审校：半夏 邓卓 赵维杰
[C ii] 158-μm emission from the host galaxies of damped Lyman-alpha systems
阻尼莱曼α系中宿主星系的158μm C [ii]发射线
Marcel Neeleman, Nissim Kanekar, J. Xavier Prochaska, Marc Rafelski, Chris L. Carilli, Arthur M. Wolfe
（导读 肖坤） 通过观察背景类星体的吸收线可以研究高红移星系的气体成分。本研究使用Atacama毫米/亚毫米波阵列望远镜（ALMA），探测到两个星系及其背景类星体在红移量z~4时的158μm [C II] 发射线和尘埃连续谱，发现这些类星体的宿主星系包裹在富集的中性氢气中，其物理性质与大量恒星组成的星系类似。
Gas surrounding high-redshift galaxies has been studied through observations of absorption line systems toward background quasars for decades. However, it has proven difficult to identify and characterize the galaxies associated with these absorbers due to the intrinsic faintness of the galaxies compared with the quasars at optical wavelengths. Using the Atacama Large Millimeter/Submillimeter Array, we report on detections of [C II] 158-μm line and dust-continuum emission from two galaxies associated with two such absorbers at a redshift of z ~ 4. Our results indicate that the hosts of these high-metallicity absorbers have physical properties similar to massive star-forming galaxies and are embedded in enriched neutral hydrogen gas reservoirs that extend well beyond the star-forming interstellar medium of these galaxies.
Transition from turbulent to coherent flows in confined three-dimensional active fluids
Kun-Ta Wu, Jean Bernard Hishamunda, Daniel T. N. Chen …Seth Fraden, Zvonimir Dogic
（导读 许雅澜） 传统的流体只能在外部压力下流动。本研究报导了一种由微管和分子马达组成的各向同性主动流体能够自主流过一米长的三维通道，并且可以对自组织流动的大小，速度变化和方向进行控制。研究结果为自组织生物活性机器的提供了设计思路。
Transport of fluid through a pipe is essential for the operation of macroscale machines and microfluidic devices. Conventional fluids only flow in response to external pressure. We demonstrate that an active isotropic fluid, composed of microtubules and molecular motors, autonomously flows through meter-long three-dimensional channels. We establish control over the magnitude, velocity profile, and direction of the self-organized flows and correlate these to the structure of the extensile microtubule bundles. The inherently three-dimensional transition from bulk-turbulent to confined-coherent flows occurs concomitantly with a transition in the bundle orientational order near the surface and is controlled by a scale-invariant criterion related to the channel profile. The nonequilibrium transition of confined isotropic active fluids can be used to engineer self-organized soft machines.
Extremely efficient internal exciton dissociation through edge states in layered 2D perovskites
J.-C. Blancon, H. Tsai, W. Nie …J. J. Crochet, A. D. Mohite
（导读 王腾） 对新型半导体量子阱中电荷运动的理解与控制有助于实现高转化效率的光电器件。本研究报道了一种有别于经典激子模型的光物理机制。该机制基于Ruddlesden-Popper钙钛矿薄膜的边缘能态，能够使激子解离成具有更长寿命的自由载流子，并可显著提高光电器件的性能。
Understanding and controlling charge and energy flow in state-of-the-art semiconductor quantum wells has enabled high-efficiency optoelectronic devices. Two-dimensional (2D) Ruddlesden-Popper perovskites are solution-processed quantum wells wherein the band gap can be tuned by varying the perovskite-layer thickness, which modulates the effective electron-hole confinement. We report that, counterintuitive to classical quantum-confined systems where photogenerated electrons and holes are strongly bound by Coulomb interactions or excitons, the photophysics of thin films made of Ruddlesden-Popper perovskites with a thickness exceeding two perovskite-crystal units (>1.3 nanometers) is dominated by lower-energy states associated with the local intrinsic electronic structure of the edges of the perovskite layers. These states provide a direct pathway for dissociating excitons into longer-lived free carriers that substantially improve the performance of optoelectronic devices.
