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Drain the swamp to beat glioma p.460

Efforts to treat brain tumours by targeting cancer cells have had only modest clinical success. It emerges that targeting a protein secreted from neurons adjacent to the tumour might be a useful alternative approach. See Letter p.533

Michael D. Taylor & Vijay Ramaswamy

doi: 10.1038/nature24141

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Evaporating planetesimals p.461

Two studies show that evaporation of molten rock was intrinsic to the formation of Earth and other rocky bodies in the Solar System, suggesting that violent collisions played a key part in the formation process. See Letters p.507 & p.511

Edward D. Young

doi: 10.1038/549461a

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Vitamin C regulates stem cells and cancer p.462

It emerges that high levels of vitamin C in blood-forming stem cells influence the number and function of the cells and affect the development of leukaemia, through binding to a tumour-suppressor protein, Tet2. See Article p.476

Peter G. Miller & Benjamin L. Ebert

doi: 10.1038/nature23548

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Taking control of spin currents p.464

Conventional wisdom dictates that an electron's magnetic moment and momentum are strongly coupled only in materials made of heavy elements. An experiment demonstrates a striking counterexample. See Letter p.492

Zhi-Xun Shen & Jonathan Sobota

doi: 10.1038/549464a

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Bad blood promotes tumour progression p.465

Mutations that drive the abnormal expansion of progenitor subpopulations of blood cells are known to cause leukaemia. A genetic analysis reveals that these clonal blood stem-cell mutations are also common in people who have solid tumours.

Catriona Jamieson

doi: 10.1038/549465a

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Mum's bacteria linked to baby's behaviour p.466

Infection during pregnancy increases the risk of neurodevelopmental disorders, such as autism, in offspring. Mouse studies now reveal a link between gut bacteria and atypical brain-circuit connections. See Article p.482 & Letter p.528

Craig M. Powell

doi: 10.1038/nature24139

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Articles

Axonal synapse sorting in medial entorhinal cortex p.469

Path-length-dependent axonal synapse sorting of local presynaptic axons of excitatory neurons in the rat medial entorhinal cortex results in sequential targeting of inhibitory and excitatory neurons, which are connected by a cellular feedforward inhibition circuit.

Helene Schmidt, Anjali Gour, Jakob Straehle, Kevin M. Boergens, Michael Brecht & Moritz Helmstaedter

doi: 10.1038/nature24005

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Ascorbate regulates haematopoietic stem cell function and leukaemogenesis p.476

Ascorbate depletion in mice increased haematopoietic stem-cell frequency and promoted leukaemogenesis, partly by reducing the function of the Tet2 tumour suppressor enzyme.

Michalis Agathocleous, Corbin E. Meacham, Rebecca J. Burgess, Elena Piskounova, Zhiyu Zhao, Genevieve M. Crane, Brianna L. Cowin, Emily Bruner, Malea M. Murphy, Weina Chen + et al.

doi: 10.1038/nature23876

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Reversing behavioural abnormalities in mice exposed to maternal inflammation p.482

The authors define a specific cortical subregion of the somatosensory cortex as a critical region of dysfunction that is causal to the emergence of abnormal social and repetitive behaviours in mice exposed to maternal inflammation.

Yeong Shin Yim, Ashley Park, Janet Berrios, Mathieu Lafourcade, Leila M. Pascual, Natalie Soares, Joo Yeon Kim, Sangdoo Kim, Hyunju Kim, Ari Waisman + et al.

doi: 10.1038/nature23909

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Letters

The close environments of accreting massive black holes are shaped by radiative feedback p.488

Radiation pressure on dusty gas is the main physical mechanism that regulates the distribution of the circumnuclear material that obscures many supermassive black holes.

Claudio Ricci, Benny Trakhtenbrot, Michael J. Koss, Yoshihiro Ueda, Kevin Schawinski, Kyuseok Oh, Isabella Lamperti, Richard Mushotzky, Ezequiel Treister, Luis C. Ho + et al.

doi: 10.1038/nature23906

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Maximal Rashba-like spin splitting via kinetic-energy-coupled inversion-symmetry breaking p.492

Asymmetry in surface hopping energies in different atomic layers of delafossite oxides results in some of the largest known Rashba-like spin splittings.

Veronika Sunko, H. Rosner, P. Kushwaha, S. Khim, F. Mazzola, L. Bawden, O. J. Clark, J. M. Riley, D. Kasinathan, M. W. Haverkort + et al.

doi: 10.1038/nature23898

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Mimicking biological stress–strain behaviour with synthetic elastomers p.497

A polymer code based on a triplet of parameters—network strand length, side-chain length and grafting density—enables materials to be designed with specific combinations of mechanical properties to mimic biological materials.

Mohammad Vatankhah-Varnosfaderani, William F. M. Daniel, Matthew H. Everhart, Ashish A. Pandya, Heyi Liang, Krzysztof Matyjaszewski, Andrey V. Dobrynin & Sergei S. Sheiko

doi: 10.1038/nature23673

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Magnesium isotope evidence that accretional vapour loss shapes planetary compositions p.511

The measurement of magnesium isotope ratios at improved accuracy suggests that planetary compositions result from fractionation between liquid and vapour, followed by vapour escape during accretionary growth.

