Du bien nommer. Étapes de parcours et méthode de recherche

Le problème de la place et du rôle de l’homme dans le monde, et en particulier de l’homme d’aujourd’hui dans le monde de l’anthropocène, et de son écosystème en particulier était le point de départ de cette étude. Dans ce questionnement et les réponses à proposer, notre parcours s’est appliqué à souligner l’importance d’une méthode d’approche de l’objet de pensée, l’importance d’une délimitation propre de cet « objet » particulier dans le réel, dans la réalité du monde ainsi que l’importance des outils de langue au service des opérations de saisie par les sens (la vue, l’ouïe). Une saisie de nature sensible sera relayée par une saisie conceptuelle et linguistique. Nous avons souligné le jeu que permet la langue et ses structures (impersonnelle-imparticulière vs personnelle) et ses personnes (personne d’univers-personne humaine) pour aller et venir de l’imparticulier au particulier dans le monde de la perception comme dans le monde de la pensée

Short-Term Feeding of a High-Fat Diet Disturbs Lipid Raft/Tgf-Beta Signaling-Mediated Quiescence of Hematopoietic Stem Cells in C57bl/6j Mouse Bone Marrow

IF 7.702International audienc

Short-Term Feeding of a High-Fat Diet Disturbs Lipid Raft/Tgf-Beta Signaling-Mediated Quiescence of Hematopoietic Stem Cells in C57bl/6j Mouse Bone Marrow

IF 7.702International audienc

Short-Term Feeding of a High-Fat Diet Disturbs Lipid Raft/Tgf-Beta Signaling-Mediated Quiescence of Hematopoietic Stem Cells in C57bl/6j Mouse Bone Marrow

IF 7.702International audienc

Nanofitins targeting heat shock protein 110: An innovative immunotherapeutic modality in cancer.

The presence of an inactivating heat shock protein 110 (HSP110) mutation in colorectal cancers has been correlated with an excellent prognosis and with the ability of HSP110 to favor the formation of tolerogenic (M2-like) macrophages. These clinical and experimental results suggest a potentially powerful new strategy against colorectal cancer: the inhibition of HSP110. In this work, as an alternative to neutralizing antibodies, Nanofitins (scaffold ~7 kDa proteins) targeting HSP110 were isolated from the screening of a synthetic Nanofitin library, and their capacity to bind (immunoprecipitation, biolayer interferometry) and to inhibit HSP110 was analyzed in vitro and in vivo. Three Nanofitins were found to inhibit HSP110 chaperone activity. Interestingly, they share a high degree of homology in their variable domain and target the peptide-binding domain of HSP110. In vitro, they inhibited the ability of HSP110 to favor M2-like macrophages. The Nanofitin with the highest affinity, A-C2, was studied in the CT26 colorectal cancer mice model. Our PET/scan experiments demonstrate that A-C2 may be localized within the tumor area, in accordance with the reported HSP110 abundance in the tumor microenvironment. A-C2 treatment reduced tumor growth and was associated with an increase in immune cells infiltrating the tumor and particularly cytotoxic macrophages. These results were confirmed in a chicken chorioallantoic membrane tumor model. Finally, we showed the complementarity between A-C2 and an anti-PD-L1 strategy in the in vivo and in ovo tumor models. Overall, Nanofitins appear to be promising new immunotherapeutic lead compounds

Elucidating the role of lipid rafts on g protein-coupled receptor function in the mouse kidney: An in vivo approach

© 2021, Springer Science+Business Media, LLC, part of Springer Nature. Numerous G protein-coupled receptors (GPCRs) and GPCR-signaling molecules reside in lipid rafts and thus, are inherently regulated in these microdomains. However, the limitations of current methods to investigate lipid raft biology and GPCR activity in situ have hindered the complete understanding of the molecular underpinnings of GPCR trafficking and signaling, especially in the whole organism. This book chapter details an innovative in vivo approach to study the crucial role of lipid rafts on the workings of GPCRs in the mouse kidney. This protocol involves the use of a modified mini osmotic pump to deliver an agent that selectively disrupts the lipid raft in the kidney