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Cerebellar 5HT-2A receptor mediates stress-induced onset of dystonia Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Jung Eun Kim, Sujin Chae, Sungsoo Kim, Yeon-Joo Jung, Myoung-Goo Kang, Won Do Heo, Daesoo Kim
Stress is a key risk factor for dystonia, a debilitating motor disorder characterized by cocontractions of muscles leading to abnormal body posture. While the serotonin (5HT) system is known to control emotional responses to stress, its role in dystonia remains unclear. Here, we reveal that 5HT neurons in the dorsal raphe nuclei (DRN) send projections to the fastigial deep cerebellar nuclei (fDCN)
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Durable memories and efficient neural coding through mnemonic training using the method of loci Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 I. C. Wagner, B. N. Konrad, P. Schuster, S. Weisig, D. Repantis, K. Ohla, S. Kühn, G. Fernández, A. Steiger, C. Lamm, M. Czisch, M. Dresler
Mnemonic techniques, such as the method of loci, can powerfully boost memory. We compared memory athletes ranked among the world’s top 50 in memory sports to mnemonics-naïve controls. In a second study, participants completed a 6-week memory training, working memory training, or no intervention. Behaviorally, memory training enhanced durable, longer-lasting memories. Functional magnetic resonance imaging
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Modulation of intercolumnar synchronization by endogenous electric fields in cerebral cortex Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Beatriz Rebollo, Bartosz Telenczuk, Alvaro Navarro-Guzman, Alain Destexhe, Maria V. Sanchez-Vives
Neurons synaptically interacting in a conductive medium generate extracellular endogenous electric fields (EFs) that reciprocally affect membrane potential. Exogenous EFs modulate neuronal activity, and their clinical applications are being profusely explored. However, whether endogenous EFs contribute to network synchronization remains unclear. We analyzed spontaneously generated slow-wave activity
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Host-microbe cross-talk governs amino acid chirality to regulate survival and differentiation of B cells Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 M. Suzuki, T. Sujino, S. Chiba, Y. Harada, M. Goto, R. Takahashi, M. Mita, K. Hamase, T. Kanai, M. Ito, M.K. Waldor, M. Yasui, J. Sasabe
Organisms use l-amino acids (l-aa) for most physiological processes. Unlike other organisms, bacteria chiral-convert l-aa to d-configurations as essential components of their cell walls and as signaling molecules in their ecosystems. Mammals recognize microbe-associated molecules to initiate immune responses, but roles of bacterial d-amino acids (d-aa) in mammalian immune systems remain largely unknown
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Global political responsibility for the conservation of albatrosses and large petrels Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Martin Beal, Maria P. Dias, Richard A. Phillips, Steffen Oppel, Carolina Hazin, Elizabeth J. Pearmain, Josh Adams, David J. Anderson, Michelle Antolos, Javier A. Arata, José Manuel Arcos, John P. Y. Arnould, Jill Awkerman, Elizabeth Bell, Mike Bell, Mark Carey, Ryan Carle, Thomas A. Clay, Jaimie Cleeland, Valentina Colodro, Melinda Conners, Marta Cruz-Flores, Richard Cuthbert, Karine Delord, Lorna
Migratory marine species cross political borders and enter the high seas, where the lack of an effective global management framework for biodiversity leaves them vulnerable to threats. Here, we combine 10,108 tracks from 5775 individual birds at 87 sites with data on breeding population sizes to estimate the relative year-round importance of national jurisdictions and high seas areas for 39 species
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Exonuclease VII repairs quinolone-induced damage by resolving DNA gyrase cleavage complexes Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Shar-yin N. Huang, Stephanie A. Michaels, Brianna B. Mitchell, Nadim Majdalani, Arnaud Vanden Broeck, Andres Canela, Yuk-Ching Tse-Dinh, Valerie Lamour, Yves Pommier
The widely used quinolone antibiotics act by trapping prokaryotic type IIA topoisomerases, resulting in irreversible topoisomerase cleavage complexes (TOPcc). Whereas the excision repair pathways of TOPcc in eukaryotes have been extensively studied, it is not known whether equivalent repair pathways for prokaryotic TOPcc exist. By combining genetic, biochemical, and molecular biology approaches, we
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Mantis shrimp–inspired organic photodetector for simultaneous hyperspectral and polarimetric imaging Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Ali Altaqui, Pratik Sen, Harry Schrickx, Jeromy Rech, Jin-Woo Lee, Michael Escuti, Wei You, Bumjoon J. Kim, Robert Kolbas, Brendan T. O’Connor, Michael Kudenov
Combining hyperspectral and polarimetric imaging provides a powerful sensing modality with broad applications from astronomy to biology. Existing methods rely on temporal data acquisition or snapshot imaging of spatially separated detectors. These approaches incur fundamental artifacts that degrade imaging performance. To overcome these limitations, we present a stomatopod-inspired sensor capable of
