Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy

Schnyder crystalline corneal dystrophy (SCCD, MIM 121800) is a rare autosomal dominant disease characterized by progressive opacification of the cornea resulting from the local accumulation of lipids, and associated in some cases with systemic dyslipidemia. Although previous studies of the genetics of SCCD have localized the defective gene to a 1.58 Mbp interval on chromosome 1p, exhaustive sequencing of positional candidate genes has thus far failed to reveal causal mutations. We have ascertained a large multigenerational family in Nova Scotia affected with SCCD in which we have confirmed linkage to the same general area of chromosome 1. Intensive fine mapping in our family revealed a 1.3 Mbp candidate interval overlapping that previously reported. Sequencing of genes in our interval led to the identification of five putative causal mutations in gene UBIAD1, in our family as well as in four other small families of various geographic origins. UBIAD1 encodes a potential prenyltransferase, and is reported to interact physically with apolipoprotein E. UBIAD1 may play a direct role in intracellular cholesterol biochemistry, or may prenylate other proteins regulating cholesterol transport and storage

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

Novel instrumentation calculation method to determine the phase-shift of ultrasound waves for non-destructive material characterization

8 pagesInternational audienceAn efficient method for material characterization consists in emitting ultrasound waves in a medium, and processing both the emitted and received signals to determine the morphological characteristics of the medium under test, whether static or under low flow [J. Max, Traitement du signal et applications aux mesures physiques, 4th eacuted., Vol. 1, MASSON, 1985. J. Perdijon, Le Controcircle non destructif par ultrasons, Traiteacute des nouvelles Technologies, seacuterie mateacuteriaux, (in French) HERMES. A. Ravasoo, and J. Janno, Nondestructive characterization of materials with variable properties, Acta Mechanica, 151 (2001), pp. 217-233. J. SAPRIEL, Techniques de l'Ingeacutenieur (in French) Traiteacute eacutelectronique, E1910.]. In this article we present an instrumentation calculation method to determine the phase-shift of ultrasound waves at 40 kHz using a data acquisition card limited to 200 kHz. We describe the experimental platform, then the theoretical development for results exploitation, and two applications using the system: a distance measurement in air medium, and a speed sound measurement in sea water/fresh water mixture

Novel intrumentation calculation methods to determine the phase-shift of ultrasound waves for non-destructive material characterization

16 pagesInternational audienceAn efficient method for material characterization consists in emitting ultrasound waves in a medium, and processing both the emitted and received signals to determine the morphological characteristics of the medium under test, wether static or under low flow. We present in this paper an instrumentation calculation method to determine the phase-shift of ultrasound waves at 40 kHz using a data acquisition card limited to 200 kHz. We describe the experimental platform, then the theoretical development for results exploitation, and two applications using the system : a distance measurement in air medium, and a speed sound measurement in sea-water/fresh water mixtur

25 siècles de bains collectifs en Orient.

International audienceSince 2006 the Balnéorient team has been studying ancient (from the Early Hellenistic period on) to contemporary collective baths in the Eastern Mediterranean. This federative program aimed at examining the various aspects of this hugely attested social practice in an area that had never been, so far, taken as the focal point of a survey on both the longue durée and this wide geographical context.The present book includes 63 articles, case studies and syntheses, together with a common bibliography. These articles examine the bathing phenomenon within the broader Middle Eastern context and allow for a panoramic view of the phenomenon that underlines its complexity and highlights the striking wealth of bath-related heritage in this region. The diachronic approach, in particular, suggests a history of the bathing phenomenon across times that differs from the one which was presented elsewhere as being made of peaks, such as the Roman and Ottoman periods, and stagnant phases or declines, such as the end of Antiquity or the modern era. On the contrary, this book demonstrates the extreme richness and diversity of the Middle East bath-related heritage, in all periods and in all countries in which we conducted our study

Stage-specific gene expression during spermatogenesis in the dogfish (Scyliorhinus canicula).

International audienceIn the dogfish testis the cystic arrangement and polarisation of germ cell stages makes it possible to observe all stages of spermatogenesis in a single transverse section. By taking advantage of the zonation of this organ we have used suppressive subtractive libraries construction, real-time PCR and in situ hybridisation to identify 32 dogfish genes showing differential expressions during spermatogenesis. These include homologues of genes already known to be expressed in the vertebrate testis, but found here to be specifically expressed either in pre-meiotic and/or meiotic zones (ribosomal protein S8, high-mobility group box 3, ubiquitin carboxyl-terminal esterase L3, 20beta-hydroxysteroid dehydrogenase or cyclophilin B), or in post-meiotic zone (speriolin, Soggy, zinc finger protein 474, calreticulin or phospholipase c-zeta). We also report for the first time testis-specific expression patterns for dogfish genes coding for A-kinase anchor protein 5, ring finger protein 152 or F-box only protein 7. Finally, the study highlights the differential expression of new sequences whose identity remains to be assessed. This study provides the first molecular characterisation of spermatogenesis in a chondrichthyan, a key species to gain insight into the evolution of this process in gnathostomes

Impact d’une technique de stimulation manuelle veino-lymphatique selon la méthode Schiltz sur la récupération de la mobilité du genou suite à une arthroplastie totale de genou : un essai comparatif randomisé

International audienceIntroduction. – L’œdème postopératoire après arthroplastie totale de genou freine la récupération articulaire. L’objectif de cet essai était d’évaluer l’effi cacité d’une technique de massage par stimulation manuelle veino-lymphatique durant la première semaine d’hospitalisation sur la récupération de la mobilité du genou suite à une arthroplastie totale de genou par rapport à la kinésithérapie habituelle seule.Méthode. – Cet essai clinique de supériorité, contrôlé, randomisé, a été mené en ouvert et en deux groupes parallèles : un groupe expérimental bénéfi ciait de la kinésithérapie habituelle associée à une technique de massage selon la méthode de stimulation manuelle veino-lymphatique (méthode de Schiltz), un groupe contrôle bénéfi ciait de la kinésithérapie habituelle. L’amplitude de fl exion du genou était mesurée à j7.Résultats. – De 2014 à 2017, 44 patients ont été inclus (98 requis) : 22 dans le groupe expérimental, 22 dans le groupe contrôle. Un écart moyen de 2° a été constaté entre les deux groupes, sans différence statistiquement signifi cative.Conclusion. – Une tendance à la diminution de la douleur dans le groupe expérimental incite à envisager d’autres études sur un échantillon plus important. Il s’agira aussi de prendre en compte le type d’œdème (superfi ciel ou profond) afi n de vérifi er l’effet de la stimulation manuelle veino-lymphatique sur l’œdème superfi ciel et donc sur la récupération de la mobilité articulaire