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The discovery of new natural products is a very long and expensive process ; it is therefore important to detect previously known compounds in the studied matrices, to avoid an useless second isolation. This is the aim of annotation (partial but quick identification of compounds) and of dereplication (application of annotation to avoid reisolation).Thanks to its unequaled sensibility and to the "big data" era, the high performance liquid chromatography hyphenated to tandem mass spectrometry has become a reference technique in this field. Indeed, its use is generally implemented by informatic tools, as "molecular networking", because of the large amount of generated data.This thesis is divided into two parts : the first one deals with extraction of new compounds from a very well-known Apocynaceae plant, Picralima nitida. The second one is about the application of "molecular networking" to biomimetic chemistry in mixtures, especially about "3-alkylpiperidines" alkaloids., La découverte de nouvelles entités naturelles est un processus particulièrement long et coûteux ; il faut donc réussir le plus tôt possible à détecter les composés connus dans les matrices étudiées, afin de ne pas les ré-isoler inutilement. C’est tout l’enjeu de l’annotation (c’est-à-dire l’identification partielle mais rapide de composés) et de la déréplication (autrement dit, l’application de l’annotation en vue d’écarter les molécules déjà connues du processus d’isolement).Grâce à sa sensibilité inégalée et à l’avènement de l’ère du « big data », la chromatographie liquide à haute performance couplée à la spectrométrie de masse tandem (CLHP-SM/SM) s’est imposée comme l’un des outils de référence dans cette démarche. En effet, son utilisation implique bien souvent le recours à des méthodes de traitement informatiques, comme le « molecular networking », de par la quantité considérable de données générées.La thèse se présente donc en deux parties : la première, portée sur l'extraction de nouveaux composés à partir d'une plante de la famille des Apocynaceae déjà très étudiée, Picralima nitida. La seconde propose une application des réseaux moléculaires à de la chimie biomimétique en mélanges, autour des alcaloïdes de type « 3-alkylpipéridines ».

International audience

International audience

Le processus de mise à la retraite ne se termine pas par l’abandon de l’activité professionnelle, mais requiert une phase postérieure d’adaptation à la nouvelle condition. Le processus d’adaptation entendue comme le degré de bien-être et de satisfaction maintenus pendant la retraite, peut être influencée par des ressources psychologiques et dispositionnelles et par certains facteurs de contexte. Cette étude se propose comme objectif de vérifier l’influence du niveau d’activité et du support social sur le bien-être maintenu pendant la retraite en comparant la condition d’un groupe de retraités italiens et d’un groupe espagnol. Les résultats montrent que dans l’échantillon italien la relation entre la préférence pour les activités sociales et le bien-être est médiée par le niveau d’activité maintenu pendant la retraite. L’hypothèse que le support social modère la relation entre les préférences d’activités et le bien-être n’est confirmée dans aucune des deux populations considérées. Les résultats relatifs à l’effet positif du niveau d’activité suggèrent qu’une plus grande participation au marché du travail des personnes âgées de plus de cinquante ans, semble favoriser une meilleure adaptation et un meilleur bien-être pendant l’âge mûr.

International audience; Adaptive immune responses are initiated by the recognition of antigens by T lymphocytes. Antigen recognition triggers the generation of immunological synapses. These are dynamic and finely organized cell-cell contacts formed between T lymphocytes and antigen presenting cells. Immunological synapse formation results from a major T cell reorganization process, involving the polarization of the actin cytoskeleton, the microtubule network and the intracellular vesicle traffic. These processes facilitate the generation, the dynamics and the regulation of molecular complexes at the synapse that are responsible for T cell activation. The human immunodeficiency virus (HIV) targets in various manners immunological synapse generation and function, thus modifying the capacity of infected T cells to respond to further antigen stimulation.

International audience; Adaptive immune responses are initiated by the recognition of antigens by T lymphocytes. Antigen recognition triggers the generation of immunological synapses. These are dynamic and finely organized cell-cell contacts formed between T lymphocytes and antigen presenting cells. Immunological synapse formation results from a major T cell reorganization process, involving the polarization of the actin cytoskeleton, the microtubule network and the intracellular vesicle traffic. These processes facilitate the generation, the dynamics and the regulation of molecular complexes at the synapse that are responsible for T cell activation. The human immunodeficiency virus (HIV) targets in various manners immunological synapse generation and function, thus modifying the capacity of infected T cells to respond to further antigen stimulation.

International audience

International audience

La transmission par contact cellulaire est récemment apparue comme le mécanisme de dissémination privilégié des rétrovirus lymphotropes humains. L’étude des structures intercellulaires mises en jeu et la caractérisation du matériel viral infectieux transmis au niveau de ces contacts cellulaires devraient permettre de définir de nouvelles cibles thérapeutiques antirétrovirales.

