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  • In situ semi-quantitative assessment of single-cell viability by resonance Raman spectroscopy
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-20
    Zhu Mao, Zhuo Liu, Jin Yang, Xiao Xia Han, Bing Zhao, Chun Zhao

    Currently, studies are increasingly focusing on the cytotoxic effects of anticancer drugs. Such investigations urgently warrant the assessment of single-cell viability. Here, we developed a novel method for quantifying single-cell viability with high selectivity by resonance Raman scattering. We report on this powerful tool that will allow researchers to study cellular metabolism at the level of a single cell.

    更新日期:2018-04-20
  • Dynamics of the phospholipid shell of microbubbles: a fluorescence photoselection and spectral phasor approach
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-20
    Eli Slenders, Senne Seneca, Sumit Kumar Pramanik, Nick Smisdom, Peter Adriaensens, M. vandeVen, Anitha Ethirajan, Marcel Ameloot

    The lipid organization of microbubbles is important in many applications. By monitoring the photoselection and emission spectrum of the fluorescent probe Laurdan in perfluorobutane gas-filled DPPC microbubbles with a two-photon laser scanning microscope, we observed a transition to a more rigid lipid organization in 30 minutes to several hours.

    更新日期:2018-04-20
  • A reaction-based ratiometric fluorescent sensor for detection of Hg(II) ions both in cells and bacteria
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-20
    Xiao-Qi Yu, Sheng-Lin Pan, Kun Li, Ling-Ling Li, Meng-Yang Li, Lei Shi, Yanhong Liu

    A novel reaction-based fluorescent probe (ATC-Hg) was designed and synthesized via “covalent assembly” principle, which exhibtied excellent selectivity and high sensitivity for Hg2+ and CH3Hg+. Moreover, it is the first Hg(II) senstive fluorescent probe that has been succesfully applied in imaging in both cells and Escherichia coli.

    更新日期:2018-04-20
  • Site selectivity in the halogenation of titanium-functionalized polyoxovanadate-alkoxide clusters
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-20
    Lauren E VanGelder, Patrick L Forrestel, William W. Brennessel, Ellen Matson

    Herein, we report the synthesis and characterization of a di-titanium-functionalised polyoxovanadate-alkoxide cluster. The incorperation of a second heterometal within the cluster core results in striking differences in reactivity of the multimetallic complex. Chlorination of the metal-oxide cluster is reported, revealing the directing role of titanium in M-O bond cleavage.

    更新日期:2018-04-20
  • Electrophysiological measurements reveal that a succinyl linker enhances performance of the synthetic chloride channel SCMTR
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-13
    Farnaz Minooei, Michael D. Martin, J. R. Fried, J. Patrick Brian
    更新日期:2018-04-20
  • 更新日期:2018-04-20
  • Well defined difluorogold(III) complexes supported by N-ligands
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-12
    Mohammad Albayer, Robert Corbo, Jason L. Dutton
    更新日期:2018-04-20
  • Decorating an individual living cell with a shell of controllable thickness by cytocompatible surface initiated graft polymerization
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-12
    Guan Wang, Kai Zhang, Yindian Wang, Changwen Zhao, Bin He, Yuhong Ma, Wantai Yang
    更新日期:2018-04-20
  • A photoactive semisynthetic metalloenzyme exhibits complete selectivity for CO2 reduction in water
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-10
    Camille R. Schneider, Anastasia C. Manesis, Michael J. Stevenson, Hannah S. Shafaat
    更新日期:2018-04-20
  • Zinc-ion-mediated self-assembly of forky peptides for prostate cancer-specific drug delivery
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-10
    Mingtao Tao, Keming Xu, Suyun He, Hongmei Li, Li Zhang, Xuefang Luo, Wenying Zhong
    更新日期:2018-04-20
  • Chiral separation and characterization of triazatruxene-based face-rotating polyhedra: the role of non-covalent facial interactions
    Chem. Commun. (IF 6.319) Pub Date : 2018-04-09
    Pei Zhang, Xinchang Wang, Wei Xuan, Pixian Peng, Zhihao Li, Ruqiang Lu, Shuang Wu, Zhongqun Tian, Xiaoyu Cao
    更新日期:2018-04-20
  • Emergence of Uranium as a Distinct Metal Center for Building Intrinsic X‐ray Scintillators
    Angew. Chem. Int. Ed. (IF 11.994) Pub Date : 2018-04-20
    Yaxing Wang; Xuemiao Yin; Wei Liu; Jian Xie; Junfeng Chen; Mark A. Silver; Daopeng Sheng; Lanhua Chen; Juan Diwu; Ning Liu; Zhifang Chai; Thomas E. Albrecht‐Schmitt; Shuao Wang
    更新日期:2018-04-20
  • 更新日期:2018-04-20
  • A Dynamic Chemical Network for Cystinuria Diagnosis
    Angew. Chem. Int. Ed. (IF 11.994) Pub Date : 2018-04-20
    Maria Lafuente; Jordi Solà; Ignacio Alfonso
    更新日期:2018-04-20
  • Electrochemical Aziridination by Alkene Activation Using a Sulfamate as the Nitrogen Source
    Angew. Chem. Int. Ed. (IF 11.994) Pub Date : 2018-04-20
    Jin Li; Wenhao Huang; Jingzhi Chen; Lingfeng He; Xu Cheng; Guigen Li
    更新日期:2018-04-20
  • Employing an Unsaturated Th4+ Site in a Porous Thorium–Organic Framework for Kr/Xe Uptake and Separation
    Angew. Chem. Int. Ed. (IF 11.994) Pub Date : 2018-04-20
    Yanlong Wang; Wei Liu; Zhuanling Bai; Tao Zheng; Mark A. Silver; Yuxiang Li; Yaxing Wang; Xia Wang; Juan Diwu; Zhifang Chai; Shuao Wang
    更新日期:2018-04-20
  • Reversible disassembly of metallasupramolecular structures mediated by a metastable-state photoacid
    Chem. Sci. (IF 8.668) Pub Date : 2018-04-20
    Suzanne M. Jansze, Giacomo Cecot, Kay Severin
    更新日期:2018-04-20
  • Catalytic Reduction of Molecular Dinitrogen to Ammonia and Hydrazine Using Vanadium Complexes
    Angew. Chem. Int. Ed. (IF 11.994) Pub Date : 2018-04-20
    Yoshiya Sekiguchi; Kazuya Arashiba; Hiromasa Tanaka; Aya Eizawa; Kazunari Nakajima; Kazunari Yoshizawa; Yoshiaki Nishibayashi
    更新日期:2018-04-20
  • Asymmetric Synthesis of Multiple Quaternary Stereocentre Containing Cyclopentyls by Oxazolidinone-Promoted Nazarov Cyclizations
    Chem. Sci. (IF 8.668) Pub Date : 2018-04-20
    Rohan Volpe, Romain Lepage, Jonathan White, Elizabeth Krenske, Bernard L. Flynn

