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

Association of Autoimmune Thyroid Disease with Anti-GAD Antibody ELISA Test Positivity and Risk for Insulin Deficiency in Slowly Progressive Type 1 Diabetes

The presence of antiglutamic acid decarboxylase antibody (GADA) is required for the diagnosis of slowly progressive type 1 diabetes (SPT1D). We examined the factors influencing GADA determination by radioimmunoassay (GADA-RIA) and by enzyme-linked immunosorbent assay (GADA-ELISA). Sixty patients with SPT1D and 154 patients with type 2 diabetes were examined by both GADA-RIA and GADA-ELISA and for the presence of autoimmune thyroid disease (AITD). We compared the clinical characteristics of these patients based on the positivity or negativity of GADA-RIA and GADA-ELISA, and the existence or nonexistence of AITD. Thirty of 60 (50.0%) GADA-RIA-positive patients were GADA-ELISA negative, whereas none of the 154 GADA-RIA-negative patients were GADA-ELISA positive. Concomitant AITD was significantly less in patients with GADA-RIA and without GADA-ELISA and was significantly more in patients with GADA-RIA and GADA-ELISA. In GADA-RIA-positive patients, there was no significant difference in the GADA-RIA titer among the GADA-ELISA-negative patients with and without AITD, and the GADA-ELISA-positive patients without AITD; whereas the frequency of insulin deficiency was significantly higher in the patients with AITD and/or GADA-ELISA than in those without AITD and GADA-ELISA. Examination of GADA-ELISA and AITD in GADA-RIA-positive patients might be useful in predicting insulin deficiency in these patients

Human Pluripotent Stem Cell Culture Outcome Predicted by Deep Learning

This is the dataset of the manuscript. This deep learning model predicts the percentage of the area expressing RAX on the image from a bright-field image of a developing hypothalamic-pituitary complex. The input is the image of the developing organoid (day30), and the predicted result is output as A (70More detail of this model are shown in our paper; Human Pluripotent Stem Cell Culture Outcome Predicted by Deep Learning.</p