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Discriminating alpha-synuclein strains in Parkinson's disease and multiple system atrophy 期刊论文
NATURE, 2020, 578 (7794) : 273-+
作者:  Senior, Andrew W.;  Evans, Richard;  Jumper, John;  Kirkpatrick, James;  Sifre, Laurent;  Green, Tim;  Qin, Chongli;  Zidek, Augustin;  Nelson, Alexander W. R.;  Bridgland, Alex;  Penedones, Hugo;  Petersen, Stig;  Simonyan, Karen;  Crossan, Steve;  Kohli, Pushmeet;  Jones, David T.;  Silver, David;  Kavukcuoglu, Koray;  Hassabis, Demis
收藏  |  浏览/下载：40/0  |  提交时间：2020/07/03

Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of alpha-synuclein, including Parkinson'  s disease, dementia with Lewy bodies and multiple system atrophy(1). Clinically, it is challenging to differentiate Parkinson'  s disease and multiple system atrophy, especially at the early stages of disease(2). Aggregates of alpha-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of alpha-synuclein that can self-propagate and spread from cell to cell(3-6). Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect alpha-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity(7,8). Here we show that the alpha-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson'  s disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of alpha-synuclein-PMCA, and found that the characteristics of the alpha-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson'  s disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that alpha-synuclein aggregates that are associated with Parkinson'  s disease and multiple system atrophy correspond to different conformational strains of alpha-synuclein, which can be amplified and detected by alpha-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of alpha-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson'  s disease and multiple system atrophy.


Protein misfolding cyclic amplification (PMCA) technology can discriminate between patients with Parkinson'  s disease and patients with multiple system atrophy on the basis of the characteristics of the alpha-synuclein aggregates in the cerebrospinal fluid.


  
Initial results from the New Horizons exploration of 2014 MU69, a small Kuiper Belt object 期刊论文
SCIENCE, 2019, 364 (6441) : 649-+
作者:  Stern, S. A.;  Weaver, H. A.;  Spencer, J. R.;  Olkin, C. B.;  Gladstone, G. R.;  Grundy, W. M.;  Moore, J. M.;  Cruikshank, D. P.;  Elliott, H. A.;  McKinnon, W. B.;  Parker, J. Wm.;  Verbiscer, A. J.;  Young, L. A.;  Aguilar, D. A.;  Albers, J. M.;  Andert, T.;  Andrews, J. P.;  Bagenal, F.;  Banks, M. E.;  Bauer, B. A.;  Bauman, J. A.;  Bechtold, K. E.;  Beddingfield, C. B.;  Behrooz, N.;  Beisser, K. B.;  Benecchi, S. D.;  Bernardoni, E.;  Beyer, R. A.;  Bhaskaran, S.;  Bierson, C. J.;  Binzel, R. P.;  Birath, E. M.;  Bird, M. K.;  Boone, D. R.;  Bowman, A. F.;  Bray, V. J.;  Britt, D. T.;  Brown, L. E.;  Buckley, M. R.;  Buie, M. W.;  Buratti, B. J.;  Burke, L. M.;  Bushman, S. S.;  Careich, B.;  Chaikin, A. L.;  Chavez, C. L.;  Cheng, A. F.;  Colwell, E. J.;  Conard, S. J.;  Conner, M. P.;  Conrad, C. A.;  Cook, J. C.;  Cooper, S. B.;  Custodio, O. S.;  Ore, C. M. Dalle;  Deboy, C. C.;  