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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

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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.

California鈥檚 methane super-emitters 期刊论文
Nature, 2019, 575: 180-184
作者: Riley M. Duren; Andrew K. Thorpe; Kelsey T. Foster; Talha Rafiq; Francesca M. Hopkins; Vineet Yadav; Brian D. Bue; David R. Thompson; Stephen Conley; Nadia K. Colombi; Christian Frankenberg; Ian B. McCubbin; Michael L. Eastwood; Matthias Falk; Jorn D. Herner; Bart E. Croes; Robert O. Green; Charles E. Miller

收藏 | 浏览/下载：15/0 | 提交时间：2019/11/27

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

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

2012 Annual Site Environmental Report 科技报告
来源：US Department of Energy (DOE). 出版年： 2013
作者: Ratel K. M.; Pohlot, P.; Lee, R.; Williams, J.; Remien, J.; Green, T.; Paquette, D.; Dorsch, W.; Hooda, B.; Burke, J.

收藏 | 浏览/下载：1/0 | 提交时间：2019/04/05

2011 Site Environmental Report 科技报告
来源：US Department of Energy (DOE). 出版年： 2012
作者: Ratel K. M.; Pohlot, P.; Lee, R.; Williams, J.; Remien, J.; Green, T.; Paquette, D.; Dorsch, W.; Hooda, B.; Burke, J.

收藏 | 浏览/下载：0/0 | 提交时间：2019/04/05

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