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  • Structures of the CRISPR genome integration complex
    Science (IF 37.205) Pub Date : 2017-07-20 00:00:00
    Addison V. Wright, Jun-Jie Liu, Gavin J. Knott, Kevin W. Doxzen, Eva Nogales, Jennifer A. Doudna

    CRISPR-Cas systems depend on the Cas1-Cas2 integrase to capture and integrate short foreign DNA fragments into the CRISPR locus, enabling adaptation to new viruses. We present crystal structures of Cas1-Cas2 bound to both donor and target DNA in intermediate and product integration complexes, as well as a cryo-electron microscopy structure of the full CRISPR locus integration complex including the accessory protein Integration Host Factor (IHF). The structures show unexpectedly that indirect sequence recognition dictates integration site selection by favoring deformation of the repeat and the flanking sequences. IHF binding bends the DNA sharply, bringing an upstream recognition motif into contact with Cas1 to increase both the specificity and efficiency of integration. These results explain how the Cas1-Cas2 CRISPR integrase recognizes a sequence-dependent DNA structure to ensure site-selective CRISPR array expansion during the initial step of bacterial adaptive immunity.

    更新日期:2017-07-21
  • Optical imaging of surface chemistry and dynamics in confinement
    Science (IF 37.205) Pub Date : 2017-07-20 00:00:00
    Carlos Macias-Romero, Igor Nahalka, Halil I. Okur, Sylvie Roke

    We imaged the interfacial structure and dynamics of water in a microscopically confined geometry in three dimensions and on millisecond time scales with a 3D structurally illuminated wide-field second harmonic microscope. Image contrast reports on the orientational order of interfacial water, induced by charge-dipole interactions between water molecules and surface charges. The images were converted into surface potential maps. Spatially resolved surface acid dissociation constant pKa,s values were determined for the silica deprotonation reaction by following pH induced chemical changes on the curved and confined surfaces of a glass micro-capillary immersed in aqueous solutions. These values ranged from 2.3 to 10.7 along the wall of a single capillary, because of surface heterogeneities. Water molecules that rotate along an oscillating external electric field were also imaged.

    更新日期:2017-07-21
  • Cash for carbon: A randomized trial of payments for ecosystem services to reduce deforestation
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Seema Jayachandran, Joost de Laat, Eric F. Lambin, Charlotte Y. Stanton, Robin Audy, Nancy E. Thomas

    We evaluated a program of payments for ecosystem services in Uganda that offered forest-owning households annual payments of 70,000 Ugandan shillings per hectare if they conserved their forest. The program was implemented as a randomized controlled trial in 121 villages, 60 of which received the program for 2 years. The primary outcome was the change in land area covered by trees, measured by classifying high-resolution satellite imagery. We found that tree cover declined by 4.2% during the study period in treatment villages, compared to 9.1% in control villages. We found no evidence that enrollees shifted their deforestation to nearby land. We valued the delayed carbon dioxide emissions and found that this program benefit is 2.4 times as large as the program costs.

    更新日期:2017-07-21
  • Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Stephanie N. Gates, Adam L. Yokom, JiaBei Lin, Meredith E. Jackrel, Alexandrea N. Rizo, Nathan M. Kendsersky, Courtney E. Buell, Elizabeth A. Sweeny, Korrie L. Mack, Edward Chuang, Mariana P. Torrente, Min Su, James Shorter, Daniel R. Southworth

    Hsp100 polypeptide translocases are conserved members of the AAA+ family (adenosine triphosphatases associated with diverse cellular activities) that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase from Saccharomyces cerevisiae solubilizes stress-induced amorphous aggregates and amyloids. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo–electron microscopy structures at near-atomic resolution of Hsp104 in different translocation states. Substrate interactions are mediated by conserved, pore-loop tyrosines that contact an 80-angstrom-long unfolded polypeptide along the axial channel. Two protomers undergo a ratchet-like conformational change that advances pore loop–substrate interactions by two amino acids. These changes are coupled to activation of specific nucleotide hydrolysis sites and, when transmitted around the hexamer, reveal a processive rotary translocation mechanism and substrate-responsive flexibility during Hsp104-catalyzed disaggregation.

    更新日期:2017-07-21
  • Highly elastic binders integrating polyrotaxanes for silicon microparticle anodes in lithium ion batteries
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Sunghun Choi, Tae-woo Kwon, Ali Coskun, Jang Wook Choi

    Lithium-ion batteries with ever-increasing energy densities are needed for batteries for advanced devices and all-electric vehicles. Silicon has been highlighted as a promising anode material because of its superior specific capacity. During repeated charge-discharge cycles, silicon undergoes huge volume changes. This limits cycle life via particle pulverization and an unstable electrode-electrolyte interface, especially when the particle sizes are in the micrometer range. We show that the incorporation of 5 weight % polyrotaxane to conventional polyacrylic acid binder imparts extraordinary elasticity to the polymer network originating from the ring sliding motion of polyrotaxane. This binder combination keeps even pulverized silicon particles coalesced without disintegration, enabling stable cycle life for silicon microparticle anodes at commercial-level areal capacities.

    更新日期:2017-07-21
  • Photoinduced decarboxylative borylation of carboxylic acids
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Alexander Fawcett, Johan Pradeilles, Yahui Wang, Tatsuya Mutsuga, Eddie L. Myers, Varinder K. Aggarwal

    The conversion of widely available carboxylic acids into versatile boronic esters would be highly enabling for synthesis. We found that this transformation can be effected by illuminating the N-hydroxyphthalimide ester derivative of the carboxylic acid under visible light at room temperature in the presence of the diboron reagent bis(catecholato)diboron. A simple workup allows isolation of the pinacol boronic ester. Experimental evidence suggests that boryl radical intermediates are involved in the process. The methodology is illustrated by the transformation of primary, secondary, and tertiary alkyl carboxylic acids as well as a diverse range of natural-product carboxylic acids, thereby demonstrating its broad utility and functional group tolerance.

    更新日期:2017-07-21
  • Bismuthene on a SiC substrate: A candidate for a high-temperature quantum spin Hall material
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    F. Reis, G. Li, L. Dudy, M. Bauernfeind, S. Glass, W. Hanke, R. Thomale, J. Schäfer, R. Claessen

    Quantum spin Hall materials hold the promise of revolutionary devices with dissipationless spin currents but have required cryogenic temperatures owing to small energy gaps. Here we show theoretically that a room-temperature regime with a large energy gap may be achievable within a paradigm that exploits the atomic spin-orbit coupling. The concept is based on a substrate-supported monolayer of a high–atomic number element and is experimentally realized as a bismuth honeycomb lattice on top of the insulating silicon carbide substrate SiC(0001). Using scanning tunneling spectroscopy, we detect a gap of ~0.8 electron volt and conductive edge states consistent with theory. Our combined theoretical and experimental results demonstrate a concept for a quantum spin Hall wide-gap scenario, where the chemical potential resides in the global system gap, ensuring robust edge conductance.

    更新日期:2017-07-21
  • Remobilization of crustal carbon may dominate volcanic arc emissions
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Emily Mason, Marie Edmonds, Alexandra V. Turchyn

    The flux of carbon into and out of Earth’s surface environment has implications for Earth’s climate and habitability. We compiled a global data set for carbon and helium isotopes from volcanic arcs and demonstrated that the carbon isotope composition of mean global volcanic gas is considerably heavier, at –3.8 to –4.6 per mil (), than the canonical mid-ocean ridge basalt value of –6.0. The largest volcanic emitters outgas carbon with higher 13C and are located in mature continental arcs that have accreted carbonate platforms, indicating that reworking of crustal limestone is an important source of volcanic carbon. The fractional burial of organic carbon is lower than traditionally determined from a global carbon isotope mass balance and may have varied over geological time, modulated by supercontinent formation and breakup.

    更新日期:2017-07-21
  • Chiral Majorana fermion modes in a quantum anomalous Hall insulator–superconductor structure
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Qing Lin He, Lei Pan, Alexander L. Stern, Edward C. Burks, Xiaoyu Che, Gen Yin, Jing Wang, Biao Lian, Quan Zhou, Eun Sang Choi, Koichi Murata, Xufeng Kou, Zhijie Chen, Tianxiao Nie, Qiming Shao, Yabin Fan, Shou-Cheng Zhang, Kai Liu, Jing Xia, Kang L. Wang

    Majorana fermion is a hypothetical particle that is its own antiparticle. We report transport measurements that suggest the existence of one-dimensional chiral Majorana fermion modes in the hybrid system of a quantum anomalous Hall insulator thin film coupled with a superconductor. As the external magnetic field is swept, half-integer quantized conductance plateaus are observed at the locations of magnetization reversals, giving a distinct signature of the Majorana fermion modes. This transport signature is reproducible over many magnetic field sweeps and appears at different temperatures. This finding may open up an avenue to control Majorana fermions for implementing robust topological quantum computing.

    更新日期:2017-07-21
  • Experimentally realized mechanochemistry distinct from force-accelerated scission of loaded bonds
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Sergey Akbulatov, Yancong Tian, Zhen Huang, Timothy J. Kucharski, Qing-Zheng Yang, Roman Boulatov

    Stretching polymer chains accelerates dissociation of a variety of internal covalent bonds, to an extent that correlates well with the force experienced by the scissile bond. Recent theory has also predicted scenarios in which applied force accelerates dissociation of unloaded bonds and kinetically strengthens strained bonds. We report here unambiguous experimental validation of this hypothesis: Detailed kinetic measurements demonstrate that stretching phosphotriesters accelerates dissociation of the unloaded phosphorus-oxygen bond orthogonal to the pulling axis, whereas stretching organosiloxanes inhibits dissociation of the aligned loaded silicon-oxygen bonds. Qualitatively, the outcome is determined by phosphoester elongation and siloxane contraction along the pulling axis in the respective rate-determining transition states. Quantitatively, the results agree with a simple mechanochemical kinetics model.

    更新日期:2017-07-21
  • Tailored semiconductors for high-harmonic optoelectronics
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Murat Sivis, Marco Taucer, Giulio Vampa, Kyle Johnston, André Staudte, Andrei Yu. Naumov, D. M. Villeneuve, Claus Ropers, P. B. Corkum

    The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes.

    更新日期:2017-07-21
  • An organic-inorganic perovskite ferroelectric with large piezoelectric response
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Yu-Meng You, Wei-Qiang Liao, Dewei Zhao, Heng-Yun Ye, Yi Zhang, Qionghua Zhou, Xianghong Niu, Jinlan Wang, Peng-Fei Li, Da-Wei Fu, Zheming Wang, Song Gao, Kunlun Yang, Jun-Ming Liu, Jiangyu Li, Yanfa Yan, Ren-Gen Xiong

    Molecular piezoelectrics are highly desirable for their easy and environment-friendly processing, light weight, low processing temperature, and mechanical flexibility. However, although 136 years have passed since the discovery in 1880 of the piezoelectric effect, molecular piezoelectrics with a piezoelectric coefficient d33 comparable with piezoceramics such as barium titanate (BTO; ~190 picocoulombs per newton) have not been found. We show that trimethylchloromethyl ammonium trichloromanganese(II), an organic-inorganic perovskite ferroelectric crystal processed from aqueous solution, has a large d33 of 185 picocoulombs per newton and a high phase-transition temperature of 406 kelvin (K) (16 K above that of BTO). This makes it a competitive candidate for medical, micromechanical, and biomechanical applications.

    更新日期:2017-07-21
  • Hydraulic control of tuna fins: A role for the lymphatic system in vertebrate locomotion
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Vadim Pavlov, Benyamin Rosental, Nathaniel F. Hansen, Jody M. Beers, George Parish, Ian Rowbotham, Barbara A. Block

    The lymphatic system in teleost fish has genetic and developmental origins similar to those of the mammalian lymphatic system, which is involved in immune response and fluid homeostasis. Here, we show that the lymphatic system of tunas functions in swimming hydrodynamics. Specifically, a musculo-vascular complex, consisting of fin muscles, bones, and lymphatic vessels, is involved in the hydraulic control of median fins. This specialization of the lymphatic system is associated with fish in the family Scombridae and may have evolved in response to the demand for swimming and maneuvering control in these high-performance species.

    更新日期:2017-07-21
  • Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Gideon Coster, John F. X. Diffley

    Bidirectional replication from eukaryotic DNA replication origins requires the loading of two ring-shaped minichromosome maintenance (MCM) helicases around DNA in opposite orientations. MCM loading is orchestrated by binding of the origin recognition complex (ORC) to DNA, but how ORC coordinates symmetrical MCM loading is unclear. We used natural budding yeast DNA replication origins and synthetic DNA sequences to show that efficient MCM loading requires binding of two ORC molecules to two ORC binding sites. The relative orientation of these sites, but not the distance between them, was found to be critical for MCM loading in vitro and origin function in vivo. We propose that quasi-symmetrical loading of individual MCM hexamers by ORC and directed MCM translocation into double hexamers acts as a unifying mechanism for the establishment of bidirectional replication in archaea and eukaryotes.

    更新日期:2017-07-21
  • Epigenetic plasticity and the hallmarks of cancer
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    William A. Flavahan, Elizabeth Gaskell, Bradley E. Bernstein

    Chromatin and associated epigenetic mechanisms stabilize gene expression and cellular states while also facilitating appropriate responses to developmental or environmental cues. Genetic, environmental, or metabolic insults can induce overly restrictive or overly permissive epigenetic landscapes that contribute to pathogenesis of cancer and other diseases. Restrictive chromatin states may prevent appropriate induction of tumor suppressor programs or block differentiation. By contrast, permissive or "plastic" states may allow stochastic oncogene activation or nonphysiologic cell fate transitions. Whereas many stochastic events will be inconsequential "passengers," some will confer a fitness advantage to a cell and be selected as "drivers." We review the broad roles played by epigenetic aberrations in tumor initiation and evolution and their potential to give rise to all classic hallmarks of cancer.

    更新日期:2017-07-21
  • Comment on “The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport”
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Andrey G. Baranovskiy, Nigar D. Babayeva, Yinbo Zhang, Luis Blanco, Youri I. Pavlov, Tahir H. Tahirov

    O’Brien et al. (Research Article, 24 February 2017, eaag1789) proposed a novel mechanism of primase function based on redox activity of the iron-sulfur cluster buried inside the C-terminal domain of the large primase subunit (p58C). Serious problems in the experimental design and data interpretation raise concerns about the validity of the conclusions.

