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  • Excised linear introns regulate growth in yeast
    Nature (IF 41.577) Pub Date : 2019-01-16
    Jeffrey T. Morgan, Gerald R. Fink, David P. Bartel
    更新日期:2019-01-19
  • A kiwellin disarms the metabolic activity of a secreted fungal virulence factor
    Nature (IF 41.577) Pub Date : 2019-01-16
    Xiaowei Han, Florian Altegoer, Wieland Steinchen, Lynn Binnebesel, Jan Schuhmacher, Timo Glatter, Pietro I. Giammarinaro, Armin Djamei, Stefan A. Rensing, Stefanie Reissmann, Regine Kahmann, Gert Bange
    更新日期:2019-01-19
  • HIF-1α metabolically controls collagen synthesis and modification in chondrocytes
    Nature (IF 41.577) Pub Date : 2019-01-16
    Steve Stegen, Kjell Laperre, Guy Eelen, Gianmarco Rinaldi, Peter Fraisl, Sophie Torrekens, Riet Van Looveren, Shauni Loopmans, Geert Bultynck, Stefan Vinckier, Filip Meersman, Patrick H. Maxwell, Jyoti Rai, MaryAnn Weis, David R. Eyre, Bart Ghesquière, Sarah-Maria Fendt, Peter Carmeliet, Geert Carmeliet
    更新日期:2019-01-19
  • Interacting neural ensembles in orbitofrontal cortex for social and feeding behaviour
    Nature (IF 41.577) Pub Date : 2019-01-16
    Joshua H. Jennings, Christina K. Kim, James H. Marshel, Misha Raffiee, Li Ye, Sean Quirin, Sally Pak, Charu Ramakrishnan, Karl Deisseroth
    更新日期:2019-01-19
  • Introns are mediators of cell response to starvation
    Nature (IF 41.577) Pub Date : 2019-01-16
    Julie Parenteau, Laurine Maignon, Mélodie Berthoumieux, Mathieu Catala, Vanessa Gagnon, Sherif Abou Elela
    更新日期:2019-01-19
  • Magnetic and magnetic inverse spin Hall effects in a non-collinear antiferromagnet
    Nature (IF 41.577) Pub Date : 2019-01-16
    Motoi Kimata, Hua Chen, Kouta Kondou, Satoshi Sugimoto, Prasanta K. Muduli, Muhammad Ikhlas, Yasutomo Omori, Takahiro Tomita, Allan. H. MacDonald, Satoru Nakatsuji, Yoshichika Otani
    更新日期:2019-01-19
  • News at a glance
    Science (IF 41.058) Pub Date : 2019-01-18
    American Association for the Advancement of Science

    In science news around the world, a 2012 water-sharing agreement in Australia, touted for its balancing of societal and environmental needs, has failed to live up to its promise, with more than 1 million fish dying in recent weeks. India moves into quantum computing with a $12 million investment. Nobel laureate James Watson loses his honorary titles at Cold Spring Harbor Laboratory in New York. The U.S. House of Representatives science committee introduces three bills, including one to make agencies adopt common policies on sexual harassment. Germany reaches a deal with Wiley, and it includes open access to papers by authors at more than 700 institutions. And Europe unveils plans for its next-generation atom smasher.

    更新日期:2019-01-18
  • Shake-up threatens novel U.S. ecology facility
    Science (IF 41.058) Pub Date : 2019-01-18
    Jeffrey Mervis

    The National Ecological Observatory Network (NEON), a half-billion-dollar facility funded by the National Science Foundation (NSF), hopes to revolutionize ecology by collecting an unprecedented amount of data about long-term environmental changes across North America. But as NEON prepares to begin full operations, an abrupt leadership shake-up threatens to alienate the scientists who will be using those data and, thus, are essential to its success. On 8 January, Sharon Collinge, NEON's chief scientist and principal investigator, resigned 4 days after Battelle Memorial Institute, which manages the network, fired two senior managers without her knowledge or consent. Within hours of Collinge's resignation, Battelle dissolved NEON's 20-member technical advisory committee, heading off a possible mass resignation of panel members opposed to Battelle's actions.

    更新日期:2019-01-18
  • Did neurons arise from an early secretory cell?
    Science (IF 41.058) Pub Date : 2019-01-18
    Elizabeth Pennisi

    Swimming through the oceans, voraciously consuming plankton and other small creatures—and occasionally startling a swimmer—the beautiful gelatinous masses known as comb jellies won't be joining Mensa anytime soon. But these fragile creatures have nerve cells—and they offer insights about the evolutionary origins of all nervous systems, including our own. Inspired by their studies of a glue-secreting cell unique to these plankton predators, researchers have now proposed that in the last common ancestor to today's animals, the earliest neurons arose from secretory cells whose primary function was to release chemicals into the environment. The researchers also unearthed additional evidence in jellyfish, hydra, and fruit flies that neurons and other secretory cell types come from the same progenitor cells in embryos. The work could help resolve a long debate about whether the nervous system evolved twice early in animal life.

    更新日期:2019-01-18
  • In Congo, fighting a virus and a groundswell of fake news
    Science (IF 41.058) Pub Date : 2019-01-18
    Laura Spinney

    Occurring in a conflict zone amid controversial presidential elections, the current Ebola epidemic in the Democratic Republic of the Congo (DRC) has proved to be fertile ground for conspiracy theories and political manipulation, which can hamper efforts to treat patients and fight the virus's spread. Public health workers have mounted an unprecedented effort to counter false rumors. For the first time in an Ebola outbreak, the United Nations International Children's Emergency Fund and other agencies have joined forces in a single response team, which answers to the DRC's Ministry of Health and includes dozens of social scientists. They use the airwaves, social media, and meetings with community and religious leaders to fight misinformation.

