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Charfet Le couvent où se trouve la bibliothèque de manuscrits Cliché mission française « Manuscrits syriaques de Charfet » La bibliothèque du patriarcat syro-catholique, préservée dans le monastère de Charfet, au Liban (voir ill. ci-contre), est située dans la montagne au-dessus de Jounieh, dans l’ancienne résidence patriarcale qui est restée aussi le séjour d’été des patriarches. La collection comprend environ 2 000 manuscrits syriaques, garshuni (arabe en caractères syriaques) et arabes. C...

Tight control of the concentration of acetylcholine at cholinergic synapses requires precise regulation of the number and state of the acetylcholine receptors, and of the synthesis and degradation of the neurotransmitter. In particular, the cholinesterase activity has to be controlled exquisitely. In the genome of the first experimental models used (man, mouse, zebrafish and drosophila), there are only one or two genes coding for cholinesterases, whereas there are more genes for their closest relatives the carboxylesterases. Natural amplification of cholinesterase genes was first found to occur in some cancer cells and in insect species subjected to evolutionary pressure by insecticides. Analysis of the complete genome sequences of numerous representatives of the various metazoan phyla show that moderate amplification of cholinesterase genes is not uncommon in molluscs, echinoderms, hemichordates, prochordates or lepidosauria. Amplification of acetylcholinesterase genes is also a feature of parasitic nematodes or ticks. In these parasites, over-production of cholinesterase-like proteins in secreted products and the saliva are presumed to have effector roles related to host infection. These amplification events raise questions about the role of the amplified gene products, and the adaptation processes necessary to preserve efficient cholinergic transmission. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.

Ce troisieme livret des NEPP (« Notes d’epigraphie et de philologie pheniciennes ») contient des remarques ou propositions breves, surtout d’ordre technique (epigraphique, philologique ou encore hi...

Timothée Ier, une des figures savantes les plus prestigieuses du monde syriaque, fut le catholicos de l’Église de l’Orient. Ainsi nommait-on le chef de l’Église de Mésopotamie, dont le siège se situait à son époque à Bagdad. Par rapport aux érudits évoqués dans cet ouvrage, il a évolué dans un monde différent à plus d’un titre : ecclésialement, puisqu’il était le chef d’une Église déjà autocéphale depuis plus de trois cents ans et qui se revendiquait sur certains plans comme le centre du mond...

L’érudition renvoie à la collecte, à la lecture et à l’exploitation des sources. Pendant quinze siècles, du IIIe au XVIIIe siècle, dans l’Europe de culture gréco-latine et au Proche-Orient, les érudits ont abondamment puisé dans les écrits des Anciens, mais loin d’être de simples compilateurs, ils s’appropriaient les écrits qu’ils citaient, s’efforçaient de les rendre accessibles à leurs lecteurs et les mettaient au service d’un projet pédagogique ou intellectuel cohérent. Les écrits des érudits renseignent sur leur manière de travailler et sur les objectifs qu’ils poursuivaient. L’érudition fut-elle neutre ? Avait-elle pour seule mission de diffuser des savoirs et d’accroître la connaissance dans différentes disciplines ? Quels que fussent ses objectifs, elle reposait sur des pratiques que l’on retrouve pendant quinze siècles : l’apprentissage de langues étrangères, l’emprunt de manuscrits, le recours constant à la correspondance. Les aspects matériels de l’érudition sont un aspect important de la vie intellectuelle. Le travail effectué dans les scriptoria, la mise au point d’index et de tables des matières, la publication de lieux communs aidèrent les savants dans leurs recherches. Au XVIIIe siècle, la figure de l’honnête homme, qui supplanta celle de l’érudit, posa des problèmes spécifiques aux éditeurs qui durent mettre en œuvre de nouvelles stratégies pour minimiser les risques que leur posaient les livres érudits. À côté des savants et des humanistes reconnus, des hommes et des femmes participaient à la vie intellectuelle de leur époque, sans rédiger d’œuvres majeures. Membres de réseaux de correspondants, vulgarisateurs éclairés, lecteurs attentifs, ils contribuaient à la diffusion de la culture savante en enseignant, en encourageant la vie de l’esprit et en faisant connaître par leurs écrits les idées nouvelles.