Grain boundary stability governs hardening and softening in extremely fine nanograined metals
J. Hu, Y. N. Shi, X. Sauvage, G. Sha, K. Lu（卢柯，中科院沈阳金属所）
（导读 王腾） 传统金属的硬度会随着晶粒尺寸的减小而增加。然而某些合金在达到纳米尺度时晶粒会出现软化现象。本研究报导了通过调控晶界（GB）的稳定性来实现对超细纳米晶金属的塑性变形机制和其硬度的控制，为制备新型纳米晶金属提供了除晶粒尺寸控制以外的方法。
Conventional metals become harder with decreasing grain sizes, following the classical Hall-Petch relationship. However, this relationship fails and softening occurs at some grain sizes in the nanometer regime for some alloys. In this study, we discovered that plastic deformation mechanism of extremely fine nanograined metals and their hardness are adjustable through tailoring grain boundary (GB) stability. The electrodeposited nanograined nickel-molybdenum (Ni–Mo) samples become softened for grain sizes below 10 nanometers because of GB-mediated processes. With GB stabilization through relaxation and Mo segregation, ultrahigh hardness is achieved in the nanograined samples with a plastic deformation mechanism dominated by generation of extended partial dislocations. Grain boundary stability provides an alternative dimension, in addition to grain size, for producing novel nanograined metals with extraordinary properties.
Active sites for CO2 hydrogenation to methanol on Cu/ZnO catalysts
Shyam Kattel, Pedro J. Ramírez, Jingguang G. Chen, José A. Rodriguez, Ping Liu（刘萍，美国布鲁克海文国家实验室）
（导读 卓思琪） 本文比较了ZnCu和ZnO/Cu催化剂催化生成甲醇的模型。实验和理论结果都显示ZnCu在反应条件下表面被氧化，Zn转化为ZnO，从而使ZnCu与ZnO/Cu的Zn覆盖率和催化能力相同。研究结果表明Cu和ZnO的交界面处产生甲酸盐中间体并最终合成甲醇，为催化活性位点。
The active sites over commercial copper/zinc oxide/aluminum oxide (Cu/ZnO/Al2O3) catalysts for carbon dioxide (CO2) hydrogenation to methanol, the Zn-Cu bimetallic sites or ZnO-Cu interfacial sites, have recently been the subject of intense debate. We report a direct comparison between the activity of ZnCu and ZnO/Cu model catalysts for methanol synthesis. By combining x-ray photoemission spectroscopy, density functional theory, and kinetic Monte Carlo simulations, we can identify and characterize the reactivity of each catalyst. Both experimental and theoretical results agree that ZnCu undergoes surface oxidation under the reaction conditions so that surface Zn transforms into ZnO and allows ZnCu to reach the activity of ZnO/Cu with the same Zn coverage. Our results highlight a synergy of Cu and ZnO at the interface that facilitates methanol synthesis via formate intermediates.
How “you” makes meaning
Ariana Orvell, Ethan Kross, Susan A. Gelman
（导读 郭思瑶） “you（你）”是英语里最常见的单词之一。虽然它常指谈话对象，但其也可泛指人们。研究人员表明这个被称作“generic-you（泛化的你）”的语言学策略有着强大的造义功能。“泛化的你”可用做普通语境或情感类语境中的表达准则。当表达负面经历时，人们可以通过扩展其含义来使经历“正常化”。
“You” is one of the most common words in the English language. Although it typically refers to the person addressed (“How are you?”), “you” is also used to make timeless statements about people in general (“You win some, you lose some.”). Here, we demonstrate that this ubiquitous but understudied linguistic device, known as “generic-you,” has important implications for how people derive meaning from experience. Across six experiments, we found that generic-you is used to express norms in both ordinary and emotional contexts and that producing generic-you when reflecting on negative experiences allows people to “normalize” their experience by extending it beyond the self. In this way, a simple linguistic device serves a powerful meaning-making function.
