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Revealing enigmatic mucus structures in the deep sea using DeepPIV 期刊论文
NATURE, 2020, 583 (7814) : 78-+
作者:  Nguyen, Ngoc Uyen Nhi;  Canseco, Diana C.;  Xiao, Feng;  Nakada, Yuji;  Li, Shujuan;  Lam, Nicholas T.;  Muralidhar, Shalini A.;  Savla, Jainy J.;  Hill, Joseph A.;  Le, Victor;  Zidan, Kareem A.;  El-Feky, Hamed W.;  Wang, Zhaoning;  Ahmed, Mahmoud Salama;  Hubbi, Maimon E.;  Menendez-Montes, Ivan
收藏  |  浏览/下载:13/0  |  提交时间:2020/06/09

Advanced deep-sea imaging tools yield insights into the structure and function of mucus filtration houses built by midwater giant larvaceans.


Many animals build complex structures to aid in their survival, but very few are built exclusively from materials that animals create (1,2). In the midwaters of the ocean, mucoid structures are readily secreted by numerous animals, and serve many vital functions(3,4). However, little is known about these mucoid structures owing to the challenges of observing them in the deep sea. Among these mucoid forms, the '  houses'  of larvaceans are marvels of nature(5), and in the ocean twilight zone giant larvaceans secrete and build mucus filtering structures that can reach diameters of more than 1 m(6). Here we describe in situ laser-imaging technology(7) that reconstructs three-dimensional models of mucus forms. The models provide high-resolution views of giant larvacean houses and elucidate the role that house structure has in food capture and predator avoidance. Now that tools exist to study mucus structures found throughout the ocean, we can shed light on some of nature'  s most complex forms.


  
Impaired cell fate through gain-of-function mutations in a chromatin reader 期刊论文
NATURE, 2020, 577 (7788) : 121-+
作者:  Wan, Liling;  Chong, Shasha;  Xuan, Fan;  Liang, Angela;  Cui, Xiaodong;  Gates, Leah;  Carroll, Thomas S.;  Li, Yuanyuan;  Feng, Lijuan;  Chen, Guochao;  Wang, Shu-Ping;  Ortiz, Michael V.;  Daley, Sara K.;  Wang, Xiaolu;  Xuan, Hongwen;  Kentsis, Alex;  Muir, Tom W.;  Roeder, Robert G.;  Li, Haitao;  Li, Wei;  Tjian, Robert;  Wen, Hong;  Allis, C. David
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by '  reader'  proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatinreader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.


  
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.


  
IGF1R is an entry receptor for respiratory syncytial virus (vol 53, pg 861, 2020) 期刊论文
NATURE, 2020, 583 (7815) : E22-E22
作者:  Smith, Jacob A.;  Wilson, Katy B.;  Sonstrom, Reilly E.;  Kelleher, Patrick J.;  Welch, Kevin D.;  Pert, Emmit K.;  Westendorff, Karl S.;  Dickie, Diane A.;  Wang, Xiaoping;  Pate, Brooks H.;  Harman, W. Dean
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


  
Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation throughS-palmitoylation (vol 573, pg 139, 2019) (Retraction of Vol 573, Pg 139, 2020) 期刊论文
NATURE, 2020, 583 (7814) : 154-154
作者:  Zhang, Hao;  Liu, Chun-Xiao;  Gazibegovic, Sasa;  Xu, Di;  Logan, John A.;  Wang, Guanzhong;  van Loo, Nick;  Bommer, Jouri D. S.;  de Moor, Michiel W. A.;  Car, Diana;  Op Het Veld, Roy L. M.;  van Veldhoven, Petrus J.;  Koelling, Sebastian;  Verheijen, Marcel A.;  Pendharkar, Mihir;  Pennachio, Daniel J.;  Shojaei, Borzoyeh;  Lee, Joon Sue;  Palmstrom, Chris J.;  Bakkers, Erik P. A. M.;  Sarma, S. Das;  Kouwenhoven, Leo P.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03
The fate of carbon in a mature forest under carbon dioxide enrichment 期刊论文
NATURE, 2020, 580 (7802) : 227-+
作者:  Sun, P. Z.;  Yang, Q.;  Kuang, W. J.;  Stebunov, Y. V.;  Xiong, W. Q.;  Yu, J.;  Nair, R. R.;  Katsnelson, M. I.;  Yuan, S. J.;  Grigorieva, I. V.;  Lozada-Hidalgo, M.;  Wang, F. C.;  Geim, A. K.
收藏  |  浏览/下载:70/0  |  提交时间:2020/05/13

