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Ice front blocking of ocean heat transport to an Antarctic ice shelf 期刊论文
NATURE, 2020, 578 (7796) : 568-+
作者:  Alexandrov, Ludmil B.;  Kim, Jaegil;  Haradhvala, Nicholas J.;  Huang, Mi Ni;  Ng, Alvin Wei Tian;  Wu, Yang;  Boot, Arnoud;  Covington, Kyle R.;  Gordenin, Dmitry A.;  Bergstrom, Erik N.;  Islam, S. M. Ashiqul;  Lopez-Bigas, Nuria;  Klimczak, Leszek J.;  McPherson, John R.;  Morganella, Sandro;  Sabarinathan, Radhakrishnan;  Wheeler, David A.;  Mustonen, Ville;  Getz, Gad;  Rozen, Steven G.;  Stratton, Michael R.
收藏  |  浏览/下载:10/0  |  提交时间:2020/05/13

The front of the Getz Ice Shelf in West Antarctica creates an abrupt topographic step that deflects ocean currents, suppressing 70% of the heat delivery to the ice sheet.


Mass loss from the Antarctic Ice Sheet to the ocean has increased in recent decades, largely because the thinning of its floating ice shelves has allowed the outflow of grounded ice to accelerate(1,2). Enhanced basal melting of the ice shelves is thought to be the ultimate driver of change(2,3), motivating a recent focus on the processes that control ocean heat transport onto and across the seabed of the Antarctic continental shelf towards the ice(4-6). However, the shoreward heat flux typically far exceeds that required to match observed melt rates(2,7,8), suggesting that other critical controls exist. Here we show that the depth-independent (barotropic) component of the heat flow towards an ice shelf is blocked by the marked step shape of the ice front, and that only the depth-varying (baroclinic) component, which is typically much smaller, can enter the sub-ice cavity. Our results arise from direct observations of the Getz Ice Shelf system and laboratory experiments on a rotating platform. A similar blocking of the barotropic component may occur in other areas with comparable ice-bathymetry configurations, which may explain why changes in the density structure of the water column have been found to be a better indicator of basal melt rate variability than the heat transported onto the continental shelf(9). Representing the step topography of the ice front accurately in models is thus important for simulating ocean heat fluxes and induced melt rates.


  
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:37/0  |  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.


