Transmettre la science autrement, par le débat scientifique en classe : une investigation autour des phases de la lune.

Atelier 2 : Compétences et innovations pédagogiquesNous posons avec Weil (1949/1999), la question de la transmission de la culture pour tous, comme élément d'une société qui trouve son enracinement dans le " trésor amassé par l'espèce humaine au cours des siècles ". Adoptant un double point de vue alliant didactique professionnelle (Pastré, 2011) et didactique disciplinaire, nous considérons les conceptualisations transmises et construites selon les perspectives de Piaget et Vygotsky revisitées par Bruner (1996) et Vergnaud (1996). L'étude présentée, invite à considérer la transmission de la culture scientifique à partir de l'analyse comparée d'une situation de débat relative à l'investigation scientifique autour des phases de la lune au CM2. Nous repérerons si les élèves énoncent des conceptualisations et construisent une problématisation (Fabre, 1999 ; Villeret, 2008)

L’art délicat du raffinage du sucre : la discrète évolution des techniques (France, fin xviie-fin xviiie siècle)

Alors qu’à la fin du xviie siècle, le royaume de France importait du sucre raffiné en provenance d’Europe du Nord, en particulier des Provinces-Unies, à la fin du xviiie siècle, les raffineurs sont parvenus à satisfaire les besoins des consommateurs français. Grâce aux encouragements de l’État, à l’arrivée d’ouvriers étrangers qualifiés et à l’audace de certains négociants, le royaume de France est désormais auto-suffisant et la technique du raffinage maîtrisée. L’objectif de cette contribution est de comprendre comment le savoir-faire a été assimilé par les entrepreneurs français et comment les techniques ont évolué pour répondre à la demande croissante.While at the end of the seventeenth century, the kingdom of France was importing refined sugar from Northern Europe, especially from the Dutch Republic, at the end of the eighteenth century, French refiners were able to meet French consumers’ needs. Thanks to government incentives, to the arrival of skilled foreign workers and to the audacity of some traders, the kingdom of France was self-sufficient and it mastered the refinement process. The aim of this paper is to grasp how the refining expertise was assimilated by French entrepreneurs and how techniques evolved to meet the growing demand

Effect of Pharmaceutical Potential Endocrine Disruptor Compounds on Protein Disulfide Isomerase Reductase Activity Using Di-Eosin-Oxidized-Glutathion

Background: Protein Disulfide Isomerase (PDI) in the endoplasmic reticulum of all cells catalyzes the rearrangement of disulfide bridges during folding of membrane and secreted proteins. As PDI is also known to bind various molecules including hormones such as estradiol and thyroxin, we considered the hypothesis that adverse effects of endocrinedisrupter compounds (EDC) could be mediated through their interaction with PDI leading to defects in membrane or secreted proteins. Methodology/Principal Findings: Taking advantage of the recent description of the fluorescence self quenched substrate di-eosin-oxidized-glutathion (DiE-GSSG), we determined kinetically the effects of various potential pharmaceutical EDCs on the in-vitro reductase activity of bovine liver PDI by measuring the fluorescence of the reaction product (E-GSH). Our data show that estrogens (ethynylestradiol and bisphenol-A) as well as indomethacin exert an inhibition whereas medroxyprogesteroneacetate and nortestosterone exert a potentiation of bovine PDI reductase activity. Conclusions: The present data indicate that the tested EDCs could not only affect endocrine target cells through nuclear receptors as previously shown, but could also affect these and all other cells by positively or negatively affecting PDI activity. The substrate DiE-GSSG has been demonstrated to be a convenient substrate to measure PDI reductase activity in the presence of various potential EDCs. It will certainely be usefull for the screening of potential effect of all kinds of chemical

Coopérer pour se former par le débriefing en formation au concours « Ma thèse en 180 secondes »

International audienceLa formation au concours « Ma thèse en 180 secondes » permet au doctorants de préparer le concours mais surtout leur permet de développer des compétences de médiation, de structuration, d'éloquence et d'ouverture à d'autres thématiques. La mise en place dans la formation d'un dispositif d'analyse réflexive leur permet surtout de se former individuellement dans un dispositif collectif basé sur la coopération

Poly(ADP-ribose) Polyremase-1 (PARP-1) Inhibition: A Promising Therapeutic Strategy for ETS-Expressing Tumours.

ETS transcription factors are a highly conserved family of proteins involved in the progression of many cancers, such as breast and prostate carcinomas, Ewing's sarcoma, and leukaemias. This significant involvement can be explained by their roles at all stages of carcinogenesis progression. Generally, their expression in tumours is associated with a poor prognosis and an aggressive phenotype. Until now, no efficient therapeutic strategy had emerged to specifically target ETS-expressing tumours. Nevertheless, there is evidence that pharmacological inhibition of poly(ADP-ribose) polymerase-1 (PARP-1), a key DNA repair enzyme, specifically sensitises ETS-expressing cancer cells to DNA damage and limits tumour progression by leading some of the cancer cells to death. These effects result from a strong interplay between ETS transcription factors and the PARP-1 enzyme. This review summarises the existing knowledge of this molecular interaction and discusses the promising therapeutic applications

