Nature 555, 7697 (2018). doi:10.1038/d41586-018-03389-w

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The mathematics of Joseph Fourier, born 250 years ago this week, shows the value of intellectual boldness.

Nature 555, 7697 (2018). doi:10.1038/d41586-018-03388-x

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Dialogue with the public requires a nuanced approach and a willingness to accept uncomfortable truths.

Nature 555, 7697 (2018). doi:10.1038/d41586-018-03254-w

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Transdisciplinary programme explores the pervasive presence of symmetry violations.

Nature 555, 7697 (2018). http://www.nature.com/doifinder/10.1038/d41586-018-03264-8

Author: Ji-Bum Chung

In South Korea, hundreds ofwell-informed citizens voted on behalf of their country — a technique that should be used more widely, says Ji-Bum Chung.

Nature 555, 7697 (2018). http://www.nature.com/doifinder/10.1038/d41586-018-03266-6

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The week in science: 16–22 March 2018.

Nature 555, 7697 (2018). http://www.nature.com/doifinder/10.1038/d41586-018-03171-y

Author: Amy Maxmen

Reforms put in place after Ebola epidemic in West Africa have built Nigeria's capacity to diagnose diseases and track their spread.

Nature 555, 7697 (2018). http://www.nature.com/doifinder/10.1038/d41586-018-02921-2

Author: Dalmeet Singh Chawla

Blacklists that warn against questionable publishers are in demand.

Nature 555, 7697 (2018). http://www.nature.com/doifinder/10.1038/d41586-018-02957-4

Author: Davide Castelvecchi

Physicist and icon of science dies aged 76.

Nature 555, 7697 (2018). http://www.nature.com/doifinder/10.1038/d41586-018-03244-y

Author: Jeff Tollefson

Excavations in Kenya suggest improvements in stone tools and other human changes are linked to variations in climate.

Nature 555, 7697 (2018). http://www.nature.com/doifinder/10.1038/d41586-018-03246-w

Author: David Cyranoski

Overhaul prompts fears of an erosion in funding for basic science.

Nature 555, 7697 (2018). http://www.nature.com/doifinder/10.1038/d41586-018-03268-4

Author: David Cyranoski

After 20 years of hope, promise and controversy, human embryonic stem cells are reshaping biological concepts and starting to move into the clinic.

Nature 555, 7697 (2018). http://www.nature.com/doifinder/10.1038/d41586-018-03267-5

Author: Jo Marchant

Commonly prescribed drugs called fluoroquinolones cause rare, disabling side effects. Researchers are struggling to work out why.

Nature 555, 7697 (2018). doi:10.1038/d41586-018-03270-w

Authors: Sheila Jasanoff & J. Benjamin Hurlbut

Sheila Jasanoff and J. Benjamin Hurlbut call for an international network of scholars and organizations to support a new kind of conversation.

Nature 555, 7697 (2018). doi:10.1038/d41586-018-03269-3

Author: Simon Burall

The breadth of social and moral questions raised requires a new architecture for democratic debate, insists Simon Burall.

Nature 555, 7697 (2018). doi:10.1038/d41586-018-03272-8

Author: Natalie Wolchover

Natalie Wolchover enjoys Philip Ball’s grapple with slippery questions about the quantum revolution.

Nature 555, 7697 (2018). doi:10.1038/d41586-018-03273-7

Author: Barbara Kiser

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

Nature 555, 7697 (2018). doi:10.1038/d41586-018-03271-9

Author: Anthony King

Anthony King enjoys an exhibition of hoaxes, frauds, simulacra and substitutes.

Nature 555, 7697 (2018). doi:10.1038/d41586-018-03309-y

Author: John Cooper Hamilton

A ray of hope.

Nature 555, 7697 (2018). doi:10.1038/nature25771

Authors: Carla Vicinanza, Iolanda Aquila, Eleonora Cianflone, Mariangela Scalise, Fabiola Marino, Teresa Mancuso, Francesca Fumagalli, Emilia Dora Giovannone, Francesca Cristiano, Enrico Iaccino, Pina Marotta, Annalaura Torella, Roberto Latini, Valter Agosti, Pierangelo Veltri, Konrad Urbanek, Andrea M. Isidori, Dieter Saur, Ciro Indolfi, Bernardo Nadal-Ginard & Daniele Torella

ARISING FROM J. H.van Berloet al. Nature509, 337–341 (2014); doi:10.1038/nature13309In a cell fate-mapping study using a cre-knock-in (KI) into the Kit locus, and in two other studies that used a

Nature 555, 7697 (2018). doi:10.1038/nature25772

Authors: Jop H. van Berlo, Onur Kanisicak, Marjorie Maillet, Ronald J. Vagnozzi, Jason Karch, Suh-Chin J. Lin, Ryan C. Middleton, Eduardo Marbán & Jeffery D. Molkentin

REPLYING TO C.Vicinanzaet al. Nature55510.1038/nature25771 (2018)The accompanying Comment by Vicinanza et al. does not agree with our previous study regarding the utility of c-Kitpos (also known as Kitpos) cells

Nature 555, 7697 (2018). doi:10.1038/d41586-018-02881-7

Authors: Derek Wong & Stephen Yip

Brain tumours are often classified by visual assessment of tumour cells, yet such diagnoses can vary depending on the observer. Machine-learning methods to spot molecular patterns could improve cancer diagnosis.

