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N Leo, V Carolus, J S White, M Kenzelmann, M Hudl, P Tolédano, T Honda, T Kimura, S A Ivanov, M Weil, Th Lottermoser, D Meier, M Fiebig
Four incorrect figure citations in this Letter have been corrected online.
September 20, 2018: Nature
Daniela Latorre, Ulf Kallweit, Eric Armentani, Mathilde Foglierini, Federico Mele, Antonino Cassotta, Sandra Jovic, David Jarrossay, Johannes Mathis, Francesco Zellini, Burkhard Becher, Antonio Lanzavecchia, Ramin Khatami, Mauro Manconi, Mehdi Tafti, Claudio L Bassetti, Federica Sallusto
Narcolepsy is a chronic sleep disorder caused by the loss of neurons that produce hypocretin. The close association with HLA-DQB1*06:02, evidence for immune dysregulation and increased incidence upon influenza vaccination together suggest that this disorder has an autoimmune origin. However, there is little evidence of autoreactive lymphocytes in patients with narcolepsy. Here we used sensitive cellular screens and detected hypocretin-specific CD4+ T cells in all 19 patients that we tested; T cells specific for tribbles homologue 2-another self-antigen of hypocretin neurons-were found in 8 out of 13 patients...
September 19, 2018: Nature
Sean D Willett, Scott W McCoy, Helen W Beeson
Ecosystem diversity and human activity in dry climates depend not just on the magnitude of rainfall, but also on the landscape's ability to retain water. This is illustrated dramatically in the High Plains of North America, where despite the semi-arid modern and past climate, the hydrologic conditions are diverse. Large rivers sourced in the Rocky Mountains cut through elevated plains that exhibit limited river drainage but widespread surface water in the form of ephemeral (seasonal) playa lakes1 , as well as extensive groundwater hosted in the High Plains aquifer of the Ogallala formations2 ...
September 19, 2018: Nature
Gautam Reddy, Jerome Wong-Ng, Antonio Celani, Terrence J Sejnowski, Massimo Vergassola
Soaring birds often rely on ascending thermal plumes (thermals) in the atmosphere as they search for prey or migrate across large distances1-4 . The landscape of convective currents is rugged and shifts on timescales of a few minutes as thermals constantly form, disintegrate or are transported away by the wind5,6 . How soaring birds find and navigate thermals within this complex landscape is unknown. Reinforcement learning7 provides an appropriate framework in which to identify an effective navigational strategy as a sequence of decisions made in response to environmental cues...
September 19, 2018: Nature
Christos Gatsogiannis, Felipe Merino, Daniel Roderer, David Balchin, Evelyn Schubert, Anne Kuhlee, Manajit Hayer-Hartl, Stefan Raunser
Tc toxins secrete toxic enzymes into host cells using a unique syringe-like injection mechanism. They are composed of three subunits, TcA, TcB and TcC. TcA forms the translocation channel and the TcB-TcC heterodimer functions as a cocoon that shields the toxic enzyme. Binding of the cocoon to the channel triggers opening of the cocoon and translocation of the toxic enzyme into the channel. Here we show in atomic detail how the assembly of the three components activates the toxin. We find that part of the cocoon completely unfolds and refolds into an alternative conformation upon binding...
September 19, 2018: Nature
Januka S Athukoralage, Christophe Rouillon, Shirley Graham, Sabine Grüschow, Malcolm F White
The CRISPR system provides adaptive immunity against mobile genetic elements in prokaryotes, using small CRISPR RNAs that direct effector complexes to degrade invading nucleic acids1-3 . Type III effector complexes were recently demonstrated to synthesize a novel second messenger, cyclic oligoadenylate, on binding target RNA4,5 . Cyclic oligoadenylate, in turn, binds to and activates ribonucleases and other factors-via a CRISPR-associated Rossman-fold domain-and thereby induces in the cell an antiviral state that is important for immunity...
September 19, 2018: Nature
Junho Choe, Shuibin Lin, Wencai Zhang, Qi Liu, Longfei Wang, Julia Ramirez-Moya, Peng Du, Wantae Kim, Shaojun Tang, Piotr Sliz, Pilar Santisteban, Rani E George, William G Richards, Kwok-Kin Wong, Nicolas Locker, Frank J Slack, Richard I Gregory
N6 -methyladenosine (m6 A) modification of mRNA is emerging as an important regulator of gene expression that affects different developmental and biological processes, and altered m6 A homeostasis is linked to cancer1-5 . m6 A modification is catalysed by METTL3 and enriched in the 3' untranslated region of a large subset of mRNAs at sites close to the stop codon5 . METTL3 can promote translation but the mechanism and relevance of this process remain unknown1 . Here we show that METTL3 enhances translation only when tethered to reporter mRNA at sites close to the stop codon, supporting a mechanism of mRNA looping for ribosome recycling and translational control...
