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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



 



Liquid-biopsies success highlights power of combining basic and clinical research

2017-04-26

Using free-floating DNA to detect lung cancer brings benefits to researchers and patients alike.



More surgeons must start doing basic science

2017-04-21

They say they don't have the time or incentives to do research — and that’s dangerous for translational medicine.



Announcement: Nature journals support the San Francisco Declaration on Research Assessment

2017-04-26

Nature Research will this week formally sign up to the principles outlined in the San Francisco Declaration on Research Assessment, commonly known as DORA. Nature Research (the Nature-branded journals, Scientific Reports, Scientific Data and the Nature Partner Journals) has long been editorially aligned with



Planetariums — not just for kids

2017-04-25

Planetariums are not just for education, or even astronomy: they could display all sorts of data, if only scientists thought to use them, says Tom Kwasnitschka.






California’s $3-billion bet on stem cells faces final test

2017-04-26

Major investment in regenerative medicine enters its last stage — and the money might run out before treatments are ready.



Ripple effects of New Zealand earthquake continue to this day

2017-04-24

November tremor sparked slow, deep movements in Earth’s crust that increase the chances of a similar severe quake within a year.



Mining threatens Chinese fossil site that revealed planet's earliest animals

2017-04-20

Protests sparked by the destruction of three key fossil-hunting areas result in a temporary halt of phosphate mining.



What happened at March for Science events around the world

2017-04-21

Nature reported from marches in cities including Sydney, Washington DC and Paris, as people took to the streets in support of science.



Surprise El Niño causes devastation but offers lessons for ecologists

2017-04-25

How Peruvian coastal deserts respond to rains will aid future disaster response.



The next big hit in molecule Hollywood

2017-04-26

Superfast imaging techniques are giving researchers their best views yet of what happens in the atomic world.



Reviewers are blinkered by bibliometrics

2017-04-26

Science panels still rely on poor proxies to judge quality and impact. That results in risk-averse research, say Paula Stephan, Reinhilde Veugelers and Jian Wang.



Artificial Intelligence: Chess match of the century

2017-04-26

Demis Hassabis lauds Garry Kasparov's account of battling supercomputer Deep Blue.



Psychology: Science in spite of itself

2017-04-26

Barbara A. Spellman hails an analysis of reproducibility in psychology by a champion for change.



Books in brief

2017-04-26

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



Predatory journals: fortify the defences

2017-04-26

Ongoing initiatives are crucial for keeping researchers informed about predatory journals and the fraudulent strategies they use to recruit submissions (see P.Sorokowskiet al. Nature543, 481–483; 2017). For example, these journals will often add names of real



Predatory journals: Beall's List is missed

2017-04-26

Beall's List of predatory publishers, now withdrawn, was instrumental in the fight against the dubious practices of some online open-access science journals (see P.Sorokowskiet al. Nature543, 481–483; 2017). To borrow a metaphor from James Woolsey, director



Neurosurgery: Gentler alternatives to chips in the brain

2017-04-26

As physicians and neuroscientists, we are concerned about the clinical and scientific limitations of chip-in-the-brain technology. Until these problems are overcome, we argue that less invasive methods could be used.Implantation of an electronic chip requires opening the skull and inserting the chip into the



Commerce: Help bigger palm oil yields to save land

2017-04-26

Technological innovation in oil-palm farming could help both to boost yields of palm oil and to reduce deforestation, but only if higher productivity causes palm-oil prices to drop sufficiently to discourage additional cultivation (see Nature543, 306–308;10.1038/543306a2017). If



Environment: An old clue to the secret of longevity

2017-04-26

Epidemiologists are seeking to identify the lifestyle and environmental factors that make the Greek inhabitants of Ikaria, a small island in the Aegean Sea, one of the world's longest-lived populations (see go.nature.com/2nzec7y and P.Pietriet al. J. Am. Coll. Cardiol.66,



Politics: Turbulence ahead

2017-04-26

US science faces a political storm, and early-career researchers should prepare themselves.



Harassment: University transparency

2017-04-26

Australian institutions aim for open policy on sexual-assault data.



Physics: Degrees of progress

2017-04-26

More women than ever earn US physics PhDs.