National audience

The Lettres diverses attributed to Henry Le Bret were published anonymously, without any date nor place of publication. This article deals with three problems : authorship, datation and Le Bret’s direct involvement in its publication.Le Bret’s paternity of Lettres diverses, included the only letter addressed to himself, is proven mainly by his signature found in many of them and by his attested private relationships with the majority of addressees. The publication date is resolved after a meticulous comparison of Lettres diverses and Recueil de quelques discours et lettres écrites à des personnes studieuses sur differentes matieres (1692), in which 15 letters (out of the 64 of Lettres diverses) are present with some variations. From an omission in the Recueil I theorized that a great number of pages from a published copy of Lettres diverses were detached/untied and reused as a material hypotext for the Recueil ; this theory is substantiated and confirmed by a lot of informations related to events, books, and people, especially to Bossuet, Queen Marie-Thérèse and the Clergy Assembly of 1665. All these data lead to the conclusion that Lettres diverses were published between 1678 and May 1681, which invalidates all previous datations proposed by Lacroix, Forestié, Cioranescu, and myself in 2004.And finally there is no historical evidence nor objective argument for believing that Le Bret did not want his readers to know that he was responsible for the publication of these letters : the book was obviously destined to a private and chosen group of friends, which was not uncommon in xviith century. In 1692, given his geographic and not so private new public, Le Bret withdrew from Lettres diverses all the ones addressed to his Parisian friends as well as some destined to Toulousan ladies in which good taste was questionable (like his Eloge de la petite vérole, i. e. small-pox).We can now reformulate the bibliographical description of this book : Lettres diverses par Henry Le Bret, prévôt de l’église cathédrale de Montauban, Montauban (?), ca 1678-1681.Among the addenda completing this article are a brief account of the controversy between Le Bret and the minister Pierre Isarn, a restitution of one of his remarks concerning Boileau’s Satire IX, and his quasi unknown éloge de la petite vérole.

This article deals mainly with Henry Le Bret, Cyrano’s friend and editor. Only Le Bret’s Parisian years are concerned here, the ones which preceeded his clerical career in Montauban.Till now very little was known of Le Bret’s Parisian period and nothing at all of his career as a « avocat au Conseil Privé du Roi ». Long investigations in Archives Nationales (Paris, CARAN), mainly in notarial deeds (Minutier Central) and in Conseil Privé’s archives (series V6), as well as in Archives départementales de Tarn-et-Garonne (Montauban), allowed me to revive many of his friends and clients : in the second category can be found Bishop of Albi, Gaspard de Daillon du Lude, related to the Roquelaures, and to Cyrano through the wealthy Feydeau family ; in the first category appear many people named in Le Bret’s posthumous preface of Cyrano’s Etats et Empires de la Lune (1657), like the Cuigys, the Durets, Captain Carbon de Casteljaloux, the engraver Bignon and the dramatist and historian Royer de Prade. They were all living in a delimited area of the « Marais » (Right Bank : rues de la Verrerie, des Billettes, Sainte-Croix de la Bretonnerie, Simon Lefranc and Sainte-Avoye) ; even Cyrano’s protectors were there, Regnault des Boisclairs at rue de la Verrerie, and Duke of Arpajon, whose residence partly burnt in January 1655, at Vieille rue du Temple. A precious notarial deed reveals that Le Bret was a cleric before Cyrano died, situation which should bring a new light on the making of the posthumous edition, published with numerous cuts (« lacunes ») and variants ; another notarized document concerns the donation of Clamard « seigneurie » to Cuigy junior in 1656, donation which not only explains a variant of the posthumous edition but also provides an irrefutable evidence that Cyrano’s novel was altered after his death.Among the addenda completing this article are the autograph last will of Casteljaloux, written in 1642 in Clamard where he died in 1654, the donation of Clamard to Cuigy junior (1656) and a substantial repayment to Le Bret by Royer de Prade (1657) just before the former went to Montauban.

International audience

International audience

Alcover Madeleine. Statistique et critique d’attribution : l’édition posthume des États et Empires de la Lune. In: Littératures classiques. Supplément au n°53,2004. Cyrano de Bergerac. Les États et Empires de la Lune et du Soleil pp. 295-311.

In 1936, Randall formulated a hypothesis concerning stone formation related to the renal papillae. Randall's hypothesis, discussed for many years, was confirmed by Cifuentes in 1983. The authors studied 830 cases of papillary stones, eliminated spontaneously, 16 of which had a typical Randall plaque with mineralized collecting tubules (1.9%). This study was conducted by scanning electronic microscopy (SEM) using an EDX system. The papillary origin of several renal stones can be confirmed in this way. The origin of these stones would remain unknown without the use of these modern techniques.

The presence of bone tissue in renal stones has been described for a long time. Two cases of heterotopic ossification are reported in this study. Stone analysis was performed by stereoscopic microscopy, infrared spectrophotometry and fine slice petrographic section and polarized light microscopy. This last technique revealed the existence of osteocytic filling defects inside the stones, an unquestionable sign of mineralized bone tissue.

