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Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease 期刊论文
NATURE, 2020, 577 (7788) : 103-+
作者:  Lalaoui, Najoua;  Boyden, Steven E.;  Oda, Hirotsugu;  Wood, Geryl M.;  Stone, Deborah L.;  Chau, Diep;  Liu, Lin;  Stoffels, Monique;  Kratina, Tobias;  Lawlor, Kate E.;  Zaal, Kristien J. M.;  Hoffmann, Patrycja M.;  Etemadi, Nima;  Shield-Artin, Kristy;  Biben, Christine;  Tsai, Wanxia Li;  Blake, Mary D.;  Kuehn, Hye Sun;  Yang, Dan;  Anderton, Holly;  Silke, Natasha;  Wachsmuth, Laurens;  Zheng, Lixin;  Moura, Natalia Sampaio;  Beck, David B.;  Gutierrez-Cruz, Gustavo;  Ombrello, Amanda K.;  Pinto-Patarroyo, Gineth P.;  Kueh, Andrew J.;  Herold, Marco J.;  Hall, Cathrine;  Wang, Hongying;  Chae, Jae Jin;  Dmitrieva, Natalia I.;  McKenzie, Mark;  Light, Amanda;  Barham, Beverly K.;  Jones, Anne;  Romeo, Tina M.;  Zhou, Qing;  Aksentijevich, Ivona;  Mullikin, James C.;  Gross, Andrew J.;  Shum, Anthony K.;  Hawkins, Edwin D.;  Masters, Seth L.;  Lenardo, Michael J.;  Boehm, Manfred;  Rosenzweig, Sergio D.;  Pasparakis, Manolis;  Voss, Anne K.;  Gadina, Massimo;  Kastner, Daniel L.;  Silke, John
收藏  |  浏览/下载:23/0  |  提交时间:2020/07/03

RIPK1 is a key regulator of innate immune signalling pathways. To ensure an optimal inflammatory response, RIPK1 is regulated post-translationally by well-characterized ubiquitylation and phosphorylation events, as well as by caspase-8-mediated cleavage1-7. The physiological relevance of this cleavage event remains unclear, although it is thought to inhibit activation of RIPK3 and necroptosis8. Here we show that the heterozygous missense mutations D324N, D324H and D324Y prevent caspase cleavage of RIPK1 in humans and result in an early-onset periodic fever syndrome and severe intermittent lymphadenopathy-a condition we term '  cleavage-resistant RIPK1-induced autoinflammatory syndrome'  . To define the mechanism for this disease, we generated a cleavage-resistant Ripk1(D325A) mutant mouse strain. Whereas Ripk1(-/-) mice died postnatally from systemic inflammation, Ripk1(D325A/D325A) mice died during embryogenesis. Embryonic lethality was completely prevented by the combined loss of Casp8 and Ripk3, but not by loss of Ripk3 or Mlkl alone. Loss of RIPK1 kinase activity also prevented Ripk1(D325A/D325A) embryonic lethality, although the mice died before weaning from multi-organ inflammation in a RIPK3-dependent manner. Consistently, Ripk1(D325A/D325A) and Ripk1(D325A/+) cells were hypersensitive to RIPK3-dependent TNF-induced apoptosis and necroptosis. Heterozygous Ripk1(D325A/+) mice were viable and grossly normal, but were hyper-responsive to inflammatory stimuli in vivo. Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase cleavage of RIPK1 not only inhibits necroptosis but also maintains inflammatory homeostasis throughout life.


