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Science 论文导读0505

时间: 2017年05月15日 | 作者: admin | 来源: 未知
1 Impact of cytosine methylation on DNA binding specificities of human transcription factors 【生物】胞嘧啶甲基化对人转录因子 DNA结合特异性的影响 Yimeng Yin, Ekaterina Morgunova, Arttu Jolma…Charles Vinson, Jussi T

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1 Impact of cytosine methylation on DNA binding specificities of human transcription factors

【生物】胞嘧啶甲基化对人转录因子DNA结合特异性的影响

Yimeng Yin, Ekaterina Morgunova, Arttu Jolma…Charles Vinson, Jussi Taipale

http://science.sciencemag.org/content/356/6337/eaaj2239

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图片来源:sciencemag.org

 

(导读 柳寒石)人类基因组中,发生于CpG序列的胞嘧啶甲基化常常会阻碍转录因子的结合。研究人员对542个转录因子进行甲基化敏感的SELEX分析却发现,有许多转录因子会更倾向于与甲基化的CpG序列相结合,这些转录因子中的大多数属于同源盒家族。研究还从结构角度分析了同源盒家族蛋白与甲基化DNA相结合的机制。

3分

The majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences. Most of these are in the extended homeodomain family. Structural analysis showed that homeodomain specificity for methylcytosine depends on direct hydrophobic interactions with the methylcytosine 5-methyl group. This study provides a systematic examination of the effect of an epigenetic DNA modification on human TF binding specificity and reveals that many developmentally important proteins display preference for mCpG-containing sequences.


2 Self-organized Notch dynamics generate stereotyped sensory organ patterns in Drosophila

【生物】果蝇中自组织Notch动态改变产生典型感觉器官模式

Francis Corson, Lydie Couturier, Hervé Rouault, Khalil Mazouni, François Schweisguth

http://science.sciencemag.org/content/356/6337/eaai7407

(导读 陈月欣)在果蝇的感觉器官发育过程中,细胞的空间模式形成主要分为两步:模式前因子在局部提高原神经元活性,随后Notch的侧支性抑制作用挑选出神经元前体细胞。本研究发现,Notch信号介导的这一自组织行为也参与了果蝇喉部感觉性刚毛的排列形成。这一过程通过Delta配体的梯度表达及条纹间、条纹内的抑制性信号传导实现。

The emergence of spatial patterns in developing multicellular organisms relies on positional cues and cell-cell communication. Drosophila sensory organs have informed a paradigm in which these operate in two distinct steps: Prepattern factors drive localized proneural activity, then Notch-mediated lateral inhibition singles out neural precursors. Here we show that self-organization through Notch signaling also establishes the proneural stripes that resolve into rows of sensory bristles on the fly thorax. Patterning, initiated by a gradient of Delta ligand expression, progresses through inhibitory signaling between and within stripes. Thus, Notch signaling can support self-organized tissue patterning as a prepattern is transduced by cell-cell interactions into a refined arrangement of cellular fates.


3 Integration of CpG-free DNA induces de novo methylation of CpG islands in pluripotent stem cells

【生物】无CpG DNA的引入可诱导多能干细胞CpG岛重新甲基化

Yuta Takahashi, Jun Wu, Keiichiro Suzuki…Ignacio Sancho-Martinez1, Juan Carlos Izpisua Belmonte

http://science.sciencemag.org/content/356/6337/503

(导读 陈月欣) CpG岛(CGI)是基因组中主要与启动子相关且多未被甲基化的区域,但CGI不被甲基化的原因尚不明确。本研究发现,将不含CpG的DNA整合入CGI中可诱导人类多能干细胞中CGI发生甲基化。这一甲基化作用稳定并可遗传至子细胞。这一发现为实现表观遗传编辑及其临床应用提供了新途径。

5分

CpG islands (CGIs) are primarily promoter-associated genomic regions and are mostly unmethylated within highly methylated mammalian genomes. The mechanisms by which CGIs are protected from de novo methylation remain elusive. Here we show that insertion of CpG-free DNA into targeted CGIs induces de novo methylation of the entire CGI in human pluripotent stem cells (PSCs). The methylation status is stably maintained even after CpG-free DNA removal, extensive passaging, and differentiation. By targeting the DNA mismatch repair gene MLH1 CGI, we could generate a PSC model of a cancer-related epimutation. Furthermore, we successfully corrected aberrant imprinting in induced PSCs derived from an Angelman syndrome patient. Our results provide insights into how CpG-free DNA induces de novo CGI methylation and broaden the application of targeted epigenome editing for a better understanding of human development and disease.


4 DeepStack: Expert-level artificial intelligence in heads-up no-limit poker

信息】deepstack:人工智能成为德州扑克专家

Matej Moravčík, Martin Schmid, Neil Burch…Michael Johanson, Michael Bowling

http://science.sciencemag.org/content/356/6337/508

 

(导读 唐诗语)人工智能如何在扑克等“信息不对称”游戏中胜出一直是重要挑战。新型算法“DeepStack”在“一对一无限注”德州扑克中击败职业选手标志着又一突破。结合了递归推演、分解运算以及深度学习技术,该算法原理可能有助于解决现实世界中“信息不对称”问题。

Artificial intelligence has seen several breakthroughs in recent years, with games often serving as milestones. A common feature of these games is that players have perfect information. Poker, the quintessential game of imperfect information, is a long-standing challenge problem in artificial intelligence. We introduce DeepStack, an algorithm for imperfect-information settings. It combines recursive reasoning to handle information asymmetry, decomposition to focus computation on the relevant decision, and a form of intuition that is automatically learned from self-play using deep learning. In a study involving 44,000 hands of poker, DeepStack defeated, with statistical significance, professional poker players in heads-up no-limit Texas hold’em. The approach is theoretically sound and is shown to produce strategies that are more difficult to exploit than prior approaches.


5 Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages

【生物】巨噬细胞代谢重编程介导IL-10的抗炎作用

W. K. Eddie Ip1, Namiko Hoshi, Dror S. Shouval, Scott Snapper, Ruslan Medzhitov

http://science.sciencemag.org/content/356/6337/513

 

(导读 柳寒石)白细胞介素-10(IL-10)是一种抗炎细胞因子,在控制免疫反应中发挥着重要作用。本文发现IL-10能够拮抗巨噬细胞中由炎症刺激诱导的代谢重编程转换。IL-10能抑制糖摄取和糖酵解,促进氧化磷酸化,此外其通过抑制mTOR的活性以促进线粒体自噬,清除功能失常的线粒体。IL-10的信号传导缺失导致NLRP3炎症小体的失调激活和IL-1β的产生

4.9

Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays a critical role in the control of immune responses. However, its mechanisms of action remain poorly understood. Here, we show that IL-10 opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, we show that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. Furthermore, IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4. Consequently, IL-10 promotes mitophagy that eliminates dysfunctional mitochondria characterized by low membrane potential and a high level of reactive oxygen species. In the absence of IL-10 signaling, macrophages accumulate damaged mitochondria in a mouse model of colitis and inflammatory bowel disease patients, and this results in dysregulated activation of the NLRP3 inflammasome and production of IL-1β.


6 Thermal processing of diblock copolymer melts mimics metallurgy

【材料】二嵌段共聚物熔体的热处理模拟冶金

Kyungtae Kim, Morgan W. Schulze, Akash Arora…Kevin D. Dorfman, Frank S. Bates

http://science.sciencemag.org/content/356/6337/520

 

(导读 卓思琪) 二段共聚物的小角X射线散射实验显示出的热经历的极度依赖:晶体或准晶态依赖于样品从离散状态冷却至有序-无序相变温度以下的方式。将合金中直接冷却时形成的是记忆形态;淬火回温后形成六方晶相C14和立方晶相C15的拉弗斯相。平均自洽场理论的计算暗示热经历驱使材料进入亚稳定状态中。

Small-angle x-ray scattering experiments conducted with compositionally asymmetric low molar mass poly(isoprene)-b-poly(lactide) diblock copolymers reveal an extraordinary thermal history dependence. The development of distinct periodic crystalline or aperiodic quasicrystalline states depends on how specimens are cooled from the disordered state to temperatures below the order-disorder transition temperature. Whereas direct cooling leads to the formation of documented morphologies, rapidly quenched samples that are then heated from low temperature form the hexagonal C14 and cubic C15 Laves phases commonly found in metal alloys. Self-consistent mean-field theory calculations show that these, and other associated Frank-Kasper phases, have nearly degenerate free energies, suggesting that processing history drives the material into long-lived metastable states defined by self-assembled particles with discrete populations of volumes and polyhedral shapes.


