SHH Pathway and Cerebellar Development

The morphogenetic factor Sonic hedgehog (SHH) has been discovered as one of the masterplayers in cerebellar patterning and was subjected to intensive investigation during the last decade. During early postnatal development, this continuously secreted cholesterol-modified protein drives the expansion of the largest neuronal population of the brain, the granular cells. Moreover, it acts on Bergmann glia differentiation and would potentially affect Purkinje cells homeostasis at adult age. The cerebellar cortex constituted an ideal developmental model to dissect out the upstream mechanisms and downstream targets of this complex pathway. Its deep understanding discloses some of the mechanistic disorders underlying pediatric tumorigenesis, congenital ataxia, and mental retardation. Therapeutical use of its regulators has been consolidated on murine transgenic models and is now considered as a realistic human clinical application. Here, we will review the most recent advances made in the comprehensive understanding of SHH involvement in cerebellar development and patholog

HP1 modulates the transcription of cell-cycle regulators in Drosophila melanogaster

Heterochromatin protein 1 (HP1) was originally described as a non-histone chromosomal protein and is required for transcriptional gene silencing and the formation of heterochromatin. Although it is localized primarily at pericentric heterochromatin, a scattered distribution over a large number of euchromatic loci is also evident. Here, we provide evidence that Drosophila HP1 is essential for the maintenance of active transcription of euchromatic genes functionally involved in cell-cycle progression, including those required for DNA replication and mitosis. Depletion of HP1 in proliferating embryonic cells caused aberrant progression of the cell cycle at S phase and G2/M phase, linked to aberrant chromosome segregation, cytokinesis, and an increase in apoptosis. The chromosomal distribution of Aurora B, and the level of phosphorylation of histone H3 serine 10 were also altered in the absence of HP1. Using chromatin immunoprecipitation analysis, we further demonstrate that the promoters of a number of cell-cycle regulator genes are bound to HP1, supporting a direct role for HP1 in their active transcription. Overall, our data suggest that HP1 is essential for the maintenance of cell-cycle progression and the transcription of cell-cycle regulatory genes. The results also support the view that HP1 is a positive regulator of transcription in euchromati

Développement d'un modèle de simulation d'une épidémie foliaire tropicale à l'échelle de la plante: cas des cercosporioses du bananier

Les cercosporioses du bananier dues à Mycosphaerella fijiensis (agent de la maladie des raies noires (MRN) ou cercosporiose noire) et M. musicola (agent de la maladie de Sigatoka (MS) ou cercosporiose jaune) sont considérées comme les maladies foliaires les plus graves pour les productions bananières. Ces pathogènes sont présents dans la majorité des zones de cultures bananières intertropicales. Le contrôle de ces maladies indispensable pour l'exportation des fruits, consiste actuellement en des applications fréquentes de fongicides par voie aérienne, méthode néfaste pour l'environnement. Un modèle de simulation des cercosporioses a été conçu pour approfondir les connaissances du pathosystème et tester de nouvelles méthodes de lutte, en particulier l'utilisation de variétés résistantes. Un modèle mécaniste de simulation des cercosporioses en temps discret est en cours de développement. Il décrit, sans spatialisation et en conditions climatiques optimales, le développement de la maladie sur un bananier représentatif d'une parcelle pendant un cycle de culture. Ce modèle permettra d'évaluer l'efficacité de différentes composantes de résistance partielle dans le contrôle des cercosporioses et d'étudier la compétition entre les 2 espèces fongiques en cas d'invasion de la MRN (contexte parasitaire actuel en Martinique). Il se décompose en deux sous-modèles, le premier simulant la croissance du bananier, le second simulant la propagation de l'épidémie. Le sous modèle " croissance de la plante " est appréhendé de manière déterministe alors que le sous modèle " propagation de la maladie " est lui stochastique. Ce dernier décrit le fonctionnement du pathogène sur son hôte: contamination, reproduction asexuée (production de conidies), rencontre de lésions, reproduction sexuée (production d'ascospores), dispersion des spores. Les données disponibles pour calibrer le modèle ont été recueillies au Cameroun (MRN) et aux Antilles (MRN et MS) en conditions naturelles d'infestation et en conditions contrôlées (croissance des lésions, nombre de spores émises par lésion). L'estimation des paramètres de ce second sous-modèle a été réalisée dans un cadre Bayésien par le biais de techniques MCMC (Markov Chain of Monte Carlo). On obtient alors une distribution à posteriori de l'ensemble des paramètres du modèle ainsi qu'une distribution a postériori de la variance résiduelle. L'inférence des paramètres et les résultats des premières simulations seront présentés et discutés. (Résumé d'auteur

CANABIC: CANnabis and Adolescents: effect of a Brief Intervention on their Consumption - study protocol for a randomized controlled trial.

