Macrophage autophagy plays a protective role in advanced atherosclerosis

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Highlights? Proapoptotic oxidative stress induces autophagy in macrophages (M?s) ? Inhibition of autophagy enhances oxidative stress and apoptosis in M?s ? Atheromata of M?-Atg5^?/?Ldlr^?/? mice have increased apoptosis and plaque necrosis ? Apoptotic Atg5^?/? M?s are poorly recognized by phagocytes in vitro and in atheromata     

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     

Saturated fatty acid and TLR signaling link β cell dysfunction and islet inflammation

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Highlights? Palmitate induces β cell dysfunction by activating inflammatory processes in islets ? β cells sense palmitate via the TLR4 pathway and recruit M1 macrophages to islets ? M1 macrophages play a pivotal role in palmitate-induced β cell dysfunction ? M1 macrophages and inflammation also play a role in β cell dysfunction in T2D models     

Integration of Chemical and RNAi Multiparametric Profiles Identifies Triggers of Intracellular Mycobacterial Killing

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Highlights? A high-content chemical screen identifies modulators of intracellular mycobacteria ? Three compounds that kill bacteria by altering host processes were validated ? Multiparametric chemical and genetic data sets integrated to identify mode of action ? Modulation of autophagy and endosomal trafficking identified as mode of action     

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     

Insights into Negative Regulation by the Glucocorticoid Receptor from Genome-wide Profiling of Inflammatory Cistromes

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Highlights? TLR4 activation dramatically remodels the GR cistrome in macrophages ? Both negative and positive GR enhancers include GREs, NF-κB, and AP-1 sites ? Classical models fail to predict positive or negative polarity of GR regulation ? Hormone treatment marks negative enhancers by histone deacetylation     

Reprogramming Adult Schwann Cells to Stem Cell-like Cells by Leprosy Bacilli Promotes Dissemination of Infection

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Highlights? Leprosy bacteria reprogram adult Schwann cells by altering host-gene expression ? Bacterially reprogrammed cells resemble progenitor/stem-like cells (pSLC) of mesenchymal trait ? pSLC promote bacterial spread to mesenchymal tissues by redifferentiation ? pSLC secrete immune factors, recruit macrophages, transfer bacteria, form granulomas, and disseminate infection     

Antiviral Instruction of Bone Marrow Leukocytes during Respiratory Viral Infections

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Highlights? Lung-produced type I interferons instruct bone marrow cells during respiratory virus infections ? IFN-exposed bone marrow leukocytes become resistant to virus infection ? Primed and protected bone marrow leukocytes migrate to the infected lung and contribute to virus clearance     

HRG1 Is Essential for Heme Transport from the Phagolysosome of Macrophages during Erythrophagocytosis

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Highlights? Humans have about 25 trillion RBCs, each containing over a billion heme moieties ? Five million senescent RBCs are recycled per second by erythrophagocytosis in macrophages to make new RBCs ? HRG1, the mammalian homolog of C. elegans heme transporter, recycles heme-iron from the macrophage phagolysosome ? Missense polymorphisms in human HRG1 may be genetic modifiers of iron metabolism     

A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

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Highlights? RIP3 deficiency in macrophages reduces advanced atherosclerotic lesions ? RIP3 deficiency reduces primary necrosis of macrophages in advanced lesions ? RIP3-dependent macrophage necrosis is not postapoptotic cell death ? Increased RIP3 converts apoptosis to necrosis in advanced lesional macrophages     

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     

Protein Phosphatase 2A Catalytic Subunit α Plays a MyD88-Dependent,Central Role in the Gene-Specific Regulation of Endotoxin Tolerance

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Highlights? PP2Ac is constitutively activated and targets MyD88 in LPS-tolerized macrophages ? Constitutively active PP2Ac shifts a proinflammatory MyD88 to its prosurvival mode ? Constitutively active PP2Ac reprograms gene-specific chromatin modification landscape ? Constitutively active PP2Ac broadly defines ET at both signaling and epigenetic levels     

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     

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     

C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity

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Highlights? C/EBPα converts selected human lymphoma and leukemia B cell lines into macrophages ? During transdifferentiation, cells become phagocytic and quiescent ? Cells retain their macrophage phenotype even after withdrawal of the C/EBPα inducer ? C/EBPα impairs the tumorigenicity of responsive lymphoma/leukemia cells     

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     

Protein model discrimination using mutational sensitivity derived from deep sequencing

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Highlights? Individual mutant phenotypes in a saturation library derived via deep sequencing ? Residue depth and active-site residue derivation from mutant phenotypes ? Mutant-phenotype-derived parameters used for protein model discrimination ? Derivation of sequence-structure-function relationships without protein isolation     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia