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Subduction megathrust heterogeneity characterized from 3D seismic data 期刊论文
NATURE GEOSCIENCE, 2020, 13 (5)
作者:  Kirkpatrick, James D.;  Edwards, Joel H.;  Verdecchia, Alessandro;  Kluesner, Jared W.;  Harrington, Rebecca M.;  Silver, Eli A.
收藏  |  浏览/下载:9/0  |  提交时间:2020/05/13
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.


  
Earthquake slip surfaces identified by biomarker thermal maturity within the 2011 Tohoku-Oki earthquake fault zone 期刊论文
NATURE COMMUNICATIONS, 2020, 11 (1)
作者:  Rabinowitz, Hannah S.;  Savage, Heather M.;  Polissar, Pratigya J.;  Rowe, Christie D.;  Kirkpatrick, James D.
收藏  |  浏览/下载:6/0  |  提交时间:2020/05/13
Plan S: A threat to quality of science? 期刊论文
SCIENCE, 2019, 363 (6426) : 462-462
作者:  Spedding, Michael;  Barrett, James;  Morgan, Edward T.;  Vore, Mary;  Geraghty, Dominic;  Kirkpatrick, Carl;  Cascorbi, Ingolf
收藏  |  浏览/下载:3/0  |  提交时间:2019/11/27
Corrugated megathrust revealed offshore from Costa Rica (vol 11, pg 197, 2018) 期刊论文
NATURE GEOSCIENCE, 2018, 11 (5) : 375-375
作者:  Edwards, Joel H.;  Kluesner, Jared W.;  Silver, Eli A.;  Brodsky, Emily E.;  Brothers, Daniel S.;  Bangs, Nathan L.;  Kirkpatrick, James D.;  Wood, Ruby;  Okamoto, Kristina
收藏  |  浏览/下载:9/0  |  提交时间:2019/04/09
Corrugated megathrust revealed offshore from Costa Rica 期刊论文
NATURE GEOSCIENCE, 2018, 11 (3) : 197-+
作者:  Edwards, Joel H.;  Kluesner, Jared W.;  Silver, Eli A.;  Brodsky, Emily E.;  Brothers, Daniel S.;  Bangs, Nathan L.;  Kirkpatrick, James D.;  Wood, Ruby;  Okamoto, Kristina
收藏  |  浏览/下载:9/0  |  提交时间:2019/04/09
Conventional intensive logging promotes loss of organic carbon from the mineral soil 期刊论文
GLOBAL CHANGE BIOLOGY, 2017, 23 (1) : 43476
作者:  Dean, Christopher;  Kirkpatrick, James B.;  Friedland, Andrew J.
收藏  |  浏览/下载:4/0  |  提交时间:2019/04/09
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