Nature 555, 7697 (2018). doi:10.1038/d41586-018-03000-2

Authors: Laura Pontano Vaites & J. Wade Harper

Low-complexity protein aggregates are a hallmark of neurodegeneration. High-resolution snapshots of the structure of one such aggregate offer an unprecedented view of how these proteins disrupt crucial cellular functions.

Nature 555, 7697 (2018). doi:10.1038/d41586-018-02861-x

Authors: Sedeer el-Showk & Ari Pekka Mähönen

Water-conducting tissues inside plant roots are surrounded by impermeable cells. This protective barrier is punctured by ‘passage cells’, which are thought to regulate nutrient uptake. How these cells form has now been revealed.

Nature 555, 7697 (2018). doi:10.1038/nature25999

Authors: Christian Mayer, Christoph Hafemeister, Rachel C. Bandler, Robert Machold, Renata Batista Brito, Xavier Jaglin, Kathryn Allaway, Andrew Butler, Gord Fishell & Rahul Satija

Diverse subsets of cortical interneurons have vital roles in higher-order brain functions. To investigate how this diversity is generated, here we used single-cell RNA sequencing to profile the transcriptomes of mouse cells collected along a developmental time course. Heterogeneity within mitotic progenitors in the ganglionic

Nature 555, 7697 (2018). doi:10.1038/nature26002

Authors: Vicente Perez-Garcia, Elena Fineberg, Robert Wilson, Alexander Murray, Cecilia Icoresi Mazzeo, Catherine Tudor, Arnold Sienerth, Jacqueline K. White, Elizabeth Tuck, Edward J. Ryder, Diane Gleeson, Emma Siragher, Hannah Wardle-Jones, Nicole Staudt, Neha Wali, John Collins, Stefan Geyer, Elisabeth M. Busch-Nentwich, Antonella Galli, James C. Smith, Elizabeth Robertson, David J. Adams, Wolfgang J. Weninger, Timothy Mohun & Myriam Hemberger

Large-scale phenotyping efforts have demonstrated that approximately 25–30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic

Nature 555, 7697 (2018). doi:10.1038/nature26000

Authors: David Capper, David T. W. Jones, Martin Sill, Volker Hovestadt, Daniel Schrimpf, Dominik Sturm, Christian Koelsche, Felix Sahm, Lukas Chavez, David E. Reuss, Annekathrin Kratz, Annika K. Wefers, Kristin Huang, Kristian W. Pajtler, Leonille Schweizer, Damian Stichel, Adriana Olar, Nils W. Engel, Kerstin Lindenberg, Patrick N. Harter, Anne K. Braczynski, Karl H. Plate, Hildegard Dohmen, Boyan K. Garvalov, Roland Coras, Annett Hölsken, Ekkehard Hewer, Melanie Bewerunge-Hudler, Matthias Schick, Roger Fischer, Rudi Beschorner, Jens Schittenhelm, Ori Staszewski, Khalida Wani, Pascale Varlet, Melanie Pages, Petra Temming, Dietmar Lohmann, Florian Selt, Hendrik Witt, Till Milde, Olaf Witt, Eleonora Aronica, Felice Giangaspero, Elisabeth Rushing, Wolfram Scheurlen, Christoph Geisenberger, Fausto J. Rodriguez, Albert Becker, Matthias Preusser, Christine Haberler, Rolf Bjerkvig, Jane Cryan, Michael Farrell, Martina Deckert, Jürgen Hench, Stephan Frank, Jonathan Serrano, Kasthuri Kannan, Aristotelis Tsirigos, Wolfgang Brück, Silvia Hofer, Stefanie Brehmer, Marcel Seiz-Rosenhagen, Daniel Hänggi, Volkmar Hans, Stephanie Rozsnoki, Jordan R. Hansford, Patricia Kohlhof, Bjarne W. Kristensen, Matt Lechner, Beatriz Lopes, Christian Mawrin, Ralf Ketter, Andreas Kulozik, Ziad Khatib, Frank Heppner, Arend Koch, Anne Jouvet, Catherine Keohane, Helmut Mühleisen, Wolf Mueller, Ute Pohl, Marco Prinz, Axel Benner, Marc Zapatka, Nicholas G. Gottardo, Pablo Hernáiz Driever, Christof M. Kramm, Hermann L. Müller, Stefan Rutkowski, Katja von Hoff, Michael C. Frühwald, Astrid Gnekow, Gudrun Fleischhack, Stephan Tippelt, Gabriele Calaminus, Camelia-Maria Monoranu, Arie Perry, Chris Jones, Thomas S. Jacques, Bernhard Radlwimmer, Marco Gessi, Torsten Pietsch, Johannes Schramm, Gabriele Schackert, Manfred Westphal, Guido Reifenberger, Pieter Wesseling, Michael Weller, Vincent Peter Collins, Ingmar Blümcke, Martin Bendszus, Jürgen Debus, Annie Huang, Nada Jabado, Paul A. Northcott, Werner Paulus, Amar Gajjar, Giles W. Robinson, Michael D. Taylor, Zane Jaunmuktane, Marina Ryzhova, Michael Platten, Andreas Unterberg, Wolfgang Wick, Matthias A. Karajannis, Michel Mittelbronn, Till Acker, Christian Hartmann, Kenneth Aldape, Ulrich Schüller, Rolf Buslei, Peter Lichter, Marcel Kool, Christel Herold-Mende, David W. Ellison, Martin Hasselblatt, Matija Snuderl, Sebastian Brandner, Andrey Korshunov, Andreas von Deimling & Stefan M. Pfister