    更新日期:2017-07-21
  • Response to Comments on “The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport”
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Elizabeth O’Brien, Marilyn E. Holt, Matthew K. Thompson, Lauren E. Salay, Aaron C. Ehlinger, Walter J. Chazin, Jacqueline K. Barton

    Baranovskiy et al. and Pellegrini argue that, based on structural data, the path for charge transfer through the [4Fe4S] domain of primase is not feasible. Our manuscript presents electrochemical data directly showing charge transport through DNA to the [4Fe4S] cluster of a primase p58C construct and a reversible switch in the DNA-bound signal with oxidation/reduction, which is inhibited by mutation of three tyrosine residues. Although the dispositions of tyrosines differ in different constructs, all are within range for microsecond electron transfer.

    更新日期:2017-07-21
  • Comment on “The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport”
    Science (IF 37.205) Pub Date : 2017-07-21 00:00:00
    Luca Pellegrini

    O’Brien et al. (Research Article, 24 February 2017, eaag1789) report that the iron-sulfur cluster of primase has a redox role in enzyme activity. Their analysis is based on a partially misfolded structure of the iron-sulfur cluster domain of primase. In the correctly folded structure, two of the three tyrosines putatively involved in electron transfer, Y345 and Y347, contact the RNA/DNA helix, providing an alternative explanation for the data of O’Brien et al.

    更新日期:2017-07-21
  • Driving improvements in emerging disease surveillance through locally relevant capacity strengthening
    Science (IF 37.205) Pub Date : 2017-07-14
    Jo E. B. Halliday, Katie Hampson, Nick Hanley, Tiziana Lembo, Joanne P. Sharp, Daniel T. Haydon, Sarah Cleaveland

    Emerging infectious diseases (EIDs) threaten the health of people, animals, and crops globally, but our ability to predict their occurrence is limited. Current public health capacity and ability to detect and respond to EIDs is typically weakest in low- and middle-income countries (LMICs). Many known drivers of EID emergence also converge in LMICs. Strengthening capacity for surveillance of diseases of relevance to local populations can provide a mechanism for building the cross-cutting and flexible capacities needed to tackle both the burden of existing diseases and EID threats. A focus on locally relevant diseases in LMICs and the economic, social, and cultural contexts of surveillance can help address existing inequalities in health systems, improve the capacity to detect and contain EIDs, and contribute to broader global goals for development.

    更新日期:2017-07-14
  • Opportunities and challenges in modeling emerging infectious diseases
    Science (IF 37.205) Pub Date : 2017-07-14
    C. Jessica E. Metcalf, Justin Lessler

    The term "pathogen emergence" encompasses everything from previously unidentified viruses entering the human population to established pathogens invading new populations and the evolution of drug resistance. Mathematical models of emergent pathogens allow forecasts of case numbers, investigation of transmission mechanisms, and evaluation of control options. Yet, there are numerous limitations and pitfalls to their use, often driven by data scarcity. Growing availability of data on pathogen genetics and human ecology, coupled with computational and methodological innovations, is amplifying the power of models to inform the public health response to emergence events. Tighter integration of infectious disease models with public health practice and development of resources at the ready has the potential to increase the timeliness and quality of responses.

    更新日期:2017-07-14
  • Improving vaccine trials in infectious disease emergencies
    Science (IF 37.205) Pub Date : 2017-07-14
    Marc Lipsitch, Nir Eyal

    Unprecedented global effort is under way to facilitate the testing of countermeasures in infectious disease emergencies. Better understanding of the various options for trial design is needed in advance of outbreaks, as is preliminary global agreement on the most suitable designs for the various scenarios. What would enhance the speed, validity, and ethics of clinical studies of such countermeasures? Focusing on studies of vaccine efficacy and effectiveness in emergencies, we highlight three needs: for formal randomized trials—even in most emergencies; for individually randomized trials—even in many emergencies; and for six areas of innovation in trial methodology. These needs should inform current updates of protocols and roadmaps.

    更新日期:2017-07-14
  • When an emerging disease becomes endemic
    Science (IF 37.205) Pub Date : 2017-07-14
    Graham F. Medley, Anna Vassall

    Epidemics, such as HIV in the early 1980s and Ebola in 2014, inspire decisive government investment and action, and individual and societal concern, sometimes bordering on panic. By contrast, endemic diseases, such as HIV in 2017 and tuberculosis, struggle to maintain the same attention. For many, the paradox is that endemic disease, in its totality, continues to impose a far higher public health burden than epidemic disease. Overall, the swift political response to epidemics has resulted in success. It has proven possible to eradicate epidemic diseases, often without the availability of vaccines and other biomedical technologies. In recent times, only HIV has made the transition from epidemic to endemic, but diseases that have existed for centuries continue to cause most of the infectious disease burden.

    更新日期:2017-07-14
  • History of winning remodels thalamo-PFC circuit to reinforce social dominance
    Science (IF 37.205) Pub Date : 2017-07-14
    Tingting Zhou, Hong Zhu, Zhengxiao Fan, Fei Wang, Yang Chen, Hexing Liang, Zhongfei Yang, Lu Zhang, Longnian Lin, Yang Zhan, Zheng Wang, Hailan Hu

    Mental strength and history of winning play an important role in the determination of social dominance. However, the neural circuits mediating these intrinsic and extrinsic factors have remained unclear. Working in mice, we identified a dorsomedial prefrontal cortex (dmPFC) neural population showing "effort"-related firing during moment-to-moment competition in the dominance tube test. Activation or inhibition of the dmPFC induces instant winning or losing, respectively. In vivo optogenetic-based long-term potentiation and depression experiments establish that the mediodorsal thalamic input to the dmPFC mediates long-lasting changes in the social dominance status that are affected by history of winning. The same neural circuit also underlies transfer of dominance between different social contests. These results provide a framework for understanding the circuit basis of adaptive and pathological social behaviors.

    更新日期:2017-07-14
  • Global analysis of protein folding using massively parallel design, synthesis, and testing
    Science (IF 37.205) Pub Date : 2017-07-14
    Gabriel J. Rocklin, Tamuka M. Chidyausiku, Inna Goreshnik, Alex Ford, Scott Houliston, Alexander Lemak, Lauren Carter, Rashmi Ravichandran, Vikram K. Mulligan, Aaron Chevalier, Cheryl H. Arrowsmith, David Baker

    Proteins fold into unique native structures stabilized by thousands of weak interactions that collectively overcome the entropic cost of folding. Although these forces are "encoded" in the thousands of known protein structures, "decoding" them is challenging because of the complexity of natural proteins that have evolved for function, not stability. We combined computational protein design, next-generation gene synthesis, and a high-throughput protease susceptibility assay to measure folding and stability for more than 15,000 de novo designed miniproteins, 1000 natural proteins, 10,000 point mutants, and 30,000 negative control sequences. This analysis identified more than 2500 stable designed proteins in four basic folds—a number sufficient to enable us to systematically examine how sequence determines folding and stability in uncharted protein space. Iteration between design and experiment increased the design success rate from 6% to 47%, produced stable proteins unlike those found in nature for topologies where design was initially unsuccessful, and revealed subtle contributions to stability as designs became increasingly optimized. Our approach achieves the long-standing goal of a tight feedback cycle between computation and experiment and has the potential to transform computational protein design into a data-driven science.

    更新日期:2017-07-14
  • Snap deconvolution: An informatics approach to high-throughput discovery of catalytic reactions
    Science (IF 37.205) Pub Date : 2017-07-14
    Konstantin Troshin, John F. Hartwig

    We present an approach to multidimensional high-throughput discovery of catalytic coupling reactions that integrates molecular design with automated analysis and interpretation of mass spectral data. We simultaneously assessed the reactivity of three pools of compounds that shared the same functional groups (halides, boronic acids, alkenes, and alkynes, among other groups) but carried inactive substituents having specifically designed differences in masses. The substituents were chosen such that the products from any class of reaction in multiple reaction sets would have unique differences in masses, thus allowing simultaneous identification of the products of all transformations in a set of reactants. In this way, we easily distinguished the products of new reactions from noise and known couplings. Using this method, we discovered an alkyne hydroallylation and a nickel-catalyzed variant of alkyne diarylation.

    更新日期:2017-07-14
  • High-temperature quantum oscillations caused by recurring Bloch states in graphene superlattices
    Science (IF 37.205) Pub Date : 2017-07-14
    R. Krishna Kumar, X. Chen, G. H. Auton, A. Mishchenko, D. A. Bandurin, S. V. Morozov, Y. Cao, E. Khestanova, M. Ben Shalom, A. V. Kretinin, K. S. Novoselov, L. Eaves, I. V. Grigorieva, L. A. Ponomarenko, V. I. Fal’ko, A. K. Geim

    Cyclotron motion of charge carriers in metals and semiconductors leads to Landau quantization and magneto-oscillatory behavior in their properties. Cryogenic temperatures are usually required to observe these oscillations. We show that graphene superlattices support a different type of quantum oscillation that does not rely on Landau quantization. The oscillations are extremely robust and persist well above room temperature in magnetic fields of only a few tesla. We attribute this phenomenon to repetitive changes in the electronic structure of superlattices such that charge carriers experience effectively no magnetic field at simple fractions of the flux quantum per superlattice unit cell. Our work hints at unexplored physics in Hofstadter butterfly systems at high temperatures.

    更新日期:2017-07-14
  • Reconciling solar and stellar magnetic cycles with nonlinear dynamo simulations
    Science (IF 37.205) Pub Date : 2017-07-14
    A. Strugarek, P. Beaudoin, P. Charbonneau, A. S. Brun, J.-D. do Nascimento

    The magnetic fields of solar-type stars are observed to cycle over decadal periods—11 years in the case of the Sun. The fields originate in the turbulent convective layers of stars and have a complex dependency upon stellar rotation rate. We have performed a set of turbulent global simulations that exhibit magnetic cycles varying systematically with stellar rotation and luminosity. We find that the magnetic cycle period is inversely proportional to the Rossby number, which quantifies the influence of rotation on turbulent convection. The trend relies on a fundamentally nonlinear dynamo process and is compatible with the Sun’s cycle and those of other solar-type stars.

    更新日期:2017-07-14
  • Tuning quantum nonlocal effects in graphene plasmonics
    Science (IF 37.205) Pub Date : 2017-07-14
    Mark B. Lundeberg, Yuanda Gao, Reza Asgari, Cheng Tan, Ben Van Duppen, Marta Autore, Pablo Alonso-González, Achim Woessner, Kenji Watanabe, Takashi Taniguchi, Rainer Hillenbrand, James Hone, Marco Polini, Frank H. L. Koppens

    The response of electron systems to electrodynamic fields that change rapidly in space is endowed by unique features, including an exquisite spatial nonlocality. This can reveal much about the materials’ electronic structure that is invisible in standard probes that use gradually varying fields. Here, we use graphene plasmons, propagating at extremely slow velocities close to the electron Fermi velocity, to probe the nonlocal response of the graphene electron liquid. The near-field imaging experiments reveal a parameter-free match with the full quantum description of the massless Dirac electron gas, which involves three types of nonlocal quantum effects: single-particle velocity matching, interaction-enhanced Fermi velocity, and interaction-reduced compressibility. Our experimental approach can determine the full spatiotemporal response of an electron system.

    更新日期:2017-07-14
  • All-oxide–based synthetic antiferromagnets exhibiting layer-resolved magnetization reversal
    Science (IF 37.205) Pub Date : 2017-07-14
    Binbin Chen, Haoran Xu, Chao Ma, Stefan Mattauch, Da Lan, Feng Jin, Zhuang Guo, Siyuan Wan, Pingfan Chen, Guanyin Gao, Feng Chen, Yixi Su, Wenbin Wu

    Synthesizing antiferromagnets with correlated oxides has been challenging, owing partly to the markedly degraded ferromagnetism of the magnetic layer at nanoscale thicknesses. Here we report on the engineering of an antiferromagnetic interlayer exchange coupling (AF-IEC) between ultrathin but ferromagnetic La2/3Ca1/3MnO3 layers across an insulating CaRu1/2Ti1/2O3 spacer. The layer-resolved magnetic switching leads to sharp steplike hysteresis loops with magnetization plateaus depending on the repetition number of the stacking bilayers. The magnetization configurations can be switched at moderate fields of hundreds of oersted. Moreover, the AF-IEC can also be realized with an alternative magnetic layer of La2/3Sr1/3MnO3 that possesses a Curie temperature near room temperature. The findings will add functionalities to devices with correlated-oxide interfaces.

    更新日期:2017-07-14
  • Control and local measurement of the spin chemical potential in a magnetic insulator
    Science (IF 37.205) Pub Date : 2017-07-14
    Chunhui Du, Toeno van der Sar, Tony X. Zhou, Pramey Upadhyaya, Francesco Casola, Huiliang Zhang, Mehmet C. Onbasli, Caroline A. Ross, Ronald L. Walsworth, Yaroslav Tserkovnyak, Amir Yacoby

    The spin chemical potential characterizes the tendency of spins to diffuse. Probing this quantity could provide insight into materials such as magnetic insulators and spin liquids and aid optimization of spintronic devices. Here we introduce single-spin magnetometry as a generic platform for nonperturbative, nanoscale characterization of spin chemical potentials. We experimentally realize this platform using diamond nitrogen-vacancy centers and use it to investigate magnons in a magnetic insulator, finding that the magnon chemical potential can be controlled by driving the system’s ferromagnetic resonance. We introduce a symmetry-based two-fluid theory describing the underlying magnon processes, measure the local thermomagnonic torque, and illustrate the detection sensitivity using electrically controlled spin injection. Our results pave the way for nanoscale control and imaging of spin transport in mesoscopic systems.

    更新日期:2017-07-14
  • Effects of network modularity on the spread of perturbation impact in experimental metapopulations
    Science (IF 37.205) Pub Date : 2017-07-14
    Luis J. Gilarranz, Bronwyn Rayfield, Gustavo Liñán-Cembrano, Jordi Bascompte, Andrew Gonzalez

    Networks with a modular structure are expected to have a lower risk of global failure. However, this theoretical result has remained untested until now. We used an experimental microarthropod metapopulation to test the effect of modularity on the response to perturbation. We perturbed one local population and measured the spread of the impact of this perturbation, both within and between modules. Our results show the buffering capacity of modular networks. To assess the generality of our findings, we then analyzed a dynamical model of our system. We show that in the absence of perturbations, modularity is negatively correlated with metapopulation size. However, even when a small local perturbation occurs, this negative effect is offset by a buffering effect that protects the majority of the nodes from the perturbation.

