The retinoid agonist Tazarotene promotes angiogenesis and wound healing

Therapeutic angiogenesis is a major goal ofregenerative medicine, but no clinically approved small molecule exists that enhancesnew blood vessel formation. Here we show, using a phenotype-driven high-content imaging screen of an annotated chemical library of 1280 bioactive small molecules, that the retinoid agonist Tazarotene, enhances in vitroangiogenesis, promoting branching morphogenesis, and tubule remodeling. The pro-angiogenic phenotype is mediated by Retinoic Acid Receptor (RAR) but not Retinoic X Receptor(RXR) activation, and is characterized by secretion of the pro-angiogenic factors Hepatocyte Growth Factor (HGF), Vascular Endothelial Growth Factor (VEGFA), Plasminogen Activator, Urokinase (PLAU) and Placental Growth Factor (PGF), and reduced secretion of the antiangiogenic factor Pentraxin-3 (PTX3) from adjacent fibroblasts. In vivo, Tazarotene enhanced the growth of mature and functional microvessels in Matrigel implants and wound healing models, and increased blood flow. Notably, in ear punch wound healing model, Tazarotene promoted tissue repair characterized by rapid ear punch closure with normal-appearing skin containing new hair follicles, and maturing collagen fibers. Our study suggests that Tazarotene, an FDA-approved small molecule, could be potentially exploited for therapeutic applications in neovascularization and wound healing

Les Cruchades, Combronde (63)

International audienc

Les Cruchades, Combronde (63)

International audienc

Les Cruchades, Combronde (63)

International audienc

Capability of electronic monitoring system to inform the hauling process of French tuna purse seiners catch

Electronic monitoring systems (EMS) have increasingly been used as an alternative technology to complement onboard observer programs and improve the management of tuna fisheries. EMS was installed on French purse seiners in 2014 in the frame of the OCUP program and pilot studies have shown that the system allows in-depth monitoring of fishing activities by providing information on catch composition and handling on deck and below deck. In this study, we further explore the potential of EMS for monitoring the hauling process of tropical tuna purse seiners' catch from the net to the deck. Using information collected during brailing (number of brailers, timing, fullness) on board 5 vessels of the Indian Ocean during 2018-2019, we evaluate the suitability of EMS as a tool to describe the main trends in brailing operations over 50 fishing sets. Our results indicate a large variability in brailer fullness among fishing sets and a relatively fast loading of the catch onto the deck with brailing operations generally consisting of 4 to 5 brailers transferred on board in less than 15 minutes. Results confirm the potential of EMS for collecting complementary data to monitor brailing operations of tropical tuna purse seiners

Capability of electronic monitoring system to inform the hauling process of French tuna purse seiners catch

Electronic monitoring systems (EMS) have increasingly been used as an alternative technology to complement onboard observer programs and improve the management of tuna fisheries. EMS was installed on French purse seiners in 2014 in the frame of the OCUP program and pilot studies have shown that the system allows in-depth monitoring of fishing activities by providing information on catch composition and handling on deck and below deck. In this study, we further explore the potential of EMS for monitoring the hauling process of tropical tuna purse seiners' catch from the net to the deck. Using information collected during brailing (number of brailers, timing, fullness) on board 5 vessels of the Indian Ocean during 2018-2019, we evaluate the suitability of EMS as a tool to describe the main trends in brailing operations over 50 fishing sets. Our results indicate a large variability in brailer fullness among fishing sets and a relatively fast loading of the catch onto the deck with brailing operations generally consisting of 4 to 5 brailers transferred on board in less than 15 minutes. Results confirm the potential of EMS for collecting complementary data to monitor brailing operations of tropical tuna purse seiners

The S enantiomer of 2-hydroxyglutarate increases central memory CD8 populations and improves CAR-T therapy outcome.

Cancer immunotherapy is advancing rapidly and gene-modified T cells expressing chimeric antigen receptors (CARs) show particular promise. A challenge of CAR-T cell therapy is that the ex vivo-generated CAR-T cells become exhausted during expansion in culture, and do not persist when transferred back to patients. It has become clear that naive and memory CD8 T cells perform better than the total CD8 T-cell populations in CAR-T immunotherapy because of better expansion, antitumor activity, and persistence, which are necessary features for therapeutic success and prevention of disease relapse. However, memory CAR-T cells are rarely used in the clinic due to generation challenges. We previously reported that mouse CD8 T cells cultured with the S enantiomer of the immunometabolite 2-hydroxyglutarate (S-2HG) exhibit enhanced antitumor activity. Here, we show that clinical-grade human donor CAR-T cells can be generated from naive precursors after culture with S-2HG. S-2HG-treated CAR-T cells establish long-term memory cells in vivo and show superior antitumor responses when compared with CAR-T cells generated with standard clinical protocols. This study provides the basis for a phase 1 clinical trial evaluating the activity of S-2HG-treated CD19-CAR-T cells in patients with B-cell malignancies

Matières premières et gestion des ressources

Retour aux sources ! Ayant scruté dans les Archéo.Doct précédents les « Objets et symboles » ; les « Territoires et économies » ; « Les images », « Les marqueurs du pouvoir » ; l'« Adoption et adaptation », les jeunes archéologues préparant un doctorat à l'université Paris 1 ont choisi pour leur journée doctorale de 2012, désormais au sein de la communauté heSam Université avec les jeunes archéologues de l’École pratique des hautes études, d’échanger leurs découvertes sur « Matières premières et gestion des ressources ». Rien n’est plus au cœur du métier de l’archéologue fouilleur qui, si fréquemment, se demande avec une enfantine curiosité : « En quoi est-ce ? » ou « D’où cela peut-il venir ? ». Questions rudimentaires mais souvent bien difficiles à traiter – que l’essor prodigieux, néanmoins, des archéosciences et de l’archéologie environnementale permet de résoudre, au coup par coup et sauf exceptions –, questions rudimentaires, oui, mais au coeur de toute la réflexion archéologique sur le local et l’importé, le brut et le travaillé, l’original et le recyclé. Il suffit de le dire ainsi pour que tout lecteur porté vers les sciences humaines ou de la nature se sente lui aussi impliqué : il ne sera pas déçu. « Que d’eaux, que d’os ! », ont plaisanté les auditeurs de mai 2012 : certes, les jeunes savants dont nous avons ici rassemblé les écrits font feu de tout bois, et les pierres ou les plantes ne sont pas oubliées, mais le lecteur constatera à son tour l’étonnante convergence spontanée de nombre de contributions vers l’utilisation des matières premières animales d’une part, le traitement des ressources hydriques, ou concernant l’eau, d’autre part. C’est le reflet des développements très heuristiques qu’ont connus ces dernières années l’archéozoologie et les études hydrauliques dans la discipline. Comme l’écrivent les éditrices, « cette lecture résonne fort dans nos sociétés, puisque les questions de changements climatiques, de surexploitation des ressources et de préservation de la planète occupent de plus en plus les esprits »

Indocyanine Green-based Nanoprobe for In Vivo Detection of Cellular Senescence.

There is an urgent need to improve conventional cancer-treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo- or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self-assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy