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Science论文导读 1027

时间: 2017年11月06日 | 作者: admin | 来源: 未知
S20171027 1 【生物】 Potent peptidic fusion inhibitors of influenza virus Rameshwar U. Kadam and Jarek Juraszek , et.al 针对 流感病毒的 有效 肽 段 融合抑制 剂 http://science.sciencemag.org/content/358/6362/496 图 片来

S20171027

 

1 【生物】Potent peptidic fusion inhibitors of influenza virus

Rameshwar U. Kadam and  Jarek Juraszek et.al

 

针对流感病毒的有效融合抑制

 

http://science.sciencemag.org/content/358/6362/496

 

图片2.png 

片来源:Science

 

导读 郭思瑶)流感治急需新的靶与机制以避免流感大爆和病毒持。本文中基于人体中抗血球凝集素广谱中和抗体的互补决定环状区域设计了有效的肽段抑制剂。优化后的肽段抑制剂识别高度保守的茎干表位并抑制膜融合,可以有效地中和A组1类流感病毒,这为流感治疗提供了新的思路。

 

Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

 

2 Toughening elastomers using mussel-inspired iron-catechol complexes

【材料】受贻贝启发的铁-儿茶酚复合物增韧弹性体

J. Herbert Waite and Megan T. Valentine, et.al

http://science.sciencemag.org/content/358/6362/502

 

(导读 宋伊梦)材料的硬度和延展性常常此消彼长本研究在贻贝足丝结构启发下,制备了含有铁-儿茶酚交联结构的固态复合物。在松散共价聚合物中,加入铁离子形成可逆的离子交联,可使复合物的硬度、抗拉强度等性能提高2~3数量级,同时延展性降低。与之前原理类似的水凝胶材料相比,该固态材料的性能更加优异

 

Materials often exhibit a trade-off between stiffness and extensibility; for example, strengthening elastomers by increasing their cross-link density leads to embrittlement and decreased toughness. Inspired by cuticles of marine mussel byssi, we circumvent this inherent trade-off by incorporating sacrificial, reversible iron-catechol cross-links into a dry, loosely cross-linked epoxy network. The iron-containing network exhibits two to three orders of magnitude increases in stiffness, tensile strength, and tensile toughness compared to its iron-free precursor while gaining recoverable hysteretic energy dissipation and maintaining its original extensibility. Compared to previous realizations of this chemistry in hydrogels, the dry nature of the network enables larger property enhancement owing to the cooperative effects of both the increased cross-link density given by the reversible iron-catecholate complexes and the chain-restricting ionomeric nanodomains that they form.

 

3 Atomic structure of sensitive battery materials and interfaces revealed by cryo-electron microscopy

【材料】通过冷冻电镜观察敏感电池材料界面原子结构

Yuzhang Li, Yanbin Li and Yi Cui, et.al

http://science.sciencemag.org/content/358/6362/506

 

(导读 宋伊梦)传统的透射电子显微镜难以用于观察对电子束敏感的锂电材料。本研究利用冷冻电镜技术原位观测锂原子及界面结构,发现碳酸盐基电解质中的枝晶沿着<111>(优先),<110>或<211>方向生长为单晶纳米线,同时并观察到晶体缺陷。研究还揭示了在不同电解质中形成的不同的固体-电解质界面(SEI)纳米结构。

 

Whereas standard transmission electron microscopy studies are unable to preserve the native state of chemically reactive and beam-sensitive battery materials after operation, such materials remain pristine at cryogenic conditions. It is then possible to atomically resolve individual lithium metal atoms and their interface with the solid electrolyte interphase (SEI). We observe that dendrites in carbonate-based electrolytes grow along the <111> (preferred), <110>, or <211> directions as faceted, single-crystalline nanowires. These growth directions can change at kinks with no observable crystallographic defect. Furthermore, we reveal distinct SEI nanostructures formed in different electrolytes.

 

 

 

4 Size effect in ion transport through angstrom-scale slits

【物理】离子通过埃尺度缝隙传输的尺寸效应

R. R. Nair and A. K. Geim, et.al

http://science.sciencemag.org/content/358/6362/511

 

(导读 宋伊梦)纳米流体学中一项重要但仍未实现的工作是制备出尺寸接近微小离子和水分子的毛细管结构。本研究展示了一种可用于离子输运的通道。该通道的尺度达到埃级别,且表面电荷密度极低。研究发现水合直径大于通道尺寸的水合离子仍可以渗透通过狭缝研究结果为探究埃尺度空间限域效应在纳米流体等技术中的应用提供了新的思路。

 

In the field of nanofluidics, it has been an ultimate but seemingly distant goal to controllably fabricate capillaries with dimensions approaching the size of small ions and water molecules. We report ion transport through ultimately narrow slits that are fabricated by effectively removing a single atomic plane from a bulk crystal. The atomically flat angstrom-scale slits exhibit little surface charge, allowing elucidation of the role of steric effects. We find that ions with hydrated diameters larger than the slit size can still permeate through, albeit with reduced mobility. The confinement also leads to a notable asymmetry between anions and cations of the same diameter. Our results provide a platform for studying the effects of angstrom-scale confinement, which is important for the development of nanofluidics, molecular separation, and other nanoscale technologies.

