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Carbenium ion-mediated oligomerization of methylglyoxal for secondary organic aerosol formation 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (24) : 13294-13299
作者:  Ji, Yuemen;  Shi, Qiuju;  Li, Yixin;  An, Taicheng;  Zheng, Jun;  Peng, Jianfei;  Gao, Yanpeng;  Chen, Jiangyao;  Li, Guiying;  Wang, Yuan;  Zhang, Fang;  Zhang, Annie L.;  Zhao, Jiayun;  Molina, Mario J.;  Zhang, Renyi
收藏  |  浏览/下载:15/0  |  提交时间:2020/06/09
secondary organic aerosol  aqueous  oligomerization  brown carbon  cationic  
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:23/0  |  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.


  
Localization and delocalization of light in photonic moire lattices 期刊论文
NATURE, 2020, 577 (7788) : 42-+
作者:  Wang, Peng;  Zheng, Yuanlin;  Chen, Xianfeng;  Huang, Changming;  Kartashov, Yaroslav V.;  Torner, Lluis;  Konotop, Vladimir V.;  Ye, Fangwei
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Moire lattices consist of two superimposed identical periodic structures with a relative rotation angle. Moire lattices have several applications in everyday life, including artistic design, the textile industry, architecture, image processing, metrology and interferometry. For scientific studies, they have been produced using coupled graphene-hexagonal boron nitride monolayers(1,2), graphene-graphene layers(3,4) and graphene quasicrystals on a silicon carbide surface(5). The recent surge of interest in moire lattices arises from the possibility of exploring many salient physical phenomena in such systems  examples include commensurable-incommensurable transitions and topological defects(2), the emergence of insulating states owing to band flattening(3,6), unconventional superconductivity(4) controlled by the rotation angle(7,8), the quantum Hall effect(9), the realization of non-Abelian gauge potentials(10) and the appearance of quasicrystals at special rotation angles(11). A fundamental question that remains unexplored concerns the evolution of waves in the potentials defined by moire lattices. Here we experimentally create two-dimensional photonic moire lattices, which-unlike their material counterparts-have readily controllable parameters and symmetry, allowing us to explore transitions between structures with fundamentally different geometries (periodic, general aperiodic and quasicrystal). We observe localization of light in deterministic linear lattices that is based on flatband physics(6), in contrast to previous schemes based on light diffusion in optical quasicrystals(12), where disorder is required(13) for the onset of Anderson localization(14) (that is, wave localization in random media). Using commensurable and incommensurable moire patterns, we experimentally demonstrate the twodimensional localization-delocalization transition of light. Moire lattices may feature an almost arbitrary geometry that is consistent with the crystallographic symmetry groups of the sublattices, and therefore afford a powerful tool for controlling the properties of light patterns and exploring the physics of periodic-aperiodic phase transitions and two-dimensional wavepacket phenomena relevant to several areas of science, including optics, acoustics, condensed matter and atomic physics.


  
A neurotransmitter produced by gut bacteria modulates host sensory behaviour 期刊论文
NATURE, 2020
作者:  Zhao, Xiaoxu;  Song, Peng;  Wang, Chengcai;  Riis-Jensen, Anders C.;  Fu, Wei;  Deng, Ya;  Wan, Dongyang;  Kang, Lixing;  Ning, Shoucong;  Dan, Jiadong;  Venkatesan, T.;  Liu, Zheng;  Zhou, Wu;  Thygesen, Kristian S.;  Luo, Xin;  Pennycook, Stephen J.;  Loh, Kian Ping
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

A neuromodulator produced by commensalProvidenciabacteria that colonize the gut ofCaenorhabditis elegansmimics the functions of the cognate host molecule to manipulate a sensory decision of the host.


Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms(1). Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts(2,3). However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that inCaenorhabditis elegans, the neuromodulator tyramine produced by commensalProvidenciabacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine beta-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis inProvidencia, and show that these genes are necessary for the modulation of host behaviour. We further find thatC. eleganscolonized byProvidenciapreferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.


  
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.


  
Variability in the analysis of a single neuroimaging dataset by many teams 期刊论文
NATURE, 2020
作者:  Liu, Jifeng;  Soria, Roberto;  Zheng, Zheng;  Zhang, Haotong;  Lu, Youjun;  Wang, Song;  Yuan, Hailong
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.


The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.


  
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.