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  • Phosphatidylcholines from Pieris brassicae eggs activate an immune response in Arabidopsis
    eLife (IF 7.08) Pub Date : 2020-09-28
    André Schmiesing; Elia Stahl; Emerson Ferreira Queiroz; Howard Riezman; Isabelle Riezman; Jean-Luc Wolfender; Laurence Marcourt; Olivier Hilfiker; Philippe Reymond; Théo Brillatz

    Recognition of conserved microbial molecules activates immune responses in plants, a process termed pattern-triggered immunity (PTI). Similarly, insect eggs trigger defenses that impede egg development or attract predators, but information on the nature of egg-associated elicitors is scarce. We performed an unbiased bioactivity-guided fractionation of eggs of the butterfly Pieris brassicae. Nuclear

    更新日期:2020-09-28
  • Defining the function of OmpA in the Rcs stress response
    eLife (IF 7.08) Pub Date : 2020-09-28
    Benjamin Elias; Bogdan I Iorga; Cédric Laguri; Jean-Francois Collet; Jean-Pierre Simorre; Juliette Létoquart; Kilian Dekoninck; Olivia Dehu; Pascal Demange; Robin Bevernaegie; Seung-Hyun Cho

    OmpA, a protein commonly found in the outer membrane of Gram-negative bacteria, has served as a paradigm for the study of b-barrel proteins for several decades. In Escherichia coli, OmpA was previously reported to form complexes with RcsF, a surface-exposed lipoprotein that triggers the Rcs stress response when damage occurs in the outer membrane and the peptidoglycan. How OmpA interacts with RcsF

    更新日期:2020-09-28
  • The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migration in vivo
    eLife (IF 7.08) Pub Date : 2020-09-28
    Alessandra Pecora; Armen Saghatelyan; Cedric Bressan; Dave Gagnon; Marina Snapyan; Martin Parent; Paul De Koninck; Simon Labrecque

    Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mice revealed that decreases in ATP levels force cells into the stationary

    更新日期:2020-09-28
  • Characterization of the mechanism by which the RB/E2F pathway controls expression of the cancer genomic DNA deaminase APOBEC3B
    eLife (IF 7.08) Pub Date : 2020-09-28
    Boon Haow Chua; Chai Yeen Goh; Dennis Kappei; Jennifer L McCann; John WM Martens; Matthew C Jarvis; Michael A Carpenter; Paul N Span; Pieter A Roelofs; Rebecca M McDougle; Reuben S Harris; Teneale A Stewart

    APOBEC3B (A3B)-catalyzed DNA cytosine deamination contributes to the overall mutational landscape in breast cancer. Molecular mechanisms responsible for A3B upregulation in cancer are poorly understood. Here, we show that a single E2F cis-element mediates repression in normal cells and that expression is activated by its mutational disruption in a reporter construct or the endogenous A3B gene. The

    更新日期:2020-09-28
  • Direct translation of climbing fiber burst-mediated sensory coding into post-synaptic Purkinje cell dendritic calcium
    eLife (IF 7.08) Pub Date : 2020-09-28
    Chang-Eop Kim; Changhyeon Ryu; Paul F Worley; Sang Jeong Kim; Seung-Eon Roh; Seung Ha Kim; Sun Kwang Kim; Yong Gyu Kim

    Climbing fibers (CFs) generate complex spikes (CS) and Ca2+ transients in cerebellar Purkinje cells (PCs), serving as instructive signals. The so-called 'all-or-none' character of CSs has been questioned since the CF burst was described. Although recent studies have indicated a sensory-driven enhancement of PC Ca2+ signals, how CF responds to sensory events and contributes to PC dendritic Ca2+ and

    更新日期:2020-09-28
  • Testicular hormones mediate robust sex differences in impulsive choice in rats
    eLife (IF 7.08) Pub Date : 2020-09-28
    Alexa-Rae Wheeler; Barry Setlow; Caesar M Hernandez; Caitlin Orsini; Chase C Labiste; Jennifer L Bizon; Noelle G Wright; Sara M Betzhold; Tyler W Ten Eyck

    Impairments in choosing optimally between immediate and delayed rewards are associated with numerous psychiatric disorders. Such ‘intertemporal’ choice is influenced by genetic and experiential factors; however, the contributions of biological sex are understudied and data to date are largely inconclusive. Rats were used to determine how sex and gonadal hormones influence choices between small, immediate

    更新日期:2020-09-28
  • Experience, circuit dynamics and forebrain recruitment in larval zebrafish prey capture
    eLife (IF 7.08) Pub Date : 2020-09-28
    Adam Hoagland; Alex R Huth; Andrew Prendergast; Claire S Oldfield; Claire Wyart; Ehud Y Isacoff; Elizabeth C Carroll; Irene Grossrubatscher; Jack L Gallant; Mario Chávez; Tony Qu