7 Selective anaerobic oxidation of methane enables direct synthesis of methanol

【化学】甲烷选择性厌氧氧化能直接合成甲醇

  Vitaly L. Sushkevich, Dennis Palagin, Marco Ranocchiari, Jeroen A. van Bokhoven

http://science.sciencemag.org/content/356/6337/523

 

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甲烷氧化合成甲醇的现用方法(上)、直接方法(中)和本文提出的方法(下)

(导读 唐诗语)甲醇的生产是一个昂贵且极度耗能的过程。本研究发现了一种将甲烷转化成甲醇的低成本方法:先利用沸石中的铜将甲烷氧化成甲氧基中间体,再向体系中加入水,使铜被氧化的同时释放出甲醇和氢气。如果该工艺得以投入使用,天然气井中多余的甲烷气体将可以被转化为便于储存和运输的液体甲醇,而不是被直接烧掉。

4.5分

Direct functionalization of methane in natural gas remains a key challenge. We present a direct stepwise method for converting methane into methanol with high selectivity (~97%) over a copper-containing zeolite, based on partial oxidation with water. The activation in helium at 673 kelvin (K), followed by consecutive catalyst exposures to 7 bars of methane and then water at 473 K, consistently produced 0.204 mole of CH3OH per mole of copper in zeolite. Isotopic labeling confirmed water as the source of oxygen to regenerate the zeolite active centers and renders methanol desorption energetically favorable. On the basis of in situ x-ray absorption spectroscopy, infrared spectroscopy, and density functional theory calculations, we propose a mechanism involving methane oxidation at CuII oxide active centers, followed by CuI reoxidation by water with concurrent formation of hydrogen.


8 The complex effects of ocean acidification on the prominent N2-fixing cyanobacterium Trichodesmium

【生态】海洋酸化对固氮蓝藻cyanobacterium Trichodesmium的复杂影响

 

Haizheng Hong, Rong Shen, Futing Zhang…François M. M. Morel, Dalin Shi

http://science.sciencemag.org/content/356/6337/527

(导读 谭坤)研究发现海水酸化引起胞浆pH降低,会提高重要固氮蓝藻Trichodesmium的固氮酶浓度但降低固氮效率。在缺铁环境中由于不能获得更多类囊体膜离子泵和三磷酸腺苷进而加剧酸化的影响,导致固氮效率更低。

 

Acidification of seawater caused by anthropogenic carbon dioxide (CO2) is anticipated to influence the growth of dinitrogen (N2)–fixing phytoplankton, which contribute a large fraction of primary production in the tropical and subtropical ocean. We found that growth and N2-fixation of the ubiquitous cyanobacterium Trichodesmium decreased under acidified conditions, notwithstanding a beneficial effect of high CO2. Acidification resulted in low cytosolic pH and reduced N2-fixation rates despite elevated nitrogenase concentrations. Low cytosolic pH required increased proton pumping across the thylakoid membrane and elevated adenosine triphosphate production. These requirements were not satisfied under field or experimental iron-limiting conditions, which greatly amplified the negative effect of acidification.


9 Noise pollution is pervasive in U.S. protected areas

【环境】美国保护地普通存在噪声污染

Rachel T. Buxton, Megan F. McKenna, Daniel Mennitt, Kurt Fristrup, Kevin Crooks, Lisa Angeloni, George Wittemyer

http://science.sciencemag.org/content/356/6337/531

(导读 谭坤)研究发现63%的美国保护地承受着高达背景音2倍的人为噪音,21%的达到10倍,14%受胁物种的栖息地也承受了10倍噪音,影响了造访者以及野生动植物的行为、适合度以及群落组成,结果显示噪音污染多与交通、发展和土地过度利用相关,为开展干预措施提供指导。

 

Anthropogenic noise threatens ecological systems, including the cultural and biodiversity resources in protected areas. Using continental-scale sound models, we found that anthropogenic noise doubled background sound levels in 63% of U.S. protected area units and caused a 10-fold or greater increase in 21%, surpassing levels known to interfere with human visitor experience and disrupt wildlife behavior, fitness, and community composition. Elevated noise was also found in critical habitats of endangered species, with 14% experiencing a 10-fold increase in sound levels. However, protected areas with more stringent regulations had less anthropogenic noise. Our analysis indicates that noise pollution in protected areas is closely linked with transportation, development, and extractive land use, providing insight into where mitigation efforts can be most effective.


