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Table of Contents for this page:

  • Current Issue
  • Advanced Online Publications Articles

  • Current Issue of Nature

    Nature - Issue - science feeds

  • Early-career researchers need fewer burdens and more support

  • Academia is more difficult than ever for young scientists. That’s bad for them, and bad for science

  • Mars-probe loss is a chance for ESA to learn

  • Failure of ExoMars lander will pave the way for the next mission.

  • How researchers cleared the name of HIV Patient Zero

  • Genetic analysis of historical virus samples proves the epidemic arrived by another route.

  • Divisive campaigning damages democracy

  • In the final days before the US election, political leaders must speak out to boost confidence in the democratic process, says Andrew Daniller.

  • Genomics: Bison's history in DNA and cave art

  • Europe's largest land mammal may be a hybrid of two extinct species.Julien Soubrier and Alan Cooper at the University of Adelaide in Australia and their colleagues analysed mitochondrial DNA from 65 fossil specimens of bison, including the threatened European bison (Bison bonasus),

  • Glaciology: Cooling no aid to shrinking glacier

  • A temporary cooling of the ocean around Antarctica's fastest-melting glacier failed to stop its retreat into the sea.The Pine Island Glacier in West Antarctica is currently the largest glacial contributor to global sea-level rise. Knut Christianson at the University of Washington in Seattle and

  • Neuropsychology: Pain passed on by smell

  • Mice housed in the same room as one another can pass certain types of pain to each other through smell.Exposure to inflammatory molecules or withdrawal from drugs or alcohol can cause hyperalgesia, a painful hypersensitivity to touch, heat or chemical irritants. Andrey Ryabinin and

  • Materials: Film self-heals like insects do

  • The browning of fruit and healing in insects has inspired the development of a material that regenerates and 'heals' itself after being damaged.Surface injuries in fruit and insects expose phenolic compounds, which are then oxidized, forming a protective surface. Haeshin Lee and his colleagues

  • Evolution: How snakes lost their legs

  • Two studies pinpoint a stretch of DNA that could explain how snakes evolved from four-limbed animals.A team led by Len Pennacchio and Axel Visel at Lawrence Berkeley National Laboratory in California analysed the ZRS DNA sequence— which regulates a key limb-development gene called

  • Plant science: How some plants adapt to shade

  • Shade-loving Begonia plants have iridescent blue leaves as a result of a cell organelle that allows them to efficiently harvest light in low-light conditions.Plants rely on organelles called chloroplasts for photosynthesis. Heather Whitney at the University of Bristol, UK, and her colleagues used

  • Evolution: Fast but invisible evolution

  • The rate of evolution is consistent across many fossil lineages, even if some show little physical change.Such seemingly unchanged fossils— described as being in stasis — have often been interpreted as evidence for slow evolution. Kjetil Lysne Voje at the University of Oslo

  • Cancer immunotherapy: Multi-pronged tumour attack

  • A cocktail of antibodies and proteins can wipe out large tumours in mice— even if the tumours are not particularly visible to the immune system.Immunotherapies unleash immune-system responses against cancer, but generally fail against large, established tumours in mice. Dane Wittrup and Darrell

  • Environmental science: Heat-polluted rivers ranked

  • The Mississippi and Rhine rivers are two of the most polluted by heat, mainly as a result of warm-water discharge from power plants.Catherine Raptis at the Swiss Federal Institute of Technology in Zurich and her colleagues studied this 'thermal pollution', which can disrupt aquatic

  • Electronics: Quantum bits wired up

  • Scientists have demonstrated a device that can interconnect as many as 100 qubits— the units of information future quantum computers will use to perform calculations that are impossible for conventional computers.The 'quantum socket' — built by Matteo Mariantoni at the University of Waterloo

  • Hungarian science spat, Kuwait’s DNA law and a transparency milestone

  • The week in science: 21–27 October 2016

  • Computing glitch may have doomed Mars lander

  • Researchers sift through clues after Schiaparelli crash in hopes of averting mistakes in 2020 mission.

  • Scientific challenges loom for Canada’s popular prime minister

  • Justin Trudeau draws praise for boosting budgets and unmuzzling scientists, but tough challenges lie ahead.

  • @ScientistTrump will make science great again

  • Florida ecologist uses a parody Twitter account as a way of highlighting issues in science and academia.

  • Icy heart could be key to Pluto’s strange geology

  • NASA’s New Horizons mission plumbs complex interplay between the dwarf planet's surface and its sky.

  • Europe’s drug regulator opens vaults of clinical-trials data

  • EMA becomes first major drugs agency to publish clinical-study reports online.

  • Violence escalates at South African universities

  • Protests over rising tuition fees have stopped classes, closed institutions and slowed research.

  • The plight of young scientists

  • A special issue explores how the research enterprise keeps early-career scientists from pursuing the most important work, and what can be done to help.

  • Young scientists under pressure: what the data show

  • Young researchers are having to fight harder than past generations for a smaller share of the academic pie.

  • Young, talented and fed-up: scientists tell their stories

  • Scientists starting labs say that they are under historically high pressure to publish, secure funding and earn permanent positions— leaving precious little time for actual research.

  • Let researchers try new paths

  • Demand for steady output stymies discovery. To pursue the most important research, scientists must be allowed to shift their focus, say Tolu Oni and colleagues.

  • Fewer numbers, better science

  • Scientific quality is hard to define, and numbers are easy to look at. But bibliometrics are warping science— encouraging quantity over quality. Leaders at two research institutions describe how they do things differently.

  • Economic history: The roots of growth

  • Brad DeLong examines a study that places the origins of the Industrial Revolution in fifteenth-century Europe.

  • Extremophiles: Life at the deep end

  • Sonja-Verena Albers reviews a riveting chronicle tracing the discovery of archaea.

  • Sustainability: Laying waste

  • Edward Humes weighs up an analysis of dangerously partial solutions to environmental damage.