    Experience strongly influences behavior, but little is known about how experience is encoded in the brain, and how changes in neural activity are implemented at a network level to improve performance. Here we investigate how differences in experience impact brain circuitry and behavior in larval zebrafish prey capture. We find that experience of live prey compared to inert food increases capture success

    更新日期:2020-09-28
  • Symbiont-mediated cytoplasmic incompatibility: what have we learned in 50 years?
    eLife (IF 7.08) Pub Date : 2020-09-25
    Brittany Leigh; J Dylan Shropshire; Seth R Bordenstein

    Cytoplasmic incompatibility (CI) is the most common symbiont-induced reproductive manipulation. Specifically, symbiont-induced sperm modifications cause catastrophic mitotic defects in the fertilized embryo and ensuing lethality in crosses between symbiotic males and either aposymbiotic females or females harboring a different symbiont strain. However, if the female carries the same symbiont strain

    更新日期:2020-09-25
  • Molecular basis for substrate specificity of the Phactr1/PP1 phosphatase holoenzyme
    eLife (IF 7.08) Pub Date : 2020-09-25
    Abbey Butler; Ambrosius P Snijders; Helen R Flynn; Magdalena Přechová; Nicola O'Reilly; Noreen Eder; Rebecca Lee; Richard Treisman; Roman O Fedoryshchak; Sila Ultanir; Stephane Mouilleron

    PPP-family phosphatases such as PP1 have little intrinsic specificity. Cofactors can target PP1 to substrates or subcellular locations, but it remains unclear how they might confer sequence-specificity on PP1. The cytoskeletal regulator Phactr1 is a neuronally-enriched PP1 cofactor that is controlled by G-actin. Structural analysis showed that Phactr1 binding remodels PP1's hydrophobic groove, creating

    更新日期:2020-09-25
  • Phosphatidylinositol 3-phosphate and Hsp70 protect Plasmodium falciparum from heat-induced cell death
    eLife (IF 7.08) Pub Date : 2020-09-25
    Charisse Flerida A Pasaje; David R Loiselle; Emily Derbyshire; Jacquin C Niles; Kuan-Yi Lu; Tamanna Srivastava

    Phosphatidylinositol 3-phosphate (PI(3)P) levels in Plasmodium falciparum correlate with tolerance to cellular stresses caused by artemisinin and environmental factors. However, PI(3)P function during the Plasmodium stress response was unknown. Here, we used PI3K inhibitors and antimalarial agents to examine the importance of PI(3)P under thermal conditions recapitulating malarial fever. Live cell

    更新日期:2020-09-25
  • Photosynthesis without β-carotene
    eLife (IF 7.08) Pub Date : 2020-09-25
    Daniel Karcher; Gert Schansker; Ludwik W Bielczynski; Pengqi Xu; Ralph Bock; Roberta Croce; Volha U Chukhutsina; Wojciech J Nawrocki; Yinghong Lu

    Carotenoids are essential in oxygenic photosynthesis: they stabilize the pigment-protein complexes, are active in harvesting sunlight and in photoprotection. In plants, they are present as carotenes and their oxygenated derivatives, xanthophylls. While mutant plants lacking xanthophylls are capable of photoautotrophic growth, no plants without carotenes in their photosystems have been reported so far

    更新日期:2020-09-25
  • POMK regulates dystroglycan function via LARGE-mediated elongation of matriglycan
    eLife (IF 7.08) Pub Date : 2020-09-25
    Adnan Manzur; Ameya S Walimbe; David Venzke; Francesco Muntoni; Hidehiko Okuma; Jack E Dixon; Jeffrey M Hord; Junyu Xiao; Kevin P Campbell; Liping Yu; Marco Cuellar; Mary E Anderson; Megan Devereaux; Sally Prouty; Saul Ocampo Landa; Silvia Torelli; Soumya Joseph; Takahiro Yonekawa; Tiandi Yang

    Matriglycan [-GlcA-β1,3-Xyl-α1,3-]n serves as a scaffold in many tissues for extracellular matrix proteins containing laminin-G domains including laminin, agrin, and perlecan. Like-acetylglucosaminyltransferase-1 (LARGE1) synthesizes and extends matriglycan on α-dystroglycan (α-DG) during skeletal muscle differentiation and regeneration; however, the mechanisms which regulate matriglycan elongation

    更新日期:2020-09-25
  • A multi-layered and dynamic apical extracellular matrix shapes the vulva lumen in Caenorhabditis elegans
    eLife (IF 7.08) Pub Date : 2020-09-25
    Alessandro P Sparacio; Alexandra C Belfi; Alison R Frand; David H Hall; Hannah Maul-Newby; Jennifer D Cohen; Meera V Sundaram; Rachel Forman-Rubinsky

    Biological tubes must develop and maintain their proper diameter in order to transport materials efficiently. These tubes are molded and protected in part by apical extracellular matrices (aECMs) that line their lumens. Despite their importance, aECMs are difficult to image in vivo and therefore poorly understood. The C. elegans vulva has been a paradigm for understanding many aspects of organogenesis