Dharmavaram, P.;  Dhingra, R. D.;  Dunn, G. F.;  Earle, A. M.;  Egan, A. F.;  Eisig, J.;  El-Maarry, M. R.;  Engelbrecht, C.;  Enke, B. L.;  Ercol, C. J.;  Fattig, E. D.;  Ferrell, C. L.;  Finley, T. J.;  Firer, J.;  Fischetti, J.;  Folkner, W. M.;  Fosbury, M. N.;  Fountain, G. H.;  Freeze, J. M.;  Gabasova, L.;  Glaze, L. S.;  Green, J. L.;  Griffith, G. A.;  Guo, Y.;  Hahn, M.;  Hals, D. W.;  Hamilton, D. P.;  Hamilton, S. A.;  Hanley, J. J.;  Harch, A.;  Harmon, K. A.;  Hart, H. M.;  Hayes, J.;  Hersman, C. B.;  Hill, M. E.;  Hill, T. A.;  Hofgartner, J. D.;  Holdridge, M. E.;  Horanyi, M.;  Hosadurga, A.;  Howard, A. D.;  Howett, C. J. A.;  Jaskulek, S. E.;  Jennings, D. E.;  Jensen, J. R.;  Jones, M. R.;  Kang, H. K.;  Katz, D. J.;  Kaufmann, D. E.;  Kavelaars, J. J.;  Keane, J. T.;  Keleher, G. P.;  Kinczyk, M.;  Kochte, M. C.;  Kolmnann, P.;  Krimigis, S. M.;  Kruizinga, G. L.;  Kusnierkiewicz, D. Y.;  Lahr, M. S.;  Lauer, T. R.;  Lawrence, G. B.;  Lee, J. E.;  Lessac-Chenen, E. J.;  Linscott, I. R.;  Lisse, C. M.;  Lunsford, A. W.;  Mages, D. M.;  Mallder, V. A.;  Martin, N. P.;  May, B. H.;  McComas, D. J.;  MeNutt, R. L., Jr.;  Mehoke, D. S.;  Mehoke, T. S.;  Nelson, D. S.;  Nguyen, H. D.;  Nunez, J. I.;  Ocampo, A. C.;  Owen, W. M.;  Oxton, G. K.;  Parker, A. H.;  Patzold, M.;  Pelgrift, J. Y.;  Pelletier, F. J.;  Pineau, J. P.;  Piquette, M. R.;  Porter, S. B.;  Protopapa, S.;  Quirico, E.;  Redfern, J. A.;  Regiec, A. L.;  Reitsema, H. J.;  Reuter, D. C.;  Richardson, D. C.;  Riedel, J. E.;  Ritterbush, M. A.;  Robbins, S. J.;  Rodgers, D. J.;  Rogers, G. D.;  Rose, D. M.;  Rosendal, P. E.;  Runyon, K. D.;  Ryschkewitsch, M. G.;  Saina, M. M.;  Salinas, M. J.;  Schenk, P. M.;  Scherrer, J. R.;  Schlei, W. R.;  Schmitt, B.;  Schultz, D. J.;  Schurr, D. C.;  Scipioni, F.;  Sepan, R. L.;  Shelton, R. G.;  Showalter, M. R.;  Simon, M.;  Singer, K. N.;  Stahlheber, E. W.;  Stanbridge, D. R.;  Stansberry, J. A.;  Steffi, A. J.;  Strobel, D. F.;  Stothoff, M. M.;  Stryk, T.;  Stuart, J. M.;  Summers, M. E.;  Tapley, M. B.;  Taylor, A.;  Taylor, H. W.;  Tedford, R. M.;  Throop, H. B.;  Turner, L. S.;  Umurhan, O. M.;  Van Eck, J.;  Velez, D.;  Versteeg, M. H.;  Vincent, M. A.;  Webbert, R. W.;  Weidner, S. E.;  Ii, G. E. Weigle;  Wendel, J. R.;  White, O. L.;  Whittenburg, K. E.;  Williams, B. G.;  Williams, K. E.;  Williams, S. P.;  Wimters, H. L.;  Zangari, A. M.;  Zurbuchen, T. H.
收藏  |  浏览/下载：13/0  |  提交时间：2019/11/27
Stratification of reactivity determines nitrate removal in groundwater 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (7) : 2494-2499
作者:  Kolbe, Tamara;  de Dreuzy, Jean-Raynald;  Abbott, Benjamin W.;  Aquilina, Luc;  Babey, Tristan;  Green, Christopher T.;  Fleckenstein, Jan H.;  Labasque, Thierry;  Laverman, Anniet M.;  Marcais, Jean;  Peiffer, Stefan;  Thomas, Zahra;  Pinay, Gilles
收藏  |  浏览/下载：8/0  |  提交时间：2019/11/27
groundwater  denitrification  reactivity pattern  transit times  reaction times  
Evidence of a Shared Value for Nature 期刊论文
ECOLOGICAL ECONOMICS, 2018, 154: 107-116
作者:  Wainger, Lisa A.;  Helcoski, Ryan;  Farge, Kevin W.;  Espinola, Brandy A.;  Green, Gary T.
