Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons

Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER

Space Demonstration of Two-Layer Pop-Up Origami Deployable Membrane Reflectarray Antenna by 3U CubeSat OrigamiSat-2

3U CubeSat OrigamiSat-2 demonstrates a 50-cm × 50-cm two-layer pop-up Origami deployable membrane reflectarray antenna in space. The membrane has small stowage volume and high gain even though it has low flatness because of a large enough antenna area to cover its un-flatness. C-band transmitter is equipped in the CubeSat and offers 20-Mbps amateur satellite communication. In 3U size, a 1-m length deployable gravity gradient mast and magnetic torquer are equipped to stabilize and control its attitude. A camera is attached to the satellite to measure the shape of the membrane antenna. OrigamiSat-2 was selected as the Innovative Satellite Technology Demonstration-4 by Japan Aerospace Exploration Agency (JAXA) and is going to be launched in 2024 by Epsilon Launch Vehicle

State-Targeting Stabilization of Adenosine A_2A Receptor by Fusing a Custom-Made De Novo Designed α-Helical Protein

G-protein coupled receptors (GPCRs) are known for their low stability and large conformational changes upon transitions between multiple states. A widely used method for stabilizing these receptors is to make chimeric receptors by fusing soluble proteins (i.e., fusion partner proteins) into the intracellular loop 3 (ICL3) connecting the transmembrane helices 5 and 6 (TM5 and TM6). However, this fusion approach requires experimental trial and error to identify appropriate soluble proteins, residue positions, and linker lengths for making the fusion. Moreover, this approach has not provided state-targeting stabilization of GPCRs. Here, to rationally stabilize a class A GPCR, adenosine A2A receptor (A2AR) in a target state, we carried out the custom-made de novo design of α-helical fusion partner proteins, which can fix the conformation of TM5 and TM6 to that in an inactive state of A2AR through straight helical connections without any kinks or intervening loops. The chimeric A2AR fused with one of the designs (FiX1) exhibited increased thermal stability. Moreover, compared with the wild type, the binding affinity of the chimera against the agonist NECA was significantly decreased, whereas that against the inverse agonist ZM241385 was similar, indicating that the inactive state was selectively stabilized. Our strategy contributes to the rational state-targeting stabilization of GPCRs

Compressed Beef Marbling Image Database with Browser-based Retrieval System

The system we are proposing in this paper demonstrates the capability of a robust multi-user access database management system by which compressed beef carcass rib-eye images, together with other related information, can be easily accessed on the Internet through web browsers in a client-server distributed fashion. This framework, we believe, can pioneer a new direction in information reuse and sharing among different users of the Japanese livestock industry that is non-existent at present. The compression technique we employ has its basis in a class of functions which we termed Fluency functions that enables highly efficient storage and retrieval of image data over the Internet with limited bandwidth. Eventually, we envision that the characteristics of the compressed data could provide insights into creating efficient image matching and retrieval algorithms that constitute a layer above the functions being provided by current database management systems. Such research, we believe, could contribute to a wider range of application domains involving images such as cartographic data and medical images, etc