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DNA-repair enzyme turns to translation 期刊论文
NATURE, 2020, 579 (7798) : 198-199
作者:  Bian, Zhilei;  Gong, Yandong;  Huang, Tao;  Lee, Christopher Z. W.;  Bian, Lihong;  Bai, Zhijie;  Shi, Hui;  Zeng, Yang;  Liu, Chen;  He, Jian;  Zhou, Jie;  Li, Xianlong;  Li, Zongcheng;  Ni, Yanli;  Ma, Chunyu;  Cui, Lei;  Zhang, Rui;  Chan, Jerry K. Y.;  Ng, Lai Guan;  Lan, Yu;  Ginhoux, Florent;  Liu, Bing
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

A key DNA-repair enzyme has a surprising role during the early steps in the assembly of ribosomes - the molecular machines that translate the genetic code into protein.


  
A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1 期刊论文
NATURE, 2020, 577 (7788) : 109-+
作者:  Tao, Panfeng;  Sun, Jinqiao;  Wu, Zheming;  Wang, Shihao;  Wang, Jun;  Li, Wanjin;  Pan, Heling;  Bai, Renkui;  Zhang, Jiahui;  Wang, Ying;  Lee, Pui Y.;  Ying, Wenjing;  Zhou, Qinhua;  Hou, Jia;  Wang, Wenjie;  Sun, Bijun;  Yang, Mi;  Liu, Danru;  Fang, Ran;  Han, Huan;  Yang, Zhaohui;  Huang, Xin;  Li, Haibo;  Deuitch, Natalie;  Zhang, Yuan;  Dissanayake, Dilan;  Haude, Katrina;  McWalter, Kirsty;  Roadhouse, Chelsea;  MacKenzie, Jennifer J.;  Laxer, Ronald M.;  Aksentijevich, Ivona;  Yu, Xiaomin;  Wang, Xiaochuan;  Yuan, Junying;  Zhou, Qing
收藏  |  浏览/下载:21/0  |  提交时间:2020/07/03

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways(1). Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development(2,3). However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomaldominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients'  peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts.


  
The water lily genome and the early evolution of flowering plants 期刊论文
NATURE, 2020, 577 (7788) : 79-+
作者:  Zhang, Liangsheng;  Chen, Fei;  Zhang, Xingtan;  Li, Zhen;  Zhao, Yiyong;  Lohaus, Rolf;  Chang, Xiaojun;  Dong, Wei;  Ho, Simon Y. W.;  Liu, Xing;  Song, Aixia;  Chen, Junhao;  Guo, Wenlei;  Wang, Zhengjia;  Zhuang, Yingyu;  Wang, Haifeng;  Chen, Xuequn;  Hu, Juan;  Liu, Yanhui;  Qin, Yuan;  Wang, Kai;  Dong, Shanshan;  Liu, Yang;  Zhang, Shouzhou;  Yu, Xianxian;  Wu, Qian;  Wang, Liangsheng;  Yan, Xueqing;  Jiao, Yuannian;  Kong, Hongzhi;  Zhou, Xiaofan;  Yu, Cuiwei;  Chen, Yuchu;  Li, Fan;  Wang, Jihua;  Chen, Wei;  Chen, Xinlu;  Jia, Qidong;  Zhang, Chi;  Jiang, Yifan;  Zhang, Wanbo;  Liu, Guanhua;  Fu, Jianyu;  Chen, Feng;  Ma, Hong;  Van de Peer, Yves;  Tang, Haibao
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Water lilies belong to the angiosperm order Nymphaeales. Amborellales, Nymphaeales and Austrobaileyales together form the so-called ANA-grade of angiosperms, which are extant representatives of lineages that diverged the earliest from the lineage leading to the extant mesangiosperms(1-3). Here we report the 409-megabase genome sequence of the blue-petal water lily (Nymphaea colorata). Our phylogenomic analyses support Amborellales and Nymphaeales as successive sister lineages to all other extant angiosperms. The N. colorata genome and 19 other water lily transcriptomes reveal a Nymphaealean whole-genome duplication event, which is shared by Nymphaeaceae and possibly Cabombaceae. Among the genes retained from this whole-genome duplication are homologues of genes that regulate flowering transition and flower development. The broad expression of homologues of floral ABCE genes in N. colorata might support a similarly broadly active ancestral ABCE model of floral organ determination in early angiosperms. Water lilies have evolved attractive floral scents and colours, which are features shared with mesangiosperms, and we identified their putative biosynthetic genes in N. colorata. The chemical compounds and biosynthetic genes behind floral scents suggest that they have evolved in parallel to those in mesangiosperms. Because of its unique phylogenetic position, the N. colorata genome sheds light on the early evolution of angiosperms.


