Tectonique intraocéanique décrochante à l'ouest des îles Fidji (bassin nord-fidjien) : campagne SEAPSO III du N.O. Jean-Charcot

Un levé bathymétrique au moyen du sondeur multifaisceaux (Seabeam) et un levé de sismique réflexion continue du secteur oriental du Bassin Nord-Fidjien ont été réalisés lors du leg III de la campagne SEAPSO. Une exploitation préliminaire des données montre que ce secteur, précédemment interprété comme axe d'accrétion, est en réalité une zone de déformation intraocéanique décrochante. (Résumé d'auteur

Naturally occurring C-terminal splice variants of nuclear receptors

Alternative mRNA splicing in the region encoding the C-terminus of nuclear receptors results in receptor variants lacking the entire ligand-binding domain (LBD), or a part of it, and instead contain a sequence of splice variant-specific C-terminal amino acids. A total of thirteen such splice variants have been shown to occur in vertebrates, and at least nine occur in humans. None of these receptor variants appear to be able to bind endogenous ligands and to induce transcription on promoters containing the response element for the respective canonical receptor variant. Interestingly, ten of these C-terminal splice variants have been shown to display dominant-negative activity on the transactivational properties of their canonical equivalent. Research on most of these splice variants has been limited, and the dominant-negative effect of these receptor variants has only been demonstrated in reporter assays in vitro, using transiently transfected receptors and reporter constructs. Therefore, the in vivo function and relevance of most C-terminal splice variants remains unclear. By reviewing the literature on the human glucocorticoid receptor β-isoform (hGRβ), we show that the dominant-negative effect of hGRβ is well established using more physiologically relevant readouts. The hGR β-isoform may alter gene transcription independent from the canonical receptor and increased hGRβ levels correlate with glucocorticoid resistance and the occurrence of several immune-related diseases. Thus, available data suggests that C-terminal splice variants of nuclear receptors act as dominant-negative inhibitors of receptor-mediated signaling in vivo, and that aberrant expression of these isoforms may be involved in the pathogenesis of a variety of diseases

Object Kinetic Monte Carlo calculations of irradiated Fe-Cr dilute alloys: The effect of the interaction radius between substitutional Cr and self-interstitial Fe

ObjectKineticMonteCarlo models allow for the study of the evolution of the damage created by irradiation to time scales that are comparable to those achieved experimentally. Therefore, the essential ObjectKineticMonteCarlo parameters can be validated through comparison with experiments. However, this validation is not trivial since a large number of parameters is necessary, including migration energies of point defects and their clusters, binding energies of point defects in clusters, as well as the interactionradii. This is particularly cumbersome when describing an alloy, such as the Fe–Cr system, which is of interest for fusion energy applications. In this work we describe an ObjectKineticMonteCarlo model for Fe–Cr alloys in the dilute limit. The parameters used in the model come either from density functional theory calculations or from empirical interatomic potentials. This model is used to reproduce isochronal resistivity recovery experiments of electron irradiateddiluteFe–Cr alloys performed by Abe and Kuramoto. The comparison between the calculated results and the experiments reveal that an important parameter is the capture radius between substitutionalCr and self-interstitialFe atoms. A parametric study is presented on the effect of the capture radius on the simulated recovery curves

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)

Extended mobility scale (AMEXO) for assessing mobilization and setting goals after gastrointestinal and oncological surgery: a before-after study

Background: Early structured mobilization has become a key element of Enhanced Recovery After Surgery programs to improve patient outcomes and decrease length of hospital stay. With the intention to assess and improve early mobilization levels, the 8-point ordinal John Hopkins Highest Level of Mobility (JH-HLM) scale was implemented at two gastrointestinal and oncological surgery wards in the Netherlands. After the implementation, however, healthcare professionals perceived a ceiling effect in assessing mobilization after gastrointestinal and oncological surgery. This study aimed to quantify this perceived ceiling effect, and aimed to determine if extending the JH-HLM scale with four additional response categories into the AMsterdam UMC EXtension of the JOhn HOpkins Highest Level of mObility (AMEXO) scale reduced this ceiling effect. Methods: All patients who underwent gastrointestinal and oncological surgery and had a mobility score on the first postoperative day before (July-December 2018) or after (July-December 2019) extending the JH-HLM into the AMEXO scale were included. The primary outcome was the before-after difference in the percentage of ceiling effects on the first three postoperative days. Furthermore, the before-after changes and distributions in mobility scores were evaluated. Univariable and multivariable logistic regression analysis were used to assess these differences. Results: Overall, 373 patients were included (JH-HLM n = 135; AMEXO n = 238). On the first postoperative day, 61 (45.2%) patients scored the highest possible mobility score before extending the JH-HLM into the AMEXO as compared to 4 (1.7%) patients after (OR = 0.021, CI = 0.007-0.059, p Pathophysiology, epidemiology and therapy of agein

Sex differences in characteristics and outcome in acute coronary syndrome patients in the Netherlands