Carbon dioxide enrichment of a mature forest resulted in the emission of the excess carbon back into the atmosphere via enhanced ecosystem respiration, suggesting that mature forests may be limited in their capacity to mitigate climate change.


Atmospheric carbon dioxide enrichment (eCO(2)) can enhance plant carbon uptake and growth(1-5), thereby providing an important negative feedback to climate change by slowing the rate of increase of the atmospheric CO2 concentration(6). Although evidence gathered from young aggrading forests has generally indicated a strong CO2 fertilization effect on biomass growth(3-5), it is unclear whether mature forests respond to eCO(2) in a similar way. In mature trees and forest stands(7-10), photosynthetic uptake has been found to increase under eCO(2) without any apparent accompanying growth response, leaving the fate of additional carbon fixed under eCO(2) unclear(4,5,7-11). Here using data from the first ecosystem-scale Free-Air CO2 Enrichment (FACE) experiment in a mature forest, we constructed a comprehensive ecosystem carbon budget to track the fate of carbon as the forest responded to four years of eCO(2) exposure. We show that, although the eCO(2) treatment of +150 parts per million (+38 per cent) above ambient levels induced a 12 per cent (+247 grams of carbon per square metre per year) increase in carbon uptake through gross primary production, this additional carbon uptake did not lead to increased carbon sequestration at the ecosystem level. Instead, the majority of the extra carbon was emitted back into the atmosphere via several respiratory fluxes, with increased soil respiration alone accounting for half of the total uptake surplus. Our results call into question the predominant thinking that the capacity of forests to act as carbon sinks will be generally enhanced under eCO(2), and challenge the efficacy of climate mitigation strategies that rely on ubiquitous CO2 fertilization as a driver of increased carbon sinks in global forests.


  
The projected timing of abrupt ecological disruption from climate change 期刊论文
NATURE, 2020, 580 (7804) : 496-+
作者:  Gorgulla, Christoph;  Boeszoermenyi, Andras;  Wang, Zi-Fu;  Fischer, Patrick D.;  Coote, Paul W.;  Padmanabha Das, Krishna M.;  Malets, Yehor S.;  Radchenko, Dmytro S.;  Moroz, Yurii S.;  Scott, David A.;  Fackeldey, Konstantin;  Hoffmann, Moritz;  Iavniuk, Iryna;  Wagner, Gerhard;  Arthanari, Haribabu
收藏  |  浏览/下载:55/0  |  提交时间:2020/05/13

As anthropogenic climate change continues the risks to biodiversity will increase over time, with future projections indicating that a potentially catastrophic loss of global biodiversity is on the horizon(1-3). However, our understanding of when and how abruptly this climate-driven disruption of biodiversity will occur is limited because biodiversity forecasts typically focus on individual snapshots of the future. Here we use annual projections (from 1850 to 2100) of temperature and precipitation across the ranges of more than 30,000 marine and terrestrial species to estimate the timing of their exposure to potentially dangerous climate conditions. We project that future disruption of ecological assemblages as a result of climate change will be abrupt, because within any given ecological assemblage the exposure of most species to climate conditions beyond their realized niche limits occurs almost simultaneously. Under a high-emissions scenario (representative concentration pathway (RCP) 8.5), such abrupt exposure events begin before 2030 in tropical oceans and spread to tropical forests and higher latitudes by 2050. If global warming is kept below 2 degrees C, less than 2% of assemblages globally are projected to undergo abrupt exposure events of more than 20% of their constituent species  however, the risk accelerates with the magnitude of warming, threatening 15% of assemblages at 4 degrees C, with similar levels of risk in protected and unprotected areas. These results highlight the impending risk of sudden and severe biodiversity losses from climate change and provide a framework for predicting both when and where these events may occur.


