Incidence du processus de vieillissement et des traits d'histoire de vie sur l'évolution de l'ADN mitochondrial chez les bivalves

RÉSUMÉ: Les bivalves sont de bons modèles biologiques pour l’étude du vieillissement cellulaire en raison de leurs grandes variations de longévités. L’objectif principal de la maîtrise était de comprendre le mode d’évolution de l’ADN mitochondrial (ADNmt) en lien avec le vieillissement cellulaire chez les bivalves. Pour répondre à cet objectif, deux études ont été réalisées. La première étude a permis de décrire les génomes mitochondriaux de neuf espèces de la sous-classe des Heterodonta, de reconstituer la phylogénie des Heterodonta et d’étudier la répartition génétique de l’espèce Arctica islandica. La deuxième étude a permis d’étudier le mode d’évolution de l’ADNmt par rapport à trois traits d’histoire de vie (longévité, temps de génération et température maximale létale). La composition des génomes mitochondriaux des neuf espèces d’Heterodonta correspond à celle retrouvée généralement chez les animaux : 13 gènes codant pour les protéines, 2 gènes ribonucléiques ribosomiques et 22 gènes ribonucléiques de transfert ; même si quelques particularités propres aux bivalves ont été observées (duplication du gène COX2, addition de gènes tRNA-Met, absence du gène ATP8 et configuration du gène CYTB en deux cadres de lecture). Les phylogénies des Heterodonta réalisées à partir de la concaténation des séquences nucléotidiques de 12 gènes mitochondriaux codant pour les protéines ont permis de confirmer les précédentes phylogénies et d’établir une relation de parenté solide entre les espèces Arctica islandica et Corbicula fluminea. L’étude sur la répartition génétique de l’espèce Arctica islandica montre que la population du golfe du Saint-Laurent est génétiquement plus proche de la population de la mer Baltique, que des populations de la mer du Nord et d’Islande. Le vieillissement, représenté par la longévité dans la deuxième étude, est expliqué à 68% par le temps de génération et à 22% par la température. Le taux de substitution synonyme est expliqué en partie (entre 9 et 30%) par la longévité. Les autres traits d’histoire de vie étudiés (temps de génération et température maximale létale) n’influencent pas l’évolution de l’ADNmt chez les bivalves. Nous présentons ici, la première étude sur l’impacte de la longévité sur le mode d’évolution de l’ADNmt chez des invertébrés. -- Mot(s) clé(s) en français : vieillissement, génome mitochondrial, bivalve, phylogénie Bayésienne, évolution des traits d'histoire de vie, taux de substitution, Arctica islandica. -- ABSTRACT: Bivalves are good model for studying evolutionary processes related to aging as they exhibit great variations in longevities among species. The aim of this Master was to understand how mitochondrial DNA (mtDNA) has evolved in relation to aging in bivalves. Two studies were performed to answer this question. The first chapter examines the description of the mitochondrial genomes of nine species of the subclass Heterodonta, provides a new Heterodonta phylogeny, and examines intraspecific variation in Arctica islandica using the full mitochondria genomes. The second study focus on the evolution of mtDNA relative to three life-history traits (longevity, generation time, and maximum lethal temperature). Mitochondrial genome cartography for the nine Heterodonta species corresponds to what is generally found in animals: 13 protein-coding genes, 2 ribosomal RNA genes and 22 transfer RNA genes. Some characters specific to bivalves were observed (duplication of COX2 gene, addition of tRNA-Met genes, lack of ATP8 gene and two reading frames for CYTB gene). Heterodonta phylogenies performed from the concatenation of 12 protein-coding genes nucleotide sequences confirmed previous phylogenies and established a strong relationship between the species Arctica islandica and Corbicula fluminea. Results on genetics repartition of Arctica islandica showed that the population from the Gulf of St. Lawrence was genetically closer to Baltic Sea population than to populations from the North Sea and Iceland. Aging, represented by longevity in the second chapter, was explained by generation time (68%) and by temperature (22%). The synonymous substitution rate is explained in part (between 9 and 30%) by longevity. Other life history traits studied (generation time and maximum lethal temperature) did not influence mtDNA evolution in bivalves. We present here, the first study on the evolution of mtDNA relative to longevity in invertebrates. -- Mot(s) clé(s) en anglais : aging, mitochondrial genome, bivalve, Bayesian phylogeny, life-history evolution, substitution rates, Arctica islandica

Tumor control and radiobiological fingerprint after Gamma Knife radiosurgery for posterior fossa meningiomas: A series of 46 consecutive cases.