  • Policy: UK research reforms in a Brexit world

  • Contrary to your view that the UK Higher Education and Research Bill could spell the end of independence for British research and universities (Nature538, 5;10.1038/538005a2016), I believe that, with safeguards, it can provide a strong coherent voice for

  • Religion and science: boost sustainability

  • We wholeheartedly share Kathryn Pritchard's view that“Religion and science can have a true dialogue” (Nature537, 451;10.1038/537451a2016). So, too, do those who wish to solve our planet's environmental problems by promoting greater cooperation between the sciences and world

  • Religion and science: not a true dialogue

  • With the rise of religious fundamentalism worldwide and the expansion of education in 'faith' schools, I consider that promoting the idea that religion and science have some kind of equivalence risks making societies more divisive and backward-looking (see K.PritchardNature537, 451;

  • Open data: towards full transparency

  • We suggest that public archiving of data and setting standards for data citations may not be enough to ensure scientific transparency (Nature537, 13810.1038/537138a (2016) and see D.RocheNature538, 41;10.1038/538041c2016).Verification

  • Measurements: Resistance to SI units pervades medicine

  • More than half a century after SI units became standard, pockets of resistance to their adoption still persist— at least in medicine (see also Nature537, 279;10.1038/537279a2016).Many specialists in the radiological disciplines, including myself, still think in terms

  • Agents of change

  • Three advocates explain how their groups are trying to improve junior researchers' experiences.

  • Turning point: Cream of the crop

  • William Tracy is one of only two sweetcorn breeders in the United States. Here's how he hopes to train a new generation.

  • The offering

  • A well-kept secret.

  • Parkinson's disease

  • Two hundred steps

  • In the 200 years since Parkinson's disease was first described, the understanding and management of the disease has come a long way. But researchers have yet to unlock all of its secrets. By Liam Drew.

  • Perspective: Data sharing for discovery

  • Biomarkers will be essential if research on Parkinson's is to progress, but their discovery depends on scientists sharing data, says Mark Frasier.

  • Diagnosis: Warning signs

  • Non-motor symptoms such as sleep disorders and a poor sense of smell may hold the key to diagnosing Parkinson's disease before the characteristic tremor starts.

  • Technology: Monitoring gets personal

  • By bootstrapping existing technologies, researchers can gain a minute-by-minute understanding of a patient's disease.

  • Electrotherapy: Shock value

  • Deep brain stimulation is a proven treatment for Parkinson's disease. The only thing left to find out is how it works.

  • Pathology: The prion principle

  • A controversial theory that could revolutionize our understanding of Parkinson's disease is gaining ground. But not everybody is convinced that misfolded proteins that spread in the brain are the cause of the disease.

  • Parkinson's disease: 4 big questions

  • The characteristic brain pathology and motor symptoms of Parkinson's disease are well established. But the details of the disease's cause and course are much murkier.

  • How foreign is the past?

  • arising fromS. K.Lyonset al. 529, 80–83 (2016); Humboldt and Darwin, ecologists have puzzled over what determines community assembly and structure and how community structure may change with time. Human activity is one potential

  • Lyons et al. reply

  • replying toR. J.Telfordet al. Nature538, (2016)In the accompanying Comment, Telford et al. claim that many of the modern datasets we used previouslywere inappropriate for the analysis, and that the pattern through

  • Clarification

  • The News Feature‘The troubled minds of migrants’ (Nature538, 158-160; 2016) stated that the Berlin-based clearing centre was opened by psychiatrist Malek Bajbouj of the Charité university hospital. The centre is actually run jointly by his and two other psychiatric departments of

  • Synthetic biology: Precision timing in a cell

  • A 16-year-old synthetic genetic circuit that produces gene-expression oscillations in bacterial cells has been given an upgrade, making it an exceptionally precise biological clock. See Letter p.514

  • In retrospect: Twenty-five years of low-cost solar cells

  • In 1991, an energy-efficient solar cell was reported that was both simple in design and relatively inexpensive. This invention has since inspired the development of solar cells that have even higher efficiencies.

  • 50 aamp; 100 Years Ago

  • 50 Years AgoThe mandibular gland secretion of the worker honeybee Apis mellifera L., contains 10-hydroxy-Δ2-decenoic acid and ... 2-heptanone ... I have shown that 10-hydroxydecenoic acid does not repel foraging honeybees but that 2-heptanone does ... Foragers were strongly repelled by

  • Social science: Female genital cutting under the spotlight

  • Variations in opinion between members of a community can be exploited to facilitate desirable changes in attitude, as exemplified by films that explore different beliefs about female genital cutting. See Letter p.506

  • Astrophysics: Birth of stellar siblings

  • Binary and multiple star systems result from the fragmentation of dense material in young molecular clouds. Observations reveal that this can occur on small scales, supporting a previous model of star formation. See Letter p.483

  • Artificial intelligence: Deep neural reasoning

  • The human brain can solve highly abstract reasoning problems using a neural network that is entirely physical. The underlying mechanisms are only partially understood, but an artificial network provides valuable insight. See Article p.471

  • Palaeontology: Ancient avian aria from Antarctica

  • A discovery of the sound-producing vocal organ known as the syrinx in a bird fossil from the end of the 'age of dinosaurs' highlights the anatomical basis for myriad aspects of avian social and behavioural evolution. See Letter p.502

  • Correction

  • The News aamp; Views article 'Genomics: A matched set of frog sequences' by Shawn Burgess (Nature538, 320–321;10.1038/538320a2016) incorrectly stated that the two paired sets of chromosomes in Xenopus laevis are referred to as S and

  • Hybrid computing using a neural network with dynamic external memory

  • Artificial neural networks are remarkably adept at sensory processing, sequence learning and reinforcement learning, but are limited in their ability to represent variables and data structures and to store data over long timescales, owing to the lack of an external memory. Here we introduce a

  • The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

  • Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here

  • A triple protostar system formed via fragmentation of a gravitationally unstable disk

  • Binary and multiple star systems are a frequent outcome of the star formation process and as a result almost half of all stars with masses similar to that of the Sun have at least one companion star. Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large-scale fragmentation of turbulent gas cores and filaments or smaller-scale fragmentation of a massive protostellar disk due to gravitational instability. Observational evidence for turbulent fragmentation on scales of more than 1,000 astronomical units has recently emerged. Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems. The triple protostar system L1448 IRS3B is an ideal system with which to search for evidence of disk fragmentation as it is in an early phase of the star formation process, it is likely to be less than 150,000 years old and all of the protostars in the system are separated by less than 200 astronomical units. Here we report observations of dust and molecular gas emission that reveal a disk with a spiral structure surrounding the three protostars. Two protostars near the centre of the disk are separated by 61 astronomical units and a tertiary protostar is coincident with a spiral arm in the outer disk at a separation of 183 astronomical units. The inferred mass of the central pair of protostellar objects is approximately one solar mass, while the disk surrounding the three protostars has a total mass of around 0.30 solar masses. The tertiary protostar itself has a minimum mass of about 0.085 solar masses. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150 and 320 astronomical units, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.

  • 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.

  • Quantum dynamics of simultaneously measured non-commuting observables

  • In quantum mechanics, measurements cause wavefunction collapse that yields precise outcomes, whereas for non-commuting observables such as position and momentum Heisenberg’s uncertainty principle limits the intrinsic precision of a state. Although theoretical work has demonstrated that it should be possible to perform simultaneous non-commuting measurements and has revealed the limits on measurement outcomes, only recently has the dynamics of the quantum state been discussed. To realize this unexplored regime, we simultaneously apply two continuous quantum non-demolition probes of non-commuting observables to a superconducting qubit. We implement multiple readout channels by coupling the qubit to multiple modes of a cavity. To control the measurement observables, we implement a ‘single quadrature’ measurement by driving the qubit and applying cavity sidebands with a relative phase that sets the observable. Here, we use this approach to show that the uncertainty principle governs the dynamics of the wavefunction by enforcing a lower bound on the measurement-induced disturbance. Consequently, as we transition from measuring identical to measuring non-commuting observables, the dynamics make a smooth transition from standard wavefunction collapse to localized persistent diffusion and then to isotropic persistent diffusion. Although the evolutionof the state differs markedly from that of a conventional measurement, information about both non-commuting observables is extracted by keeping track of the time ordering of the measurement record, enabling quantum state tomography without alternating measurements. Our work creates novel capabilities for quantum control, including rapid state purification, adaptive measurement, measurement-based state steering and continuous quantum error correction. As physical systems often interact continuously with their environment via non-commuting degrees of freedom, our work offers a way to study how notions of contemporary quantum foundations arise in such settings.

  • 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.

  • 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.

  • Fossil evidence of the avian vocal organ from the Mesozoic

  • From complex songs to simple honks, birds produce sounds using a unique vocal organ called the syrinx. Located close to the heart at the tracheobronchial junction, vocal folds or membranes attached to modified mineralized rings vibrate to produce sound. Syringeal components were not thought to commonly enter the fossil record, and the few reported fossilized parts of the syrinx are geologically young (from the Pleistocene and Holocene (approximately 2.5 million years ago to the present)). The only known older syrinx is an Eocene specimen that was not described or illustrated. Data on the relationship between soft tissue structures and syringeal three-dimensional geometry are also exceptionally limited. Here we describe the first remains, to our knowledge, of a fossil syrinx from the Mesozoic Era, which are preserved in three dimensions in a specimen from the Late Cretaceous (approximately 66 to 69 million years ago) of Antarctica. With both cranial and postcranial remains, the new Vegavis iaai specimen is the most complete to be recovered from a part of the radiation of living birds (Aves). Enhanced-contrast X-ray computed tomography (CT) of syrinx structure in twelve extant non-passerine birds, as well as CT imaging of the Vegavis and Eocene syrinxes, informs both the reconstruction of ancestral states in birds and properties of the vocal organ in the extinct species. Fused rings in Vegavis form a well-mineralized pessulus, a derived neognath bird feature, proposed to anchor enlarged vocal folds or labia. Left-right bronchial asymmetry, as seen in Vegavis, is only known in extant birds with two sets of vocal fold sound sources. The new data show the fossilization potential of the avian vocal organ and beg the question why these remains have not been found in other dinosaurs. The lack of other Mesozoic tracheobronchial remains, and the poorly mineralized condition in archosaurian taxa without a syrinx, may indicate that a complex syrinx was a late arising feature in the evolution of birds, well after the origin of flight and respiratory innovations.

  • Changing cultural attitudes towards female genital cutting

  • As globalization brings people with incompatible attitudes into contact, cultural conflicts inevitably arise. Little is known about how to mitigate conflict and about how the conflicts that occur can shape the cultural evolution of the groups involved. Female genital cutting is a prominent example. Governments and international agencies have promoted the abandonment of cutting for decades, but the practice remains widespread with associated health risks for millions of girls and women. In their efforts to end cutting, international agents have often adopted the view that cutting is locally pervasive and entrenched. This implies the need to introduce values and expectations from outside the local culture. Members of the target society may view such interventions as unwelcome intrusions, and campaigns promoting abandonment have sometimes led to backlash as they struggle to reconcile cultural tolerance with the conviction that cutting violates universal human rights. Cutting, however, is not necessarily locally pervasive and entrenched. We designed experiments on cultural change that exploited the existence of conflicting attitudes within cutting societies. We produced four entertaining movies that served as experimental treatments in two experiments in Sudan, and we developed an implicit association test to unobtrusively measure attitudes about cutting. The movies depart from the view that cutting is locally pervasive by dramatizing members of an extended family as they confront each other with divergent views about whether the family should continue cutting. The movies significantly improved attitudes towards girls who remain uncut, with one in particular having a relatively persistent effect. These results show that using entertainment to dramatize locally discordant views can provide a basis for applied cultural evolution without accentuating intercultural divisions.

