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Science论文导读 0804

时间: 2017年08月14日 | 作者: admin | 来源: 未知
1 UBE2O remodels the proteome during terminal erythroid differentiation 【生物 - 生化】 UBE2O 重塑红细胞终末分化过程中的蛋白质组 Anthony T. Nguyen, Miguel A. Prado, Paul J. Schmidt … Mark D. Fleming, Daniel Finley h

1 UBE2O remodels the proteome during terminal erythroid differentiation

 

【生物-生化】UBE2O重塑红细胞终末分化过程中的蛋白质组

 

Anthony T. Nguyen, Miguel A. Prado, Paul J. SchmidtMark D. Fleming, Daniel Finley

 

http://science.sciencemag.org/content/357/6350/eaan0218

 

During terminal differentiation, the global protein complement is remodeled, as epitomized by erythrocytes, whose cytosol is ~98% globin. The erythroid proteome undergoes a rapid transition at the reticulocyte stage; however, the mechanisms driving programmed elimination of preexisting cytosolic proteins are unclear. We found that a mutation in the murine Ube2o gene, which encodes a ubiquitin-conjugating enzyme induced during erythropoiesis, results in anemia. Proteomic analysis suggested that UBE2O is a broad-spectrum ubiquitinating enzyme that remodels the erythroid proteome. In particular, ribosome elimination, a hallmark of reticulocyte differentiation, was defective in Ube2o/mutants. UBE2O recognized ribosomal proteins and other substrates directly, targeting them to proteasomes for degradation. Thus, in reticulocytes, the induction of ubiquitinating factors may drive the transition from a complex to a simple proteome.

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(导读 郭怿暄)从网织红细胞向红细胞的终末分化过程中伴随着蛋白质组由复杂多样向单一血红蛋白的巨大转变。这一研究发现在这个转变过程中UBE2O起到关键作用,它可定向泛素化核糖体蛋白,使其降解,诱导网织红细胞的成熟。突变这一基因造成小鼠出现贫血症状。

 

 

 2 UBE2O is a quality control factor for orphans of multiprotein complexes

 

【生物-生化】UBE2O是多分子蛋白复合物中孤儿蛋白的质量控制因子

 

Kota Yanagitani, Szymon Juszkiewicz, Ramanujan S. Hegde

 

http://science.sciencemag.org/content/357/6350/472

 

 

Many nascent proteins are assembled into multiprotein complexes of defined stoichiometry. Imbalances in the synthesis of individual subunits result in orphans. How orphans are selectively eliminated to maintain protein homeostasis is poorly understood. Here, we found that the conserved ubiquitin-conjugating enzyme UBE2O directly recognized juxtaposed basic and hydrophobic patches on unassembled proteins to mediate ubiquitination without a separate ubiquitin ligase. In reticulocytes, where UBE2O is highly up-regulated, unassembled α-globin molecules that failed to assemble with β-globin were selectively ubiquitinated by UBE2O. In nonreticulocytes, ribosomal proteins that did not engage nuclear import factors were targets for UBE2O. Thus, UBE2O is a self-contained quality control factor that comprises substrate recognition and ubiquitin transfer activities within a single protein to efficiently target orphans of multiprotein complexes for degradation.

 

(导读 郭怿暄)多分子蛋白复合物中各种亚基按照一定比例构成复合物,过量合成的多余亚基被称为孤儿蛋白。本研究发现泛素连接酶UBE2O可以独立完成对网织红细胞中未装配的α-球蛋白以及非网织红细胞中核糖体蛋白的选择性识别和泛素转移,从而定向降解这些孤儿蛋白,为多分子蛋白复合物的装配质量进行把关。

 

3 Mechanochemical unzipping of insulating polyladderene to semiconducting polyacetylene

【化学】绝缘聚酯机械化学解离为半导体聚乙炔

Zhixing Chen, Jaron A. M. Mercer, Xiaolei ZhuNoah Z. Burns, Yan Xia(夏岩,斯坦福大学)

http://science.sciencemag.org/content/357/6350/475

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图片来源:science.sciencemag.org

 

Biological systems sense and respond to mechanical stimuli in a complex manner. In an effort to develop synthetic materials that transduce mechanical force into multifold changes in their intrinsic properties, we report on a mechanochemically responsive nonconjugated polymer that converts to a conjugated polymer via an extensive rearrangement of the macromolecular structure in response to force. Our design is based on the facile mechanochemical unzipping of polyladderene, a polymer inspired by a lipid natural product structure and prepared via direct metathesis polymerization. The resultant polyacetylene block copolymers exhibit long conjugation length and uniform trans-configuration and self-assemble into semiconducting nanowires. Calculations support a tandem unzipping mechanism of the ladderene units.

(导读:阿金)为了开发能够将机械力转化为自身性质变化的合成材料,本实验利用机械化学方法解离聚酯,能够在应力作用下产生大分子结构重新排列,将机械化学响应非共轭型聚合物转化为共轭聚合物。结果制成的聚乙炔嵌段共聚物具有很长的共轭长度,能够自我组装成为半导体纳米线。这种结构可以进一步开发其实际的工业用途。

 

4 Direct atomic-level insight into the active sites of a high-performance PGM-free ORR catalyst

【化学】对高性能无铂族金属(PGM-Free)氧化还原(ORR)催化剂活性位点的原子水平直接观测

Hoon T. Chung, David A. Cullen, Drew HigginsKarren L. More, Piotr Zelenay

http://science.sciencemag.org/content/357/6350/479

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图片来源:science.sciencemag.org


Platinum group metalfree (PGM-free) metal-nitrogen-carbon catalysts have emerged as a promising alternative to their costly platinum (Pt)based counterparts in polymer electrolyte fuel cells (PEFCs) but still face some major challenges, including (i) the identification of the most relevant catalytic site for the oxygen reduction reaction (ORR) and (ii) demonstration of competitive PEFC performance under automotive-application conditions in the hydrogen (H2)air fuel cell. Herein, we demonstrate H2-air performance gains achieved with an iron-nitrogen-carbon catalyst synthesized with two nitrogen precursors that developed hierarchical porosity. Current densities recorded in the kinetic region of cathode operation, at fuel cell voltages greater than ~0.75 V, were the same as those obtained with a Pt cathode at a loading of 0.1 milligram of Pt per centimeter squared. The proposed catalytic active site, carbon-embedded nitrogen-coordinated iron (FeN4), was directly visualized with aberration-corrected scanning transmission electron microscopy, and the contributions of these active sites associated with specific lattice-level carbon structures were explored computationally.

(导读:阿金)无铂族金属(PGM-Free)的金属碳氮基化合物是有效的电解质燃料电池(PEFCs)催化剂,但是仍需要确定其在ORR反应中的活性位点以及实际应用效果。本研究针对两种氮前驱体合成具有分层孔隙结构的Fe-N-C基催化剂,利用球差校正扫描电镜确认其活性位点为嵌入碳的FeN4结构。此成果有助于进一步开发廉价的高性能催化剂。

 

5 Revealing hidden antiferromagnetic correlations in doped Hubbard chains via string correlators

【物理】借助串关连子揭示掺杂Hubbard链中的反铁磁性关联

 

Timon A. Hilker, Guillaume Salomon, Fabian Grusdt…Immanuel Bloch, Christian Gross

 

http://science.sciencemag.org/content/357/6350/484

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Topological phases, like the Haldane phase in spin-1 chains, defy characterization through local order parameters. Instead, nonlocal string order parameters can be employed to reveal their hidden order. Similar diluted magnetic correlations appear in doped one-dimensional lattice systems owing to the phenomenon of spin-charge separation. Here we report on the direct observation of such hidden magnetic correlations via quantum gas microscopy of hole-doped ultracold Fermi-Hubbard chains. The measurement of nonlocal spin-density correlation functions reveals a hidden finite-range antiferromagnetic order, a direct consequence of spin-charge separation. Our technique, which measures nonlocal order directly, can be readily extended to higher dimensions to study the complex interplay between magnetic order and density fluctuations.

非局域串有序度参数可以揭示拓扑相中所隐藏的有序度。本研究借助量子气显微直接观测到了空穴掺杂超冷Fermi-Hubbard链的隐藏磁关联,其对非局域自旋密度关联函数的测量揭示了隐藏的有限程反铁磁序。这一种直接测量非局域有序度的技术可在更高维度上用来研究磁序与密度涨落的相互关系。

 

 

 

6 Complete measurement of helicity and its dynamics in vortex tubes

【物理】涡流管中螺旋度及其动力学的全面测量

 

Martin W. Scheeler, Wim M. van Rees, Hridesh Kedia, Dustin Kleckner, William T. M. Irvine

 

http://science.sciencemag.org/content/357/6350/487

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Helicity, a topological measure of the intertwining of vortices in a fluid flow, is a conserved quantity in inviscid fluids but can be dissipated by viscosity in real flows. Despite its relevance across a range of flows, helicity in real fluids remains poorly understood because the entire quantity is challenging to measure. We measured the total helicity of thin-core vortex tubes in water. For helical vortices that are stretched or compressed by a second vortex, we found conservation of total helicity. For an isolated helical vortex, we observed evolution toward and maintenance of a constant helicity state after the dissipation of twist helicity by viscosity. Our results show that helicity can remain constant even in a viscous fluid and provide an improved basis for understanding and manipulating helicity in real flows.