Using annual projections of temperature and precipitation to estimate when species will be exposed to potentially harmful climate conditions reveals that disruption of ecological assemblages as a result of climate change will be abrupt and could start as early as the current decade.


  
Securin-independent regulation of separase by checkpoint-induced shugoshin-MAD2 期刊论文
NATURE, 2020, 580 (7804) : 536-+
作者:  Redhai, Siamak;  Pilgrim, Clare;  Gaspar, Pedro;  van Giesen, Lena;  Lopes, Tatiana;  Riabinina, Olena;  Grenier, Theodore;  Milona, Alexandra;  Chanana, Bhavna;  Swadling, Jacob B.;  Wang, Yi-Fang;  Dahalan, Farah;  Yuan, Michaela;  Wilsch-Brauninger, Michaela;  Lin, Wei-hsiang;  Dennison, Nathan;  Capriotti, Paolo;  Lawniczak, Mara K. N.;  Baines, Richard A.;  Warnecke, Tobias;  Windbichler, Nikolai;  Leulier, Francois;  Bellono, Nicholas W.;  Miguel-Aliaga, Irene
收藏  |  浏览/下载:32/0  |  提交时间:2020/07/03

Shugoshin and MAD2 regulate separase-mediated chromosome separation during mitosis, in parallel to a previously identified mechanism involving the anaphase inhibitor securin.


Separation of eukaryotic sister chromatids during the cell cycle is timed by the spindle assembly checkpoint (SAC) and ultimately triggered when separase cleaves cohesion-mediating cohesin(1-3). Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin(1). In the absence of securin, mammalian chromosomes still segregate on schedule, but it is unclear how separase is regulated under these conditions(4,5). Here we show that human shugoshin 2 (SGO2), an essential protector of meiotic cohesin with unknown functions in the soma(6,7), is turned into a separase inhibitor upon association with SAC-activated MAD2. SGO2-MAD2 can functionally replace securin and sequesters most separase in securin-knockout cells. Acute loss of securin and SGO2, but not of either protein individually, resulted in separase deregulation associated with premature cohesin cleavage and cytotoxicity. Similar to securin(8,9), SGO2 is a competitive inhibitor that uses a pseudo-substrate sequence to block the active site of separase. APC/C-dependent ubiquitylation and action of the AAA-ATPase TRIP13 in conjunction with the MAD2-specific adaptor p31(comet) liberate separase from SGO2-MAD2 in vitro. The latter mechanism facilitates a considerable degree of sister chromatid separation in securin-knockout cells that lack APC/C activity. Thus, our results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC.


  
A conserved dendritic-cell regulatory program limits antitumour immunity 期刊论文
NATURE, 2020, 580 (7802) : 257-+
作者:  Perry, Rachel J.;  Zhang, Dongyan;  Guerra, Mateus T.;  Brill, Allison L.;  Goedeke, Leigh;  Nasiri, Ali R.;  Rabin-Court, Aviva;  Wang, Yongliang;  Peng, Liang;  Dufour, Sylvie;  Zhang, Ye;  Zhang, Xian-Man;  Butrico, Gina M.;  Toussaint, Keshia;  Nozaki, Yuichi;  Cline, Gary W.;  Petersen, Kitt Falk;  Nathanson, Michael H.;  Ehrlich, Barbara E.;  Shulman, Gerald I.
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

After taking up tumour-associated antigens, dendritic cells in mouse and human tumours upregulate a regulatory gene program that limits dendritic cell immunostimulatory function, and modulating this program can rescue antitumor immunity in mice.


