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A new sea-level record for the Neogene/Quaternary boundary reveals transition to a more stable East Antarctic Ice Sheet 期刊论文
Proceedings of the National Academy of Science, 2020
作者:  Kim A. Jakob;  Paul A. Wilson;  Jörg Pross;  Thomas H. G. Ezard;  Jens Fiebig;  Janne Repschläger;  Oliver Friedrich
收藏  |  浏览/下载:6/0  |  提交时间:2020/11/30
HBO1 is required for the maintenance of leukaemia stem cells 期刊论文
NATURE, 2020, 577 (7789) : 266-+
作者:  MacPherson, Laura;  Anokye, Juliana;  Yeung, Miriam M.;  Lam, Enid Y. N.;  Chan, Yih-Chih;  Weng, Chen-Fang;  Yeh, Paul;  Knezevic, Kathy;  Butler, Miriam S.;  Hoegl, Annabelle;  Chan, Kah-Lok;  Burr, Marian L.;  Gearing, Linden J.;  Willson, Tracy;  Liu, Joy;  Choi, Jarny;  Yang, Yuqing;  Bilardi, Rebecca A.;  Falk, Hendrik;  Nghi Nguyen;  Stupple, Paul A.;  Peat, Thomas S.;  Zhang, Ming;  de Silva, Melanie;  Carrasco-Pozo, Catalina;  Avery, Vicky M.;  Khoo, Poh Sim;  Dolezal, Olan;  Dennis, Matthew L.;  Nuttall, Stewart;  Surjadi, Regina;  Newman, Janet;  Ren, Bin;  Leaver, David J.;  Sun, Yuxin;  Baell, Jonathan B.;  Dovey, Oliver;  Vassiliou, George S.;  Grebien, Florian;  Dawson, Sarah-Jane;  Street, Ian P.;  Monahan, Brendon J.;  Burns, Christopher J.;  Choudhary, Chunaram;  Blewitt, Marnie E.;  Voss, Anne K.;  Thomas, Tim;  Dawson, Mark A.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, but most show only modest efficacy owing to an inability to effectively eradicate leukaemia stem cells (LSCs)(1). Here, to specifically identify novel dependencies in LSCs, we screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of LSCs. We identify the MYST acetyltransferase HBO1 (also known as KAT7 or MYST2) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance. Using CRISPR domain screening and quantitative mass spectrometry, we identified the histone acetyltransferase domain of HBO1 as being essential in the acetylation of histone H3 at K14. H3 acetylated at K14 (H3K14ac) facilitates the processivity of RNA polymerase II to maintain the high expression of key genes (including Hoxa9 and Hoxa10) that help to sustain the functional properties of LSCs. To leverage this dependency therapeutically, we developed a highly potent small-molecule inhibitor of HBO1 and demonstrate its mode of activity as a competitive analogue of acetyl-CoA. Inhibition of HBO1 phenocopied our genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients. These biological, structural and chemical insights into a therapeutic target in AML will enable the clinical translation of these findings.


  
Temperate rainforests near the South Pole during peak Cretaceous warmth 期刊论文
NATURE, 2020, 580 (7801) : 81-+
作者:  Johann P. Klages;  Ulrich Salzmann;  Torsten Bickert;  Claus-Dieter Hillenbrand;  Karsten Gohl;  Gerhard Kuhn;  Steven M. Bohaty;  ;  rgen Titschack;  Juliane Mü;  ller;  Thomas Frederichs;  Thorsten Bauersachs;  Werner Ehrmann;  Tina van de Flierdt;  Patric Simõ;  es Pereira;  Robert D. Larter;  Gerrit Lohmann;  Igor Niezgodzki;  Gabriele Uenzelmann-Neben;  Maximilian Zundel;  Cornelia Spiegel;  Chris Mark;  David Chew;  Jane E. Francis;  Gernot Nehrke;  Florian Schwarz;  James A. Smith;  Tim Freudenthal;  Oliver Esper;  Heiko Pä;  like;  Thomas A. Ronge;  Ricarda Dziadek
收藏  |  浏览/下载:12/0  |  提交时间:2020/05/13

