Nature contents: 31 July 2014

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Volume 511 Number 7511      nature •Visit Nature homepage •Subscribe to Nature •View Table of Contents The science that matters. Every week.               A*STAR Research - Highlighting the best of research at the Agency for Science, Technology and Research (A*STAR), Singapore's premier research organization  Recent Highlights  Cancer: Modified drug gives a 'green light' for its own success | Energy: Dyes help harvest light | Immunology: Putting the squeeze on the Singapore sneeze  Download the A*STAR Research app now!        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 ▼   Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression   This study shows that treating rhesus macaques infected with SIV — the simian equivalent of HIV — with interventions that alter inflammatory responses can have dual effects on the development of disease. Administration type 1 interferon, which is known to trigger antiviral responses and inflammation, is beneficial at the onset of infection but is detrimental in chronic infection. The results indicate that investigations of similar therapeutic approaches in the treatment and prevention of HIV infection should be approached with caution.       Physical Sciences More Physical sciences ▼   Mapping the optimal route between two quantum states   Classical systems are unmoved when a measurement is performed. Not so quantum systems, where continuous monitoring can direct the quantum state along a random path. Steve Weber et al. have tracked the quantum trajectories in a qubit and managed to determine which of the possible paths between an initial and a final quantum state is the most probable. This work opens up new possibilities for first-principles synthesis of control sequences for complex quantum systems and in information processing.       Earth & Environmental Sciences More Earth & Environmental sciences ▼   Widespread mixing and burial of Earth's Hadean crust by asteroid impacts   Little is known about the bombardment history of the early Earth following the Moon-forming giant impact. Simone Marchi et al. have now developed a new model for Earth's collisional evolution, calibrated using existing lunar and terrestrial data. They show that the Earth's surface would have been widely reprocessed by impacts through mixing and melting during the Hadean period, 4 to 4.5 billion years ago.             Podcast & Video     In this week's podcast: replaying evolution in the lab, dam-busting to let rivers run free, and the time when asteroids boiled the Earth’s oceans.         News & Comment Read daily news coverage▶ ▲top               THIS WEEK           Editorials                   Safety doesn’t happen by accident ▶     To create a strong biosafety culture, information on mishaps involving deadly pathogens must be reported and shared fully and transparently.             Fishy business ▶     Delays in approving genetically engineered salmon may be a taste of worse to come.             World View                   Cause is not everything in mental illness ▶     Welcome steps have been made in uncovering a biological basis for schizophrenia, but for many, the question of ‘why’ is unimportant, says David Adam.             Seven Days                   Seven days: 25–31 July 2014 ▶     The week in science: Scripps president resigns; record-breaking drive on Mars; and Poland creates a space agency.             NEWS IN FOCUS           Biosafety controls come under fire ▶     Experts call for a stronger safety culture at secure sites after incidents involving anthrax and flu in a US laboratory.             Project drills deep into coming quake ▶     Sensors in borehole at New Zealand seismic fault will peek under the surface of impending rupture.             Contamination hits cell work ▶     Mycoplasma infestations are widespread and costing laboratories millions of dollars in lost research.             FDA debates trial-data secrecy ▶     US drug regulator weighs up merits of disclosing preliminary results.             Ebola treatments caught in limbo ▶     Logistics and lack of funds keep experimental drugs and vaccines from being used in Africa outbreak.             Features                   Dam removals: Rivers on the run ▶     As the United States destroys its old dams, species are streaming back into the unfettered rivers.             Cancer biomarkers: Written in blood ▶     DNA circulating in the bloodstream could guide cancer treatment — if researchers can work out how best to use it.             