Remco C. Hin, Christopher D. Coath, Philip J. Carter, Francis Nimmo, Yi-Jen Lai, Philip A. E. Pogge von Strandmann, Matthias Willbold, Zoë M. Leinhardt, Michael J. Walter & Tim Elliott

doi: 10.1038/nature23899

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Early trace of life from 3.95 Ga sedimentary rocks in Labrador, Canada p.516

The authors provide evidence for the existence of life on Earth in the earliest known sedimentary rocks and suggest that the presence of organic carbon, and low stable-isotope values of graphite from sedimentary rocks in Labrador pushes back the existence of organic life to beyond 3.95 billion years.

Takayuki Tashiro, Akizumi Ishida, Masako Hori, Motoko Igisu, Mizuho Koike, Pauline Méjean, Naoto Takahata, Yuji Sano & Tsuyoshi Komiya

doi: 10.1038/nature24019

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Parental influence on human germline de novo mutations in 1,548 trios from Iceland p.519

Whole-genome sequencing data of 14,688 Icelanders, including 1,548 parent–offspring trios, show how the age and sex of parents affect the rate and spectrum of de novo mutations.

Hákon Jónsson, Patrick Sulem, Birte Kehr, Snaedis Kristmundsdottir, Florian Zink, Eirikur Hjartarson, Marteinn T. Hardarson, Kristjan E. Hjorleifsson, Hannes P. Eggertsson, Sigurjon Axel Gudjonsson + et al.

doi: 10.1038/nature24018

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ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy p.523

ApoE4 exacerbates tau pathogenesis, neuroinflammation and tau-mediated neurodegeneration independently of brain amyloid-β pathology, and exerts a ‘toxic’ gain of function whereas its absence is protective.

Yang Shi, Kaoru Yamada, Shane Antony Liddelow, Scott T. Smith, Lingzhi Zhao, Wenjie Luo, Richard M. Tsai, Salvatore Spina, Lea T. Grinberg, Julio C. Rojas + et al.

doi: 10.1038/nature24016

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Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma p.533

The growth of adult and paediatric brain tumours depends on a microenvironmental signalling pathway involving the activity-regulated secretion of neuroligin-3 (NLGN3) from normal neurons and oligodendrocyte precursor cells, highlighting the potential of NLGN3 as a therapeutic target.

Humsa S. Venkatesh, Lydia T. Tam, Pamelyn J. Woo, James Lennon, Surya Nagaraja, Shawn M. Gillespie, Jing Ni, Damien Y. Duveau, Patrick J. Morris, Jean J. Zhao + et al.

doi: 10.1038/nature24014

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Comparative glycoproteomics of stem cells identifies new players in ricin toxicity p.538

A novel quantitative approach to identify intact glycopeptides from comparative proteomic data sets, allowing inference of complex glycan structures and direct mapping of them to sites within the associated proteins at the proteome scale.

Johannes Stadlmann, Jasmin Taubenschmid, Daniel Wenzel, Anna Gattinger, Gerhard Dürnberger, Frederico Dusberger, Ulrich Elling, Lukas Mach, Karl Mechtler & Josef M. Penninger

doi: 10.1038/nature24015

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Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer p.543

In mammals, the canonical somatic DNA methylation landscape is established upon specification of the embryo proper and subsequently disrupted within many cancer types. However, the underlying mechanisms that direct this genome-scale transformation remain elusive, with no clear model for its systematic acquisition or potential developmental utility. Here, we analysed global remethylation from the mouse preimplantation embryo into the early epiblast and extraembryonic ectoderm. We show that these two states acquire highly divergent genomic distributions with substantial disruption of bimodal, CpG density-dependent methylation in the placental progenitor. The extraembryonic epigenome includes specific de novo methylation at hundreds of embryonically protected CpG island promoters, particularly those that are associated with key developmental regulators and are orthologously methylated across most human cancer types. Our data suggest that the evolutionary innovation of extraembryonic tissues may have required co-option of DNA methylation-based suppression as an alternative to regulation by Polycomb-group proteins, which coordinate embryonic germ-layer formation in response to extraembryonic cues. Moreover, we establish that this decision is made deterministically, downstream of promiscuously used—and frequently oncogenic—signalling pathways, via a novel combination of epigenetic cofactors. Methylation of developmental gene promoters during tumorigenesis may therefore reflect the misappropriation of an innate trajectory and the spontaneous reacquisition of a latent, developmentally encoded epigenetic landscape.

Zachary D. Smith, Jiantao Shi, Hongcang Gu, Julie Donaghey, Kendell Clement, Davide Cacchiarelli, Andreas Gnirke, Franziska Michor & Alexander Meissner

doi: 10.1038/nature23891

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Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN p.548

CYREN is a direct inhibitor of classical non-homologous end joining that promotes error-free repair by homologous recombination during the S and G2 phases of the cell cycle.

Nausica Arnoult, Adriana Correia, Jiao Ma, Anna Merlo, Sara Garcia-Gomez, Marija Maric, Marco Tognetti, Christopher W. Benner, Simon J. Boulton, Alan Saghatelian + et al.

doi: 10.1038/nature24023

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