Stroma Regulates Increased Epithelial Lateral Cell Adhesion in 3D Culture: A Role for Actin/Cadherin Dynamics

Cell shape and tissue architecture are controlled by changes to junctional proteins and the cytoskeleton. How tissues control the dynamics of adhesion and cytoskeletal tension is unclear. We have studied epithelial tissue architecture using 3D culture models and found that adult primary prostate epithelial cells grow into hollow acinus-like spheroids. Importantly, when co-cultured with stroma the epithelia show increased lateral cell adhesions. To investigate this mechanism further we aimed to: identify a cell line model to allow repeatable and robust experiments; determine whether or not epithelial adhesion molecules were affected by stromal culture; and determine which stromal signalling molecules may influence cell adhesion in 3D epithelial cell cultures.The prostate cell line, BPH-1, showed increased lateral cell adhesion in response to stroma, when grown as 3D spheroids. Electron microscopy showed that 9.4% of lateral membranes were within 20 nm of each other and that this increased to 54% in the presence of stroma, after 7 days in culture. Stromal signalling did not influence E-cadherin or desmosome RNA or protein expression, but increased E-cadherin/actin co-localisation on the basolateral membranes, and decreased paracellular permeability. Microarray analysis identified several growth factors and pathways that were differentially expressed in stroma in response to 3D epithelial culture. The upregulated growth factors TGFβ2, CXCL12 and FGF10 were selected for further analysis because of previous associations with morphology. Small molecule inhibition of TGFβ2 signalling but not of CXCL12 and FGF10 signalling led to a decrease in actin and E-cadherin co-localisation and increased paracellular permeability.In 3D culture models, paracrine stromal signals increase epithelial cell adhesion via adhesion/cytoskeleton interactions and TGFβ2-dependent mechanisms may play a key role. These findings indicate a role for stroma in maintaining adult epithelial tissue morphology and integrity

Synergies and divergence between LCA human toxicity assessment and Risk Assessment approaches

International audienceIntroduction Beyond the assessment of toxic effects and risks within the framework of European regulations, such as REACh and CLP, other assessment methods for sanitary risks exist but differ from one country to another. Methodologies are different but always based on the founding principles of dose-response relationships and exposure scenarios describing the source-to-target vector. The complementarity of Life Cycle Assessment (LCA) and Chemical Risk Assessment (RA) may yield a more accurate and exhaustive approach to assess human toxicity. Various approaches to assess human toxicity risks exist and allow to supply toxicity data. The classifications, such as those established by the European Union, allow to identify hazards of substances. Risk and hazard based approaches typically apply (reasonable) worst-case assumptions for modelling and data selection. In contrast, LCA toxicity assessment methods apply the concept of best-estimates. Another important difference is that RA is site-specific whereas LCA is site-generic. A number of relevant methods for human toxicity assessment within the LCA and RA frameworks have been analysed in order to allow for a mapping of the methods. The results and the divergences identified between the methods are presented in a condensed way. The methods have been analysed according to many criteria. This talk will underline the similarities and differences as well as the advantages and the associated drawbacks linked to each method. To support this analysis, a comparison based on a case study applying both LCA and RA methods was performed for the human toxicity assessment of a paraben-free cosmetic formula. A detergent was also analysed with different methods. Throughout the study, independent scientific experts have been associated to assure a peer-review of this study. Propositions for the correct interpretation of results as well as their limitations and research needs were identified. Methodological issues will be discussed. Moreover, guidelines and recommendations for human toxicity assessment will be proposed, detailing which method serves which purpose, where they overlap and where they complement one another. This study invites experts to work together to find solutions to the current issues in human toxicity assessment

When pliers become fingers in the monkey motor system

The capacity to use tools is a fundamental evolutionary achievement. Its essence stands in the capacity to transfer a proximal goal (grasp a tool) to a distal goal (e.g., grasp food). Where and how does this goal transfer occur? Here, we show that, in monkeys trained to use tools, cortical motor neurons, active during hand grasping, also become active during grasping with pliers, as if the pliers were now the hand fingers. This motor embodiment occurs both for normal pliers and for "reverse pliers," an implement that requires finger opening, instead of their closing, to grasp an object. We conclude that the capacity to use tools is based on an inherently goal-centered functional organization of primate cortical motor areas

Transfert de polluants organiques persistants vers l’oeuf de consommation : état des lieux, modalités et facteurs de risques

Textes issus des travaux du programme Casdar "Innovation et Partenariat" de 2007 et présentés lors d'un colloque le 4 décembre 2012, sous l'égide du GIS Relance AgronomiqueNational audienceThe transfer modalities of persistent organic pollutants (POPs) into eggs were studied in a research program CAS DAR. At first, the sanitary quality of eggs produced in France was established with regard to some POPs and the risk factors in farms were identified. Secondly, all steps of the evaluation of risk transfer of these contaminants into eggs were approached, by generating original data about 1) exposure level of hens, 2) contaminant bioavailability according to properties of the POP sources and 3) transfer level into eggs, of absorbed contaminants, which depends on molecule and animal characteristics. Finally, a modeling approach of transfer was introduced, based on the data integration, in order to evaluate the egg contamination according to exposure and physiological characteristics of hens.Les modalités de transfert des polluants organiques persistants (POP) vers l’oeuf de consommation ont été étudiées dans le cadre d’un programme de recherche CasDAR (7106). Dans un premier temps, la qualité sanitaire des oeufs produits en France a été établie au regard de certains POP et les facteurs de risque en élevage ont été identifiés. Dans un second temps, les différentes étapes de l’évaluation du risque de transfert de ces contaminants vers l’oeuf ont été abordées, en générant des données originales sur 1) le niveau d’exposition des poules, 2) la biodisponibilité du contaminant en fonction des propriétés de la source de POP et sur 3) le niveau de transfert vers l’oeuf, du contaminant absorbé, qui dépend de la molécule et de l’animal. Pour finir, une démarche de modélisation du transfert a été initiée, basée sur l’intégration des données disponibles, en vue d’estimer la contamination des oeufs en fonction de l’exposition et des caractéristiques physiologiques des poules