    更新日期:2020-09-25
  • Hedgehog signaling is required for endomesodermal patterning and germ cell development in the sea anemone Nematostella vectensis.
    eLife (IF 7.08) Pub Date : 2020-09-24
    Cheng-Yi Chen,Sean A McKinney,Lacey R Ellington,Matthew C Gibson

    Two distinct mechanisms for primordial germ cell (PGC) specification are observed within Bilatera: early determination by maternal factors or late induction by zygotic cues. Here we investigate the molecular basis for PGC specification in Nematostella, a representative pre-bilaterian animal where PGCs arise as paired endomesodermal cell clusters during early development. We first present evidence that

    更新日期:2020-09-24
  • MondoA regulates gene expression in cholesterol biosynthesis-associated pathways required for zebrafish epiboly.
    eLife (IF 7.08) Pub Date : 2020-09-24
    Meltem Weger,Benjamin D Weger,Andrea Schink,Masanari Takamiya,Johannes Stegmaier,Cédric Gobet,Alice Parisi,Andrei Yu Kobitski,Jonas Mertes,Nils Krone,Uwe Strähle,Gerd Ulrich Nienhaus,Ralf Mikut,Frédéric Gachon,Philipp Gut,Thomas Dickmeis

    The glucose-sensing Mondo pathway regulates expression of metabolic genes in mammals. Here, we characterized its function in the zebrafish and revealed an unexpected role of this pathway in vertebrate embryonic development. We showed that knockdown of mondoa impaired the early morphogenetic movement of epiboly in zebrafish embryos and caused microtubule defects. Expression of genes in the terpenoid

    更新日期:2020-09-24
  • Molecular mechanism for direct actin force-sensing by α-catenin.
    eLife (IF 7.08) Pub Date : 2020-09-24
    Lin Mei,Santiago Espinosa de Los Reyes,Matthew J Reynolds,Rachel Leicher,Shixin Liu,Gregory M Alushin

    The actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force, but it is unclear how interactions between actin filaments (F-actin) and associated proteins are mechanically regulated. Here, we employ both optical trapping and biochemical reconstitution with myosin motor proteins to show

    更新日期:2020-09-24
  • Correction: A nuclear role for the DEAD-box protein Dbp5 in tRNA export.
    eLife (IF 7.08) Pub Date : 2020-09-24
    Azra Lari,Arvind Arul Nambi Rajan,Rima Sandhu,Taylor Reiter,Rachel Montpetit,Barry P Young,Chris Jr Loewen,Ben Montpetit

    更新日期:2020-09-24
  • Stoichiometric interactions explain spindle dynamics and scaling across 100 million years of nematode evolution.
    eLife (IF 7.08) Pub Date : 2020-09-23
    Reza Farhadifar,Che-Hang Yu,Gunar Fabig,Hai-Yin Wu,David B Stein,Matthew Rockman,Thomas Müller-Reichert,Michael J Shelley,Daniel J Needleman

    The spindle shows remarkable diversity, and changes in an integrated fashion, as cells vary over evolution. Here, we provide a mechanistic explanation for variations in the first mitotic spindle in nematodes. We used a combination of quantitative genetics and biophysics to rule out broad classes of models of the regulation of spindle length and dynamics, and to establish the importance of a balance

    更新日期:2020-09-23
  • Light-Regulated allosteric switch enables temporal and subcellular control of enzyme activity.
    eLife (IF 7.08) Pub Date : 2020-09-23
    Mark Shaaya,Jordan Fauser,Anastasia Zhurikhina,Jason E Conage-Pough,Vincent Huyot,Martin Brennan,Cameron T Flower,Jacob Matsche,Shahzeb Khan,Viswanathan Natarajan,Jalees Rehman,Pradeep Kota,Forest M White,Denis Tsygankov,Andrei V Karginov

    Engineered allosteric regulation of protein activity provides significant advantages for the development of robust and broadly applicable tools. However, the application of allosteric switches in optogenetics has been scarce and suffers from critical limitations. Here, we report an optogenetic approach that utilizes an engineered Light-Regulated (LightR) allosteric switch module to achieve tight spatiotemporal

    更新日期:2020-09-23
  • Live imaging of hair bundle polarity acquisition demonstrates a critical timeline for transcription factor Emx2.
    eLife (IF 7.08) Pub Date : 2020-09-23
    Yosuke Tona,Doris K Wu

    The asymmetric hair bundle on top of hair cells (HCs), comprises a kinocilium and stereocilia staircase, dictates HC's directional sensitivity. The mother centriole (MC) forms the base of the kinocilium, where stereocilia are subsequently built next to it. Previously we showed that transcription factor Emx2 reverses hair bundle orientation and its expression in the mouse vestibular utricle is restricted