    Carbometalation of oxazolidinone(Ox)-substituted ynamides is used to generate highly substituted Ox-divinyl (and aryl vinyl) ketones for use in Nazarov cyclizations. The Ox-group serves as a remarkably effective chiral activating group, enabling the torquoselective Nazarov cyclization of these sterically congested substrates to be performed under mild conditions. It also serves as charge-stabilizing group in the intermediate oxyallyl cation, supressing undesired [1,2]-sigmatropic shifts of neighboring substituents and facilitating the regio- and stereoselective incorporation of nucleophiles to yield cyclopentanoids containing up to three contiguous all-carbon quaternary (4°) stereocentres.

    更新日期:2018-04-20
  • 更新日期:2018-04-20
  • C4-H Indole Functionalisation: Precedent and Prospects
    Chem. Sci. (IF 8.668) Pub Date : 2018-04-20
    Jagadeesh Kalepu, Gandeepan Parthasarathy, Lutz Ackermann, Lukasz Pilarski

    C4-decorated indoles feature in a plethora of bioactive and functional compounds of importance to natural product synthesis, material sciences, as well as crop protection and pharmaceutical industries. Traditionally, their syntheses largely involved harsh stoichiometric metalations and radical reactions. However, transition metal catalysed C‒H activation has recently evolved into a powerful strategy for the late-stage diversification of indoles at the C4‒H position. Modern photoredox, enzymatic and precious transition metal catalysis represent the key stimuli for developing challenging C‒C and C‒Het bond forming transformations under mild reaction conditions. Herein, we discuss the evolution and application of these methods for the step-economical transformations of otherwise inert C4‒H bonds up to December 2017.

    更新日期:2018-04-20
  • Enantioselective Direct Mannich-Type Reactions of 2-Benzylpyridine N-Oxides Catalyzed by Chiral Bis(guanidino)iminophosphorane Organosuperbase
    Chem. Sci. (IF 8.668) Pub Date : 2018-04-20
    Qiupeng Hu, Azusa Kondoh, Masahiro Terada

    2-Benzylpyridine N-oxides possessing less acidic α-protons were utilized as pronucleophiles for the first time in enantioselective addition reactions under Brønsted base catalysis. A chiral bis(guanidino)iminophosphorane was able to overcome the inherent issue of low acidity of the pronucleophiles, establishing the diastereo- and enantioselective direct Mannich-type reaction with N-Boc imines. The control experiments indicated that the N-oxide moiety of the substrates played a critical role in achieving the high stereoselectivity.

    更新日期:2018-04-20
  • Catalytic Enantioselective 1,3‐Alkyl Shift in Alkyl Aryl Ethers: Efficient Synthesis of Optically Active 3,3′‐Diaryloxindoles
    Angew. Chem. Int. Ed. (IF 11.994) Pub Date : 2018-04-20
    Amol B. Gade; Pradip N. Bagle; Popat S. Shinde; Vipin Bhardwaj; Subhrashis Banerjee; Ajit Chande; Nitin T. Patil
    更新日期:2018-04-20
  • Reductive Coupling of Benzyl Oxalates with Highly Functionalized Alkyl Bromides by Nickel Catalysis
    Chem. Sci. (IF 8.668) Pub Date : 2018-04-20
    Xiao-Biao Yan, Chun-Ling Li, Wen-Jie Jin, Peng Guo, Xing-Zhong Shu

    Coupling reactions involving non-sulfonated C–O electrophiles provide a promising method for forming C–C bonds, but the incorporation of functionalized or secondary alkyl groups remains a challenge due to the requirement for well-defined alkylmetal species. In this study, we report a reductive nickel-catalyzed cross-coupling of benzyl oxalates with alkyl bromides, using oxalate as a new leaving group. A broad range of highly functionalized alkyl units (such as functional groups: alkyl chloride, alcohol, aldehyde, amine, amide, boronate ester, ether, ester, heterocycle, phosphonate, strained ring) were efficiently incorporated at the benzylic position. The utility of this synthetic method was further demonstrated by late-stage modification of complex bioactive compounds. Preliminary mechanistic experiments revealed that a radical process might be involved in the reaction.

