nature中文摘要 2015.4.2

陆地生物多样性；自闭症遗传机构；双原子干涉实验；早泥盆世硬骨鱼状颅骨特征；miRNA初级转录物编码；人类抗体中识别登革热病毒

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Volume 520 Number 7545， 2 April 2015

 

Global effects of land use on local terrestrial biodiversity

全球土地使用对当地陆地生物多样性的影响 

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http://www.nature.com/nature/journal/v520/n7545/full/nature14324.html

人类活动，尤其是栖息地的改变和退化，正在导致全球生物多样性的减少。在这种情况下，当地生态组合的反馈方式目前尚不清楚。由于他们对很多生态系统的功能和服务十分重要，这种认识的缺乏应引起一定担忧。本文以前所未有的地理面积和种群覆盖范围对一处陆地生物组合数据库进行了分析，以量化当地的生物多样性对土地使用及相关变化的反应。本文展示出，在受影响最强烈的栖息地中，这些外界压力使样本范围内物种的丰富度平均降低了76.5%，整体数量降低了39.5%，稀有生物丰富度降低了40.3%。我们估计，这些压力已经造成样本范围内全球的平均物种丰富度、整体数量和稀有生物丰富度下降,幅度分别达13.6%，10.7%和8.1%，并伴随有显著的空间变化。如按照现行的土地利用方案，未来预计会出现进一步的快速物种流失；2100年前，全球样本范围内的丰富度将继续下降3.4%，损失主要集中在生物多样但经济落后的国家。有力的缓解措施可产生更多积极的生物多样性变化（高达平均1.9%的增长），而这类改变则与国家的社会经济地位没有太大关联。

 

Loss of δ-catenin function in severe autism

严重自闭症中δ-连环蛋白的功能缺失

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http://www.nature.com/nature/journal/v520/n7545/full/nature14186.html

 

自闭症是一种多因子神经发育障碍，其对于男性的影响远超过女性。因此，在多因子遗传假设下，女性只有在跨越更高的生物学阈值后才会受到影响。本文假设，有严重病症的多女性多发病家庭中，严重病患的基因组中富集了保守残基的有害变异变。这样选取样本增加了在病例数量中等情况下，检测到关键自闭症基因的可能。本研究即应用了此策略。本研究组识别了多女性多发病家庭中编码粘附连接δ-连环蛋白（CTNND2）的基因中的错义突变和剂量序列变异。进一步地，通过针对斑马鱼胚胎和来自野生型及CTNND2缺失小鼠胚胎的人工培养海马神经元的功能分析，证明了CTNND2功能缺失的影响。最后，借助基因表达和网络分析，本文指出CTNND2在神经发育方面的关键作用及其与染色质生物学的密切关系。本文的数据有助于对自闭症遗传结构的理解，并且其结果证明，极端表型的遗传学分析——如在多女性多发病家庭中的研究——在多因子障碍研究方面有着特殊的重要性。

 

Planet heating prevents inward migration of planetary cores

行星加热防止行星核向内迁移

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http://www.nature.com/nature/journal/v520/n7545/full/nature14277.html

行星系统诞生于包围在新形成的恒星周边的气体、尘埃和岩石碎片组成的圆面之中。固形物组成体积更大的岩石碎片，最终变成行星胚胎。然后，通过圆盘中剩余材料的吸积作用，行星胚胎继续增长扩大。同时，圆盘内的潮汐效应在行星的初期轨道上引起径向漂移，这一过程被称为迁移。理论预测，出现快速的向内迁移的胚胎质量要小于地球质量的3～4倍。若只有向内迁移作用，太阳系中比地球更远的行星胚胎将几乎不可能变成巨行星，这显然与观察结果相悖。对此，我们提出，与吸积落入物质有关的温度上升的不对称性产生一种力（这种效应我们称之为“热转矩”)，抵消了向内迁移，为巨行星的形成提供一条途径，也解释了重金属元素含量高的母恒星与其周围巨行星金属丰度的相关关系。

 

Atomic Hong–Ou–Mandel experiment

原子的Hong–Ou–Mandel实验揭示量子力学本质

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http://www.nature.com/nature/journal/v520/n7545/full/nature14331.html