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Neonatal wearable device for colorimetry-based real-time detection of jaundice with simultaneous sensing of vitals Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Go Inamori, Umihiro Kamoto, Fumika Nakamura, Yutaka Isoda, Azusa Uozumi, Ryosuke Matsuda, Masaki Shimamura, Yusuke Okubo, Shuichi Ito, Hiroki Ota
Neonatal jaundice occurs in >80% of newborns in the first week of life owing to physiological hyperbilirubinemia. Severe hyperbilirubinemia could cause brain damage owing to its neurotoxicity, a state commonly known as kernicterus. Therefore, periodic bilirubin monitoring is essential to identify infants at-risk and to initiate treatment including phototherapy. However, devices for continuous measurements
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A single-molecule electrical approach for amino acid detection and chirality recognition Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Zihao Liu, Xingxing Li, Hiroshi Masai, Xinyi Huang, Susumu Tsuda, Jun Terao, Jinlong Yang, Xuefeng Guo
One of the ultimate goals of analytic chemistry is to efficiently discriminate between amino acids. Here we demonstrate this ability using a single-molecule electrical methodology based on molecular nanocircuits formed from stable graphene-molecule-graphene single-molecule junctions. These molecular junctions are fabricated by covalently bonding a molecular machine featuring a permethylated-β-cyclodextrin
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Reading between the lines: Listener’s vmPFC simulates speaker cooperative choices in communication games Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Qingtian Mi, Cong Wang, Colin F. Camerer, Lusha Zhu
Humans have a remarkable ability to understand what is and is not being said by conversational partners. It has been hypothesized that listeners decode the intended meaning of a communicative signal by assuming speakers speak cooperatively, rationally simulating the speaker’s choice process and inverting it to recover the speaker’s most probable meaning. We investigated whether and how rational simulations
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Iodine reduction for reproducible and high-performance perovskite solar cells and modules Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Shangshang Chen, Xun Xiao, Hangyu Gu, Jinsong Huang
Perovskite-based electronic materials and devices such as perovskite solar cells (PSCs) have notoriously bad reproducibility, which greatly impedes both fundamental understanding of their intrinsic properties and real-world applications. Here, we report that organic iodide perovskite precursors can be oxidized to I2 even for carefully sealed precursor powders or solutions, which markedly deteriorates
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The cryo-EM structure of an ERAD protein channel formed by tetrameric human Derlin-1 Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Bing Rao, Shaobai Li, Deqiang Yao, Qian Wang, Ying Xia, Yi Jia, Yafeng Shen, Yu Cao
Endoplasmic reticulum–associated degradation (ERAD) is a process directing misfolded proteins from the ER lumen and membrane to the degradation machinery in the cytosol. A key step in ERAD is the translocation of ER proteins to the cytosol. Derlins are essential for protein translocation in ERAD, but the mechanism remains unclear. Here, we solved the structure of human Derlin-1 by cryo–electron microscopy
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Anti-EGFR VHH-armed death receptor ligand–engineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Yohei Kitamura, Nobuhiko Kanaya, Susana Moleirinho, Wanlu Du, Clemens Reinshagen, Nada Attia, Agnieszka Bronisz, Esther Revai Lechtich, Hikaru Sasaki, Joana Liliana Mora, Priscilla Kaliopi Brastianos, Jefferey L. Falcone, Aldebaran M. Hofer, Arnaldo Franco, Khalid Shah
Basal-like breast cancer (BLBC) shows brain metastatic (BM) capability and overexpresses EGFR and death-receptors 4/5 (DR4/5); however, the anatomical location of BM prohibits efficient drug-delivery to these targetable markers. In this study, we developed BLBC-BM mouse models featuring different patterns of BMs and explored the versatility of estem cell (SC)–mediated bi-functional EGFR and DR4/5-targeted
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Enhanced tunable second harmonic generation from twistable interfaces and vertical superlattices in boron nitride homostructures Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Kaiyuan Yao, Nathan R. Finney, Jin Zhang, Samuel L. Moore, Lede Xian, Nicolas Tancogne-Dejean, Fang Liu, Jenny Ardelean, Xinyi Xu, Dorri Halbertal, K. Watanabe, T. Taniguchi, Hector Ochoa, Ana Asenjo-Garcia, Xiaoyang Zhu, D. N. Basov, Angel Rubio, Cory R. Dean, James Hone, P. James Schuck
Broken symmetries induce strong even-order nonlinear optical responses in materials and at interfaces. Unlike conventional covalently bonded nonlinear crystals, van der Waals (vdW) heterostructures feature layers that can be stacked at arbitrary angles, giving complete control over the presence or lack of inversion symmetry at a crystal interface. Here, we report highly tunable second harmonic generation
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Highly selective and high-performance osmotic power generators in subnanochannel membranes enabled by metal-organic frameworks Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Yi-Cheng Liu, Li-Hsien Yeh, Min-Jie Zheng, Kevin C.-W. Wu
The electric organs of electric eels are able to convert ionic gradients into high-efficiency electricity because their electrocytes contain numerous “subnanoscale” protein ion channels that can achieve highly selective and ultrafast ion transport. Despite increasing awareness of blue energy production through nanochannel membranes, achieving high-performance energy output remains considerably unexplored