    更新日期:2018-04-20
  • Molecular species forming at the α-Fe2O3 Nanoparticle – Aqueous Solution Interface
    Chem. Sci. (IF 8.668) Pub Date : 2018-04-20
    Hebatallah Ali, Robert Seidel, Marvin Pohl, Bernd Winter

    We report on electronic structure measurements of the interface between hematite nanoparticles (6 nm diameter) and aqueous solutions. Using soft X-ray photoelectron spectroscopy from a liquid microjet we detect valence and core-level photoelectrons as well as Auger-electrons from liquid water, from the nanoparticle – water interface, and from the interior of the aqueous-phase nanoparticles. Most noteworthy, the method is shown to be sufficiently sensitive for the detection of adsorbed hydroxyl species, resulting from H2O dissociation at the nanoparticle surface in aqueous solution. We obtain signal from surface OH from resonant, non-resonant, and from so-called partial-electron-yield X-ray absorption (PEY-XA) spectra. In addition, we report resonant photoelectron measurements at the iron 2p excitation. The respective Fe iron 2p3/2 edge (L3-edge) PEY-XA spectra exhibit two main absorption peaks with their energies being sensitive to the chemical environment of the Fe3+ ions at the nanoparticle–solution interface. This manifests in the 10Dq value which is a measure of the ligand-field strength. Furthermore, an observed intensity variation of the pre-peak, when comparing the PEY-XA spectra for different iron Auger-decay channels, can be assigned to different extents of electron delocalization. From the experimental fraction of local versus non-local autoionization signals we then find a very fast, approximately 1 fs, charge transfer time from interfacial Fe3+ into the environment. The present study, which is complementary to ambient-pressure photoemission studies on solid – electrolyte systems, also highlights the multiple aspects of photoemission that need to be explored for a full characterization of the transition-metal-oxide nanoparticle surface in aqueous phase.

    更新日期:2018-04-20
  • Multistate Photoswitches: Macrocyclic Dihydroazulene/Azobenzene Conjugates
    Angew. Chem. Int. Ed. (IF 11.994) Pub Date : 2018-04-20
    Alexandru Vlasceanu; Mads Koerstz; Anders B. Skov; Kurt V. Mikkelsen; Mogens Brøndsted Nielsen
    更新日期:2018-04-20
  • Diastereoisomers of L-proline-linked trityl-nitroxide biradicals: synthesis and effect of chiral configurations on exchange interactions
    Chem. Sci. (IF 8.668) Pub Date : 2018-04-05
    Weixiang Zhai, Yalan Feng, Huiqiang Liu, Antal Rockenbauer, Deni Mance, Shaoyong Li, Yuguang Song, Marc Baldus, Yangping Liu
    更新日期:2018-04-20
  • Biases in forensic experts
    Science (IF 37.205) Pub Date : 2018-04-20
    Itiel E. Dror

    Forensic evidence plays a critical role in court proceedings and the administration of justice. It is a powerful tool that can help convict the guilty and avoid wrongful conviction of the innocent. Unfortunately, flaws in forensic evidence are increasingly becoming apparent. Assessments of forensic science have too often focused only on the data and the underlying science, as if they exist in isolation, without sufficiently addressing the process by which forensic experts evaluate and interpret the evidence. After all, it is the forensic expert who observes the data and makes interpretations, and therefore forensic evidence is mediated by human and cognitive factors. A U.S. National Research Council examination of forensic science in 2009, followed by a 2016 evaluation by a presidential panel, along with a U.K. inquiry into fingerprinting in 2011 and a 2015 guidance by the U.K. Forensic Science Regulator, have all expressed concerns about biases in forensic expert decision-making. Where does forensic bias come from, and how can we minimize it?

    更新日期:2018-04-20
  • News at a glance
    Science (IF 37.205) Pub Date : 2018-04-20
    American Association for the Advancement of Science

    In science news around the world, the second annual March for Science features rallies in cities around the world to support the use of scientific analysis and evidence in public policy. The U.S. National Institutes of Health (NIH) in Bethesda, Maryland, broadens the scope of its investigation into ties between the alcohol industry and NIH's alcoholism institute to include funding decisions by the institute's director. Members of the United Nations's International Maritime Organization in London agree to cut greenhouse gas emissions from international shipping to 50% of 2008 levels by 2050. The U.S. National Science Foundation awards its prestigious prize for young scientists to Kristina Olson of the University of Washington in Seattle, the first psychologist ever to receive it and the first woman so honored since 2004. The U.S. Food and Drug Administration announces the first approval of artificial intelligence–based disease screening software that doesn't need a clinician to interpret the results—a computer program that analyzes digital images of a patient's retina to detect diabetic retinopathy, a common complication of diabetes that causes blindness.

    更新日期:2018-04-20
  • NASA lander to probe interior of Mars
    Science (IF 37.205) Pub Date : 2018-04-20
    Paul Voosen

    Next month, NASA will launch the $814 million InSight lander to Mars, meant to peer inside the planet's interior. InSight, which lands in late November, sports three instruments, including a seismometer that will detect "marsquakes." It marks a return to planetary seismology after 4 decades. By capturing quakes caused by the contraction of the planet's crust, and hammering a heat probe down 5 meters below the surface, InSight should allow scientists to measure the thickness and composition of the planet's crust, mantle, and core. Knowing those dimensions should reveal how the planet formed and how it lost its magnetic field, constraining a zoo of potential models.

    更新日期:2018-04-20
  • Department of State's air pollution sensors go global
    Science (IF 37.205) Pub Date : 2018-04-20
    Eli Kintisch

    In October 2010, as heavy smog hung over Beijing, the U.S. embassy's Twitter feed reported that its rooftop air pollution sensor had detected "crazy bad" levels of hazardous microparticles. Fine particulate matter had shot up to about 550 micrograms per cubic meter—a level to which programmers had given the sardonic label because they thought it would never be reached. The undiplomatic language ruffled feathers in Beijing. Yet the incident and others like it spurred public complaints that eventually elicited more aggressive efforts to tame the pollution. By now, rooftop sensors like those that drew attention to Beijing's pollution sprout from 26 diplomatic posts in 16 countries. Their immediate goal is to protect the health of U.S. citizens. But they are raising concerns about air pollution from Sarajevo to New Delhi and supplying data to research efforts.

