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DJ-1 protects cell death from a mitochondrial oxidative stress due to GBA1 deficiency
Nam Younwoo,Na Jiyeon,Ma Shi-Xun,Park Ha-Eun,Park Hyeonwoo,Lee Eunmin,Kim Hyerynn,Jang Sang-Min,Ko Han Seok,Kim Sangjune 한국유전학회 2024 Genes & Genomics Vol.46 No.5
Background GBA1 mutations are the most common genetic risk factor for development of Parkinson’s disease (PD). The loss of catalytic activity in GBA1, as well as the reduction of the GBA1 protein in certain cellular compartment, may increase disease progression. However, the mechanisms underlying cellular dysfunction caused by GBA1 deficiency are still mostly unknown. Objective In this study, we focus on the genetic interaction between GBA1 deficiency and PD-causing genes, such as DJ-1, in mitochondrial dysfunction. Methods GBA1 knockout (KO) SH-SY5Y cells were used to assess DJ-1 functions against oxidative stress in vitro. The levels of cellular reactive oxygen species were monitored with MitoSOX reagent. The expression of the PARK7 gene was analyzed using the quantitative real-time PCR (qRT-PCR). To understand the mechanism underlying DJ-1 upregulation in GBA1 KO cells, we assess ROS levels, antioxidant protein, and cell viability in GBA1 KO cells with treatment of ROS inhibitor N-acetyl-cysteine or miglustat, which is an inhibitor of glucosylceramide synthase. Dopaminergic degeneration was assessed from Gba1 L444P heterozygous mice mated with Park7 knockout mice. Results We find that DJ-1 is significantly upregulated in GBA1 KO cells. Elevated levels of DJ-1 are attributed to the transcriptional expression of PARK7 mRNA, but not the inhibition of DJ-1 protein degradation. Because DJ-1 expression is highly linked to oxidative stress, we observe cellular reactive oxygen species (ROS) in GBA1 KO cells. Moreover, several antioxidant gene expressions and protein levels are increased in GBA1 KO cells. To this end, GBA1 KO cells are more susceptible to H2O2-induced cell death. Importantly, there is a significant reduction in dopaminergic neurons in the midbrain from Gba1 L444P heterozygous mice mated with Park7 knockout mice, followed by mild motor dysfunction. Conclusion Taken together, our results suggest that DJ-1 upregulation due to GBA1 deficiency has a protective role against oxidative stress. It may be supposed that mutations or malfunctions in the DJ-1 protein may have disadvantages in the survival of dopaminergic neurons in the brains of patients harboring GBA1 mutations. Background GBA1 mutations are the most common genetic risk factor for development of Parkinson’s disease (PD). The loss of catalytic activity in GBA1, as well as the reduction of the GBA1 protein in certain cellular compartment, may increase disease progression. However, the mechanisms underlying cellular dysfunction caused by GBA1 deficiency are still mostly unknown. Objective In this study, we focus on the genetic interaction between GBA1 deficiency and PD-causing genes, such as DJ-1, in mitochondrial dysfunction. Methods GBA1 knockout (KO) SH-SY5Y cells were used to assess DJ-1 functions against oxidative stress in vitro. The levels of cellular reactive oxygen species were monitored with MitoSOX reagent. The expression of the PARK7 gene was analyzed using the quantitative real-time PCR (qRT-PCR). To understand the mechanism underlying DJ-1 upregulation in GBA1 KO cells, we assess ROS levels, antioxidant protein, and cell viability in GBA1 KO cells with treatment of ROS inhibitor N-acetyl-cysteine or miglustat, which is an inhibitor of glucosylceramide synthase. Dopaminergic degeneration was assessed from Gba1 L444P heterozygous mice mated with Park7 knockout mice. Results We find that DJ-1 is significantly upregulated in GBA1 KO cells. Elevated levels of DJ-1 are attributed to the transcriptional expression of PARK7 mRNA, but not the inhibition of DJ-1 protein degradation. Because DJ-1 expression is highly linked to oxidative stress, we observe cellular reactive oxygen species (ROS) in GBA1 KO cells. Moreover, several antioxidant gene expressions and protein levels are increased in GBA1 KO cells. To this end, GBA1 KO cells are more susceptible to H2O2-induced cell death. Importantly, there is a significant reduction in dopaminergic neurons in the midbrain from Gba1 L444P heterozygous mice mated with Park7 knockout mice, followed by mild motor dysfunction. Conclusion Taken together, our results suggest that DJ-1 upregulation due to GBA1 deficiency has a protective role against oxidative stress. It may be supposed that mutations or malfunctions in the DJ-1 protein may have disadvantages in the survival of dopaminergic neurons in the brains of patients harboring GBA1 mutations.
