MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16

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Highlights? Satellite cells can differentiate into brown adipocytes ? MicroRNA-133 targets Prdm16 3′UTR and controls brown adipose determination ? MicroRNA-133 antagonism induces active brown adipocytes within regenerating muscle ? MicroRNA-133 antagonism impedes the development of obesity     

EBF2 Determines and Maintains Brown Adipocyte Identity

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Highlights? Ebf2 is selectively expressed in brown relative to white adipocytes and binds to chromatin at brown fat-specific target sites of Pparγ ? Ebf2 expression in white fat or muscle precursor cells recruits Pparγ to its brown fat-specific gene targets and drives a complete program of brown adipocyte differentiation ? Brown adipose cells and tissue from Ebf2-deficient mice display a complete loss of thermogenic characteristics while gaining molecular attributes of white adipose     

Class II Major Histocompatibility Complex Plays an Essential Role in Obesity-Induced Adipose Inflammation

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Highlights? Obesity enhances MHCII expression in primary human and mouse adipocytes ? Adipocytes activate CD4+ ARTs via MHCII and leptin to induce adipose inflammation ? Macrophage changes in adipose follow adipocyte and T cell interactions during HFD ? Adaptive immune mechanisms are essential to obesity-induced adipose inflammation     

PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein

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Highlights? PPARγ full agonists induce a brown fat phenotype in subcutaneous WAT ? PRDM16 is required for the development of PPARγ agonist-inducible brow adipocytes ? PRDM16 and PPARγ agonists synergistically activate the brown fat gene program ? Browning effect is mediated through the enhanced stability of the PRDM16 protein     

Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis

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Highlights? Two-way modulations of adipose VEGF were generated with aP2-Cre transgene ? Adipose VEGF KO reduces vasculature, increases hypoxia and inflammation in fat ? Adipose VEGF KO accelerates the development of metabolic disease in high-fat diet ? Induced adipose VEGF has opposite effect on fat and restores metabolic homeostasis     

Imbalance between Neutrophil Elastase and its Inhibitor α1-Antitrypsin in Obesity Alters Insulin Sensitivity,Inflammation, and Energy Expenditure

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Highlights? Obese men and mice have decreased serum A1AT levels and increased NE activity ? Neutrophil infiltration and NE deposition occur in adipose tissue from HFD-fed mice ? NE^?/? and A1AT Tg mice have reduced HFD-induced insulin resistance and inflammation ? NE deletion increases AMPK signaling and fatty acid oxidation in liver and BAT     

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     

Deubiquitination of NLRP3 by BRCC3 Critically Regulates Inflammasome Activity

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Highlights? Inhibition of deubiquitination blocks inflammasome activation ? Inhibition of deubiquitination induces NLRP3 polyubiquitination ? Deubiquitination of NLRP3 regulates the activation of inflammasome ? The deubiquitinating enzyme BRCC3 deubiquitinates the LRR domain of NLRP3     

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     

Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases

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Highlights? Crystal structure of CCM3-MST4 heterodimeric complex ? Structural mechanism driving CCM3-GCKIII heterodimerization ? Conformational changes required for CCM3-GCKIII heterodimerization ? Synergistic effects of CCM3-MST4 complex on cell proliferation and migration     

BLOC-3 Mutated in Hermansky-Pudlak Syndrome Is a Rab32/38 Guanine Nucleotide Exchange Factor

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Highlights? The Hps1-Hps4 complex (BLOC-3) is a guanine nucleotide exchange factor (GEF) ? Purified BLOC-3 has specific GEF activity toward Rab32 and Rab38 ? BLOC-3 can promote recruitment of Rab32 and Rab38 to membranes ? BLOC-3 and its target Rabs act in the biogenesis of melanosomes     

The RNA Pol II Elongation Factor Ell3 Marks Enhancers in ES Cells and Primes Future Gene Activation

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Highlights? Ell3 is preferentially found at active, poised, and inactive enhancers in ES cells ? Promoter-proximal Pol II occupancy at key developmental genes requires Ell3 ? Cohesin functions in Ell3-associated enhancer-promoter communication ? Recruitment of P-TEFb within SEC during differentiation is Ell3 dependent     

Repeated Origin of Three-Dimensional Leaf Venation Releases Constraints on the Evolution of Succulence in Plants

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Highlights? The evolution of extreme succulence in leaves is constrained by low vein density ? An unusual 3D leaf venation has evolved repeatedly in the most succulent leaves ? 3D leaves maintain veins in close proximity to photosynthetic tissues ? 3D venation facilitates the evolution of previously inaccessible phenotypes     

Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

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Highlights? Snx3 is highly expressed in vertebrate hematopoietic tissues ? Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates ? Snx3 and Vps35 physically interact with Tfrc ? Snx3 is required for endosomal recycling of Tf-Tfrc complex     

Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCι in complex with a substrate peptide from Par-3

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Highlights? The 3D structure of PKCι in complex with a peptide from Par-3 is determined ? PKCι does not need phosphorylation of Thr402 in its activation loop for its activity ? aPKCs do not need a priming kinase for their activations ? The PKCι/Par-3 structure reveals a unique substrate recognition patterns for aPKCs     

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     

An ERK-p38 Subnetwork Coordinates Host Cell Apoptosis and Necrosis during Coxsackievirus B3 Infection

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Highlights? Intracellular signaling predicts the fate of coxsackievirus B3 (CVB3)-infected cells ? p38 and ERK signaling pathways are tightly interconnected during CVB3 infection ? CVB3-induced apoptosis of cardiomyocytes is inhibited by ERK5 and ERK1/2 pathways ? CVB3 induces necrosis of cardiomyocytes via p38 activation     

ANGUSTIFOLIA3 Signaling Coordinates Proliferation between Clonally Distinct Cells in Leaves

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Highlights? AN3 is produced specifically in mesophyll cells and moves into epidermal cells ? AN3 participates in the control of epidermal cell proliferation ? AN3 signaling is essential for normal leaf development ? AN3 movement does not require the action of the type II chaperonin complex     

Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA

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Highlights? Neil3 is an Fpg/Nei DNA glycosylase of the base excision repair pathway ? Neil3 excises a broad spectrum of base lesions, with a marked preference for ssDNA ? We report a crystal structure of Neil3 DNA glycosylase ? The structure provides valuable insights into Neil3′s unusual substrate specificity