    更新日期:2018-04-20
  • Cannabis, opium use part of ancient Near Eastern cultures
    Science (IF 37.205) Pub Date : 2018-04-20
    Andrew Lawler

    For as long as there has been civilization, there have been mind-altering drugs. Alcohol has been around for at least 10,000 years, but recent advances in chemical analysis of old pots reveal that other psychoactive drugs were present at the dawn of the first complex societies some 5000 years ago in the ancient Middle East. Ancient people from Turkey to Egypt experimented with local substances such as blue water lily, while imports like cannabis and opium made from poppies spread through early international trade networks. Armed with the new data, archaeologists are probing just how these drugs impacted early societies and beliefs. Some argue that the impact of these psychoactive substances has been underestimated, and that a drug culture was central to ritual in Mesopotamia, Anatolia, Egypt, and the Levant.

    更新日期:2018-04-20
  • Plan for 2020 U.S. census is fatally flawed, critics say
    Science (IF 37.205) Pub Date : 2018-04-20
    Jeffrey Mervis

    A plan by U.S. Commerce Secretary Wilbur Ross to ensure a "complete and accurate" 2020 census is seriously flawed, say former agency officials and other experts in survey research. The problem lies not simply with Ross's controversial, eleventh-hour decision last month to add a citizenship question to the decennial census, although civil rights groups, local and state governments, and business leaders believe the question will depress participation and jeopardize an accurate head count in 2020. Ross has also ordered the Census Bureau to expand its use of administrative records, the massive amount of information that other government agencies already possess on U.S. residents. The two-pronged strategy, Ross wrote in a 26 March memo explaining his decision, will "maximize" the bureau's ability to carry out its constitutionally mandated requirement to conduct an accurate head count. But social scientists say that's a mission impossible, at least in the 2 years before Census Day.

    更新日期:2018-04-20
  • Ancient DNA untangles South Asian roots
    Science (IF 37.205) Pub Date : 2018-04-20
    Lizzie Wade

    Today, the population of South Asia is divided into dozens of ethnic, linguistic, and religious groups that live side by side—but not always in harmony. A contentious border separates India and Pakistan; political movements draw stark lines between India's Muslim and Hindu populations. Groups don't mix much, as people tend to marry those who share their ethnicity and tongue. Now, a study of the first ancient DNA recovered from South Asia shows that populations there mingled repeatedly thousands of years ago. Nearly all of the Indian subcontinent's ethnic and linguistic groups are the product of three ancient Eurasian populations who met and mixed: local hunter-gatherers, Middle Eastern farmers, and Central Asian herders. Three similar groups also mingled in ancient Europe, giving the two subcontinents surprisingly parallel histories. The study also strengthens the claim that Proto-Indo-European—the ancestral language that gave rise to languages from English to Russian to Hindi—originated on the steppes of Asia.

    更新日期:2018-04-20
  • Proposal to rescue postdocs from limbo draws darts
    Science (IF 37.205) Pub Date : 2018-04-20
    Michael Price

    An expert panel has offered some new solutions to an old problem in U.S. biomedical research: too many young scientists vying for scarce academic research jobs and stable funding. Although many of its recommendations echo past proposals that have largely failed to gain traction, a few—including one to limit postdoctoral researchers to receiving just 3 years of funding from their principal investigators (PIs), and another to create a new federal oversight council—are catalyzing heated debate. The problem with current funding practices, the panel says, is that they encourage some PIs to view postdocs primarily as labor and provide little career mentoring. As a result, postdocs can linger in relatively poorly paid positions for years. But the proposed 3-year postdoc cap has drawn fierce opposition, which some researchers worry could prematurely end careers.

    更新日期:2018-04-20
  • Omen in the blood
    Science (IF 37.205) Pub Date : 2018-04-20
    Stephen S. Hall

    In an elegant but still unfolding story of molecular detective work, researchers hunting for a cause of chronic kidney disease have homed in on a protein known as soluble urokinase plasminogen activator receptor (suPAR). Historically, the leading risk factors for the disease have been high blood pressure, diabetes, and certain mutations that are more common in African-Americans. But recent findings have convinced some researchers that suPAR can directly attack the kidney, and that high levels increase risk far more than any other factor. Others aren't convinced. But people on both sides are fascinated by suPAR, a molecular marker that, at elevated levels in the blood, seems to presage many health calamities, such as heart attacks, diabetes, and premature death. The molecule appears to be a potent signal broadcast by an immune system under siege. It is exquisitely sensitive to inflammation, an accelerant for many diseases.

    更新日期:2018-04-20
  • Risk-based reboot for global lab biosafety
    Science (IF 37.205) Pub Date : 2018-04-20
    Kazunobu Kojima, Catherine Makison Booth, Kathrin Summermatter, Allan Bennett, Marianne Heisz, Stuart D. Blacksell, Michelle McKinney

    Laboratory biosafety is fundamental to controlling exposure to pathogens, protecting the laboratory workforce and the wider community against inadvertent exposures or releases. Since 1983, the World Health Organization (WHO) Laboratory Biosafety Manual (LBM) has encouraged countries to implement basic concepts in biological safety and to develop national codes of practice for the safe handling of pathogenic microorganisms in laboratories. But as technologies continue to evolve, and with them potential threats and benefits to laboratory safety, so too must approaches to biosafety. With revision toward the fourth edition of the LBM under way, we propose a shift in focus to a risk-based, technology-neutral, and cost-effective approach to biosafety, making sure that laboratory facilities, safety equipment, and work practices are locally relevant, proportionate, and sustainable. This will allow more flexibility in laboratory design, reduce focus on pathogen risk groups and biosafety levels as the de facto starting point of laboratory considerations, and place more emphasis on human factors and worker training. Improved sustainability of laboratory operations through lower construction and operating costs, particularly in resource-limited settings, may pave the way for equitable access to clinical and public health laboratory tests and biomedical research opportunities, without compromising safety.