    更新日期:2017-07-14
  • Ravens parallel great apes in flexible planning for tool-use and bartering
    Science (IF 37.205) Pub Date : 2017-07-14
    Can Kabadayi, Mathias Osvath

    The ability to flexibly plan for events outside of the current sensory scope is at the core of being human and is crucial to our everyday lives and society. Studies on apes have shaped a belief that this ability evolved within the hominid lineage. Corvids, however, have shown evidence of planning their food hoarding, although this has been suggested to reflect a specific caching adaptation rather than domain-general planning. Here, we show that ravens plan for events unrelated to caching—tool-use and bartering—with delays of up to 17 hours, exert self-control, and consider temporal distance to future events. Their performance parallels that seen in apes and suggests that planning evolved independently in corvids, which opens new avenues for the study of cognitive evolution.

    更新日期:2017-07-14
  • Mouse models of acute and chronic hepacivirus infection
    Science (IF 37.205) Pub Date : 2017-07-14
    Eva Billerbeck, Raphael Wolfisberg, Ulrik Fahnøe, Jing W. Xiao, Corrine Quirk, Joseph M. Luna, John M. Cullen, Alex S. Hartlage, Luis Chiriboga, Kalpana Ghoshal, W. Ian Lipkin, Jens Bukh, Troels K. H. Scheel, Amit Kapoor, Charles M. Rice

    An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections in laboratory mice with immunological features resembling those seen in human viral hepatitis. Whereas immune-compromised mice developed persistent infection, immune-competent mice cleared the virus within 3 to 5 weeks. Acute clearance was T cell dependent and associated with liver injury. Transient depletion of CD4+ T cells before infection resulted in chronic infection, characterized by high levels of intrahepatic regulatory T cells and expression of inhibitory molecules on intrahepatic CD8+ T cells. Natural killer cells controlled early infection but were not essential for viral clearance. This model may provide mechanistic insights into hepatic antiviral immunity, a prerequisite for the development of HCV vaccines.

    更新日期:2017-07-14
  • Guanine glycation repair by DJ-1/Park7 and its bacterial homologs
    Science (IF 37.205) Pub Date : 2017-07-14
    Gilbert Richarme, Cailing Liu, Mouadh Mihoub, Jad Abdallah, Thibaut Leger, Nicolas Joly, Jean-Claude Liebart, Ula V. Jurkunas, Marc Nadal, Philippe Bouloc, Julien Dairou, Aazdine Lamouri

    DNA damage induced by reactive carbonyls (mainly methylglyoxal and glyoxal), called DNA glycation, is quantitatively as important as oxidative damage. DNA glycation is associated with increased mutation frequency, DNA strand breaks, and cytotoxicity. However, in contrast to guanine oxidation repair, how glycated DNA is repaired remains undetermined. Here, we found that the parkinsonism-associated protein DJ-1 and its bacterial homologs Hsp31, YhbO, and YajL could repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids. DJ-1–depleted cells displayed increased levels of glycated DNA, DNA strand breaks, and phosphorylated p53. Deglycase-deficient bacterial mutants displayed increased levels of glycated DNA and RNA and exhibited strong mutator phenotypes. Thus, DJ-1 and its prokaryotic homologs constitute a major nucleotide repair system that we name guanine glycation repair.

    更新日期:2017-07-14
  • Germ line–inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition
    Science (IF 37.205) Pub Date : 2017-07-14
    Fides Zenk, Eva Loeser, Rosaria Schiavo, Fabian Kilpert, Ozren Bogdanović, Nicola Iovino

    Gametes carry parental genetic material to the next generation. Stress-induced epigenetic changes in the germ line can be inherited and can have a profound impact on offspring development. However, the molecular mechanisms and consequences of transgenerational epigenetic inheritance are poorly understood. We found that Drosophila oocytes transmit the repressive histone mark H3K27me3 to their offspring. Maternal contribution of the histone methyltransferase Enhancer of zeste, the enzymatic component of Polycomb repressive complex 2, is required for active propagation of H3K27me3 during early embryogenesis. H3K27me3 in the early embryo prevents aberrant accumulation of the active histone mark H3K27ac at regulatory regions and precocious activation of lineage-specific genes at zygotic genome activation. Disruption of the germ line–inherited Polycomb epigenetic memory causes embryonic lethality that cannot be rescued by late zygotic reestablishment of H3K27me3. Thus, maternally inherited H3K27me3, propagated in the early embryo, regulates the activation of enhancers and lineage-specific genes during development.

    更新日期:2017-07-14
  • Comment on “Molecular and neural basis of contagious itch behavior in mice”
    Science (IF 37.205) Pub Date : 2017-07-14
    Jaquette Liljencrantz, Mark H. Pitcher, Lucie A. Low, Lucy Bauer, M. Catherine Bushnell

    Yu et al. (Reports, 10 March 2017, p. 1072) state that contagious itch occurs in mice based on imitative scratching in normal mice observing excessive scratching in genetically modified demonstrator mice. However, despite employing multiple behavioral analysis approaches, we were unable to extend these findings to normal mice observing the well-established histamine model of acute itch in demonstrator mice.

    更新日期:2017-07-14
  • Response to Comment on “Molecular and neural basis of contagious itch behavior in mice”
    Science (IF 37.205) Pub Date : 2017-07-14
    Devin M. Barry, Yao-Qing Yu, Yan Hao, Xue-Ting Liu, Zhou-Feng Chen

    Liljencrantz et al. report the failure of observing contagious itch behavior using mice injected with histamine as the demonstrators. Analysis of their results shows that the histamine model is limited by inadequate frequency and duration of scratching bouts required for contagious itch test. To streamline the contagious itch test, the screen paradigm is highly recommended.

    更新日期:2017-07-14
  • Large-amplitude transfer motion of hydrated excess protons mapped by ultrafast 2D IR spectroscopy
    Science (IF 37.205) Pub Date : 2017-07-13
    Fabian Dahms, Benjamin P. Fingerhut, Erik T. J. Nibbering, Ehud Pines, Thomas Elsaesser

    Solvation and transport of excess protons in aqueous systems play a fundamental role in acid-base chemistry and biochemical processes. Here, we map ultrafast proton excursions along the proton transfer coordinate by 2D infrared (IR) spectroscopy, both in bulk water and in a Zundel cation (H5O2)+ motif selectively prepared in acetonitrile. Electric fields from the environment and stochastic hydrogen bond motions induce fluctuations of the proton double-minimum potential. Within the lifetime of a particular hydration geometry, the proton explores a multitude of positions on a sub-100 fs time scale. The proton transfer vibration is strongly damped by its 20 to 40 fs population decay. Our results suggest a central role of Zundel-like geometries in aqueous proton solvation and transport.

