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Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping 期刊论文
NATURE, 2020, 583 (7817) : 638-+
作者:  Lin, Yiheng;  Leibrandt, David R.;  Leibfriedz, Dietrich;  Chou, Chin-wen
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

A method termed ac(4)C-seq is introduced for the transcriptome-wide mapping of the RNA modificationN(4)-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.


N-4-acetylcytidine (ac(4)C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA(1-3). However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac(4)C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac(4)C at single-nucleotide resolution. In human and yeast mRNAs, ac(4)C sites are not detected but can be induced-at a conserved sequence motif-via the ectopic overexpression of eukaryotic acetyltransferase complexes. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac(4)C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. (AcC)-C-4 is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac(4)C and its potential thermoadaptive role. Our studies quantitatively define the ac(4)C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease(4-6).


  
The online competition between pro- and anti-vaccination views 期刊论文
NATURE, 2020, 582 (7811) : 230-+
作者:  Wu, Fan;  Zhao, Su;  Yu, Bin;  Chen, Yan-Mei;  Wang, Wen;  Song, Zhi-Gang;  Hu, Yi;  Tao, Zhao-Wu;  Tian, Jun-Hua;  Pei, Yuan-Yuan;  Yuan, Ming-Li;  Zhang, Yu-Ling;  Dai, Fa-Hui;  Liu, Yi;  Wang, Qi-Min;  Zheng, Jiao-Jiao;  Xu, Lin;  Holmes, Edward C.;  Zhang, Yong-Zhen
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.


Distrust in scientific expertise(1-14) is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks(2-4), as happened for measles in 2019(5,6). Homemade remedies(7,8) and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice(9-11). There is a lack of understanding about how this distrust evolves at the system level(13,14). Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change(11), and highlight the key role of network cluster dynamics in multi-species ecologies(15).


  
Sex-specific adipose tissue imprinting of regulatory T cells 期刊论文
NATURE, 2020, 579 (7800) : 581-+
作者:  Qureshi, Abdul Aziz;  Suades, Albert;  Matsuoka, Rei;  Brock, Joseph;  McComas, Sarah E.;  Nji, Emmanuel;  Orellana, Laura;  Claesson, Magnus;  Delemotte, Lucie;  Drew, David
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

Adipose tissue is an energy store and a dynamic endocrine organ(1,2). In particular, visceral adipose tissue (VAT) is critical for the regulation of systemic metabolism(3,4). Impaired VAT function-for example, in obesity-is associated with insulin resistance and type 2 diabetes(5,6). Regulatory T (T-reg) cells that express the transcription factor FOXP3 are critical for limiting immune responses and suppressing tissue inflammation, including in the VAT(7-9). Here we uncover pronounced sexual dimorphism in T-reg cells in the VAT. Male VAT was enriched for T-reg cells compared with female VAT, and T-reg cells from male VAT were markedly different from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. Heightened inflammation in the male VAT facilitated the recruitment of T-reg cells via the CCL2-CCR2 axis. Androgen regulated the differentiation of a unique IL-33-producing stromal cell population specific to the male VAT, which paralleled the local expansion of T-reg cells. Sex hormones also regulated VAT inflammation, which shaped the transcriptional landscape of VAT-resident T-reg cells in a BLIMP1 transcription factor-dependent manner. Overall, we find that sex-specific differences in T-reg cells from VAT are determined by the tissue niche in a sex-hormone-dependent manner to limit adipose tissue inflammation.


Visceral adipose tissue contains populations of regulatory T cells that exhibit sexual dimorphism, determined by the surrounding niche, and differ between male and female mice in terms of cell number, phenotype, transcriptional landscape and chromatin accessibility.