News & Views                   Quantum physics: Andreev states taken to the next level ▶     Simon Gustavsson, William D. Oliver             50 & 100 Years Ago ▶             Particle physics: Let it B ▶     Yosef Nir             Condensed-matter physics: Dark and heavy ▶     Christoph Becker             Research Highlights                   Materials science: Liquid metal printed in 3D | Physiology: Bulging muscles gain strength         NEWS & COMMENT           The benefits of brain mapping | Light show | Lasers boost space communications | Education online: The virtual lab | Neuroscience: Solving the brain | Reproducibility: Two more red flags for suspect work | Asteroid plan looks rocky             More Physical Sciences ▶               Earth & Environmental Sciences ▲top             RESEARCH           Articles and Letters                   Increase in forest water-use efficiency as atmospheric carbon dioxide concentrations rise ▶     Trevor F. Keenan, David Y. Hollinger, Gil Bohrer et al.     Present-day forests use water more efficiently, probably owing to the effect of increased atmospheric carbon dioxide on leaf stomata, which partially close to maintain a near-constant level of carbon dioxide inside the leaves despite increasing atmospheric levels.             Ratios of S, Se and Te in the silicate Earth require a volatile-rich late veneer ▶     Zaicong Wang, Harry Becker     Newly determined ratios and abundances of sulphur, selenium and tellurium in mantle peridotites are consistent with the view that a 'late veneer' of slightly volatile-depleted, carbonaceous-chondrite-like material supplied between 20 and 100 per cent of the silicate Earth's highly volatile elements, such as hydrogen and carbon.             News & Views                   Biogeochemistry: Carbon dioxide and water use in forests ▶     Belinda Medlyn & Martin De Kauwe             Research Highlights                   Conservation science: Conserved coasts curb storm damage         NEWS & COMMENT           Fukushima offers real-time ecolab             More Earth & Environmental Sciences ▶                 Naturejobs presents the: Naturejobs Career Expo September 19, 2013 The Business Design Centre, London, UK Click here for more information or to register for this conference today!         Careers & Jobs ▲top               Online learning: How to make a MOOC ▶     With forethought and support, science instructors can design effective massive open online courses.                   Turning point: Thijn Brummelkamp ▶     Geneticist finds recognition as an innovator and toolmaker.             Careers related news & comment                   Don't market stem-cell products ahead of proof Paolo Bianco | Seven days: 12–18 July 2013 | Hunt for mystery GM wheat hots up Heidi Ledford | NIH gambles on recycled drugs Meredith Wadman | Education online: The virtual lab M. Mitchell Waldrop | Digital learning: Look, then leap Michael M. Crow | Education: Online on-ramps Hazel Sive, Sanjay Sarma | Russian science: Academy reform needs a reality check Sergey V. Razin, Yegor S. Vassetzky               naturejobs.com Science jobs of the week       Postdoctoral Research Scientist     Columbia University - Allergy Immunology Medicine             Research Assistant     Medical Research Council            Research Assistant     Istituto Italiano di Tecnologia            Scientist Vascular Biology     Goethe Universität Frankfurt          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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