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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.


  
An orbital water-ice cycle on comet 67P from colour changes 期刊论文
NATURE, 2020, 578 (7793) : 49-+
作者:  Oh, Myoung Hwan;  Cho, Min Gee;  Chung, Dong Young;  Park, Inchul;  Kwon, Youngwook Paul;  Ophus, Colin;  Kim, Dokyoon;  Kim, Min Gyu;  Jeong, Beomgyun;  Gu, X. Wendy;  Jo, Jinwoung;  Yoo, Ji Mun;  Hong, Jaeyoung;  McMains, Sara;  Kang, Kisuk;  Sung, Yung-Eun;  Alivisatos, A. Paul;  Hyeon, Taeghwan
收藏  |  浏览/下载:52/0  |  提交时间:2020/07/03

Solar heating of a cometary surface provides the energy necessary to sustain gaseous activity, through which dust is removed(1,2). In this dynamical environment, both the coma(3,4) and the nucleus(5,6) evolve during the orbit, changing their physical and compositional properties. The environment around an active nucleus is populated by dust grains with complex and variegated shapes(7), lifted and diffused by gases freed from the sublimation of surface ices(8,9). The visible colour of dust particles is highly variable: carbonaceous organic material-rich grains(10) appear red while magnesium silicate-rich(11,12) and water-ice-rich(13,14) grains appear blue, with some dependence on grain size distribution, viewing geometry, activity level and comet family type. We know that local colour changes are associated with grain size variations, such as in the bluer jets made of submicrometre grains on comet Hale-Bopp(15) or in the fragmented grains in the coma(16) of C/1999 S4 (LINEAR). Apart from grain size, composition also influences the coma'  s colour response, because transparent volatiles can introduce a substantial blueing in scattered light, as observed in the dust particles ejected after the collision of the Deep Impact probe with comet 9P/Tempel 1(17). Here we report observations of two opposite seasonal colour cycles in the coma and on the surface of comet 67P/Churyumov-Gerasimenko through its perihelion passage(18). Spectral analysis indicates an enrichment of submicrometre grains made of organic material and amorphous carbon in the coma, causing reddening during the passage. At the same time, the progressive removal of dust from the nucleus causes the exposure of more pristine and bluish icy layers on the surface. Far from the Sun, we find that the abundance of water ice on the nucleus is reduced owing to redeposition of dust and dehydration of the surface layer while the coma becomes less red.


  
Using Google Street View to investigate the association between street greenery and physical activity 期刊论文
LANDSCAPE AND URBAN PLANNING, 2019, 191
作者:  Lu, Yi
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/27
Street greenery  Urban greenspace  Google Street View (GSV)  Physical activity  Healthy city  
The influence of green streets on cycling behavior in European cities 期刊论文
LANDSCAPE AND URBAN PLANNING, 2019, 190
作者:  Nawrath, Maximilian;  Kowarik, Ingo;  Fischer, Leonie K.
收藏  |  浏览/下载:11/0  |  提交时间:2019/11/27
Green cycling routes  Physical activity  Preference  Urban green infrastructure  Urban greenways  Vegetated streets  
Physical activity areas in urban parks and their use by the elderly from two cities in China and Germany 期刊论文
LANDSCAPE AND URBAN PLANNING, 2018, 178: 261-269
作者:  Duan, Yanping;  Wagner, Petra;  Zhang, Ru;  Wulff, Hagen;  Brehrn, Walter
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09
Urban parks  Physical activity areas  Elderly  Park-based physical activity  Health enhancing physical activity  
An evaluation of participatory mapping methods to assess urban park benefits 期刊论文
LANDSCAPE AND URBAN PLANNING, 2018, 178: 18-31
作者:  Brown, Greg;  Rhodes, Jonathan;  Dade, Marie
收藏  |  浏览/下载:3/0  |  提交时间:2019/04/09
Urban parks  Physical activity  Benefits  Public participation GIS  PPGIS  Urban planning  
Advantages of public green spaces in enhancing population health 期刊论文
LANDSCAPE AND URBAN PLANNING, 2018, 178: 12-17
作者:  Sugiyama, Takemi;  Carver, Alison;  Koohsari, Mohammad Javad;  Veitch, Jenny
收藏  |  浏览/下载:2/0  |  提交时间:2019/04/09
Park  Natural area  Physical activity  Contact with nature  
Neighbourhood greenspace is related to physical activity in England, but only for dog owners 期刊论文
LANDSCAPE AND URBAN PLANNING, 2018, 174: 18-23
作者:  White, Mathew P.;  Elliott, Lewis R.;  Wheeler, Benedict W.;  Fleming, Lora E.
收藏  |  浏览/下载:4/0  |  提交时间:2019/04/09
Greenspace  Physical activity  Dog-ownership  Health promotion  
Every breath you take, every move you make: Visits to the outdoors and physical activity help to explain the relationship between air pollution and subjective wellbeing 期刊论文
ECOLOGICAL ECONOMICS, 2018, 147: 96-113
作者:  Laffan, Kate
收藏  |  浏览/下载:3/0  |  提交时间:2019/04/09
Subjective wellbeing  Air pollution  Environmental quality  Mediation  Physical activity  Visits outdoors  
Testing spatial measures of public open space planning standards with walking and physical activity health outcomes: Findings from the Australian national liveability study 期刊论文
LANDSCAPE AND URBAN PLANNING, 2018, 171: 57-67
作者:  Hooper, Paula;  Boruff, Bryan;  Beesley, Bridget;  Badland, Hannah;  Giles-Corti, Billie
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09
Public open space  Urban planning  Walking  Physical activity  Policy