  • Genomic insights into the peopling of the Southwest Pacific

  • The appearance of people associated with the Lapita culture in the South Pacific around 3,000 years ago marked the beginning of the last major human dispersal to unpopulated lands. However, the relationship of these pioneers to the long-established Papuan people of the New Guinea region is unclear. Here we present genome-wide ancient DNA data from three individuals from Vanuatu (about 3,100–2,700 years before present) and one from Tonga (about 2,700–2,300 years before present), and analyse them with data from 778 present-day East Asians and Oceanians. Today, indigenous people of the South Pacific harbour a mixture of ancestry from Papuans and a population of East Asian origin that no longer exists in unmixed form, but is a match to the ancient individuals. Most analyses have interpreted the minimum of twenty-five per cent Papuan ancestry in the region today as evidence that the first humans to reach Remote Oceania, including Polynesia, were derived from population mixtures near New Guinea, before their further expansion into Remote Oceania. However, our finding that the ancient individuals had little to no Papuan ancestry implies that later human population movements spread Papuan ancestry through the South Pacific after the first peopling of the islands.

  • Synchronous long-term oscillations in a synthetic gene circuit

  • Synthetically engineered genetic circuits can perform a wide variety of tasks but are generally less accurate than natural systems. Here we revisit the first synthetic genetic oscillator, the repressilator, and modify it using principles from stochastic chemistry in single cells. Specifically, we sought to reduce error propagation and information losses, not by adding control loops, but by simply removing existing features. We show that this modification created highly regular and robust oscillations. Furthermore, some streamlined circuits kept 14 generation periods over a range of growth conditions and kept phase for hundreds of generations in single cells, allowing cells in flasks and colonies to oscillate synchronously without any coupling between them. Our results suggest that even the simplest synthetic genetic networks can achieve a precision that rivals natural systems, and emphasize the importance of noise analyses for circuit design in synthetic biology.

  • T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments

  • It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.

  • Chromosome conformation elucidates regulatory relationships in developing human brain

  • Three-dimensional physical interactions within chromosomes dynamically regulate gene expression in a tissue-specific manner. However, the 3D organization of chromosomes during human brain development and its role in regulating gene networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia, are unknown. Here we

  • TET-mediated DNA demethylation controls gastrulation by regulating Lefty–Nodal signalling

  • Mammalian genomes undergo epigenetic modifications, including cytosine methylation by DNA methyltransferases (DNMTs). Oxidation of 5-methylcytosine by the Ten-eleven translocation (TET) family of dioxygenases can lead to demethylation. Although cytosine methylation has key roles in several processes such as genomic imprinting and X-chromosome inactivation, the functional significance of cytosine methylation and demethylation in mouse embryogenesis remains to be fully determined. Here we show that inactivation of all three Tet genes in mice leads to gastrulation phenotypes, including primitive streak patterning defects in association with impaired maturation of axial mesoderm and failed specification of paraxial mesoderm, mimicking phenotypes in embryos with gain-of-function Nodal signalling. Introduction of a single mutant allele of Nodal in the Tet mutant background partially restored patterning, suggesting that hyperactive Nodal signalling contributes to the gastrulation failure of Tet mutants. Increased Nodal signalling is probably due to diminished expression of the Lefty1 and Lefty2 genes, which encode inhibitors of Nodal signalling. Moreover, reduction in Lefty gene expression is linked to elevated DNA methylation, as both Lefty–Nodal signalling and normal morphogenesis are largely restored in Tet-deficient embryos when the Dnmt3a and Dnmt3b genes are disrupted. Additionally, a point mutation in Tet that specifically abolishes the dioxygenase activity causes similar morphological and molecular abnormalities as the null mutation. Taken together, our results show that TET-mediated oxidation of 5-methylcytosine modulates Lefty–Nodal signalling by promoting demethylation in opposition to methylation by DNMT3A and DNMT3B. These findings reveal a fundamental epigenetic mechanism featuring dynamic DNA methylation and demethylation crucial to regulation of key signalling pathways in early body plan formation.

  • Mechanism for DNA transposons to generate introns on genomic scales

  • The discovery of introns four decades ago was one of the most unexpected findings in molecular biology. Introns are sequences interrupting genes that must be removed as part of messenger RNA production. Genome sequencing projects have shown that most eukaryotic genes contain at least one intron, and frequently many. Comparison of these genomes reveals a history of long evolutionary periods during which few introns were gained, punctuated by episodes of rapid, extensive gain. However, although several detailed mechanisms for such episodic intron generation have been proposed, none has been empirically supported on a genomic scale. Here we show how short, non-autonomous DNA transposons independently generated hundreds to thousands of introns in the prasinophyte Micromonas pusilla and the pelagophyte Aureococcus anophagefferens. Each transposon carries one splice site. The other splice site is co-opted from the gene sequence that is duplicated upon transposon insertion, allowing perfect splicing out of the RNA. The distributions of sequences that can be co-opted are biased with respect to codons, and phasing of transposon-generated introns is similarly biased. These transposons insert between pre-existing nucleosomes, so that multiple nearby insertions generate nucleosome-sized intervening segments. Thus, transposon insertion and sequence co-option may explain the intron phase biases and prevalence of nucleosome-sized exons observed in eukaryotes. Overall, the two independent examples of proliferating elements illustrate a general DNA transposon mechanism that can plausibly account for episodes of rapid, extensive intron gain during eukaryotic evolution.

  • Pore architecture of TRIC channels and insights into their gating mechanism

  • Intracellular Ca2+ signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis. Release of Ca2+ from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca2+ through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen. Genetic ablations or mutations of TRIC channels are associated with hypertension, heart disease, respiratory defects and brittle bone disease. Despite the pivotal function of TRIC channels in Ca2+ signalling, their pore architectures and gating mechanisms remain unknown. Here we present the structures of TRIC-B1 and TRIC-B2 channels from Caenorhabditis elegans in complex with endogenous phosphatidylinositol-4,5-biphosphate (PtdIns(4,5)P2, also known as PIP2) lipid molecules. The TRIC-B1/B2 proteins and PIP2 assemble into a symmetrical homotrimeric complex. Each monomer contains an hourglass-shaped hydrophilic pore contained within a seven-transmembrane-helix domain. Structural and functional analyses unravel the central role of PIP2 in stabilizing the cytoplasmic gate of the ion permeation pathway and reveal a marked Ca2+-induced conformational change in a cytoplasmic loop above the gate. A mechanistic model has been proposed to account for the complex gating mechanism of TRIC channels.

