A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles

Background : Cumulative evidence indicates that statins induce myotoxicity. However, the lack of understanding of how statins affect skeletal muscles at the structural, functional, and physiological levels hampers proper healthcare management. The purpose of the present study was to investigate the early after-effects of lovastatin on the slow-twitch soleus (Sol) and fast-twitch extensor digitorum longus (EDL) muscles. Methods : Adult C57BL/6 mice were orally administrated with placebo or lovastatin [50 mg/kg/d] for 28 days. At the end of the treatment, the isometric ex vivo contractile properties of the Sol and EDL muscles were measured. Subtetanic and tetanic contractions were assessed and contraction kinetics were recorded. The muscles were then frozen for immunohistochemical analyses. Data were analyzed by two-way ANOVA followed by an a posteriori Tukey’s test. Results : The short-term lovastatin treatment did not induce muscle mass loss, muscle fiber atrophy, or creatine kinase (CK) release. It had no functional impact on slow-twitch Sol muscles. However, subtetanic stimulations at 10 Hz provoked greater force production in fast-twitch EDL muscles. The treatment also decreased the maximal rate of force development (dP/dT) of twitch contractions and prolonged the half relaxation time (1/2RT) of tetanic contractions of EDL muscles. Conclusions : An early short-term statin treatment induced subtle but significant changes in some parameters of the contractile profile of EDL muscles, providing new insights into the selective initiation of statin-induced myopathy in fast-twitch muscles

Physiological role of receptor activator nuclear factor-kB (RANK) in denervation-induced muscle atrophy and dysfunction

The bone remodeling and homeostasis are mainly controlled by the receptor-activator of nuclear factor kB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin (OPG) pathway. While there is a strong association between osteoporosis and skeletal muscle dysfunction, the functional relevance of a particular biological pathway that synchronously regulates bone and skeletal muscle physiopathology remains elusive. Our recent article published in the American Journal of Physiology (Cell Physiology) showed that RANK is also expressed in fully differentiated C2C12 myotubes and skeletal muscles. We used the Cre-Lox approach to inactivate muscle RANK (RANKmko) and showed that RANK deletion preserves the force of denervated fast-twitch EDL muscles. However, RANK deletion had no positive impact on slow-twitch Sol muscles. In addition, denervating RANKmko EDL muscles induced an increase in the total calcium concentration ([CaT]), which was associated with a surprising decrease in SERCA activity. Interestingly, the levels of STIM-1, which mediates Ca2+ influx following the depletion of SR Ca2+ stores, were markedly higher in denervated RANKmko EDL muscles. We speculated that extracellular Ca2+ influx mediated by STIM-1 may be important for the increase in [CaT] and the gain of force in denervated RANKmko EDL muscles. Overall, these findings showed for the first time that the RANKL/RANK interaction plays a role in denervation-induced muscle atrophy and dysfunction

Template-growth of periodically domain-structured KTiOPO4

International audienceWe performed the first growth, from a high temperature solution, of a 38.86 μm-periodicity PPKTP crystal of good optical quality over a thickness of more than 800 μm onto each of the two faces perpendicular to the c direction of a PPKTP substrate previously obtained by electric field poling. The quasi-phase matched second harmonic generation properties in the grown layer and substrate are similar and in accordance with calculation

EmoNets: Multimodal deep learning approaches for emotion recognition in video

The task of the emotion recognition in the wild (EmotiW) Challenge is to assign one of seven emotions to short video clips extracted from Hollywood style movies. The videos depict acted-out emotions under realistic conditions with a large degree of variation in attributes such as pose and illumination, making it worthwhile to explore approaches which consider combinations of features from multiple modalities for label assignment. In this paper we present our approach to learning several specialist models using deep learning techniques, each focusing on one modality. Among these are a convolutional neural network, focusing on capturing visual information in detected faces, a deep belief net focusing on the representation of the audio stream, a K-Means based "bag-of-mouths" model, which extracts visual features around the mouth region and a relational autoencoder, which addresses spatio-temporal aspects of videos. We explore multiple methods for the combination of cues from these modalities into one common classifier. This achieves a considerably greater accuracy than predictions from our strongest single-modality classifier. Our method was the winning submission in the 2013 EmotiW challenge and achieved a test set accuracy of 47.67% on the 2014 dataset

Muscle RANK is a key regulator of calcium storage, SERCA activity, and function of fast-twitch skeletal muscles

Receptor-activator of nuclear factor kB (RANK), its ligand RANKL and the soluble decoy receptor osteoprotegerin (OPG)are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion (RANKmko) has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscle preventing the loss of maximum specific force while promoting muscle atrophy, fatigability and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 (Stim1) content, a calcium sensor, and altered activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) modulating Ca2+ storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus (Sol) muscles. These data identify a novel role for RANK as a key regulator of calcium storage and SERCA activity, ultimately affecting denervated skeletal muscle function