COMMENT           Public health: A sustainable plan for China's drinking water ▶     Tackling pollution and using different grades of water for different tasks is more efficient than making all water potable, say Tao Tao and Kunlun Xin.             Diversity: Energy studies need social science ▶     A broader pool of expertise is needed to understand how human behaviour affects energy demand and the uptake of technologies, says Benjamin K. Sovacool.             Books and Arts                   Neuroscience: Looking-glass wars ▶     Patricia Smith Churchland welcomes a critique of the mirror-neuron theory linking brain and behaviour.             Books in brief ▶             Correspondence                   Emissions: Carbon cost will not stop oil-sands work Andrew Leach, Branko Boskovic | European Commission: Put brain project back on course Zachary F. Mainen, Alexandre Pouget | Invasive species: Review risks before eradicating toads Sven Mecke | Faculty cuts: University managers misled by metrics Thomas Butts             Corrections                   Correction ▶             Correction ▶                 Biological Sciences ▲top             RESEARCH           Latest Online                   Cancer: One cell at a time ▶     Edward J. Fox, Lawrence A. Loeb             Evolution: Tooth structure re-engineered ▶     Zhe-Xi Luo             Ageing: Old blood stem cells feel the stress ▶     Jiri Bartek, Zdenek Hodny             RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer ▶     Andrew L. Wolfe, Kamini Singh, Yi Zhong et al.     The translation of many messenger RNAs that encode important oncogenes and transcription factors depends on the eIF4A RNA helicase to resolve G-quadruplex structures, implying eIF4A inhibition as an effective cancer therapy.             Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity ▶     Andriy Marusyk, Doris P. Tabassum, Philipp M. Altrock et al.     To investigate the role of sub-clonal tumour heterogeneity in cancer progression, a mouse xenograft model was used which revealed that tumour growth can be driven by a minor cell subpopulation by a non-cell-autonomous mechanism, although this minor subpopulation can be outcompeted by faster proliferating competitors.             Clonal evolution in breast cancer revealed by single nucleus genome sequencing ▶     Yong Wang, Jill Waters, Marco L. Leung et al.     To investigate genomic diversity within tumours, a new type of whole-genome and exome single cell sequencing has been developed using G2/M nuclei; the technique was used to sequence single nuclei from an oestrogen-positive breast cancer and a triple-negative ductal carcinoma—aneuploidy rearrangements emerged as early events in tumour formation and then point mutations evolved gradually over time.             Replaying evolutionary transitions from the dental fossil record ▶     Enni Harjunmaa, Kerstin Seidel, Teemu Häkkinen et al.     Gradual changes that occur to mammalian tooth morphology across evolutionary time were modelled in vitro and in vivo by modulation of signalling pathways in the mouse, and computer modelling was used to provide further analysis of the parameters influencing tooth morphology.             DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier ▶     Margarida A. Santos, Robert B. Faryabi, Aysegul V. Ergen et al.     Histone methyl-transferase MLL4 is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL–AF9 oncogene.             The neurotrophic factor receptor RET drives haematopoietic stem cell survival and function ▶     Diogo Fonseca-Pereira, Sílvia Arroz-Madeira, Mariana Rodrigues-Campos et al.     Haematopoietic stem cells are direct targets for neurotrophic factors, indicating that haematopoietic stem cells and neurons are regulated by similar signals.             Glial origin of mesenchymal stem cells in a tooth model system ▶     Nina Kaukua, Maryam Khatibi Shahidi, Chrysoula Konstantinidou et al.     In the mouse, nerve-associated peripheral glial cells give rise to mesenchymal stem cells that contribute to the development and growth of adult teeth.             Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy ▶     Bernardo Tavora, Louise E. Reynolds, Silvia Batista et al.     The tumour microenvironment can influence its response to anticancer therapies; here, the enzyme FAK in endothelial cells is shown to have a role in the induction of a number of cytokines during chemotherapy or irradiation, which in turn protect tumours from DNA-damaging agents.             eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies ▶     Lise Boussemart, Hélène Malka-Mahieu, Isabelle Girault et al.     BRAF mutations occur frequently in melanomas, but patients generally develop resistance to agents targeting mutant BRAF; now, the persistent formation of the translation initiation complex eIF4F has been described as an indicator of multiple mechanisms of resistance that arise in BRAF-mutated tumours and as a promising therapeutic target.             Antifungal drug resistance evoked via RNAi-dependent epimutations ▶     Silvia Calo, Cecelia Shertz-Wall, Soo Chan Lee et al.     The human fungal pathogen Mucor circinelloides develops spontaneous resistance to an antifungal drug both through mutation and through a newly identified epigenetic RNA-mediated pathway; RNA interference is spontaneously triggered to silence the fkbA gene, giving rise to drug-resistant epimutants that revert to being drug-sensitive once again when grown in the absence of drug.             Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease ▶     Carolin Anders, Ole Niewoehner, Alessia Duerst et al.     Crystal structure of the RNA-guided endonuclease Cas9 bound to a guide RNA and a target DNA duplex reveals how base-specific recognition of a short motif known as PAM in the DNA target results in localized strand separation in the DNA immediately upstream of the PAM, allowing the target DNA strand to hybridize to the guide RNA.             Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells ▶     Johanna Flach, Sietske T. Bakker, Mary Mohrin et al.     Haematopoietic stem cell (HSC) function is known to degrade with age; here, replication stress is shown to be a potent driver of the functional decline of HSCs during physiological ageing in mice due to decreased expression of mini-chromosome maintenance helicase components and reduced activity of the DNA replication machinery.             Articles and Letters                   Comprehensive molecular profiling of lung adenocarcinoma OPEN ▶     An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.             Topoisomerase II mediates meiotic crossover interference ▶     Liangran Zhang, Shunxin Wang, Shen Yin et al.     Topoisomerase II mediates meiotic crossover interference by adjusting the protein/DNA meshwork of chromosome axes.             Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain ▶     Andrew S. Doré, Krzysztof Okrasa, Jayesh C. Patel et al.     An X-ray structure is presented for metabotropic glutamate receptor 5, a class C G-protein-coupled glutamate receptor linked to fragile X syndrome and neurological disorders; this study provides insights into the protein’s mechanism of action.             Seasonal not annual rainfall determines grassland biomass response to carbon dioxide ▶     Mark J. Hovenden, Paul C. D. Newton, Karen E. Wills     Large annual variation in the stimulation of above-ground biomass by elevated carbon dioxide in a mixed C3/C4 temperate grassland can be predicted accurately using seasonal rainfall totals.             PTEX is an essential nexus for protein export in malaria parasites ▶     Brendan Elsworth, Kathryn Matthews, Catherine Q. Nie et al.     This paper demonstrates that a protein complex known as PTEX translocates all malaria parasite proteins destined for export into the cytosol of their host red blood cell.             PTEX component HSP101 mediates export of diverse malaria effectors into host erythrocytes ▶     Josh R. Beck, Vasant Muralidharan, Anna Oksman et al.     Plasmodium parasites, the causative agent of malaria, infect and remodel red blood cells by exporting hundreds of proteins into the red blood cell cytosol, a topological conundrum given that the parasite resides in a compartment known as the parasitophorous vacuole; here a dihydrofolate-reductase-based destabilization domain approach is used to inactivate HSP101, part of the Plasmodium translocon of exported proteins, and to demonstrate that it is required for the secretion of all classes of exported Plasmodium proteins.             Equalizing excitation–inhibition ratios across visual cortical neurons ▶     Mingshan Xue, Bassam V. Atallah, Massimo Scanziani     Different amounts of excitation received by different pyramidal cells of primary visual cortex are matched by proportional amounts of inhibition.             Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression ▶     Netanya G. Sandler, Steven E. Bosinger, Jacob D. Estes et al.     