Query, Queue, Repeat

2017-04-26

Digital dilemma.



Food security

2017-04-26




Nutrition: A world of insecurity

2017-04-26

Malnutrition is a global problem. With population and consumption set to rise over the coming decades, achieving food security will require action on many fronts.



Agrobiodiversity: The living library

2017-04-26

Wild and heirloom plants are giving major crop varieties, and the global food system, a genetic makeover.



Bioengineering: Solar upgrade

2017-04-26

Plant scientists are redesigning photosynthesis to improve crop yields and feed a growing population.



Egypt: Space to grow

2017-04-26

Fertile land is at a premium in Egypt. Reclaiming the desert is repeatedly proposed as the solution, but should the country be doing more with what it already has?



Perspective: Look beyond production

2017-04-26

Malnutrition is the new normal. Addressing it will require changes across the entire food system, says John Ingram.



Sustainability: A meaty issue

2017-04-26

Our insatiable appetite for red meat is bad for our health and for the planet. Sustainable alternatives are in the pipeline, but will they convince us to make the switch?



Technology: The Future of Agriculture

2017-04-26

A technological revolution in farming led by advances in robotics and sensing technologies looks set to disrupt modern practice.



Animal behaviour: How to build a better dad

2017-04-19

Oldfield mice and deer mice differ in their parental care, most dramatically in the behaviour of fathers. A study reveals the genetic and neuronal contributions to variation in parental care. See Article p.434



Particle physics: Strangeness in the proton

2017-04-12

The proton can contain pairs of elementary particles known as strange quarks. The contribution of these particles to the proton's electric-charge distribution and magnetic moment has been determined.



Archaeology: Unexpectedly early signs of Americans

2017-04-26

Humans are thought to have reached the Americas less than 15,000 years ago. But evidence of stone tool use on an animal carcass excavated in California points to a much earlier arrival of human relatives from the genus Homo. See Letter p.479



Atmospheric science: Severe weather in a warming climate

2017-04-26

During the past few decades, the Sahara Desert has become even hotter. Satellite observations suggest that this warming has led to a rise in the frequency of extreme storms in the Sahel region of West Africa. See Letter p.475



Microscopy: A larger palette for biological imaging

2017-04-26

Biological molecules are often imaged by attaching fluorescent labels — but only a few label types can be used at a time. A method that could smash the record for the number of labels that can be used together is now reported. See Letter p.465



Plant science: Genomic compartments in barley

2017-04-26

A high-quality barley genome reveals a surprising compartmentalization of genes and repetitive sequences in chromosomes. This advance paves the way for improved genetic optimization of cereals. See Article p.427



Correction

2017-04-26

In the News & Views article 'Marine conservation: How to heal an ocean' by Boris Worm (Nature543, 630–631; 2017), the picture credit was incorrect — it should have been Jiangang Luo/Univ. Miami Rosenstiel School. The online version of



A chromosome conformation capture ordered sequence of the barley genome

2017-04-26

Cereal grasses of the Triticeae tribe have been the major food source in temperate regions since the dawn of agriculture. Their large genomes are characterized by a high content of repetitive elements and large pericentromeric regions that are virtually devoid of meiotic recombination. Here we



The genetic basis of parental care evolution in monogamous mice

2017-04-19

Parental care is essential for the survival of mammals, yet the mechanisms underlying its evolution remain largely unknown. Here we show that two sister species of mice, Peromyscus polionotus and Peromyscus maniculatus, have large and heritable differences in parental behaviour. Using quantitative genetics,



Mechanism of chromatin remodelling revealed by the Snf2-nucleosome structure

2017-04-19

Chromatin remodellers are helicase-like, ATP-dependent enzymes that alter chromatin structure and nucleosome positions to allow regulatory proteins access to DNA. Here we report the cryo-electron microscopy structure of chromatin remodeller Switch/sucrose non-fermentable (SWI2/SNF2) from Saccharomyces cerevisiae bound to the nucleosome. The structure shows that



Structure and allosteric inhibition of excitatory amino acid transporter 1

2017-04-19

Human members of the solute carrier 1 (SLC1) family of transporters take up excitatory neurotransmitters in the brain and amino acids in peripheral organs. Dysregulation of the function of SLC1 transporters is associated with neurodegenerative disorders and cancer. Here we present crystal structures of a



