IGFBPL1 Regulates Axon Growth through IGF-1-mediated Signaling Cascades

Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa, IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system

DEM simulation of binary sphere packing densification under vertical vibration

The densification of random binary sphere packings subjected to vertical vibration was modeled by using the discrete element method (DEM). The influences of operating parameters such as the vibration conditions, sphere size ratio (diameter ratio of larger versus small spheres), and composition (volume fraction of large spheres) of the binary mixture on the fractional packing density φ (defined as the volume of spheres divided by the volume of container) were studied. Two packing states, i.e., random loose packing (RLP) and random close packing (RCP), were reproduced and their micro properties such as the coordination number (CN), radial distribution function (RDF), and force structure were characterized and compared. The results indicate that properly controlling vibration conditions can realize the transition of binary packing structure from the RLP to RCP state when the sphere size ratio and composition are fixed, and the fractional packing density for RCP after vibration can reach φRCP ≈ 0.86. Different packing characteristics from RLP and RCP identify that RCP shows much denser and more uniform structure than RLP. The current modeling results are in good agreement with those obtained from both the physical experiments and the proposed empirical models in the literature