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Peta–electron volt gamma-ray emission from the Crab Nebula 期刊论文
Science, 2021
作者:  The LHAASO Collaboration*†;  Zhen Cao;  F. Aharonian;  Q. An;  Axikegu;  L. X. Bai;  Y. X. Bai;  Y. W. Bao;  D. Bastieri;  X. J. Bi;  Y. J. Bi;  H. Cai;  J. T. Cai;  Zhe Cao;  J. Chang;  J. F. Chang;  B. M. Chen;  E. S. Chen;  J. Chen;  Liang Chen;  Liang Chen;  Long Chen;  M. J. Chen;  M. L. Chen;  Q. H. Chen;  S. H. Chen;  S. Z. Chen;  T. L. Chen;  X. L. Chen;  Y. Chen;  N. Cheng;  Y. D. Cheng;  S. W. Cui;  X. H. Cui;  Y. D. Cui;  B. D’Ettorre Piazzoli;  B. Z. Dai;  H. L. Dai;  Z. G. Dai;  Danzengluobu;  D. della Volpe;  X. J. Dong;  K. K. Duan;  J. H. Fan;  Y. Z. Fan;  Z. X. Fan;  J. Fang;  K. Fang;  C. F. Feng;  L. Feng;  S. H. Feng;  Y. L. Feng;  B. Gao;  C. D. Gao;  L. Q. Gao;  Q. Gao;  W. Gao;  M. M. Ge;  L. S. Geng;  G. H. Gong;  Q. B. Gou;  M. H. Gu;  F. L. Guo;  J. G. Guo;  X. L. Guo;  Y. Q. Guo;  Y. Y. Guo;  Y. A. Han;  H. H. He;  H. N. He;  J. C. He;  S. L. He;  X. B. He;  Y. He;  M. Heller;  Y. K. Hor;  C. Hou;  X. Hou;  H. B. Hu;  S. Hu;  S. C. Hu;  X. J. Hu;  D. H. Huang;  Q. L. Huang;  W. H. Huang;  X. T. Huang;  X. Y. Huang;  Z. C. Huang;  F. Ji;  X. L. Ji;  H. Y. Jia;  K. Jiang;  Z. J. Jiang;  C. Jin;  T. Ke;  D. Kuleshov;  K. Levochkin;  B. B. Li;  Cheng Li;  Cong Li;  F. Li;  H. B. Li;  H. C. Li;  H. Y. Li;  Jian Li;  Jie Li;  K. Li;  W. L. Li;  X. R. Li;  Xin Li;  Xin Li;  Y. Li;  Y. Z. Li;  Zhe Li;  Zhuo Li;  E. W. Liang;  Y. F. Liang;  S. J. Lin;  B. Liu;  C. Liu;  D. Liu;  H. Liu;  H. D. Liu;  J. Liu;  J. L. Liu;  J. S. Liu;  J. Y. Liu;  M. Y. Liu;  R. Y. Liu;  S. M. Liu;  W. Liu;  Y. Liu;  Y. N. Liu;  Z. X. Liu;  W. J. Long;  R. Lu;  H. K. Lv;  B. Q. Ma;  L. L. Ma;  X. H. Ma;  J. R. Mao;  A. Masood;  Z. Min;  W. Mitthumsiri;  T. Montaruli;  Y. C. Nan;  B. Y. Pang;  P. Pattarakijwanich;  Z. Y. Pei;  M. Y. Qi;  Y. Q. Qi;  B. Q. Qiao;  J. J. Qin;  D. Ruffolo;  V. Rulev;  A. Saiz;  L. Shao;  O. Shchegolev;  X. D. Sheng;  J. Y. Shi;  H. C. Song;  Yu. V. Stenkin;  V. Stepanov;  Y. Su;  Q. N. Sun;  X. N. Sun;  Z. B. Sun;  P. H. T. Tam;  Z. B. Tang;  W. W. Tian;  B. D. Wang;  C. Wang;  H. Wang;  H. G. Wang;  J. C. Wang;  J. S. Wang;  L. P. Wang;  L. Y. Wang;  R. N. Wang;  Wei Wang;  Wei Wang;  X. G. Wang;  X. J. Wang;  X. Y. Wang;  Y. Wang;  Y. D. Wang;  Y. J. Wang;  Y. P. Wang;  Z. H. Wang;  Z. X. Wang;  Zhen Wang;  Zheng Wang;  D. M. Wei;  J. J. Wei;  Y. J. Wei;  T. Wen;  C. Y. Wu;  H. R. Wu;  S. Wu;  W. X. Wu;  X. F. Wu;  S. Q. Xi;  J. Xia;  J. J. Xia;  G. M. Xiang;  D. X. Xiao;  G. Xiao;  H. B. Xiao;  G. G. Xin;  Y. L. Xin;  Y. Xing;  D. L. Xu;  R. X. Xu;  L. Xue;  D. H. Yan;  J. Z. Yan;  C. W. Yang;  F. F. Yang;  J. Y. Yang;  L. L. Yang;  M. J. Yang;  R. Z. Yang;  S. B. Yang;  Y. H. Yao;  Z. G. Yao;  Y. M. Ye;  L. Q. Yin;  N. Yin;  X. H. You;  Z. Y. You;  Y. H. Yu;  Q. Yuan;  H. D. Zeng;  T. X. Zeng;  W. Zeng;  Z. K. Zeng;  M. Zha;  X. X. Zhai;  B. B. Zhang;  H. M. Zhang;  H. Y. Zhang;  J. L. Zhang;  J. W. Zhang;  L. X. Zhang;  Li Zhang;  Lu Zhang;  P. F. Zhang;  P. P. Zhang;  R. Zhang;  S. R. Zhang;  S. S. Zhang;  X. Zhang;  X. P. Zhang;  Y. F. Zhang;  Y. L. Zhang;  Yi Zhang;  Yong Zhang;  B. Zhao;  J. Zhao;  L. Zhao;  L. Z. Zhao;  S. P. Zhao;  F. Zheng;  Y. Zheng;  B. Zhou;  H. Zhou;  J. N. Zhou;  P. Zhou;  R. Zhou;  X. X. Zhou;  C. G. Zhu;  F. R. Zhu;  H. Zhu;  K. J. Zhu;  X. Zuo
收藏  |  浏览/下载:14/0  |  提交时间:2021/07/27
MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO 期刊论文
Science, 2021
作者:  Lucia Ichino;  Brandon A. Boone;  Luke Strauskulage;  C. Jake Harris;  Gundeep Kaur;  Matthew A. Gladstone;  Maverick Tan;  Suhua Feng;  Yasaman Jami-Alahmadi;  Sascha H. Duttke;  James A. Wohlschlegel;  Xiaodong Cheng;  Sy Redding;  Steven E. Jacobsen
收藏  |  浏览/下载:19/0  |  提交时间:2021/07/27
3D genomics across the tree of life reveals condensin II as a determinant of architecture type 期刊论文
Science, 2021
作者:  Claire Hoencamp;  Olga Dudchenko;  Ahmed M. O. Elbatsh;  Sumitabha Brahmachari;  Jonne A. Raaijmakers;  Tom van Schaik;  Ángela Sedeño Cacciatore;  Vinícius G. Contessoto;  Roy G. H. P. van Heesbeen;  Bram van den Broek;  Aditya N. Mhaskar;  Hans Teunissen;  Brian Glenn St Hilaire;  David Weisz;  Arina D. Omer;  Melanie Pham;  Zane Colaric;  Zhenzhen Yang;  Suhas S. P. Rao;  Namita Mitra;  Christopher Lui;  Weijie Yao;  Ruqayya Khan;  Leonid L. Moroz;  Andrea Kohn;  Judy St. Leger;  Alexandria Mena;  Karen Holcroft;  Maria Cristina Gambetta;  Fabian Lim;  Emma Farley;  Nils Stein;  Alexander Haddad;  Daniel Chauss;  Ayse Sena Mutlu;  Meng C. Wang;  Neil D. Young;  Evin Hildebrandt;  Hans H. Cheng;  Christopher J. Knight;  Theresa L. U. Burnham;  Kevin A. Hovel;  Andrew J. Beel;  Pierre-Jean Mattei;  Roger D. Kornberg;  Wesley C. Warren;  Gregory Cary;  José Luis Gómez-Skarmeta;  Veronica Hinman;  Kerstin Lindblad-Toh;  Federica Di Palma;  Kazuhiro Maeshima;  Asha S. Multani;  Sen Pathak;  Liesl Nel-Themaat;  Richard R. Behringer;  Parwinder Kaur;  René H. Medema;  Bas van Steensel;  Elzo de Wit;  José N. Onuchic;  Michele Di Pierro;  Erez Lieberman Aiden;  Benjamin D. Rowland
收藏  |  浏览/下载:13/0  |  提交时间:2021/06/07
Role of iodine oxoacids in atmospheric aerosol nucleation 期刊论文
Science, 2021
作者:  Xu-Cheng He;  Yee Jun Tham;  Lubna Dada;  Mingyi Wang;  Henning Finkenzeller;  Dominik Stolzenburg;  Siddharth Iyer;  Mario Simon;  Andreas Kürten;  Jiali Shen;  Birte Rörup;  Matti Rissanen;  Siegfried Schobesberger;  Rima Baalbaki;  Dongyu S. Wang;  Theodore K. Koenig;  Tuija Jokinen;  Nina Sarnela;  Lisa J. Beck;  João Almeida;  Stavros Amanatidis;  António Amorim;  Farnoush Ataei;  Andrea Baccarini;  Barbara Bertozzi;  Federico Bianchi;  Sophia Brilke;  Lucía Caudillo;  Dexian Chen;  Randall Chiu;  Biwu Chu;  António Dias;  Aijun Ding;  Josef Dommen;  Jonathan Duplissy;  Imad El Haddad;  Loïc Gonzalez Carracedo;  Manuel Granzin;  Armin Hansel;  Martin Heinritzi;  Victoria Hofbauer;  Heikki Junninen;  Juha Kangasluoma;  Deniz Kemppainen;  Changhyuk Kim;  Weimeng Kong;  Jordan E. Krechmer;  Aleksander Kvashin;  Totti Laitinen;  Houssni Lamkaddam;  Chuan Ping Lee;  Katrianne Lehtipalo;  Markus Leiminger;  Zijun Li;  Vladimir Makhmutov;  Hanna E. Manninen;  Guillaume Marie;  