《自然》（20181108出版）一周论文导读

Nature, Volume 563 Issue 7730, 8 November 2018

《自然》2018年11月8日第563卷第7730期

图片来源 Nik Spencer/Nature

封面：自下而上的生物学

为了解开细胞如何运作的谜团，标准的方法是自上而下分析各种细胞组件在自然环境中相互作用的方式。但现在，技术进步使研究人员可以利用工程学原理自下而上重建生物过程。

这期特刊探讨了自下而上的细胞生物学的潜力和可能存在的局限。

从开发细胞膜和代谢途径到为医疗应用设计类似细胞的系统，再到创建可拉伸和变形的细胞层，研究人员正在拼接这个复杂的细胞世界。

Cover:Bottom-up biology

In trying to unpick the mysteries of how cells work, the standard approach has been to work from the top down, dissecting the way various cellular components interact in their natural environment. But technical advances now allow researchers to use engineering principles to reconstruct biological processes from the bottom up. This special issue explores the potential and possible limits of bottom-up cell biology. From developing membranes and metabolic pathways to designing cell-like systems for medical applications, and creating cell layers that stretch and deform, researchers are piecing together the complex world of the cell.

免疫学Immunology

Gene expression variability across cells and species shapes innate immunity

不同细胞和物种间的基因表达差异形成先天免疫

▲ 作者：Tzachi Hagai, Xi Chen, Michael Lässig, Sarah A. Teichmann, et al.

▲ 相关论文信息：

https://www.nature.com/articles/s41586-018-0657-2

▲导读：

细胞作为抵御病原体的第一道防线，具有先天免疫应答，且各个细胞间的免疫应答存在较大差异。这种应答是强有力的，但需要小心控制，以避免自我伤害。

然而，人们对于这些限制因素如何影响先天免疫进化仍然知之甚少。

研究者描述了先天免疫反应在物种间的转录分化和细胞间表达的差异。利用来自不同物种的成纤维细胞和单核吞噬细胞的群体和单细胞转录，在免疫刺激下，研究者绘制了先天免疫反应的结构。

转录分化基因（包括编码细胞因子和趋化因子的基因）在不同细胞间存在差异，并且具有不同的启动子结构。

相反，参与调节这种反应的基因（例如编码转录因子和激酶的基因）在物种之间是保守的，在表达上表现出细胞间的低差异性。

研究者认为，这种在不同物种和条件下观察到的表达模式已经进化为一种精细调节机制，从而实现有效而平衡的反应。

▲ Abstract

As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response’s transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response.

生物学Biology

Active superelasticity in three-dimensional epithelia of controlled shape

上皮片是主动超弹性材料

▲ 作者：Ernest Latorre, Sohan Kale, Laura Casares, Marino Arroyo, Xavier Trepat, et al.

▲ 相关论文信息：

https://www.nature.com/articles/s41586-018-0671-4

▲导读：

基本生物过程是由封闭加压腔的弯曲上皮片进行的。这些上皮片如何发展和承受三维变形仍不清楚。

研究者将测量上皮张力和形状与理论模型相结合，表明上皮片是主动超弹性材料。研究者用可控几何形状制作了一系列上皮穹状构造。

血管内壁压力和上皮张力的定量分析显示，在若干倍面积分布区的菌株上存在张力高地。这些组织中的极端菌株在细胞水平上被高度异质菌株容纳，这似乎与测量的张力均匀性相矛盾。

这种现象让人想起超弹性——通常归因于金属合金中微观材料不稳定性的一种行为。研究者表示，在上皮细胞中，这种不稳定性是由拉伸诱导的肌动蛋白皮质稀释引起的，并被中间的纤维网络拯救。

