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  •   Plasma lipids and growth faltering: A longitudinal cohort study in rural Gambian children
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Gerard Bryan Gonzales, Daniella Brals, Bakary Sonko, Fatou Sosseh, Andrew M. Prentice, Sophie E. Moore, Albert Koulman

    Growth faltering in children arises from metabolic and endocrine dysfunction driven by complex interactions between poor diet, persistent infections, and immunopathology. Here, we determined the progression of the plasma lipidome among Gambian children (n = 409) and assessed its association with growth faltering during the first 2 years of life using the panel vector autoregression method. We further

  •   The prevalence and specificity of local protein synthesis during neuronal synaptic plasticity
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Chao Sun, Andreas Nold, Claudia M. Fusco, Vidhya Rangaraju, Tatjana Tchumatchenko, Mike Heilemann, Erin M. Schuman

    To supply proteins to their vast volume, neurons localize mRNAs and ribosomes in dendrites and axons. While local protein synthesis is required for synaptic plasticity, the abundance and distribution of ribosomes and nascent proteins near synapses remain elusive. Here, we quantified the occurrence of local translation and visualized the range of synapses supplied by nascent proteins during basal and

  •   Establishment of strigolactone-producing bacterium-yeast consortium
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Sheng Wu, Xiaoqiang Ma, Anqi Zhou, Alex Valenzuela, Kang Zhou, Yanran Li

    Strigolactones (SLs) are a class of phytohormones playing diverse roles in plant growth and development, yet the limited access to SLs is largely impeding SL-based foundational investigations and applications. Here, we developed Escherichia coli–Saccharomyces cerevisiae consortia to establish a microbial biosynthetic platform for the synthesis of various SLs, including carlactone, carlactonoic acid

  •   The role of protected areas in maintaining natural vegetation in Brazil
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Daniel Gonçalves-Souza, Bruno Vilela, Ben Phalan, Ricardo Dobrovolski

    The destruction of natural vegetation in recent decades has been concentrated in the tropics, where ecosystem processes underpin global homeostasis and harbor most of the world’s biodiversity. Protected areas (PAs) are the primary societal tool to avoid this destruction, yet their effectiveness is often questioned. Here, we quantified the impact of PAs and indigenous lands in avoiding 34 years of vegetation

  •   Ancient genomics reveals tripartite origins of Japanese populations
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Niall P. Cooke, Valeria Mattiangeli, Lara M. Cassidy, Kenji Okazaki, Caroline A. Stokes, Shin Onbe, Satoshi Hatakeyama, Kenichi Machida, Kenji Kasai, Naoto Tomioka, Akihiko Matsumoto, Masafumi Ito, Yoshitaka Kojima, Daniel G. Bradley, Takashi Gakuhari, Shigeki Nakagome

    Prehistoric Japan underwent rapid transformations in the past 3000 years, first from foraging to wet rice farming and then to state formation. A long-standing hypothesis posits that mainland Japanese populations derive dual ancestry from indigenous Jomon hunter-gatherer-fishers and succeeding Yayoi farmers. However, the genomic impact of agricultural migration and subsequent sociocultural changes remains

  •   Scalable 3D printing of aperiodic cellular structures by rotational stacking of integral image formation
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Seok Kim, Jordan J. Handler, Young Tae Cho, George Barbastathis, Nicholas X. Fang

    The limitation of projection microstereolithography in additive manufacturing methods is that they typically use a single-aperture imaging configuration, which restricts their ability to produce microstructures in large volumes owing to the trade-off between image resolution and image field area. Here, we propose an integral lithography based on integral image reconstruction coupled with a planar lens

  •   Volcanic CO2 tracks the incubation period of basaltic paroxysms
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Alessandro Aiuppa, Marcello Bitetto, Dario Delle Donne, Francesco Paolo La Monica, Giancarlo Tamburello, Diego Coppola, Massimo Della Schiava, Lorenzo Innocenti, Giorgio Lacanna, Marco Laiolo, Francesco Massimetti, Marco Pistolesi, Maria Cristina Silengo, Maurizio Ripepe

    The ordinarily benign activity of basaltic volcanoes is periodically interrupted by violent paroxysmal explosions ranging in size from Hawaiian to Plinian in the most extreme examples. These paroxysms often occur suddenly and with limited or no precursors, leaving their causal mechanisms still incompletely understood. Two such events took place in summer 2019 at Stromboli, a volcano otherwise known

  •   Load-bearing entanglements in polymer glasses
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Cynthia Bukowski, Tianren Zhang, Robert A. Riggleman, Alfred J. Crosby

    Through a combined approach of experiment and simulation, this study quantifies the role of entanglements in determining the mechanical properties of glassy polymer blends. Uniaxial extension experiments on 100-nm films containing a bidisperse mixture of polystyrene enable quantitative comparison with molecular dynamics (MD) simulations of a coarse-grained model for polymer glasses, where the bidisperse

  •   Racial attention deficit
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Sheen S. Levine, Charlotte Reypens, David Stark

    Despite efforts toward equity in organizations and institutions, minority members report that they are often ignored, their contributions undervalued. Against this backdrop, we conduct a large-sample, multiyear experimental study to investigate patterns of attention. The findings provide causal evidence of a racial attention deficit: Even when in their best interest, White Americans pay less attention