    更新日期:2018-04-20
  • Plant responses to CO2 are a question of time
    Science (IF 37.205) Pub Date : 2018-04-20
    Mark Hovenden, Paul Newton

    Rising carbon dioxide (CO2) concentrations in the atmosphere as a result of fossil fuel burning are expected to fertilize plants, resulting in faster growth. However, this change is not expected to be the same for all plants. Rather, scientists believe that differences in photosynthetic mechanism favor one plant group—the C3 plants—over the other, the C4 plants. On page 317 of this issue, Reich et al. (1) show that, although this expectation is met in the first few years of a long-term experiment, the situation reverses after 15 to 20 years, with important implications for future crop production and ecosystems.

    更新日期:2018-04-20
  • On the quest for the strongest materials
    Science (IF 37.205) Pub Date : 2018-04-20
    Javier LLorca

    The strength of a material is a measure of its ability to withstand a load without breaking. Scientists in search of the strongest materials have recently turned their attention to nanomaterials, which have few of the defects that typically reduce a material's strength. On page 300 of this issue, Banerjee et al. (1) show that when nanoscale single-crystal diamond needles are elastically deformed, they fail at a maximum local tensile stress of ∼89 to 98 GPa, which is very close to the theoretical limit for this material.

    更新日期:2018-04-20
  • Whispering neurons fuel cortical highways
    Science (IF 37.205) Pub Date : 2018-04-20
    Alejandro F. Schinder, Guillermo M. Lanuza

    The mammalian neocortex is one of the most intricate entities found in nature, both in terms of structure and function. It is the brain region responsible for the execution of high-order functions, including sensory perception, motor control, cognition, and speech. Its development is equally complex because it requires that millions to billions (depending on the species) of neurons assemble in distinct layers and connect with exquisite precision to perform complicated information processing operations. During embryonic development, formation of the cerebral cortex involves the migration of excitatory neurons generated in the ventricular zone toward the cortical plate, where they establish their final position in six well-defined horizontal layers consisting of different types of neurons and architecture. Along this migratory phase, developing neurons undergo a morphological transition from multipolar shape to bipolar morphology. Bipolar neurons exhibit faster locomotion, quickly reaching their final destination. On page 313 of this issue, Ohtaka-Maruyama et al. (1) reveal that this important switch to bipolar neurons is influenced by glutamate release from neurons located at the subplate, just beneath the cortical plate. Subplate neurons trigger this transformation by making transient synaptic contacts with multipolar neurons in transit to the cortical laminae. Understanding this process is important because disruption of neocortical migration results in several human neuro-developmental diseases.

    更新日期:2018-04-20
  • Parkin function in Parkinson's disease
    Science (IF 37.205) Pub Date : 2018-04-20
    Connor Arkinson, Helen Walden

    Parkinson's disease (PD) is the second most common neurodegenerative disease, and is characterized by involuntary shaking, muscle rigidity, and the progressive loss of dopaminergic neurons. In ∼5 to 10% of PD cases there is a genetic association, with almost 20 genes attributed to date. One example is early-onset autosomal recessive PD (ARPD), for which the majority of cases are linked to mutations in the Parkin gene (PRKN; also known as PARK2). PRKN encodes the E3 ubiquitin ligase Parkin, which plays important roles in mitochondrial quality control and turnover. Parkin, although localized to the mitochondria under certain conditions, is primarily cytosolic (1). A second ARPD-associated gene, PINK1 (PTEN-induced putative kinase 1), encodes a mitochondrially tethered kinase that regulates Parkin activity through phosphorylation events. Mutations in PINK1, although rare, are associated with a phenotype similar to that of ARPD patients with PRKN mutations. Numerous mutations throughout PRKN are linked to ARPD, making the functional examination of Parkin crucial to understanding ARPD pathogenesis. A wealth of structural studies have transformed our knowledge of Parkin regulation and catalytic mechanisms. However, the current picture is incomplete, leading to several possible models of Parkin catalysis, which has implications for understanding how the ARPD-associated mutations affect the protein and thus PD pathogenesis.

    更新日期:2018-04-20
  • If two deletions don't stop growth, try three
    Science (IF 37.205) Pub Date : 2018-04-20
    Albertha J. M. Walhout

    How many and which genes does an organism need at a minimum to sustain growth? With the identification of essential genes in a variety of organisms such as yeast (1), worms (2), and human cultured cells (3–5), the answer may seem obvious: Remove all nonessential genes, and the organism should be able to continue to survive and grow. In the yeast Saccharomyces cerevisiae, the workhorse of genetic interaction mapping, ∼1000 of the ∼6000 (∼17%) protein-coding genes are essential for viability (1). So theoretically, one might think that one could remove the other ∼5000 nonessential genes and still have a growing yeast. The reason this does not work is that genes interact with each other to drive different traits, including viability and growth. On page 283 of this issue, Kuzmin et al. (6) provide the first systematic analysis of trigenic interactions in yeast in which three gene deletions are combined in individual strains in order to ascertain the importance of multigene interactions for growth. This study shows that higher-order genetic interactions are abundant, which has implications for the interpretation of human gene variants that may interact to affect health and disease.

    更新日期:2018-04-20
  • A unifying concept in vascular health and disease
    Science (IF 37.205) Pub Date : 2018-04-20
    Martin A. Schwartz, Dietmar Vestweber, Michael Simons

    Not unlike Tolstoy's remark about happy versus unhappy families, current wisdom in vascular biology holds that healthy blood vessels are mostly similar, whereas vessels in different vascular diseases are mostly different. But is this really the case? An evaluation of the literature suggests that unresolved vascular remodeling may be a key element of virtually all vascular diseases. This commonality raises the possibility of unifying principles that govern vascular remodeling and the possibility that methods to restore normal remodeling could effectively treat multiple disease states.

    更新日期:2018-04-20
  • Reconsidering the Nobel Prize
    Science (IF 37.205) Pub Date : 2018-04-20
    Paul Halpern

    Losing the Nobel Prize, by astrophysicist Brian Keating, offers a riveting account of the rise and fall of the seeming confirmation of the cosmological theory of inflation. Occluding Keating's account, however, are his personal beefs about "losing" the Nobel Prize. Such gripes taint Keating's otherwise thoughtful analysis of ways the Nobel committee's selection process could be improved.