September 19, 2018: Nature
William R L Anderegg, Alexandra G Konings, Anna T Trugman, Kailiang Yu, David R Bowling, Robert Gabbitas, Daniel S Karp, Stephen Pacala, John S Sperry, Benjamin N Sulman, Nicole Zenes
Plants influence the atmosphere through fluxes of carbon, water and energy1 , and can intensify drought through land-atmosphere feedback effects2-4 . The diversity of plant functional traits in forests, especially physiological traits related to water (hydraulic) transport, may have a critical role in land-atmosphere feedback, particularly during drought. Here we combine 352 site-years of eddy covariance measurements from 40 forest sites, remote-sensing observations of plant water content and plant functional-trait data to test whether the diversity in plant traits affects the response of the ecosystem to drought...
September 19, 2018: Nature
Tyler J Bussian, Asef Aziz, Charlton F Meyer, Barbara L Swenson, Jan M van Deursen, Darren J Baker
Cellular senescence, which is characterized by an irreversible cell-cycle arrest1 accompanied by a distinctive secretory phenotype2 , can be induced through various intracellular and extracellular factors. Senescent cells that express the cell cycle inhibitory protein p16INK4A have been found to actively drive naturally occurring age-related tissue deterioration3,4 and contribute to several diseases associated with ageing, including atherosclerosis5 and osteoarthritis6 . Various markers of senescence have been observed in patients with neurodegenerative diseases7-9 ; however, a role for senescent cells in the aetiology of these pathologies is unknown...
September 19, 2018: Nature
Shiwei Liu, Mijung Kwon, Mark Mannino, Nachen Yang, Fioranna Renda, Alexey Khodjakov, David Pellman
Defects in the architecture or integrity of the nuclear envelope are associated with a variety of human diseases1 . Micronuclei, one common nuclear aberration, are an origin for chromothripsis2 , a catastrophic mutational process that is commonly observed in cancer3-5 . Chromothripsis occurs after micronuclei spontaneously lose nuclear envelope integrity, which generates chromosome fragmentation6 . Disruption of the nuclear envelope exposes DNA to the cytoplasm and initiates innate immune proinflammatory signalling7 ...
September 19, 2018: Nature
Oleksiy Kovtun, Natalya Leneva, Yury S Bykov, Nicholas Ariotti, Rohan D Teasdale, Miroslava Schaffer, Benjamin D Engel, David J Owen, John A G Briggs, Brett M Collins
Eukaryotic cells traffic proteins and lipids between different compartments using protein-coated vesicles and tubules. The retromer complex is required to generate cargo-selective tubulovesicular carriers from endosomal membranes1-3 . Conserved in eukaryotes, retromer controls the cellular localization and homeostasis of hundreds of transmembrane proteins, and its disruption is associated with major neurodegenerative disorders4-7 . How retromer is assembled and how it is recruited to form coated tubules is not known...
September 17, 2018: Nature
Stephan Lautenschlager, Pamela G Gill, Zhe-Xi Luo, Michael J Fagan, Emily J Rayfield
The evolution of the mammalian jaw is one of the most important innovations in vertebrate history, and underpins the exceptional radiation and diversification of mammals over the last 220 million years1,2 . In particular, the transformation of the mandible into a single tooth-bearing bone and the emergence of a novel jaw joint-while incorporating some of the ancestral jaw bones into the mammalian middle ear-is often cited as a classic example of the repurposing of morphological structures3,4 . Although it is remarkably well-documented in the fossil record, the evolution of the mammalian jaw still poses the paradox of how the bones of the ancestral jaw joint could function both as a joint hinge for powerful load-bearing mastication and as a mandibular middle ear that was delicate enough for hearing...
September 17, 2018: Nature
Jae Woong Yoon, Youngsun Choi, Choloong Hahn, Gunpyo Kim, Seok Ho Song, Ki-Yeon Yang, Jeong Yub Lee, Yongsung Kim, Chang Seung Lee, Jai Kwang Shin, Hong-Seok Lee, Pierre Berini
Topological operations around exceptional points1-8 -time-varying system configurations associated with non-Hermitian singularities-have been proposed as a robust approach to achieving far-reaching open-system dynamics, as demonstrated in highly dissipative microwave transmission3 and cryogenic optomechanical oscillator4 experiments. In stark contrast to conventional systems based on closed-system Hermitian dynamics, environmental interferences at exceptional points are dynamically engaged with their internal coupling properties to create rotational stimuli in fictitious-parameter domains, resulting in chiral systems that exhibit various anomalous physical phenomena9-16 ...
September 17, 2018: Nature
Y Kate Hong, Clay O Lacefield, Chris C Rodgers, Randy M Bruno
For many of our senses, the role of the cerebral cortex in detecting stimuli is controversial1-17 . Here we examine the effects of both acute and chronic inactivation of the primary somatosensory cortex in mice trained to move their large facial whiskers to detect an object by touch and respond with a lever to obtain a water reward. Using transgenic mice, we expressed inhibitory opsins in excitatory cortical neurons. Transient optogenetic inactivation of the primary somatosensory cortex, as well as permanent lesions, initially produced both movement and sensory deficits that impaired detection behaviour, demonstrating the link between sensory and motor systems during active sensing...
September 17, 2018: Nature
Warren A Whyte, Steve Bilodeau, David A Orlando, Heather A Hoke, Garrett M Frampton, Charles T Foster, Shaun M Cowley, Richard A Young
In this Letter, the western blot for LSD1 in the right panel of Fig. 2b ('TCP +') was inadvertently duplicated from the tubulin blot immediately below. The actual tubulin western blot shows the same result, with no significant change to the levels of tubulin (see Fig. 1 of this Amendment). In addition, the western blots for LSD1 and HDAC1 of Fig. 3b and c have been corrected to include vertical black lines to delineate the juxtaposition of lanes that were non-adjacent in the original blotting experiment (see Fig...
September 12, 2018: Nature
Yi-Lynn Liang, Maryam Khoshouei, Giuseppe Deganutti, Alisa Glukhova, Cassandra Koole, Thomas S Peat, Mazdak Radjainia, Jürgen M Plitzko, Wolfgang Baumeister, Laurence J Miller, Deborah L Hay, Arthur Christopoulos, Christopher A Reynolds, Denise Wootten, Patrick M Sexton
Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that has a major role in sensory neurotransmission. The CGRP receptor is a heterodimer of the calcitonin receptor-like receptor (CLR) class B G-protein-coupled receptor and a type 1 transmembrane domain protein, receptor activity-modifying protein 1 (RAMP1). Here we report the structure of the human CGRP receptor in complex with CGRP and the Gs -protein heterotrimer at 3.3 Å global resolution, determined by Volta phase-plate cryo-electron microscopy...
September 12, 2018: Nature
Gregory M Findlay, Riza M Daza, Beth Martin, Melissa D Zhang, Anh P Leith, Molly Gasperini, Joseph D Janizek, Xingfan Huang, Lea M Starita, Jay Shendure
Variants of uncertain significance fundamentally limit the clinical utility of genetic information. The challenge they pose is epitomized by BRCA1, a tumour suppressor gene in which germline loss-of-function variants predispose women to breast and ovarian cancer. Although BRCA1 has been sequenced in millions of women, the risk associated with most newly observed variants cannot be definitively assigned. Here we use saturation genome editing to assay 96.5% of all possible single-nucleotide variants (SNVs) in 13 exons that encode functionally critical domains of BRCA1...
September 12, 2018: Nature
Jia-Xin Yin, Songtian S Zhang, Hang Li, Kun Jiang, Guoqing Chang, Bingjing Zhang, Biao Lian, Cheng Xiang, Ilya Belopolski, Hao Zheng, Tyler A Cochran, Su-Yang Xu, Guang Bian, Kai Liu, Tay-Rong Chang, Hsin Lin, Zhong-Yi Lu, Ziqiang Wang, Shuang Jia, Wenhong Wang, M Zahid Hasan
Owing to the unusual geometry of kagome lattices-lattices made of corner-sharing triangles-their electrons are useful for studying the physics of frustrated, correlated and topological quantum electronic states1-9 . In the presence of strong spin-orbit coupling, the magnetic and electronic structures of kagome lattices are further entangled, which can lead to hitherto unknown spin-orbit phenomena. Here we use a combination of vector-magnetic-field capability and scanning tunnelling microscopy to elucidate the spin-orbit nature of the kagome ferromagnet Fe3 Sn2 and explore the associated exotic correlated phenomena...
September 12, 2018: Nature
Marco Seehawer, Florian Heinzmann, Luana D'Artista, Jule Harbig, Pierre-François Roux, Lisa Hoenicke, Hien Dang, Sabrina Klotz, Lucas Robinson, Grégory Doré, Nir Rozenblum, Tae-Won Kang, Rishabh Chawla, Thorsten Buch, Mihael Vucur, Mareike Roth, Johannes Zuber, Tom Luedde, Bence Sipos, Thomas Longerich, Mathias Heikenwälder, Xin Wei Wang, Oliver Bischof, Lars Zender
Primary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and responses to therapy. However, the regulatory molecules and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here we show that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumorigenesis. Whereas a necroptosis-associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes containing identical oncogenic drivers give rise to HCC if they are surrounded by apoptotic hepatocytes...
September 12, 2018: Nature
Yuanyuan Liu, Alban Latremoliere, Xinjian Li, Zicong Zhang, Mengying Chen, Xuhua Wang, Chao Fang, Junjie Zhu, Chloe Alexandre, Zhongyang Gao, Bo Chen, Xin Ding, Jin-Yong Zhou, Yiming Zhang, Chinfei Chen, Kuan Hong Wang, Clifford J Woolf, Zhigang He
Current models of somatosensory perception emphasize transmission from primary sensory neurons to the spinal cord and on to the brain1-4 . Mental influence on perception is largely assumed to occur locally within the brain. Here we investigate whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex. Although the corticospinal tract (CST) is traditionally viewed as a primary motor pathway5 , a subset of corticospinal neurons (CSNs) originating in the primary and secondary somatosensory cortex directly innervate the spinal dorsal horn via CST axons...
September 12, 2018: Nature
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