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Ine Vandewauw, Katrien De Clercq, Marie Mulier, Katharina Held, Silvia Pinto, Nele Van Ranst, Andrei Segal, Thierry Voet, Rudi Vennekens, Katharina Zimmermann, Joris Vriens, Thomas Voets
Acute pain represents a crucial alarm signal to protect us from injury. Whereas the nociceptive neurons that convey pain signals were described more than a century ago, the molecular sensors that detect noxious thermal or mechanical insults have yet to be fully identified. Here we show that acute noxious heat sensing in mice depends on a triad of transient receptor potential (TRP) ion channels: TRPM3, TRPV1, and TRPA1. We found that robust somatosensory heat responsiveness at the cellular and behavioural levels is observed only if at least one of these TRP channels is functional...
March 14, 2018: Nature
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...
March 14, 2018: Nature
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...
March 14, 2018: Nature
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 tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting...
March 14, 2018: Nature
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...
March 14, 2018: Nature
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 of the yeast Saccharomyces cerevisiae at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents. The nuclear pore complex incorporates sturdy diagonal columns and connector cables attached to these columns, imbuing the structure with strength and flexibility...
March 14, 2018: Nature
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...
March 14, 2018: Nature
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...
March 14, 2018: Nature
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...
March 14, 2018: Nature
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 lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies...
March 14, 2018: Nature
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...
March 12, 2018: Nature
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...
March 12, 2018: Nature
Peter W S Hill, Harry G Leitch, Cristina E Requena, Zhiyi Sun, Rachel Amouroux, Monica Roman-Trufero, Malgorzata Borkowska, Jolyon Terragni, Romualdas Vaisvila, Sarah Linnett, Hakan Bagci, Gopuraja Dharmalingham, Vanja Haberle, Boris Lenhard, Yu Zheng, Sriharsa Pradhan, Petra Hajkova
Gametes are highly specialized cells that can give rise to the next generation through their ability to generate a totipotent zygote. In mice, germ cells are first specified in the developing embryo around embryonic day (E) 6.25 as primordial germ cells (PGCs). Following subsequent migration into the developing gonad, PGCs undergo a wave of extensive epigenetic reprogramming around E10.5-E11.5, including genome-wide loss of 5-methylcytosine. The underlying molecular mechanisms of this process have remained unclear, leading to our inability to recapitulate this step of germline development in vitro...
March 7, 2018: Nature
Benjamin L Turner, Tania Brenes-Arguedas, Richard Condit
Phosphorus availability is widely assumed to limit primary productivity in tropical forests, but support for this paradigm is equivocal. Although biogeochemical theory predicts that phosphorus limitation should be prevalent on old, strongly weathered soils, experimental manipulations have failed to detect a consistent response to phosphorus addition in species-rich lowland tropical forests. Here we show, by quantifying the growth of 541 tropical tree species across a steep natural phosphorus gradient in Panama, that phosphorus limitation is widespread at the level of individual species and strengthens markedly below a threshold of two parts per million exchangeable soil phosphate...
March 7, 2018: Nature
Patrick Kennedy, Andrew D Higginson, Andrew N Radford, Seirian Sumner
The evolution of altruism-costly self-sacrifice in the service of others-has puzzled biologists since The Origin of Species. For half a century, attempts to understand altruism have developed around the concept that altruists may help relatives to have extra offspring in order to spread shared genes. This theory-known as inclusive fitness-is founded on a simple inequality termed Hamilton's rule. However, explanations of altruism have typically not considered the stochasticity of natural environments, which will not necessarily favour genotypes that produce the greatest average reproductive success...
March 7, 2018: Nature
Zhenling Cui, Hongyan Zhang, Xinping Chen, Chaochun Zhang, Wenqi Ma, Chengdong Huang, Weifeng Zhang, Guohua Mi, Yuxin Miao, Xiaolin Li, Qiang Gao, Jianchang Yang, Zhaohui Wang, Youliang Ye, Shiwei Guo, Jianwei Lu, Jianliang Huang, Shihua Lv, Yixiang Sun, Yuanying Liu, Xianlong Peng, Jun Ren, Shiqing Li, Xiping Deng, Xiaojun Shi, Qiang Zhang, Zhiping Yang, Li Tang, Changzhou Wei, Liangliang Jia, Jiwang Zhang, Mingrong He, Yanan Tong, Qiyuan Tang, Xuhua Zhong, Zhaohui Liu, Ning Cao, Changlin Kou, Hao Ying, Yulong Yin, Xiaoqiang Jiao, Qingsong Zhang, Mingsheng Fan, Rongfeng Jiang, Fusuo Zhang, Zhengxia Dou
Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance...
March 7, 2018: Nature
Aparna Gorthi, July Carolina Romero, Eva Loranc, Lin Cao, Liesl A Lawrence, Elicia Goodale, Amanda Balboni Iniguez, Xavier Bernard, V Pragathi Masamsetti, Sydney Roston, Elizabeth R Lawlor, Jeffrey A Toretsky, Kimberly Stegmaier, Stephen L Lessnick, Yidong Chen, Alexander J R Bishop
Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress...
March 7, 2018: Nature
Nate Yoder, Craig Yoshioka, Eric Gouaux
Acid-sensing ion channels (ASICs) are trimeric, proton-gated and sodium-selective members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout vertebrate central and peripheral nervous systems. Gating of ASICs occurs on a millisecond time scale and the mechanism involves three conformational states: high pH resting, low pH open and low pH desensitized. Existing X-ray structures of ASIC1a describe the conformations of the open and desensitized states, but the structure of the high pH resting state and detailed mechanisms of the activation and desensitization of the channel have remained elusive...
March 7, 2018: Nature
Shawn F Sorrells, Mercedes F Paredes, Arantxa Cebrian-Silla, Kadellyn Sandoval, Dashi Qi, Kevin W Kelley, David James, Simone Mayer, Julia Chang, Kurtis I Auguste, Edward F Chang, Antonio J Gutierrez, Arnold R Kriegstein, Gary W Mathern, Michael C Oldham, Eric J Huang, Jose Manuel Garcia-Verdugo, Zhengang Yang, Arturo Alvarez-Buylla
New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons...
March 7, 2018: Nature
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 eminences is driven by a highly conserved maturation trajectory, alongside eminence-specific transcription factor expression that seeds the emergence of later diversity. Upon becoming postmitotic, progenitors diverge and differentiate into transcriptionally distinct states, including an interneuron precursor state...
March 5, 2018: Nature
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