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Understanding and managing the interactive impacts of growth in urban land use and climate change on freshwater biota: A case study using the platypus (Ornithorhynchus anatinus) 期刊论文
Global Change Biology, 2021
作者:  Rhys A. Coleman;  Yung En Chee;  Nick R. Bond;  Andrew Weeks;  Josh Griffiths;  Melody Serena;  Geoff A. Williams;  Christopher J. Walsh
收藏  |  浏览/下载:10/0  |  提交时间:2022/01/14
Landmarks of human embryonic development inscribed in somatic mutations 期刊论文
Science, 2021
作者:  Sara Bizzotto;  Yanmei Dou;  Javier Ganz;  Ryan N. Doan;  Minseok Kwon;  Craig L. Bohrson;  Sonia N. Kim;  Taejeong Bae;  Alexej Abyzov;  NIMH Brain Somatic Mosaicism Network†;  Peter J. Park;  Christopher A. Walsh
收藏  |  浏览/下载:12/0  |  提交时间:2021/03/29
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:23/0  |  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.


  
Emissions of trace gases from Australian temperate forest fires: emission factors and dependence on modified combustion efficiency 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2018, 18 (5) : 3717-3735
作者:  Guerette, Elise-Andree;  Paton-Walsh, Clare;  Desservettaz, Maximilien;  Smith, Thomas E. L.;  Volkova, Liubov;  Weston, Christopher J.;  Meyer, Carl P.
收藏  |  浏览/下载:5/0  |  提交时间:2019/04/09
Aging and neurodegeneration are associated with increased mutations in single human neurons 期刊论文
SCIENCE, 2018, 359 (6375) : 555-558
作者:  Lodato, Michael A.;  Rodin, Rachel E.;  Bohrson, Craig L.;  Coulter, Michael E.;  Barton, Alison R.;  Kwon, Minseok;  Sherman, Maxwell A.;  Vitzthum, Carl M.;  Luquette, Lovelace J.;  Yandava, Chandri N.;  Yang, Pengwei;  Chittenden, Thomas W.;  Hatem, Nicole E.;  Ryu, Steven C.;  Woodworth, Mollie B.;  Park, Peter J.;  Walsh, Christopher A.
收藏  |  浏览/下载:7/0  |  提交时间:2019/11/27
Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network 期刊论文
SCIENCE, 2017, 356 (6336)
作者:  McConnell, Michael J.;  Moran, John V.;  Abyzov, Alexej;  Akbarian, Schahram;  Bae, Taejeong;  Cortes-Ciriano, Isidro;  Erwin, Jennifer A.;  Fasching, Liana;  Flasch, Diane A.;  Freed, Donald;  Ganz, Javier;  Jaffe, Andrew E.;  Kwan, Kenneth Y.;  Kwon, Minseok;  Lodato, Michael A.;  Mills, Ryan E.;  Paquola, Apua C. M.;  Rodin, Rachel E.;  Rosenbluh, Chaggai;  Sestan, Nenad;  Sherman, Maxwell A.;  Shin, Joo Heon;  Song, Saera;  Straub, Richard E.;  Thorpe, Jeremy;  Weinberger, Daniel R.;  Urban, Alexander E.;  Zhou, Bo;  Gage, Fred H.;  Lehner, Thomas;  Senthil, Geetha;  Walsh, Christopher A.;  Chess, Andrew;  Courchesne, Eric;  Gleeson, Joseph G.;  Kidd, Jeffrey M.;  Park, Peter J.;  Pevsner, Jonathan;  Vaccarino, Flora M.
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27