Floridoside Extracted from the Red Alga Mastocarpus stellatus Is a Potent Activator of the Classical Complement Pathway

Many biological properties of algae have been found to have useful applications in human health, particularly in the fields of oncology and immunology. Floridoside, extracted from the red alga Mastocarpus stellatus, has a structure similar to the xenoantigen Gal alpha 1–3 Gal. This xenoantigen has been described to induce a high immune response in human xenografts and is mediated by natural anti-gal antibodies that activate the classical complement pathway. Based on this property, we analyzed the potential activities of floridoside on the immune system. We demonstrated that floridoside activates a complement cascade via the classical complement pathway, through the recruitment and activation of natural IgM. This algal molecule could represent an important step in the development of a potent new anticomplementary agent for use in therapeutic complement depletion

Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling

Abstract Oligosaccharides are implicated in the development of the immune response notably in complement activation. Anti-tumoural immunotherapy by monoclonal antibodies (mAbs) offers some advantages to chemotherapy including cell targeting but some of them are inefficient to generate cytotoxicity dependent complement (CDC) known to be important in the antibody\u2019s efficacy. The aim of this study is to give a CDC activity of mAb by linkage of a complement activating oligosaccharide to this antibody via a hetero-bifunctional linker allowing control of the conjugation reaction. We worked on non Hodgkin Burkitt\u2019s lymphoma as cancer source, Fab fragments of rituximab devoid of complement activity as mAb and the trisaccharide Gal\u3b1(1\u21923)Gal\u3b2(1\u21924)GlcNAc as immunogenic glycan. The bioconjugate Fab-Gal was characterized by biochemical methods and we demonstrated that the \u3b1-Gal epitope was recognized by seric immunoglobulins. After checking the recognition capacity of the Fab- Gal conjugate for the CD20 epitope, in vitro assays were performed to evaluate the activation of the complement cascade by the Fab-Gal conjugate. The effect of this bioconjugate was confirmed by the evaluation of the proliferation response of Burkitt\u2019s cell line. The relative facility realization of this strategy represents new approaches to increase activities of mAbs

Mature T Cells Depend on Signaling through the IKK Complex

AbstractThe transcription factor NF-κB is implicated in various aspects of T cell development and function. The IκB kinase (IKK) complex, consisting of two kinases, IKK1/α and IKK2/β, and the NEMO/IKKγ regulatory subunit, mediates NF-κB activation by most known stimuli. Adoptive transfer experiments had demonstrated that IKK1 and IKK2 are dispensable for T cell development. We show here that T lineage-specific deletion of IKK2 allows survival of naive peripheral T cells but interferes with the generation of regulatory and memory T cells. T cell-specific ablation of NEMO or replacement of IKK2 with a kinase-dead mutant prevent development of peripheral T cells altogether. Thus, IKK-induced NF-κB activation, mediated by either IKK1 or IKK2, is essential for the generation and survival of mature T cells, and IKK2 has an additional role in regulatory and memory T cell development

The roots of future rice harvests

The authors thank the Global Rice Science Partnership and Agropolis Fondation (Special grant n° 1400–009 and Rhizopolis grant n° 1001–005) benefiting from a national ANR Investissement d’Avenir” grant ANR-10-LABX-001-01) for supporting the workshop. They acknowledge the assistance of Nathalie Pivot, Cirad and Véronique Rafin, INRA in workshop organization. The root research at Cirad and University of Aberdeen is supported by the European Grant (FP7/2007-2013) under grant agreement n° 289300.27 EURoot “Enhancing resource Uptake from ROOTs under stress in cereal crops”. Research at IRRI is supported by the Generation Challenge Program and the Bill and Melinda Gates Foundation. J.X. is supported by the AcRF Tier 2 grant (MOE2009-T2-1-060) from the Ministry of Education of Singapore and National Research Foundation Singapore under its Competitive Research Programme (CRP Award No. NRF2010 NRF-CRP002-018). Doan Trung Luu is supported by the EU Marie Curie International Outgoing Fellowship 'ORYZAQUA – Cell Biology of Rice Aquaporins' (PIOF-GA-2011-300150). AP acknowledges the Generation Challenge Programme funded project “Targeting drought avoidance root traits to enhance rice productivity under water limited environments”. Financial support for A.G. Diedhiou was provided by the Université Cheikh Anta Diop (UCAD, VE12/13, CpVIII-Ar4 ) and GRISP. *This paper is dedicated to the late memory of Pr Ping Wu who passed away in a tragic car accident on June 12th, 2014.Peer reviewedPublisher PD

La dimension territoriale d’un projet d’infrastructure fluviale : le canal Seine-Nord Europe. Réflexion sur les outils et méthodes de l’évaluation socio-économique

The analysis of the spatial dimensions of the canal “Seine-North Europe” being built between Seine basin and those of north-west Europe is an interesting opportunity for study again these aspects of such a large building project. It also allows to discuss one more time some methodological locks already examined in earlier studies but renewed by more knowledge needs.L’analyse de la dimension territoriale du projet de canal à grand gabarit « Seine-Nord Europe » à réaliser entre les bassins de la Seine et ceux du nord-ouest de l’Europe donne l’occasion de revenir sur l’intérêt de la prise en compte de cette dimension dans un équipement de cette nature. Elle permet de revenir aussi sur certains verrous méthodologiques déjà évoqués dans des travaux antérieurs, alors même que le besoin de connaissances dans ce champ ne cesse de se faire plus exigeant

Glycoimmunothérapie (une nouvelle approche thérapeutique fondée sur la conjugaison de dérivés osidiques bioactifs à un anticorps thérapeutique)

Actuellement, le traitement du cancer ne peut se concevoir sans un ciblage spécifique de la cellule tumorale. Parmi ces nouvelles thérapies ciblées l utilisation d immunoglobulines spécifiquement dirigées contre des antigènes tumoraux constitue une véritable révolution, permettant, en clinique, d augmenter l efficacité des traitements conventionnels anti-cancéreux. Le rituximab, commercialisé sous le nom de Mabthera® en France et de Rituxan® aux Etats-Unis, est le premier anticorps monoclonal à visée thérapeutique utilisé en oncologie possédant une autorisation de mise sur le marché et approuvé par la FDA dans le traitement du lymphome B. Cependant, une résistance cliniqu aux anticorps thérapeutiques est observée et seulement 40 à 50 % des patients répondent à ce type de traitment. Cette résistance clinique est expliquée par un polymorphisme de la résistance de la cellule tumorale à ces nouveaux traitements. L objectif de ce travail est de lever ces phénomènes de résistance en développant de nouvelles voies thérapeutiques par la modulation ciblée du système immunitaire propre du patient. Ces approches, fondées sur la conjugaison de dérivés osidiques bioactifs à un anticorps thérapeutique, entreront dans ce que nous définirons comme la stratégie de glycoimmunothérapie. Ce travail, a permis d ouvrir de nouvelles voies immunothérapeutiques dans e traitement du cancer par le rituximab. En effet, en se situant à l interface entre la chimie et la biologie en passant par l expérimentation animale, nous avons exploré l activité de nouvelles molécules naturelles de structures originales sur la stimulation du système immunitaire.BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF