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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.


  
Injured adult neurons regress to an embryonic transcriptional growth state 期刊论文
NATURE, 2020, 581 (7806) : 77-+
作者:  Wang, Ruicong;  Li, Hongda;  Wu, Jianfeng;  Cai, Zhi-Yu;  Li, Baizhou;  Ni, Hengxiao;  Qiu, Xingfeng;  Chen, Hui;  Liu, Wei;  Yang, Zhang-Hua;  Liu, Min;  Hu, Jin;  Liang, Yaoji;  Lan, Ping;  Han, Jiahuai;  Mo, Wei
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

Grafts of spinal-cord-derived neural progenitor cells (NPCs) enable the robust regeneration of corticospinal axons and restore forelimb function after spinal cord injury(1)  however, the molecular mechanisms that underlie this regeneration are unknown. Here we perform translational profiling specifically of corticospinal tract (CST) motor neurons in mice, to identify their '  regenerative transcriptome'  after spinal cord injury and NPC grafting. Notably, both injury alone and injury combined with NPC grafts elicit virtually identical early transcriptomic responses in host CST neurons. However, in mice with injury alone this regenerative transcriptome is downregulated after two weeks, whereas in NPC-grafted mice this transcriptome is sustained. The regenerative transcriptome represents a reversion to an embryonic transcriptional state of the CST neuron. The huntingtin gene (Htt) is a central hub in the regeneration transcriptome  deletion of Htt significantly attenuates regeneration, which shows that Htt has a key role in neural plasticity after injury.


In mouse models of central nervous system injury, Htt is shown to be a key component of the regulatory program associated with reversion of the neuronal transcriptome to a less-mature state.


  
Electromechanical coupling in the hyperpolarization-activated K+ channel KAT1 期刊论文
NATURE, 2020, 583 (7814) : 145-+
作者:  Jin, Zhenming;  Du, Xiaoyu;  Xu, Yechun;  Deng, Yongqiang;  Liu, Meiqin;  Zhao, Yao;  Zhang, Bing;  Li, Xiaofeng;  Zhang, Leike;  Peng, Chao;  Duan, Yinkai;  Yu, Jing;  Wang, Lin;  Yang, Kailin;  Liu, Fengjiang;  Jiang, Rendi;  Yang, Xinglou;  You, Tian;  Liu, Xiaoce
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

Voltage-gated potassium (K-v) channels coordinate electrical signalling and control cell volume by gating in response to membrane depolarization or hyperpolarization. However, although voltage-sensing domains transduce transmembrane electric field changes by a common mechanism involving the outward or inward translocation of gating charges(1-3), the general determinants of channel gating polarity remain poorly understood(4). Here we suggest a molecular mechanism for electromechanical coupling and gating polarity in non-domain-swapped K-v channels on the basis of the cryo-electron microscopy structure of KAT1, the hyperpolarization-activated K-v channel from Arabidopsis thaliana. KAT1 displays a depolarized voltage sensor, which interacts with a closed pore domain directly via two interfaces and indirectly via an intercalated phospholipid. Functional evaluation of KAT1 structure-guided mutants at the sensor-pore interfaces suggests a mechanism in which direct interaction between the sensor and the C-linker hairpin in the adjacent pore subunit is the primary determinant of gating polarity. We suggest that an inward motion of the S4 sensor helix of approximately 5-7 angstrom can underlie a direct-coupling mechanism, driving a conformational reorientation of the C-linker and ultimately opening the activation gate formed by the S6 intracellular bundle. This direct-coupling mechanism contrasts with allosteric mechanisms proposed for hyperpolarization-activated cyclic nucleotide-gated channels(5), and may represent an unexpected link between depolarization- and hyperpolarization-activated channels.


The cryo-electron microscopy structure of the hyperpolarization-activated K+ channel KAT1 points to a direct-coupling mechanism between S4 movement and the reorientation of the C-linker.


  
Half-precessional cycle of thermocline temperature in the western equatorial Pacific and its bihemispheric dynamics 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (13) : 7044-7051
作者:  Jian, Zhimin;  Wang, Yue;  Dang, Haowen;  Lea, David W.;  Liu, Zhengyu;  Jin, Haiyan;  Yin, Yaqian
收藏  |  浏览/下载:6/0  |  提交时间:2020/05/13
thermocline temperature  half-precession  western equatorial Pacific  meridional gradient  
Extreme weather events recorded by daily to hourly resolution biogeochemical proxies of marine giant clam shells 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (13) : 7038-7043
作者:  Yan, Hong;  Liu, Chengcheng;  An, Zhisheng;  Yang, Wei;  Yang, Yuanjian;  Huang, Ping;  Qiu, Shican;  Zhou, Pengchao;  Zhao, Nanyu;  Fei, Haobai;  Ma, Xiaolin;  Shi, Ge;  Dodson, John;  Hao, Jialong;  Yu, Kefu;  Wei, Gangjian;  Yang, Yanan;  Jin, Zhangdong;  Zhou, Weijian
收藏  |  浏览/下载:14/0  |  提交时间:2020/05/13
Tridacna shell  daily growth bands  ultra-high resolution  biogeochemical proxies  weather-timescale extreme events  
The gut-brain axis mediates sugar preference 期刊论文
NATURE, 2020, 580 (7804) : 511-+
作者:  Wang, Ruicong;  Li, Hongda;  Wu, Jianfeng;  Cai, Zhi-Yu;  Li, Baizhou;  Ni, Hengxiao;  Qiu, Xingfeng;  Chen, Hui;  Liu, Wei;  Yang, Zhang-Hua;  Liu, Min;  Hu, Jin;  Liang, Yaoji;  Lan, Ping;  Han, Jiahuai;  Mo, Wei
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

