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Pharmacologic fibroblast reprogramming into photoreceptors restores vision 期刊论文
NATURE, 2020, 581 (7806) : 83-+
作者:  Jiang, Mingkai;  Medlyn, Belinda E.;  Drake, John E.;  Duursma, Remko A.;  Anderson, Ian C.;  Barton, Craig V. M.;  Boer, Matthias M.;  Carrillo, Yolima;  Castaneda-Gomez, Laura;  Collins, Luke;  Crous, Kristine Y.;  De Kauwe, Martin G.;  dos Santos, Bruna M.;  Emmerson, Kathryn M.;  Facey, Sarah L.;  Gherlenda, Andrew N.;  Gimeno, Teresa E.;  Hasegawa, Shun;  Johnson, Scott N.;  Kannaste, Astrid;  Macdonald, Catriona A.;  Mahmud, Kashif;  Moore, Ben D.;  Nazaries, Loic;  Neilson, Elizabeth H. J.;  Nielsen, Uffe N.;  Niinemets, Ulo;  Noh, Nam Jin;  Ochoa-Hueso, Raul;  Pathare, Varsha S.;  Pendall, Elise;  Pihlblad, Johanna;  Pineiro, Juan;  Powell, Jeff R.;  Power, Sally A.;  Reich, Peter B.;  Renchon, Alexandre A.;  Riegler, Markus;  Rinnan, Riikka;  Rymer, Paul D.;  Salomon, Roberto L.;  Singh, Brajesh K.;  Smith, Benjamin;  Tjoelker, Mark G.;  Walker, Jennifer K. M.;  Wujeska-Klause, Agnieszka;  Yang, Jinyan;  Zaehle, Soenke;  Ellsworth, David S.
收藏  |  浏览/下载:45/0  |  提交时间:2020/07/03

Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision(1,2). Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss  however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the subretinal space of rod degeneration mice (homozygous for rd1, also known as Pde6b) leads to partial restoration of the pupil reflex and visual function. We show that mitonuclear communication is a key determining factor for the reprogramming of fibroblasts into CiPCs. Specifically, treatment with these five compounds leads to the translocation of AXIN2 to the mitochondria, which results in the production of reactive oxygen species, the activation of NF-kappa B and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision.


A set of five small molecules can induce the transformation of fibroblasts into rod photoreceptor-like cells, which can partially restore pupil reflex and visual function when transplanted into a rod degeneration mouse model.


  
Oceanic forcing of penultimate deglacial and last interglacial sea-level rise 期刊论文
NATURE, 2020, 577 (7792) : 660-+
作者:  Rizal, Yan;  Westaway, Kira E.;  Zaim, Yahdi;  van den Bergh, Gerrit D.;  Bettis, E. Arthur, III;  Morwood, Michael J.;  Huffman, O. Frank;  Grun, Rainer;  Joannes-Boyau, Renaud;  Bailey, Richard M.;  Sidarto;  Westaway, Michael C.;  Kurniawan, Iwan;  Moore, Mark W.;  Storey, Michael;  Aziz, Fachroel;  Suminto;  Zhao, Jian-xin;  Aswan;  Sipola, Maija E.;  Larick, Roy;  Zonneveld, John-Paul;  Scott, Robert;  Putt, Shelby;  Ciochon, Russell L.
收藏  |  浏览/下载:21/0  |  提交时间:2020/05/13

Sea-level histories during the two most recent deglacial-interglacial intervals show substantial differences(1-3) despite both periods undergoing similar changes in global mean temperature(4,5) and forcing from greenhouse gases(6). Although the last interglaciation (LIG) experienced stronger boreal summer insolation forcing than the present interglaciation(7), understanding why LIG global mean sea level may have been six to nine metres higher than today has proven particularly challenging(2). Extensive areas of polar ice sheets were grounded below sea level during both glacial and interglacial periods, with grounding lines and fringing ice shelves extending onto continental shelves(8). This suggests that oceanic forcing by subsurface warming may also have contributed to ice-sheet loss(9-12) analogous to ongoing changes in the Antarctic(13,14) and Greenland(15) ice sheets. Such forcing would have been especially effective during glacial periods, when the Atlantic Meridional Overturning Circulation (AMOC) experienced large variations on millennial timescales(16), with a reduction of the AMOC causing subsurface warming throughout much of the Atlantic basin(9,12,17). Here we show that greater subsurface warming induced by the longer period of reduced AMOC during the penultimate deglaciation can explain the more-rapid sea-level rise compared with the last deglaciation. This greater forcing also contributed to excess loss from the Greenland and Antarctic ice sheets during the LIG, causing global mean sea level to rise at least four metres above modern levels. When accounting for the combined influences of penultimate and LIG deglaciation on glacial isostatic adjustment, this excess loss of polar ice during the LIG can explain much of the relative sea level recorded by fossil coral reefs and speleothems at intermediate- and far-field sites.