The timing of type I interferon signalling determines the disease course of SIV infection.             The DNA methylation landscape of human early embryos ▶     Hongshan Guo, Ping Zhu, Liying Yan et al.     Base-resolution maps of DNA methylation in human gametes and early embryos offer novel insights into human methylation dynamics and the functional relationship between DNA methylation and gene expression.             DNA methylation dynamics of the human preimplantation embryo ▶     Zachary D. Smith, Michelle M. Chan, Kathryn C. Humm et al.     Genome-scale DNA methylation maps over early human embryogenesis and embryonic stem cell derivation provide insights into shared and unique modes of regulation when compared to the mouse model, including relationships to gene expression, transposable element activity, and maternal-specific methylation.             Targeting transcription regulation in cancer with a covalent CDK7 inhibitor ▶     Nicholas Kwiatkowski, Tinghu Zhang, Peter B. Rahl et al.     Here, a covalent inhibitor targeting cyclin-dependent kinase 7 (CDK7) demonstrates in vitro and in vivo efficacy against T-cell acute lymphoblastic leukaemia by downregulating oncogenic transcriptional programs.             News & Views                   HIV: The mixed blessing of interferon ▶     Amalio Telenti             50 & 100 Years ago ▶             Epigenetics: Cellular memory erased in human embryos ▶     Wolf Reik, Gavin Kelsey             Malaria: Protein-export pathway illuminated ▶     Sanjay A. Desai, Louis H. Miller             Cancer: One cell at a time ▶     Edward J. Fox, Lawrence A. Loeb             Evolution: Tooth structure re-engineered ▶     Zhe-Xi Luo             Ageing: Old blood stem cells feel the stress ▶     Jiri Bartek, Zdenek Hodny             Retraction                   Retraction: Generation of pluripotent stem cells from adult human testis ▶     Sabine Conrad, Markus Renninger, Jörg Hennenlotter et al.             Research Highlights                   Ecology: Predictable patterns for coral-reef pest | Chemistry: Fighting ants make rare fluid | Immunology: Inflammation on the clock | Evolution: Sperm are speedier in groups | Beef's big impact on Earth         NEWS & COMMENT           Cause is not everything in mental illness | Dam removals: Rivers on the run | Cancer biomarkers: Written in blood | Fishy business | Neuroscience: Looking-glass wars | Books in brief | European Commission: Put brain project back on course | Invasive species: Review risks before eradicating toads | Correction | Safety doesn’t happen by accident | Biosafety controls come under fire | Contamination hits cell work | FDA debates trial-data secrecy | Ebola treatments caught in limbo             More Biological Sciences ▶                 Nature Milestones in Crystallography Nature Milestones in Crystallography is a collaboration from Nature, Nature Materials, Nature Nanotechnology and Nature Structural & Molecular Biology, and celebrates the International Year of Crystallography 2014. Access the Milestones supplement FREE online for six months.    Associated Society International Union of Crystallography Produced with support from the worldwide network of neutron and X-ray sources         Health Sciences ▲top             RESEARCH           Latest Online                   Cancer: One cell at a time ▶     Edward J. Fox, Lawrence A. Loeb             RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer ▶     Andrew L. Wolfe, Kamini Singh, Yi Zhong et al.     The translation of many messenger RNAs that encode important oncogenes and transcription factors depends on the eIF4A RNA helicase to resolve G-quadruplex structures, implying eIF4A inhibition as an effective cancer therapy.             Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity ▶     Andriy Marusyk, Doris P. Tabassum, Philipp M. Altrock et al.     To investigate the role of sub-clonal tumour heterogeneity in cancer progression, a mouse xenograft model was used which revealed that tumour growth can be driven by a minor cell subpopulation by a non-cell-autonomous mechanism, although this minor subpopulation can be outcompeted by faster proliferating competitors.             Clonal evolution in breast cancer revealed by single nucleus genome sequencing ▶     Yong Wang, Jill Waters, Marco L. Leung et al.     To investigate genomic diversity within tumours, a new type of whole-genome and exome single cell sequencing has been developed using G2/M nuclei; the technique was used to sequence single nuclei from an oestrogen-positive breast cancer and a triple-negative ductal carcinoma—aneuploidy rearrangements emerged as early events in tumour formation and then point mutations evolved gradually over time.             DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier ▶     Margarida A. Santos, Robert B. Faryabi, Aysegul V. Ergen et al.     Histone methyl-transferase MLL4 is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL–AF9 oncogene.             Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy ▶     Bernardo Tavora, Louise E. Reynolds, Silvia Batista et al.     The tumour microenvironment can influence its response to anticancer therapies; here, the enzyme FAK in endothelial cells is shown to have a role in the induction of a number of cytokines during chemotherapy or irradiation, which in turn protect tumours from DNA-damaging agents.             eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies ▶     Lise Boussemart, Hélène Malka-Mahieu, Isabelle Girault et al.     BRAF mutations occur frequently in melanomas, but patients generally develop resistance to agents targeting mutant BRAF; now, the persistent formation of the translation initiation complex eIF4F has been described as an indicator of multiple mechanisms of resistance that arise in BRAF-mutated tumours and as a promising therapeutic target.             Articles and Letters                   Comprehensive molecular profiling of lung adenocarcinoma OPEN ▶     An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.             Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression ▶     Netanya G. Sandler, Steven E. Bosinger, Jacob D. Estes et al.     The timing of type I interferon signalling determines the disease course of SIV infection.             Targeting transcription regulation in cancer with a covalent CDK7 inhibitor ▶     Nicholas Kwiatkowski, Tinghu Zhang, Peter B. Rahl et al.     Here, a covalent inhibitor targeting cyclin-dependent kinase 7 (CDK7) demonstrates in vitro and in vivo efficacy against T-cell acute lymphoblastic leukaemia by downregulating oncogenic transcriptional programs.             News & Views                   HIV: The mixed blessing of interferon ▶     Amalio Telenti             Cancer: One cell at a time ▶     Edward J. Fox, Lawrence A. Loeb             Research Highlights                   Beef's big impact on Earth         NEWS & COMMENT           Cause is not everything in mental illness | Cancer biomarkers: Written in blood | Books in brief | Safety doesn’t happen by accident | Biosafety controls come under fire | FDA debates trial-data secrecy | Ebola treatments caught in limbo             More Health Sciences ▶               Physical Sciences ▲top             RESEARCH           Latest Online                   The origin of the local 1/4-keV X-ray flux in both charge exchange and a hot bubble ▶     M. Galeazzi, M. Chiao, M. R. Collier et al.     The contribution of solar-wind ions exchanging electrons with helium and hydrogen near the Sun is shown to be only about 40 per cent of the 1/4-keV X-ray flux observed in the Galactic plane; this supports the existence of a local ‘hot bubble’ filled with X-ray-emitting gas, accounting for the rest of the flux.             The tidal–rotational shape of the Moon and evidence for polar wander ▶     Ian Garrick-Bethell, Viranga Perera, Francis Nimmo et al.     Analysis of the Moon's topography reveals that when its largest basins are removed, the lunar shape is consistent with processes controlled by early Earth tides, and implies a reorientation of the Moon's principal shape axes.             Articles and Letters                   Velocity anti-correlation of diametrically opposed galaxy satellites in the low-redshift Universe ▶     Neil G. Ibata, Rodrigo A. Ibata, Benoit Famaey et al.     Measurements of the velocities of pairs of diametrically opposed satellite galaxies of host galaxies in the local Universe show that satellite pairs out to a distance of 150 kiloparsecs from their hosts are anti-correlated in their velocities and that galaxies in the larger-scale environment are strongly clumped along the axis joining the inner satellite pair.             Misaligned protoplanetary disks in a young binary star system ▶     Eric L. N. Jensen, Rachel Akeson     Observations show that one or both of the protoplanetary disks in the young binary system HK Tauri are significantly inclined to the binary orbital plane, demonstrating that the necessary conditions exist for the misalignment-driven mechanisms thought to produce the unusual orbits of some extrasolar planets.             