The Thymus-Specific Serine Protease TSSP/PRSS16 Is Crucial for the Antitumoral Role of CD4+ T Cells

In cancer, immune cells can play conflicting roles, either protective, by elimination of tumor cells during immune surveillance, or detrimental, by promoting carcinogenesis during inflammation. We report here that the thymus-specific serine protease (TSSP), which is involved in CD4+ T cell maturation in the thymus, exerts a tumor suppressor activity. Mice genetically deficient for TSSP are highly prone to spontaneous cancer development. The absence of TSSP also increases the rate of induced colitis-associated colorectal (CAC) tumor formation, through exacerbated colon inflammation. Adoptive transfer of T cells in various combinations (CD4+ and CD8+ from wild-type and/or knockout mice) into T cell-deficient mice showed that the TSSP-deficient CD4+ T cell compartment promotes tumor development, associated with high levels of the cytokine IL-17A. Inhibition of IL-17A during CAC tumor formation prevents the increased carcinogenesis and colic immune disequilibrium observed in TSSP-deficient mice. Therefore, our data demonstrate that antitumoral immune surveillance requires thymic TSSP-driven production of CD4+ T cells contributing to inflammatory balance

Stratégie de conception d'expérience patient

National audienceRéflexion collective, codesign, construction collaborative, conception participative ou encore design thinking, les sciences participatives révèlent toute leur pertinence dans une époque où les enjeux écosystémiques sont prégnants. L'intelligence collective, sur laquelle est basée cette culture de la création par et pour les usagers, nécessite la participation de toutes les parties prenantes de votre projet. Cette interdisciplinarité au cœur de la e-santé est une thématique peu abordée dans la littérature non-scientifique. Expliquée et intégrée à la démarche de conception d'expérience utilisateur en santé, elle recèle des atouts précieux pour concevoir une expérience patient éthique, souveraine et durable. Les dimensions d'épanouissement et de liberté individuelle y sont centrales. Un livre incontournable si vous êtes entrepreneur du numérique ou designer d'expérience en santé

Retour d’expérience sur la comparaison des modèles d’agro-écosystème

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Retour d’expérience sur la comparaison des modèles d’agro-écosystème

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Zetacism and Sigmatism in proto-turkic

Donated by Klaus Kreise

1-Aminocyclopropane-1-carboxylic acid oxidase: insight into cofactor binding from experimental and theoretical studies

International audience1-Aminocyclopropane-1-carboxylic acid oxi-dase (ACCO) is a nonheme Fe(II)-containing enzyme that is related to the 2-oxoglutarate-dependent dioxygenase family. The binding of substrates/cofactors to tomato ACCO was investigated through kinetics, tryptophan fluorescence quenching, and modeling studies. a-Amin-ophosphonate analogs of the substrate (1-aminocyclopro-pane-1-carboxylic acid, ACC), 1-aminocyclopropane-1-phosphonic acid (ACP) and (1-amino-1-methyl)ethyl-phosphonic acid (AMEP), were found to be competitive inhibitors versus both ACC and bicarbonate (HCO 3-) ions. The measured dissociation constants for Fe(II) and ACC clearly indicate that bicarbonate ions improve both Fe(II) and ACC binding, strongly suggesting a stabilization role for this cofactor. A structural model of tomato ACCO was constructed and used for docking experiments, providing a model of possible interactions of ACC, HCO 3-, and ascorbate at the active site. In this model, the ACC and bicarbonate binding sites are located close together in the active pocket. HCO 3-is found at hydrogen-bond distance from ACC and interacts (hydrogen bonds or electrostatic interactions) with residues K158, R244, Y162, S246, and R300 of the enzyme. The position of ascorbate is also predicted away from ACC. Individually docked at the active site, the inhibitors ACP and AMEP were found coordinating the metal ion in place of ACC with the phosphonate groups interacting with K158 and R300, thus interlocking with both ACC and bicarbonate binding sites. In conclusion, HCO 3-and ACC together occupy positions similar to the position of 2-oxoglutarate in related enzymes, and through a hydrogen bond HCO 3-likely plays a major role in the stabilization of the substrate in the active pocket

Retour d'expérience sur la comparaison des modèles dans le cadre du projet CLIMATOR

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Retour d'expérience sur la comparaison des modèles dans le cadre du projet CLIMATOR

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Mesurer et standardiser : les technologies politiques du gouvernement de l’Afrique

Les instruments de mesure sont devenus des outils de gouvernement de l’Afrique contemporaine et de réforme de l’aide au développement. Ils transforment les modalités d’intervention et reconfigurent les politiques. Mobilisant des experts et savoirs spécifiques, ils créent les conditions d’une infiltration où les bailleurs internationaux s’immiscent au sein des États africains. Measurement instruments have become tools for contemporary African governance and development aid reform. They are transforming the modalities of intervention and reconfiguring policies. By mobilizing specific experts and knowledge, they create the conditions for infiltration where international donors interfere in African states. Los instrumentos de medición se han convertido en herramientas para la gobernanza africana contemporánea y la reforma de la ayuda al desarrollo. Están transformando las modalidades de intervención y reconfigurando las políticas. Mediante la movilización de expertos y conocimientos específicos, crean las condiciones para la infiltración donde los donantes internacionales interfieren en los Estados africanos

Change in recharge of aquifers under several cropping systems due to climate change. Consequences on land use at territorial level

session 2 : Adapation au changement climatiqueClimate change will produce a decrease in rainfall over French territory, especially in western France. Cropping systems pattern is a key factor in water resources management at catchment basin level. In the frame of the ANR French project ―Climator‖, we have undertaken an analysis of the relationship between rainfall and the annual supply of water to the aquifers under several cropping systems and ecosystems. This was performed through crop modelling using agroclimatic data provided either by measurements at 12 experimental sites in France (1971-2000) or by using regionalised outputs of the French climatological model Arpege (2021-2050 and 2071-2100). The simulations highlight the important differences in aquifers recharge between cropping systems (rainfed vs irrigated but also winter vs spring crops and annual crops vs perennial vegetation). For the 12 sites, they also give an estimate of the decrease with time of the annual recharge under each cropping system (at least 2/3 of rain decrease). In the driest locations, that decrease may lead to a partial change in cropping systems pattern in order to match the total water demand at catchment level. Such change could be devoted either to increase annual recharge when irrigation water is pumped from large aquifers or to reduce summer water demand when irrigation water comes from rivers. Both cases are illustrated