    更新日期:2018-04-20
  • Wielding new genomic tools wisely
    Science (IF 37.205) Pub Date : 2018-04-20
    María C. Ávila Arcos

    In Who We Are and How We Got Here, David Reich gracefully describes how recent advances in genomics have enabled the study of ancient genomes and how this, in turn, has significantly affected the study of the evolutionary and demographic history of our species. Although scientifically solid and comprehensive, the book overlooks some of the most profound issues inherent in this type of work, specifically with regard to the practices surrounding the collection and processing of human DNA samples.

    更新日期:2018-04-20
  • Multidimensional quantum entanglement with large-scale integrated optics
    Science (IF 37.205) Pub Date : 2018-04-20
    Jianwei Wang, Stefano Paesani, Yunhong Ding, Raffaele Santagati, Paul Skrzypczyk, Alexia Salavrakos, Jordi Tura, Remigiusz Augusiak, Laura Mančinska, Davide Bacco, Damien Bonneau, Joshua W. Silverstone, Qihuang Gong, Antonio Acín, Karsten Rottwitt, Leif K. Oxenløwe, Jeremy L. O’Brien, Anthony Laing, Mark G. Thompson

    The ability to control multidimensional quantum systems is central to the development of advanced quantum technologies. We demonstrate a multidimensional integrated quantum photonic platform able to generate, control, and analyze high-dimensional entanglement. A programmable bipartite entangled system is realized with dimensions up to 15 × 15 on a large-scale silicon photonics quantum circuit. The device integrates more than 550 photonic components on a single chip, including 16 identical photon-pair sources. We verify the high precision, generality, and controllability of our multidimensional technology, and further exploit these abilities to demonstrate previously unexplored quantum applications, such as quantum randomness expansion and self-testing on multidimensional states. Our work provides an experimental platform for the development of multidimensional quantum technologies.

    更新日期:2018-04-20
  • Probing the ultimate plasmon confinement limits with a van der Waals heterostructure
    Science (IF 37.205) Pub Date : 2018-04-20
    David Alcaraz Iranzo, Sébastien Nanot, Eduardo J. C. Dias, Itai Epstein, Cheng Peng, Dmitri K. Efetov, Mark B. Lundeberg, Romain Parret, Johann Osmond, Jin-Yong Hong, Jing Kong, Dirk R. Englund, Nuno M. R. Peres, Frank H. L. Koppens

    The ability to confine light into tiny spatial dimensions is important for applications such as microscopy, sensing, and nanoscale lasers. Although plasmons offer an appealing avenue to confine light, Landau damping in metals imposes a trade-off between optical field confinement and losses. We show that a graphene-insulator-metal heterostructure can overcome that trade-off, and demonstrate plasmon confinement down to the ultimate limit of the length scale of one atom. This is achieved through far-field excitation of plasmon modes squeezed into an atomically thin hexagonal boron nitride dielectric spacer between graphene and metal rods. A theoretical model that takes into account the nonlocal optical response of both graphene and metal is used to describe the results. These ultraconfined plasmonic modes, addressed with far-field light excitation, enable a route to new regimes of ultrastrong light-matter interactions.

    更新日期:2018-04-20
  • Capillarity-induced folds fuel extreme shape changes in thin wicked membranes
    Science (IF 37.205) Pub Date : 2018-04-20
    Paul Grandgeorge, Natacha Krins, Aurélie Hourlier-Fargette, Christel Laberty-Robert, Sébastien Neukirch, Arnaud Antkowiak

    Soft deformable materials are needed for applications such as stretchable electronics, smart textiles, or soft biomedical devices. However, the design of a durable, cost-effective, or biologically compatible version of such a material remains challenging. Living animal cells routinely cope with extreme deformations by unfolding preformed membrane reservoirs available in the form of microvilli or membrane folds. We synthetically mimicked this behavior by creating nanofibrous liquid-infused tissues that spontaneously form similar reservoirs through capillarity-induced folding. By understanding the physics of membrane buckling within the liquid film, we developed proof-of-concept conformable chemical surface treatments and stretchable basic electronic circuits.

    更新日期:2018-04-20
  • Ultralarge elastic deformation of nanoscale diamond
    Science (IF 37.205) Pub Date : 2018-04-20
    Amit Banerjee, Daniel Bernoulli, Hongti Zhang, Muk-Fung Yuen, Jiabin Liu, Jichen Dong, Feng Ding, Jian Lu, Ming Dao, Wenjun Zhang, Yang Lu, Subra Suresh

    Diamonds have substantial hardness and durability, but attempting to deform diamonds usually results in brittle fracture. We demonstrate ultralarge, fully reversible elastic deformation of nanoscale (~300 nanometers) single-crystalline and polycrystalline diamond needles. For single-crystalline diamond, the maximum tensile strains (up to 9%) approached the theoretical elastic limit, and the corresponding maximum tensile stress reached ~89 to 98 gigapascals. After combining systematic computational simulations and characterization of pre- and postdeformation structural features, we ascribe the concurrent high strength and large elastic strain to the paucity of defects in the small-volume diamond nanoneedles and to the relatively smooth surfaces compared with those of microscale and larger specimens. The discovery offers the potential for new applications through optimized design of diamond nanostructure, geometry, elastic strains, and physical properties.

    更新日期:2018-04-20
  • Five-dimensional imaging of freezing emulsions with solute effects
    Science (IF 37.205) Pub Date : 2018-04-20
    Dmytro Dedovets, Cécile Monteux, Sylvain Deville

    The interaction of objects with a moving solidification front is a common feature of many industrial and natural processes such as metal processing, the growth of single crystals, the cryopreservation of cells, or the formation of sea ice. Interaction of solidification fronts with objects leads to different outcomes, from total rejection of the objects to their complete engulfment. We imaged the freezing of emulsions in five dimensions (space, time, and solute concentration) with confocal microscopy. We showed that the solute induces long-range interactions that determine the solidification microstructure. The local increase of solute concentration enhances premelting, which controls the engulfment of droplets by the front and the evolution of grain boundaries. Freezing emulsions may be a good analog of many solidification systems where objects interact with a solidification interface.