  •   Millimeter-scale chip–based supercontinuum generation for optical coherence tomography
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Xingchen Ji, Diana Mojahed, Yoshitomo Okawachi, Alexander L. Gaeta, Christine P. Hendon, Michal Lipson

    Supercontinuum sources for optical coherence tomography (OCT) have raised great interest as they provide broad bandwidth to enable high resolution and high power to improve imaging sensitivity. Commercial fiber-based supercontinuum systems require high pump powers to generate broad bandwidth and customized optical filters to shape/attenuate the spectra. They also have limited sensitivity and depth

  •   Cell patterning by secretion-induced plasma membrane flows
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Veneta Gerganova, Iker Lamas, David M. Rutkowski, Aleksandar Vještica, Daniela Gallo Castro, Vincent Vincenzetti, Dimitrios Vavylonis, Sophie G. Martin

    Cells self-organize using reaction-diffusion and fluid-flow principles. Whether bulk membrane flows contribute to cell patterning has not been established. Here, using mathematical modeling, optogenetics, and synthetic probes, we show that polarized exocytosis causes lateral membrane flows away from regions of membrane insertion. Plasma membrane–associated proteins with sufficiently low diffusion and/or

  •   An asymmetric mechanical code ciphers curvature-dependent proprioceptor activity
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Ravi Das, Li-Chun Lin, Frederic Català-Castro, Nawaphat Malaiwong, Neus Sanfeliu-Cerdán, Montserrat Porta-de-la-Riva, Aleksandra Pidde, Michael Krieg

    A repetitive gait cycle is an archetypical component within the behavioral repertoire of many animals including humans. It originates from mechanical feedback within proprioceptors to adjust the motor program during locomotion and thus leads to a periodic orbit in a low-dimensional space. Here, we investigate the mechanics, molecules, and neurons responsible for proprioception in Caenorhabditis elegans

  •   High- and low-latitude forcings drive Atacama Desert rainfall variations over the past 16,000 years
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Francisco J. González-Pinilla, Claudio Latorre, Maisa Rojas, John Houston, M. Ignacia Rocuant, Antonio Maldonado, Calogero M. Santoro, Jay Quade, Julio L. Betancourt

    Late Quaternary precipitation dynamics in the central Andes have been linked to both high- and low-latitude atmospheric teleconnections. We use present-day relationships between fecal pellet diameters from ashy chinchilla rats (Abrocoma cinerea) and mean annual rainfall to reconstruct the timing and magnitude of pluvials (wet episodes) spanning the past 16,000 years in the Atacama Desert based on 81

  •   Massively parallel quantification of phenotypic heterogeneity in single-cell drug responses
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Benjamin B. Yellen, Jon S. Zawistowski, Eric A. Czech, Caleb I. Sanford, Elliott D. SoRelle, Micah A. Luftig, Zachary G. Forbes, Kris C. Wood, Jeff Hammerbacher

    Single-cell analysis tools have made substantial advances in characterizing genomic heterogeneity; however, tools for measuring phenotypic heterogeneity have lagged due to the increased difficulty of handling live biology. Here, we report a single-cell phenotyping tool capable of measuring image-based clonal properties at scales approaching 100,000 clones per experiment. These advances are achieved

  •   Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Manuel F. López-Aranda, Ishanu Chattopadhyay, Gayle M. Boxx, Elizabeth R. Fraley, Tawnie K. Silva, Miou Zhou, Miranda Phan, Isaiah Herrera, Sunrae Taloma, Rochelle Mandanas, Karen Bach, Michael Gandal, Daniel H. Geschwind, Genhong Cheng, Andrey Rzhetsky, Stephanie A. White, Alcino J. Silva

    There is growing evidence that prenatal immune activation contributes to neuropsychiatric disorders. Here, we show that early postnatal immune activation resulted in profound impairments in social behavior, including in social memory in adult male mice heterozygous for a gene responsible for tuberous sclerosis complex (Tsc2+/−), a genetic disorder with high prevalence of autism. Early postnatal immune

  •   Targeting lysophospholipid acid receptor 1 and ROCK kinases promotes antiviral innate immunity
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Chi Zhang, Weiyun Li, Xiaobo Lei, Zhenfei Xie, Linlin Qi, Hui Wang, Xia Xiao, Jun Xiao, Yuxiao Zheng, Chen Dong, Xin Zheng, Shiyang Chen, Jianfeng Chen, Bing Sun, Jun Qin, Qiwei Zhai, Jinsong Li, Bin Wei, Jianwei Wang, Hongyan Wang

    Growing evidence indicates the vital role of lipid metabolites in innate immunity. The lipid lysophosphatidic acid (LPA) concentrations are enhanced in patients upon HCV or SARS-CoV-2 infection, but the function of LPA and its receptors in innate immunity is largely unknown. Here, we found that viral infection promoted the G protein–coupled receptor LPA1 expression, and LPA restrained type I/III interferon

  •   Diversity of non-equilibrium patterns and emergence of activity in confined electrohydrodynamically driven liquids
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Geet Raju, Nikos Kyriakopoulos, Jaakko V. I. Timonen

    Spontaneous emergence of organized states in materials driven by non-equilibrium conditions is of notable fundamental and technological interest. In many cases, the states are complex, and their emergence is challenging to predict. Here, we show that an unexpectedly diverse collection of dissipative organized states emerges in a simple system of two liquids under planar confinement when driven by electrohydrodynamic

  •   Ultrafast, sensitive, and portable detection of COVID-19 IgG using flexible organic electrochemical transistors
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Hong Liu, Anneng Yang, Jiajun Song, Naixiang Wang, Puiyiu Lam, Yuenling Li, Helen Ka-wai Law, Feng Yan

    The outbreak of COVID-19 and its continued spread have seriously threatened public health. Antibody testing is essential for infection diagnosis, seroepidemiological analysis, and vaccine evaluation. However, convenient, fast, and accurate antibody detection remains a challenge in this protracted battle. Here, we report an ultrafast, low-cost, label-free, and portable SARS-CoV-2 immunoglobulin G (IgG)

  •   Overcoming the quantum limit of optical amplification in monolithic waveguides
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Zhichao Ye, Ping Zhao, Krishna Twayana, Magnus Karlsson, Victor Torres-Company, Peter A. Andrekson

    Optical amplifiers are essential in numerous photonic applications. Parametric amplifiers, relying on a nonlinear material to create amplification, are uniquely promising as they can amplify without generating excess noise. Here, we demonstrate amplification based on the third-order nonlinearity in a single chip while, in addition, reporting a noise figure significantly below the conventional quantum

  •   Capturing 3D atomic defects and phonon localization at the 2D heterostructure interface
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Xuezeng Tian, Xingxu Yan, Georgios Varnavides, Yakun Yuan, Dennis S. Kim, Christopher J. Ciccarino, Polina Anikeeva, Ming-Yang Li, Lain-Jong Li, Prineha Narang, Xiaoqing Pan, Jianwei Miao

    The three-dimensional (3D) local atomic structures and crystal defects at the interfaces of heterostructures control their electronic, magnetic, optical, catalytic, and topological quantum properties but have thus far eluded any direct experimental determination. Here, we use atomic electron tomography to determine the 3D local atomic positions at the interface of a MoS2-WSe2 heterojunction with picometer

  •   TIPE2 is a checkpoint of natural killer cell maturation and antitumor immunity
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Jiacheng Bi, Chen Cheng, Chaoyue Zheng, Chen Huang, Xiaohu Zheng, Xiaochun Wan, Youhai H. Chen, Zhigang Tian, Haoyu Sun

    The maturation process of NK cells determines their functionality during which IL-15 plays a critical role. However, very few checkpoints specifically targeting this process have been discovered. Here, we report that TIPE2 expression gradually increased during NK cell ontogenesis correlating to their maturation stages in both mice and humans. NK-specific TIPE2 deficiency increased mature NK cells in

  •   Biological resurfacing in a canine model of hip osteoarthritis
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Bradley T. Estes, Masataka Enomoto, Franklin T. Moutos, Megan A. Carson, Jeffrey M. Toth, Peter Eggert, Jonathan Stallrich, Vincent P. Willard, Deborah J. Veis, Dianne Little, Farshid Guilak, B. Duncan X. Lascelles

    Articular cartilage has unique load-bearing properties but has minimal capacity for intrinsic repair. Here, we used three-dimensional weaving, additive manufacturing, and autologous mesenchymal stem cells to create a tissue-engineered, bicomponent implant to restore hip function in a canine hip osteoarthritis model. This resorbable implant was specifically designed to function mechanically from the

  •   The carrier transition from Li atoms to Li vacancies in solid-state lithium alloy anodes
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Yang Lu, Chen-Zi Zhao, Rui Zhang, Hong Yuan, Li-Peng Hou, Zhong-Heng Fu, Xiang Chen, Jia-Qi Huang, Qiang Zhang

    The stable cycling of energy-dense solid-state batteries is highly relied on the kinetically stable solid-state Li alloying reactions. The Li metal precipitation at solid-solid interfaces is the primary cause of interface fluctuations and battery failures, whose formation requires a clear mechanism interpretation, especially on the key kinetic short board. Here, we introduce the lithium alloy anode

  •   Extinction of austral diatoms in response to large-scale climate dynamics in Antarctica
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Eveline Pinseel, Bart Van de Vijver, Alexander P. Wolfe, Margaret Harper, Dermot Antoniades, Allan C. Ashworth, Luc Ector, Adam R. Lewis, Bianca Perren, Dominic A. Hodgson, Koen Sabbe, Elie Verleyen, Wim Vyverman

    Despite evidence for microbial endemism, an understanding of the impact of geological and paleoclimate events on the evolution of regional protist communities remains elusive. Here, we provide insights into the biogeographical history of Antarctic freshwater diatoms, using lacustrine fossils from mid-Miocene and Quaternary Antarctica, and dovetail this dataset with a global inventory of modern freshwater

  •   Social prediction modulates activity of macaque superior temporal cortex
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Lea Roumazeilles, Matthias Schurz, Mathilde Lojkiewiez, Lennart Verhagen, Urs Schüffelgen, Kevin Marche, Ali Mahmoodi, Andrew Emberton, Kelly Simpson, Olivier Joly, Mehdi Khamassi, Matthew F. S. Rushworth, Rogier B. Mars, Jérôme Sallet