Ruby Marten;  Serge Mathot;  Roy L. Mauldin;  Bernhard Mentler;  Ottmar Möhler;  Tatjana Müller;  Wei Nie;  Antti Onnela;  Tuukka Petäjä;  Joschka Pfeifer;  Maxim Philippov;  Ananth Ranjithkumar;  Alfonso Saiz-Lopez;  Imre Salma;  Wiebke Scholz;  Simone Schuchmann;  Benjamin Schulze;  Gerhard Steiner;  Yuri Stozhkov;  Christian Tauber;  António Tomé;  Roseline C. Thakur;  Olli Väisänen;  Miguel Vazquez-Pufleau;  Andrea C. Wagner;  Yonghong Wang;  Stefan K. Weber;  Paul M. Winkler;  Yusheng Wu;  Mao Xiao;  Chao Yan;  Qing Ye;  Arttu Ylisirniö;  Marcel Zauner-Wieczorek;  Qiaozhi Zha;  Putian Zhou;  Richard C. Flagan;  Joachim Curtius;  Urs Baltensperger;  Markku Kulmala;  Veli-Matti Kerminen;  Theo Kurtén;  Neil M. Donahue;  Rainer Volkamer;  Jasper Kirkby;  Douglas R. Worsnop;  Mikko Sipilä
收藏  |  浏览/下载:13/0  |  提交时间:2021/02/17
Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms 期刊论文
Science, 2020
作者:  David E. Gordon;  Joseph Hiatt;  Mehdi Bouhaddou;  Veronica V. Rezelj;  Svenja Ulferts;  Hannes Braberg;  Alexander S. Jureka;  Kirsten Obernier;  Jeffrey Z. Guo;  Jyoti Batra;  Robyn M. Kaake;  Andrew R. Weckstein;  Tristan W. Owens;  Meghna Gupta;  Sergei Pourmal;  Erron W. Titus;  Merve Cakir;  Margaret Soucheray;  Michael McGregor;  Zeynep Cakir;  Gwendolyn Jang;  Matthew J. O’Meara;  Tia A. Tummino;  Ziyang Zhang;  Helene Foussard;  Ajda Rojc;  Yuan Zhou;  Dmitry Kuchenov;  Ruth Hüttenhain;  Jiewei Xu;  Manon Eckhardt;  Danielle L. Swaney;  Jacqueline M. Fabius;  Manisha Ummadi;  Beril Tutuncuoglu;  Ujjwal Rathore;  Maya Modak;  Paige Haas;  Kelsey M. Haas;  Zun Zar Chi Naing;  Ernst H. Pulido;  Ying Shi;  Inigo Barrio-Hernandez;  Danish Memon;  Eirini Petsalaki;  Alistair Dunham;  Miguel Correa Marrero;  David Burke;  Cassandra Koh;  Thomas Vallet;  Jesus A. Silvas;  Caleigh M. Azumaya;  Christian Billesbølle;  Axel F. Brilot;  Melody G. Campbell;  Amy Diallo;  Miles Sasha Dickinson;  Devan Diwanji;  Nadia Herrera;  Nick Hoppe;  Huong T. Kratochvil;  Yanxin Liu;  Gregory E. Merz;  Michelle Moritz;  Henry C. Nguyen;  Carlos Nowotny;  Cristina Puchades;  Alexandrea N. Rizo;  Ursula Schulze-Gahmen;  Amber M. Smith;  Ming Sun;  Iris D. Young;  Jianhua Zhao;  Daniel Asarnow;  Justin Biel;  Alisa Bowen;  Julian R. Braxton;  Jen Chen;  Cynthia M. Chio;  Un Seng Chio;  Ishan Deshpande;  Loan Doan;  Bryan Faust;  Sebastian Flores;  Mingliang Jin;  Kate Kim;  Victor L. Lam;  Fei Li;  Junrui Li;  Yen-Li Li;  Yang Li;  Xi Liu;  Megan Lo;  Kyle E. Lopez;  Arthur A. Melo;  Frank R. Moss;  Phuong Nguyen;  Joana Paulino;  Komal Ishwar Pawar;  Jessica K. Peters;  Thomas H. Pospiech;  Maliheh Safari;  Smriti Sangwan;  Kaitlin Schaefer;  Paul V. Thomas;  Aye C. Thwin;  Raphael Trenker;  Eric Tse;  Tsz Kin Martin Tsui;  Feng Wang;  Natalie Whitis;  Zanlin Yu;  Kaihua Zhang;  Yang Zhang;  Fengbo Zhou;  Daniel Saltzberg;  QCRG Structural Biology Consortium12†;  Anthony J. Hodder;  Amber S. Shun-Shion;  Daniel M. Williams;  Kris M. White;  Romel Rosales;  Thomas Kehrer;  Lisa Miorin;  Elena Moreno;  Arvind H. Patel;  Suzannah Rihn;  Mir M. Khalid;  Albert Vallejo-Gracia;  Parinaz