    更新日期:2017-07-14
  • East not least for Pacific bluefin tuna
    Science (IF 37.205) Pub Date : 2017-07-13
    By Daniel J. Madigan, Andre Boustany, Bruce B. Collette

    More Pacific bluefin migrate across the ocean than previously recognized

    更新日期:2017-07-14
  • Emergent cellular self-organization and mechanosensation initiate follicle pattern in the avian skin
    Science (IF 37.205) Pub Date : 2017-07-13
    Amy E. Shyer, Alan R. Rodrigues, Grant G. Schroeder, Elena Kassianidou, Sanjay Kumar, Richard M. Harland

    The spacing of hair in mammals and feathers in birds is one of the most apparent morphological features of the skin. This pattern arises when uniform fields of progenitor cells diversify their molecular fate while adopting higher-order structure. Using the nascent skin of the developing chicken embryo as a model system, we find that morphological and molecular symmetries are simultaneously broken by an emergent process of cellular self-organization. The key initiators of heterogeneity are dermal progenitors, which spontaneously aggregate through contractility-driven cellular pulling. Concurrently, this dermal cell aggregation triggers the mechanosensitive activation of β-catenin in adjacent epidermal cells, initiating the follicle gene expression program. Taken together, this mechanism provides a means of integrating mechanical and molecular perspectives of organ formation.

    更新日期:2017-07-14
  • Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy
    Science (IF 37.205) Pub Date : 2017-07-13
    Robert W. Myers, Hong-Ping Guan, Juliann Ehrhart, Aleksandr Petrov, Srinivasa Prahalada, Effie Tozzo, Xiaodong Yang, Marc M. Kurtz, Maria Trujillo, Dinko Gonzalez Trotter, Danqing Feng, Shiyao Xu, George Eiermann, Marie A. Holahan, Daniel Rubins, Stacey Conarello, Xiaoda Niu, Sandra C. Souza, Corin Miller, Jinqi Liu, Ku Lu, Wen Feng, Ying Li, Ronald E. Painter, James A. Milligan, Huaibing He, Franklin Liu, Aimie Ogawa, Douglas Wisniewski, Rory J. Rohm, Liyang Wang, Michelle Bunzel, Ying Qian, Wei Zhu, Hongwu Wang, Bindu Bennet, Lisa LaFranco Scheuch, Guillermo E. Fernandez, Cai Li, Michael Klimas, Gaochao Zhou, Margaret van Heek, Tesfaye Biftu, Ann Weber, David E. Kelley, Nancy Thornberry, Mark D. Erion, Daniel M. Kemp, Iyassu K. Sebhat

    5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite investigations over three decades, the biological roles of AMPK and its potential as a drug target remain incompletely understood, due largely to the lack of optimized pharmacological tools. We now report MK-8722, a potent, direct, allosteric activator of all twelve mammalian AMPK complexes. In rodents and rhesus monkeys, MK-8722-mediated AMPK activation in skeletal muscle induces robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia. These effects translate across species, including diabetic rhesus monkeys, but manifest with concomitant cardiac hypertrophy and increased cardiac glycogen without apparent functional sequelae.

    更新日期:2017-07-14
  • AI, people, and society
    Science (IF 37.205) Pub Date : 2017-07-07
    Eric Horvitz

    In an essay about his science fiction, Isaac Asimov reflected that “it became very common…to picture robots as dangerous devices that invariably destroyed their creators.” He rejected this view and formulated the “laws of robotics,” aimed at ensuring the safety and benevolence of robotic systems. Asimov's stories about the relationship between people and robots were only a few years old when the phrase “artificial intelligence” (AI) was used for the first time in a 1955 proposal for a study on using computers to “…solve kinds of problems now reserved for humans.” Over the half-century since that study, AI has matured into subdisciplines that have yielded a constellation of methods that enable perception, learning, reasoning, and natural language understanding.

    更新日期:2017-07-11
  • News at a glance
    Science (IF 37.205) Pub Date : 2017-07-07
    American Association for the Advancement of Science

    In science news around the world, a report finds that Canada's science enterprise is suffering from a funding crunch and misguided government and granting council policies, a plan to build up to 100 incinerator plants to burn municipal waste for power draws sharp criticism from opponents, the United Kingdom reassures scientists who use the Joint European Torus that it will continue to support the device for two more years despite the country's pending exit from the European Union, a polio vaccine is on its way to war-torn Syria to combat an outbreak that has so far paralyzed 22 children, and more. Also, U.S. President Donald Trump nominates the former health minister of Indiana to be the country's surgeon general. And Science takes a closer look at three young scientists in NASA's new astronaut class.

    更新日期:2017-07-11
  • New technologies boost genome quality
    Science (IF 37.205) Pub Date : 2017-07-07
    Elizabeth Pennisi

    Biologists and informatics experts are launching a quiet revolution aimed at building better genomes, one made possible by newer sequencing technologies, novel methods for locating sequences on chromosomes, and improved software for piecing DNA together. In the past 6 months, these approaches have led to a flood of high-quality animal and plant genomes in preprints and published papers. Often far better than even prized sequences such as the original mouse and human genomes, such polished genomes are "now going to become super mainstream," says Timothy P.L. Smith, an animal geneticist with the U.S. Department of Agriculture Agricultural Research Service in Clay Center, Nebraska. They promise new details about evolutionary history, such as genome duplications and invasions by rogue DNA, and make it easier to find specific DNA involved in traits important for an organism's survival or for agricultural improvements.

    更新日期:2017-07-11
  • Lawmakers balk at most Trump cuts
    Science (IF 37.205) Pub Date : 2017-07-07
    David Malakoff, Jeffrey Mervis

    Lawmakers in the U.S. House of Representatives are saying no to President Donald Trump's request to make deep cuts next year to the budgets of several key science funding agencies. Last week House appropriators advanced a half-dozen 2018 budget bills that mostly ignore the proposed double-digit cuts, and chose to hold spending at many agencies roughly at current levels. Still, key climate and earth science programs would take a hit in the House bills, which mark the first step in what is expected to be a lengthy battle to set federal spending for the 2018 fiscal year that begins 1 October. The budget for the Office of Science at the Department of Energy (DOE), for example, would hold steady at its 2017 level of $5.39 billion rather than plunge by 17%. The National Science Foundation (NSF) would come up 1.8% short of its current $7.47 billion budget, but that's much better than the 11% cut that Trump proposed last May. NASA's science programs would actually rise by a 1% boost, to $5.9 billion, fueled in part by a $220 million increase for a planned multibillion-dollar mission to Jupiter's moon Europa. Not all the news was good, however. NASA's earth science budget would shrink by 11%, or $217 million, to $1.7 billion. Climate science at the National Oceanic and Atmospheric Administration would drop by a reported 19%, and DOE's $300-million-a-year Advanced Research Projects Agency-Energy would disappear, in line with Trump's request. NSF would retain current funding levels for its six research directorates, but it would not get $105 million requested to start building the first two of three new research ships.

    更新日期:2017-07-11
  • NASA armada targets thaw in Arctic soil
    Science (IF 37.205) Pub Date : 2017-07-07
    Paul Voosen

    This summer, hundreds of field sites in Alaska and Canada's Yukon and Northwest Territories will be surveyed as part of a $100 million, 10-year, NASA-led campaign to study the permafrost. Thanks to global warming, permafrost—soil that remains in part frozen throughout the year—is thawing across much the north, shifting ecosystems and potentially unlocking a vast pool of ancient carbon for slow release to the atmosphere, amplifying the greenhouse effect. Local influences like topography and the water content in the soil, however, prevent long-term field sites from extrapolating their results to the landscape at large. It's hoped that the NASA project's nine aircraft, armed with advanced laser altimeters and radar, will help knit these local measures into a broad tapestry portraying the Arctic's future.