 

 

5 【物理】Tunable porous nanoallotropes prepared by post-assembly etching of binary nanoparticle superlattices

Thumu Udayabhaskararao, et.al

通过二元纳米颗粒超晶格的后组装蚀刻制备可调谐的多纳米同素异形体

http://science.sciencemag.org/content/358/6362/514

(导读 阿金)无机纳米颗粒的自组装可用来制备多种胶体晶体,但因颗粒必须密集堆积而使得其应用有所限制。本研究展示了可选择性去除组成二元纳米颗粒超晶格的两个成分之中的一个,首先在液-气界面制备不同二元纳米颗粒超晶格,其稳定后,可转化为不同尺度结构的“纳米同素异形体”,从而制造出非密集堆积型纳米颗粒阵列。

Self-assembly of inorganic nanoparticles has been used to prepare hundreds of different colloidal crystals, but almost invariably with the restriction that the particles must be densely packed. Here, we show that non–close-packed nanoparticle arrays can be fabricated through the selective removal of one of two components comprising binary nanoparticle superlattices. First, a variety of binary nanoparticle superlattices were prepared at the liquid-air interface, including several arrangements that were previously unknown. Molecular dynamics simulations revealed the particular role of the liquid in templating the formation of superlattices not achievable through self-assembly in bulk solution. Second, upon stabilization, all of these binary superlattices could be transformed into distinct “nanoallotropes”—nanoporous materials having the same chemical composition but differing in their nanoscale architectures.

 

 

 

6 【生物】Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion

Armiyaw S. Nasamu, et.al

参与疟原虫出入细胞的天冬氨酰蛋白酶IX和X成为药物介入靶标

http://science.sciencemag.org/content/358/6362/518

(导读 阿金)恶性疟原虫蛋白酶长期作为药物靶标进行研究,但是其中天冬氨酸蛋白酶IX和X(PMIX和PMX)的功能尚未知晓。本研究鉴定出PMIX是入侵宿主红细胞的必要介质,而PMX则同时参与疟原虫入侵和迁出宿主细胞。同时鉴定出PMX为靶向的强抗疟活性化合物。

Proteases of the malaria parasite Plasmodium falciparum have long been investigated as drug targets. The P. falciparum genome encodes 10 aspartic proteases called plasmepsins, which are involved in diverse cellular processes. Most have been studied extensively but the functions of plasmepsins IX and X (PMIX and PMX) were unknown. Here we show that PMIX is essential for erythrocyte invasion, acting on rhoptry secretory organelle biogenesis. In contrast, PMX is essential for both egress and invasion, controlling maturation of the subtilisin-like serine protease SUB1 in exoneme secretory vesicles. We have identified compounds with potent antimalarial activity targeting PMX, including a compound known to have oral efficacy in a mouse model of malaria.

 

7 【生物】A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress

Paco Pino  et.al

多级抗疟药物阻断参与疟原虫出入细胞的蛋白酶PMIX和PMX

http://science.sciencemag.org/content/358/6362/522

(导读 阿金)通过细胞器调控胞吐作用对疟原虫出入细胞至关重要。本研究报道一种多级抗疟活性抑制药物——基于羟乙基胺架构的化合物49c。该化合物能够分别靶向相应的PMIX和PMX成熟因子,抑制棒状体和微线体蛋白的前胞吐过程。标志抗疟药物开发进入一个新阶段。

Regulated exocytosis by secretory organelles is important for malaria parasite invasion and egress. Many parasite effector proteins, including perforins, adhesins, and proteases, are extensively proteolytically processed both pre- and postexocytosis. Here we report the multistage antiplasmodial activity of the aspartic protease inhibitor hydroxyl-ethyl-amine–based scaffold compound 49c. This scaffold inhibits the preexocytosis processing of several secreted rhoptry and microneme proteins by targeting the corresponding maturases plasmepsins IX (PMIX) and X (PMX), respectively. Conditional excision of PMIX revealed its crucial role in invasion, and recombinantly active PMIX and PMX cleave egress and invasion factors in a 49c-sensitive manner.

