Vol 508, No. 7494, April 2014, Malign Cooperation

Human evolution: Fifty years after Homo habilis Bernard Wood explains why the announcement of , handy man, in April 1964 threw the field of hominin evolution into a turmoil that continues to this day. Development: Mobilize citizens to track sustainability Businesses and the public can keep watch when governments fail to provide environmental data, say Angel Hsu and colleagues. Policy: Free Indian science As elections begin in India, Mathai Joseph and Andrew Robinson call for an end to the stultifying bureaucracy that has held back the nation, s science for decades. Tudor technology: Shakespeare and science To mark the 450th anniversary of the bard, s birth, Jennifer Rampling probes how mathematics and technology shaped his era. Earth systems: No place like home The newest chapter in James Lovelock, s Gaia saga holds out hope, finds Tim Lenton. Review of A Rough Ride to the Future: The Next Evolution of Gaia James Lovelock Psychology: The clamorous mind Susanne Ahmari reviews a personal and scientific journey through obsessive compulsive disorder. Review of The Man Who Couldn, t Stop: OCD, and the True Story of a Life Lost in Thought David Adam Cancer treatment: Sharp shooters Beams of charged particles can treat cancer more safely and effectively than X-rays. Physicists and biomedical researchers are working to refine the technology for wider use. Vivien Marx Schizophrenia Herb Brody Aetiology: Searching for schizophrenia, s roots Emily Elert Language: Lost in translation David Noonan Genetics: Unravelling complexity Jessica Wright Drug development: The modelling challenge Alla Katsnelson Therapeutics: Negative feedback Elie Dolgin Prevention: Before the break Michele Solis Developing countries: The outcomes paradox T. V. Padma Ageing: Live faster, die younger Emily Anthes Perspective: Retreat from the radical Stephen R. Marder Perspective: Revealing molecular secrets Steven E. Hyman Interneuron subtypes and orientation tuning Seung-Hee Lee, Alex C. Kwan & Yang Dan Atallah et al. reply Bassam V. Atallah, Massimo Scanziani & Matteo Carandini El-Boustani et al. reply Sami El-Boustani, Nathan R. Wilson, Caroline A. Runyan & Mriganka Sur Articles Top Capillary pericytes regulate cerebral blood flow in health and disease Catherine N. Hall, Clare Reynell, Bodil Gesslein, Nicola B. Hamilton, Anusha Mishra + et al. Neuronal activity relaxes pericytes, leading to capillary dilation and increased blood flow, before arterioles dilate, suggesting that pericytes initiate blood-oxygen-level-dependent (BOLD) functional imaging signals, pericytes constrict and die in rigor in ischaemia, which will cause a long-lasting blood flow decrease after stroke, and damage the blood brain barrier. See also News & Views by Greif & Eichmann Mechanism of Tc toxin action revealed in molecular detail Dominic Meusch, Christos Gatsogiannis, Rouslan G. Efremov, Alexander E. Lang, Oliver Hofnagel + et al. High-resolution structures of the Photorhabdus luminescens TcA toxin subunit and the entire Tc toxin complex reveal important new insights into Tc complex structure and function. Poly(A)-tail profiling reveals an embryonic switch in translational control Alexander O. Subtelny, Stephen W. Eichhorn, Grace R. Chen, Hazel Sive & David P. Bartel A new high-throughput sequencing method to determine mRNA poly(A)-tail length enabled studies of individual RNAs across species and developmental stages to investigate the role of poly(A) length in translational regulation, the relationship between poly(A) length and translational efficiency shown in early embryo systems does not occur later in development, a finding that explains different regulatory consequences of microRNAs acting at different developmental times. Letters Top A ring system detected around the Centaur (10199) Chariklo F. Braga-Ribas, B. Sicardy, J. L. Ortiz, C. Snodgrass, F. Roques + et al. Observations of a stellar occultation by (10199) Chariklo, a minor body that orbits the Sun between Jupiter and Neptune, reveal that it has a ring system, a property previously observed only for the four giant planets of the Solar System. See also News & Views by Burns Efficient rotational cooling of Coulomb-crystallized molecular ions by a helium buffer gas A. K. Hansen, O. O. Versolato, A. KBosowski, S. B. Kristensen, A. Gingell + et al. In combination with sympathetic cooling of translational degrees of freedom (leading to Coulomb crystallization), cooling of the rotational degrees of freedom of magnesium hydride ions using a helium buffer gas leads to temperatures in a tunable range from 60 kelvin down to about 7 kelvin for a single ion, the lowest such temperature so far recorded. Coherent control of the waveforms of recoilless -ray photons Farit