Non-syndromic arthrogryposis multiplex congenita (AMC) is characterized by multiple congenital contractures resulting from reduced fetal mobility. Genetic mapping and whole exome sequencing (WES) were performed in 31 multiplex and/or consanguineous undiagnosed AMC families. Although this approach identified known AMC genes, we here report pathogenic mutations in two new genes. Homozygous frameshift mutations in CNTNAP1 were found in four unrelated families. Patients showed a marked reduction in motor nerve conduction velocity (<10 m/s) and transmission electron microscopy (TEM) of sciatic nerve in the index cases revealed severe abnormalities of both nodes of Ranvier width and myelinated axons. CNTNAP1 encodes CASPR, an essential component of node of Ranvier domains which underlies saltatory conduction of action potentials along the myelinated axons, an important process for neuronal function. A homozygous missense mutation in adenylate cyclase 6 gene (ADCY6) was found in another family characterized by a lack of myelin in the peripheral nervous system (PNS) as determined by TEM. Morpholino knockdown of the zebrafish orthologs led to severe and specific defects in peripheral myelin in spite of the presence of Schwann cells. ADCY6 encodes a protein that belongs to the adenylate cyclase family responsible for the synthesis of cAMP. Elevation of cAMP can mimic axonal contact in vitro and upregulates myelinating signals. Our data indicate an essential and so far unknown role of ADCY6 in PNS myelination likely through the cAMP pathway. Mutations of genes encoding proteins of Ranvier domains or involved in myelination of Schwann cells are responsible for novel and severe human axoglial diseases.

This paper describes an interdisciplinary study of the Neolithic causewayed enclosure of Bellevue (Chenommet, France). Geophysical investigations and archaeological excavations were used alternately in order to optimize the acquisition of accurate data at different spatial scales: mapping of major structures was obtained by magnetic prospection of the whole site, while excavation identified small features weakly expressed in the prospecting results. Measurements of magnetic susceptibility and total magnetic field anomalies were also recorded during the excavation in order to identify the source of the magnetic signal of the ditches. This mutual transdisciplinary contribution is also methodological: the geophysics reveals archaeological information invisible to the eye of the archaeologist and, in turn, the excavation allows refinement of the interpretation of the geophysical data by identifying the sources of signal variations. This article presents the results of the first comprehensive magnetic mapping of a Neolithic causewayed enclosure in the west of France.

This article focusses on an original magnetic survey protocol and its data processing chain. The use of a high sensitive magnetometer combined with a motorized total station permits production of a magnetic map with a high spatial resolution and a high precision of magnetic and positional measurements. The data processing enhances the final magnetic map by the removal and restoring the outlier values, measurement errors and magnetic disturbances. The magnetic survey was undertaken on the Neolithic site of Le Pontet at Saint-Nazaire-sur-Charente (French Atlantic coast, between Bordeaux and La Rochelle). The site was chosen for geographical and archaeological characteristics such as its settlement period, the topography and the presence of different magnetic disturbances (proximity to roads and residential area). The data processing is mainly made on ungridded data and the gridding is the second to last step. The last step is to correct the relative height variation of the sensors between the prospecting lines (tracks) induced by the topography and operators. The use of a motorized total station allows accurate height determination of the sensors and an upward continuation is performed to correct the slight magnetic intensity variation induced by the relative height variation of the sensors. The results of the magnetic map bring out several causewayed enclosures, pits and postholes. This map will serve as a working basis for interdisciplinary studies and future archaeological studies of this site.