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Travaillant sur l’appropriation de l’espace en Toulousain au Moyen Âge, un mot étrange, dex, avait suscité l’attention ; l’idée de mener une enquête linguistique à son propos s’était imposée. Pour des historiens du droit médiéval, le terme ne prêtait pas à difficulté : il signifiait le « territoire communal ». Mais comment y parvenir et en partant d’où ? Au début de cette recherche se trouvait une assertion d’un historien du xixe siècle : lors d’un procès entre l’évêque de Toulouse et le prie...

L'historien médiéviste ne vit pas qu'au milieu des parchemins ou sur les monticules de fouille. Il entend aussi reprendre une interrogation centrale de nos civilisations contemporaines : les rapports entre les hommes et leurs espaces de vie. Il s'agit de partir en quête de ce que la période médiévale a pu élaborer dans ce domaine, avec la disparition des cadres politiques des empires antiques et de leurs héritiers carolingiens. La démarche adoptée ici se caractérise par une prise en compte délibérée, à travers le discours, de la dimension consciente et vécue du territoire. Pour mesurer le chemin parcouru dans le renouvellement de ce domaine de recherche, il convenait de partir de l'étude des œuvres des grands écrivains de l'histoire rurale française. Ont donc été analysés leur vocabulaire, leurs concepts, leur sensibilité. Mais le cœur de l'approche s'attache à l'étude des mots que les hommes du Moyen Âge ont eux-mêmes employés, selon la diversité des acteurs, des types de documents, de la chronologie abordée. Cela étant fait, on ne peut aujourd'hui tenter de restituer les espaces vécus du Moyen Âge en ignorant les apports des autres disciplines. Il a donc été demandé de dresser, en fonction des questions que se posent les médiévistes, un état de l'art de l'étude des territoires à des spécialistes de la géographie, de la sociologie, de l'archéologie, de l'ethnoanthropologie et des sciences paléoenvironnementales. Une équipe de seize chercheurs a ainsi œuvré pendant plusieurs années, affinant les grilles d'analyse et les protocoles de travail. Au total, les contributions portant sur le millénaire médiéval ont choisi la France méridionale comme champ d'observation, avec pour parti pris un souple jeu d'échelles entre sites et régions. La prise en considération d'un long Moyen Âge, depuis les gisements tardoantiques jusqu'aux compoix des xve et xviesiècles, offre la possibilité d'examiner les séquences temporelles et les tournants significatifs. On est souvent allé chercher dans l'époque médiévale les origines des états et des nations de l'Europe actuelle. Ce livre constitue en fin de compte une contribution à la genèse de ses « pays » et de ses terroirs.

Une palette lexicale riche Des sources et des méthodes L’examen des sources employées par ces historiens, autres que le noyau dur textuel qu’ils maîtrisent parfaitement, montre leur vaste curiosité. Bloch, le premier, exploite les données des terriers, des enquêtes sur le terrain mais aussi au cadastre, des photos aériennes, des documents planimétriques ; il a recours aussi à la linguistique, l’archéologie, la géographie et à la sociologie naissante. L’intérêt de Déléage pour les cadastres, l...

Questo saggio, concepito come riflessione introduttiva al volume di Roland Mousnier, La costituzione nello Stato assoluto, individua nella civilizzazione statuale il tratto saliente sia della produzione del grande storico transalpino delle istituzioni sia del modello assolutistico francese in Età moderna. Contrariamente a ciò che spesso si ritiene, l'organizzazione politico-istituzionale della Francia non é affatto solo focalizzata sullo Stato inteso come apparato ma è una struttura a più livelli che coinvolge tutta la società. Questa interazione continua tra istituzioni e base sociale e tra diversi livelli istituzionali e sociali, che Mousnier chiama «solidarietà verticali», e che è stata pure definita la società della fiducia (A. Peyrefitte, La société de confiance), è il tratto saliente dell'esperienza costituzionale francese in Età moderna. Lo Stato assoluto, lungi dall'identificarsi con il dispotismo o la tirannia, diede un contributo decisivo al costituzionalismo e all'affermarsi dello Stato di diritto (in ciò la Rivoluzione, come notò Tocqueville, coronò il processo iniziato fin dal Medioevo), plasmando la società e favondo dinamiche molto profonde di interazione e cooperazione nella psicologia sociale. Attraverso una raffinata astuzia della ragione giuridica,consistente nel positivizzare le consuetudini, i re francesi riuscirono a far accettare gradualmente e senza forzature e violenze il principio di sovranità. Nacque così, con il progressivo affermarsi dello Stato, la statualità, ossia un progetto comune di organizzazione sociale che fa di quel Paese la quintessenza dello spirito delle istituzioni. Tra gli aspetti più interessanti da sottolineare vi è il fatto che il cattolicissimo Mousnier fu lo studioso che più di tutti valorizzò questo modello istituzionale imperniato sulla statualità. Simbolicamente è di grande impatto osservare come tra il cattolico osservante Ravaillac e il libertino machiavellico Enrico IV, egli non ebbe dubbi nell'indicare nel sovrano assassinato e nella sua coraggiosa azione il valore politico da ammirare. Il motivo è chiaro: anche la dimensione religiosa entrava a far parte integrante di quel grande progetto politico di cooperazione e di solidarietà che Mousnier vedeva nella statualità.

Introduction Les donnees sur la population des personnes epileptiques accueillies en ESMS sont rares et mal connues. Il a ete realise une etude de population dans les ESMS de la region des Pays-de-la-Loire. Objectifs L’objectif principal etait de definir le nombre de personnes epileptiques accueillies dans les ESMS de cette region, dans les objectifs secondaires la gravite de l’epilepsie et des troubles associes a ete analysee. Patients et methodes Enquete epidemiologique realisee en fevrier–mai 2015 par auto-questionnaires (premiere partie : donnees generales de fonctionnement de la structure, deuxieme partie : fiches individuelles, descriptives, anonymes, de chaque personne epileptique accueillie au moment de l’enquete ayant presentee au moins une crise en 2014) aupres des 778 ESMS de la region (66 % d’ESMS adultes, 34 % d’ESMS enfants-adolescents). Resultats Le taux de personnes epileptiques est de 13 % (IC95 % [12,3–13,4]) dont 42 % ont une epilepsie active avec 9 % des crises quotidiennes et 33 % au moins un EME/an. En post-critique, 6 % presentent une agressivite. En dehors des periodes peri-critiques, 93 % presentent des troubles intellectuels dont 45 % severes, 72 % des troubles moteurs dont 49 % severes, 70 % des troubles du comportement dont 12 % severes. Dix-huit pour cent des cas presentent une epilepsie grave et au moins un trouble associe severe. Discussion REPEHRES et les rares etudes epidemiologiques deja realisees permettent d’estimer le taux de personnes epileptiques en ESMS en France entre 13 et 18 %. REPEHERES permet d’estimer qu’1/4 des epilepsies non stabilisees sont severes et de souligner que les troubles du comportement ne sont pas les troubles associes les plus importants aussi bien dans les periodes peri-critiques qu’inter-critiques. Conclusion REPEHRES permet d’avoir des donnees actualisees sur les personnes epileptiques accueillies en ESMS et contribue a une meilleure connaissance de la population associant une epilepsie severe et des troubles graves.

The replication of picornaviruses has been described to cause fragmentation of the Golgi apparatus that blocks the secretory pathway. The inhibition of major histocompatibility complex class I upregulation and cytokine, chemokine and interferon secretion may have important implications for host defense. Previous studies have shown that disruption of the secretory pathway can be replicated by expression of individual nonstructural proteins; however the situation with different serotypes of human rhinovirus (HRV) is unclear. The expression of 3A protein from HRV14 or HRV2 did not cause Golgi apparatus disruption or a block in secretion, whereas other studies showed that infection of cells with HRV1A did cause Golgi apparatus disruption which was replicated by the expression of 3A. HRV16 is the serotype most widely used in clinical HRV challenge studies; consequently, to address the issue of Golgi apparatus disruption for HRV16, we have systematically and quantitatively examined the effect of HRV16 on both Golgi apparatus fragmentation and protein secretion in HeLa cells. First, we expressed each individual nonstructural protein and examined their cellular localization and their disruption of endoplasmic reticulum and Golgi apparatus architecture. We quantified their effects on the secretory pathway by measuring secretion of the reporter protein Gaussia luciferase. Finally, we examined the same outcomes following infection of cells with live virus. We demonstrate that expression of HRV16 3A and 3AB and, to a lesser extent, 2B caused dispersal of the Golgi structure, and these three nonstructural proteins also inhibited protein secretion. The infection of cells with HRV16 also caused significant Golgi apparatus dispersal; however, this did not result in the inhibition of protein secretion. IMPORTANCE The ability of replicating picornaviruses to influence the function of the secretory pathway has important implications for host defense. However, there appear to be differences between different members of the family and inconsistent results when comparing infection with live virus to expression of individual nonstructural proteins. We demonstrate that individual nonstructural HRV16 proteins, when expressed in HeLa cells, can both fragment the Golgi apparatus and block secretion, whereas viral infection fragments the Golgi apparatus without blocking secretion. This has major implications for how we interpret mechanistic evidence derived from the expression of single viral proteins.

The hallmark of enteropathogenic Escherichia coli (EPEC) infection is the formation of actin-rich pedestal-like structures, which are generated following phosphorylation of the bacterial effector Tir by cellular Src and Abl family tyrosine kinases. This leads to recruitment of the Nck–WIP–N-WASP complex that triggers Arp2/3-dependent actin polymerization in the host cell. The same phosphorylation-mediated signalling network is also assembled downstream of the Vaccinia virus protein A36 and the phagocytic Fc-gamma receptor FcγRIIa. Here we report that the EPEC type-III secretion system effector EspJ inhibits autophosphorylation of Src and phosphorylation of the Src substrates Tir and FcγRIIa. Consistent with this, EspJ inhibits actin polymerization downstream of EPEC, Vaccinia virus and opsonized red blood cells. We identify EspJ as a unique adenosine diphosphate (ADP) ribosyltransferase that directly inhibits Src kinase by simultaneous amidation and ADP ribosylation of the conserved kinase-domain residue, Src E310, resulting in glutamine-ADP ribose., Non-receptor tyrosine kinases such as Src play fundamental roles in host–pathogen interactions and phagocytosis. Here, Young et al. show that an enteropathogenic Escherichia coli (EPEC) protein, EspJ, inhibits Src activity by simultaneous amidation and ADP ribosylation of a conserved residue on the kinase.