研究揭示了一种机械行为，作者称之为主动超弹性，它使上皮细胞在恒定的张力下维持极限拉伸。

▲ Abstract

Fundamentalbiological processes are carried out by curved epithelialsheets thatenclose a pressurized lumen. How these sheets develop andwithstand three-dimensional deformations has remained unclear. Here wecombine measurementsof epithelial tension and shape with theoreticalmodellingtoshow thatepithelial sheets are active superelastic materials. We produce arraysof epithelialdomes with controlled geometry. Quantification of luminalpressure andepithelial tension reveals a tensional plateau over several-foldareal strains. These extreme strains in the tissue are accommodated byhighly heterogeneousstrains at a cellular level, in seemingcontradictiontothe measuredtensional uniformity. This phenomenon is reminiscentof superelasticity, abehaviourthat is generally attributed tomicroscopic materialinstabilities in metal alloys. We show that in epithelial cellsthis instabilityis triggered by a stretch-induced dilution of the actin cortex,and isrescued by the intermediate filament network. Our study reveals a typeof mechanical behaviour—which we term active superelasticity—thatenable sepithelialsheets to sustain extreme stretching under constant tension.

图示：生成大小和形状可控的上皮穹状构造。

古微生物学Paleomicrobiology

Reassessing evidence of life in 3,700-million-year-old rocks of Greenland

重新评估格陵兰岛3700万年前岩石中的生命证据

▲ 作者：Abigail C.Allwood, Minik T. Rosing, Joel A. Hurowitz, Christopher M. Heirwegh, et al.

▲ 相关论文信息：

https://www.nature.com/articles/s41586-018-0610-4

▲导读：

格陵兰岛古太古代上壳岩带含有地球上最古老的岩石，是寻找地球上最早生命证据的主要地点。然而，变质作用在很大程度上抹去了原始岩石的结构和组成，对保存生物特征形成了挑战。

最近对格陵兰岛伊苏阿上壳岩带3700万年前的岩石进行的一项研究描述了一个罕见的区域，其中较低的形变和封闭的变质体系有助于保存主要的沉积特征，包括推定的锥状和穹状叠层石（由微生物介导的沉积形成的叠层结构）。

这些结构的形态、层状结构、矿物、化学和地质背景被认为是在37亿年前地球岩石记录开始时在浅海环境中形成微生物垫层的原因。

新研究则展示了这种结构的非生物的、沉积后的起源。通过对宿主岩石结构的形态和方向进行三维分析，同时结合对主岩石结构和微量元素化学的结构特征分析，研究表明“叠层石”更有可能被解释为埋藏很久之后在碳酸盐—蚀变变质岩中形成的变形结构组合的一部分。

对伊苏阿上壳岩带结构的研究有助于为寻找火星过去的生命迹象起到警示作用，它强调了在适当尺度下对岩石形态、结构和地球化学进行三维综合分析的重要性。

▲ Abstract

The Palaeoarcheansupracrustalbelts in Greenland contain Earth’soldest rocksand are a prime target in the search for the earliest evidence of lifeon Earth. However, metamorphism has largely obliterated original rock texturesand compositions, posing a challenge to the preservation of biological signatures. Arecent study of 3,700-million-year-old rocks of the Isuasupracrustalbeltin Greenlanddescribed a rare zone in which low deformation and aclosed metamorphicsystem allowed preservation of primary sedimentary features, includingputative conical and domical stromatolites ( laminatedaccretionary structuresformed by microbially mediated sedimentation). The morphology, layering, mineralogy, chemistry and geological context of the structures wereattributed tothe formation of microbial mats in a shallow marine environment by 3,700 million years ago, at the start of Earth’s rock record.Here wereport new research that shows a non-biological, post-depositionalorigin forthe structures. Three-dimensional analysis of the morphologyand orientationof the structures within the context of host rock fabrics,combined withtexture-specific analyses of major and trace element chemistry, showthat the‘stromatolites’ are more plausibly interpreted as part of an assemblageof deformationstructures formed in carbonate-altered metasediments longafter burial. The investigation of the structures of the Isuasupracrustal belt servesas a cautionary tale in the search for signs of past life on Mars, highlightingthe importance of three-dimensional, integrated analysisof morphology, rock fabrics and geochemistry at appropriate scales.