A universal model for solar eruptions

2017-04-26

Magnetically driven eruptions on the Sun, from stellar-scale coronal mass ejections to small-scale coronal X-ray and extreme-ultraviolet jets, have frequently been observed to involve the ejection of the highly stressed magnetic flux of a filament. Theoretically, these two phenomena have been thought to arise through very different mechanisms: coronal mass ejections from an ideal (non-dissipative) process, whereby the energy release does not require a change in the magnetic topology, as in the kink or torus instability; and coronal jets from a resistive process involving magnetic reconnection. However, it was recently concluded from new observations that all coronal jets are driven by filament ejection, just like large mass ejections. This suggests that the two phenomena have physically identical origin and hence that a single mechanism may be responsible, that is, either mass ejections arise from reconnection, or jets arise from an ideal instability. Here we report simulations of a coronal jet driven by filament ejection, whereby a region of highly sheared magnetic field near the solar surface becomes unstable and erupts. The results show that magnetic reconnection causes the energy release via ‘magnetic breakout’—a positive-feedback mechanism between filament ejection and reconnection. We conclude that if coronal mass ejections and jets are indeed of physically identical origin (although on different spatial scales) then magnetic reconnection (rather than an ideal process) must also underlie mass ejections, and that magnetic breakout is a universal model for solar eruptions.



Predicting crystal growth via a unified kinetic three-dimensional partition model

2017-04-03

Understanding and predicting crystal growth is fundamental to the control of functionality in modern materials. Despite investigations for more than one hundred years, it is only recently that the molecular intricacies of these processes have been revealed by scanning probe microscopy. To organize and understand this large amount of new information, new rules for crystal growth need to be developed and tested. However, because of the complexity and variety of different crystal systems, attempts to understand crystal growth in detail have so far relied on developing models that are usually applicable to only one system. Such models cannot be used to achieve the wide scope of understanding that is required to create a unified model across crystal types and crystal structures. Here we describe a general approach to understanding and, in theory, predicting the growth of a wide range of crystal types, including the incorporation of defect structures, by simultaneous molecular-scale simulation of crystal habit and surface topology using a unified kinetic three-dimensional partition model. This entails dividing the structure into ‘natural tiles’ or Voronoi polyhedra that are metastable and, consequently, temporally persistent. As such, these units are then suitable for re-construction of the crystal via a Monte Carlo algorithm. We demonstrate our approach by predicting the crystal growth of a diverse set of crystal types, including zeolites, metal–organic frameworks, calcite, urea and l-cystine.



Ultrastrong steel via minimal lattice misfit and high-density nanoprecipitation

2017-04-10

Next-generation high-performance structural materials are required for lightweight design strategies and advanced energy applications. Maraging steels, combining a martensite matrix with nanoprecipitates, are a class of high-strength materials with the potential for matching these demands. Their outstanding strength originates from semi-coherent precipitates, which unavoidably exhibit a heterogeneous distribution that creates large coherency strains, which in turn may promote crack initiation under load. Here we report a counterintuitive strategy for the design of ultrastrong steel alloys by high-density nanoprecipitation with minimal lattice misfit. We found that these highly dispersed, fully coherent precipitates (that is, the crystal lattice of the precipitates is almost the same as that of the surrounding matrix), showing very low lattice misfit with the matrix and high anti-phase boundary energy, strengthen alloys without sacrificing ductility. Such low lattice misfit (0.03 ± 0.04 per cent) decreases the nucleation barrier for precipitation, thus enabling and stabilizing nanoprecipitates with an extremely high number density (more than 1024 per cubic metre) and small size (about 2.7 ± 0.2 nanometres). The minimized elastic misfit strain around the particles does not contribute much to the dislocation interaction, which is typically needed for strength increase. Instead, our strengthening mechanism exploits the chemical ordering effect that creates backstresses (the forces opposing deformation) when precipitates are cut by dislocations. We create a class of steels, strengthened by Ni(Al,Fe) precipitates, with a strength of up to 2.2 gigapascals and good ductility (about 8.2 per cent). The chemical composition of the precipitates enables a substantial reduction in cost compared to conventional maraging steels owing to the replacement of the essential but high-cost alloying elements cobalt and titanium with inexpensive and lightweight aluminium. Strengthening of this class of steel alloy is based on minimal lattice misfit to achieve maximal precipitate dispersion and high cutting stress (the stress required for dislocations to cut through coherent precipitates and thus produce plastic deformation), and we envisage that this lattice misfit design concept may be applied to many other metallic alloys.