Legionella pneumophila, the causative agent of Legionnaires’ disease, uses the Dot/Icm type IV secretion system (T4SS) to translocate more than 300 effectors into host cells, where they subvert host cell signaling. The function and host cell targets of most effectors remain unknown. PieE is a 69-kDa Dot/Icm effector containing three coiled-coil (CC) regions and 2 transmembrane (TM) helices followed by a fourth CC region. Here, we report that PieE dimerized by an interaction between CC3 and CC4. We found that ectopically expressed PieE localized to the endoplasmic reticulum (ER) and induced the formation of organized smooth ER, while following infection PieE localized to the Legionella-containing vacuole (LCV). To identify the physiological targets of PieE during infection, we established a new purification method for which we created an A549 cell line stably expressing the Escherichia coli biotin ligase BirA and infected the cells with L. pneumophila expressing PieE fused to a BirA-specific biotinylation site and a hexahistidine tag. Following tandem Ni2+ nitrilotriacetic acid (NTA) and streptavidin affinity chromatography, the effector-target complexes were analyzed by mass spectrometry. This revealed interactions of PieE with multiple host cell proteins, including the Rab GTPases 1a, 1b, 2a, 5c, 6a, 7, and 10. Binding of the Rab GTPases, which was validated by yeast two-hybrid binding assays, was mediated by the PieE CC1 and CC2. In summary, using a novel, highly specific strategy to purify effector complexes from infected cells, which is widely applicable to other pathogens, we identified PieE as a multidomain LCV protein with promiscuous Rab GTPase-binding capacity., IMPORTANCE The respiratory pathogen Legionella pneumophila uses the Dot/Icm type IV secretion system to translocate more than 300 effector proteins into host cells. The function of most effectors in infection remains unknown. One of the bottlenecks for their characterization is the identification of target proteins. Frequently used in vitro approaches are not applicable to all effectors and suffer from high rates of false positives or missed interactions, as they are not performed in the context of an infection. Here, we determine key functional domains of the effector PieE and describe a new method to identify host cell targets under physiological infection conditions. Our approach, which is applicable to other pathogens, uncovered the interaction of PieE with several proteins involved in membrane trafficking, in particular Rab GTPases, revealing new details of the Legionella infection strategy and demonstrating the potential of this method to greatly advance our understanding of the molecular basis of infection.

International audience; Purposes. A new methodology to evaluate the medication-use system based on a risk cartography tool, has been developed. This work has been promoted by the Observatoire du medicament et des dispositifs m dicaux steriles et de l'innovation therapeutique (OMEDIT) from Provence- Alpes-Cote d'Azur (PACA)-Corse regions. Methods. This new methodology has been developed with Excel (Microsoft (R)) and has led to the mediEVAL tool. It consists in two categories of Excel files: evaluating Excel files (1 for each job of the medication-use system) and synthesis Excel files which allow to compile a group of evaluating files for a defined area (department, hospital.). Results and conclusion. mediEVAL is a new tool to evaluate quality and risk management of the entire medication-use system which has to be used by private or public hospitals of PACA and Corsica areas in their appropriate medication-use contract. Then, the OMEDIT can get data to provide an inventory of fixtures of the PACA-Corse area medication-use system situation.

BACKGROUND To assess subclavian vein (SCV) patency and long-term functional outcomes following surgical decompression of the thoracic outlet (SDTO) for Paget-Schroetter Syndrome (PSS). METHODS Between January 1978 and January 2013, we identified 33 patients with PSS who underwent SDTO. Demographic, clinical and radiological data were extracted from electronic databases and patient records. All patients were invited to update their follow-up data during dedicated outpatient visits between October and December 2013. Outcome measures included long-term SCV patency and clinical success rates during follow-up. Clinical success was defined as the combined absence of functional symptoms and patient's ability to maintain normal professional activities at final follow-up. The QuickDASH score was also determined. RESULTS The study population comprised 17 men and 16 women (mean age 34 years; range: 14-53 years) with PSS. Diagnosis was reached by venography (29 cases) or duplex scan (4 cases). SDTO was performed via the transaxillary route (25 cases) or using the combined supra-infraclavicular approach (8 cases). The procedure was carried out within 10 days in 13 patients (early-group), and between 30 to 120 days in the remaining 20 patients (late-group). The former had SCV recanalization obtained actively by thrombolysis (3 cases), thrombectomy (9 cases) or endovenectomy followed by patch venoplasty (1 case). The latter were maintained under chronic oral anticoagulation to allow SCV recanalization. There was neither postoperative death nor major bleeding complications. At a median follow-up of 240 months, 11 SCV remained patent in the early group, while in the other there was 3 re-occlusions, 4 residual stenoses and 5 chronic SCV occlusions. Clinical success was achieved in 73% of patients for the whole cohort, but was significantly better in patients operated on in the early stages (100% vs. 55%; P=0.005). The mean Quick Disabilities of the Arm, Shoulder, and Hand Score was 3.5 (95% CI: 1.5-5.4) in the early-group and 17.3 (95% CI: 8.4-26.2) in the late-group (P=0.01). CONCLUSIONS Our data shows that long-term functional outcomes and SCV patency remained better in PSS patients who underwent early SDTO and active SCV recanalization techniques.