收藏  |  浏览/下载：3/0  |  提交时间：2019/04/09
Nonuse value  Passive use value  Ecosystem services  Socio-demographic variability  Social media  
Regional Variability of Nitrate Fluxes in the Unsaturated Zone and Groundwater, Wisconsin, USA 期刊论文
WATER RESOURCES RESEARCH, 2018, 54 (1) : 301-322
作者:  Green, Christopher T.;  Liao, Lixia;  Nolan, Bernard T.;  Juckem, Paul F.;  Shope, Christopher L.;  Tesoriero, Anthony J.;  Jurgens, Bryant C.
收藏  |  浏览/下载：11/0  |  提交时间：2019/04/09
Observation of coherent elastic neutrino-nucleus scattering 期刊论文
SCIENCE, 2017, 357 (6356) : 1123-+
作者:  Akimov, D.;  Albert, J. B.;  An, P.;  Awe, C.;  Barbeau, P. S.;  Becker, B.;  Belov, V.;  Brown, A.;  Bolozdynya, A.;  Cabrera-Palmer, B.;  Cervantes, M.;  Collar, J. I.;  Cooper, R. J.;  Cooper, R. L.;  Cuesta, C.;  Dean, D. J.;  Detwiler, J. A.;  Eberhardt, A.;  Efremenko, Y.;  Elliott, S. R.;  Erkela, E. M.;  Fabris, L.;  Febbraro, M.;  Fields, N. E.;  Fox, W.;  Fu, Z.;  Galindo-Uribarri, A.;  Green, M. P.;  Hai, M.;  Heath, M. R.;  Hedges, S.;  Hornback, D.;  Hossbach, T. W.;  Iverson, E. B.;  Kaufman, L. J.;  Ki, S.;  Klein, S. R.;  Khromov, A.;  Konovalov, A.;  Kremer, M.;  Kumpan, A.;  Leadbetter, C.;  Li, L.;  Lu, W.;  Mann, K.;  Markoff, D. M.;  Miller, K.;  Moreno, H.;  Mueller, P. E.;  Newby, J.;  Orrell, J. L.;  Overman, C. T.;  Parno, D. S.;  Penttila, S.;  Perumpilly, G.;  Ray, H.;  Raybern, J.;  Reyna, D.;  Rich, G. C.;  Rimal, D.;  Rudik, D.;  Scholberg, K.;  Scholz, B. J.;  Sinev, G.;  Snow, W. M.;  Sosnovtsev, V.;  Shakirov, A.;  Suchyta, S.;  Suh, B.;  Tayloe, R.;  Thornton, R. T.;  Tolstukhin, I.;  Vanderwerp, J.;  Varner, R. L.;  Virtue, C. J.;  Wan, Z.;  Yoo, J.;  Yu, C. -H.;  Zawada, A.;  Zettlemoyer, J.;  Zderic, A. M.
收藏  |  浏览/下载：10/0  |  提交时间：2019/11/27
Green Space and Adult Obesity in the United States 期刊论文
ECOLOGICAL ECONOMICS, 2017, 136
作者:  Ghimire, Ramesh;  Ferreira, Susana;  Green, Gary T.;  Poudyal, Neelam C.;  Cordell, H. Ken;  Thapa, Janani R.
收藏  |  浏览/下载：9/0  |  提交时间：2019/04/09
Forests  Green space  Outdoor recreation  Public health  Adult obesity  Body mass index (BMI)  
Creating a safe operating space for wetlands in a changing climate 期刊论文
FRONTIERS IN ECOLOGY AND THE ENVIRONMENT, 2017, 15 (2)
作者:  Green, Andy J.;  Alcorlo, Paloma;  Peeters, Edwin T. H. M.;  Morris, Edward P.;  Espinar, Jose L.;  Angel Bravo-Utrera, Miguel;  Bustamante, Javier;  Diaz-Delgado, Ricardo;  Koelmans, Albert A.;  Mateo, Rafael;  Mooij, Wolf M.;  Rodriguez-Rodriguez, Miguel;  van Nes, Egbert H.;  Scheffer, Marten
收藏  |  浏览/下载：8/0  |  提交时间：2019/04/09