图示：格陵兰岛的叠层石。

心理学Phychology

Credibility-enhancing displayspromote the provision of non-normative public goods

行动比语言更易增强可信度促进非规范性公共产品的推广

▲ 作者：Gordon T.Kraft-Todd, Bryan Bollinger, Kenneth Gillingham, Stefan Lamp, et al.

▲ 相关论文信息：

https://www.nature.com/articles/s41586-018-0647-4

▲ 导读：

促进公众采用尚未被广泛接受的公共产品是一项极具挑战性的工作。在这项研究中，研究者分析了倡导者如何成功地促进非规范性（即稀少或不流行的）公共产品。

研究者利用增强可信度的文化进化理论进行这一研究。该理论认为，与单独用语言传播相比，信念可以通过行动得到更有效的传播，因为行动提供了关于行为人真实信念的信息。

正如预测的那样，一项在美国58个城镇推广安装太阳能电池板项目（共140万居民）的实地研究发现，自己安装太阳能电池板的社区组织者比没有安装太阳能电池板的社区组织者多招募了62.8%的居民。

这一效应在3个预先登记的随机调查实验中得到了重复。这些实验也支持这样的理论预测，即这种效应是由参试者对社区组织者对太阳能电池板的看法（即二级信念）所驱动的，并证明了对其他4种高度非规范性行为的可推广性。

这一发现揭示了如何传播非规范性的亲社会行为，提供了一种增强可信度的实证，对实践者和决策者有实质性的影响。

▲ Abstract

Promotingthe adoption of public goods that are not yet widely acceptedis particularlychallenging. Here we examine how advocates cansuccessfully promotenon-normative (that is, rare or unpopular) public goods. We do soby applyingthe cultural evolutionary theory of credibility-enhancing displays, whichargues that beliefs are spread more effectively by actions than bywords alone—because actions provide information about the actor’strue beliefs. As predicted, a field study of a programme that promotesresidential solarpanel installation in 58 towns in the United States—comprising1.4millionresidents in total—found that community organizers who themselves installed throughthe programmerecruited 62.8% more residents to install solar panels thancommunity organizerswho did not. This effect was replicated in three pre-registered randomizedsurvey experiments. These experiments also support thethe oreticalpredictionthat this effect is specifically driven by subjects’beliefs aboutwhat the community organizer believes about solar panels (that is, second-orderbeliefs), and demonstrate generalizability to four otherhighly non-normativebehaviours. Our findings shed light on how tospread non-normative prosocialbehaviours, offer an empirical demonstrationof credibility-enhancing displays and have substantial implicationsfor practitionersand policy-makers.

图示：通过太阳能计划安装太阳能电池板的组织者比不安装太阳能电池板的组织者更能成功说服他人加入其中。

农业Agriculture

Transcriptional regulation of nitrogen-associated metabolism and growth

氮相关代谢和生长的转录调节

▲ 作者：Allison Gaudinier, JoelRodriguez-Medina, Lifang Zhang, Doreen Ware, Siobhan M. Brady, et al.

▲ 相关论文信息：

https://www.nature.com/articles/s41586-018-0656-3

▲导读：

氮是植物生长和基本代谢过程所必需的宏量营养素。氮肥的应用提高了产量，这是绿色革命的一个重要因素。

然而，从生态学角度看，过度施用化肥会产生诸如富营养化等灾难性的影响。更好地了解植物如何调节氮代谢对于提高植物产量和减少肥料的过度使用至关重要。

研究者提出了调节根茎系统结构的一个转录调控网络和21个转录因子，从而对氮可获得性的变化作出应答。这些转录因子一个子集的遗传扰动揭示了参与氮代谢的酶的协调转录调控。通过氮代谢的遗传扰动，该网络中的转录调节由相关反馈进行转录修饰。

文章鉴定的网络、基因和基因调控模块对提高农业生产率至关重要。

▲ Abstract

Nitrogen is anessential macronutrientfor plant growth and basic metabolic processes. Theapplication ofnitrogen-containing fertilizer increases yield, which has been asubstantial factorin the green revolution. Ecologically, however, excessive applicationof fertilizerhas disastrous effects such as eutrophication. Abetter understandingof how plants regulate nitrogen metabolism is criticalto increaseplant yield and reduce fertilizer overuse. Here we presenta transcriptionalregulatory network and twenty-one transcription factorsthat regulatethe architecture of root and shoot systems in response to changesin nitrogenavailability. Genetic perturbation of a subset of thesetranscription factorsrevealed coordinate transcriptional regulation of enzymes involvedin nitrogenmetabolism. Transcriptional regulators in the networkare transcriptionallymodified by feedback via genetic perturbation ofnitrogen metabolism. The network, genes and gene-regulatory modules identified herewill provecritical to increasing agricultural productivity.