The chemokine receptor CCR4 has at least two natural agonist ligands, MDC (CCL22) and TARC (CCL17) which bind to the same orthosteric site with a similar affinity. Both ligands are known to evoke chemotaxis of CCR4-bearing T cells and also elicit CCR4 receptor internalization. A series of small molecule allosteric antagonists have been described which displace the agonist ligand, and inhibit chemotaxis. The aim of this study was to determine which cellular coupling pathways are involved in internalization, and if antagonists binding to the CCR4 receptor could themselves evoke receptor internalization. CCL22 binding coupled CCR4 efficiently to β-arrestin and stimulated GTPγS binding however CCL17 did not couple to β-arrestin and only partially stimulated GTPγS binding. CCL22 potently induced internalization of almost all cell surface CCR4, while CCL17 showed only weak effects. We describe four small molecule antagonists that were demonstrated to bind to two distinct allosteric sites on the CCR4 receptor, and while both classes inhibited agonist ligand binding and chemotaxis, one of the allosteric sites also evoked receptor internalization. Furthermore, we also characterize an N-terminally truncated version of CCL22 which acts as a competitive antagonist at the orthosteric site, and surprisingly also evokes receptor internalization without demonstrating any agonist activity. Collectively this study demonstrates that orthosteric and allosteric antagonists of the CCR4 receptor are capable of evoking receptor internalization, providing a novel strategy for drug discovery against this class of target.

International audience

The karyophilic properties of the human immunodeficiency virus, type I (HIV-1) pre-integration complex (PIC) allow the virus to infect non-dividing cells. To better understand the mechanisms responsible for nuclear translocation of the PIC, we investigated nuclear import of HIV-1 integrase (IN), a PIC-associated viral enzyme involved in the integration of the viral genome in the host cell DNA. Accumulation of HIV-1 IN into nuclei of digitonin-permeabilized cells does not result from passive diffusion but rather from an active transport that occurs through the nuclear pore complexes. HIV-1 IN is imported by a saturable mechanism, implying that a limiting cellular factor is responsible for this process. Although IN has been previously proposed to contain classical basic nuclear localization signals, we found that nuclear accumulation of IN does not involve karyopherins alpha, beta1, and beta2-mediated pathways. Neither the non-hydrolyzable GTP analog, guanosine 5'-O-(thiotriphosphate), nor the GTP hydrolysis-deficient Ran mutant, RanQ69L, significantly affects nuclear import of IN, which depends instead on ATP hydrolysis. Therefore these results support the idea that IN import is not mediated by members of the karyopherin beta family. More generally, in vitro nuclear import of IN does not require addition of cytosolic factors, suggesting that cellular factor(s) involved in this active but atypical pathway process probably remain associated with the nuclear compartment or the nuclear pore complexes from permeabilized cells.

Mireille Mousnier, Dono unum hominem meum. Désignations de la dépendance du XIe au XIIIe siècle en Languedoc occidental, p. 51-60. Le vocabulaire de la dépendance est-il celui, juridiquement opposé, de la liberté et de la servitude? Servus reste absent. La nature de la dépendance est davantage sollicitée. Elle est fondée sur la propriété : Homo s'accompagne de meus, ou d'épithètes proches (proprius); ligius et naturalis insistent sur l'origine (par appartenance au patrimoine, ou par la naissance). Elle est aussi physique : l'expression de corpore bien connue par ailleurs ne devient juridiquement stéréotypée qu'après le milieu du XIIIe siècle. Mais elle a une dimension anthropologique liée sans doute à l'hommage. La dépendance se transmet à la descendance, de manière très biologique : elle est congénitale. Le lien avec le maître est donc fortement personnel. Même la jouissance d'une tenencia le rappelle. Le caractère juridique de la tenure servile n'est apparent qu'avec l'emploi de caselage, fréquent après 1240. La différenciation juridique est nette à la fin du XIIIe siècle entre servage réel et personnel., Mousnier Mireille. Dono unum hominem meum. Désignations de la dépendance du XIe au XIIIe siècle en Languedoc occidental. In: Mélanges de l'École française de Rome. Moyen-Age, tome 111, n°1. 1999. pp. 51-60.