  
Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution 期刊论文
NATURE, 2017, 545 (7655) : 446-+
作者:  Abbosh, Christopher;  Birkbak, Nicolai J.;  Wilson, Gareth A.;  Jamal-Hanjani, Mariam;  Constantin, Tudor;  Salari, Raheleh;  Le Quesne, John;  Moore, David A.;  Veeriah, Selvaraju;  Rosenthal, Rachel;  Marafioti, Teresa;  Kirkizlar, Eser;  Watkins, Thomas B. K.;  McGranahan, Nicholas;  Ward, Sophia;  Martinson, Luke;  Riley, Joan;  Fraioli, Francesco;  Al Bakir, Maise;  Gronroos, Eva;  Zambrana, Francisco;  Endozo, Raymondo;  Bi, Wenya Linda;  Fennessy, Fiona M.;  Sponer, Nicole;  Johnson, Diana;  Laycock, Joanne;  Shafi, Seema;  Czyzewska-Khan, Justyna;  Rowan, Andrew;  Chambers, Tim;  Matthews, Nik;  Turajlic, Samra;  Hiley, Crispin;  Lee, Siow Ming;  Forster, Martin D.;  Ahmad, Tanya;  Falzon, Mary;  Borg, Elaine;  Lawrence, David;  Hayward, Martin;  Kolvekar, Shyam;  Panagiotopoulos, Nikolaos;  Janes, Sam M.;  Thakrar, Ricky;  Ahmed, Asia;  Blackhall, Fiona;  Summers, Yvonne;  Hafez, Dina;  Naik, Ashwini;  Ganguly, Apratim;  Kareht, Stephanie;  Shah, Rajesh;  Joseph, Leena;  Quinn, Anne Marie;  Crosbie, Phil A.;  Naidu, Babu;  Middleton, Gary;  Langman, Gerald;  Trotter, Simon;  Nicolson, Marianne;  Remmen, Hardy;  Kerr, Keith;  Chetty, Mahendran;  Gomersall, Lesley;  Fennell, Dean A.;  Nakas, Apostolos;  Rathinam, Sridhar;  Anand, Girija;  Khan, Sajid;  Russell, Peter;  Ezhil, Veni;  Ismail, Babikir;  Irvin-Sellers, Melanie;  Prakash, Vineet;  Lester, Jason F.;  Kornaszewska, Malgorzata;  Attanoos, Richard;  Adams, Haydn;  Davies, Helen;  Oukrif, Dahmane;  Akarca, Ayse U.;  Hartley, John A.;  Lowe, Helen L.;  Lock, Sara;  Iles, Natasha;  Bell, Harriet;  Ngai, Yenting;  Elgar, Greg;  Szallasi, Zoltan;  Schwarz, Roland F.;  Herrero, Javier;  Stewart, Aengus;  Quezada, Sergio A.;  Peggs, Karl S.;  Van Loo, Peter;  Dive, Caroline;  Lin, C. Jimmy;  Rabinowitz, Matthew;  Aerts, Hugo J. W. L.;  Hackshaw, Allan;  Shaw, Jacqui A.;  Zimmermann, Bernhard G.;  Swanton, Charles;  Jamal-Hanjani, Mariam;  Abbosh, Christopher;  Veeriah, Selvaraju;  Shafi, Seema;  Czyzewska-Khan, Justyna;  Johnson, Diana;  Laycock, Joanne;  Bosshard-Carter, Leticia;  Goh, Gerald;  Rosenthal, Rachel;  Gorman, Pat;  Murugaesu, Nirupa;  Hynds, Robert E.;  Wilson, Gareth A.;  Birkbak, Nicolai J.;  Watkins, Thomas B. K.;  McGranahan, Nicholas;  Horswell, Stuart;  Al Bakir, Maise;  Gronroos, Eva;  Mitter, Richard;  Escudero, Mickael;  Stewart, Aengus;  Van Loo, Peter;  Rowan, Andrew;  Xu, Hang;  Turajlic, Samra;  Hiley, Crispin;  Goldman, Jacki;  Stone, Richard Kevin;  Denner, Tamara;  Matthews, Nik;  Elgar, Greg;  Ward, Sophia;  Biggs, Jennifer;  Costa, Marta;  Begum, Sharmin;  Phillimore, Ben;  Chambers, Tim;  Nye, Emma;  Graca, Sofia;  Joshi, Kroopa;  Furness, Andrew;  Ben Aissa, Assma;  Wong, Yien Ning Sophia;  Georgiou, Andy;  Quezada, Sergio A.;  Peggs, Karl S.;  Hartley, John A.;  Lowe, Helen L.;  Herrero, Javier;  Lawrence, David;  Hayward, Martin;  Panagiotopoulos, Nikolaos;  Kolvekar, Shyam;  Falzon, Mary;  Borg, Elaine;  Marafioti, Teresa;  Simeon, Celia;  