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The source of the major solar energetic particle events from super active region 11944 Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 David H. Brooks, Stephanie L. Yardley
Shock waves associated with fast coronal mass ejections (CMEs) accelerate solar energetic particles (SEPs) in the long duration, gradual events that pose hazards to crewed spaceflight and near-Earth technological assets, but the source of the CME shock-accelerated plasma is still debated. Here, we use multi-messenger observations from the Heliophysics System Observatory to identify plasma confined
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Hallmarks of Alpha- and Betacoronavirus non-structural protein 7+8 complexes Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Boris Krichel, Ganesh Bylapudi, Christina Schmidt, Clement Blanchet, Robin Schubert, Lea Brings, Martin Koehler, Renato Zenobi, Dmitri Svergun, Kristina Lorenzen, Ramakanth Madhugiri, John Ziebuhr, Charlotte Uetrecht
Coronaviruses infect many different species including humans. The last two decades have seen three zoonotic coronaviruses, with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causing a pandemic in 2020. Coronaviral non-structural proteins (nsps) form the replication-transcription complex (RTC). Nsp7 and nsp8 interact with and regulate the RNA-dependent RNA-polymerase and other enzymes
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Hunting bats adjust their echolocation to receive weak prey echoes for clutter reduction Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Laura Stidsholt, Stefan Greif, Holger R. Goerlitz, Kristian Beedholm, Jamie Macaulay, Mark Johnson, Peter Teglberg Madsen
How animals extract information from their surroundings to guide motor patterns is central to their survival. Here, we use echo-recording tags to show how wild hunting bats adjust their sensory strategies to their prey and natural environment. When searching, bats maximize the chances of detecting small prey by using large sensory volumes. During prey pursuit, they trade spatial for temporal information
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Hyaluronan orders water molecules in its nanoscale extended hydration shells Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 J. Dedic, H. I. Okur, S. Roke
Hyaluronan (HA) is an anionic, highly hydrated bio-polyelectrolyte found in the extracellular environment, like the synovial fluid between joints. We explore the extended hydration shell structure of HA in water using femtosecond elastic second-harmonic scattering (fs-ESHS). HA enhances orientational water-water correlations. Angle-resolved fs-ESHS measurements and nonlinear optical modeling show that
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Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Biao Qiu, Doreen Matthies, Eva Fortea, Zhiheng Yu, Olga Boudker
Human excitatory amino acid transporter 3 (hEAAT3) mediates glutamate uptake in neurons, intestine, and kidney. Here, we report cryo-EM structures of hEAAT3 in several functional states where the transporter is empty, bound to coupled sodium ions only, or fully loaded with three sodium ions, a proton, and the substrate aspartate. The structures suggest that hEAAT3 operates by an elevator mechanism
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Coherent electric field manipulation of Fe3+ spins in PbTiO3 Sci. Adv. (IF 13.116) Pub Date : 2021-03-03 Junjie Liu, Valentin V. Laguta, Katherine Inzani, Weichuan Huang, Sujit Das, Ruchira Chatterjee, Evan Sheridan, Sinéad M. Griffin, Arzhang Ardavan, Ramamoorthy Ramesh
Magnetoelectrics, materials that exhibit coupling between magnetic and electric degrees of freedom, not only offer a rich environment for studying the fundamental materials physics of spin-charge coupling but also present opportunities for future information technology paradigms. We present results of electric field manipulation of spins in a ferroelectric medium using dilute ferric ion–doped lead
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Strong local, not global, controls on marine pyrite sulfur isotopes Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 V. Pasquier, R. N. Bryant, D. A. Fike, I. Halevy
Understanding variation in the sulfur isotopic composition of sedimentary pyrite (δ34Spyr) is motivated by the key role of sulfur biogeochemistry in regulating Earth’s surface oxidation state. Until recently, the impact of local depositional conditions on δ34Spyr has remained underappreciated, and stratigraphic variations in δ34Spyr were interpreted mostly to reflect global changes in biogeochemical
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The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Tom Hodgkinson, P. Monica Tsimbouri, Virginia Llopis-Hernandez, Paul Campsie, David Scurr, Peter G. Childs, David Phillips, Sam Donnelly, Julia A. Wells, Fergal J. O’Brien, Manuel Salmeron-Sanchez, Karl Burgess, Morgan Alexander, Massimo Vassalli, Richard O. C. Oreffo, Stuart Reid, David J. France, Matthew J. Dalby
Bioactive metabolites have wide-ranging biological activities and are a potential source of future research and therapeutic tools. Here, we use nanovibrational stimulation to induce osteogenic differentiation of mesenchymal stem cells, in the absence of off-target, nonosteogenic differentiation. We show that this differentiation method, which does not rely on the addition of exogenous growth factors