Resume En 47 mois, 162 adultes (85 hommes, 77 femmes, âge moyen : 68 ± 19 ans) et 21 enfants (âge moyen : 6 ± 5 ans) ont ete traites par Alimentation Enterale a Domicile (AED) pendant 231 ± 370 jours (1-1 902 j) pour une pathologie neurologique (44%), digestive (20%), un cancer ORL (13%), une carence d'apport (9%), une pathologie post-traumatique (4%), un SIDA (3%), ou des raisons diverses (7%). Les probabilites de survie a 1 et 5 ans etaient respectivement de 44% et 29%. Pour 19 patients (10,4%, 48 ± 25 ans), l'AED, poursuivie depuis 1 069 ± 558 j, etait definitive. L'etiologie etait le plus souvent neurologique (68%). Chez 51 patients (27,9%, 50 ± 31 ans), l'AED a pu etre stoppee apres 159 ± 174 j grâce a une amelioration. Dans ce groupe, la probabilite de survie a 4 ans etait de 68%. 93 patients (50,8%) sont decedes en cours d'AED, dont 35 (19,1%, 76 ± 16 ans) pendant le premier mois, et 58 (31,7%, 69 ± 21 ans) apres plus d'un mois d'AED (180 ± 166 j). Enfin, chez 20 patients (10,9%, 52 ± 30 ans), l'AED a ete stoppee apres 150 ± 204 j pour des raisons diverses dont 11 (6%) pour rehospitalisation, 6 (3,3%) pour intolerance et 3 (1,6%) pour changement de domicile.

The Dot/Icm type IV secretion system (T4SS) of Legionella pneumophila is crucial for the pathogen to survive in protozoa and cause human disease. Although more than 275 effector proteins are delivered into the host cell by the T4SS, the function of the majority is unknown. Here we have characterized the Dot/Icm effector LtpD. During infection, LtpD localized to the cytoplasmic face of the membrane of the Legionella -containing vacuole (LCV). In A549 lung epithelial cells, ectopically expressed LtpD localized to large vesicular structures that contained markers of endosomal compartments. Systematic analysis of LtpD fragments identified an internal 17-kDa fragment, LtpD 471-626 , which was essential for targeting ectopically expressed LtpD to vesicular structures and for the association of translocated LtpD with the LCV. LtpD 471-626 bound directly to phosphatidylinositol 3-phosphate [PtdIns(3)P] in vitro and colocalized with the PtdIns(3)P markers FYVE and SetA in cotransfected cells. LtpD was also found to bind the host cell enzyme inositol ( myo )-1 (or 4)-monophosphatase 1, an important phosphatase involved in phosphoinositide production. Analysis of the role of LtpD in infection showed that LtpD is involved in bacterial replication in THP-1 macrophages, the larvae of Galleria mellonella , and mouse lungs. Together, these data suggest that LtpD is a novel phosphoinositide-binding L. pneumophila effector that has a role in intracellular bacterial replication.

A new methodology to evaluate the medication-use system based on a risk cartography tool, has been developed. This work has been promoted by the Observatoire du médicament et des dispositifs médicaux stériles et de l'innovation thérapeutique (OMEDIT) from Provence-Alpes-Côte d'Azur (PACA)-Corse regions.This new methodology has been developed with Excel (Microsoft(®)) and has led to the mediEVAL tool. It consists in two categories of Excel files: evaluating Excel files (1 for each job of the medication-use system) and synthesis Excel files which allow to compile a group of evaluating files for a defined area (department, hospital…).mediEVAL is a new tool to evaluate quality and risk management of the entire medication-use system which has to be used by private or public hospitals of PACA and Corsica areas in their appropriate medication-use contract. Then, the OMEDIT can get data to provide an inventory of fixtures of the PACA-Corse area medication-use system situation.

Introduction L’association epilepsie partielle idiopathique et migraine est bien connue dans la litterature mais le lien entre epilepsie–absence et migraine est peu decrit. Nous rapportons trois cas de patientes presentant cette association. Observation Une femme de 28 ans presente une epilepsie–absence depuis l’âge de 9 ans. L’electroencephalogramme montre des anomalies typiques d’absence. Elle decrit des cephalees dont les caracteristiques sont compatibles avec des migraines avec aura visuelle. Une adolescente de 17 ans presente une epilepsie–absence depuis l’âge de 12 ans secondairement associe a des migraines sans aura et complique d’un etat de mal migraineux en 2013. L’epilepsie est bien controlee sous LAMICTAL pour ces deux patientes. Le troisieme cas concerne une enfant de 14 ans presentant depuis l’âge de 10 ans des crises de migraine avec aura visuelle a type d amaurose et phosphene. Dans ces antecedents familiaux on note un oncle decede au decours d’une crise d’epilepsie. Le premier EEG montrait des bouffees de pointes et polypointes ondes generalisees a predominance anterieure, faisant evoquer le diagnostique d’epilepsie. Un traitement par TEGRETOL avait ete introduit en 2012 devant une crise generalisee. En 2013, des absences etaient notees et un EEG montrait des pointes ondes generalisees, le diagnostic d’epilepsie–absence est pose. Discussion Des mutations des canaux calciques ont ete decrites chez des modeles murins atteints d’une epilepsie-absence. Ces mutations des canaux calciques sont egalement a l’origine des formes familiales de migraine et pourrait rentrer dans le cadre d’une canalopathie cerebrale. L’association epilepsie–absence–migraine ne serait donc pas une simple comorbidite. Conclusion L’association epilepsie-absence de l’adolescent et migraine est peu connue et necessite des etudes complementaires. L’hypothese d’une canalopathie cerebrale primitive est evoquee pour expliquer cette association. Informations complementaires Numero de dossier : 000355246, 1065579, 1393316.

Introduction Nous rapportons le cas d’un patient presentant une epilepsie temporale atypique ainsi que deux variants heterozygotes reputes pathogenes du gene polymerase gamma (POLG). Observation Ce patient de 37 ans, ayant comme antecedents une epilepsie–absence a 4 ans et une epilepsie–absence precoce chez sa fille, a consulte pour une symptomatologie stereotypee : perplexite, perseverations phasiques et ideatoires. L’examen neurologique etait normal. L’EEG montrait une activite de fond normale surchargee d’ondes lentes pointues, diffuses, bifrontales, rythmiques ou pseudo-periodiques. La videoEEG prolongee montrait d’abondantes decharges, de 20 minutes a 1 heure, stereotypees, composees d’ondes lentes rythmiques theta, initialement temporales gauches, evoluant vers des ondes lentes pointues des regions bifrontales laissant place a des ondes lentes triphasiques puis a un aspect de burst suppression . Ces decharges sont concomitantes de troubles de la concentration, de la comprehension, d’un langage reduit, de perseverations. La neuroimagerie et la lactatorachie etaient normales. Deux variants heterozygotes reputes pathogenes du gene POLG ont ete revelees : c.752C>T (p.thre251ile) et c.1760C>T (p.pro587leu). Les mutations ont ete retrouvees chez sa mere asymptomatique mais pas chez sa fille. Plusieurs medicaments antiepileptiques ont ete prescrits, sans succes. Discussion Dans les mutations POLG, l’epilepsie est habituellement a type de crises generalisees tonicocloniques, de crises partielles motrices et occipitales, de myoclonies et d’etats de mal. Le phenotype decrit est rare avec des crises temporales atypiques, paucisymptomatiques, prolongees, refractaires. Il peut etre lie aux mutations POLG, a confirmer par une analyse moleculaire par exome etant donne l’absence de segregation familiale. Conclusion L’imputabilite des variants POLG retrouves chez ce patient reste a prouver. Cependant, la suspicion d’une mitochondriopathie contre-indique le valproate, ce dernier etant a risque d’entrainer une insuffisance hepatique fatale.

Cet article presente une typologie et une problematique du recensement des sources du patrimoine industriel aux Antilles qui permet d'approcher la complexite de la realite domaniale des habitations sucrieres. Les aspects presentes ici ont ete rassembles dans le cadre d'un programme de recherches sur l'archeologie industrielle aux Antilles. Ces travaux ont montres la diversite des sources et une grille d'analyse peut se degager de cette analyse. En fonction des donnees recoltees il est peut-etre possible de parvenir a certains resultats : typologie de la documentation, methodologie d'exploitation, problematique

The translocation of effector proteins by the Dot/Icm type IV secretion system is central to the ability of Legionella pneumophila to persist and replicate within eukaryotic cells. The subcellular localization of translocated Dot/Icm proteins in host cells provides insight into their function. Through co-staining with host cell markers, effector proteins may be localized to specific subcellular compartments and membranes, which frequently reflects their host cell target and mechanism of action. In this chapter, we describe protocols to (1) localize effector proteins within cells by ectopic expression using green fluorescent protein fusions and (2) localize effector proteins within infected cells using epitope-tagged effector proteins and immuno-fluorescence microscopy.

Translocation of effector proteins via a type III secretion system (T3SS) is a widespread infection strategy among Gram-negative bacterial pathogens. Each pathogen translocates a particular set of effectors that subvert cell signaling in a way that suits its particular infection cycle. However, as effector unbalance might lead to cytotoxicity, the pathogens must employ mechanisms that regulate the intracellular effector concentration. We present evidence that the effector EspZ controls T3SS effector translocation from enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli. Consistently, an EPEC espZ mutant is highly cytotoxic. Following ectopic expression, we found that EspZ inhibited the formation of actin pedestals as it blocked the translocation of Tir, as well as other effectors, including Map and EspF. Moreover, during infection EspZ inhibited effector translocation following superinfection. Importantly, while EspZ of EHEC O157:H7 had a universal “translocation stop” activity, EspZ of EPEC inhibited effector translocation from typical EPEC strains but not from EHEC O157:H7 or its progenitor, atypical EPEC O55:H7. We found that the N and C termini of EspZ, which contains two transmembrane domains, face the cytosolic leaflet of the plasma membrane at the site of bacterial attachment, while the extracellular loop of EspZ is responsible for its strain-specific activity. These results show that EPEC and EHEC acquired a sophisticated mechanism to regulate the effector translocation., IMPORTANCE Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are important diarrheal pathogens responsible for significant morbidity and mortality in developing countries and the developed world, respectively. The virulence strategy of EPEC and EHEC revolves around a conserved type III secretion system (T3SS), which translocates bacterial proteins known as effectors directly into host cells. Previous studies have shown that when cells are infected in two waves with EPEC, the first wave inhibits effector translocation by the second wave in a T3SS-dependent manner, although the factor involved was not known. Importantly, we identified EspZ as the effector responsible for blocking protein translocation following a secondary EPEC infection. Interestingly, we found that while EspZ of EHEC can block protein translocation from both EPEC and EHEC strains, EPEC EspZ cannot block translocation from EHEC. These studies show that EPEC and EHEC employ a novel infection strategy to regulate T3SS translocation.

