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Ken-Ichi Uchida, Shunsuke Daimon, Ryo Iguchi, Eiji Saitoh
The Peltier effect, discovered in 1834, converts a charge current into a heat current in a conductor, and its performance is described by the Peltier coefficient, which is defined as the ratio of the generated heat current to the applied charge current1,2 . To exploit the Peltier effect for thermoelectric cooling or heating, junctions of two conductors with different Peltier coefficients have been believed to be indispensable. Here we challenge this conventional wisdom by demonstrating Peltier cooling and heating in a single material without junctions...
May 21, 2018: Nature
Yuan Liu, Jian Guo, Enbo Zhu, Lei Liao, Sung-Joon Lee, Mengning Ding, Imran Shakir, Vincent Gambin, Yu Huang, Xiangfeng Duan
The junctions formed at the contact between metallic electrodes and semiconductor materials are crucial components of electronic and optoelectronic devices 1 . Metal-semiconductor junctions are characterized by an energy barrier known as the Schottky barrier, whose height can, in the ideal case, be predicted by the Schottky-Mott rule2-4 on the basis of the relative alignment of energy levels. Such ideal physics has rarely been experimentally realized, however, because of the inevitable chemical disorder and Fermi-level pinning at typical metal-semiconductor interfaces2,5-12 ...
May 16, 2018: Nature
M Rodell, J S Famiglietti, D N Wiese, J T Reager, H K Beaudoing, F W Landerer, M-H Lo
Freshwater availability is changing worldwide. Here we quantify 34 trends in terrestrial water storage observed by the Gravity Recovery and Climate Experiment (GRACE) satellites during 2002-2016 and categorize their drivers as natural interannual variability, unsustainable groundwater consumption, climate change or combinations thereof. Several of these trends had been lacking thorough investigation and attribution, including massive changes in northwestern China and the Okavango Delta. Others are consistent with climate model predictions...
May 16, 2018: Nature
Marlies Meisel, Reinhard Hinterleitner, Alain Pacis, Li Chen, Zachary M Earley, Toufic Mayassi, Joseph F Pierre, Jordan D Ernest, Heather J Galipeau, Nikolaus Thuille, Romain Bouziat, Manuel Buscarlet, Daina L Ringus, Yitang Wang, Ye Li, Vu Dinh, Sangman M Kim, Benjamin D McDonald, Matthew A Zurenski, Mark W Musch, Glaucia C Furtado, Sergio A Lira, Gottfried Baier, Eugene B Chang, A Murat Eren, Christopher R Weber, Lambert Busque, Lucy A Godley, Elena F Verdú, Luis B Barreiro, Bana Jabri
Somatic mutations in tet methylcytosine dioxygenase 2 (TET2), which encodes an epigenetic modifier enzyme, drive the development of haematopoietic malignancies1-7 . In both humans and mice, TET2 deficiency leads to increased self-renewal of haematopoietic stem cells with a net developmental bias towards the myeloid lineage1,4,8,9 . However, pre-leukaemic myeloproliferation (PMP) occurs in only a fraction of Tet2-/- mice8,9 and humans with TET2 mutations1,3,5-7 , suggesting that extrinsic non-cell-autonomous factors are required for disease onset...
May 16, 2018: Nature
Veit Rothhammer, Davis M Borucki, Emily C Tjon, Maisa C Takenaka, Chun-Cheih Chao, Alberto Ardura-Fabregat, Kalil Alves de Lima, Cristina Gutiérrez-Vázquez, Patrick Hewson, Ori Staszewski, Manon Blain, Luke Healy, Tradite Neziraj, Matilde Borio, Michael Wheeler, Loic Lionel Dragin, David A Laplaud, Jack Antel, Jorge Ivan Alvarez, Marco Prinz, Francisco J Quintana
Microglia and astrocytes modulate inflammation and neurodegeneration in the central nervous system (CNS)1-3 . Microglia modulate pro-inflammatory and neurotoxic activities in astrocytes, but the mechanisms involved are not completely understood4,5 . Here we report that TGFα and VEGF-B produced by microglia regulate the pathogenic activities of astrocytes in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Microglia-derived TGFα acts via the ErbB1 receptor in astrocytes to limit their pathogenic activities and EAE development...
May 16, 2018: Nature
Rong Zhang, Arthur S Kim, Julie M Fox, Sharmila Nair, Katherine Basore, William B Klimstra, Rebecca Rimkunas, Rachel H Fong, Hueylie Lin, Subhajit Poddar, James E Crowe, Benjamin J Doranz, Daved H Fremont, Michael S Diamond
Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease 1 . The host factors required for alphavirus entry remain poorly characterized 2 . Here we use a genome-wide CRISPR-Cas9-based screen to identify the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses, including chikungunya, Ross River, Mayaro and O'nyong nyong viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced levels of viral infection of cells and, reciprocally, ectopic expression of these genes resulted in increased infection...
May 16, 2018: Nature
Daohua Jiang, Tamer M Gamal El-Din, Christopher Ing, Peilong Lu, Régis Pomès, Ning Zheng, William A Catterall
Potassium-sensitive hypokalaemic and normokalaemic periodic paralysis are inherited skeletal muscle diseases characterized by episodes of flaccid muscle weakness1,2 . They are caused by single mutations in positively charged residues ('gating charges') in the S4 transmembrane segment of the voltage sensor of the voltage-gated sodium channel Nav 1.4 or the calcium channel Cav 1.11,2 . Mutations of the outermost gating charges (R1 and R2) cause hypokalaemic periodic paralysis1,2 by creating a pathogenic gating pore in the voltage sensor through which cations leak in the resting state3,4 ...
May 16, 2018: Nature
Dawid Deneka, Marta Sawicka, Andy K M Lam, Cristina Paulino, Raimund Dutzler
Volume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family that co-assemble to form hexameric complexes. Here, using cryo-electron microscopy and X-ray crystallography, we determine the structure of a homomeric channel of the obligatory subunit LRRC8A. This protein conducts ions and has properties in common with endogenous heteromeric channels. Its modular structure consists of a transmembrane pore domain followed by a cytoplasmic leucine-rich repeat domain...
May 16, 2018: Nature
Yannick Simoni, Etienne Becht, Michael Fehlings, Chiew Yee Loh, Si-Lin Koo, Karen Wei Weng Teng, Joe Poh Sheng Yeong, Rahul Nahar, Tong Zhang, Hassen Kared, Kaibo Duan, Nicholas Ang, Michael Poidinger, Yin Yeng Lee, Anis Larbi, Alexis J Khng, Emile Tan, Cherylin Fu, Ronnie Mathew, Melissa Teo, Wan Teck Lim, Chee Keong Toh, Boon-Hean Ong, Tina Koh, Axel M Hillmer, Angela Takano, Tony Kiat Hon Lim, Eng Huat Tan, Weiwei Zhai, Daniel S W Tan, Iain Beehuat Tan, Evan W Newell
Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4 . Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6 . Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10 , in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown...
May 16, 2018: Nature
Gang Wan, Brandon D Fields, George Spracklin, Aditi Shukla, Carolyn M Phillips, Scott Kennedy
Non-membrane-bound organelles such as nucleoli, processing bodies, Cajal bodies and germ granules form by the spontaneous self-assembly of specific proteins and RNAs. How these biomolecular condensates form and interact is poorly understood. Here we identify two proteins, ZNFX-1 and WAGO-4, that localize to Caenorhabditis elegans germ granules (P granules) in early germline blastomeres. Later in germline development, ZNFX-1 and WAGO-4 separate from P granules to define an independent liquid-like condensate that we term the Z granule...
May 16, 2018: Nature
Emmanuelle Szenker-Ravi, Umut Altunoglu, Marc Leushacke, Célia Bosso-Lefèvre, Muznah Khatoo, Hong Thi Tran, Thomas Naert, Rivka Noelanders, Amin Hajamohideen, Claire Beneteau, Sergio B de Sousa, Birsen Karaman, Xenia Latypova, Seher Başaran, Esra Börklü Yücel, Thong Teck Tan, Lena Vlaeminck, Shalini S Nayak, Anju Shukla, Katta Mohan Girisha, Cédric Le Caignec, Natalia Soshnikova, Zehra Oya Uyguner, Kris Vleminckx, Nick Barker, Hülya Kayserili, Bruno Reversade
The four R-spondin secreted ligands (RSPO1-RSPO4) act via their cognate LGR4, LGR5 and LGR6 receptors to amplify WNT signalling1-3 . Here we report an allelic series of recessive RSPO2 mutations in humans that cause tetra-amelia syndrome, which is characterized by lung aplasia and a total absence of the four limbs. Functional studies revealed impaired binding to the LGR4/5/6 receptors and the RNF43 and ZNRF3 transmembrane ligases, and reduced WNT potentiation, which correlated with allele severity. Unexpectedly, however, the triple and ubiquitous knockout of Lgr4, Lgr5 and Lgr6 in mice did not recapitulate the known Rspo2 or Rspo3 loss-of-function phenotypes...
May 16, 2018: Nature
Jie Chen, Yuhui Ou, Yanyan Yang, Wen Li, Ye Xu, Yuntao Xie, Ying Liu
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that responds to a diverse set of environmental cues, including amino acids1,2 . Deregulation of mTORC1 has been linked with metabolic diseases, cancer and ageing2-4 . In response to amino acids, mTORC1 is recruited by the Rag GTPases to the lysosome, its site of activation5,6 . The GATOR1 complex, consisting of DEPDC5, NPRL3 and NPRL2, displays GAP activity to inactivate Rag GTPases under amino-acid-deficient conditions 7 ...
May 16, 2018: Nature
My-Nuong Vo, Markus Terrey, Jeong Woong Lee, Bappaditya Roy, James J Moresco, Litao Sun, Hongjun Fu, Qi Liu, Thomas G Weber, John R Yates, Kurt Fredrick, Paul Schimmel, Susan L Ackerman
Editing domains of aminoacyl tRNA synthetases correct tRNA charging errors to maintain translational fidelity. A mutation in the editing domain of alanyl tRNA synthetase (AlaRS) in Aars sti mutant mice results in an increase in the production of serine-mischarged tRNAAla and the degeneration of cerebellar Purkinje cells. Here, using positional cloning, we identified Ankrd16, a gene that acts epistatically with the Aars sti mutation to attenuate neurodegeneration. ANKRD16, a vertebrate-specific protein that contains ankyrin repeats, binds directly to the catalytic domain of AlaRS...
May 16, 2018: Nature
Zhiye Wang, Zeyang Ma, Claudia Castillo-González, Di Sun, Yanjun Li, Bin Yu, Baoyu Zhao, Pingwei Li, Xiuren Zhang
Chromatin remodelling factors (CHRs) typically function to alter chromatin structure. CHRs also reside in ribonucleoprotein complexes, but little is known about their RNA-related functions. Here we show that CHR2 (also known as BRM), the ATPase subunit of the large switch/sucrose non-fermentable (SWI/SNF) complex, is a partner of the Microprocessor component Serrate (SE). CHR2 promotes the transcription of primary microRNA precursors (pri-miRNAs) while repressing miRNA accumulation in vivo. Direct interaction with SE is required for post-transcriptional inhibition of miRNA accumulation by CHR2 but not for its transcriptional activity...
May 16, 2018: Nature
Morgan N Price, Kelly M Wetmore, R Jordan Waters, Mark Callaghan, Jayashree Ray, Hualan Liu, Jennifer V Kuehl, Ryan A Melnyk, Jacob S Lamson, Yumi Suh, Hans K Carlson, Zuelma Esquivel, Harini Sadeeshkumar, Romy Chakraborty, Grant M Zane, Benjamin E Rubin, Judy D Wall, Axel Visel, James Bristow, Matthew J Blow, Adam P Arkin, Adam M Deutschbauer
One-third of all protein-coding genes from bacterial genomes cannot be annotated with a function. Here, to investigate the functions of these genes, we present genome-wide mutant fitness data from 32 diverse bacteria across dozens of growth conditions. We identified mutant phenotypes for 11,779 protein-coding genes that had not been annotated with a specific function. Many genes could be associated with a specific condition because the gene affected fitness only in that condition, or with another gene in the same bacterium because they had similar mutant phenotypes...
