Quelles connaissances du Plan S et de la stratégie de non-cession des droits ??

Cette enquête intitulée « Quelle·s connaissance·s du Plan S et de la stratégie de rétention [non-cession] des droits ? » a été menée à la fin de l’année 2022 par le groupe juridique du groupe de travail science ouverte du Consortium Couperin (GTSO). Diffusée sous forme d’un questionnaire en ligne, elle s’adressait aux professionnels de l’information scientifique et technique (IST) et personnels des services d’appui à la recherche, travaillant dans des universités, organismes de recherche et grandes écoles. L’objectif de cette enquête était de mesurer le niveau de connaissance et d’appropriation du Plan S de ces professionnels, leurs besoins éventuels d’accompagnement, alors qu’il n’existe pas à ce jour de cadre d’application global du Plan S dans les établissements et structures de recherche françaises

Opposite Modulation of RAC1 by Mutations in TRIO Is Associated with Distinct, Domain-Specific Neurodevelopmental Disorders

The Rho-guanine nucleotide exchange factor (RhoGEF) TRIO acts as a key regulator of neuronal migration, axonal outgrowth, axon guidance, and synaptogenesis by activating the GTPase RAC1 and modulating actin cytoskeleton remodeling. Pathogenic variants in TRIO are associated with neurodevelopmental diseases, including intellectual disability (ID) and autism spectrum disorders (ASD). Here, we report the largest international cohort of 24 individuals with confirmed pathogenic missense or nonsense variants in TRIO. The nonsense mutations are spread along the TRIO sequence, and affected individuals show variable neurodevelopmental phenotypes. In contrast, missense variants cluster into two mutational hotspots in the TRIO sequence, one in the seventh spectrin repeat and one in the RAC1-activating GEFD1. Although all individuals in this cohort present with developmental delay and a neuro-behavioral phenotype, individuals with a pathogenic variant in the seventh spectrin repeat have a more severe ID associated with macrocephaly than do most individuals with GEFD1 variants, who display milder ID and microcephaly. Functional studies show that the spectrin and GEFD1 variants cause a TRIO-mediated hyper- or hypo-activation of RAC1, respectively, and we observe a striking correlation between RAC1 activation levels and the head size of the affected individuals. In addition, truncations in TRIO GEFD1 in the vertebrate model X. tropicalis induce defects that are concordant with the human phenotype. This work demonstrates distinct clinical and molecular disorders clustering in the GEFD1 and seventh spectrin repeat domains and highlights the importance of tight control of TRIO-RAC1 signaling in neuronal development.<br/

Transient Neuronal Populations Are Required to Guide Callosal Axons: A Role for Semaphorin 3C

Neurons, glia, and callosal axons operate as a “ménage à trois” in the development of the corpus callosum

Heterologous Expression of Membrane Proteins: Choosing the Appropriate Host

International audienceBACKGROUND: Membrane proteins are the targets of 50% of drugs, although they only represent 1% of total cellular proteins. The first major bottleneck on the route to their functional and structural characterisation is their overexpression; and simply choosing the right system can involve many months of trial and error. This work is intended as a guide to where to start when faced with heterologous expression of a membrane protein. METHODOLOGY/PRINCIPAL FINDINGS: The expression of 20 membrane proteins, both peripheral and integral, in three prokaryotic (E. coli, L. lactis, R. sphaeroides) and three eukaryotic (A. thaliana, N. benthamiana, Sf9 insect cells) hosts was tested. The proteins tested were of various origins (bacteria, plants and mammals), functions (transporters, receptors, enzymes) and topologies (between 0 and 13 transmembrane segments). The Gateway system was used to clone all 20 genes into appropriate vectors for the hosts to be tested. Culture conditions were optimised for each host, and specific strategies were tested, such as the use of Mistic fusions in E. coli. 17 of the 20 proteins were produced at adequate yields for functional and, in some cases, structural studies. We have formulated general recommendations to assist with choosing an appropriate system based on our observations of protein behaviour in the different hosts. CONCLUSIONS/SIGNIFICANCE: Most of the methods presented here can be quite easily implemented in other laboratories. The results highlight certain factors that should be considered when selecting an expression host. The decision aide provided should help both newcomers and old-hands to select the best system for their favourite membrane protein

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Production de materiaux carbonés poreux à base de boue activée issue de station d'épuration (application en épuration d'effluents industriels)