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Implementing graph-theoretic quantum algorithms on a silicon photonic quantum walk processor Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Xiaogang Qiang, Yizhi Wang, Shichuan Xue, Renyou Ge, Lifeng Chen, Yingwen Liu, Anqi Huang, Xiang Fu, Ping Xu, Teng Yi, Fufang Xu, Mingtang Deng, Jingbo B. Wang, Jasmin D. A. Meinecke, Jonathan C. F. Matthews, Xinlun Cai, Xuejun Yang, Junjie Wu
Applications of quantum walks can depend on the number, exchange symmetry and indistinguishability of the particles involved, and the underlying graph structures where they move. Here, we show that silicon photonics, by exploiting an entanglement-driven scheme, can realize quantum walks with full control over all these properties in one device. The device we realize implements entangled two-photon
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Microglia control small vessel calcification via TREM2 Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Yvette Zarb, Sucheta Sridhar, Sina Nassiri, Sebastian Guido Utz, Johanna Schaffenrath, Upasana Maheshwari, Elisabeth J. Rushing, K. Peter R. Nilsson, Mauro Delorenzi, Marco Colonna, Melanie Greter, Annika Keller
Microglia participate in central nervous system (CNS) development and homeostasis and are often implicated in modulating disease processes. However, less is known about the role of microglia in the biology of the neurovascular unit (NVU). In particular, data are scant on whether microglia are involved in CNS vascular pathology. In this study, we use a mouse model of primary familial brain calcification
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Exploring complex graphs using three-dimensional quantum walks of correlated photons Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Max Ehrhardt, Robert Keil, Lukas J. Maczewsky, Christoph Dittel, Matthias Heinrich, Alexander Szameit
Graph representations are a powerful concept for solving complex problems across natural science, as patterns of connectivity can give rise to a multitude of emergent phenomena. Graph-based approaches have proven particularly fruitful in quantum communication and quantum search algorithms in highly branched quantum networks. Here, we introduce a previously unidentified paradigm for the direct experimental
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A unified vegetation index for quantifying the terrestrial biosphere Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Gustau Camps-Valls, Manuel Campos-Taberner, Álvaro Moreno-Martínez, Sophia Walther, Grégory Duveiller, Alessandro Cescatti, Miguel D. Mahecha, Jordi Muñoz-Marí, Francisco Javier García-Haro, Luis Guanter, Martin Jung, John A. Gamon, Markus Reichstein, Steven W. Running
Empirical vegetation indices derived from spectral reflectance data are widely used in remote sensing of the biosphere, as they represent robust proxies for canopy structure, leaf pigment content, and, subsequently, plant photosynthetic potential. Here, we generalize the broad family of commonly used vegetation indices by exploiting all higher-order relations between the spectral channels involved
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Emergent stereoselective interactions and self-recognition in polar chiral active ellipsoids Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Pragya Arora, A. K. Sood, Rajesh Ganapathy
In many active matter systems, particle trajectories have a well-defined handedness or chirality. Whether such chiral activity can introduce stereoselective interactions between particles is not known. Here, we developed a strategy to tune the nature of chiral activity of three-dimensionally printed granular ellipsoids without altering their shape or size. In vertically agitated monolayers of these
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Extended amygdala-parabrachial circuits alter threat assessment and regulate feeding Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Andrew T. Luskin, Dionnet L. Bhatti, Bernard Mulvey, Christian E. Pedersen, Kasey S. Girven, Hannah Oden-Brunson, Kate Kimbell, Taylor Blackburn, Abbie Sawyer, Robert W. Gereau, Joseph D. Dougherty, Michael R. Bruchas
An animal’s evolutionary success depends on the ability to seek and consume foods while avoiding environmental threats. However, how evolutionarily conserved threat detection circuits modulate feeding is unknown. In mammals, feeding and threat assessment are strongly influenced by the parabrachial nucleus (PBN), a structure that responds to threats and inhibits feeding. Here, we report that the PBN
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People accurately predict the transition probabilities between actions Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Mark A. Thornton, Diana I. Tamir
Social life is a complex dance. To coordinate gracefully with one’s partners, one must predict their actions. Here, we investigated how people predict others’ actions. We hypothesized that people can accurately predict others’ future actions based on knowledge of their current actions, coupled with knowledge of action transitions. To test whether people have accurate knowledge of the transition probabilities
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Diversified transcriptional responses of myeloid and glial cells in spinal cord injury shaped by HDAC3 activity Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Shalaka Wahane, Xianxiao Zhou, Xiang Zhou, Lei Guo, Marie-Sophie Friedl, Michael Kluge, Aarthi Ramakrishnan, Li Shen, Caroline C. Friedel, Bin Zhang, Roland H. Friedel, Hongyan Zou