Fozouni;  Camille R. Simoneau;  Theodore L. Roth;  David Wu;  Mohd Anisul Karim;  Maya Ghoussaini;  Ian Dunham;  Francesco Berardi;  Sebastian Weigang;  Maxime Chazal;  Jisoo Park;  James Logue;  Marisa McGrath;  Stuart Weston;  Robert Haupt;  C. James Hastie;  Matthew Elliott;  Fiona Brown;  Kerry A. Burness;  Elaine Reid;  Mark Dorward;  Clare Johnson;  Stuart G. Wilkinson;  Anna Geyer;  Daniel M. Giesel;  Carla Baillie;  Samantha Raggett;  Hannah Leech;  Rachel Toth;  Nicola Goodman;  Kathleen C. Keough;  Abigail L. Lind;  Zoonomia Consortium‡;  Reyna J. Klesh;  Kafi R. Hemphill;  Jared Carlson-Stevermer;  Jennifer Oki;  Kevin Holden;  Travis Maures;  Katherine S. Pollard;  Andrej Sali;  David A. Agard;  Yifan Cheng;  James S. Fraser;  Adam Frost;  Natalia Jura;  Tanja Kortemme;  Aashish Manglik;  Daniel R. Southworth;  Robert M. Stroud;  Dario R. Alessi;  Paul Davies;  Matthew B. Frieman;  Trey Ideker;  Carmen Abate;  Nolwenn Jouvenet;  Georg Kochs;  Brian Shoichet;  Melanie Ott;  Massimo Palmarini;  Kevan M. Shokat;  Adolfo García-Sastre;  Jeremy A. Rassen;  Robert Grosse;  Oren S. Rosenberg;  Kliment A. Verba;  Christopher F. Basler;  Marco Vignuzzi;  Andrew A. Peden;  Pedro Beltrao;  Nevan J. Krogan
收藏  |  浏览/下载:27/0  |  提交时间:2020/12/07
Control of zeolite pore interior for chemoselective alkyne/olefin separations 期刊论文
Science, 2020
作者:  Yuchao Chai;  Xue Han;  Weiyao Li;  Shanshan Liu;  Sikai Yao;  Chong Wang;  Wei Shi;  Ivan da-Silva;  Pascal Manuel;  Yongqiang Cheng;  Luke D. Daemen;  Anibal J. Ramirez-Cuesta;  Chiu C. Tang;  Ling Jiang;  Sihai Yang;  Naijia Guan;  Landong Li
收藏  |  浏览/下载:7/0  |  提交时间:2020/06/01
A lower X-gate in TASK channels traps inhibitors within the vestibule 期刊论文
NATURE, 2020
作者:  Chen, Tao;  Nomura, Kinya;  Wang, Xiaolin;  Sohrabi, Reza;  Xu, Jin;  Yao, Lingya;  Paasch, Bradley C.;  Ma, Li;  Kremer, James;  Cheng, Yuti;  Zhang, Li;  Wang, Nian;  Wang, Ertao;  Xin, Xiu-Fang;  He, Sheng Yang
收藏  |  浏览/下载:35/0  |  提交时间:2020/07/03

TWIK-related acid-sensitive potassium (TASK) channels-members of the two pore domain potassium (K-2P) channel family-are found in neurons(1), cardiomyocytes(2-4) and vascular smooth muscle cells(5), where they are involved in the regulation of heart rate(6), pulmonary artery tone(5,7), sleep/wake cycles(8) and responses to volatile anaesthetics(8-11). K-2P channels regulate the resting membrane potential, providing background K+ currents controlled by numerous physiological stimuli(12-15). Unlike other K-2P channels, TASK channels are able to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates. As such, these channels are attractive drug targets, and TASK-1 inhibitors are currently in clinical trials for obstructive sleep apnoea and atrial fibrillation(16). In general, potassium channels have an intramembrane vestibule with a selectivity filter situated above and a gate with four parallel helices located below  however, the K-2P channels studied so far all lack a lower gate. Here we present the X-ray crystal structure of TASK-1, and show that it contains a lower gate-which we designate as an '  