  
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:16/0  |  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.


  
Electrical manipulation of a topological antiferromagnetic state 期刊论文
NATURE, 2020, 580 (7805) : 608-+
作者:  Chabon, Jacob J.;  Hamilton, Emily G.;  Kurtz, David M.;  Esfahani, Mohammad S.;  Moding, Everett J.;  Stehr, Henning;  Schroers-Martin, Joseph;  Nabet, Barzin Y.;  Chen, Binbin;  Chaudhuri, Aadel A.;  Liu, Chih Long;  Hui, Angela B.;  Jin, Michael C.;  Azad, Tej D.;  Almanza, Diego;  Jeon, Young-Jun;  Nesselbush, Monica C.;  Keh, Lyron Co Ting;  Bonilla, Rene F.;  Yoo, Christopher H.;  Ko, Ryan B.;  Chen, Emily L.;  Merriott, David J.;  Massion, Pierre P.;  Mansfield, Aaron S.;  Jen, Jin;  Ren, Hong Z.;  Lin, Steven H.;  Costantino, Christina L.;  Burr, Risa;  Tibshirani, Robert;  Gambhir, Sanjiv S.;  Berry, Gerald J.;  Jensen, Kristin C.;  West, Robert B.;  Neal, Joel W.;  Wakelee, Heather A.;  Loo, Billy W., Jr.;  Kunder, Christian A.;  Leung, Ann N.;  Lui, Natalie S.;  Berry, Mark F.;  Shrager, Joseph B.;  Nair, Viswam S.;  Haber, Daniel A.;  Sequist, Lecia V.;  Alizadeh, Ash A.;  Diehn, Maximilian
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

Room-temperature electrical switching of a topological antiferromagnetic state in polycrystalline Mn3Sn thin films is demonstrated using the same protocol as that used for conventional ferromagnetic metals.


Electrical manipulation of phenomena generated by nontrivial band topology is essential for the development of next-generation technology using topological protection. A Weyl semimetal is a three-dimensional gapless system that hosts Weyl fermions as low-energy quasiparticles(1-4). It has various exotic properties, such as a large anomalous Hall effect (AHE) and chiral anomaly, which are robust owing to the topologically protected Weyl nodes(1-16). To manipulate such phenomena, a magnetic version of Weyl semimetals would be useful for controlling the locations of Weyl nodes in the Brillouin zone. Moreover, electrical manipulation of antiferromagnetic Weyl metals would facilitate the use of antiferromagnetic spintronics to realize high-density devices with ultrafast operation(17,18). However, electrical control of a Weyl metal has not yet been reported. Here we demonstrate the electrical switching of a topological antiferromagnetic state and its detection by the AHE at room temperature in a polycrystalline thin film(19) of the antiferromagnetic Weyl metal Mn3Sn9,10,12,20, which exhibits zero-field AHE. Using bilayer devices composed of Mn3Sn and nonmagnetic metals, we find that an electrical current density of about 10(10) to 10(11) amperes per square metre induces magnetic switching in the nonmagnetic metals, with a large change in Hall voltage. In addition, the current polarity along the bias field and the sign of the spin Hall angle of the nonmagnetic metals-positive for Pt (ref. (21)), close to 0 for Cu and negative for W (ref. (22))-determines the sign of the Hall voltage. Notably, the electrical switching in the antiferromagnet is achieved with the same protocol as that used for ferromagnetic metals(23,24). Our results may lead to further scientific and technological advances in topological magnetism and antiferromagnetic spintronics.


