GSTDTAP

浏览/检索结果: 共75条,第1-10条 帮助

限定条件        
已选(0)清除 条数/页:   排序方式:
Effects of climate change on the movement of future landfalling Texas tropical cyclones 期刊论文
NATURE COMMUNICATIONS, 2020, 11 (1)
作者:  Hassanzadeh, Pedram;  Lee, Chia-Ying;  Nabizadeh, Ebrahim;  Camargo, Suzana J.;  Ma, Ding;  Yeung, Laurence Y.
收藏  |  浏览/下载:4/0  |  提交时间:2020/07/06
Greater flood risks in response to slowdown of tropical cyclones over the coast of China 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (26) : 14751-14755
作者:  Lai, Yangchen;  Li, Jianfeng;  Gu, Xihui;  Chen, Yongqin David;  Kong, Dongdong;  Gan, Thian Yew;  Liu, Maofeng;  Li, Qingquan;  Wu, Guofeng
收藏  |  浏览/下载:16/0  |  提交时间:2020/06/22
tropical cyclones  translation speed  local rainfall totals  flood risks  
DNA-repair enzyme turns to translation 期刊论文
NATURE, 2020, 579 (7798) : 198-199
作者:  Bian, Zhilei;  Gong, Yandong;  Huang, Tao;  Lee, Christopher Z. W.;  Bian, Lihong;  Bai, Zhijie;  Shi, Hui;  Zeng, Yang;  Liu, Chen;  He, Jian;  Zhou, Jie;  Li, Xianlong;  Li, Zongcheng;  Ni, Yanli;  Ma, Chunyu;  Cui, Lei;  Zhang, Rui;  Chan, Jerry K. Y.;  Ng, Lai Guan;  Lan, Yu;  Ginhoux, Florent;  Liu, Bing
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

A key DNA-repair enzyme has a surprising role during the early steps in the assembly of ribosomes - the molecular machines that translate the genetic code into protein.


  
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.


  
Potential circadian effects on translational failure for neuroprotection 期刊论文
NATURE, 2020
作者:  Sakai, Akito;  Minami, Susumu;  Koretsune, Takashi;  Chen, Taishi;  Higo, Tomoya;  Wang, Yangming;  Nomoto, Takuya;  Hirayama, Motoaki;  Miwa, Shinji;  Nishio-Hamane, Daisuke;  Ishii, Fumiyuki;  Arita, Ryotaro;  Nakatsuji, Satoru
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Neuroprotectant strategies that have worked in rodent models of stroke have failed to provide protection in clinical trials. Here we show that the opposite circadian cycles in nocturnal rodents versus diurnal humans(1,2) may contribute to this failure in translation. We tested three independent neuroprotective approaches-normobaric hyperoxia, the free radical scavenger alpha-phenyl-butyl-tert-nitrone (alpha PBN), and the N-methyl-d-aspartic acid (NMDA) antagonist MK801-in mouse and rat models of focal cerebral ischaemia. All three treatments reduced infarction in day-time (inactive phase) rodent models of stroke, but not in night-time (active phase) rodent models of stroke, which match the phase (active, day-time) during which most strokes occur in clinical trials. Laser-speckle imaging showed that the penumbra of cerebral ischaemia was narrower in the active-phase mouse model than in the inactive-phase model. The smaller penumbra was associated with a lower density of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive dying cells and reduced infarct growth from 12 to 72 h. When we induced circadian-like cycles in primary mouse neurons, deprivation of oxygen and glucose triggered a smaller release of glutamate and reactive oxygen species, as well as lower activation of apoptotic and necroptotic mediators, in '  active-phase'  than in '  inactive-phase'  rodent neurons. alpha PBN and MK801 reduced neuronal death only in '  inactive-phase'  neurons. These findings suggest that the influence of circadian rhythm on neuroprotection must be considered for translational studies in stroke and central nervous system diseases.


Studies in rats and mice at different times of day suggest that the failure of neuroprotective strategies for stroke in translational studies might be related to the difference in circadian cycles between humans and rodents.


  
Plant 22-nt siRNAs mediate translational repression and stress adaptation 期刊论文
NATURE, 2020, 581 (7806) : 89-+
作者:  Roulis, Manolis;  Kaklamanos, Aimilios;  Schernthanner, Marina;  Bielecki, Piotr;  Zhao, Jun;  Kaffe, Eleanna;  Frommelt, Laura-Sophie;  Qu, Rihao;  Knapp, Marlene S.;  Henriques, Ana;  Chalkidi, Niki;  Koliaraki, Vasiliki;  Jiao, Jing;  Brewer, J. Richard;  Bacher, Maren;  Blackburn, Holly N.;  Zhao, Xiaoyun;  Breyer, Richard M.;  Aidinis, Vassilis;  Jain, Dhanpat;  Su, Bing;  Herschman, Harvey R.;  Kluger, Yuval;  Kollias, George;  Flavell, Richard A.
收藏  |  浏览/下载:32/0  |  提交时间:2020/07/03

Characterization of 22-nucleotide short interfering RNAs in plants finds that they accumulate in response to environmental stress, causing translational repression, inhibition of plant growth and enhanced stress responses.


