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Jean-Yves Sgro
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Table of Contents for this page:

  • Current Issue
  • Advanced Online Publications Articles

  • Current Issue of Nature

    Nature - Issue - science feeds

  • Academia must resist political confirmation bias

  • It is crucial to fight discrimination in all its forms, but it is unhelpful to exclude conservative voices from debate.

  • Post-publication criticism is crucial, but should be constructive

  • In an era of online discussion, debate must remain nuanced and courteous.

  • Researchers serve up suggestions to reduce food waste

  • A change in cultural and social factors— such as overcoming a distaste for doggy bags — will be required to shift people’s behaviour.

  • Post-truth: a guide for the perplexed

  • If politicians can lie without condemnation, what are scientists to do? Kathleen Higgins offers some explanation.

  • Immunology: Macaque social status alters immunity

  • Changing the social status of macaques also changes their immune systems.Low social status has been linked to multiple health problems in humans and other primates, some of which may not be linked to the accessibility of food and other resources.Jenny Tung of Duke

  • Catalysts: Silicon added to life's toolbox

  • Molecules containing both carbon and silicon have become a standard part of synthetic chemistry, but life uses silicon only in inorganic compounds such as the shells of diatoms.Now, Frances Arnold and her collaborators at the California Institute of Technology in Pasadena have engineered bacteria

  • Cancer: 'Jet lag' increases mouse cancer risk

  • Mice with simulated jet lag have an increased risk of developing liver cancer.Sleeping out of step with the day–night cycle has been linked to various health disorders in humans. David Moore, Loning Fu and their colleagues at Baylor College of Medicine in Houston, Texas,

  • Seismology: Gravity changes before quake hits

  • Researchers have for the first time detected temporary changes in Earth's gravitational field just before an earthquake.Jean-Paul Montagner at the CNRS Institute of Earth Physics in Paris and his team analysed gravimetric and seismic data recorded during the massive 2011 Tohoku earthquake in Japan.

  • Climate change: Shifting niches spell trouble

  • Plants and animals will probably be unable to respond to changes in environmental conditions fast enough to keep pace with climate change.Tereza Jezkova and John Wiens of the University of Arizona, Tucson, looked at 56 plant and animal species and documented shifts in their

  • Palaeontology: Ancient reptile had a diaphragm

  • The muscle that allows mammals to breathe deeply— the diaphragm — may have been present in some reptiles 300 million years ago, about 50 million years before it was thought to have appeared.Markus Lambertz at the University of Bonn in Germany and his

  • Quantum physics: Record set for linked photons

  • Particles that have linked quantum states, known as 'entangled' particles, can affect each other's states even if they are physically separated. Now scientists have set a record by entangling ten photons— two more than achieved previously.Entangled particles should one day enable quantum computing

  • Materials science: Atom-thick coats for copper

  • Coating metals with a high-quality, single-atom-thick layer of 2D boron nitride can protect them from corrosion.Layers of 2D materials have been touted for use as protective coatings on surfaces but have shown mixed results, with some apparently even increasing corrosion rates in the long

  • Materials: Sensor detects UV exposure

  • A sensor that sticks to the skin can give colour-coded readouts of ultraviolet light levels from the Sun, the leading cause of skin cancer.John Rogers at the University of Illinois at Urbana–Champaign and his colleagues developed the stretchable device (pictured), which is

  • Epigenetics: Gut microbes shape DNA

  • Gut microbes and the fatty acids they produce can regulate gene expression by influencing the 3D shape of their hosts' DNA.Intestinal bacteria are known to affect several aspects of host health, including the risk of cardiovascular and metabolic diseases. To study the mechanisms by

  • Chernobyl's shield, dodo skeleton and HIV vaccines

  • The week in science: 25 November–1 December 2016.

  • Failed Alzheimer’s trial does not kill leading theory of disease

  • The drug, and others based on the‘amyloid hypothesis’, are still being tested in other, different trials.

  • UK scientists excited by surprise£2-billion government windfall

  • Cash to include fund modelled on DARPA, the US defence department’s research arm — but how much will go to basic research is unclear.

  • Experimental treatments aim to prevent brain damage in babies

  • Advances in neuroscience are driving the development of therapies that could save thousands of the most vulnerable patients.

  • Speedy Antarctic drills start hunt for Earth’s oldest ice

  • British team is first to seek site of 1.5-million-year-old sample.

  • Weaponized antibodies use new tricks to fight cancer

  • Next generation of Trojan-horse drugs designed to minimize damage to healthy cells.

  • Updated: NgAgo gene-editing controversy escalates in peer-reviewed papers

  • String of publications describes attempts— mostly unsuccessful — to use proposed CRISPR rival.

  • Can old computers bring Palestinians and Israelis together?

  • Some of the most toxic refuse from modern society ends up in poor communities. Researchers are helping one area in the Middle East clean up its electronic-waste problem.

  • Four routes to better maritime governance

  • Challenges in preventing pollution from ballast water highlight reforms needed in global shipping regulation, write Zheng Wan and colleagues.

  • A new global research agenda for food

  • Lawrence Haddad, Corinna Hawkes and colleagues propose ten ways to shift the focus from feeding people to nourishing them.

  • Fix food metrics

  • For sustainable, equitable nutrition we must count the true global costs and benefits of food production, urge Pavan Sukhdev, Peter May and Alexander Müller.

  • Book publishing: University presses adapt

  • Roger Schonfeld analyses how the sector's scientific books are faring in the digitized, open-access era.

  • Books in brief

  • Barbara Kiser reviews five of the week's best science picks.

  • Phylogeny: 'Tree of life' took root 150 years ago

  • As thousands of scientists and policymakers gather in Mexico this month for the COP13 summit on biodiversity (see, we should take a moment to celebrate the earliest 'tree of life' model of biodiversity.Charles Darwin published the idea of a tree of life

  • Conservation: smart advocacy needs data

  • We agree that data alone will not save species (A. M.EllisonNature538, 141;10.1038/538141a2016). However, using data in combination with smart advocacy can make a difference.For example, ecologists specializing in seabirds, fishes and coral reefs shared their

  • Conservation: big data boost in China

  • I disagree with Aaron Ellison's contention that biodiversity data only rarely drive conservation decisions (Nature538, 141;10.1038/538141a2016). In China, better data are guiding changes in conservation policies and on-the-ground actions.For instance, huge long-term data sets on species, ecosystems

  • Conservation: thrive on slings and arrows

  • Aaron Ellison rightly calls for conservation scientists to engage more actively in the political process (Nature538, 141;10.1038/538141a2016). Unfortunately, those doing so can become targets for physical and verbal threats, personal abuse, bullying and trolling on social media.As