Super-multiplex vibrational imaging

2017-04-19

The ability to visualize directly a large number of distinct molecular species inside cells is increasingly essential for understanding complex systems and processes. Even though existing methods have successfully been used to explore structure–function relationships in nervous systems, to profile RNA in situ, to reveal the heterogeneity of tumour microenvironments and to study dynamic macromolecular assembly, it remains challenging to image many species with high selectivity and sensitivity under biological conditions. For instance, fluorescence microscopy faces a ‘colour barrier’, owing to the intrinsically broad (about 1,500 inverse centimetres) and featureless nature of fluorescence spectra that limits the number of resolvable colours to two to five (or seven to nine if using complicated instrumentation and analysis). Spontaneous Raman microscopy probes vibrational transitions with much narrower resonances (peak width of about 10 inverse centimetres) and so does not suffer from this problem, but weak signals make many bio-imaging applications impossible. Although surface-enhanced Raman scattering offers high sensitivity and multiplicity, it cannot be readily used to image specific molecular targets quantitatively inside live cells. Here we use stimulated Raman scattering under electronic pre-resonance conditions to image target molecules inside living cells with very high vibrational selectivity and sensitivity (down to 250 nanomolar with a time constant of 1 millisecond). We create a palette of triple-bond-conjugated near-infrared dyes that each displays a single peak in the cell-silent Raman spectral window; when combined with available fluorescent probes, this palette provides 24 resolvable colours, with the potential for further expansion. Proof-of-principle experiments on neuronal co-cultures and brain tissues reveal cell-type-dependent heterogeneities in DNA and protein metabolism under physiological and pathological conditions, underscoring the potential of this 24-colour (super-multiplex) optical imaging approach for elucidating intricate interactions in complex biological systems.



Abrasion-set limits on Himalayan gravel flux

2017-04-26

Rivers sourced in the Himalayan mountain range carry some of the largest sediment loads on the planet, yet coarse gravel in these rivers vanishes within approximately 10–40 kilometres on entering the Ganga Plain (the part of the North Indian River Plain containing the Ganges River). Understanding the fate of gravel is important for forecasting the response of rivers to large influxes of sediment triggered by earthquakes or storms. Rapid increase in gravel flux and subsequent channel bed aggradation (that is, sediment deposition by a river) following the 1999 Chi-Chi and 2008 Wenchuan earthquakes reduced channel capacity and increased flood inundation. Here we present an analysis of fan geometry, sediment grain size and lithology in the Ganga Basin. We find that the gravel fluxes from rivers draining the central Himalayan mountains, with upstream catchment areas ranging from about 350 to 50,000 square kilometres, are comparable. Our results show that abrasion of gravel during fluvial transport can explain this observation; most of the gravel sourced more than 100 kilometres upstream is converted into sand by the time it reaches the Ganga Plain. These findings indicate that earthquake-induced sediment pulses sourced from the Greater Himalayas, such as that following the 2015 Gorkha earthquake, are unlikely to drive increased gravel aggradation at the mountain front. Instead, we suggest that the sediment influx should result in an elevated sand flux, leading to distinct patterns of aggradation and flood risk in the densely populated, low-relief Ganga Plain.



Frequency of extreme Sahelian storms tripled since 1982 in satellite observations