    更新日期:2019-01-18
  • Pain spreads from shutdown
    Science (IF 41.058) Pub Date : 2019-01-18
    David Malakoff

    The pain from the partial shutdown of the U.S. government—now in its record fourth week—is spreading throughout the research community. Scientists aren't getting paychecks. Experiments are being delayed or halted. Funding agencies are canceling dozens of meetings where thousands of funding proposals were going to be reviewed. A major graduate student fellowship program is at risk of crippling delays. Those are just some of the consequences of a funding impasse between Congress and President Donald Trump over spending $5.7 billion on a border wall, which has shuttered about one-quarter of the federal government. The shutdown also could soon paralyze federally funded scientific facilities and research centers that have been largely insulated from the pain because they are operated by contractors who get paid in advance, often on a quarterly basis. "But now that quarterly check may or may not be coming," says Benjamin Corb, public affairs director at the American Society for Biochemistry and Molecular Biology in Rockville, Maryland. "The uncertainty is creating a real mess."

    更新日期:2019-01-18
  • Flotilla launches large survey of Antarctic krill
    Science (IF 41.058) Pub Date : 2019-01-18
    Erik Stokstad

    Researchers have launched a broad international survey of krill in the Southern Ocean to learn whether the fishing industry is leaving enough for this important crustacean's natural predators, including whales and penguins. Six vessels will spend nearly 2 months mapping the abundance of krill in and around the Scotia Sea. Researchers will also test wave gliders and other tools for cheaper, more frequent surveys that could improve the management of the fishery. The survey itself won't be able to reveal how the overall krill population in the Scotia Sea might have changed since the previous large survey, in 2000, but it could help confirm whether current fishing limits are precautionary enough.

    更新日期:2019-01-18
  • The bones of Bears Ears
    Science (IF 41.058) Pub Date : 2019-01-18
    April Reese

    Thousands of Permian and Triassic fossils pepper Bears Ears National Monument, a sweep of buttes and badlands in southwestern Utah whose sedimentary rocks catalog hundreds of millions of years of Earth's history. The region's rich paleontological and archaeological record persuaded former President Barack Obama to designate the area a national monument in the waning days of his administration. But in December 2017, President Donald Trump slashed the size of the monument by 85%, prompting the typically apolitical Society for Vertebrate Paleontology to sue—along with environmentalists, archaeologists, outdoor companies, and five Native American tribes. If they win, the ruling could set a precedent that would help safeguard the boundaries of 158 national monuments; if they lose, future presidents could gain new powers to downsize them. Paleontologists fear a ruling against them would have devastating consequences for Bears Ears, just as they are starting to uncover fossils there that could rewrite Earth's early history.

    更新日期:2019-01-18
  • The brain's traffic problems
    Science (IF 41.058) Pub Date : 2019-01-18
    Elie Dolgin

    Multiple research groups have linked brain disease such as amyotrophic lateral sclerosis (Lou Gehrig's disease), Huntington, and Alzheimer's to defects in the cellular transport system that carries proteins back and forth across the nuclear membrane. Somehow, the resulting abnormal pileups of proteins become rogue neuronal killers in those ailments. The findings promise to transform understanding of these diseases. They are also inspiring therapeutic efforts to address the cause of general age-related neurodegeneration—a goal that has largely eluded drug developers. Several biotech companies have jumped on that idea, exploring it in animal models and planning the first human trials of drugs that target intracellular transport this year.

    更新日期:2019-01-18
  • When Earth got pummeled
    Science (IF 41.058) Pub Date : 2019-01-18
    Christian Koeberl

    Collisions and impact processes have been important throughout the history of the solar system, including that of Earth. Small bodies in the early solar system, the planetesimals, grew through collisions, ultimately forming the planets. Recognizing the remnants of impact events on Earth is difficult because terrestrial processes either cover or erase the surface expression of impact structures in geologically short timespans. Because Earth and the Moon are subjected to the same flux of impactors, the latter's crater record serves as a proxy for that of Earth. On page 253 of this issue, Mazrouei et al. (1) report that infrared images of the Moon taken by the Lunar Reconnaissance Orbiter Diviner instrument can be used to estimate the ages of young lunar craters. They find the impact rate increased within the last ∼500 million years.

    更新日期:2019-01-18
  • Iron hits the mark
    Science (IF 41.058) Pub Date : 2019-01-18
    Elizabeth R. Young, Amanda Oldacre

    Solar energy can enable our society to thrive as we endeavor to reduce our dependence on fossil fuels. However, the Sun is an intermittent form of energy. Solar-cell technology is well suited for daytime electricity generation and usage, but our society uses energy around the clock. Thus, it is not only important to generate electricity for daytime use but also to store solar energy for nighttime use. Chemists see huge potential in molecules and materials that absorb light (that is, solar energy) and use that energy to generate electrons that then carry out chemical reactions to turn low-energy feedstocks into high-energy fuels. To date, the transition metal complex (TMC) photosensitzers that have sufficiently long excited-state lifetimes to enable this chemistry (1) contain expensive and scarce metals, such as complexes of ruthenium (Ru), osmium, and iridium. On page 249 of this issue, Kjær et al. (2) report an iron (Fe)–based photosensitizer with a quantum efficiency surpassing that of [Ru(bpy)3]2+ (where bpy is 2,2′-bipyridine), the historical standard bearer. Furthermore, the new iron-based photosensitizer has an excited-state lifetime of 2 ns, which is sufficiently long to transfer electrons to other compounds (see the figure).