  • Cities: factor in their biological impact

  • Richard Forman and Jianguo Wu identify several zones around the world that might be suitable for future urbanization (Nature537, 608–611;10.1038/537608a2016). We suggest that the problem of supporting a growing population needs to be considered from a

  • Cities: new fringes to act as safety nets

  • Richard Forman and Jianguo Wu suggest that sustainable city expansion should be restricted to selected urban peripheries (Nature537, 608–611;10.1038/537608a2016). Our investigations across five Indian cities indicate that proper planning of such peri-urban areas is crucial.We

  • Trump: voters show importance of SDGs

  • Many of the factors that contributed to Donald Trump's win in the 2016 US presidential election are those that make achievement of the United Nations' Sustainable Development Goals (SDGs) so pressing. Drawn up to end poverty (goal 1) and inequality (goal 10) and to ensure

  • Trump: offset fracking risks

  • Unconventional gas extraction ('fracking') is likely to be central to the energy policy of president-elect Donald Trump. I urge the US Congress to tighten current regulations and strike a balance between energy independence and the safeguarding of public health and the environment (see also J.

  • Trump: polls right, models wrong

  • Contrary to popular opinion, the polls were not wrong in last month's US presidential election (see also Nature539, 339;10.1038/539339a2016). The most recent polls in each state predicted the outcome for individual states— but only when the 95% confidence

  • Susan Lee Lindquist (1949–2016)

  • Biologist who found unexpected power in protein folding.

  • Human behaviour: Find your voice

  • Technology and practice can help shy and introverted researchers to succeed when reticence is risky.

  • Gender: Co-author differences

  • Women have fewer co-authors than men over the course of their careers.

  • Income: UK pay gap

  • The pay gap between men and women in UK science is narrowing.

  • The first fragmented church of entropy

  • Order from chaos.

  • Multiple sclerosis

  • Biology: A degenerative affliction

  • Multiple sclerosis often strikes between the ages of 20 and 40, when people are entering the workforce and raising families.

  • Aetiology: Neighbourhood watch

  • Emerging evidence points to a viral infection, low levels of vitamin D and genetics as culprits in multiple sclerosis, but how they combine to cause the disease is unclear.

  • Therapies: Progressive steps

  • New drugs are beginning to show promise for people with one of the less common, and harder to treat, forms of multiple sclerosis.

  • Perspective: Who dares, wins

  • It is time for a bolder approach to developing drugs for progressive multiple sclerosis, says Bibi Bielekova.

  • Stem cells: Stemming the tide

  • Could a high-risk treatment play a part in tackling multiple sclerosis?

  • Diet: Changing the recipe

  • Dietary changes may be able to alleviate the symptoms of multiple sclerosis, but testing the effects of diet will need a different protocol to the one used for drugs.

  • Consistency in large pharmacogenomic studies

  • arising fromB.Haibe-Kainset al. Nature504, 389–393 (2013); doi:10.1038/nature12831Haibe-Kains et al. reported inconsistency between two large-scale pharmacogenomic studies—the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Genome Project (CGP). Upon careful analysis of the

  • Safikhani et al. reply

  • replying toP.Geeleher, E. R.Gamazon, C.Seoighe, N. J.Cox aamp; R. S.HuangNature540, (2016).In the accompanying Comment, Geeleher et al. claim to have discovered overall consistency between the

  • Consistency in drug response profiling

  • arising fromB.Haibe-Kainset al. Nature504, 389–393 (2013); doi:10.1038/nature12831The comparative analysis by Haibe-Kains et al. concluded that data from two large-scale studies of cancer cell lines showed highly discordant results for drug sensitivity measurements, whereas

  • Safikhani et al. reply

  • replying toJ. P.Mpindiet al. Nature540, (2016).The accompanying Comment by Mpindi et al. is an important contribution to the discussion of pharmacogenomic consistency for several reasons. Mpindi et al. were able

  • Drug response consistency in CCLE and CGP

  • arising fromB.Haibe-Kainset al. Nature504, 389–393 (2013); doi:10.1038/nature12831The Cancer Cell Line Encyclopedia (CCLE) and Cancer Genome Project (CGP) are two independent large-scale efforts to characterize genomes, mRNA expression, and anti-cancer drug dose–responses across cell lines,

  • Safikhani et al. reply

  • replying toM.Bouhaddouet al. Nature540, (2016).In the accompanying Comment, the authors make two main claims: (1) that viability metrics computed over the drug concentration range shared between datasets yield higher consistency than the same

  • Planetary science: Pluto's telltale heart

  • Studies of a large frost-filled basin on Pluto show that this feature altered the dwarf planet's spin axis, driving tectonic activity on its surface, and hint at the presence of a subsurface ocean. See Letters p.86, p.90, p.94 aamp; p.97

  • Cell biology: Double agents for mitochondrial division

  • Mitochondrial organelles— the energy powerhouses of the cell — must divide and fuse dynamically to function. It emerges that two distinct dynamin enzymes enable mitochondrial division. See Letter p.139

  • Quantum computing: Efficient fault tolerance

  • Dealing with errors in a quantum computer typically requires complex programming and many additional quantum bits. A technique for controlling errors has been proposed that alleviates both of these problems.

  • Cell biology: Sort of unexpected

  • To reach the cell surface, membrane proteins are first targeted to an organelle called the endoplasmic reticulum. Several targeting pathways are known, but it now emerges that there is yet another pathway. See Letter p.134

  • Biogeochemistry: Projections of the soil-carbon deficit

  • Changes in the amount of carbon stored in soil might be a crucial feedback to climate change. Experimental field studies show that warming-induced soil carbon losses are greatest where carbon stocks are largest. See Letter p.104

  • Astronomy: A black hole changes its feeding habits

  • In the 1980s, the gas surrounding a black hole in a nearby galaxy began to emit much more radiation than before. This change has unexpectedly reversed in the past five years, questioning our understanding of these extreme phenomena.