2017-04-26

The hydrological cycle is expected to intensify under global warming, with studies reporting more frequent extreme rain events in many regions of the world, and predicting increases in future flood frequency. Such early, predominantly mid-latitude observations are essential because of shortcomings within climate models in their depiction of convective rainfall. A globally important group of intense storms—mesoscale convective systems (MCSs)—poses a particular challenge, because they organize dynamically on spatial scales that cannot be resolved by conventional climate models. Here, we use 35 years of satellite observations from the West African Sahel to reveal a persistent increase in the frequency of the most intense MCSs. Sahelian storms are some of the most powerful on the planet, and rain gauges in this region have recorded a rise in ‘extreme’ daily rainfall totals. We find that intense MCS frequency is only weakly related to the multidecadal recovery of Sahel annual rainfall, but is highly correlated with global land temperatures. Analysis of trends across Africa reveals that MCS intensification is limited to a narrow band south of the Sahara desert. During this period, wet-season Sahelian temperatures have not risen, ruling out the possibility that rainfall has intensified in response to locally warmer conditions. On the other hand, the meridional temperature gradient spanning the Sahel has increased in recent decades, consistent with anthropogenic forcing driving enhanced Saharan warming. We argue that Saharan warming intensifies convection within Sahelian MCSs through increased wind shear and changes to the Saharan air layer. The meridional gradient is projected to strengthen throughout the twenty-first century, suggesting that the Sahel will experience particularly marked increases in extreme rain. The remarkably rapid intensification of Sahelian MCSs since the 1980s sheds new light on the response of organized tropical convection to global warming, and challenges conventional projections made by general circulation models.



A 130,000-year-old archaeological site in southern California, USA

2017-04-26

The earliest dispersal of humans into North America is a contentious subject, and proposed early sites are required to meet the following criteria for acceptance: (1) archaeological evidence is found in a clearly defined and undisturbed geologic context; (2) age is determined by reliable radiometric dating; (3) multiple lines of evidence from interdisciplinary studies provide consistent results; and (4) unquestionable artefacts are found in primary context. Here we describe the Cerutti Mastodon (CM) site, an archaeological site from the early late Pleistocene epoch, where in situ hammerstones and stone anvils occur in spatio-temporal association with fragmentary remains of a single mastodon (Mammut americanum). The CM site contains spiral-fractured bone and molar fragments, indicating that breakage occured while fresh. Several of these fragments also preserve evidence of percussion. The occurrence and distribution of bone, molar and stone refits suggest that breakage occurred at the site of burial. Five large cobbles (hammerstones and anvils) in the CM bone bed display use-wear and impact marks, and are hydraulically anomalous relative to the low-energy context of the enclosing sandy silt stratum. 230Th/U radiometric analysis of multiple bone specimens using diffusion–adsorption–decay dating models indicates a burial date of 130.7 ± 9.4 thousand years ago. These findings confirm the presence of an unidentified species of Homo at the CM site during the last interglacial period (MIS 5e; early late Pleistocene), indicating that humans with manual dexterity and the experiential knowledge to use hammerstones and anvils processed mastodon limb bones for marrow extraction and/or raw material for tool production. Systematic proboscidean bone reduction, evident at the CM site, fits within a broader pattern of Palaeolithic bone percussion technology in Africa, Eurasia and North America. The CM site is, to our knowledge, the oldest in situ, well-documented archaeological site in North America and, as such, substantially revises the timing of arrival of Homo into the Americas.



The earliest bird-line archosaurs and the assembly of the dinosaur body plan

2017-04-12

The relationship between dinosaurs and other reptiles is well established, but the sequence of acquisition of dinosaurian features has been obscured by the scarcity of fossils with transitional morphologies. The closest extinct relatives of dinosaurs either have highly derived morphologies or are known from poorly preserved or incomplete material. Here we describe one of the stratigraphically lowest and phylogenetically earliest members of the avian stem lineage (Avemetatarsalia), Teleocrater rhadinus gen. et sp. nov., from the Middle Triassic epoch. The anatomy of T. rhadinus provides key information that unites several enigmatic taxa from across Pangaea into a previously unrecognized clade, Aphanosauria. This clade is the sister taxon of Ornithodira (pterosaurs and birds) and shortens the ghost lineage inferred at the base of Avemetatarsalia. We demonstrate that several anatomical features long thought to characterize Dinosauria and dinosauriforms evolved much earlier, soon after the bird–crocodylian split, and that the earliest avemetatarsalians retained the crocodylian-like ankle morphology and hindlimb proportions of stem archosaurs and early pseudosuchians. Early avemetatarsalians were substantially more species-rich, widely geographically distributed and morphologically diverse than previously recognized. Moreover, several early dinosauromorphs that were previously used as models to understand dinosaur origins may represent specialized forms rather than the ancestral avemetatarsalian morphology.