L'étude présentée porte sur la fabrication de matériaux carbonés poreux par valorisation d'un déchet industriel, les boues de station d'épuration. Les applications envisagées pour l'adsorbant produit s'inscrivent dans le domaine de l'épuration des effluents industriels. Dans un premier temps, les boues biologiques utilisées, issues de la station d'épuration de Nantes-Tougas, sont caractérisées exhaustivement. Représentatives des boues de stations d'épuration française, elles présentent une faible surface spécifique (~ 3 m2 g-1) et sont macroporeuses à plus de 97 %. De surface basique, elles possèdent une teneur en carbone élevée (40 % mass.) qui en font un précurseur intéressant pour la fabrication de matériau carboné poreux. Dans un second temps, deux voies d'activation sont étudiées en parallèle et optimisées par la méthodologie des plans d'expériences : 1- une voie d'activation " chimique ", par imprégnation dans H2SO4 3 M pendant 6 h, suivie d'une activation à l'azote pendant 2 h à 700 ʿC ; 2- une voie d'activation " physique " consistant en une carbonisation sous N2 à 600ʿC pendant 1 h, suivie d'une oxydation par le dioxyde de carbone (900ʿC, 0,5 h, 2,5 L.min-1) ou la vapeur d'eau (800ʿC, 1,5 h, 2,5 L.min-1). Dans les deux cas, les procédés d'activation permettent de développer la porosité des adsorbants pour atteindre des surfaces spécifiques comprises entre 270 et 350 m2 g-1, soit 500 à 700 m2 g-1 de carbone en tenant compte du taux de cendres élevé des matériaux produits (50 % mass.). Leur distribution poreuse est constituée à la fois de micro et de mésopores, à hauteur de 45 et 55 % vol. respectivement. Enfin, les propriétés de traitement des matériaux produits sont déterminées par rapport à différents polluants représentatifs de pollutions industrielles et comparées à celles de charbons actifs (CA) commerciaux. Leurs propriétés d'adsorption par rapport aux micropolluants organiques sont proportionnelles à la microporosité développée, comprises entre 90 et 150 mg.g-1 pour des COV en phase gaz et le phénol en phase aqueuse. De plus, la mésoporosité de ces matériaux leur confère d'intéressantes propriétés d'élimination de macromolécules telles que les colorants (Qe = 175 - 200 mg.g1). Enfin, les fonctions de surface et les ions Ca2+ contenus dans le matériau précurseur permettent d'obtenir des capacités d'adsorption des ions métalliques de l'ordre de 140 mg g-1, équivalentes à celles obtenues sur des CA commerciaux.This study is devoted to the adsorption processes involving new materials : carbonaceous porous sorbents from sewage sludge. Firstly, physico-chemical characterization of biological sludge and limed sludge collected at municipal wastewater treatment plant of Nantes-Tougas is carried out. Sludges develop very low specific surface area (~ 3 m2 g-1) and their structure is macroporous (97 % vol.). Their surface is basic in nature. And, their high carbon content (40 % mass.) confirm that sewage sludge constitute an adapted precursor for carbonaceous porous sorbent preparation. Then, two activation methods are studied and optimized using experimental design methodology: 1- a " chemical " activation process, by impregnation in 3 M H2SO4 aqueous solution during 6 h, followed by an activation under nitrogen atmosphere for 2 h at 700 ʿC ; 2- a " physical " activation process consisting in a carbonization step under nitrogen atmosphere at 600 ʿC for 1 h, followed by an oxidation using carbon dioxide (900ʿC, 0,5 h, 2,5 L min-1) or steam (800ʿC, 1,5 h, 2,5 L.min-1). These activation process allow specific surface area of carbonaceous sorbents to be developed between 270 et 350 m2 g-1, corresponding to 500 to 700 m2 g-1 of carbon taking into account high ash content of resulting materials. Their porous structure is composed of both micro- and mesopores. Finally, The adsorptive properties of the sorbents made from sludge are estimated with regard of various pollutants representative of industrial pollution and compared with commercial activated carbon one. The adsorption capacities of organic micropollutants are proportional to their microporosity, between 90 and 150 mg.g-1 for VOC in gas phase and phenol in aqueous solution. Then, The important mesoporosity of the materials leads to interesting properties for macromolecules removal, like dyes (Qe = 175 - 200 mg.g1). Their surface functional groups and Ca2+ ions within the materials allow high metallic ions adsorption capacities of 140 mg g-1 to be obtained which are equivalent to those obtained with commercial activated carbon.NANTES-BU Sciences (441092104) / SudocNANTES-Ecole Centrale (441092306) / SudocSudocFranceF