• Nat. Commun. (IF 12.124) Pub Date : 2018-01-17
Friederike Flachsbart, Janina Dose, Liljana Gentschew, Claudia Geismann, Amke Caliebe, Carolin Knecht, Marianne Nygaard, Nandini Badarinarayan, Abdou ElSharawy, Sandra May, Anne Luzius, Guillermo G. Torres, Marlene Jentzsch, Michael Forster, Robert Häsler, Kathrin Pallauf, Wolfgang Lieb, Céline Derbois, Pilar Galan, Dmitriy Drichel, Alexander Arlt, Andreas Till, Ben Krause-Kyora, Gerald Rimbach, Hélène Blanché, Jean-François Deleuze, Lene Christiansen, Kaare Christensen, Michael Nothnagel, Philip Rosenstiel, Stefan Schreiber, Andre Franke, Susanne Sebens, Almut Nebel

The original version of this Article contained an error in the spelling of the author Robert Häsler, which was incorrectly given as Robert Häesler. This has now been corrected in both the PDF and HTML versions of the Article.

更新日期：2018-01-17
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Sinan Kilic, Suren Felekyan, Olga Doroshenko, Iuliia Boichenko, Mykola Dimura, Hayk Vardanyan, Louise C. Bryan, Gaurav Arya, Claus A. M. Seidel, Beat Fierz

The dynamic architecture of chromatin fibers, a key determinant of genome regulation, is poorly understood. Here, we employ multimodal single-molecule Förster resonance energy transfer studies to reveal structural states and their interconversion kinetics in chromatin fibers. We show that nucleosomes engage in short-lived (micro- to milliseconds) stacking interactions with one of their neighbors. This results in discrete tetranucleosome units with distinct interaction registers that interconvert within hundreds of milliseconds. Additionally, we find that dynamic chromatin architecture is modulated by the multivalent architectural protein heterochromatin protein 1α (HP1α), which engages methylated histone tails and thereby transiently stabilizes stacked nucleosomes. This compacted state nevertheless remains dynamic, exhibiting fluctuations on the timescale of HP1α residence times. Overall, this study reveals that exposure of internal DNA sites and nucleosome surfaces in chromatin fibers is governed by an intrinsic dynamic hierarchy from micro- to milliseconds, allowing the gene regulation machinery to access compact chromatin.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Laura A. Velazquez-Villegas, Alessia Perino, Vera Lemos, Marika Zietak, Mitsunori Nomura, Thijs Willem Hendrik Pols, Kristina Schoonjans

Remodelling of energy storing white fat into energy expending beige fat could be a promising strategy to reduce adiposity. Here, we show that the bile acid-responsive membrane receptor TGR5 mediates beiging of the subcutaneous white adipose tissue (scWAT) under multiple environmental cues including cold exposure and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective bile acid mimetics to thermoneutral housed mice leads to the appearance of beige adipocyte markers and increases mitochondrial content in the scWAT of Tgr5 +/+ mice but not in their Tgr5 −/− littermates. This phenotype is recapitulated in vitro in differentiated adipocytes, in which TGR5 activation increases free fatty acid availability through lipolysis, hence fuelling β-oxidation and thermogenic activity. TGR5 signalling also induces mitochondrial fission through the ERK/DRP1 pathway, further improving mitochondrial respiration. Taken together, these data identify TGR5 as a druggable target to promote beiging with potential applications in the management of metabolic disorders.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Alex P. Gaiduk, Tuan Anh Pham, Marco Govoni, Francesco Paesani, Giulia Galli

Understanding redox and photochemical reactions in aqueous environments requires a precise knowledge of the ionization potential and electron affinity of liquid water. The former has been measured, but not the latter. We predict the electron affinity of liquid water and of its surface from first principles, coupling path-integral molecular dynamics with ab initio potentials, and many-body perturbation theory. Our results for the surface (0.8 eV) agree well with recent pump-probe spectroscopy measurements on amorphous ice. Those for the bulk (0.1–0.3 eV) differ from several estimates adopted in the literature, which we critically revisit. We show that the ionization potential of the bulk and surface are almost identical; instead their electron affinities differ substantially, with the conduction band edge of the surface much deeper in energy than that of the bulk. We also discuss the significant impact of nuclear quantum effects on the fundamental gap and band edges of the liquid.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Qilin Hua, Junlu Sun, Haitao Liu, Rongrong Bao, Ruomeng Yu, Junyi Zhai, Caofeng Pan, Zhong Lin Wang

Mechanosensation electronics (or Electronic skin, e-skin) consists of mechanically flexible and stretchable sensor networks that can detect and quantify various stimuli to mimic the human somatosensory system, with the sensations of touch, heat/cold, and pain in skin through various sensory receptors and neural pathways. Here we present a skin-inspired highly stretchable and conformable matrix network (SCMN) that successfully expands the e-skin sensing functionality including but not limited to temperature, in-plane strain, humidity, light, magnetic field, pressure, and proximity. The actualized specific expandable sensor units integrated on a structured polyimide network, potentially in three-dimensional (3D) integration scheme, can also fulfill simultaneous multi-stimulus sensing and achieve an adjustable sensing range and large-area expandability. We further construct a personalized intelligent prosthesis and demonstrate its use in real-time spatial pressure mapping and temperature estimation. Looking forward, this SCMN has broader applications in humanoid robotics, new prosthetics, human–machine interfaces, and health-monitoring technologies.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Vadims Parfejevs, Julien Debbache, Olga Shakhova, Simon M. Schaefer, Mareen Glausch, Michael Wegner, Ueli Suter, Una Riekstina, Sabine Werner, Lukas Sommer

Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here, we report that peripheral glia are crucially involved in this process. Using a mouse model of wound healing, combined with in vivo fate mapping, we show that injury activates peripheral glia by promoting de-differentiation, cell-cycle re-entry and dissemination of the cells into the wound bed. Moreover, injury-activated glia upregulate the expression of many secreted factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling. Accordingly, depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion promotes myofibroblast formation. Thus, injury-activated glia and/or their secretome might have therapeutic potential in human wound healing disorders.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Ying-Chu Chen, Yu-Kuei Hsu, Radian Popescu, Dagmar Gerthsen, Yan-Gu Lin, Claus Feldmann

Full-spectrum utilization of diffusive solar energy by a photocatalyst for environmental remediation and fuel generation has long been pursued. In contrast to tremendous efforts in the UV-to-VIS light regime of the solar spectrum, the NIR and IR areas have been barely addressed although they represent about 50% of the solar flux. Here we put forward a biomimetic photocatalyst blueprint that emulates the growth pattern of a natural plant—a peapod—to address this issue. This design is exemplified via unidirectionally seeding core-shell Au@Nb nanoparticles in the cavity of semiconducting H x K1−xNbO3 nanoscrolls. The biomimicry of this nanopeapod (NPP) configuration promotes near-field plasmon–plasmon coupling between bimetallic Au@Nb nanoantennas (the peas), endowing the UV-active H x K1−xNbO3 semiconductor (the pods) with strong VIS and NIR light harvesting abilities. Moreover, the characteristic 3D metal-semiconductor junction of the Au@Nb@H x K1−xNbO3 NPPs favors the transfer of plasmonic hot carriers to trigger dye photodegradation and water photoelectrolysis as proofs-of-concept. Such broadband solar spectral response renders the Au@Nb@H x K1−xNbO3 NPPs highly promising for widespread photoactive devices.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Erin S. Calipari, Arthur Godino, Emily G. Peck, Marine Salery, Nicholas L. Mervosh, Joseph A. Landry, Scott J. Russo, Yasmin L. Hurd, Eric J. Nestler, Drew D. Kiraly

Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF injections potentiate cocaine place preference and enhance motivation to self-administer cocaine, while not affecting responses to natural rewards. Infusion of G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate cocaine’s behavioral effects, providing a direct link between central G-CSF action in NAc and cocaine reward. These results demonstrate that manipulating G-CSF is sufficient to alter the motivation for cocaine, but not natural rewards, providing a pharmacotherapeutic avenue to manipulate addictive behaviors without abuse potential.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Diana Z. Sousa, Michael Visser, Antonie H. Gelder, Sjef Boeren, Mervin M. Pieterse, Martijn W. H. Pinkse, Peter D. E. M. Verhaert, Carsten Vogt, Steffi Franke, Steffen Kümmel, Alfons J. M. Stams

Methanol is generally metabolized through a pathway initiated by a cobalamine-containing methanol methyltransferase by anaerobic methylotrophs (such as methanogens and acetogens), or through oxidation to formaldehyde using a methanol dehydrogenase by aerobes. Methanol is an important substrate in deep-subsurface environments, where thermophilic sulfate-reducing bacteria of the genus Desulfotomaculum have key roles. Here, we study the methanol metabolism of Desulfotomaculum kuznetsovii strain 17T, isolated from a 3000-m deep geothermal water reservoir. We use proteomics to analyze cells grown with methanol and sulfate in the presence and absence of cobalt and vitamin B12. The results indicate the presence of two methanol-degrading pathways in D. kuznetsovii, a cobalt-dependent methanol methyltransferase and a cobalt-independent methanol dehydrogenase, which is further confirmed by stable isotope fractionation. This is the first report of a microorganism utilizing two distinct methanol conversion pathways. We hypothesize that this gives D. kuznetsovii a competitive advantage in its natural environment.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Saroj K. Rout, Michael P. Friedmann, Roland Riek, Jason Greenwald

The prebiotic replication of information-coding molecules is a central problem concerning life’s origins. Here, we report that amyloids composed of short peptides can direct the sequence-selective, regioselective and stereoselective condensation of amino acids. The addition of activated DL-arginine and DL-phenylalanine to the peptide RFRFR-NH2 in the presence of the complementary template peptide Ac-FEFEFEFE-NH2 yields the isotactic product FRFRFRFR-NH2, 1 of 64 possible triple addition products, under conditions in which the absence of template yields only single and double additions of mixed stereochemistry. The templating mechanism appears to be general in that a different amyloid formed by (Orn)V(Orn)V(Orn)V(Orn)V-NH2 and Ac-VDVDVDVDV-NH2 is regioselective and stereoselective for N-terminal, L-amino-acid addition while the ornithine-valine peptide alone yields predominantly sidechain condensation products with little stereoselectivity. Furthermore, the templating reaction is stable over a wide range of pH (5.6–8.6), salt concentration (0–4 M NaCl), and temperature (25–90 °C), making the amyloid an attractive model for a prebiotic peptide replicating system.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Philipp Neumann, Nicolas Jaé, Andrea Knau, Simone F. Glaser, Youssef Fouani, Oliver Rossbach, Marcus Krüger, David John, Albrecht Bindereif, Phillip Grote, Reinier A. Boon, Stefanie Dimmeler

Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial–mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Soyun Lee, Seunghee Oh, Kwiwan Jeong, Hyelim Jo, Yoonjung Choi, Hogyu David Seo, Minhoo Kim, Joonho Choe, Chang Seob Kwon, Daeyoup Lee

Dot1 (disruptor of telomeric silencing-1, DOT1L in humans) is the only known enzyme responsible for histone H3 lysine 79 methylation (H3K79me) and is evolutionarily conserved in most eukaryotes. Yeast Dot1p lacks a SET domain and does not methylate free histones and thus may have different actions with respect to other histone methyltransferases. Here we show that Dot1p displays histone chaperone activity and regulates nucleosome dynamics via histone exchange in yeast. We show that a methylation-independent function of Dot1p is required for the cryptic transcription within transcribed regions seen following disruption of the Set2–Rpd3S pathway. Dot1p can assemble core histones to nucleosomes and facilitate ATP-dependent chromatin-remodeling activity through its nucleosome-binding domain, in vitro. Global analysis indicates that Dot1p appears to be particularly important for histone exchange and chromatin accessibility on the transcribed regions of long-length genes. Our findings collectively suggest that Dot1p-mediated histone chaperone activity controls nucleosome dynamics in transcribed regions.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Hong-Hua Fang, Sampson Adjokatse, Shuyan Shao, Jacky Even, Maria Antonietta Loi

A long-lived hot carrier population is critical in order to develop working hot carrier photovoltaic devices with efficiencies exceeding the Shockley–Queisser limit. Here, we report photoluminescence from hot-carriers with unexpectedly long lifetime (a few ns) in formamidinium tin triiodide. An unusual large blue shift of the time-integrated photoluminescence with increasing excitation power (150 meV at 24 K and 75 meV at 293 K) is displayed. On the basis of the analysis of energy-resolved and time-resolved photoluminescence, we posit that these phenomena are associated with slow hot carrier relaxation and state-filling of band edge states. These observations are both important for our understanding of lead-free hybrid perovskites and for an eventual future development of efficient lead-free perovskite photovoltaics.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Xia Liu, Wei Mo, Jian Ye, Lingyun Li, Yanping Zhang, Eddy C. Hsueh, Daniel F. Hoft, Guangyong Peng

Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence. Human Treg-induced T-cell senescence can be prevented via inhibition of the DNA damage response and/or STAT signaling in T-cell adoptive transfer mouse models. These studies identify molecular mechanisms of human Treg cell suppression and indicate that targeting Treg-induced T-cell senescence is a checkpoint for immunotherapy against cancer and other diseases associated with Treg cells.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Jasper F. Kok, Daniel S. Ward, Natalie M. Mahowald, Amato T. Evan

Feedbacks between the global dust cycle and the climate system might have amplified past climate changes. Yet, it remains unclear what role the dust–climate feedback will play in future anthropogenic climate change. Here, we estimate the direct dust–climate feedback, arising from changes in the dust direct radiative effect (DRE), using a simple theoretical framework that combines constraints on the dust DRE with a series of climate model results. We find that the direct dust–climate feedback is likely in the range of −0.04 to +0.02 Wm −2 K−1, such that it could account for a substantial fraction of the total aerosol feedbacks in the climate system. On a regional scale, the direct dust–climate feedback is enhanced by approximately an order of magnitude close to major source regions. This suggests that it could play an important role in shaping the future climates of Northern Africa, the Sahel, the Mediterranean region, the Middle East, and Central Asia.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Jacob W. Crandall, Mayada Oudah, Tennom, Fatimah Ishowo-Oloko, Sherief Abdallah, Jean-François Bonnefon, Manuel Cebrian, Azim Shariff, Michael A. Goodrich, Iyad Rahwan