The mid-Cretaceous period was one of the warmest intervals of the past 140 million years(1-5), driven by atmospheric carbon dioxide levels of around 1,000 parts per million by volume(6). In the near absence of proximal geological records from south of the Antarctic Circle, it is disputed whether polar ice could exist under such environmental conditions. Here we use a sedimentary sequence recovered from the West Antarctic shelf-the southernmost Cretaceous record reported so far-and show that a temperate lowland rainforest environment existed at a palaeolatitude of about 82 degrees S during the Turonian-Santonian age (92 to 83 million years ago). This record contains an intact 3-metre-long network of in situ fossil roots embedded in a mudstone matrix containing diverse pollen and spores. A climate model simulation shows that the reconstructed temperate climate at this high latitude requires a combination of both atmospheric carbon dioxide concentrations of 1,120-1,680 parts per million by volume and a vegetated land surface without major Antarctic glaciation, highlighting the important cooling effect exerted by ice albedo under high levels of atmospheric carbon dioxide.


  
Asynchronous carbon sink saturation in African and Amazonian tropical forests 期刊论文
NATURE, 2020, 579 (7797) : 80-+
作者:  Wannes Hubau;  Simon L. Lewis;  Oliver L. Phillips;  Kofi Affum-Baffoe;  Hans Beeckman;  Aida Cuní;  -Sanchez;  Armandu K. Daniels;  Corneille E. N. Ewango;  Sophie Fauset;  Jacques M. Mukinzi;  Douglas Sheil;  Bonaventure Sonké;  Martin J. P. Sullivan;  Terry C. H. Sunderland;  Hermann Taedoumg;  Sean C. Thomas;  Lee J. T. White;  Katharine A. Abernethy;  Stephen Adu-Bredu;  Christian A. Amani;  Timothy R. Baker;  Lindsay F. Banin;  Fidè;  le Baya;  Serge K. Begne;  Amy C. Bennett;  Fabrice Benedet;  Robert Bitariho;  Yannick E. Bocko;  Pascal Boeckx;  Patrick Boundja;  Roel J. W. Brienen;  Terry Brncic;  Eric Chezeaux;  George B. Chuyong;  Connie J. Clark;  Murray Collins;  James A. Comiskey;  David A. Coomes;  Greta C. Dargie;  Thales de Haulleville;  Marie Noel Djuikouo Kamdem;  Jean-Louis Doucet;  Adriane Esquivel-Muelbert;  Ted R. Feldpausch;  Alusine Fofanah;  Ernest G. Foli;  Martin Gilpin;  Emanuel Gloor;  Christelle Gonmadje;  Sylvie Gourlet-Fleury;  Jefferson S. Hall;  Alan C. Hamilton;  David J. Harris;  Terese B. Hart;  Mireille B. N. Hockemba;  Annette Hladik;  Suspense A. Ifo;  Kathryn J. Jeffery;  Tommaso Jucker;  Emmanuel Kasongo Yakusu;  Elizabeth Kearsley;  David Kenfack;  Alexander Koch;  Miguel E. Leal;  Aurora Levesley;  Jeremy A. Lindsell;  Janvier Lisingo;  Gabriela Lopez-Gonzalez;  Jon C. Lovett;  Jean-Remy Makana;  Yadvinder Malhi;  Andrew R. Marshall;  Jim Martin;  Emanuel H. Martin;  Faustin M. Mbayu;  Vincent P. Medjibe;  Vianet Mihindou;  Edward T. A. Mitchard;  Sam Moore;  Pantaleo K. T. Munishi;  Natacha Nssi Bengone;  Lucas Ojo;  Fidè;  le Evouna Ondo;  Kelvin S.-H. Peh;  Georgia C. Pickavance;  Axel Dalberg Poulsen;  John R. Poulsen;  Lan Qie;  Jan Reitsma;  Francesco Rovero;  Michael D. Swaine;  Joey Talbot;  James Taplin;  David M. Taylor;  Duncan W. Thomas;  Benjamin Toirambe;  John Tshibamba Mukendi;  Darlington Tuagben;  Peter M. Umunay;  Geertje M. F. van der Heijden;  Hans Verbeeck;  Jason Vleminckx;  Simon Willcock;  Hannsjö;  rg Wö;  ll;  John T. Woods;  Lise Zemagho
收藏  |  浏览/下载:23/0  |  提交时间:2020/05/13