  • Biological rhythms: Wild times

  • Little is known about the biological rhythms that emerge from social behaviours in the wild. A study of shorebird pairs shows that rhythms of nest-incubation duties are mainly governed by strategies to avoid predators. See Letter p.109

  • Stem cells and interspecies chimaeras

  • Chimaeras are both monsters of the ancient imagination and a long-established research tool. Recent advances, particularly those dealing with the identification and generation of various kinds of stem cells, have broadened the repertoire and utility of mammalian interspecies chimaeras and carved out new paths towards

  • Organization and functions of mGlu and GABAB receptor complexes

  • The neurotransmitters glutamate andγ-aminobutyric acid (GABA) transmit synaptic signals by activating fast-acting ligand-gated ion channels and more slowly acting G-protein-coupled receptors (GPCRs). The GPCRs for these neurotransmitters, metabotropic glutamate (mGlu) and GABAB receptors, are atypical GPCRs with a large extracellular domain and

  • The genomic basis of circadian and circalunar timing adaptations in a midge

  • Organisms use endogenous clocks to anticipate regular environmental cycles, such as days and tides. Natural variants resulting in differently timed behaviour or physiology, known as chronotypes in humans, have not been well characterized at the molecular level. We sequenced the genome of Clunio marinus,

  • Correcting mitochondrial fusion by manipulating mitofusin conformations

  • Mitochondria are dynamic organelles that exchange contents and undergo remodelling during cyclic fusion and fission. Genetic mutations in MFN2 (the gene encoding mitofusin 2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A (CMT2A). It has not yet been possible

  • The pathway to GTPase activation of elongation factor SelB on the ribosome

  • In all domains of life, selenocysteine (Sec) is delivered to the ribosome by selenocysteine-specific tRNA (tRNASec) with the help of a specialized translation factor, SelB in bacteria. Sec-tRNASec recodes a UGA stop codon next to a downstream mRNA stem–loop. Here we

  • Observed glacier and volatile distribution on Pluto from atmosphere–topography processes

  • Pluto has a variety of surface frosts and landforms as well as a complex atmosphere. There is ongoing geological activity related to the massive Sputnik Planitia glacier, mostly made of nitrogen (N2) ice mixed with solid carbon monoxide and methane, covering the 4-kilometre-deep, 1,000-kilometre-wide basin of Sputnik Planitia near the anti-Charon point. The glacier has been suggested to arise from a source region connected to the deep interior, or from a sink collecting the volatiles released planetwide. Thin deposits of N2 frost, however, were also detected at mid-northern latitudes and methane ice was observed to cover most of Pluto except for the darker, frost-free equatorial regions. Here we report numerical simulations of the evolution of N2, methane and carbon monoxide on Pluto over thousands of years. The model predicts N2 ice accumulation in the deepest low-latitude basin and the threefold increase in atmospheric pressure that has been observed to occur since 1988. This points to atmospheric–topographic processes as the origin of Sputnik Planitia’s N2 glacier. The same simulations also reproduce the observed quantities of volatiles in the atmosphere and show frosts of methane, and sometimes N2, that seasonally cover the mid- and high latitudes, explaining the bright northern polarcap reported in the 1990s and the observed ice distribution in 2015. The model also predicts that most of these seasonal frosts should disappear in the next decade.

  • Reorientation and faulting of Pluto due to volatile loading within Sputnik Planitia

  • Pluto is an astoundingly diverse, geologically dynamic world. The dominant feature is Sputnik Planitia—a tear-drop-shaped topographic depression approximately 1,000 kilometres in diameter possibly representing an ancient impact basin. The interior of Sputnik Planitia is characterized by a smooth, craterless plain three to four kilometres beneath the surrounding rugged uplands, and represents the surface of a massive unit of actively convecting volatile ices (N2, CH4 and CO) several kilometres thick. This large feature is very near the Pluto–Charon tidal axis. Here we report that the location of Sputnik Planitia is the natural consequence of the sequestration of volatile ices within the basin and the resulting reorientation (true polar wander) of Pluto. Loading of volatile ices within a basin the size of Sputnik Planitia can substantially alter Pluto’s inertia tensor, resulting in a reorientation of the dwarf planet of around 60 degrees with respect to the rotational and tidal axes. The combination of this reorientation, loading and global expansion due to the freezing of a possible subsurface ocean generates stresses within the planet’s lithosphere, resulting in a global network of extensional faults that closely replicate the observed fault networks on Pluto. Sputnik Planitia probably formed northwest of its present location, and was loaded with volatiles over million-year timescales as a result of volatile transport cycles on Pluto. Pluto’s past, present and future orientation is controlled by feedbacks between volatile sublimation and condensation, changing insolation conditions and Pluto’s interior structure.

  • Reorientation of Sputnik Planitia implies a subsurface ocean on Pluto

  • The deep nitrogen-covered basin on Pluto, informally named Sputnik Planitia, is located very close to the longitude of Pluto’s tidal axis and may be an impact feature, by analogy with other large basins in the Solar System. Reorientation of Sputnik Planitia arising from tidal and rotational torques can explain the basin’s present-day location, but requires the feature to be a positive gravity anomaly, despite its negative topography. Here we argue that if Sputnik Planitia did indeed form as a result of an impact and if Pluto possesses a subsurface ocean, the required positive gravity anomaly would naturally result because of shell thinning and ocean uplift, followed by later modest nitrogen deposition. Withouta subsurface ocean, a positive gravity anomaly requires an implausibly thick nitrogen layer (exceeding 40 kilometres). To prolong the lifetime of such a subsurface ocean to the present day and to maintain ocean uplift, a rigid, conductive water-ice shell is required. Because nitrogen deposition is latitude-dependent, nitrogen loading and reorientation may have exhibited complex feedbacks.

  • The rapid formation of Sputnik Planitia early in Pluto’s history

  • Pluto’s Sputnik Planitia is a bright, roughly circular feature that resembles a polar ice cap. It is approximately 1,000 kilometres across and is centred on a latitude of 25 degrees north and a longitude of 175 degrees, almost directly opposite the side of Pluto that always faces Charon as a result oftidal locking. One explanation for its location includes the formation of a basin in a giant impact, with subsequent upwelling of a dense interior ocean. Once the basin was established, ice would naturally have accumulated there. Then, provided that the basin was a positive gravity anomaly (with orwithout the ocean), true polar wander could have moved the feature towards the Pluto–Charon tidal axis, on the far side of Pluto from Charon. Here we report modelling that shows that ice quickly accumulates on Pluto near latitudes of 30 degrees north and south, even in the absence of a basin, because, averaged over its orbital period, those are Pluto’s coldest regions. Within a million years of Charon’s formation, ice deposits on Pluto concentrate into a single cap centred near a latitude of 30 degrees, owing to the runaway albedo effect. This accumulation of ice causes a positive gravity signature that locks, as Pluto’s rotation slows, to a longitude directly opposite Charon. Once locked, Charon raises a permanent tidal bulge on Pluto, which greatly enhances the gravity signature of the ice cap. Meanwhile, the weight of the ice in Sputnik Planitia causes the crust under it to slump, creating its own basin (as has happened on Earth in Greenland). Even if the feature is now a modest negative gravity anomaly, it remains locked in place because of the permanent tidal bulge raised by Charon. Any movement of the feature away from 30 degrees latitude is countered by the preferential recondensation of ices near the coldest extremities of the cap. Therefore, our modelling suggests that Sputnik Planitia formed shortly after Charon did and has been stable, albeit gradually losing volume, over the age of the Solar System.