Since Alan Turing envisioned artificial intelligence, technical progress has often been measured by the ability to defeat humans in zero-sum encounters (e.g., Chess, Poker, or Go). Less attention has been given to scenarios in which human–machine cooperation is beneficial but non-trivial, such as scenarios in which human and machine preferences are neither fully aligned nor fully in conflict. Cooperation does not require sheer computational power, but instead is facilitated by intuition, cultural norms, emotions, signals, and pre-evolved dispositions. Here, we develop an algorithm that combines a state-of-the-art reinforcement-learning algorithm with mechanisms for signaling. We show that this algorithm can cooperate with people and other algorithms at levels that rival human cooperation in a variety of two-player repeated stochastic games. These results indicate that general human–machine cooperation is achievable using a non-trivial, but ultimately simple, set of algorithmic mechanisms.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Na Luo, Mellissa J. Nixon, Paula I. Gonzalez-Ericsson, Violeta Sanchez, Susan R. Opalenik, Huili Li, Cynthia A. Zahnow, Michael L. Nickels, Fei Liu, Mohammed N. Tantawy, Melinda E. Sanders, H. Charles Manning, Justin M. Balko

Potentiating anti-tumor immunity by inducing tumor inflammation and T cell-mediated responses are a promising area of cancer therapy. Immunomodulatory agents that promote these effects function via a wide variety of mechanisms, including upregulation of antigen presentation pathways. Here, we show that major histocompatibility class-I (MHC-I) genes are methylated in human breast cancers, suppressing their expression. Treatment of breast cancer cell lines with a next-generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in response to interferon-γ. In murine tumor models of breast cancer, guadecitabine upregulates MHC-I in tumor cells promoting recruitment of CD8+ T cells to the microenvironment. Finally, we show that MHC-I genes are upregulated in breast cancer patients treated with hypomethylating agents. Thus, the immunomodulatory effects of hypomethylating agents likely involve upregulation of class-I antigen presentation to potentiate CD8+ T cell responses. These strategies may be useful to potentiate anti-tumor immunity and responses to checkpoint inhibition in immune-refractory breast cancers.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Josephine Elia, Grace Ungal, Charlly Kao, Alexander Ambrosini, Nilsa Jesus-Rosario, Lene Larsen, Rosetta Chiavacci, Tiancheng Wang, Christine Kurian, Kanani Titchen, Brian Sykes, Sharon Hwang, Bhumi Kumar, Jacqueline Potts, Joshua Davis, Jeffrey Malatack, Emma Slattery, Ganesh Moorthy, Athena Zuppa, Andrew Weller, Enda Byrne, Yun R. Li, Walter K. Kraft, Hakon Hakonarson

The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12–17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50–800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at baseline vs. 2.33 at week 5 (P < 0.001) and 4.83 at baseline vs. 3.86 at week 5 (P < 0.001). Parental Vanderbilt scores showed significant improvement for subjects with mGluR Tier 1 variants (P < 0.035). There were no differences in the incidence of adverse events between placebo week and weeks on active drug. The trial is registered at https://clinicaltrials.gov/ct2/show/study/NCT02286817 .

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Brice Lagrange, Sacha Benaoudia, Pierre Wallet, Flora Magnotti, Angelina Provost, Fanny Michal, Amandine Martin, Flaviana Di Lorenzo, Bénédicte F. Py, Antonio Molinaro, Thomas Henry

Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipopolysaccharide (LPS), to induce the activation of non-canonical inflammasome. Pathogens such as Francisella novicida express an under-acylated lipid A and escape caspase-11 recognition in mice. Here, we show that caspase-4 drives inflammasome responses to F. novicida infection in human macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be recapitulated by transfection of under-acylated LPS from different bacterial species or synthetic tetra-acylated lipid A into cytosol of human macrophage. Our results indicate functional differences between human caspase-4 and murine caspase-11. We further establish that human Guanylate-binding proteins promote inflammasome responses to under-acylated LPS. Altogether, our data demonstrate a broader reactivity of caspase-4 to under-acylated LPS than caspase-11, which may have important clinical implications for management of sepsis.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Tristan J. Horner, Helena V. Pryer, Sune G. Nielsen, Peter W. Crockford, Julia M. Gauglitz, Boswell A. Wing, Richard D. Ricketts

The original version of this Article contained an error in the barite saturation state equation in the fourth paragraph of the Introduction and incorrectly read ‘Ωbarite=({134Ba2+}⋅{SO42−})/Ksp)’. The correct version removes the superscript 134 next to ‘Ba2+’. This error has now been corrected in both the PDF and HTML versions of the Article.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Daniela Rupp, Nils Monserud, Bruno Langbehn, Mario Sauppe, Julian Zimmermann, Yevheniy Ovcharenko, Thomas Möller, Fabio Frassetto, Luca Poletto, Andrea Trabattoni, Francesca Calegari, Mauro Nisoli, Katharina Sander, Christian Peltz, Marc J. Vrakking, Thomas Fennel, Arnaud Rouzée

In the original version of this Article, the affiliation for Luca Poletto was incorrectly given as ‘European XFEL GmbH, Holzkoppel 4, 22869 Schenefeld, Hamburg, Germany’, instead of the correct ‘CNR, Istituto di Fotonica e Nanotecnologie Padova, Via Trasea 7, 35131 Padova, Italy’. This has now been corrected in both the PDF and HTML versions of the Article.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Jiyeon Kweon, An-Hee Jang, Da-eun Kim, Jin Wook Yang, Mijung Yoon, Ha Rim Shin, Jin-Soo Kim, Yongsub Kim

The originally published version of this Article contained an error in the spelling of the author Da-eun Kim, which was incorrectly given as Da-Eun Kim. Furthermore, in Figure 1a, the Cas9 protein was positioned incorrectly during typesetting. These errors have now been corrected in both the PDF and HTML versions of the Article.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-16
Xianghe Meng, Hao Zhang, Jianmin Song, Xinjian Fan, Lining Sun, Hui Xie

In the original version of this Article, the text labels on the bottom-right graph in Fig. 1c were inadvertently displaced during the production process. This has now been corrected in both the PDF and HTML versions of the Article.

更新日期：2018-01-16
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Dongyu Hu, Julia A. Clarke, Chad M. Eliason, Rui Qiu, Quanguo Li, Matthew D. Shawkey, Cuilin Zhao, Liliana D’Alba, Jinkai Jiang, Xing Xu

The Jurassic Yanliao theropods have offered rare glimpses of the early paravian evolution and particularly of bird origins, but, with the exception of the bizarre scansoriopterygids, they have shown similar skeletal and integumentary morphologies. Here we report a distinctive new Yanliao theropod species bearing prominent lacrimal crests, bony ornaments previously known from more basal theropods. It shows longer arm and leg feathers than Anchiornis and tail feathers with asymmetrical vanes forming a tail surface area even larger than that in Archaeopteryx. Nanostructures, interpreted as melanosomes, are morphologically similar to organized, platelet-shaped organelles that produce bright iridescent colours in extant birds. The new species indicates the presence of bony ornaments, feather colour and flight-related features consistent with proposed rapid character evolution and significant diversity in signalling and locomotor strategies near bird origins.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Veronica Tamsitt, Henri F. Drake, Adele K. Morrison, Lynne D. Talley, Carolina O. Dufour, Alison R. Gray, Stephen M. Griffies, Matthew R. Mazloff, Jorge L. Sarmiento, Jinbo Wang, Wilbert Weijer