Self-assembly of genetically encoded DNA-protein hybrid nanoscale shapes
Florian Praetorius, Hendrik Dietz（封面文章）
（导读 卓思琪） 基于转录因子的定制蛋白“订书钉”（custom protein staple）能将双链DNA折叠成想要的结构，它们能识别和连接双链DNA模板序列中的特定位置。本文呈现了建造兆道尔顿级别DNA-蛋白质复合物的方法，这是一种单步骤DNA-蛋白质纳米复合物自组装的方法。
We describe an approach to bottom-up fabrication that allows integration of the functional diversity of proteins into designed three-dimensional structural frameworks. A set of custom staple proteins based on transcription activator–like effector proteins folds a double-stranded DNA template into a user-defined shape. Each staple protein is designed to recognize and closely link two distinct double-helical DNA sequences at separate positions on the template. We present design rules for constructing megadalton-scale DNA-protein hybrid shapes; introduce various structural motifs, such as custom curvature, corners, and vertices; and describe principles for creating multilayer DNA-protein objects with enhanced rigidity. We demonstrate self-assembly of our hybrid nanostructures in one-pot mixtures that include the genetic information for the designed proteins, the template DNA, RNA polymerase, ribosomes, and cofactors for transcription and translation.
Dynamics of cortical dendritic membrane potential and spikes in freely behaving rats
Jason J. Moore, Pascal M. Ravassard, David Ho, Lavanya Acharya, Ashley L. Kees, Cliff Vuong, Mayank R. Mehta
（导读 董堃） 神经组织中90%以上为树突，然而始终没有测量在体远端树突膜电位和峰电位的方法。本研究发明了一种新技术，能够稳定记录自由活动的动物新皮层远端树突的阈下膜电位和峰电位，树突电位的特点可能与神经编码和可塑性关系密切。
Neural activity in vivo is primarily measured using extracellular somatic spikes, which provide limited information about neural computation. Hence, it is necessary to record from neuronal dendrites, which can generate dendritic action potentials (DAPs) in vitro, which can profoundly influence neural computation and plasticity. We measured neocortical sub- and suprathreshold dendritic membrane potential (DMP) from putative distal-most dendrites using tetrodes in freely behaving rats over multiple days with a high degree of stability and submillisecond temporal resolution. DAP firing rates were several-fold larger than somatic rates. DAP rates were also modulated by subthreshold DMP fluctuations, which were far larger than DAP amplitude, indicating hybrid, analog-digital coding in the dendrites. Parietal DAP and DMP exhibited egocentric spatial maps comparable to pyramidal neurons. These results have important implications for neural coding and plasticity.
Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation
Wei Lü, Juan Du, April Goehring, Eric Gouaux
（导读 卓思琪） 本文利用冷冻电镜技术解析了结合或不结合别构调节剂Ro 25-6981（Ro）时，异三源四聚体离子通道N-甲基-D-天冬氨酸受体（NMDAR），即GluN1/GluN2A/GluN2B的结构。Ro的结合可以以不同方式改变GluN2A和Glu2B的构象并调节通道的开放与闭合。
N-methyl-D-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B receptor in the absence or presence of the GluN2B-specific allosteric modulator Ro 25-6981 (Ro), determined by cryogenic electron microscopy (cryo-EM). In the absence of Ro, the GluN2A and GluN2B amino-terminal domains (ATDs) adopt “closed” and “open” clefts, respectively. Upon binding Ro, the GluN2B ATD clamshell transitions from an open to a closed conformation. Consistent with a predominance of the GluN2A subunit in ion channel gating, the GluN2A subunit interacts more extensively with GluN1 subunits throughout the receptor, in comparison with the GluN2B subunit. Differences in the conformation of the pseudo-2-fold–related GluN1 subunits further reflect receptor asymmetry. The triheteromeric NMDAR structures provide the first view of the most common NMDA receptor assembly and show how incorporation of two different GluN2 subunits modifies receptor symmetry and subunit interactions, allowing each subunit to uniquely influence receptor structure and function, thus increasing receptor complexity.
Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity
Vincent C. Luca, Byoung Choul Kim, Chenghao G …K. Christopher Garcia
（导读 陈月欣） Notch受体的激活依赖机械外力和蛋白质糖基化，在细胞命运决定中发挥作用。本研究在Notch1与改造Jag1蛋白复合物的晶体结构中发现了一个高度保守的结合接口，两蛋白结合时，Jag1发生构象改变，促进Notch的激活。本研究为力学信号激活Notch信号提供了分子解读。
Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation. The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein. O-Linked fucose modifications on Notch1 epidermal growth factor–like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand. Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation. This mechanism enables cellular forces to regulate binding, discriminate among Notch ligands, and potentiate Notch signaling.
A macrophage relay for long-distance signaling during postembryonic tissue remodeling
Dae Seok Eom, David M. Parichy
（导读 榴莲君） 本研究发现，巨噬细胞可以识别黄色素祖细胞表面呈现的磷脂酰丝氨酸，并介导黄色素祖细胞末端突起与黑色素细胞之间的信号传递，而这一远程信号传递过程对斑马鱼胚后发育中体表条纹的正确形成至关重要。这是首次发现巨噬细胞可以介导非免疫细胞间的信号传递。
Macrophages have diverse functions in immunity as well as in development and homeostasis. We identified a function for these cells in long-distance communication during postembryonic tissue remodeling. Ablation of macrophages in zebrafish prevented melanophores from coalescing into adult pigment stripes. Melanophore organization depends on signals provided by cells of the yellow xanthophore lineage via airinemes, long filamentous projections with vesicles at their tips. We show that airineme extension from originating cells, as well as vesicle deposition on target cells, depend on interactions with macrophages. These findings identify a role for macrophages in relaying long-range signals between nonimmune cells. This signaling modality may function in the remodeling and homeostasis of other tissues during normal development and disease.
Dengue diversity across spatial and temporal scales: Local structure and the effect of host population size
Henrik Salje, Justin Lessler, Irina Maljkovic Berry …Derek A. T. Cummings
（导读 郭思瑶） 研究人员利用谱系地理学方法，根据地理定位的病例基因型和血清型数据发现在泰国曼谷，登革热病例有效传播链的数量与患者住所间距离和人口密度正相关，但此种传播链的地理分布会在一个流行季节内迅速消失。这表明密集人口社区是病毒多样性的主要来源，对病毒防控有重大意义。
A fundamental mystery for dengue and other infectious pathogens is how observed patterns of cases relate to actual chains of individual transmission events. These pathways are intimately tied to the mechanisms by which strains interact and compete across spatial scales. Phylogeographic methods have been used to characterize pathogen dispersal at global and regional scales but have yielded few insights into the local spatiotemporal structure of endemic transmission. Using geolocated genotype (800 cases) and serotype (17,291 cases) data, we show that in Bangkok, Thailand, 60% of dengue cases living <200 meters apart come from the same transmission chain, as opposed to 3% of cases separated by 1 to 5 kilometers. At distances <200 meters from a case (encompassing an average of 1300 people in Bangkok), the effective number of chains is 1.7. This number rises by a factor of 7 for each 10-fold increase in the population of the “enclosed” region. This trend is observed regardless of whether population density or area increases, though increases in density over 7000 people per square kilometer do not lead to additional chains. Within Thailand these chains quickly mix, and by the next dengue season viral lineages are no longer highly spatially structured within the country. In contrast, viral flow to neighboring countries is limited. These findings are consistent with local, density-dependent transmission and implicate densely populated communities as key sources of viral diversity, with home location the focal point of transmission. These findings have important implications for targeted vector control and active surveillance.
Brian M. Castellano, Ashley M. Thelen, Ofer Moldavski…Roberto Zoncu
（导读 榴莲君） 本研究发现细胞内胆固醇-mTORC1信号通路受SLC38A9与NPC1蛋白调控。SLC38A9通过其保守的CARC-CRAC基序提高溶酶体胆固醇含量，激活mTORC1信号通路；NPC1与mTORC1支架复合物作用降低胆固醇含量，抑制mTORC1信号通路。研究揭示了胆固醇-mTORC1通路维持体内代谢平衡的重要作用。
The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that becomes activated at the lysosome in response to nutrient cues. Here, we identify cholesterol, an essential building block for cellular growth, as a nutrient input that drives mTORC1 recruitment and activation at the lysosomal surface. The lysosomal transmembrane protein, SLC38A9, is required for mTORC1 activation by cholesterol through conserved cholesterol-responsive motifs. Moreover, SLC38A9 enables mTORC1 activation by cholesterol independently from its arginine-sensing function. Conversely, the Niemann-Pick C1 (NPC1) protein, which regulates cholesterol export from the lysosome, binds to SLC38A9 and inhibits mTORC1 signaling through its sterol transport function. Thus, lysosomal cholesterol drives mTORC1 activation and growth signaling through the SLC38A9-NPC1 complex.
A conserved NAD+ binding pocket that regulates protein-protein interactions during aging
Jun Li, Michael S. Bonkowski, Sébastien Moniot…David A. Sinclair
（导读 榴莲君） 本研究发现DBC1与PARP结合抑制PARP1的活性，使DNA损伤积累。NAD+可直接与DBC1的NHD结构域结合，瓦解PARP1-DBC1复合物，恢复体内依赖PARP1活性的非同源末端结合（NHEJ）和同源重组（HR）DNA修复机制。研究揭示了NAD+在维持DNA损伤修复中的重要作用。
DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD+ (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD+ to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate–ribose) polymerase], a critical DNA repair protein. As mice age and NAD+concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD+. Thus, NAD+directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.
PI3K pathway regulates ER-dependent transcription in breast cancer through the epigenetic regulator KMT2D
Eneda Toska, Hatice U. Osmanbeyoglu, Pau Castel …Scott A. Armstrong, José Baselga
（导读 陈月欣） PIK3CA基因的激活性突变常见于雌激素受体阳性的乳腺癌患者，而PI3Kα抑制剂的治疗效果因会引发代偿性内质网依赖转录而受限。本研究发现，PI3Kα抑制会增强KMT2D活性。KMT2D是一种组蛋白H3L4甲基化酶，通过表观遗传调节帮助内质网激活。这一发现为乳腺癌患者提供了新的药物靶点。
Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)–positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples. KMT2D, a histone H3 lysine 4 methyltransferase, is required for FOXA1, PBX1, and ER recruitment and activation. AKT binds and phosphorylates KMT2D, attenuating methyltransferase activity and ER function, whereas PI3Kα inhibition enhances KMT2D activity. These findings uncover a mechanism that controls the activation of ER by the posttranslational modification of epigenetic regulators, providing a rationale for epigenetic therapy in ER-positive breast cancer.
Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention
Cristian Tomasetti, Lu Li, Bert Vogelstein
（导读 榴莲君） 引起癌症的突变可能来源于遗传、环境因素或DNA复制错误（R）。通过对69个国家的17种癌症进行研究，研究人员发现癌症的发生率与正常干细胞的分裂有着较高的相关性（中值=0.8），表明R突变在癌症发病中起主要作用，强调了早期检测和干预对减少R突变引起癌症死亡的重要性。
Cancers are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replication errors (R). We studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries throughout the world. The data revealed a strong correlation (median = 0.80) between cancer incidence and normal stem cell divisions in all countries, regardless of their environment. The major role of R mutations in cancer etiology was supported by an independent approach, based solely on cancer genome sequencing and epidemiological data, which suggested that R mutations are responsible for two-thirds of the mutations in human cancers. All of these results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment. Moreover, they accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable R mutations.
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