Background Sex differences in acute coronary syndrome (ACS) have been reported, but little is known about the situation in the Netherlands. M

CT angiography and CT perfusion improve prediction of infarct volume in patients with anterior circulation stroke

Introduction: We investigated whether baseline CT angiography (CTA) and CT perfusion (CTP) in acute ischemic stroke could improve prediction of infarct presence and infarct volume on follow-up imaging. Methods: We analyzed 906 patients with suspected anterior circulation stroke from the prospective multicenter Dutch acute stroke study (DUST). All patients underwent baseline non-contrast CT, CTA, and CTP and follow-up non-contrast CT/MRI after 3 days. Multivariable regression models were developed including patient characteristics and non-contrast CT, and subsequently, CTA and CTP measures were added. The increase in area under the curve (AUC) and R2 was assessed to determine the additional value of CTA and CTP. Results: At follow-up, 612 patients (67.5 %) had a detectable infarct on CT/MRI; median infarct volume was 14.8 mL (interquartile range (IQR) 2.8–69.6). Regarding infarct presence, the AUC of 0.82 (95 % confidence interval (CI) 0.79–0.85) for patient characteristics and non-contrast CT was improved with addition of CTA measures (AUC 0.85 (95 % CI 0.82–0.87); p < 0.001) and was even higher after addition of CTP measures (AUC 0.89 (95 % CI 0.87–0.91); p < 0.001) and combined CTA/CTP measures (AUC 0.89 (95 % CI 0.87–0.91); p < 0.001). For infarct volume, adding combined CTA/CTP measures (R2 = 0.58) was superior to patient characteristics and non-contrast CT alone (R2 = 0.44) and to addition of CTA alone (R2 = 0.55) or CTP alone (R2 = 0.54; all p < 0.001). Conclusion: In the acute stage, CTA and CTP have additional value over patient characteristics and non-contrast CT for predicting infarct presence and infarct volume on follow-up imaging. These findings could be applied for patient selection in future trials on ischemic stroke treatment

Prediction of outcome in patients with suspected acute ischaemic stroke with CT perfusion and CT angiography: The Dutch acute stroke trial (DUST) study protocol

Background: Prediction of clinical outcome in the acute stage of ischaemic stroke can be difficult when based on patient characteristics, clinical findings and on non-contrast CT. CT perfusion and CT angiography may provide additional prognostic information and guide treatment in the early stage. We present the study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess the prognostic value of CT perfusion and CT angiography in predicting stroke outcome, in addition to patient characteristics and non-contrast CT. For this purpose, individualised prediction models for clinical outcome after stroke based on the best predictors from patient characteristics and CT imaging will be developed and validated.Methods/design: The DUST is a prospective multi-centre cohort study in 1500 patients with suspected acute ischaemic stroke. All patients undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after onset of the neurological deficits, and, if possible, follow-up imaging after 3 days. The primary outcome is a dichotomised score on the modified Rankin Scale, assessed at 90 days. A score of 0-2 represents good outcome, and a score of 3-6 represents poor outcome. Three logistic regression models will be developed, including patient characteristics and non-contrast CT (model A), with addition of CT angiography (model B), and CT perfusion parameters (model C). Model derivation will be performed in 60% of the study population, and model validation in the remaining 40% of the patients. Additional prognostic value of the models will be determined with the area under the curve (AUC) from the receiver operating characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and likelihood ratio tests.Discussion: This study will provide insight in the added prognosti

Large-Scale Expansion of Human iPSC-Derived Skeletal Muscle Cells for Disease Modeling and Cell-Based Therapeutic Strategies

Although skeletal muscle cells can be generated from human induced pluripotent stem cells (iPSCs), transgene-free protocols include only limited options for their purification and expansion. In this study, we found that fluorescence-activated cell sorting-purified myogenic progenitors generated from healthy controls and Pompe disease iPSCs can be robustly expanded as much as 5 × 1011-fold. At all steps during expansion, cells could be cryopreserved or differentiated into myotubes with a high fusion index. In vitro, cells were amenable to maturation into striated and contractile myofibers. Insertion of acid α-glucosidase cDNA into the AAVS1 locus in iPSCs using CRISPR/Cas9 prevented glycogen accumulation in myotubes generated from a patient with classic infantile Pompe disease. In vivo, the expression of human-specific nuclear and sarcolemmar antigens indicated that myogenic progenitors engraft into murine muscle to form human myofibers. This protocol is useful for modeling of skeletal muscle disorders and for using patient-derived, gene-corrected cells to develop cell-based strategies. Van der Wal et al. present a robust protocol for the transgene-free generation and purification of myogenic progenitors from human iPSCs and for their expansion up to 5 × 1011-fold. After gene editing in vitro, these myogenic progenitors matured into contractile skeletal muscle cells, reversing Pompe disease pathology. In vivo, myogenic progenitors contributed to muscle regeneration