The original version of this Article contained errors in Fig. 6. In panel a, the grey highlights obscured the curves for CESM, CM2.6 and SOSE, and the labels indicating SWIR, KP, MR, PAR, and DP were inadvertently omitted. These have now been corrected in both the PDF and HTML versions of the Article.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
L. Vanduyfhuys, S. M. J. Rogge, J. Wieme, S. Vandenbrande, G. Maurin, M. Waroquier, V. Van Speybroeck

Knowledge of the thermodynamic potential in terms of the independent variables allows to characterize the macroscopic state of the system. However, in practice, it is difficult to access this potential experimentally due to irreversible transitions that occur between equilibrium states. A showcase example of sudden transitions between (meta)stable equilibrium states is observed for soft porous crystals possessing a network with long-range structural order, which can transform between various states upon external stimuli such as pressure, temperature and guest adsorption. Such phase transformations are typically characterized by large volume changes and may be followed experimentally by monitoring the volume change in terms of certain external triggers. Herein, we present a generalized thermodynamic approach to construct the underlying Helmholtz free energy as a function of the state variables that governs the observed behaviour based on microscopic simulations. This concept allows a unique identification of the conditions under which a material becomes flexible.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Jordan P. Abberley, Ross Killah, Rebecca Walker, John M. D. Storey, Corrie T. Imrie, Mirosław Salamończyk, Chenhui Zhu, Ewa Gorecka, Damian Pociecha

Chiral symmetry breaking in soft matter is a hot topic of current research. Recently, such a phenomenon was found in a fluidic phase showing orientational order of molecules—the nematic phase; although built of achiral molecules, the phase can exhibit structural chirality—average molecular direction follows a short-pitch helix. Here, we report a series of achiral asymmetric dimers with an odd number of atoms in the spacer, which form twisted structures in nematic as well as in lamellar phases. The tight pitch heliconical nematic (NTB) phase and heliconical tilted smectic C (SmCTB) phase are formed. The formation of a variety of helical structures is accompanied by a gradual freezing of molecular rotation. In the lowest temperature smectic phase, HexI, the twist is expressed through the formation of hierarchical structure: nanoscale helices and mesoscopic helical filaments. The short-pitch helical structure in the smectic phases is confirmed by resonant X-ray measurements.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Jiankai Zhang, Wenshou Tian, Fei Xie, Martyn P. Chipperfield, Wuhu Feng, Seok-Woo Son, N. Luke Abraham, Alexander T. Archibald, Slimane Bekki, Neal Butchart, Makoto Deushi, Sandip Dhomse, Yuanyuan Han, Patrick Jöckel, Douglas Kinnison, Ole Kirner, Martine Michou, Olaf Morgenstern, Fiona M. O’Connor, Giovanni Pitari, David A. Plummer, Laura E. Revell, Eugene Rozanov, Daniele Visioni, Wuke Wang, Guang Zeng

The Montreal Protocol has succeeded in limiting major ozone-depleting substance emissions, and consequently stratospheric ozone concentrations are expected to recover this century. However, there is a large uncertainty in the rate of regional ozone recovery in the Northern Hemisphere. Here we identify a Eurasia-North America dipole mode in the total column ozone over the Northern Hemisphere, showing negative and positive total column ozone anomaly centres over Eurasia and North America, respectively. The positive trend of this mode explains an enhanced total column ozone decline over the Eurasian continent in the past three decades, which is closely related to the polar vortex shift towards Eurasia. Multiple chemistry-climate-model simulations indicate that the positive Eurasia-North America dipole trend in late winter is likely to continue in the near future. Our findings suggest that the anticipated ozone recovery in late winter will be sensitive not only to the ozone-depleting substance decline but also to the polar vortex changes, and could be substantially delayed in some regions of the Northern Hemisphere extratropics.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Yaguang Peng, Hongliang Huang, Yuxi Zhang, Chufan Kang, Shuangming Chen, Li Song, Dahuan Liu, Chongli Zhong

Current technologies for removing heavy metal ions are typically metal ion specific. Herein we report the development of a broad-spectrum heavy metal ion trap by incorporation of ethylenediaminetetraacetic acid into a robust metal-organic framework. The capture experiments for a total of 22 heavy metal ions, covering hard, soft, and borderline Lewis metal ions, show that the trap is very effective, with removal efficiencies of >99% for single-component adsorption, multi-component adsorption, or in breakthrough processes. The material can also serve as a host for metal ion loading with arbitrary selections of metal ion amounts/types with a controllable uptake ratio to prepare well-dispersed single or multiple metal catalysts. This is supported by the excellent performance of the prepared Pd2+-loaded composite toward the Suzuki coupling reaction. This work proposes a versatile heavy metal ion trap that may find applications in the fields of separation and catalysis.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
A. Mignot, R. Ferrari, H. Claustre

The North Atlantic bloom corresponds to a strong seasonal increase in phytoplankton that produces organic carbon through photosynthesis. It is still debated what physical and biological conditions trigger the bloom, because comprehensive time series of the vertical distribution of phytoplankton biomass are lacking. Vertical profiles from nine floats that sampled the waters of the North Atlantic every few days for a couple of years reveal that phytoplankton populations start growing in early winter at very weak rates. A proper bloom with rapidly accelerating population growth rates instead starts only in spring when atmospheric cooling subsides and the mixed layer rapidly shoals. While the weak accumulation of phytoplankton in winter is crucial to maintaining a viable population, the spring bloom dominates the overall seasonal production of organic carbon.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Fidel Ramírez, Vivek Bhardwaj, Laura Arrigoni, Kin Chung Lam, Björn A. Grüning, José Villaveces, Bianca Habermann, Asifa Akhtar, Thomas Manke

Despite an abundance of new studies about topologically associating domains (TADs), the role of genetic information in TAD formation is still not fully understood. Here we use our software, HiCExplorer (hicexplorer.readthedocs.io) to annotate >2800 high-resolution (570 bp) TAD boundaries in Drosophila melanogaster. We identify eight DNA motifs enriched at boundaries, including a motif bound by the M1BP protein, and two new boundary motifs. In contrast to mammals, the CTCF motif is only enriched on a small fraction of boundaries flanking inactive chromatin while most active boundaries contain the motifs bound by the M1BP or Beaf-32 proteins. We demonstrate that boundaries can be accurately predicted using only the motif sequences at open chromatin sites. We propose that DNA sequence guides the genome architecture by allocation of boundary proteins in the genome. Finally, we present an interactive online database to access and explore the spatial organization of fly, mouse and human genomes, available at http://chorogenome.ie-freiburg.mpg.de .