The innate immune response influences neural repair after spinal cord injury (SCI). Here, we combined myeloid-specific transcriptomics and single-cell RNA sequencing to uncover not only a common core but also temporally distinct gene programs in injury-activated microglia and macrophages (IAM). Intriguingly, we detected a wide range of microglial cell states even in healthy spinal cord. Upon injury
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Long-lived charge separation following pump-wavelength–dependent ultrafast charge transfer in graphene/WS2 heterostructures Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Shuai Fu, Indy du Fossé, Xiaoyu Jia, Jingyin Xu, Xiaoqing Yu, Heng Zhang, Wenhao Zheng, Sven Krasel, Zongping Chen, Zhiming M. Wang, Klaas-Jan Tielrooij, Mischa Bonn, Arjan J. Houtepen, Hai I. Wang
Van der Waals heterostructures consisting of graphene and transition metal dichalcogenides have shown great promise for optoelectronic applications. However, an in-depth understanding of the critical processes for device operation, namely, interfacial charge transfer (CT) and recombination, has so far remained elusive. Here, we investigate these processes in graphene-WS2 heterostructures by complementarily
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Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Amélie Cachot, Mariia Bilous, Yen-Cheng Liu, Xiaokang Li, Margaux Saillard, Mara Cenerenti, Georg Alexander Rockinger, Tania Wyss, Philippe Guillaume, Julien Schmidt, Raphaël Genolet, Giuseppe Ercolano, Maria Pia Protti, Walter Reith, Kalliopi Ioannidou, Laurence de Leval, Joseph A. Trapani, George Coukos, Alexandre Harari, Daniel E. Speiser, Alexander Mathis, David Gfeller, Hatice Altug, Pedro Romero
CD4 T cells have been implicated in cancer immunity for their helper functions. Moreover, their direct cytotoxic potential has been shown in some patients with cancer. Here, by mining single-cell RNA-seq datasets, we identified CD4 T cell clusters displaying cytotoxic phenotypes in different human cancers, resembling CD8 T cell profiles. Using the peptide-MHCII-multimer technology, we confirmed ex
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The global network of ports supporting high seas fishing Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Jorge P. Rodríguez, Juan Fernández-Gracia, Carlos M. Duarte, Xabier Irigoien, Víctor M. Eguíluz
Fisheries in waters beyond national jurisdiction (“high seas”) are difficult to monitor and manage. Their regulation for sustainability requires critical information on how fishing effort is distributed across fishing and landing areas, including possible border effects at the exclusive economic zone (EEZ) limits. We infer the global network linking harbors supporting fishing vessels to fishing areas
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Ultrasound Doppler-guided real-time navigation of a magnetic microswarm for active endovascular delivery Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Qianqian Wang, Kai Fung Chan, Kathrin Schweizer, Xingzhou Du, Dongdong Jin, Simon Chun Ho Yu, Bradley J. Nelson, Li Zhang
Swarming micro/nanorobots offer great promise in performing targeted delivery inside diverse hard-to-reach environments. However, swarm navigation in dynamic environments challenges delivery capability and real-time swarm localization. Here, we report a strategy to navigate a nanoparticle microswarm in real time under ultrasound Doppler imaging guidance for active endovascular delivery. A magnetic
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Late-stage stitching enabled by manganese-catalyzed C─H activation: Peptide ligation and access to cyclopeptides Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Nikolaos Kaplaneris, Felix Kaltenhӓuser, Giedre Sirvinskaite, Shuang Fan, Tiago De Oliveira, Lena-Christin Conradi, Lutz Ackermann
Bioorthogonal late-stage diversification of structurally complex peptides bears enormous potential for drug discovery and molecular imaging. Despite major accomplishments, these strategies heavily rely on noble-metal catalysis. Herein, we report on a manganese(I)-catalyzed peptide C─H hydroarylation that enabled the stitching of peptidic and sugar fragments, under exceedingly mild and racemization-free
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Molecular architecture of the endocytic TPLATE complex Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Klaas Yperman, Jie Wang, Dominique Eeckhout, Joanna Winkler, Lam Dai Vu, Michael Vandorpe, Peter Grones, Evelien Mylle, Michael Kraus, Romain Merceron, Jonah Nolf, Eliana Mor, Pieter De Bruyn, Remy Loris, Martin Potocký, Savvas N. Savvides, Bert De Rybel, Geert De Jaeger, Daniël Van Damme, Roman Pleskot
Eukaryotic cells rely on endocytosis to regulate their plasma membrane proteome and lipidome. Most eukaryotic groups, except fungi and animals, have retained the evolutionary ancient TSET complex as an endocytic regulator. Unlike other coatomer complexes, structural insight into TSET is lacking. Here, we reveal the molecular architecture of plant TSET [TPLATE complex (TPC)] using an integrative structural