B-cell activation yields abundant cell death in parallel to clonal amplification and remodeling of immunoglobulin (Ig) genes by activation-induced deaminase (AID). AID promotes affinity maturation of Ig variable regions and class switch recombination (CSR) in mature B lymphocytes. In the IgH locus, these processes are under control of the 3’ regulatory region (3’RR) super-enhancer, a region demonstrated in the mouse to be both transcribed and itself targeted by AID-mediated recombination. Alternatively to CSR, IgH deletions joining Sμ to “like-switch” DNA repeats that flank the 3’ super-enhancer can thus accomplish so-called “locus suicide recombination” (LSR) in mouse B-cells. Using an optimized LSR-seq high throughput method, we now show that AID-mediated LSR is evolutionarily conserved and also actively occurs in humans, providing an activation-induced cell death pathway in multiple conditions of B-cell activation. LSR either focuses on the functional IgH allele or is bi-allelic, and its signature is mainly detected when LSR is ongoing while it vanishes from fully differentiated plasma cells or from “resting” blood memory B-cells. Highly diversified breakpoints are distributed either within the upstream (3’RR1) or downstream (3’RR2) copies of the IgH 3’ super-enhancer and all conditions activating CSR in vitro also seem to trigger LSR although TLR ligation appeared the most efficient. Molecular analysis of breakpoints and junctions confirms that LSR is AID-dependent and reveals junctional sequences somehow similar to CSR junctions but with increased usage of microhomologies., Author summary Class switch recombination, initiated by the activation-induced deaminase enzyme rearranges immunoglobulin (Ig) genes in order to replace expression of IgM by IgG, IgA or IgE. A variant form of this event, locus suicide recombination (LSR), was previously reported in mouse B-lymphocytes and simply deletes all functional Ig constant genes, thus terminating B-cell function. This study first demonstrates that the structure of the human Ig heavy chain locus provides an ideal target for LSR, and is thus actively (but transiently) affected by this deletion process at the activated B-cell stage. LSR then yields recombined genes that do not support B-cell survival and which thus becomes almost undetectable among long-lived memory B-cells or plasma cells.

Within the alpha/beta hydrolase fold superfamily of proteins, the COesterase group (carboxylesterase type B, block C, cholinesterases …) diverged from the other groups through simultaneous integration of an N-terminal, first disulfide bond and a significant increase in the protein mean size. This first disulfide bond ties a large Cys loop, which in the cholinesterases is named the omega loop and forms the upper part of the active center gorge, essential for the high catalytic activity of these enzymes. In some non-catalytic members of the family, the loop may be necessary for heterologous partner recognition. Reshuffling of this protein portion occurred at the time of emergence of the fungi/metazoan lineage. Homologous proteins with this first disulfide bond are absent in plants but they are found in a limited number of bacterial genomes. In prokaryotes, the genes coding for such homologous proteins may have been acquired by horizontal transfer. However, the cysteines of the first disulfide bond are often lost in bacteria. Natural expression in bacteria of CO-esterases comprising this disulfide bond may have required compensatory mutations or expression of new chaperones. This disulfide bond may also challenge expression of the eukaryote-specific cholinesterases in prokaryotic cells. Yet recently, catalytically active human cholinesterase variants with enhanced thermostability were successfully expressed in E. coli. The key was the use of a peptidic sequence optimized through the Protein Repair One Stop Shop process, an automated structure- and sequence-based algorithm for expression of properly folded, soluble and stable eukaryotic proteins. Surprisingly however, crystal structures of the optimized cholinesterase variants expressed in bacteria revealed co-existing formed and unformed states of the first disulfide bond. Whether the bond never formed, or whether it properly formed then broke during the production/analysis process, cannot be inferred from the structural data. Yet, these features suggest that the recently acquired first disulfide bond is difficult to maintain in E. coli-expressed cholinesterases. To explore the fate of the first disulfide bond throughout the cholinesterase relatives, we reanalyzed the crystal structures of representative COesterases members from natural prokaryotic or eukaryotic sources or produced as recombinant proteins in E. coli. We found that in most cases this bond is absent.

A. Ferjaoui, T. Redissi (éd.)Volume III – La mort, la religion Tunis, Institut national du patrimoine, 2019ISBN : 978-9973-0974-2-2