GSTDTAP

浏览/检索结果: 共170条,第1-10条 帮助

限定条件                        
已选(0)清除 条数/页:   排序方式:
Last glacial atmospheric CO(2)decline due to widespread Pacific deep-water expansion 期刊论文
NATURE GEOSCIENCE, 2020
作者:  Yu, J.;  Menviel, L.;  Jin, Z. D.;  Anderson, R. F.;  Jian, Z.;  Piotrowski, A. M.;  Ma, X.;  Rohling, E. J.;  Zhang, F.;  Marino, G.;  McManus, J. F.
收藏  |  浏览/下载:12/0  |  提交时间:2020/08/09
Vertical profiles of droplet size distributions derived from cloud-side observations by the research scanning polarimeter: Tests on simulated data 期刊论文
ATMOSPHERIC RESEARCH, 2020, 239
作者:  Alexandrov, Mikhail D.;  Miller, Daniel J.;  Rajapakshe, Chamara;  Fridlind, Ann;  van Diedenhoven, Bastiaan;  Cairns, Brian;  Ackerman, Andrew S.;  Zhang, Zhibo
收藏  |  浏览/下载:12/0  |  提交时间:2020/08/18
Clouds  Remote sensing  Cloud droplet size  Vertical profile  Radiometry  Polarization  
Carbenium ion-mediated oligomerization of methylglyoxal for secondary organic aerosol formation 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (24) : 13294-13299
作者:  Ji, Yuemen;  Shi, Qiuju;  Li, Yixin;  An, Taicheng;  Zheng, Jun;  Peng, Jianfei;  Gao, Yanpeng;  Chen, Jiangyao;  Li, Guiying;  Wang, Yuan;  Zhang, Fang;  Zhang, Annie L.;  Zhao, Jiayun;  Molina, Mario J.;  Zhang, Renyi
收藏  |  浏览/下载:15/0  |  提交时间:2020/06/09
secondary organic aerosol  aqueous  oligomerization  brown carbon  cationic  
PM2.5 in Abuja, Nigeria: Chemical characterization, source apportionment, temporal variations, transport pathways and the health risks assessment 期刊论文
ATMOSPHERIC RESEARCH, 2020, 237
作者:  Sulaymon, Ishaq Dimeji;  Mei, Xiaodong;  Yang, Shujian;  Chen, Sumin;  Zhang, Yang;  Hopke, Philip K.;  Schauer, James J.;  Zhang, Yuanxun
收藏  |  浏览/下载:18/0  |  提交时间:2020/07/02
Source apportionment  Regional long-range transport  PMF  Heavy metals  Health risks  Abuja  
Improvement of aerosol activation/ice nucleation in a source-oriented WRF-Chem model to study a winter Storm in California 期刊论文
ATMOSPHERIC RESEARCH, 2020, 235
作者:  Lee, Hsiang-He;  Chen, Shu-Hua;  Kumar, Anikender;  Zhang, Hongliang;  Kleeman, Michael J.
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/02
A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1 期刊论文
NATURE, 2020, 577 (7788) : 109-+
作者:  Tao, Panfeng;  Sun, Jinqiao;  Wu, Zheming;  Wang, Shihao;  Wang, Jun;  Li, Wanjin;  Pan, Heling;  Bai, Renkui;  Zhang, Jiahui;  Wang, Ying;  Lee, Pui Y.;  Ying, Wenjing;  Zhou, Qinhua;  Hou, Jia;  Wang, Wenjie;  Sun, Bijun;  Yang, Mi;  Liu, Danru;  Fang, Ran;  Han, Huan;  Yang, Zhaohui;  Huang, Xin;  Li, Haibo;  Deuitch, Natalie;  Zhang, Yuan;  Dissanayake, Dilan;  Haude, Katrina;  McWalter, Kirsty;  Roadhouse, Chelsea;  MacKenzie, Jennifer J.;  Laxer, Ronald M.;  Aksentijevich, Ivona;  Yu, Xiaomin;  Wang, Xiaochuan;  Yuan, Junying;  Zhou, Qing
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways(1). Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development(2,3). However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomaldominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients'  peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts.


  
HBO1 is required for the maintenance of leukaemia stem cells 期刊论文
NATURE, 2020, 577 (7789) : 266-+
作者:  MacPherson, Laura;  Anokye, Juliana;  Yeung, Miriam M.;  Lam, Enid Y. N.;  Chan, Yih-Chih;  Weng, Chen-Fang;  Yeh, Paul;  Knezevic, Kathy;  Butler, Miriam S.;  Hoegl, Annabelle;  Chan, Kah-Lok;  Burr, Marian L.;  Gearing, Linden J.;  Willson, Tracy;  Liu, Joy;  Choi, Jarny;  Yang, Yuqing;  Bilardi, Rebecca A.;  Falk, Hendrik;  Nghi Nguyen;  Stupple, Paul A.;  Peat, Thomas S.;  Zhang, Ming;  de Silva, Melanie;  Carrasco-Pozo, Catalina;  Avery, Vicky M.;  Khoo, Poh Sim;  Dolezal, Olan;  Dennis, Matthew L.;  Nuttall, Stewart;  Surjadi, Regina;  Newman, Janet;  Ren, Bin;  Leaver, David J.;  Sun, Yuxin;  Baell, Jonathan B.;  Dovey, Oliver;  Vassiliou, George S.;  Grebien, Florian;  Dawson, Sarah-Jane;  Street, Ian P.;  Monahan, Brendon J.;  Burns, Christopher J.;  Choudhary, Chunaram;  Blewitt, Marnie E.;  Voss, Anne K.;  Thomas, Tim;  Dawson, Mark A.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, but most show only modest efficacy owing to an inability to effectively eradicate leukaemia stem cells (LSCs)(1). Here, to specifically identify novel dependencies in LSCs, we screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of LSCs. We identify the MYST acetyltransferase HBO1 (also known as KAT7 or MYST2) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance. Using CRISPR domain screening and quantitative mass spectrometry, we identified the histone acetyltransferase domain of HBO1 as being essential in the acetylation of histone H3 at K14. H3 acetylated at K14 (H3K14ac) facilitates the processivity of RNA polymerase II to maintain the high expression of key genes (including Hoxa9 and Hoxa10) that help to sustain the functional properties of LSCs. To leverage this dependency therapeutically, we developed a highly potent small-molecule inhibitor of HBO1 and demonstrate its mode of activity as a competitive analogue of acetyl-CoA. Inhibition of HBO1 phenocopied our genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients. These biological, structural and chemical insights into a therapeutic target in AML will enable the clinical translation of these findings.