    The ability to attribute thoughts to others, also called theory of mind (TOM), has been extensively studied in humans; however, its evolutionary origins have been challenged. Computationally, the basis of TOM has been interpreted within the predictive coding framework and associated with activity in the temporoparietal junction (TPJ). Here, we revealed, using a nonlinguistic task and functional magnetic

  •   Nanoscale molecular architecture controls calcium diffusion and ER replenishment in dendritic spines
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Kanishka Basnayake, David Mazaud, Lilia Kushnireva, Alexis Bemelmans, Nathalie Rouach, Eduard Korkotian, David Holcman

    Dendritic spines are critical components of neuronal synapses as they receive and transform synaptic inputs into a succession of calcium-regulated biochemical events. The spine apparatus (SA), an extension of smooth endoplasmic reticulum, regulates slow and fast calcium dynamics in spines. Calcium release events deplete SA calcium ion reservoir rapidly, yet the next cycle of signaling requires its

  •   Nondiffractive beam shaping for enhanced optothermal control in metal additive manufacturing
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Thejaswi U. Tumkur, Thomas Voisin, Rongpei Shi, Philip J. Depond, Tien T. Roehling, Sheldon Wu, Michael F. Crumb, John D. Roehling, Gabe Guss, Saad A. Khairallah, Manyalibo J. Matthews

    High thermal gradients and complex melt pool instabilities involved in powder bed fusion–based metal additive manufacturing using focused Gaussian-shaped beams often lead to high porosity, poor morphological quality, and degraded mechanical performance. We show here that Bessel beams offer unprecedented control over the spatiotemporal evolution of the melt pool in stainless steel (SS 316L) in comparison

  •   Microcellular sensing media with ternary transparency states for fast and intuitive identification of unknown liquids
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Kyeong Min Song, Shinho Kim, Sungmin Kang, Tae Won Nam, Geon Yeong Kim, Hunhee Lim, Eugene N. Cho, Kwang Ho Kim, Se Hun Kwon, Min Seok Jang, Yeon Sik Jung

    Rapid, accurate, and intuitive detection of unknown liquids is greatly important for various fields such as food and drink safety, management of chemical hazards, manufacturing process monitoring, and so on. Here, we demonstrate a highly responsive and selective transparency-switching medium for on-site, visual identification of various liquids. The light scattering–based sensing medium, which is designed

  •   MYO10 drives genomic instability and inflammation in cancer
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Franklin Mayca Pozo, Xinran Geng, Ilaria Tamagno, Mark W. Jackson, Ernest G. Heimsath, John A. Hammer, Richard E. Cheney, Youwei Zhang

    Genomic instability is a hallmark of human cancer; yet the underlying mechanisms remain poorly understood. Here, we report that the cytoplasmic unconventional Myosin X (MYO10) regulates genome stability, through which it mediates inflammation in cancer. MYO10 is an unstable protein that undergoes ubiquitin-conjugating enzyme H7 (UbcH7)/β-transducin repeat containing protein 1 (β-TrCP1)–dependent degradation

  •   Correlated oxide Dirac semimetal in the extreme quantum limit
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Jong Mok Ok, Narayan Mohanta, Jie Zhang, Sangmoon Yoon, Satoshi Okamoto, Eun Sang Choi, Hua Zhou, Megan Briggeman, Patrick Irvin, Andrew R. Lupini, Yun-Yi Pai, Elizabeth Skoropata, Changhee Sohn, Haoxiang Li, Hu Miao, Benjamin Lawrie, Woo Seok Choi, Gyula Eres, Jeremy Levy, Ho Nyung Lee

    Quantum materials (QMs) with strong correlation and nontrivial topology are indispensable to next-generation information and computing technologies. Exploitation of topological band structure is an ideal starting point to realize correlated topological QMs. Here, we report that strain-induced symmetry modification in correlated oxide SrNbO3 thin films creates an emerging topological band structure

  •   The sardine run in southeastern Africa is a mass migration into an ecological trap
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Peter R. Teske, Arsalan Emami-Khoyi, Tirupathi R. Golla, Jonathan Sandoval-Castillo, Tarron Lamont, Brent Chiazzari, Christopher D. McQuaid, Luciano B. Beheregaray, Carl D. van der Lingen

    The KwaZulu-Natal sardine run, popularly known as the “greatest shoal on Earth,” is a mass migration of South African sardines from their temperate core range into the subtropical Indian Ocean. It has been suggested that this represents the spawning migration of a distinct subtropical stock. Using genomic and transcriptomic data from sardines collected around the South African coast, we identified

  •   Sensing low intracellular potassium by NLRP3 results in a stable open structure that promotes inflammasome activation
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Ana Tapia-Abellán, Diego Angosto-Bazarra, Cristina Alarcón-Vila, María C. Baños, Iva Hafner-Bratkovič, Baldomero Oliva, Pablo Pelegrín

    The NLRP3 inflammasome is activated by a wide range of stimuli and drives diverse inflammatory diseases. The decrease of intracellular K+ concentration is a minimal upstream signal to most of the NLRP3 activation models. Here, we found that cellular K+ efflux induces a stable structural change in the inactive NLRP3, promoting an open conformation as a step preceding activation. This conformational

