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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.


  
Alternatives to genetic affinity as a context for within-species response to climate 期刊论文
NATURE CLIMATE CHANGE, 2019, 9 (10) : 787-+
作者:  Smith, Adam B.;  Beever, Erik A.;  Kessler, Aimee E.;  Johnston, Aaron N.;  Ray, Chris;  Epps, Clinton W.;  Lanier, Hayley C.;  Klinger, Rob C.;  Rodhouse, Thomas J.;  Varner, Johanna;  Perrine, John D.;  Seglund, Amy;  Hall, L. Embere;  Galbreath, Kurt;  MacGlover, Chris;  Billman, Peter;  Blatz, Gretchen;  Brewer, Jason;  Vardaro, Jessica Castillo;  Chalfoun, Anna D.;  Collins, Gail;  Craighead, April;  Curlis, Chris;  Daly, Christopher;  Doak, Daniel F.;  East, Mitch;  Edwards, Mark;  Erb, Liesl;  Ernest, Kristina A.;  Fauver, Brian;  Foresman, Kerry R.;  Goehring, Ken;  Hagar, Joan;  Hayes, Charles L.;  Henry, Philippe;  Hersey, Kimberly;  Hilty, Shannon L.;  Jacobson, Jim;  Jeffress, Mackenzie R.;  Manning, Tom;  Masching, Amy;  Maxell, Bryce;  McCollough, Rayo;  McFarland, Corrie;  Miskow, Eric;  Morelli, Toni Lyn;  Moyer-Horner, Lucas;  Mueller, Megan;  Nugent, Martin;  Pratt, Beth;  Rasmussen-Flores, Mary;  Rickman, Tom H.;  Robison, Hillary;  Rodriguez, Arthur;  Rowe, Karen;  Rowe, Kevin;  Russello, Michael A.;  Saab, Vicki;  Schmidt, Angie;  Stewart, Joseph A. E.;  Stuart, James N.;  Svancara, Leona K.;  Thompson, Will;  Timmins, Julie;  Treinish, Gregg;  Waterhouse, Matthew D.;  Westover, Marie L.;  Wilkening, Jennifer;  Yandow, Leah
收藏  |  浏览/下载：13/0  |  提交时间：2019/11/27
Defining a spectrum of integrative trait-based vegetation canopy structural types 期刊论文
ECOLOGY LETTERS, 2019
作者:  Fahey, Robert T.;  Atkins, Jeff W.;  Gough, Christopher M.;  Hardiman, Brady S.;  Nave, Lucas E.;  Tallant, Jason M.;  Nadehoffer, Knute J.;  Vogel, Christoph;  Scheuermann, Cynthia M.;  Stuart-Haentjens, Ellen;  Haber, Lisa T.;  Fotis, Alexander T.;  Ricarts, Raleigh;  Curtis, Peter S.
收藏  |  浏览/下载：13/0  |  提交时间：2019/11/27
Canopy  complexity  lidar  structure  traits  
The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight 期刊论文
SCIENCE, 2019, 364 (6436) : 144-+
作者:  Garrett-Bakelman, Francine E.;  Darshi, Manjula;  Green, Stefan J.;  Gur, Ruben C.;  Lin, Ling;  Macias, Brandon R.;  McKenna, Miles J.;  Meydan, Cem;  Mishra, Tejaswini;  Nasrini, Jad;  Piening, Brian D.;  Rizzardi, Lindsay F.;  Sharma, Kumar;  Siamwala, Jamila H.;  Taylor, Lynn;  Vitaterna, Martha Hotz;  Afkarian, Maryam;  Afshinnekoo, Ebrahim;  Ahadi, Sara;  Ambati, Aditya;  Arya, Maneesh;  Bezdan, Daniela;  Callahan, Colin M.;  Chen, Songjie;  Choi, Augustine M. K.;  Chlipala, George E.;  Contrepois, Kevin;  Covington, Marisa;  Crucian, Brian E.;  De Vivo, Immaculata;  Dinges, David F.;  Ebert, Douglas J.;  Feinberg, Jason I.;  Gandara, Jorge A.;  George, Kerry A.;  Goutsias, John;  Grills, George S.;  Hargens, Alan R.;  Heer, Martina;  Hillary, Ryan P.;  Hoofnagle, Andrew N.;  Hook, Vivian Y. H.;  Jenkinson, Garrett;  Jiang, Peng;  Keshavarzian, Ali;  Laurie, Steven S.;  Lee-McMullen, Brittany;  Lumpkins, Sarah B.;  MacKay, Matthew;  Maienschein-Cline, Mark G.;  Melnick, Ari M.;  Moore, Tyler M.;  Nakahira, Kiichi;  Patel, Hemal H.;  Pietrzyk, Robert;  Rao, Varsha;  Saito, Rintaro;  Salins, Denis N.;  Schilling, Jan M.;  Sears, Dorothy D.;  Sheridan, Caroline K.;  Stenger, Michael B.;  Tryggvadottir, Rakel;  Urban, Alexander E.;  Vaisar, Tomas;  Van Espen, Benjamin;  Zhang, Jing;  Ziegler, Michael G.;  Zwart, Sara R.;  Charles, John B.;  Kundrot, Craig E.;  Scott, Graham B. I.;  Bailey, Susan M.;  Basner, Mathias;  Feinberg, Andrew P.;  Lee, Stuart M. C.;  Mason, Christopher E.;  Mignot, Emmanuel;  Rana, Brinda K.;  Smith, Scott M.;  Snyder, Michael P.;  Turek, Fred W.
收藏  |  浏览/下载：38/0  |  提交时间：2019/11/27
Pervasive iron limitation at subsurface chlorophyll maxima of the California Current 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (52) : 13300-13305
作者:  Hogle, Shane L.;  Dupont, Christopher L.;  Hopkinson, Brian M.;  King, Andrew L.;  Buck, Kristen N.;  Roe, Kelly L.;  Stuart, Rhona K.;  Allen, Andrew E.;  Mann, Elizabeth L.;  Johnson, Zackary I.;  Barbeau, Katherine A.
收藏  |  浏览/下载：11/0  |  提交时间：2019/11/27
nutrient limitation  iron  light  California Current  deep chlorophyll maximum  
A Directional Crack Damage Memory Effect in Sandstone Under True Triaxial Loading 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2018, 45 (14) : 6878-6886
作者:  Browning, John;  Meredith, Philip G.;  Stuart, Christopher;  Harland, Sophie;  Healy, David;  Mitchell, Thomas M.
收藏  |  浏览/下载：8/0  |  提交时间：2019/04/09
High-resolution comparative analysis of great ape genomes 期刊论文
SCIENCE, 2018, 360 (6393) : 1085-+
作者:  Kronenberg, Zev N.;  Fiddes, Ian T.;  Gordon, David;  Murali, Shwetha;  Cantsilieris, Stuart;  Meyerson, Olivia S.;  Underwood, Jason G.;  Nelson, Bradley J.;  Chaisson, Mark J. P.;  Dougherty, Max L.;  Munson, Katherine M.;  Hastie, Alex R.;  Diekhans, Mark;  Hormozdiari, Fereydoun;  Lorusso, Nicola;  Hoekzema, Kendra;  Qiu, Ruolan;  Clark, Karen;  Raja, Archana;  Welch, AnneMarie E.;  Sorensen, Melanie;  Baker, Carl;  Fulton, Robert S.;  Armstrong, Joel;  Graves-Lindsay, Tina A.;  Denli, Ahmet M.;  Hoppe, Emma R.;  Hsieh, PingHsun;  Hill, Christopher M.;  Pang, Andy Wing Chun;  Lee, Joyce;  Lam, Ernest T.;  Dutcher, Susan K.;  Gage, Fred H.;  Warren, Wesley C.;  Shendure, Jay;  Haussler, David;  Schneider, Valerie A.;  Cao, Han;  Ventura, Mario;  Wilson, Richard K.;  Paten, Benedict;  Pollen, Alex;  Eichler, Evan E.
收藏  |  浏览/下载：12/0  |  提交时间：2019/11/27
A Pan-African Convection-Permitting Regional Climate Simulation with the Met Office Unified Model: CP4-Africa 期刊论文
JOURNAL OF CLIMATE, 2018, 31 (9) : 3485-3508
作者:  Stratton, Rachel A.;  Senior, Catherine A.;  Vosper, Simon B.;  Folwell, Sonja S.;  Boutle, Ian A.;  Earnshaw, Paul D.;  Kendon, Elizabeth;  Lock, Adrian P.;  Malcolm, Andrew;  Manners, James;  Morcrette, Cyril J.;  Short, Christopher;  Stirling, Alison J.;  Taylor, Christopher M.;  Tucker, Simon;  Webster, Stuart;  Wilkinson, Jonathan M.
收藏  |  浏览/下载：11/0  |  提交时间：2019/04/09
Intermediaries' perspectives on the public's role in the energy transitions needed to deliver UK climate change policy goals 期刊论文
ENERGY POLICY, 2018, 116: 267-276
作者:  Shaw, Christopher;  Hurth, Victoria;  Capstick, Stuart;  Cox, Emily
收藏  |  浏览/下载：5/0  |  提交时间：2019/04/09
Public  Policy  Intermediaries  Engagement  Participation  Targets  
Volatile chemical products emerging as largest petrochemical source of urban organic emissions 期刊论文
SCIENCE, 2018, 359 (6377) : 760-764
作者:  McDonald, Brian C.;  de Gouw, Joost A.;  Gilman, Jessica B.;  Jathar, Shantanu H.;  Akherati, Ali;  Cappa, Christopher D.;  Jimenez, Jose L.;  Lee-Taylor, Julia;  Hayes, Patrick L.;  McKeen, Stuart A.;  Cui, Yu Yan;  Kim, Si-Wan;  Gentner, Drew R.;  Isaacman-VanWertz, Gabriel;  Goldstein, Allen H.;  Harley, Robert A.;  Frost, Gregory J.;  Roberts, James M.;  Ryerson, Thomas B.;  Trainer, Michael
收藏  |  浏览/下载：13/0  |  提交时间：2019/11/27