  
Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform 期刊论文
NATURE, 2020
作者:  Touat, Mehdi;  Li, Yvonne Y.;  Boynton, Adam N.;  Spurr, Liam F.;  Iorgulescu, J. Bryan;  Bohrson, Craig L.;  Cortes-Ciriano, Isidro;  Birzu, Cristina;  Geduldig, Jack E.;  Pelton, Kristine;  Lim-Fat, Mary Jane;  Pal, Sangita;  Ferrer-Luna, Ruben;  Ramkissoon, Shakti H.;  Dubois, Frank;  Bellamy, Charlotte;  Currimjee, Naomi;  Bonardi, Juliana;  Qian Kenin;  Ho, Patricia;  Malinowski, Seth;  Taquet, Leon;  Jones, Robert E.;  Shetty, Aniket;  Chow, Kin-Hoe;  Sharaf, Radwa;  Pavlick, Dean;  Albacker, Lee A.;  Younan, Nadia;  Baldini, Capucine;  Verreault, Maite;  Giry, Marine;  Guillerm, Erell;  Ammari, Samy;  Beuvon, Frederic;  Mokhtari, Karima;  Alentorn, Agusti;  Dehais, Caroline;  Houillier, Caroline;  Laigle-Donadey, Florence;  Psimaras, Dimitri;  Lee, Eudocia Q.;  Nayak, Lakshmi;  McFaline-Figueroa, J. Ricardo;  Carpentier, Alexandre;  Cornu, Philippe;  Capelle, Laurent;  Mathon, Bertrand;  Barnholtz-Sloan, Jill S.;  Chakravarti, Arnab;  Bi, Wenya Linda;  Chiocca, E. Antonio;  Fehnel, Katie Pricola;  Alexandrescu, Sanda;  Chi, Susan N.;  Haas-Kogan, Daphne;  Batchelor, Tracy T.;  Frampton, Garrett M.;  Alexander, Brian M.;  Huang, Raymond Y.;  Ligon, Azra H.;  Coulet, Florence;  Delattre, Jean-Yves;  Hoang-Xuan, Khe;  Meredith, David M.;  Santagata, Sandro;  Duval, Alex;  Sanson, Marc;  Cherniack, Andrew D.;  Wen, Patrick Y.;  Reardon, David A.;  Marabelle, Aurelien;  Park, Peter J.;  Idbaih, Ahmed;  Beroukhim, Rameen;  Bandopadhayay, Pratiti;  Bielle, Franck;  Ligon, Keith L.
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Reverse genetics has been an indispensable tool to gain insights into viral pathogenesis and vaccine development. The genomes of large RNA viruses, such as those from coronaviruses, are cumbersome to clone and manipulate inEscherichia coliowing to the size and occasional instability of the genome(1-3). Therefore, an alternative rapid and robust reverse-genetics platform for RNA viruses would benefit the research community. Here we show the full functionality of a yeast-based synthetic genomics platform to genetically reconstruct diverse RNA viruses, including members of theCoronaviridae,FlaviviridaeandPneumoviridaefamilies. Viral subgenomic fragments were generated using viral isolates, cloned viral DNA, clinical samples or synthetic DNA, and these fragments were then reassembled in one step inSaccharomyces cerevisiaeusing transformation-associated recombination cloning to maintain the genome as a yeast artificial chromosome. T7 RNA polymerase was then used to generate infectious RNA to rescue viable virus. Using this platform, we were able to engineer and generate chemically synthesized clones of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(4), which has caused the recent pandemic of coronavirus disease (COVID-19), in only a week after receipt of the synthetic DNA fragments. The technical advance that we describe here facilitates rapid responses to emerging viruses as it enables the real-time generation and functional characterization of evolving RNA virus variants during an outbreak.


A yeast-based synthetic genomics platform is used to reconstruct and characterize large RNA viruses from synthetic DNA fragments  this technique will facilitate the rapid analysis of RNA viruses, such as SARS-CoV-2, during an outbreak.


  
Simulation of Hubbard model physics in WSe2/WS2 moire superlattices 期刊论文
NATURE, 2020, 579 (7799) : 353-+
作者:  Stein, Reed M.;  Kang, Hye Jin;  McCorvy, John D.;  Glatfelter, Grant C.;  Jones, Anthony J.;  Che, Tao;  Slocum, Samuel;  Huang, Xi-Ping;  Savych, Olena;  Moroz, Yurii S.;  Stauch, Benjamin;  Johansson, Linda C.;  Cherezov, Vadim;  Kenakin, Terry;  Irwin, John J.;  Shoichet, Brian K.;  Roth, Bryan L.;  Dubocovich, Margarita L.
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

Study of WSe2/WS2 moire superlattices reveals the phase diagram of the triangular-lattice Hubbard model, including a Mott insulating state at half-filling and a possible magnetic quantum phase transition near 0.6 filling.