Vagizov, Vladimir Antonov, Y. V. Radeonychev, R. N. Shakhmuratov & Olga Kocharovskaya The resonant interaction between -ray photons and an ensemble of nuclei with a periodically modulated resonant transition frequency can be used to control the waveforms of the photons coherently, for example, individual -ray photons can be converted into a coherent, ultrashort pulse train or into a double pulse. Highly siderophile elements in Earth s mantle as a clock for the Moon-forming impact Seth A. Jacobson, Alessandro Morbidelli, Sean N. Raymond, David P. O, Brien, Kevin J. Walsh + et al. A large number of N-body simulations of the giant-impact phase of planet formation, combined with the measured concentrations of highly siderophile elements in Earth s mantle, reveal that the Moon must have formed at least 40 million years after the condensation of the first solids of the Solar System. See also News & Views by Chambers The hippocampal CA2 region is essential for social memory Frederick L. Hitti & Steven A. Siegelbaum CA2 neuron inactivation leads to a severe deficit in social memory, while having little effect on other well-known hippocampal functions such as contextual or spatial memory. Mouse liver repopulation with hepatocytes generated from human fibroblasts Saiyong Zhu, Milad Rezvani, Jack Harbell, Aras N. Mattis, Alan R. Wolfe + et al. Human fibroblasts can be converted into hepatocytes capable of repopulating mouse livers by shortcutting reprogramming to pluripotency with factors promoting endoderm and hepatocyte differentiation. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia Yilong Li, Claire Schwab, Sarra L. Ryan, Elli Papaemmanuil, Hazel M. Robinson + et al. A rare constitutional translocation between chromosomes 15 and 21 predisposes to catastrophic chromosomal damage followed by amplification of megabase regions, causing a specific subtype of acute lymphoblastic leukaemia. XBP1 promotes triple-negative breast cancer by controlling the HIF1 pathway Xi Chen, Dimitrios Iliopoulos, Qing Zhang, Qianzi Tang, Matthew B. Greenblatt + et al. This study finds that triple-negative breast cancers (TNBC) show an increased basal level of endoplasmic reticulum stress and activation of the XBP1 branch of the unfolded protein response, furthermore, XBP1 promotes tumour formation of TNBC cell lines by interacting with and regulating HIF1 . Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides K1vanç Birsoy, Richard Possemato, Franziska K. Lorbeer, Erol C. Bayraktar, Prathapan Thiru + et al. New apparatus is used to maintain proliferating cancer cells in low-glucose conditions, demonstrating that mitochondrial oxidative phosphorylation (OXPHOS) is essential for optimal proliferation in these conditions, the most sensitive cell lines are defective in OXPHOS upregulation and may therefore be sensitive to current antidiabetic drugs that inhibit OXPHOS. Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers Allison S. Cleary, Travis L. Leonard, Shelley A. Gestl & Edward J. Gunther In a mouse model of tumours initiated by Wnt signalling in which a proportion of tumours are biclonal, that is, composed of basal and luminal clones with distinct genetic alterations, these clones are shown to cooperate to maintain tumour growth in a Wnt-dependent manner. See also News & Views by Polyak & Marusyk Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma Chong Sun, Liqin Wang, Sidong Huang, Guus J. J. E. Heynen, Anirudh Prahallad + et al. Patients with melanomas carrying an activating BRAF mutation respond to treatment with BRAF inhibitors although resistance to the inhibitor usually emerges, this resistance is shown to arise through increased expression of receptor tyrosine kinases such as EGFR, however, these changes decrease cell fitness and during a break from inhibitor treatment these cells are selected against, revealing that some patients who acquire EGFR expression may benefit from inhibitor re-treatment after a drug holiday. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity Serge A. van de Pavert, Manuela Ferreira, Rita G. Domingues, Hélder Ribeiro, Rosalie Molenaar + et al. Dietary vitamin A during pregnancy is required for the formation of secondary lymphoid organs of the developing embryo and affects the offspring s immune competence in adulthood. See also News & Views by Eberl Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans En-Zhi Shen, Chun-Qing Song, Yuan Lin, Wen-Hong Zhang, Pei-Fang Su + et al. In Caenorhabditis elegans, mitochondrial activity as measured by the frequency of the mitochondrial flash in young adult animals is a powerful predictor of lifespan across genetic, environmental and stochastic factors. gepflegtes Exemplar, nur kleine Lesespuren

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