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

  • Nature529, 80–83 (2016); doi:10.1038/nature16447It has come to our attention that in this Letter, there were some errors in the categorization of some of the modern datasets (R. Telford et al., personal communication). These errors affect 19

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

  • Nature534, 383–386 (2016); doi:10.1038/nature18303We wish to clarify the statistical methods used in this Letter. Owing to the limited number of observations, blastocyst quality in Fig. 2d was analysed by pooling grades A and B to compare

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

  • Nature536, 104–107 (2016); doi:10.1038/nature18966In this Letter, author B.C. ( should have also been included as a corresponding author; this has been corrected online.

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  • Cancer: Bad neighbours cause bad blood

  • Expression of a blood-cancer-associated genetic mutation in the non-blood cells of the bone marrow is sufficient to cause blood cancer in mice. This finding could point to new approaches to treating an often-fatal disease.

  • In retrospect: Eighty years of stress

  • The discovery in 1936 that rats respond to various damaging stimuli with a general response that involves alarm, resistance and exhaustion launched the discipline of stress research.

  • Linguistics: Sound and meaning in the world's languages

  • The sounds of words that represent particular meanings are usually thought to vary arbitrarily across languages. However, a large-scale study of languages finds that some associations between sound and meaning are widespread.

  • Molecular biology: Mature proteins braced by a chaperone

  • Hsp70 chaperone molecules help other proteins to fold, and were thought to bind mainly to unfolded proteins. Single-molecule experiments now suggest that Hsp70s can also stabilize almost fully folded proteins.

  • Transplanted embryonic neurons integrate into adult neocortical circuits

  • Transplanted embryonic neurons in mice mature and achieve adult-like properties within 4–8 weeks, receiving appropriate inputs and establishing stimulus-selective responses.

  • Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development

  • HAND2 is an ancestral regulator of heart development and one of four transcription factors that control the reprogramming of fibroblasts into cardiomyocytes. Deletion of Hand2 in mice results in right ventricle hypoplasia and embryonic lethality. Hand2 expression is tightly regulated by upstream enhancers that reside within a super-enhancer delineated by histone H3 acetyl Lys27 (H3K27ac) modifications. Here we show that transcription of a Hand2-associated long non-coding RNA, which we named upperhand (Uph), is required to maintain the super-enhancer signature and elongation of RNA polymerase II through the Hand2 enhancer locus. Blockade of Uph transcription, but not knockdown of the mature transcript, abolished Hand2 expression, causing right ventricular hypoplasia and embryonic lethality in mice. Given the substantial number of uncharacterized promoter-associated long non-coding RNAs encoded by the mammalian genome, the Uph–Hand2 regulatory partnership offers a mechanism by which divergent non-coding transcription can establish a permissive chromatin environment.

  • Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment

  • Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11), a positive regulator of the RAS signalling pathway, are found in 50% of patients with Noonan syndrome. These patients have an increased risk of developing leukaemia, especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity. However, the effect of these mutations in the bone marrow microenvironment remains unclear. Here we report that Ptpn11 activating mutations in the mouse bone marrow microenvironment promote the development and progression of MPN through profound detrimental effects on haematopoietic stem cells (HSCs). Ptpn11 mutations in mesenchymal stem/progenitor cells and osteoprogenitors, but not in differentiated osteoblasts or endothelial cells, cause excessive production of the CC chemokine CCL3 (also known as MIP-1α), which recruits monocytes to the area in which HSCs also reside. Consequently, HSCs are hyperactivated by interleukin-1β and possibly other proinflammatory cytokines produced by monocytes, leading to exacerbated MPN and to donor-cell-derived MPN following stem cell transplantation. Remarkably,administration of CCL3 receptor antagonists effectively reverses MPN development induced by the Ptpn11-mutated bone marrow microenvironment. This study reveals the critical contribution of Ptpn11 mutations in the bone marrow microenvironment to leukaemogenesis and identifies CCL3 as a potential therapeutic target for controlling leukaemic progression in Noonan syndrome and for improving stem cell transplantation therapy in Noonan-syndrome-associated leukaemias.

  • Local regulation of gene expression by lncRNA promoters, transcription and splicing

  • Mammalian genomes are pervasively transcribed to produce thousands of long non-coding RNAs (lncRNAs). A few of these lncRNAs have been shown to recruit regulatory complexes through RNA–protein interactions to influence the expression of nearby genes, and it has been suggested that many other lncRNAs can also act as local regulators. Such local functions could explain the observation that lncRNA expression is often correlated with the expression of nearby genes. However, these correlations have been challenging to dissect and could alternatively result from processes that are not mediated by the lncRNA transcripts themselves. For example, some gene promoters have been proposed to have dual functions as enhancers, and the process of transcription itself may contribute to gene regulation by recruiting activating factors or remodelling nucleosomes. Here we use genetic manipulation in mouse cell lines to dissect 12 genomic loci that produce lncRNAs and find that 5 of these loci influence the expression of a neighbouring gene in cis. Notably, none of these effects requires the specific lncRNA transcripts themselves and instead involves general processes associated with their production, including enhancer-like activity of gene promoters, the process of transcription, and the splicing of the transcript. Furthermore, such effects are not limited to lncRNA loci: we find that four out of six protein-coding loci also influence the expression of a neighbour. These results demonstrate that cross-talk among neighbouring genes is a prevalent phenomenon that can involve multiple mechanisms and cis-regulatory signals, including a role for RNA splice sites. These mechanisms may explain the function and evolution of some genomic loci that produce lncRNAs and broadly contribute to the regulation of both coding and non-coding genes.