  
Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis 期刊论文
NATURE, 2020, 578 (7796) : 577-+
作者:  Bogomilov, M.;  Tsenov, R.;  Vankova-Kirilova, G.;  Song, Y. P.;  Tang, J. Y.;  Li, Z. H.;  Bertoni, R.;  Bonesini, M.;  Chignoli, F.;  Mazza, R.;  Palladino, V;  de Bari, A.;  Orestano, D.;  Tortora, L.;  Kuno, Y.;  Sakamoto, H.;  Sato, A.;  Ishimoto, S.;  Chung, M.;  Sung, C. K.;  Filthaut, F.;  Jokovic, D.;  Maletic, D.;  Savic, M.;  Jovancevic, N.;  Nikolov, J.;  Vretenar, M.;  Ramberger, S.;  Asfandiyarov, R.;  Blondel, A.;  Drielsma, F.;  Karadzhov, Y.;  Boyd, S.;  Greis, J. R.;  Lord, T.;  Pidcott, C.;  Taylor, I;  Charnley, G.;  Collomb, N.;  Dumbell, K.;  Gallagher, A.;  Grant, A.;  Griffiths, S.;  Hartnett, T.;  Martlew, B.;  Moss, A.;  Muir, A.;  Mullacrane, I;  Oates, A.;  Owens, P.;  Stokes, G.;  Warburton, P.;  White, C.;  Adams, D.;  Bayliss, V;  Boehm, J.;  Bradshaw, T. W.;  Brown, C.;  Courthold, M.;  Govans, J.;  Hills, M.;  Lagrange, J-B;  Macwaters, C.;  Nichols, A.;  Preece, R.;  Ricciardi, S.;  Rogers, C.;  Stanley, T.;  Tarrant, J.;  Tucker, M.;  Watson, S.;  Wilson, A.;  Bayes, R.;  Nugent, J. C.;  Soler, F. J. P.;  Chatzitheodoridis, G. T.;  Dick, A. J.;  Ronald, K.;  Whyte, C. G.;  Young, A. R.;  Gamet, R.;  Cooke, P.;  Blackmore, V. J.;  Colling, D.;  Dobbs, A.;  Dornan, P.;  Franchini, P.;  Hunt, C.;  Jurj, P. B.;  Kurup, A.;  Long, K.;  Martyniak, J.;  Middleton, S.;  Pasternak, J.;  Uchida, M. A.;  Cobb, J. H.;  Booth, C. N.;  Hodgson, P.;  Langlands, J.;  Overton, E.;  Pec, V;  Smith, P. J.;  Wilbur, S.;  Ellis, M.;  Gardener, R. B. S.;  Kyberd, P.;  Nebrensky, J. J.;  DeMello, A.;  Gourlay, S.;  Lambert, A.;  Li, D.;  Luo, T.;  Prestemon, S.;  Virostek, S.;  Palmer, M.;  Witte, H.;  Adey, D.;  Bross, A. D.;  Bowring, D.;  Liu, A.;  Neuffer, D.;  Popovic, M.;  Rubinov, P.;  Freemire, B.;  Hanlet, P.;  Kaplan, D. M.;  Mohayai, T. A.;  Rajaram, D.;  Snopok, P.;  Torun, Y.;  Cremaldi, L. M.;  Sanders, D. A.;  Summers, D. J.;  Coney, L. R.;  Hanson, G. G.;  Heidt, C.
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

Hydrogen peroxide (H2O2) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues(1-4). H2O2 enters cells through aquaporin membrane proteins and covalently modifies cytoplasmic proteins to regulate signalling and cellular processes. However, whether sensors for H2O2 also exist on the cell surface remains unknown. In plant cells, H2O2 triggers an influx of Ca2+ ions, which is thought to be involved in H2O2 sensing and signalling. Here, by using forward genetic screens based on Ca2+ imaging, we isolated hydrogen-peroxide-induced Ca(2+)increases (hpca) mutants in Arabidopsis, and identified HPCA1 as a leucine-rich-repeat receptor kinase belonging to a previously uncharacterized subfamily that features two extra pairs of cysteine residues in the extracellular domain. HPCA1 is localized to the plasma membrane and is activated by H2O2 via covalent modification of extracellular cysteine residues, which leads to autophosphorylation of HPCA1. HPCA1 mediates H2O2-induced activation of Ca2+ channels in guard cells and is required for stomatal closure. Our findings help to identify how the perception of extracellular H2O2 is integrated with responses to various external stresses and internal cues in plants, and have implications for the design of crops with enhanced fitness.