  
Integrated genomic and molecular characterization of cervical cancer 期刊论文
NATURE, 2017, 543 (7645) : 378-+
作者:  Burk, Robert D.;  Chen, Zigui;  Saller, Charles;  Tarvin, Katherine;  Carvalho, Andre L.;  Scapulatempo-Neto, Cristovam;  Silveira, Henrique C.;  Fregnani, Jose H.;  Creighton, Chad J.;  Anderson, Matthew L.;  Castro, Patricia;  Wang, Sophia S.;  Yau, Christina;  Benz, Christopher;  Robertson, A. Gordon;  Mungall, Karen;  Lim, Lynette;  Bowlby, Reanne;  Sadeghi, Sara;  Brooks, Denise;  Sipahimalani, Payal;  Mar, Richard;  Ally, Adrian;  Clarke, Amanda;  Mungall, Andrew J.;  Tam, Angela;  Lee, Darlene;  Chuah, Eric;  Schein, Jacqueline E.;  Tse, Kane;  Kasaian, Katayoon;  Ma, Yussanne;  Marra, Marco A.;  Mayo, Michael;  Balasundaram, Miruna;  Thiessen, Nina;  Dhalla, Noreen;  Carlsen, Rebecca;  Moore, Richard A.;  Holt, Robert A.;  Jones, Steven J. M.;  Wong, Tina;  Pantazi, Angeliki;  Parfenov, Michael;  Kucherlapati, Raju;  Hadjipanayis, Angela;  Seidman, Jonathan;  Kucherlapati, Melanie;  Ren, Xiaojia;  Xu, Andrew W.;  Yang, Lixing;  Park, Peter J.;  Lee, Semin;  Rabeno, Brenda;  Huelsenbeck-Dill, Lori;  Borowsky, Mark;  Cadungog, Mark;  Iacocca, Mary;  Petrelli, Nicholas;  Swanson, Patricia;  Ojesina, Akinyemi I.;  Le, Xuan;  Sandusky, George;  Adebamowo, Sally N.;  Akeredolu, Teniola;  Adebamowo, Clement;  Reynolds, Sheila M.;  Shmulevich, Ilya;  Shelton, Candace;  Crain, Daniel;  Mallery, David;  Curley, Erin;  Gardner, Johanna;  Penny, Robert;  Morris, Scott;  Shelton, Troy;  Liu, Jia;  Lolla, Laxmi;  Chudamani, Sudha;  Wu, Ye;  Birrer, Michael;  McLellan, Michael D.;  Bailey, Matthew H.;  Miller, Christopher A.;  Wyczalkowski, Matthew A.;  Fulton, Robert S.;  Fronick, Catrina C.;  Lu, Charles;  Mardis, Elaine R.;  Appelbaum, Elizabeth L.;  Schmidt, Heather K.;  Fulton, Lucinda A.;  Cordes, Matthew G.;  Li, Tiandao;  Ding, Li;  Wilson, Richard K.;  Rader, Janet S.;  Behmaram, Behnaz;  Uyar, Denise;  Bradley, William;  Wrangle, John;  Pastore, Alessandro;  Levine, Douglas A.;  Dao, Fanny;  Gao, Jianjiong;  Schultz, Nikolaus;  Sander, Chris;  Ladanyi, Marc;  Einstein, Mark;  Teeter, Randall;  Benz, Stephen;  Wentzensen, Nicolas;  Felau, Ina;  Zenklusen, Jean C.;  Bodelon, Clara;  Demchok, John A.;  Yang, Liming;  Sheth, Margi;  Ferguson, Martin L.;  Tarnuzzer, Roy;  Yang, Hannah;  Schiffman, Mark;  Zhang, Jiashan;  Wang, Zhining;  Davidsen, Tanja;  Olaniyan, Olayinka;  Hutter, Carolyn M.;  Sofia, Heidi J.;  Gordenin, Dmitry A.;  Chan, Kin;  Roberts, Steven A.;  Klimczak, Leszek J.;  Van Waes, Carter;  Chen, Zhong;  Saleh, Anthony D.;  Cheng, Hui;  Parfitt, Jeremy;  Bartlett, John;  Albert, Monique;  Arnaout, Angel;  Sekhon, Harman;  Gilbert, Sebastien;  Peto, Myron;  Myers, Jerome;  Harr, Jodi;  Eckman, John;  Bergsten, Julie;  Tucker, Kelinda;  Zach, Leigh Anne;  Karlan, Beth Y.;  Lester, Jenny;  Orsulic, Sandra;  Sun, Qiang;  Naresh, Rashi;  Pihl, Todd;  Wan, Yunhu;  Zaren, Howard;  Sapp, Jennifer;  Miller, Judy;  Drwiega, Paul;  Ojesina, Akinyemi I.;  Murray, Bradley A.;  Zhang, Hailei;  Cherniack, Andrew D.;  Sougnez, Carrie;  Pedamallu, Chandra Sekhar;  Lichtenstein, Lee;  Meyerson, Matthew;  Noble, Michael S.;  Heiman, David I.;  Voet, Doug;  Getz, Gad;  Saksena, Gordon;  Kim, Jaegil;  Shih, Juliann;  Cho, Juok;  Lawrence, Michael S.;  Gehlenborg, Nils;  Lin, Pei;  Beroukhim, Rameen;  Frazer, Scott;  Gabriel, Stacey B.;  Schumacher, Steven E.;  Leraas, Kristen M.;  Lichtenberg, Tara M.;  Zmuda, Erik;  Bowen, Jay;  Frick, Jessica;  Gastier-Foster, Julie M.;  Wise, Lisa;  Gerken, Mark;  Ramirez, Nilsa C.;  Danilova, Ludmila;  Cope, Leslie;  Baylin, Stephen B.;  Salvesen, Helga B.;  Vellano, Christopher P.;  Ju, Zhenlin;  Diao, Lixia;  Zhao, Hao;  Chong, Zechen;  Ryan, Michael C.;  Martinez-Ledesma, Emmanuel;  Verhaak, Roeland G.;  Byers, Lauren Averett;  Yuan, Yuan;  Chen, Ken;  Ling, Shiyun;  Mills, Gordon B.;  Lu, Yiling;  Akbani, Rehan;  Seth, Sahil;  Liang, Han;  Wang, Jing;  Han, Leng;  Weinstein, John N.;  Bristow, Christopher A.;  Zhang, Wei;  Mahadeshwar, Harshad S.;  Sun, Huandong;  Tang, Jiabin;  Zhang, Jianhua;  Song, Xingzhi;  Protopopov, Alexei;  Shaw, Kenna R. Mills;  Chin, Lynda;  Olabode, Oluwole;  Ojesina, Akinyemi I.;  DiSaia, Philip;  Radenbaugh, Amie;  Haussler, David;  Zhu, Jingchun;  Stuart, Josh;  Chalise, Prabhakar;  Koestler, Devin;  Fridley, Brooke L.;  Godwin, Andrew K.;  Madan, Rashna;  Ciriello, Giovanni;  Martinez, Cathleen;  Higgins, Kelly;  Bocklage, Therese;  Auman, J. Todd;  Perou, Charles M.;  Tan, Donghui;  Parker, Joel S.;  Hoadley, Katherine A.;  Wilkerson, Matthew D.;  Mieczkowski, Piotr A.;  Skelly, Tara;  Veluvolu, Umadevi;  Hayes, D. Neil;  Rathmell, W. Kimryn;  Hoyle, Alan P.;  Simons, Janae V.;  Wu, Junyuan;  Mose, Lisle E.;  Soloway, Matthew G.;  Balu, Saianand;  Meng, Shaowu;  Jefferys, Stuart R.;  Bodenheimer, Tom;  Shi, Yan;  Roach, Jeffrey;  Thorne, Leigh B.;  Boice, Lori;  Huang, Mei;  Jones, Corbin D.;  Zuna, Rosemary;  Walker, Joan;  Gunderson, Camille;  Snowbarger, Carie;  Brown, David;  Moxley, Katherine;  Moore, Kathleen;  Andrade, Kelsi;  Landrum, Lisa;  Mannel, Robert;  McMeekin, Scott;  Johnson, Starla;  Nelson, Tina;  Elishaev, Esther;  Dhir, Rajiv;  Edwards, Robert;  Bhargava, Rohit;  Tiezzi, Daniel G.;  Andrade, Jurandyr M.;  Noushmehr, Houtan;  Carlotti, Carlos Gilberto, Jr.;  Tirapelli, Daniela Pretti da Cunha;  Weisenberger, Daniel J.;  Van Den Berg, David J.;  Maglinte, Dennis T.;  Bootwalla, Moiz S.;  Lai, Phillip H.;  Triche, Timothy, Jr.;  Swisher, Elizabeth M.;  Agnew, Kathy J.;  Shelley, Carl Simon;  Laird, Peter W.;  Schwarz, Julie;  Grigsby, Perry;  Mutch, David
收藏  |  浏览/下载:13/0  |  提交时间:2019/04/09