Large-Scale Population Analysis Challenges the Current Criteria for the Molecular Diagnosis of Fascioscapulohumeral Muscular Dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is a common hereditary myopathy causally linked to reduced numbers (<= 8) of 3.3 kilobase D4Z4 tandem repeats at 4q35. However, because individuals carrying D4Z4-reduced alleles and no FSHD and patients with FSHD and no short allele have been observed, additional markers have been proposed to support an FSHD molecular diagnosis. In particular a reduction in the number of D4Z4 elements combined with the 4A(159/161/168)PAS haplotype (which provides the possibility of expressing DUX4) is currently used as the genetic signature uniquely associated with FSHD. Here, we analyzed these DNA elements in more than 800 Italian and Brazilian samples of normal individuals unrelated to any FSHD patients. We find that 3% of healthy subjects carry alleles with a reduced number (4-8) of D4Z4 repeats on chromosome 4q and that one-third of these alleles, 1.3%, occur in combination with the 4A161PAS haplotype. We also systematically characterized the 4q35 haplotype in 253 unrelated FSHD patients. We find that only 127 of them (50.1%) carry alleles with 1-8 D4Z4 repeats associated with 4A161PAS, whereas the remaining FSHD probands carry different haplotypes or alleles with a greater number of D4Z4 repeats. The present study shows that the current genetic signature of FSHD is a common polymorphism and that only half of FSHD probands carry this molecular signature. Our results suggest that the genetic basis of FSHD, which is remarkably heterogeneous, should be revisited, because this has important implications for genetic counseling and prenatal diagnosis of at-risk families.

Non-linear magnetohydrodynamic simulations of density evolution in Tore Supra sawtoothing plasmas

The plasma density evolution in sawtooth regime on the Tore Supra tokamak is analyzed. The density is measured using fast-sweeping X-mode reflectometry which allows tomographic reconstructions. There is evidence that density is governed by the perpendicular electric flows, while temperature evolution is dominated by parallel diffusion. Postcursor oscillations sometimes lead to the formation of a density plateau, which is explained in terms of convection cells associated with the kink mode. A crescent-shaped density structure located inside q = 1 is often visible just after the crash and indicates that some part of the density withstands the crash. 3D full MHD nonlinear simulations with the code XTOR-2F recover this structure and show that it arises from the perpendicular flows emerging from the reconnection layer. The proportion of density reinjected inside the q = 1 surface is determined, and the implications in terms of helium ash transport are discussed. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4766893]

An integrated stratigraphic record of the Palaeocene-lower Eocene at Gubbio (Italy): new insights into the early Palaeogene hyperthermals and carbon isotope excursions

Terra Nova, 24, 380386, 2012 Abstract A high-resolution, integrated stratigraphic framework (stable isotope stratigraphy, standard calcareous nannofossil and foraminiferal biostratigraphy, magnetostratigraphy) together with geochemical and rock magnetic properties analyses of a complete and well-preserved succession at Contessa Valley (Gubbio, central Italy) have offered an excellent opportunity to identify and constrain the Palaeocene to early Eocene hyperthermals and carbon isotope excursions (CIEs). In addition, we provide the first evidence in the Tethys Ocean of CIEs, previously identified in the Pacific, Atlantic and Southern Oceans, highlighting their global significance and of some unknown CIEs. Their characteristics are compared with those reported for deep-sea cores and other land-based sections to test whether the signature associated with CIEs documented in our composite section might give evidence for tracing them over wider areas. The Contessa composite section thus represents a reference succession also for insight into the magnetobiochronostratigraphy and the magnitude of early Palaeogene hyperthermals and CIEs.