SMARCA2-deficiency confers sensitivity to targeted inhibition of SMARCA4 in esophageal squamous cell carcinoma cell lines

SMARCA4/BRG1 and SMARCA2/BRM, the two mutually exclusive catalytic subunits of the BAF complex, display a well-established synthetic lethal relationship in SMARCA4-deficient cancers. Using CRISPR-Cas9 screening, we identify SMARCA4 as a novel dependency in SMARCA2-deficient esophageal squamous cell carcinoma (ESCC) models, reciprocal to the known synthetic lethal interaction. Restoration of SMARCA2 expression alleviates the dependency on SMARCA4, while engineered loss of SMARCA2 renders ESCC models vulnerable to concomitant depletion of SMARCA4. Dependency on SMARCA4 is linked to its ATPase activity, but not to bromodomain function. We highlight the relevance of SMARCA4 as a drug target in esophageal cancer using an engineered ESCC cell model harboring a SMARCA4 allele amenable to targeted proteolysis and identify SMARCA4-dependent cell models with low or absent SMARCA2 expression from additional tumor types. These findings expand the concept of SMARCA2/SMARCA4 paralog dependency and suggest that pharmacological inhibition of SMARCA4 represents a novel therapeutic opportunity for SMARCA2-deficient cancers

Allogreffe de sang placentaire (étude clermontoise et perspectives)

Notre travail est une étude rétrospective de 10 enfants allogreffés avec une unité de sang placentaire entre 1999 et 2006 dans le centre régionale de cancérologie et de thérapie cellulaire pédiatrique de Clermont-Ferrand. Cette série montre une corrélation entre la richesse du greffon, la sortie d'aplasie et la survie et met en évidence un faible taux de GVH par rapport aux nombreuses complications infectieuses. Le sang placentaire, par sa richesse en progéniteurs hématopoïétiques, par le caractère immature de ses cellules et par sa disponibilité est devenu une source de cellules souches hématopoïétiques de plus en plus utilisée. Une des voies à développer pour améliorer le pronostic de ce type de greffes est l'augmentation de la richesse du greffon qui permet d'accélérer la reconstitution hématologique et immunologique. D'autres perspectives s'ouvrent pour la potentialisation et l'élargissement de l'utilisation du sang placentaire.CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

The Sge1 protein of Saccharomyces cerevisiae is a membrane-associated multidrug transporter

In this study, we report the further characterization of the Saccharomyces cerevisiae crystal violet-resistance protein Sge1. Sge1 is a highly hydrophobic 59 kDa protein with 14 predicted membrane-spanning domains. It shares homologies with several drug-resistance proteins and sugar transporters of the major facilitator superfamily. Here, we have demonstrated that Sge1 is not only a crystal violet-resistance protein, but that it also confers resistance to ethidium bromide and methylmethane sulfonate. Disruption of SGE1 leads to increased sensitivity towards all three compounds, thus designating Sge1 as a multiple drug-resistance protein. Subcellular fractionation as well as immunolocalization on whole yeast cells demonstrated that Sge1 was tightly associated with the yeast plasma membrane. Furthermore, Sge1 was highly enriched in preparations of yeast plasma membranes. In analogy to other multidrug-resistance proteins, we suggest that Sge1 functions as a drug export permease

Eleven strategies for making reproducible research and open science training the norm at research institutions

Peer reviewed: TrueReproducible research and open science practices have the potential to accelerate scientific progress by allowing others to reuse research outputs, and by promoting rigorous research that is more likely to yield trustworthy results. However, these practices are uncommon in many fields, so there is a clear need for training that helps and encourages researchers to integrate reproducible research and open science practices into their daily work. Here, we outline eleven strategies for making training in these practices the norm at research institutions. The strategies, which emerged from a virtual brainstorming event organized in collaboration with the German Reproducibility Network, are concentrated in three areas: (i) adapting research assessment criteria and program requirements; (ii) training; (iii) building communities. We provide a brief overview of each strategy, offer tips for implementation, and provide links to resources. We also highlight the importance of allocating resources and monitoring impact. Our goal is to encourage researchers – in their roles as scientists, supervisors, mentors, instructors, and members of curriculum, hiring or evaluation committees – to think creatively about the many ways they can promote reproducible research and open science practices in their institutions.</jats:p

Eleven strategies for making reproducible research and open science training the norm at research institutions

Kohrs FE, Auer S, Bannach-Brown A, et al. Eleven strategies for making reproducible research and open science training the norm at research institutions. eLife . 2023;12: e89736.Reproducible research and open science practices have the potential to accelerate scientific progress by allowing others to reuse research outputs, and by promoting rigorous research that is more likely to yield trustworthy results. However, these practices are uncommon in many fields, so there is a clear need for training that helps and encourages researchers to integrate reproducible research and open science practices into their daily work. Here, we outline eleven strategies for making training in these practices the norm at research institutions. The strategies, which emerged from a virtual brainstorming event organized in collaboration with the German Reproducibility Network, are concentrated in three areas: (i) adapting research assessment criteria and program requirements; (ii) training; (iii) building communities. We provide a brief overview of each strategy, offer tips for implementation, and provide links to resources. We also highlight the importance of allocating resources and monitoring impact. Our goal is to encourage researchers - in their roles as scientists, supervisors, mentors, instructors, and members of curriculum, hiring or evaluation committees - to think creatively about the many ways they can promote reproducible research and open science practices in their institutions. © 2023, Kohrs et al