The taste of sugar is one of the most basic sensory percepts for humans and other animals. Animals can develop a strong preference for sugar even if they lack sweet taste receptors, indicating a mechanism independent of taste(1-3). Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the vagal ganglia and brainstem are activated via the gut-brain axis to create preference for sugar. These neurons are stimulated in response to sugar but not artificial sweeteners, and are activated by direct delivery of sugar to the gut. Using functional imaging we monitored activity of the gut-brain axis, and identified the vagal neurons activated by intestinal delivery of glucose. Next, we engineered mice in which synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of behavioural preference for sugar. Moreover, we show that co-opting this circuit by chemogenetic activation can create preferences to otherwise less-preferred stimuli. Together, these findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. In addition, they explain the neural basis for differences in the behavioural effects of sweeteners versus sugar, and uncover an essential circuit underlying the highly appetitive effects of sugar.


Experiments in mice show that a population of neurons in the vagal ganglia respond to the presence of glucose in the gut and connect to neurons in the brainstem, revealing the circuit that underlies the neural basis for the behavioural preference for sugar.


  
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.


  
High thermoelectric performance in low-cost SnS0.91Se0.09 crystals 期刊论文
SCIENCE, 2019, 365 (6460) : 1418-+
作者:  He, Wenke;  Wang, Dongyang;  Wu, Haijun;  Xiao, Yu;  Zhang, Yang;  He, Dongsheng;  Feng, Yue;  Hao, Yu-Jie;  Dong, Jin-Feng;  Chetty, Raju;  Hao, Lijie;  Chen, Dongfeng;  Qin, Jianfei;  Yang, Qiang;  Li, Xin;  Song, Jian-Ming;  Zhu, Yingcai;  Xu, Wei;  Niu, Changlei;  Li, Xin;  Wang, Guangtao;  Liu, Chang;  Ohta, Michibiro;  Pennycook, Stephen J.;  He, Jiaqing;  Li, Jing-Feng;  Zhao, Li-Dong
收藏  |  浏览/下载:22/0  |  提交时间:2019/11/27
Resetting histone modifications during human parental-to-zygotic transition 期刊论文
SCIENCE, 2019, 365 (6451) : 353-+
作者:  Xia, Weikun;  Xu, Jiawei;  Yu, Guang;  Yao, Guidong;  Xu, Kai;  Ma, Xueshan;  Zhang, Nan;  Liu, Bofeng;  Li, Tong;  Lin, Zili;  Chen, Xia;  Li, Lijia;  Wang, Qiujun;  Shi, Dayuan;  Shi, Senlin;  Zhang, Yile;  Song, Wenyan;  Jin, Haixia;  Hu, Linli;  Bu, Zhiqin;  Wang, Yang;  Na, Jie;  Xie, Wei;  Sun, Ying-Pu
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27
Impacts of species richness on productivity in a large-scale subtropical forest experiment 期刊论文
SCIENCE, 2018, 362 (6410) : 80-+
作者:  Huang, Yuanyuan;  Chen, Yuxin;  Castro-Izaguirre, Nadia;  Baruffol, Martin;  Brezzi, Matteo;  Lang, Anne;  Li, Ying;  Haerdtle, Werner;  von Oheimb, Goddert;  Yang, Xuefei;  Liu, Xiaojuan;  Pei, Kequan;  Both, Sabine;  Yang, Bo;  Eichenberg, David;  Assmann, Thorsten;  Bauhus, Juergen;  Behrens, Thorsten;  Buscot, Francois;  Chen, Xiao-Yong;  Chesters, Douglas;  Ding, Bing-Yang;  Durka, Walter;  Erfmeier, Alexandra;  Fang, Jingyun;  Fischer, Markus;  Guo, Liang-Dong;  Guo, Dali;  Gutknecht, Jessica L. M.;  He, Jin-Sheng;  He, Chun-Ling;  Hector, Andy;  Hoenig, Lydia;  Hu, Ren-Yong;  Klein, Alexandra-Maria;  Kuehn, Peter;  Liang, Yu;  Li, Shan;  Michalski, Stefan;  Scherer-Lorenzen, Michael;  Schmidt, Karsten;  Scholten, Thomas;  Schuldt, Andreas;  Shi, Xuezheng;  Tan, Man-Zhi;  Tang, Zhiyao;  Trogisch, Stefan;  Wang, Zhengwen;  Welk, Erik;  Wirth, Christian;  Wubet, Tesfaye;  Xiang, Wenhua;  Yu, Mingjian;  Yu, Xiao-Dong;  Zhang, Jiayong;  Zhang, Shouren;  Zhang, Naili;  Zhou, Hong-Zhang;  Zhu, Chao-Dong;  Zhu, Li;  Bruelheide, Helge;  Ma, Keping;  Niklaus, Pascal A.;  Schmid, Bernhard
收藏  |  浏览/下载:13/0  |  提交时间:2019/11/27