    更新日期:2019-01-18
  • The cerebellum gets social
    Science (IF 41.058) Pub Date : 2019-01-18
    Egidio D'Angelo

    The cerebellum contains the second main cortex of the brain and ∼50% of the neurons that constitute the brain. Although the cerebellum has long been thought to subserve motor learning and coordination, more recently it has been recognized to take part in cognitive and emotional processing. Additionally, evidence for cerebellar involvement in autism spectrum disorder (ASD), schizophrenia, and addiction is growing. On page 248 of this issue, Carta et al. (1) extend this theme and show that the cerebellum can activate the ventral tegmental area (VTA). The VTA is a mesencephalic nucleus giving rise to the mesocortical and mesolimbic fiber bundles that release dopamine to the prefrontal cortex and ventral striatum. Dopamine, in turn, plays a fundamental role in cognitive and emotional functioning by regulating motivation and reward. This places the cerebellum into the main circuits regulating brain states and social behavior.

    更新日期:2019-01-18
  • Adaptations of an ancient modular machine
    Science (IF 41.058) Pub Date : 2019-01-18
    Ulrich Brandt

    All expressions of life ultimately depend on energy derived from redox chemistry and photosynthesis. On page 257 of this issue, Schuller et al. (1) report the structure of photosynthetic complex I at atomic resolution. The authors have analyzed how the distinct NADH [reduced form of oxidized nicotinamide adenine dinucleotide (NAD+)] dehydrogenase subunit S (NdhS) facilitates electron transfer from ferredoxin, thereby establishing efficient cyclic electron flow around photosystem I. The findings add an important piece to the puzzle of deciphering the enigmatic mechanisms at work in the remarkable molecular machines of the complex I superfamily encompassing photosynthetic and respiratory complex I, as well as proton pumping hydrogenases. In combination with high resolution structures of respiratory complex I from bacteria (2), mitochondria (3–5), and membrane bound hydrogenase (6), it is now possible to trace the modular evolution and functional adaptations of the complex I superfamily at the atomic level.

    更新日期:2019-01-18
  • Gene therapy for pathologic gene expression
    Science (IF 41.058) Pub Date : 2019-01-18
    Lindsey E. Montefiori, Marcelo A. Nobrega

    Haploinsufficiency arises when one copy of a gene is functionally lost, often through nonsense or frameshift mutations or small chromosomal deletions. The resulting monoallelic expression is not sufficiently compensated for by the intact allele, ultimately leading to decreased expression of the gene product and resulting in pathologic phenotypes (1). What are the therapeutic options for diseases rooted in insufficient gene expression? One possible viable option is to restore normal gene expression levels by enhancing their transcription in a targeted fashion. On page 246 in this issue, Matharu et al. (2) report a CRISPR-based gene-activation approach that can increase the expression of normal endogenous genes in a tissue-specific manner, setting the stage for the development of new gene-regulating therapies for gene dosage–associated diseases.

    更新日期:2019-01-18
  • B cells, CMV, and stem cell transplant
    Science (IF 41.058) Pub Date : 2019-01-18
    Maria-Luisa Alegre

    Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for various malignant and nonmalignant conditions but can be complicated by infections such as reactivation of cytomegalovirus (CMV). CMV is a ubiquitous DNA herpes virus comprising various distinct strains (1). Around 60 to 90% of healthy adults are seropositive, indicating past exposure to the virus, although infections in healthy people are often mild or asymptomatic. After initial acute infection, CMV enters a latent phase, similar to other herpes viruses. It has been suggested that CMV infection may confer an immunological benefit, perhaps explaining its prevalence, because comparison of seropositive and seronegative individuals has shown that CMV infection results in greater responses to the flu vaccine (2). The immune system is essential to control the initial infection and to prevent later CMV reactivation, as demonstrated by the high incidence of CMV reactivation in immunosuppressed patients such as HSCT recipients. Whereas the incidence and severity of CMV transcriptional reactivation and cell-to-cell dissemination after HSCT has substantially diminished since the adoption of prophylactic or preemptive antiviral therapies (3), CMV remains the most important viral infection after HSCT, especially in high-risk patients (such as seropositive recipients of seronegative donors), and can lead to life-threatening CMV disease in ∼10% of HSCT recipients (4). On page 288 of this issue, Martins et al. (5) make the unexpected observation, in mice undergoing bone marrow transplantation (BMT) as a model of HSCT, that strain-specific CMV antibodies made by host B cells play a crucial role in preventing CMV dissemination after BMT. They propose that passive transfer of antibodies that are matched to the latent CMV strain in HSCT recipients might constitute a powerful and easy therapeutic approach to prevent CMV disease.

    更新日期:2019-01-18
  • Oversight of direct-to-consumer neurotechnologies
    Science (IF 41.058) Pub Date : 2019-01-18
    Anna Wexler, Peter B. Reiner

    Marketed for the purpose of modulating cognition or a variety of affective and mental states, a growing ecosystem of neurotechnology products is being sold direct to consumers (DTC) without necessitating the physician as intermediary. Offering individuals the prospect of monitoring and manipulating a range of brain functions from memory to mental health, the major product categories are neuromonitoring devices, cognitive training applications, neurostimulation devices, and mental health apps. The market for these products is predicted to top $3 billion by 2020 (1). Yet there are good reasons to conclude that regulatory oversight of DTC neurotechnologies is insufficient. We suggest ways to provide systematic support for regulatory agencies, funding bodies, and a public that is thirsty for knowledge about the efficacy of DTC neurotechnology products.

    更新日期:2019-01-18
  • The revealing history of a revered waterway
    Science (IF 41.058) Pub Date : 2019-01-18
    Anne Rademacher

    Sudipta Sen's Ganges: The Many Pasts of an Indian River invites its reader across the space and time of this iconic riverscape. Through a sweeping yet carefully textured history, the layers of the Ganges's past assume a life that is both consequential and contemporary.

    更新日期:2019-01-18
  • Nuclear power and promise
    Science (IF 41.058) Pub Date : 2019-01-18
    Jacob Darwin Hamblin

    Confessions of a Rogue Nuclear Regulator, written by former chairman of the U.S. Nuclear Regulatory Commission Gregory Jaczko, is one part engrossing memoir and another part seething diatribe, depicting a government agency that routinely caves to industry pressure.