螺旋度是对流体中旋涡纠缠程度的一种拓扑描述,在非粘性流体中守恒。而真实流体中螺旋度会被粘性耗散,因此对其测量非常困难。本研究测量了水中薄芯涡流管的总螺旋度,并发现无论是否与另一个涡旋相互作用,粘性流体中涡旋的螺旋度都是守恒的。研究结果为真实流体中螺旋度的控制提供重要参考。

 

 

 

7 Large-amplitude transfer motion of hydrated excess protons mapped by ultrafast 2D IR spectroscopy

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【物理】利用超快
2D红外光谱对水合过剩质子的大振幅转移运动进行成像

 

Fabian Dahms, Benjamin P. Fingerhut, Erik T. J. Nibbering, Ehud Pines, Thomas Elsaesser

 

http://science.sciencemag.org/content/357/6350/491

 

Solvation and transport of excess protons in aqueous systems play a fundamental role in acid-base chemistry and biochemical processes. We mapped ultrafast proton excursions along the proton transfer coordinate by means of two-dimensional infrared spectroscopy, both in bulk water and in a Zundel cation (H5O2)+ motif selectively prepared in acetonitrile. Electric fields from the environment and stochastic hydrogen bond motions induce fluctuations of the proton double-minimum potential. Within the lifetime of a particular hydration geometry, the proton explores a multitude of positions on a sub-100-femtosecond time scale. The proton transfer vibration is strongly damped by its 20- to 40-femtosecond population decay. Our results suggest a central role of Zundel-like geometries in aqueous proton solvation and transport.

 

过剩质子的溶剂化与转移在酸碱化学与生化过程中起重要作用。本研究借助二维红外光谱成像,在体相水和乙腈中选择性制备 Zundel 阳离子 (H5O2)+ 两种环境下,沿着质子转移坐标绘制了质子运动路径。研究结果表明了类-Zundel 几何构型在水溶液质子溶剂化和运输中的重要作用。

 

 

8 Winter storms drive rapid phenotypic, regulatory, and genomic shifts in the green anole lizard

【生物】冬季风暴快速驱动绿色变色龙蜥蜴表型,调控,以及基因组的变化

Shane C. Campbell-Staton, Zachary A. Cheviron, Nicholas Rochette, Julian Catchen, Jonathan B. Losos, Scott V. Edwards

http://science.sciencemag.org/content/357/6350/495

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图片来源:science

Extreme environmental perturbations offer opportunities to observe the effects of natural selection in wild populations. During the winter of 20132014, the southeastern United States endured an extreme cold event. We used thermal performance, transcriptomics, and genome scans to measure responses of lizard populations to storm-induced selection. We found significant increases in cold tolerance at the speciessouthern limit. Gene expression in southern survivors shifted toward patterns characteristic of northern populations. Comparing samples before and after the extreme winter, 14 genomic regions were differentiated in the surviving southern population; four also exhibited signatures of local adaptation across the latitudinal gradient and implicate genes involved in nervous system function. Together, our results suggest that extreme winter events can rapidly produce strong selection on natural populations at multiple biological levels that recapitulate geographic patterns of local adaptation.

 (导读 郭思瑶)极端环境变化展示了自然选择对野生种群的影响。2013-2014年冬天,美国东南部遭遇了极寒天气。科研人员利用热力性能,转录组和基因组分析了蜥蜴种群, 发现南部种群耐寒极限大幅提高,南部幸存蜥蜴的基因表达向北部种群的基因特征靠拢。这说明极端气候事件可以迅速对自然种群产生极大的选择作用。

 

9 The microbial metabolite desaminotyrosine protects from influenza through type I interferon

【生物-感染】微生物代谢产物脱氨基酪氨酸通过I型干扰素保护宿主免受流感 

Ashley L. Steed, George P. Christophi, Gerard E. KaikoDeborah J. Lenschow, Thaddeus S. Stappenbeck

http://science.sciencemag.org/content/357/6350/498

图片8.png图片来源:Science

 

The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, Clostridium orbiscindens,produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN.

