Deficiency of lipoprotein lipase in neurons modifies the regulation of energy balance and leads to obesity

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Highlights? Mice with lipoprotein lipase deficiency in neurons (NEXLPL) are obese ? NEXLPL mice develop obesity by modifying both food intake and energy expenditure ? NEXLPL mice have increases in hypothalamic AgRP/NPY gene expression before obesity ? NEXLPL mice demonstrate deficiencies in n-3 fatty acids in the hypothalamus     

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     

Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment

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Highlights? Cohesin is required for the association of its loader, Scc2/4, with centromeres ? The Ctf19 kinetochore subcomplex targets the loader to centromeres ? Centromere-loaded cohesin ensures pericentromeric cohesion establishment ? Cohesin ring formation triggers cohesin loading via Scc2/4     

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     

Kinetochores Generate Microtubules with Distal Plus Ends: Their Roles and Limited Lifetime in Mitosis

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Highlights? A short-lived population of kinetochore-derived microtubules (MTs) has distal plus ends ? These MTs are generated in early mitosis and regulated by Stu2 ? They interact with spindle pole-derived MTs before kinetochore attachment ? Once kinetochores attach to spindle-pole MTs, the short-lived MT population disappears     

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     

Transcriptional Cofactor TBLR1 Controls Lipid Mobilization in White Adipose Tissue

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Highlights? TBLR1 controls cAMP-dependent lipolysis in adipocytes ? Adipocyte-specific deletion of TBLR1 in mice impairs fasting-induced lipolysis ? Lack of TBLR1 in adipocytes aggravates diet-induced obesity and metabolic dysfunction ? TBLR1 mRNA levels in WAT are elevated under lipolytic conditions in mice and humans     

The n-SET Domain of Set1 Regulates H2B Ubiquitylation-Dependent H3K4 Methylation

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Highlights? H2B ubiquitylation directly stimulates H3K4 methylation by the yeast Set1 complex ? Swd2 is not directly required for the H3K4 methylation activity of the yeast Set1 complex ? The Set1 n-SET domain plays a critical role in H2Bub-dependent H3K4 methylation ? Spp1 is conditionally involved in n-SET- and H2Bub-dependent H3K4 methylation     

p58IPK-Mediated Attenuation of the Proapoptotic PERK-CHOP Pathway Allows Malignant Progression upon Low Glucose

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Highlights? Transformation-associated glucose shortage triggers ER stress ? The ER stress acts as barrier to malignancy by triggering UPR-dependent apoptosis ? p58^IPK expression removes the UPR barrier by attenuating its PERK-CHOP branch ? This adaptive mechanism enables implementation of UPR cytoprotective features     

O-GlcNAc Signaling Entrains the Circadian Clock by Inhibiting BMAL1/CLOCK Ubiquitination

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Highlights? The hexosamine/O-GlcNAc pathway regulates cellular clock oscillation ? OGT promotes expression of BMAL1/CLOCK target genes in cultured cells and liver ? Rhythmic O-GlcNAcylation stabilizes BMAL1 and CLOCK by inhibiting their ubiquitination ? Hepatic manipulation of OGT perturbs the diurnal rhythm of glucose homeostasis     

Inhibition of Leptin Regulation of Parasympathetic Signaling as a Cause of Extreme Body Weight-Associated Asthma

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Highlights? Leptin regulates airway diameter, independently of body weight and inflammation ? Leptin uses the parasympathetic tone to regulate airway diameter ? Modulating the parasympathetic tone can correct bronchoconstriction in obese mice     

Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

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Highlights? c-Src phosphorylates syndecan-4 in response to extracellular stimuli ? Syndecan-4 phosphorylation and engagement regulate Arf6 activity ? Syndecan-4-mediated Arf6 activity regulates differential integrin recycling ? Syndecan-4-mediated integrin recycling controls FA dynamics and cell migration     

Two distinct binding modes define the interaction of Brox with the C-terminal tails of CHMP5 and CHMP4B

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Highlights? CHMP5 binds and recruits Brox to membrane fractions through its C-terminal tail ? The CHMP5 C-terminal tail adopts a tandem β-hairpin structure ? The CHMP4B C-terminal tail α helix binds at a concave surface of Brox ? The CHMP5 β-hairpins and CHMP4B α helix bind the same surface at Brox     

LSD2/KDM1B and Its Cofactor NPAC/GLYR1 Endow a Structural and Molecular Model for Regulation of H3K4 Demethylation

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Highlights? Identifying NPAC as a novel LSD2 cofactor stimulating H3K4 demethylation ? Structure determination of LSD2 alone or in complex with NPAC and histone H3 peptide ? Defining the key NPAC residues essential for its intrinsic LSD2 cofactor activity ? Establishing a molecular model for how a cofactor regulates histone demethylation     

Cap-assisted internal initiation of translation of histone H4

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Highlights? Two structural elements of histone H4 mRNA drive translation initiation ? Ribosome is tethered by an eIF4E-binding site located in the coding region ? A RNA three-way helix junction element positions ribosome on the start codon ? The m⁷G cap-binding pocket formed by the mRNA controls histone translation     

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     

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     

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