Cooperation of Mtmr8 with PI3K Regulates Actin Filament Modeling and Muscle Development in Zebrafish

Background: It has been shown that mutations in at least four myotubularin family genes (MTM1, MTMR1, 2 and 13) are causative for human neuromuscular disorders. However, the pathway and regulative mechanism remain unknown. Methodology/Principal Findings: Here, we reported a new role for Mtmr8 in neuromuscular development of zebrafish. Firstly, we cloned and characterized zebrafish Mtmr8, and revealed the expression pattern predominantly in the eye field and somites during early somitogenesis. Using morpholino knockdown, then, we observed that loss-of-function of Mtmr8 led to defects in somitogenesis. Subsequently, the possible underlying mechanism and signal pathway were examined. We first checked the Akt phosphorylation, and observed an increase of Akt phosphorylation in the morphant embryos. Furthermore, we studied the PH/G domain function within Mtmr8. Although the PH/G domain deletion by itself did not result in embryonic defect, addition of PI3K inhibitor LY294002 did give a defective phenotype in the PH/G deletion morphants, indicating that the PH/G domain was essential for Mtmr8's function. Moreover, we investigated the cooperation of Mtmr8 with PI3K in actin filament modeling and muscle development, and found that both Mtmr8-MO1 and Mtmr8-MO2+LY294002 led to the disorganization of the actin cytoskeleton. In addition, we revealed a possible participation of Mtmr8 in the Hedgehog pathway, and cell transplantation experiments showed that Mtmr8 worked in a non-cell autonomous manner in actin modeling. Conclusion/Significance: The above data indicate that a conserved functional cooperation of Mtmr8 with PI3K regulates actin filament modeling and muscle development in zebrafish, and reveal a possible participation of Mtmr8 in the Hedgehog pathway. Therefore, this work provides a new clue to study the physiological function of MTM family members.

Modeling sub-threshold current-voltage characteristics in thin film transistors

In this paper, we present a physically-based compact model for the sub-threshold behavior in a TFT with an amorphous semiconductor channel. Both drift and diffusion current components are considered and combined using an harmonic average. Here, the diffusion component describes the exponential current behavior due to interfacial deep states, while the drift component is associated with presence of localized deep states formed by dangling bonds broken from weak bonds in the bulk and follows a power law. The proposed model yields good agreement with measured results. © 2013 IEEE.

Corrugated all-composite sandwich structures. Part 1: Modeling

An analytical model for the compressive and shear response of monolithic and hierarchical corrugated composite cores has been developed. The stiffness model considers the contribution in stiffness from the bending- and the shear deformations of the core members in addition to the stretching deformation. The strength model is based on the normal stress and shear stress distribution over each core member when subjected to a shear or compressive load condition. The strength model also accounts for initial imperfections. In part 1 of this series, the analytical model is described and the results are compared to finite element predictions. In part 2, the analytical model is compared to experimental results and the behaviour of the corrugated structures is investigated more thoroughly using failure mechanism maps. © 2008 Elsevier Ltd. All rights reserved.