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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).


  
Loopy Levy flights enhance tracer diffusion in active suspensions 期刊论文
NATURE, 2020, 579 (7799) : 364-+
作者:  Hu, Bo;  Jin, Chengcheng;  Zeng, Xing;  Resch, Jon M.;  Jedrychowski, Mark P.;  Yang, Zongfang;  Desai, Bhavna N.;  Banks, Alexander S.;  Lowell, Bradford B.;  Mathis, Diane;  Spiegelman, Bruce M.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

A theoretical framework describing the hydrodynamic interactions between a passive particle and an active medium in out-of-equilibrium systems predicts long-range Levy flights for the diffusing particle driven by the density of the active component.


Brownian motion is widely used as a model of diffusion in equilibrium media throughout the physical, chemical and biological sciences. However, many real-world systems are intrinsically out of equilibrium owing to energy-dissipating active processes underlying their mechanical and dynamical features(1). The diffusion process followed by a passive tracer in prototypical active media, such as suspensions of active colloids or swimming microorganisms(2), differs considerably from Brownian motion, as revealed by a greatly enhanced diffusion coefficient(3-10) and non-Gaussian statistics of the tracer displacements(6,9,10). Although these characteristic features have been extensively observed experimentally, there is so far no comprehensive theory explaining how they emerge from the microscopic dynamics of the system. Here we develop a theoretical framework to model the hydrodynamic interactions between the tracer and the active swimmers, which shows that the tracer follows a non-Markovian coloured Poisson process that accounts for all empirical observations. The theory predicts a long-lived Levy flight regime(11) of the loopy tracer motion with a non-monotonic crossover between two different power-law exponents. The duration of this regime can be tuned by the swimmer density, suggesting that the optimal foraging strategy of swimming microorganisms might depend crucially on their density in order to exploit the Levy flights of nutrients(12). Our framework can be applied to address important theoretical questions, such as the thermodynamics of active systems(13), and practical ones, such as the interaction of swimming microorganisms with nutrients and other small particles(14) (for example, degraded plastic) and the design of artificial nanoscale machines(15).


  
Clades of huge phages from across Earth's ecosystems 期刊论文
NATURE, 2020, 578 (7795) : 425-+
作者:  Zhang, Bing;  Ma, Sai;  Rachmin, Inbal;  He, Megan;  Baral, Pankaj;  Choi, Sekyu;  Goncalves, William A.;  Shwartz, Yulia;  Fast, Eva M.;  Su, Yiqun;  Zon, Leonard I.;  Regev, Aviv;  Buenrostro, Jason D.;  Cunha, Thiago M.;  Chiu, Isaac M.
收藏  |  浏览/下载:37/0  |  提交时间:2020/07/03

Bacteriophages typically have small genomes(1) and depend on their bacterial hosts for replication(2). Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth'  s ecosystems.


Genomic analyses of major clades of huge phages sampled from across Earth'  s ecosystems show that they have diverse genetic inventories, including a variety of CRISPR-Cas systems and translation-relevant genes.


  
Increasing nest predation will be insufficient to maintain polar bear body condition in the face of sea ice loss 期刊论文
GLOBAL CHANGE BIOLOGY, 2017, 23 (5)
作者:  Dey, Cody J.;  Richardson, Evan;  McGeachy, David;  Iverson, Samuel A.;  Gilchrist, Hugh G.;  Semeniuk, Christina A. D.
收藏  |  浏览/下载:5/0  |  提交时间:2019/04/09
agent-based model  Arctic  biological interaction  climate change  ecological forecast  foraging  individual based-model