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Yuki Ohuchi, Jobu Matsuno, Naoki Ogawa, Yusuke Kozuka, Masaki Uchida, Yoshinori Tokura, Masashi Kawasaki

One of the key goals in spintronics is to tame the spin-orbit coupling (SOC) that links spin and motion of electrons, giving rise to intriguing magneto-transport properties in itinerant magnets. Prominent examples of such SOC-based phenomena are the anomalous and topological Hall effects. However, controlling them with electric fields has remained unachieved since an electric field tends to be screened in itinerant magnets. Here we demonstrate that both anomalous and topological Hall effects can be modulated by electric fields in oxide heterostructures consisting of ferromagnetic SrRuO3 and nonmagnetic SrIrO3. We observe a clear electric field effect only when SrIrO3 is inserted between SrRuO3 and a gate dielectric. Our results establish that strong SOC of nonmagnetic materials such as SrIrO3 is essential in electrical tuning of these Hall effects and possibly other SOC-related phenomena.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Wen Gao, Yuhui Sun, Michelle Cai, Yujie Zhao, Wenhua Cao, Zhenhua Liu, Guanwei Cui, Bo Tang

Atherosclerosis is characterized by the accumulation of lipids within the arterial wall. Although activation of TRPV1 cation channels by capsaicin may reduce lipid storage and the formation of atherosclerotic lesions, a clinical use for capsaicin has been limited by its chronic toxicity. Here we show that coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells (VSMCs) using near-infrared light. Upon irradiation, local increases of temperature open thermo-sensitive TRPV1 channels and cause Ca2+ influx. The increase in intracellular Ca2+ activates autophagy and impedes foam cell formation in VSMCs treated with oxidized low-density lipoprotein. In vivo, CuS-TRPV1 allows photoacoustic imaging of the cardiac vasculature and reduces lipid storage and plaque formation in ApoE−/− mice fed a high-fat diet, with no obvious long-term toxicity. Together, this suggests CuS-TRPV1 may represent a therapeutic tool to locally and temporally attenuate atherosclerosis.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Jin-Soo Kim, Jong-Seong Kug, Su-Jong Jeong

In the original version of this Article, the affiliation for Su-Jon Jeong was incorrectly given as ‘Southern University of Science and Technology of China (SUSTECH)’, instead of ‘Southern University of Science and Technology (SUSTECH)’. This has now been corrected in both the PDF and HTML versions of the Article.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Daniel S. Terry, Rachel A. Kolster, Matthias Quick, Michael V. LeVine, George Khelashvili, Zhou Zhou, Harel Weinstein, Jonathan A. Javitch, Scott C. Blanchard

Neurotransmitter:sodium symporters (NSS), targets of antidepressants and psychostimulants, clear neurotransmitters from the synaptic cleft through sodium (Na+)-coupled transport. Substrate and Na+ are thought to be transported from the extracellular to intracellular space through an alternating access mechanism by coordinated conformational rearrangements in the symporter that alternately expose the binding sites to each side of the membrane. However, the mechanism by which the binding of ligands coordinates conformational changes occurring on opposite sides of the membrane is not well understood. Here, we report the use of single-molecule fluorescence resonance energy transfer (smFRET) techniques to image transitions between distinct conformational states on both the extracellular and intracellular sides of the prokaryotic NSS LeuT, including partially open intermediates associated with transport activity. The nature and functional context of these hitherto unidentified intermediate states shed new light on the allosteric mechanism that couples substrate and Na+ symport by the NSS family through conformational dynamics.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Rahul Nahar, Weiwei Zhai, Tong Zhang, Angela Takano, Alexis J. Khng, Yin Yeng Lee, Xingliang Liu, Chong Hee Lim, Tina P. T. Koh, Zaw Win Aung, Tony Kiat Hon Lim, Lavanya Veeravalli, Ju Yuan, Audrey S. M. Teo, Cheryl X. Chan, Huay Mei Poh, Ivan M. L. Chua, Audrey Ann Liew, Dawn Ping Xi Lau, Xue Lin Kwang, Chee Keong Toh, Wan-Teck Lim, Bing Lim, Wai Leong Tam, Eng-Huat Tan, Axel M. Hillmer, Daniel S. W. Tan

EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high-amplitude amplifications and deletions that potentially beget drug resistant clones. We highlight the association between genomic architecture and clinical phenotypes, such as co-occurring truncal drivers and primary TKI resistance. Through comparative analysis with published smoking-related LUAD, we postulate that the high intra-tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an early dominant driver, genomic instability, and low background mutation rates.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Paul E. Ohno, Hong-fei Wang, Franz M. Geiger

The original version of this Article contained an error in Equation 3b. A ‘ + ’ sign incorrectly appeared instead of a ‘–’ sign in the denominator of the right-hand side of the equation and incorrectly read: $$\left( {\chi _1^{\left( 3 \right)} + i\chi _2^{\left( 3 \right)}} \right) = \left( {\frac{{\kappa ^2}}{{\kappa ^2 + \left( {\Delta k_z} \right)^2}}\chi ^{\left( 3 \right)} + i\frac{{\kappa \Delta k_z}}{{\kappa ^2 + \left( {\Delta k_z} \right)^2}}\chi ^{\left( 3 \right)}} \right) = \frac{\kappa }{{\kappa + i\Delta k_z}}\chi ^{\left( 3 \right)}$$ χ 1 3 + i χ 2 3 = κ 2 κ 2 + Δ k z 2 χ 3 + i κ Δ k z κ 2 + Δ k z 2 χ 3 = κ κ + i Δ k z χ 3 The correct form of the equation is as follows: $$\left( {\chi _1^{\left( 3 \right)} + i\chi _2^{\left( 3 \right)}} \right) = \left( {\frac{{\kappa ^2}}{{\kappa ^2 + \left( {\Delta k_z} \right)^2}}\chi ^{\left( 3 \right)} + i\frac{{\kappa \Delta k_z}}{{\kappa ^2 + \left( {\Delta k_z} \right)^2}}\chi ^{\left( 3 \right)}} \right) = \frac{\kappa }{{\kappa - i\Delta k_z}}\chi ^{\left( 3 \right)}$$ χ 1 3 + i χ 2 3 = κ 2 κ 2 + Δ k z 2 χ 3 + i κ Δ k z κ 2 + Δ k z 2 χ 3 = κ κ - i Δ k z χ 3 This has now been corrected in both the PDF and HTML versions of the Article.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Yosep Kim, Yong-Su Kim, Sang-Yun Lee, Sang-Wook Han, Sung Moon, Yoon-Ho Kim, Young-Wook Cho

The weak value concept has enabled fundamental studies of quantum measurement and, recently, found potential applications in quantum and classical metrology. However, most weak value experiments reported to date do not require quantum mechanical descriptions, as they only exploit the classical wave nature of the physical systems. In this work, we demonstrate measurement of the sequential weak value of two incompatible observables by making use of two-photon quantum interference so that the results can only be explained quantum physically. We then demonstrate that the sequential weak value measurement can be used to perform direct quantum process tomography of a qubit channel. Our work not only demonstrates the quantum nature of weak values but also presents potential new applications of weak values in analyzing quantum channels and operations.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Joonki Suh, Teck Leong Tan, Weijie Zhao, Joonsuk Park, Der-Yuh Lin, Tae-Eon Park, Jonghwan Kim, Chenhao Jin, Nihit Saigal, Sandip Ghosh, Zicong Marvin Wong, Yabin Chen, Feng Wang, Wladyslaw Walukiewicz, Goki Eda, Junqiao Wu

Doping of traditional semiconductors has enabled technological applications in modern electronics by tailoring their chemical, optical and electronic properties. However, substitutional doping in two-dimensional semiconductors is at a comparatively early stage, and the resultant effects are less explored. In this work, we report unusual effects of degenerate doping with Nb on structural, electronic and optical characteristics of MoS2 crystals. The doping readily induces a structural transformation from naturally occurring 2H stacking to 3R stacking. Electronically, a strong interaction of the Nb impurity states with the host valence bands drastically and nonlinearly modifies the electronic band structure with the valence band maximum of multilayer MoS2 at the Γ point pushed upward by hybridization with the Nb states. When thinned down to monolayers, in stark contrast, such significant nonlinear effect vanishes, instead resulting in strong and broadband photoluminescence via the formation of exciton complexes tightly bound to neutral acceptors.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Anuwat Aunkham, Michael Zahn, Anusha Kesireddy, Karunakar Reddy Pothula, Albert Schulte, Arnaud Baslé, Ulrich Kleinekathöfer, Wipa Suginta, Bert Berg