  •   NSG-Pro mouse model for uncovering resistance mechanisms and unique vulnerabilities in human luminal breast cancers
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Yunguang Sun, Ning Yang, Fransiscus E. Utama, Sameer S. Udhane, Junling Zhang, Amy R. Peck, Alicia Yanac, Katherine Duffey, John F. Langenheim, Vindhya Udhane, Guanjun Xia, Jess F. Peterson, Julie M. Jorns, Marja T. Nevalainen, Romain Rouet, Peter Schofield, Daniel Christ, Christopher J. Ormandy, Anne L. Rosenberg, Inna Chervoneva, Shirng-Wern Tsaih, Michael J. Flister, Serge Y. Fuchs, Kay-Uwe Wagner

    Most breast cancer deaths are caused by estrogen receptor-α–positive (ER+) disease. Preclinical progress is hampered by a shortage of therapy-naïve ER+ tumor models that recapitulate metastatic progression and clinically relevant therapy resistance. Human prolactin (hPRL) is a risk factor for primary and metastatic ER+ breast cancer. Because mouse prolactin fails to activate hPRL receptors, we developed

  •   H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Cemil Kerimoglu, Linh Pham, Anton B. Tonchev, M. Sadman Sakib, Yuanbin Xie, Godwin Sokpor, Pauline Antonie Ulmke, Lalit Kaurani, Eman Abbas, Huong Nguyen, Joachim Rosenbusch, Alexandra Michurina, Vincenzo Capece, Meglena Angelova, Nenad Maricic, Beate Brand-Saberi, Miriam Esgleas, Mareike Albert, Radoslav Minkov, Emil Kovachev, Ulrike Teichmann, Rho H. Seong, Wieland B. Huttner, Huu Phuc Nguyen, Anastassia

    Increase in the size of human neocortex―acquired in evolution―accounts for the unique cognitive capacity of humans. This expansion reflects the evolutionarily enhanced proliferative ability of basal progenitors (BPs), including the basal radial glia and basal intermediate progenitors (bIPs) in mammalian cortex, which may have been acquired through epigenetic alterations in BPs. However, how the epigenome

  •   Temporal teleportation with pseudo-density operators: How dynamics emerges from temporal entanglement
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Chiara Marletto, Vlatko Vedral, Salvatore Virzì, Alessio Avella, Fabrizio Piacentini, Marco Gramegna, Ivo Pietro Degiovanni, Marco Genovese

    We show that, by using temporal quantum correlations as expressed by pseudo-density operators (PDOs), it is possible to recover formally the standard quantum dynamical evolution as a sequence of teleportations in time. We demonstrate that any completely positive evolution can be formally reconstructed by teleportation with different temporally correlated states. This provides a different interpretation

  •   Parallel characterization of cis-regulatory elements for multiple genes using CRISPRpath
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Xingjie Ren, Mengchi Wang, Bingkun Li, Kirsty Jamieson, Lina Zheng, Ian R. Jones, Bin Li, Maya Asami Takagi, Jerry Lee, Lenka Maliskova, Tsz Wai Tam, Miao Yu, Rong Hu, Lindsay Lee, Armen Abnousi, Gang Li, Yun Li, Ming Hu, Bing Ren, Wei Wang, Yin Shen

    Current pooled CRISPR screens for cis-regulatory elements (CREs), based on transcriptional output changes, are typically limited to characterizing CREs of only one gene. Here, we describe CRISPRpath, a scalable screening strategy for parallelly characterizing CREs of genes linked to the same biological pathway and converging phenotypes. We demonstrate the ability of CRISPRpath for simultaneously identifying

  •   Ameliorating the hallmarks of cellular senescence in skeletal muscle myogenic progenitors in vitro and in vivo
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Aref Shahini, Nika Rajabian, Debanik Choudhury, Shahryar Shahini, Kalyan Vydiam, Thy Nguyen, Joseph Kulczyk, Tyler Santarelli, Izuagie Ikhapoh, Yali Zhang, Jianmin Wang, Song Liu, Aimee Stablewski, Ramkumar Thiyagarajan, Kenneth Seldeen, Bruce R. Troen, Jennifer Peirick, Pedro Lei, Stelios T. Andreadis

    Senescence of myogenic progenitors impedes skeletal muscle regeneration. Here, we show that overexpression of the transcription factor NANOG in senescent myoblasts can overcome the effects of cellular senescence and confer a youthful phenotype to senescent cells. NANOG ameliorated primary hallmarks of cellular senescence including genomic instability, loss of proteostasis, and mitochondrial dysfunction

  •   Dynamics of sex chromosome evolution in a rapid radiation of cichlid fishes
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Athimed El Taher, Fabrizia Ronco, Michael Matschiner, Walter Salzburger, Astrid Böhne

    Sex is a fundamental trait determined by environmental and/or genetic factors, including sex chromosomes. Sex chromosomes are studied in species scattered across the tree of life, yet little is known about tempo and mode of sex chromosome evolution among closely related species. Here, we examine sex chromosome evolution in the adaptive radiation of cichlid fishes in Lake Tanganyika. Through the analysis

  •   Mutation-induced DNMT1 cleavage drives neurodegenerative disease
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Wencai Wang, Xingsen Zhao, Yanjiao Shao, Xiaoya Duan, Yaling Wang, Jialun Li, Jiwen Li, Dali Li, Xuekun Li, Jiemin Wong

