Mitochondrial dysfunction and calcium deregulation by the RanBP9-cofilin pathway.

Mitochondrial dysfunction and synaptic damage are important features of Alzheimer's disease (AD) associated with amyloid ß (Aß) and tau. We reported previously that the scaffolding protein RanBP9, which is overall increased in brains of patients with AD and in mutant APP transgenic mice, simultaneously promotes Aß generation and focal adhesion disruption by accelerating the endocytosis of APP and ß1-integrin, respectively. Moreover, RanBP9 induces neurodegeneration in vitro and in vivo and mediates Aß-induced neurotoxicity. Here we show in primary hippocampal neurons that RanBP9 potentiates Aß-induced reactive oxygen species (ROS) overproduction, apoptosis, and calcium deregulation. Analyses of calcium-handling measures demonstrate that RanBP9 selectively delays the clearance of cytosolic Ca(2+) mediated by the mitochondrial calcium uniporter through a process involving the translocation of cofilin into mitochondria and oxidative mechanisms. Further, RanBP9 retards the anterograde axonal transport of mitochondria in primary neurons and decreases synaptic mitochondrial activity in brain. These data indicate that RanBP9, cofilin, and Aß mimic and potentiate each other to produce mitochondrial dysfunction, ROS overproduction, and calcium deregulation, which leads to neurodegenerative changes reminiscent of those seen in AD.

Hot Electron Tunneling in Pt/LaAlO3/SrTiO3 Heterostructures for Enhanced Photodetection.

LaAlO3/SrTiO3 (LAO/STO) heterostructures, in which a highly mobile two-dimensional electron gas (2DEG) is formed, have great potential for optoelectronic applications. However, the inherently high density of the 2DEG hinders the observation of photo-excitation effects in oxide heterostructures. Herein, a strong photoresponse of the 2DEG in a Pt/LAO/STO heterostructure is achieved by adopting a vertical tunneling configuration. The tunneling of the 2DEG through an ultrathin LAO layer is significantly enhanced by UV light irradiation, showing a maximum photoresponsivity of ∼1.11 × 107%. The strong and reversible photoresponse is attributed to the thermionic emission of photoexcited hot electrons from the oxygen-deficient STO. Notably, the oxygen vacancy defects play a critical role in enhancing the tunneling photocurrent. Our systematic study on the hysteresis behavior and the light power dependency of the tunneling current consistently support the fact that the photoexcited hot electrons from the oxygen vacancies strongly contribute to the tunneling conduction under the UV light. This work offers valuable insights into a novel photodetection mechanism based on the 2DEG as well as into developing ultrathin optoelectronic devices based on the oxide heterostructures.

Recent Developments and Prospects of M13- Bacteriophage Based Piezoelectric Energy Harvesting Devices.

Recently, biocompatible energy harvesting devices have received a great deal of attention for biomedical applications. Among various biomaterials, viruses are expected to be very promising biomaterials for the fabrication of functional devices due to their unique characteristics. While other natural biomaterials have limitations in mass-production, low piezoelectric properties, and surface modification, M13 bacteriophages (phages), which is one type of virus, are likely to overcome these issues with their mass-amplification, self-assembled structure, and genetic modification. Based on these advantages, many researchers have started to develop virus-based energy harvesting devices exhibiting superior properties to previous biomaterial-based devices. To enhance the power of these devices, researchers have tried to modify the surface properties of M13 phages, form biomimetic hierarchical structures, control the dipole alignments, and more. These methods for fabricating virus-based energy harvesting devices can form a powerful strategy to develop high-performance biocompatible energy devices for a wide range of practical applications in the future. In this review, we discuss all these issues in detail.