Multicellular tumor spheroid model to evaluate spatio-temporal dynamics effect of chemotherapeutics: application to the gemcitabine/CHK1 inhibitor combination in pancreatic cancer

International audienceUNLABELLED: ABSTRACT: BACKGROUND: The multicellular tumor spheroid (MCTS) is an in vitro model associating malignant-cell microenvironment and 3D organization as currently observed in avascular tumors. METHODS: In order to evaluate the relevance of this model for pre-clinical studies of drug combinations, we analyzed the effect of gemcitabine alone and in combination with the CHIR-124 CHK1 inhibitor in a Capan-2 pancreatic cell MCTS model. RESULTS: Compared to monolayer cultures, Capan-2 MCTS exhibited resistance to gemcitabine cytotoxic effect. This resistance was amplified in EGF-deprived quiescent spheroid suggesting that quiescent cells are playing a role in gemcitabine multicellular resistance. After a prolonged incubation with gemcitabine, DNA damages and massive apoptosis were observed throughout the spheroid while cell cycle arrest was restricted to the outer cell layer, indicating that gemcitabine-induced apoptosis is directly correlated to DNA damages. The combination of gemcitabine and CHIR-124 in this MCTS model, enhanced the sensitivity to the gemcitabine antiproliferative effect in correlation with an increase in DNA damage and apoptosis. CONCLUSIONS: These results demonstrate that our pancreatic MCTS model, suitable for both screening and imaging analysis, is a valuable advanced tool for evaluating the spatio-temporal effect of drugs and drug combinations in a chemoresistant and microenvironment-depending tumor model

Meeting of the Ecosystem Approach Correspondence Group on on Pollution Monitoring (CorMon Pollution)

In accordance with the UNEP/MAP Programme of Work adopted by COP 21 for the biennium 2020-2021, the United Nations Environment Programme/Mediterranean Action Plan-Barcelona Convention Secretariat (UNEP/MAP) and its Programme for the Assessment and Control of Marine Pollution in the Mediterranean (MED POL) organized the Meeting of the Ecosystem Approach Correspondence Group on Pollution Monitoring (CorMon on Pollution Monitoring). The Meeting was held via videoconference on 26-27 April 2021. 2. The main objectives of the Meeting were to: a) Review the Monitoring Guidelines/Protocols for IMAP Common Indicator 18, as well as the Monitoring Guidelines/Protocols for Analytical Quality Assurance and Reporting of Monitoring Data for IMAP Common Indicators 13, 14, 17, 18 and 20; b) Take stock of the state of play of inter-laboratory testing and good laboratory practice related to IMAP Ecological Objectives 5 and 9; c) Analyze the proposal for the integration and aggregation rules for IMAP Ecological Objectives 5, 9 and 10 and assessment criteria for contaminants and nutrients; d) Recommend the ways and means to strengthen implementation of IMAP Pollution Cluster towards preparation of the 2023 MED Quality Status Report

Du sol dépend la vie sur terre

International audienceDissimulés sous nos pieds, les sols constituent une pellicule d’à peine un mètre d’épaisseur à la surface des continents. Rapportée au rayon de la terre, cette couche semble même dérisoire. Pourtant ce compartiment, qu’on appelle la pédosphère, est une véritable interface protectrice et d’échange entre la lithosphère, l’atmosphère, l’hydrosphère et la biosphère[1]. En effet, la consistance organo-minérale singulière des sols, couplée à leur biodiversité exceptionnelle, leur confèrent un rôle fondamental pour les écosystèmes terrestres et pour l’Homme

Decapod crustacean larvae and hydrodynamic processes in the northwestern Mediterranean Sea

Geomorphology and hydrodynamic processes shape the aggregation and dispersion of planktonic communities. [...]Peer reviewe

Selection of soil health indicators for modelling soil functions to promote smart urban planning

