Volume 548 Number 7668



Head injuries in sport must be taken more seriously p.371

Sports organizations are only starting to understand the harm that can be inflicted by high-contact activities. Science must play its part in highlighting the problem and in aiding diagnosis.

doi: 10.1038/548371a


Magnetic antiparticle expands strange field of swirling science p.371

Antiskyrmion offers promise for superfast spintronic computers.

doi: 10.1038/548371b



How machine learning could help to improve climate forecasts p.379

Mixing artificial intelligence with climate science helps researchers to identify previously unknown atmospheric processes and rank climate models.

doi: 10.1038/548379a


Supernova’s messy birth casts doubt on reliability of astronomical yardstick p.380

Brightness of exploding stars may vary more than researchers realized.

doi: 10.1038/nature.2017.22066


Ecologists protest Australia’s plans to cut funding for environment-monitoring network p.381

Scientists say the move will reduce the country’s capacity to predict future ecosystem changes.

doi: 10.1038/nature.2017.22453


Mysteries of turbulence unravelled p.382

Simulations follow how swirls in a fluid transfer and dissipate energy.

doi: 10.1038/nature.2017.22474


Theft of South African relics riles researchers p.383

Efforts to relocate artefacts to sites of origin could stall after gold robbery at national park.

doi: 10.1038/nature.2017.22479

News Features


Creeping earth could hold secret to deadly landslides p.384


doi: 10.1038/548384a

News & Views


Neurobiology: Diversity reaches the stars p.396


doi: 10.1038/548396a


Gravitational waves: History of black holes revealed by their spin p.397


doi: 10.1038/548397a


Biotechnology: At the heart of gene edits in human embryos p.398

今回、遺伝子編集技術CRISPR–Casをin vitroで育てられたヒト胚に用いて、疾患関連変異が修正された。編集した構成要素を受精時に導入すると、修復効率が向上した。

doi: 10.1038/nature23533


Materials science: Magnetic molecules back in the race p.400


doi: 10.1038/548400a


Genetics: Role of mutation in fly-wing evolution p.401


doi: 10.1038/nature23536


Atmospheric science: Ancient ice and the global methane cycle p.403


doi: 10.1038/548403a


Global health: Probiotic prevents infections in newborns p.404


doi: 10.1038/nature23540



A randomized synbiotic trial to prevent sepsis among infants in rural India p.407

A synbiotic preparation of Lactobacillus plantarum and fructooligosaccharide was found to significantly reduce sepsis and infections of the lower respiratory tract in a trial involving newborns from rural India.

doi: 10.1038/nature23480


Correction of a pathogenic gene mutation in human embryos p.413

CRISPR–Cas9 genome editing is used to induce a DNA repair response and correct a disease-causing heterozygous mutation in human embryos with reduced mosaicism and preferential repair using the wild-type copy of the gene.

doi: 10.1038/nature23305


The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis p.420

An atomic model of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex in neuronal exocytosis accounting for vesicle priming and cooperation in synchronizing and activating evoked release on the sub-millisecond timescale.

doi: 10.1038/nature23484



Distinguishing spin-aligned and isotropic black hole populations with gravitational waves p.426

The spins of the black holes involved in each of the four mergers that have been detected in gravitational waves so far were either small or not aligned with the binary orbit.

doi: 10.1038/nature23453


Large turbulent reservoirs of cold molecular gas around high-redshift starburst galaxies p.430

Starburst galaxies at the peak of cosmic star formation are among the most extreme star-forming engines in the Universe, producing stars over about 100 million years (ref. 2). The star-formation rates of these galaxies, which exceed 100 solar masses per year, require large reservoirs of cold molecular gas to be delivered to their cores, despite strong feedback from stars or active galactic nuclei. Consequently, starburst galaxies are ideal for studying the interplay between this feedback and the growth of a galaxy. The methylidyne cation, CH+, is a most useful molecule for such studies because it cannot form in cold gas without suprathermal energy input, so its presence indicates dissipation of mechanical energy or strong ultraviolet irradiation. Here we report the detection of CH+ (J = 1–0) emission and absorption lines in the spectra of six lensed starburst galaxies at redshifts near 2.5. This line has such a high critical density for excitation that it is emitted only in very dense gas, and is absorbed in low-density gas. We find that the CH+ emission lines, which are broader than 1,000 kilometres per second, originate in dense shock waves powered by hot galactic winds. The CH+ absorption lines reveal highly turbulent reservoirs of cool (about 100 kelvin), low-density gas, extending far (more than 10 kiloparsecs) outside the starburst galaxies (which have radii of less than 1 kiloparsec). We show that the galactic winds sustain turbulence in the 10-kiloparsec-scale environments of the galaxies, processing these environments into multiphase, gravitationally bound reservoirs. However, the mass outflow rates are found to be insufficient to balance the star-formation rates. Another mass input is therefore required for these reservoirs, which could be provided by ongoing mergers or cold-stream accretion. Our results suggest that galactic feedback, coupled jointly to turbulence and gravity, extends the starburst phase of a galaxy instead of quenching it.

doi: 10.1038/nature23298


Epitaxy of advanced nanowire quantum devices p.434

A finely tuned growth strategy to generate nanowire networks that fulfil all the prerequisites for braiding may lead to a demonstration of Majorana braiding.

doi: 10.1038/nature23468

化学:ジスプロソセニウムにおける60 Kでの分子の磁気ヒステリシス

Molecular magnetic hysteresis at 60 kelvin in dysprosocenium p.439

Magnetic hysteresis is observed in a dysprosocenium complex at temperatures of up to 60 kelvin, the origin of which is the localized metal–ligand vibrational modes unique to dysprosocenium.

doi: 10.1038/nature23447


Minimal geological methane emissions during the Younger Dryas–Preboreal abrupt warming event p.443

Methane (CH4) is a powerful greenhouse gas and plays a key part in global atmospheric chemistry. Natural geological emissions (fossil methane vented naturally from marine and terrestrial seeps and mud volcanoes) are thought to contribute around 52 teragrams of methane per year to the global methane source, about 10 per cent of the total, but both bottom-up methods (measuring emissions) and top-down approaches (measuring atmospheric mole fractions and isotopes) for constraining these geological emissions have been associated with large uncertainties. Here we use ice core measurements to quantify the absolute amount of radiocarbon-containing methane (14CH4) in the past atmosphere and show that geological methane emissions were no higher than 15.4 teragrams per year (95 per cent confidence), averaged over the abrupt warming event that occurred between the Younger Dryas and Preboreal intervals, approximately 11,600 years ago. Assuming that past geological methane emissions were no lower than today, our results indicate that current estimates of today’s natural geological methane emissions (about 52 teragrams per year) are too high and, by extension, that current estimates of anthropogenic fossil methane emissions are too low. Our results also improve on and confirm earlier findings that the rapid increase of about 50 per cent in mole fraction of atmospheric methane at the Younger Dryas–Preboreal event was driven by contemporaneous methane from sources such as wetlands; our findings constrain the contribution from old carbon reservoirs (marine methane hydrates, permafrost and methane trapped under ice) to 19 per cent or less (95 per cent confidence). To the extent that the characteristics of the most recent deglaciation and the Younger Dryas–Preboreal warming are comparable to those of the current anthropogenic warming, our measurements suggest that large future atmospheric releases of methane from old carbon sources are unlikely to occur.

doi: 10.1038/nature23316


Mutation predicts 40 million years of fly wing evolution p.447

A detailed analysis of fly wing phenotypes reveals a strong positive relationship between variation produced by mutation, standing genetic variation, and evolutionary rate over the past 40 million years.

doi: 10.1038/nature23473


Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis p.451

Myofibroblast-derived R-spondin 3 orchestrates regeneration of antral stomach epithelium via Wnt signalling in Axin2+ stem cells.

doi: 10.1038/nature23642

幹細胞:Polyloxバーコーディングによってin vivoで明らかになった造血幹細胞の運命

Polylox barcoding reveals haematopoietic stem cell fates realized in vivo p.456

Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping1 has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites2, viral barcodes3, and strategies based on transposons4 and CRISPR–Cas9 genome editing5; however, temporal and tissuespecific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre–loxP recombination system6,7. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs8–10. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryoderived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid–erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure.

doi: 10.1038/nature23653


cGAS surveillance of micronuclei links genome instability to innate immunity p.461

The cytoplasmic DNA sensor cGAS detects DNA in ruptured micronuclei and activates an innate immune response.

doi: 10.1038/nature23449


Mitotic progression following DNA damage enables pattern recognition within micronuclei p.466

The authors report a link between mitosis, the formation of micronuclei and DNA-damage-induced cGAS-dependent inflammation.

doi: 10.1038/nature23470


CDK4/6 inhibition triggers anti-tumour immunity p.471

Mouse models of breast carcinoma and other solid tumours show that selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors not only induce tumour cell cycle arrest but also promote anti-tumour immunity.

doi: 10.1038/nature23465


Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity p.476

A vaccine-driven approach shows that the prominent stimulant features of the psychoactive profile of fenethylline can be attributed to amphetamine, with synergistic support from theophylline, and no direct contributions from the parent drug molecule.

doi: 10.1038/nature23464


Mechanism of intracellular allosteric β2AR antagonist revealed by X-ray crystal structure p.480

G-protein-coupled receptors (GPCRs) pose challenges for drug discovery efforts because of the high degree of structural homology in the orthosteric pocket, particularly for GPCRs within a single subfamily, such as the nine adrenergic receptors. Allosteric ligands may bind to less-conserved regions of these receptors and therefore are more likely to be selective. Unlike orthosteric ligands, which tonically activate or inhibit signalling, allosteric ligands modulate physiologic responses to hormones and neurotransmitters, and may therefore have fewer adverse effects. The majority of GPCR crystal structures published to date were obtained with receptors bound to orthosteric antagonists, and only a few structures bound to allosteric ligands have been reported. Compound 15 (Cmpd-15) is an allosteric modulator of the β2 adrenergic receptor (β2AR) that was recently isolated from a DNA-encoded small-molecule library. Orthosteric β-adrenergic receptor antagonists, known as beta-blockers, are amongst the most prescribed drugs in the world and Cmpd-15 is the first allosteric beta-blocker. Cmpd-15 exhibits negative cooperativity with agonists and positive cooperativity with inverse agonists. Here we present the structure of the β2AR bound to a polyethylene glycol-carboxylic acid derivative (Cmpd-15PA) of this modulator. Cmpd-15PA binds to a pocket formed primarily by the cytoplasmic ends of transmembrane segments 1, 2, 6 and 7 as well as intracellular loop 1 and helix 8. A comparison of this structure with inactive- and active-state structures of the β2AR reveals the mechanism by which Cmpd-15 modulates agonist binding affinity and signalling.

doi: 10.1038/nature23652

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