Reliability and Validity of the Korean Version of the Spinal Cord Independence Measure III.

OBJECTIVE: Given the lack of a Korean version of the Spinal Cord Independence Measure III (KSCIM-III) that accurately reflects the contextual and cultural aspect of the assessment tool, the aims of the study were to develop a new Korean version of the Spinal Cord Independence Measure III and to investigate its reliability and validity. DESIGN: Forty (N = 40) consecutive patients with spinal cord injury were included in this prospective study. Backward and forward translation of the Spinal Cord Independence Measure III was performed by fluent speakers in both languages. To measure the validity of Korean version of the Spinal Cord Independence Measure III, the scores were compared with the Modified Barthel Index. Each patient was examined by two occupational therapists. For test-retest reliability assessment, follow-up evaluation was repeated 1 mo after the initial assessment by the same evaluator. RESULTS: Reliability between the Korean version of the Spinal Cord Independence Measure III evaluators showed values of 0.710-1.000, and test-retest reliability showed high values ranging from 0.295 to 0.664. The validity of Korean version of the Spinal Cord Independence Measure III was confirmed by the close correlation with Modified Barthel Index (r = 0.953, P < 0.001). CONCLUSIONS: The results of this study showed high interrater and substantial test-retest reliability. The Korean version of the Spinal Cord Independence Measure III is an appropriate tool to assess the activities of daily living in terms of independence for patients with spinal cord injury.

Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons.

Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis. Transcription factor enrichment analysis identified CREB3L1/CrebA, which regulates COPII gene expression. CrebA overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP synthesis, and PM supply. Chromatin immunoprecipitation (ChIP)-PCR revealed that CrebA expression is regulated by CREB-binding protein (CBP), which is sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restores the polyQ-induced dendrite pathology. Collectively, our results suggest that GOPs impaired by polyQ proteins contribute to dendrite pathology through the CBP-CrebA-COPII pathway.

Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) constitutes a genetic disease wherein an aging phenotype manifests in childhood. Recent studies indicate that reactive oxygen species (ROS) play important roles in HGPS phenotype progression. Thus, pharmacological reduction in ROS levels has been proposed as a potentially effective treatment for patient with this disorder. In this study, we performed high-throughput screening to find compounds that could reduce ROS levels in HGPS fibroblasts and identified rho-associated protein kinase (ROCK) inhibitor (Y-27632) as an effective agent. To elucidate the underlying mechanism of ROCK in regulating ROS levels, we performed a yeast two-hybrid screen and discovered that ROCK1 interacts with Rac1b. ROCK activation phosphorylated Rac1b at Ser71 and increased ROS levels by facilitating the interaction between Rac1b and cytochrome c. Conversely, ROCK inactivation with Y-27632 abolished their interaction, concomitant with ROS reduction. Additionally, ROCK activation resulted in mitochondrial dysfunction, whereas ROCK inactivation with Y-27632 induced the recovery of mitochondrial function. Furthermore, a reduction in the frequency of abnormal nuclear morphology and DNA double-strand breaks was observed along with decreased ROS levels. Thus, our study reveals a novel mechanism through which alleviation of the HGPS phenotype is mediated by the recovery of mitochondrial function upon ROCK inactivation.