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A lower X-gate in TASK channels traps inhibitors within the vestibule 期刊论文
NATURE, 2020
作者:  Chen, Tao;  Nomura, Kinya;  Wang, Xiaolin;  Sohrabi, Reza;  Xu, Jin;  Yao, Lingya;  Paasch, Bradley C.;  Ma, Li;  Kremer, James;  Cheng, Yuti;  Zhang, Li;  Wang, Nian;  Wang, Ertao;  Xin, Xiu-Fang;  He, Sheng Yang
收藏  |  浏览/下载:35/0  |  提交时间:2020/07/03

TWIK-related acid-sensitive potassium (TASK) channels-members of the two pore domain potassium (K-2P) channel family-are found in neurons(1), cardiomyocytes(2-4) and vascular smooth muscle cells(5), where they are involved in the regulation of heart rate(6), pulmonary artery tone(5,7), sleep/wake cycles(8) and responses to volatile anaesthetics(8-11). K-2P channels regulate the resting membrane potential, providing background K+ currents controlled by numerous physiological stimuli(12-15). Unlike other K-2P channels, TASK channels are able to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates. As such, these channels are attractive drug targets, and TASK-1 inhibitors are currently in clinical trials for obstructive sleep apnoea and atrial fibrillation(16). In general, potassium channels have an intramembrane vestibule with a selectivity filter situated above and a gate with four parallel helices located below  however, the K-2P channels studied so far all lack a lower gate. Here we present the X-ray crystal structure of TASK-1, and show that it contains a lower gate-which we designate as an '  X-gate'  -created by interaction of the two crossed C-terminal M4 transmembrane helices at the vestibule entrance. This structure is formed by six residues ((VLRFMT248)-V-243) that are essential for responses to volatile anaesthetics(10), neurotransmitters(13) and G-protein-coupled receptors(13). Mutations within the X-gate and the surrounding regions markedly affect both the channel-open probability and the activation of the channel by anaesthetics. Structures of TASK-1 bound to two high-affinity inhibitors show that both compounds bind below the selectivity filter and are trapped in the vestibule by the X-gate, which explains their exceptionally low washout rates. The presence of the X-gate in TASK channels explains many aspects of their physiological and pharmacological behaviour, which will be beneficial for the future development and optimization of TASK modulators for the treatment of heart, lung and sleep disorders.


The X-ray crystal structure of the potassium channel TASK-1 reveals the presence of an X-gate, which traps small-molecule inhibitors in the intramembrane vestibule and explains their low washout rates from the channel.


  
An Example of Augmenting Regional Sensitivity Analysis Using Machine Learning Software 期刊论文
WATER RESOURCES RESEARCH, 2020, 56 (4)
作者:  Spear, Robert C.;  Cheng, Qu;  Wu, Sean L.
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/02
Corncob cellulose nanosphere as an eco-friendly detergent 期刊论文
NATURE SUSTAINABILITY, 2020, 3 (6) : 448-458
作者:  Liu, Bin;  Li, Tao;  Wang, Wenya;  Sagis, Leonard M. C.;  Yuan, Qipeng;  Lei, Xingen;  Stuart, Martien A. Cohen;  Li, Dan;  Bao, Cheng;  Bai, Jie;  Yu, Zhengquan;  Ren, Fazheng;  Li, Yuan
收藏  |  浏览/下载:13/0  |  提交时间:2020/05/13
The dental proteome of Homo antecessor 期刊论文
NATURE, 2020, 580 (7802) : 235-+
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03

Analyses of the proteomes of dental enamel from Homo antecessor and Homo erectus demonstrate that the Early Pleistocene H. antecessor is a close sister lineage of later Homo sapiens, Neanderthal and Denisovan populations in Eurasia.


The phylogenetic relationships between hominins of the Early Pleistocene epoch in Eurasia, such as Homo antecessor, and hominins that appear later in the fossil record during the Middle Pleistocene epoch, such as Homo sapiens, are highly debated(1-5). For the oldest remains, the molecular study of these relationships is hindered by the degradation of ancient DNA. However, recent research has demonstrated that the analysis of ancient proteins can address this challenge(6-8). Here we present the dental enamel proteomes of H. antecessor from Atapuerca (Spain)(9,10) and Homo erectus from Dmanisi (Georgia)(1), two key fossil assemblages that have a central role in models of Pleistocene hominin morphology, dispersal and divergence. We provide evidence that H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans. This placement implies that the modern-like face of H. antecessor-that is, similar to that of modern humans-may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form. By recovering AMELY-specific peptide sequences, we also conclude that the H. antecessor molar fragment from Atapuerca that we analysed belonged to a male individual. Finally, these H. antecessor and H. erectus fossils preserve evidence of enamel proteome phosphorylation and proteolytic digestion that occurred in vivo during tooth formation. Our results provide important insights into the evolutionary relationships between H. antecessor and other hominin groups, and pave the way for future studies using enamel proteomes to investigate hominin biology across the existence of the genus Homo.


  
Listeria monocytogenes impairs SUMOylation for efficient infection (vol 464, pg 1192, 2010) 期刊论文
NATURE, 2020, 580 (7805) : E20-E20
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:9/0  |  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.


  
Neuronal programming by microbiota regulates intestinal physiology 期刊论文
NATURE, 2020, 578 (7794) : 284-+
作者:  Li, Yilong;  Roberts, Nicola D.;  Wala, Jeremiah A.;  Shapira, Ofer;  Schumacher, Steven E.;  Kumar, Kiran;  Khurana, Ekta;  Waszak, Sebastian;  Korbel, Jan O.;  Haber, James E.;  Imielinski, Marcin;  Weischenfeldt, Joachim;  Beroukhim, Rameen;  Campbell, Peter J.;  Akdemir, Kadir C.;  Alvarez, Eva G.;  Baez-Ortega, Adrian;  Boutros, Paul C.;  Bowtell, David D. L.;  Brors, Benedikt;  Burns, Kathleen H.;  Chan, Kin;  Chen, Ken;  Cortes-Ciriano, Isidro;  Dueso-Barroso, Ana;  Dunford, Andrew J.;  Edwards, Paul A.;  Estivill, Xavier;  Etemadmoghadam, Dariush;  Feuerbach, Lars;  Fink, J. Lynn;  Frenkel-Morgenstern, Milana;  Garsed, Dale W.;  Gerstein, Mark;  Gordenin, Dmitry A.;  Haan, David;  Hess, Julian M.;  Hutter, Barbara;  Jones, David T. W.;  Ju, Young Seok;  Kazanov, Marat D.;  Klimczak, Leszek J.;  Koh, Youngil;  Lee, Eunjung Alice;  Lee, Jake June-Koo;  Lynch, Andy G.;  Macintyre, Geoff;  Markowetz, Florian;  Martincorena, Inigo;  Martinez-Fundichely, Alexander;  Meyerson, Matthew;  Miyano, Satoru;  Nakagawa, Hidewaki;  Navarro, Fabio C. P.;  Ossowski, Stephan;  Park, Peter J.;  Pearson, John, V;  Puiggros, Montserrat;  Rippe, Karsten;  Roberts, Steven A.;  Rodriguez-Martin, Bernardo;  Scully, Ralph;  Shackleton, Mark;  Sidiropoulos, Nikos;  Sieverling, Lina;  Stewart, Chip;  Torrents, David;  Tubio, Jose M. C.;  Villasante, Izar;  Waddell, Nicola;  Yang, Lixing;  Yao, Xiaotong;  Yoon, Sung-Soo;  Zamora, Jorge;  Zhang, Cheng-Zhong
收藏  |  浏览/下载:40/0  |  提交时间:2020/07/03

Neural control of the function of visceral organs is essential for homeostasis and health. Intestinal peristalsis is critical for digestive physiology and host defence, and is often dysregulated in gastrointestinal disorders(1). Luminal factors, such as diet and microbiota, regulate neurogenic programs of gut motility(2-5), but the underlying molecular mechanisms remain unclear. Here we show that the transcription factor aryl hydrocarbon receptor (AHR) functions as a biosensor in intestinal neural circuits, linking their functional output to the microbial environment of the gut lumen. Using nuclear RNA sequencing of mouse enteric neurons that represent distinct intestinal segments and microbiota states, we demonstrate that the intrinsic neural networks of the colon exhibit unique transcriptional profiles that are controlled by the combined effects of host genetic programs and microbial colonization. Microbiota-induced expression of AHR in neurons of the distal gastrointestinal tract enables these neurons to respond to the luminal environment and to induce expression of neuron-specific effector mechanisms. Neuron-specific deletion of Ahr, or constitutive overexpression of its negative feedback regulator CYP1A1, results in reduced peristaltic activity of the colon, similar to that observed in microbiota-depleted mice. Finally, expression of Ahr in the enteric neurons of mice treated with antibiotics partially restores intestinal motility. Together, our experiments identify AHR signalling in enteric neurons as a regulatory node that integrates the luminal environment with the physiological output of intestinal neural circuits to maintain gut homeostasis and health.


