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Structure and mechanism of human diacylglycerol O-acyltransferase 1 期刊论文
NATURE, 2020, 581 (7808) : 329-+
作者:  Wu, Fan;  Zhao, Su;  Yu, Bin;  Chen, Yan-Mei;  Wang, Wen;  Song, Zhi-Gang;  Hu, Yi;  Tao, Zhao-Wu;  Tian, Jun-Hua;  Pei, Yuan-Yuan;  Yuan, Ming-Li;  Zhang, Yu-Ling;  Dai, Fa-Hui;  Liu, Yi;  Wang, Qi-Min;  Zheng, Jiao-Jiao;  Xu, Lin;  Holmes, Edward C.;  Zhang, Yong-Zhen
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

The structure of human diacylglycerol O-acyltransferase 1, a membrane protein that synthesizes triacylglycerides, is solved with cryo-electron microscopy, providing insight into its function and mechanism of enzymatic activity.


Diacylglycerol O-acyltransferase 1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans(1). DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins(2,3). How human DGAT1 and other mammalian members of the MBOAT family recognize their substrates and catalyse their reactions is unknown. The absence of three-dimensional structures also hampers rational targeting of DGAT1 for therapeutic purposes. Here we present the cryo-electron microscopy structure of human DGAT1 in complex with an oleoyl-CoA substrate. Each DGAT1 protomer has nine transmembrane helices, eight of which form a conserved structural fold that we name the MBOAT fold. The MBOAT fold in DGAT1 forms a hollow chamber in the membrane that encloses highly conserved catalytic residues. The chamber has separate entrances for each of the two substrates, fatty acyl-CoA and diacylglycerol. DGAT1 can exist as either a homodimer or a homotetramer and the two forms have similar enzymatic activity. The N terminus of DGAT1 interacts with the neighbouring protomer and these interactions are required for enzymatic activity.


  
The online competition between pro- and anti-vaccination views 期刊论文
NATURE, 2020, 582 (7811) : 230-+
作者:  Wu, Fan;  Zhao, Su;  Yu, Bin;  Chen, Yan-Mei;  Wang, Wen;  Song, Zhi-Gang;  Hu, Yi;  Tao, Zhao-Wu;  Tian, Jun-Hua;  Pei, Yuan-Yuan;  Yuan, Ming-Li;  Zhang, Yu-Ling;  Dai, Fa-Hui;  Liu, Yi;  Wang, Qi-Min;  Zheng, Jiao-Jiao;  Xu, Lin;  Holmes, Edward C.;  Zhang, Yong-Zhen
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.


Distrust in scientific expertise(1-14) is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks(2-4), as happened for measles in 2019(5,6). Homemade remedies(7,8) and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice(9-11). There is a lack of understanding about how this distrust evolves at the system level(13,14). Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change(11), and highlight the key role of network cluster dynamics in multi-species ecologies(15).


  
CRISPR screen in regulatory T cells reveals modulators of Foxp3 期刊论文
NATURE, 2020
作者:  Xu, Daqian;  Wang, Zheng;  Xia, Yan;  Shao, Fei;  Xia, Weiya;  Wei, Yongkun;  Li, Xinjian;  Qian, Xu;  Lee, Jong-Ho;  Du, Linyong;  Zheng, Yanhua;  Lv, Guishuai;  Leu, Jia-shiun;  Wang, Hongyang;  Xing, Dongming;  Liang, Tingbo;  Hung, Mien-Chie;  Lu, Zhimin
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

Regulatory T (T-reg) cells are required to control immune responses and maintain homeostasis, but are a significant barrier to antitumour immunity(1). Conversely, T-reg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of proinflammatory properties(2), can promote autoimmunity and/or facilitate more effective tumour immunity(3,4). A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective T-reg therapies for autoimmune disease and cancer. The availability of new functional genetic tools has enabled the possibility of systematic dissection of the gene regulatory programs that modulate Foxp3 expression. Here we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse T-reg cells and applied this technology to perform a targeted loss-of-function screen of around 500 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We identified several modulators of Foxp3 expression, including ubiquitin-specific peptidase 22 (Usp22) and ring finger protein 20 (Rnf20). Usp22, a member of the deubiquitination module of the SAGA chromatin-modifying complex, was revealed to be a positive regulator that stabilized Foxp3 expression  whereas the screen suggested that Rnf20, an E3 ubiquitin ligase, can serve as a negative regulator of Foxp3. T-reg-specific ablation of Usp22 in mice reduced Foxp3 protein levels and caused defects in their suppressive function that led to spontaneous autoimmunity but protected against tumour growth in multiple cancer models. Foxp3 destabilization in Usp22-deficient T-reg cells could be rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch in T-reg cells. These results reveal previously unknown modulators of Foxp3 and demonstrate a screening method that can be broadly applied to discover new targets for T-reg immunotherapies for cancer and autoimmune disease.


A CRISPR-based screening platform was used to identify previously uncharacterized genes that regulate the regulatory T cell-specific master transcription factor Foxp3, indicating that this screening method may be broadly applicable for the discovery of other genes involved in autoimmunity and immune responses to cancer.