International audienceThe contribution of soil health to global health receives a growing interest, especially in urban environment. Therefore, there is a true need to develop methods to evaluate ecological functions provided by urban soils in order to promote smart urban planning. This work aims first at identifying relevant soil indicators based either on in situ description, in situ measurement or lab analysis. Then, 9 soil functions and sub-functions were selected to meet the main expectations regarding soil health in urban contexts. A crucial step of the present research was then to select adequate indicators for each soil function and then to create adapted reference frameworks; they were in the form of 4 classes with scores ranging from 0 to 3. All the reference frameworks were developed to evaluate soil indicators in order to score soil functions, either by using existing scientific or technical standards or references or based on the expertise of the co-authors. Our model was later tested on an original database of 109 different urban soils located in 7 cities of Western Europe and under various land uses. The scores calculated for 8 soil functions of 109 soils followed a Gaussian distribution. The scoring successfully expressed the strong contrasts between the various soils; the lowest scores were calculated for sealed soils and soils located in urban brownfields, whereas the highest were found for soils located in city parks or urban agriculture. Despite requiring a soil expertise, the proposed approach is easy to implement and could help reveal their true potential of urban soils in order to promote smart urban planning and enhance their contribution to global health

Tomorrows soil quality indicators to promote vegetation within urban development and planning

International audienceThere is an increasing demand of nature in cities worldwide. However, urban soils can be degraded by, for example, diffuse or point-source pollution loss of organic matter. In addition, the European strategy to achieve no net land take by 2050 promotes the renaturation of artificialized soils. There is a lack of knowledge and tools to help optimise the management of urban soils within redevelopment and planning strategies. To address this lack, one of the objective of the R&D project SUPRA was to prepare a decision aid tool to help optimise the qualification of urban soils that could be considered for vegetation growth, including food production and other purposes. Within this framework, we developed a set of indicators to assess the soil functions linked to 3 services associated with vegetation growth: production of biomass, contaminants regulation and climate regulation. This work is based on a literature review and a working group of experts on urban soils. The first step was to link services, functions and indicators of soil condition. A set of functions and subfunctions was then decided. For each of them, we listed the corresponding parameters, the existence or not of normative methods and the range of reference values. Discussions were held to select a set of minimum indicators. The existing range of reference values was used to set threshold that would allow the evaluation of each indicators. In case there was no reference, and the indicators were considered essential, new threshold value were proposed. A first version of decision aid tool was also developed and first tests allowed comparing the results obtained for some characterised soils.The following 6 functions were selected: i) Storage, recycling and transformation of organic matter ; ii) Retention and supply of nutrients / Supply-recycling of nutrients (decomposition of organic matter) ; iii) Physical support – housing ; iv) Water retention, circulation and infiltration ; v) Retention, filtration, degradation of contaminants ; vi) Support of biodiversity. The minimum data set includes 30 indicators of which 11 correspond to field observations and others to measurements (in situ or in the laboratory). The level of expertise and an assessment of the cost of acquisition are also described. The first tests of the tool need to be continued with more soils to verify the scoring of soil quality with the assessment of soil experts. A longer term objective would be to map the results of soil quality scoring that could be used within urban strategies for biomass production

Quels indicateurs de qualité des sols pour promouvoir la nature en ville en planification et aménagement ?

International audienceThere is an increasing demand of nature in cities worldwide. However, urban soils can be degraded by, for example, pollution or loss of organic matter. In addition, the European strategy to achieve no net land take by 2050 promotes the renaturation of artificialized soils. There is a lack of knowledge and tools however to help optimise the management of urban soils within redevelopment and planning strategies. To address this lack, one of the objective of the R&D project SUPRA was to prepare a decision aid tool to help optimise the qualification of urban soils that could be considered for vegetation growth, including food production and other purposes. Within this framework, we developed a set of indicators to assess the soil functions linked to 3 services associated with vegetation growth: production of biomass, contaminants regulation and climate regulation. This work is based on a literature review and a working group of experts on urban soils. The first step linked services, functions and indicators of soil condition. A set of functions and subfunctions was then decided. For each of them, we listed the corresponding parameters, the existence or not of normative methods and the range of reference values. Discussions were held to select a set of minimum indicators. The existing range of reference values was used to set threshold that would allow the evaluation of each indicators. In case there was no reference, and the indicators were considered essential, new threshold value were proposed. A first version of decision aid tool was also developed and first tests allowed comparing the results obtained for some characterised soils.The following 6 functions were selected: i) Storage, recycling and transformation of organic matter ; ii) Retention and supply of nutrients / Supply-recycling of nutrients (decomposition of organic matter) ; iii) Physical support – housing ; iv) Water retention, circulation and infiltration ; v) Retention, filtration, degradation of contaminants ; vi) Support of biodiversity. The minimum data set includes 30 indicators of which 11 correspond to field observations and others to measurements (in situ or in the laboratory). The level of expertise and an assessment of the cost of acquisition are also described. The first tests of the tool need to be continued with more soils to verify the scoring of soil quality with the assessment of soil experts. A longer-term objective would be to map the results of soil quality scoring that could be used within urban strategies for biomass production

Etude du poids socio-économique de la filière pêche dans le quartier maritime de Bayonne

En 2007, le CIDPMEM 64-40 (alors CLPMEM de Bayonne), avait porté une étude sur le poids socio-économique de la filière pêche du quartier maritime de Bayonne. Elle avait permis de décrire le système halieutique local et de quantifier l’impact économique et social de l’activité de pêche sur le territoire par la quantification des flux monétaires entre acteurs et la quantification des emplois générés par l’activité de pêche. Même si les indicateurs définis lors cette précédente étude font toujours référence, le contexte de la filière a très sensiblement évolué en 10 ans et il est apparu indispensable non seulement de mettre à jour les différents indicateurs mais aussi de s'intéresser à des focus particuliers. Le CIDPMEM64-40 a donc à nouveau réuni un ensemble de structures partenaires pour mettre en commun et analyser différentes sources de données complémentaires. Plus précisément, le travail a porté sur : - L’actualisation des indicateurs du poids socio-économique de la filière pêche dans le quartier maritime de Bayonne ; - La réalisation de fiches socio-économiques par métier ; - L’amélioration des connaissances sur la caractérisation des apports commercialisés par les navires du quartier ; - Un focus sur l’activité socio-économique des navires des armements à capitaux franco-communautaires du quartier ; - L’amélioration de la collecte et de l’analyse des données sur les entreprises de l’aval et de l’amont de la filière sur le territoire. Ce rapport de 2019 présente les résultats obtenus et les pistes de réflexion identifiées dans la continuité de cette étude

Known genotoxic compounds identified with the DDR-Act-Fp reporter system amongst 1,280 pharmacologically compounds of the LOPAC library.

<p>Results are expressed as percentage of the fluorescence intensity measured in cells treated with 10μM Etoposide. ID number, compound name and putative mode of action are indicated.</p

Monitoring the Activation of the DNA Damage Response Pathway in a 3D Spheroid Model

<div><p>Monitoring the DNA-Damage Response (DDR) activated pathway in multicellular tumor spheroid models is an important challenge as these 3D models have demonstrated their major relevance in pharmacological evaluation. Herein we present DDR-Act-FP, a fluorescent biosensor that allows detection of DDR activation through monitoring of the p21 promoter p53-dependent activation. We show that cells expressing the DDR-Act-FP biosensor efficiently report activation of the DDR pathway after DNA damage and its pharmacological manipulation using ATM kinase inhibitors. We also report the successful use of this assay to screen a small compound library in order to identify activators of the DDR response. Finally, using multicellular spheroids expressing the DDR-Act-FP we demonstrate that DDR activation and its pharmacological manipulation with inhibitory and activatory compounds can be efficiently monitored in live 3D spheroid model. This study paves the way for the development of innovative screening and preclinical evaluation assays.</p></div