《自然》（20181108出版）一周論文導讀

Nature, Volume 563 Issue 7730, 8 November 2018

《自然》2018年11月8日第563卷第7730期

封面：自下而上的生物學

為了解開細胞如何運作的謎團，標準的方法是自上而下分析各種細胞組件在自然環境中相互作用的方式。但現在，技術進步使研究人員可以利用工程學原理自下而上重建生物過程。

這期特刊探討了自下而上的細胞生物學的潛力和可能存在的局限。

從開發細胞膜和代謝途徑到為醫療應用設計類似細胞的系統，再到創建可拉伸和變形的細胞層，研究人員正在拼接這個複雜的細胞世界。

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.

免疫學Immunology

Gene expression variability across cells and species shapes innate immunity

不同細胞和物種間的基因表達差異形成先天免疫

作者：Tzachi Hagai, Xi Chen, Michael L?ssig, Sarah A. Teichmann, et al.

相關論文信息：

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

導讀：

細胞作為抵禦病原體的第一道防線，具有先天免疫應答，且各個細胞間的免疫應答存在較大差異。這種應答是強有力的，但需要小心控制，以避免自我傷害。

然而，人們對於這些限制因素如何影響先天免疫進化仍然知之甚少。

研究者描述了先天免疫反應在物種間的轉錄分化和細胞間表達的差異。利用來自不同物種的成纖維細胞和單核吞噬細胞的群體和單細胞轉錄，在免疫刺激下，研究者繪製了先天免疫反應的結構。

轉錄分化基因（包括編碼細胞因子和趨化因子的基因）在不同細胞間存在差異，並且具有不同的啟動子結構。

相反，參與調節這種反應的基因（例如編碼轉錄因子和激酶的基因）在物種之間是保守的，在表達上表現出細胞間的低差異性。

研究者認為，這種在不同物種和條件下觀察到的表達模式已經進化為一種精細調節機制，從而實現有效而平衡的反應。

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.

生物學Biology

Active superelasticity in three-dimensional epithelia of controlled shape

上皮片是主動超彈性材料

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

相關論文信息：

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

導讀：

基本生物過程是由封閉加壓腔的彎曲上皮片進行的。這些上皮片如何發展和承受三維變形仍不清楚。

研究者將測量上皮張力和形狀與理論模型相結合，表明上皮片是主動超彈性材料。研究者用可控幾何形狀製作了一系列上皮穹狀構造。

血管內壁壓力和上皮張力的定量分析顯示，在若干倍面積分布區的菌株上存在張力高地。這些組織中的極端菌株在細胞水平上被高度異質菌株容納，這似乎與測量的張力均勻性相矛盾。

這種現象讓人想起超彈性——通常歸因於金屬合金中微觀材料不穩定性的一種行為。研究者表示，在上皮細胞中，這種不穩定性是由拉伸誘導的肌動蛋白皮質稀釋引起的，並被中間的纖維網路拯救。

研究揭示了一種機械行為，作者稱之為主動超彈性，它使上皮細胞在恆定的張力下維持極限拉伸。

Abstract

Fundamental biological processes are carried out by curved epithelial sheets that enclose a pressurized lumen. How these sheets develop and withstand three-dimensional deformations has remained unclear. Here we combine measurements of epithelial tension and shape with theoretical modelling to show that epithelial sheets are active superelastic materials. We produce arrays of epithelial domes with controlled geometry. Quantification of luminal pressure and epithelial tension reveals a tensional plateau over several-fold areal strains. These extreme strains in the tissue are accommodated by highly heterogeneous strains at a cellular level, in seeming contradiction to the measured tensional uniformity. This phenomenon is reminiscent of superelasticity, a behaviour that is generally attributed to microscopic material instabilities in metal alloys. We show that in epithelial cells this instability is triggered by a stretch-induced dilution of the actin cortex, and is rescued by the intermediate filament network. Our study reveals a type of mechanical behaviour—which we term active superelasticity—that enable sepithelial sheets to sustain extreme stretching under constant tension.