  
Nanoplasma-enabled picosecond switches for ultrafast electronics (vol 579, pg 534, 2020) 期刊论文
NATURE, 2020, 580 (7803) : E8-E8
作者:  Li, Jing;  Xu, Chuanliang;  Lee, Hyung Joo;  Ren, Shancheng;  Zi, Xiaoyuan;  Zhang, Zhiming;  Wang, Haifeng;  Yu, Yongwei;  Yang, Chenghua;  Gao, Xiaofeng;  Hou, Jianguo;  Wang, Linhui;  Yang, Bo;  Yang, Qing;  Ye, Huamao;  Zhou, Tie;  Lu, Xin;  Wang, Yan;  Qu, Min;  Yang, Qingsong;  Zhang, Wenhui;  Shah, Nakul M.;  Pehrsson, Erica C.;  Wang, Shuo;  Wang, Zengjun;  Jiang, Jun;  Zhu, Yan;  Chen, Rui;  Chen, Huan;  Zhu, Feng;  Lian, Bijun;  Li, Xiaoyun;  Zhang, Yun;  Wang, Chao;  Wang, Yue;  Xiao, Guangan;  Jiang, Junfeng;  Yang, Yue;  Liang, Chaozhao;  Hou, Jianquan;  Han, Conghui;  Chen, Ming;  Jiang, Ning;  Zhang, Dahong;  Wu, Song;  Yang, Jinjian;  Wang, Tao;  Chen, Yongliang;  Cai, Jiantong;  Yang, Wenzeng;  Xu, Jun;  Wang, Shaogang;  Gao, Xu;  Wang, Ting;  Sun, Yinghao
收藏  |  浏览/下载:25/0  |  提交时间:2020/07/03
Signatures of self-organized criticality in an ultracold atomic gas (vol 577, pg 481, 2020) 期刊论文
NATURE, 2020, 579 (7800) : E13-E13
作者:  Zhou, Xiaoling;  Feng, Zongqiang;  Zhu, Linli;  Xu, Jianing;  Miyagi, Lowell;  Dong, Hongliang;  Sheng, Hongwei;  Wang, Yanju;  Li, Quan;  Ma, Yanming;  Zhang, Hengzhong;  Yan, Jinyuan;  Tamura, Nobumichi;  Kunz, Martin;  Lutker, Katie;  Huang, Tianlin;  Hughes, Darcy A.;  Huang, Xiaoxu;  Chen, Bin
收藏  |  浏览/下载:17/0  |  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.


  
Palmitoylation of NOD1 and NOD2 is required for bacterial sensing 期刊论文
SCIENCE, 2019, 366 (6464) : 460-+
作者:  Lu, Yan;  Zheng, Yuping;  Coyaud, Etienne;  Zhang, Chao;  Selvabaskaran, Apiraam;  Yu, Yuyun;  Xu, Zizhen;  Weng, Xialian;  Chen, Ji Shun;  Meng, Ying;  Warner, Neil;  Cheng, Xiawei;  Liu, Yangyang;  Yao, Bingpeng;  Hu, Hu;  Xia, Zonping;  Muise, Aleixo M.;  Klip, Amira;  Brumell, John H.;  Girardin, Stephen E.;  Ying, Songmin;  Fairn, Gregory D.;  Raught, Brian;  Sun, Qiming;  Neculai, Dante
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
Fermi-arc diversity on surface terminations of the magnetic Weyl semimetal Co3Sn2S2 期刊论文
SCIENCE, 2019, 365 (6459) : 1286-+
作者:  Morali, Noam;  Batabyal, Rajib;  Nag, Pranab Kumar;  Liu, Enke;  Xu, Qiunan;  Sun, Yan;  Yan, Binghai;  Felser, Claudia;  Avraham, Nurit;  Beidenkopf, Haim
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/27
Strongly correlated quantum walks with a 12-qubit superconducting processor 期刊论文
SCIENCE, 2019, 364 (6442) : 753-+
作者:  Yan, Zhiguang;  Zhang, Yu-Ran;  Gong, Ming;  Wu, Yulin;  Zheng, Yarui;  Li, Shaowei;  Wang, Can;  Liang, Futian;  Lin, Jin;  Xu, Yu;  Guo, Cheng;  Sun, Lihua;  Peng, Cheng-Zhi;  Xia, Keyu;  Deng, Hui;  Rong, Hao;  You, J. Q.;  Nori, Franco;  Fan, Heng;  Zhu, Xiaobo;  Pan, Jian-Wei
收藏  |  浏览/下载:16/0  |  提交时间:2019/11/27
A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex 期刊论文
NATURE, 2018, 555 (7697) : 524-+
作者:  Zhong, Suijuan;  Zhang, Shu;  Fan, Xiaoying;  Wu, Qian;  Yan, Liying;  Dong, Ji;  Zhang, Haofeng;  Li, Long;  Sun, Le;  Pan, Na;  Xu, Xiaohui;  Tang, Fuchou;  Zhang, Jun;  Qiao, Jie;  Wang, Xiaoqun
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
Long-term functional maintenance of primary human hepatocytes in vitro 期刊论文
SCIENCE, 2019, 364 (6438) : 399-+
作者:  Xiang, Chengang;  Du, Yuanyuan;  Meng, Gaofan;  Yi, Liew Soon;  Sun, Shicheng;  Song, Nan;  Zhang, Xiaonan;  Xiao, Yiwei;  Wang, Jie;  Yi, Zhigang;  Liu, Yifang;  Xie, Bingqing;  Wu, Min;  Shu, Jun;  Sun, Da;  Jia, Jun;  Liang, Zhen;  Sun, Dong;  Huang, Yanxiang;  Shi, Yan;  Xu, Jun;  Lu, Fengmin;  Li, Cheng;  Xiang, Kuanhui;  Yuan, Zhenghong;  Lu, Shichun;  Deng, Hongkui
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27