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.

BackgroundThis study aimed to investigate the effects of shift work on abdominal obesity among young and middle-aged female nurses during a 5-year retrospective study.MethodsThis retrospective study included female nurses (20–39 years old) who worked at a university hospital in Korea and had available health screening results from 2010–2015. Among 2,611 employees, 934 healthy 20–39-year-old female nurses were identified, and data regarding their demographic information (age and date of employment), waist circumferences (WC), and lifestyle factors (alcohol and exercise) were obtained. Abdominal obesity was defined as a WC of ≥80 cm, based on the World Health Organization’s Asia-West Pacific standard in 2000. The mean WC change from baseline was analyzed using the paired t test, and the association between shift work and abdominal obesity was analyzed using the generalized estimating equation.ResultsCompared to all day workers (both age groups), the 20–29-year-old nurses did not exhibit significant changes in WC at each follow-up. However, among the 30–39-year-old nurses, shift workers exhibited a significant change in WC (vs. baseline) during years 4 and 5, compared to day workers. After adjusting for effective confounders and stratifying the participants according to age, the 20–29-year-old nurses exhibited an odds ratio of 3.21 (95 % confidence interval: 1.29–7.98) for shift work-associated obesity, although the odds ratio for the 30–39-year-old nurses was not statistically significant.ConclusionIn the study population, shift work was associated with a significant change in mean WC among 30–39-year-old nurses, and the shift work-associated risk of abdominal obesity was significant among 20–29-year-old nurses. These results indicate that shift work may influence abdominal obesity differently in 20–29-year-old and 30–39-year-old female nurses.

SummaryHippocampal synaptic function and plasticity deteriorate with age, often resulting in learning and memory deficits. As MicroRNAs (miRNAs) are important regulators of neuronal protein expression, we examined whether miRNAs may contribute to this age‐associated decline in hippocampal function. We first compared the small RNA transcriptome of hippocampal tissues from young and old mice. Among 269 hippocampal miRNAs, 80 were differentially expressed (≥ twofold) among the age groups. We focused on 36 miRNAs upregulated in the old mice compared with those in the young mice. The potential targets of these 36 miRNAs included 11 critical Eph/Ephrin synaptic signaling components. The expression levels of several genes in the Eph/Ephrin pathway, including EphB2, were significantly downregulated in the aged hippocampus. EphB2 is a known regulator of synaptic plasticity in hippocampal neurons, in part by regulating the surface expression of the NMDA receptor NR1 subunit. We found that EphB2 is a direct target of miR‐204 among miRNAs that were upregulated with age. The transfection of primary hippocampal neurons with a miR‐204 mimic suppressed both EphB2 mRNA and protein expression and reduced the surface expression of NR1. Transfection of miR‐204 also decreased the total expression of NR1. miR‐204 induces senescence‐like phenotype in fully matured neurons as evidenced by an increase in p16‐positive cells. We suggest that aging is accompanied by the upregulation of miR‐204 in the hippocampus, which downregulates EphB2 and results in reduced surface and total NR1 expression. This mechanism may contribute to age‐associated decline in hippocampal synaptic plasticity and the related cognitive functions.

ObjectivesTo assess the effectiveness of a comprehensive workplace stress management program consisting of participatory action-oriented training (PAOT) and individual management.MethodsA comprehensive workplace stress management program was conducted in a medium-sized enterprise. The baseline survey was conducted in September 2011, using the Korean Occupational Stress Scale (KOSS) and Worker’s Stress Response Inventory (WSRI). After implementing both organizational and individual level interventions, the follow up evaluation was conducted in November 2011.ResultsMost of the workers participated in the organizational level PAOT and made Team-based improvement plans. Based on the stress survey, 24 workers were interviewed by a researcher. After the organizational and individual level interventions, there was a reduction of several adverse psychosocial factors and stress responses. In the case of blue-collar workers, psychosocial factors such as the physical environment, job demands, organizational system, lack of rewards, and occupational climate were significantly improved; in the case of white-collar workers, the occupational climate was improved.ConclusionsIn light of these results, we concluded that the comprehensive stress management program was effective in reducing work-related stress in a short-term period. A persistent long-term follow up is necessary to determine whether the observed effects are maintained over time. Both team-based improvement activities and individual interviews have to be sustainable and complementary to each other under the long-term plan.

Objective For the proper treatment of first-episode psychosis, assessment of treatment response, remission, relapse, and recovery is important. Therefore, the present study aimed to develop operational definitions of clinical outcomes in first-episode psychosis.Methods A questionnaire was developed by a panel of experts and underwent three revisions. The final survey was presented to 150 psychiatrists who were members of the Korean Society for Schizophrenia Research. Respondents selected factors that they believed were important to consider while defining treatment response, remission, relapse, and recovery using a 6-point Likert scale. Selected factors that constituted each definition were statistically extracted, and operational definitions were developed.Results A total of 91 experts responded to the survey. The extent of reduction in psychopathology, socio-occupational functioning, and duration of each state were the core factors of each definition. Outcomes obtained from discussions and consultations by experts have been summarized and proposed.Conclusion The criteria developed in this survey tended to be somewhat stricter than those used by other studies. The fundamental reason for this is that this survey focused on first-episode psychosis. A better understanding of each definition in first-episode psychosis is necessary to improve effective treatment outcomes.