Hector, Gemma;  Smith, Amy;  Aranda, Marie;  Novelli, Marco;  Oukrif, Dahmane;  Akarca, Ayse U.;  Janes, Sam M.;  Thakrar, Ricky;  Forster, Martin D.;  Ahmad, Tanya;  Lee, Siow Ming;  Papadatos-Pastos, Dionysis;  Carnell, Dawn;  Mendes, Ruheena;  George, Jeremy;  Navani, Neal;  Ahmed, Asia;  Taylor, Magali;  Choudhary, Junaid;  Summers, Yvonne;  Califano, Raffaele;  Taylor, Paul;  Shah, Rajesh;  Krysiak, Piotr;  Rammohan, Kendadai;  Fontaine, Eustace;  Booton, Richard;  Evison, Matthew;  Crosbie, Phil A.;  Moss, Stuart;  Idries, Faiza;  Joseph, Leena;  Bishop, Paul;  Chaturvedi, Anshuman;  Quinn, Anne Marie;  Doran, Helen;  Leek, Angela;  Harrison, Phil;  Moore, Katrina;  Waddington, Rachael;  Novasio, Juliette;  Blackhall, Fiona;  Rogan, Jane;  Smith, Elaine;  Dive, Caroline;  Tugwood, Jonathan;  Brady, Ged;  Rothwell, Dominic G.;  Chemi, Francesca;  Pierce, Jackie;  Gulati, Sakshi;  Naidu, Babu;  Langman, Gerald;  Trotter, Simon;  Bellamy, Mary;  Bancroft, Hollie;  Kerr, Amy;  Kadiri, Salma;  Webb, Joanne;  Middleton, Gary;  Djearaman, Madava;  Fennell, Dean A.;  Shaw, Jacqui A.;  Le Quesne, John;  Moore, David A.;  Thomas, Anne;  Walter, Harriet;  Riley, Joan;  Martinson, Luke;  Nakas, Apostolos;  Rathinam, Sridhar;  Monteiro, William;  Marshall, Hilary;  Nelson, Louise;  Bennett, Jonathan;  Primrose, Lindsay;  Anand, Girija;  Khan, Sajid;  Amadi, Anita;  Nicolson, Marianne;  Kerr, Keith;  Palmer, Shirley;  Remmen, Hardy;  Miller, Joy;  Buchan, Keith;  Chetty, Mahendran;  Gomersall, Lesley;  Lester, Jason F.;  Edwards, Alison;  Morgan, Fiona;  Adams, Haydn;  Davies, Helen;  Kornaszewska, Malgorzata;  Attanoos, Richard;  Lock, Sara;  Verjee, Azmina;  MacKenzie, Mairead;  Wilcox, Maggie;  Bell, Harriet;  Iles, Natasha;  Hackshaw, Allan;  Ngai, Yenting;  Smith, Sean;  Gower, Nicole;  Ottensmeier, Christian;  Chee, Serena;  Johnson, Benjamin;  Alzetani, Aiman;  Shaw, Emily;  Lim, Eric;  De Sousa, Paulo;  Barbosa, Monica Tavares;  Bowman, Alex;  Jordan, Simon;  Rice, Alexandra;  Raubenheimer, Hilgardt;  Proli, Chiara;  Cufari, Maria Elena;  Ronquillo, John Carlo;  Kwayie, Angela;  Bhayani, Harshil;  Hamilton, Morag;  Bakar, Yusura;  Mensah, Natalie;  Ambrose, Lyn;  Devaraj, Anand;  Buderi, Silviu;  Finch, Jonathan;  Azcarate, Leire;  Chavan, Hema;  Green, Sophie;  Mashinga, Hillaria;  Nicholson, Andrew G.;  Lau, Kelvin;  Sheaff, Michael;  Schmid, Peter;  Conibear, John;  Ezhil, Veni;  Ismail, Babikir;  Irvin-Sellers, Melanie;  Prakash, Vineet;  Russell, Peter;  Light, Teresa;  Horey, Tracey;  Danson, Sarah;  Bury, Jonathan;  Edwards, John;  Hill, Jennifer;  Matthews, Sue;  Kitsanta, Yota;  Suvarna, Kim;  Fisher, Patricia;  Keerio, Allah Dino;  Shackcloth, Michael;  Gosney, John;  Postmus, Pieter;  Feeney, Sarah;  Asante-Siaw, Julius;  Constantin, Tudor;  Salari, Raheleh;  Sponer, Nicole;  Naik, Ashwini;  Zimmermann, Bernhard G.;  Rabinowitz, Matthew;  Aerts, Hugo J. W. L.;  Dentro, Stefan;  Dessimoz, Christophe
收藏  |  浏览/下载:25/0  |  提交时间:2019/04/09
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:14/0  |  提交时间:2019/04/09