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      • ARD1에 의한 PRMT5 아세틸화가 암세포 증식에 미치는 영향 연구

        응웬 히엔 계명대학교 대학원 2022 국내석사

        RANK : 234047

        단백질 아르기닌 메틸전달효소 5(PRMT5)는 종양유발단백질로 다양한 종류의 암 발생에 기여한다고 알려져 있다. 이전의 연구에서 PRMT5는 여러 종류의 암세포에서 세포질에 위치하는 반면, 대부분의 정상 조직에서는 핵에 위치하는 것으로 밝혀졌다. 그러나 PRMT5의 위치와 기능을 조절하는 분자 메커니즘에 대해서는 알려진 바가 없다. 본 연구에서는 PRMT5의 위치가 ARD1에 의한 아세틸화에 의해 조절된다는 것을 발견했다. PRMT5는 세포질에서 국소적으로 발현되지만, 490번 라이신 잔기가 변이되어 탈아세틸화 된 PRMT5 K490R은 핵으로 전위되었다. 또한 정상 PRMT5는 암세포 성장을 촉진하는 반면, PRMT5 K490R은 암세포 증식을 촉진하지 못하였다. 기전 연구를 통해 PRMT5의 세포질 위치는 NF-κB 경로의 활성화에 필요하며, 이는 세포 주기 진행에 필요한 NF-kB 표적 유전자의 발현으로 이어짐을 규명하였다. 따라서 본 논문에서는 ARD1에 의한 PRMT5 아세틸화가 세포질의 NF-κB 활성을 증가시켜 암세포의 증식을 촉진함을 규명하였다. Protein Arginine Methyltransferase 5 (PRMT5) is known as an oncoprotein and contributes to the development of many types of cancer. In previous studies, PRMT5 was discovered to localize in cytosol in several types of cancer cells but localize in nucleus in almost of normal tissues. However, the molecular mechanism that regulates PRMT5 localization and its function remains unclear. In this study, I found that PRMT5 localization is regulated by ARD1-mediated acetylation. I observed that wild-type PRMT5 localizes in cytosol, while non-acetylated form (K490R) of PRMT5 translocates into nucleus. In addition, I found that cytosolic localization of PRMT5 is essential for cancer cell proliferation. Wild-type PRMT5, but not PRMT5 K490R, enhances the cancer cell growth. Mechanistic study revealed that cytosolic localization of PRMT5 is required for NF-κB pathway activation, leading to the expression of NF-kB target genes required for cell cycle progression. Taken together, ARD1-mediated PRMT5 acetylation is essential for its cytosolic localization, then promoting cell proliferation by activating NF-κB activity.

      • Effect of directional switching frequency on gasoline biodegradation in a biofilter

        응웬 히엔 명지대학교 대학원 2005 국내석사

        RANK : 234031

        To ensure stable long-term biofilter performance, one of known solutions is directional switching (DS) operation, in which the air stream direction is periodically reversed through the reactor. In this study, the effect of DS frequency on gasoline degradation in a vapor-phase biofilter was investigated. Glass columns (ø 100 × 600mm working height) packed with a mixture of wormcast and woodchip blend (4:1, v/v) were used as biofilters. Three bench-scale biofilters with different switching frequency (SF): 3.5 days, 1 week and 2 weeks were used, and a gasoline mixture was used as a model compound. The UD biofilter was used as a control biofilter. Overall, the DS system performed better than UD system. Among the three switching frequencies examined, the 3.5-day SF yielded the most efficient performance by balancing re-acclimation requirements with minimum biodegradation activity loss. Following each airstream reversal, the biofilter operated at 1-week and 2-week SFs required 51.5 and 71.5 hours, respectively to fully restore biodegradation capacity in the inlet biofilter section. In contrast, the biofilter with 3.5-day SF required only 24 hours for restoration of its activity. The distribution of heterotrophic bacteria as well as the electron transport system activity (ETSA) along the height of the biofilter was most uniform in the biofilter with 3.5-day SF. On the contrary, the bacterial population concentrated highest at the bottom and lowest at the top in the biofilter with 2-week SF. These results show that the DS operation can enhance the efficiency of long-term operation of vapor-phase biofilters. However, it is necessary to further investigate the microbial community dynamics during biofilter performance using phospholipids fatty acid (PLFA) or terminal restriction fragment length polymorphism (T-RFLP) analysis. Another way can also ensure stable long-term performance of biofilter is using starvation periods. In the present study, the dynamic behavior of biofilter exposed to period of starvation was also investigated. As a biofilter, a glass column was used and the volume of filter bed was 1.3 L. Filter media materials used was the mixture of wormcast and woodchip blend (4:1, v/v). The experimental protocol consisted of starving biofilter under various time conditions of starvation: 1day, 2days, 4days, 1week, 2weeks and 1month. The duration of starvation period, only humidified air was passing through the biofilters. The results show that the re-acclimation times to re-establish full performance of gasoline-degrading biofilters after periods of nonuse is short. The short time of starvations period is almost no effect on biofilter performance (In the case of 1day and 2 days). Longer periods of starvation required longer periods of re-acclimation (4day: 24 h; 1 week: 33 h; 2weeks: 51 h and 1month: 70 h). The biofilter were capable of withstanding for 1 to 30 days and recovered full performance after starvation without any evident lag period.

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