Structurally intact tropical forests sequestered about half of the global terrestrial carbon uptake over the 1990s and early 2000s, removing about 15 per cent of anthropogenic carbon dioxide emissions(1-3). Climate-driven vegetation models typically predict that this tropical forest '  carbon sink'  will continue for decades(4,5). Here we assess trends in the carbon sink using 244 structurally intact African tropical forests spanning 11 countries, compare them with 321 published plots from Amazonia and investigate the underlying drivers of the trends. The carbon sink in live aboveground biomass in intact African tropical forests has been stable for the three decades to 2015, at 0.66 tonnes of carbon per hectare per year (95 per cent confidence interval 0.53-0.79), in contrast to the long-term decline in Amazonian forests(6). Therefore the carbon sink responses of Earth'  s two largest expanses of tropical forest have diverged. The difference is largely driven by carbon losses from tree mortality, with no detectable multi-decadal trend in Africa and a long-term increase in Amazonia. Both continents show increasing tree growth, consistent with the expected net effect of rising atmospheric carbon dioxide and air temperature(7-9). Despite the past stability of the African carbon sink, our most intensively monitored plots suggest a post-2010 increase in carbon losses, delayed compared to Amazonia, indicating asynchronous carbon sink saturation on the two continents. A statistical model including carbon dioxide, temperature, drought and forest dynamics accounts for the observed trends and indicates a long-term future decline in the African sink, whereas the Amazonian sink continues to weaken rapidly. Overall, the uptake of carbon into Earth'  s intact tropical forests peaked in the 1990s. Given that the global terrestrial carbon sink is increasing in size, independent observations indicating greater recent carbon uptake into the Northern Hemisphere landmass(10) reinforce our conclusion that the intact tropical forest carbon sink has already peaked. This saturation and ongoing decline of the tropical forest carbon sink has consequences for policies intended to stabilize Earth'  s climate.


  
Live-animal imaging of native haematopoietic stem and progenitor cells 期刊论文
NATURE, 2020, 578 (7794) : 278-+
作者:  Gerstung, Moritz;  Jolly, Clemency;  Leshchiner, Ignaty;  Dentro, Stefan C.;  Gonzalez, Santiago;  Rosebrock, Daniel;  Mitchell, Thomas J.;  Rubanova, Yulia;  Anur, Pavana;  Yu, Kaixian;  Tarabichi, Maxime;  Deshwar, Amit;  Wintersinger, Jeff;  Kleinheinz, Kortine;  Vazquez-Garcia, Ignacio;  Haase, Kerstin;  Jerman, Lara;  Sengupta, Subhajit;  Macintyre, Geoff;  Malikic, Salem;  Donmez, Nilgun;  Livitz, Dimitri G.;  Cmero, Marek;  Demeulemeester, Jonas;  Schumacher, Steven;  Fan, Yu;  Yao, Xiaotong;  Lee, Juhee;  Schlesner, Matthias;  Boutros, Paul C.;  Bowtell, David D.;  Zhu, Hongtu;  Getz, Gad;  Imielinski, Marcin;  Beroukhim, Rameen;  Sahinalp, S. Cenk;  Ji, Yuan;  Peifer, Martin;  Markowetz, Florian;  Mustonen, Ville;  Yuan, Ke;  Wang, Wenyi;  Morris, Quaid D.;  Spellman, Paul T.;  Wedge, David C.;  Van Loo, Peter;  Deshwar, Amit G.;  Adams, David J.;  Campbell, Peter J.;  Cao, Shaolong;  Christie, Elizabeth L.;  Cun, Yupeng;  Dawson, Kevin J.;  Drews, Ruben M.;  Eils, Roland;  Fittall, Matthew;  Garsed, Dale W.;  Ha, Gavin;  Lee-Six, Henry;  Martincorena, Inigo;  Oesper, Layla;  Peto, Myron;  Raphael, Benjamin J.;  Salcedo, Adriana;  Shi, Ruian;  Shin, Seung Jun;  Spiro, Oliver;  Stein, Lincoln D.;  Vembu, Shankar;  Wheeler, David A.;  Yang, Tsun-Po
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions(1,2). It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow(3-5). We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.


A dual genetic strategy enables the labelling and in vivo imaging of native long-term haematopoietic stem cells in the mouse calvarial bone marrow.


  
Signatures of self-organized criticality in an ultracold atomic gas 期刊论文
NATURE, 2020, 577 (7791) : 481-+
作者:  MacPherson, Laura;  Anokye, Juliana;  Yeung, Miriam M.;  Lam, Enid Y. N.;  Chan, Yih-Chih;  Weng, Chen-Fang;  Yeh, Paul;  Knezevic, Kathy;  Butler, Miriam S.;  Hoegl, Annabelle;  Chan, Kah-Lok;  Burr, Marian L.;  Gearing, Linden J.;  Willson, Tracy;  Liu, Joy;  Choi, Jarny;  Yang, Yuqing;  Bilardi, Rebecca A.;  Falk, Hendrik;  Nghi Nguyen;  Stupple, Paul A.;  Peat, Thomas S.;  Zhang, Ming;  De Silva, Melanie;  Carrasco-Pozo, Catalina;  Avery, Vicky M.;  Khoo, Sim;  Dolezal, Olan;  Dennis, Matthew L.;  Nuttall, Stewart;  Surjadi, Regina;  Newman, Janet;  Ren, Bin;  Leaver, David J.;  Sun, Yuxin;  Baell, Jonathan B.;  Dovey, Oliver;  Vassiliou, George S.;  Grebien, Florian;  Dawson, Sarah-Jane;  Street, Ian P.;  Monahan, Brendon J.;  Burns, Christopher J.;  Choudhary, Chunaram;  Blewitt, Marnie E.;  Voss, Anne K.;  Thomas, Tim;  Dawson, Mark A.
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

Self-organized criticality is an elegant explanation of how complex structures emerge and persist throughout nature(1), and why such structures often exhibit similar scale-invariant properties(2-9). Although self-organized criticality is sometimes captured by simple models that feature a critical point as an attractor for the dynamics(10-15), the connection to real-world systems is exceptionally hard to test quantitatively(16-21). Here we observe three key signatures of self-organized criticality in the dynamics of a driven-dissipative gas of ultracold potassium atoms: self-organization to a stationary state that is largely independent of the initial conditions  scale-invariance of the final density characterized by a unique scaling function  and large fluctuations of the number of excited atoms (avalanches) obeying a characteristic power-law distribution. This work establishes a well-controlled platform for investigating self-organization phenomena and non-equilibrium criticality, with experimental access to the underlying microscopic details of the system.


A driven-dissipative gas of ultracold potassium atoms is used to demonstrate three key signatures of self-organized criticality, and provides a system in which the phenomenon can be experimentally tested.


