p73α isoforms drive opposite transcriptional and post-transcriptional regulation of MYCN expression in neuroblastoma cells

MYCN activation, mainly by gene amplification, is one of the most frequent molecular events in neuroblastoma (NB) oncogenesis, and is associated with increased malignancy and decreased neuronal differentiation propensity. The frequency of concomitant loss of heterozygosity at the 1p36.3 locus, which harbours the p53 anti-oncogene homologue TP73, indicates that MYCN and p73 alterations may cooperate in the pathogenesis of NB. We have previously shown that p73 isoforms are deregulated in NB tumours and that TAp73 co-operates synergistically with p53 for apoptosis of NB cells, whereas ΔNp73 activates the expression of neuronal differentiation genes such as BTG2. Herein, using both ectopic expression and RNA interference-mediated silencing of p73 in MYCN amplified NB cells, we show that p73α isoforms inhibit MYCN expression at both transcript and protein levels, in spite of transactivator effects on MYCN promoter. To explain this paradox, we found that TAp73α exerts negative post-transcriptional effects leading to reduced MYCN mRNA stability. RNA immunoprecipitation experiments suggest that this dominant inhibitory post-transcriptional effect could be due to an interaction between the p73 protein and MYCN mRNA, a hypothesis also raised for the regulation of certain genes by the p53 protein

Professional categories in social law : a reflective contrasting between the executive and non-executive categories

Préciser la notion de catégorie professionnelle est un exercice essentiel. Les enjeux sont multiples. Ils intéressent la rémunération, le temps de travail, la protection sociale complémentaire, la représentation collective, etc. La reconnaissance des catégories professionnelles, notamment au travers de la distinction des cadres et des non-cadres, participe à l’organisation de l’entreprise et contribue au respect du principe d’égalité de traitement. Cet exercice se révèle néanmoins délicat : le législateur n’a pas précisé les contours du concept de catégorie professionnelle ; la mutation des formes de travail, se traduisant parfois par une uniformisation des fonctions dans l’entreprise, modifie le paysage. Le rôle des partenaires sociaux pour apporter quelque clarté est souvent décisif.The conceptual definition of professional classifications is an essential exercise since the stakes are high. It affects wages, working hours, complementary social security, collective representation, etc. The identification of professional categories, particularly between the executive and non-executive categories, helps in the organization of companies and contributes to the application of equal treatment principle. This exercise is nevertheless delicate because the legislator has not previously provided a precise conceptual delineation of professional categories ; the changes in the forms of work, sometimes reflected by a standardization of the roles within the company, is changing the landscape. The role of social partners is often critical in providing some clarification

Nano-organocatalysts synthesis: Boc vs Fmoc protection

International audienceWe report the elaboration of new l-Proline functionalized superparamagnetic iron oxide nanoparticles that can act as a new enantioselective organocatalyst. Boc-l-Proline and Fmoc-l-Proline are grafted using two different methodologies on a nanoplateform constituted of 10 nm maghemite (γ-Fe2O3) nanoparticle stabilized by bidendate coating agent Alendronate. We show that coupling is far more efficient using microwave assisted methodology and that only Fmoc deprotection is compatible with our nanoplatform. Moreover the fluorenyl group is used for indirect quantification of grafted Proline onto nanoparticles

Microwave Assisted Functionalization of Materials: from the Mesoscale to the Nanoscale

International audienc

Nanoparticles under the light: click functionalization by photochemical thiol-yne reaction, towards double click functionalization.

International audienceA light click away: The first application of the thiol-yne reaction to nanoparticle functionalization is described (see figure). This metal-free click chemistry approach is compatible with the addition of various molecules at the surface and can be combined with CuAAC methodology to perform chemoselective double functionalization

L'approche PICT pour évaluer in situ l'adaptation et la résilience de biofilms périphytiques aux substances pharmaceutiques : expérience de translocation dans un cours d'eau contaminé