    Specific mutations within the replication foci targeting sequence (RFTS) domain of human DNMT1 are causative of two types of adult-onset neurodegenerative diseases, HSAN1E and ADCA-DN, but the underlying mechanisms are largely unknown. We generated Dnmt1-M1 and Dnmt1-M2 knock-in mouse models that are equivalent to Y495C and D490E-P491Y mutation in patients with HSAN1E, respectively. We found that both

  •   A chemical biology approach reveals a dependency of glioblastoma on biotin distribution
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Jeehyun Yoon, Oleg V. Grinchuk, Srinivasaraghavan Kannan, Melgious Jin Yan Ang, Zhenglin Li, Emmy Xue Yun Tay, Ker Zhing Lok, Bernice Woon Li Lee, You Heng Chuah, Kimberly Chia, Roberto Tirado Magallanes, Chenfei Liu, Haonan Zhao, Jin Hui Hor, Jhin Jieh Lim, Touati Benoukraf, Tan Boon Toh, Edward Kai-Hua Chow, Jean-Paul Kovalik, Jianhong Ching, Shi-Yan Ng, Ming Joo Koh, Xiaogang Liu, Chandra Shekhar

    Glioblastoma (GBM) is a uniformly lethal disease driven by glioma stem cells (GSCs). Here, we use a chemical biology approach to unveil previously unknown GBM dependencies. By studying sulconazole (SN) with anti-GSC properties, we find that SN disrupts biotin distribution to the carboxylases and histones. Transcriptomic and metabolomic analyses of SN-treated GSCs reveal metabolic alterations that are

  •   De novo design of peptides that coassemble into β sheet–based nanofibrils
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Xingqing Xiao, Yiming Wang, Dillon T. Seroski, Kong M. Wong, Renjie Liu, Anant K. Paravastu, Gregory A. Hudalla, Carol K. Hall

    Peptides’ hierarchical coassembly into nanostructures enables controllable fabrication of multicomponent biomaterials. In this work, we describe a computational and experimental approach to design pairs of charge-complementary peptides that selectively coassemble into β-sheet nanofibers when mixed together but remain unassembled when isolated separately. The key advance is a peptide coassembly design

  •   Memory CD8+ T cells mediate early pathogen-specific protection via localized delivery of chemokines and IFNγ to clusters of monocytes
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Marie Boutet, Zachary Benet, Erik Guillen, Caroline Koch, Saidi M’Homa Soudja, Fabien Delahaye, David Fooksman, Grégoire Lauvau

    While cognate antigen drives clonal expansion of memory CD8+ T (CD8+ TM) cells to achieve sterilizing immunity in immunized hosts, not much is known on how cognate antigen contributes to early protection before clonal expansion occurs. Here, using distinct models of immunization, we establish that cognate antigen recognition by CD8+ TM cells on dendritic cells initiates their rapid and coordinated

  •   Podocyte-specific KLF4 is required to maintain parietal epithelial cell quiescence in the kidney
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Jesse A. Pace, Robert Bronstein, Yiqing Guo, Yaqi Yang, Chelsea C. Estrada, Nehaben Gujarati, David J. Salant, John Haley, Agnieszka B. Bialkowska, Vincent W. Yang, John C. He, Sandeep K. Mallipattu

    Podocyte loss triggering aberrant activation and proliferation of parietal epithelial cells (PECs) is a central pathogenic event in proliferative glomerulopathies. Podocyte-specific Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, is essential for maintaining podocyte homeostasis and PEC quiescence. Using mice with podocyte-specific knockdown of Klf4, we conducted glomerular RNA-sequencing

  •   Bottom-up assembly of biomedical relevant fully synthetic extracellular vesicles
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Oskar Staufer, Franziska Dietrich, Rahul Rimal, Martin Schröter, Sebastian Fabritz, Heike Boehm, Smriti Singh, Martin Möller, Ilia Platzman, Joachim Pius Spatz

    Extracellular vesicles (EVs) are fundamental for intercellular communication and influence nearly every process in cell physiology. However, because of their intricate molecular complexity, quantitative knowledge on their signaling mechanisms is missing, particularly impeding their therapeutic application. We used a complementary and quantitative engineering approach based on sequential synthetic bottom-up

  •   STAT1 maintains naïve CD8+ T cell quiescence by suppressing the type I IFN-STAT4-mTORC1 signaling axis
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Yoon-Chul Kye, Gil-Woo Lee, Sung-Woo Lee, Young-Jun Ju, Hee-Ok Kim, Cheol-Heui Yun, Jae-Ho Cho

    Naïve CD8+ T cell quiescence is maintained at a steady state. Although this state of quiescence involves various cell-intrinsic and cell-extrinsic regulators, the mechanisms underlying this regulation remain incompletely understood. Here, we found that signal transducer and activator of transcription 1 (STAT1), a key transcription factor downstream of interferon receptor (IFNR) signaling, plays a cell-intrinsic

