Un plaidoyer pour la transmission des bibliothèques privées des intellectuels et enseignants : la bonne fortune du numérique

Avec la dispersion de la bibliothèque d’un enseignant à son décès, c’est tout un pan de connaissance sur le savoir constitué qui disparaît. La bibliothèque privée d’intellectuel a un double statut de patrimoine matériel et immatériel, elle est la trace du cheminement de sa pensée, du contexte et du cadre culturel de l’élaboration du savoir en jeu. L’ère du numérique et des bibliothèques virtuelles permet aujourd’hui de transmettre la valeur d’ensemble de la bibliothèque et de son contenu, indépendamment des questions d’héritage, de succession liées à la valeur vénale des ouvrages. Historienne et architecte, l’auteure a participé aux débats sur le devenir de deux bibliothèques privées de deux de ses enseignants, fondateurs de l’École nationale supérieure d’architecture de Paris-La Villette, alors UP6, Robert Joly et Michel Vernes, décédés en 2012 et 2013. Cette contribution propose, en partant de ces deux exemples, vite devenus douze, un plaidoyer et un apport méthodologique

mRNP3 and mRNP4 are phosphorylatable by casein kinase II in Xenopus oocytes, but phosphorylation does not modify RNA-binding affinity

AbstractmRNP3 and mRNP4 (also called FRGY2) are two mRNA-binding proteins which are major constituents of the maternal RNA storage particles of Xenopus laevis oocytes. The phosphorylation of mRNP3–4 has been implicated in the regulation of mRNA masking. In this study, we have investigated their phosphorylation by casein kinase II and its consequence on their affinity for RNA. Comparison of the phosphopeptide map of mRNP3–4 phosphorylated in vivo with that obtained after phosphorylation in vitro by purified Xenopus laevis casein kinase II strongly suggests that casein kinase II is responsible for the in vivo phosphorylation of mRNP3–4 in oocytes. The phosphorylation occurs on a serine residue in a central domain of the proteins. The affinity of mRNP3–4 for RNA substrates remained unchanged after the treatment with casein kinase II or calf intestine phosphatase in vitro. This suggests that phosphorylation of these proteins does not regulate their interaction with RNA but rather controls their interactions with other proteins

La transmission des savoirs à l’ère numérique

Nouveaux outils, nouveaux usages, nouveaux publics : la révolution technologique a changé la manière de produire, organiser et partager les savoirs. Pour interroger les modalités de cette transmission, l’ouvrage donne la parole à des chercheurs et à des collectionneurs. La diversité de leurs témoignages offre un ensemble original de réflexions et d’orientations méthodologiques qui sont autant d’études de cas dans un contexte de mobilités ergonomiques et participatives. Le Congrès national des sociétés historiques et scientifiques rassemble chaque année universitaires, membres de sociétés savantes et jeunes chercheurs. Ce recueil est issu de travaux présentés lors du 143e Congrès sur le thème « La transmission des savoirs »

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Genomic studies in AIDS: problems and answers. Development of a statistical model integrating both longitudinal cohort studies and transversal observations of extreme cases.

Genomic studies developed to understand HIV-1 infection and pathogenesis have often lead to conflicting results. This is linked to various factors, including differences in cohort design and selection, the numbers of patients involved, the influence of population substructure, the ethnic origins of the participants, and phenotypic definition. These difficulties in the interpretation of results are examined through published studies on the role of polymorphisms in HLA and the chemokine receptors genes in AIDS. Our analysis suggests that the use of haplotypes will strengthen the results obtained in a given cohort, and meta-analysis including multiple cohorts to gather large-enough numbers of patients should also allow clarification of the genetic associations observed. A P-value of 0.001 appears to be a good compromise for significance on candidate genes in a genetic study. Due to the generally limited size of available cohorts, results will have to be validated in other cohorts.We developed a model to fit transversal case studies (extreme case-control studies) with longitudinal cohorts (all-stages patients) for observations on two gene polymorphisms of CCR5 and NQO1. Interestingly, we observe a protective effect for the CCR5-Delta32 mutant allele in 95% of the simulations based on that model when using a population of 600 subjects; however, when using populations of 250 subjects we find a significant protection in only 59% of the simulations. Our model gives thus an explanation for the discrepancies observed in the various genomic studies published in AIDS on CCR5-Delta32 and other gene polymorphisms: they result from statistical fluctuations due to a lack of power. The sizes of most seroconverter cohorts presently available seem thus insufficient since they include less than a few hundred subjects. This result underlines the power and usefulness of the transversal studies involving extreme patients and their complementarity to longitudinal studies involving seroconverter cohorts. The transposition approach of extreme case-control data into longitudinal analysis should prove useful not only in AIDS but also in other diseases induced by chronic exposure to a foreign agent or with chronic clinical manifestations

Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening

BACKGROUND: Increased age at surgery has a negative impact on results of the Kasai operation for biliary atresia in infancy and early childhood. It remained unclear if an age threshold exists and if this effect persists with extended follow-up. In this study we examined the relationship between increased age at surgery and its results in adolescence. METHODS: All patients with biliary atresia who were living in France and born between 1986 and 2002 were included. Median follow-up in survivors was 7 years. RESULTS: Included in the study were 743 patients with biliary atresia, 695 of whom underwent a Kasai operation; 2-, 5-, 10-, and 15-year survival rates with native liver were 57.1%, 37.9%, 32.4%, and 28.5%, respectively. Median age at Kasai operation was 60 days and was stable over the study period. Whatever the follow-up (2, 5, 10, or 15 years), survival rates with native liver decreased when age at surgery increased ( ≤ 30, 31-45, 46-60, 61-75, and 76-90 days). Accordingly, we estimated that if every patient with biliary atresia underwent the Kasai operation before 46 days of age, 5.7% of all liver transplantations performed annually in France in patients younger than 16 years could be spared. CONCLUSIONS: Increased age at surgery had a progressive and sustained deleterious effect on the results of the Kasai operation until adolescence. These findings indicate a rational basis for biliary atresia screening to reduce the need for liver transplantations in infancy and childhood