International audienceLa contamination des milieux aquatiques par les substances pharmaceutiques impacte les communautés microbiennes périphytiques exposées. Cela peut se traduire, entre autres, par une modification de la diversité microbienne associée à une augmentation de la tolérance de la communauté à ces substances, conformément au concept PICT (pollution induced community tolerance). Cependant, les liens de causalité entre les niveaux d’exposition aux substances pharmaceutiques et les niveaux de tolérance à leur toxicité restent à établir. Pour tester la pertinence de l’approche PICT pour évaluer in situ l’adaptation et la résilience de biofilms périphytiques aux substances pharmaceutiques, nous avons mené une expérience de translocation sur une rivière présentant un gradient de contamination. Du périphyton a été déplacé entre l’amont (référence) et l’aval (contaminé) pour simuler, durant 6 semaines, une dégradation (vers l’aval) ou une restauration (vers l’amont) de la qualité chimique de l’eau (caractérisée à l’aide d’échantillonneurs passifs, POCIS). Sept substances modèles ont été considérées pour l’approche PICT et la diversité des communautés périphytiques a été appréhendée par métabarcoding (ADNr16S et 23S, rbcL).Dans la station aval contaminée, nous avons observé une forte tolérance des communautés phototrophes au diclofénac et à l’aténolol. Pour ces deux substances, la translocation a permis d’observer progressivement une adaptation (tolérance accrue) ou au contraire une résilience (perte de tolérance) de ces communautés suite à leur déplacement vers l’aval et vers l’amont, respectivement. L’approche PICT est donc prometteuse pour évaluer in situ l’adaptation ou la résilience microbienne aux substances pharmaceutiques et contribuer au diagnostic de leur impact environnemental

Diagnostic des impacts écotoxicologiques des substances pharmaceutiques en cours d'eau : translocation de communautés microbiennes périphytiques et mesures de tolérance (PICT)

National audienc

In situ translocation experiment to assess the adaptation and resilience of periphytic communities to pharmaceutical substances using a PICT approach

International audienceNumerous studies have demonstrated the worldwide occurrence of pharmaceutical contamination in aquatic environments, in which they can affect microbial periphytic communities. Recent monitoring in a small river located in Lake Bourget watershed (Tillet River, Savoie, France) showed the accumulation of pharmaceuticals in its downtream urban section. In this context, we sought to (i) assess if this chronic exposure to contamination can cause an increase in the tolerance of microbial communities to a set of pharmaceutical substances (‘pollution induced community tolerance’ concept, PICT) and (ii) study the tolerance dynamics (tolerance acquisition, or loss) according to exposure level changes.To reach these objectives, we carried out an in situ translocation study in the Tillet River, considering an upstream (reference) and a downstream (contaminated) site. After a 4-week growth phase in each site, periphytic biofilms were transferred between the sites to simulate, during 6 weeks, a restoration (down- to upstream) or deterioration (up- to downstream) of the chemical water quality. Water contamination was monitored using polar organic chemical integrative samplers (POCIS), and biofilm community tolerance was assessed using a PICT approach. Acute toxicity tests were performed on biofilms sampled every 2 weeks, using 7 pharmaceuticals tested individually (ofloxacin, atenolol, diclofenac, paracetamol, erythromycin, sulfamethoxazole, sulfamethazine) and measuring the following biological activities: β-glucosidase, photosynthesis, or growth. Our results confirmed the expected increase in pharmaceutical concentrations in surface water from up- to downstream. In parallel, an increased biofilm tolerance mainly towards diclofenac and atenolol was observed at the downstream station, from the toxicity tests on photosynthesis. The translocation approach also revealed an increase of tolerance levels in communities transferred downstream, and a decrease of tolerance levels in communities transferred upstream, suggesting resilience processes. This work demonstrates the relevance of the PICT approach for in situ diagnosis of the impact of pharmaceuticals on natural microbial communities

Clay and DOPA containing polyelectrolyte multilayer film for imparting anticorrosion properties to galvanized steel

A facile and green approach is developed to impart remarkable protection against corrosion to galvanized steel. A protecting multilayer film is formed by alternating the deposition of a polycation bearing catechol groups, used as corrosion inhibitors, with clay that induces barrier properties. This coating does not affect the esthetical aspect of the surface and does not release any toxic molecules in the environment