HPCA1, a member of a previously uncharacterized subfamily of leucine-rich-repeat receptor-like kinases, is the hydrogen-peroxide sensor at the plasma membrane in Arabidopsis.


  
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.


  
B cells and tertiary lymphoid structures promote immunotherapy response 期刊论文
NATURE, 2020, 577 (7791) : 549-+
作者:  Zhang, Liangsheng;  Chen, Fei;  Zhang, Xingtan;  Li, Zhen;  Zhao, Yiyong;  Lohaus, Rolf;  Chang, Xiaojun;  Dong, Wei;  Ho, Simon Y. W.;  Liu, Xing;  Song, Aixia;  Chen, Junhao;  Guo, Wenlei;  Wang, Zhengjia;  Zhuang, Yingyu;  Wang, Haifeng;  Chen, Xuequn;  Hu, Juan;  Liu, Yanhui;  Qin, Yuan;  Wang, Kai;  Dong, Shanshan;  Liu, Yang;  Zhang, Shouzhou;  Yu, Xianxian;  Wu, Qian;  Wang, Liangsheng;  Yan, Xueqing;  Jiao, Yuannian;  Kong, Hongzhi;  Zhou, Xiaofan;  Yu, Cuiwei;  Chen, Yuchu;  Li, Fan;  Wang, Jihua;  Chen, Wei;  Chen, Xinlu;  Jia, Qidong;  Zhang, Chi;  Jiang, Yifan;  Zhang, Wanbo;  Liu, Guanhua;  Fu, Jianyu;  Chen, Feng;  Ma, Hong;  Van de Peer, Yves;  Tang, Haibao
收藏  |  浏览/下载:41/0  |  提交时间:2020/07/03

Multiomic profiling of several cohorts of patients treated with immune checkpoint blockade highlights the presence and potential role of B cells and tertiary lymphoid structures in promoting therapy response.


Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers(1-10) and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity(11-15), although these have been less well-studied in ICB treatment(16). A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling(17) that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter(18)) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.


  
The evolutionary history of 2,658 cancers 期刊论文
NATURE, 2020, 578 (7793) : 122-+
作者:  Tao, Panfeng;  Sun, Jinqiao;  Wu, Zheming;  Wang, Shihao;  Wang, Jun;  Li, Wanjin;  Pan, Heling;  Bai, Renkui;  Zhang, Jiahui;  Wang, Ying;  Lee, Pui Y.;  Ying, Wenjing;  Zhou, Qinhua;  Hou, Jia;  Wang, Wenjie;  Sun, Bijun;  Yang, Mi;  Liu, Danru;  Fang, Ran;  Han, Huan;  Yang, Zhaohui;  Huang, Xin;  Li, Haibo;  Deuitch, Natalie;  Zhang, Yuan;  Dissanayake, Dilan;  Haude, Katrina;  McWalter, Kirsty;  Roadhouse, Chelsea;  MacKenzie, Jennifer J.;  Laxer, Ronald M.;  Aksentijevich, Ivona;  Yu, Xiaomin;  Wang, Xiaochuan;  Yuan, Junying;  Zhou, Qing
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

Cancer develops through a process of somatic evolution(1,2). Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes(3). Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)(4), we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.


  
Metabolic regulation of gene expression by histone lactylation 期刊论文
NATURE, 2019, 574 (7779) : 575-+
作者:  Zhang, Di;  Tang, Zhanyun;  Huang, He;  Zhou, Guolin;  Cui, Chang;  Weng, Yejing;  Liu, Wenchao;  Kim, Sunjoo;  Lee, Sangkyu;  Perez-Neut, Mathew;  Ding, Jun;  Czyz, Daniel;  Hu, Rong;  Ye, Zhen;  He, Maomao;  Zheng, Y. George;  Shuman, Howard A.;  Dai, Lunzhi;  Ren, Bing;  Roeder, Robert G.;  Becker, Lev;  Zhao, Yingming
收藏  |  浏览/下载:28/0  |  提交时间:2019/11/27