Mapping the optimal route between two quantum states ▶     S. J. Weber, A. Chantasri, J. Dressel et al.     Reconstruction of the quantum trajectories of a superconducting circuit that evolves under the competing influences of continuous weak measurement and Rabi drive makes it possible to deduce the most probable path through quantum state space.             News & Views                   Quantum physics: The path most travelled ▶     Adrian Lupascu             Research Highlights                   Materials: Sponge takes light to make steam | Chemistry: Fighting ants make rare fluid | Optics: Transistor uses single photons         NEWS & COMMENT           Diversity: Energy studies need social science             More Physical Sciences ▶               Earth & Environmental Sciences ▲top             RESEARCH           Latest Online                   The tidal–rotational shape of the Moon and evidence for polar wander ▶     Ian Garrick-Bethell, Viranga Perera, Francis Nimmo et al.     Analysis of the Moon's topography reveals that when its largest basins are removed, the lunar shape is consistent with processes controlled by early Earth tides, and implies a reorientation of the Moon's principal shape axes.             Articles and Letters                   Antarctic glaciation caused ocean circulation changes at the Eocene–Oligocene transition ▶     A. Goldner, N. Herold, M. Huber     A climate model is used to show that the growth of the Antarctic ice sheet at about 34 Myr ago drove changes in ocean circulation, but the opening of ocean gateways had relatively little impact.             Widespread mixing and burial of Earth’s Hadean crust by asteroid impacts ▶     S. Marchi, W. F. Bottke, L. T. Elkins-Tanton et al.     A new bombardment model of the early Earth, calibrated with existing lunar and terrestrial data, shows that the Earth’s surface would have been widely reprocessed by impacts through mixing and burial by impact-generated melt; the model may also explain the age distribution of ancient zircons and the absence of early terrestrial rocks.             Seasonal not annual rainfall determines grassland biomass response to carbon dioxide ▶     Mark J. Hovenden, Paul C. D. Newton, Karen E. Wills     Large annual variation in the stimulation of above-ground biomass by elevated carbon dioxide in a mixed C3/C4 temperate grassland can be predicted accurately using seasonal rainfall totals.             News & Views                   Palaeoclimate science: Causes and effects of Antarctic ice ▶     Dan Lunt             Research Highlights                   Glaciology: Data mix-up in sea-ice record | Geomorphology: Beaches erode without storms | Climate science: Warming from coupled climates         NEWS & COMMENT           Dam removals: Rivers on the run | Public health: A sustainable plan for China's drinking water | Emissions: Carbon cost will not stop oil-sands work | Project drills deep into coming quake             More Earth & Environmental Sciences ▶                   NEW DEALS: Lab equipment and services   Browse our library of savings and information!   Check Marketplace first   VISIT MARKETPLACE TODAY          Careers & Jobs ▲top               Patent law: Finding a balance ▶     Scientists who decide to pursue a legal career can enjoy fresh challenges while staying connected to the research world.                   Education: Graduate skills survey ▶     Study to probe matching US graduate programmes with employers' needs.                   Funding: Marion Mason award ▶     Award offers female chemists support for equipment, travel and publishing costs.                   Financial outlook: Continued squeezes ▶     Negative outlook for US universities could pinch borrowing and hiring.             Careers related news & comment                   Seven days: 25–31 July 2014 | European Commission: Put brain project back on course Zachary F. Mainen, Alexandre Pouget | Faculty cuts: University managers misled by metrics Thomas Butts | Safety doesn’t happen by accident | Biosafety controls come under fire Declan Butler               naturejobs.com Science jobs of the week       Postdoctoral Fellow     Baylor College of Medicine (BCM)            PhD Position     Otto-Von-Guericke University Magdeburg            Research Fellow     University of Exeter            Junior Research / Travel Fellowships 2015     The Kay Kendall Leukaemia Fund          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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