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An alternative approach for quantitatively estimating climate variability over China under the effects of ENSO events 期刊论文
ATMOSPHERIC RESEARCH, 2020, 238
作者:  Zhou, Ping;  Liu, Zhiyong;  Cheng, Linyin
收藏  |  浏览/下载:7/0  |  提交时间:2020/08/18
Multivariate  Conditional copula  Climate variability  ENSO  China  
Structure of nevanimibe-bound tetrameric human ACAT1 期刊论文
NATURE, 2020, 581 (7808) : 339-U214
作者:  Ma, Xiyu;  Claus, Lucas A. N.;  Leslie, Michelle E.;  Tao, Kai;  Wu, Zhiping;  Liu, Jun;  Yu, Xiao;  Li, Bo;  Zhou, Jinggeng;  Savatin, Daniel V.;  Peng, Junmin;  Tyler, Brett M.;  Heese, Antje;  Russinova, Eugenia;  He, Ping;  Shan, Libo
收藏  |  浏览/下载:28/0  |  提交时间:2020/07/03

The structure of human ACAT1 in complex with the inhibitor nevanimibe is resolved by cryo-electron microscopy.


Cholesterol is an essential component of mammalian cell membranes, constituting up to 50% of plasma membrane lipids. By contrast, it accounts for only 5% of lipids in the endoplasmic reticulum (ER)(1). The ER enzyme sterol O-acyltransferase 1 (also named acyl-coenzyme A:cholesterol acyltransferase, ACAT1) transfers a long-chain fatty acid to cholesterol to form cholesteryl esters that coalesce into cytosolic lipid droplets. Under conditions of cholesterol overload, ACAT1 maintains the low cholesterol concentration of the ER and thereby has an essential role in cholesterol homeostasis(2,3). ACAT1 has also been implicated in Alzheimer'  s disease(4), atherosclerosis(5) and cancers(6). Here we report a cryo-electron microscopy structure of human ACAT1 in complex with nevanimibe(7), an inhibitor that is in clinical trials for the treatment of congenital adrenal hyperplasia. The ACAT1 holoenzyme is a tetramer that consists of two homodimers. Each monomer contains nine transmembrane helices (TMs), six of which (TM4-TM9) form a cavity that accommodates nevanimibe and an endogenous acyl-coenzyme A. This cavity also contains a histidine that has previously been identified as essential for catalytic activity(8). Our structural data and biochemical analyses provide a physical model to explain the process of cholesterol esterification, as well as details of the interaction between nevanimibe and ACAT1, which may help to accelerate the development of ACAT1 inhibitors to treat related diseases.


  
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:9/0  |  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.


  
A distal enhancer at risk locus 11q13.5 promotes suppression of colitis by T-reg cells 期刊论文
NATURE, 2020
作者:  Ma, Xiyu;  Claus, Lucas A. N.;  Leslie, Michelle E.;  Tao, Kai;  Wu, Zhiping;  Liu, Jun;  Yu, Xiao;  Li, Bo;  Zhou, Jinggeng;  Savatin, Daniel V.;  Peng, Junmin;  Tyler, Brett M.;  Heese, Antje;  Russinova, Eugenia;  He, Ping;  Shan, Libo
收藏  |  浏览/下载:40/0  |  提交时间:2020/07/03

Genetic variations underlying susceptibility to complex autoimmune and allergic diseases are concentrated within noncoding regulatory elements termed enhancers(1). The functions of a large majority of disease-associated enhancers are unknown, in part owing to their distance from the genes they regulate, a lack of understanding of the cell types in which they operate, and our inability to recapitulate the biology of immune diseases in vitro. Here, using shared synteny to guide loss-of-function analysis of homologues of human enhancers in mice, we show that the prominent autoimmune and allergic disease risk locus at chromosome 11q13.5(2-7) contains a distal enhancer that is functional in CD4(+) regulatory T (T-reg) cells and required for T-reg-mediated suppression of colitis. The enhancer recruits the transcription factors STAT5 and NF-kappa B to mediate signal-driven expression of Lrrc32, which encodes the protein glycoprotein A repetitions predominant (GARP). Whereas disruption of the Lrrc32 gene results in early lethality, mice lacking the enhancer are viable but lack GARP expression in Foxp3(+) T-reg cells, which are unable to control colitis in a cell-transfer model of the disease. In human T-reg cells, the enhancer forms conformational interactions with the promoter of LRRC32 and enhancer risk variants are associated with reduced histone acetylation and GARP expression. Finally, functional fine-mapping of 11q13.5 using CRISPR-activation (CRISPRa) identifies a CRISPRa-responsive element in the vicinity of risk variant rs11236797 capable of driving GARP expression. These findings provide a mechanistic basis for association of the 11q13.5 risk locus with immune-mediated diseases and identify GARP as a potential target in their therapy.


Shared synteny guides loss-of-function analysis of human enhancer homologues in mice, identifying a distal enhancer at the autoimmune and allergic disease risk locus at chromosome 11q13.5 whose function in regulatory T cells provides a mechanistic basis for its role in disease.


  
Global Response of Evapotranspiration Ratio to Climate Conditions and Watershed Characteristics in a Changing Environment 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2020, 125 (7)
作者:  Liu, Zhiyong;  Cheng, Linyin;  Zhou, Guoyi;  Chen, Xiaohong;  Lin, Kairong;  Zhang, Wenfeng;  Chen, Xiuzhi;  Zhou, Ping
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/02
hydrological response  evapotranspiration  watershed characteristics  aridity index  relative contribution  
Multiscale Variability of Meiyu and Its Prediction: A New Review 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2020, 125 (7)
作者:  Ding, Yihui;  Liang, Ping;  Liu, Yanju;  Zhang, Yaocun
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/02
Meiyu  multiscale variability  East Asian summer monsoon  Meiyu prediction  
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:23/0  |  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.


  
Vertical characteristics of aerosol hygroscopicity and impacts on optical properties over the North China Plain during winter 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2020, 20 (6) : 3931-3944
作者:  Liu, Quan;  Liu, Dantong;  Gao, Qian;  Tian, Ping;  Wang, Fei;  Zhao, Delong;  Bi, Kai;  Wu, Yangzhou;  Ding, Shuo;  Hu, Kang;  Zhang, Jiale;  Ding, Deping;  Zhao, Chunsheng
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/02
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:17/0  |  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.