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Evidence confirms an anthropic origin of Amazonian Dark Earths 期刊论文
Nature Communications, 2022
作者:  Lombardo, Umberto;  Arroyo-Kalin, Manuel;  Schmidt, Morgan;  Huisman, Hans;  Lima, Helena P.;  de Paula Moraes, Claide;  Neves, Eduardo G.;  Clement, Charles R.;  Aires da Fonseca, Joã;  o;  de Almeida, Fernando Ozorio;  Vieira Alho, Carlos Francisco Brazã;  o;  Bronk Ramsey, Christopher;  Brown, George G.;  Cavallini, Marta S.;  Lima da Costa, Marcondes;  Cunha, Luí;  s;  dos Anjos, Lú;  cia Helena C.;  Denevan, William M.;  Fausto, Carlos;  Fernandes Caromano, Caroline;  Fontana, Ademir;  Franchetto, Bruna;  Glaser, Bruno;  Heckenberger, Michael J.;  Hecht, Susanna;  Honorato, Vinicius;  Jarosch, Klaus A.;  Braga Junqueira, André;  Kater, Thiago;  Tamanaha, Eduardo K.;  Kuyper, Thomas W.;  Lehmann, Johannes;  Madella, Marco;  Maezumi, S. Yoshi;  Matthews Cascon, Leandro;  Mayle, Francis E.;  McKey, Doyle;  Moraes, Bruno;  Morcote-Rí;  os, Gaspar;  Palheta Barbosa, Carlos A.;  Magalhã;  es, Marcos Pereira;  Prestes-Carneiro, Gabriela;  Pugliese, Francisco;  Pupim, Fabiano N.;  Raczka, Marco F.;  Py-Daniel, Anne Rapp;  Riris, Philip;  Cigaran da Rocha, Bruna;  Rodrigues, Leonor;  Rostain, Sté;  phen;  Macedo, Rodrigo Santana;  Shock, Myrtle P.;  Sprafke, Tobias;  Stampanoni Bassi, Filippo;  Valle, Raoni;  Vidal-Torrado, Pablo;  Villagrá;  n, Ximena S.;  Watling, Jennifer;  Weber, Sadie L.;  Teixeira, Wenceslau Geraldes
收藏  |  浏览/下载：21/0  |  提交时间：2022/06/24
Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation 期刊论文
NATURE, 2020, 580 (7803) : 391-+
作者:  Zhang, Zhibin;  Zhang, Ying;  Xia, Shiyu;  Kong, Qing;  Li, Shunying;  Liu, Xing;  Junqueira, Caroline;  Meza-Sosa, Karla F.;  Mok, Temy Mo Yin;  Ansara, James;  Sengupta, Satyaki;  Yao, Yandan;  Wu, Hao;  Lieberman, Judy
收藏  |  浏览/下载：13/0  |  提交时间：2020/07/03

The biological function of Z-DNA and Z-RNA, nucleic acid structures with a left-handed double helix, is poorly understood(1-3). Z-DNA-binding protein 1 (ZBP1  also known as DAI or DLM-1) is a nucleic acid sensor that contains two Z alpha domains that bind Z-DNA(4,5) and Z-RNA(6-8). ZBP1 mediates host defence against some viruses(6,7,9-14) by sensing viral nucleic acids(6,7,10). RIPK1 deficiency, or mutation of its RIP homotypic interaction motif (RHIM), triggers ZBP1-dependent necroptosis and inflammation in mice(15,16). However, the mechanisms that induce ZBP1 activation in the absence of viral infection remain unknown. Here we show that Z alpha-dependent sensing of endogenous ligands induces ZBP1-mediated perinatal lethality in mice expressing RIPK1 with mutated RHIM (Ripk1(mR/mR)), skin inflammation in mice with epidermis-specific RIPK1 deficiency (RIPK1(E-KO)) and colitis in mice with intestinal epithelial-specific FADD deficiency (FADD(IEC-KO)). Consistently, functional Z alpha domains were required for ZBP1-induced necroptosis in fibroblasts that were treated with caspase inhibitors or express RIPK1 with mutated RHIM. Inhibition of nuclear export triggered the Z alpha-dependent activation of RIPK3 in the nucleus resulting in cell death, which suggests that ZBP1 may recognize nuclear Z-form nucleic acids. We found that ZBP1 constitutively bound cellular double-stranded RNA in a Z alpha-dependent manner. Complementary reads derived from endogenous retroelements were detected in epidermal RNA, which suggests that double-stranded RNA derived from these retroelements may act as a Z alpha-domain ligand that triggers the activation of ZBP1. Collectively, our results provide evidence that the sensing of endogenous Z-form nucleic acids by ZBP1 triggers RIPK3-dependent necroptosis and inflammation, which could underlie the development of chronic inflammatory conditions-particularly in individuals with mutations in RIPK1 and CASP8(17-20).