圖示：生成大小和形狀可控的上皮穹狀構造。

古微生物學Paleomicrobiology

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

重新評估格陵蘭島3700萬年前岩石中的生命證據

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

相關論文信息：

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

導讀：

格陵蘭島古太古代上殼岩帶含有地球上最古老的岩石，是尋找地球上最早生命證據的主要地點。然而，變質作用在很大程度上抹去了原始岩石的結構和組成，對保存生物特徵形成了挑戰。

最近對格陵蘭島伊蘇阿上殼岩帶3700萬年前的岩石進行的一項研究描述了一個罕見的區域，其中較低的形變和封閉的變質體系有助於保存主要的沉積特徵，包括推定的錐狀和穹狀疊層石（由微生物介導的沉積形成的疊層結構）。

這些結構的形態、層狀結構、礦物、化學和地質背景被認為是在37億年前地球岩石記錄開始時在淺海環境中形成微生物墊層的原因。

新研究則展示了這種結構的非生物的、沉積後的起源。通過對宿主岩石結構的形態和方向進行三維分析，同時結合對主岩石結構和微量元素化學的結構特徵分析，研究表明「疊層石」更有可能被解釋為埋藏很久之後在碳酸鹽—蝕變變質岩中形成的變形結構組合的一部分。

對伊蘇阿上殼岩帶結構的研究有助於為尋找火星過去的生命跡象起到警示作用，它強調了在適當尺度下對岩石形態、結構和地球化學進行三維綜合分析的重要性。

Abstract

The Palaeoarchean supracrustal belts in Greenland contain Earth』s oldest rocks and are a prime target in the search for the earliest evidence of life on Earth. However, metamorphism has largely obliterated original rock textures and compositions, posing a challenge to the preservation of biological signatures. A recent study of 3,700-million-year-old rocks of the Isua supracrustal belt in Greenland described a rare zone in which low deformation and a closed metamorphic system allowed preservation of primary sedimentary features, including putative conical and domical stromatolites ( laminated accretionary structures formed by microbially mediated sedimentation). The morphology, layering, mineralogy, chemistry and geological context of the structures were attributed to the formation of microbial mats in a shallow marine environment by 3,700 million years ago, at the start of Earth』s rock record. Here we report new research that shows a non-biological, post-depositional origin for the structures. Three-dimensional analysis of the morphology and orientation of the structures within the context of host rock fabrics, combined with texture-specific analyses of major and trace element chemistry, show that the 『stromatolites』 are more plausibly interpreted as part of an assemblage of deformation structures formed in carbonate-altered metasediments long after burial. The investigation of the structures of the Isua supracrustal belt serves as a cautionary tale in the search for signs of past life on Mars, highlighting the importance of three-dimensional, integrated analysis of morphology, rock fabrics and geochemistry at appropriate scales.

圖示：格陵蘭島的疊層石。

心理學Phychology

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

行動比語言更易增強可信度 促進非規範性公共產品的推廣

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

相關論文信息：

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

導讀：

促進公眾採用尚未被廣泛接受的公共產品是一項極具挑戰性的工作。在這項研究中，研究者分析了倡導者如何成功地促進非規範性（即稀少或不流行的）公共產品。

研究者利用增強可信度的文化進化理論進行這一研究。該理論認為，與單獨用語言傳播相比，信念可以通過行動得到更有效的傳播，因為行動提供了關於行為人真實信念的信息。

正如預測的那樣，一項在美國58個城鎮推廣安裝太陽能電池板項目（共140萬居民）的實地研究發現，自己安裝太陽能電池板的社區組織者比沒有安裝太陽能電池板的社區組織者多招募了62.8%的居民。

這一效應在3個預先登記的隨機調查實驗中得到了重複。這些實驗也支持這樣的理論預測，即這種效應是由參試者對社區組織者對太陽能電池板的看法（即二級信念）所驅動的，並證明了對其他4種高度非規範性行為的可推廣性。