    更新日期:2019-01-18
  • Luminescence and reactivity of a charge-transfer excited iron complex with nanosecond lifetime
    Science (IF 41.058) Pub Date : 2019-01-18
    Kasper Skov Kjær, Nidhi Kaul, Om Prakash, Pavel Chábera, Nils W. Rosemann, Alireza Honarfar, Olga Gordivska, Lisa A. Fredin, Karl-Erik Bergquist, Lennart Häggström, Tore Ericsson, Linnea Lindh, Arkady Yartsev, Stenbjörn Styring, Ping Huang, Jens Uhlig, Jesper Bendix, Daniel Strand, Villy Sundström, Petter Persson, Reiner Lomoth, Kenneth Wärnmark

    Iron’s abundance and rich coordination chemistry are potentially appealing features for photochemical applications. However, the photoexcitable charge-transfer states of most iron complexes are limited by picosecond or subpicosecond deactivation through low-lying metal-centered states, resulting in inefficient electron-transfer reactivity and complete lack of photoluminescence. In this study, we show that octahedral coordination of iron(III) by two mono-anionic facial tris-carbene ligands can markedly suppress such deactivation. The resulting complex [Fe(phtmeimb)2]+, where phtmeimb is {phenyl[tris(3-methylimidazol-1-ylidene)]borate}−, exhibits strong, visible, room temperature photoluminescence with a 2.0-nanosecond lifetime and 2% quantum yield via spin-allowed transition from a doublet ligand-to-metal charge-transfer (2LMCT) state to the doublet ground state. Reductive and oxidative electron-transfer reactions were observed for the 2LMCT state of [Fe(phtmeimb)2]+ in bimolecular quenching studies with methylviologen and diphenylamine.

    更新日期:2019-01-18
  • Earth and Moon impact flux increased at the end of the Paleozoic
    Science (IF 41.058) Pub Date : 2019-01-18
    Sara Mazrouei, Rebecca R. Ghent, William F. Bottke, Alex H. Parker, Thomas M. Gernon

    The terrestrial impact crater record is commonly assumed to be biased, with erosion thought to eliminate older craters, even on stable terrains. Given that the same projectile population strikes Earth and the Moon, terrestrial selection effects can be quantified by using a method to date lunar craters with diameters greater than 10 kilometers and younger than 1 billion years. We found that the impact rate increased by a factor of 2.6 about 290 million years ago. The terrestrial crater record shows similar results, suggesting that the deficit of large terrestrial craters between 300 million and 650 million years ago relative to more recent times stems from a lower impact flux, not preservation bias. The almost complete absence of terrestrial craters older than 650 million years may indicate a massive global-scale erosion event near that time.

    更新日期:2019-01-18
  • Structural adaptations of photosynthetic complex I enable ferredoxin-dependent electron transfer
    Science (IF 41.058) Pub Date : 2019-01-18
    Jan M. Schuller, James A. Birrell, Hideaki Tanaka, Tsuyoshi Konuma, Hannes Wulfhorst, Nicholas Cox, Sandra K. Schuller, Jacqueline Thiemann, Wolfgang Lubitz, Pierre Sétif, Takahisa Ikegami, Benjamin D. Engel, Genji Kurisu, Marc M. Nowaczyk

    Photosynthetic complex I enables cyclic electron flow around photosystem I, a regulatory mechanism for photosynthetic energy conversion. We report a 3.3-angstrom-resolution cryo–electron microscopy structure of photosynthetic complex I from the cyanobacterium Thermosynechococcus elongatus. The model reveals structural adaptations that facilitate binding and electron transfer from the photosynthetic electron carrier ferredoxin. By mimicking cyclic electron flow with isolated components in vitro, we demonstrate that ferredoxin directly mediates electron transfer between photosystem I and complex I, instead of using intermediates such as NADPH (the reduced form of nicotinamide adenine dinucleotide phosphate). A large rate constant for association of ferredoxin to complex I indicates efficient recognition, with the protein subunit NdhS being the key component in this process.

    更新日期:2019-01-18
  • Observation of magnetically tunable Feshbach resonances in ultracold 23Na40K + 40K collisions
    Science (IF 41.058) Pub Date : 2019-01-18
    Huan Yang, De-Chao Zhang, Lan Liu, Ya-Xiong Liu, Jue Nan, Bo Zhao, Jian-Wei Pan

    Resonances in ultracold collisions involving heavy molecules are difficult to simulate theoretically and have proven challenging to detect. Here we report the observation of magnetically tunable Feshbach resonances in ultracold collisions between potassium-40 (40K) atoms and sodium-23–potassium-40 (23Na40K) molecules in the rovibrational ground state. We prepare the atoms and molecules in various hyperfine levels of their ground states and observe the loss of molecules as a function of the magnetic field. The atom-molecule Feshbach resonances are identified by observing an enhancement of the loss. We have observed 11 resonances in the magnetic field range of 43 to 120 gauss. The observed atom-molecule Feshbach resonances at ultralow temperatures probe the three-body potential energy surface with exceptional resolution and will help to improve understanding of ultracold collisions.

