The molecular determinants of muscle progenitor impairment to regenerate aged muscles are currently unclear. We show that, in a mouse model of replicative senescence, decline in muscle satellite cell-mediated regeneration coincides with activation of DNA damage response (DDR) and impaired ability to differentiate into myotubes. Inhibition of DDR restored satellite cell differentiation ability. Moreover, in replicative human senescent fibroblasts, DDR precluded MYOD-mediated activation of the myogenic program. A DDR-resistant MYOD mutant could overcome this barrier by resuming cell cycle progression. Likewise, DDR inhibition could also restore MYOD's ability to activate the myogenic program in human senescent fibroblasts. Of note, we found that cell cycle progression is necessary for the DDR-resistant MYOD mutant to reverse senescence-mediated inhibition of the myogenic program. These data provide the first evidence of DDR-mediated functional antagonism between senescence and MYOD-activated gene expression and indicate a previously unrecognized requirement of cell cycle progression for the activation of the myogenic program.
This article presents a new numerical method for facial reconstruction. The problem is the following: given a dry skull, reconstruct a virtual face that would help in the identification of the subject. The approach combines classical features as the use of a skulls/faces database and more original aspects: (1) an original shape matching method is used to link the unknown skull to the database templates; (2) the final face is seen as an elastic 3D mask that is deformed and adapted onto the unknown skull. In this method, the skull is considered as a whole surface and not restricted to some anatomical landmarks, allowing a dense description of the skull/face relationship. Also, the approach is fully automated. Various results are presented to show its efficiency.
The purpose of this article is to discuss several modern aspects of remeshing, which is the task of modifying an ill-shaped tetrahedral mesh with bad size elements so that it features an appropriate density of high-quality elements. After a brief sketch of classical stakes about meshes and local mesh operations, we notably expose (i) how the local size of the elements of a mesh can be adapted to a user-defined prescription (guided, e.g., by an error estimate attached to a numerical simulation), (ii) how a mesh can be deformed to efficiently track the motion of the underlying domain, (iii) how to construct a mesh of an implicitly-defined domain, and (iv) how remeshing procedures can be conducted in a parallel fashion when large-scale applications are targeted. These ideas are illustrated with several applications involving high-performance computing. In particular, we show how mesh adaptation and parallel remeshing strategies make it possible to achieve a high accuracy in large-scale simulations of complex flows, and how the aforementioned methods for meshing implicitly defined surfaces allow to represent faithfully intricate geophysical interfaces, and to account for the dramatic evolutions of shapes featured by shape optimization processes.
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