双粒子干涉是量子力学的一个本质特征，甚至比单粒子的波粒二象性还要违反直觉。在这种波粒二象性中，经典的波和粒子的概念仍可以使用，因此在普通的时空中就能发生干涉。另一方面，双粒子干涉仅仅发生在数学空间中，因而没有经典对应。而纠缠，正是与这种干涉的本质相关的一种现象，同时也成为检验贝尔不等式不成立，从而反映量子力学的本质。Hong-Ou-Mandel实验是在概念上稍微简化之后的一种情况，描述的是双光子振幅之间的干涉会导致经典模型所无法解释的现象。巴黎第十一大学的研究者近期用原子代替光子进行了Hong-Ou-Mandel实验。他们制造出一个源，可以发射出成对的原子，并让每对原子中的其中一个通过分束器，进入两个入射通道的一个，另一个原子进入另一个入射通道。而如果这对原子在空间上是重叠的因而无法区分，它们就永远只能一起出现在一个出射通道中。这一结果表明，借用量子光学中的方法，通过对有质量的物体进行力学观测（如动量等）也可以检测贝尔不等式是否成立，并检验量子与经典之间的过渡理论。这一工作也提供了一种新的方式用以对非经典原子源进行基准测试，这可能在量子信息处理与量子模拟方面发挥作用。

 

Osteichthyan-like cranial conditions in an Early Devonian stem gnathostome

早泥盆世干群有颌类出现硬骨鱼状颅骨特征

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http://www.nature.com/nature/journal/v520/n7545/full/nature14065.html

志留纪和泥盆纪（距今443－358百万年）鱼类的系统发生一直是现代有颌类（有颌的脊椎生物）起源研究中的首要问题。其中心问题在于现生有颌脊椎生物最后一个共同祖先的形态学特征，该生物更接近硬骨鱼还是软骨鱼，两种假说为此争论不休。本文报道了一个新属新种，Janusiscus schultzei gen. et sp. nov.［斜体］，是一种来自西伯利亚早泥盆世（约415百万年前）的有颌类，此前被认为是辐鳍鱼。该标本为接近软骨鱼和硬骨鱼最后一个共同祖先的颅骨解剖学特征提供了重要的新信息。Janusiscus属的颅顶甲（skull roof）与早期硬骨鱼相似，巨大的骨板上具有蠕虫状的脊以及半封闭的感觉管（sensory canal）。高分辨率的计算机断层扫描（CT）显示，其脑壳具有可与软骨鱼（容纳颈内动脉的较大垂体末端开口）或硬骨鱼（面部神经通过颈静脉管穿出，淋巴导管从颅顶甲后部穿出）相关的典型特征，但缺少内颅腹裂，该形态的存在被认为是冠群有颌类的衍生特征。Janusiscus属中发育良好的颅骨连接过程有助于统一早期有颌脊椎动物脑颅形态的比较解剖学研究，阐释清楚“盾皮鱼”，软骨鱼和硬骨鱼的最初同源性。系统发生分析进一步支持软骨鱼纲与“棘鱼纲”亲缘关系更近的说法，并将Janusiscus属和神秘的Ramirosuarezia归为冠群有颌类。Janusiscus属与硬骨鱼纲的颅骨甲之间紧密的相关性表明，有颌脊椎动物的最后一个共同祖先已经具有一个广义的膜质骨骼，但Ramirosuarezia的解剖学特征中的某些不确定性又产生了一些疑问。Janusiscus属的内骨骼结构与其表面类似硬骨鱼的膜质骨骼之间意外的反差说明，其它不完全为人所知的志留－泥盆纪‘硬骨鱼’对于重建现代有颌类起源的特征演化模型具有潜在的重要性。

 

Evolution of the snake body form reveals homoplasy in amniote Hox gene function

蛇体形的演化揭示羊膜动物Hox基因功能的趋同现象

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http://www.nature.com/nature/journal/v520/n7545/full/nature14042.html

本文结合几何形态测定和最大似然分析，证明了身体延长、四肢退化的蜥蜴类和蛇类的前泄殖腔腹部区域与有肢体的类群相比，并没有显示出去区域化；同时，爬行动物腹部形态的种系发生研究结果也不认为蛇在演化过程中经历了区域化的丢失。本文证明，蛇的形态特征区域之间的界线，与测得的基因表达区域之间的界线相吻合，这说明参与腹部区域形成的Hox基因的功能是完全正常的。将化石和现代的羊膜动物的腹部骨骼，与羊膜动物的Hox基因表达分布相比较，发现在羊膜动物演化分枝上的主干物种和现存的蜥蜴（包括蛇类）中，功能性的、按顺序表达的Hox基因沿动物身体的前-后轴形成了一个微小的形态学梯度。现存的古蜥和哺乳动物的高度区域化的骨骼源自Hox密码的独立演化，并不代表存在蛇形体形的共同祖先。因此，蛇类发育上的起源的最佳解释是腹部跟背部区域的去偶联，以及体节数目的增加，而不是腹部Hox基因功能的改变。

 

