Neurotrophins are expressed in giant cell arteritis lesions and may contribute to vascular remodeling

International audienceIntroduction: Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels. Neurotrophins (NTs) and their receptors (NTRs) are protein factors for growth, differentiation and survival of neurons. They are also involved in the migration of vascular smooth muscle cells (VSMCs). Our aim was to investigate whether NTs and NTRs are involved in vascular remodelling of GCA.Methods: We included consecutive patients who underwent a temporal artery biopsy for suspected GCA. We developed an enzymatic digestion method to obtain VSMCs from smooth muscle cells in GCA patients and controls. Neurotrophin protein and gene expression and functional assays were studied from these VSMCs. Neurotrophin expression was also analysed by immunohistochemistry in GCA patients and controls.Results: Whereas temporal arteries of both GCA patients (n = 22) and controls (n = 21) expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and sortilin, immunostaining was more intense in GCA patients, especially in the media and intima, while neurotrophin-3 (NT-3) and P75 receptor (P75NTR) were only detected in TA from GCA patients. Expression of TrkB, a BDNF receptor, was higher in GCA patients with ischaemic complications. Serum NGF was significantly higher in GCA patients (n = 28) vs. controls (n = 48), whereas no significant difference was found for BDNF and NT-3. NGF and BDNF enhanced GCA-derived temporal artery VSMC proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls.Conclusions: Our results suggest that NTs and NTRs are involved in vascular remodelling of GCA. In GCA-derived temporal artery VSMC, NGF promoted proliferation and BDNF enhanced migration by binding to TrkB and p75NTR receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results

La querelle de l'antimoine : Guy Patin sur la sellette

[eng] Guy Patin's lawsuit against Jean Chartier, his colleague in the Faculty of Medicine of Paris, has long been familiar. Patin gave his version of the affair in his private correspondence and in the official Acts of his deanship ; Chartier presented his side of the case in a controversial pamphlet. These traditional sources are now supplemented by the documents of the trial itself, discovered in the archives of the Parlement of Paris and published here for the first time. The reader is thereby enabled to perceive the criminal trial as part of a strategy of civil litigation - a typical example of conflict under the Old Regime. [fre] On connaît depuis longtemps le procès de Patin contre Jean Chartier, son collègue de la de Médecine de Paris. La version de Patin se lit dans correspondance personnelle et dans les Actes de décanat ; celle de son adversaire dans un factum. A sources traditionnelles viennent s'ajouter les d'instruction retrouvées dans les archives du Parlement. La publication ici de ces dernières permet d'apprécier le procès criminel comme une fortuite du litige civil et faisant partie d'une procédurière typique de la vie conflictuelle sous l'Ancien Régime.

Ultra Deep Sequencing of a Baculovirus Population Reveals Widespread Genomic Variations

National audienceViruses rely on widespread genetic variation and large population size for adaptation. Large DNA virus populations are thought to harbor little variation though natural populations may be polymorphic. To measure the genetic variation present in a dsDNA virus population, we deep sequenced a natural strain of the baculovirus Autographa californica multiple nucleopolyhedrovirus. With 124,221X average genome coverage of our 133,926 bp long consensus, we could detect low frequency mutations (0.025%). K-means clustering was used to classify the mutations in four categories according to their frequency in the population. We found 60 high frequency non-synonymous mutations under balancing selection distributed in all functional classes. These mutants could alter viral adaptation dynamics, either through competitive or synergistic processes. Lastly, we developed a technique for the delimitation of large deletions in next generation sequencing data. We found that large deletions occur along the entire viral genome, with hotspots located in homologous repeat regions (hrs). Present in 25.4% of the genomes, these deletion mutants presumably require functional complementation to complete their infection cycle. They Viruses 2015, 7 3626 might thus have a large impact on the fitness of the baculovirus population. Altogether, we found a wide breadth of genomic variation in the baculovirus population, suggesting it has high adaptive potential

Correspondance de Pierre Bayle. Tome quinzième. Bibliographie et index général

International audienc

Correspondance de Pierre Bayle. Tome quinzième. Bibliographie et index général

International audienc