De la conception à la pratique Reconfiguration d'un dispositif de formation des enseignants aux technologies de l'information et de la communication.

Constatant que la formation des enseignants aux technologies de l'information et de la communication (TIC) pose des problèmes spécifiques, cet article a pour but d'engager une réflexion sur ce thème. Nos réflexions s'appuient sur une expérience de formation réalisée dans 23 écoles professionnelles suisses engagées dans un programme national de soutien à l'utilisation pédagogique des TIC. L'article décrit la manière dont le dispositif de formation prévu a été mis en pratique, les difficultés auxquelles il a donné lieu et les réponses que les acteurs ont élaborées pour faire face à ces difficultés. Nous montrons qu'une analyse du déroulement effectif d'un dispositif de formation et des transformations qu'il subit constitue un élément essentiel pour orienter les futures actions de formation et penser la place des apprenants dans un dispositif de formation.

Edar/Eda interactions regulate enamel knot formation in tooth morphogenesis.

tabby and downless mutant mice have apparently identical defects in teeth, hair and sweat glands. Recently, genes responsible for these spontaneous mutations have been identified. downless (Dl) encodes Edar, a novel member of the tumour necrosis factor (TNF) receptor family, containing the characteristic extracellular cysteine rich fold, a single transmembrane region and a death homology domain close to the C terminus. tabby (Ta) encodes ectodysplasin-A (Eda) a type II membrane protein of the TNF ligand family containing an internal collagen-like domain. As predicted by the similarity in adult mutant phenotype and the structure of the proteins, we demonstrate that Eda and Edar specifically interact in vitro. We have compared the expression pattern of Dl and Ta in mouse development, taking the tooth as our model system, and find that they are not expressed in adjacent cells as would have been expected. Teeth develop by a well recorded series of epithelial-mesenchymal interactions, similar to those in hair follicle and sweat gland development, the structures found to be defective in tabby and downless mice. We have analysed the downless mutant teeth in detail, and have traced the defect in cusp morphology back to initial defects in the structure of the tooth enamel knot at E13. Significantly, the defect is distinct from that of the tabby mutant. In the tabby mutant, there is a recognisable but small enamel knot, whereas in the downless mutant the knot is absent, but enamel knot cells are organised into a different shape, the enamel rope, showing altered expression of signalling factors (Shh, Fgf4, Bmp4 and Wnt10b). By adding a soluble form of Edar to tooth germs, we were able to mimic the tabby enamel knot phenotype, demonstrating the involvement of endogenous Eda in tooth development. We could not, however, reproduce the downless phenotype, suggesting the existence of yet another ligand or receptor, or of ligand-independent activation mechanisms for Edar. Changes in the structure of the enamel knot signalling centre in downless tooth germs provide functional data directly linking the enamel knot with tooth cusp morphogenesis. We also show that the Lef1 pathway, thought to be involved in these mutants, functions independently in a parallel pathway.

La diégèse selon Souriau. Naissance, postérité et productivité d'un concept

Popularisée par l'usage extensif (et de ce fait quelque peu galvaudé) qu'en fit Gérard Genette en narratologie littéraire, la « diégèse » constitue certes la notion vedette des filmologues, mais elle fut pendant plusieurs décennies le lieu d'une certaine occultation de son champ originel en raison des appropriations non référencées qu'en firent poéticiens et sémiologues. En suivant le fil historiographique des différents emplois et acceptions de cette notion associée à Etienne Souriau dans l'espace francophone, le présent article propose un état des lieux qui, par la petite porte d'une entrée terminologique, entend s'interroger sur les conséquences théoriques des variations que le terme « diégèse » a subies et, plus généralement, sur la question du statut octroyé au courant filmologique. En examinant les différentes implications de la définition première qu'il s'agit parfois de délester de sens dont on l'a ultérieurement investie, cet article tente de montrer que le cadre dans lequel la diégèse a été conceptualisée contient des potentialités théoriques qui n'ont pas encore été épuisées aujourd'hui, et qui convergent avec certains champs d'étude récents (comme celui de la logique des mondes possibles) dont l'application au cinéma n'a probablement jamais été aussi pertinent qu'à l'ère des images de synthèse, des mondes virtuels et des environnements de jeux vidéo.

Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that induces cancer cell death by apoptosis with some selectivity. TRAIL-induced apoptosis is mediated by the transmembrane receptors death receptor 4 (DR4) (also known as TRAIL-R1) and DR5 (TRAIL-R2). TRAIL can also bind decoy receptor 1 (DcR1) (TRAIL-R3) and DcR2 (TRAIL-R4) that fail to induce apoptosis since they lack and have a truncated cytoplasmic death domain, respectively. In addition, DcR1 and DcR2 inhibit DR4- and DR5-mediated, TRAIL-induced apoptosis and we demonstrate here that this occurs through distinct mechanisms. While DcR1 prevents the assembly of the death-inducing signaling complex (DISC) by titrating TRAIL within lipid rafts, DcR2 is corecruited with DR5 within the DISC, where it inhibits initiator caspase activation. In addition, DcR2 prevents DR4 recruitment within the DR5 DISC. The specificity of DcR1- and DcR2-mediated TRAIL inhibition reveals an additional level of complexity for the regulation of TRAIL signaling.

Proof of concept for microarray-based detection of DNA-binding oncogenes in cell extracts.

The function of DNA-binding proteins is controlled not just by their abundance, but mainly at the level of their activity in terms of their interactions with DNA and protein targets. Moreover, the affinity of such transcription factors to their target sequences is often controlled by co-factors and/or modifications that are not easily assessed from biological samples. Here, we describe a scalable method for monitoring protein-DNA interactions on a microarray surface. This approach was designed to determine the DNA-binding activity of proteins in crude cell extracts, complementing conventional expression profiling arrays. Enzymatic labeling of DNA enables direct normalization of the protein binding to the microarray, allowing the estimation of relative binding affinities. Using DNA sequences covering a range of affinities, we show that the new microarray-based method yields binding strength estimates similar to low-throughput gel mobility-shift assays. The microarray is also of high sensitivity, as it allows the detection of a rare DNA-binding protein from breast cancer cells, the human tumor suppressor AP-2. This approach thus mediates precise and robust assessment of the activity of DNA-binding proteins and takes present DNA-binding assays to a high throughput level.

Lack of in vitro biofilm formation does not attenuate the virulence of Streptococcus gordonii in experimental endocarditis.

The ability to induce experimental endocarditis of biofilm-deficient mutants of Streptococcus gordonii was studied in an isogenic background. Strains were inactivated in either comD, fruK or pbp2b genes, which are involved in biofilm formation. These strains were clearly impaired (>75% reduction) in biofilm production in vitro. However, this did not result in a decreased severity of infection in vivo.

Inefficacité de la gestion de l'hyperglycémie du patient hospitalisé: origines et remèdes [The inefficacy of glycemic control in the hospitalized patient: origins and solutions]

La prévalence du diabète peut être estimée entre 20 et 30% parmi les patients en hôpital aigu. Il a été démontré que l'hyperglycémie, même modérée, est associée à une augmentation de la morbi-mortalité hospitalière, tandis que le contrôle glycémique efficace a un impact favorable sur celle-ci. La prise en charge de l'hyperglycémie demeure pourtant largement inefficace hors des soins intensifs, en raison de la persistance d'une pratique inadaptée. Nous développons actuellement un projet de soins destiné à faire changer les pratiques. Pour un contrôle glycémique efficace, une formation des soignants à une gestion basée sur le concept de couverture des besoins en insuline du patient est nécessaire. La démarche doit être intégrée à une approche de type systémique, prenant en compte le contexte dans lequel les soignants évoluent. The hospital inpatient prevalence of diabetes mellitus can be estimated between 20 and 30%. Even moderate hyperglycemia is associated with increased morbidity and mortality in the acute care setting, whereas efficient glycemic control has been shown to improve both of them significantly. Glycemic control however remains largely inefficient outside of the intensive care unit due to the persistance of an inadequate glycemic management practice. We are currently developing a clinical care project aimed at changing this practice. For an efficient glycemic control, a training programme for health care professionals based on the concept of covering the insulin needs of the patient is mandatory. This programme needs to be integrated in a systemic approach, which takes the professionals' context in account.

Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner.

BACKGROUND & AIMS: Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation. METHODS: We performed a retrospective study using the Swiss EoE Database, collecting data on 200 patients with symptomatic EoE (153 men; mean age at diagnosis, 39 ± 15 years old). Stricture severity was graded based on the degree of difficulty associated with passing of the standard adult endoscope. RESULTS: The median delay in diagnosis of EoE was 6 years (interquartile range, 2-12 years). With increasing duration of delay in diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy, increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay, >20 years; P = .020). Similarly, the prevalence of esophageal strictures increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2 years) to 70.8% (diagnostic delay, >20 years; P < .001). Diagnostic delay was the only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08; 95% confidence interval: 1.040-1.122; P < .001). CONCLUSIONS: The prevalence of esophageal strictures correlates with the duration of untreated disease. These findings indicate the need to minimize delay in diagnosis of EoE.

The half-size ABC transporters STR1 and STR2 are indispensable for mycorrhizal arbuscule formation in rice.

The central structure of the symbiotic association between plants and arbuscular mycorrhizal (AM) fungi is the fungal arbuscule that delivers minerals to the plant. Our earlier transcriptome analyses identified two half-size ABCG transporters that displayed enhanced mRNA levels in mycorrhizal roots. We now show specific transcript accumulation in arbusculated cells of both genes during symbiosis. Presently, arbuscule-relevant factors from monocotyledons have not been reported. Mutation of either of the Oryza sativa (rice) ABCG transporters blocked arbuscule growth of different AM fungi at a small and stunted stage, recapitulating the phenotype of Medicago truncatula stunted arbuscule 1 and 2 (str1 and str2) mutants that are deficient in homologous ABCG genes. This phenotypic resemblance and phylogenetic analysis suggest functional conservation of STR1 and STR2 across the angiosperms. Malnutrition of the fungus underlying limited arbuscular growth was excluded by the absence of complementation of the str1 phenotype by wild-type nurse plants. Furthermore, plant AM signaling was found to be intact, as arbuscule-induced marker transcript accumulation was not affected in str1 mutants. Strigolactones have previously been hypothesized to operate as intracellular hyphal branching signals and possible substrates of STR1 and STR2. However, full arbuscule development in the strigolactone biosynthesis mutants d10 and d17 suggested strigolactones to be unlikely substrates of STR1/STR2. Interestingly, rice STR1 is associated with a cis-natural antisense transcript (antiSTR1). Analogous to STR1 and STR2, at the root cortex level, the antiSTR1 transcript is specifically detected in arbusculated cells, suggesting unexpected modes of STR1 regulation in rice.

Interplay of mechanotransduction, FOXC2, connexins, and calcineurin signaling in lymphatic valve formation.

The directional flow of lymph is maintained by hundreds of intraluminal lymphatic valves. Lymphatic valves are crucial to prevent lymphedema, accumulation of fluid in the tissues, and to ensure immune surveillance; yet, the mechanisms of valve formation are only beginning to be elucidated. In this chapter, we will discuss the main steps of lymphatic valve morphogenesis, the important role of mechanotransduction in this process, and the genetic program regulated by the transcription factor Foxc2, which is indispensable for all steps of valve development. Failure to form mature collecting lymphatic vessels and valves causes the majority of postsurgical lymphedema, e.g., in breast cancer patients. Therefore, this knowledge will be useful for diagnostics and development of better treatments of secondary lymphedema.