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Transcriptional disturbance is implicated in the pathology of polyglutamine diseases, including Huntington's disease (HD). However, it is unknown whether transcriptional repression leads to neuronal death or what forms that death might take. We found transcriptional repression-induced atypical death (TRIAD) of neurons to be distinct from apoptosis, necrosis, or autophagy. The progression of TRIAD was extremely slow in comparison with other types of cell death. Gene expression profiling revealed the reduction of full-length yes-associated protein (YAP), a p73 cofactor to promote apoptosis, as specific to TRIAD. Furthermore, novel neuron-specific YAP isoforms (YAP[DELTA]Cs) were sustained during TRIAD to suppress neuronal death in a dominant-negative fashion. YAP[DELTA]Cs and activated p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin (htt) transgenic mice. YAP[DELTA]Cs also markedly attenuated Htt-induced neuronal death in primary neuron and Drosophila melanogaster models. Collectively, transcriptional repression induces a novel prototype of neuronal death associated with the changes of YAP isoforms and p73, which might be relevant to the HD pathology.

BackgroundChildren with profound intellectual and multiple disabilities (PIMD) or severe motor and intellectual disabilities (SMID) only communicate through movements, vocalizations, body postures, muscle tensions, or facial expressions on a pre- or protosymbolic level. Yet, to the best of our knowledge, there are few systems developed to specifically aid in categorizing and interpreting behaviors of children with PIMD or SMID to facilitate independent communication and mobility. Further, environmental data such as weather variables were found to have associations with human affects and behaviors among typically developing children; however, studies involving children with neurological functioning impairments that affect communication or those who have physical and/or motor disabilities are unexpectedly scarce. ObjectiveThis paper describes the design and development of the ChildSIDE app, which collects and transmits data associated with children’s behaviors, and linked location and environment information collected from data sources (GPS, iBeacon device, ALPS Sensor, and OpenWeatherMap application programming interface [API]) to the database. The aims of this study were to measure and compare the server/API performance of the app in detecting and transmitting environment data from the data sources to the database, and to categorize the movements associated with each behavior data as the basis for future development and analyses. MethodsThis study utilized a cross-sectional observational design by performing multiple single-subject face-to-face and video-recorded sessions among purposively sampled child-caregiver dyads (children diagnosed with PIMD/SMID, or severe or profound intellectual disability and their primary caregivers) from September 2019 to February 2020. To measure the server/API performance of the app in detecting and transmitting data from data sources to the database, frequency distribution and percentages of 31 location and environment data parameters were computed and compared. To categorize which body parts or movements were involved in each behavior, the interrater agreement κ statistic was used. ResultsThe study comprised 150 sessions involving 20 child-caregiver dyads. The app collected 371 individual behavior data, 327 of which had associated location and environment data from data collection sources. The analyses revealed that ChildSIDE had a server/API performance >93% in detecting and transmitting outdoor location (GPS) and environment data (ALPS sensors, OpenWeatherMap API), whereas the performance with iBeacon data was lower (82.3%). Behaviors were manifested mainly through hand (22.8%) and body movements (27.7%), and vocalizations (21.6%). ConclusionsThe ChildSIDE app is an effective tool in collecting the behavior data of children with PIMD/SMID. The app showed high server/API performance in detecting outdoor location and environment data from sensors and an online API to the database with a performance rate above 93%. The results of the analysis and categorization of behaviors suggest a need for a system that uses motion capture and trajectory analyses for developing machine- or deep-learning algorithms to predict the needs of children with PIMD/SMID in the future.

Nuclear dysfunction is a key feature of the pathology of polyglutamine (polyQ) diseases. It has been suggested that mutant polyQ proteins impair functions of nuclear factors by interacting with them directly in the nucleus. However, a systematic analysis of quantitative changes in soluble nuclear proteins in neurons expressing mutant polyQ proteins has not been performed. Here, we perform a proteome analysis of soluble nuclear proteins prepared from neurons expressing huntingtin (Htt) or ataxin-1 (AT1) protein, and show that mutant AT1 and Htt similarly reduce the concentration of soluble high mobility group B1/2 (HMGB1/2) proteins. Immunoprecipitation and pulldown assays indicate that HMGBs interact with mutant AT1 and Htt. Immunohistochemistry showed that these proteins were reduced in the nuclear region outside of inclusion bodies in affected neurons. Compensatory expression of HMGBs ameliorated polyQ-induced pathology in primary neurons and in Drosophila polyQ models. Furthermore, HMGBs repressed genotoxic stress signals induced by mutant Htt or transcriptional repression. Thus, HMGBs may be critical regulators of polyQ disease pathology and could be targets for therapy development. [ABSTRACT FROM AUTHOR]

During the period from 1965 to 1980, 263 Vibrio anguillarum strains from ayu, Plecoglossus altivelis (Temminck & Schlegel), two from rainbow trout, Salrno gairdneri Richardson, and two from eel, Anguilla japonica (Ternminck & Schlegel), were collected from fish suffering from vibriosis in various parts of Japan. On the basis of cross-agglutination and cross-absorption tests with thermostable (O) antigens, six distinct serotypes (A, B, C, D, E and F) were established among 12 selected strains of V. anguillarum. 241 strains isolated from ayu and two strains from rainbow trout belonged to serotype A, six strains from ayu and one strain from eel to serotype B, 12 strains from ayu to serotype C, three strains from ayu to serotype D, one strain from ayu to serotype F, and one strain from eel to serotype F. V. anguillarum strains belonging to serotypes D, E and F have not been detected from ayu, rainbow trout and eel since 1973; these serotypes appear to be minor types. V. anguillaruin strain NCMB 6 and 1669 belong to our serotype A and V. anguillarum 813 to our serotype C. [ABSTRACT FROM AUTHOR]

Nuclear dysfunction is a key feature of the pathology of polyglutamine (polyQ) diseases. It has been suggested that mutant polyQ proteins impair functions of nuclear factors by interacting with them directly in the nucleus. However, a systematic analysis of quantitative changes in soluble nuclear proteins in neurons expressing mutant polyQ proteins has not been performed. Here, we perform a proteome analysis of soluble nuclear proteins prepared from neurons expressing huntingtin (Htt) or ataxin-1 (AT1) protein, and show that mutant AT1 and Htt similarly reduce the concentration of soluble high mobility group B1/2 (HMGB1/2) proteins. Immunoprecipitation and pulldown assays indicate that HMGBs interact with mutant AT1 and Htt. Immunohistochemistry showed that these proteins were reduced in the nuclear region outside of inclusion bodies in affected neurons. Compensatory expression of HMGBs ameliorated polyQ-induced pathology in primary neurons and in Drosophila polyQ models. Furthermore, HMGBs repressed genotoxic stress signals induced by mutant Htt or transcriptional repression. Thus, HMGBs may be critical regulators of polyQ disease pathology and could be targets for therapy development.