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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:41/0  |  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.


  
Olfactory receptor and circuit evolution promote host specialization 期刊论文
NATURE, 2020
作者:  Chen, Tse-An;  Chuu, Chih-Piao;  Tseng, Chien-Chih;  Wen, Chao-Kai;  Wong, H. -S. Philip;  Pan, Shuangyuan;  Li, Rongtan;  Chao, Tzu-Ang;  Chueh, Wei-Chen;  Zhang, Yanfeng;  Fu, Qiang;  Yakobson, Boris I.;  Chang, Wen-Hao;  Li, Lain-Jong
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

The evolution of animal behaviour is poorly understood(1,2). Despite numerous correlations between interspecific divergence in behaviour and nervous system structure and function, demonstrations of the genetic basis of these behavioural differences remain rare(3-5). Here we develop a neurogenetic model, Drosophila sechellia, a species that displays marked differences in behaviour compared to its close cousin Drosophila melanogaster(6,7), which are linked to its extreme specialization on noni fruit (Morinda citrifolia)(8-16). Using calcium imaging, we identify olfactory pathways in D. sechellia that detect volatiles emitted by the noni host. Our mutational analysis indicates roles for different olfactory receptors in long- and short-range attraction to noni, and our cross-species allele-transfer experiments demonstrate that the tuning of one of these receptors is important for species-specific host-seeking. We identify the molecular determinants of this functional change, and characterize their evolutionary origin and behavioural importance. We perform circuit tracing in the D. sechellia brain, and find that receptor adaptations are accompanied by increased sensory pooling onto interneurons as well as species-specific central projection patterns. This work reveals an accumulation of molecular, physiological and anatomical traits that are linked to behavioural divergence between species, and defines a model for investigating speciation and the evolution of the nervous system.


A neurogenetic model, Drosophila sechellia-a relative of Drosophila melanogaster that has developed an extreme specialization for a single host plant-sheds light on the evolution of interspecific differences in behaviour.


  
In situ NMR metrology reveals reaction mechanisms in redox flow batteries 期刊论文
NATURE, 2020, 579 (7798) : 224-+
作者:  Ma, Jianfei;  You, Xin;  Sun, Shan;  Wang, Xiaoxiao;  Qin, Song;  Sui, Sen-Fang
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Large-scale energy storage is becoming increasingly critical to balancing renewable energy production and consumption(1). Organic redox flow batteries, made from inexpensive and sustainable redox-active materials, are promising storage technologies that are cheaper and less environmentally hazardous than vanadium-based batteries, but they have shorter lifetimes and lower energy density(2,3). Thus, fundamental insight at the molecular level is required to improve performance(4,5). Here we report two in situ nuclear magnetic resonance (NMR) methods of studying redox flow batteries, which are applied to two redox-active electrolytes: 2,6-dihydroxyanthraquinone (DHAQ) and 4,4 '  -((9,10-anthraquinone-2,6-diyl)dioxy) dibutyrate (DBEAQ). In the first method, we monitor the changes in the H-1 NMR shift of the liquid electrolyte as it flows out of the electrochemical cell. In the second method, we observe the changes that occur simultaneously in the positive and negative electrodes in the full electrochemical cell. Using the bulk magnetization changes (observed via the H-1 NMR shift of the water resonance) and the line broadening of the H-1 shifts of the quinone resonances as a function of the state of charge, we measure the potential differences of the two single-electron couples, identify and quantify the rate of electron transfer between the reduced and oxidized species, and determine the extent of electron delocalization of the unpaired spins over the radical anions. These NMR techniques enable electrolyte decomposition and battery self-discharge to be explored in real time, and show that DHAQ is decomposed electrochemically via a reaction that can be minimized by limiting the voltage used on charging. We foresee applications of these NMR methods in understanding a wide range of redox processes in flow and other electrochemical systems.


  
From supply to demand factors: What are the determinants of attractiveness for outdoor recreation? 期刊论文
ECOLOGICAL ECONOMICS, 2019, 161: 163-175
作者:  Tardieu, Lea;  Tuffery, Laetitia
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27
Forest recreational attractiveness  Supply and demand factors  Travel cost method  Function benefit transfer  Regional park strategy  
Improving the Spectral Analysis of Hydrological Signals to Efficiently Constrain Watershed Properties 期刊论文
WATER RESOURCES RESEARCH, 2019, 55 (5) : 4043-4065
作者:  Schuite, J.;  Flipo, N.;  Massei, N.;  Riviere, A.;  Baratelli, F.
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/26
hydrosystem  spectral analysis  transfer function  data analysis  catchment  watershed  
Incorporating local adaptation into forecasts of species' distribution and abundance under climate change 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (3) : 775-793
作者:  Peterson, Megan L.;  Doak, Daniel F.;  Morris, William F.
收藏  |  浏览/下载:7/0  |  提交时间:2019/04/09
climate change  forecast  landscape demography  local adaptation  mechanistic distribution model  response function  species distribution model  transfer function  
A Structure Function Model Recovers the Many Formulations for Air-Water Gas Transfer Velocity 期刊论文
WATER RESOURCES RESEARCH, 2018, 54 (9) : 5905-5920
作者:  Katul, Gabriel;  Mammarella, Ivan;  Gronholm, Tiia;  Vesala, Timo
收藏  |  浏览/下载:12/0  |  提交时间:2019/04/09
air-water gas exchange  gas transfer velocity  structure function  microeddy model  scaling laws  turbulence  
Using Sensor Data to Dynamically Map Large-Scale Models to Site-Scale Forecasts: A Case Study Using the National Water Model 期刊论文
WATER RESOURCES RESEARCH, 2018, 54 (8) : 5636-5653
作者:  Fries, Kevin J.;  Kerkez, Branko
收藏  |  浏览/下载:4/0  |  提交时间:2019/04/09
Transfer Function  Flood Forecasting  Data Driven Modeling  
Testate amoeba records indicate regional 20th-century lowering of water tables in ombrotrophic peatlands in central-northern Alberta, Canada 期刊论文
GLOBAL CHANGE BIOLOGY, 2018, 24 (7) : 2758-2774
作者:  van Bellen, Simon;  Magnan, Gabriel;  Davies, Lauren;  Froese, Duane;  Mullan-Boudreau, Gillian;  Zaccone, Claudio;  Garneau, Michelle;  Shotyk, William
收藏  |  浏览/下载:15/0  |  提交时间:2019/04/09
functional trait  Little Ice Age  oil sands  peat bog  permafrost  Sphagnum  transfer function  water table  
East European chironomid-based calibration model for past summer temperature reconstructions 期刊论文
CLIMATE RESEARCH, 2018, 77 (1) : 63-76
作者:  Luoto, Tomi P.;  Kotrys, Bartosz;  Plociennik, Mateusz
收藏  |  浏览/下载:10/0  |  提交时间:2019/04/09
Chironomidae  Climate reconstruction  Finland  Holocene  Late Glacial  Paleoclimate  Poland  Training set  Transfer function