Botulinum Toxins, Diversity, Mode of Action, Epidemiology of Botulism in France

Botulinum toxins (BoNTs) are the most potent toxins and are responsible for botulism, which is a neurological disease in man and animals. Botulism is characterized by flaccid paralysis and inhibition of secretions. BoNTs are produced by distinct clostridial species including Clostridium botulinum that consist in four physiological and genetic groups, atypical strains of C. baratii and C. butyricum. Recently, nonclostridial bacteria have been found to synthesize BoNTs. The particularity of BoNTs is to associate with nontoxic proteins to form large-size complexes that are resistant to acidic pH and protease degradation of the digestive tract. BoNTs are divided into 10 types based on neutralization by specific antisera and into more than 40 subtypes according to their sequence variations. All BoNTs retain a common core structure and mode of action, which consists in the inhibition of neurotransmitter release, notably acetylcholine. Human botulism occurs in three main forms: foodborne botulism, botulism by intestinal colonization including infant botulism, and wound botulism. In France, type B foodborne botulism is the most prevalent form, resulting from the traditional consumption of pork products such as home-made cured ham. Albeit less frequent, human botulism is still present in France including diverse types and origins

Un graveur héraldiste du XVIIIe siècle : Pierre-Paul Dubuisson

En 1757 paraissait à Paris, « aux dépens de l’Auteur », sous le nom de Pierre-Paul Dubuisson, un Armorial des principales maisons et familles du royaume, particulièrement de celles de Paris et de l’Isle de France, contenant les armes des princes, seigneurs, grands officiers de la couronne & de la Maison du Roi, celles des cours souveraines, &c. avec l’explication de tous les blasons, en deux petits volumes in-12° à pagination multiple. Ce véritable « Bottin mondain » de la seconde moitié du x..

Exploiting the Time-Reversal Operator for Adaptive Optics, Selective Focusing and Scattering Pattern Analysis

We report on the experimental measurement of the backscattering matrix of a weakly scattering medium in optics, composed of a few dispersed gold nanobeads. The DORT method (Decomposition of the Time Reversal Operator) is applied to this matrix and we demonstrate selective and efficient focusing on individual scatterers, even through an aberrating layer. Moreover, we show that this approach provides the decomposition of the scattering pattern of a single nanoparticle. These results open important perspectives for optical imaging, characterization and selective excitation of nanoparticles.Comment: 10 page

Involvement of a small GTP binding protein in HIV-1 release

BACKGROUND: There is evidence suggesting that actin binding to HIV-1 encoded proteins, or even actin dynamics themselves, might play a key role in virus budding and/or release from the infected cell. A crucial step in the reorganisation of the actin cytoskeleton is the engagement of various different GTP binding proteins. We have thus studied the involvement of GTP-binding proteins in the final steps of the HIV-1 viral replication cycle. RESULTS: Our results demonstrate that virus production is abolished when cellular GTP binding proteins involved in actin polymerisation are inhibited with specific toxins. CONCLUSION: We propose a new HIV budding working model whereby Gag interactions with pre-existing endosomal cellular tracks as well as with a yet non identified element of the actin polymerisation pathway are required in order to allow HIV-1 to be released from the infected cell

About a novel type of botulinum toxin

A novel type (type H) of botulinum toxin has been identified, which represents a novel pathology and also novel potential threat for human. The non disclosure of scientific information and non distribution of the novel strain to other expert laboratories raise the question of confidentiality of new sensitive data and security strategy to be developed in the diagnosis and research laboratories regarding the handling of new potentially very virulent pathogensUn nouveau type de toxine botulique a été identifié (type H) qui représente une nouvelle entité pathologique mais aussi une nouvelle menace potentielle pour l’homme. La non divulgation des informations scientifiques et la non distribution de la nouvelle souche à d’autres laboratoires experts posent le problème de la confidentialité de nouvelles données sensibles et de la stratégie de sécurité à adopter dans les laboratoires de diagnostic et de recherche sur la manipulation de nouveaux agents pouvant se révéler très pathogène

Mode of action of botulinum and tetanus neurotoxins

Clostridium botulinum and Clostridium tetani synthesize botulinum neurotoxins (A to G) and the tetanus toxin, which are responsible for botulism and tetanus, respectively. These toxins cause nervous disorders, either a flaccid paralysis (botulism) or a spastic paralysis (tetanus), which are severe and often lethal. Botulinum and tetanus neurotoxins prevent the release of neurotransmitters. Botulinum neurotoxins inhibit the release of acetylcholine at the neuromuscular junction, whereas tetanus toxin acts on the inhibitory interneurons in the central nervous system. They are metalloproteases, which cleave one of the three proteins in the SNARE complex, which plays a key role in neuroexocytosis. Although neurotoxins are potent poisons, they also are sometimes used as therapeutic agents; for instance, botulinum neurotoxins are largely used in the treatment of dystonia.Clostridium botulinum et Clostridium tetani synthétisent les neurotoxines botuliques (A à G) et la neurotoxine tétanique, qui sont à l'origine du botulisme et du tétanos, respectivement. Ces affections nerveuses, paralysies flasques pour le botulisme et paralysie spastique pour le tétanos, sont graves et souvent mortelles. Les neurotoxines botuliques et tétanique bloquent la libération de neuromédiateur. Alors que les neurotoxines botuliques inhibent la libération d'acétylcholine au niveau des jonctions neuromusculaires, la toxine tétanique agit sur les interneurones inhibiteurs du système nerveux central. Ce sont des métalloprotéases qui clivent une des trois protéines des complexes SNAREs ayant un rôle clé dans le processus de neuroexocytose. Si les neurotoxines clostridiennes sont de puissants poisons, elles sont aussi des agents thérapeutiques, notamment les neurotoxines botuliques qui sont largement utilisées dans le traitement des dystonies

Bacterial toxins modifying the actin cytoskeleton

Numerous bacterial toxins recognize the actin cytoskeleton as a target. The clostridial binary toxins (Iota and C2 families) ADP-ribosylate the actin monomers causing the dissociation of the actin filaments. The large clostridial toxins from Clostridium difficile, Clostridium sordellii and Clostridium novyi inactivate, by glucosylation, proteins from the Rho family that regulate actin polymerization. In contrast, the cytotoxic necrotic factor from Escherichia coli activates Rho by deamidation and increases the formation of actin filaments. The enterotoxin of Bacteroides fragilis is a protease specific for E-cadherin and it promotes the reorganization of the actin cytoskeleton. The bacterial toxins that modify the actin cytoskeleton induce various cell disfunctions including changes in cell barrier permeability and disruption of intercellular junctions