Primary transcripts of microRNAs encode regulatory peptides

微小RNA(miRNA)的初级转录物编码调节肽

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http://www.nature.com/nature/journal/v520/n7545/full/nature14346.html

微小RNA（miRNAs）是通过结合并断裂特定目标基因的信使RNA或通过抑制其翻译过程，从而抑制其表达的小调节型RNA分子。起先，miRNA的基因被转录为比miRNA大得多的miRNA前体(pri-mRNAs)。其作用尚未被完全理解。本文证明，植物的miRNA前体含有编码调节肽的短开放阅读框。蒺藜苜蓿（Medicago truncatula）的pri-miR171b和拟南芥（Arabidopsis thaliana）的pri-miR165a均可产生多肽（分别被命名为miPEP171b和miPEP165a），并且可加强其相应成熟miRNAs的积累，导致有关根部发育的目的基因下调。miRNA编码肽（miRNA-encoded peptide ，miPEP）作用机制涉及pri-miRNA转录的上调。拟南芥和蒺藜苜蓿中的另外五个pri-miRNA也编码有活性的miPEP，表明miPEP在植物界中广泛存在。人工合成的miPEP171b和miPEP165a肽应用于植物后，特定地引发了miR171b和miR165a的积累，分别减少侧根发育，刺激主根生长。这些结果表明miPEPs有农艺学应用的潜力。

 

G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons

下丘脑神经元中MC4R与Kir7.1不依赖G蛋白的耦合

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http://www.nature.com/nature/journal/v520/n7545/full/nature14051.html

中央神经系统离散的下丘脑弓形神经元，调节性释放抑制食欲的a-黑色素细胞促进激素（anorexigenic α-melanocyte stimulating hormone，α-MSH）和促进食欲的Agouti相关蛋白（Agouti-related protein，AgRP）到共同的靶位点，这在能量稳态方面起着重要的作用。这两种多肽对黑色素皮质激素受体4（melanocortin-4 receptor，MC4R）都有很强的结合能力；目前的数据表明α-MSH作为一种激动剂能使该受体与Gas 信号通路相偶联，而AgRP能竞争性阻碍α-MSH的结合，并阻止该受体的类配体氨基酸末端结构域结合后导致的组成型活性。本文证明，在小鼠中α-MSH和AgRP调节的下丘脑室旁核（paraventricular nucleus of the hypothalamus，PVN）神经元的电活动可以不依赖Gas信号通路，而是由配体诱导MC4R与向内整流的钾通道--Kir7.1的关闭相偶联。此外， 我们还发现，AgRP是个有偏向性的激动剂，除了抑制α-MSH结合MC4R外，还能开放Kir7.1通道，从而超极化神经元。因此，Kir7.1的信号通路似乎处于PVN中黑色素皮质激素调节的能量稳态的中心。MC4R与Kir7.1通道的偶联可以解释由黑色素皮质激素信号所控制的能量稳态的特殊问题，包括MC4R的基因剂量效应和AgRP在进食方面的持续影响。

 

Recognition determinants of broadly neutralizing human antibodies against dengue viruses

广谱杀灭性人类抗体中识别登革热病毒的决定性部分

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http://www.nature.com/nature/journal/v520/n7545/full/nature14130.html

登革热由四种不同的登革热血清型病毒引起。登革热每年平均感染3900万人，其中的25%会显示出症状，然而现在并没有针对登革热的合格疫苗。最近进入三期试验的疫苗只有部分保护作用，而且对登革热血清型2病毒完全无效。目前为止的结构研究，利用血清型特异性的人类抗体，仅仅解析了病毒的抗原决定簇。本研究组近期分离出的人类抗体，能有效杀灭全部四种血清型的病毒。本文描述了四种广谱杀灭性的抗体与从血清型2登革热病毒中获得的包膜糖蛋白E形成的复合物的X射线结构。结果表明（广泛抗体）识别的关键部分位于E二聚物分界面的一个血清型保守位点上，包含暴露在外的E融合环主链和两条隐藏的糖链。“E二聚物依赖的抗原决定簇”也是病毒糖蛋白prM在受感染细胞分泌途径中，病毒成熟期间结合位置。这解释了该位点在不同血清型之间的保守性，也揭示了该病毒在抗体杀灭过程中的致命弱点。这些发现将有助设计新型免疫原，保护人类同时不受四种登革热病毒血清型的感染。

 

Ferroptosis as a p53-mediated activity during tumour suppression

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http://www.nature.com/nature/journal/v520/n7545/full/nature14344.html

Although p53-mediated cell-cycle arrest, senescence and apoptosis serve as critical barriers to cancer development, emerging evidence suggests that the metabolic activities of p53 are also important. Here we show that p53 inhibits cystine uptake and sensitizes cells to ferroptosis, a non-apoptotic form of cell death, by repressing expression of SLC7A11, a key component of the cystine/glutamate antiporter. Notably, p533KR, an acetylation-defective mutant that fails to induce cell-cycle arrest, senescence and apoptosis, fully retains the ability to regulate SLC7A11 expression and induce ferroptosis upon reactive oxygen species (ROS)-induced stress. Analysis of mutant mice shows that these non-canonical p53 activities contribute to embryonic development and the lethality associated with loss of Mdm2. Moreover, SLC7A11 is highly expressed in human tumours, and its overexpression inhibits ROS-induced ferroptosis and abrogates p533KR-mediated tumour growth suppression in xenograft models. Our findings uncover a new mode of tumour suppression based on p53 regulation of cystine metabolism, ROS responses and ferroptosis.

 

Monolayer semiconductor nanocavity lasers with ultralow thresholds

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http://www.nature.com/nature/journal/v520/n7545/full/nature14290.html

Engineering the electromagnetic environment of a nanometre-scale light emitter by use of a photonic cavity can significantly enhance its spontaneous emission rate, through cavity quantum electrodynamics in the Purcell regime. This effect can greatly reduce the lasing threshold of the emitter1, 2, 3, 4, 5, providing a low-threshold laser system with small footprint, low power consumption and ultrafast modulation. An ultralow-threshold nanoscale laser has been successfully developed by embedding quantum dots into a photonic crystal cavity (PCC)6, 7, 8. However, several challenges impede the practical application of this architecture, including the random positions and compositional fluctuations of the dots7, extreme difficulty in current injection8, and lack of compatibility with electronic circuits7, 8. Here we report a new lasing strategy: an atomically thin crystalline semiconductor—that is, a tungsten diselenide monolayer—is non-destructively and deterministically introduced as a gain medium at the surface of a pre-fabricated PCC. A continuous-wave nanolaser operating in the visible regime is thereby achieved with an optical pumping threshold as low as 27 nanowatts at 130 kelvin, similar to the value achieved in quantum-dot PCC lasers7. The key to the lasing action lies in the monolayer nature of the gain medium, which confines direct-gap excitons to within one nanometre of the PCC surface. The surface-gain geometry gives unprecedented accessibility and hence the ability to tailor gain properties via external controls such as electrostatic gating and current injection, enabling electrically pumped operation. Our scheme is scalable and compatible with integrated photonics for on-chip optical communication technologies.

 

Shape-changing magnetic assemblies as high-sensitivity NMR-readable nanoprobes

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http://www.nature.com/nature/journal/v520/n7545/full/nature14294.html

Fluorescent and plasmonic labels and sensors have revolutionized molecular biology, helping visualize cellular and biomolecular processes1, 2, 3. Increasingly, such probes are now being designed to respond to wavelengths in the near-infrared region, where reduced tissue autofluorescence and photon attenuation enable subsurface in vivo sensing4. But even in the near-infrared region, optical resolution and sensitivity decrease rapidly with increasing depth. Here we present a sensor design that obviates the need for optical addressability by operating in the nuclear magnetic resonance (NMR) radio-frequency spectrum, where signal attenuation and distortion by tissue and biological media are negligible, where background interferences vanish, and where sensors can be spatially located using standard magnetic resonance imaging (MRI) equipment. The radio-frequency-addressable sensor assemblies presented here comprise pairs of magnetic disks spaced by swellable hydrogel material; they reversibly reconfigure in rapid response to chosen stimuli, to give geometry-dependent, dynamic NMR spectral signatures. The sensors can be made from biocompatible materials, are themselves detectable down to low concentrations, and offer potential responsive NMR spectral shifts that are close to a million times greater than those of traditional magnetic resonance spectroscopies. Inherent adaptability should allow such shape-changing systems to measure numerous different environmental and physiological indicators, thus providing broadly generalizable, MRI-compatible, radio-frequency analogues to optically based probes for use in basic chemical, biological, medical and engineering research.

 

Orbital-specific mapping of the ligand exchange dynamics of Fe(CO)5 in solution

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http://www.nature.com/nature/journal/v520/n7545/full/nature14296.html

Transition-metal complexes have long attracted interest for fundamental chemical reactivity studies and possible use in solar energy conversion1, 2. Electronic excitation, ligand loss from the metal centre, or a combination of both, creates changes in charge and spin density at the metal site3, 4, 5, 6, 7, 8, 9, 10, 11 that need to be controlled to optimize complexes for photocatalytic hydrogen production8 and selective carbon–hydrogen bond activation9, 10, 11. An understanding at the molecular level of how transition-metal complexes catalyse reactions, and in particular of the role of the short-lived and reactive intermediate states involved, will be critical for such optimization. However, suitable methods for detailed characterization of electronic excited states have been lacking. Here we show, with the use of X-ray laser-based femtosecond-resolution spectroscopy and advanced quantum chemical theory to probe the reaction dynamics of the benchmark transition-metal complex Fe(CO)5 in solution, that the photo-induced removal of CO generates the 16-electron Fe(CO)4 species, a homogeneous catalyst12, 13 with an electron deficiency at the Fe centre14, 15, in a hitherto unreported excited singlet state that either converts to the triplet ground state or combines with a CO or solvent molecule to regenerate a penta-coordinated Fe species on a sub-picosecond timescale. This finding, which resolves the debate about the relative importance of different spin channels in the photochemistry of Fe(CO)5 (refs 4, 16,17,18,19 and 20), was made possible by the ability of femtosecond X-ray spectroscopy to probe frontier-orbital interactions with atom specificity. We expect the method to be broadly applicable in the chemical sciences, and to complement approaches that probe structural dynamics in ultrafast processes.

 

Growth and host interaction of mouse segmented filamentous bacteria in vitro

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http://www.nature.com/nature/journal/v520/n7545/full/nature14027.html

The gut microbiota plays a crucial role in the maturation of the intestinal mucosal immune system of its host1, 2. Within the thousand bacterial species present in the intestine, the symbiont segmented filamentous bacterium (SFB) is unique in its ability to potently stimulate the post-natal maturation of the B- and T-cell compartments and induce a striking increase in the small-intestinal Th17 responses3, 4, 5. Unlike other commensals, SFB intimately attaches to absorptive epithelial cells in the ileum and cells overlying Peyer’s patches6, 7. This colonization does not result in pathology; rather, it protects the host from pathogens4. Yet, little is known about the SFB–host interaction that underlies the important immunostimulatory properties of SFB, because SFB have resisted in vitro culturing for more than 50 years. Here we grow mouse SFB outside their host in an SFB–host cell co-culturing system. Single-celled SFB isolated from monocolonized mice undergo filamentation, segmentation, and differentiation to release viable infectious particles, the intracellular offspring, which can colonize mice to induce signature immune responses. In vitro, intracellular offspring can attach to mouse and human host cells and recruit actin. In addition, SFB can potently stimulate the upregulation of host innate defence genes, inflammatory cytokines, and chemokines. In vitro culturing thereby mimics the in vivo niche, provides new insights into SFB growth requirements and their immunostimulatory potential, and makes possible the investigation of the complex developmental stages of SFB and the detailed dissection of the unique SFB–host interaction at the cellular and molecular levels.

 

Commensal–dendritic-cell interaction specifies a unique protective skin immune signature

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http://www.nature.com/nature/journal/v520/n7545/full/nature14052.html

The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity1, 2, 3, 4. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges5, 6, 7. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A+ CD8+ T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.

 

Tel1ATM-mediated interference suppresses clustered meiotic double-strand-break formation

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http://www.nature.com/nature/journal/v520/n7545/full/nature13993.html

Meiotic recombination is a critical step in gametogenesis for many organisms, enabling the creation of genetically diverse haploid gametes. In each meiotic cell, recombination is initiated by numerous DNA double-strand breaks (DSBs) created by Spo11, the evolutionarily conserved topoisomerase-like protein1, but how these DSBs are distributed relatively uniformly across the four chromatids that make up each chromosome pair is poorly understood. Here we employ Saccharomyces cerevisiae to demonstrate distance-dependent DSB interference in cis (in which the occurrence of a DSB suppresses adjacent DSB formation)—a process that is mediated by the conserved DNA damage response kinase, Tel1ATM. The inhibitory function of Tel1 acts on a relatively local scale, while over large distances DSBs have a tendency to form independently of one another even in the presence of Tel1. Notably, over very short distances, loss of Tel1 activity causes DSBs to cluster within discrete zones of concerted DSB activity. Our observations support a hierarchical view of recombination initiation where Tel1ATM prevents clusters of DSBs, and further suppresses DSBs within the surrounding chromosomal region. Such collective negative regulation will help to ensure that recombination events are dispersed evenly and arranged optimally for genetic exchange and efficient chromosome segregation.

 

（来自《自然》，翻译：赵欢，高睿，丁家琦，李伯勋，魏若妍，王文佳，黄安娜；审校：程孙雪子，李伯勋，丁家琦）

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