  • Nanoscale thermal imaging of dissipation in quantum systems

  • Energy dissipation is a fundamental process governing the dynamics of physical, chemical and biological systems. It is also one of the main characteristics that distinguish quantum from classical phenomena. In particular, in condensed matter physics, scattering mechanisms, loss of quantum information or breakdown of topological protection are deeply rooted in the intricate details of how and where the dissipation occurs. Yet the microscopic behaviour of a system is usually not formulated in terms of dissipation because energy dissipation is not a readily measurable quantity on the micrometre scale. Although nanoscale thermometry has gained much recent interest, existing thermal imaging methods are not sensitive enough for the study of quantum systems and are also unsuitable for the low-temperature operation that is required. Here we report a nano-thermometer based on a superconducting quantum interference device with a diameter of less than 50 nanometres that resides at the apex of a sharp pipette: it provides scanning cryogenic thermal sensing that is four orders of magnitude more sensitive than previous devices—below 1 μK Hz−1/2. This non-contact, non-invasive thermometry allows thermal imaging of very low intensity, nanoscale energy dissipation down to the fundamental Landauer limit of 40 femtowatts for continuous readout of a single qubit at one gigahertz at 4.2 kelvin. These advances enable theobservation of changes in dissipation due to single-electron charging of individual quantum dots in carbon nanotubes. They also reveal a dissipation mechanism attributable to resonant localized states in graphene encapsulated within hexagonal boron nitride, opening the door to direct thermal imaging of nanoscale dissipation processes in quantum matter.

  • Alternative modes of client binding enable functional plasticity of Hsp70

  • The Hsp70 system is a central hub of chaperone activity in all domains of life. Hsp70 performs a plethora of tasks, including folding assistance, protection against aggregation, protein trafficking, and enzyme activity regulation, and interacts with non-folded chains, as well as near-native, misfolded, and aggregated proteins. Hsp70 is thought to achieve its many physiological roles by binding peptide segments that extend from these different protein conformers within a groove that can be covered by an ATP-driven helical lid. However, it has been difficult to test directly how Hsp70 interacts with protein substrates in different stages of folding and how it affects their structure. Moreover, recent indications of diverse lid conformations in Hsp70–substrate complexes raise the possibility of additional interaction mechanisms. Addressing these issues is technically challenging, given the conformational dynamics of both chaperone and client, the transient nature of their interaction, and the involvement of co-chaperones and the ATP hydrolysis cycle. Here, using optical tweezers, we show that the bacterial Hsp70 homologue (DnaK) binds and stabilizes not only extended peptide segments, but also partially folded and near-native protein structures. The Hsp70 lid and groove act synergistically when stabilizing folded structures: stabilization is abolished when the lid is truncated and less efficient when the groove is mutated. The diversity of binding modes has important consequences: Hsp70 can both stabilize and destabilize folded structures, in a nucleotide-regulated manner; like Hsp90 and GroEL, Hsp70 can affect the late stages ofprotein folding; and Hsp70 can suppress aggregation by protecting partially folded structures as well as unfolded protein chains. Overall, these findings in the DnaK system indicate an extension of the Hsp70 canonical model that potentially affects a wide range of physiological roles of the Hsp70 system.

  • 1970s and‘Patient 0’ HIV-1 genomes illuminate early HIV/AIDS history in North America

  • The emergence of HIV-1 group M subtype B in North American men who have sex with men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have suggested cryptic subtype B circulation in the United States (US) throughout the 1970s and an even older presence in the Caribbean. However, these temporal and geographical inferences, based upon partial HIV-1 genomes that postdate the recognition of AIDS in 1981, remain contentious and the earliest movements of the virus within the US are unknown. We serologically screened ggt;2,000 1970s serum samples and developed a highly sensitive approach for recovering viral RNA from degraded archival samples. Here, we report eight coding-complete genomes from US serum samples from 1978–1979—eight of the nine oldest HIV-1 group M genomes to date. This early, full-genome ‘snapshot’ reveals that the US HIV-1 epidemic exhibited extensive genetic diversity in the 1970s but also provides strong evidence for its emergence from a pre-existing Caribbean epidemic. Bayesian phylogenetic analyses estimate the jump to the US at around 1970 and place the ancestral US virus in New York City with 0.99 posterior probability support, strongly suggesting this was the crucial hub of early US HIV/AIDS diversification. Logistic growth coalescent models reveal epidemic doubling times of 0.86 and 1.12 years for the US and Caribbean, respectively, suggesting rapid early expansion in each location. Comparisons with more recent data reveal many of these insights to be unattainable without archival, full-genome sequences. We also recovered the HIV-1 genome from the individual known as ‘Patient 0’ (ref. 5) and found neither biological nor historical evidence that he was the primary case in the US or for subtype B as a whole. We discuss the genesis and persistence of this belief in the light of these evolutionary insights.

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

  • Defining synonymous codon compression schemes by genome recoding

  • REXER, a new method that allows long sections of DNA to be inserted or replaced in the genome of the bacterium Escherichia coli, is used to investigate codon replacement schemes for the generation of synthetic genomes.

  • Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase

  • Vacuolar-type ATPases (V-ATPases) are ATP-powered proton pumps involved in processes such as endocytosis, lysosomal degradation, secondary transport, TOR signalling, and osteoclast and kidney function. ATP hydrolysis in the soluble catalytic V1 region drives proton translocation through the membrane-embedded VO region via rotation of a rotor subcomplex. Variability in the structure of the intact enzyme has prevented construction of an atomic model for the membrane-embedded motor of any rotary ATPase. We induced dissociation and auto-inhibition of the V1 and VO regions of the V-ATPase by starving the yeast Saccharomyces cerevisiae, allowing us to obtain a ~3.9-Å resolution electron cryomicroscopy map of the VO complex and build atomic models for the majority of its subunits. The analysis reveals the structures of subunits ac8c′c″de and a protein that we identify and propose to be a new subunit (subunit f). A large cavity between subunit a and the c-ring creates a cytoplasmic half-channel for protons. The c-ring has an asymmetric distribution of proton-carrying Glu residues, with the Glu residue of subunit c″ interacting with Arg735 of subunit a. The structure suggests sequential protonation and deprotonation of the c-ring, with ATP-hydrolysis-driven rotation causing protonation of a Glu residue at the cytoplasmic half-channel and subsequent deprotonation of a Glu residue at a luminal half-channel.

