The complete mouse nebulin gene sequence and the identification of cardiac nebulin

Nebulin is a giant (Mr 750-850kDa), modular sarcomeric protein proposed to regulate the assembly, and to specify the precise lengths of actin (thin) filaments in vertebrate skeletal muscles. Nebulin's potential role as a molecular template is based on its structural and biochemical properties. Its central ∼700kDa portion associates with actin along the entire length of the thin filament, its N-terminal region extends to thin filament pointed ends, and ∼80kDa of its C-terminal region integrates within the Z-line lattice. Here, we determined the exon/intron organization of the entire mouse nebulin gene, which contains 165 exons in a 202kb segment. We identified 16 novel exons, 15 of which encode nebulin-repeat motifs (12 from its central region and 3 from its Z-line region). One novel exon shares high sequence homology to the 20 residue repeats of the tight-junction protein, ZO-1. RT-PCR analyses revealed that all 16 novel exons are expressed in mouse skeletal muscle. Surprisingly, we also amplified mRNA transcripts from mouse and human heart cDNA using primers designed along the entire length of nebulin. The expression of cardiac-specific nebulin transcripts was confirmed by in situ hybridization in fetal rat cardiomyocytes and in embryonic Xenopus laevis (frog) heart. On the protein level, antibodies specific for skeletal muscle nebulin's N and C-terminal regions stained isolated rat cardiac myofibrils at the pointed and barbed ends of thin filaments, respectively. These data indicate a conserved molecular layout of the nebulin filament systems in both cardiac and skeletal myofibrils. We propose that thin filament length regulation in cardiac and skeletal muscles may share conserved nebulin-based mechanisms, and that nebulin isoform diversity may contribute to thin filament length differences in cardiac and skeletal muscle

Dynamics of the Earth's particle radiation environment

The physical processes affecting the dynamics of the Earth's particle radiation environment are reviewed along with scientific and engineering models developed for its description. The emphasis is on models that are either operational engineering models or models presently under development for this purpose. Three components of the radiation environment, i.e., galactic cosmic rays (GCRs), solar energetic particles (SEPs) and trapped radiation, are considered separately. In the case of SEP models, we make a distinction between statistical flux/fluence models and those aimed at forecasting events. Models of the effects of particle radiation on the atmosphere are also reviewed. Further, we summarize the main features of the models and discuss the main outstanding issues concerning the models and their possible use in operational space weather forecasting. We emphasize the need for continuing the development of physics-based models of the Earth's particle radiation environment, and their validation with observational data, until the models are ready to be used for nowcasting and/or forecasting the dynamics of the environment