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Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all


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



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 & 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



The News & 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 (>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 constraints of 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 evolution of 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 Point Barrow 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.