    更新日期:2018-04-20
  • Recurrences in an isolated quantum many-body system
    Science (IF 37.205) Pub Date : 2018-04-20
    Bernhard Rauer, Sebastian Erne, Thomas Schweigler, Federica Cataldini, Mohammadamin Tajik, Jörg Schmiedmayer

    The complexity of interacting quantum many-body systems leads to exceedingly long recurrence times of the initial quantum state for all but the smallest systems. For large systems, one cannot probe the full quantum state in all its details. Thus, experimentally, recurrences can only be determined on the level of the accessible observables. Realizing a commensurate spectrum of collective excitations in one-dimensional superfluids, we demonstrate recurrences of coherence and long-range order in an interacting quantum many-body system containing thousands of particles. Our findings will enable the study of the coherent dynamics of large quantum systems even after they have reached a transient thermal-like state.

    更新日期:2018-04-20
  • Body size downgrading of mammals over the late Quaternary
    Science (IF 37.205) Pub Date : 2018-04-20
    Felisa A. Smith, Rosemary E. Elliott Smith, S. Kathleen Lyons, Jonathan L. Payne

    Since the late Pleistocene, large-bodied mammals have been extirpated from much of Earth. Although all habitable continents once harbored giant mammals, the few remaining species are largely confined to Africa. This decline is coincident with the global expansion of hominins over the late Quaternary. Here, we quantify mammalian extinction selectivity, continental body size distributions, and taxonomic diversity over five time periods spanning the past 125,000 years and stretching approximately 200 years into the future. We demonstrate that size-selective extinction was already under way in the oldest interval and occurred on all continents, within all trophic modes, and across all time intervals. Moreover, the degree of selectivity was unprecedented in 65 million years of mammalian evolution. The distinctive selectivity signature implicates hominin activity as a primary driver of taxonomic losses and ecosystem homogenization. Because megafauna have a disproportionate influence on ecosystem structure and function, past and present body size downgrading is reshaping Earth’s biosphere.

    更新日期:2018-04-20
  • Synaptic transmission from subplate neurons controls radial migration of neocortical neurons
    Science (IF 37.205) Pub Date : 2018-04-20
    Chiaki Ohtaka-Maruyama, Mayumi Okamoto, Kentaro Endo, Minori Oshima, Noe Kaneko, Kei Yura, Haruo Okado, Takaki Miyata, Nobuaki Maeda

    The neocortex exhibits a six-layered structure that is formed by radial migration of excitatory neurons, for which the multipolar-to-bipolar transition of immature migrating multipolar neurons is required. Here, we report that subplate neurons, one of the first neuron types born in the neocortex, manage the multipolar-to-bipolar transition of migrating neurons. By histochemical, imaging, and microarray analyses on the mouse embryonic cortex, we found that subplate neurons extend neurites toward the ventricular side of the subplate and form transient glutamatergic synapses on the multipolar neurons just below the subplate. NMDAR (N-methyl-d-aspartate receptor)–mediated synaptic transmission from subplate neurons to multipolar neurons induces the multipolar-to-bipolar transition, leading to a change in migration mode from slow multipolar migration to faster radial glial-guided locomotion. Our data suggested that transient synapses formed on early immature neurons regulate radial migration.

    更新日期:2018-04-20
  • Unexpected reversal of C3 versus C4 grass response to elevated CO2 during a 20-year field experiment
    Science (IF 37.205) Pub Date : 2018-04-20
    Peter B. Reich, Sarah E. Hobbie, Tali D. Lee, Melissa A. Pastore

    Theory predicts and evidence shows that plant species that use the C4 photosynthetic pathway (C4 species) are less responsive to elevated carbon dioxide (eCO2) than species that use only the C3 pathway (C3 species). We document a reversal from this expected C3-C4 contrast. Over the first 12 years of a 20-year free-air CO2 enrichment experiment with 88 C3 or C4 grassland plots, we found that biomass was markedly enhanced at eCO2 relative to ambient CO2 in C3 but not C4 plots, as expected. During the subsequent 8 years, the pattern reversed: Biomass was markedly enhanced at eCO2 relative to ambient CO2 in C4 but not C3 plots. Soil net nitrogen mineralization rates, an index of soil nitrogen supply, exhibited a similar shift: eCO2 first enhanced but later depressed rates in C3 plots, with the opposite true in C4 plots, partially explaining the reversal of the eCO2 biomass response. These findings challenge the current C3-C4 eCO2 paradigm and show that even the best-supported short-term drivers of plant response to global change might not predict long-term results.

    更新日期:2018-04-20
  • Two-billion-year-old evaporites capture Earth’s great oxidation
    Science (IF 37.205) Pub Date : 2018-04-20
    C. L. Blättler, M. W. Claire, A. R. Prave, K. Kirsimäe, J. A. Higgins, P. V. Medvedev, A. E. Romashkin, D. V. Rychanchik, A. L. Zerkle, K. Paiste, T. Kreitsmann, I. L. Millar, J. A. Hayles, H. Bao, A. V. Turchyn, M. R. Warke, A. Lepland

    Major changes in atmospheric and ocean chemistry occurred in the Paleoproterozoic era (2.5 to 1.6 billion years ago). Increasing oxidation dramatically changed Earth’s surface, but few quantitative constraints exist on this important transition. This study describes the sedimentology, mineralogy, and geochemistry of a 2-billion-year-old, ~800-meter-thick evaporite succession from the Onega Basin in Russian Karelia. The deposit consists of a basal unit dominated by halite (~100 meters) followed by units dominated by anhydrite-magnesite (~500 meters) and dolomite-magnesite (~200 meters). The evaporite minerals robustly constrain marine sulfate concentrations to at least 10 millimoles per kilogram of water, representing an oxidant reservoir equivalent to more than 20% of the modern ocean-atmosphere oxidizing capacity. These results show that substantial amounts of surface oxidant accumulated during this critical transition in Earth’s oxygenation.