图示：硝酸盐反应的转录调节网络。

人工智能

Artificial Intelligence

Vowel recognition with four coupled spin-torque nano-oscillators

纳米振荡器硬件网络可识别元音

▲ 作者：Miguel Romera, Philippe Talatchian, Sumito Tsunegi, Flavio Abreu Araujo, et al.

▲ 相关论文信息：

https://www.nature.com/articles/s41586-018-0632-y

▲导读：

近年来，人工神经网络已成为人工智能的旗舰算法。

研究者展示了自旋纳米振荡器的卓越可调谐性——即通过电流和磁场精确控制其频率的可能性。研究者成功地训练了一个由4个自旋转矩纳米振荡器组成的硬件网络，通过根据自动实时学习规则调整其频率来识别发出的元音。

研究者证明了高实验识别率源于这些振荡器的同步能力。研究结果表明，可通过赋予小硬件神经网络非线性动力学特性，如振荡和同步特性，来完成非平凡的模式分类任务。

▲ Abstract

In recent years, artificial neural networks have become the flagship algorithm of artificial intelligence. Here we show that the outstanding tunability of spintronic nano-oscillators—that is, the possibility of accurately controlling their frequency across a wide range, through electrical current and magnetic field. We successfully train a hardware network of four spin-torque nano-oscillators to recognize spoken vowels by tuning their frequencies according to an automatic real-time learning rule. We show that the high experimental recognition rates stem from the ability of these oscillators to synchronize. Our results demonstrate that non-trivial pattern classification tasks can be achieved with small hardware neural networks by endowing them with nonlinear dynamical features such as oscillations and synchronization.

天文学Astronomy

Apopulation of luminous accreting blackholes with hidden mergers

光吸积黑洞群的隐性合并

▲ 作者：Michael J. Koss, Laura Blecha, Claudio Ricci, Sylvain Veilleux, DavidB. Sanders, et al.

▲ 相关论文信息：

https://www.nature.com/articles/s41586-018-0652-7

▲导读：

大型星系合并被认为在推动超大质量黑洞的成长过程中扮演了重要角色。然而，在观测方面对这一假设的支持情况却并不乐观，一些研究表明合并星系和发光类星体之间存在关联，而另一些研究则表示没有这种关联。

最近的观察表明，即使在合并早期阶段，当星系被很好地分离（5到40千秒差距）时，黑洞也很可能在合并引起的气体和尘埃中变得非常模糊。合并模拟进一步表明，当两个星系核在很近的距离分开（小于3千秒差距）时，这种模糊的黑洞吸积会在最后合并阶段达到峰值。

了解这一最后阶段需要结合高空间分辨率红外成像和高灵敏度硬X射线观测，以检测高度模糊的源。

然而，进来通过X射线观测在附近（距离在250百万秒差距以下）发现了大量模糊的光吸积超大质量黑洞。

研究者报告了对硬X射线发现的黑洞的高分辨率红外观测，以及发现的模糊的核合并发现，这是超大质量黑洞合并的母体。

研究者发现，与恒星质量和恒星形成速率（1.1%）相匹配的不活跃的星系样本相比，模糊的发光黑洞（辐射热光度高于每秒2×1044尔格）表现出显著（P < 0.001）后期核合并（17.6%）过剩，这些与理论预测一致。

