Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy

Muscle contraction upon nerve stimulation relies on excitation–contraction coupling (ECC) to promote the rapid and generalized release of calcium within myofibers. In skeletal muscle, ECC is performed by the direct coupling of a voltage-gated L-type Ca2+ channel (dihydropyridine receptor; DHPR) located on the T-tubule with a Ca2+ release channel (ryanodine receptor; RYR1) on the sarcoplasmic reticulum (SR) component of the triad. Here, we characterize a novel class of congenital myopathy at the morphological, molecular, and functional levels. We describe a cohort of 11 patients from 7 families presenting with perinatal hypotonia, severe axial and generalized weakness. Ophthalmoplegia is present in four patients. The analysis of muscle biopsies demonstrated a characteristic intermyofibrillar network due to SR dilatation, internal nuclei, and areas of myofibrillar disorganization in some samples. Exome sequencing revealed ten recessive or dominant mutations in CACNA1S (Cav1.1), the pore-forming subunit of DHPR in skeletal muscle. Both recessive and dominant mutations correlated with a consistent phenotype, a decrease in protein level, and with a major impairment of Ca2+ release induced by depolarization in cultured myotubes. While dominant CACNA1S mutations were previously linked to malignant hyperthermia susceptibility or hypokalemic periodic paralysis, our findings strengthen the importance of DHPR for perinatal muscle function in human. These data also highlight CACNA1S and ECC as therapeutic targets for the development of treatments that may be facilitated by the previous knowledge accumulated on DHPR

Dependence of CO oxidation on Pt nanoparticle shape: a shape-selective approach to the synthesis of PEMFC catalysts

In real catalyst system, it si difficult to establish a correlation between catalytic properties and the shape (crystal planes, corners and steps) of the active catalytic particles. In this paper we present a clear shape dependence of the catalytic properties of a Vulcan-supported fuel cell catalyst having 4 nm cubo-octahedral platinum(0) nanocrystallites with (111) and (100) surfaces stabilized by sodium polyacrylate. The electrode materials were characterized by CO-stripping cyclic voltammetry and transmission electron microscopy (TEM), showing that no agglomeration had occured among the nanoparticles on the catalyst surfaces

Metallic Barium: A Versatile and Efficient Hydrogenation Catalyst

Abstract Ba metal was activated by evaporation and cocondensation with heptane. This black powder is a highly active hydrogenation catalyst for the reduction of a variety of unactivated (non‐conjugated) mono‐, di‐ and tri‐substituted alkenes, tetraphenylethylene, benzene, a number of polycyclic aromatic hydrocarbons, aldimines, ketimines and various pyridines. The performance of metallic Ba in hydrogenation catalysis tops that of the hitherto most active molecular group 2 metal catalysts. Depending on the substrate, two different catalytic cycles are proposed. A: a classical metal hydride cycle and B: the Ba metal cycle. The latter is proposed for substrates that are easily reduced by Ba0, that is, conjugated alkenes, alkynes, annulated rings, imines and pyridines. In addition, a mechanism in which Ba0 and BaH2 are both essential is discussed. DFT calculations on benzene hydrogenation with a simple model system (Ba/BaH2) confirm that the presence of metallic Ba has an accelerating effect

Approach to the diagnosis of congenital myopathies

AbstractOver the past decade there have been major advances in defining the genetic basis of the majority of congenital myopathy subtypes. However the relationship between each congenital myopathy, defined on histological grounds, and the genetic cause is complex. Many of the congenital myopathies are due to mutations in more than one gene, and mutations in the same gene can cause different muscle pathologies. The International Standard of Care Committee for Congenital Myopathies performed a literature review and consulted a group of experts in the field to develop a summary of (1) the key features common to all forms of congenital myopathy and (2) the specific features that help to discriminate between the different genetic subtypes. The consensus statement was refined by two rounds of on-line survey, and a three-day workshop. This consensus statement provides guidelines to the physician assessing the infant or child with hypotonia and weakness. We summarise the clinical features that are most suggestive of a congenital myopathy, the major differential diagnoses and the features on clinical examination, investigations, muscle pathology and muscle imaging that are suggestive of a specific genetic diagnosis to assist in prioritisation of genetic testing of known genes. As next generation sequencing becomes increasingly used as a diagnostic tool in clinical practise, these guidelines will assist in determining which sequence variations are likely to be pathogenic

Geowissenschaftliche Untersuchungen an der aktiven Konvergenzzone zwischen der ost-eurasischen und indisch-australischen Platte im Bereich Indonesiens (GINCO I) FS SONNE Fahrt SO-137 Fachlicher Abschlussbericht

Available from TIB Hannover: F02B1582 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung, Berlin (Germany); Forschungszentrum Juelich GmbH (Germany). Projekttraeger Biologie, Energie, Umwelt (BEO)DEGerman