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These experiments confirm that flow-induced GCX degradation can enable metastatic CTC arrest. This work, therefore, provides new insight into pathways of secondary tumor formation. © 2020 Federation of American Societies for Experimental Biology.Retinol-binding protein-4 (RBP4) is elevated in serum and adipose tissue (AT) in obesity-induced insulin resistance and correlates inversely with insulin-stimulated glucose disposal. But its role in insulin-mediated suppression of lipolysis, free fatty acids (FFA), and endogenous glucose production (EGP) in humans is unknown. RBP4 mRNA or protein levels were higher in liver, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in morbidly obese subjects undergoing Roux-en-Y gastric bypass surgery compared to lean controls undergoing elective laparoscopic cholecystectomy. RBP4 mRNA expression in SAT correlated with the expression of several macrophage and other inflammation markers. Serum RBP4 levels correlated inversely with glucose disposal and insulin-mediated suppression of lipolysis, FFA, and EGP. Mechanistically, RBP4 treatment of human adipocytes in vitro directly stimulated basal lipolysis. Treatment of adipocytes with conditioned media from RBP4-activated macrophages markedly increased basal lipolysis and impaired insulin-mediated lipolysis suppression. RBP4 treatment of macrophages increased TNFα production. These data suggest that elevated serum or adipose tissue RBP4 levels in morbidly obese subjects may cause hepatic and systemic insulin resistance by stimulating basal lipolysis and by activating macrophages in adipose tissue, resulting in release of pro-inflammatory cytokines that impair lipolysis suppression. While we have demonstrated this mechanism in human adipocytes in vitro, and correlations from our flux studies in humans strongly support this, further studies are needed to determine whether this mechanism explains RBP4-induced insulin resistance in humans. © 2020 The Authors. selleck kinase inhibitor The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology.Research has focused on the role of theory of mind (ToM) for positive social behaviour, while the association between ToM and negative social behaviours is less well understood. This longitudinal study compares two mediation models examining the role of ToM and peer-rated social preference at ages 5 and 6 for bullying at age 7. Participants were 114 children (58 boys, Mage  = 67 months) at entry to primary school (T1). At Time 2 (T2), 106 children and, at Time 3 (T3), 96 children remained. Teacher-rated externalizing problems and children's language ability were controlled at T1. Poor ToM was found to indirectly predict later bullying via poor social preference, while for boys only, greater earlier ToM directly predicted greater bullying 2 years later. These results suggest that there are different pathways to bullying via ToM and social preference, which has implications for interventions to prevent the development of bullying behaviour. © 2020 The British Psychological Society.The social parasitic beetle Paussus favieri (Coleoptera, Carabidae, Paussini) performs different types of stridulations, which selectively mimic those emitted by different ant castes of its host Pheidole pallidula (Hymenoptera, Formicidae, Myrmicinae). However, the significance of this acoustical mimicry for the success of the parasitic strategy and the behaviors elicited in the host ants by stridulations was unknown. We reared Paussus favieri in Pheidole pallidula colonies and filmed their interacting behaviors. We analyzed in slow motion the behavior of ants near a stridulating beetle. We analyzed separately trains of pulse (Pa+Pb, produced by repeated rubbings) and single pulse (Pc, produced by a single rubbing) of stridulations, clearly recognizable from the shaking up and down of the beetle hind legs, and associated them with different ant responses. The full repertoire of sounds produced by P. favieri elicited benevolent responses both in workers and soldiers. We found that different signals elicit different (sometimes multiple) behaviors in ants, with different frequency in the two ant castes. However, Pc (alone or in conjunction with other types of pulses) appears to be the type of acoustic signal mostly responsible for all recorded behaviors. These results indicate that the acoustic channel plays a pivotal role in the host-parasite interaction. Finding that a parasite uses the acoustical channel so intensively, and in such a complicated way to trigger ant behaviors, indicates that acoustic signals may be more important in ant societies than commonly recognized. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Primary cilia are sensory organelles that are essential for eukaryotic development and health. These antenna-like structures are synthesized by intraflagellar transport protein complexes, IFT-B and IFT-A, which mediate bidirectional protein trafficking along the ciliary axoneme. Here using mouse embryonic fibroblasts (MEF), we investigate the ciliary roles of two mammalian orthologues of Chlamydomonas IFT-A gene, IFT139, namely Thm1 (also known as Ttc21b) and Thm2 (Ttc21a). Thm1 loss causes perinatal lethality, and Thm2 loss allows survival into adulthood. At E14.5, the number of Thm1;Thm2 double mutant embryos is lower than that for a Mendelian ratio, indicating deletion of Thm1 and Thm2 causes mid-gestational lethality. We examined the ciliary phenotypes of mutant MEF. Thm1-mutant MEF show decreased cilia assembly, increased cilia disassembly, shortened primary cilia, a retrograde IFT defect for IFT and BBS proteins, and reduced ciliary entry of membrane-associated proteins. Thm1-mutant cilia also show a retrograde transport defect for the Hedgehog transducer, Smoothened, and an impaired response to Smoothened agonist, SAG. Thm2-null MEF show normal ciliary dynamics and Hedgehog signaling, but additional loss of a Thm1 allele impairs response to SAG. Further, Thm1;Thm2 double-mutant MEF show enhanced cilia disassembly, and increased impairment of INPP5E ciliary import. Thus, Thm1 and Thm2 have unique and redundant roles in MEF. Thm1 regulates cilia assembly, and alone and together with Thm2, regulates cilia disassembly, ciliary entry of membrane-associated protein, Hedgehog signaling, and embryogenesis. These findings shed light on mechanisms underlying Thm1-, Thm2- or IFT-A-mediated ciliopathies. © 2020 Federation of American Societies for Experimental Biology.