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging—with substantial inter-observer variability in the histopathological diagnosis of many

Nature 555, 7697 (2018). doi:10.1038/nature26003

Authors: Seung Joong Kim, Javier Fernandez-Martinez, Ilona Nudelman, Yi Shi, Wenzhu Zhang, Barak Raveh, Thurston Herricks, Brian D. Slaughter, Joanna A. Hogan, Paula Upla, Ilan E. Chemmama, Riccardo Pellarin, Ignacia Echeverria, Manjunatha Shivaraju, Azraa S. Chaudhury, Junjie Wang, Rosemary Williams, Jay R. Unruh, Charles H. Greenberg, Erica Y. Jacobs, Zhiheng Yu, M. Jason de la Cruz, Roxana Mironska, David L. Stokes, John D. Aitchison, Martin F. Jarrold, Jennifer L. Gerton, Steven J. Ludtke, Christopher W. Akey, Brian T. Chait, Andrej Sali & Michael P. Rout

Nuclear pore complexes play central roles as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm. However, their large size and dynamic nature have impeded a full structural and functional elucidation. Here we determined the structure of the entire 552-protein nuclear pore complex

Nature 555, 7697 (2018). doi:10.1038/nature25756

Authors: Michael A. Beasley, Ignacio Trujillo, Ryan Leaman & Mireia Montes

Massive galaxies are thought to form in two phases: an initial collapse of gas and giant burst of central star formation, followed by the later accretion of material that builds up their stellar and dark-matter haloes. The systems of globular clusters within such galaxies are believed to form in a similar manner. The initial central burst forms metal-rich (spectrally red) clusters, whereas more metal-poor (spectrally blue) clusters are brought in by the later accretion of less-massive satellites. This formation process is thought to result in the multimodal optical colour distributions that are seen in the globular cluster systems of massive galaxies. Here we report optical observations of the massive relic-galaxy candidate NGC 1277—a nearby, un-evolved example of a high-redshift ‘red nugget’ galaxy. We find that the optical colour distribution of the cluster system of NGC 1277 is unimodal and entirely red. This finding is in strong contrast to other galaxies of similar and larger stellar mass, the cluster systems of which always exhibit (and are generally dominated by) blue clusters. We argue that the colour distribution of the cluster system of NGC 1277 indicates that the galaxy has undergone little (if any) mass accretion after its initial collapse, and use simulations of possible merger histories to show that the stellar mass due to accretion is probably at most ten per cent of the total stellar mass of the galaxy. These results confirm that NGC 1277 is a genuine relic galaxy and demonstrate that blue clusters constitute an accreted population in present-day massive galaxies.

Nature 555, 7697 (2018). doi:10.1038/nature25988

Authors: Bo Zhu, Jeremiah Z. Liu, Stephen F. Cauley, Bruce R. Rosen & Matthew S. Rosen