  
Layered nanocomposites by shear-flow-induced alignment of nanosheets (vol 580, pg 210, 2020) 期刊论文
NATURE, 2020, 582 (7811) : E4-E4
作者:  Chen, Guorui;  Sharpe, Aaron L.;  Fox, Eli J.;  Zhang, Ya-Hui;  Wang, Shaoxin;  Jiang, Lili;  Lyu, Bosai;  Li, Hongyuan;  Watanabe, Kenji;  Taniguchi, Takashi;  Shi, Zhiwen;  Senthil, T.;  Goldhaber-Gordon, David;  Zhang, Yuanbo;  Wang, Feng
收藏  |  浏览/下载:31/0  |  提交时间:2020/07/03
Massively multiplexed nucleic acid detection with Cas13 期刊论文
NATURE, 2020, 582 (7811) : 277-+
作者:  Mahato, Biraj;  Kaya, Koray Dogan;  Fan, Yan;  Sumien, Nathalie;  Shetty, Ritu A.;  Zhang, Wei;  Davis, Delaney;  Mock, Thomas;  Batabyal, Subrata;  Ni, Aiguo;  Mohanty, Samarendra;  Han, Zongchao;  Farjo, Rafal;  Forster, Michael J.;  Swaroop, Anand;  Chavala, Sai H.
收藏  |  浏览/下载:62/0  |  提交时间:2020/07/03

CRISPR-based nucleic acid detection is used in a platform that can simultaneously detect 169 human-associated viruses in multiple samples, providing scalable, multiplexed pathogen detection aimed at routine surveillance for public health.


The great majority of globally circulating pathogens go undetected, undermining patient care and hindering outbreak preparedness and response. To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples(1-3)while simultaneously testing for many pathogens(4-6). Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanolitre droplets containing CRISPR-based nucleic acid detection reagents(7)self-organize in a microwell array(8)to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN-Cas13) enables robust testing of more than 4,500 crRNA-target pairs on a single array. Using CARMEN-Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with at least 10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN-Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. The intrinsic multiplexing and throughput capabilities of CARMEN make it practical to scale, as miniaturization decreases reagent cost per test by more than 300-fold. Scalable, highly multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health(9-11).


  
The first dinosaur egg was soft 期刊论文
NATURE, 2020
作者:  Rodstrom, Karin E. J.;  Kiper, Aytug K.;  Zhang, Wei;  Rinne, Susanne;  Pike, Ashley C. W.;  Goldstein, Matthias;  Conrad, Linus J.;  Delbeck, Martina;  Hahn, Michael G.;  Meier, Heinrich;  Platzk, Magdalena;  Quigley, Andrew;  Speedman, David;  Shrestha, Leela;  Mukhopadhyay, Shubhashish M. M.
收藏  |  浏览/下载:47/0  |  提交时间:2020/07/03

Molecular analyses of newly discovered, embryo-bearing ornithischian and sauropod dinosaur eggs suggest that the ancestral dinosaur egg was soft-shelled, and that hard-shelled eggs evolved independently at least three times in the major dinosaur lineages.


Calcified eggshells protect developing embryos against environmental stress and contribute to reproductive success(1). As modern crocodilians and birds lay hard-shelled eggs, this eggshell type has been inferred for non-avian dinosaurs. Known dinosaur eggshells are characterized by an innermost membrane, an overlying protein matrix containing calcite, and an outermost waxy cuticle(2-7). The calcitic eggshell consists of one or more ultrastructural layers that differ markedly among the three major dinosaur clades, as do the configurations of respiratory pores. So far, only hadrosaurid, a few sauropodomorph and tetanuran eggshells have been discovered  the paucity of the fossil record and the lack of intermediate eggshell types challenge efforts to homologize eggshell structures across all dinosaurs(8-18). Here we present mineralogical, organochemical and ultrastructural evidence for an originally non-biomineralized, soft-shelled nature of exceptionally preserved ornithischianProtoceratopsand basal sauropodomorphMussauruseggs. Statistical evaluation of in situ Raman spectra obtained for a representative set of hard- and soft-shelled, fossil and extant diapsid eggshells clusters the originally organic but secondarily phosphatizedProtoceratopsand the organicMussauruseggshells with soft, non-biomineralized eggshells. Histology corroborates the organic composition of these soft-shelled dinosaur eggs, revealing a stratified arrangement resembling turtle soft eggshell. Through an ancestral-state reconstruction of composition and ultrastructure, we compare eggshells fromProtoceratopsandMussauruswith those from other diapsids, revealing that the first dinosaur egg was soft-shelled. The calcified, hard-shelled dinosaur egg evolved independently at least three times throughout the Mesozoic era, explaining the bias towards eggshells of derived dinosaurs in the fossil record.