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A dynein-associated photoreceptor protein prevents ciliary acclimation to blue light Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Osamu Kutomi, Ryosuke Yamamoto, Keiko Hirose, Katsutoshi Mizuno, Yuuhei Nakagiri, Hiroshi Imai, Akira Noga, Jagan Mohan Obbineni, Noemi Zimmermann, Masako Nakajima, Daisuke Shibata, Misa Shibata, Kogiku Shiba, Masaki Kita, Hideo Kigoshi, Yui Tanaka, Yuya Yamasaki, Yuma Asahina, Chihong Song, Mami Nomura, Mamoru Nomura, Ayako Nakajima, Mia Nakachi, Lixy Yamada, Shiori Nakazawa, Hitoshi Sawada, Kazuyoshi
Light-responsive regulation of ciliary motility is known to be conducted through modulation of dyneins, but the mechanism is not fully understood. Here, we report a novel subunit of the two-headed f/I1 inner arm dynein, named DYBLUP, in animal spermatozoa and a unicellular green alga. This subunit contains a BLUF (sensors of blue light using FAD) domain that appears to directly modulate dynein activity
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Insulin signaling in AgRP neurons regulates meal size to limit glucose excursions and insulin resistance Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 Garron T. Dodd, Seung Jae Kim, Mathieu Méquinion, Chrysovalantou E. Xirouchaki, Jens C. Brüning, Zane B. Andrews, Tony Tiganis
The importance of hypothalamic insulin signaling on feeding and glucose metabolism remains unclear. We report that insulin acts on AgRP neurons to acutely decrease meal size and thereby limit postprandial glucose and insulin excursions. The promotion of insulin signaling in AgRP neurons decreased meal size without altering total caloric intake, whereas the genetic ablation of the insulin receptor had
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Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver Sci. Adv. (IF 13.116) Pub Date : 2021-02-26 M. Kim, M. Jeong, S. Hur, Y. Cho, J. Park, H. Jung, Y. Seo, H. A. Woo, K. T. Nam, K. Lee, H. Lee
Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here, we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and
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Spatial heterogeneity and environmental predictors of permafrost region soil organic carbon stocks Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Umakant Mishra, Gustaf Hugelius, Eitan Shelef, Yuanhe Yang, Jens Strauss, Alexey Lupachev, Jennifer W. Harden, Julie D. Jastrow, Chien-Lu Ping, William J. Riley, Edward A. G. Schuur, Roser Matamala, Matthias Siewert, Lucas E. Nave, Charles D. Koven, Matthias Fuchs, Juri Palmtag, Peter Kuhry, Claire C. Treat, Sebastian Zubrzycki, Forrest M. Hoffman, Bo Elberling, Philip Camill, Alexandra Veremeeva,
Large stocks of soil organic carbon (SOC) have accumulated in the Northern Hemisphere permafrost region, but their current amounts and future fate remain uncertain. By analyzing dataset combining >2700 soil profiles with environmental variables in a geospatial framework, we generated spatially explicit estimates of permafrost-region SOC stocks, quantified spatial heterogeneity, and identified key environmental
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Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Zhengnan Yang, Wei Wang, Linjie Zhao, Xin Wang, Ryan C. Gimple, Lian Xu, Yuan Wang, Jeremy N. Rich, Shengtao Zhou
Ovarian cancer represents a highly lethal disease that poses a substantial burden for females, with four main molecular subtypes carrying distinct clinical outcomes. Here, we demonstrated that plasma cells, a subset of antibody-producing B cells, were enriched in the mesenchymal subtype of high-grade serous ovarian cancers (HGSCs). Plasma cell abundance correlated with the density of mesenchymal cells
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Chimpanzees behave prosocially in a group-specific manner Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Edwin J. C. van Leeuwen, Sarah E. DeTroy, Stephan P. Kaufhold, Clara Dubois, Sebastian Schütte, Josep Call, Daniel B. M. Haun
Chimpanzees act cooperatively in the wild, but whether they afford benefits to others, and whether their tendency to act prosocially varies across communities, is unclear. Here, we show that chimpanzees from neighboring communities provide valuable resources to group members at personal cost, and that the magnitude of their prosocial behavior is group specific. Provided with a resource-donation experiment
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Enhancement of liver-directed transgene expression at initial and repeat doses of AAV vectors admixed with ImmTOR nanoparticles Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Petr O. Ilyinskii, Alicia M. Michaud, Christopher J. Roy, Gina L. Rizzo, Stephanie L. Elkins, Teresa Capela, Aparajita C. Chowdhury, Sheldon S. Leung, Takashi K. Kishimoto
Systemic AAV (adeno-associated virus) gene therapy is a promising approach for the treatment of inborn errors of metabolism, but questions remain regarding its potency and durability. Tolerogenic ImmTOR nanoparticles encapsulating rapamycin have been shown to block the formation of neutralizing anti-capsid antibodies, thereby enabling vector re-administration. Here, we further demonstrate that ImmTOR
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The unequal impact of parenthood in academia Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Allison C. Morgan, Samuel F. Way, Michael J. D. Hoefer, Daniel B. Larremore, Mirta Galesic, Aaron Clauset
Across academia, men and women tend to publish at unequal rates. Existing explanations include the potentially unequal impact of parenthood on scholarship, but a lack of appropriate data has prevented its clear assessment. Here, we quantify the impact of parenthood on scholarship using an extensive survey of the timing of parenthood events, longitudinal publication data, and perceptions of research