  • Olfactory receptor pseudo-pseudogenes

  • Pseudogenes are generally considered to be non-functional DNA sequences that arise through nonsense or frame-shift mutations of protein-coding genes. Although certain pseudogene-derived RNAs have regulatory roles, and some pseudogene fragments are translated, no clear functions for pseudogene-derived proteins are known. Olfactory receptor families contain many pseudogenes, which reflect low selection pressures on loci no longer relevant to the fitness of a species. Here we report the characterization of a pseudogene in the chemosensory variant ionotropic glutamate receptor repertoire of Drosophila sechellia, an insect endemic to the Seychelles that feeds almost exclusively on the ripe fruit of Morinda citrifolia. This locus, D. sechellia Ir75a, bears a premature termination codon (PTC) that appears to be fixed in the population. However, D. sechellia Ir75a encodes a functional receptor, owing to efficient translational read-through of the PTC. Read-through is detected only in neurons and is independent of the type of termination codon, but depends on the sequence downstream of the PTC. Furthermore, although the intact Drosophila melanogaster Ir75a orthologue detects acetic acid—a chemical cue important for locating fermenting food found only at trace levels in Morinda fruit—D. sechellia Ir75a has evolved distinct odour-tuning properties through amino-acid changes in its ligand-binding domain. We identify functional PTC-containing loci within different olfactory receptor repertoires and species, suggesting that such ‘pseudo-pseudogenes’ could represent a widespread phenomenon.

  • Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall

  • The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere. Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin (for example, ref. 2) and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions, but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear. Here we present aircraft- and ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. This rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.

  • DNA repair: Telomere-lengthening mechanism revealed

  • Shortening of the ends of chromosomes limits a cell's lifespan. Some cancer cells avoid this fate through a mechanism called alternative lengthening of telomeres, molecular details of which have now been defined.

  • Behavioural biology: Stones that could cause ripples

  • Monkeys have been observed pounding stones and unintentionally forming sharp-edged, tool-like fragments. This deliberate breakage raises questions about the evolution of intentional stone modification.

  • Break-induced telomere synthesis underlies alternative telomere maintenance

  • Alternative lengthening of telomeres in cancer cells is initiated by a specialized replisome and noncanonical homologous recombination at damaged telomeres, culminating in the synthesis of long tracts of telomere DNA.

  • Fluvial sediment supply to a mega-delta reduced by shifting tropical-cyclone activity

  • The world’s rivers deliver 19 billion tonnes of sediment to the coastal zone annually, with a considerable fraction being sequestered in large deltas, home to over 500 million people. Most (more than 70 per cent) large deltas are under threat from a combination of rising sea levels, ground surface subsidence and anthropogenic sediment trapping, and a sustainable supply of fluvial sediment is therefore critical to prevent deltas being ‘drowned’ by rising relative sea levels. Here we combine suspended sediment load data from the Mekong River with hydrological model simulations to isolate the role of tropical cyclones in transmitting suspended sediment to one of the world’s great deltas. We demonstrate that spatial variations in the Mekong’s suspended sediment load are correlated (r = 0.765, P llt; 0.1) with observed variations in tropical-cyclone climatology, and that a substantial portion (32 per cent) of the suspended sediment load reaching the delta is delivered by runoff generated by rainfall associated with tropical cyclones. Furthermore, we estimate that the suspended load to the delta has declined by 52.6 ± 10.2 megatonnes over recent years (1981–2005), of which 33.0 ± 7.1 megatonnes is due to a shift in tropical-cyclone climatology. Consequently, tropical cyclones have a key role in controlling the magnitude of, and variability in, transmission of suspended sediment to the coast. It is likely that anthropogenic sediment trapping in upstream reservoirs is a dominant factor in explaining past, and anticipating future, declines in suspended sediment loads reaching the world’s major deltas. However, our study shows that changes in tropical-cyclone climatology affect trends in fluvial suspended sediment loads and thus are also key to fully assessing the risk posed to vulnerable coastal systems.

  • Wild monkeys flake stone tools

  • Our understanding of the emergence of technology shapes how we view the origins of humanity. Sharp-edged stone flakes, struck from larger cores, are the primary evidence for the earliest stone technology. Here we show that wild bearded capuchin monkeys (Sapajus libidinosus) in Brazil deliberately break stones, unintentionally producing recurrent, conchoidally fractured, sharp-edged flakes and cores that have the characteristics and morphology of intentionally produced hominin tools. The production of archaeologically visible cores and flakes is therefore no longer unique to the human lineage, providing a comparative perspective on the emergence of lithic technology. This discovery adds an additional dimension to interpretations of the human Palaeolithic record, the possible function of early stone tools, and the cognitive requirements for the emergence of stone flaking.

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

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

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

  • The stem osteichthyan Andreolepis and the origin of tooth replacement

  • The extinct Andreolepis, an early fish that is close to the common ancestor of all bony fish and land vertebrates, shed its teeth by basal resportion—the earliest example of this mode of tooth replacement.

  • Reconstitution in vitro of the entire cycle of the mouse female germ line

  • The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the entire process of oogenesis from mouse pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells and from induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts. Moreover, pluripotent stem cell lines were re-derived from the eggs that were generated in vitro, thereby reconstituting the full female germline cycle in a dish. This culture system will provide a platform for elucidating the molecular mechanisms underlying totipotency and the production of oocytes of other mammalian species in culture.

  • Mantle dynamics inferred from the crystallographic preferred orientation of bridgmanite

  • Seismic shear wave anisotropy is observed in Earth’s uppermost lower mantle around several subducted slabs. The anisotropy caused by the deformation-induced crystallographic preferred orientation (CPO) of bridgmanite (perovskite-structured (Mg,Fe)SiO3) is the most plausible explanation for these seismic observations. However, the rheological properties of bridgmanite are largely unknown. Uniaxial deformation experiments have been carried out to determine the deformation texture of bridgmanite, but the dominant slip system (the slip direction and plane) has not been determined. Here we report the CPO pattern and dominant slip system of bridgmanite under conditions that correspond to the uppermost lower mantle (25 gigapascals and 1,873 kelvin) obtained through simple shear deformation experiments using the Kawai-type deformation-DIA apparatus. The fabrics obtained are characterized by [100] perpendicular to the shear plane and [001] parallel to the shear direction, implying that the dominant slip system of bridgmanite is [001](100). The observed seismic shear- wave anisotropies near several subducted slabs (Tonga–Kermadec, Kurile, Peru and Java) can be explained in terms of the CPO of bridgmanite as induced by mantle flow parallel to the direction of subduction.

  • Catalytic alkylation of remote C–H bonds enabled by proton-coupled electron transfer

  • Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen–hydrogen (N–H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon–hydrogen (C–H) bond functionalization. In the latter process—a subset of the classical Hofmann–Löffler–Freytag reaction—amidyl radicals remove hydrogen atoms from unactivated aliphatic C–H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon–carbon (C–C) bonds. Here we report an approach that overcomes these limitations by homolysing the N–H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C–H abstraction and radical alkylation steps. This C–H alkylation represents a catalytic variant of the Hofmann–Löffler–Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C–C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using traditional HAT-based approaches.

  • Amide-directed photoredox-catalysed C–C bond formation at unactivated sp3 C–H bonds

  • Carbon–carbon (C–C) bond formation is paramount in the synthesis of biologically relevant molecules, modern synthetic materials and commodity chemicals such as fuels and lubricants. Traditionally, the presence of a functional group is required at the site of C–C bond formation. Strategies that allow C–C bond formation at inert carbon–hydrogen (C–H) bonds enable access to molecules that would otherwise be inaccessible and the development of more efficient syntheses of complex molecules. Here we report a method for the formation of C–C bonds by directed cleavage of traditionally non-reactive C–H bonds and their subsequent coupling with readily available alkenes. Our methodology allows for amide-directed selective C–C bond formation at unactivated sp3 C–H bonds in molecules that contain many such bonds that are seemingly indistinguishable. Selectivity arises through a relayedphotoredox-catalysed oxidation of a nitrogen–hydrogen bond. We anticipate that our findings will serve as a starting point for functionalization at inert C–H bonds through a strategy involving hydrogen-atom transfer.

  • Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state

  • The fin-to-limb transition represents one of the major vertebrate morphological innovations associated with the transition from aquatic to terrestrial life and is an attractive model for gaining insights into the mechanisms of morphological diversity between species. One of the characteristic features of limbs is the presence of digits at their extremities. Although most tetrapods have limbs with five digits (pentadactyl limbs), palaeontological data indicate that digits emerged in lobed fins of early tetrapods, which were polydactylous. How the transition to pentadactyl limbs occurred remains unclear. Here we show that the mutually exclusive expression of the mouse genes Hoxa11 and Hoxa13, which were previously proposed to be involved in the origin of the tetrapod limb, is required for the pentadactyl state. We further demonstrate that the exclusion of Hoxa11 from the Hoxa13 domain relies on an enhancer that drives antisense transcription at the Hoxa11 locus after activation by HOXA13 and HOXD13. Finally, we show that the enhancer that drives antisense transcription of the mouse Hoxa11 gene is absent in zebrafish, which, together with the largely overlapping expression of hoxa11 and hoxa13 genes reported in fish, suggests that this enhancer emerged in the course of the fin-to-limb transition. On the basis of the polydactyly that we observed after expression of Hoxa11 in distal limbs, we propose that the evolution of Hoxa11 regulation contributed to the transition from polydactyl limbs in stem-group tetrapods to pentadactyl limbs in extant tetrapods.

  • Metal–organic frameworks as selectivity regulators for hydrogenation reactions

  • Owing to the limited availability of natural sources, the widespread demand of the flavouring, perfume and pharmaceutical industries for unsaturated alcohols is met by producing them fromα,β-unsaturated aldehydes, through the selective hydrogenation of the carbon–oxygen group (in preference to the carbon–carbon group). However, developing effective catalysts for this transformation is challenging, because hydrogenation of the carbon–carbon group is thermodynamically favoured. This difficulty is particularly relevant for one major category of heterogeneous catalyst: metal nanoparticles supported on metal oxides. These systems are generally incapable of significantly enhancing the selectivity towards thermodynamically unfavoured reactions, because only the edges of nanoparticles that are in direct contact with the metal-oxide support possess selective catalytic properties; most of the exposed nanoparticle surfaces do not. This has inspired the use of metal–organic frameworks (MOFs) to encapsulate metal nanoparticles within their layers or inside their channels, to influence the activity of the entire nanoparticle surface while maintaining efficient reactant and product transport owing to the porous nature of the material. Here we show that MOFs can also serve as effective selectivity regulators for the hydrogenation of α,β-unsaturated aldehydes. Sandwiching platinum nanoparticles between an inner core and an outer shell composed of an MOF with metal nodes of Fe3+, Cr3+ or both (known as MIL-101; refs 19, 20, 21) results in stable catalysts that convert a range of α,β-unsaturated aldehydes with high efficiency and with significantly enhanced selectivity towards unsaturated alcohols. Calculations reveal that preferential interaction of MOF metal sites with the carbon–oxygen rather than the carbon–carbon group renders hydrogenation of the former by the embedded platinum nanoparticles a thermodynamically favoured reaction. We anticipate that our basic design strategy will allow the development of other selective heterogeneous catalysts for important yet challenging transformations.

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

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

  • Corrigendum: Slowly fading super-luminous supernovae that are not pair-instability explosions

  • 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.

  • 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

  • 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.

  • 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.

  • 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.

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

  • 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

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

  • Corrigendum: Lytic to temperate switching of viral communities

  • 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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