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Accurate prediction of protein structures and interactions using a three-track neural network 期刊论文
Science, 2021
作者:  Minkyung Baek;  Frank DiMaio;  Ivan Anishchenko;  Justas Dauparas;  Sergey Ovchinnikov;  Gyu Rie Lee;  Jue Wang;  Qian Cong;  Lisa N. Kinch;  R. Dustin Schaeffer;  Claudia Millán;  Hahnbeom Park;  Carson Adams;  Caleb R. Glassman;  Andy DeGiovanni;  Jose H. Pereira;  Andria V. Rodrigues;  Alberdina A. van Dijk;  Ana C. Ebrecht;  Diederik J. Opperman;  Theo Sagmeister;  Christoph Buhlheller;  Tea Pavkov-Keller;  Manoj K. Rathinaswamy;  Udit Dalwadi;  Calvin K. Yip;  John E. Burke;  K. Christopher Garcia;  Nick V. Grishin;  Paul D. Adams;  Randy J. Read;  David Baker
收藏  |  浏览/下载:19/0  |  提交时间:2021/08/25
Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings 期刊论文
Science, 2021
作者:  Nicholas A. Steinmetz;  Cagatay Aydin;  Anna Lebedeva;  Michael Okun;  Marius Pachitariu;  Marius Bauza;  Maxime Beau;  Jai Bhagat;  Claudia Böhm;  Martijn Broux;  Susu Chen;  Jennifer Colonell;  Richard J. Gardner;  Bill Karsh;  Fabian Kloosterman;  Dimitar Kostadinov;  Carolina Mora-Lopez;  John O’Callaghan;  Junchol Park;  Jan Putzeys;  Britton Sauerbrei;  Rik J. J. van Daal;  Abraham Z. Vollan;  Shiwei Wang;  Marleen Welkenhuysen;  Zhiwen Ye;  Joshua T. Dudman;  Barundeb Dutta;  Adam W. Hantman;  Kenneth D. Harris;  Albert K. Lee;  Edvard I. Moser;  John O’Keefe;  Alfonso Renart;  Karel Svoboda;  Michael Häusser;  Sebastian Haesler;  Matteo Carandini;  Timothy D. Harris
收藏  |  浏览/下载:14/0  |  提交时间:2021/04/20
Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events 期刊论文
Science, 2021
作者:  Jacob E. Lemieux;  Katherine J. Siddle;  Bennett M. Shaw;  Christine Loreth;  Stephen F. Schaffner;  Adrianne Gladden-Young;  Gordon Adams;  Timelia Fink;  Christopher H. Tomkins-Tinch;  Lydia A. Krasilnikova;  Katherine C. DeRuff;  Melissa Rudy;  Matthew R. Bauer;  Kim A. Lagerborg;  Erica Normandin;  Sinéad B. Chapman;  Steven K. Reilly;  Melis N. Anahtar;  Aaron E. Lin;  Amber Carter;  Cameron Myhrvold;  Molly E. Kemball;  Sushma Chaluvadi;  Caroline Cusick;  Katelyn Flowers;  Anna Neumann;  Felecia Cerrato;  Maha Farhat;  Damien Slater;  Jason B. Harris;  John A. Branda;  David Hooper;  Jessie M. Gaeta;  Travis P. Baggett;  James O’Connell;  Andreas Gnirke;  Tami D. Lieberman;  Anthony Philippakis;  Meagan Burns;  Catherine M. Brown;  Jeremy Luban;  Edward T. Ryan;  Sarah E. Turbett;  Regina C. LaRocque;  William P. Hanage;  Glen R. Gallagher;  Lawrence C. Madoff;  Sandra Smole;  Virginia M. Pierce;  Eric Rosenberg;  Pardis C. Sabeti;  Daniel J. Park;  Bronwyn L. MacInnis
收藏  |  浏览/下载:18/0  |  提交时间:2021/02/17
Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms 期刊论文
Science, 2020
作者:  David E. Gordon;  Joseph Hiatt;  Mehdi Bouhaddou;  Veronica V. Rezelj;  Svenja Ulferts;  Hannes Braberg;  Alexander S. Jureka;  Kirsten Obernier;  Jeffrey Z. Guo;  Jyoti Batra;  Robyn M. Kaake;  Andrew R. Weckstein;  Tristan W. Owens;  Meghna Gupta;  Sergei Pourmal;  Erron W. Titus;  Merve Cakir;  Margaret Soucheray;  Michael McGregor;  Zeynep Cakir;  Gwendolyn Jang;  Matthew J. O’Meara;  Tia A. Tummino;  Ziyang Zhang;  Helene Foussard;  Ajda Rojc;  Yuan Zhou;  Dmitry Kuchenov;  Ruth Hüttenhain;  Jiewei Xu;  Manon Eckhardt;  Danielle L. Swaney;  Jacqueline M. Fabius;  Manisha Ummadi;  Beril Tutuncuoglu;  Ujjwal Rathore;  Maya Modak;  Paige Haas;  Kelsey M. Haas;  Zun Zar Chi Naing;  Ernst H. Pulido;  Ying Shi;  Inigo Barrio-Hernandez;  Danish Memon;  Eirini Petsalaki;  Alistair Dunham;  Miguel Correa Marrero;  David Burke;  Cassandra Koh;  Thomas Vallet;  Jesus A. Silvas;  Caleigh M. Azumaya;  Christian Billesbølle;  Axel F. Brilot;  Melody G. Campbell;  Amy Diallo;  Miles Sasha Dickinson;  Devan Diwanji;  Nadia Herrera;  Nick Hoppe;  Huong T. Kratochvil;  Yanxin Liu;  Gregory E. Merz;  Michelle Moritz;  Henry C. Nguyen;  Carlos Nowotny;  Cristina Puchades;  Alexandrea N. Rizo;  Ursula Schulze-Gahmen;  Amber M. Smith;  Ming Sun;  Iris D. Young;  Jianhua Zhao;  Daniel Asarnow;  Justin Biel;  Alisa Bowen;  Julian R. Braxton;  Jen Chen;  Cynthia M. Chio;  Un Seng Chio;  Ishan Deshpande;  Loan Doan;  Bryan Faust;  Sebastian Flores;  Mingliang Jin;  Kate Kim;  Victor L. Lam;  Fei Li;  Junrui Li;  Yen-Li Li;  Yang Li;  Xi Liu;  Megan Lo;  Kyle E. Lopez;  Arthur A. Melo;  Frank R. Moss;  Phuong Nguyen;  Joana Paulino;  Komal Ishwar Pawar;  Jessica K. Peters;  Thomas H. Pospiech;  Maliheh Safari;  Smriti Sangwan;  Kaitlin Schaefer;  Paul V. Thomas;  Aye C. Thwin;  Raphael Trenker;  Eric Tse;  Tsz Kin Martin Tsui;  Feng Wang;  Natalie Whitis;  Zanlin Yu;  Kaihua Zhang;  Yang Zhang;  Fengbo Zhou;  Daniel Saltzberg;  QCRG Structural Biology Consortium12†;  Anthony J. Hodder;  Amber S. Shun-Shion;  Daniel M. Williams;  Kris M. White;  Romel Rosales;  Thomas Kehrer;  Lisa Miorin;  Elena Moreno;  Arvind H. Patel;  Suzannah Rihn;  Mir M. Khalid;  Albert Vallejo-Gracia;  Parinaz Fozouni;  Camille R. Simoneau;  Theodore L. Roth;  David Wu;  Mohd Anisul Karim;  Maya Ghoussaini;  Ian Dunham;  Francesco Berardi;  Sebastian Weigang;  Maxime Chazal;  Jisoo Park;  James Logue;  Marisa McGrath;  Stuart Weston;  Robert Haupt;  C. James Hastie;  Matthew Elliott;  Fiona Brown;  Kerry A. Burness;  Elaine Reid;  Mark Dorward;  Clare Johnson;  Stuart G. Wilkinson;  Anna Geyer;  Daniel M. Giesel;  Carla Baillie;  Samantha Raggett;  Hannah Leech;  Rachel Toth;  Nicola Goodman;  Kathleen C. Keough;  Abigail L. Lind;  Zoonomia Consortium‡;  Reyna J. Klesh;  Kafi R. Hemphill;  Jared Carlson-Stevermer;  Jennifer Oki;  Kevin Holden;  Travis Maures;  Katherine S. Pollard;  Andrej Sali;  David A. Agard;  Yifan Cheng;  James S. Fraser;  Adam Frost;  Natalia Jura;  Tanja Kortemme;  Aashish Manglik;  Daniel R. Southworth;  Robert M. Stroud;  Dario R. Alessi;  Paul Davies;  Matthew B. Frieman;  Trey Ideker;  Carmen Abate;  Nolwenn Jouvenet;  Georg Kochs;  Brian Shoichet;  Melanie Ott;  Massimo Palmarini;  Kevan M. Shokat;  Adolfo García-Sastre;  Jeremy A. Rassen;  Robert Grosse;  Oren S. Rosenberg;  Kliment A. Verba;  Christopher F. Basler;  Marco Vignuzzi;  Andrew A. Peden;  Pedro Beltrao;  Nevan J. Krogan
收藏  |  浏览/下载:27/0  |  提交时间:2020/12/07
The N-glycome regulates the endothelial-to-hematopoietic transition 期刊论文
Science, 2020
作者:  Dionna M. Kasper;  Jared Hintzen;  Yinyu Wu;  Joey J. Ghersi;  Hanna K. Mandl;  Kevin E. Salinas;  William Armero;  Zhiheng He;  Ying Sheng;  Yixuan Xie;  Daniel W. Heindel;  Eon Joo Park;  William C. Sessa;  Lara K. Mahal;  Carlito Lebrilla;  Karen K. Hirschi;  Stefania Nicoli
收藏  |  浏览/下载:9/0  |  提交时间:2020/12/07
Comment on “Ancient origins of allosteric activation in a Ser-Thr kinase” 期刊论文
Science, 2020
作者:  Yeonwoo Park;  Jaeda E. J. Patton;  Georg K. A. Hochberg;  Joseph W. Thornton
收藏  |  浏览/下载:5/0  |  提交时间:2020/11/24
Structure-based design of prefusion-stabilized SARS-CoV-2 spikes 期刊论文
Science, 2020