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Groundwater depletion will reduce cropping intensity in India Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Meha Jain, Ram Fishman, Pinki Mondal, Gillian L. Galford, Nishan Bhattarai, Shahid Naeem, Upmanu Lall, Balwinder-Singh, Ruth S. DeFries
Groundwater depletion is becoming a global threat to food security, yet the ultimate impacts of depletion on agricultural production and the efficacy of available adaptation strategies remain poorly quantified. We use high-resolution satellite and census data from India, the world’s largest consumer of groundwater, to quantify the impacts of groundwater depletion on cropping intensity, a crucial driver
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Atmospheric aging enhances the ice nucleation ability of biomass-burning aerosol Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Lydia G. Jahl, Thomas A. Brubaker, Michael J. Polen, Leif G. Jahn, Kerrigan P. Cain, Bailey B. Bowers, William D. Fahy, Sara Graves, Ryan C. Sullivan
Ice-nucleating particles (INPs) in biomass-burning aerosol (BBA) that affect cloud glaciation, microphysics, precipitation, and radiative forcing were recently found to be driven by the production of mineral phases. BBA experiences extensive chemical aging as the smoke plume dilutes, and we explored how this alters the ice activity of the smoke using simulated atmospheric aging of authentic BBA in
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Islet expression of type I interferon response sensors is associated with immune infiltration and viral infection in type 1 diabetes Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Paola S. Apaolaza, Diana Balcacean, Jose Zapardiel-Gonzalo, Grace Nelson, Nataliya Lenchik, Pouria Akhbari, Ivan Gerling, Sarah J. Richardson, Teresa Rodriguez-Calvo, nPOD-Virus Group
Previous results indicate the presence of an interferon (IFN) signature in type 1 diabetes (T1D), capable of inducing chronic inflammation and compromising b cell function. Here, we determined the expression of the IFN response markers MxA, PKR, and HLA-I in the islets of autoantibody-positive and T1D donors. We found that these markers can be coexpressed in the same islet, are more abundant in insulin-containing
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Injectable hydrogel with MSNs/microRNA-21-5p delivery enables both immunomodification and enhanced angiogenesis for myocardial infarction therapy in pigs Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Yan Li, Xin Chen, Ronghua Jin, Lu Chen, Ming Dang, Hao Cao, Yun Dong, Bolei Cai, Guo Bai, J. Justin Gooding, Shiyu Liu, Duohong Zou, Zhiyuan Zhang, Chi Yang
Current therapeutic strategies such as angiogenic therapy and anti-inflammatory therapy for treating myocardial infarction have limited success. An effective approach may benefit from resolution of excessive inflammation combined with enhancement of angiogenesis. Here, we developed a microRNA-21-5p delivery system using functionalized mesoporous silica nanoparticles (MSNs) with additional intrinsic
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Functional antagonism of chromatin modulators regulates epithelial-mesenchymal transition Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Michela Serresi, Sonia Kertalli, Lifei Li, Matthias Jürgen Schmitt, Yuliia Dramaretska, Jikke Wierikx, Danielle Hulsman, Gaetano Gargiulo
Epithelial-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to modulate proliferation, migration, and stress response. Whereas kinase signaling is believed to be an EMT driver, the molecular mechanisms underlying epithelial-mesenchymal interconversion are incompletely understood. Here, we show that the impact of chromatin regulators on EMT interconversion is broader
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Cryo-EM structure of enteric adenovirus HAdV-F41 highlights structural variations among human adenoviruses Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Marta Pérez-Illana, Marta Martínez, Gabriela N. Condezo, Mercedes Hernando-Pérez, Casandra Mangroo, Martha Brown, Roberto Marabini, Carmen San Martín
Enteric adenoviruses, one of the main causes of viral gastroenteritis in the world, must withstand the harsh conditions found in the gut. This requirement suggests that capsid stability must be different from that of other adenoviruses. We report the 4-Å-resolution structure of a human enteric adenovirus, HAdV-F41, and compare it with that of other adenoviruses with respiratory (HAdV-C5) and ocular
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Intrinsically stretchable organic light-emitting diodes Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Jin-Hoon Kim, Jin-Woo Park
Soft and conformable optoelectronic devices for wearable and implantable electronics require mechanical stretchability. However, very few researches have been done for intrinsically stretchable light-emitting diodes. Here, we present an intrinsically stretchable organic light-emitting diode, whose constituent materials are all highly stretchable. The resulting intrinsically stretchable organic light-emitting
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Glucocorticoid counteracts cellular mechanoresponses by LINC01569-dependent glucocorticoid receptor–mediated mRNA decay Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Huayu Zhu, Jun Li, Yize Li, Zhao Zheng, Hao Guan, Hongtao Wang, Ke Tao, Jiaqi Liu, Yunchuan Wang, Wanfu Zhang, Chao Li, Jie Li, Lintao Jia, Wendong Bai, Dahai Hu
