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Distinct formation history for deep-mantle domains reflected in geochemical differences 期刊论文
NATURE GEOSCIENCE, 2020, 13 (7) : 511-+
作者:  Doucet, Luc S.;  Li, Zheng-Xiang;  Gamal El Dien, Hamed;  Pourteau, Amaury;  Murphy, J. Brendan;  Collins, William J.;  Mattielli, Nadine;  Olierook, Hugo K. H.;  Spencer, Christopher J.;  Mitchell, Ross N.
收藏  |  浏览/下载:6/0  |  提交时间:2020/07/06
A developmental landscape of 3D-cultured human pre-gastrulation embryos 期刊论文
NATURE, 2020, 577 (7791) : 537-+
作者:  Xiang, Lifeng;  Yin, Yu;  Zheng, Yun;  Ma, Yanping;  Li, Yonggang;  Zhao, Zhigang;  Guo, Junqiang;  Ai, Zongyong;  Niu, Yuyu;  Duan, Kui;  He, Jingjing;  Ren, Shuchao;  Wu, Dan;  Bai, Yun;  Shang, Zhouchun;  Dai, Xi;  Ji, Weizhi;  Li, Tianqing
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

Our understanding of how human embryos develop before gastrulation, including spatial self-organization and cell type ontogeny, remains limited by available two-dimensional technological platforms(1,2) that do not recapitulate the in vivo conditions(3-5). Here we report a three-dimensional (3D) blastocyst-culture system that enables human blastocyst development up to the primitive streak anlage stage. These 3D embryos mimic developmental landmarks and 3D architectures in vivo, including the embryonic disc, amnion, basement membrane, primary and primate unique secondary yolk sac, formation of anterior-posterior polarity and primitive streak anlage. Using single-cell transcriptome profiling, we delineate ontology and regulatory networks that underlie the segregation of epiblast, primitive endoderm and trophoblast. Compared with epiblasts, the amniotic epithelium shows unique and characteristic phenotypes. After implantation, specific pathways and transcription factors trigger the differentiation of cytotrophoblasts, extravillous cytotrophoblasts and syncytiotrophoblasts. Epiblasts undergo a transition to pluripotency upon implantation, and the transcriptome of these cells is maintained until the generation of the primitive streak anlage. These developmental processes are driven by different pluripotency factors. Together, findings from our 3D-culture approach help to determine the molecular and morphogenetic developmental landscape that occurs during human embryogenesis.


A 3D culture system to model human embryonic development, together with single-cell transcriptome profiling, provides insights into the molecular developmental landscape during human post-implantation embryogenesis.


  
Proton-assisted growth of ultra-flat graphene films 期刊论文
NATURE, 2020, 577 (7789) : 204-+
作者:  Yuan, Guowen;  Lin, Dongjing;  Wang, Yong;  Huang, Xianlei;  Chen, Wang;  Xie, Xuedong;  Zong, Junyu;  Yuan, Qian-Qian;  Zheng, Hang;  Wang, Di;  Xu, Jie;  Li, Shao-Chun;  Zhang, Yi;  Sun, Jian;  Xi, Xiaoxiang;  Gao, Libo
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

Graphene films grown by chemical vapour deposition have unusual physical and chemical properties that offer promise for applications such as flexible electronics and high-frequency transistors(1-10). However, wrinkles invariably form during growth because of the strong coupling to the substrate, and these limit the large-scale homogeneity of the film(1-4,11,12). Here we develop a proton-assisted method of chemical vapour deposition to grow ultra-flat graphene films that are wrinkle-free. Our method of proton penetration(13-17) and recombination to form hydrogen can also reduce the wrinkles formed during traditional chemical vapour deposition of graphene. Some of the wrinkles disappear entirely, owing to the decoupling of van der Waals interactions and possibly an increase in distance from the growth surface. The electronic band structure of the as-grown graphene films shows a V-shaped Dirac cone and a linear dispersion relation within the atomic plane or across an atomic step, confirming the decoupling from the substrate. The ultra-flat nature of the graphene films ensures that their surfaces are easy to clean after a wet transfer process. A robust quantum Hall effect appears even at room temperature in a device with a linewidth of 100 micrometres. Graphene films grown by proton-assisted chemical vapour deposition should largely retain their intrinsic performance, and our method should be easily generalizable to other nanomaterials for strain and doping engineering.


