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

Bestimmung seismischer Geschwindigkeiten aus Steilwinkelreflexionen im p-#tau#-Bereich

Modification of slant stacks by coherency weighting and hyperbolic velocity filtering largely improved p-#tau# and p"2-#tau#"2 reflection imaging without formation of artefacts. The efficiency of the p-#tau# plane wave approach to the analysis of seismic data is demonstrated by application to steep angle reflection data from continental deep seismic, marine seismic and explorational seismic studies. On account of increased interpretation accuracy, the method is especially suited for deep seismic crystal studies. (WEN)SIGLEAvailable from TIB Hannover: RN 2688(40) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Abschaetzung seismischer Geschwindigkeiten an DEKORP-Daten durch Weiterentwicklung filtertheoretischer Methoden. Analyse kinematischer und dynamischer Signalparameter an DEKORP-Daten Endbericht

New methods for the treatment and analysis of depth seismic data have been developed, and their efficiency was proved on data gathered during the DEKORP project (1992-1993). The development includes a procedure for evaluation of stacking velocities in the p-T region, a reliable method for signal estimation from noisy data, and the introduction of adaptive filters. In addition, by analysis of data from the 3D-expanding-spread-experiment (ISO-89 experiment) at the location of the continental deep borehole, velocity-depth-functions were derived and anisotropies in the velocity field were investigated. The application of the CMP technique for reflexion seismic investigations of crystallines were significantly improved. (WEN)SIGLEAvailable from TIB Hannover: F94B1455+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

SINUS: Seismic Investigations at the Ninetyeast Ridge Observatory using SONNE and JOIDES RESOLUTION during ODP Leg 179 (BGR-Begleitantrag: Erzeugung der seismischen Signale und 3D-Bearbeitung) Final report

Available from TIB Hannover: F01B1790 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman

Bestimmung der Feinstruktur des kristallinen Untergrunds durch Auswertung von DEKORP-Daten vor dem Stapeln Endbericht

SIGLEAvailable from TIB Hannover: F97B1129+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Krustensplitter. 3D-Makro-Geschwindigkeitsbestimmungen und 3D-Tiefenmigration des seismischen 3D-Costa-Rica-Datensatzes

For the 3D-marine seismic data reflection set (area 15km x 30 km), received in 1992 by BGR on the active east Pacific continental margin, it was possible to derive a detailed 3D-velocity model (macro-model B) during the second project phase, thanks to a special 3D-prestack-migration technique (two-pass procedure). By this two-pass process the prestack 3D-seismic data will be first migrated on some selected 2D-profiles by using a partial 3D-time-migration in crossline direction. The results are prestack data on 2D-lines in inline direction, showing an elimination of the 3D-side-effects. By application of a 2D-prestack-migration process and a 2D-focusing analysis 2D-depth sections and 2D-macro-velocity fields are derived for some single 2D-lines. Both represent a vertical view through the 3D-depth model respectively through the 3D-macro-velocity field. Such a two-pass-migration technique was successfully applicated on the 3D-Costa-Rica data set. The single 2D-macro-velocity fields were subsequently area-interpolated and smoothed. Finally they produced the requested 3D-macro-velocity field B. Contrary to the macro-velocity field A, produced during the first project phase and generated from stacked velocities, this 3D-macro-velocity field B shows an improved lateral and vertical resolution, better precision especially for deep structures and evident relations to geology. (orig.)Available from TIB Hannover: RR 1846(91) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDeutsche Forschungsgemeinschaft (DFG), Bonn (Germany)DEGerman

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