Small interfering RNAs (siRNAs) are essential for proper development and immunity in eukaryotes(1). Plants produce siRNAs with lengths of 21, 22 or 24 nucleotides. The 21- and 24-nucleotide species mediate cleavage of messenger RNAs and DNA methylation(2,3), respectively, but the biological functions of the 22-nucleotide siRNAs remain unknown. Here we report the identification and characterization of a group of endogenous 22-nucleotide siRNAs that are generated by the DICER-LIKE 2 (DCL2) protein in plants. When cytoplasmic RNA decay and DCL4 are deficient, the resulting massive accumulation of 22-nucleotide siRNAs causes pleiotropic growth disorders, including severe dwarfism, meristem defects and pigmentation. Notably, two genes that encode nitrate reductases-NIA1 and NIA2-produce nearly half of the 22-nucleotide siRNAs. Production of 22-nucleotide siRNAs triggers the amplification of gene silencing and induces translational repression both gene specifically and globally. Moreover, these 22-nucleotide siRNAs preferentially accumulate upon environmental stress, especially those siRNAs derived from NIA1/2, which act to restrain translation, inhibit plant growth and enhance stress responses. Thus, our research uncovers the unique properties of 22-nucleotide siRNAs, and reveals their importance in plant adaptation to environmental stresses.


  
C9orf72 suppresses systemic and neural inflammation induced by gut bacteria 期刊论文
NATURE, 2020
作者:  Nikoo, Mohammad Samizadeh;  Jafari, Armin;  Perera, Nirmana;  Zhu, Minghua;  Santoruvo, Giovanni;  Matioli, Elison
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia(1,2). The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration(3-9). The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins(5) before its non-canonical translation into neural-toxic dipeptide proteins(3,4). The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation(6-9). Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria(10,11) protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.


Reduced abundance of immune-stimulating gut bacteria ameliorated the inflammatory and autoimmune phenotypes of mice with mutations in C9orf72, which in the human orthologue are linked to amyotrophic lateral sclerosis and frontotemporal dementia.


  
Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA 期刊论文
NATURE, 2020, 583 (7814) : 139-+
作者:  Muniz, Juan A.;  Barberena, Diego;  Lewis-Swan, Robert J.;  Young, Dylan J.;  Cline, Julia R. K.;  Rey, Ana Maria;  Thompson, James K.
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

MicroRNAs (miRNAs) regulate the levels of translation of messenger RNAs (mRNAs). At present, the major parameter that can explain the selection of the target mRNA and the efficiency of translation repression is the base pairing between the '  seed'  region of the miRNA and its counterpart mRNA(1). Here we use R-1 rho relaxation-dispersion nuclear magnetic resonance(2) and molecular simulations(3) to reveal a dynamic switch-based on the rearrangement of a single base pair in the miRNA-mRNA duplex-that elongates a weak five-base-pair seed to a complete seven-base-pair seed. This switch also causes coaxial stacking of the seed and supplementary helix fitting into human Argonaute 2 protein (Ago2), reminiscent of an active state in prokaryotic Ago(4,5). Stabilizing this transient state leads to enhanced repression of the target mRNA in cells, revealing the importance of this miRNA-mRNA structure. Our observations tie together previous findings regarding the stepwise miRNA targeting process from an initial '  screening'  state to an '  active'  state, and unveil the role of the RNA duplex beyond the seed in Ago2.


Repression of a messenger RNA by a cognate microRNA depends not only on complementary base pairing, but also on the rearrangement of a single base pair, producing a conformation that fits better within the human Ago2 protein.


  
Ionic solids from common colloids 期刊论文
NATURE, 2020, 580 (7804) : 487-+
作者:  Delord, T.;  Huillery, P.;  Nicolas, L.;  Hetet, G.
收藏  |  浏览/下载:6/0  |  提交时间:2020/07/03

Oppositely charged colloidal particles are assembled in water through an approach that allows electrostatic interactions to be precisely tuned to generate macroscopic single crystals.


From rock salt to nanoparticle superlattices, complex structure can emerge from simple building blocks that attract each other through Coulombic forces(1-4). On the micrometre scale, however, colloids in water defy the intuitively simple idea of forming crystals from oppositely charged partners, instead forming non-equilibrium structures such as clusters and gels(5-7). Although various systems have been engineered to grow binary crystals(8-11), native surface charge in aqueous conditions has not been used to assemble crystalline materials. Here we form ionic colloidal crystals in water through an approach that we refer to as polymer-attenuated Coulombic self-assembly. The key to crystallization is the use of a neutral polymer to keep particles separated by well defined distances, allowing us to tune the attractive overlap of electrical double layers, directing particles to disperse, crystallize or become permanently fixed on demand. The nucleation and growth of macroscopic single crystals is demonstrated by using the Debye screening length to fine-tune assembly. Using a variety of colloidal particles and commercial polymers, ionic colloidal crystals isostructural to caesium chloride, sodium chloride, aluminium diboride and K4C60 are selected according to particle size ratios. Once fixed by simply diluting out solution salts, crystals are pulled out of the water for further manipulation, demonstrating an accurate translation from solution-phase assembly to dried solid structures. In contrast to other assembly approaches, in which particles must be carefully engineered to encode binding information(12-18), polymer-attenuated Coulombic self-assembly enables conventional colloids to be used as model colloidal ions, primed for crystallization.


  
New insights into US flood vulnerability revealed from flood insurance big data 期刊论文
NATURE COMMUNICATIONS, 2020, 11 (1)
作者:  Wing, Oliver E. J.;  Pinter, Nicholas;  Bates, Paul D.;  Kousky, Carolyn
收藏  |  浏览/下载:13/0  |  提交时间:2020/05/13