Galectin-3 Mediates Cross-Talk between K-Ras and Let-7c Tumor Suppressor microRNA

International audienceBACKGROUND: Galectin-3 (Gal-3) and active (GTP-bound) K-Ras contribute to the malignant phenotype of many human tumors by increasing the rate of cell proliferation, survival, and migration. These Gal-3-mediated effects result from a selective binding to K-Ras.GTP, causing increased nanoclustering in the cell membrane and leading to robust Ras signaling. Regulation of the interactions between Gal-3 and active K-Ras is not fully understood. METHODS AND FINDINGS: To gain a better understanding of what regulates the critical interactions between these two proteins, we examined the role of Gal-3 in the regulation of K-Ras by using Gal-3-knockout mouse embryonic-fibroblasts (Gal-3-/- MEFs) and/or Gal-3/Gal-1 double-knockout MEFs. We found that knockout of Gal-3 induced strong downregulation (∼60%) of K-Ras and K-Ras.GTP. The downregulation was somewhat more marked in the double-knockout MEFs, in which we also detected robust inhibition(∼50%) of ERK and Akt activation. These additional effects are probably attributable to inhibition of the weak interactions of K-Ras.GTP with Gal-1. Re-expression of Gal-3 reversed the phenotype of the Gal-3-/- MEFs and dramatically reduced the disappearance of K-Ras in the presence of cycloheximide to the levels seen in wild-type MEFs. Furthermore, phosphorylation of Gal-3 by casein kinase-1 (CK-1) induced translocation of Gal-3 from the nucleus to the cytoplasm and the plasma membrane, leading to K-Ras stabilization accompanied by downregulation of the tumor suppressor miRNA let-7c, known to negatively control K-Ras transcription. CONCLUSIONS: Our results suggest a novel cross-talk between Gal-3-mediated downregulation of let 7c microRNA (which in turn negatively regulates K-Ras transcription) and elucidates the association among Gal-3 let-7c and K-Ras transcription/translation, cellular compartmentalization and activity

"Time sweet time": circadian characterization of galectin-1 null mice

International audienceABSTRACT: BACKGROUND: Recent evidence suggests a two-way interaction between the immune and circadian systems. Circadian control of immune factors, as well as the effect of immunological variables on circadian rhythms, might be key elements in both physiological and pathological responses to the environment. Among these relevant factors, galectin-1 is a member of a family of evolutionarily-conserved glycan-binding proteins with both extracellular and intracellular effects, playing important roles in immune cell processes and inflammatory responses. Many of these actions have been studied through the use of mice with a null mutation in the galectin-1 (Lgals1) gene. To further analyze the role of endogenous galectin-1 in vivo, we aimed to characterize the circadian behavior of galectin-1 null (Lgals1-/-) mice. METHODS: We analyzed wheel-running activity in light-dark conditions, constant darkness, phase responses to light pulses (LP) at circadian time 15, and reentrainment to 6 hour shifts in light-dark schedule in wild-type (WT) and Lgals1-/- mice. RESULTS: We found significant differences in free-running period, which was longer in mutant than in WT mice (24.02 vs 23.57 h, p<0.005), phase delays in response to LP (2.92 vs 1.90 circadian h, p<0.05), and also in alpha (14.88 vs. 12.35 circadian h, p<0.05). CONCLUSIONS: Given the effect of a null mutation on circadian period and entrainment, we indicate that galectin-1 could be involved in the regulation of murine circadian rhythmicity. This is the first study implicating galectin-1 in the mammalian circadian system

Impaired B cell development at the pre-BII cell stage in galectin-1 deficient mice due to inefficient pre-BII-stromal cell interactions.