박현우(Hyeonwoo Park),안성희(SungHee Ahn) 한국HCI학회 2022 한국HCI학회 학술대회 Vol.2022 No.2
본 연구는 자율주행 3.5 단계를 새롭게 세분화하여 운전대의 부재가 사용자에게 주는 불안감을 해소할 수 있는 대안적인 단계를 위한 운전대(이하 스티어링 휠)의 설계를 위한 UX 디자인을 진행하였다. 자율주행과 반자율주행의 장점을 결합하여 ‘자율주행 3.5 단계’로 설정된 드라이빙 모드를 가설로 사용자 경험연구를 진행하고 드라이빙 인터페이스와 커뮤니케이션 인터페이스를 디자인 개발하였다. 본연구에서 개발한 "오메가" 스티어링 휠은 주행 중 중요시되는 기존의 대쉬보드에 컨트롤 인터페이스와 개인용 모바일기기들의 인터페이스를 모두 휠 스크린으로 흡수하여 자유롭게 사용자가 커스터마이징 할 수 있도록 설계하였다. 자율주행 시 스티어링 휠은 아래쪽으로 이동, 축소되어 완전히 없어지지 않고 돌발상황 때 일어나는 위험요소들을 대기할 수 있도록 해주어 운전자들에게 심리적 안정감을 제공하도록 사람과 자동차의 인터랙션을 설계하였다.
Distinctive Clinical Correlates of Psychotic Major Depression: The CRESCEND Study
SeonCheol Park,HwaYoung Lee,JeongKyu Sakong,TaeYoun Jun,MinSoo Lee,JaeMin Kim,JungBum Kim,HyeonWoo Yim,YongChon Park 대한신경정신의학회 2014 PSYCHIATRY INVESTIGATION Vol.11 No.3
Objective-The purpose of this investigation was to identify distinctive clinical correlates of psychotic major depression (PMD) as compared with non-psychotic major depression (NPMD) in a large cohort of Korean patients with major depressive disorder (MDD). Methods-We recruited 966 MDD patients of age over 18 years from the Clinical Research Center for Depression of South Korea (CRESCEND) study. Diagnoses of PMD (n=24) and NPMD (n=942) were made with the DSM-IV definitions and confirmed with SCID. Psychometric scales were used to assess overall psychiatric symptoms (BPRS), depression (HAMD), anxiety (HAMA), global severity (CGI-S), suicidal ideation (SSI-Beck), functioning (SOFAS), and quality of life (WHOQOL-BREF). Using independent t-tests and χ2 tests, we compared clinical characteristics of patients with PMD and NPMD. A binary logistic regression model was constructed to identify factors independently associated with increased likelihood of PMD. Results-PMD subjects were characterized by a higher rate of inpatient enrollment, and higher scores on many items on BPRS (somatic concern, anxiety, emotional withdrawal, guilt feelings, tension, depression, suspiciousness, hallucination, motor retardation, blunted affect and excitement) global severity (CGI-s), and suicidal ideation (SSI-Beck). The explanatory factor model revealed that high levels of tension, excitement, and suicidal ideation were associated with increased likelihood of PMD. Conclusion-Our findings partly support the view that PMD has its own distinctive clinical manifestation and course, and may be considered a diagnostic entity separate from NPMD.
Hyeonwoo Kim,Jiwon Kim,Ji Won Cho,Kwang-Sung Ahn,Dong-Il Park,Sangsoo Kim Korea Genome Organization 2023 Genomics & informatics Vol.21 No.3
Microbial community profiling using 16S rRNA amplicon sequencing allows for taxonomic characterization of diverse microorganisms. While amplicon sequence variant (ASV) methods are increasingly favored for their fine-grained resolution of sequence variants, they often discard substantial portions of sequencing reads during quality control, particularly in datasets with large number samples. We present a streamlined pipeline that integrates FastP for read trimming, HmmUFOtu for operational taxonomic units (OTU) clustering, Vsearch for chimera checking, and Kraken2 for taxonomic assignment. To assess the pipeline's performance, we reprocessed two published stool datasets of normal Korean populations: one with 890 and the other with 1,462 independent samples. In the first dataset, HmmUFOtu retained 93.2% of over 104 million read pairs after quality trimming, discarding chimeric or unclassifiable reads, while DADA2, a commonly used ASV method, retained only 44.6% of the reads. Nonetheless, both methods yielded qualitatively similar β-diversity plots. For the second dataset, HmmUFOtu retained 89.2% of read pairs, while DADA2 retained a mere 18.4% of the reads. HmmUFOtu, being a closed-reference clustering method, facilitates merging separately processed datasets, with shared OTUs between the two datasets exhibiting a correlation coefficient of 0.92 in total abundance (log scale). While the first two dimensions of the β-diversity plot exhibited a cohesive mixture of the two datasets, the third dimension revealed the presence of a batch effect. Our comparative evaluation of ASV and OTU methods within this streamlined pipeline provides valuable insights into their performance when processing large-scale microbial 16S rRNA amplicon sequencing data. The strengths of HmmUFOtu and its potential for dataset merging are highlighted.