Image reconstruction is essential for imaging applications across the physical and life sciences, including optical and radar systems, magnetic resonance imaging, X-ray computed tomography, positron emission tomography, ultrasound imaging and radio astronomy. During image acquisition, the sensor encodes an intermediate representation of an object in the sensor domain, which is subsequently reconstructed into an image by an inversion of the encoding function. Image reconstruction is challenging because analytic knowledge of the exact inverse transform may not exist a priori, especially in the presence of sensor non-idealities and noise. Thus, the standard reconstruction approach involves approximating the inverse function with multiple ad hoc stages in a signal processing chain, the composition of which depends on the details of each acquisition strategy, and often requires expert parameter tuning to optimize reconstruction performance. Here we present a unified framework for image reconstruction—automated transform by manifold approximation (AUTOMAP)—which recasts image reconstruction as a data-driven supervised learning task that allows a mapping between the sensor and the image domain to emerge from an appropriate corpus of training data. We implement AUTOMAP with a deep neural network and exhibit its flexibility in learning reconstruction transforms for various magnetic resonance imaging acquisition strategies, using the same network architecture and hyperparameters. We further demonstrate that manifold learning during training results in sparse representations of domain transforms along low-dimensional data manifolds, and observe superior immunity to noise and a reduction in reconstruction artefacts compared with conventional handcrafted reconstruction methods. In addition to improving the reconstruction performance of existing acquisition methodologies, we anticipate that AUTOMAP and other learned reconstruction approaches will accelerate the development of new acquisition strategies across imaging modalities.

Nature 555, 7697 (2018). doi:10.1038/nature25970

Authors: Jonathan D. Breeze, Enrico Salvadori, Juna Sathian, Neil McN. Alford & Christopher W. M. Kay

The maser—the microwave progenitor of the optical laser—has been confined to relative obscurity owing to its reliance on cryogenic refrigeration and high-vacuum systems. Despite this, it has found application in deep-space communications and radio astronomy owing to its unparalleled performance as a low-noise amplifier and oscillator. The recent demonstration of a room-temperature solid-state maser that utilizes polarized electron populations within the triplet states of photo-excited pentacene molecules in a p-terphenyl host paves the way for a new class of maser. However, p-terphenyl has poor thermal and mechanical properties, and the decay rates of the triplet sublevel of pentacene mean that only pulsed maser operation has been observed in this system. Alternative materials are therefore required to achieve continuous emission: inorganic materials that contain spin defects, such as diamond and silicon carbide, have been proposed. Here we report a continuous-wave room-temperature maser oscillator using optically pumped nitrogen–vacancy defect centres in diamond. This demonstration highlights the potential of room-temperature solid-state masers for use in a new generation of microwave devices that could find application in medicine, security, sensing and quantum technologies.

Nature 555, 7697 (2018). doi:10.1038/nature25989

Authors: Mojtaba Abdi-Jalebi, Zahra Andaji-Garmaroudi, Stefania Cacovich, Camille Stavrakas, Bertrand Philippe, Johannes M. Richter, Mejd Alsari, Edward P. Booker, Eline M. Hutter, Andrew J. Pearson, Samuele Lilliu, Tom J. Savenije, Håkan Rensmo, Giorgio Divitini, Caterina Ducati, Richard H. Friend & Samuel D. Stranks

Metal halide perovskites are of great interest for various high-performance optoelectronic applications. The ability to tune the perovskite bandgap continuously by modifying the chemical composition opens up applications for perovskites as coloured emitters, in building-integrated photovoltaics, and as components of tandem photovoltaics to increase the power conversion efficiency. Nevertheless, performance is limited by non-radiative losses, with luminescence yields in state-of-the-art perovskite solar cells still far from 100 per cent under standard solar illumination conditions. Furthermore, in mixed halide perovskite systems designed for continuous bandgap tunability (bandgaps of approximately 1.7 to 1.9 electronvolts), photoinduced ion segregation leads to bandgap instabilities. Here we demonstrate substantial mitigation of both non-radiative losses and photoinduced ion migration in perovskite films and interfaces by decorating the surfaces and grain boundaries with passivating potassium halide layers. We demonstrate external photoluminescence quantum yields of 66 per cent, which translate to internal yields that exceed 95 per cent. The high luminescence yields are achieved while maintaining high mobilities of more than 40 square centimetres per volt per second, providing the elusive combination of both high luminescence and excellent charge transport. When interfaced with electrodes in a solar cell device stack, the external luminescence yield—a quantity that must be maximized to obtain high efficiency—remains as high as 15 per cent, indicating very clean interfaces. We also demonstrate the inhibition of transient photoinduced ion-migration processes across a wide range of mixed halide perovskite bandgaps in materials that exhibit bandgap instabilities when unpassivated. We validate these results in fully operating solar cells. Our work represents an important advance in the construction of tunable metal halide perovskite films and interfaces that can approach the efficiency limits in tandem solar cells, coloured-light-emitting diodes and other optoelectronic applications.

