The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity,Is Regulated by Phosphorylation

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Highlights? SAMHD1 only exhibits antiviral activity when expressed in noncycling cells ? SAMHD1 is unphosphorylated in noncycling cells ? Reverse genetics revealed that phosphorylated SAMHD1 is repressive for restriction ? SAMHD1 phosphorylation regulates restriction, but not the cellular levels of dNTPs     

CED-1, CED-7, and TTR-52 regulate surface phosphatidylserine expression on apoptotic and phagocytic cells

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Highlights? PS is expressed on the surface of apoptotic and phagocytic cells during apoptosis ? CED-7 and TTR-52 mediate time-dependent loss of PS from surface of apoptotic cells ? CED-7 and TTR-52 promote generation of extracellular PS vesicles ? CED-7/TTR-52/CED-1 promote phagocyte PS expression, important for corpse engulfment     

Pou5f1-Dependent EGF Expression Controls E-Cadherin Endocytosis,Cell Adhesion,and Zebrafish Epiboly Movements

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Highlights? Pou5f1 regulates EGF expression during oogenesis ? EGFR signaling controls E-cadherin trafficking at blastula and gastrula stages ? E-cadherin subcellular trafficking controls adhesion and cell migration ? Dynamics of E-cadherin adhesion is essential for effective cell migration     

Insights into FlaI Functions in Archaeal Motor Assembly and Motility from Structures,Conformations, and Genetics

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Highlights? Cross-subunit interface forms building block for transmission of ATPase force ? Structures and mutants reveal functional components for assembly and motility ? The directionality of movement explains FlaI activities and GspE differences ? The phosphate released by ATP hydrolysis triggers subunit rearrangements     

Structural Basis for dsRNA Recognition,Filament Formation,and Antiviral Signal Activation by MDA5

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Highlights? MDA5 forms an open, C-shaped ring around the viral dsRNA stem ? The CTD of MDA5 has a different orientation and flexibility compared to RIG-I ? MDA5 forms filaments by stacking monomers head-to-tail with a 70° turn per monomer ? The 2CARD domain assembles into oligomers that activate interferon signaling via MAVS     

Kinetic,Energetic, and Mechanical Differences between Dark-State Rhodopsin and Opsin

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Highlights? Mapping the stability of opsin from the rod outer segment of the mouse eye ? Compared to dark-state rhodopsin opsin increases mechanical stability and rigidity ? Compared to dark-state rhodopsin opsin reduces lifetime and free energy ? Compared to dark-state rhodopsin opsin is pliable and adopts alternate conformations     

Repeated,Long-Term Cycling of Putative Stem Cells between Niches in a Basal Chordate

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Highlights? Identification of a niche for germline and somatic stem cells in a basal chordate ? Stem cells repeatedly migrate between aged or damaged niches into developing niches     

A DNA-Damage Selective Role for BRCA1 E3 Ligase in Claspin Ubiquitylation,CHK1 Activation,and DNA Repair

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Highlights? BRCA1 E3 ligase activity is essential for a subset of DNA damage responses ? BRCA1 V26A mutant cells are sensitive to topoisomerase inhibitors but not mitomycin C ? BRCA1 selectively ubiquitylates claspin after topoisomerase inhibition ? BRCA1 E3 ligase inactivation selectively impairs CHK1 activation     

Dendritic Filopodia,Ripped Pocket,NOMPC, and NMDARs Contribute to the Sense of Touch in Drosophila Larvae

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Highlights? Larval multidendritic neurons are required for sensing gentle touch in Drosophila ? Optogenetic activation of defined multidendritic neurons triggers touch behaviors ? Sensory filopodia are dynamic, F-actin-rich organelles necessary for mechanosensing ? A high-throughput touch screen identifies NMDARs, NOMPC, and Ripped Pocket     

HIV Nef,Paxillin, and Pak1/2 Regulate Activation and Secretion of TACE/ADAM10 Proteases

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Highlights? HIV-Nef translocates activated TACE/ADAM17 into extracellular vesicles (EVs) ? The mechanism is initiated by interaction of Eed and paxillin with TACE ? Translocation of TACE into EVs is regulated by Pak2 ? Melanoma cells activate the same mechanism to upload activated ADAM10 into EVs     

Directed microtubule growth, +TIPs, and kinesin-2 are required for uniform microtubule polarity in dendrites

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Highlights? Uniform microtubule polarity in dendrites requires directed microtubule growth ? Growing microtubule plus ends use stable microtubules as directional tracks ? Dendrite microtubule polarity is disrupted when kinesin-2 and +TIP levels are reduced ? Kinesin-2 attachment to microtubule plus ends might allow directed microtubule growth     

Structure of NPP1, an Ectonucleotide Pyrophosphatase/Phosphodiesterase Involved in Tissue Calcification

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Highlights? We determine the crystal structure of mouse NPP1 ? We elucidate the mechanism of NPP1 dimer formation and secretion ? The structure explains the dramatic functional differences between NPP1 and NPP2 ? The structure allows defining the impact of pathogenic mutations in human NPP1     

Sustained Activation of mTORC1 in Skeletal Muscle Inhibits Constitutive and Starvation-Induced Autophagy and Causes a Severe,Late-Onset Myopathy

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Highlights? mTORC1 inhibition is required for constitutive and starvation-induced autophagy ? Sustained activation of mTORC1 causes a severe myopathy due to autophagy impairment ? TSC1 depletion is sufficient to activate mTORC1 irrespective of other stimuli ? mTORC1 inactivation is sufficient to trigger LC3 lipidation     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

The Architecture of EssB,an Integral Membrane Component of the Type VII Secretion System

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Highlights? EssB, a membrane-bound component of the type VII secretion system, forms a dimer ? The cytoplasmic segment EssB-N is remarkably similar to pseudokinases ? The extracellular C-terminal domain displays a helical fold ? PELDOR spectroscopy enabled construction of a model of the complete dimer     

Genetic Control of Obesity and Gut Microbiota Composition in Response to High-Fat,High-Sucrose Diet in Mice

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Highlights? Detailed analysis of diet-induced obesity in more than 100 inbred mouse strains ? Identification of 11 genetic loci associated with obesity and dietary responsiveness ? Significant overlap between mouse loci with human GWAS loci for obesity ? Strain-specific shifts in gut microbiota composition in response to dietary intervention     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice