Tetraphenylethylene-based glycoclusters with aggregation-induced emission (AIE) properties as high-affinity ligands of bacterial lectins

International audienceTetraphenylethylene (TPE) is fluorescent through aggregation induced emission (AIE) in water. Herein, TPE was used as the core of glycoclusters that target the bacterial lectins LecA and LecB of Pseudomonas aeruginosa. Synthesis of these TPE-based glycoclusters was accomplished by using azide-alkyne "click" chemistry. The AIE properties of the resulting glycoclusters could be readily verified, but imaging could not be pursued due to the overlap of the fluorescence signals from cells and bacteria. Nonetheless, the glycoclusters displayed nanomolar affinities toward LecA and LecB. Further evaluation in a cell-based anti-adhesive assay highlighted a limited decrease in adhesion (20%) for the fucosylated glycocluster. This confirmed that these TPE-based glycoclusters are indeed LecA and LecB high-affinity ligands. Nevertheless, the hypotheses involving their application in imaging or anti-adhesive therapy could not be verified

Quantifier la réponse de la biodiversité à l'exploitation forestière

Le projet Gestion forestière, Naturalité et Biodiversité a pour but d'étudier le lien entre biodiversité, exploitation forestière et naturalité en comparant des parcelles exploitées à des parcelles non-exploitées (Réserves Biologiques Intégrales ou parties intégrales de Réserves Naturelles). En partenariat avec l'ONF, RNF et l'INRA, nous travaillons depuis 2008 sur des réserves intégrales soustraites à l'exploitation depuis au moins 20 ans. L'étude repose sur l'échantillonnage de 7 groupes taxonomiques : plantes vasculaires, mousses, champignons, chauve-souris, oiseaux, coléoptères carabiques et saproxyliques

Forest management cessation and biodiversity: a synthesis of a nationwide French project

Extending the network of strict forest reserves is one of the conservation measures promoted by the French National Strategy for Biodiversity improvement. According to the scientific literature, strict forest reserves may help preserving a part of the biodiversity that is threatened by forestry. However, this strategy is based on poor knowledge in the temperate context and available studies may suffer from methodological shortcomings. The national-scale project named "Forest management, Naturalness and Biodiversity" aims at quantifying the effects on forest structure and biodiversity of management abandonment in strict reserves. Based on a meta-analysis of worldwide literature and original data from 213 study plots set up in 15 forest sites throughout France - around half of the plots in forests left unmanaged for from 8 to 148 years (mean: 46 years)- , we analyzed the response of 7 taxonomic groups to management abandonment. The meta-analysis demonstrates that forestry affects total richness of saproxylic taxa worldwide, which is verified in our national dataset. However, management abandonment per se is not always the best explanation of the differences between managed and unmanaged forests, but other variables, notably linked to deadwood, better explain the observed patterns for saproxylic groups. For other taxa, the response is weaker and depends more on structural features than on management abandonment. In terms of policy, our project has allowed methodological advances thanks to the development of inventory and remote sensing protocols, as well as statistical methods. The dataset we have gathered is also a first comparison of structure and biodiversity between strict forest reserves and managed forests for France. This network may therefore constitute a first basis for long term biodiversity monitoring in French forests

GNB: Projet de recherche finalisée à l’interface recherche-gestion et ses interactions avec BGF

La gestion durable des forêts repose largement sur la biodiversité dont le fonctionnement reste cependant encore très insuffisamment connu. Il en découle la nécessité d’améliorer, de manière générale, le socle de connaissances relatif à la biodiversité et, plus particulièrement, d’analyser les interactions entre changement climatique, productivité forestière et biodiversité en forêt. Par ailleurs, les stratégies et décisions des acteurs influent sur ces interactions et constituent également des objets d’étude à privilégier. C’est pourquoi le programme de recherche « Biodiversité, gestion forestière et politiques publiques » a lancé en 2013 un appel à projets de recherche avec deux entrées : - l’une par les sciences de la nature axée sur le changement climatique, les mesures de gestion et la dynamique de la biodiversité dans les écosystèmes ; - l’autre par les sciences humaines et sociales sur les stratégies et décisions des acteurs, la gouvernance et les politiques publiques correspondant à la première entrée. Le présent colloque a pour objectifs de : - présenter les résultats des cinq projets de recherche qui ont été sélectionnés à cette occasion sur chacune des deux entrées en les accompagnant en tant que de besoin de regards complémentaires et en illustrant l’un des projets par une visite sur le terrain ; - initier une réflexion sur le progrès des connaissances dans ce domaine, en s’inspirant du devenir de projets antérieurs et en identifiant les principales lacunes à combler. Il se déroulera en trois sessions, chacune introduite par des exposés d’une quinzaine de minutes et conclue par une table ronde permettant un débat avec les participants et les invités

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Funding Information: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R21AI160576), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High-Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer's Research Foundation, the Meyer Foundation, the JBP Foundation, the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANR GenMISC (ANR-21-COVR-039), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the ANR-RHU program (ANR-21-RHUS-08), the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the ANR-RHU Program ANR-21-RHUS-08 (COVIFERON), the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Cité University. We acknowledge support from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH under award R01AI104887 to R.H.S. and S.R.W. The Laboratory of Human Evolutionary Genetics (Institut Pasteur) is supported by the Institut Pasteur, the Collège de France, the French Government's Investissement d'Avenir program, Laboratoires d'Excellence "Integrative Biology of Emerging Infectious Diseases" (ANR-10-LABX-62-IBEID) and "Milieu Intérieur" (ANR-10-LABX-69-01), the Fondation de France (no. 00106080), the FRM (Equipe FRM DEQ20180339214 team), and the ANR COVID-19-POPCELL (ANR-21-CO14-0003-01). A. Puj. is supported by ACCI20-759 CIBERER, EasiGenomics H2020 Marató TV3 COVID 2021-31-33, the HORIZON-HLTH-2021-ID: 101057100 (UNDINE), the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342), and the CERCA Program/Generalitat de Catalunya. The Canarian Health System sequencing hub was funded by the Instituto de Salud Carlos III (COV20-01333 and COV20-01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación MAPFRE Guanarteme (OA21/131), and Cabildo Insular de Tenerife (CGIEU0000219140 and "Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19"). The CoV-Contact Cohort was funded by the French Ministry of Health and the European Commission (RECOVER project). Our studies are also funded by the Ministry of Health of the Czech Republic Conceptual Development of Research Organization (FNBr, 65269705) and ANID COVID0999 funding in Chile. G. Novelli and A. Novelli are supported by Regione Lazio (Research Group Projects 2020) No. A0375-2020-36663, GecoBiomark. A.M.P., M.L.D., and J.P.-T. are supported by the Inmungen-CoV2 project of CSIC. This work was supported in part by the Intramural Research Program of the NIAID, NIH. The research work of A.M.P, M.L.D., and J.P.-T. was funded by the European Commission-NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global). I.M. is a senior clinical investigator at FWO Vlaanderen supported by a VIB GC PID grant, by FWO grants G0B5120N (DADA2) and G0E8420N, and by the Jeffrey Modell Foundation. I.M. holds an ERC-StG MORE2ADA2 grant and is also supported by ERN-RITA. A.Y. is supported by fellowships from the European Academy of Dermatology and Venereology and the Swiss National Science Foundation and by an Early Career Award from the Thrasher Research Fund. Y.-H.C. is supported by an A*STAR International Fellowship (AIF). M.O. was supported by the David Rockefeller Graduate Program, the New York Hideyo Noguchi Memorial Society (HNMS), the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the National Cancer Institute (NCI) F99 Award (F99CA274708). A.A.A. was supported by Ministerio de Ciencia Tecnología e Innovación MINCIENCIAS, Colombia (111584467551/CT 415-2020). D.L. is supported by a fellowship from the FRM for medical residents and fellows. E.H. received funding from the Bank of Montreal Chair of Pediatric Immunology, Foundation of CHU Sainte-Justine, CIHR grants PCC-466901 and MM1-181123, and a Canadian Pediatric Society IMPACT study. Q.P.-H. received funding from the European Union's Horizon 2020 research and innovation program (ATAC, 101003650), the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, R01AI091707-10S1, and R01AI161444; a George Mason University Fast Grant; the G. Harold and Leila Y. Mathers Charitable Foundation; the Meyer Foundation; and the Bawd Foundation. R.P.L. is on the board of directors of both Roche and the Roche subsidiary Genentech. J.L.P. was supported by a Francois Wallace Monahan Postdoctoral Fellowship at the Rockefeller University and by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). Publisher Copyright: © 2023 American Association for the Advancement of Science. All rights reserved.Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.publishersversionpublishe

Germline bi-allelic <i>SH2B3/LNK</i> alteration predisposes to a neonatal juvenile myelomonocytic leukemia-like disorder

Juvenile myelomonocytic leukemia (JMML) is a rare, generally aggressive myeloproliferative neoplasm affecting young children. It is characterized by granulomonocytic expansion, with monocytosis infiltrating peripheral tissues. JMML is initiated by mutations upregulating RAS signaling. Approximately 10% of cases remain without an identified driver event. Exome sequencing of 2 unrelated cases of familial JMML of unknown genetics and analysis of the French JMML cohort identified 11 patients with variants in SH2B3, encoding LNK, a negative regulator of the JAK-STAT pathway. All variants were absent from healthy population databases, and mutation spectrum was consistent with a loss of function of the LNK protein. A stoploss variant was shown to affect both protein synthesis and stability. The other variants were either truncating or missense, the latter affecting the SH2 domain that interacts with activated JAK. Of the 11 patients, 8 from 5 families inherited pathogenic bi-allelic SH2B3 germline variants from their unaffected heterozygous parents. These children represent half of the cases with no identified causal mutation in the French cohort. They displayed typical clinical and hematological JMML features with neonatal onset and marked thrombocytopenia. They were characterized by absence of additional genetic alterations and a hypomethylated DNA profile with fetal characteristics. All patients showed partial or complete spontaneous clinical resolution. However, progression to thrombocythemia and immunity-related pathologies may be of concern later in life. Bi-allelic SH2B3 germline mutations thus define a new condition predisposing to a JMML-like disorder, suggesting that the JAK pathway deregulation is capable of initiating JMML, and opening new therapeutic options

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Outillage agricole et établissements ruraux autour de Reims/Durocortorum et sur le territoire des Rèmes

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L'outillage agricole des établissements rèmes : première approche fonctionnelle et spatiale

International audienceThanks to an exhaustive inventory of rural settlements discovered in the territory of the Remi, it is possible to draw up a first assessment of the types of tools and their evolution between the Late Iron Age and the Roman period. The latter are mainly oriented towards agropastoral activities. Comparison with carpological, archaeozoological data and storage structures confirms this observation. The study of the distribution of sites from the Roman period reveals a well-considered location of rural settlements near rivers and urban centres.L’inventaire exhaustif des établissements ruraux découverts en territoire rème permet de dresser un premier bilan des types d’outils et de leur évolution entre La Tène finale et la période romaine. Ces derniers sont principalement tournés vers des activités agro-pastorales. La confrontation des données carpologiques, archéozoologiques et des structures de stockages confirme cette observation. L’étude de la répartition des découvertes datées de la période romaine met en lumière une implantation réfléchie des établissements ruraux près des cours d’eau et des centres urbains

Phytosterols: comparison of data from mainstream literature with data from the scientific literature

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