Nature 555, 7697 (2018). doi:10.1038/nature25984

Authors: Mohammad Asadi, Baharak Sayahpour, Pedram Abbasi, Anh T. Ngo, Klas Karis, Jacob R. Jokisaari, Cong Liu, Badri Narayanan, Marc Gerard, Poya Yasaei, Xuan Hu, Arijita Mukherjee, Kah Chun Lau, Rajeev S. Assary, Fatemeh Khalili-Araghi, Robert F. Klie, Larry A. Curtiss & Amin Salehi-Khojin

Lithium–air batteries are considered to be a potential alternative to lithium-ion batteries for transportation applications, owing to their high theoretical specific energy. So far, however, such systems have been largely restricted to pure oxygen environments (lithium–oxygen batteries) and have a limited cycle life owing to side reactions involving the cathode, anode and electrolyte. In the presence of nitrogen, carbon dioxide and water vapour, these side reactions can become even more complex. Moreover, because of the need to store oxygen, the volumetric energy densities of lithium–oxygen systems may be too small for practical applications. Here we report a system comprising a lithium carbonate-based protected anode, a molybdenum disulfide cathode and an ionic liquid/dimethyl sulfoxide electrolyte that operates as a lithium–air battery in a simulated air atmosphere with a long cycle life of up to 700 cycles. We perform computational studies to provide insight into the operation of the system in this environment. This demonstration of a lithium–oxygen battery with a long cycle life in an air-like atmosphere is an important step towards the development of this field beyond lithium-ion technology, with a possibility to obtain much higher specific energy densities than for conventional lithium-ion batteries.

Nature 555, 7697 (2018). doi:10.1038/nature25990

Authors: Martin Schiller, Martin Bizzarro & Vera Assis Fernandes

Nucleosynthetic isotope variability among Solar System objects is often used to probe the genetic relationship between meteorite groups and the rocky planets (Mercury, Venus, Earth and Mars), which, in turn, may provide insights into the building blocks of the Earth–Moon system. Using this approach, it has been inferred that no primitive meteorite matches the terrestrial composition and the protoplanetary disk material from which Earth and the Moon accreted is therefore largely unconstrained. This conclusion, however, is based on the assumption that the observed nucleosynthetic variability of inner-Solar-System objects predominantly reflects spatial heterogeneity. Here we use the isotopic composition of the refractory element calcium to show that the nucleosynthetic variability in the inner Solar System primarily reflects a rapid change in the mass-independent calcium isotope composition of protoplanetary disk solids associated with early mass accretion to the proto-Sun. We measure the mass-independent 48Ca/44Ca ratios of samples originating from the parent bodies of ureilite and angrite meteorites, as well as from Vesta, Mars and Earth, and find that they are positively correlated with the masses of their parent asteroids and planets, which are a proxy of their accretion timescales. This correlation implies a secular evolution of the bulk calcium isotope composition of the protoplanetary disk in the terrestrial planet-forming region. Individual chondrules from ordinary chondrites formed within one million years of the collapse of the proto-Sun reveal the full range of inner-Solar-System mass-independent 48Ca/44Ca ratios, indicating a rapid change in the composition of the material of the protoplanetary disk. We infer that this secular evolution reflects admixing of pristine outer-Solar-System material into the thermally processed inner protoplanetary disk associated with the accretion of mass to the proto-Sun. The identical calcium isotope composition of Earth and the Moon reported here is a prediction of our model if the Moon-forming impact involved protoplanets or precursors that completed their accretion near the end of the protoplanetary disk’s lifetime.

Nature 555, 7697 (2018). doi:10.1038/nature25967

Authors: Eugene I. Smith, Zenobia Jacobs, Racheal Johnsen, Minghua Ren, Erich C. Fisher, Simen Oestmo, Jayne Wilkins, Jacob A. Harris, Panagiotis Karkanas, Shelby Fitch, Amber Ciravolo, Deborah Keenan, Naomi Cleghorn, Christine S. Lane, Thalassa Matthews & Curtis W. Marean

Approximately 74 thousand years ago (ka), the Toba caldera erupted in Sumatra. Since the magnitude of this eruption was first established, its effects on climate, environment and humans have been debated. Here we describe the discovery of microscopic glass shards characteristic of the Youngest Toba Tuff—ashfall from the Toba eruption—in two archaeological sites on the south coast of South Africa, a region in which there is evidence for early human behavioural complexity. An independently derived dating model supports a date of approximately 74 ka for the sediments containing the Youngest Toba Tuff glass shards. By defining the input of shards at both sites, which are located nine kilometres apart, we are able to establish a close temporal correlation between them. Our high-resolution excavation and sampling technique enable exact comparisons between the input of Youngest Toba Tuff glass shards and the evidence for human occupation. Humans in this region thrived through the Toba event and the ensuing full glacial conditions, perhaps as a combined result of the uniquely rich resource base of the region and fully evolved modern human adaptation.