In a mouse model, aryl hydrocarbon receptor signalling in enteric neurons is revealed as a mechanism that helps to maintain gut homeostasis by integrating the luminal environment with the physiology of intestinal neural circuits.


  
A simple dynamic model explains the diversity of island birds worldwide 期刊论文
NATURE, 2020
作者:  Li, Junxue;  Wilson, C. Blake;  Cheng, Ran;  Lohmann, Mark;  Kavand, Marzieh;  Yuan, Wei;  Aldosary, Mohammed;  Agladze, Nikolay;  Wei, Peng;  Sherwin, Mark S.;  Shi, Jing
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

Colonization, speciation and extinction are dynamic processes that influence global patterns of species richness(1-6). Island biogeography theory predicts that the contribution of these processes to the accumulation of species diversity depends on the area and isolation of the island(7,8). Notably, there has been no robust global test of this prediction for islands where speciation cannot be ignored(9), because neither the appropriate data nor the analytical tools have been available. Here we address both deficiencies to reveal, for island birds, the empirical shape of the general relationships that determine how colonization, extinction and speciation rates co-vary with the area and isolation of islands. We compiled a global molecular phylogenetic dataset of birds on islands, based on the terrestrial avifaunas of 41 oceanic archipelagos worldwide (including 596 avian taxa), and applied a new analysis method to estimate the sensitivity of island-specific rates of colonization, speciation and extinction to island features (area and isolation). Our model predicts-with high explanatory power-several global relationships. We found a decline in colonization with isolation, a decline in extinction with area and an increase in speciation with area and isolation. Combining the theoretical foundations of island biogeography(7,8) with the temporal information contained in molecular phylogenies(10) proves a powerful approach to reveal the fundamental relationships that govern variation in biodiversity across the planet.


Using a global molecular phylogenetic dataset of birds on islands, the sensitivity of island-specific rates of colonization, speciation and extinction to island features (area and isolation) is estimated.


  
Masonry walls as sieve of urban plant assemblages and refugia of native species in Chongqing, China 期刊论文
LANDSCAPE AND URBAN PLANNING, 2019, 191
作者:  Huang, Li;  Qian, Shenhua;  Li, Ting;  Jim, C. Y.;  Jin, Cheng;  Zhao, Liang;  Lin, Dunmei;  Shang, Kankan;  Yang, Yongchuan
收藏  |  浏览/下载:15/0  |  提交时间:2019/11/27
Masonry wall plant  Ruderal habitat  Urban biodiversity  Vertical green infrastructure  Recruitment dynamics  Sieving-elimination model  
Satellite testing of a gravitationally induced quantum decoherence model 期刊论文
SCIENCE, 2019, 366 (6461) : 132-+
作者:  Xu, Ping;  Ma, Yiqiu;  Ren, Ji-Gang;  Yong, Hai-Lin;  Ralph, Timothy C.;  Liao, Sheng-Kai;  Yin, Juan;  Liu, Wei-Yue;  Cai, Wen-Qi;  Han, Xuan;  Wu, Hui-Nan;  Wang, Wei-Yang;  Li, Feng-Zhi;  Yang, Meng;  Lin, Feng-Li;  Li, Li;  Liu, Nai-Le;  Chen, Yu-Ao;  Lu, Chao-Yang;  Chen, Yanbei;  Fan, Jingyun;  Peng, Cheng-Zhi;  Pan, Jian-Wei
收藏  |  浏览/下载:15/0  |  提交时间:2019/11/27
Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia 期刊论文
NATURE COMMUNICATIONS, 2017, 8
作者:  Jiang, Xi;  Hu, Chao;  Ferchen, Kyle;  Nie, Ji;  Cui, Xiaolong;  Chen, Chih-Hong;  Cheng, Liting;  Zuo, Zhixiang;  Seibel, William;  He, Chunjiang;  Tang, Yixuan;  Skibbe, Jennifer R.;  Wunderlich, Mark;  Reinhold, William C.;  Dong, Lei;  Shen, Chao;  Arnovitz, Stephen;  Ulrich, Bryan;  Lu, Jiuwei;  Weng, Hengyou;  Su, Rui;  Huang, Huilin;  Wang, Yungui;  Li, Chenying;  Qin, Xi;  Mulloy, James;  Zheng, Yi;  Diao, Jiajie;  Jin, Jie;  Li, Chong;  Liu, Paul P.;  He, Chuan;  Chen, Yuan;  Chen, Jianjun
收藏  |  浏览/下载:17/0  |  提交时间:2019/11/27