Management of patients with biliary atresia in France: results of a decentralized policy 1986-2002

This study analyzed the results of the decentralized management of biliary atresia (BA) in France, where an improved collaboration between centers has been promoted since 1997. Results were compared to those obtained in England and Wales, where BA patients have been centralized in three designated centers since 1999. According to their birth dates, BA patients were divided into two cohorts: cohort A, with patients born between 1986 and 1996, had 472 patients; and cohort B, with patients born between 1997 and 2002, had 271 patients. Survival rates were calculated according to the Kaplan-Meier method and compared by using the log rank test and the Cox model. Four-year overall BA patient survival was 73.6% (95% CI 69.5%-77.7%) and 87.1% (CI 82.6%-91.6%) in cohorts A and B, respectively (P < .001). Median age at time of the Kasai operation was 61 and 57 days in cohorts A and B, respectively (NS). Four-year survival with native liver after the Kasai operation was 40.1% and 42.7% in cohorts A and B, respectively (NS): 33.9% (cohort A) and 33.4% (cohort B) in the centers with two or fewer caseloads a year, 30.9% (cohort A) and 44.5% (cohort B) in the centers with 3-5 cases/year, 47.8% (cohort A) and 47.7% (cohort B) in the center with more than 20 caseloads a year. In cohorts A and B, 74 (15.7%) and 19 (7%) patients, respectively, died without liver transplantation (LT). Four-year survival after LT was 75.1% and 88.8% in cohorts A and B, respectively (P = .006). In conclusion, BA patients currently have the same chance of survival in France as in England and Wales. The early success rate of the Kasai operation remains inferior in the centers with limited caseloads in France, leading to a greater need for LTs in infancy and early childhood

Patient with locally advanced and metastatic skin spinocellular carcinoma treated with Cemiplimab

Le traitement du carcinome spinocellulaire cutané (cSCC) localement avancé et/ou métastasique repose essentiellement sur la chirurgie et, éventuellement, une radiothérapie de la zone chirurgicale et de l’aire ganglionnaire afférente. Malheureusement, certains cas ne sont plus opérables ou accessibles à la radiothérapie et un traitement systémique est alors indiqué. Les chimiothérapies sont peu efficaces et potentiellement toxiques. Une étude récente évaluant l’efficacité et la tolérance du cemiplimab, un antagoniste PD1, dans les cSCC localement avancés et métastasiques démontre une réponse objective confirmée de 49 % et de 47 %, respectivement, avec un maintien de la réponse d’au moins 6 mois de 63 % et de 60 %, respectivement. Nous présentons le cas d’un patient avec un cSCC localement avancé au niveau du front, avec effraction osseuse et adénopathies cervicales, ayant eu de multiples chirurgies et radiothérapies. Il a présenté une réponse partielle au cemiplimab avec un profil de tolérance satisfaisant

Locally advanced and metastatic cutaneous squamous cell carcinoma treated with cemiplimab

peer reviewedThe treatment of locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) essentially relies on surgery and eventually radiotherapy of the treated site and afferent lymph nodes. Unfortunately, some cases are no candidates for surgery or radiotherapy and a systemic treatment may be indicated. Chemotherapies are only partially efficacious and associated with potential toxicities. A recent study evaluating the efficacy and tolerance of cemiplimab, a PD1 antagonist for locally advanced and metastatic cSCC demonstrated an objective response rate of 49 % and 47 % for locally advanced and metastatic cSCC, while maintaining a response of at least 6 months of 63 % and 60 %, respectively. We present a clinical case of a patient with a locally advanced cSCC of the forehead with bone resorption and cervical lymphadenopathies. After failure of multiple surgical interventions and radiotherapies, he responded partially to cemiplimab immunotherapy with a good safety profile

Renaissances du Mystère en Europe

Destin extraordinaire que celui du mystère ! Secret à ses origines, puis extrêmement populaire au Moyen Âge et de ce fait interdit en France. Quasi oublié dans les siècles qui suivent, toujours repris, souvent trahi, le genre du mystère ressurgit en force à la fin du xixe siècle un peu partout en Europe, et semble toujours bien vivace en ce début du xxie siècle. Mais les spectacles pluriels qu'il désigne, les pratiques théâtrales qu'il implique, n'affichent plus qu'un lointain rapport avec les modèles antique et médiéval. De Dumas à Castellucci, de Lorca à Pommerat, de Claudel à Dario Fo, de Barnes à Tabori, quel sens faut-il donc donner au mot mystère ? Les formes modernes qui se développent depuis la fin du xixe siècle relèvent-elles du genre du mystère ? Et d'ailleurs, est-on fondé à parler de genre ? Si les mystères antiques, réservés aux seuls initiés, ont gardé nombre de leurs secrets, les travaux des spécialistes du Moyen Âge ont éclairé les formes et les enjeux didactiques et spectaculaires des mystères médiévaux. Il manquait une étude générale sur les formes modernes, voire contemporaines, du mystère en Europe. C'est désormais chose faite. Des chercheurs français et étrangers issus de plusieurs disciplines, des praticiens du théâtre, des romanciers se sont attachés à comprendre la pérennité du mystère jusqu'à nos jours, à en cerner les déclinaisons et réinvestissements, tout en faisant apparaître les enjeux que lui confère la modernité