LARGE-SCALE DISTRIBUTION OF ARRIVAL DIRECTIONS OF COSMIC RAYS DETECTED ABOVE 10(18) eV AT THE PIERRE AUGER OBSERVATORY

A thorough search for large-scale anisotropies in the distribution of arrival directions of cosmic rays detected above 10(18) eV at the Pierre Auger Observatory is presented. This search is performed as a function of both declination and right ascension in several energy ranges above 10(18) eV, and reported in terms of dipolar and quadrupolar coefficients. Within the systematic uncertainties, no significant deviation from isotropy is revealed. Assuming that any cosmic-ray anisotropy is dominated by dipole and quadrupole moments in this energy range, upper limits on their amplitudes are derived. These upper limits allow us to test the origin of cosmic rays above 10(18) eV from stationary Galactic sources densely distributed in the Galactic disk and predominantly emitting light particles in all directions.

Mutation Spectrum in the Large GTPase Dynamin 2, and Genotype-Phenotype Correlation in Autosomal Dominant Centronuclear Myopathy

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT. Hum Mutat 33: 949-959, 2012. (C) 2012 Wiley Periodicals, Inc.