The Hubbard model, formulated by physicist John Hubbard in the 1960s(1), is a simple theoretical model of interacting quantum particles in a lattice. The model is thought to capture the essential physics of high-temperature superconductors, magnetic insulators and other complex quantum many-body ground states(2,3). Although the Hubbard model provides a greatly simplified representation of most real materials, it is nevertheless difficult to solve accurately except in the one-dimensional case(2,3). Therefore, the physical realization of the Hubbard model in two or three dimensions, which can act as an analogue quantum simulator (that is, it can mimic the model and simulate its phase diagram and dynamics(4,5)), has a vital role in solving the strong-correlation puzzle, namely, revealing the physics of a large number of strongly interacting quantum particles. Here we obtain the phase diagram of the two-dimensional triangular-lattice Hubbard model by studying angle-aligned WSe2/WS2 bilayers, which form moire superlattices(6) because of the difference between the lattice constants of the two materials. We probe the charge and magnetic properties of the system by measuring the dependence of its optical response on an out-of-plane magnetic field and on the gate-tuned carrier density. At half-filling of the first hole moire superlattice band, we observe a Mott insulating state with antiferromagnetic Curie-Weiss behaviour, as expected for a Hubbard model in the strong-interaction regime(2,3,7-9). Above half-filling, our experiment suggests a possible quantum phase transition from an antiferromagnetic to a weak ferromagnetic state at filling factors near 0.6. Our results establish a new solid-state platform based on moire superlattices that can be used to simulate problems in strong-correlation physics that are described by triangular-lattice Hubbard models.


  
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
收藏  |  浏览/下载:38/0  |  提交时间:2020/07/03

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.


  
Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids 期刊论文
NATURE, 2020
作者:  Nixon, Christopher C.;  Mavigner, Maud;  Sampey, Gavin C.;  Brooks, Alyssa D.;  Spagnuolo, Rae Ann;  Irlbeck, David M.;  Mattingly, Cameron;  Ho, Phong T.;  Schoof, Nils;  Cammon, Corinne G.;  Tharp, Greg K.;  Kanke, Matthew;  Wang, Zhang;  Cleary, Rachel A.;  Upadhyay, Amit A.;  De, Chandrav;  Wills, Saintedym R.;  Falcinelli, Shane D.;  Galardi, Cristin;  Walum, Hasse;  Schramm, Nathaniel J.;  Deutsch, Jennifer;  Lifson, Jeffrey D.;  Fennessey, Christine M.;  Keele, Brandon F.;  Jean, Sherrie;  Maguire, Sean;  Liao, Baolin;  Browne, Edward P.;  Ferris, Robert G.;  Brehm, Jessica H.;  Favre, David;  Vanderford, Thomas H.;  Bosinger, Steven E.;  Jones, Corbin D.;  Routy, Jean-Pierre;  Archin, Nancie M.;  Margolis, David M.;  Wahl, Angela;  Dunham, Richard M.;  Silvestri, Guido;  Chahroudi, Ann;  Garcia, J. Victor
收藏  |  浏览/下载:34/0  |  提交时间:2020/07/03

Single-cell RNA sequencing and spatial transcriptomics reveal that the somitogenesis clock is active in mouse gastruloids, which can be induced to generate somites with the correct rostral-caudal patterning.


Gastruloids are three-dimensional aggregates of embryonic stem cells that display key features of mammalian development after implantation, including germ-layer specification and axial organization(1-3). To date, the expression pattern of only a small number of genes in gastruloids has been explored with microscopy, and the extent to which genome-wide expression patterns in gastruloids mimic those in embryos is unclear. Here we compare mouse gastruloids with mouse embryos using single-cell RNA sequencing and spatial transcriptomics. We identify various embryonic cell types that were not previously known to be present in gastruloids, and show that key regulators of somitogenesis are expressed similarly between embryos and gastruloids. Using live imaging, we show that the somitogenesis clock is active in gastruloids and has dynamics that resemble those in vivo. Because gastruloids can be grown in large quantities, we performed a small screen that revealed how reduced FGF signalling induces a short-tail phenotype in embryos. Finally, we demonstrate that embedding in Matrigel induces gastruloids to generate somites with the correct rostral-caudal patterning, which appear sequentially in an anterior-to-posterior direction over time. This study thus shows the power of gastruloids as a model system for exploring development and somitogenesis in vitro in a high-throughput manner.


  
Meeting the looming policy challenge of sea-level change and human migration 期刊论文
NATURE CLIMATE CHANGE, 2019, 9 (12) : 898-901
作者:  Wrathall, D. J.;  Mueller, V.;  Clark, P. U.;  Bell, A.;  Oppenheimer, M.;  Hauer, M.;  Kulp, S.;  Gilmore, E.;  Adams, H.;  Kopp, R.;  Abel, K.;  Call, M.;  Chen, J.;  deSherbinin, A.;  Fussell, E.;  Hay, C.;  Jones, B.;  Magliocca, N.;  Marino, E.;  Slangen, A.;  Warner, K.
收藏  |  浏览/下载:9/0  |  提交时间:2020/02/16
Angiosperm symbioses with non-mycorrhizal fungal partners enhance N acquisition from ancient organic matter in a warming maritime Antarctic 期刊论文
ECOLOGY LETTERS, 2019
作者:  Hill, Paul W.;  Broughton, Richard;  Bougoure, Jeremy;  Havelange, William;  Newsham, Kevin K.;  Grant, Helen;  Murphy, Daniel, V;  Clode, Peta;  Ramayah, Soshila;  Marsden, Karina A.;  Quilliam, Richard S.;  Roberts, Paula;  Brown, Caley;  Read, David J.;  Deluca, Thomas H.;  Bardgett, Richard D.;  Hopkins, David W.;  Jones, Davey L.
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27
carbon cycle  climate change  dark septate endophytes  enantiomers  nitrogen cycle  polar  soil  
Zones of influence for soil organic matter dynamics: A conceptual framework for data and models 期刊论文
GLOBAL CHANGE BIOLOGY, 2019
作者:  Cagnarini, Claudia;  Blyth, Eleanor;  Emmett, Bridget A.;  Evans, Chris D.;  Griffiths, Robert, I;  Keith, Aidan;  Jones, Laurence;  Lebron, Inma;  McNamara, Niall P.;  Puissant, Jeremy;  Reinsch, Sabine;  Robinson, David A.;  Rowe, Edwin C.;  Thomas, Amy R. C.;  Smart, Simon M.;  Whitaker, Jeanette;  Cosby, Bernard J.
收藏  |  浏览/下载:14/0  |  提交时间:2019/11/27
conceptual framework  connectivity  soil depth  SOM model  SOM persistence  sustainable land management  UNSDG-15  zones of influence  
Multicomponent Satellite Assessment of Drought Severity in the Contiguous United States From 2002 to 2017 Using AMSR-E and AMSR2 期刊论文
WATER RESOURCES RESEARCH, 2019, 55 (7) : 5394-5412
作者:  Du, J.;  Kimball, J. S.;  Velicogna, I;  Zhao, M.;  Jones, L. A.;  Watts, J. D.;  Kim, Y.
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27
Close Cassini flybys of Saturn's ring moons Pan, Daphnis, Atlas, Pandora, and Epimetheus 期刊论文
SCIENCE, 2019, 364 (6445) : 1053-+
作者:  Buratti, B. J.;  Thomas, P. C.;  Roussos, E.;  Howett, C.;  Seiss, M.;  Hendrix, A. R.;  Helfenstein, P.;  Brown, R. H.;  Clark, R. N.;  Denk, T.;  Filacchione, G.;  Hoffmann, H.;  Jones, G. H.;  Khawaja, N.;  Kollmann, P.;  Krupp, N.;  Lunine, J.;  Momary, T. W.;  Paranicas, C.;  Postberg, F.;  Sachse, M.;  Spahn, F.;  Spencer, J.;  Srama, R.;  Albin, T.;  Baines, K. H.;  Ciarniello, M.;  Economou, T.;  Hsu, H. -W.;  Kempf, S.;  Krimigis, S. M.;  Mitchell, D.;  Moragas-Klostermeyer, G.;  Nicholson, P. D.;  Porco, C. C.;  Rosenberg, H.;  Simolka, J.;  Soderblom, L. A.
收藏  |  浏览/下载:14/0  |  提交时间:2019/11/27