Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy

BACKGROUND: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. RESULTS: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. CONCLUSIONS: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities

DMRN+16: Digital Music Research Network One-day Workshop 2021

DMRN+16: Digital Music Research Network One-day Workshop 2021 Queen Mary University of London Tuesday 21st December 2021 Keynote speakers Keynote 1. Prof. Sophie Scott -Director, Institute of Cognitive Neuroscience, UCL. Title: "Sound on the brain - insights from functional neuroimaging and neuroanatomy" Abstract In this talk I will use functional imaging and models of primate neuroanatomy to explore how sound is processed in the human brain. I will demonstrate that sound is represented cortically in different parallel streams. I will expand this to show how this can impact on the concept of auditory perception, which arguably incorporates multiple kinds of distinct perceptual processes. I will address the roles that subcortical processes play in this, and also the contributions from hemispheric asymmetries. Keynote 2: Prof. Gus Xia - Assistant Professor at NYU Shanghai Title: "Learning interpretable music representations: from human stupidity to artificial intelligence" Abstract Gus has been leading the Music X Lab in developing intelligent systems that help people better compose and learn music. In this talk, he will show us the importance of music representation for both humans and machines, and how to learn better music representations via the design of inductive bias. Once we got interpretable music representations, the potential applications are limitless

Time Invariant Global Stabilization of a Mobile Robot

. In this paper we present time invariant controllers which globally asymptotically stabilize a simple mobile robot to an equilibrium posture. For both kinematics and dynamics the construction follows a strategy which in fact allows for a family of controllers parameterized by the initial state and ensures smoothness of each motion. 1. Introduction From the vast literature on wheeled mobile robots (see [4] for references) it is well known that both kinematical and dynamical models of such robots appear as nonholonomic control systems. Due to a theorem by Brockett [2] they cannot be stabilized to an equilibrium point by time invariant state feedback which is smooth on a neighborhood of that point. Among the diverse proposals which have been given in order to manage this unpleasant feature mainly two different types of strategies can be observed: (i) Take the smooth system as it is (up to feasible transformations), accept Brockett's conclusion and, thus, once for all search for time var..