Problèmes de psychologie collective

L'auteur passe en revue les théories classiques de la psychologie collective. Aux thèses de la psychologie des foules (Tarde, Le Bon) qui s'appuient sur les notions d'unité mentale et de contagion, il oppose les résultats de la psychologie des phénomènes de masse : mise en évidence de séquences régulières de comportement (cas de lynchages, catastrophes), étude des variations sociologiques et quantitatives des populations. Il évoque plus brièvement les théories de l'opinion publique et de l'information collective avant 1960

Atypical Retinal Phenotype in a Patient With Alström Syndrome and Biallelic Novel Pathogenic Variants in ALMS1, Including a de novo Variation

Alström syndrome (ALMS) is a rare autosomal recessive multi-organ syndrome considered to date as a ciliopathy and caused by variations in ALMS1. Phenotypic variability is well-documented, particularly for the systemic disease manifestations; however, early-onset progressive retinal degeneration affecting both cones and rods (cone-rod type) is universal, leading to blindness by the teenage years. Other features include cardiomyopathy, kidney dysfunction, sensorineural deafness, and childhood obesity associated with hyperinsulinemia and type 2 diabetes mellitus. Here, we present an unusual and delayed retinal dystrophy phenotype associated with ALMS in a 14-year-old female, with affected cone function and surprising complete preservation of rod function on serial electroretinograms (ERGs). High-throughput sequencing of the affected proband revealed compound heterozygosity with two novel nonsense variations in the ALMS1 gene, including one variant of de novo inheritance, an unusual finding in autosomal recessive diseases. To confirm the diagnosis in the context of an unusually mild phenotype and identification of novel variations, we demonstrated the biallelic status of the compound heterozygous variations (c.[286C > T];[1211C > G], p.[(Gln96*)];[(Ser404*)]). This unique case extends our knowledge of the phenotypic variability and the pathogenic variation spectrum in ALMS patients

Identification and Characterization of Known Biallelic Mutations in the IFT27 (BBS19) Gene in a Novel Family With Bardet-Biedl Syndrome

Bardet-Biedl syndrome (BBS; MIM 209900) is a rare ciliopathy characterized by retinitis pigmentosa, postaxial polydactyly, obesity, hypogonadism, cognitive impairment and kidney dysfunction. Mutations in 22 BBS genes have been identified to cause the disease. We report a family with typical BBS features (retinitis pigmentosa, postaxial polydactyly, obesity, cognitive impairment, and atrioventricular septal defect) mutated in IFT27/BBS19. IFT27 is part of the Intraflagellar transport (IFT), a bidirectional mechanism allowing the protein motility within the cilia. Using whole exome sequencing, two compound heterozygous mutations were found in the proband (NM_006860.4:c.[104A > G];[349+1G > T], p.[Tyr35Cys];[?]) consistent with the expected autosomal recessive inheritance mode. These two mutations have already been reported but independently in other families and lacking either familial segregation or functional validation. This is the third report of IFT27 mutations in BBS patients confirming IFT27 as a BBS gene (BBS19). Mutations in IFT genes (IFT27, IFT172 and IFT74) confirm the IFT-pathway as a pathomechanism for BBS

Proteasome subunit variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

The ubiquitin–proteasome system degrades ubiquitin‐modified proteins to maintain protein homeostasis and to control signalling. Whole‐genome sequencing of patients with severe deafness and early‐onset cataracts as part of a neurological, sensorial and cutaneous novel syndrome identified a unique deep intronic homozygous variant in the PSMC3 gene, encoding the proteasome ATPase subunit Rpt5, which lead to the transcription of a cryptic exon. The proteasome content and activity in patient\u27s fibroblasts was however unaffected. Nevertheless, patient\u27s cells exhibited impaired protein homeostasis characterized by accumulation of ubiquitinated proteins suggesting severe proteotoxic stress. Indeed, the TCF11/Nrf1 transcriptional pathway allowing proteasome recovery after proteasome inhibition is permanently activated in the patient\u27s fibroblasts. Upon chemical proteasome inhibition, this pathway was however impaired in patient\u27s cells, which were unable to compensate for proteotoxic stress although a higher proteasome content and activity. Zebrafish modelling for knockout in PSMC3 remarkably reproduced the human phenotype with inner ear development anomalies as well as cataracts, suggesting that Rpt5 plays a major role in inner ear, lens and central nervous system development

VaRank: a simple and powerful tool for ranking genetic variants:

Background. Most genetic disorders are caused by single nucleotide variations (SNVs) or small insertion/deletions (indels). High throughput sequencing has broadened the catalogue of human variation, including common polymorphisms, rare variations or disease causing mutations. However, identifying one variation among hundreds or thousands of others is still a complex task for biologists, geneticists and clinicians. Results. We have developed VaRank, a command-line tool for the ranking of genetic variants detected by high-throughput sequencing. VaRank scores and prioritizes variants annotated either by Alamut Batch or SnpEff. A barcode allows users to quickly view the presence/absence of variants (with homozygote/heterozygote status) in analyzed samples. VaRank supports the commonly used VCF input format for variants analysis thus allowing it to be easily integrated into NGS bioinformatics analysis pipelines. VaRank has been successfully applied to disease-gene identification as well as to molecular diagnostics setup for several hundred patients. Conclusions. VaRank is implemented in Tcl/Tk, a scripting language which is platform-independent but has been tested only on Unix environment. The source code is available under the GNU GPL, and together with sample data and detailed documentation can be downloaded from http://www.lbgi.fr/VaRank/

Fouilles de plusieurs occupations du Paléolithique moyen à Mutzig-Rain (Alsace) Premiers résultats

International audienceLe site de Mutzig, découvert fortuitement en 1992 (Sainty et al., 1994) est fouillé en contexte programmé depuis 2009. Localisé en Alsace (Bas-Rhin), il est à l’heure actuelle un des seuls témoins fiables attribués au Paléolithique moyen dans la région, permettant ainsi de documenter une zone assez méconnue pour la Préhistoire ancienne. La très bonne conservation des vestiges s’y retrouvant ainsi que son importante stratigraphie en font potentiellement un site de référence pour les analyses environnementales et comportementales au Paléolithique moyen dans la région. Néanmoins, les études étant en cours, ce sont les premiers résultats qui sont présentés dans cet article.Les occupations sont situées au débouché de la vallée la Bruche, au pied de la falaise du Felsbourg. Véritable attrait de par la vue imprenable sur la plaine d’Alsace qu’il expose, cet emplacement topographique a été vraisemblablement le témoin de nombreuses occupations répétées.L’ensemble de la séquence se rapporte au Paléolithique moyen. Si les niveaux supérieurs (couches 1 à 4) pourraient être le reflet de colluvionnements d’occupations sur une des terrasses supérieures qui se seraient démantelées, les couches 5, 7A, 7C1, 7C2 et 7D semblent en revanche en place, et se sont vraisemblablement déposées sous abri, ce dernier étant affecté par différentes phases d’effondrement. Les couches 8, 9 et 10, plus anciennes, appréhendées uniquement en sondage, révèlent des occupations sur un replat d’environ un mètre en contre-bas. Le substrat n’ayant pas été atteint, il est possible que la séquence soit encore plus importante.Les grands mammifères (mammouth laineux, cheval des steppes, bison des steppes et rhinocéros laineux) et la microfaune reflètent une même ambiance environnementale relativement froide de type steppe sur toute la séquence. Ces données, couplées aux dates OSL obtenues pour le moment, placent les occupations de Mutzig au Début Glaciaire du Weichselien (MIS 5, vers 90000 BP).Les vestiges archéologiques sont très nombreux au sein des différentes couches. L’industrie lithique est assez homogène sur toute la séquence. Les artisans ont exploité différents types de matériaux locaux et les méthodes d’exploitation sont assez simples, les tailleurs ayant mis à profit des convexités naturelles, révélant une phase de sélection des supports assez drastique. Peu d’outils retouchés sont recensés, mais les nombreux éclats de retouche récoltés attestent d’une circulation de ces outils. D’un point de vue typotechnologique, l’industrie se démarque de ses homologues sub-contemporains outre-Vosges et outre-Rhin.Au moins quatre niveaux archéologiques (couches 5, 7A, 7C1 et 7D) révèlent la présence d’éléments brûlés, avec pour l’un d’entre eux (couche 7C1) la présence d’une structure de combustion (couche 7C1).Le site de Mutzig paraît lié à une activité de chasse importante puisque les restes fauniques sont non seulement très nombreux, mais présentent également de fréquentes traces anthropiques (stries et fractures volontaires). Néanmoins, la question de l’acquisition des très grands herbivores reste posée.Enfin, si l’ensemble de la séquence est assez homogène, de légères différences tendent néanmoins à apparaître. Certaines couches se distinguent notamment par la représentation de certains taxons fauniques (mammouth dominant dans la couche 7A, à l’inverse de la couche 7C1 pour laquelle le renne est majoritaire) ainsi que par la présence de charbons de bois ou d’os brûlés dans les structures de combustion, peut-être à relier à des couverts forestiers distincts. La poursuite de la fouille devra

Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

Amelogenesis imperfecta (AI) designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20) produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe

Psychologie sociale appliquée

Stoetzel Jean. Psychologie sociale appliquée. In: Bulletin de psychologie, tome 12 n°156, 1958. pp. 232-235

Psychologie sociale des âges

Stoetzel Jean. Psychologie sociale des âges. In: Bulletin de psychologie, tome 22 n°272, 1968. pp. 34-37