Nature 555, 7697 (2018). doi:10.1038/nature25968

Authors: Rebecca Albright, Yuichiro Takeshita, David A. Koweek, Aaron Ninokawa, Kennedy Wolfe, Tanya Rivlin, Yana Nebuchina, Jordan Young & Ken Caldeira

Coral reefs feed millions of people worldwide, provide coastal protection and generate billions of dollars annually in tourism revenue. The underlying architecture of a reef is a biogenic carbonate structure that accretes over many years of active biomineralization by calcifying organisms, including corals and algae. Ocean acidification poses a chronic threat to coral reefs by reducing the saturation state of the aragonite mineral of which coral skeletons are primarily composed, and lowering the concentration of carbonate ions required to maintain the carbonate reef. Reduced calcification, coupled with increased bioerosion and dissolution, may drive reefs into a state of net loss this century. Our ability to predict changes in ecosystem function and associated services ultimately hinges on our understanding of community- and ecosystem-scale responses. Past research has primarily focused on the responses of individual species rather than evaluating more complex, community-level responses. Here we use an in situ carbon dioxide enrichment experiment to quantify the net calcification response of a coral reef flat to acidification. We present an estimate of community-scale calcification sensitivity to ocean acidification that is, to our knowledge, the first to be based on a controlled experiment in the natural environment. This estimate provides evidence that near-future reductions in the aragonite saturation state will compromise the ecosystem function of coral reefs.

Nature 555, 7697 (2018). doi:10.1038/nature25966

Authors: Karl A. G. Kremling, Shu-Yun Chen, Mei-Hsiu Su, Nicholas K. Lepak, M. Cinta Romay, Kelly L. Swarts, Fei Lu, Anne Lorant, Peter J. Bradbury & Edward S. Buckler

Here we report a multi-tissue gene expression resource that represents the genotypic and phenotypic diversity of modern inbred maize, and includes transcriptomes in an average of 255 lines in seven tissues. We mapped expression quantitative trait loci and characterized the contribution of rare genetic variants to extremes in gene expression. Some of the new mutations that arise in the maize genome can be deleterious; although selection acts to keep deleterious variants rare, their complete removal is impeded by genetic linkage to favourable loci and by finite population size. Modern maize breeders have systematically reduced the effects of this constant mutational pressure through artificial selection and self-fertilization, which have exposed rare recessive variants in elite inbred lines. However, the ongoing effect of these rare alleles on modern inbred maize is unknown. By analysing this gene expression resource and exploiting the extreme diversity and rapid linkage disequilibrium decay of maize, we characterize the effect of rare alleles and evolutionary history on the regulation of expression. Rare alleles are associated with the dysregulation of expression, and we correlate this dysregulation to seed-weight fitness. We find enrichment of ancestral rare variants among expression quantitative trait loci mapped in modern inbred lines, which suggests that historic bottlenecks have shaped regulation. Our results suggest that one path for further genetic improvement in agricultural species lies in purging the rare deleterious variants that have been associated with crop fitness.

Nature 555, 7697 (2018). doi:10.1038/nature25980

Authors: Suijuan Zhong, Shu Zhang, Xiaoying Fan, Qian Wu, Liying Yan, Ji Dong, Haofeng Zhang, Long Li, Le Sun, Na Pan, Xiaohui Xu, Fuchou Tang, Jun Zhang, Jie Qiao & Xiaoqun Wang

The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex. However, it is still difficult to identify cell types in the developing human prefrontal cortex and to distinguish their developmental features. Here we analyse more than 2,300 single cells in the developing human prefrontal cortex from gestational weeks 8 to 26 using RNA sequencing. We identify 35 subtypes of cells in six main classes and trace the developmental trajectories of these cells. Detailed analysis of neural progenitor cells highlights new marker genes and unique developmental features of intermediate progenitor cells. We also map the timeline of neurogenesis of excitatory neurons in the prefrontal cortex and detect the presence of interneuron progenitors in early developing prefrontal cortex. Moreover, we reveal the intrinsic development-dependent signals that regulate neuron generation and circuit formation using single-cell transcriptomic data analysis. Our screening and characterization approach provides a blueprint for understanding the development of the human prefrontal cortex in the early and mid-gestational stages in order to systematically dissect the cellular basis and molecular regulation of prefrontal cortex function in humans.

Nature 555, 7697 (2018). doi:10.1038/nature25976

Authors: Tonni Grube Andersen, Sadaf Naseer, Robertas Ursache, Brecht Wybouw, Wouter Smet, Bert De Rybel, Joop E. M. Vermeer & Niko Geldner

In vascular plants, the root endodermis surrounds the central vasculature as a protective sheath that is analogous to the polarized epithelium in animals, and contains ring-shaped Casparian strips that restrict diffusion. After an initial lag phase, individual endodermal cells suberize in an apparently random fashion to produce ‘patchy’ suberization that eventually generates a zone of continuous suberin deposition. Casparian strips and suberin lamellae affect paracellular and transcellular transport, respectively. Most angiosperms maintain some isolated cells in an unsuberized state as so-called ‘passage cells’, which have previously been suggested to enable uptake across an otherwise-impermeable endodermal barrier. Here we demonstrate that these passage cells are late emanations of a meristematic patterning process that reads out the underlying non-radial symmetry of the vasculature. This process is mediated by the non-cell-autonomous repression of cytokinin signalling in the root meristem, and leads to distinct phloem- and xylem-pole-associated endodermal cells. The latter cells can resist abscisic acid-dependent suberization to produce passage cells. Our data further demonstrate that, during meristematic patterning, xylem-pole-associated endodermal cells can dynamically alter passage-cell numbers in response to nutrient status, and that passage cells express transporters and locally affect the expression of transporters in adjacent cortical cells.