    更新日期:2020-09-23
  • Ribosome recycling is not critical for translational coupling in E. coli.
    eLife (IF 7.08) Pub Date : 2020-09-23
    Kazuki Saito,Rachel Green,Allen R Buskirk

    We used ribosome profiling to characterize the biological role of ribosome recycling factor (RRF) in E. coli. As expected, RRF depletion leads to enrichment of post-termination 70S complexes in 3'-UTRs. We also observe that elongating ribosomes are unable to complete translation because they are blocked by non-recycled ribosomes at stop codons. Previous studies have suggested a role for recycling in

    更新日期:2020-09-23
  • Unbiased homeologous recombination during pneumococcal transformation allows for multiple chromosomal integration events.
    eLife (IF 7.08) Pub Date : 2020-09-23
    Jun Kurushima,Nathalie Campo,Renske van Raaphorst,Guillaume Cerckel,Patrice Polard,Jan-Willem Veening

    The spread of antimicrobial resistance and vaccine escape in the human pathogen Streptococcus pneumoniae can be largely attributed to competence-induced transformation. Here, we studied this process at the single-cell level. We show that within isogenic populations, all cells become naturally competent and bind exogenous DNA. We find that transformation is highly efficient and that the chromosomal

    更新日期:2020-09-23
  • Why scientific societies should involve more early-career researchers.
    eLife (IF 7.08) Pub Date : 2020-09-23
    Adriana Bankston,Stephanie M Davis,Elisabeth Moore,Caroline A Niziolek,Vincent Boudreau

    Early-career researchers (ECRs) make up a large portion of the academic workforce. Yet, most leadership positions in scientific societies are held by senior scientists, and ECRs have little to no say over the decisions that will shape the future of research. This article looks at the level of influence ECRs have in 20 scientific societies based in the US and UK, and provides guidelines on how societies

    更新日期:2020-09-23
  • Alstrom syndrome gene is a stem cell-specific regulator of centriole duplication in the Drosophila testis.
    eLife (IF 7.08) Pub Date : 2020-09-23
    Cuie Chen,Yukiko M Yamashita

    Asymmetrically dividing stem cells often show asymmetric behavior of the mother versus daughter centrosomes, whereby the self-renewing stem cell selectively inherits the mother or daughter centrosome. Although the asymmetric centrosome behavior is widely conserved, its biological significance remains largely unclear. Here we show that Alms1a, a Drosophila homolog of the human ciliopathy gene Alstrom

    更新日期:2020-09-23
  • Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration.
    eLife (IF 7.08) Pub Date : 2020-09-23
    Shashank Gandhi,Erica J Hutchins,Krystyna Maruszko,Jong H Park,Matthew Thomson,Marianne E Bronner

    During gastrulation, neural crest cells are specified at the neural plate border, as characterized by Pax7 expression. Using single-cell RNA sequencing coupled with high resolution in situ hybridization to identify novel transcriptional regulators, we show that chromatin remodeler Hmga1 is highly expressed prior to specification and maintained in migrating chick neural crest cells. Temporally-controlled

    更新日期:2020-09-23
  • Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Hajnalka L Pálinkás,Angéla Békési,Gergely Róna,Lőrinc Pongor,Gábor Papp,Gergely Tihanyi,Eszter Holub,Ádám Póti,Carolina Gemma,Simak Ali,Michael J Morten,Eli Rothenberg,Michele Pagano,Dávid Szűts,Balázs Győrffy,Beáta G Vértessy

    Numerous anti-cancer drugs perturb thymidylate biosynthesis and lead to genomic uracil incorporation contributing to their antiproliferative effect. Still, it is not yet characterized if uracil incorporations have any positional preference. Here, we aimed to uncover genome-wide alterations in uracil pattern upon drug treatments in human cancer cell line models derived from HCT116. We developed a straightforward

    更新日期:2020-09-22
  • Spectral clustering of risk score trajectories stratifies sepsis patients by clinical outcome and interventions received.
    eLife (IF 7.08) Pub Date : 2020-09-22
    Ran Liu,Joseph L Greenstein,James C Fackler,Melania M Bembea,Raimond L Winslow

    Sepsis is not a monolithic disease, but a loose collection of symptoms with diverse outcomes. Thus, stratification and subtyping of sepsis patients is of great importance. We examine the temporal evolution of patient state using our previously-published method for computing risk of transition from sepsis into septic shock. Risk trajectories diverge into four clusters following early prediction of septic

    更新日期:2020-09-22
  • Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis.
    eLife (IF 7.08) Pub Date : 2020-09-22
    Jennifer L Elliott,Jenna Eve Eschbach,Pratibha C Koneru,Wen Li,Maritza Puray Chavez,Dana Townsend,Dana Q Lawson,Alan N Engelman,Mamuka Kvaratskhelia,Sebla Bulent Kutluay

    A number of human immunodeficiency virus 1 integrase (IN) alterations, referred to as class II substitutions, exhibit pleotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of three distinct mechanisms: i) markedly reducing IN levels

    更新日期:2020-09-22
  • Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons.
    eLife (IF 7.08) Pub Date : 2020-09-22
    Claudia Scheckel,Marigona Imeri,Petra Schwarz,Adriano Aguzzi

    Prion diseases are caused by PrPSc, a self-replicating pathologically misfolded protein that exerts toxicity predominantly in the brain. The administration of PrPSc causes a robust, reproducible and specific disease manifestation. Here we have applied a combination of translating ribosome affinity purification and ribosome profiling to identify biologically relevant prion-induced changes during disease

    更新日期:2020-09-22
  • Nutrient status shapes selfish mitochondrial genome dynamics across different levels of selection.
    eLife (IF 7.08) Pub Date : 2020-09-22
    Bryan L Gitschlag,Ann T Tate,Maulik R Patel

    Cooperation and cheating are widespread evolutionary strategies. While cheating confers an advantage to individual entities within a group, competition between groups favors cooperation. Selfish or cheater mitochondrial DNA (mtDNA) proliferates within hosts while being selected against at the level of host fitness. How does environment shape cheater dynamics across different selection levels? Focusing

    更新日期:2020-09-22
  • BiteOscope, an open platform to study mosquito biting behavior.
    eLife (IF 7.08) Pub Date : 2020-09-22
    Felix Jh Hol,Louis Lambrechts,Manu Prakash

    Female mosquitoes need a blood meal to reproduce, and in obtaining this essential nutrient they transmit deadly pathogens. Although crucial for the spread of mosquito-borne diseases, blood feeding remains poorly understood due to technological limitations. Indeed, studies often expose human subjects to assess biting behavior. Here, we present the biteOscope, a device that attracts mosquitoes to a host

    更新日期:2020-09-22
  • Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease.
    eLife (IF 7.08) Pub Date : 2020-09-22
    Henri Leinonen,Nguyen C Pham,Taylor Boyd,Johanes Santoso,Krzysztof Palczewski,Frans Vinberg

    Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cells expected to support normal vision. Whether such homeostatic plasticity

    更新日期:2020-09-22
  • Evolution of island lizards remains a mystery.
    eLife (IF 7.08) Pub Date : 2020-09-22
    Kathryn D Kavanagh

    Lizards that live in the Greater Antilles exploit a large range of skeletal variations to adapt to similar habitats, in defiance of the theory of plasticity-led evolution.

    更新日期:2020-09-22
  • Host-induced spermidine production in motile Pseudomonas aeruginosa triggers phagocytic uptake.
    eLife (IF 7.08) Pub Date : 2020-09-22
    Sebastian Felgner,Matthias Preusse,Ulrike Beutling,Stephanie Stahnke,Vinay Pawar,Manfred Rohde,Mark Brönstrup,Theresia Stradal,Susanne Häussler

    Exploring the complexity of host-pathogen communication is vital to understand why microbes persist within a host, while others are cleared. Here, we employed a Dual-sequencing approach to unravel conversational turn-taking of dynamic host-pathogen communications. We demonstrate that upon hitting a host cell, motile Pseudomonas aeruginosa induce a specific gene expression program. This results in the

    更新日期:2020-09-22
  • Tuning movement for sensing in an uncertain world.
    eLife (IF 7.08) Pub Date : 2020-09-22
    Chen Chen,Todd D Murphey,Malcolm A MacIver

    While animals track or search for targets, sensory organs make small unexplained movements on top of the primary task-related motions. While multiple theories for these movements exist—in that they support infotaxis, gain adaptation, spectral whitening, and high-pass filtering—predicted trajectories show poor fit to measured trajectories. We propose a new theory for these movements called energy-constrained

    更新日期:2020-09-22
  • The perils of cheating.
    eLife (IF 7.08) Pub Date : 2020-09-22
    M Florencia Camus

    Experiments on mitochondrial DNA in worms highlight that cheating does not always pay off.

    更新日期:2020-09-22
  • PTPRG is an ischemia risk locus essential for HCO3--dependent regulation of endothelial function and tissue perfusion.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Kristoffer B Hansen,Christian Staehr,Palle D Rohde,Casper Homilius,Sukhan Kim,Mette Nyegaard,Vladimir V Matchkov,Ebbe Boedtkjer

    Acid-base conditions modify artery tone and tissue perfusion but the involved vascular sensing mechanisms and disease consequences remain unclear. We experimentally investigated transgenic mice and performed genetic studies in a UK-based human cohort. We show that endothelial cells express the putative HCO3–-sensor receptor-type tyrosine-protein phosphatase RPTPg, which enhances endothelial intracellular

    更新日期:2020-09-21
  • The effect of hybridization on transposable element accumulation in an undomesticated fungal species.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Mathieu Hénault,Souhir Marsit,Guillaume Charron,Christian R Landry

    Transposable elements (TEs) are mobile genetic elements that can profoundly impact the evolution of genomes and species. A long-standing hypothesis suggests that hybridization could deregulate TEs and trigger their accumulation, although it received mixed support from studies in plants and animals. Here, we tested this hypothesis in fungi using incipient species of the undomesticated yeast Saccharomyces

    更新日期:2020-09-21
  • Therapeutic effects of anodal transcranial direct current stimulation in a rat model of ADHD.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Da Hee Jung,Sung Min Ahn,Malk Eun Pak,Hong Ju Lee,Young Jin Jung,Kibong Kim,Yong-Il Shin,Hwa Kyoung Shin,Byung Tae Choi

    Most therapeutic candidates for treating attention deficit hyperactivity disorder (ADHD) have focused on modulating the dopaminergic neurotransmission system with neurotrophic factors. Regulation of this system by transcranial direct current stimulation (tDCS) could contribute to the recovery of cognitive symptoms observed in patients with ADHD. Here, male spontaneously hypertensive (SHR) rats were

    更新日期:2020-09-21
  • Genetic mapping of etiologic brain cell types for obesity.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Pascal N Timshel,Jonatan J Thompson,Tune H Pers

    The underlying cell types mediating predisposition to obesity remain largely obscure. Here, we integrated recently published single-cell RNA-sequencing (scRNA-seq) data from 727 peripheral and nervous system cell types spanning 17 mouse organs with body mass index (BMI) genome-wide association study (GWAS) data from >457,000 individuals. Developing a novel strategy for integrating scRNA-seq data with

    更新日期:2020-09-21
  • Site-specific effects of neurosteroids on GABAA receptor activation and desensitization.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Yusuke Sugasawa,Wayland Wl Cheng,John R Bracamontes,Zi-Wei Chen,Lei Wang,Allison L Germann,Spencer R Pierce,Thomas C Senneff,Kathiresan Krishnan,David E Reichert,Douglas F Covey,Gustav Akk,Alex S Evers

    This study examines how site-specific binding to three identified neurosteroid binding sites in the α1β3 GABAA receptor (GABAAR) contributes to neurosteroid allosteric modulation. We found that the potentiating neurosteroid, allopregnanolone, but not its inhibitory 3β-epimer epi-allopregnanolone, binds to the canonical β3(+)–α1(-) intersubunit site that mediates receptor activation by neurosteroids

    更新日期:2020-09-21
  • AANAT1 functions in astrocytes to regulate sleep homeostasis.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Sejal Davla,Gregory Artiushin,Yongjun Li,Daryan Chitsaz,Sally Li,Amita Sehgal,Donald J van Meyel

    How the brain controls the need and acquisition of recovery sleep after prolonged wakefulness is an important issue in sleep research. The monoamines serotonin and dopamine are key regulators of sleep in mammals and in Drosophila. We found that the enzyme arylalkylamine N-acetyltransferase 1 (AANAT1) is expressed by Drosophila astrocytes and specific subsets of neurons in the adult brain. AANAT1 acetylates

    更新日期:2020-09-21
  • Deciphering the regulatory genome of Escherichia coli, one hundred promoters at a time.
    eLife (IF 7.08) Pub Date : 2020-09-21
    William T Ireland,Suzannah M Beeler,Emanuel Flores-Bautista,Nicholas S McCarty,Tom Röschinger,Nathan M Belliveau,Michael J Sweredoski,Annie Moradian,Justin B Kinney,Rob Phillips

    Advances in DNA sequencing have revolutionized our ability to read genomes. However, even in the most well-studied of organisms, the bacterium Escherichia coli, for ≈ 65% of promoters we remain ignorant of their regulation. Until we crack this regulatory Rosetta Stone, efforts to read and write genomes will remain haphazard. We introduce a new method, Reg-Seq, that links massively-parallel reporter

    更新日期:2020-09-21
  • Apelin signaling drives vascular endothelial cells towards a pro-angiogenic state.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Christian Sm Helker,Jean Eberlein,Kerstin Wilhelm,Toshiya Sugino,Julian Malchow,Annika Schuermann,Stefan Baumeister,Hyouk-Bum Kwon,Hans-Martin Maischein,Michael Potente,Wiebke Herzog,Didier Yr Stainier

    To form new blood vessels (angiogenesis), endothelial cells (ECs) must be activated and acquire highly migratory and proliferative phenotypes. However, the molecular mechanisms that govern these processes are incompletely understood. Here, we show that Apelin signaling functions to drive ECs into such an angiogenic state. Zebrafish lacking Apelin signaling exhibit defects in endothelial tip cell morphology

    更新日期:2020-09-21
  • Dynamic encoding of social threat and spatial context in the hypothalamus.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Piotr Krzywkowski,Beatrice Penna,Cornelius T Gross

    Social aggression and avoidance are defensive behaviors expressed by territorial animals in a manner appropriate to spatial context and experience. The ventromedial hypothalamus controls both social aggression and avoidance, suggesting that it may encode a general internal state of threat modulated by space and experience. Here, we show that neurons in the mouse ventromedial hypothalamus are activated

