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Table of Contents for this page:

  • Current Issue
  • Advanced Online Publications Articles

  • Current Issue of Nature

    Nature - Issue - science feeds

  • Young researchers thrive in life after academia

  • Alternative career paths should be celebrated, not seen as a compromise.

  • The maximum climate ambition needs a firm research backing

  • We need to know what the 1.5°C warming target will involve — even if we don’t reach it.

  • The challenges facing Habitat III

  • United Nations conference on cities needs to set goals for the next 20 years.

  • Encourage governments to heed scientific advice

  • To stop evidence-based policy losing its clout, researchers need to engage with policymakers and understand their needs, says Bill Colglazier.

  • Glaciology: Greenland ice loss underestimated

  • Greenland's glaciers could be shrinking more in response to climate warming than scientists had thought.Shfaqat Khan of the Technical University of Denmark in Lyngby and his colleagues used data from a network of Global Positioning System stations across Greenland (pictured) to measure the rise

  • Biotechnology: Portable way to make proteins

  • Freeze-dried pellets of cellular proteins can be mixed with DNA sequences to produce vaccines, antibodies and other therapeutics without the need for specialized equipment.Engineered living cells are commonly used to mass-produce drugs, but the techniques involved are hard to perform in remote areas. To

  • Epigenetics: CRISPR edits gene methylation

  • The CRISPR gene-editing tool has been modified so that it can add or remove methyl groups at specific positions on DNA, allowing researchers to test how such changes affect gene expression.DNA methylation helps to regulate gene expression, but its role at specific sites has

  • Stem cells: Targeting pain of spinal-cord injury

  • Neurons derived from human embryonic stem cells can reduce pain and other effects of spinal-cord injury in mice.Persistent nerve pain and loss of bladder control often follow spinal-cord injury, and may be linked to reduced signalling by the inhibitory neurotransmitter GABA. Thomas Fandel and

  • Materials: Graphene jiggles up and down

  • Nanometre-scale measurements have revealed, with record precision, how atom-thick layers of carbon called graphene vibrate vertically.Paul Thibado of the University of Arkansas in Fayetteville and his colleagues used a scanning tunnelling microscope to study how a free-standing sheet of graphene moves owing to random

  • Agriculture: Maize engineered to kill pest

  • A bacterial protein protects maize (corn) from a major insect pest that has grown resistant to other insecticides.The larvae of western corn rootworm feed on maize roots, and cause substantial crop losses across North America and Europe. Transgenic 'Bt' maize plants expressing insecticidal proteins

  • Astronomy: Early star-forming gas found

  • Astronomers have identified distant gas-rich galaxies that probably caused the Universe's rate of star formation to peak some 10 billion years ago.Several teams used the Atacama Large Millimeter/submillimeter Array (ALMA) telescope in Chile to probe a well-studied patch of sky called the 'Hubble Ultra

  • Neuroscience: Ants get addicted to morphine

  • Ants get hooked on morphine much like humans do, showing similar changes in behaviour and brain chemistry.Until now, only mammals have been shown to seek out addictive drugs in the absence of a concurrent natural reward such as sugar. Brian Entler, Timothy Cannon and

  • Computer science: Ancient scroll virtually unrolled

  • Researchers have revealed the hidden contents of a fragile and damaged biblical scroll, thanks to computer scanning and imaging techniques.The En-Gedi scroll dates back to at least the fourth century AD— the oldest Hebrew scroll found, other than the Dead Sea Scrolls

  • Ecology: Rats and cats drive extinctions

  • Non-native predatory mammals such as cats and rats can wreak havoc on native animal populations, especially on islands.Tim Doherty of Deakin University in Melbourne, Australia, and his colleagues studied the International Union for Conservation of Nature (IUCN) Red List of threatened species. They found

  • African elephants, forensic science and China’s gene bank

  • The week in science: 23–29 September

  • Daring Chinese telescope is poised to transform astronomy

  • Construction of the Five-hundred-meter Aperture Spherical Radio Telescope (FAST) is complete, but debugging has only just begun.

  • Facebook couple commits $3 billion to cure disease

  • Chan Zuckerberg Initiative aims to have major impact by 2100.

  • Cuban crocodiles pose conservation conundrum

  • Genetic analyses of endangered animals reveal high level of interbreeding with hardier American species.

  • Worldwide brain-mapping project sparks excitement— and concern

  • Worries include how to coordinate research programmes and resources from different countries.

  • Solar on the steppe: Ukraine embraces renewables revolution

  • Former Soviet nation bids for independence from Russian fossil fuels.

  • Zimbabwean scientists fight to preserve national academy

  • Research struggles in a country in economic free-fall.

  • Can Cuban science go global?

  • Tensions between Cuba and the United States are easing. But researchers still struggle to join the scientific world.

  • Boost resilience of small and mid-sized cities

  • Smaller settlements are growing faster than megacities— and they need more protection from extreme events, write Joern Birkmann and colleagues.

  • Where to put the next billion people

  • Richard T. T. Forman and Jianguo Wu call for global and regional approaches to urban planning.

  • Give cities a seat at the top table

  • Building more strategic links between urban innovation and global governance will help to tackle today's grand challenges, argues Michele Acuto.

  • Cities: Humanizing the urban fabric

  • Austin Williams examines two books that probe the dynamic relationship between people and city.

  • Books in brief

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

  • Physics: Finding the time

  • Andrew Jaffe takes the measure of two books on the tangled concept of the temporal.

  • Food systems: Nourish as well as feed the world

  • The report released last week by the Global Panel on Agriculture and Food Systems for Nutrition warns that only a response comparable in scale and commitment to that directed against HIV/AIDS and malaria will be sufficient to meet the challenge of changing food systems (see

  • Species loss: diverse takes on biodiversity

  • Sean Maxwell and colleagues argue that agriculture is one of the greatest enemies of biodiversity— yet agriculture itself depends on biodiversity (Nature536, 143–145; 10.1038/536143a2016). To make sense of this, we need to recognize that perspectives on

  • Species loss: a crude view of climate

  • We contend that Sean Maxwell and colleagues' analysis of risk factors for biodiversity loss should have included a more nuanced view of climate change (Nature536, 143–145; 10.1038/536143a2016) .For example, the authors seem to rely too much

  • Species loss: climate plan saves only trees

  • We agree that the challenge of protecting biodiversity— to be considered at the upcoming Conference of the Parties to the Convention on Biological Diversity — must not be eclipsed by climate-change concerns (see S.Maxwellet al. Nature536, 143–145

  • Meteorology: Mobile networks aid weather monitoring

  • Competition over the bandwidths used by mobile phones and time-critical weather transmissions is only part of the story (see Nature535, 208–209; 10.1038/535208a2016). In fact, mobile networks are themselves becoming an important tool for monitoring the weather.Because weather

  • Reproducibility: Seek out stronger science

  • Want to learn how to design an experiment or analyse data? Training is there if you look.

  • The sixth circle

  • How to connect with history.

  • The dark universe

  • Dark matter: What's the matter?

  • The leading theory of dark matter is running out of room to hide.

  • Revealing the unseen Universe

  • Astronomy is entering an era in which gravitational waves and neutrinos will be used to complement existing techniques and to uncover the hidden features of our Universe.