  •   The anti-fibrotic drug pirfenidone inhibits liver fibrosis by targeting the small oxidoreductase glutaredoxin-1
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Yue Xi, Yanping Li, Pengfei Xu, Sihan Li, Zhengsheng Liu, Hung-chun Tung, Xinran Cai, Jingyuan Wang, Haozhe Huang, Menglin Wang, Meishu Xu, Songrong Ren, Song Li, Min Zhang, Yong J. Lee, Leaf Huang, Da Yang, Jinhan He, Zhiying Huang, Wen Xie

    Activation of the hepatic stellate cells (HSCs) is a key pathogenic event in liver fibrosis. Protein S-glutathionylation (PSSG) of cysteine residues is a distinct form of oxidative response that modifies protein structures and functions. Glutaredoxin-1 (GLRX) reverses PSSG by liberating glutathione (GSH). In this study, we showed that pirfenidone (PFD), an anti-lung fibrosis drug, inhibited HSC activation

  •   Cell-free DNA TAPS provides multimodal information for early cancer detection
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Paulina Siejka-Zielińska, Jingfei Cheng, Felix Jackson, Yibin Liu, Zahir Soonawalla, Srikanth Reddy, Michael Silva, Luminita Puta, Misti Vanette McCain, Emma L. Culver, Noor Bekkali, Benjamin Schuster-Böckler, Pier Francesco Palamara, Derek Mann, Helen Reeves, Eleanor Barnes, Shivan Sivakumar, Chun-Xiao Song

    Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA

  •   Microglia promote autoimmune inflammation via the noncanonical NF-κB pathway
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Zuliang Jie, Chun-Jung Ko, Hui Wang, Xiaoping Xie, Yanchuan Li, Meidi Gu, Lele Zhu, Jin-Young Yang, Tianxiao Gao, Wenjuan Ru, Shao-Jun Tang, Xuhong Cheng, Shao-Cong Sun

    Microglia have been implicated in neuroinflammatory diseases, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). We demonstrate that microglia mediate EAE disease progression via a mechanism relying on the noncanonical nuclear factor kB (NF-κB) pathway. Microglia-specific deletion of the noncanonical NF-κB-inducing kinase (NIK) impairs EAE disease progression

  •   INTS11 regulates hematopoiesis by promoting PRC2 function
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Peng Zhang, Pinpin Sui, Shi Chen, Ying Guo, Ying Li, Guo Ge, Ganqian Zhu, Hui Yang, Cody M. Rogers, Patrick Sung, Stephen D. Nimer, Mingjiang Xu, Feng-Chun Yang

    INTS11, the catalytic subunit of the Integrator (INT) complex, is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. However, the role of INTS11 in hematopoietic stem and progenitor cell (HSPC) biology is unknown. Here, we report that INTS11 is required for normal hematopoiesis and hematopoietic-specific genetic deletion of Ints11 leads to cell cycle arrest and impairment of fetal

  •   NPF transporters in synaptic-like vesicles control delivery of iron and copper to seeds
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Zhen-Fei Chao, Ya-Ling Wang, Yuan-Yuan Chen, Chu-Ying Zhang, Peng-Yun Wang, Tao Song, Chu-Bin Liu, Qiao-Yan Lv, Mei-Ling Han, Shan-Shan Wang, Jianbing Yan, Ming-Guang Lei, Dai-Yin Chao

    Accumulation of iron in seeds is essential for both plant reproduction and human nutrition. Transport of iron to seeds requires the chelator nicotianamine (NA) to prevent its precipitation in the plant vascular tissues. However, how NA is transported to the apoplast for forming metal-NA complexes remains unknown. Here, we report that two members of the nitrate/peptide transporter family, NAET1 and

  •   Rare genetic variability in human drug target genes modulates drug response and can guide precision medicine
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Yitian Zhou, Gabriel Herras Arribas, Ainoleena Turku, Tuuli Jürgenson, Souren Mkrtchian, Kristi Krebs, Yi Wang, Barbora Svobodova, Lili Milani, Gunnar Schulte, Jan Korabecny, Stefano Gastaldello, Volker M. Lauschke

    Interindividual variability in drug response constitutes a major concern in pharmacotherapy. While polymorphisms in genes involved in drug disposition have been extensively studied, drug target variability remains underappreciated. By mapping the genomic variability of all human drug target genes onto high-resolution crystal structures of drug target complexes, we identified 1094 variants localized

  •   Cristae-dependent quality control of the mitochondrial genome
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Christopher Jakubke, Rodaria Roussou, Andreas Maiser, Christina Schug, Felix Thoma, David Bunk, David Hörl, Heinrich Leonhardt, Peter Walter, Till Klecker, Christof Osman

    Mitochondrial genomes (mtDNA) encode essential subunits of the mitochondrial respiratory chain. Mutations in mtDNA can cause a shortage in cellular energy supply, which can lead to numerous mitochondrial diseases. How cells secure mtDNA integrity over generations has remained unanswered. Here, we show that the single-celled yeast Saccharomyces cerevisiae can intracellularly distinguish between functional

  •   Single-cell transcriptome of early hematopoiesis guides arterial endothelial-enhanced functional T cell generation from human PSCs
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Jun Shen, Yingxi Xu, Shuo Zhang, Shuzhen Lyu, Yingying Huo, Yaoyao Zhu, Kejing Tang, Junli Mou, Xinjie Li, Dixie L. Hoyle, Min Wang, Jianxiang Wang, Xin Li, Zack Z. Wang, Tao Cheng