Mechanical stimuli on cells and mechanotransduction are essential in many biological and pathological processes. Glucocorticoid is an important hormone, roles, and mechanisms of which in cellular mechanotransduction remain unknown. Here, we report that glucocorticoid counteracted cellular mechanoresponses dependently on a novel long noncoding RNA (lncRNA), LINC01569. Further, LINC01569 mediated glucocorticoid
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Goal-dependent tuning of muscle spindle receptors during movement preparation Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Stylianos Papaioannou, Michael Dimitriou
Voluntary movements are believed to undergo preparation before they are executed. Preparatory activity can benefit reaction time and the quality of planned movements, but the neural mechanisms at work during preparation are unclear. For example, there are no overt changes in muscle force during preparation. Here, using an instructed-delay manual task, we demonstrate a decrease in human muscle afferent
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Nanoscale optical writing through upconversion resonance energy transfer Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 S. Lamon, Y. Wu, Q. Zhang, X. Liu, M. Gu
Nanoscale optical writing using far-field super-resolution methods provides an unprecedented approach for high-capacity data storage. However, current nanoscale optical writing methods typically rely on photoinitiation and photoinhibition with high beam intensity, high energy consumption, and short device life span. We demonstrate a simple and broadly applicable method based on resonance energy transfer
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The regulatory enzymes and protein substrates for the lysine β-hydroxybutyrylation pathway Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 He Huang, Di Zhang, Yejing Weng, Kyle Delaney, Zhanyun Tang, Cong Yan, Shankang Qi, Chao Peng, Philip A. Cole, Robert G. Roeder, Yingming Zhao
Metabolism-mediated epigenetic changes represent an adapted mechanism for cellular signaling, in which lysine acetylation and methylation have been the historical focus of interest. We recently discovered a β-hydroxybutyrate–mediated epigenetic pathway that couples metabolism to gene expression. However, its regulatory enzymes and substrate proteins remain unknown, hindering its functional study. Here
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Globally distributed iridium layer preserved within the Chicxulub impact structure Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Steven Goderis, Honami Sato, Ludovic Ferrière, Birger Schmitz, David Burney, Pim Kaskes, Johan Vellekoop, Axel Wittmann, Toni Schulz, Stepan M. Chernonozhkin, Philippe Claeys, Sietze J. de Graaff, Thomas Déhais, Niels J. de Winter, Mikael Elfman, Jean-Guillaume Feignon, Akira Ishikawa, Christian Koeberl, Per Kristiansson, Clive R. Neal, Jeremy D. Owens, Martin Schmieder, Matthias Sinnesael, Frank Vanhaecke
The Cretaceous-Paleogene (K-Pg) mass extinction is marked globally by elevated concentrations of iridium, emplaced by a hypervelocity impact event 66 million years ago. Here, we report new data from four independent laboratories that reveal a positive iridium anomaly within the peak-ring sequence of the Chicxulub impact structure, in drill core recovered by IODP-ICDP Expedition 364. The highest concentration
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Large sulfur isotope fractionation in lunar volcanic glasses reveals the magmatic differentiation and degassing of the Moon Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Alberto E. Saal, Erik H. Hauri
Sulfur isotope variations in mantle-derived lavas provide important constraints on the evolution of planetary bodies. Here, we report the first in situ measurements of sulfur isotope ratios dissolved in primitive volcanic glasses and olivine-hosted melt inclusions recovered from the Moon by the Apollo 15 and 17 missions. The new data reveal large variations in 34S/32S ratios, which positively correlates
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The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Fei Yi, Ying Zhang, Zhijun Wang, Zhuo Wang, Ziwei Li, Tingting Zhou, Hongde Xu, Jingwei Liu, Bo Jiang, Xiaoman Li, Liang Wang, Ning Bai, Qiqiang Guo, Yi Guan, Yanling Feng, Zhiyong Mao, Guangjian Fan, Shengping Zhang, Chuangui Wang, Longyue Cao, Brian P. O’Rourke, Yang Wang, Yanmei Wu, Boquan Wu, Shilong You, Naijin Zhang, Junlin Guan, Xiaoyu Song, Yingxian Sun, Shi Wei, Liu Cao
Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses of human cancerous tissue revealed that the NAD-dependent deacetylase SIRT2 is up-regulated in early-stage
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Cryo-EM structure of a proton-activated chloride channel TMEM206 Sci. Adv. (IF 13.116) Pub Date : 2021-02-24 Zengqin Deng, Yonghui Zhao, Jing Feng, Jingying Zhang, Haiyan Zhao, Michael J. Rau, James A. J. Fitzpatrick, Hongzhen Hu, Peng Yuan
TMEM206 has been recently identified as an evolutionarily conserved chloride channel that underlies ubiquitously expressed, proton-activated, outwardly rectifying anion currents. Here, we report the cryo–electron microscopy structure of pufferfish TMEM206, which forms a trimeric channel, with each subunit comprising two transmembrane segments and a large extracellular domain. An ample vestibule in
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