International audienceActivation of the pre-B cell receptor (pre-BCR) in the bone marrow depends on both tonic and ligand-induced signaling and leads to pre-BII cell proliferation and differentiation. Using normal mouse bone marrow pre-BII cells, we demonstrate that the ligand-induced pre-BCR activation depends on pre-BCR/galectin-1/integrin interactions leading to pre-BCR clustering at the pre-BII/stromal cell synapse. In contrast, heparan sulfates, shown to be pre-BCR ligands in mice, are not implicated in pre-BCR relocalization. Inhibition of pre-BCR/ galectin-1/integrin interactions has functional consequences, since pre-BII cell proliferation and differentiation are impaired in an in vitro B cell differentiation assay, without affecting cellular apoptosis. Most strikingly, although galectin-1 deficient mice do not show an apparent B cell phenotype, the kinetics of de novo B cell reconstitution after hydroxyurea-treatment indicates a specific delay in pre-BII cell recovery due to a decrease in pre-BII cell differentiation and proliferation. Thus, although it remains possible that the pre-BCR interacts with other ligands, these results highlight the role played by the stromal cell-derived galectin-1 for the efficient development of normal pre-BII cells and suggest the existence of pre-BII specific stromal cell niches in normal bone marrow

"Time sweet time": circadian characterization of galectin-1 null mice

Abstract Background Recent evidence suggests a two-way interaction between the immune and circadian systems. Circadian control of immune factors, as well as the effect of immunological variables on circadian rhythms, might be key elements in both physiological and pathological responses to the environment. Among these relevant factors, galectin-1 is a member of a family of evolutionarily-conserved glycan-binding proteins with both extracellular and intracellular effects, playing important roles in immune cell processes and inflammatory responses. Many of these actions have been studied through the use of mice with a null mutation in the galectin-1 (Lgals1) gene. To further analyze the role of endogenous galectin-1 in vivo, we aimed to characterize the circadian behavior of galectin-1 null (Lgals1-/-) mice. Methods We analyzed wheel-running activity in light-dark conditions, constant darkness, phase responses to light pulses (LP) at circadian time 15, and reentrainment to 6 hour shifts in light-dark schedule in wild-type (WT) and Lgals1-/- mice. Results We found significant differences in free-running period, which was longer in mutant than in WT mice (24.02 vs 23.57 h, p alpha (14.88 vs. 12.35 circadian h, p Conclusions Given the effect of a null mutation on circadian period and entrainment, we indicate that galectin-1 could be involved in the regulation of murine circadian rhythmicity. This is the first study implicating galectin-1 in the mammalian circadian system.</p

Inspecter les zones d’altitude: Programme TAHMM ou le développement d’une procédure multi-source pour la prospection archéologique des terrains d’altitude

International audienceUntil the last thirty years, mountain areas were considered to be unchanging. Their modes of access and management, their evolutionary dynamics and the agro-pastoral practices were perceived as atonic. It took the establishment of a dialogue between the human sciences (archaeology, history, ethnology) and natural sciences (anthracology, palynology) and the insertion of new tools (DGPS - Digital Global Positioning System- and GIS -Geographic Information System-) for these territories to be considered differently. Today, mountains are the subject of interdisciplinary questioning that reveals long and complex histories.An essential prerequisite for any archaeological research, prospecting in high mountains presents its own specificities and challenges: limited access, great variability in the perception of infrastructures. The question then arises as to how, in practice, to systematise acquisitions in order to be able to deal with larger territories and to enrich the information in order to detect all the developments that archaeologists are currently missing. Technological advances, the diversification and miniaturisation of sensors, the democratisation of drones and progress in usability now make it possible to think about setting up a new data acquisition, processing and fusion procedure. This is what the TAHMM (Remote Archaeological Sensing in the High and Middle Mountains) research programme has been undertaking since 2018 around four workshop areas located in Occitania and New Aquitaine. By developing a multi-source approach with high spatial, spectral, radiometric and temporal resolution, it aims to optimise the detection of archaeological remains in high altitude environments during the prospecting phase.Jusqu’à ces trente dernières années, les zones de montagne ont été considérées comme immuables. Leurs modes d’accès et de gestion, leurs dynamiques d’évolution et les pratiques agro-pastorales étaient jusque-là perçus atones. Il a fallu la mise en place d’un dialogue entre les sciences humaines (archéologie, histoire, ethnologie) et naturelles (anthracologie, palynologie) et l’insertion de nouveaux outils (DGPS – Digital Global Positionning System- et SIG -Système d’Information Géographique-) pour que ces territoires soient considérés différemment. Aujourd'hui, les montagnes font l'objet de questionnements interdisciplinaires qui révèlent des histoires longues et complexes.Préalable indispensable à toute recherche archéologique, la prospection en haute montagne présente des spécificités et des enjeux qui lui sont propres : limitation d’accès, forte variabilité de perception des infrastructures. Se pose alors la question de savoir comment, pratiquement, systématiser les acquisitions, pour arriver à traiter de plus vastes territoires et enrichir l'information pour parvenir à détecter tous les aménagements qui échappent actuellement aux yeux des archéologues. Les avancées technologiques, la diversification et la miniaturisation des capteurs, la démocratisation des drones et les progrès en matière d'ergonomie informatique permettent aujourd’hui de réfléchir à la mise en place d'une nouvelle procédure d'acquisition, de traitement et de fusion des données. C'est ce que fait le programme de recherche TAHMM (Télédétection Archéologique en Haute et Moyenne Montagne) depuis 2018 autour de quatre zones ateliers situées en Occitanie et Nouvelle Aquitaine. Par le développement d'une approche multi-source à haute résolution spatiale, spectrale, radiométrique et temporelle, il vise à optimiser la détection des vestiges archéologiques en milieux d’altitude durant la phase de prospection

Inspecter les zones d’altitude: Programme TAHMM ou le développement d’une procédure multi-source pour la prospection archéologique des terrains d’altitude

International audienceUntil the last thirty years, mountain areas were considered to be unchanging. Their modes of access and management, their evolutionary dynamics and the agro-pastoral practices were perceived as atonic. It took the establishment of a dialogue between the human sciences (archaeology, history, ethnology) and natural sciences (anthracology, palynology) and the insertion of new tools (DGPS - Digital Global Positioning System- and GIS -Geographic Information System-) for these territories to be considered differently. Today, mountains are the subject of interdisciplinary questioning that reveals long and complex histories.An essential prerequisite for any archaeological research, prospecting in high mountains presents its own specificities and challenges: limited access, great variability in the perception of infrastructures. The question then arises as to how, in practice, to systematise acquisitions in order to be able to deal with larger territories and to enrich the information in order to detect all the developments that archaeologists are currently missing. Technological advances, the diversification and miniaturisation of sensors, the democratisation of drones and progress in usability now make it possible to think about setting up a new data acquisition, processing and fusion procedure. This is what the TAHMM (Remote Archaeological Sensing in the High and Middle Mountains) research programme has been undertaking since 2018 around four workshop areas located in Occitania and New Aquitaine. By developing a multi-source approach with high spatial, spectral, radiometric and temporal resolution, it aims to optimise the detection of archaeological remains in high altitude environments during the prospecting phase.Jusqu’à ces trente dernières années, les zones de montagne ont été considérées comme immuables. Leurs modes d’accès et de gestion, leurs dynamiques d’évolution et les pratiques agro-pastorales étaient jusque-là perçus atones. Il a fallu la mise en place d’un dialogue entre les sciences humaines (archéologie, histoire, ethnologie) et naturelles (anthracologie, palynologie) et l’insertion de nouveaux outils (DGPS – Digital Global Positionning System- et SIG -Système d’Information Géographique-) pour que ces territoires soient considérés différemment. Aujourd'hui, les montagnes font l'objet de questionnements interdisciplinaires qui révèlent des histoires longues et complexes.Préalable indispensable à toute recherche archéologique, la prospection en haute montagne présente des spécificités et des enjeux qui lui sont propres : limitation d’accès, forte variabilité de perception des infrastructures. Se pose alors la question de savoir comment, pratiquement, systématiser les acquisitions, pour arriver à traiter de plus vastes territoires et enrichir l'information pour parvenir à détecter tous les aménagements qui échappent actuellement aux yeux des archéologues. Les avancées technologiques, la diversification et la miniaturisation des capteurs, la démocratisation des drones et les progrès en matière d'ergonomie informatique permettent aujourd’hui de réfléchir à la mise en place d'une nouvelle procédure d'acquisition, de traitement et de fusion des données. C'est ce que fait le programme de recherche TAHMM (Télédétection Archéologique en Haute et Moyenne Montagne) depuis 2018 autour de quatre zones ateliers situées en Occitanie et Nouvelle Aquitaine. Par le développement d'une approche multi-source à haute résolution spatiale, spectrale, radiométrique et temporelle, il vise à optimiser la détection des vestiges archéologiques en milieux d’altitude durant la phase de prospection