May 16, 2018: Nature
Earl T Campbell, Barbara M Terhal, Christophe Vuillot
In Fig. 2b of this Review, two of the gates were inadvertently swapped. At the top right, 'Xa+c ' should have been 'Z b ', and at the bottom right 'Z b ' should have been 'Xa+c '. Fig. 2b has been corrected online. The Supplementary Information of this Author Correction contains the original, incorrect Fig. 2b, for transparency.
May 16, 2018: Nature
Carsten Bahr, Lisa von Paleske, Veli V Uslu, Silvia Remeseiro, Naoya Takayama, Stanley W Ng, Alex Murison, Katja Langenfeld, Massimo Petretich, Roberta Scognamiglio, Petra Zeisberger, Amelie S Benk, Ido Amit, Peter W Zandstra, Mathieu Lupien, John E Dick, Andreas Trumpp, François Spitz
In the originally published version of this Letter, ref. 43 was erroneously provided twice. In the 'Estimation of relative cell-type-specific composition of AML samples' section in the Methods, the citation to ref. 43 after the GEO dataset GSE24759 is correct. However, in the 'Mice' section of the Methods, the citation to ref. 43 after 'TAMERE' should have been associated with a new reference1. The original Letter has been corrected online (with the new reference included as ref. 49).
May 16, 2018: Nature
Loren M Lasko, Clarissa G Jakob, Rohinton P Edalji, Wei Qiu, Debra Montgomery, Enrico L Digiammarino, T Matt Hansen, Roberto M Risi, Robin Frey, Vlasios Manaves, Bailin Shaw, Mikkel Algire, Paul Hessler, Lloyd T Lam, Tamar Uziel, Emily Faivre, Debra Ferguson, Fritz G Buchanan, Ruth L Martin, Maricel Torrent, Gary G Chiang, Kannan Karukurichi, J William Langston, Brian T Weinert, Chunaram Choudhary, Peter de Vries, Arthur F Kluge, Michael A Patane, John H Van Drie, Ce Wang, David McElligott, Edward A Kesicki, Ronen Marmorstein, Chaohong Sun, Philip A Cole, Saul H Rosenberg, Michael R Michaelides, Albert Lai, Kenneth D Bromberg
In the originally published version of this Letter, the authors Arthur F. Kluge, Michael A. Patane and Ce Wang were inadvertently omitted from the author list. Their affiliations are: I-to-D, Inc., PO Box 6177, Lincoln, Massachusetts 01773, USA (A.F.K.); Mitobridge, Inc. 1030 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA (M.A.P.); and China Novartis Institutes for BioMedical Research, No. 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong District, Shanghai 201203, China (C.W.). These authors contributed to the interpretation of results and design of compounds...
May 16, 2018: Nature
Min Peng, Na Yin, Ming O Li
In the originally published version of this Letter, there was an error in Extended Data Fig. 7e and the corresponding uncropped blots in the Supplementary Information. The actin bands in the last blot of Extended Data Fig. 7e were duplicates  of the corresponding actin bands in the last blot of Extended Data Fig. 7 f. (In the uncropped blot for Extended Data Fig. 7e, the actin bands were mislabelled as 'WDR59' and this led to the error.) Extended Data Fig. 7 and the Supplementary Information of the original Letter have been corrected online...
May 16, 2018: Nature
A Kurnosov, H Marquardt, D J Frost, T Boffa Ballaran, L Ziberna
In Extended Data Table 1 of this Letter, some of the elastic constants were reported incorrectly. This occurred as a result of an error in the script used to generate the numbers. The values of the elastic constants at room pressure cited in the manuscript on page 544 were derived using the same erroneous script, and the correct values and 1σ-uncertainties in the last given digit are C11 = 461.3(17) GPa instead of 462.7(17) GPa; C22 = 509.7(26) GPa instead of 504.9(26) GPa; C33 = 425.7(5) GPa instead of 426...
May 16, 2018: Nature
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