    更新日期:2020-09-21
  • Localized inhibition in the Drosophila mushroom body.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Hoger Amin,Anthi A Apostolopoulou,Raquel Suárez-Grimalt,Eleftheria Vrontou,Andrew C Lin

    Many neurons show compartmentalized activity, in which activity does not spread readily across the cell, allowing input and output to occur locally. However, the functional implications of compartmentalized activity for the wider neural circuit are often unclear. We addressed this problem in the Drosophila mushroom body, whose principal neurons, Kenyon cells, receive feedback inhibition from a non-spiking

    更新日期:2020-09-21
  • Ubiquitin-interacting motifs of ataxin-3 regulate its polyglutamine toxicity through Hsc70-4-dependent aggregation.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Sean L Johnson,Bedri Ranxhi,Kozeta Libohova,Wei-Ling Tsou,Sokol V Todi

    Spinocerebellar ataxia type 3 (SCA3) belongs to the family of polyglutamine neurodegenerations. Each disorder stems from the abnormal lengthening of a glutamine repeat in a different protein. Although caused by a similar mutation, polyglutamine disorders are distinct, implicating non-polyglutamine regions of disease proteins as regulators of pathogenesis. SCA3 is caused by polyglutamine expansion in

    更新日期:2020-09-21
  • Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Sthitapranjya Pati,Kamal Saba,Sonali S Salvi,Praachi Tiwari,Pratik R Chaudhari,Vijaya Verma,Sourish Mukhopadhyay,Darshana Kapri,Shital Suryavanshi,James P Clement,Anant B Patel,Vidita A Vaidya

    Early adversity is a risk factor for the development of adult psychopathology. Common across multiple rodent models of early adversity is increased signaling via forebrain Gq-coupled neurotransmitter receptors. We addressed whether enhanced Gq-mediated signaling in forebrain excitatory neurons during postnatal life can evoke persistent mood-related behavioral changes. Excitatory hM3Dq DREADD-mediated

    更新日期:2020-09-21
  • Serine phosphorylation regulates the P-type potassium pump KdpFABC.
    eLife (IF 7.08) Pub Date : 2020-09-21
    Marie E Sweet,Xihui Zhang,Hediye Erdjument-Bromage,Vikas Dubey,Himanshu Khandelia,Thomas A Neubert,Bjorn P Pedersen,David L Stokes

    KdpFABC is an ATP-dependent K+ pump that ensures bacterial survival in K+-deficient environments. Whereas transcriptional activation of kdpFABC expression is well studied, a mechanism for down regulation when K+ levels are restored has not been described. Here we show that KdpFABC is inhibited when cells return to a K+-rich environment. The mechanism of inhibition involves phosphorylation of Ser162

    更新日期:2020-09-21
  • External location of touch is constructed post-hoc based on limb choice.
    eLife (IF 7.08) Pub Date : 2020-09-18
    Femke Maij,Christian Seegelke,W Pieter Medendorp,Tobias Heed

    When humans indicate on which hand a tactile stimulus occurred, they often err when their hands are crossed. This finding seemingly supports the view that the automatically determined touch location in external space affects limb assignment: the crossed right hand is localized in left space, and this conflict presumably provokes hand assignment errors. Here, participants judged on which hand the first

    更新日期:2020-09-20
  • A novel DNA primase-helicase pair encoded by SCCmec elements.
    eLife (IF 7.08) Pub Date : 2020-09-18
    Aleksandra Bebel,Melissa A Walsh,Ignacio Mir-Sanchis,Phoebe A Rice

    Mobile genetic elements (MGEs) are a rich source of new enzymes, and conversely, understanding the activities of MGE-encoded proteins can elucidate MGE function. Here we biochemically characterize 3 proteins encoded by a conserved operon carried by the Staphylococcal Cassette Chromosome (SCCmec), an MGE that confers methicillin resistance to Staphylococcus aureus, creating MRSA strains. The first of

    更新日期:2020-09-20
  • WDR90 is a centriolar microtubule wall protein important for centriole architecture integrity.
    eLife (IF 7.08) Pub Date : 2020-09-18
    Emmanuelle Steib,Marine H Laporte,Davide Gambarotto,Natacha Olieric,Celine Zheng,Susanne Borgers,Vincent Olieric,Maeva Le Guennec,France Koll,Anne-Marie Tassin,Michel O Steinmetz,Paul Guichard,Virginie Hamel

    Centrioles are characterized by a nine-fold arrangement of microtubule triplets held together by an inner protein scaffold. These structurally robust organelles experience strenuous cellular processes such as cell division or ciliary beating while performing their function. However, the molecular mechanisms underlying the stability of microtubule triplets, as well as centriole architectural integrity

    更新日期:2020-09-20
  • Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency.
    eLife (IF 7.08) Pub Date : 2020-09-18
    Richard B Crouse,Kristen Kim,Hannah M Batchelor,Eric M Girardi,Rufina Kamaletdinova,Justin Chan,Prithviraj Rajebhosale,Steven T Pittenger,Lorna W Role,David A Talmage,Miao Jing,Yulong Li,Xiao-Bing Gao,Yann S Mineur,Marina R Picciotto

    The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found

    更新日期:2020-09-20
  • Cell-cycle-gated feedback control mediates desensitization to interferon stimulation.
    eLife (IF 7.08) Pub Date : 2020-09-18
    Anusorn Mudla,Yanfei Jiang,Kei-Ichiro Arimoto,Bingxian Xu,Adarsh Rajesh,Andy P Ryan,Wei Wang,Matthew D Daugherty,Dong-Er Zhang,Nan Hao

    Cells use molecular circuits to interpret and respond to extracellular cues, such as hormones and cytokines, which are often released in a temporally varying fashion. In this study, we combine microfluidics, time-lapse microscopy, and computational modeling to investigate how the type I interferon (IFN)-responsive regulatory network operates in single human cells to process repetitive IFN stimulation

    更新日期:2020-09-20
  • The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies.
    eLife (IF 7.08) Pub Date : 2020-09-18
    Jennifer El Diaz,Mehmet Eren Ahsen,Thomas Schaffter,Xintong Chen,Ronald B Realubit,Charles Karan,Andrea Califano,Bojan Losic,Gustavo Stolovitzky

    Our ability to discover effective drug combinations is limited, in part by insufficient understanding of how the transcriptional response of two monotherapies results in that of their combination. We analyzed matched time course RNAseq profiling of cells treated with single drugs and their combinations and found that the transcriptional signature of the synergistic combination was unique relative to

    更新日期:2020-09-20
  • Topological constraints in early multicellularity favor reproductive division of labor.
    eLife (IF 7.08) Pub Date : 2020-09-17
    David Yanni,Shane Jacobeen,Pedro Márquez-Zacarías,Joshua S Weitz,William C Ratcliff,Peter J Yunker

    Reproductive division of labor (e.g., germ-soma specialization) is a hallmark of the evolution of multicellularity, signifying the emergence of a new type of individual and facilitating the evolution of increased organismal complexity. A large body of work from evolutionary biology, economics, and ecology has shown that specialization is beneficial when further division of labor produces an accelerating

    更新日期:2020-09-18
  • A whole-brain connectivity map of mouse insular cortex.
    eLife (IF 7.08) Pub Date : 2020-09-17
    Daniel August Gehrlach,Caroline Weiand,Thomas N Gaitanos,Eunjae Cho,Alexandra S Klein,Alexandru A Hennrich,Karl-Klaus Conzelmann,Nadine Gogolla

    The insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent. We employed cell-type specific monosynaptic rabies virus tracings to characterize afferent

    更新日期:2020-09-18
  • Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons.
    eLife (IF 7.08) Pub Date : 2020-09-17
    Feline W Lindhout,Robbelien Kooistra,Sybren Portegies,Lotte J Herstel,Riccardo Stucchi,Basten L Snoek,Af Maarten Altelaar,Harold D MacGillavry,Corette J Wierenga,Casper C Hoogenraad

    The differentiation of neuronal stem cells into polarized neurons is a well-coordinated process which has mostly been studied in classical non-human model systems, but to what extent these findings are recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured hiPSC-derived neurons, characterized early developmental stages, measured electrophysiological

    更新日期:2020-09-18
  • A dual role for Cav1.4 Ca2+ channels in the molecular and structural organization of the rod photoreceptor synapse.
    eLife (IF 7.08) Pub Date : 2020-09-17
    J Wesley Maddox,Kate L Randall,Ravi P Yadav,Brittany Williams,Jussara Hagen,Paul J Derr,Vasily Kerov,Luca Della Santina,Sheila A Baker,Nikolai Artemyev,Mrinalini Hoon,Amy Lee

    Synapses are fundamental information processing units that rely on voltage-gated Ca2+ (Cav) channels to trigger Ca2+-dependent neurotransmitter release. Cav channels also play Ca2+-independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Cav1.4 L-type channels for the formation of rod photoreceptor

    更新日期:2020-09-18
  • MAPK activity dynamics regulate non-cell autonomous effects of oncogene expression.
    eLife (IF 7.08) Pub Date : 2020-09-17
    Timothy J Aikin,Amy F Peterson,Michael J Pokrass,Helen R Clark,Sergi Regot

    A large fraction of human cancers contain genetic alterations within the Mitogen Activated Protein Kinase (MAPK) signaling network that promote unpredictable phenotypes. Previous studies have shown that the temporal patterns of MAPK activity (i.e. signaling dynamics) differentially regulate cell behavior. However, the role of signaling dynamics in mediating the effects of cancer driving mutations has

    更新日期:2020-09-18
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