  • Ghost imaging with atoms

  • Ghost imaging is a counter-intuitive phenomenon—first realized in quantum optics—that enables the image of a two-dimensional object (mask) to be reconstructed using the spatio-temporal properties of a beam of particles with which it never interacts. Typically, two beams of correlated photons are used: one passes through the mask to a single-pixel (bucket) detector while the spatial profile of the other is measured by a high-resolution (multi-pixel) detector. The second beam never interacts with the mask. Neither detector can reconstruct the mask independently, but temporal cross-correlation between the two beams can be used to recovera ‘ghost’ image. Here we report the realization of ghost imaging using massive particles instead of photons. In our experiment, the two beams are formed by correlated pairs of ultracold, metastable helium atoms, which originate from s-wave scattering of two colliding Bose–Einstein condensates. We use higher-order Kapitza–Dirac scattering to generate a large number of correlated atom pairs, enabling the creation of a clear ghost image with submillimetre resolution. Future extensions of our technique could lead to the realization of ghost interference, and enable tests of Einstein–Podolsky–Rosen entanglement and Bell’s inequalities with atoms.

  • Quantifying global soil carbon losses in response to warming

  • The majority of the Earth’s terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within ayear, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12–17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon–climate feedback that could accelerate climate change.

  • Unexpected diversity in socially synchronized rhythms of shorebirds

  • The behavioural rhythms of organisms are thought to be under strong selection, influenced by the rhythmicity of the environment. Such behavioural rhythms are well studied in isolated individuals under laboratory conditions, but free-living individuals have to temporally synchronize their activities with those of others, including potential mates, competitors, prey and predators. Individuals can temporally segregate their daily activities (for example, prey avoiding predators, subordinates avoiding dominants) or synchronize their activities (for example, group foraging, communal defence, pairs reproducing or caring for offspring). The behavioural rhythms that emerge from such social synchronization and the underlying evolutionary and ecological drivers that shape them remain poorly understood. Here we investigate these rhythms in the context of biparental care, a particularly sensitive phase of social synchronization where pair members potentially compromise their individual rhythms. Using data from 729 nests of 91 populations of 32 biparentally incubating shorebird species, where parents synchronize to achieve continuous coverage of developing eggs, we report remarkable within- and between-species diversity in incubation rhythms. Between species, the median length of one parent’s incubation bout varied from 1–19 h, whereas period length—the time in which a parent’s probability to incubate cycles once between its highest and lowest value—varied from 6–43 h. The length of incubation bouts was unrelated to variables reflecting energetic demands, but species relying on crypsis (the ability to avoid detection by other animals) had longer incubation bouts than those that are readily visible or who actively protect their nest against predators. Rhythms entrainable to the 24-h light–dark cycle were less prevalent at high latitudes and absent in 18 species. Our results indicate that even under similar environmental conditions and despite 24-h environmental cues, social synchronization can generate far more diverse behavioural rhythms than expected from studies of individuals in captivity. The risk of predation, not the risk of starvation, may be a key factor underlying the diversity in these rhythms.

  • Genomic evolution and chemoresistance in germ-cell tumours

  • Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types. These tumours also acquire KRAS mutations during the development from precursor to primary disease, and primary testicular GCTs (TGCTs) are uniformly wild type for TP53. In addition, by functional measurement of apoptotic signalling (BH3 profiling) of fresh tumour and adjacent tissue, we find that primary TGCTs have high mitochondrial priming that facilitates chemotherapy-induced apoptosis. Finally, by phylogenetic analysis of serial TGCTs that emerge with chemotherapy resistance, we show how TGCTs gain additional reciprocal loss of heterozygosity and that this is associated with loss of pluripotency markers (NANOG and POU5F1) in chemoresistant teratomas or transformed carcinomas. Our results demonstrate the distinct genomic features underlying the origins of this disease and associated with the chemosensitivity phenotype, as well as the rare progression to chemoresistance. These results identify the convergence of cancer genomics, mitochondrial priming and GCT evolution, and may provide insights into chemosensitivity and resistance in other cancers.

  • Inhibition of mTOR induces a paused pluripotent state

  • Cultured pluripotent stem cells are a cornerstone of regenerative medicine owing to their ability to give rise to all cell types of the body. Although pluripotent stem cells can be propagated indefinitely in vitro, pluripotency is paradoxically a transient state in vivo, lasting 2–3 days around the time of blastocyst implantation. The exception to this rule is embryonic diapause, a reversible state of suspended development triggered by unfavourable conditions. Diapause is a physiological reproductive strategy widely employed across the animal kingdom, including in mammals, but its regulation remains poorly understood. Here we report that the partial inhibition of mechanistic target of rapamycin (mTOR), a major nutrient sensor and promoter of growth, induces reversible pausing of mouse blastocyst development and allows their prolonged culture ex vivo. Paused blastocysts remain pluripotent and competent—able to give rise to embryonic stem (ES) cells and live, fertile mice. We show that both naturally diapaused blastocysts in vivo and paused blastocysts ex vivo display pronounced reductions in mTOR activity, translation, histone modifications associated with gene activity and transcription. Pausing can be induced directly in cultured ES cells and sustained for weeks without appreciable cell death or deviations from cell cycle distributions. We show that paused ES cells display a remarkable global suppression of transcription, maintain a gene expression signature of diapaused blastocysts and remain pluripotent. These results uncover a new pluripotent stem cell state corresponding to the epiblast of the diapaused blastocyst and indicate that mTOR regulates developmental timing at the peri-implantation stage. Our findings have implications in the fields of assisted reproduction, regenerative medicine, cancer, metabolic disorders and ageing.

  • RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation

  • Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation through kinase-dependent and -independent functions. RIPK1 kinase activity induces caspase-8-dependent apoptosis and RIPK3 and mixed lineage kinase like (MLKL)-dependent necroptosis. In addition, RIPK1 inhibits apoptosis and necroptosis through kinase-independent functions, which are important for late embryonic development and the prevention of inflammation in epithelial barriers. The mechanism by which RIPK1 counteracts RIPK3–MLKL-mediated necroptosis has remained unknown. Here we show that RIPK1 prevents skin inflammation by inhibiting activation of RIPK3–MLKL-dependent necroptosis mediated by Z-DNA binding protein 1 (ZBP1, also known as DAI or DLM1). ZBP1 deficiency inhibited keratinocyte necroptosis and skin inflammation in mice with epidermis-specific RIPK1 knockout. Moreover, mutation of the conserved RIP homotypic interaction motif (RHIM) of endogenous mouse RIPK1 (RIPK1mRHIM) caused perinatal lethality that was prevented by RIPK3, MLKL or ZBP1 deficiency. Furthermore, mice expressing only RIPK1mRHIM inkeratinocytes developed skin inflammation that was abrogated by MLKL or ZBP1 deficiency. Mechanistically, ZBP1 interacted strongly with phosphorylated RIPK3 in cells expressing RIPK1mRHIM, suggesting that the RIPK1 RHIM prevents ZBP1 from binding and activating RIPK3. Collectively, these results show that RIPK1 prevents perinatal death as well as skin inflammation in adult mice by inhibiting ZBP1-induced necroptosis. Furthermore, these findings identify ZBP1 as a critical mediator of inflammation beyond its previously known role in antiviral defence and suggest that ZBP1 might be implicated in the pathogenesis of necroptosis-associated inflammatory diseases.

