Identifying Disease Signatures in the Spinocerebellar Ataxia Type 1 Mouse Cortex.

The neurodegenerative disease spinocerebellar ataxia type 1 (SCA1) is known to lead to the progressive degeneration of specific neuronal populations, including cerebellar Purkinje cells (PCs), brainstem cranial nerve nuclei and inferior olive nuclei, and spinocerebellar tracts. The disease-causing protein ataxin-1 is fairly ubiquitously expressed throughout the brain and spinal cord, but most studies have primarily focused on the role of ataxin-1 in the cerebellum and brainstem. Therefore, the functions of ataxin-1 and the effects of SCA1 mutations in other brain regions including the cortex are not well-known. Here, we characterized pathology in the motor cortex of a SCA1 mouse model and performed RNA sequencing in this brain region to investigate the impact of mutant ataxin-1 towards transcriptomic alterations. We identified progressive cortical pathology and significant transcriptomic changes in the motor cortex of a SCA1 mouse model. We also identified progressive, region-specific, colocalization of p62 protein with mutant ataxin-1 aggregates in broad brain regions, but not the cerebellum or brainstem. A cross-regional comparison of the SCA1 cortical and cerebellar transcriptomic changes identified both common and unique gene expression changes between the two regions, including shared synaptic dysfunction and region-specific kinase regulation. These findings suggest that the cortex is progressively impacted via both shared and region-specific mechanisms in SCA1.

Influence of Support for Career Development Intelligence Building for College Graduates on their Job Performance: The Case of South Korea.

This study conducted to identify the influence of support for career development intelligence building for college graduates, who are early career employees, and to prove the mediating effect of learning transfer and self-esteem. An analysis was conducted using the Graduate Occupational Mobility Survey panel data from the Korea Employment Information Service. The data analysis was conducted using the SPSS21.0, AMOS22.0, and PROCESS macro programs. The findings are as follows. The influence of support for career development intelligence building on learning transfer is significantly positive, as is the influence of learning transfer on self-esteem. In addition, self-esteem had a significantly positive influence on job performance. However, the relationship between learning transfer and job performance was negative, and the relationship between support for career development intelligence building and self-esteem was insignificant. Lastly, the PROCESS macro analysis showed a mediating effect of learning transfer and self-esteem between support for career development intelligence building and job performance. Thus, it is suggested that support for career development intelligence building for early career employees should precede the development of specific programs to increase their self-esteem and enhance their job performance.

Differential effects of Wnt-ß-catenin signaling in Purkinje cells and Bergmann glia in spinocerebellar ataxia type 1.

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease characterized by progressive ataxia and degeneration of specific neuronal populations, including Purkinje cells (PCs) in the cerebellum. Previous studies have demonstrated a critical role for various evolutionarily conserved signaling pathways in cerebellar patterning, such as the Wnt-ß-catenin pathway; however, the roles of these pathways in adult cerebellar function and cerebellar neurodegeneration are largely unknown. In this study, we found that Wnt-ß-catenin signaling activity was progressively enhanced in multiple cell types in the adult SCA1 mouse cerebellum, and that activation of this signaling occurs in an ataxin-1 polyglutamine (polyQ) expansion-dependent manner. Genetic manipulation of the Wnt-ß-catenin signaling pathway in specific cerebellar cell populations revealed that activation of Wnt-ß-catenin signaling in PCs alone was not sufficient to induce SCA1-like phenotypes, while its activation in astrocytes, including Bergmann glia (BG), resulted in gliosis and disrupted BG localization, which was replicated in SCA1 mouse models. Our studies identify a mechanism in which polyQ-expanded ataxin-1 positively regulates Wnt-ß-catenin signaling and demonstrate that different cell types have distinct responses to the enhanced Wnt-ß-catenin signaling in the SCA1 cerebellum, underscoring an important role of BG in SCA1 pathogenesis.

Influence of Self-Esteem of Middle School Students for Mental Care on Academic Achievement: Based on the Mediation Effect of GRIT and Academic Enthusiasm.

The purpose of this study is to identify how self-esteem of middle school students for mental care influences their academic achievement and to verify the mediation effect of GRIT on academic enthusiasm. Data of 2590 first graders in middle school from the Kora Children and Youth Panel Survey 2019 was used to support this study. Data analysis was performed by using SPSS21.0, AMOS22.0, and PROCESS macro program. The results are as follows. Comparison of the model fits of each full mediation model and partial mediation model with χ2 showed that the full mediation model was more suitable for this study. In more detail, the influence of self-esteem on GRIT and the influence of GRIT on academic enthusiasm were significantly positive. Lastly, the study identified that there was a mediation effect between self-esteem and academic achievement through GRIT and academic enthusiasm. It indicates that self-esteem is the key to improve academic achievement and that specific programs should be supplemented in order to enhance self-esteem, GRIT, and academic enthusiasm.