Gamma Knife radiosurgery (GKR) can be a valuable treatment option for posterior cranial fossa meningiomas (PCFM). We retrospectively analyzed outcomes of GKR for PCFM. Were included forty-six patients with 47 PCFM. Primary endpoint was tumor control. Secondary endpoint was clinical improvement. Biologically effective dose (BED) was evaluated in relationship to primary and secondary outcomes. Mean marginal dose was 12.4 Gy (median 12, 12-14). Mean BED was 63.6 Gy (median 65, 49.1-88.3). Mean target volume (TV) was 2.21 cc (range 0.3-8.9 cc). Overall tumor control rate was 93.6% (44/47) after mean follow-up of 47.8 months ± 28.46 months (median 45.5, range 6-108). Radiological progression-free survival at 5 years was 94%. Higher pretherapeutic TVs were predictive for higher likelihood of tumor progression (Odds ratio, OR 1.448, 95% confidence interval - CI 1.001-2.093, p = 0.049). At last clinical follow-up, 28 patients (71.8%) remained stable, 10 (25.6%) improved and 1 patient (2.6%) worsened. Using logistic regression, the relationship between BED and clinical improvement was assessed (OR 0.903, standard error 0.59, coefficient 0.79-1.027, CI -0.10; 0.01; p = 0.14). The highest probability of clinical improvement corresponded to a range of BED values between 56 and 61 Gy. Primary GKR for PCFM is safe and effective. Higher pretherapeutic TV was predictor of volumetric progression. Highest probability of clinical improvement might correspond to a range of BED values between 56 and 61 Gy, although this was not statistically significant. The importance of BED should be further validated in larger cohorts, other anatomical locations and other pathologies

Fulminant Meningoencephalitis as the First Clinical Sign of an Invasive Pituitary Macroadenoma

We report the case of a young woman who presented with an acute fulminant meningoencephalitis as the first sign of an invasive pituitary macroadenoma. This rare and dramatic complication is described in detail, and the different management steps, from the lumbar puncture to the bifrontal craniectomy, are discussed. In conclusion, this clinical presentation highlights the importance of early diagnosis and urgent management of this uncommon complication

Traitement et valorisation d\u27archives épigraphiques de l\u27UMR 5189 Histoire et Sources des Mondes Antiques

Rapport de stage du Master SIB, sciences de l’information et des bibliothèques, option SDN "services documentaires numériques" portant sur la mise en place d\u27une base de données permettant de traiter et de valoriser les archives épigraphiques de l\u27UMR 5189 Histoire et Sources des Mondes Antiques (HiSoMA)

Meningiomas’ Management: An Update of the Literature

Meningiomas are the most common primary intracranial tumors in the adult population [1]. They are generally considered benign lesions but after the 2007 WHO classification, the proportion of atypical meningiomas has steeply increased. Surgery is considered the mainstay of the treatment and a complete resection is considered curative in WHO grade I meningiomas. The role of adjuvant treatments like radiotherapy (stereotactic radiosurgery or conventional external beam irradiation) and chemotherapy in more aggressive cases is still discussed, above all in WHO grade II meningiomas. We would like to expose the most important advances in meningiomas’ management in accordance with the recent literature evidences

Gamma knife radiosurgery for arteriovenous malformations: general principles and preliminary results in a Swiss cohort.

Arteriovenous malformations (AVMs) are a type of vascular malformation characterised by an abnormal connection between arteries and veins, bypassing the capillary system. This absence of capillaries generates an elevated pressure (hyperdebit), in both the AVM and the venous drainage, increasing the risk of rupture. Management modalities are: observation, microsurgical clipping, endovascular treatment and radiosurgery. The former can be used alone or in the frame of a multidisciplinary approach. We review our single-institution experience with gamma knife radiosurgery (GKR) over a period of 5 years. The study was open-label, prospective and nonrandomised. Fifty-seven consecutive patients, benefitting from 64 GKR treatments, were included. All were treated with Leksell Gamma Knife Perfexion (Elekta Instruments, AB, Sweden) between July 2010 and August 2015. All underwent stereotactic multimodal imaging: standard digital subtraction angiography, magnetic resonance imaging and computed tomography angiography. We report obliteration rates, radiation-induced complications and haemorrhages during follow-up course. The mean age was 46 years (range 13-79 years). The mean follow-up period was 36.4 months (median 38, range 12-75 months). Most common pretherapeutic clinical presentation was haemorrhage (50%). The most common Pollock-Flickinger score was between 1.01 and 1.5 (46%) and Spetzler-Martin grade III (46%). In 39 (60.1%) of cases, GKR was performed as upfront therapeutic option. The mean gross target volume (GTV) was 2.3 ml (median 1.2, range 0.03-11.3 ml). Mean marginal dose was 22.4 Gy (median 24, range 18-24 Gy). The mean prescription isodose volume (PIV) was 2.9 ml (median 1.8, range 0.065-14.6 ml). The overall obliteration rates (all treatments combined) at 12, 24, 36, 48 and 60 months were 4.8, 16.9%, 37.4, 63.6 and 78.4%, respectively. The main predictive factors for complete obliteration were: higher mean marginal dose (23.3 vs 21.0 Gy), lower GTV (mean 1.5 vs 3.5 ml) and absence of previous embolisation (at 60 months 61.8% prior embolisation compared with 82.4% without prior embolisation) (for all p <0.05). Eight (14%) patients experienced complications after GKR. Overall definitive morbidity rate was 3.1%. No patient died from causes related to GKR. However, during the obliteration period, one case of extremely rare fatal haemorrhage occurred. Radiosurgery is a safe and effective treatment modality for intracranial AVMs in selected cases. It can be used as upfront therapy or in the frame of a combined management. Obliteration rates are high, with minimal morbidity. The treatment effect is progressive and subsequent and regular clinical and radiological follow-up is needed to evaluate this effect