  
Large-scale ruminant genome sequencing provides insights into their evolution and distinct traits 期刊论文
SCIENCE, 2019, 364 (6446) : 1152-+
作者:  Chen, Lei;  Qin, Qiang;  Jiang, Yu;  Wang, Kun;  Lin, Zeshan;  Li, Zhipeng;  Bibi, Faysal;  Yang, Yongzhi;  Wang, Jinhuan;  Nie, Wenhui;  Su, Weiting;  Liu, Guichun;  Li, Qiye;  Fu, Weiwei;  Pan, Xiangyu;  Liu, Chang;  Yang, Jie;  Zhang, Chenzhou;  Yin, Yuan;  Wang, Yu;  Zhao, Yue;  Zhang, Chen;  Wang, Zhongkai;  Qin, Yanli;  Liu, Wei;  Wang, Bao;  Ren, Yandong;  Zhang, Ru;  Zeng, Yan;  da Fonseca, Rute R.;  Wei, Bin;  Li, Ran;  Wan, Wenting;  Zhao, Ruoping;  Zhu, Wenbo;  Wang, Yutao;  Duan, Shengchang;  Gao, Yun;  Zhang, Yong E.;  Chen, Chunyan;  Hvilsom, Christina;  Epps, Clinton W.;  Chemnick, Leona G.;  Doug, Yang;  Mirarab, Siavash;  Siegismund, Hans Redlef;  Ryder, Oliver A.;  Gilbert, M. Thomas P.;  Lewin, Harris A.;  Zhang, Guojie;  Heller, Rasmus;  Wang, Wen
收藏  |  浏览/下载:18/0  |  提交时间:2019/11/27
Multiproxy evidence highlights a complex evolutionary legacy of maize in South America 期刊论文
SCIENCE, 2018, 362 (6420) : 1309-+
作者:  Kistler, Logan;  Maezumi, S. Yoshi;  de Souza, Jonas Gregorio;  Przelomska, Natalia A. S.;  Costa, Flaviane Malaquias;  Smith, Oliver;  Loiselle, Hope;  Ramos-Madrigal, Jazmin;  Wales, Nathan;  Ribeiro, Eduardo Rivail;  Morrison, Ryan R.;  Grimaldo, Claudia;  Prous, Andre P.;  Arriaza, Bernardo;  Gilbert, M. Thomas P.;  Freitas, Fabio de Oliveira;  Allaby, Robin G.
收藏  |  浏览/下载:20/0  |  提交时间:2019/11/27
Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation 期刊论文
SCIENCE, 2018, 362 (6416) : 834-+
作者:  Visnes, Torkild;  Cazares-Korner, Armando;  Hao, Wenjing;  Wallner, Olov;  Masuyer, Geoffrey;  Loseva, Olga;  Mortusewicz, Oliver;  Wiita, Elisee;  Sarno, Antonio;  Manoilov, Aleksandr;  Astorga-Wells, Juan;  Jemth, Ann-Sofie;  Pan, Lang;  Sanjiv, Kumar;  Karsten, Stella;  Gokturk, Camilla;  Grube, Maurice;  Homan, Evert J.;  Hanna, Bishoy M. F.;  Paulin, Cynthia B. J.;  Pham, Therese;  Rasti, Azita;  Berglund, Ulrika Warpman;  von Nicolai, Catharina;  Benitez-Buelga, Carlos;  Koolmeister, Tobias;  Ivanic, Dag;  Iliev, Petar;  Scobie, Martin;  Krokan, Hans E.;  Baranczewski, Pawel;  Artursson, Per;  Altun, Mikael;  Jensen, Annika Jenmalm;  Kalderen, Christina;  Ba, Xueqing;  Zubarev, Roman A.;  Stenmark, Pal;  Boldogh, Istvan;  Helleday, Thomas
收藏  |  浏览/下载:7/0  |  提交时间:2019/11/27
Aircraft-based observations of isoprene-epoxydiol-derived secondary organic aerosol (IEPOX-SOA) in the tropical upper troposphere over the Amazon region 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2018, 18 (20) : 14979-15001
作者:  Schulz, Christiane;  Schneider, Johannes;  Holanda, Bruna Amorim;  Appel, Oliver;  Costa, Anja;  de Sa, Suzane S.;  Dreiling, Volker;  Fuetterer, Daniel;  Jurkat-Witschas, Tina;  Klimach, Thomas;  Knote, Christoph;  Kraemer, Martina;  Martin, Scot T.;  Mertes, Stephan;  Poehlker, Mira L.;  Sauer, Daniel;  Voigt, Christiane;  Walser, Adrian;  Weinzierl, Bernadett;  Ziereis, Helmut;  Zoeger, Martin;  Andreae, Meinrat O.;  Artaxo, Paulo;  Machado, Luiz A. T.;  Poeschl, Ulrich;  Wendisch, Manfred;  Borrmann, Stephan
收藏  |  浏览/下载:21/0  |  提交时间:2019/04/09