Ets-1 interacts through a similar binding interface with Ku70 and Poly (ADP-Ribose) Polymerase-1

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Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity

TLRs trigger immunity by detecting microbe-associated molecular patterns (MAMPs). Flagellin is a unique MAMP because it harbors 1) an antigenic hypervariable region and 2) a conserved domain involved in TLR5-dependent systemic and mucosal proinflammatory and adjuvant activities. In this study, the contribution of the flagellin domains in TLR5 activation was investigated. We showed that TLR5 signaling can be neutralized in vivo by flagellin-specific Abs, which target the conserved domain. However, deletions of flagellin's hypervariable region abrogated the protein's intrinsic ability to trigger the production of neutralizing Abs. The fact that MAMP-specific Abs block TLR-mediated responses shows that this type of neutralization is a novel mechanism for down-regulating innate immunity. The stimulation of mucosal innate immunity and adjuvancy to foreign Ag was not altered by the hypervariable domain deletions. In contrast, this domain is essential to trigger systemic innate immunity, suggesting that there are distinct mechanisms for TLR5 activation in systemic and mucosal compartments. In summary, specific MAMP determinants control the production of neutralizing Abs and the compartmentalization of innate responses.Laboratorio de Investigaciones del Sistema Inmun

Discordance in cathepsin B and cystatin C expressions in bronchoalveolar fluids between murine bleomycin-induced fibrosis and human idiopathic fibrosis

International audienceAbstractThe activity of cysteine cathepsin B increased markedly in lung homogenates and in bronchoalveolar lavage fluids (BALF) of the mouse model of bleomycin-induced lung fibrosis after 14 days of challenge. In contrast the level of the cysteine cathepsin inhibitor cystatin C was unaffected in BALF of wild-type and cathepsin B-deficient mice. Therefore, murine cystatin C is not a reliable marker of fibrosis during bleomycin-induced lung fibrosis. Current data are in sharp contrast to previous analysis carried on human BALF from patients with idiopathic pulmonary fibrosis, for which the level of cathepsin B remained unchanged while cystatin C was significantly increased

The Mediator complex subunit MED25 is targeted by the N-terminal transactivation domain of the PEA3 group members

International audiencePEA3, ERM and ER81 belong to the PEA3 subfamily of Ets transcription factors and play important roles in a number of tissue-specific processes. Transcriptional activation by PEA3 subfamily factors requires their characteristic amino-terminal acidic transactivation domain (TAD). However, the cellular targets of this domain remain largely unknown. Using ERM as a prototype, we show that the minimal N-terminal TAD activates transcription by contacting the activator interacting domain (ACID)/Prostate tumor overexpressed protein 1 (PTOV) domain of the Mediator complex subunit MED25. We further show that depletion of MED25 disrupts the association of ERM with the Mediator in vitro . Small interfering RNA-mediated knockdown of MED25 as well as the overexpression of MED25-ACID and MED25-VWA domains efficiently inhibit the transcriptional activity of ERM. Moreover, mutations of amino acid residues that prevent binding of MED25 to ERM strongly reduce transactivation by ERM. Finally we show that siRNA depletion of MED25 diminishes PEA3-driven expression of MMP-1 and Mediator recruitment. In conclusion, this study identifies the PEA3 group members as the first human transcriptional factors that interact with the MED25 ACID/PTOV domain and establishes MED25 as a crucial transducer of their transactivation potential

Use of Toll-Like Receptor Agonists to Induce Ectopic Lymphoid Structures in Myasthenia Gravis Mouse Models

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. MG symptoms are characterized by muscle weaknesses. The thymus of MG patients is very often abnormal and possesses all the characteristics of tertiary lymphoid organs such as neoangiogenesis processes, overexpression of inflammatory cytokines and chemokines, and infiltration of B lymphocytes leading to ectopic germinal center (GC) development. We previously demonstrated that injections of mice with polyinosinic–polycytidylic acid [Poly(I:C)], a synthetic double-stranded RNA mimicking viral infection, induce thymic changes and trigger MG symptoms. Upon Poly(I:C) injections, we observed increased thymic expressions of α-AChR, interferon-β and chemokines such as CXCL13 and CCL21 leading to B-cell recruitment. However, these changes were only transient. In order to develop an experimental MG model associated with thymic GCs, we used Poly(I:C) in the classical experimental autoimmune MG model induced by immunizations with purified AChR emulsified in complete Freund’s adjuvant. We observed that Poly(I:C) strongly favored the development of MG as almost all mice displayed MG symptoms. Nevertheless, we did not observe any ectopic GC development. We next challenged mice with Poly(I:C) together with other toll-like receptor (TLR) agonists known to be involved in GC development and that are overexpressed in MG thymuses. Imiquimod and CpG oligodeoxynucleotides that activate TLR7 and TLR9, respectively, did not induce thymic changes. In contrast, lipopolysaccharide that activates TLR4 potentiated Poly(I:C) effects and induced a significant expression of CXCL13 mRNA in the thymus associated with a higher recruitment of B cells that induced over time thymic B-lymphoid structures. Altogether, these data suggest that tertiary lymphoid genesis in MG thymus could result from a combined activation of TLR signaling pathways