The collect of 973 Fleas on various small terrestrial mammals, from December 1987 till May 1988, in the Neuquén Province (Argentina), has given 20 taxa. Hectopsylla pascuali n. sp., Plocopsylla consobrina n. sp., Agastopsylla boxi gibbosa n. ssp., Chiliopsylla allophyla tonnii n. ssp. are described. Plocopsylla diana Beaucournu, Gallardo and Launay, 1986, Ctenoparia inopinata Rothschild, 1909, Neotyphloceras crassispina chilensis Jordan, 1936, Tetrapsyllus satyrus Beaucournu and Torrés-Mura, 1986, Ectinorus martini Lewis, 1976, are new from Argentina.

The results of therapy have been analyzed in a series of 192 patients admitted for status epilepticus over 7 years in two intensive care units. Most (142 cases without any prior epilepsy) corresponded to secondary forms. In 2/3 of the cases, the patients were admitted because of failure of benzodiazepines and/or phenobarbitone. Sodium thiopentone achieved control of seizures in 75%; short-acting barbiturates should be especially prescribed in grand mal status with impending brain anoxia. Diphenylhydantoin would appear suitable in non-life-threatening conditions such as serial seizures or partial status. Chlormethiazole often succeeds in controlling convulsive status which has proved refractory to other treatment. Supportive management is mandatory: 52% of patients required respiratory assistance. Fatalities (36%) exclusively correspond to the underlying cerebral conditions and systemic disorders.

EEG, EMG and clinical correlates of myoclonus due to poisoning are reviewed. The authors propose a classification into two groups. I. Sporadic diffuse asynchronous asymmetrical myoclonic jerks, responding to treatment. These states are encountered essentially in acute intoxication by vegetal poisons (strychnine), rodenticide (chloralose) and various medications (isoniazide, tricyclic antidepressant agent, lithium). These transitory manifestations are functional and prognosis is favourable. II. Subintrant generalized synchronous symmetrical myoclonus, uncontrolled by therapeutics. These myoclonus states observed over weeks or months are frequently consecutive to organic injuries due to direct toxicity (methylbromide) or after anoxia (toxic cardiac arrest). EEG and EMG correlations are very inconstant in both groups. EEG abnormalities are a sign of cortical and/or subcortical dysfunction. Normal EEG suggests a disease of the lower central nervous structure (brain stem, medulla). Chronic bismuth and dialysis encephalopathies are also related. Withdrawal syndrome with myoclonus jerks after sudden cessation of barbiturate or benzodiazepine long-term treatment is mentioned.

Three new cases of methyl bromide poisoning (leakage from a fire extinguisher) are reported. Two of these were characterized, after an initial period of coma and myoclonic status, by an action myoclonus. Electrical data are presented. A follow up of 4 and 8 years allowed to study the effect of drugs, two of which (clonazepam and baclofene) being pecularly contributive. The third patient outlived for 5 years in a stuporous state with myoclonus. The anatomical findings consisted mainly of a necrosis of both inferior colliculi with gliosis in the upper brain stem reticular formation and moderate changes in the dentate and pontine nuclei. Their significance is discussed in view of physiological and experimental knowledge.

The present study, conducted between January 1975 and June 1983, includes 282 adult patients admitted for status epilepticus (SE) in 2 intensive care units (3.5% of all admissions). In their great majority, i.e., 201, patients had no previous history of epilepsy, and initiated the SE during the course of recent affections such as brain or systemic diseases. In 81 patients with previous seizure, epilepsy was idiopathic in 20, and symptomatic in 61, the 3 main causes being cranial traumatism, cerebrovascular accident and chronic alcoholism. SE was of various causes. The most frequent were cerebro-vascular disease, post-anoxic encephalopathy, intoxication, bacterial or viral meningo-encephalitis. In some patients, SE was preceded by manifestations such as convulsions, behavorial disturbances or conscience impairment. One should be aware of these facts and undertake or increase an anticonvulsivant medication at their onset. Duration of SE, when clearly established, was highly variable but had no apparent correlation to sequelae or death occurrences. SE itself was directly related to death in only 2 cases; in all other instances death was the consequence of the primary disease. These results are consistent with previous reports: presently SE occurs more frequently in the course of other affections than in prior epileptic patients. The better vital prognosis of SE is due to the simultaneous conjunction of new anticonvulsivant medication and supportive care associated with the cure of the causative disease.

Rhadinopsylla (R.) eivissensis B. and A. of Eivissa, Balearic Isles (Spain) belongs to the masculana complex, which is defined by the authors. This species is easily characterized in the male with the characters of the sternum VII, of the tergum IX, and the phallosome. The female is closely related to that of the R. masculana. The masculana complex includes actually, in addition to R. masculana Jordan and Rothschild from North Africa, R. eivissensis and R. beillardae Beaucournu and Launay (stat. nov.) from Spain. The biogeographical interest of this complex, primitively bound to the Gerbillidae, is stressed.