Chitin, an insoluble polymer of N-acetylglucosamine, is one of the most abundant biopolymers on Earth. By degrading chitin, chitinolytic bacteria such as Vibrio harveyi are critical for chitin recycling and maintenance of carbon and nitrogen cycles in the world’s oceans. A decisive step in chitin degradation is the uptake of chito-oligosaccharides by an outer membrane protein channel named chitoporin (ChiP). Here, we report X-ray crystal structures of ChiP from V. harveyi in the presence and absence of chito-oligosaccharides. Structures without bound sugar reveal a trimeric assembly with an unprecedented closing of the transport pore by the N-terminus of a neighboring subunit. Substrate binding ejects the pore plug to open the transport channel. Together with molecular dynamics simulations, electrophysiology and in vitro transport assays our data provide an explanation for the exceptional affinity of ChiP for chito-oligosaccharides and point to an important role of the N-terminal gate in substrate transport.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Long-Gang Pang, Kai Zhou, Nan Su, Hannah Petersen, Horst Stöcker, Xin-Nian Wang

A primordial state of matter consisting of free quarks and gluons that existed in the early universe a few microseconds after the Big Bang is also expected to form in high-energy heavy-ion collisions. Determining the equation of state (EoS) of such a primordial matter is the ultimate goal of high-energy heavy-ion experiments. Here we use supervised learning with a deep convolutional neural network to identify the EoS employed in the relativistic hydrodynamic simulations of heavy ion collisions. High-level correlations of particle spectra in transverse momentum and azimuthal angle learned by the network act as an effective EoS-meter in deciphering the nature of the phase transition in quantum chromodynamics. Such EoS-meter is model-independent and insensitive to other simulation inputs including the initial conditions for hydrodynamic simulations.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Donghua Liu, Xiaosong Chen, Yibin Hu, Tai Sun, Zhibo Song, Yujie Zheng, Yongbin Cao, Zhi Cai, Min Cao, Lan Peng, Yuli Huang, Lei Du, Wuli Yang, Gang Chen, Dapeng Wei, Andrew Thye Shen Wee, Dacheng Wei

Graphene is regarded as a potential surface-enhanced Raman spectroscopy (SERS) substrate. However, the application of graphene quantum dots (GQDs) has had limited success due to material quality. Here, we develop a quasi-equilibrium plasma-enhanced chemical vapor deposition method to produce high-quality ultra-clean GQDs with sizes down to 2 nm directly on SiO2/Si, which are used as SERS substrates. The enhancement factor, which depends on the GQD size, is higher than conventional graphene sheets with sensitivity down to 1 × 10−9 mol L−1 rhodamine. This is attributed to the high-quality GQDs with atomically clean surfaces and large number of edges, as well as the enhanced charge transfer between molecules and GQDs with appropriate diameters due to the existence of Van Hove singularities in the electronic density of states. This work demonstrates a sensitive SERS substrate, and is valuable for applications of GQDs in graphene-based photonics and optoelectronics.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Lin Wang, Joseph T. Wu

Over the past few decades, global metapopulation epidemic simulations built with worldwide air-transportation data have been the main tool for studying how epidemics spread from the origin to other parts of the world (e.g., for pandemic influenza, SARS, and Ebola). However, it remains unclear how disease epidemiology and the air-transportation network structure determine epidemic arrivals for different populations around the globe. Here, we fill this knowledge gap by developing and validating an analytical framework that requires only basic analytics from stochastic processes. We apply this framework retrospectively to the 2009 influenza pandemic and 2014 Ebola epidemic to show that key epidemic parameters could be robustly estimated in real-time from public data on local and global spread at very low computational cost. Our framework not only elucidates the dynamics underlying global spread of epidemics but also advances our capability in nowcasting and forecasting epidemics.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Rafael Renteria, Emily T. Baltz, Christina M. Gremel

Addiction involves a predominance of habitual control mediated through action selection processes in dorsal striatum. Research has largely focused on neural mechanisms mediating a proposed progression from ventral to dorsal lateral striatal control in addiction. However, over reliance on habit striatal processes may also arise from reduced cortical input to striatum, thereby disrupting executive control over action selection. Here, we identify novel mechanisms through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts top-down control over goal-directed action selection processes to produce habits. We find CIE results in decreased excitability of orbital frontal cortex (OFC) excitatory circuits supporting goal-directed control, and, strikingly, selectively reduces OFC output to the direct output pathway in dorsal medial striatum. Increasing the activity of OFC circuits restores goal-directed control in CIE-exposed mice. Our findings show habitual control in alcohol dependence can arise through disrupted communication between top-down, goal-directed processes onto basal ganglia pathways controlling action selection.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Wenbin Li, Longjuan Kong, Baojie Feng, Huixia Fu, Hui Li, Xiao Cheng Zeng, Kehui Wu, Lan Chen

Some two-dimensional liquid systems are theoretically predicted to have an anomalous phase transition due to unique intermolecular interactions, for example the first-order transition between two-dimensional high-density water and low-density amorphous ice. However, it has never been experimentally observed, to the best of our knowledge. Here we report an entropy-driven phase transition between a high-density liquid crystal and low-density crystalline solid, directly observed by scanning tunneling microscope in carbon monoxide adsorbed on Cu(111). Combined with first principle calculations, we find that repulsive dipole–dipole interactions between carbon monoxide molecules lead to unconventional thermodynamics. This finding of unconventional thermodynamics in two-dimensional carbon monoxide not only provides a platform to study the fundamental principles of anomalous phase transitions in two-dimensional liquids at the atomic scale, but may also help to design and develop more efficient copper-based catalysis.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Michael Uckelmann, Ruth M. Densham, Roy Baas, Herrie H. K. Winterwerp, Alexander Fish, Titia K. Sixma, Joanna R. Morris

BRCA1-BARD1-catalyzed ubiquitination of histone H2A is an important regulator of the DNA damage response, priming chromatin for repair by homologous recombination. However, no specific deubiquitinating enzymes (DUBs) are known to antagonize this function. Here we identify ubiquitin specific protease-48 (USP48) as a H2A DUB, specific for the C-terminal BRCA1 ubiquitination site. Detailed biochemical analysis shows that an auxiliary ubiquitin, an additional ubiquitin that itself does not get cleaved, modulates USP48 activity, which has possible implications for its regulation in vivo. In cells we reveal that USP48 antagonizes BRCA1 E3 ligase function and in BRCA1-proficient cells loss of USP48 results in positioning 53BP1 further from the break site and in extended resection lengths. USP48 repression confers a survival benefit to cells treated with camptothecin and its activity acts to restrain gene conversion and mutagenic single-strand annealing. We propose that USP48 promotes genome stability by antagonizing BRCA1 E3 ligase function.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Xiang Zhang, Kuan Zhang, Yangchao Shen, Shuaining Zhang, Jing-Ning Zhang, Man-Hong Yung, Jorge Casanova, Julen S. Pedernales, Lucas Lamata, Enrique Solano, Kihwan Kim

Quantum field theories describe a variety of fundamental phenomena in physics. However, their study often involves cumbersome numerical simulations. Quantum simulators, on the other hand, may outperform classical computational capacities due to their potential scalability. Here we report an experimental realization of a quantum simulation of fermion–antifermion scattering mediated by bosonic modes, using a multilevel trapped ion, which is a simplified model of fermion scattering in both perturbative and non-perturbative quantum electrodynamics. The simulated model exhibits prototypical features in quantum field theory including particle pair creation and annihilation, as well as self-energy interactions. These are experimentally observed by manipulating four internal levels of a 171Yb+ trapped ion, where we encode the fermionic modes, and two motional degrees of freedom that simulate the bosonic modes. Our experiment establishes an avenue towards the efficient implementation of field modes, which may prove useful in studies of quantum field theories including non-perturbative regimes.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Liu Ye, Qiang-Shuai Gu, Yu Tian, Xiang Meng, Guo-Cong Chen, Xin-Yuan Liu

The development of a general catalytic method for the direct and stereoselective construction of cyclopropanes bearing highly congested vicinal all-carbon quaternary stereocenters remains a formidable challenge in chemical synthesis. Here, we report an intramolecular radical cyclopropanation of unactivated alkenes with simple α-methylene group of aldehydes as C1 source via a Cu(I)/secondary amine cooperative catalyst, which enables the single-step construction of bicyclo[3.1.0]hexane skeletons with excellent efficiency, broad substrate scope covering various terminal, internal alkenes as well as diverse (hetero)aromatic, alkenyl, alkyl-substituted geminal alkenes. Moreover, this reaction has been successfully realized to an asymmetric transformation, providing an attractive approach for the construction of enantioenriched bicyclo[3.1.0]hexanes bearing two crucial vicinal all-carbon quaternary stereocenters with good to excellent enantioselectivity. The utility of this method is illustrated by facile transformations of the products into various useful chiral synthetic intermediates. Preliminary mechanistic studies support a stepwise radical process for this formal [2 + 1] cycloaddition.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Matthias Kaiser, Florian Jug, Thomas Julou, Siddharth Deshpande, Thomas Pfohl, Olin K. Silander, Gene Myers, Erik van Nimwegen

Much is still not understood about how gene regulatory interactions control cell fate decisions in single cells, in part due to the difficulty of directly observing gene regulatory processes in vivo. We introduce here a novel integrated setup consisting of a microfluidic chip and accompanying analysis software that enable long-term quantitative tracking of growth and gene expression in single cells. The dual-input Mother Machine (DIMM) chip enables controlled and continuous variation of external conditions, allowing direct observation of gene regulatory responses to changing conditions in single cells. The Mother Machine Analyzer (MoMA) software achieves unprecedented accuracy in segmenting and tracking cells, and streamlines high-throughput curation with a novel leveraged editing procedure. We demonstrate the power of the method by uncovering several novel features of an iconic gene regulatory program: the induction of Escherichia coli’s lac operon in response to a switch from glucose to lactose.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Shengzhe Zhang, Meiying Zhang, Ying Jing, Xia Yin, Pengfei Ma, Zhenfeng Zhang, Xiaojie Wang, Wen Di, Guanglei Zhuang

MCL1 is a pivot member of the anti-apoptotic BCL-2 family proteins. While a distinctive feature of MCL1 resides in its efficient ubiquitination and destruction, the deubiquitinase USP9X has been implicated in the preservation of MCL1 expression by removing the polyubiquitin chains. Here we perform an unbiased siRNA screen and identify that the second deubiquitinase, USP13, regulates MCL1 stability in lung and ovarian cancer cells. Mechanistically, USP13 interacts with and stabilizes MCL1 via deubiquitination. As a result, USP13 depletion using CRISPR/Cas9 nuclease system inhibits tumor growth in xenografted nude mice. We further report that genetic or pharmacological inhibition of USP13 considerably reduces MCL1 protein abundance and significantly increases tumor cell sensitivity to BH3 mimetic inhibitors targeting BCL-2 and BCL-XL. Collectively, we nominate USP13 as a novel deubiquitinase which regulates MCL1 turnover in diverse solid tumors and propose that USP13 may be a potential therapeutic target for the treatment of various malignancies.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Ji-Min Ju, Min Ho Jung, Giri Nam, Woojin Kim, Sehwa Oh, Hyun Duk Kim, Joo Young Kim, Jun Chang, Sung Hak Lee, Gyeong Sin Park, Chang-Ki Min, Dong-Sup Lee, Moon Gyo Kim, Kyungho Choi, Eun Young Choi

Whether hematopoietic cell-restricted distribution of antigens affects the degree of thymic negative selection has not been investigated in detail. Here, we show that T cells specific for hematopoietic cell-restricted antigens (HRA) are not completely deleted in the thymus, using the mouse minor histocompatibility antigen H60, the expression of which is restricted to hematopoietic cells. As a result, low avidity T cells escape from thymic deletion. This incomplete thymic deletion occurs to the T cells developing de novo in the thymus of H60-positive recipients in H60-mismatched bone marrow transplantation (BMT). H60-specific thymic deletion escapee CD8+ T cells exhibit effector differentiation potentials in the periphery and contribute to graft-versus-leukemia effects in the recipients of H60-mismatched BMT, regressing H60+ hematological tumors. These results provide information essential for understanding thymic negative selection and developing a strategy to treat hematological tumors.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Qi Wang, Qiu Sun, Daniel M. Czajkowsky, Zhifeng Shao

Topologically associating domains (TADs) are fundamental elements of the eukaryotic genomic structure. However, recent studies suggest that the insulating complexes, CTCF/cohesin, present at TAD borders in mammals are absent from those in Drosophila melanogaster, raising the possibility that border elements are not conserved among metazoans. Using in situ Hi-C with sub-kb resolution, here we show that the D. melanogaster genome is almost completely partitioned into >4000 TADs, nearly sevenfold more than previously identified. The overwhelming majority of these TADs are demarcated by the insulator complexes, BEAF-32/CP190, or BEAF-32/Chromator, indicating that these proteins may play an analogous role in flies as that of CTCF/cohesin in mammals. Moreover, extended regions previously thought to be unstructured are shown to consist of small contiguous TADs, a property also observed in mammals upon re-examination. Altogether, our work demonstrates that fundamental features associated with the higher-order folding of the genome are conserved from insects to mammals.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Y. T. Fanchiang, K. H. M. Chen, C. C. Tseng, C. C. Chen, C. K. Cheng, S. R. Yang, C. N. Wu, S. F. Lee, M. Hong, J. Kwo

Harnessing the spin–momentum locking of topological surface states in conjunction with magnetic materials is the first step to realize novel topological insulator-based devices. Here, we report strong interfacial coupling in Bi2Se3/yttrium iron garnet (YIG) bilayers manifested as large interfacial in-plane magnetic anisotropy (IMA) and enhancement of damping probed by ferromagnetic resonance. The interfacial IMA and damping enhancement reaches a maximum when the Bi2Se3 film approaches its two-dimensional limit, indicating that topological surface states play an important role in the magnetization dynamics of YIG. Temperature-dependent ferromagnetic resonance of Bi2Se3/YIG reveals signatures of the magnetic proximity effect of TC as high as 180 K, an emerging low-temperature perpendicular magnetic anisotropy competing the high-temperature IMA, and an increasing exchange effective field of YIG steadily increasing toward low temperature. Our study sheds light on the effects of topological insulators on magnetization dynamics, essential for the development of topological insulator-based spintronic devices.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Shao-Qian Zhang, Li-Heng Che, Yun Li, Liang, Hong Pang, Adam Ślipiński, Peng Zhang