Nature 555, 7697 (2018). doi:10.1038/nature25982

Authors: Jeffrey B. McQuaid, Adam B. Kustka, Miroslav Oborník, Aleš Horák, John P. McCrow, Bogumil J. Karas, Hong Zheng, Theodor Kindeberg, Andreas J. Andersson, Katherine A. Barbeau & Andrew E. Allen

In vast areas of the ocean, the scarcity of iron controls the growth and productivity of phytoplankton. Although most dissolved iron in the marine environment is complexed with organic molecules, picomolar amounts of labile inorganic iron species (labile iron) are maintained within the euphotic zone and serve as an important source of iron for eukaryotic phytoplankton and particularly for diatoms. Genome-enabled studies of labile iron utilization by diatoms have previously revealed novel iron-responsive transcripts, including the ferric iron-concentrating protein ISIP2A, but the mechanism behind the acquisition of picomolar labile iron remains unknown. Here we show that ISIP2A is a phytotransferrin that independently and convergently evolved carbonate ion-coordinated ferric iron binding. Deletion of ISIP2A disrupts high-affinity iron uptake in the diatom Phaeodactylum tricornutum, and uptake is restored by complementation with human transferrin. ISIP2A is internalized by endocytosis, and manipulation of the seawater carbonic acid system reveals a second-order dependence on the concentrations of labile iron and carbonate ions. In P. tricornutum, the synergistic interaction of labile iron and carbonate ions occurs at environmentally relevant concentrations, revealing that carbonate availability co-limits iron uptake. Phytotransferrin sequences have a broad taxonomic distribution and are abundant in marine environmental genomic datasets, suggesting that acidification-driven declines in the concentration of seawater carbonate ions will have a negative effect on this globally important eukaryotic iron acquisition mechanism.

Nature 555, 7697 (2018). doi:10.1038/nature25981

Authors: Darren A. Cusanovich, James P. Reddington, David A. Garfield, Riza M. Daza, Delasa Aghamirzaie, Raquel Marco-Ferreres, Hannah A. Pliner, Lena Christiansen, Xiaojie Qiu, Frank J. Steemers, Cole Trapnell, Jay Shendure & Eileen E. M. Furlong

Understanding how gene regulatory networks control the progressive restriction of cell fates is a long-standing challenge. Recent advances in measuring gene expression in single cells are providing new insights into lineage commitment. However, the regulatory events underlying these changes remain unclear. Here we investigate the dynamics of chromatin regulatory landscapes during embryogenesis at single-cell resolution. Using single-cell combinatorial indexing assay for transposase accessible chromatin with sequencing (sci-ATAC-seq), we profiled chromatin accessibility in over 20,000 single nuclei from fixed Drosophila melanogaster embryos spanning three landmark embryonic stages: 2–4 h after egg laying (predominantly stage 5 blastoderm nuclei), when each embryo comprises around 6,000 multipotent cells; 6–8 h after egg laying (predominantly stage 10–11), to capture a midpoint in embryonic development when major lineages in the mesoderm and ectoderm are specified; and 10–12 h after egg laying (predominantly stage 13), when each of the embryo’s more than 20,000 cells are undergoing terminal differentiation. Our results show that there is spatial heterogeneity in the accessibility of the regulatory genome before gastrulation, a feature that aligns with future cell fate, and that nuclei can be temporally ordered along developmental trajectories. During mid-embryogenesis, tissue granularity emerges such that individual cell types can be inferred by their chromatin accessibility while maintaining a signature of their germ layer of origin. Analysis of the data reveals overlapping usage of regulatory elements between cells of the endoderm and non-myogenic mesoderm, suggesting a common developmental program that is reminiscent of the mesendoderm lineage in other species. We identify 30,075 distal regulatory elements that exhibit tissue-specific accessibility. We validated the germ-layer specificity of a subset of these predicted enhancers in transgenic embryos, achieving an accuracy of 90%. Overall, our results demonstrate the power of shotgun single-cell profiling of embryos to resolve dynamic changes in the chromatin landscape during development, and to uncover the cis-regulatory programs of metazoan germ layers and cell types.

Nature 555, 7697 (2018). doi:10.1038/nature25991

Author: Sven Reischauer, Oliver A. Stone, Alethia Villasenor, Neil Chi, Suk-Won Jin, Marcel Martin, Miler T. Lee, Nana Fukuda, Michele Marass, Alec Witty, Ian Fiddes, Taiyi Kuo, Won-Suk Chung, Sherveen Salek, Robert Lerrigo, Jessica Alsiö, Shujun Luo, Dominika Tworus, Sruthy M. Augustine, Sophie Mucenieks, Björn Nystedt, Antonio J. Giraldez, Gary P. Schroth, Olov Andersson & Didier Y. R. Stainier

Nature535, 294–298 (2016); doi:10.1038/nature18614In the Author Information section of this Letter, LT571435 from the SRA was provided as the accession number for the PacBio whole-genome sequencing data. Immediately after publication, we noted that LT571435 is

Nature 555, 7697 (2018). doi:10.1038/nature25994

Author: Y. Erin Chen, Michael A. Fischbach & Yasmine Belkaid

Nature553, 427–436 (2018); doi:10.1038/nature25177Owing to a technical error, authors Y. Erin Chen and Michael A. Fischbach were both listed as corresponding authors instead of authors Michael A. Fischbach and Yasmine Belkaid in the HTML version of

Nature 555, 7697 (2018). doi:10.1038/nature26164

Author: Iñigo Olalde, Selina Brace, Morten E. Allentoft, Ian Armit, Kristian Kristiansen, Thomas Booth, Nadin Rohland, Swapan Mallick, Anna Szécsényi-Nagy, Alissa Mittnik, Eveline Altena, Mark Lipson, Iosif Lazaridis, Thomas K. Harper, Nick Patterson, Nasreen Broomandkhoshbacht, Yoan Diekmann, Zuzana Faltyskova, Daniel Fernandes, Matthew Ferry, Eadaoin Harney, Peter de Knijff, Megan Michel, Jonas Oppenheimer, Kristin Stewardson, Alistair Barclay, Kurt Werner Alt, Corina Liesau, Patricia Ríos, Concepción Blasco, Jorge Vega Miguel, Roberto Menduiña García, Azucena Avilés Fernández, Eszter Bánffy, Maria Bernabò-Brea, David Billoin, Clive Bonsall, Laura Bonsall, Tim Allen, Lindsey Büster, Sophie Carver, Laura Castells Navarro, Oliver E. Craig, Gordon T. Cook, Barry Cunliffe, Anthony Denaire, Kirsten Egging Dinwiddy, Natasha Dodwell, Michal Ernée, Christopher Evans, Milan Kuchařík, Joan Francès Farré, Chris Fowler, Michiel Gazenbeek, Rafael Garrido Pena, María Haber-Uriarte, Elżbieta Haduch, Gill Hey, Nick Jowett, Timothy Knowles, Ken Massy, Saskia Pfrengle, Philippe Lefranc, Olivier Lemercier, Arnaud Lefebvre, César Heras Martínez, Virginia Galera Olmo, Ana Bastida Ramírez, Joaquín Lomba Maurandi, Tona Majó, Jacqueline I. McKinley, Kathleen McSweeney, Balázs Gusztáv Mende, Alessandra Modi, Gabriella Kulcsár, Viktória Kiss, András Czene, Róbert Patay, Anna Endrődi, Kitti Köhler, Tamás Hajdu, Tamás Szeniczey, János Dani, Zsolt Bernert, Maya Hoole, Olivia Cheronet, Denise Keating, Petr Velemínský, Miroslav Dobeš, Francesca Candilio, Fraser Brown, Raúl Flores Fernández, Ana-Mercedes Herrero-Corral, Sebastiano Tusa, Emiliano Carnieri, Luigi Lentini, Antonella Valenti, Alessandro Zanini, Clive Waddington, Germán Delibes, Elisa Guerra-Doce, Benjamin Neil, Marcus Brittain, Mike Luke, Richard Mortimer, Jocelyne Desideri, Marie Besse, Günter Brücken, Mirosław Furmanek, Agata Hałuszko, Maksym Mackiewicz, Artur Rapiński, Stephany Leach, Ignacio Soriano, Katina T. Lillios, João Luís Cardoso, Michael Parker Pearson, Piotr Włodarczak, T. Douglas Price, Pilar Prieto, Pierre-Jérôme Rey, Roberto Risch, Manuel A. Rojo Guerra, Aurore Schmitt, Joël Serralongue, Ana Maria Silva, Václav Smrčka, Luc Vergnaud, João Zilhão, David Caramelli, Thomas Higham, Mark G. Thomas, Douglas J. Kennett, Harry Fokkens, Volker Heyd, Alison Sheridan, Karl-Göran Sjögren, Philipp W. Stockhammer, Johannes Krause, Ron Pinhasi, Wolfgang Haak, Ian Barnes, Carles Lalueza-Fox & David Reich

Nature555, 190–196 (2018); doi:10.1038/nature25738In this Article, the surname of author Alessandra Modi was incorrectly listed as ‘Mod’. This has been corrected online.