  • RIPK1 inhibits ZBP1-driven necroptosis during development

  • Receptor-interacting protein kinase 1 (RIPK1) promotes cell survival—mice lacking RIPK1 die perinatally, exhibiting aberrant caspase-8-dependent apoptosis and mixed lineage kinase-like (MLKL)-dependent necroptosis. However, mice expressing catalytically inactive RIPK1 are viable, and an ill-defined pro-survival function for the RIPK1 scaffold has therefore been proposed. Here we show that the RIP homotypic interaction motif (RHIM) in RIPK1 prevents the RHIM-containing adaptor protein ZBP1 (Z-DNA binding protein 1; also known as DAI or DLM1) from activating RIPK3 upstream of MLKL. Ripk1RHIM/RHIM mice that expressed mutant RIPK1 with critical RHIM residues IQIG mutated to AAAA died around birth and exhibited RIPK3 autophosphorylation on Thr231 and Ser232, which is a hallmark of necroptosis, in the skin and thymus. Blocking necroptosis with catalytically inactive RIPK3(D161N), RHIM mutant RIPK3, RIPK3 deficiency, or MLKL deficiency prevented lethality inRipk1RHIM/RHIM mice. Loss of ZBP1, which engages RIPK3 in response to certain viruses but previously had no defined role in development, also prevented perinatal lethality in Ripk1RHIM/RHIM mice. Consistent with the RHIM of RIPK1 functioning as a brake that prevents ZBP1 from engaging the RIPK3 RHIM, ZBP1 interacted with RIPK3 in Ripk1RHIM/RHIMMlkl−/− macrophages, but not in wild-type, Mlkl−/− or Ripk1RHIM/RHIMRipk3RHIM/RHIM macrophages. Collectively, these findings indicate that the RHIM of RIPK1 is critical for preventing ZBP1/RIPK3/MLKL-dependent necroptosis during development.

  • The SND proteins constitute an alternative targeting route to the endoplasmic reticulum

  • In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments. Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40) and homologous yeast guided entry of tail-anchored proteins (GET) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay. We set out to uncover additional targeting proteins using unbiased high-content screening approaches. To this end, we performed a systematic visual screen using the yeast Saccharomyces cerevisiae, and uncovered three uncharacterized proteins whose loss affected targeting. We suggest that these proteins work together and demonstrate that they function in parallel with SRP and GET to target a broad range of substrates to the endoplasmic reticulum. The three proteins, which we name Snd1, Snd2 and Snd3 (for SRP-independent targeting), can synthetically compensate for the loss of both the SRP and GET pathways, and act as a backup targeting system. This explains why it has previously been difficult to demonstrate complete loss of targeting for some substrates. Our discovery thus puts in place an essential piece of the endoplasmic reticulum targeting puzzle, highlighting how the targeting apparatus of the eukaryotic cell is robust, interlinked and flexible.

  • Multiple dynamin family members collaborate to drive mitochondrial division

  • Mitochondria cannot be generated de novo; they must grow, replicate their genome, and divide in order to be inherited by each daughter cell during mitosis. Mitochondrial division is a structural challenge that requires the substantial remodelling of membrane morphology. Although division factors differ across organisms, the need for multiple constriction steps and a dynamin-related protein (Drp1, Dnm1 in yeast) has been conserved. In mammalian cells, mitochondrial division has been shown to proceed with at least two sequential constriction steps: the endoplasmic reticulum and actin must first collaborate to generate constrictions suitable for Drp1 assembly on the mitochondrial outer membrane; Drp1 then further constricts membranes until mitochondrial fission occurs. In vitro experiments, however, indicate that Drp1 does not have the dynamic range to complete membrane fission. In contrast to Drp1, the neuron-specific classical dynamin dynamin-1 (Dyn1) has been shown to assemble on narrower lipid profiles and facilitate spontaneous membrane fission upon GTP hydrolysis. Here we report that the ubiquitously expressed classical dynamin-2 (Dyn2) is a fundamental component of the mitochondrial division machinery. A combination of live-cell and electron microscopy in three different mammalian cell lines reveals that Dyn2 works in concert with Drp1 to orchestrate sequential constriction events that build up to division. Our work underscores the biophysical limitations of Drp1 and positions Dyn2, which has intrinsic membrane fission properties, at the final step of mitochondrial division.

  • In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

  • Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.

  • Erratum: Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion

  • Nature536, 479–483 (2016); doi:10.1038/nature19084In this Letter, during the production process, one of the images in Fig. 3a was inadvertently labelled with the incorrect PDAC cell line name. The second picture from the left should have been

  • Erratum: Pore-forming activity and structural autoinhibition of the gasdermin family

  • Nature535, 111–116 (2016); doi:10.1038/nature18590In this Article, owing to a typesetter error the ‘received date’ was incorrectly shown as ‘6 March 2015’ instead of ‘6 March 2016’; this has been corrected in the online versions of the

  • Corrigendum: Design of a hyperstable 60-subunit protein icosahedron

  • Nature535, 136–139 (2016); doi:10.1038/nature18010In this Letter, the 60-subunit protein assembly presented more strongly resembles a wireframe dodecahedron than an icosahedron. We thank the reader who drew this to our attention and we agree that all instances

  • Corrigendum: Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition

  • Nature537, 544–547 (2016); doi:10.1038/nature19353In this Letter, the ArrayExpress accession number provided for the gene expression data for Sdhb-deficient cells should have been ‘ E-MTAB-4349’, rather than the Affymetrix GeneChip platform accession ‘A-AFFY-130’; this has been

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  • Biomedicine: An eye on retinal recovery

  • Retinal-cell transplants restore vision in mouse models of retinal degeneration. It emerges that the transplant leads to an exchange of material between donor and host cells— not to donor-cell integration into the retina, as had been presumed.