  • Qaamp;A: George Smoot

  • George Smoot shared the 2006 Nobel Prize in Physics for the discovery of small temperature variations in the cosmic microwave background radiation, providing support for Big Bang theory. Smoot spoke to Nature about last year's big cosmological discovery, gravitational waves.

  • Dark energy: Staring into darkness

  • The path to understanding dark energy begins with a single question: has it always been the same throughout the history of the Universe?

  • Qaamp;A: Brian Schmidt

  • In 1998, Brian Schmidt discovered that, contrary to expectations, the expansion of the Universe is accelerating. The discovery won him a share of the 2011 Nobel Prize in Physics and launched the search to uncover the nature of dark energy.

  • The dark universe: 4 big questions

  • Scientists have theories about dark matter and dark energy— and some observations — but both are poorly understood. Here are four of their biggest questions.

  • Correction

  • The News Feature‘Chemistry on the fast track’ (Nature537, 156–158; 2016) implied that birth defects were definitely caused by one chiral configuration of thalidomide, but the actual mechanism remains unclear.

  • Plant science: Hybrid vigour characterized

  • Crossing different plant varieties to improve yield and fertility is common practice. A dissection of the genomic architecture that underlies such hybrid vigour might help to inform future crop-improvement strategies. See Article p.629

  • Imaging techniques: MRI illuminated byγ-rays

  • A technique that combines magnetic resonance with nuclear medicine has been used to image the distribution of a radioactive tracer, potentially opening up a powerful and innovative approach to medical imaging. See Letter p.652

  • Microbiology: The bacterial cell wall takes centre stage

  • An unexpected function has been assigned to part of the molecular machinery that synthesizes the bacterial cell wall— a dramatic shift in our understanding that may have major implications for antibiotic development. See Article p.634

  • Food security: A collaboration worth its weight in grain

  • Interventions to improve crop yields in rural China through collaboration between researchers and farmers illustrate how the goal of increasing global food production can be approached locally. See Letter p.671

  • Biogeochemistry: Long-term effects of permafrost thaw

  • Carbon emissions from the Arctic tundra could increase drastically as global warming thaws permafrost. Clues now obtained about the long-term effects of such thawing on carbon dioxide emissions highlight the need for more data.

  • Physiology: Forecast for water balance

  • Disturbances in internal water equilibrium can be debilitating for mammals. Two studies pinpoint areas of the mouse brain that respond to and anticipate thirst, preserving systematic fluid regulation. See Letters p.680 aamp; p.685

  • Chemistry: Small molecular replicators go organic

  • The emergence of complex, dynamic molecular behaviour might have had a role in the origin of life. Such behaviour has now been seen in a reaction network involving small, organic, self-replicating molecules of biological relevance. See Letter p.656

  • Genomic architecture of heterosis for yield traits in rice

  • Increasing grain yield is a long-term goal in crop breeding to meet the demand for global food security. Heterosis, when a hybrid shows higher performance for a trait than both parents, offers an important strategy for crop breeding. To examine the genetic basis of heterosis

  • SEDS proteins are a widespread family of bacterial cell wall polymerases

  • Elongation of rod-shaped bacteria is mediated by a dynamic peptidoglycan-synthetizing machinery called the Rod complex. Here we report that, in Bacillus subtilis, this complex is functional in the absence of all known peptidoglycan polymerases. Cells lacking these enzymes survive by inducing an envelope stress

  • The architecture of the mammalian respirasome

  • The respiratory chain complexes I, III and IV (CI, CIII and CIV) are present in the bacterial membrane or the inner mitochondrial membrane and have a role of transferring electrons and establishing the proton gradient for ATP synthesis by complex V. The respiratory chain complexes

  • The architecture of respiratory supercomplexes

  • Mitochondrial electron transport chain complexes are organized into supercomplexes responsible for carrying out cellular respiration. Here we present three architectures of mammalian (ovine) supercomplexes determined by cryo-electron microscopy. We identify two distinct arrangements of supercomplex CICIII2CIV (the respirasome)—a major ‘tight’ form and a

  • The awakening of a classical nova from hibernation

  • Cataclysmic variable stars—novae, dwarf novae, and nova-likes—are close binary systems consisting of a white dwarf star (the primary) that is accreting matter from a low-mass companion star (the secondary). From time to time such systems undergo large-amplitude brightenings. The most spectacular eruptions, with a ten-thousandfold increase in brightness, occur in classical novae and are caused by a thermonuclear runaway on the surface of the white dwarf. Such eruptions are thought to recur on timescales of ten thousand to a million years. In between, the system’s properties depend primarily on the mass-transfer rate: if it is lower than a billionth of a solar mass per year, the accretion becomes unstable and the matter is dumped onto the white dwarf during quasi-periodic dwarf nova outbursts. The hibernation hypothesis predicts that nova eruptions strongly affect the mass-transfer rate in the binary, keeping it high for centuries after the event. Subsequently, the mass-transfer rate should significantly decrease for a thousand to a million years, starting the hibernation phase. After that the nova awakes again—with accretion returning to the pre-eruption level and leading to a new nova explosion. The hibernation model predicts cyclical evolution of cataclysmic variables through phases of high and low mass-transfer. The theory gained some support from the discovery of ancient nova shells around the dwarf novae Z Camelopardalis and AT Cancri, but direct evidence for considerable mass-transfer changes prior, during and after nova eruptions has not hitherto been found. Here we report long-term observations of the classical nova V1213 Cen (Nova Centauri 2009) covering its pre- and post-eruption phases and precisely documenting its evolution. Within the six years before the explosion, the system revealed dwarf nova outbursts indicative of a low mass-transfer rate. The post-nova is two orders of magnitude brighter than the pre-nova at minimum light with no trace of dwarf nova behaviour, implying that the mass-transfer rate increased considerably as a result of the nova explosion.

  • A method for imaging and spectroscopy usingγ-rays and magnetic resonance

  • Magnetic resonance imaging (MRI) provides fine spatial resolution, spectral sensitivity and a rich variety of contrast mechanisms for diagnostic medical applications. Nuclear imaging usingγ-ray cameras offers the benefits of using small quantities of radioactive tracers that seek specific targets of interest within the body. Here we describe an imaging and spectroscopic modality that combines favourable aspects of both approaches. Spatial information is encoded into the spin orientations of tiny amounts of a polarized radioactive tracer using pulses of both radio-frequency electromagnetic radiation and magnetic-field gradients, as in MRI. However, rather than detecting weak radio-frequency signals, imaging information is obtained through the detection of γ-rays. A single γ-ray detector can be used to acquire an image; no γ-ray camera is needed. We demonstrate the feasibility of our technique by producing images and spectra from a glass cell containing only about 4 × 1013 atoms (about 1 millicurie) of the metastable isomer 131mXe that were polarized using the laser technique of spin-exchange optical pumping. If the cell had instead been filled with water and imaged using conventional MRI, then it would have contained more than 1024 water molecules. The high sensitivity of our modality expands the breadth of applications of magnetic resonance, and could leadto a new class of radioactive tracers.

  • Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions

  • Networks of organic chemical reactions are important in life and probably played a central part in its origin. Network dynamics regulate cell division, circadian rhythms, nerve impulses and chemotaxis, and guide the development of organisms. Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics such as spontaneous pattern formation, bistability and periodic oscillations, the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood. Here we describe a network of biologically relevant organic reactions (amide formation, thiolate–thioester exchange, thiolate–disulfide interchange and conjugate addition) that displays bistability and oscillations in the concentrations of organic thiols and amides. Oscillations arise from the interaction between three subcomponents of the network: an autocatalytic cycle that generates thiols and amides from thioesters and dialkyl disulfides; a trigger that controls autocatalytic growth; and inhibitory processes that remove activating thiol species that are produced during the autocatalytic cycle. In contrast to previous studies that have demonstrated oscillations and bistability using highly evolved biomolecules (enzymes and DNA) or inorganic molecules of questionable biochemical relevance (for example, those used in Belousov–Zhabotinskii-type reactions), the organic molecules we use are relevant to metabolism and similar to those that might have existed on the early Earth.By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed. Modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks and of synthetic self-regulating and evolving chemical systems.

  • Directed evolution of artificial metalloenzymes for in vivo metathesis

  • The field of biocatalysis has advanced from harnessing natural enzymes to using directed evolution to obtain new biocatalysts with tailor-made functions. Several tools have recently been developed to expand the natural enzymatic repertoire with abiotic reactions. For example, artificial metalloenzymes, which combine the versatile reaction scope of transition metals with the beneficial catalytic features of enzymes, offer an attractive means to engineer new reactions. Three complementary strategies exist: repurposing natural metalloenzymes for abiotic transformations; in silico metalloenzyme (re-)design; and incorporation of abiotic cofactors into proteins. The third strategy offers the opportunity to design a wide variety of artificial metalloenzymes for non-natural reactions. However, many metal cofactors are inhibited by cellular components and therefore require purification of the scaffold protein. This limits the throughput of genetic optimization schemes applied to artificial metalloenzymes and their applicability in vivo to expand natural metabolism. Here we report the compartmentalization and in vivo evolution of an artificial metalloenzyme for olefin metathesis, which represents an archetypal organometallic reaction without equivalent in nature. Building on previous work on an artificial metallohydrolase, we exploit the periplasm of Escherichia coli as a reaction compartment for the‘metathase’ because it offers an auspicious environment for artificial metalloenzymes, mainly owing to low concentrations of inhibitors such as glutathione, which has recently been identified as a major inhibitor. This strategy facilitated the assembly of a functional metathase in vivo and its directed evolution with substantially increased throughput compared to conventional approaches that rely on purified protein variants. The evolved metathase compares favourably with commercial catalysts, shows activity for different metathesis substrates and can be further evolved in different directions by adjusting the workflow. Our results represent the systematic implementation and evolution of an artificial metalloenzyme that catalyses an abiotic reaction in vivo, with potential applications in, for example, non-natural metabolism.

  • Key new pieces of the HIMU puzzle from olivines and diamond inclusions

  • Mantle melting, which leads to the formation of oceanic and continental crust, together with crust recycling through plate tectonics, are the primary processes that drive the chemical differentiation of the silicate Earth. The present-day mantle, as sampled by oceanic basalts, shows large chemical and isotopic variability bounded by a few end-member compositions. Among these, the HIMU end-member (having a high U/Pb ratio,μ) has been generally considered to represent subducted/recycled basaltic oceanic crust. However, this concept has been challenged by recent studies of the mantle source of HIMU magmas. For example, analyses of olivine phenocrysts in HIMU lavas indicate derivation from the partial melting of peridotite, rather than from the pyroxenitic remnants of recycled oceanic basalt. Here we report data that elucidate the source of these lavas: high-precision trace-element analyses of olivine phenocrysts point to peridotite that has been metasomatized by carbonatite fluids. Moreover, similarities in thetrace-element patterns of carbonatitic melt inclusions in diamonds and HIMU lavas indicate that the metasomatism occurred in the subcontinental lithospheric mantle, fused to the base of the continental crust and isolated from mantle convection. Taking into account evidence from sulfur isotope data for Archean to early Proterozoic surface material in the deep HIMU mantle source, a multi-stage evolution is revealed for the HIMU end-member, spanning more than half of Earth’s history. Before entrainment in the convecting mantle, storage in a boundary layer, upwelling as a mantle plume and partial melting to become ocean island basalt, the HIMU source formed as Archean–early Proterozoic subduction-related carbonatite-metasomatized subcontinental lithospheric mantle.

  • Closing yield gaps in China by empowering smallholder farmers

  • Sustainably feeding the world’s growing population is a challenge, and closing yield gaps (that is, differences between farmers’ yields and what are attainable for a given region) is a vital strategy to address this challenge. The magnitude of yield gaps is particularly large in developing countries where smallholder farming dominates the agricultural landscape. Many factors and constraints interact to limit yields, and progress in problem-solving to bring about changes at the ground level is rare. Here we present an innovative approach for enabling smallholders to achieve yield and economic gains sustainably via theScience and Technology Backyard (STB) platform. STB involves agricultural scientists living in villages among farmers, advancing participatory innovation and technology transfer, and garnering public and private support. We identified multifaceted yield-limiting factors involving agronomic, infrastructural, and socioeconomic conditions. When these limitations and farmers’ concerns were addressed, the farmers adopted recommended management practices, thereby improving production outcomes. In one region in China, the five-year average yield increased from 67.9% of the attainable level to 97.0% among 71 leading farmers, and from 62.8% to 79.6% countywide (93,074 households); this was accompanied by resource and economic benefits.

  • CHD8 haploinsufficiency results in autistic-like phenotypes in mice

  • Autism spectrum disorder (ASD) comprises a range of neurodevelopmental disorders characterized by deficits in social interaction and communication as well as by restricted and repetitive behaviours. ASD has a strong genetic component with high heritability. Exome sequencing analysis has recently identified many de novo mutations in a variety of genes in individuals with ASD, with CHD8, a gene encoding a chromatin remodeller, being most frequently affected. Whether CHD8 mutations are causative for ASD and how they might establish ASD traits have remained unknown. Here we show that mice heterozygous for Chd8 mutations manifest ASD-like behavioural characteristics including increased anxiety, repetitive behaviour, and altered social behaviour. CHD8 haploinsufficiency did not result in prominent changes in the expression of a few specific genes but instead gave rise to small but global changes in gene expression in the mouse brain, reminiscent of those in the brains of patients with ASD. Gene set enrichment analysis revealed that neurodevelopment was delayed in the mutant mouse embryos. Furthermore, reduced expression of CHD8 was associated with abnormal activation of RE-1 silencing transcription factor (REST), which suppresses the transcription of many neuronal genes. REST activation was also observed in the brains of humans with ASD, and CHD8 was found to interact physically with REST in the mouse brain. Our results are thus consistent with the notion that CHD8 haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis probably resulting from a delay in neurodevelopment.

  • Thirst neurons anticipate the homeostatic consequences of eating and drinking

  • Thirst motivates animals to drink in order to maintain fluid balance. Thirst has conventionally been viewed as a homeostatic response to changes in blood volume or tonicity. However, most drinking behaviour is regulated too rapidly to be controlled by blood composition directly, and instead seems to anticipate homeostatic imbalances before they arise. How this is achieved remains unknown. Here we reveal an unexpected role for the subfornical organ (SFO) in the anticipatory regulation of thirst in mice. By monitoring deep-brain calcium dynamics, we show that thirst-promoting SFO neurons respond to inputs from the oral cavity during eating and drinking and then integrate these inputs with information about the composition of the blood. This integration allows SFO neurons to predict how ongoing food and water consumption will alter fluid balance in the future and then to adjust behaviour pre-emptively. Complementary optogenetic manipulations show that this anticipatory modulation is necessary for drinking in several contexts. These findings provide a neural mechanism to explain longstanding behavioural observations, including the prevalence of drinking during meals, the rapid satiation of thirst, and the fact that oral cooling is thirst-quenching.

  • Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep

  • Circadian rhythms have evolved to anticipate and adapt animals to the constraints of the earth’s 24-hour light cycle. Although the molecular processes that establish periodicity in clock neurons of the suprachiasmatic nucleus (SCN) are well understood, the mechanisms by which axonal projections from the central clock drive behavioural rhythms are unknown. Here we show that the sleep period in mice (Zeitgeber time, ZT0–12) is preceded by an increase in water intake promoted entirely by the central clock, and not motivated by physiological need. Mice denied this surge experienced significant dehydration near the end of the sleep period, indicating that this water intake contributes to the maintenance of overnight hydromineral balance. Furthermore, this effect relies specifically on the activity of SCN vasopressin (VP) neurons that project to thirst neurons in the OVLT (organum vasculosum lamina terminalis), where VP is released as a neurotransmitter. SCN VP neurons become electrically active during the anticipatory period (ZT21.5–23.5), and depolarize and excite OVLT neurons through the activation of postsynaptic VP V1a receptors and downstream non-selective cation channels. Optogenetic induction of VP release before the anticipatory period (basal period; ZT19.5–21.5) excited OVLT neurons and prompted a surge in water intake. Conversely, optogenetic inhibition of VP release during the anticipatory period inhibited the firing of OVLT neurons and prevented the corresponding increase in water intake. Our findings reveal the existence of anticipatory thirst, and demonstrate this behaviour to be driven by excitatory peptidergic neurotransmission mediated by VP release from central clock neurons.

  • Ecogenomics and potential biogeochemical impacts of globally abundant ocean viruses

  • Ocean microbes drive biogeochemical cycling on a global scale. However, this cycling is constrained by viruses that affect community composition, metabolic activity, and evolutionary trajectories. Owing to challenges with the sampling and cultivation of viruses, genome-level viral diversity remains poorly described and grossly understudied, with less than 1% of observed surface-ocean viruses known. Here we assemble complete genomes and large genomic fragments from both surface- and deep-ocean viruses sampled during the Tara Oceans and Malaspina research expeditions, and analyse the resulting‘global ocean virome’ dataset to present a global map of abundant, double-stranded DNA viruses complete with genomic and ecological contexts. A total of 15,222 epipelagic and mesopelagic viral populations were identified, comprising 867 viral clusters (defined as approximately genus-level groups). This roughly triples the number of known ocean viral populations and doubles the number of candidate bacterial and archaeal virus genera, providing a near-complete sampling of epipelagic communities at both the population and viral-cluster level. We found that 38 of the 867 viral clusters were locally or globally abundant, together accounting for nearly half of the viral populations in any global ocean virome sample. While two-thirds of these clusters represent newly described viruses lacking any cultivated representative, most could be computationally linked to dominant, ecologically relevant microbial hosts. Moreover, we identified 243 viral-encoded auxiliary metabolic genes, of which only 95 were previously known. Deeper analyses of four of these auxiliary metabolic genes (dsrC, soxYZ, P-II (also known as glnB) and amoC) revealed that abundant viruses may directly manipulate sulfur and nitrogen cycling throughout the epipelagic ocean. This viral catalog and functional analyses provide a necessary foundation for the meaningful integration of viruses into ecosystem models where they act as key players in nutrient cycling and trophic networks.

  • Rewriting yeast central carbon metabolism for industrial isoprenoid production

  • A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments. Adapting these strains for biosynthesis of other isoprenoids such asβ-farnesene (C15H24), a plant sesquiterpene with versatile industrial applications, is straightforward. However, S. cerevisiae uses a chemically inefficient pathway for isoprenoid biosynthesis, resulting in yield and productivity limitations incompatible with commodity-scale production. Here we use four non-native metabolic reactions to rewire central carbon metabolism in S. cerevisiae, enabling biosynthesis of cytosolic acetyl coenzyme A (acetyl-CoA, the two-carbon isoprenoid precursor) with a reduced ATP requirement, reduced loss of carbon to CO2-emitting reactions, and improved pathway redox balance. We show that strains with rewired central metabolism can devote an identical quantity of sugar to farnesene production as control strains, yet produce 25% more farnesene with that sugar while requiring 75% less oxygen. These changes lower feedstock costs and dramatically increase productivity in industrial fermentations which are by necessity oxygen-constrained. Despite altering key regulatory nodes, engineered strains grow robustly under taxing industrial conditions, maintaining stable yield for two weeks in broth that reaches ggt;15% farnesene by volume. This illustrates that rewiring yeast central metabolism is a viable strategy for cost-effective, large-scale production of acetyl-CoA-derived molecules.

  • Single-cell analysis of mixed-lineage states leading to a binary cell fate choice

  • Delineating hierarchical cellular states, including rare intermediates and the networks of regulatory genes that orchestrate cell-type specification, are continuing challenges for developmental biology. Single-cell RNA sequencing is greatly accelerating such research, given its power to provide comprehensive descriptions of genomic states and their presumptive regulators. Haematopoietic multipotential progenitor cells, as well as bipotential intermediates, manifest mixed-lineage patterns of gene expression at a single-cell level. Such mixed-lineage states may reflect the molecular priming of different developmental potentials by co-expressed alternative-lineage determinants, namely transcription factors. Although a bistable gene regulatory network has been proposed to regulate the specification of either neutrophils or macrophages, the nature of the transition states manifested in vivo, and the underlying dynamics of the cell-fate determinants, have remained elusive. Here we use single-cell RNA sequencing coupled with a new analytic tool, iterative clustering and guide-gene selection, and clonogenic assays to delineate hierarchical genomic and regulatory states that culminate in neutrophil or macrophage specification in mice. We show that this analysis captured prevalent mixed-lineage intermediates that manifested concurrent expression of haematopoietic stem cell/progenitor and myeloid progenitor cell genes. It also revealed rare metastable intermediates that had collapsed the haematopoietic stem cell/progenitor gene expression programme, instead expressing low levels of the myeloid determinants, Irf8 and Gfi1 (refs 9, 10, 11, 12, 13). Genetic perturbations and chromatin immunoprecipitation followed by sequencing revealed Irf8 and Gfi1 as key components of counteracting myeloid-gene-regulatory networks. Combined loss of these two determinants‘trapped’ the metastable intermediate. We propose that mixed-lineage states are obligatory during cell-fate specification, manifest differing frequencies because of their dynamic instability and are dictated by counteracting gene-regulatory networks.

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  • Animal behaviour: Lethal violence deep in the human lineage

  • De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure

  • The structure of the bacterial toxin BinAB, which is used to combat mosquito-borne diseases, reveals pH-sensitive switches and carbohydrate-binding modules that may contribute to the larvicidal function of the toxin.

  • Frizzled proteins are colonic epithelial receptors for C. difficile toxin B

  • Here, a genome-wide CRISPR–Cas9 screen is used to identify the Wnt receptors frizzled as physiologically relevant Clostridium difficile toxin B receptors, providing new therapeutic targets for treating C. difficile infections.

