Crystal structure of the GalNAc/Gal-specific agglutinin from the phytopathogenic ascomycete Sclerotinia sclerotiorum reveals novel adaptation of a beta-trefoil domain

International audienceA lectin from the phytopathogenic ascomycete Sclerotinia sclerotiorum that shares only weak sequence similarity with characterized fungal lectins has recently been identified. S. sclerotiorum agglutinin (SSA) is a homodimeric protein consisting of two identical subunits of ∼ 17 kDa and displays specificity primarily towards Gal/GalNAc. Glycan array screening indicates that SSA readily interacts with Gal/GalNAc-bearing glycan chains. The crystal structures of SSA in the ligand-free form and in complex with the Gal-β1,3-GalNAc (T-antigen) disaccharide have been determined at 1.6 and 1.97 Å resolution, respectively. SSA adopts a β-trefoil domain as previously identified for other carbohydrate-binding proteins of the ricin B-like lectin superfamily and accommodates terminal non-reducing galactosyl and N-acetylgalactosaminyl glycans. Unlike other structurally related lectins, SSA contains a single carbohydrate-binding site at site α. SSA reveals a novel dimeric assembly markedly dissimilar to those described earlier for ricin-type lectins. The present structure exemplifies the adaptability of the β-trefoil domain in the evolution of fungal lectins

Mutational analysis of the carbohydrate binding activity of the tobacco lectin

At present the three-dimensional structure of the tobacco lectin, further referred to as Nictaba, and its carbohydrate-binding site are unresolved. In this paper, we propose a three-dimensional model for the Nictaba domain based on the homology between Nictaba and the carbohydrate-binding module 22 of Clostridium thermocellum Xyn10B. The suggested model nicely fits with results from circular dichroism experiments, indicating that Nictaba consists mainly of beta-sheet. In addition, the previously identified nuclear localization signal is located at the top of the protein as a part of a protruding loop. Judging from this model and sequence alignments with closely related proteins, conserved glutamic acid and tryptophan residues in the Nictaba sequence were selected for mutational analysis. The mutant DNA sequences as well as the original Nictaba sequence have been expressed in Pichia pastoris and the recombinant proteins were purified from the culture medium. Subsequently, the recombinant proteins were characterized and their carbohydrate binding properties analyzed with glycan array technology. It was shown that mutation of glutamic acid residues in the C-terminal half of the protein did not alter the carbohydrate-binding activity of the lectin. In contrast, mutation of tryptophan residues in the N-terminal half of the Nictaba domain resulted in a complete loss of carbohydrate binding activity. These results suggest that tryptophan residues play an important role in the carbohydrate binding site of Nictaba

Utilisation de connaissances expertes pour l'assemblage de programmes de simulation en agronomie

Soumis à la conférence INFORSIDThe work concerned the assembly of biological sub-systems to gain access to a functional representation of the overall system, in the case of complex biological interactions (symbiosis, etc.). The proposed method uses the statement of expert knowledge described in a literal way to establish the sub-system interface program. The use of interrogative pronouns and adverbs provides a formal framework to produce graphs from literal descriptions. In terms of results, the method enables (i) access to the vocabulary of the assembly program, (ii) identification of the transformation functions to be established, and (iii) an estimation of the valence required by programs to ensure assembly. From an operational perspective, the generic approach proposed is a theoretical construct that remains to be validated in concrete cases of application

Modélisation d'un système complexe - Une méthode déclarative

Dans le cadre de leurs travaux, les chercheurs peuvent être amenés à assembler des programmes de simulation préexistants. Le mode opératoire repose sur l'hypothèse que l'assemblage de programmes, chacun représentant un sous-système, permet d'accéder à la simulation du système global. Cette hypothèse n'est pas toujours vérifiée et la question se pose de l'identification des sous-systèmes manquants. La théorie du système général appréhende les systèmes sous la forme d'une collection d'actions enchevêtrées. L'objet de ce document est de présenter une méthode déclarative de description de système complexe reposant sur cette théorie et d'en montrer une application à un système biologique

Migration Revisited using the Categories Theory: Application to Biological Modelling Languages

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Can the impact of bed closure in intensive care units be reliably monitored?

Objective: To assess the properties of various indicators aimed at monitoring the impact on the activity and patient outcome of a bed closure in a surgical intensive care unit (ICU). Design: Comparison before and after the intervention. Setting: A surgical ICU at a university hospital. Patients: All patients admitted to the unit over two periods of 10months. Intervention: Closure of one bed out of 17. Measurements and results: Activity and outcome indicators in the ICU and the structures upstream from it (emergency department, operative theater, recovery room) and downstream from it (intermediate care units). After the bed closure, the monthly medians of admitted patients and ICU hospital days increased from 107 (interquartile range 94-112) to 113 (106-121, P=0.07) and from 360 (325-443) to 395 (345-436, P=0.48), respectively, along with the linear trend observed in our institution. All indicators of workload, patient severity, and outcome remained stable except for SAPS II score, emergency admissions, and ICU readmissions, which increased not only transiently but also on a mid-term basis (10months), indicating that the process of patient care delivery was no longer predictable. Conclusions: Health care systems, including ICUs, are extraordinary flexible, and can adapt to multiple external constraints without altering commonly used activity and outcome indicators. It is therefore necessary to set up multiple indicators to be able to reliably monitor the impact of external interventions and intervene rapidly when the system is no longer under contro

Innovative healthcare organization to deal with COVID-19 in primary health care in the Haute-Garonne department, France

Primary care health professionals (general practitioners, nurses) rapidly developed a collaborative approach to the management of COVID-19 with, on the one hand, hospital health professionals (emergency and infectiology services) and medical regulatory services and, on the other hand, local health, research and governmental stakeholders. GP stakeholders developed a secure digital tool shared between hospital and primary care and regularly updated according to the needs of health professionals. The authors identify key elements that guarantee the efficiency of primary care, which remains the “gatekeeper” of a care pathway adapted to the patient's needs.https://deepblue.lib.umich.edu/bitstream/2027.42/154862/1/Gimenez main article.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154862/2/Gimenez figures.pdfDescription of Gimenez main article.pdf : Main articleDescription of Gimenez figures.pdf : Figure

Programme evaluation training for health professionals in francophone Africa: process, competence acquisition and use

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