International audienceBACKGROUND: Cannabis is the most consumed illegal substance in France. General practitioners (GPs) are the health professionals who are most consulted by adolescents. Brief intervention (BI) is a promising care initiative for the consumption of cannabis, and could be a tool for GPs in caring for adolescents who consume cannabis. The aim of the CANABIC study is to measure the impact of a BI carried out by a GP on the consumption of cannabis by adolescents of 15 to 25 years of age. METHODS: A randomized clustered controlled trial, stratified over three areas (Auvergne, Languedoc-Roussillon, and Rhone-Alps), comparing an intervention group, which carries out the BI in consultation, and a control group, which ensures routine medical care. The main assessment criterion is the consumption of cannabis by amount of joints per month, at 12 months. The amount necessary to highlight a significant difference between the two groups of 30 % of consumption at 12 months is 250 patients (50 GPs, 5 patients per GP; risk alpha = 5 %; power = 90 %; intra-cluster correlation coefficient rho = 0.2; Hawthorne effect = 15 %; lost to follow-up rates for GPs = 10 % and for patients = 20 %). This plan is replicated for the three areas, and therefore a total of 750 patients are expected.The secondary criteria for judgment are the associated consumption of tobacco and alcohol, the perception of the consequences of consumption, and the driving of a vehicle following consumption. DISCUSSION: Research about BI for young cannabis users is underway. The aim of the CANABIC study is to validate a BI suited to adolescents who consume cannabis, which may be performed in the general practice. This would provide a tool for their treatment by a GP, which could be widely distributed during initial or further medical training.Trial registration: CANABIC is a randomized clustered trial (NCT01433692, registered 2011 Sept 12), PHRC funded: Clinical Research Hospital Program (Governmental Fund, Health Ministry). Date first patient randomized: March 2012

Oncological patients' reactions to COVID-19 pandemic: A single institution prospective study.

peer reviewedBACKGROUND: The spread of the COVID-19 pandemic has led to a rapid reorganization in all human and hospital activities, with impact on cancer patients. AIM: An analysis of cancer patients fears, and awareness of COVID-19 has been done in this study. METHODS AND RESULTS: We analyzed cancer patients' reactions to the pandemic and their perception of oncological care reorganization, through a 12-item survey, proposed at the peak of pandemic and 3 months later. Overall, 237 patients were included in the study. During the peak of pandemic 34.6% of patients were more worried about COVID-19 than cancer versus 26.4% in the post-acute phase (p = .013). Although 49.8% of patients in the acute phase and 42.3% in the post-acute phase considered their risk of death if infected ≥50%, and more than 70% of patients thought to be at higher risk of complications, the majority of them did not consider the possibility to stop or delay their treatment. Patients were more interested in following news about COVID-19 than cancer and they complied with all preventive measures in more than 90% of the cases. CONCLUSIONS: Although cancer patients worried about COVID-19 and evaluated the risk of complication or death due to COVID-19 as extremely high, they were still asking for the best oncological treatment

Unfertilized Xenopus Eggs Die by Bad-Dependent Apoptosis under the Control of Cdk1 and JNK

Ovulated eggs possess maternal apoptotic execution machinery that is inhibited for a limited time. The fertilized eggs switch off this time bomb whereas aged unfertilized eggs and parthenogenetically activated eggs fail to stop the timer and die. To investigate the nature of the molecular clock that triggers the egg decision of committing suicide, we introduce here Xenopus eggs as an in vivo system for studying the death of unfertilized eggs. We report that after ovulation, a number of eggs remains in the female body where they die by apoptosis. Similarly, ovulated unfertilized eggs recovered in the external medium die within 72 h. We showed that the death process depends on both cytochrome c release and caspase activation. The apoptotic machinery is turned on during meiotic maturation, before fertilization. The death pathway is independent of ERK but relies on activating Bad phosphorylation through the control of both kinases Cdk1 and JNK. In conclusion, the default fate of an unfertilized Xenopus egg is to die by a mitochondrial dependent apoptosis activated during meiotic maturation