  • The phylogenetic roots of human lethal violence

  • The psychological, sociological and evolutionary roots of conspecific violence in humans are still debated, despite attracting the attention of intellectuals for over two millennia. Here we propose a conceptual approach towards understanding these roots based on the assumption that aggression in mammals, including humans, has a significant phylogenetic component. By compiling sources of mortality from a comprehensive sample of mammals, we assessed the percentage of deaths due to conspecifics and, using phylogenetic comparative tools, predicted this value for humans. The proportion of human deaths phylogenetically predicted to be caused by interpersonal violence stood at 2%. This value was similar to the one phylogenetically inferred for the evolutionary ancestor of primates and apes, indicating that a certain level of lethal violence arises owing to our position within the phylogeny of mammals. It was also similar to the percentage seen in prehistoric bands and tribes, indicating that we were as lethally violent then as common mammalian evolutionary history would predict. However, the level of lethal violence has changed through human history and can be associated with changes in the socio-political organization of human populations. Our study provides a detailed phylogenetic and historical context against which to compare levels of lethal violence observed throughout our history.

  • Autocrine BDNF–TrkB signalling within a single dendritic spine

  • Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are crucial for many forms of neuronal plasticity, including structural long-term potentiation (sLTP), which is a correlate of an animal’s learning. However, it is unknown whether BDNF release and TrkB activation occur during sLTP, and if so, when and where. Here, using a fluorescence resonance energy transfer-based sensor for TrkB and two-photon fluorescence lifetime imaging microscopy, we monitor TrkB activity in single dendritic spines of CA1 pyramidal neurons in cultured murine hippocampal slices. In response to sLTP induction, we find fast (onset llt; 1 min) and sustained (ggt;20 min) activation of TrkB in the stimulated spine that depends on NMDAR (N-methyl-d-aspartate receptor) and CaMKII signalling and on postsynaptically synthesized BDNF. We confirm the presence of postsynaptic BDNF using electron microscopy to localize endogenous BDNF to dendrites and spines of hippocampal CA1 pyramidal neurons. Consistent with these findings, we also show rapid, glutamate-uncaging-evoked, time-locked BDNF release from single dendritic spines using BDNF fused to superecliptic pHluorin. We demonstrate that this postsynaptic BDNF–TrkB signalling pathway is necessary for both structural and functional LTP. Together, these findings reveal a spine-autonomous, autocrine signalling mechanism involving NMDAR–CaMKII-dependent BDNF release from stimulated dendritic spines and subsequent TrkB activation on these same spines that is crucial for structural and functional plasticity.

  • Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity

  • The Rho GTPase proteins Rac1, RhoA and Cdc42 have a central role in regulating the actin cytoskeleton in dendritic spines, thereby exerting control over the structural and functional plasticity of spines and, ultimately, learning and memory. Although previous work has shown that precise spatiotemporal coordination of these GTPases is crucial for some forms of cell morphogenesis, the nature of such coordination during structural spine plasticity is unclear. Here we describe a three-molecule model of structural long-term potentiation (sLTP) of murine dendritic spines, implicating the localized, coincident activation of Rac1, RhoA and Cdc42 as a causal signal of sLTP. This model posits that complete tripartite signal overlap in spines confers sLTP, but that partial overlap primes spines for structural plasticity. By monitoring the spatiotemporal activation patterns of these GTPases during sLTP, we find that such spatiotemporal signal complementation simultaneously explains three integral features of plasticity: the facilitation of plasticity by brain-derived neurotrophic factor (BDNF), the postsynaptic source of which activates Cdc42 and Rac1, but not RhoA; heterosynaptic facilitation of sLTP, which is conveyed by diffusive Rac1 and RhoA activity; and input specificity, which is afforded by spine-restricted Cdc42 activity. Thus, we present a form of biochemical computation in dendrites involving the controlled complementation of three molecules that simultaneously ensures signal specificity and primes the system for plasticity.

  • Genome-wide associations for birth weight and correlations with adult disease

  • Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P llt; 5 × 10−8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = −0.22, P = 5.5 × 10−13), T2D (Rg = −0.27, P = 1.1 × 10−6) and coronary artery disease (Rg = −0.30, P = 6.5 × 10−9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathwayanalyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10−4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

  • XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer

  • The common participation of oncogenic KRAS proteins in many of the most lethal human cancers, together with the ease of detecting somatic KRAS mutant alleles in patient samples, has spurred persistent and intensive efforts to develop drugs that inhibit KRAS activity. However, advances have been hindered by the pervasive inter- and intra-lineage diversity in the targetable mechanisms that underlie KRAS-driven cancers, limited pharmacological accessibility of many candidate synthetic-lethal interactions and the swift emergence of unanticipated resistance mechanisms to otherwise effective targeted therapies. Here we demonstrate the acute and specific cell-autonomous addiction of KRAS-mutant non-small-cell lung cancer cells to receptor-dependent nuclear export. A multi-genomic, data-driven approach, utilizing 106 human non-small-cell lung cancer cell lines, was used to interrogate 4,725 biological processes with 39,760 short interfering RNA pools for those selectively required for the survival of KRAS-mutant cells that harbour a broad spectrum of phenotypic variation. Nuclear transport machinery was the sole process-level discriminator of statistical significance. Chemical perturbation of the nuclear export receptor XPO1 (also known as CRM1), with a clinically available drug, revealed a robust synthetic-lethal interaction with native or engineered oncogenic KRAS both in vitro and in vivo. The primary mechanism underpinning XPO1 inhibitor sensitivity was intolerance to the accumulation of nuclear IκBα (also known as NFKBIA), with consequent inhibition of NFκB transcription factor activity. Intrinsic resistance associated with concurrent FSTL5 mutations was detected and determined to be a consequence of YAP1 activation via a previously unappreciated FSTL5–Hippo pathway regulatory axis. This occurs in approximately 17% of KRAS-mutant lung cancers, and can be overcome with the co-administration of a YAP1–TEAD inhibitor. These findings indicate that clinically available XPO1 inhibitors are a promising therapeutic strategy for a considerable cohort of patients with lung cancer when coupled to genomics-guided patient selection and observation.

  • Atom-at-a-time laser resonance ionization spectroscopy of nobelium

  • Optical spectroscopy of a primordial isotope has traditionally formed the basis for understanding the atomic structure of an element. Such studies have been conducted for most elements and theoretical modelling can be performed to high precision, taking into account relativistic effects that scale approximately as the square of the atomic number. However, for the transfermium elements (those with atomic numbers greater than 100), the atomic structure is experimentally unknown. These radioactive elements are produced in nuclear fusion reactions at rates of only a few atoms per second at most and must be studied immediately following their production, which has so far precluded their optical spectroscopy. Here we report laser resonance ionization spectroscopy of nobelium (No; atomic number 102) in single-atom-at-a-time quantities, in which we identify the ground-state transition 1S01P1. By combining this result with data from an observed Rydberg series, we obtain an upper limit for the ionization potential of nobelium. These accurate results from direct laser excitations of outer-shell electrons cannot be achieved using state-of-the-art relativistic many-body calculations that include quantum electrodynamic effects, owing to large uncertainties in the modelled transition energies of the complex systems under consideration. Our work opens the door to high-precision measurements of various atomic and nuclear properties of elements heavier than nobelium, and motivates future theoretical work.

