Murine muscle engineered from dermal precursors: an in vitro model for skeletal muscle generation, degeneration and fatty infiltration.

Skeletal muscle can be engineered by converting dermal precursors into muscle progenitors and differentiated myocytes. However, the efficiency of muscle development remains relatively low and it is currently unclear if this is due to poor characterization of the myogenic precursors, the protocols used for cell differentiation, or a combination of both. In this study, we characterized myogenic precursors present in murine dermospheres, and evaluated mature myotubes grown in a novel three-dimensional culture system. After 57 days of differentiation, we observed isolated, twitching myotubes followed by spontaneous contractions of the entire tissue-engineered muscle construct on an extracellular matrix (ECM). In vitro engineered myofibers expressed canonical muscle markers and exhibited a skeletal (not cardiac) muscle ultrastructure, with numerous striations and the presence of aligned, enlarged mitochondria, intertwined with sarcoplasmic reticula (SR). Engineered myofibers exhibited Na+- and Ca2+-dependent inward currents upon acetylcholine (ACh) stimulation and tetrodotoxin-sensitive spontaneous action potentials. Moreover, ACh, nicotine, and caffeine elicited cytosolic Ca2+ transients; fiber contractions coupled to these Ca2+ transients suggest that Ca2+ entry is activating calcium-induced calcium release from the SR. Blockade by d-tubocurarine of ACh-elicited inward currents and Ca2+ transients suggests nicotinic receptor involvement. Interestingly, after 1 month, engineered muscle constructs showed progressive degradation of the myofibers concomitant with fatty infiltration, paralleling the natural course of muscular degeneration. We conclude that mature myofibers may be differentiated on the ECM from myogenic precursor cells present in murine dermospheres, in an in vitro system that mimics some characteristics found in aging and muscular degeneration

Development and evaluation of a novel robotic platform for gait rehabilitation in patients with Cerebral Palsy: CPWalker

[EN] The term Cerebral Palsy (CP) is a set of neurological disorders that appear in infancy or early childhood and permanently affect body movement and muscle coordination. The prevalence of CP is two-three per 1000 births. Emerging rehabilitation therapies through new strategies are needed to diminish the assistance required for these patients, promoting their functional capability. This paper presents a new robotic platform called CPWalker for gait rehabilitation in patients with CP, which allows them to start experiencing autonomous locomotion through novel robot-based therapies. The platform (smart walker + exoskeleton) is controlled by a multimodal interface that gives high versatility. The therapeutic approach, as well as the details of the interactions may be defined through this interface. CPWalker concept aims to promote the earlier incorporation of patients with CP to the rehabilitation treatment and increases the level of intensity and frequency of the exercises. This will enable the maintenance of therapeutic methods on a daily basis, with the intention of leading to significant improvements in the treatment outcomes.The work presented in this paper has been carried out with the financial support from the Ministerio de Economía y Competitividad of Spain, under Contract DPI2012-39133-C03-01. Authors would like to thank Made for Movement company for providing and supporting us in the mechanical design of a NF-Walker device. Authors also would like to thank the following Brazilian agencies for supporting this research: CNPq (Processes 308529/2013-8), CAPES/Brazil (Process 8887.095626/2015- 01) and FAPES/Brazil (Process 67566480). We greatly appreciate the efforts and contributions from all the testing subjects and their families.Bayón, C.; Ramírez, O.; Serrano, J.; Del Castillo, M.; Pérez-Somarriba, A.; Belda Lois, JM.; Martínez, I.... (2017). Development and evaluation of a novel robotic platform for gait rehabilitation in patients with Cerebral Palsy: CPWalker. Robotics and Autonomous Systems. 91:101-114. https://doi.org/10.1016/j.robot.2016.12.015S1011149

Inferring Positional Homologs with Common Intervals of Sequences

International audienceInferring orthologous and paralogous genes is an important problem in whole genomes comparisons, both for functional or evolutionary studies. In this paper, we introduce a new approach for inferring candidate pairs of orthologous genes between genomes, also called positional homologs, based on the conservation of the genomic context. We consider genomes represented by their gene order -- i.e. sequences of signed integers -- and common intervals of these sequences as the anchors of the final gene matching. We show that the natural combinatorial problem of computing a maximal cover of the two genomes using the minimum number of common intervals is NP-complete and we give a simple heuristic for this problem. We illustrate the effectiveness of this first approach using common intervals of sequences on two datasets, respectively 8 $\gamma$-proteobacterial genomes and the human and mouse whole genomes