X-gate'  -created by interaction of the two crossed C-terminal M4 transmembrane helices at the vestibule entrance. This structure is formed by six residues ((VLRFMT248)-V-243) that are essential for responses to volatile anaesthetics(10), neurotransmitters(13) and G-protein-coupled receptors(13). Mutations within the X-gate and the surrounding regions markedly affect both the channel-open probability and the activation of the channel by anaesthetics. Structures of TASK-1 bound to two high-affinity inhibitors show that both compounds bind below the selectivity filter and are trapped in the vestibule by the X-gate, which explains their exceptionally low washout rates. The presence of the X-gate in TASK channels explains many aspects of their physiological and pharmacological behaviour, which will be beneficial for the future development and optimization of TASK modulators for the treatment of heart, lung and sleep disorders.


The X-ray crystal structure of the potassium channel TASK-1 reveals the presence of an X-gate, which traps small-molecule inhibitors in the intramembrane vestibule and explains their low washout rates from the channel.


  
The dental proteome of Homo antecessor 期刊论文
NATURE, 2020, 580 (7802) : 235-+
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03

Analyses of the proteomes of dental enamel from Homo antecessor and Homo erectus demonstrate that the Early Pleistocene H. antecessor is a close sister lineage of later Homo sapiens, Neanderthal and Denisovan populations in Eurasia.


The phylogenetic relationships between hominins of the Early Pleistocene epoch in Eurasia, such as Homo antecessor, and hominins that appear later in the fossil record during the Middle Pleistocene epoch, such as Homo sapiens, are highly debated(1-5). For the oldest remains, the molecular study of these relationships is hindered by the degradation of ancient DNA. However, recent research has demonstrated that the analysis of ancient proteins can address this challenge(6-8). Here we present the dental enamel proteomes of H. antecessor from Atapuerca (Spain)(9,10) and Homo erectus from Dmanisi (Georgia)(1), two key fossil assemblages that have a central role in models of Pleistocene hominin morphology, dispersal and divergence. We provide evidence that H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans. This placement implies that the modern-like face of H. antecessor-that is, similar to that of modern humans-may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form. By recovering AMELY-specific peptide sequences, we also conclude that the H. antecessor molar fragment from Atapuerca that we analysed belonged to a male individual. Finally, these H. antecessor and H. erectus fossils preserve evidence of enamel proteome phosphorylation and proteolytic digestion that occurred in vivo during tooth formation. Our results provide important insights into the evolutionary relationships between H. antecessor and other hominin groups, and pave the way for future studies using enamel proteomes to investigate hominin biology across the existence of the genus Homo.


