Oita University

Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase known to function as a tumor suppressor by promoting ubiquitination and degradation of the Myc protein. In this study, we investigated the role of cyclin-dependent kinase 5 (CDK5) in regulating GSK-3β kinase activity, as well as Myc phosphorylation and ubiquitination. Four Ewing sarcoma cell lines were used in this study. Cells were transfected with a CDK5 expression vector, and cell proliferation, cell-cycle progression, and apoptosis were analyzed. We examined whether CDK5 alters the phosphorylation status of GSK-3β. In addition, siRNA-mediated knockdown and expression vectors were used to modulate CDK5 and GSK-3β expression, and the effects on Myc ubiquitination were evaluated. Compared with control cells, CDK5-overexpressing Ewing sarcoma cells showed increased proliferative capacity and enhanced cell-cycle progression. Under these conditions, dephosphorylation of GSK-3β at Tyr216 and phosphorylation at Ser9 as well as Ser389 - patterns consistent with the inactive form of GSK-3β - were observed. Concomitantly, ubiquitination of the Myc protein was reduced. In contrast, cells transfected with a GSK-3β expression vector exhibited increased Myc phosphorylation and ubiquitination. These findings suggest that functional impairment of GSK-3β and subsequent upregulation of Myc may promote the proliferation of Ewing sarcoma cells. Myc is normally phosphorylated by GSK-3β, which triggers its ubiquitination and proteasomal degradation. Although CDK5 is recognized as a cell-cycle-related kinase, our results demonstrate that CDK5 is associated with increased inhibitory phosphorylation of GSK-3β, resulting in functional suppression of its activity. As a result, GSK-3β-mediated phosphorylation of Myc is attenuated, leading to reduced ubiquitination and accumulation of Myc. Regulation of Myc expression through CDK5-mediated modulation of GSK-3β plays a critical role in controlling Ewing sarcoma cell proliferation and may represent a promising therapeutic target.

Aim: In this study, we aimed to investigate the relationship between disaster prevention and community awareness and physical and mental health among residents of the Yunohira district of Yufuin town, Oita Prefecture, Japan. We also aimed to examine the factors that help prevent an accelerated population decline after a disaster.

bleeding during surgery, which may lead to unintentionally less radical surgery.Surgeons should be trained to precisely develop the retroperitoneal avascular spaces.

Regional differences in the gut microbiota and CRC incidence and mortality rates are well-documented. However, studies on the microbiota associated with CRC in Indonesia remain scarce. This study aimed to chracterize the gut microbiota profile of CRC in Indonesia. We collected stool samples from 14 patients with CRC (CRC), 19 patients with non-CRC bowel diseases (non-CRC), and 16 healthy controls (HC). The gut microbiota profiles across the three groups were analyzed using 16 S rRNA gene amplicon sequencing. Data analysis was performed using several software packages: QIIME2, ANCOM-BC2, and PICRUSt2. In comparison to the non-CRC and HC groups, patients with CRC demonstrated significant differences in both alpha and beta diversity. The CRC group had lower evenness and richness than the HC group. Firmicutes and Bacteroidota were identified as the predominant phyla across all groups. The differential abundance analysis identified four beneficial genera that were substantially reduced in Indonesian CRC patients: Roseburia, Dialister, Agathobacter, and Muribaculaceae. No genera were found to be significantly enriched in CRC. Functional prediction analysis revealed multiple pathways such as mTOR, mRNA surveillance, basal transcription factors, phagosome, and proteasome, were reduced in CRC. Conversely, CRC demonstrated a significant upregulation of pathways related to lipid metabolism and the biosynthesis of flavonoids, stilbenoids, diarylheptanoids, and gingerols. Our study revealed distinct gut microbiota profiles in Indonesian CRC patients, highlighting the significance of decreased abundance of certain beneficial taxa.

本研究は、生活道路における人優先意識の向上を目的とし、路面装飾に着目した社会実験を実施したものである。東京都豊島区雑司が谷を対象に、既往研究で用いられている緑と白のドットデザインを基盤としつつ、子ども向けのワークショップや住民協議を経て具体的なデザインを決定・設置する住民参加型プロセスを導入した。本論文の目的は、こうしたプロセスが通行者の路面装飾に対する愛着や受容性に与える影響を明らかにすることである。分析の結果、歩行者に対して住民参加の情報を提示することで、路面装飾への愛着が向上し、受容性に対する肯定的評価が強化される傾向が確認された。また、子どもたちの参画は、地域全体に対する好意的な評価を促す可能性が示唆された。今後は、得られた知見を踏まえ、継続的な活動のあり方を検討していく必要がある。

This study investigated whether wakeful targeted memory reactivation (TMR) during short rest intervals improves motor learning. Participants were randomly assigned to three groups and performed a sequential key-press task under each condition: (1) TMRregular group: auditory cues played at the same speed as the previous task, (2) TMRfast group: auditory cues played 1.3 times faster, and (3) TMRrandom group: auditory cues randomized in pitch. To examine the motor learning effect of cue structure, we compared motor learning across three groups (TMRregular, TMRfast, and TMRrandom). The TMRfast group enhanced early learning gains compared with the TMRregular group. Electroencephalogram data revealed stronger functional connectivity centered on the lateral orbitofrontal cortex (lOFC) in the TMRfast group than in the TMRregular group. Together, these findings suggest that wakeful TMR can enhance early motor learning depending on cue timing and structure, highlighting the importance of optimizing sensory parameters for learning improvement.