Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Brun, N. R., van Hage, P., Hunting, E. R., Haramis, A. G., Vink, S. C., Vijver, M. G., Schaaf, M. J. M., & Tudorache, C. Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish. Communications Biology, 2, (2019): 382, doi:10.1038/s42003-019-0629-6.Plastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that internalised nanoplastics may disrupt processes related to energy metabolism. Such disruption can be crucial for organisms during development and may ultimately lead to changes in behaviour. Here, we investigated the link between polystyrene nanoplastic (PSNP)-induced signalling events and behavioural changes. Larval zebrafish exhibited PSNP accumulation in the pancreas, which coincided with a decreased glucose level. By using hyperglycemic and glucocorticoid receptor (Gr) mutant larvae, we demonstrate that the PSNP-induced disruption in glucose homoeostasis coincided with increased cortisol secretion and hyperactivity in challenge phases. Our work sheds new light on a potential mechanism underlying nanoplastics toxicity in fish, suggesting that the adverse effect of PSNPs are at least in part mediated by Gr activation in response to disrupted glucose homeostasis, ultimately leading to aberrant locomotor activity.We thank Natalia Novik and Laurie Mans for technical assistance during glucose assay and in situ hybridisation, respectively, Rubén Marín-Juez for providing the ins riboprobe, and John J. Stegeman for his helpful comments on the manuscript. The research described in this work was supported by the Dutch research council NWO (MGV; 864.13.010)

Soap Operas and Fertility: Evidence from Brazil

This paper focuses on fertility choices in Brazil, a country where soap operas (novelas) portray families that are much smaller than in reality, to study the effects of television on individual behavior. Using Census data for the period 1970-1991, the paper finds that women living in areas covered by the Globo signal have significantly lower fertility. The effect is strongest for women of lower socioeconomic status and for women in the central and late phases of their fertility cycle. Finally, the paper provides evidence that novelas, rather than television in general, affected individual choices

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

A Potential Diagnostic Approach for Foetal Long-QT Syndrome, Developed and Validated in Children

In patients with Long-QT Syndrome (LQTS), mechanical abnormalities have been described. Recognition of these abnormalities could potentially be used in the diagnosis of LQTS, especially in the foetus where an ECG is not available and DNA-analysis is invasive. We aimed to develop and validate a marker for these mechanical abnormalities in children and to test its feasibility in foetuses as a proof of principle. We measured the myocardial contraction duration using colour Tissue Doppler Imaging (cTDI) in 41 LQTS children and age- and gender-matched controls. Children were chosen to develop and validate the measurement of the myocardial contraction duration, due to the availability of a simultaneously recorded ECG. Feasibility of this measurement in foetuses was tested in an additional pilot study among seven LQTS foetuses and eight controls. LQTS children had a longer myocardial contraction duration compared to controls, while there was no statistical difference in heart rate. Measuring the myocardial contraction duration in children had a high inter- and intra-observer validity and reliably correlated with the QT-interval. There was an area under the curve (AUC) of 0.71, and the optimal cut-off value showed an especially high specificity in diagnosing LQTS. Measuring the myocardial contraction duration was possible in all foetuses and had a high inter- and intra-observer validity (ICC = 0.71 and ICC = 0.88, respectively). LQTS foetuses seemed to have a longer myocardial contraction duration compared to controls. Therefore, a prolonged contraction duration may be a potential marker for the prenatal diagnosis of LQTS in the future. Further studies are required to support the measurement of the myocardial contraction duration as a diagnostic approach for foetal LQTS

Electrical remodeling after percutaneous atrial septal defect closure in pediatric and adult patients

Background: Several studies have reported changes in electrocardiographic variables after atrial septal defect (ASD) closure. However no temporal electro-and vectorcardiographic changes have been described from acute to long-term follow-up at different ages. We aimed to study electrical remodeling after percutaneous ASD closure in pediatric and adult patients. Methods: ECGs of 69 children and 75 adults (median age 6 [IQR 4–11] years and 45 [IQR 33–54] years, respectively) were retrospectively selected before percutaneous ASD closure and at acute (1–7 days), intermediate (4–14 weeks) and late (6–18 months) follow-up. Apart from electrocardiographic variables, spatial QRS-T angle and ventricular gradient (VG) were derived from mathematically-synthesized vectorcardiograms. Results: In both pediatric and adult patients, the heart rate decreased immediately post-closure, which persisted to late follow-up. The P-wave amplitude also decreased acutely post-closure, but remained unchanged at later follow-up. The PQ duration shortened immediately in children and at intermediate follow-up in adults. The QRS duration and QTc interval decreased at intermediate-term follow-up in both children and adults. In both groups the spatial QRS-T angle decreased at late follow-up. The VG magnitude increased at intermediate follow-up in children and at late follow-up in adults, after an initial decrease in children. Conclusion: In both pediatric and adult ASD patients, electrocardiographic changes mainly occurred directly after ASD closure except for shortening of QRS duration and QTc interval, which occurred at later follow-up. Adults also showed late changes in PQ duration. At 6-to-18 month post-closure, the spatial QRS-T angle decreased, reflecting increased electrocardiographic concordance. The initial acute decrease in VG in children, which was followed by a significant increase, may be the effect of action potential duration dynamics directly after percutaneous ASD closure