作者:  Ching-Lin Hsieh;  Jory A. Goldsmith;  Jeffrey M. Schaub;  Andrea M. DiVenere;  Hung-Che Kuo;  Kamyab Javanmardi;  Kevin C. Le;  Daniel Wrapp;  Alison G. Lee;  Yutong Liu;  Chia-Wei Chou;  Patrick O. Byrne;  Christy K. Hjorth;  Nicole V. Johnson;  John Ludes-Meyers;  Annalee W. Nguyen;  Juyeon Park;  Nianshuang Wang;  Dzifa Amengor;  Jason J. Lavinder;  Gregory C. Ippolito;  Jennifer A. Maynard;  Ilya J. Finkelstein;  Jason S. McLellan
收藏  |  浏览/下载:15/0  |  提交时间:2020/09/22
Transcriptomic signatures across human tissues identify functional rare genetic variation 期刊论文
Science, 2020
作者:  Nicole M. Ferraro;  Benjamin J. Strober;  Jonah Einson;  Nathan S. Abell;  Francois Aguet;  Alvaro N. Barbeira;  Margot Brandt;  Maja Bucan;  Stephane E. Castel;  Joe R. Davis;  Emily Greenwald;  Gaelen T. Hess;  Austin T. Hilliard;  Rachel L. Kember;  Bence Kotis;  YoSon Park;  Gina Peloso;  Shweta Ramdas;  Alexandra J. Scott;  Craig Smail;  Emily K. Tsang;  Seyedeh M. Zekavat;  Marcello Ziosi;  Aradhana;  TOPMed Lipids Working Group;  Kristin G. Ardlie;  Themistocles L. Assimes;  Michael C. Bassik;  Christopher D. Brown;  Adolfo Correa;  Ira Hall;  Hae Kyung Im;  Xin Li;  Pradeep Natarajan;  GTEx Consortium;  Tuuli Lappalainen;  Pejman Mohammadi;  Stephen B. Montgomery;  Alexis Battle
收藏  |  浏览/下载:12/0  |  提交时间:2020/09/14
Simultaneous observation of nuclear and electronic dynamics by ultrafast electron diffraction 期刊论文
Science, 2020
作者:  Jie Yang;  Xiaolei Zhu;  J. Pedro F. Nunes;  Jimmy K. Yu;  Robert M. Parrish;  Thomas J. A. Wolf;  Martin Centurion;  Markus Gühr;  Renkai Li;  Yusong Liu;  Bryan Moore;  Mario Niebuhr;  Suji Park;  Xiaozhe Shen;  Stephen Weathersby;  Thomas Weinacht;  Todd J. Martinez;  Xijie Wang
收藏  |  浏览/下载:14/0  |  提交时间:2020/05/25
APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline 期刊论文
NATURE, 2020, 581 (7806) : 70-+
作者:  Doherty, Tiarnan A. S.;  Winchester, Andrew J.;  Macpherson, Stuart;  Johnstone, Duncan N.;  Pareek, Vivek;  Tennyson, Elizabeth M.;  Kosar, Sofiia;  Kosasih, Felix U.;  Anaya, Miguel;  Abdi-Jalebi, Mojtaba;  Andaji-Garmaroudi, Zahra;  Wong, E. Laine;  Madeo, Julien;  Chiang, Yu-Hsien;  Park, Ji-Sang;  Jung, Young-Kwang;  Petoukhoff, Christopher E.;  Divitini, Giorgio;  Man, Michael K. L.;  Ducati, Caterina;  Walsh, Aron;  Midgley, Paul A.;  Dani, Keshav M.;  Stranks, Samuel D.
收藏  |  浏览/下载:25/0  |  提交时间:2020/07/03

Breakdown of the blood-brain barrier in individuals carrying the epsilon 4 allele of the APOE gene, but not the epsilon 3 allele, increases with and predicts cognitive impairment and is independent of amyloid beta or tau pathology.


Vascular contributions to dementia and Alzheimer'  s disease are increasingly recognized(1-6). Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction(7), including the early clinical stages of Alzheimer'  s disease(5,8-10). The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer'  s disease(11-14), leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes(15-19), which maintain BBB integrity(20-22). It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the epsilon 3/epsilon 4 or epsilon 4/epsilon 4 alleles) are distinguished from those without APOE4 (epsilon 3/epsilon 3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-beta or tau pathology measured in cerebrospinal fluid or by positron emission tomography(23). High baseline levels of the BBB pericyte injury biomarker soluble PDGFR beta(7,8) in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-beta and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway(19) in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer'  s disease pathology, and might be a therapeutic target in APOE4 carriers.