(导读 郭思瑶)肠道微生物群可调节宿主对流感的应答,其机制尚不清楚。通过流感病毒在功能获得性小鼠模型中的分析,科学家发现人类肠道细菌Clostridium orbiscindens的代谢产物脱氨基酪氨酸(DAT)可以通过I型干扰素信号调节减少肺部损伤。DAT通过I型干扰素放大环路来保护宿主。该发现确定了肠道菌群对于感染进行应答的具体成分。

 

10 Chemogenetics revealed: DREADD occupancy and activation via converted clozapine

【神经科学】化学遗传学显示:转化产物氯氮平介导DREADD系统受体占有和活化

Juan L. Gomez, Jordi Bonaventura, Wojciech Lesniak…Antonello Bonci, Michael Michaelides

http://science.sciencemag.org/content/357/6350/503

(导读 马欢) DREADD(designer receptors exclusively activated by designer drugs)的应用建立在特定受体可由特定药物n-氧化氯氮平CNO专一激活的假设下,然而其在体的作用机制尚未得到证实。本文作者通过放射性配体受体占有率测量和体内正电子发射断层扫描发现脑中表达的DREADD CNO代谢物氯氮平而非其本身激活。

The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of “designer receptors,” which are exclusively activated by the “designer drug” clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed. CNO does not enter the brain after systemic drug injections and shows low affinity for DREADDs. Clozapine, to which CNO rapidly converts in vivo, shows high DREADD affinity and potency. Upon systemic CNO injections, converted clozapine readily enters the brain and occupies central nervous system–expressed DREADDs, whereas systemic subthreshold clozapine injections induce preferential DREADD-mediated behaviors.

 

 

 

 

 

 

11 Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy

【生化】全身泛AMPK激活剂MK-8722改善血糖平衡但可导致心脏肥大

Robert W. Myers, Hong-Ping Guan, Juliann Ehrhart…Daniel M. Kemp, Iyassu K. Sebhat

http://science.sciencemag.org/content/357/6350/507

(导读 马欢)腺苷单磷酸激活蛋白激酶(AMPK)是真核生物能量稳态的主要调节剂,但AMPK作为药物靶点的研究仍是个挑战。本文作者发开的化合物MK-8722,可强效、直接地激活哺乳动物所有12AMPK复合物。文章表明,该化合物可改善动物模型的血糖过高症状且不引起低血糖,但同时引起心脏肥大和心糖原增多

 

5′-Adenosine monophosphate–activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite three decades of investigation, the biological roles of AMPK and its potential as a drug target remain incompletely understood, largely because of a lack of optimized pharmacological tools. We developed MK-8722, a potent, direct, allosteric activator of all 12 mammalian AMPK complexes. In rodents and rhesus monkeys, MK-8722–mediated AMPK activation in skeletal muscle induced robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia. These effects translated across species, including diabetic rhesus monkeys, but manifested with concomitant cardiac hypertrophy and increased cardiac glycogen without apparent functional sequelae.

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AMK-8722的化学结构

 

 

12 Genomic estimation of complex traits reveals ancient maize adaptation to temperate North America

【生物】复杂性状的基因组估测揭示了古时玉米对温带北美洲的适应性改变

Kelly Swarts, Rafal M. Gutaker, Bruce BenzEdward S. Buckler, Hernán A. Burbano

http://science.sciencemag.org/content/357/6350/512

 

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图片来源:Science

 

By 4000 years ago, people had introduced maize to the southwestern United States; full agriculture was established quickly in the lowland deserts but delayed in the temperate highlands for 2000 years. We test if the earliest upland maize was adapted for early flowering, a characteristic of modern temperate maize. We sequenced fifteen 1900-year-old maize cobs from Turkey Pen Shelter in the temperate Southwest. Indirectly validated genomic models predicted that Turkey Pen maize was marginally adapted with respect to flowering, as well as short, tillering, and segregating for yellow kernel color. Temperate adaptation drove modern population differentiation and was selected in situ from ancient standing variation. Validated prediction of polygenic traits improves our understanding of ancient phenotypes and the dynamics of environmental adaptation.

(导读 郭思瑶)4000年前,玉米被引入美国西南部,很快成为西南部低地的主要农作物,但直到 2000后才年才进入温带高地。科研人员对1900年前该地玉米棒基因组进行测序,发现其已为适应环境在花期,发芽和分枝上的发生改变。对温度的适应驱动了当代种群分化。这有利于加深我们对古代表型和环境适应动态变化的理解。