  
Listeria monocytogenes impairs SUMOylation for efficient infection (vol 464, pg 1192, 2010) 期刊论文
NATURE, 2020, 580 (7805) : E20-E20
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


  
Neuronal programming by microbiota regulates intestinal physiology 期刊论文
NATURE, 2020, 578 (7794) : 284-+
作者:  Li, Yilong;  Roberts, Nicola D.;  Wala, Jeremiah A.;  Shapira, Ofer;  Schumacher, Steven E.;  Kumar, Kiran;  Khurana, Ekta;  Waszak, Sebastian;  Korbel, Jan O.;  Haber, James E.;  Imielinski, Marcin;  Weischenfeldt, Joachim;  Beroukhim, Rameen;  Campbell, Peter J.;  Akdemir, Kadir C.;  Alvarez, Eva G.;  Baez-Ortega, Adrian;  Boutros, Paul C.;  Bowtell, David D. L.;  Brors, Benedikt;  Burns, Kathleen H.;  Chan, Kin;  Chen, Ken;  Cortes-Ciriano, Isidro;  Dueso-Barroso, Ana;  Dunford, Andrew J.;  Edwards, Paul A.;  Estivill, Xavier;  Etemadmoghadam, Dariush;  Feuerbach, Lars;  Fink, J. Lynn;  Frenkel-Morgenstern, Milana;  Garsed, Dale W.;  Gerstein, Mark;  Gordenin, Dmitry A.;  Haan, David;  Hess, Julian M.;  Hutter, Barbara;  Jones, David T. W.;  Ju, Young Seok;  Kazanov, Marat D.;  Klimczak, Leszek J.;  Koh, Youngil;  Lee, Eunjung Alice;  Lee, Jake June-Koo;  Lynch, Andy G.;  Macintyre, Geoff;  Markowetz, Florian;  Martincorena, Inigo;  Martinez-Fundichely, Alexander;  Meyerson, Matthew;  Miyano, Satoru;  Nakagawa, Hidewaki;  Navarro, Fabio C. P.;  Ossowski, Stephan;  Park, Peter J.;  Pearson, John, V;  Puiggros, Montserrat;  Rippe, Karsten;  Roberts, Steven A.;  Rodriguez-Martin, Bernardo;  Scully, Ralph;  Shackleton, Mark;  Sidiropoulos, Nikos;  Sieverling, Lina;  Stewart, Chip;  Torrents, David;  Tubio, Jose M. C.;  Villasante, Izar;  Waddell, Nicola;  Yang, Lixing;  Yao, Xiaotong;  Yoon, Sung-Soo;  Zamora, Jorge;  Zhang, Cheng-Zhong
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Neural control of the function of visceral organs is essential for homeostasis and health. Intestinal peristalsis is critical for digestive physiology and host defence, and is often dysregulated in gastrointestinal disorders(1). Luminal factors, such as diet and microbiota, regulate neurogenic programs of gut motility(2-5), but the underlying molecular mechanisms remain unclear. Here we show that the transcription factor aryl hydrocarbon receptor (AHR) functions as a biosensor in intestinal neural circuits, linking their functional output to the microbial environment of the gut lumen. Using nuclear RNA sequencing of mouse enteric neurons that represent distinct intestinal segments and microbiota states, we demonstrate that the intrinsic neural networks of the colon exhibit unique transcriptional profiles that are controlled by the combined effects of host genetic programs and microbial colonization. Microbiota-induced expression of AHR in neurons of the distal gastrointestinal tract enables these neurons to respond to the luminal environment and to induce expression of neuron-specific effector mechanisms. Neuron-specific deletion of Ahr, or constitutive overexpression of its negative feedback regulator CYP1A1, results in reduced peristaltic activity of the colon, similar to that observed in microbiota-depleted mice. Finally, expression of Ahr in the enteric neurons of mice treated with antibiotics partially restores intestinal motility. Together, our experiments identify AHR signalling in enteric neurons as a regulatory node that integrates the luminal environment with the physiological output of intestinal neural circuits to maintain gut homeostasis and health.


In a mouse model, aryl hydrocarbon receptor signalling in enteric neurons is revealed as a mechanism that helps to maintain gut homeostasis by integrating the luminal environment with the physiology of intestinal neural circuits.