Pathogenesis of vestibular schwannoma in ring chromosome 22

<p>Abstract</p> <p>Background</p> <p>Ring chromosome 22 is a rare human constitutional cytogenetic abnormality. Clinical features of neurofibromatosis type 1 and 2 as well as different tumour types have been reported in patients with ring chromosome 22. The pathogenesis of these tumours is not always clear yet.</p> <p>Methods</p> <p>We report on a female patient with a ring chromosome 22 presenting with severe mental retardation, autistic behaviour, café-au-lait macules and facial dysmorphism. Peripheral blood lymphocytes were karyotyped and array CGH was performed on extracted DNA. At the age of 20 years she was diagnosed with a unilateral vestibular schwannoma. Tumour cells were analyzed by karyotyping, array CGH and <it>NF2 </it>mutation analysis.</p> <p>Results</p> <p>Karyotype on peripheral blood lymphocytes revealed a ring chromosome 22 in all analyzed cells. A 1 Mb array CGH experiment on peripheral blood DNA showed a deletion of 5 terminal clones on the long arm of chromosome 22. Genetic analysis of vestibular schwannoma tissue revealed loss of the ring chromosome 22 and a somatic second hit in the <it>NF2 </it>gene on the remaining chromosome 22.</p> <p>Conclusion</p> <p>We conclude that tumours can arise by the combination of loss of the ring chromosome and a pathogenic <it>NF2 </it>mutation on the remaining chromosome 22 in patients with ring chromosome 22. Our findings indicate that patients with a ring 22 should be monitored for NF2-related tumours starting in adolescence.</p

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Pseudomonas aeruginosa Population Structure Revisited

At present there are strong indications that Pseudomonas aeruginosa exhibits an epidemic population structure; clinical isolates are indistinguishable from environmental isolates, and they do not exhibit a specific (disease) habitat selection. However, some important issues, such as the worldwide emergence of highly transmissible P. aeruginosa clones among cystic fibrosis (CF) patients and the spread and persistence of multidrug resistant (MDR) strains in hospital wards with high antibiotic pressure, remain contentious. To further investigate the population structure of P. aeruginosa, eight parameters were analyzed and combined for 328 unrelated isolates, collected over the last 125 years from 69 localities in 30 countries on five continents, from diverse clinical (human and animal) and environmental habitats. The analysed parameters were: i) O serotype, ii) Fluorescent Amplified-Fragment Length Polymorphism (FALFP) pattern, nucleotide sequences of outer membrane protein genes, iii) oprI, iv) oprL, v) oprD, vi) pyoverdine receptor gene profile (fpvA type and fpvB prevalence), and prevalence of vii) exoenzyme genes exoS and exoU and viii) group I pilin glycosyltransferase gene tfpO. These traits were combined and analysed using biological data analysis software and visualized in the form of a minimum spanning tree (MST). We revealed a network of relationships between all analyzed parameters and non-congruence between experiments. At the same time we observed several conserved clones, characterized by an almost identical data set. These observations confirm the nonclonal epidemic population structure of P. aeruginosa, a superficially clonal structure with frequent recombinations, in which occasionally highly successful epidemic clones arise. One of these clones is the renown and widespread MDR serotype O12 clone. On the other hand, we found no evidence for a widespread CF transmissible clone. All but one of the 43 analysed CF strains belonged to a ubiquitous P. aeruginosa “core lineage” and typically exhibited the exoS+/exoU− genotype and group B oprL and oprD alleles. This is to our knowledge the first report of an MST analysis conducted on a polyphasic data set