    更新日期:2019-01-18
  • A Eu3+-Eu2+ ion redox shuttle imparts operational durability to Pb-I perovskite solar cells
    Science (IF 41.058) Pub Date : 2019-01-18
    Ligang Wang, Huanping Zhou, Junnan Hu, Bolong Huang, Mingzi Sun, Bowei Dong, Guanghaojie Zheng, Yuan Huang, Yihua Chen, Liang Li, Ziqi Xu, Nengxu Li, Zheng Liu, Qi Chen, Ling-Dong Sun, Chun-Hua Yan

    The components with soft nature in the metal halide perovskite absorber usually generate lead (Pb)0 and iodine (I)0 defects during device fabrication and operation. These defects serve as not only recombination centers to deteriorate device efficiency but also degradation initiators to hamper device lifetimes. We show that the europium ion pair Eu3+-Eu2+ acts as the “redox shuttle” that selectively oxidized Pb0 and reduced I0 defects simultaneously in a cyclical transition. The resultant device achieves a power conversion efficiency (PCE) of 21.52% (certified 20.52%) with substantially improved long-term durability. The devices retained 92% and 89% of the peak PCE under 1-sun continuous illumination or heating at 85°C for 1500 hours and 91% of the original stable PCE after maximum power point tracking for 500 hours, respectively.

    更新日期:2019-01-18
  • Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis
    Science (IF 41.058) Pub Date : 2019-01-18
    Eric R. Welin, Aurapat Ngamnithiporn, Max Klatte, Guillaume Lapointe, Gerit M. Pototschnig, Martina S. J. McDermott, Dylan Conklin, Christopher D. Gilmore, Pamela M. Tadross, Christopher K. Haley, Kenji Negoro, Emil Glibstrup, Christian U. Grünanger, Kevin M. Allan, Scott C. Virgil, Dennis J. Slamon, Brian M. Stoltz

    The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong Gram-positive and Gram-negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet–Spengler reaction, that mimics their biosynthetic pathways. Herein, we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of nonnatural analogs.

    更新日期:2019-01-18
  • An amygdalar neural ensemble that encodes the unpleasantness of pain
    Science (IF 41.058) Pub Date : 2019-01-18
    Gregory Corder, Biafra Ahanonu, Benjamin F. Grewe, Dong Wang, Mark J. Schnitzer, Grégory Scherrer

    Pain is an unpleasant experience. How the brain’s affective neural circuits attribute this aversive quality to nociceptive information remains unknown. By means of time-lapse in vivo calcium imaging and neural activity manipulation in freely behaving mice encountering noxious stimuli, we identified a distinct neural ensemble in the basolateral amygdala that encodes the negative affective valence of pain. Silencing this nociceptive ensemble alleviated pain affective-motivational behaviors without altering the detection of noxious stimuli, withdrawal reflexes, anxiety, or reward. Following peripheral nerve injury, innocuous stimuli activated this nociceptive ensemble to drive dysfunctional perceptual changes associated with neuropathic pain, including pain aversion to light touch (allodynia). These results identify the amygdalar representations of noxious stimuli that are functionally required for the negative affective qualities of acute and chronic pain perception.

    更新日期:2019-01-18
  • Agriculturally dominated landscapes reduce bee phylogenetic diversity and pollination services
    Science (IF 41.058) Pub Date : 2019-01-18
    Heather Grab, Michael G. Branstetter, Nolan Amon, Katherine R. Urban-Mead, Mia G. Park, Jason Gibbs, Eleanor J. Blitzer, Katja Poveda, Greg Loeb, Bryan N. Danforth

    Land-use change threatens global biodiversity and may reshape the tree of life by favoring some lineages over others. Whether phylogenetic diversity loss compromises ecosystem service delivery remains unknown. We address this knowledge gap using extensive genomic, community, and crop datasets to examine relationships among land use, pollinator phylogenetic structure, and crop production. Pollinator communities in highly agricultural landscapes contain 230 million fewer years of evolutionary history; this loss was strongly associated with reduced crop yield and quality. Our study links landscape–mediated changes in the phylogenetic structure of natural communities to the disruption of ecosystem services. Measuring conservation success by species counts alone may fail to protect ecosystem functions and the full diversity of life from which they are derived.

    更新日期:2019-01-18
  • Flagellar microtubule doublet assembly in vitro reveals a regulatory role of tubulin C-terminal tails
    Science (IF 41.058) Pub Date : 2019-01-18
    M. Schmidt-Cernohorska, I. Zhernov, E. Steib, M. Le Guennec, R. Achek, S. Borgers, D. Demurtas, L. Mouawad, Z. Lansky, V. Hamel, P. Guichard

    Microtubule doublets (MTDs), consisting of an incomplete B-microtubule at the surface of a complete A-microtubule, provide a structural scaffold mediating intraflagellar transport and ciliary beating. Despite the fundamental role of MTDs, the molecular mechanism governing their formation is unknown. We used a cell-free assay to demonstrate a crucial inhibitory role of the carboxyl-terminal (C-terminal) tail of tubulin in MTD assembly. Removal of the C-terminal tail of an assembled A-microtubule allowed for the nucleation of a B-microtubule on its surface. C-terminal tails of only one A-microtubule protofilament inhibited this side-to-surface tubulin interaction, which would be overcome in vivo with binding protein partners. The dynamics of B-microtubule nucleation and its distinctive isotropic elongation was elucidated by using live imaging. Thus, inherent interaction properties of tubulin provide a structural basis driving flagellar MTD assembly.

    更新日期:2019-01-18
  • Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation
    Science (IF 41.058) Pub Date : 2019-01-18
    Jose Paulo Martins, Christopher E. Andoniou, Peter Fleming, Rachel D. Kuns, Iona S. Schuster, Valentina Voigt, Sheridan Daly, Antiopi Varelias, Siok-Keen Tey, Mariapia A. Degli-Esposti, Geoffrey R. Hill

    Cytomegalovirus infection is a frequent and life-threatening complication that significantly limits positive transplantation outcomes. We developed preclinical mouse models of cytomegalovirus reactivation after transplantation and found that humoral immunity is essential for preventing viral recrudescence. Preexisting antiviral antibodies decreased after transplant in the presence of graft-versus-host disease and were not replaced, owing to poor reconstitution of donor B cells and elimination of recipient plasma cells. Viral reactivation was prevented by the transfer of immune serum, without a need to identify and target specific antigenic determinants. Notably, serotherapy afforded complete protection, provided that the serum was matched to the infecting viral strain. Thus, we define the mechanisms for cytomegalovirus reactivation after transplantation and identify a readily translatable strategy of exceptional potency, which avoids the constraints of cellular therapies.