10 Branch-specific plasticity of a bifunctional dopamine circuit encodes protein hunger

【生物】分支特异可塑的双功能多巴胺环路编码蛋白质饥饿

Qili Liu, Masashi Tabuchi, Sha Liu…Daniel Baldoni, Mark N. Wu

http://science.sciencemag.org/content/356/6337/534

(导读 陈月欣) 野生动物对于食物的偏好会随着对特定营养物质的需求而转换,但其中的机理还不得而知。本研究鉴明了一个在果蝇中特异性编码蛋白质饥饿的多巴胺环路。环路中的神经元在蛋白质缺乏时被分支特异的塑性变化所激活,在增强蛋白质摄入的同时限制了糖分的摄入。

5

 

Free-living animals must not only regulate the amount of food they consume but also choose which types of food to ingest. The shifting of food preference driven by nutrient-specific hunger can be essential for survival, yet little is known about the underlying mechanisms. We identified a dopamine circuit that encodes protein-specific hunger inDrosophila. The activity of these neurons increased after substantial protein deprivation. Activation of this circuit simultaneously promoted protein intake and restricted sugar consumption, via signaling to distinct downstream neurons. Protein starvation triggered branch-specific plastic changes in these dopaminergic neurons, thus enabling sustained protein consumption. These studies reveal a crucial circuit mechanism by which animals adjust their dietary strategy to maintain protein homeostasis.


11 Negative selection in humans and fruit flies involves synergistic epistasis

【生物】在人类和果蝇的负选择涉及协同上位

Mashaal Sohail, Olga A. Vakhrusheva, Jae Hoon Sul…Alexey S. Kondrashov, Shamil R. Sunyaev

http://science.sciencemag.org/content/356/6337/539

(导读 谭坤)本文检测了人类和果蝇八个独立数据库中稀有的有害基因等位基因数量分布,发现分布的低扩散性,这表明对基因的负选择具有协同上位性,这可能解释了为什么有高突变率的这些种群能够持续存在。

 

Negative selection against deleterious alleles produced by mutation influences within-population variation as the most pervasive form of natural selection. However, it is not known whether deleterious alleles affect fitness independently, so that cumulative fitness loss depends exponentially on the number of deleterious alleles, or synergistically, so that each additional deleterious allele results in a larger decrease in relative fitness. Negative selection with synergistic epistasis should produce negative linkage disequilibrium between deleterious alleles and, therefore, an underdispersed distribution of the number of deleterious alleles in the genome. Indeed, we detected underdispersion of the number of rare loss-of-function alleles in eight independent data sets from human and fly populations. Thus, selection against rare protein-disrupting alleles is characterized by synergistic epistasis, which may explain how human and fly populations persist despite high genomic mutation rates.


12 Dispersals and genetic adaptation of Bantu-speaking populations in Africa and North America

【人类学】疏散和班图语的人口在非洲和北美洲的遗传适应

Etienne Patin, Marie Lopez, Rebecca Grollemund…Jean-Marie Hombert, Lluís Quintana-Murci

http://science.sciencemag.org/content/356/6337/543

(导读 谭坤)本文发现班图语使用者的扩散过程是首先穿过赤道雨林向南,然后扩散到东非和南非。并且发现这些人与当地人的基因混合促进了他们自身的适应,特别是HLA和LCT位点,并发现中非西部种群对在美非洲人的基因贡献。

 

Bantu languages are spoken by about 310 million Africans, yet the genetic history of Bantu-speaking populations remains largely unexplored. We generated genomic data for 1318 individuals from 35 populations in western central Africa, where Bantu languages originated. We found that early Bantu speakers first moved southward, through the equatorial rainforest, before spreading toward eastern and southern Africa. We also found that genetic adaptation of Bantu speakers was facilitated by admixture with local populations, particularly for the HLA and LCT loci. Finally, we identified a major contribution of western central African Bantu speakers to the ancestry of African Americans, whose genomes present no strong signals of natural selection. Together, these results highlight the contribution of Bantu-speaking peoples to the complex genetic history of Africans and African Americans.