  • The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila

  • Cancer stem cells (CSCs) may be responsible for tumour dormancy, relapse and the eventual death of most cancer patients. In addition, these cells are usually resistant to cytotoxic conditions. However, very little is known about the biology behind this resistance to therapeutics. Here we investigated stem-cell death in the digestive system of adult Drosophila melanogaster. We found that knockdown of the coat protein complex I (COPI)–Arf79F (also known as Arf1) complex selectively killed normal and transformed stem cells through necrosis, by attenuating the lipolysis pathway, but spared differentiated cells. The dying stem cells were engulfed by neighbouring differentiated cells through a draper–myoblast city–Rac1–basket (also known as JNK)-dependent autophagy pathway. Furthermore, Arf1 inhibitors reduced CSCs in human cancer cell lines. Thus, normal or cancer stem cells may rely primarily on lipid reserves for energy, in such a way that blocking lipolysis starves them to death. This finding may lead to new therapies that could help to eliminate CSCs in human cancers.

  • Projected land photosynthesis constrained by changes in the seasonal cycle of atmospheric CO2

  • Uncertainties in the response of vegetation to rising atmospheric CO2 concentrations contribute to the large spread in projections of future climate change. Climate–carbon cycle models generally agree that elevated atmospheric CO2 concentrations will enhance terrestrial gross primary productivity (GPP). However, the magnitude of this CO2 fertilization effect varies from a 20 per cent to a 60 per cent increase in GPP for a doubling of atmospheric CO2 concentrations in model studies. Here we demonstrate emergent constraints on large-scale CO2 fertilization using observed changes in the amplitude of the atmospheric CO2 seasonal cycle that are thought to be the result of increasing terrestrial GPP. Our comparison of atmospheric CO2 measurements from PointBarrow in Alaska and Cape Kumukahi in Hawaii with historical simulations of the latest climate–carbon cycle models demonstrates that the increase in the amplitude of the CO2 seasonal cycle at both measurement sites is consistent with increasing annual mean GPP, driven in part by climate warming, but with differences in CO2 fertilization controlling the spread among the model trends. As a result, the relationship between the amplitude of the CO2 seasonal cycle and the magnitude of CO2 fertilization of GPP is almost linear across the entire ensemble of models. When combined with the observed trends in the seasonal CO2 amplitude, these relationships lead to consistent emergent constraints on the CO2 fertilization of GPP. Overall, we estimate a GPP increase of 37 ± 9 per cent for high-latitude ecosystems and 32 ± 9 per cent for extratropical ecosystems under a doubling of atmospheric CO2 concentrations on the basis of the Point Barrow and Cape Kumukahi records, respectively.

  • Erratum: Replication fork stability confers chemoresistance in BRCA-deficient cells

  • Corrigendum: An early geodynamo driven by exsolution of mantle components from Earth’s core

  • Corrigendum: Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells

  • Corrigendum: An essential receptor for adeno-associated virus infection

  • Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection

  • Bacterial adaptive immune systems use CRISPRs (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas) proteins for RNA-guided nucleic acid cleavage. Although most prokaryotic adaptive immune systems generally target DNA substrates, type III and VI CRISPR systems direct interference complexes against single-stranded RNA substrates. In type VI systems, the single-subunit C2c2 protein functions as an RNA-guided RNA endonuclease (RNase). How this enzyme acquires mature CRISPR RNAs (crRNAs) that are essential for immune surveillance and how it carries out crRNA-mediated RNA cleavage remain unclear. Here we show that bacterial C2c2 possesses a unique RNase activity responsible for CRISPR RNA maturation that is distinct from its RNA-activated single-stranded RNA degradation activity. These dual RNase functions are chemically and mechanistically different from each other and from the crRNA-processing behaviour of the evolutionarily unrelated CRISPR enzyme Cpf1 (ref. 11). The two RNase activities of C2c2 enable multiplexed processing and loading of guide RNAs that in turn allow sensitive detection of cellular transcripts.

  • A cross-modal genetic framework for the development and plasticity of sensory pathways

  • Modality-specific sensory inputs from individual sense organs are processed in parallel in distinct areas of the neocortex. For each sensory modality, input follows a cortico–thalamo–cortical loop in which a ‘first-order’ exteroceptive thalamic nucleus sends peripheral input to the primary sensory cortex, which projects back to a ‘higher order’ thalamic nucleus that targets a secondary sensory cortex. This conserved circuit motif raises the possibility thatshared genetic programs exist across sensory modalities. Here we report that, despite their association with distinct sensory modalities, first-order nuclei in mice are genetically homologous across somatosensory, visual, and auditory pathways, as are higher order nuclei. We further reveal peripheral input-dependent control over the transcriptional identity and connectivity of first-order nuclei by showing that input ablation leads to induction of higher-order-type transcriptional programs and rewiring of higher-order-directed descending cortical input to deprived first-order nuclei. These findings uncover an input-dependent genetic logic for the design and plasticity of sensory pathways, in which conserved developmental programs lead to conserved circuit motifs across sensory modalities.

  • Enhanced flexoelectric-like response in oxide semiconductors

  • Flexoelectricity is a property of all dielectric materials whereby they polarize in response to deformation gradients such as those produced by bending. Although it is generally thought of as a property of dielectric insulators, insulation is not a formal requirement: in principle, semiconductors can also redistribute their free charge in response to strain gradients. Here we show that bending a semiconductor not only generates a flexoelectric-like response, but that this response can in fact be much larger than in insulators. By doping single crystals of wide-bandgap oxides to increase their conductivity, their effective flexoelectric coefficient was increased by orders of magnitude. This large response can be explained by a barrier-layer mechanism that remains important even at the macroscale, where conventional (insulator) flexoelectricity otherwise tends to be small. Our results open up the possibility of using semiconductors as active ingredients in electromechanical transducer applications.

  • Evolution of global temperature over the past two million years

  • Reconstructions of Earth’s past climate strongly influence our understanding of the dynamics and sensitivity of the climate system. Yet global temperature has been reconstructed for only a few isolated windows of time, and continuous reconstructions across glacial cycles remain elusive. Here I present a spatially weighted proxy reconstruction of global temperature over the past 2 million years estimated from a multi-proxy database of over 20,000 sea surface temperature point reconstructions. Global temperature gradually cooled until roughly 1.2 million years ago and cooling then stalled until the present. The cooling trend probably stalled before the beginning of the mid-Pleistocene transition, and pre-dated the increase in the maximum size of ice sheets around 0.9 million years ago. Thus, global cooling may have been a pre-condition for, but probably is not the sole causal mechanism of, the shift to quasi-100,000-year glacial cycles at the mid-Pleistocene transition. Over the past 800,000 years, polar amplification (the amplification of temperature change at the poles relative to global temperature change) has been stable over time, and global temperature and atmospheric greenhouse gas concentrations have been closely coupled across glacial cycles. A comparison of the new temperature reconstruction with radiative forcing from greenhouse gases estimates an Earth system sensitivity of 9 degrees Celsius (range 7 to 13 degrees Celsius, 95 per cent credible interval) change in global average surface temperature per doubling of atmospheric carbon dioxide over millennium timescales. This result suggests that stabilization at today’s greenhouse gas levels may already commit Earth to an eventual total warming of 5 degrees Celsius (range 3 to 7 degrees Celsius, 95 per cent credible interval) over the next few millennia as ice sheets, vegetation and atmospheric dust continue to respond to global warming.

  • 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.