    更新日期:2019-01-18
  • H3K9me3-heterochromatin loss at protein-coding genes enables developmental lineage specification
    Science (IF 41.058) Pub Date : 2019-01-18
    Dario Nicetto, Greg Donahue, Tanya Jain, Tao Peng, Simone Sidoli, Lihong Sheng, Thomas Montavon, Justin S. Becker, Jessica M. Grindheim, Kimberly Blahnik, Benjamin A. Garcia, Kai Tan, Roberto Bonasio, Thomas Jenuwein, Kenneth S. Zaret

    Gene silencing by chromatin compaction is integral to establishing and maintaining cell fates. Trimethylated histone 3 lysine 9 (H3K9me3)–marked heterochromatin is reduced in embryonic stem cells compared to differentiated cells. However, the establishment and dynamics of closed regions of chromatin at protein-coding genes, in embryologic development, remain elusive. We developed an antibody-independent method to isolate and map compacted heterochromatin from low–cell number samples. We discovered high levels of compacted heterochromatin, H3K9me3-decorated, at protein-coding genes in early, uncommitted cells at the germ-layer stage, undergoing profound rearrangements and reduction upon differentiation, concomitant with cell type–specific gene expression. Perturbation of the three H3K9me3-related methyltransferases revealed a pivotal role for H3K9me3 heterochromatin during lineage commitment at the onset of organogenesis and for lineage fidelity maintenance.

    更新日期:2019-01-18
  • AAAS 2019 Annual Meeting Program
    Science (IF 41.058) Pub Date : 2019-01-18
    American Association for the Advancement of Science

    This issue of Science includes the program of the 2019 AAAS Annual Meeting. The theme of the AAAS Annual Meeting in Washington, DC, 14 to 17 February 2019, is Science Transcending Boundaries. A PDF of the program as it appears in this issue is available here; for more information on the meeting (including registration forms and information on accommodations), please visit www.aaas.org/meetings/.

    更新日期:2019-01-18
  • Cerebellar modulation of the reward circuitry and social behavior
    Science (IF 41.058) Pub Date : 2019-01-18
    Ilaria Carta, Christopher H. Chen, Amanda L. Schott, Schnaude Dorizan, Kamran Khodakhah

    The cerebellum has been implicated in a number of nonmotor mental disorders such as autism spectrum disorder, schizophrenia, and addiction. However, its contribution to these disorders is not well understood. In mice, we found that the cerebellum sends direct excitatory projections to the ventral tegmental area (VTA), one of the brain regions that processes and encodes reward. Optogenetic activation of the cerebello-VTA projections was rewarding and, in a three-chamber social task, these projections were more active when the animal explored the social chamber. Intriguingly, activity in the cerebello-VTA pathway was required for the mice to show social preference in this task. Our data delineate a major, previously unappreciated role for the cerebellum in controlling the reward circuitry and social behavior.

    更新日期:2019-01-18
  • CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency
    Science (IF 41.058) Pub Date : 2019-01-18
    Navneet Matharu, Sawitree Rattanasopha, Serena Tamura, Lenka Maliskova, Yi Wang, Adelaide Bernard, Aaron Hardin, Walter L. Eckalbar, Christian Vaisse, Nadav Ahituv

    A wide range of human diseases result from haploinsufficiency, where the function of one of the two gene copies is lost. Here, we targeted the remaining functional copy of a haploinsufficient gene using CRISPR-mediated activation (CRISPRa) in Sim1 and Mc4r heterozygous mouse models to rescue their obesity phenotype. Transgenic-based CRISPRa targeting of the Sim1 promoter or its distant hypothalamic enhancer up-regulated its expression from the endogenous functional allele in a tissue-specific manner, rescuing the obesity phenotype in Sim1 heterozygous mice. To evaluate the therapeutic potential of CRISPRa, we injected CRISPRa-recombinant adeno-associated virus into the hypothalamus, which led to reversal of the obesity phenotype in Sim1 and Mc4r haploinsufficient mice. Our results suggest that endogenous gene up-regulation could be a potential strategy to treat altered gene dosage diseases.

    更新日期:2019-01-18
  • The importance of synthetic chemistry in the pharmaceutical industry
    Science (IF 41.058) Pub Date : 2019-01-18
    Kevin R. Campos, Paul J. Coleman, Juan C. Alvarez, Spencer D. Dreher, Robert M. Garbaccio, Nicholas K. Terrett, Richard D. Tillyer, Matthew D. Truppo, Emma R. Parmee

    Innovations in synthetic chemistry have enabled the discovery of many breakthrough therapies that have improved human health over the past century. In the face of increasing challenges in the pharmaceutical sector, continued innovation in chemistry is required to drive the discovery of the next wave of medicines. Novel synthetic methods not only unlock access to previously unattainable chemical matter, but also inspire new concepts as to how we design and build chemical matter. We identify some of the most important recent advances in synthetic chemistry as well as opportunities at the interface with partner disciplines that are poised to transform the practice of drug discovery and development.

