2002). Moreover, Labrador retrievers with mutated myotubularin are clinically normal at birth and begin to exhibit progressive generalized muscle weakness and atrophy from 7 weeks of
age (Beggs et al. 2010). This apparent discrepancy may be due to the fact that muscle maturation is achieved before birth in humans while late steps of maturation are completed within the first weeks after birth Inhibitors,research,lifescience,medical in mice and dogs. There was no strong correlation between the type of mutation and the age of death or the muscle defects noted on biopsies. A possible explanation is that missense and truncating mutations have a similar impact on the function of the protein. see more Indeed, previous experiments showed that Inhibitors,research,lifescience,medical most missense mutations are linked to a large decrease in the protein level, sustaining this hypothesis (Laporte et al. 2001; Tosch et al. 2010). In conclusion this sequential morphological study in myotubular myopathy has shown that in humans there is no period free from morphological abnormalities in the skeletal muscle which is in contrast to what has been observed in mammalian models.
We have also demonstrated a more general disorganization of membrane compartments as evidenced by the presence of a significant Inhibitors,research,lifescience,medical disorganization of the cytoskeletal network, the consistent proliferation of T-tubules and the cisternae of the sarcoplasmic reticulum. These changes cannot be explained solely by a delayed maturation of the muscle fiber. Acknowledgments We are very grateful to our team for their technical expertise and secretarial assistance Inhibitors,research,lifescience,medical were essential to the success of
this work (M. T. Viou, L. Manéré, G. Brocier, D. Chauveau, M. Beuvin, E. Lacène, F. Levy-Borsato). We also thank N Dondaine for technical assistance in molecular genetic studies. We thank Gillian Butler-Browne Inhibitors,research,lifescience,medical for critical reading of the manuscript. Confocal analyses were performed in the “Plate-forme d’Imagerie Cellulaire Pitié Salpêtrière.” This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Association Megestrol Acetate Française contre les Myopathies (AFM), and the Agence Nationale de la Recherche (ANR). Conflict of Interest None declared.
Attention and memory are fundamental cognitive processes of human intellectual function. Despite their interdependence, they are mostly investigated as separate processes. Recent neuroimaging studies have shown a tight relation between attentional control mechanisms and episodic memory (Chun and Turk-Browne 2007; Cabeza et al. 2008; Uncapher and Rugg 2009), demonstrating the role of attentional selection and modulation on memory encoding. It is well known that focusing and attending to a stimulus or an event greatly increases the probability to encode and retain this information (Yi et al. 2004; Kandel 2006).