Human umbilical cord plasma proteins revitalize hippocampal function in aged mice

2017-04-19

Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation and downregulated in the aged brain. In addition to revitalizing other aged tissues, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high translational value for targeting ageing- or disease-associated hippocampal dysfunction.



SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin

2017-04-19

Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα–CD47 checkpoint could be useful in treating human cancer. However, the pro-phagocytic receptor(s) responsible for tumour cell phagocytosis is(are) largely unknown. Here we find that macrophages are much more efficient at phagocytosis of haematopoietic tumour cells, compared with non-haematopoietic tumour cells, in response to SIRPα–CD47 blockade. Using a mouse lacking the signalling lymphocytic activation molecule (SLAM) family of homotypic haematopoietic cell-specific receptors, we determined that phagocytosis of haematopoietic tumour cells during SIRPα–CD47 blockade was strictly dependent on SLAM family receptors in vitro and in vivo. In both mouse and human cells, this function required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319), expressed on macrophages and tumour cell targets. In contrast to most SLAM receptor functions, SLAMF7-mediated phagocytosis was independent of signalling lymphocyte activation molecule-associated protein (SAP) adaptors. Instead, it depended on the ability of SLAMF7 to interact with integrin Mac-1 (refs 18, 19, 20) and utilize signals involving immunoreceptor tyrosine-based activation motifs. These findings elucidate the mechanism by which macrophages engulf and destroy haematopoietic tumour cells. They also reveal a novel SAP adaptor-independent function for a SLAM receptor. Lastly, they suggest that patients with tumours expressing SLAMF7 are more likely to respond to SIRPα–CD47 blockade therapy.



High-avidity IgA protects the intestine by enchaining growing bacteria

2017-04-12

Vaccine-induced high-avidity IgA can protect against bacterial enteropathogens by directly neutralizing virulence factors or by poorly defined mechanisms that physically impede bacterial interactions with the gut tissues (‘immune exclusion’). IgA-mediated cross-linking clumps bacteria in the gut lumen and is critical for protection against infection by non-typhoidal Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium). However, classical agglutination, which was thought to drive this process, is efficient only at high pathogen densities (≥108 non-motile bacteria per gram). In typical infections, much lower densities (100–107 colony-forming units per gram) of rapidly dividing bacteria are present in the gut lumen. Here we show that a different physical process drives formation of clumps in vivo: IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, and clumping is therefore dependent on growth. Enchained growth is effective at all realistic pathogen densities, and accelerates pathogen clearance from the gut lumen. Furthermore, IgA enchains plasmid-donor and -recipient clones into separate clumps, impeding conjugative plasmid transfer in vivo. Enchained growth is therefore a mechanism by which IgA can disarm and clear potentially invasive species from the intestinal lumen without requiring high pathogen densities, inflammation or bacterial killing. Furthermore, our results reveal an untapped potential for oral vaccines in combating the spread of antimicrobial resistance.



Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl

2017-04-19

Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-range chromosomal cis-interactions. Cohesin is also present at these sites, but has been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites, according to this or other models, is unknown. Here we show that the distribution of cohesin in the mouse genome depends on transcription, CTCF and the cohesin release factor Wings apart-like (Wapl). In CTCF-depleted fibroblasts, cohesin cannot be properly recruited to CTCF sites but instead accumulates at transcription start sites of active genes, where the cohesin-loading complex is located. In the absence of both CTCF and Wapl, cohesin accumulates in up to 70 kilobase-long regions at 3′-ends of active genes, in particular if these converge on each other. Changing gene expression modulates the position of these ‘cohesin islands’. These findings indicate that transcription can relocate mammalian cohesin over long distances on DNA, as previously reported for yeast cohesin, that this translocation contributes to positioning cohesin at CTCF sites, and that active genes can be freed from cohesin either by transcription-mediated translocation or by Wapl-mediated release.



Corrigendum: MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool

2017-04-26

Nature508, 215–221 (2014); doi:10.1038/nature13181In this Article, the structure of compound TH650 (4) in Fig. 4a was drawn incorrectly; the correct structure is shown as Fig. 1 to this Corrigendum. Preparative, spectroscopic and biological