  
Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease 期刊论文
NATURE, 2020, 577 (7788) : 103-+
作者:  Lalaoui, Najoua;  Boyden, Steven E.;  Oda, Hirotsugu;  Wood, Geryl M.;  Stone, Deborah L.;  Chau, Diep;  Liu, Lin;  Stoffels, Monique;  Kratina, Tobias;  Lawlor, Kate E.;  Zaal, Kristien J. M.;  Hoffmann, Patrycja M.;  Etemadi, Nima;  Shield-Artin, Kristy;  Biben, Christine;  Tsai, Wanxia Li;  Blake, Mary D.;  Kuehn, Hye Sun;  Yang, Dan;  Anderton, Holly;  Silke, Natasha;  Wachsmuth, Laurens;  Zheng, Lixin;  Moura, Natalia Sampaio;  Beck, David B.;  Gutierrez-Cruz, Gustavo;  Ombrello, Amanda K.;  Pinto-Patarroyo, Gineth P.;  Kueh, Andrew J.;  Herold, Marco J.;  Hall, Cathrine;  Wang, Hongying;  Chae, Jae Jin;  Dmitrieva, Natalia I.;  McKenzie, Mark;  Light, Amanda;  Barham, Beverly K.;  Jones, Anne;  Romeo, Tina M.;  Zhou, Qing;  Aksentijevich, Ivona;  Mullikin, James C.;  Gross, Andrew J.;  Shum, Anthony K.;  Hawkins, Edwin D.;  Masters, Seth L.;  Lenardo, Michael J.;  Boehm, Manfred;  Rosenzweig, Sergio D.;  Pasparakis, Manolis;  Voss, Anne K.;  Gadina, Massimo;  Kastner, Daniel L.;  Silke, John
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

RIPK1 is a key regulator of innate immune signalling pathways. To ensure an optimal inflammatory response, RIPK1 is regulated post-translationally by well-characterized ubiquitylation and phosphorylation events, as well as by caspase-8-mediated cleavage1-7. The physiological relevance of this cleavage event remains unclear, although it is thought to inhibit activation of RIPK3 and necroptosis8. Here we show that the heterozygous missense mutations D324N, D324H and D324Y prevent caspase cleavage of RIPK1 in humans and result in an early-onset periodic fever syndrome and severe intermittent lymphadenopathy-a condition we term '  cleavage-resistant RIPK1-induced autoinflammatory syndrome'  . To define the mechanism for this disease, we generated a cleavage-resistant Ripk1(D325A) mutant mouse strain. Whereas Ripk1(-/-) mice died postnatally from systemic inflammation, Ripk1(D325A/D325A) mice died during embryogenesis. Embryonic lethality was completely prevented by the combined loss of Casp8 and Ripk3, but not by loss of Ripk3 or Mlkl alone. Loss of RIPK1 kinase activity also prevented Ripk1(D325A/D325A) embryonic lethality, although the mice died before weaning from multi-organ inflammation in a RIPK3-dependent manner. Consistently, Ripk1(D325A/D325A) and Ripk1(D325A/+) cells were hypersensitive to RIPK3-dependent TNF-induced apoptosis and necroptosis. Heterozygous Ripk1(D325A/+) mice were viable and grossly normal, but were hyper-responsive to inflammatory stimuli in vivo. Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase cleavage of RIPK1 not only inhibits necroptosis but also maintains inflammatory homeostasis throughout life.


  
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.


  
Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins 期刊论文
NATURE, 2020, 583 (7815) : 282-+
作者:  Li, Jia;  Yang, Xiangdong;  Liu, Yang;  Huang, Bolong;  Wu, Ruixia;  Zhang, Zhengwei;  Zhao, Bei;  Ma, Huifang;  Dang, Weiqi;  Wei, Zheng;  Wang, Kai;  Lin, Zhaoyang;  Yan, Xingxu;  Sun, Mingzi;  Li, Bo;  Pan, Xiaoqing;  Luo, Jun;  Zhang, Guangyu;  Liu, Yuan;  Huang, Yu;  Duan, Xidong;  Duan, Xiangfeng
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-2(1). This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection(2).Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manisjavanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.