研究者通过水动力学模拟证实在这一最后阶段，富含气体的模糊发光黑洞主合并体的核合并过剩确实是最强的。

▲ Abstract

Major galaxy mergers are thought to play an important part in fuelling the growth of supermassive black holes. However, observational support for this hypothesis is mixed, with some studies showing a correlation between merging galaxies and luminous quasars and others showing no such association. Recent observations have shown that a black hole is likely to become heavily obscured behind merger-driven gas and dust, even in the early stages of the merger, when the galaxies are well separated (5 to 40 kiloparsecs). Merger simulations further suggest that such obscuration and black-hole accretion peaks in the final merger stage, when the two galactic nuclei are closely separated (less than 3 kiloparsecs). Resolving this final stage requires a combination of high-spatial-resolution infrared imaging and high-sensitivity hard-X-ray observations to detect highly obscured sources. However, large numbers of obscured luminous accreting supermassive black holes have been recently detected nearby (distances below 250 megaparsecs) in X-ray observations. Here we report high-resolution infrared observations of hard-X-ray-selected blackholes and the discovery of obscured nuclear mergers, the parent populations of supermassive-black-hole mergers. We find that obscured luminous black holes(bolometric luminosity higher than 2 ×1044ergs per second) show a significant (P

图示：最终阶段合并的示例图像。

Palladium-mediated enzymeactivation suggestsmultiphase initiation of glycogenesis

钯介导的酶激活表明多相糖原生成启动

▲ 作者：Matthew K. Bilyard, Henry J. Bailey, Lluís Raich, Maria A. Gafitescu, Takuya Machida, et al.

▲ 相关论文信息：

https://www.nature.com/articles/s41586-018-0644-7

▲导读：

糖原是人体、动物和真菌中必需的葡萄糖（以及能量）储存分子，其生物合成是由糖基转移酶（GYG）启动的。糖原形成缺陷会导致神经退行性和代谢性疾病，小鼠在敲除GYG和遗传人类GYG突变后会损害其糖原合成。

GYG作为糖原颗粒形成的“种子核”，通过催化其自身的逐步自糖基化，在起始位点Tyr195形成共价结合的低聚糖链。

到目前为止，由于无法获得这种蛋白（可不同寻常地同时作为催化剂和底物）的同质糖基形式，其精确机理研究一直受阻。

研究者证明了通过钯介导的酶激活“分流”过程，利用蛋白质C-C键的形成，可实现对GYG不同的、均糖基化状态的前所未有的直接获得。

仔细模仿GYG中间体可以在不同阶段重现催化活性，发现GYG使用糖基时的三相动力学和底物可塑性。研究揭示了奠定代谢过程精确性的一种包容但可“验证”的机制。

目前对活性酶中间状态的直接、化学控制研究表明，这种依赖于连接的激活可能是研究相关机制的有力工具。

▲ Abstract

Biosynthesis ofglycogen, the essential glucose (and hence energy) storage moleculein humans, animals and fungi1, is initiated by the glycosyltransferase enzyme,glycogenin(GYG). Deficiencies in glycogen formation causeneurodegenerative andmetabolic disease, and mouse knockout and inherited human mutations of GYG impair glycogen synthesis. GYG acts as a ‘seed core’ forthe formationof the glycogen particle bycatalysingits ownstep wise autoglucosylationto form a covalently boundgluco-oligosaccharidechainat initiationsite Tyr 195. Precise mechanistic studies have so far beenprevented byan inability to access homogeneous glycoforms of this protein,which unusuallyacts as both catalyst and substrate. Here we show thatunprecedented directaccess to different, homogeneously glucosylated states of GYG canbe accomplishedthrough a palladium-mediated enzyme activation ‘shunt’process usingon-protein C–C bond formation. Careful mimicry of GYG intermediatesrecapitulates catalyticactivity at distinct stages, which in turn allows discoveryof triphasickinetics and substrate plasticity in GYG’s useof sugarsubstrates. This reveals a tolerant but ‘proof-read’mechanism thatunderlies the precision of this metabolic process. Thepresent demonstrationof direct, chemically controlled access to intermediate statesof activeenzymes suggests that such ligation-dependent activation could bea powerfultool in the study of mechanism.