    更新日期:2017-07-11
  • Neandertals mated early with modern humans
    Science (IF 37.205) Pub Date : 2017-07-07
    Ann Gibbons

    For almost a century, Neandertals were considered the ancestors of modern humans. But now, in a new plot twist in the unfolding mystery of how Neandertals were related to modern humans, it seems that members of our own lineage were among the ancestors of Neandertals. Researchers sequenced ancient DNA from the mitochondria—the tiny energy factories inside cells—from a Neandertal that lived at least 100,000 years ago in southwest Germany, and found that its mitochondrial DNA (mtDNA) resembled that of modern humans. In a new report inNature Communications, researchers conclude that this Neandertal, as well as others whose mtDNA was previously sequenced, inherited their mitochondrial genomes from mating with an early ancestor ofHomo sapiens.

    更新日期:2017-07-11
  • South Korea's nuclear U-turn draws praise and darts
    Science (IF 37.205) Pub Date : 2017-07-07
    Dennis Normile

    Newly inaugurated South Korean President Moon Jae-in is acting on a campaign pledge to cut the country's reliance on coal-fired power plants and reverse a long-standing policy favoring nuclear power. His administration is eying the closure of 10 older coal-fired plants and has announced that nuclear plants will be decommissioned when they reach the end of their initial operating licenses. He wants to increase the use of renewable energy from just 4.7% of the nation's generated electricity now to 20% by 2030. He will also increase the use of natural gas as being a cleaner alternative to coal. Environmentalists welcomed the move, particularly as it will help South Korea meet its Paris agreement pledge to reduce carbon dioxide emissions 37% by 2030. But nuclear power boosters are appalled; 230 nuclear engineering faculty members issued a statement calling for reaching a social consensus before pursuing a nuclear-free energy policy.

    更新日期:2017-07-11
  • A cyclic oligonucleotide signaling pathway in type III CRISPR-Cas systems
    Science (IF 37.205) Pub Date : 2017-06-29
    Migle Kazlauskiene, Georgij Kostiuk, Česlovas Venclovas, Gintautas Tamulaitis, Virginijus Siksnys

    Type III CRISPR-Cas systems in prokaryotes provide immunity against invading nucleic acids through the coordinated degradation of transcriptionally-active DNA and its transcripts by the Csm effector complex. Cas10 subunit of the complex contains a HD-nuclease domain responsible for DNA degradation and two Palm domains with elusive functions. In addition, Csm6, an RNase that is not part of the complex, is also required to provide full immunity. We show here that target RNA binding by the Csm effector complex ofStreptococcus thermophilustriggers Cas10 to synthesize cyclic oligoadenylates cOAn(n = 2-6) via the Palm domains. Acting as signaling molecules, cOAs bind Csm6 to activate its non-specific RNA degradation. This cOA -based signaling pathway coordinates different components of CRISPR-Cas to prevent phage infection and propagation.

    更新日期:2017-07-11
  • ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice
    Science (IF 37.205) Pub Date : 2017-06-29
    Lena Ho, Marie Van Dijk, Sam Tan Jian Chye, Daniel M. Messerschmidt, Serene C. Chng, Sheena Ong, Ling Ka Yi, Souad Boussata, Grace Hui-Yi Goh, Gijs B. Afink, Chin Yan Lim, N. Ray Dunn, Davor Solter, Barbara B. Knowles, Bruno Reversade

    Pre-eclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. While PE is the leading cause of fetal and maternal morbidity/mortality, its molecular etiology is still unclear. Here, we show that ELABELA (ELA), an endogenous ligand of the apelin receptor (APLNR, or APJ), is a circulating hormone secreted by the placenta.Elabelabut notApelinknockout pregnant mice exhibit PE-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis. In mice, infusion of exogenous ELA normalizes hypertension, proteinuria, and birth weight. ELA, which is abundant in human placentas, increases the invasiveness of trophoblast-like cells, suggesting that it enhances placental development to prevent PE. The ELA-APLNR signaling axis may offer a new paradigm for the treatment of common pregnancy-related complications, including PE.

    更新日期:2017-07-11
  • Bismuthene on a SiC substrate: A candidate for a high-temperature quantum spin Hall material
    Science (IF 37.205) Pub Date : 2017-06-29
    F. Reis, G. Li, L. Dudy, M. Bauernfeind, S. Glass, W. Hanke, R. Thomale, J. Schäfer, R. Claessen

    Quantum spin Hall materials hold the promise of revolutionary devices with dissipationless spin currents, but have required cryogenic temperatures owing to small energy gaps. Here we show theoretically that a room-temperature regime with a large energy gap may be achievable within a paradigm that exploits the atomic spin-orbit coupling. The concept is based on a substrate-supported monolayer of a high-Z element, and is experimentally realized as a bismuth honeycomb lattice on top of the insulator SiC(0001). Using scanning tunneling spectroscopy, we detect a gap of ~0.8 eV and conductive edge states consistent with theory. Our combined theoretical and experimental results demonstrate a concept for a quantum spin Hall wide-gap scenario, where the chemical potential resides in the global system gap, ensuring robust edge conductance.

    更新日期:2017-07-11
  • Reconfiguration of DNA molecular arrays driven by information relay
    Science (IF 37.205) Pub Date : 2017-06-22
    Jie Song, Zhe Li, Pengfei Wang, Travis Meyer, Chengde Mao, Yonggang Ke

    Information relay at the molecular level is an essential phenomenon in numerous chemical and biological processes, such as intricate signaling cascades. One key challenge in synthetic molecular self-assembly is to construct artificial structures that imitate these complex behaviors in controllable systems. We demonstrated prescribed, long-range information relay in an artificial molecular array assembled from modular DNA structural units. The dynamic DNA molecular array exhibits transformations with programmable initiation, propagation, and regulation. The transformation of the array can be initiated at selected units and then propagated, without addition of extra triggers, to neighboring units and eventually the entire array. The specific information pathways by which this transformation occurs can be controlled by altering the design of individual units and the arrays.

    更新日期:2017-07-11
  • Atomic-layered Au clusters on α-MoC as catalysts for the low-temperature water-gas shift reaction
    Science (IF 37.205) Pub Date : 2017-06-22
    Siyu Yao, Xiao Zhang, Wu Zhou, Rui Gao, Wenqian Xu, Yifan Ye, Lili Lin, Xiaodong Wen, Ping Liu, Bingbing Chen, Ethan Crumlin, Jinghua Guo, Zhijun Zuo, Weizhen Li, Jinglin Xie, Li Lu, Christopher J. Kiely, Lin Gu, Chuan Shi, José A. Rodriguez, Ding Ma

    The water-gas shift (WGS) reaction (CO+H2O=H2+CO2) is an essential process for hydrogen generation and CO removal in various energy-related chemical operations. This equilibrium-limited reaction is favored at a low working temperature. Potential application in fuel cells also requires a WGS catalyst to be highly active, stable and energy-efficient and match the working temperature of on-site hydrogen generation and consumption units. We synthesized Au layered clusters on an α-MoC substrate to create an interfacial catalyst system for the ultra-low-temperature WGS reaction. Water was activated over α-MoC at 303 Kelvin (K), while CO adsorbed on adjacent Au sites is apt to react with surface hydroxyl groups formed from water splitting, leading to a high WGS activity at low-temperatures.

