Jeux D'échelles. Une Histoire Internationale

International audienceLe livre, paru en 1996 sous la direction de Jacques Revel, a été traduit en Italie en 2006 par les éditions de la Viella sous le titre . Cette occasion a semblé propice à un retour historiographique et épistémologique sur l'expérience microhistorique entre la France et l'Italie. Il s'agit d'entrecroiser les réflexions d'un historien français et d'un philosophe italien, pour chercher à mettre en évidence, à distance, les présupposés théoriques de la microhistoire, et à mesurer les déplacements opérés

Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 mu g/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 mu g/l, P = 0.0004; itself higher than the normal level (3.4 mu g/l, range from 0.5 to 17.2 mu g/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level >= 7 mu g/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels >= 7 mu g/l is 46%. Therefore, selection of patients with an AFP level above 7 mu g/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy

EIF4G1 in familial Parkinson's disease: pathogenic mutations or rare benign variants?

International audienceMutations in the eukaryotic translation initiation factor 4-gamma (EIF4G1) gene, encoding a component of the eIF4F translation initiation complex, were recently reported as a possible cause for the autosomal dominant form of Parkinson's disease (PD). Here, we describe the screening of all 31 EIF4G1 coding exons in a series of 251 index cases with autosomal dominant PD, mostly of French origin and in 236 European control subjects. We identified 12 rare coding variants (either nonsynonymous amino acid substitutions or in frame deletions/insertions), including 6 variants present only in cases and 3 in controls. Segregation was possible only for 1 variant (p.E462delInsGK) that was found in 2 affected siblings. In addition, we found 2 previously reported pathogenic variants in 2 isolated patients (p.G686C) and in a control subject (p.R1197W). These data do not support the pathogenicity of several EIF4G1 variants in PD, at least in the French population

Recommendations for the detection and diagnosis of Niemann-Pick disease type C: An update.

PURPOSE OF REVIEW: Niemann-Pick disease type C (NP-C) is a neurovisceral disorder that may be more prevalent than earlier estimates. Diagnosis of NP-C is often delayed; a key aim for clinical practice is to reduce this delay. Recently, substantial progress has been made in the field of NP-C screening and diagnosis, justifying an update to the existing recommendations for clinical practice. RECENT FINDINGS: New biomarker profiling and genetic analysis technologies are included as first-line diagnostic tests for NP-C. Most diagnoses can now be confirmed by combination of biomarker and genetic analyses. Filipin staining may facilitate diagnosis in uncertain cases. Recommendations are provided for psychiatrists, neuro-ophthalmologists, and radiologists, and on screening within specific at-risk patient cohorts. The NP-C diagnostic algorithm has been updated and simplified. SUMMARY: This publication provides expert recommendations for clinicians who may see patients presenting with the signs and symptoms of NP-C, including general practitioners, pediatricians, neurologists, and psychiatrists

Le savoir et le gouvernement. À propos du livre de Samantha Kelly, The New Solomon. Robert of Naples (1309-1343) and Fourteenth-Century Kingship, Brill, Leiden-Boston, 2003 (The Medieval Mediterranean, vol. 48)

Une partie de l’historiographie des vingt dernières années a été marquée par un « retour de l’histoire politique », dont cependant la méthode et les fruits n’apparaissent pas toujours clairement dans l’actualité des études médiévales, sinon sous la forme d’une alternative entre l’analyse de « représentations » souvent directement issues des « mentalités » en vogue dans les années 1970, et la réhabilitation très traditionnelle de l’histoire événementielle et institutionnelle. Cela ne signifie ..

L’historien au pays des merveilles ?

RésuméLes liens entre anthropologie et histoire, qui ont été très forts depuis les années 1960, semblent parfois se distendre depuis deux décennies. À partir d’un point de vue localisé, celui d’un historien des derniers siècles du Moyen Âge, cet article cherche à s’interroger sur la réalité actuelle des formes d’échange scientifique entre les deux disciplines. Tout en rappelant l’importance de l’anthropologie historique et des objets de recherche partagés par les historiens et les anthropologues, il cherche à mettre en évidence une autre perspective de travail, en montrant comment les interrogations des anthropologues sur l’historicité, sur la forme et le statut de l’information recueillie durant leur travail de terrain, ou sur leur propre engagement subjectif par rapport à ce terrain, offrent aux historiens, qui sont confrontés à des questionnements parallèles, des ressources nouvelles pour prolonger la fécondité des échanges interdisciplinaires.Historians in Wonderland ?The links between anthropology and history have been very tight since the 1960s but seem to have loosened during the past two decades. From a very « localized » viewpoint as a historian of the latter part of the Middle Ages, questions are raised about the current reality of forms of scientific exchanges between these two disciplines. While recalling the importance of historical anthropology and of subjects of research shared by historians and anthropologists, another perspective of work is opened by showing how anthropologists’ interrogations about historicity, the form and status of the information gathered during fieldwork, or about their own subjective commitments in relation to the field, provide historians, who face parallel interrogations, with new resources for fertilizing multidisciplinary exchanges

Satan, Descartes et Kantorowicz

Comme dans beaucoup d’autres livres d’Alain Boureau, il règne dans Satan hérétique une atmosphère énigmatique, un air d’enquête policière ; une telle impression de lecture ne peut qu’éveiller la curiosité du lecteur, peu habitué à passer sans transition du Moyen Âge à Conan Doyle, et le pousser à comprendre son origine. Ce parfum d’étrangeté semble le fruit de principes de construction repris de livre en livre : le choix de sujets singuliers et apparemment ponctuels, tant dans la thématique q..

Le nom Machiavel

Le hasard, qui gouverne un peu plus de la moitié de nos actions, a mis sur les étals des librairies de l’automne 2008 deux livres voisins, voire cousins, Léonard et Machiavel de l’historien Patrick Boucheron et Le rêve de Machiavel du romancier Christophe Bataille . En découvrant ces deux livres, la première impression est d’avoir affaire à deux projets opposés, des procédés littéraires au service d’un discours historique chez Boucheron là où, chez Bataille, ce serait le contraire. Mais rapid..

Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7

Objective : We took advantage of a large multinational recruitment to delineate genotype-phenotype correlations in a large, trans-European multicenter cohort of patients with spastic paraplegia gene 7 (SPG7). Methods : We analyzed clinical and genetic data from 241 patients with SPG7, integrating neurologic follow-up data. One case was examined neuropathologically. Results : Patients with SPG7 had a mean age of 35.5 +/- 14.3 years (n = 233) at onset and presented with spasticity (n = 89), ataxia (n = 74), or both (n = 45). At the first visit, patients with a longer disease duration (> 20 years, n = 62) showed more cerebellar dysarthria (p < 0.05), deep sensory loss (p < 0.01), muscle wasting (p < 0.01), ophthalmoplegia (p < 0.05), and sphincter dysfunction (p < 0.05) than those with a shorter duration (< 10 years, n = 93). Progression, measured by Scale for the Assessment and Rating of Ataxia evaluations, showed a mean annual increase of 1.0 +/- 1.4 points in a subgroup of 30 patients. Patients homozygous for loss of function (LOF) variants (n = 65) presented significantly more often with pyramidal signs (p < 0.05), diminished visual acuity due to optic atrophy (p < 0.0001), and deep sensory loss (p < 0.0001) than those with at least 1 missense variant (n = 176). Patients with at least 1 Ala510Val variant (58%) were older (age 37.6 +/- 13.7 vs 32.8 +/- 14.6 years, p < 0.05) and showed ataxia at onset (p < 0.05). Neuropathologic examination revealed reduction of the pyramidal tract in the medulla oblongata and moderate loss of Purkinje cells and substantia nigra neurons. Conclusions : This is the largest SPG7 cohort study to date and shows a spasticity-predominant phenotype of LOF variants and more frequent cerebellar ataxia and later onset in patients carrying at least 1 Ala510Val variant

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al