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Monitoring global education inequality 期刊论文
NATURE, 2020, 580 (7805) : 591-592
作者:  Ledford, Heidi
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

Tools have been developed to project inequalities in education around the world to 2030. They reveal that overall inequality will decline, but that all world regions will fall short of achieving universal secondary education.


  
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.


  
Lipid carrier breaks barrier in Alzheimer's disease 期刊论文
NATURE, 2020, 581 (7806) : 31-32
作者:  Leon-Velarde Servetto, Fabiola Maria
收藏  |  浏览/下载:6/0  |  提交时间:2020/07/03

People who carry the gene variant APOE4 are at higher-than-average risk of developing Alzheimer'  s disease. It emerges that this variant is linked to defects in the blood-brain barrier and subsequent cognitive decline.


A link between APOE4 and breakdown of the blood-brain barrier.


  
Virological assessment of hospitalized patients with COVID-2019 期刊论文
NATURE, 2020
作者:  Kanarek, Naama;  Petrova, Boryana;  Sabatini, David M.
收藏  |  浏览/下载:46/0  |  提交时间:2020/07/03

Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.


Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019(1,2). Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses(3). This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung(2,4)  the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 2003(5). However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission(6-8). There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 x 10(8) RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.


  
Two conserved epigenetic regulators prevent healthy ageing 期刊论文
NATURE, 2020
作者:  Yoshida, Kenichi;  Gowers, Kate H. C.;  Lee-Six, Henry;  Chandrasekharan, Deepak P.;  Coorens, Tim;  Maughan, Elizabeth F.;  Beal, Kathryn;  Menzies, Andrew;  Millar, Fraser R.;  Anderson, Elizabeth;  Clarke, Sarah E.;  Pennycuick, Adam;  Thakrar, Ricky M.;  Butler, Colin R.;  Kakiuchi, Nobuyuki;  Hirano, Tomonori;  Hynds, Robert E.;  Stratton, Michael R.;  Martincorena, Inigo;  Janes, Sam M.;  Campbell, Peter J.
收藏  |  浏览/下载:35/0  |  提交时间:2020/07/03

It has long been assumed that lifespan and healthspan correlate strongly, yet the two can be clearly dissociated(1-6). Although there has been a global increase in human life expectancy, increasing longevity is rarely accompanied by an extended healthspan(4,7). Thus, understanding the origin of healthy behaviours in old people remains an important and challenging task. Here we report a conserved epigenetic mechanism underlying healthy ageing. Through genome-wide RNA-interference-based screening of genes that regulate behavioural deterioration in ageing Caenorhabditis elegans, we identify 59 genes as potential modulators of the rate of age-related behavioural deterioration. Among these modulators, we found that a neuronal epigenetic reader, BAZ-2, and a neuronal histone 3 lysine 9 methyltransferase, SET-6, accelerate behavioural deterioration in C. elegans by reducing mitochondrial function, repressing the expression of nuclear-encoded mitochondrial proteins. This mechanism is conserved in cultured mouse neurons and human cells. Examination of human databases(8,9) shows that expression of the human orthologues of these C. elegans regulators, BAZ2B and EHMT1, in the frontal cortex increases with age and correlates positively with the progression of Alzheimer'  s disease. Furthermore, ablation of Baz2b, the mouse orthologue of BAZ-2, attenuates age-dependent body-weight gain and prevents cognitive decline in ageing mice. Thus our genome-wide RNA-interference screen in C. elegans has unravelled conserved epigenetic negative regulators of ageing, suggesting possible ways to achieve healthy ageing.


Two epigenetic regulators-identified in an RNA interference screen in Caenhorhabditis elegans, and conserved in mammals-diminish mitochondrial function and accelerate the age-related deterioration of behaviour.


  
A simple dynamic model explains the diversity of island birds worldwide 期刊论文
NATURE, 2020
作者:  Li, Junxue;  Wilson, C. Blake;  Cheng, Ran;  Lohmann, Mark;  Kavand, Marzieh;  Yuan, Wei;  Aldosary, Mohammed;  Agladze, Nikolay;  Wei, Peng;  Sherwin, Mark S.;  Shi, Jing
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

Colonization, speciation and extinction are dynamic processes that influence global patterns of species richness(1-6). Island biogeography theory predicts that the contribution of these processes to the accumulation of species diversity depends on the area and isolation of the island(7,8). Notably, there has been no robust global test of this prediction for islands where speciation cannot be ignored(9), because neither the appropriate data nor the analytical tools have been available. Here we address both deficiencies to reveal, for island birds, the empirical shape of the general relationships that determine how colonization, extinction and speciation rates co-vary with the area and isolation of islands. We compiled a global molecular phylogenetic dataset of birds on islands, based on the terrestrial avifaunas of 41 oceanic archipelagos worldwide (including 596 avian taxa), and applied a new analysis method to estimate the sensitivity of island-specific rates of colonization, speciation and extinction to island features (area and isolation). Our model predicts-with high explanatory power-several global relationships. We found a decline in colonization with isolation, a decline in extinction with area and an increase in speciation with area and isolation. Combining the theoretical foundations of island biogeography(7,8) with the temporal information contained in molecular phylogenies(10) proves a powerful approach to reveal the fundamental relationships that govern variation in biodiversity across the planet.


Using a global molecular phylogenetic dataset of birds on islands, the sensitivity of island-specific rates of colonization, speciation and extinction to island features (area and isolation) is estimated.


  
The effect of prescribed fire on Biscogniauxia infection and delta C-13 in an upland oak-pine forest 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2019, 451
作者:  Freeman, Alissa J.;  Hammond, William M.;  Dee, Justin R.;  Cobb, Richard C.;  Marek, Stephen M.;  Adams, Henry D.
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27
Prescribed burning  Fire suppression  Biscogniauxia  Oak decline  Carbon stable isotope composition  Oak health  Thinning  Hypoxylon  
Integration of WorldView-2 and airborne laser scanning data to classify defoliation levels in Quercus ilex L. Dehesas affected by root rot mortality: Management implications 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2019, 451
作者:  Navarro-Cerrillo, Rafael M.;  Varo-Martinez, Ma Angeles;  Acosta, Cristina;  Palacios Rodriguez, Guillermo;  Sanchez-Cuesta, Rafael;  Gomez, Francisco J. Ruiz
收藏  |  浏览/下载:15/0  |  提交时间:2019/11/27
Dehesas forest type  Holm oak decline  Defoliation  Predictor remote sensing datasets  Segmentation  Random forest  
Temporal and spatial trends in marine carbon isotopes in the Arctic Ocean and implications for food web studies 期刊论文
GLOBAL CHANGE BIOLOGY, 2019
作者:  de la Vega, Camille;  Jeffreys, Rachel M.;  Tuerena, Robyn;  Ganeshram, Raja;  Mahaffey, Claire
收藏  |  浏览/下载:8/0  |  提交时间:2019/11/27
base of the food web  dissolved inorganic carbon  isoscape  marine mammals  particulate organic matter  sea ice decline  Suess effect  delta C-13  
Region-wide mass mortality of Japanese oak due to ambrosia beetle infestation: Mortality factors and change in oak abundance 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2019, 449
作者:  Nakajima, Haruki
收藏  |  浏览/下载:7/0  |  提交时间:2019/11/27
Japanese oak wilt disease  Oak decline  Elevation-dependent mortality  Abandoned coppice forest  Platypus quercivorus  Quercus crispula