Electrical remodeling after percutaneous atrial septal defect closure in pediatric and adult patients

Background: Several studies have reported changes in electrocardiographic variables after atrial septal defect (ASD) closure. However no temporal electro-and vectorcardiographic changes have been described from acute to long-term follow-up at different ages. We aimed to study electrical remodeling after percutaneous ASD closure in pediatric and adult patients. Methods: ECGs of 69 children and 75 adults (median age 6 [IQR 4–11] years and 45 [IQR 33–54] years, respectively) were retrospectively selected before percutaneous ASD closure and at acute (1–7 days), intermediate (4–14 weeks) and late (6–18 months) follow-up. Apart from electrocardiographic variables, spatial QRS-T angle and ventricular gradient (VG) were derived from mathematically-synthesized vectorcardiograms. Results: In both pediatric and adult patients, the heart rate decreased immediately post-closure, which persisted to late follow-up. The P-wave amplitude also decreased acutely post-closure, but remained unchanged at later follow-up. The PQ duration shortened immediately in children and at intermediate follow-up in adults. The QRS duration and QTc interval decreased at intermediate-term follow-up in both children and adults. In both groups the spatial QRS-T angle decreased at late follow-up. The VG magnitude increased at intermediate follow-up in children and at late follow-up in adults, after an initial decrease in children. Conclusion: In both pediatric and adult ASD patients, electrocardiographic changes mainly occurred directly after ASD closure except for shortening of QRS duration and QTc interval, which occurred at later follow-up. Adults also showed late changes in PQ duration. At 6-to-18 month post-closure, the spatial QRS-T angle decreased, reflecting increased electrocardiographic concordance. The initial acute decrease in VG in children, which was followed by a significant increase, may be the effect of action potential duration dynamics directly after percutaneous ASD closure

Cross-reactivity of mouse IgG subclasses to human Fc gamma receptors: Antibody deglycosylation only eliminates IgG2b binding

Immunoglobulin G (IgG) antibodies are important for protection against pathogens and exert effector functions through binding to IgG-Fc receptors (FcγRs) on myeloid and natural killer cells, resulting in destruction of opsonized target cells. Despite interspecies differences, IgG subclasses and FcγRs show substantial similarities and functional conservation between mammals. Accordingly, binding of human IgG (hIgG) to mouse FcγRs (mFcγRs) has been utilized to study effector functions of hIgG in mice. In other applications, such as immunostaining with mouse IgG monoclonal antibodies (mAbs), these cross-reactivities are undesired and prone to misinterpretation. Despite this drawback, the binding of mouse IgG (mIgG) subclasses to human FcγR (hFcγR) classes has never been fully documented. Here, we report detailed and quantifiable characterization of binding affinities for all mIgG subclasses to hFcγRs, including functional polymorphic variants. mIgG subclasses show the strongest binding to hFcγRIa, with relative affinities mIgG2a = mIgG2c > mIgG3 >> mIgG2b, and no binding by mIgG1. hFcγRIIa/b showed general low reactivities to all mIgG (mIgG1> mIgG2a/c > mIgG2b), with no reactivity to mIgG3. A particularly high affinity was observed for mIgG1 to the hFcγRIIa-R131 polymorphic variant. hFcγRIIIa showed lower binding (mIgG2a/c > mIgG3), slightly favouring binding to the hFcγRIIIa-V158 over the F158 polymorphic variant. No binding was observed of mIgG to hFcγRIIIb. Deglycosylation of mIgG1 did not abrogate binding to hFcγRIIa-R131, nor did deglycosylation of mIgG2a/c and mIgG3 prevent hFcγRIa binding. Importantly, deglycosylation of the least cross-reactive mIgG subclass, mIgG2b, abrogated reactivity to all hFcγRs. Together, these data document for the first time the full spectrum of cross-reactivities of mouse IgG to human FcγRs