這一發現揭示了如何傳播非規範性的親社會行為，提供了一種增強可信度的實證，對實踐者和決策者有實質性的影響。

Abstract

Promoting the adoption of public goods that are not yet widely accepted is particularly challenging. Here we examine how advocates can successfully promote non-normative (that is, rare or unpopular) public goods. We do so by applying the cultural evolutionary theory of credibility-enhancing displays, which argues that beliefs are spread more effectively by actions than by words alone—because actions provide information about the actor』s true beliefs. As predicted, a field study of a programme that promotes residential solar panel installation in 58 towns in the United States—comprising1.4 million residents in total—found that community organizers who themselves installed through the programme recruited 62.8% more residents to install solar panels than community organizers who did not. This effect was replicated in three pre-registered randomized survey experiments. These experiments also support the the oreticalprediction that this effect is specifically driven by subjects』 beliefs about what the community organizer believes about solar panels (that is, second-order beliefs), and demonstrate generalizability to four other highly non-normative behaviours. Our findings shed light on how to spread non-normative prosocial behaviours, offer an empirical demonstration of credibility-enhancing displays and have substantial implications for practitioners and policy-makers.

圖示：通過太陽能計劃安裝太陽能電池板的組織者比不安裝太陽能電池板的組織者更能成功說服他人加入其中。

農業Agriculture

Transcriptional regulation of nitrogen-associated metabolism and growth

氮相關代謝和生長的轉錄調節

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

相關論文信息：

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

導讀：

氮是植物生長和基本代謝過程所必需的宏量營養素。氮肥的應用提高了產量，這是綠色革命的一個重要因素。

然而，從生態學角度看，過度施用化肥會產生諸如富營養化等災難性的影響。更好地了解植物如何調節氮代謝對於提高植物產量和減少肥料的過度使用至關重要。

研究者提出了調節根莖系統結構的一個轉錄調控網路和21個轉錄因子，從而對氮可獲得性的變化作出應答。這些轉錄因子一個子集的遺傳擾動揭示了參與氮代謝的酶的協調轉錄調控。通過氮代謝的遺傳擾動，該網路中的轉錄調節由相關反饋進行轉錄修飾。

文章鑒定的網路、基因和基因調控模塊對提高農業生產率至關重要。

Abstract

Nitrogen is an essential macronutrient for plant growth and basic metabolic processes. The application of nitrogen-containing fertilizer increases yield, which has been a substantial factor in the green revolution. Ecologically, however, excessive application of fertilizer has disastrous effects such as eutrophication. A better understanding of how plants regulate nitrogen metabolism is critical to increase plant yield and reduce fertilizer overuse. Here we present a transcriptional regulatory network and twenty-one transcription factors that regulate the architecture of root and shoot systems in response to changes in nitrogen availability. Genetic perturbation of a subset of these transcription factors revealed coordinate transcriptional regulation of enzymes involved in nitrogen metabolism. Transcriptional regulators in the network are transcriptionally modified by feedback via genetic perturbation of nitrogen metabolism. The network, genes and gene-regulatory modules identified here will prove critical to increasing agricultural productivity.

圖示：硝酸鹽反應的轉錄調節網路。

人工智慧

Artificial Intelligence

Vowel recognition with four coupled spin-torque nano-oscillators

納米振蕩器硬體網路可識別母音

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

相關論文信息：

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

導讀：

近年來，人工神經網路已成為人工智慧的旗艦演算法。

研究者展示了自旋納米振蕩器的卓越可調諧性——即通過電流和磁場精確控制其頻率的可能性。研究者成功地訓練了一個由4個自旋轉矩納米振蕩器組成的硬體網路，通過根據自動實時學習規則調整其頻率來識別發出的母音。

研究者證明了高實驗識別率源於這些振蕩器的同步能力。研究結果表明，可通過賦予小硬體神經網路非線性動力學特性，如振蕩和同步特性，來完成非平凡的模式分類任務。

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.

天文學Astronomy

Apopulation of luminous accreting blackholes with hidden mergers

光吸積黑洞群的隱性合併

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

相關論文信息：

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

導讀：

大型星系合併被認為在推動超大質量黑洞的成長過程中扮演了重要角色。然而，在觀測方面對這一假設的支持情況卻並不樂觀，一些研究表明合併星系和發光類星體之間存在關聯，而另一些研究則表示沒有這種關聯。

最近的觀察表明，即使在合併早期階段，當星系被很好地分離（5到40千秒差距）時，黑洞也很可能在合併引起的氣體和塵埃中變得非常模糊。合併模擬進一步表明，當兩個星系核在很近的距離分開（小於3千秒差距）時，這種模糊的黑洞吸積會在最後合併階段達到峰值。