    更新日期:2019-01-18
  • Prediction of higher-selectivity catalysts by computer-driven workflow and machine learning
    Science (IF 41.058) Pub Date : 2019-01-18
    Andrew F. Zahrt, Jeremy J. Henle, Brennan T. Rose, Yang Wang, William T. Darrow, Scott E. Denmark

    Catalyst design in asymmetric reaction development has traditionally been driven by empiricism, wherein experimentalists attempt to qualitatively recognize structural patterns to improve selectivity. Machine learning algorithms and chemoinformatics can potentially accelerate this process by recognizing otherwise inscrutable patterns in large datasets. Herein we report a computationally guided workflow for chiral catalyst selection using chemoinformatics at every stage of development. Robust molecular descriptors that are agnostic to the catalyst scaffold allow for selection of a universal training set on the basis of steric and electronic properties. This set can be used to train machine learning methods to make highly accurate predictive models over a broad range of selectivity space. Using support vector machines and deep feed-forward neural networks, we demonstrate accurate predictive modeling in the chiral phosphoric acid–catalyzed thiol addition to N-acylimines.

    更新日期:2019-01-18
  • Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution
    Science (IF 41.058) Pub Date : 2019-01-18
    Ruixuan Gao, Shoh M. Asano, Srigokul Upadhyayula, Igor Pisarev, Daniel E. Milkie, Tsung-Li Liu, Ved Singh, Austin Graves, Grace H. Huynh, Yongxin Zhao, John Bogovic, Jennifer Colonell, Carolyn M. Ott, Christopher Zugates, Susan Tappan, Alfredo Rodriguez, Kishore R. Mosaliganti, Shu-Hsien Sheu, H. Amalia Pasolli, Song Pang, C. Shan Xu, Sean G. Megason, Harald Hess, Jennifer Lippincott-Schwartz, Adam Hantman, Gerald M. Rubin, Tom Kirchhausen, Stephan Saalfeld, Yoshinori Aso, Edward S. Boyden, Eric Betzig

    Optical and electron microscopy have made tremendous inroads toward understanding the complexity of the brain. However, optical microscopy offers insufficient resolution to reveal subcellular details, and electron microscopy lacks the throughput and molecular contrast to visualize specific molecular constituents over millimeter-scale or larger dimensions. We combined expansion microscopy and lattice light-sheet microscopy to image the nanoscale spatial relationships between proteins across the thickness of the mouse cortex or the entire Drosophila brain. These included synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly brain region. The technology should enable statistically rich, large-scale studies of neural development, sexual dimorphism, degree of stereotypy, and structural correlations to behavior or neural activity, all with molecular contrast.

    更新日期:2019-01-18
  • Aerosol-driven droplet concentrations dominate coverage and water of oceanic low level clouds
    Science (IF 41.058) Pub Date : 2019-01-17
    Daniel Rosenfeld, Yannian Zhu, Minghuai Wang, Youtong Zheng, Tom Goren, Shaocai Yu

    Lack of reliable estimates of cloud condensation nuclei (CCN) aerosols over oceans has severely limited our ability to quantify their effects on cloud properties and extent of cooling by reflecting solar radiation – a key uncertainty in anthropogenic climate forcing. Here we introduce a methodology for ascribing cloud properties to CCN and isolating the aerosol effects from meteorological effects. Its application showed that, for a given meteorology, CCN explains 3/4 of the variability in clouds radiative cooling effect, mainly through affecting shallow cloud cover and water path. This reveals a much greater sensitivity of cloud radiative forcing to CCN than previously reported, which means too much cooling if incorporated in present climate models. This hints to yet unknown compensating aerosol warming effects, possibly through deep clouds.

    更新日期:2019-01-18
  • A degenerate Fermi gas of polar molecules
    Science (IF 41.058) Pub Date : 2019-01-17
    Luigi De Marco, Giacomo Valtolina, Kyle Matsuda, William G. Tobias, Jacob P. Covey, Jun Ye

    Experimental realization of a quantum degenerate gas of molecules would provide access to a wide range of phenomena in molecular and quantum sciences. However, the very complexity that makes ultracold molecules so enticing has made reaching degeneracy an outstanding experimental challenge over the past decade. We now report the production of a degenerate Fermi gas of ultracold polar molecules of potassium–rubidium (KRb). Through coherent adiabatic association in a deeply degenerate mixture of a rubidium Bose-Einstein condensate and a potassium Fermi gas, we produce molecules at temperatures below 0.3 times the Fermi temperature. We explore the properties of this reactive gas and demonstrate how degeneracy suppresses chemical reactions, making a long-lived degenerate gas of polar molecules a reality.

    更新日期:2019-01-18
  • Measurement and implications of Saturn’s gravity field and ring mass
    Science (IF 41.058) Pub Date : 2019-01-17
    L. Iess, B. Militzer, Y. Kaspi, P. Nicholson, D. Durante, P. Racioppa, A. Anabtawi, E. Galanti, W. Hubbard, M. J. Mariani, P. Tortora, S. Wahl, M. Zannoni

    The interior structure of Saturn, the depth of its winds and the mass and age of its rings constrain its formation and evolution. In the final phase of the Cassini mission, the spacecraft dived between the planet and the innermost ring, at altitudes 2600-3900 km above the cloud tops. During six of these crossings, a radio link with Earth was monitored to determine the gravitational field of the planet and the mass of its rings. We find that Saturn’s gravity deviates from theoretical expectations and requires differential rotation of the atmosphere extending to a depth of at least 9000 km. The total mass of the rings is (1.54 ± 0.49)×1019 kg (0.41 ± 0.13 times that of the moon Mimas), indicating that the rings may have formed 107-108 years ago.