  • Stem cells: Cause and consequence in aged-muscle decline

  • Activation of aged muscle stem cells induces changes in DNA packaging that lead to expression of the gene Hoxa9. This reactivates embryonic signalling pathways, restricting the cells' ability to repair injured muscle.

  • Stem cells: Aspiring to naivety

  • Human stem cells that can give rise to every cell type in the body are major players in biomedical research. A molecular analysis of human embryos might help to make these cultured cells more authentic imitations of their in vivo counterparts.

  • Biomedicine: Replacing the cell's power plants

  • Nuclear DNA from human eggs that harbour mutations in the DNA of organelles called mitochondria has been successfully transferred to donor eggs, bringing the prospect of therapy for mitochondrial diseases a step closer.

  • m6A modulates neuronal functions and sex determination in Drosophila

  • One of the most abundant modifications found in messenger RNAs is N6-methyladenosine (m6A); here, this modification is shown to alter gene expression during sex determination and affect neuronal functions and behaviour in Drosophila via the m6A reader protein YT521-B.

  • Land-use intensification causes multitrophic homogenization of grassland communities

  • Land-use intensification is a major driver of biodiversity loss. Alongside reductions in local species diversity, biotic homogenization at larger spatial scales is of great concern for conservation. Biotic homogenization means a decrease inβ-diversity (the compositional dissimilarity between sites). Most studies have investigated losses in local (α)-diversity and neglected biodiversity loss at larger spatial scales. Studies addressing β-diversity have focused on single or a few organism groups (for example, ref. 4), and it is thusunknown whether land-use intensification homogenizes communities at different trophic levels, above- and belowground. Here we show that even moderate increases in local land-use intensity (LUI) cause biotic homogenization across microbial, plant and animal groups, both above- and belowground, and that this is largely independent of changes in α-diversity. We analysed a unique grassland biodiversity dataset, with abundances of more than 4,000 species belonging to 12 trophic groups. LUI, and, in particular, high mowing intensity, had consistent effects on β-diversity across groups, causing a homogenization of soil microbial, fungal pathogen, plant and arthropod communities. These effects were nonlinear and the strongest declines in β-diversity occurred in the transition from extensively managed to intermediate intensity grassland. LUI tended to reduce local α-diversity in aboveground groups, whereas the α-diversity increased in belowground groups. Correlations between the β-diversity of different groups, particularly between plants and their consumers, became weaker at high LUI. This suggests a loss of specialist species and is further evidence for biotic homogenization. The consistently negative effects of LUI on landscape-scale biodiversity underscore the high value of extensively managed grasslands for conserving multitrophic biodiversity and ecosystem service provision. Indeed, biotic homogenization rather than local diversity loss could prove to be the most substantial consequence of land-use intensification.

  • m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination

  • N6-methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) and is decoded by YTH domain proteins. The mammalian mRNA m6A methylosome is a complex of nuclear proteins that includes METTL3 (methyltransferase-like 3), METTL14, WTAP (Wilms tumour 1-associated protein) and KIAA1429. Drosophila has corresponding homologues named Ime4 and KAR4 (Inducer of meiosis 4 and Karyogamy protein 4), and Female-lethal (2)d (Fl(2)d) and Virilizer (Vir). In Drosophila, fl(2)d and vir are required for sex-dependent regulation of alternative splicing of the sex determination factor Sex lethal (Sxl). However, the functions of m6A in introns in the regulation of alternative splicing remain uncertain. Here we show that m6A is absent in the mRNA of Drosophila lacking Ime4. In contrast to mouse and plant knockout models, Drosophila Ime4-null mutants remain viable, though flightless, and show a sex bias towards maleness. This is because m6A is required for female-specific alternative splicing of Sxl, which determines female physiognomy, but also translationally represses male-specific lethal 2 (msl-2) to prevent dosage compensation in females. We further show that the m6A reader protein YT521-B decodes m6A in the sex-specifically spliced intron of Sxl, as its absence phenocopies Ime4 mutants. Loss of m6A also affects alternative splicing of additional genes, predominantly in the 5′ untranslated region, and has global effects on the expression of metabolic genes. The requirement of m6A and its reader YT521-B for female-specific Sxl alternative splicing reveals that this hitherto enigmatic mRNA modification constitutes an ancient and specific mechanism to adjust levels of gene expression.

  • Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations

  • Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type mtDNA (heteroplasmy) in each cell and tissue. Pathogenic mtDNA mutations are relatively common, with an estimated 778 affected children born each year in the United States. Mitochondrial replacement therapies or techniques (MRT) circumventing mother–to–child mtDNA disease transmission involve replacement of oocyte maternal mtDNA. Here we report MRT outcomes in several families with common mtDNA syndromes. The mother’s oocytes were of normal quality and mutation levels correlated with those in existing children. Efficient replacement of oocyte mutant mtDNA was performed by spindle transfer, resulting in embryos containing ggt;99% donor mtDNA. Donor mtDNA was stably maintained in embryonic stem cells (ES cells) derived from most embryos. However, some ES cell lines demonstrated gradual loss of donor mtDNA and reversal to the maternal haplotype. In evaluating donor–to–maternal mtDNA interactions, it seems that compatibility relates to mtDNA replication efficiency rather than to mismatch or oxidative phosphorylation dysfunction. We identify a polymorphism within the conserved sequence box II region of the D-loop as a plausible cause of preferential replication of specific mtDNA haplotypes. In addition, some haplotypes confer proliferative and growth advantages to cells. Hence, we propose a matching paradigm for selecting compatible donor mtDNA for MRT.

  • Capturing pairwise and multi-way chromosomal conformations using chromosomal walks

  • Chromosomes are folded into highly compacted structures to accommodate physical constraints within nuclei and to regulate access to genomic information. Recently, global mapping of pairwise contacts showed that loops anchoring topological domains (TADs) are highly conserved between cell types and species. Whether pairwise loops synergize to form higher-order structures is still unclear. Here we develop a conformation capture assay to study higher-order organization using chromosomal walks (C-walks) that link multiple genomic loci together into proximity chains in human and mouse cells. This approach captures chromosomal structure at varying scales. Inter-chromosomal contacts constitute only 7–10% of the pairs and are restricted by interfacing TADs. About half of the C-walks stay within one chromosome, and almost half of those are restricted to intra-TAD spaces. C-walks that couple 2–4 TADs indicate stochastic associations between transcriptionally active, early replicating loci. Targeted analysis of thousands of 3-walks anchored at highly expressed genes support pairwise, rather than hub-like, chromosomal topology at active loci. Polycomb-repressed Hox domains are shown by the same approach to enrich for synergistic hubs. Together, the data indicate that chromosomal territories, TADs, and intra-TAD loops are primarily driven by nested, possibly dynamic, pairwise contacts.

  • Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals

  • The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGFβ, JAK/STAT and senescence signalling. Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.

  • Designed proteins induce the formation of nanocage-containing extracellular vesicles

  • Complex biological processes are often performed by self-organizing nanostructures comprising multiple classes of macromolecules, such as ribosomes (proteins and RNA) or enveloped viruses (proteins, nucleic acids and lipids). Approaches have been developed for designing self-assembling structures consisting of either nucleic acids or proteins, but strategies for engineering hybrid biological materials are only beginning to emerge. Here we describe the design of self-assembling protein nanocages that direct their own release from human cells inside small vesicles in a manner that resembles some viruses. We refer to these hybrid biomaterials as‘enveloped protein nanocages’ (EPNs). Robust EPN biogenesis requires protein sequence elements that encode three distinct functions: membrane binding, self-assembly, and recruitment of the endosomal sorting complexes required for transport (ESCRT) machinery. A variety of synthetic proteins withthese functional elements induce EPN biogenesis, highlighting the modularity and generality of the design strategy. Biochemical analyses and cryo-electron microscopy reveal that one design, EPN-01, comprises small (~100 nm) vesicles containing multiple protein nanocages that closely match the structure of the designed 60-subunit self-assembling scaffold. EPNs that incorporate the vesicular stomatitis viral glycoprotein can fuse with target cells and deliver their contents, thereby transferring cargoes from one cell to another. These results show how proteins can be programmed to direct the formation of hybrid biological materials that perform complex tasks, and establish EPNs as a class of designed, modular, genetically-encoded nanomaterials that can transfer molecules between cells.

  • Corrigendum: Lens regeneration using endogenous stem cells with gain of visual function

  • Safeguarding pollinators and their values to human well-being

  • Wild and managed pollinators are threatened by pressures such as environmental changes and pesticides, leading to risks for pollinator-dependent crop production, meaning more research and better policies are needed to safeguard pollinators and their services.

  • Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis

  • Platelet-derived growth factor receptorα (PDGFRα) exhibits divergent effects in skeletal muscle. At physiological levels, signalling through this receptor promotes muscle development in growing embryos and angiogenesis in regenerating adult muscle. However, both increased PDGF ligand abundance and enhanced PDGFRα pathway activity cause pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFRα in fibrosis, little is known about the cells through which this pathway acts. Here we show in mice that PDGFRα signalling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of Pdgfra with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signalling and to prevent FAP over-activation. Moreover, increasing the expression of this isoform limits fibrosis in vivo in mice, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem-cell populations.

  • Extensive degeneracy, Coulomb phase and magnetic monopoles in artificial square ice

  • Artificial spin-ice systems are lithographically patterned arrangements of interacting magnetic nanostructures that were introduced as way of investigating the effects of geometric frustration in a controlled manner. This approach has enabled unconventional states of matter to be visualized directly in real space, and has triggered research at the frontier between nanomagnetism, statistical thermodynamics and condensed matter physics. Despite efforts to create an artificial realization of the square-ice model—a two-dimensional geometrically frustrated spin-ice system defined on a square lattice—no simple geometry based on arrays of nanomagnets has successfully captured the macroscopically degenerate ground-state manifold of the model. Instead, square lattices of nanomagnets are characterized by a magnetically ordered ground state that consists of local loop configurations with alternating chirality. Here we show that all of the characteristics of the square-ice model are observed in an artificial square-ice system that consists of two sublattices of nanomagnets that are vertically separated by a small distance. The spin configurations we image after demagnetizing our arrays reveal unambiguous signatures of a Coulomb phase and algebraic spin-spin correlations, which are characterized by the presence of ‘pinch’ points in the associated magnetic structure factor. Local excitations—the classical analogues of magnetic monopoles—are free to evolve in an extensively degenerate, divergence-free vacuum. We thus provide a protocol that could be used to investigate collective magnetic phenomena, including Coulomb phases and the physics of ice-like materials.

  • Redefining the invertebrate RNA virosphere

  • Profiling the total RNA of 220 invertebrate species leads to the discovery of almost 1,500 new species of RNA virus, revealing that the RNA virosphere is much more diverse than was previously thought.

  • Sub-ice-shelf sediments record history of twentieth-century retreat of Pine Island Glacier

  • The West Antarctic Ice Sheet is one of the largest potential sources of rising sea levels. Over the past 40 years, glaciers flowing into the Amundsen Sea sector of the ice sheet have thinned at an accelerating rate, and several numerical models suggest that unstable and irreversible retreat of the grounding line—which marks the boundary between grounded ice and floating ice shelf—is underway. Understanding this recent retreat requires a detailed knowledge of grounding-line history, but the locations of the grounding line before the advent of satellite monitoring in the 1990s are poorly dated. In particular, a history of grounding-line retreat is required to understand the relative roles of contemporaneous ocean-forced change and of ongoing glacier response to an earlier perturbation in driving ice-sheet loss. Here we show that the present thinning and retreat of Pine Island Glacier in West Antarctica is part of a climatically forced trend that was triggered in the 1940s. Our conclusions arise from analysis of sediment cores recovered beneath the floating Pine Island Glacier ice shelf, and constrain the date at which the grounding line retreated from a prominent seafloor ridge. We find thatincursion of marine water beyond the crest of this ridge, forming an ocean cavity beneath the ice shelf, occurred in 1945 (±12 years); final ungrounding of the ice shelf from the ridge occurred in 1970 (±4 years). The initial opening of this ocean cavity followed a period of strong warming of West Antarctica, associated with El Niño activity. Thus our results suggest that, even when climate forcing weakened, ice-sheet retreat continued.

  • Corrigendum: The Asian monsoon over the past 640,000 years and ice age terminations

  • Water balance creates a threshold in soil pH at the global scale

  • Soil pH regulates the capacity of soils to store and supply nutrients, and thus contributes substantially to controlling productivity in terrestrial ecosystems. However, soil pH is not an independent regulator of soil fertility—rather, it is ultimately controlled by environmental forcing. In particular, small changes in water balance cause a steep transition from alkaline to acid soils across natural climate gradients. Although the processes governing this threshold in soil pH are well understood, the threshold has notbeen quantified at the global scale, where the influence of climate may be confounded by the effects of topography and mineralogy. Here we evaluate the global relationship between water balance and soil pH by extracting a spatially random sample (n = 20,000) from an extensive compilation of 60,291 soil pH measurements. We show that there is an abrupt transition from alkaline to acid soil pH that occurs at the point where mean annual precipitation begins to exceed mean annual potential evapotranspiration. We evaluate deviations from this global pattern, showing that they may result from seasonality, climate history, erosion and mineralogy. These results demonstrate that climate creates a nonlinear pattern in soil solution chemistry at the global scale; they also reveal conditions under which soils maintain pH out of equilibrium with modern climate.

  • Structure of photosystem II and substrate binding at room temperature

  • Light-induced oxidation of water by photosystem II (PS II) in plants, algae and cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a membrane-bound multi-subunit pigment protein complex, couples the one-electron photochemistry at the reaction centre with the four-electron redox chemistry of water oxidation at the Mn4CaO5 cluster in the oxygen-evolving complex (OEC). Under illumination, the OEC cycles through five intermediate S-states (S0 to S4), in which S1 is the dark-stable state and S3 is the last semi-stable state before O–O bond formation and O2 evolution. A detailed understanding of the O–O bond formation mechanism remains a challenge, and will require elucidation of both the structures of the OEC in the different S-states and the binding of the two substrate waters to the catalytic site. Here we report the use of femtosecond pulses from an X-ray free electron laser (XFEL) to obtain damage-free, room temperature structures of dark-adapted (S1), two-flash illuminated (2F; S3-enriched), and ammonia-bound two-flash illuminated (2F-NH3; S3-enriched) PS II. Although the recent 1.95 Å resolution structure of PS II at cryogenic temperature using an XFEL provided a damage-free view of the S1 state, measurements at room temperature are required to study the structural landscape of proteins under functional conditions, and also for in situ advancement of the S-states. To investigate the water-binding site(s), ammonia, a water analogue, has been used as a marker, as it binds to the Mn4CaO5 cluster in the S2 and S3 states. Since the ammonia-bound OEC is active, the ammonia-binding Mn site is not a substrate water site. This approach, together with a comparison of the native dark and 2F states, is usedto discriminate between proposed O–O bond formation mechanisms.

  • Addendum: REST and stress resistance in ageing and Alzheimer’s disease

  • Erratum: A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns

  • Structure of RNA polymerase I transcribing ribosomal DNA genes

  • RNA polymerase I (Pol I) is a highly processive enzyme that transcribes ribosomal DNA (rDNA) and regulates growth of eukaryotic cells. Crystal structures of free Pol I from the yeast Saccharomyces cerevisiae have revealed dimers of the enzyme stabilized by a‘connector’ element and an expanded cleft containing the active centre in an inactive conformation. The central bridge helix was unfolded and a Pol-I-specific ‘expander’ element occupied the DNA-template-binding site. The structure of Pol I in its active transcribing conformation has yet tobe determined, whereas structures of Pol II and Pol III have been solved with bound DNA template and RNA transcript. Here we report structures of active transcribing Pol I from yeast solved by two different cryo-electron microscopy approaches. A single-particle structure at 3.8 Å resolution reveals a contracted active centre cleft with bound DNA and RNA, and a narrowed pore beneath the active site that no longer holds the RNA-cleavage-stimulating domain of subunit A12.2. A structure at 29 Å resolution that was determined from cryo-electron tomograms of Pol I enzymes transcribing cellular rDNA confirms contraction of the cleft and reveals that incoming and exiting rDNA enclose an angle of around 150°. The structures suggest a model for the regulation of transcription elongation in which contracted and expanded polymerase conformations are associated with active and inactive states, respectively.

  • Dynamics of a seafloor-spreading episode at the East Pacific Rise

  • Seafloor spreading is largely unobserved because 98 per cent of the global mid-ocean-ridge system is below the ocean surface. Our understanding of the dynamic processes that control seafloor spreading is thus inferred largely from geophysical observations of spreading events on land at Afar in East Africa and Iceland. However, these are slow-spreading centres influenced by mantle plumes. The roles of magma pressure and tectonic stress in the development of seafloor spreading are still unclear. Here we use seismic observations to show that the most recent eruption at the fast-spreading East Pacific Rise just North of the Equator initiated at a melt-rich segment about 5 kilometres long. The change in static stress then promoted almost-concurrent rupturing along at least 35 kilometres of the ridge axis, where tectonic stress had built up to a critical level, triggering magma movement. The location of impulsive seismic events indicative of lava reaching the seafloor suggests that lava subsequently erupted from multiple isolated magma lenses (reservoir chambers) with variable magma ascent rates, mostly within 48 hours. Therefore, even at magmatically robust fast-spreading ridges, a substantial portion of the spreading may be due to tectonic stress building up to a critical level rather than magma overpressure in the underlying magma lenses.

  • Broadening not strengthening of the Agulhas Current since the early 1990s

  • Western boundary currents—such as the Agulhas Current in the Indian Ocean—carry heat poleward, moderating Earth’s climate and fuelling the mid-latitude storm tracks. They could exacerbate or mitigate warming and extreme weather events in the future, depending on their response to anthropogenic climate change. Climatemodels show an ongoing poleward expansion and intensification of the global wind systems, most robustly in the Southern Hemisphere, and linear dynamical theory suggests that western boundary currents will intensify and shift poleward as a result. Observational evidence of such changes comes from accelerated warming and air–sea heat flux rates within all western boundary currents, which are two or three times faster than global mean rates. Here we show that, despite these expectations, the Agulhas Current has not intensified since the early 1990s. Instead, we find that it has broadened as a result of more eddy activity. Recent analyses of other western boundary currents—the Kuroshio and East Australia currents—hint at similar trends. These results indicate that intensifying winds may be increasing the eddy kinetic energy of boundary currents, rather than their mean flow. This couldact to decrease poleward heat transport and increase cross-frontal exchange of nutrients and pollutants between the coastal ocean and the deep ocean. Sustained in situ measurements are needed to properly understand the role of these current systems in a changing climate.

  • Erratum: Kamakura replies

  • Corrigendum: Synergistic, ultrafast mass storage and removal in artificial mixed conductors

  • Erratum: Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection

  • Particle physics: Search for neutrinoless double-β decay

  • Neutrinos are much lighter than the other constituents of matter. One explanation for this could be that neutrinos are their own antiparticles and belong to a new class of 'Majorana' particle. An experiment sets strong constraints on this scenario.

  • Human migration: Climate and the peopling of the world

  • The human dispersal out of Africa that populated the world was probably paced by climate changes. This is the inference drawn from computer modelling of climate variability during the time of early human migration.

  • Cancer: Acidic shield puts a chink in p53's armour

  • Underactivity of the transcription factor p53 can lead to tumour development. The discovery that the SET protein binds to and inhibits p53 points to a way to unleash the tumour suppressor's activity.

  • Evolutionary biology: To mimicry and back again

  • Deadly coral snakes warn predators through striking red-black banding. New data confirm that many harmless snakes have evolved to resemble coral snakes, and suggest that the evolution of this Batesian mimicry is not always a one-way street.

  • Addendum

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