Beetles (Coleoptera) are the most diverse and species-rich group of insects, and a robust, time-calibrated phylogeny is fundamental to understanding macroevolutionary processes that underlie their diversity. Here we infer the phylogeny and divergence times of all major lineages of Coleoptera by analyzing 95 protein-coding genes in 373 beetle species, including ~67% of the currently recognized families. The subordinal relationships are strongly supported as Polyphaga (Adephaga (Archostemata, Myxophaga)). The series and superfamilies of Polyphaga are mostly monophyletic. The species-poor Nosodendridae is robustly recovered in a novel position sister to Staphyliniformia, Bostrichiformia, and Cucujiformia. Our divergence time analyses suggest that the crown group of extant beetles occurred ~297 million years ago (Mya) and that ~64% of families originated in the Cretaceous. Most of the herbivorous families experienced a significant increase in diversification rate during the Cretaceous, thus suggesting that the rise of angiosperms in the Cretaceous may have been an ‘evolutionary impetus’ driving the hyperdiversity of herbivorous beetles.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Tian Fang, Hongwei Lv, Guishuai Lv, Ting Li, Changzheng Wang, Qin Han, Lexing Yu, Bo Su, Linna Guo, Shanna Huang, Dan Cao, Liang Tang, Shanhua Tang, Mengchao Wu, Wen Yang, Hongyang Wang

The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin–NF-κB signaling in fibroblasts. Activated CAFs further promote cancer progression by secreting pro-inflammatory cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR-1247-3p levels correlate with lung metastasis in HCC patients. These results demonstrate intercellular crosstalk between tumor cells and fibroblasts is mediated by tumor-derived exosomes that control lung metastasis of HCC, providing potential targets for prevention and treatment of cancer metastasis.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Yutaro Shiraishi, Mei Natsume, Yutaka Kofuku, Shunsuke Imai, Kunio Nakata, Toshimi Mizukoshi, Takumi Ueda, Hideo Iwaï, Ichio Shimada

The C-terminal region of G-protein-coupled receptors (GPCRs), stimulated by agonist binding, is phosphorylated by GPCR kinases, and the phosphorylated GPCRs bind to arrestin, leading to the cellular responses. To understand the mechanism underlying the formation of the phosphorylated GPCR-arrestin complex, we performed NMR analyses of the phosphorylated β2-adrenoceptor (β2AR) and the phosphorylated β2AR–β-arrestin 1 complex, in the lipid bilayers of nanodisc. Here we show that the phosphorylated C-terminal region adheres to either the intracellular side of the transmembrane region or lipids, and that the phosphorylation of the C-terminal region allosterically alters the conformation around M2155.54 and M2796.41, located on transemembrane helices 5 and 6, respectively. In addition, we found that the conformation induced by the phosphorylation is similar to that corresponding to the β-arrestin-bound state. The phosphorylation-induced structures revealed in this study propose a conserved structural motif of GPCRs that enables β-arrestin to recognize dozens of GPCRs.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Meng-Yang Hu, Qiao He, Song-Jie Fan, Zi-Chen Wang, Luo-Yan Liu, Yi-Jiang Mu, Qian Peng, Shou-Fei Zhu

Transition-metal-catalyzed alkene hydrosilylation is one of the most important homogeneous catalytic reactions, and the development of methods that use base metals, especially iron, as catalysts for this transformation is a growing area of research. However, the limited number of ligand scaffolds applicable for base-metal-catalyzed alkene hydrosilylation has seriously hindered advances in this area. Herein, we report the use of 1,10-phenanthroline ligands in base-metal catalysts for alkene hydrosilylation. In particular, iron catalysts with 2,9-diaryl-1,10-phenanthroline ligands exhibit unexpected reactivity and selectivity for hydrosilylation of alkenes, including unique benzylic selectivity with internal alkenes, Markovnikov selectivity with terminal styrenes and 1,3-dienes, and excellent activity toward aliphatic terminal alkenes. According to the mechanistic studies, the unusual benzylic selectivity of this hydrosilylation initiates from π–π interaction between the phenyl of the alkene and the phenanthroline of the ligand. This ligand scaffold and its unique catalytic model will open possibilities for base-metal-catalyzed hydrosilylation reactions.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Csilla Brasko, Kevin Smith, Csaba Molnar, Nora Farago, Lili Hegedus, Arpad Balind, Tamas Balassa, Abel Szkalisity, Farkas Sukosd, Katalin Kocsis, Balazs Balint, Lassi Paavolainen, Marton Z. Enyedi, Istvan Nagy, Laszlo G. Puskas, Lajos Haracska, Gabor Tamas, Peter Horvath

Quantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Zhihong Zhu, Zhili Zheng, Futao Zhang, Yang Wu, Maciej Trzaskowski, Robert Maier, Matthew R. Robinson, John J. McGrath, Peter M. Visscher, Naomi R. Wray, Jian Yang

Health risk factors such as body mass index (BMI) and serum cholesterol are associated with many common diseases. It often remains unclear whether the risk factors are cause or consequence of disease, or whether the associations are the result of confounding. We develop and apply a method (called GSMR) that performs a multi-SNP Mendelian randomization analysis using summary-level data from genome-wide association studies to test the causal associations of BMI, waist-to-hip ratio, serum cholesterols, blood pressures, height, and years of schooling (EduYears) with common diseases (sample sizes of up to 405,072). We identify a number of causal associations including a protective effect of LDL-cholesterol against type-2 diabetes (T2D) that might explain the side effects of statins on T2D, a protective effect of EduYears against Alzheimer’s disease, and bidirectional associations with opposite effects (e.g., higher BMI increases the risk of T2D but the effect of T2D on BMI is negative).

更新日期：2018-01-15
• Nat. Commun. (IF 12.124) Pub Date : 2018-01-15
Ming-Liang Ren, Jacob S. Berger, Wenjing Liu, Gerui Liu, Ritesh Agarwal

Dynamic control of nonlinear signals is critical for a wide variety of optoelectronic applications, such as signal processing for optical computing. However, controlling nonlinear optical signals with large modulation strengths and near-perfect contrast remains a challenging problem due to intrinsic second-order nonlinear coefficients via bulk or surface contributions. Here, via electrical control, we turn on and tune second-order nonlinear coefficients in semiconducting CdS nanobelts from zero to up to 151 pm V−1, a value higher than other intrinsic nonlinear coefficients in CdS. We also observe ultrahigh ON/OFF ratio of >104 and modulation strengths ~200% V−1 of the nonlinear signal. The unusual nonlinear behavior, including super-quadratic voltage and power dependence, is ascribed to the high-field domain, which can be further controlled by near-infrared optical excitation and electrical gating. The ability to electrically control nonlinear optical signals in nanostructures can enable optoelectronic devices such as optical transistors and modulators for on-chip integrated photonics.

更新日期：2018-01-15
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.