了解這一最後階段需要結合高空間解析度紅外成像和高靈敏度硬X射線觀測，以檢測高度模糊的源。

然而，進來通過X射線觀測在附近（距離在250百萬秒差距以下）發現了大量模糊的光吸積超大質量黑洞。

研究者報告了對硬X射線發現的黑洞的高解析度紅外觀測，以及發現的模糊的核合併發現，這是超大質量黑洞合併的母體。

研究者發現，與恆星質量和恆星形成速率（1.1%）相匹配的不活躍的星系樣本相比，模糊的發光黑洞（輻射熱光度高於每秒2×10⁴⁴爾格）表現出顯著（P < 0.001）後期核合併（17.6%）過剩，這些與理論預測一致。

研究者通過水動力學模擬證實在這一最後階段，富含氣體的模糊發光黑洞主合併體的核合併過剩確實是最強的。

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<0.001) excess of late-stage nuclear mergers (17.6 percent) compared to a sample of inactive galaxies with matching stellar masses and star formation rates (1.1 percent), in agreement with theoretical predictions. Using hydrodynamic simulations, we confirm that the excess of nuclear mergers is indeed strongest for gas-rich major-merger hosts of obscured luminous black holes in this final stage.

圖示：最終階段合併的示例圖像。

Palladium-mediated enzymeactivation suggestsmultiphase initiation of glycogenesis

鈀介導的酶激活表明多相糖原生成啟動

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

相關論文信息：

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

導讀：

糖原是人體、動物和真菌中必需的葡萄糖（以及能量）儲存分子，其生物合成是由糖基轉移酶（GYG）啟動的。糖原形成缺陷會導致神經退行性和代謝性疾病，小鼠在敲除GYG和遺傳人類GYG突變後會損害其糖原合成。

GYG作為糖原顆粒形成的「種子核」，通過催化其自身的逐步自糖基化，在起始位點Tyr195形成共價結合的低聚糖鏈。

到目前為止，由於無法獲得這種蛋白（可不同尋常地同時作為催化劑和底物）的同質糖基形式，其精確機理研究一直受阻。

研究者證明了通過鈀介導的酶激活「分流」過程，利用蛋白質C-C鍵的形成，可實現對GYG不同的、均糖基化狀態的前所未有的直接獲得。

仔細模仿GYG中間體可以在不同階段重現催化活性，發現GYG使用糖基時的三相動力學和底物可塑性。研究揭示了奠定代謝過程精確性的一種包容但可「驗證」的機制。

目前對活性酶中間狀態的直接、化學控制研究表明，這種依賴於連接的激活可能是研究相關機制的有力工具。

Abstract

Biosynthesis of glycogen, the essential glucose (and hence energy) storage molecule in humans, animals and fungi1, is initiated by the glycosyltransferase enzyme, glycogenin (GYG). Deficiencies in glycogen formation cause neurodegenerative and metabolic disease, and mouse knockout and inherited human mutations of GYG impair glycogen synthesis. GYG acts as a 『seed core』 for the formation of the glycogen particle by catalysing its own step wise autoglucosylation to form a covalently bound gluco-oligosaccharide chain at initiation site Tyr 195. Precise mechanistic studies have so far been prevented by an inability to access homogeneous glycoforms of this protein, which unusually acts as both catalyst and substrate. Here we show that unprecedented direct access to different, homogeneously glucosylated states of GYG can be accomplished through a palladium-mediated enzyme activation 『shunt』 process using on-protein C–C bond formation. Careful mimicry of GYG intermediates recapitulates catalytic activity at distinct stages, which in turn allows discovery of triphasic kinetics and substrate plasticity in GYG』s use of sugar substrates. This reveals a tolerant but 『proof-read』 mechanism that underlies the precision of this metabolic process. The present demonstration of direct, chemically controlled access to intermediate states of active enzymes suggests that such ligation-dependent activation could be a powerful tool in the study of mechanism.

（晉楠）

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此次改版後，每個用戶最多可以設置12個常讀訂閱號，這些訂閱號將以往常的大圖封面展示。為了不錯過科學網的推送，請根據以下操作，將我們「星標」吧！

點擊「科學網」進入公號頁面→點擊右上角的···菜單 →選擇「設為星標」，搞定！

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