    更新日期:2019-01-18
  • Bispyrene-Based Self-Assembled Nanomaterials: In Vivo Self-Assembly, Transformation, and Biomedical Effects
    Acc. Chem. Res. (IF 20.955) Pub Date : 2019-01-17
    Ping-Ping He, Xiang-Dan Li, Lei Wang, Hao Wang
    更新日期:2019-01-18
  • 更新日期:2019-01-18
  • NHC-Catalyzed Generation of α,β-Unsaturated Acylazoliums for the Enantioselective Synthesis of Heterocycles and Carbocycles
    Acc. Chem. Res. (IF 20.955) Pub Date : 2019-01-17
    Santigopal Mondal, Santhivardhana Reddy Yetra, Subrata Mukherjee, Akkattu T. Biju
    更新日期:2019-01-18
  • High-performance oxygen evolution electrocatalysis by boronized metal sheets with self-functionalized surfaces
    Energy Environ. Sci. (IF 30.067) Pub Date : 2019-01-09
    Feifan Guo, Yuanyuan Wu, Hui Chen, Yipu Liu, Li Yang, Xuan Ai, Xiaoxin Zou
    更新日期:2019-01-18
  • Mechano‐Plastic Pyrolysis of Dynamic Covalent Polymer Network toward Hierarchical 3D Ceramics
    Adv. Mater. (IF 21.95) Pub Date : 2019-01-18
    Ning Zheng; Jingjing Hou; Hangbo Zhao; Jingjun Wu; Yingwu Luo; Hao Bai; John A. Rogers; Qian Zhao; Tao Xie
    更新日期:2019-01-18
  • Recommended Practices and Benchmark Activity for Hydrogen and Oxygen Electrocatalysis in Water Splitting and Fuel Cells
    Adv. Mater. (IF 21.95) Pub Date : 2019-01-18
    Chao Wei; Reshma R. Rao; Jiayu Peng; Botao Huang; Ifan E. L. Stephens; Marcel Risch; Zhichuan J. Xu; Yang Shao‐Horn
    更新日期:2019-01-18
  • 12.5% Flexible Nonfullerene Solar Cells by Passivating the Chemical Interaction Between the Active Layer and Polymer Interfacial Layer
    Adv. Mater. (IF 21.95) Pub Date : 2019-01-17
    Sixing Xiong; Lin Hu; Lu Hu; Lulu Sun; Fei Qin; Xianjie Liu; Mats Fahlman; Yinhua Zhou
    更新日期:2019-01-18
  • Ambipolar Conjugated Polymers with Ultrahigh Balanced Hole and Electron Mobility for Printed Organic Complementary Logic via a Two‐Step CH Activation Strategy
    Adv. Mater. (IF 21.95) Pub Date : 2019-01-17
    Zhenjie Ni; Hanlin Wang; Qiang Zhao; Jianqi Zhang; Zhixiang Wei; Huanli Dong; Wenping Hu
    更新日期:2019-01-18
  • Artificial Chiral Probes and Bioapplications
    Adv. Mater. (IF 21.95) Pub Date : 2019-01-17
    Changlong Hao; Liguang Xu; Hua Kuang; Chuanlai Xu
    更新日期:2019-01-18
  • Atomically Dispersed Molybdenum Catalysts for Efficient Ambient Nitrogen Fixation
    Angew. Chem. Int. Ed. (IF 12.102) Pub Date : 2019-01-18
    Lili Han; Xijun Liu; Jinping Chen; Ruoqian Lin; Haoxuan Liu; Fang Lü; Seongmin Bak; Zhixiu Liang; Shunzheng Zhao; Eli Stavitski; Jun Luo; Radoslav R. Adzic; Huolin L. Xin
    更新日期:2019-01-18
  • Visualizing Phase Segregation in Mixed‐Halide Perovskite Single Crystals
    Angew. Chem. Int. Ed. (IF 12.102) Pub Date : 2019-01-18
    Wenxin Mao; Christopher R. Hall; Anthony S. R. Chesman; Craig Forsyth; Yi‐Bing Cheng; Noel W. Duffy; Trevor A. Smith; Udo Bach
    更新日期:2019-01-18
  • Z‐Scheme 2D/2D Heterojunction of Black Phosphorus/Monolayer Bi2WO6 Nanosheets with Enhanced Photocatalytic Activities
    Angew. Chem. Int. Ed. (IF 12.102) Pub Date : 2019-01-18
    Jundie Hu; Dongyun Chen; Zhao Mo; Najun Li; Qingfeng Xu; Hua Li; Jinghui He; Hui Xu; Jianmei Lu
    更新日期:2019-01-18
  • External Reversal of Chirality Transfer in Photoswitches
    Angew. Chem. Int. Ed. (IF 12.102) Pub Date : 2019-01-18
    Christoph Jurissek; Fabian Berger; Fabian Eisenreich; Michael Kathan; Stefan Hecht
    更新日期:2019-01-18
  • Stereospecific Synthesis of α‐Hydroxy‐Cyclopropylboronates from Allylic Epoxides
    Angew. Chem. Int. Ed. (IF 12.102) Pub Date : 2019-01-18
    Laura Amenós; Laura Trulli; Luis Nóvoa; Alejandro Parra; Mariola Tortosa
    更新日期:2019-01-18
  • Katrina (Kate) Jolliffe
    Angew. Chem. Int. Ed. (IF 12.102) Pub Date : 2019-01-18
    更新日期:2019-01-18
  • High iso Aldehyde Selectivity in the Hydroformylation of Short‐Chain Alkenes
    Angew. Chem. Int. Ed. (IF 12.102) Pub Date : 2019-01-18
    Leo Iu; José A. Fuentes; Mesfin E. Janka; Kevin J. Fontenot; Matthew L. Clarke
    更新日期:2019-01-18
  • Broadband Cr3+, Sn4+‐Doped Oxide Nanophosphors for Infrared Mini Light‐Emitting Diodes
    Angew. Chem. Int. Ed. (IF 12.102) Pub Date : 2019-01-18
    Wen‐Tse Huang; Chiao‐Ling Cheng; Zhen Bao; Chia‐Wei Yang; Kuang‐Mao Lu; Chieh‐Yu Kang; Chih‐Min Lin; Ru‐Shi Liu
    更新日期:2019-01-18
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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