    更新日期:2018-04-20
  • Structure of a prehandover mammalian ribosomal SRP·SRP receptor targeting complex
    Science (IF 37.205) Pub Date : 2018-04-20
    Kan Kobayashi, Ahmad Jomaa, Jae Ho Lee, Sowmya Chandrasekar, Daniel Boehringer, Shu-ou Shan, Nenad Ban

    Signal recognition particle (SRP) targets proteins to the endoplasmic reticulum (ER). SRP recognizes the ribosome synthesizing a signal sequence and delivers it to the SRP receptor (SR) on the ER membrane followed by the transfer of the signal sequence to the translocon. Here, we present the cryo–electron microscopy structure of the mammalian translating ribosome in complex with SRP and SR in a conformation preceding signal sequence handover. The structure visualizes all eukaryotic-specific SRP and SR proteins and reveals their roles in stabilizing this conformation by forming a large protein assembly at the distal site of SRP RNA. We provide biochemical evidence that the guanosine triphosphate hydrolysis of SRP·SR is delayed at this stage, possibly to provide a time window for signal sequence handover to the translocon.

    更新日期:2018-04-20
  • Paternally inherited cis-regulatory structural variants are associated with autism
    Science (IF 37.205) Pub Date : 2018-04-20
    William M. Brandler, Danny Antaki, Madhusudan Gujral, Morgan L. Kleiber, Joe Whitney, Michelle S. Maile, Oanh Hong, Timothy R. Chapman, Shirley Tan, Prateek Tandon, Timothy Pang, Shih C. Tang, Keith K. Vaux, Yan Yang, Eoghan Harrington, Sissel Juul, Daniel J. Turner, Bhooma Thiruvahindrapuram, Gaganjot Kaur, Zhuozhi Wang, Stephen F. Kingsmore, Joseph G. Gleeson, Denis Bisson, Boyko Kakaradov, Amalio Telenti, J. Craig Venter, Roser Corominas, Claudio Toma, Bru Cormand, Isabel Rueda, Silvina Guijarro, Karen S. Messer, Caroline M. Nievergelt, Maria J. Arranz, Eric Courchesne, Karen Pierce, Alysson R. Muotri, Lilia M. Iakoucheva, Amaia Hervas, Stephen W. Scherer, Christina Corsello, Jonathan Sebat

    The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.

    更新日期:2018-04-20
  • Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq
    Science (IF 37.205) Pub Date : 2018-04-20
    Mariella G. Filbin, Itay Tirosh, Volker Hovestadt, McKenzie L. Shaw, Leah E. Escalante, Nathan D. Mathewson, Cyril Neftel, Nelli Frank, Kristine Pelton, Christine M. Hebert, Christine Haberler, Keren Yizhak, Johannes Gojo, Kristof Egervari, Christopher Mount, Peter van Galen, Dennis M. Bonal, Quang-De Nguyen, Alexander Beck, Claire Sinai, Thomas Czech, Christian Dorfer, Liliana Goumnerova, Cinzia Lavarino, Angel M. Carcaboso, Jaume Mora, Ravindra Mylvaganam, Christina C. Luo, Andreas Peyrl, Mara Popović, Amedeo Azizi, Tracy T. Batchelor, Matthew P. Frosch, Maria Martinez-Lage, Mark W. Kieran, Pratiti Bandopadhayay, Rameen Beroukhim, Gerhard Fritsch, Gad Getz, Orit Rozenblatt-Rosen, Kai W. Wucherpfennig, David N. Louis, Michelle Monje, Irene Slavc, Keith L. Ligon, Todd R. Golub, Aviv Regev, Bradley E. Bernstein, Mario L. Suvà

    Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models. We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.

    更新日期:2018-04-20
  • MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A
    Science (IF 37.205) Pub Date : 2018-04-20
    Agostinho G. Rocha, Antonietta Franco, Andrzej M. Krezel, Jeanne M. Rumsey, Justin M. Alberti, William C. Knight, Nikolaos Biris, Emmanouil Zacharioudakis, James W. Janetka, Robert H. Baloh, Richard N. Kitsis, Daria Mochly-Rosen, R. Reid Townsend, Evripidis Gavathiotis, Gerald W. Dorn

    Mitofusins (MFNs) promote fusion-mediated mitochondrial content exchange and subcellular trafficking. Mutations in Mfn2 cause neurodegenerative Charcot-Marie-Tooth disease type 2A (CMT2A). We showed that MFN2 activity can be determined by Met376 and His380 interactions with Asp725 and Leu727 and controlled by PINK1 kinase–mediated phosphorylation of adjacent MFN2 Ser378. Small-molecule mimics of the peptide-peptide interface of MFN2 disrupted this interaction, allosterically activating MFN2 and promoting mitochondrial fusion. These first-in-class mitofusin agonists overcame dominant mitochondrial defects provoked in cultured neurons by CMT2A mutants MFN2 Arg94→Gln94 and MFN2 Thr105→Met105, as demonstrated by amelioration of mitochondrial dysmotility, fragmentation, depolarization, and clumping. A mitofusin agonist normalized axonal mitochondrial trafficking within sciatic nerves of MFN2 Thr105→Met105 mice, promising a therapeutic approach for CMT2A and other untreatable diseases of impaired neuronal mitochondrial dynamism and/or trafficking.

    更新日期:2018-04-20
  • New Products
    Science (IF 37.205) Pub Date : 2018-04-20
    American Association for the Advancement of Science

    A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.

    更新日期:2018-04-20
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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