 

8【生物】Nε-Fatty acylation of Rho GTPases by a MARTX toxin effector

Yan Zhou and Chunfeng Huang   et.al

MARTX毒素的效应因子介导Rho GTP酶的Nε-脂肪酰化反应

http://science.sciencemag.org/content/358/6362/528

(导读 阿金)MARTX毒素能自主催化切割为多个效应因子,进入宿主细胞调节其信号转通路,而RID就是其中之一。本研究发现RID是一种Nε-脂肪酰基转移酶,能抑制Rho GTP酶活性并破坏其在宿主细胞内的信号转导。因此,确定RID能介导哺乳动物蛋白的Nε-脂肪酰化反应,促进对致命细菌致病机制的深入了解。

 

The multifunctional autoprocessing repeats-in-toxin (MARTX) toxins are a family of large toxins that are extensively distributed in bacterial pathogens. MARTX toxins are autocatalytically cleaved to multiple effector domains, which are released into host cells to modulate the host signaling pathways. The Rho guanosine triphosphatase (GTPase) inactivation domain (RID), a conserved effector domain of MARTX toxins, is implicated in cell rounding by disrupting the host actin cytoskeleton. We found that the RID is an Nε-fatty acyltransferase that covalently modifies the lysine residues in the C-terminal polybasic region of Rho GTPases. The resulting fatty acylation inhibited Rho GTPases and disrupted Rho GTPase–mediated signaling in the host. Thus, RID can mediate the lysine Nε-fatty acylation of mammalian proteins and represents a family of toxins that harbor N-fatty acyltransferase activities in bacterial pathogens.

 

9【生物】Second messenger–mediated tactile response by a bacterial rotary motor

Isabelle Hug,  et.al

 

第二信使介导的鞭毛马达触觉反应使细菌粘附到表面

 

 

http://science.sciencemag.org/content/358/6362/531

 

(导读 严冰)细菌遇到表面时会粘附到表面上,这一过程中包含的机械敏感原理和下游信号尚不清楚。本文报导,新月柄杆菌(Caulobacter crescentus)鞭毛内的旋转马达作为感受器,可促进第二信使c-di-GMP的产生,从而变构激活糖基转移酶HfsJ,快速合成多糖,使细菌粘附到表面。

 

 

When bacteria encounter surfaces, they respond with surface colonization and virulence induction. The mechanisms of bacterial mechanosensation and downstream signaling remain poorly understood. Here, we describe a tactile sensing cascade in Caulobacter crescentus in which the flagellar motor acts as sensor. Surface-induced motor interference stimulated the production of the second messenger cyclic diguanylate by the motor-associated diguanylate cyclase DgcB. This led to the allosteric activation of the glycosyltransferase HfsJ to promote rapid synthesis of a polysaccharide adhesin and surface anchoring. Although the membrane-embedded motor unit was essential for surface sensing, mutants that lack external flagellar structures were hypersensitive to mechanical stimuli. Thus, the bacterial flagellar motor acts as a tetherless sensor reminiscent of mechanosensitive channels.

 

 

10 【生物】Obstruction of pilus retraction stimulates bacterial surface sensing

Courtney K. Ellison  et.al

 

菌毛发细表面感

 

http://science.sciencemag.org/content/358/6362/535

 

图片3.png 

图片来源:Science

 

导读 郭思瑶)识别表面接触转换生理形态十分重要。菌毛在此过程中发挥重要作用但其机制尚不清楚。科学家再现了新月柄杆菌菌毛伸展和收缩的动态循环,其循环与粘着物的合成同步,物理上阻断菌毛收缩可让细菌误认为感知到表面接触,从而形成粘着物。这说明细菌是依靠菌毛收缩的阻力和粘着到表面的菌毛来完成表面接触感知的。

 

 

 

 It is critical for bacteria to recognize surface contact and initiate physiological changes required for surface-associated lifestyles. Ubiquitous microbial appendages called pili are involved in sensing surfaces and facilitating downstream behaviors, but the mechanism by which pili mediate surface sensing has been unclear. We visualized Caulobacter crescentus pili undergoing dynamic cycles of extension and retraction. Within seconds of surface contact, these cycles ceased, which coincided with synthesis of the adhesive holdfast required for attachment. Physically blocking pili imposed resistance to pilus retraction, which was sufficient to stimulate holdfast synthesis without surface contact. Thus, to sense surfaces, bacteria use the resistance on retracting, surface-bound pili that occurs upon surface contact.