The translocation of effector proteins by the Dot/Icm type IV secretion system is central to the ability of Legionella pneumophila to persist and replicate within eukaryotic cells. The subcellular localization of translocated Dot/Icm proteins in host cells provides insight into their function. Through co-staining with host cell markers, effector proteins may be localized to specific subcellular compartments and membranes, which frequently reflects their host cell target and mechanism of action. In this chapter, we describe protocols to (1) localize effector proteins within cells by ectopic expression using green fluorescent protein fusions and (2) localize effector proteins within infected cells using epitope-tagged effector proteins and immuno-fluorescence microscopy.

Objectives The objective is to report our results with the arm composite autogenous vascular access (ACAVA) using the great saphenous vein (GSV) and the femoral vein (FV) in tertiary vascular access surgery. Design Retrospective single-centre study. Prospectively collected clinical database. Methods Between August 2009 and March 2011, 17 patients with no suitable upper extremity vein, repeated prosthetic access failure and/or infection underwent the construction of an ACAVA. Outcome measures included the graft patency and complication rates. Results The median follow-up was 25 months (5–32). Thirty-day morbidity affected 10 patients (59%): four wound-healing issues, three lower limb swelling, two early thromboses and one upper limb haematoma. No postoperative death occurred. At 3 months, the primary patency rate was 88% ± 8%. At 6 months, the assisted-primary patency rate was 82.4% ± 9.2%. At 12 months, the secondary patency rate was 81.6% ± 9.6%. Twenty-four secondary interventions were performed. Steal syndrome occurred in one patient following a secondary procedure. Swelling of the lower limb remained in two patients at the end of their follow-up. Three ACAVAs developed irreversible occlusion leading to loss of access. Conclusion With a high rate of postoperative morbidity and re-intervention, the ACAVA is a useful additional technique that should be restricted to difficult cases with limited vascular access options.

We report the case of a child with isolated late-onset epileptic spasms who significantly improved after focal frontal cortectomy. Clusters of axial and limb tonic contractions with head nodding began at 2 years of age. They occurred only during sleep, lasting 15 to 20 minutes and were pharmacoresistant. The child suffered slight mental delay. Interictal EEG showed left frontal spikes in slow sleep. Ictal video-EEG showed patterns of asymmetric spasms. MRI revealed a distinct white matter abnormality in the left frontal superior gyrus, corresponding clearly to localised cortical hypometabolism on FDG-PET and PET-MRI co-recording. SEEG investigation showed that the first spasm of the clusters corresponded to a localised discharge of rapid rhythms from the electrodes placed within the area identified as a lesion by MRI. Discharges then became more diffuse across the left frontal and temporal electrodes throughout the duration of the cluster. A tailored focal frontal resection was performed at 16 years of age. Spasms were very rare during the following three years (Engel class II). This observation illustrates the fact that isolated epileptic spasms can be cured by focal cortical resection despite a lack of clearly localised EEG surface anomalies.

Resume L'objectif de ce travail bibliographique est de reunir les arguments en faveur de l'implication des canaux ioniques potentiel-dependants dans l'epileptogenese. Bien qu'aucune etude n'ait encore montre que l'epilepsie s'accompagne d'une modification de ces canaux, la connaissance, relativement recente, de leur physiologie laisse presager qu'ils puissent etre impliques dans l'epileptogenese. Les resultats de l'approche electrophysiologique sont les suivants: le courant sodium persistant permet d'accroitre l'excitabilite neuronale tandis que les courants potassium ont un role inhibiteur. Les courants potassium calcium-dependants interviennent notamment dans la phase de posthyperpolarisation succedant aux PDS. Les courants calcium sont impliques dans la genese de l'activite bursting pace-maker presentee par les neurones initiateurs presumes de l'activite epileptique. L'approche biochimique a montre qu'il existait une sous-regulation des canaux sodium et calcium consecutive a l'activite epileptique. Cette sous-regulation representerait un mecanisme compensateur de l'hyperexcitabilite neuronale. L'approche pharmacologique met en evidence d'une part, que les substances activant les canaux calcium ou inhibant les canaux potassium ont un effet convulsivant. A l'inverse, les agents bloquant les canaux calcium ou les canaux sodium ou activant les canaux potassium ont des proprietes anticonvulsivantes. Parmi ces derniers, se trouvent certains medicaments antiepileptiques. En resume, cette etude fait apparaitre que les situations susceptibles d'accroitre les courants calcium, sodium et/ou d'inhiber les courants potassium sont potentiellement epileptogenes.

The prescription drug for hypertension in children remains difficult because of the lack of pharmacological data validated for this age of life. The Food and Drug Administration (FDA) has recently proposed some antihypertensive regimens orally. The authors found it useful to reproduce a table by adding all the necessary data for its use in France. Here is a list of French medicines and doses applied to children. Similarly, they made a second table for injectable antihypertensive treatment based on American recommendations--but not yet validated by FDA.

International audience; La vision actuelle de la performance hospitalière est large et porte sur les volets économique - coût de la santé, qualitatif - qualité des activités cliniques et scientifique - avancées technologiques. Les établissements de santé, comme toute organisation, doivent être pilotés, c'est-à-dire que des personnes doivent être capables de décider et de mettre en oeuvre de manière efficiente et à bon escient des ressources, des moyens et des activités pour fournir des services reconnus d'intérêt par une clientèle exigeante. Ce pilotage nécessite plus que jamais des indicateurs adaptés et fiables. Le circuit du médicament est un processus de soins transversal par excellence, mal maîtrisé aujourd'hui, qui correspond à un système complexe, à risque spécifique. Le but de cet article est de décrire et de présenter une application d'une approche multidimensionnelle, intégrant les volets « qualité – risques – évaluation des pratiques professionnelles », de pilotage de la performance du circuit du médicament hospitalier.

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Mousnier Mireille. L'appropriation de l'espace dans les campagnes toulousaines aux XIIe et XIIIe siècle. In: Annales du Midi : revue archéologique, historique et philologique de la France méridionale, Tome 102, N°189-190, 1990. Cadre de vie et société dans le Midi médiéval : hommage à Charles Higounet. pp. 137-148.

Typical enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) employ either Nck, TccP/TccP2, or Nck and TccP/TccP2 pathways to activate the neuronal Wiskott-Aldrich syndrome protein (N-WASP) and to trigger actin polymerization in. cultured cells. This phenotype is used as a marker for the pathogenic potential of EPEC and EHEC strains. in this paper we report that EPEC O125:H6, which represents a large category of strains, lacks the ability to utilize either Nck or TccP/TccP2 and hence triggers actin polymerization in vitro only inefficiently. However, we show that infection of human intestinal biopsies with EPEC O125:H6 results in formation of typical attaching and effacing lesions. Expression of TccP in EPEC O125:H6, which harbors an EHEC O157-like Tir, resulted in efficient actin polymerization in vitro and enhanced colonization of human intestinal in vitro organ cultures with detectable N-WASP and electron-dense material at the site of bacterial adhesion. These results show the existence of a natural category of EPEC that colonizes the gut mucosa using Nck- and TccP-independent mechanisms. Importantly, the results highlight yet again the fact that conclusions made on the basis of in vitro cell culture models cannot be extrapolated wholesale to infection of mucosal surfaces and that the ability to induce actin polymerization on cultured cells should not be used as a definitive marker for EPEC and EHEC virulence. Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London SW7 2AZ, England China CDC, Natl Inst Communicable Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Beijing, Peoples R China UCL Royal Free Univ Coll Med Sch, Ctr Paediat Gastroenterol, London, England Miyazaki Univ, Frontier Sci Res Ctr, Div Bioenvironm Sci, Miyazaki 8891692, Japan Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil Web of Science

A four-year-old boy with ring chromosome 17 presenting with early-onset, pharmacoresistant epilepsy underwent repeated 24-hour video-EEG monitoring and cytogenetic analyses, including fluorescent in situ hybridization with telomeric and locus-specific probes of chromosome 17. Epilepsy was characterized by nocturnal motor seizures and by prolonged diurnal electrical status epilepticus. The 46, XY, r (17) karyotype was observed in the majority of cell lines. Fluorescent in situ hybridization revealed a deletion at the 17p telomere on the ring chromosome, whereas the 17q telomere and the Miller-Dieker lissencephaly locus were undeleted. The epileptic syndrome observed in this case of ring chromosome 17 resembles the one described in the ring chromosome 20 syndrome, raising the question of the specificity and the pathogenesis of ring chromosome epileptic syndromes. [Published with videosequences].

L'organisation defensive des communautes d'habitants s'inscrit dans un dispositif coutumier fort revelateur. En apparence, la guerre et les operations militaires n'ont laisse qu'une tres faible empreinte sur la construction normative des textes, comme si les choses les plus evidentes etaient laissees dans l'implicite. Au premier plan, en revanche, les fortifications et le guet sont l'objet d'enjeux multiples et de traitements differencies qui sont autant d'enseignements importants pour la sociologie et l'archeologie des villages meridionaux dans la seconde moitie du Moyen Âge. Dans cette rhetorique, l'enceinte, les portes et les fortifications apparaissent dotees de valeurs tres distinctes. La cloture, en particulier, parait definir un espace de sociabilite a l'abri des abus seigneuriaux, un espace mis en pratique dans l'organisation collective du guet, operation de police autant que de guerre. Mais plus encore peut-etre, la corvee d'entretien des fortifications, remparts et fosses, semble au coeur de la contrainte communautaire. Articulee par la notion de voisinage (beziau), elle dit a quel point la communaute se construit et se reconstruit en construisant et reconstruisant ses murs. Le rempart de la coutume, en reamenagements constants, pese en definitive plus sur les relations sociales qu'il n'a de valeur strategique.