  • Population genetics: A map of human wanderlust

  • Genetic studies of individuals from geographically diverse human populations provide insights into the dispersal of modern humans across the globe and how geography shaped genomic variation.

  • 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.

  • Structural insight into the role of the Ton complex in energy transduction

  • Structural studies shed light on the function and stoichiometry of the Ton complex, which harnesses the proton motive force across the bacterial inner membrane to transduce energy to the outer membrane.

  • A genomic history of Aboriginal Australia

  • Whole-genome sequence data for 108 individuals representing 28 language groups across Australia and five language groups for Papua New Guinea suggests that Aboriginal Australians and Papuans diverged from Eurasian populations approximately 60–100 thousand years ago, following a single out-of-Africa dispersal and subsequent admixture with archaic populations.

  • The Simons Genome Diversity Project: 300 genomes from 142 diverse populations

  • Deep whole-genome sequencing of 300 individuals from 142 diverse populations provides insights into key population genetic parameters, shows that all modern human ancestry outside of Africa including in Australasians is consistent with descending from a single founding population, and suggests a higher rate of accumulation of mutations in non-Africans compared to Africans since divergence.

  • Genomic analyses inform on migration events during the peopling of Eurasia

  • High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.

  • Late Pleistocene climate drivers of early human migration

  • On the basis of fossil and archaeological data it has been hypothesized that the exodus of Homo sapiens out of Africa and into Eurasia between ~50–120 thousand years ago occurred in several orbitally paced migration episodes. Crossing vegetated pluvial corridors from northeastern Africa into the Arabian Peninsula and the Levant and expanding further into Eurasia, Australia and the Americas, early H. sapiens experienced massive time-varyingclimate and sea level conditions on a variety of timescales. Hitherto it has remained difficult to quantify the effect of glacial- and millennial-scale climate variability on early human dispersal and evolution. Here we present results from a numerical human dispersal model, which is forced by spatiotemporal estimates of climate and sea level changes over the past 125 thousand years. The model simulates the overall dispersal of H. sapiens in close agreement with archaeological and fossil data and features prominent glacial migration waves across the Arabian Peninsula and the Levant region around 106–94, 89–73, 59–47 and 45–29 thousand years ago. The findings document that orbital-scale global climate swings played a key role in shaping Late Pleistocene global population distributions, whereas millennial-scale abrupt climate changes, associated with Dansgaard–Oeschger events, had a more limited regional effect.

  • 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 Planum 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 Planumnear 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 Planum’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 polar cap reported in the 1990sand the observed ice distribution in 2015. The model also predicts that most of these seasonal frosts should disappear in the next decade.

  • 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.

  • Accurate de novo design of hyperstable constrained peptides

  • Computational methods for the de novo design of conformationally restricted peptides produce exceptionally stable short peptides stabilized by backbone cyclization and/or internal disulfide bonds that are promising starting points for a new generation of peptide-based drugs.

  • X-ray structures define human P2X3 receptor gating cycle and antagonist action

  • Structures of the human P2X3 receptor in its open, closed, desensitized and antagonist-bound states show the receptor’s gating mechanism and the basis of antagonist binding.

  • The formation of Charon’s red poles from seasonally cold-trapped volatiles

  • A unique feature of Pluto’s large satellite Charon is its dark red northern polar cap. Similar colours on Pluto’s surface have been attributed to tholin-like organic macromolecules produced by energetic radiation processing of hydrocarbons. The polar location on Charon implicates the temperature extremes that result from Charon’s high obliquity and long seasons in the production of this material. The escape of Pluto’s atmosphere provides a potential feedstock for a complex chemistry. Gas from Pluto that is transiently cold-trapped and processed at Charon’s winter pole was proposed as an explanation for the dark coloration on the basis of an image of Charon’s northern hemisphere, but not modelled quantitatively. Here we report images of the southern hemisphere illuminated by Pluto-shine and also images taken during the approach phase that show the northern polar cap over a range of longitudes. We model the surface thermal environment on Charon and the supply and temporary cold-trapping of material escaping from Pluto, as well as the photolytic processing of this material into more complex and less volatile molecules while cold-trapped. The model results are consistent with the proposed mechanism for producing the observed colour pattern on Charon.

  • Accessory subunits are integral for assembly and function of human mitochondrial complex I

  • Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes. Complex I exists in supercomplex forms with respiratory chain complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP. Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson’s disease and ageing. Bacterial and human complex I share 14 core subunits that are essential for enzymatic function; however, the role and necessity of the remaining 31 human accessory subunits is unclear. The incorporation of accessory subunits into the complex increases the cellular energeticcost and has necessitated the involvement of numerous assembly factors for complex I biogenesis. Here we use gene editing to generate human knockout cell lines for each accessory subunit. We show that 25 subunits are strictly required for assembly of a functional complex and 1 subunit is essential for cell viability. Quantitative proteomic analysis of cell lines revealed that loss of each subunit affects the stability of other subunits residing in the same structural module. Analysis of proteomic changes after the loss of specific modules revealed that ATP5SL and DMAC1 are required for assembly of the distal portion of the complex I membrane arm. Our results demonstrate the broad importance of accessory subunits in the structure and function of human complex I. Coupling gene-editing technology with proteomics represents a powerful tool for dissecting large multi-subunit complexes and enables the study of complex dysfunction at a cellular level.

  • Acetylation-regulated interaction between p53 and SET reveals a widespread regulatory mode

  • Although lysine acetylation is now recognized as a general protein modification for both histones and non-histone proteins, the mechanisms of acetylation-mediated actions are not completely understood. Acetylation of the C-terminal domain (CTD) of p53 (also known as TP53) was an early example of non-histone protein acetylation and its precise role remains unclear. Lysine acetylation often creates binding sites for bromodomain-containing‘reader’ proteins. Here we use a proteomic screen to identify the oncoprotein SET as a major cellular factor whose binding with p53 is dependent on CTD acetylation status. SET profoundly inhibits p53 transcriptional activity in unstressed cells, but SET-mediated repression is abolished by stress-induced acetylation of p53 CTD. Moreover, loss of the interaction with SET activates p53, resulting in tumour regression in mouse xenograft models. Notably, the acidic domain of SET acts as a ‘reader’ for the unacetylated CTD of p53 and this mechanism of acetylation-dependent regulation is widespread in nature. For example, acetylation of p53 also modulates its interactions with similar acidic domains found in other p53 regulators including VPRBP (also known as DCAF1), DAXX and PELP1 (refs. 7, 8, 9), and computational analysis of the proteome has identified numerous proteins with the potential to serve as acidic domain readers and lysine-rich ligands. Unlike bromodomain readers, which preferentially bind the acetylated forms of their cognate ligands, the acidic domain readers specifically recognize the unacetylated forms of their ligands. Finally, the acetylation-dependent regulation of p53 was further validated in vivo by using a knock-in mouse model expressing an acetylation-mimicking form of p53. These results reveal that acidic-domain-containing factors act as a class of acetylation-dependent regulators by targeting p53 and, potentially, other proteins.

  • Erratum: Structural basis of potent Zika–dengue virus antibody cross-neutralization

  • Erratum: Structure of the adenosine A2A receptor bound to an engineered G protein

  • Corrigendum: Transfer of mitochondria from astrocytes to neurons after stroke

  • Corrigendum: Age-dependent modulation of vascular niches for haematopoietic stem cells

  • Corrigendum: Human commensals producing a novel antibiotic impair pathogen colonization

  • Potassium isotopic evidence for a high-energy giant impact origin of the Moon

  • The Earth–Moon system has unique chemical and isotopic signatures compared with other planetary bodies; any successful model for the origin of this system therefore has to satisfy these chemical and isotopic constraints. The Moon is substantially depleted in volatile elements such as potassium compared with the Earth and the bulk solar composition, and it has long been thought to be the result of a catastrophic Moon-forming giant impact event. Volatile-element-depleted bodies such as the Moon were expected to be enriched in heavy potassium isotopes during the loss of volatiles; however such enrichment was never found. Here we report new high-precision potassium isotope data for the Earth, the Moon and chondritic meteorites. We found that the lunar rocks are significantly (ggt;2σ) enriched in the heavy isotopes of potassium compared to the Earth and chondrites (by around 0.4 parts per thousand). The enrichment of the heavy isotope of potassium in lunar rocks compared with those of the Earth and chondrites can be best explained as the result of the incomplete condensation of a bulk silicate Earth vapour at an ambient pressure that is higher than 10 bar. We used these coupled constraintsof the chemical loss and isotopic fractionation of K to compare two recent dynamic models that were used to explain the identical non-mass-dependent isotope composition of the Earth and the Moon. Our K isotope result is inconsistent with the low-energy disk equilibration model, but supports the high-energy, high-angular-momentum giant impact model for the origin of the Moon. High-precision potassium isotope data can also be used as a ‘palaeo-barometer’ to reveal the physical conditions during the Moon-forming event.

  • High-molecular-weight organic matter in the particles of comet 67P/Churyumov–Gerasimenko

  • The presence of solid carbonaceous matter in cometary dust was established by the detection of elements such as carbon, hydrogen, oxygen and nitrogen in particles from comet 1P/Halley. Such matter is generally thought to have originated in the interstellar medium, but it might have formed in the solar nebula—the cloud of gas and dust that was left over after the Sun formed. This solid carbonaceous material cannot be observed from Earth, so it has eluded unambiguous characterization. Many gaseous organic molecules, however, have been observed; they come mostly from the sublimation of ices at the surface or in the subsurface of cometary nuclei. These ices could have been formed from material inherited from the interstellar medium that suffered little processing in the solar nebula. Here we report the in situ detection of solid organic matter in the dust particles emitted by comet 67P/Churyumov–Gerasimenko; the carbon in this organic material is bound in very large macromolecular compounds, analogous to the insoluble organic matter found in the carbonaceous chondrite meteorites. The organic matter in meteorites might have formed in the interstellar medium and/or the solar nebula, but was almost certainly modified in the meteorites’ parent bodies. We conclude that the observed cometary carbonaceous solid matter could have the same origin as the meteoritic insoluble organic matter, but suffered less modification before and/or after being incorporated into the comet.

  • Molecular transport through capillaries made with atomic-scale precision

  • Nanometre-scale pores and capillaries have long been studied because of their importance in many natural phenomena and their use in numerous applications. A more recent development is the ability to fabricate artificial capillaries with nanometre dimensions, which has enabled new research on molecular transport and led to the emergence of nanofluidics. But surface roughness in particular makes it challenging to produce capillaries with precisely controlled dimensions at this spatial scale. Here we report the fabrication of narrow and smooth capillaries through van der Waals assembly, with atomically flat sheets at the top and bottom separated by spacers made of two-dimensional crystals with a precisely controlled number of layers. We use graphene and its multilayers as archetypal two-dimensional materials to demonstrate this technology, which produces structures that can be viewed as if individual atomic planes had been removed from a bulk crystal to leave behind flat voids of a height chosen with atomic-scale precision. Water transport through the channels, ranging in height from one to several dozen atomic planes, is characterized by unexpectedly fast flow (up to 1 metre per second) that we attribute to high capillary pressures (about 1,000 bar) and large slip lengths. For channels that accommodate only a few layers of water, the flow exhibits a marked enhancement that we associate with an increased structural order in nanoconfined water. Our work opens up an avenue to making capillaries and cavities with sizes tunable to ångström precision, and with permeation properties further controlled through a wide choice of atomically flat materials available for channel walls.

  • Formation of new stellar populations from gas accreted by massive young star clusters

  • Nodal-chain metals

  • The band theory of solids is arguably the most successful theory of condensed-matter physics, providing a description of the electronic energy levels in various materials. Electronic wavefunctions obtained from the band theory enable a topological characterization of metals for which the electronic spectrum may host robust, topologically protected, fermionic quasiparticles. Many of these quasiparticles are analogues of the elementary particles of the Standard Model, but others do not have a counterpart in relativistic high-energy theories. A complete list of possible quasiparticles in solids is lacking, even in the non-interacting case. Here we describe the possible existence of a hitherto unrecognized type of fermionic excitation in metals. This excitation forms a nodal chain—a chain of connected loops in momentum space—along which conduction and valence bands touch. We prove that the nodal chain is topologically distinct from previously reported excitations. We discuss the symmetry requirements for the appearance of this excitation and predict that it is realized in an existing material, iridium tetrafluoride (IrF4), as well as in other compounds of this class of materials. Using IrF4 as an example, we provide a discussion of the topological surface states associated with the nodal chain. We argue that the presence of the nodal-chain fermions will result in anomalous magnetotransport properties, distinct from those of materials exhibiting previously known excitations.

  • Surface patterning of nanoparticles with polymer patches

  • Patterning of colloidal particles with chemically or topographically distinct surface domains (patches) has attracted intense research interest. Surface-patterned particles act as colloidal analogues of atoms and molecules, serve as model systems in studies of phase transitions in liquid systems, behave as‘colloidal surfactants’ and function as templates for the synthesis of hybrid particles. The generation of micrometre- and submicrometre-sized patchy colloids is now efficient, but surface patterning of inorganic colloidal nanoparticles with dimensions of the order of tens of nanometres is uncommon. Such nanoparticles exhibit size- and shape-dependent optical, electronic and magnetic properties, and their assemblies show new collective properties. At present, nanoparticle patterning is limited to the generation of two-patch nanoparticles, and nanoparticles with surface ripples or a ‘raspberry’ surface morphology. Here we demonstrate nanoparticle surface patterning, which utilizes thermodynamically driven segregation of polymer ligands from a uniform polymer brush into surface-pinned micelles following a change in solvent quality. Patch formation is reversible but can be permanently preserved using a photocrosslinking step. The methodology offers the ability to control the dimensions of patches, their spatial distribution and the number of patches per nanoparticle, in agreement with a theoretical model. The versatility of the strategy is demonstrated by patterning nanoparticles with different dimensions, shapes and compositions, tethered with various types of polymers and subjected to different external stimuli. These patchy nanocolloids have potential applications in fundamental research, the self-assembly of nanomaterials, diagnostics, sensing and colloidal stabilization.

  • Corrigendum: Lytic to temperate switching of viral communities

  • Corrigendum: Holocene shifts in the assembly of plant and animal communities implicate human impacts

  • Addendum: Non-Joulian magnetostriction

  • Corrigendum: Concerted nucleophilic aromatic substitution with 19F− and 18F−

  • Corrigendum: Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells

  • Corrigendum: Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease

  • Corrigendum: Distinct bone marrow blood vessels differentially regulate haematopoiesis

  • 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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