    更新日期:2017-07-11
  • Photoinduced decarboxylative borylation of carboxylic acids
    Science (IF 37.205) Pub Date : 2017-06-15
    Alexander Fawcett, Johan Pradeilles, Yahui Wang, Tatsuya Mutsuga, Eddie L. Myers, Varinder K. Aggarwal

    The conversion of widely available carboxylic acids into versatile boronic esters would be highly enabling for synthesis. Here we report that this transformation can be effected by illuminating theN-hydroxyphthalimide ester derivative of the carboxylic acid under visible light at room temperature in the presence of the diboron reagent, bis(catecholato)diboron. A simple workup allows isolation of the pinacol boronic ester. Experimental evidence suggests that boryl radical intermediates are involved in the process. The methodology is illustrated by the transformation of not just primary, secondary, and tertiary alkyl carboxylic acids but also a diverse range of natural product carboxylic acids, thereby demonstrating its broad utility and functional-group tolerance.

    更新日期:2017-07-11
  • Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104
    Science (IF 37.205) Pub Date : 2017-06-15
    Stephanie N. Gates, Adam L. Yokom, JiaBei Lin, Meredith E. Jackrel, Alexandrea N. Rizo, Nathan M. Kendsersky, Courtney E. Buell, Elizabeth A. Sweeny, Korrie L. Mack, Edward Chuang, Mariana P. Torrente, Min Su, James Shorter, Daniel R. Southworth

    Hsp100 polypeptide translocases are conserved AAA+ machines that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase fromS. cerevisiaesolubilizes stress-induced amorphous aggregates and amyloid. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo-EM structures at near-atomic resolution of Hsp104 in different translocation states. Substrate interactions are mediated by conserved, pore-loop tyrosines that contact an 80 Å-long unfolded polypeptide along the axial channel. Two protomers undergo a ratchet-like conformational change that advances pore-loop-substrate interactions by two-amino acids. These changes are coupled to activation of specific ATPase sites and, when transmitted around the hexamer, reveal a processive rotary translocation mechanism and a remarkable flexibility in Hsp104-catalyzed disaggregation.

    更新日期:2017-07-11
  • Guanine glycation repair by DJ-1/Park7 and its bacterial homologs
    Science (IF 37.205) Pub Date : 2017-06-08
    Gilbert Richarme, Cailing Liu, Mouadh Mihoub, Jad Abdallah, Thibaut Leger, Nicolas Joly, Jean-Claude Liebart, Ula V. Jurkunas, Marc Nadal, Philippe Bouloc, Julien Dairou, Aazdine Lamouri

    DNA damage induced by reactive carbonyls (mainly methylglyoxal and glyoxal), called DNA glycation, is quantitatively as important as oxidative damage. DNA glycation is associated with increased mutation frequency, DNA strand breaks, and cytotoxicity. However, in contrast to guanine oxidation repair, how glycated DNA is repaired remains undetermined. Here, we found that the parkinsonism-associated protein DJ-1 and its bacterial homologs Hsp31, YhbO and YajL could repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids. DJ-1-depleted cells displayed increased levels of glycated DNA, DNA strand breaks, and phosphorylated p53. Deglycase-deficient bacterial mutants displayed increased levels of glycated DNA and RNA, and exhibited strong mutator phenotypes. Thus, DJ-1 and its prokaryotic homologs constitute a major nucleotide repair system that we name guanine glycation repair.

    更新日期:2017-07-11
  • Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade
    Science (IF 37.205) Pub Date : 2017-06-08
    Dung T. Le, Jennifer N. Durham, Kellie N. Smith, Hao Wang, Bjarne R. Bartlett, Laveet K. Aulakh, Steve Lu, Holly Kemberling, Cara Wilt, Brandon S. Luber, Fay Wong, Nilofer S. Azad, Agnieszka A. Rucki, Dan Laheru, Ross Donehower, Atif Zaheer, George A. Fisher, Todd S. Crocenzi, James J. Lee, Tim F. Greten, Austin G. Duffy, Kristen K. Ciombor, Aleksandra D. Eyring, Bao H. Lam, Andrew Joe, S. Peter Kang, Matthias Holdhoff, Ludmila Danilova, Leslie Cope, Christian Meyer, Shibin Zhou, Richard M. Goldberg, Deborah K. Armstrong, Katherine M. Bever, Amanda N. Fader, Janis Taube, Franck Housseau, David Spetzler, Nianqing Xiao, Drew M. Pardoll, Nickolas Papadopoulos, Kenneth W. Kinzler, James R. Eshleman, Bert Vogelstein, Robert A. Anders, Luis A. Diaz

    The genomes of cancers deficient in mismatch repair (MMR) contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with MMR deficiency were sensitive to immune checkpoint blockade with anti-PD-1 antibodies. We have expanded this study to now evaluate efficacy of PD-1 blockade in patients with advanced MMR-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients and complete responses were achieved in 21% of patients. Responses were durable with median progression-free and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in MMR-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers’ tissue of origin.

    更新日期:2017-07-11
  • Tuning quantum nonlocal effects in graphene plasmonics
    Science (IF 37.205) Pub Date : 2017-06-08
    Mark B. Lundeberg, Yuanda Gao, Reza Asgari, Cheng Tan, Ben Van Duppen, Marta Autore, Pablo Alonso-González, Achim Woessner, Kenji Watanabe, Takashi Taniguchi, Rainer Hillenbrand, James Hone, Marco Polini, Frank H. L. Koppens

    The response of electron systems to electrodynamic fields that change rapidly in space is endowed by unique features, including an exquisite spatial nonlocality. This can reveal much about the materials’ electronic structure that is invisible in standard probes that use gradually varying fields. Here, we use graphene plasmons, propagating at extremely slow velocities close to the electron Fermi velocity, to probe the nonlocal response of the graphene electron liquid. The near-field imaging experiments reveal a parameter-free match with the full quantum description of the massless Dirac electron gas, which involves three types of nonlocal quantum effects: single-particle velocity matching, interaction-enhanced Fermi velocity, and interaction-reduced compressibility. Our experimental approach can determine the full spatiotemporal response of an electron system.

    更新日期:2017-07-11
  • The scientists' apprentice
    Science (IF 37.205) Pub Date : 2017-07-07
    Tim Appenzeller

    Big data has met its match. In field after field, the ability to collect data has exploded, overwhelming human insight and analysis. But the computing advances that helped deliver the data have also conjured powerful new tools for making sense of it all. In a revolution that extends across much of science, researchers are unleashing artificial intelligence (AI), often in the form of artificial neural networks, on these mountains of data. Unlike earlier attempts at AI, such “deep learning” systems don’t need to be programmed with a human expert’s knowledge. Instead, they learn on their own, often from large training data sets, until they can see patterns and spot anomalies in data sets far larger and messier than human beings can cope with.

    更新日期:2017-07-11
  • The cyberscientist
    Science (IF 37.205) Pub Date : 2017-07-07
    John Bohannon

    A California biotech called Zymergen is one of several efforts to augment—or even replace—the role of humans in the scientific process. Zymergen tunes up industrial microbes that produce ingredients for biofuels, plastics, or drugs. Seeking to boost production, companies send their workhorse strains to Zymergen. The robots then explore and tinker with each microbe's genome in a bid to engineer a version that makes its product compound more efficiently. AI controls the process: interpreting data, generating hypotheses, and planning experiments. The ultimate goal, says one official, is "to get rid of human intuition."

    更新日期:2017-07-11
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.
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