    Hematopoietic differentiation of human pluripotent stem cells (hPSCs) requires orchestration of dynamic cell and gene regulatory networks but often generates blood cells that lack natural function. Here, we performed extensive single-cell transcriptomic analyses to map fate choices and gene expression patterns during hematopoietic differentiation of hPSCs and showed that oxidative metabolism was dysregulated

  •   A genome-engineered bioartificial implant for autoregulated anticytokine drug delivery
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Yun-Rak Choi, Kelsey H. Collins, Luke E. Springer, Lara Pferdehirt, Alison K. Ross, Chia-Lung Wu, Franklin T. Moutos, Natalia S. Harasymowicz, Jonathan M. Brunger, Christine T. N. Pham, Farshid Guilak

    Biologic drug therapies are increasingly used for inflammatory diseases such as rheumatoid arthritis but may cause significant adverse effects when delivered continuously at high doses. We used CRISPR-Cas9 genome editing of iPSCs to create a synthetic gene circuit that senses changing levels of endogenous inflammatory cytokines to trigger a proportional therapeutic response. Cells were engineered into

  •   Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Tom G. Caniels, Ilja Bontjer, Karlijn van der Straten, Meliawati Poniman, Judith A. Burger, Brent Appelman, H. A. Ayesha Lavell, Melissa Oomen, Gert-Jan Godeke, Coralie Valle, Ramona Mögling, Hugo D. G. van Willigen, Elke Wynberg, Michiel Schinkel, Lonneke A. van Vught, Denise Guerra, Jonne L. Snitselaar, Devidas N. Chaturbhuj, Isabel Cuella Martin, Amsterdam UMC COVID-19 S3/HCW study group, John P

    Emerging SARS-CoV-2 variants of concern (VOCs) pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three VOCs (B.1.1.7, B.1.351, and P.1) in cohorts of COVID-19 convalescent patients (n = 69) and Pfizer-BioNTech vaccine recipients (n = 50). Spike binding and neutralization against all three VOCs were substantially reduced in most individuals

  •   Intense overpressurization at basaltic open-conduit volcanoes as inferred by geochemical signals: The case of the Mt. Etna December 2018 eruption
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Antonio Paonita, Marco Liuzzo, Giuseppe Salerno, Cinzia Federico, Piero Bonfanti, Antonio Caracausi, Giovanni Giuffrida, Alessandro La Spina, Tommaso Caltabiano, Sergio Gurrieri, Gaetano Giudice

    The balance between the amount of gas coexisting with mantle-derived magmas at depth and that emitted during intereruptive phases may play a key role in the eruptive potential of volcanoes. Taking the December 2018 eruption at Mt. Etna volcano as a case study, we discuss the geochemical data streams observed. The signals indicate a long-lasting prelude stage to eruption, starting in 2017 and involving

  •   Fast cortical dynamics encode tactile grating orientation during active touch
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Evan R. Harrell, Anthony Renard, Brice Bathellier

    Touch-based object recognition relies on perception of compositional tactile features like roughness, shape, and surface orientation. However, besides roughness, it remains unclear how these different tactile features are encoded by neural activity that is linked with perception. Here, we establish a cortex-dependent perceptual task in which mice discriminate tactile gratings on the basis of orientation

  •   Atypical genomic cortical patterning in autism with poor early language outcome
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Michael V. Lombardo, Lisa Eyler, Tiziano Pramparo, Vahid H. Gazestani, Donald J. HaglerJr., Chi-Hua Chen, Anders M. Dale, Jakob Seidlitz, Richard A. I. Bethlehem, Natasha Bertelsen, Cynthia Carter Barnes, Linda Lopez, Kathleen Campbell, Nathan E. Lewis, Karen Pierce, Eric Courchesne

    Cortical regionalization develops via genomic patterning along anterior-posterior (A-P) and dorsal-ventral (D-V) gradients. Here, we find that normative A-P and D-V genomic patterning of cortical surface area (SA) and thickness (CT), present in typically developing and autistic toddlers with good early language outcome, is absent in autistic toddlers with poor early language outcome. Autistic toddlers

  •   Revealing extreme twin-boundary shear deformability in metallic nanocrystals
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Qi Zhu, Lingyi Kong, Haiming Lu, Qishan Huang, Yingbin Chen, Yue Liu, Wei Yang, Ze Zhang, Frederic Sansoz, Haofei Zhou, Jiangwei Wang

    Metals containing abundant coherent twin boundaries (TBs) are able to sustain substantial plastic deformation without fracture due to shear-induced TB migration and sliding. Retaining ductility in these metals, however, has proven difficult because detwinning rapidly exhausts TB migration mechanisms at large deformation, whereas TB sliding was only evidenced for loading on very specific crystallographic

  •   Hyperbolic band theory
    Sci. Adv. (IF 14.136) Pub Date : 2021-09-01
    Joseph Maciejko, Steven Rayan

    The notions of Bloch wave, crystal momentum, and energy bands are commonly regarded as unique features of crystalline materials with commutative translation symmetries. Motivated by the recent realization of hyperbolic lattices in circuit quantum electrodynamics, we exploit ideas from algebraic geometry to construct a hyperbolic generalization of Bloch theory, despite the absence of commutative translation

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