Le pluralisme des médias en contexte numérique : application du media pluralism monitor à l’Union Européenne, à l’Albanie, au Monténégro, à la République de Macédoine du Nord, à la Serbie et à la Turquie en 2022. Rapport : France

This report presents the results of the implementation of the Media Pluralism Monitor for the year 2022 (MPM2023) in France. The MPM is a holistic tool geared at assessing the risks to media pluralism in EU member states and selected candidate countries (32 European countries in total, including Albania, Montenegro, the Republic of North Macedonia, Serbia, and Turkey). The MPM takes into account legal, political and economic variables that are relevant to analysing the levels of plurality of media systems in a democratic society. The Media Pluralism Monitor has been implemented, on a regular basis, by the Centre for Media Pluralism and Media Freedom, since 2013/2014.Ce rapport présente les résultats de l’implémentation du Media Pluralism Monitor pour l'année 2022 (MPM2023) en France. Le MPM est un outil holistique destiné à évaluer les risques pour le pluralisme des médias dans les États membres de l'UE et dans certains pays candidats (32 pays européens au total, dont l'Albanie, le Monténégro, la République de Macédoine du Nord, la Serbie et la Turquie). Le MPM prend en compte des variables légales, politiques et économiques qui sont pertinentes pour analyser les niveaux de pluralisme des médias dans une société démocratique. Le Media Pluralism Monitor est régulièrement conduit par le Centre pour le pluralisme et la liberté des médias depuis 2013/2014.The Centre for Media Pluralism and Media Freedom is co-financed by the European Unio

PDGF-C Induces Maturation of Blood Vessels in a Model of Glioblastoma and Attenuates the Response to Anti-VEGF Treatment

Recent clinical trials of VEGF inhibitors have shown promise in the treatment of recurrent glioblastomas (GBM). However, the survival benefit is usually short-lived as tumors escape anti-VEGF therapies. Here we tested the hypothesis that Platelet Derived Growth Factor-C (PDGF-C), an isoform of the PDGF family, affects GBM progression independent of VEGF pathway and hinders anti-VEGF therapy.We first showed that PDGF-C is present in human GBMs. Then, we overexpressed or downregulated PDGF-C in a human GBM cell line, U87MG, and grew them in cranial windows in nude mice to assess vessel structure and function using intravital microscopy. PDGF-C overexpressing tumors had smaller vessel diameters and lower vascular permeability compared to the parental or siRNA-transfected tumors. Furthermore, vessels in PDGF-C overexpressing tumors had more extensive coverage with NG2 positive perivascular cells and a thicker collagen IV basement membrane than the controls. Treatment with DC101, an anti-VEGFR-2 antibody, induced decreases in vessel density in the parental tumors, but had no effect on the PDGF-C overexpressing tumors.These results suggest that PDGF-C plays an important role in glioma vessel maturation and stabilization, and that it can attenuate the response to anti-VEGF therapy, potentially contributing to escape from vascular normalization

Expression of P. falciparum var Genes Involves Exchange of the Histone Variant H2A.Z at the Promoter

Plasmodium falciparum employs antigenic variation to evade the human immune response by switching the expression of different variant surface antigens encoded by the var gene family. Epigenetic mechanisms including histone modifications and sub-nuclear compartmentalization contribute to transcriptional regulation in the malaria parasite, in particular to control antigenic variation. Another mechanism of epigenetic control is the exchange of canonical histones with alternative variants to generate functionally specialized chromatin domains. Here we demonstrate that the alternative histone PfH2A.Z is associated with the epigenetic regulation of var genes. In many eukaryotic organisms the histone variant H2A.Z mediates an open chromatin structure at promoters and facilitates diverse levels of regulation, including transcriptional activation. Throughout the asexual, intraerythrocytic lifecycle of P. falciparum we found that the P. falciparum ortholog of H2A.Z (PfH2A.Z) colocalizes with histone modifications that are characteristic of transcriptionally-permissive euchromatin, but not with markers of heterochromatin. Consistent with this finding, antibodies to PfH2A.Z co-precipitate the permissive modification H3K4me3. By chromatin-immunoprecipitation we show that PfH2A.Z is enriched in nucleosomes around the transcription start site (TSS) in both transcriptionally active and silent stage-specific genes. In var genes, however, PfH2A.Z is enriched at the TSS only during active transcription in ring stage parasites. Thus, in contrast to other genes, temporal var gene regulation involves histone variant exchange at promoter nucleosomes. Sir2 histone deacetylases are important for var gene silencing and their yeast ortholog antagonises H2A.Z function in subtelomeric yeast genes. In immature P. falciparum parasites lacking Sir2A or Sir2B high var transcription levels correlate with enrichment of PfH2A.Z at the TSS. As Sir2A knock out parasites mature the var genes are silenced, but PfH2A.Z remains enriched at the TSS of var genes; in contrast, PfH2A.Z is lost from the TSS of de-repressed var genes in mature Sir2B knock out parasites. This result indicates that PfH2A.Z occupancy at the active var promoter is antagonized by PfSir2A during the intraerythrocytic life cycle. We conclude that PfH2A.Z contributes to the nucleosome architecture at promoters and is regulated dynamically in active var genes

Particulates from hydrophilic-coated guiding sheaths embolise to the brain

available in PMC 2016 March 23Aims: We sought to evaluate the incidence of embolic material in porcine brains following vascular interventions using hydrophilic-coated sheaths. Methods and results: A new self-expanding stent and delivery system (SDS) was deployed through a hydrophilic-coated (Flexor® Ansel; Cook Medical, Bloomington, IN, USA) guiding sheath into the iliac and/or carotid arteries of 23 anaesthetised Yucatan mini swine. The animals were euthanised at three, 30, 90 and 180 days and their brains were removed for histological analysis. In an additional single control animal, the guiding sheath was advanced but no SDS was deployed. Advancement of the coated guiding sheath with or without the SDS was associated with frequent foreign material in the arterioles of the brain. The embolic material was amorphous, non-refractile, non-crystalline, non-birefringent and typically lightly basophilic with a slightly stippled appearance on haematoxylin and eosin (H&E) stain. Material was observed at all time points involving 54% of all study animals (i.e., test and control) and in vitro after incubation in 0.9% saline. Conclusions: The hydrophilic coating on a clinically used guiding sheath readily avulses and embolises to the brain during deployment in a porcine model. Further documentation of this effect and monitoring in clinical scenarios are warranted.National Institutes of Health (U.S.) (NIH (R01 GM 49039)

Machine behaviour

Machines powered by artificial intelligence increasingly mediate our social, cultural, economic and political interactions. Understanding the behaviour of artificial intelligence systems is essential to our ability to control their actions, reap their benefits and minimize their harms. Here we argue that this necessitates a broad scientific research agenda to study machine behaviour that incorporates and expands upon the discipline of computer science and includes insights from across the sciences. We first outline a set of questions that are fundamental to this emerging field and then explore the technical, legal and institutional constraints on the study of machine behaviour