Faire résonner politique et ontologie du changement. Comment passer d’une politique du changement à une relation ontologique au changement

peer reviewedLe basculement dans l’anthropocène appelle à accélérer « le » changement : transformer les pratiques et les modes de vie ou encore les relations aux autres vivants Une tension se manifeste dès lors entre l’ambition d’opérer des changements attendus, efficacement et amplement, et celle de co-construire des solutions inédites résultant d’une transformation, non plus de mode d’habiter généraux mais bien de relations situées. La capacité de collectif à faire des choix politiques et socio-techniques transformatifs est interrogées : comment faire entrer en résonance l’injonction de changement ambitieux avec une réalité complexe et ancrée ? Rassembler de façon large des acteurs dans des processus de type participatif (forum, agora, etc.) peut entrer en effet en conflit avec rassembler qualitativement et de façon inclusive : les deux voies nourrissant deux formes différentes de légitimité scientifique et politique. Cette proposition est traitée à travers l’analyse et les conclusions tirées de l’expérience transdisciplinaire TRIAL menée par l’équipe de chercheurs du SEED de 2019 à 2021. Celle- ci s’inscrit dans un enjeu majeur de l’anthropocène : celui de l’évolution de la forêt et en conséquence de la gestion de sa biodiversité. Elle visait concrètement, dans un cadre réglementaire spécifique définit à l’échelle politique régionale, à mettre en place à animer une agora citoyenne. Celle-ci était chargée de nourrir en propositions et de « colorer d’un point de vue citoyen" un master plan pour un projet inédit, le projet Nassonia, de partenariat public/privé entre l’administration wallonne et une Fondation. Ce Master plan a défini le cadre de la gestion « différentiée » de 1500 hectares, au sein de la plus grande forêt belge, a un horizon de quatre fois vingt ans autour de quatre thématiques : la naturalité, le tourisme, l’économie et la gouvernance. Sans chercher à trancher, nous montrons comment différentes relations ontologiques au changement en tension ont co-existé. Nous en défendons le caractère expérimental et notamment l’enjeu et la difficulté de passer d’une politique du changement à une relation ontologique au changement.15. Life on land17. Partnerships for the goals16. Peace, justice and strong institution

Effect of methylergobasine maleate on serum gonadotrophin and prolactin in humans

Intramuscular injection of 0.2 methylergobasine maleate (Methergin, Sandoz) in women on day 3 post partum, in regularly menstruating women and in adult men, is followed within 30 to 75 min by a 50% decrease in serum prolactin concentration: the levels remain low until 180 min and increase between 180 and 240 min. The amplitude of the decrease is the same when prolactin is measured in terms of the same serum prolactin standard by a homologous ovine assay and by a homologous human assay. However, in the case of regularly menstruating women and of men serum prolactin concentration is some three times higher when estimated by the ovine assay than when estimated by the human assay. This difference between assay results obtained by the two radioimmunoassay methods could be due to heterogeneity of serum prolactin. However, non specific effects of serum are not excluded. In regularly menstruating women and in men, intramuscular injection of 0.2 mg methylergobasine maleate is followed within 45 to 75 min by a 50% decrease in immunoreactive serum LH concentration without concomitant change in immunoreactive FSH. The depression of LH secretion lasts for 1 to 2 h. The circulating levels of HCG in post partum women are not modified after intramuscular injection of Methergin. In humans as in animals and in in vitro studies, inhibition of prolactin and LH release induced by ergot drugs are likely due to both an indirect effect via the hypothalamus and to a direct effect on the pituitary cells.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Pyocin S2 (Sa) Kills Pseudomonas aeruginosa Strains via the FpvA Type I Ferripyoverdine Receptor▿ †

Soluble (S-type) pyocins are Pseudomonas aeruginosa bacteriocins that kill nonimmune P. aeruginosa strains via a specific receptor. The genes coding for pyocin Sa (consisting of a killing protein and an immunity protein) were cloned and expressed in Escherichia coli. Sequence analysis revealed that Sa is identical to pyocin S2. Seventy-nine strains of P. aeruginosa were tested for their sensitivity to pyocins S1, S2, and S3, and their ferripyoverdine receptors were typed by multiplex PCR. No strain was found to be sensitive to both S2 and S3, suggesting that the receptors for these two pyocins cannot coexist in one strain. As expected, all S3-sensitive strains had the type II ferripyoverdine receptor fpvA gene, confirming our previous reports. S1 killed strains irrespective of the type of ferripyoverdine receptor they produced. All S2-sensitive strains had the type I fpvA gene, and the inactivation of type I fpvA in an S2-sensitive strain conferred resistance to the S2 pyocin. Accordingly, complementation with type I fpvA in trans restored sensitivity to S2. Some S2-resistant type I fpvA-positive strains were detected, the majority (all but five) of which had the S1-S2 immunity gene. Comparison of type I fpvA sequences from immunity gene-negative S2-sensitive and S2-resistant strains revealed only a valine-to-isoleucine substitution at position 46 of type I FpvA. However, both type I fpvA genes conferred the capacity for type I pyoverdine utilization and sensitivity to S2. When these two type I fpvA genes were introduced into strain 7NSK2 carrying mutations in type II fpvA (encoding the type II pyoverdine receptor) and fpvB (encoding the alternative type I receptor), growth in the presence of type I pyoverdine was observed and the strain became sensitive to S2. We also found that type I pyoverdine could signal type II pyoverdine production via the type I FpvA receptor in 7NSK2

Elusive Lambda. Co-construction and cooperation of skills in a forest participation project

peer reviewedQui peut prétendre au statut de “citoyen lambda” dans un processus participatif ? Quelles sont les attentes des acteurs - scientifiques, politiques, ou autres - qui font appel à lui ? Dans quelles conditions des individus peuvent l’incarner et quels effets peuvent-elles avoir sur leurs compétences ou sur la reconnaissance et la valorisation de celles-ci ? Nous abordons ces questions dans une démarche réflexive par le biais d’une analyse a posteriori d’une expérience de recherche action participative mise en place dans le cadre d’un projet de recherche transdisciplinaire. Notre approche s’inscrit dans une logique de compétences dynamiques, relationnelles, situées et distribuées entre les citoyens mobilisés et les autres acteurs du projet, dont des chercheurs. Sur un territoire marqué par une longue tradition de gestion de l’environnement confiée à une administration soutenue par des experts scientifiques, un dispositif de participation innovant est invoqué pour co-construire une vision de la gestion durable d’un territoire forestier nourrie de propositions citoyennes. Nous analysons les différentes étapes de ce projet participatif, de la sélection d’un mini-public par tirage au sort, à la mise en délibération du résultat de leur travail, en passant par la constitution progressive des citoyens en collectif informé et susceptible d’utiliser sa légitimé pour modifier les équilibres et les jeux d’acteurs sur le territoire.Who can claim the status of "ordinary citizen" in a participatory process? What are the expectations of the actors - scientific, political or others - who call upon it? Under what conditions can individuals embody it and what effects can they have on their skills or on the recognition and valorisation of these skills? We address these questions in a reflexive way through an a posteriori analysis of a participatory action research experience set up in the framework of a transdisciplinary research project. Our approach is based on a logic of dynamic, relational, situated and distributed competences between the mobilised citizens and the other actors of the project, including the researchers. In a territory marked by a long tradition of environmental management entrusted to an administration supported by scientific experts, an innovative participation mechanism is invoked to co-construct a vision of the sustainable management of a forest territory nourished by citizen proposals. We analyse the different stages of this participatory project, from the selection of a mini-public by drawing lots, to the deliberation of the result of their work, through the gradual constitution of the citizens as an informed collective likely to use its legitimacy to modify the balances and games of actors on the territory MOTS-CLÉS. Compétences, Méthodologie, Participation, Transformations environnementales, Tirage au sort. KEYWORDS. Skills, Methodology, Participation, Environmental transformations, Random draw.Quelle science écocitoyenne pour un territoire durable?13. Climate action15. Life on land17. Partnerships for the goals16. Peace, justice and strong institution

Ataxie sensitive par axonopathie centrale.

Sensory ataxia with central axonopathy. A case of sensory ataxia of undefined origin is described and the differential diagnosis is discussed. The originality of the case lies in the fact that the nerve sensory potentials are preserved whereas the medullary and cortical somesthesic potentials no longer exist. This situates the pathological process in the central axon of the sensory ganglion, as in tabes or clioquinol poisoning.SCOPUS: ar.jinfo:eu-repo/semantics/publishe