ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

Two Deubiquitylases Act on Mitofusin and Regulate Mitochondrial Fusion along Independent Pathways

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Highlights? Mitochondrial fusion is regulated by independent ubiquitylation pathways ? The deubiquitylase Ubp2 promotes fusion, whereas Ubp12 inhibits fusion events ? Self-assembly and ubiquitylation cooperatively enable mitochondrial fusion ? Yeast mitofusin is sequentially ubiquitylated     

Homeodomain-interacting protein kinase regulates yorkie activity to promote tissue growth

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Highlights? Hipk induces tissues overgrowth and leads to activation of Yki target genes ? Hipk is required for activity of hyperactive Yki ? Hipk kinase function is essential to promote Yki target genes     

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     

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     

Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis

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Highlights? Discovery that Rspo3 binds syndecan 4 ? Rspo3/Sdc4 induce Wnt/PCP signaling via clathrin-mediated endocytosis ? Rspo3/PCP signaling is essential for gastrulation and cartilage morphogenesis     

Impaired Cholesterol Efflux in Senescent Macrophages Promotes Age-Related Macular Degeneration

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Highlights? Macrophage senescence impairs cholesterol efflux and promotes macular degeneration ? Senescent macrophages polarize to a proangiogenic, disease-promoting phenotype ? Macrophage cholesterol efflux is regulated by miR33 and its target ABCA1 ? Age-related decrease in macrophage cholesterol efflux is therapeutically reversible     

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     

The WW Domain Protein Kibra Acts Upstream of Hippo in Drosophila

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Highlights? The WW domain protein Kibra is a Hippo signalling component ? Kibra restricts organ size via Yorkie and acts upstream of Hippo and Merlin ? Kibra synergizes with Expanded and binds to Merlin     

Screening and in situ synthesis using crystals of a NAD kinase lead to a potent antistaphylococcal compound

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Highlights? Precise interaction mapping using substrate analogs and X-ray crystallography ? Amidation of 5′-amino-5′-deoxy-adenosine is promoted by crystallized LmNADK1 ? Structures guide fragment bridging to design a new antistaphylococcal compound     

Cofactors required for TLR7- and TLR9-dependent innate immune responses

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Highlights? RNAi and systems-based analysis identified 190 TLR7/9 signaling cofactors ? Pathway crossprofiling enabled mapping cofactors to specific NFκB signaling modules ? HRS is a mediator of ubiquitin-dependent nondegradative endosomal TLR sorting     

Imparting Regenerative Capacity to Limbs by Progenitor Cell Transplantation

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Highlights? Transplantation of limb progenitor cells promotes multiple digit regenerates ? Wnt/β-catenin activation is required to stimulate adult frog limb regeneration ? Growth factors promote cell survival and growth and give pattern information ? Regeneration-incompetent host limb cells contribute to the regenerated limbs     

Design of a Phosphorylatable PDZ Domain with Peptide-Specific Affinity Changes

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Highlights? Successful design of phosphorylation sites into a globular protein ? Redesigned PDZ domain phosphorylation is associated with local destabilization ? Phosphorylation switches peptide binding function ? Phosphorylation switches peptide recognition specificity     

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     

Allosteric Mechanism Controls Traffic in the Chaperone/Usher Pathway

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Highlights? Allosteric mechanism controls traffic in the chaperone/usher pathway ? Usher-binding site in free chaperone is conformationally locked ? Subunit binding opens the lock in the chaperone, allowing usher targeting     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

Conserved and Divergent Roles of FGF Signaling in Mouse Epiblast Stem Cells and Human Embryonic Stem Cells

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Highlights? Nanog is a direct target of Activin and SMAD2/3 but not FGF-ERK in EpiSCs ? FGF signaling inhibits neuroectodermal commitment of EpiSCs and hESCs ? FGF inhibition relieves Klf2 repression and reverts EpiSCs to an ESC-like state ? mESCs transition to an EpiSC-like state with LIF inhibition and FGF activation     

Functional Classification of Immune Regulatory Proteins

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Highlights? An intermediate sequence based clustering algorithm, Brotherhood, is introduced ? The Brotherhood method is used to assign functional families within the human IgSF ? Newly annotated nectin-like family member, CRTAM, structure is solved ? Homophilic transinteraction is observed for CRTAM