Checkpoint blockade therapies have improved cancer treatment, but such immunotherapy regimens fail in a large subset of patients. Conventional type 1 dendritic cells (DC1s) control the response to checkpoint blockade in preclinical models and are associated with better overall survival in patients with cancer, reflecting the specialized ability of these cells to prime the responses of CD8(+) T cells(1-3). Paradoxically, however, DC1s can be found in tumours that resist checkpoint blockade, suggesting that the functions of these cells may be altered in some lesions. Here, using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, we identify a cluster of dendritic cells (DCs) that we name '  mature DCs enriched in immunoregulatory molecules'  (mregDCs), owing to their coexpression of immunoregulatory genes (Cd274, Pdcd1lg2 and Cd200) and maturation genes (Cd40, Ccr7 and Il12b). We find that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumour antigens. We further find that upregulation of the programmed death ligand 1 protein-a key checkpoint molecule-in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin (IL)-12 depends strictly on interferon-gamma and is controlled negatively by IL-4 signalling. Blocking IL-4 enhances IL-12 production by tumour-antigen-bearing mregDC1s, expands the pool of tumour-infiltrating effector T cells and reduces tumour burden. We have therefore uncovered a regulatory module associated with tumour-antigen uptake that reduces DC1 functionality in human and mouse cancers.


  
U1 snRNP regulates chromatin retention of noncoding RNAs 期刊论文
NATURE, 2020
作者:  Dehollain, J. P.;  Mukhopadhyay, U.;  Michal, V. P.;  Wang, Y.;  Wunsch, B.;  Reichl, C.;  Wegscheider, W.;  Rudner, M. S.;  Demler, E.;  Vandersypen, L. M. K.
收藏  |  浏览/下载:23/0  |  提交时间:2020/07/03

Long noncoding RNAs (lncRNAs) and promoter- or enhancer-associated unstable transcripts locate preferentially to chromatin, where some regulate chromatin structure, transcription and RNA processing(1-13). Although several RNA sequences responsible for nuclear localization have been identified-such as repeats in the lncRNA Xist and Alu-like elements in long RNAs14-16-how lncRNAs as a class are enriched at chromatin remains unknown. Here we describe a random, mutagenesis-coupled, high-throughput method that we name '  RNA elements for subcellular localization by sequencing'  (mutREL-seq). Using this method, we discovered an RNA motif that recognizes the U1 small nuclear ribonucleoprotein (snRNP) and is essential for the localization of reporter RNAs to chromatin. Across the genome, chromatin-bound lncRNAs are enriched with 5 '  splice sites and depleted of 3 '  splice sites, and exhibit high levels of U1 snRNA binding compared with cytoplasm-localized messenger RNAs. Acute depletion of U1 snRNA or of the U1 snRNP protein component SNRNP70 markedly reduces the chromatin association of hundreds of lncRNAs and unstable transcripts, without altering the overall transcription rate in cells. In addition, rapid degradation of SNRNP70 reduces the localization of both nascent and polyadenylated lncRNA transcripts to chromatin, and disrupts the nuclear and genome-wide localization of the lncRNA Malat1. Moreover, U1 snRNP interacts with transcriptionally engaged RNA polymerase II. These results show that U1 snRNP acts widely to tether and mobilize lncRNAs to chromatin in a transcription-dependent manner. Our findings have uncovered a previously unknown role of U1 snRNP beyond the processing of precursor mRNA, and provide molecular insight into how lncRNAs are recruited to regulatory sites to carry out chromatin-associated functions.


Long noncoding RNAs and certain unstable transcripts tend to localize to chromatin, in a process that is shown here to depend on an RNA motif that recognizes the small nuclear ribonuclear protein U1, and to rely on transcription.