  
Universal quantum logic in hot silicon qubits 期刊论文
NATURE, 2020, 580 (7803) : 355-+
作者:  Li, Jia;  Yang, Xiangdong;  Liu, Yang;  Huang, Bolong;  Wu, Ruixia;  Zhang, Zhengwei;  Zhao, Bei;  Ma, Huifang;  Dang, Weiqi;  Wei, Zheng;  Wang, Kai;  Lin, Zhaoyang;  Yan, Xingxu;  Sun, Mingzi;  Li, Bo;  Pan, Xiaoqing;  Luo, Jun;  Zhang, Guangyu;  Liu, Yuan;  Huang, Yu;  Duan, Xidong;  Duan, Xiangfeng
收藏  |  浏览/下载:40/0  |  提交时间:2020/07/03

Quantum computation requires many qubits that can be coherently controlled and coupled to each other(1). Qubits that are defined using lithographic techniques have been suggested to enable the development of scalable quantum systems because they can be implemented using semiconductor fabrication technology(2-5). However, leading solid-state approaches function only at temperatures below 100 millikelvin, where cooling power is extremely limited, and this severely affects the prospects of practical quantum computation. Recent studies of electron spins in silicon have made progress towards a platform that can be operated at higher temperatures by demonstrating long spin lifetimes(6), gate-based spin readout(7) and coherent single-spin control(8). However, a high-temperature two-qubit logic gate has not yet been demonstrated. Here we show that silicon quantum dots can have sufficient thermal robustness to enable the execution of a universal gate set at temperatures greater than one kelvin. We obtain single-qubit control via electron spin resonance and readout using Pauli spin blockade. In addition, we show individual coherent control of two qubits and measure single-qubit fidelities of up to 99.3 per cent. We demonstrate the tunability of the exchange interaction between the two spins from 0.5 to 18 megahertz and use it to execute coherent two-qubit controlled rotations. The demonstration of '  hot'  and universal quantum logic in a semiconductor platform paves the way for quantum integrated circuits that host both the quantum hardware and its control circuitry on the same chip, providing a scalable approach towards practical quantum information processing.


  
Nagaoka ferromagnetism observed in a quantum dot plaquette 期刊论文
NATURE, 2020, 579 (7800) : 528-533
作者:  Yu, Yong;  Ma, Fei;  Luo, Xi-Yu;  Jing, Bo;  Sun, Peng-Fei;  Fang, Ren-Zhou;  Yang, Chao-Wei;  Liu, Hui;  Zheng, Ming-Yang;  Xie, Xiu-Ping;  Zhang, Wei-Jun;  You, Li-Xing;  Wang, Zhen;  Chen, Teng-Yun;  Zhang, Qiang;  Bao, Xiao-Hui;  Pan, Jian-Wei
收藏  |  浏览/下载:31/0  |  提交时间:2020/07/03

A quantum dot device designed to host four electrons is used to demonstrate Nagaoka ferromagnetism-a model of itinerant magnetism that has so far been limited to theoretical investigation.


Engineered, highly controllable quantum systems are promising simulators of emergent physics beyond the simulation capabilities of classical computers(1). An important problem in many-body physics is itinerant magnetism, which originates purely from long-range interactions of free electrons and whose existence in real systems has been debated for decades(2,3). Here we use a quantum simulator consisting of a four-electron-site square plaquette of quantum dots(4) to demonstrate Nagaoka ferromagnetism(5). This form of itinerant magnetism has been rigorously studied theoretically(6-9) but has remained unattainable in experiments. We load the plaquette with three electrons and demonstrate the predicted emergence of spontaneous ferromagnetic correlations through pairwise measurements of spin. We find that the ferromagnetic ground state is remarkably robust to engineered disorder in the on-site potentials and we can induce a transition to the low-spin state by changing the plaquette topology to an open chain. This demonstration of Nagaoka ferromagnetism highlights that quantum simulators can be used to study physical phenomena that have not yet been observed in any experimental system. The work also constitutes an important step towards large-scale quantum dot simulators of correlated electron systems.