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Premature mortality related to United States cross-state air pollution 期刊论文
NATURE, 2020, 578 (7794) : 261-+
作者:  Helmink, Beth A.;  Reddy, Sangeetha M.;  Gao, Jianjun;  Zhang, Shaojun;  Basar, Rafet;  Thakur, Rohit;  Yizhak, Keren;  Sade-Feldman, Moshe;  Blando, Jorge;  Han, Guangchun;  Gopalakrishnan, Vancheswaran;  Xi, Yuanxin;  Zhao, Hao;  Amaria, Rodabe N.;  Tawbi, Hussein A.;  Cogdill, Alex P.;  Liu, Wenbin;  LeBleu, Valerie S.;  Kugeratski, Fernanda G.;  Patel, Sapna;  Davies, Michael A.;  Hwu, Patrick;  Lee, Jeffrey E.;  Gershenwald, Jeffrey E.;  Lucci, Anthony;  Arora, Reetakshi;  Woodman, Scott;  Keung, Emily Z.;  Gaudreau, Pierre-Olivier;  Reuben, Alexandre;  Spencer, Christine N.;  Burton, Elizabeth M.;  Haydu, Lauren E.;  Lazar, Alexander J.;  Zapassodi, Roberta;  Hudgens, Courtney W.;  Ledesma, Deborah A.;  Ong, SuFey;  Bailey, Michael;  Warren, Sarah;  Rao, Disha;  Krijgsman, Oscar;  Rozeman, Elisa A.;  Peeper, Daniel;  Blank, Christian U.;  Schumacher, Ton N.;  Butterfield, Lisa H.;  Zelazowska, Monika A.;  McBride, Kevin M.;  Kalluri, Raghu;  Allison, James;  Petitprez, Florent;  Fridman, Wolf Herman;  Sautes-Fridman, Catherine;  Hacohen, Nir;  Rezvani, Katayoun;  Sharma, Padmanee;  Tetzlaff, Michael T.;  Wang, Linghua;  Wargo, Jennifer A.
收藏  |  浏览/下载:37/0  |  提交时间:2020/05/13

Outdoor air pollution adversely affects human health and is estimated to be responsible for five to ten per cent of the total annual premature mortality in the contiguous United States(1-3). Combustion emissions from a variety of sources, such as power generation or road traffic, make a large contribution to harmful air pollutants such as ozone and fine particulate matter (PM2.5)(4). Efforts to mitigate air pollution have focused mainly on the relationship between local emission sources and local air quality(2). Air quality can also be affected by distant emission sources, however, including emissions from neighbouring federal states(5,6). This cross-state exchange of pollution poses additional regulatory challenges. Here we quantify the exchange of air pollution among the contiguous United States, and assess its impact on premature mortality that is linked to increased human exposure to PM2.5 and ozone from seven emission sectors for 2005 to 2018. On average, we find that 41 to 53 per cent of air-quality-related premature mortality resulting from a state'  s emissions occurs outside that state. We also find variations in the cross-state contributions of different emission sectors and chemical species to premature mortality, and changes in these variations over time. Emissions from electric power generation have the greatest cross-state impacts as a fraction of their total impacts, whereas commercial/residential emissions have the smallest. However, reductions in emissions from electric power generation since 2005 have meant that, by 2018, cross-state premature mortality associated with the commercial/residential sector was twice that associated with power generation. In terms of the chemical species emitted, nitrogen oxides and sulfur dioxide emissions caused the most cross-state premature deaths in 2005, but by 2018 primary PM2.5 emissions led to cross-state premature deaths equal to three times those associated with sulfur dioxide emissions. These reported shifts in emission sectors and emission species that contribute to premature mortality may help to guide improvements to air quality in the contiguous United States.


  
Genomic basis for RNA alterations in cancer 期刊论文
NATURE, 2020, 578 (7793) : 129-+
作者:  Petitprez, Florent;  39;han
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

Transcript alterations often result from somatic changes in cancer genomes(1). Various forms of RNA alterations have been described in cancer, including overexpression(2), altered splicing(3) and gene fusions(4)  however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)(5). Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed '  bridged'  fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.