FGF13 이 지방산에 의한 골격근 인슐린 저항성에 미치는 영향

학위논문 (석사)-- 서울대학교 융합과학기술대학원 : 분자의학 및 바이오제약학과, 2015. 8. 박경수.Fibroblast growth factors (FGFs) are categorized as paracrine, endocrine and intracrine and are involved in development, cell proliferation, differentiation and metabolism. The secreted FGFs function by interacting with FGF receptors while intracellular non-secreting FGFs interact with voltage gated sodium channels. FGF13 is a member of the intracellular fibroblast growth factor family. FGF13 has various transcript variants by alternatively splicing at 5 end. This study was aimed to investigate the regulation of FGF13 in diet induced obese mice and in fatty acid induced insulin resistance in skeletal muscle. FGF13 isoform 1 was mainly distributed in brain and adipose tissues while FGF13 isoform 2 was predominantly expressed in heart and muscle. I have demonstrated that both muscle and adipose expression of FGF13 was reduced in 12 week high fat fed mice. 24 hour exposure to palmitate decreased FGF13 isoform 2 in C2C12 muscle cells. I also found that palmitate decreased FGF13 through TLR4 pathway. Moreover, when FGF13 was knockdown, immediate early genes of downstream ERK/JNK was suppressed. To further investigate the role of FGF13 in insulin signaling model, FGF13 was overexpressed or knocked down on C2C12 myotubes. I was able to confirm that overexpressing FGF13 could recover AKT signaling during palmitate treatment while knockdown reduced phospho-AKT. Moreover, overexpression of FGF13 reduced phospho-JNK which is known to affect insulin signaling. These findings suggests that FGF13 protein have a role in insulin signaling pathway in fatty acid induced insulin resistance.Abstract ……………………………………………………… 1 List of Figures ……………………………………………… 4 List of Tables……………………………………………… 6 Introduction …..…………………………………………… 7 Materials and Methods ………………………………………… 10 Results …….…………………………………………………….. 17 Discussion ……………………………………………………… 38 Conclusion ………………………………………………… 41 References …………………………………………………… 42 국문초록………………………………….……………………… 45Maste

In vitro erythrocyte production using human-induced pluripotent stem cells: determining the best hematopoietic stem cell sources

Background: Blood transfusion is an essential part of medicine. However, many countries have been facing a national blood crisis. To address this ongoing blood shortage issue, there have been efforts to generate red blood cells (RBCs) in vitro, especially from human-induced pluripotent stem cells (hiPSCs). However, the best source of hiPSCs for this purpose is yet to be determined. Methods: In this study, hiPSCs were established from three different hematopoietic stem cell sources—peripheral blood (PB), cord blood (CB) and bone marrow (BM) aspirates (n = 3 for each source)—using episomal reprogramming vectors and differentiated into functional RBCs. Various time-course studies including immunofluorescence assay, quantitative real-time PCR, flow cytometry, karyotyping, morphological analysis, oxygen binding capacity analysis, and RNA sequencing were performed to examine and compare the characteristics of hiPSCs and hiPSC-differentiated erythroid cells. Results: hiPSC lines were established from each of the three sources and were found to be pluripotent and have comparable characteristics. All hiPSCs differentiated into erythroid cells, but there were discrepancies in differentiation and maturation efficiencies: CB-derived hiPSCs matured into erythroid cells the fastest while PB-derived hiPSCs required a longer time for maturation but showed the highest degree of reproducibility. BM-derived hiPSCs gave rise to diverse types of cells and exhibited poor differentiation efficiency. Nonetheless, erythroid cells differentiated from all hiPSC lines mainly expressed fetal and/or embryonic hemoglobin, indicating that primitive erythropoiesis occurred. Their oxygen equilibrium curves were all left-shifted. Conclusions: Collectively, both PB- and CB-derived hiPSCs were favorably reliable sources for the clinical production of RBCs in vitro, despite several challenges that need to be overcome. However, owing to the limited availability and the large amount of CB required to produce hiPSCs, and the results of this study, the advantages of using PB-derived hiPSCs for RBC production in vitro may outweigh those of using CB-derived hiPSCs. We believe that our findings will facilitate the selection of optimal hiPSC lines for RBC production in vitro in the near future.ope

Genetic diagnosis of inborn errors of immunity using clinical exome sequencing

Inborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, clinical utility of clinical exome sequencing (CES) for diagnosis of IEI was evaluated. For 37 Korean patients with suspected symptoms, signs, or laboratory abnormalities associated with IEI, CES that covers 4,894 genes including genes related to IEI was performed. Their clinical diagnosis, clinical characteristics, family history of infection, and laboratory results, as well as detected variants, were reviewed. With CES, genetic diagnosis of IEI was made in 15 out of 37 patients (40.5%). Seventeen pathogenic variants were detected from IEI-related genes, BTK, UNC13D, STAT3, IL2RG, IL10RA, NRAS, SH2D1A, GATA2, TET2, PRF1, and UBA1, of which four variants were previously unreported. Among them, somatic causative variants were identified from GATA2, TET2, and UBA4. In addition, we identified two patients incidentally diagnosed IEI by CES, which was performed to diagnose other diseases of patients with unrecognized IEI. Taken together, these results demonstrate the utility of CES for the diagnosis of IEI, which contributes to accurate diagnosis and proper treatments.ope

Direct eletion reform adn democratization in the Chinese primary level government

Thesis(master`s)--서울大學校 國際大學院 :國際學科, 國際地域學專攻,2006.Maste

F. P. Schubert의 후기 피아노 소나타(D.958, D.959, D.960)에 관한 연구

학위논문(석사)--서울대학교 대학원 :음악과 피아노전공,1997.Maste

Vitamin이 Magnaporthe grisea의 부착기 형성에 미치는 영향

Thesis (master`s)--서울대학교 대학원 :농생물학과 식물병리전공,2000.Maste

드럼세탁기 내 직물거동분석 -3.25kg 세탁 부하량을 중심으로-

학위논문 (석사)-- 서울대학교 대학원 : 의류학과, 2015. 2. 박정희.본 연구에서는 실제 세탁 부하량 조건에서 드럼 세탁기 내 직물 거동을 분석하고 직물 거동 특성에 따른 세척성의 차이를 알아보고자 하였다. 이를 위하여, 3.25kg의 세탁 부하량에서 세탁 회전 속도를 달리하여 다양한 직물 거동을 유도하였다. 집합적 차원과 개별적 차원의 두 관점에서 직물 거동을 분석하였고, 이를 수치화 및 시각화 하였다. 마지막으로, 직물 거동 특성과 세척성의 상관관계를 분석하여 세척성 향상에 영향을 미치는 중요한 인자를 도출하였다. 세탁 회전 속도에 따라 직물 거동 특성에 차이가 있었는데, 집합적 차원의 직물 거동 분석으로부터, 직물이 세탁기 내에서 차지하는 면적에 차이가 있음을 알았다. 또한, 개별적 차원의 직물 거동 분석으로는 표지 직물 거동이 12가지로 분류되었고, 각 세탁 회전 속도에서의 표지 직물 거동 양상과 직물 간 상호작용의 정도가 달라짐을 보았다. 세척성 평가 결과, 집합적 및 개별적 직물 거동 특성의 차이로 인해 세탁 회전 속도 46rpm에서 최대의 세척성을 나타냄을 알 수 있었다. 집합적 및 개별적 직물 거동 특성을 수치화한 10가지의 직물 거동 지수의 유의성과 세척성과의 상관성을 통계적으로 분석하였다. 그 결과, 세척성에 영향을 미치는 직물 거동 지수로 세탁물 집합의 차지 면적 최대값/최소값, 세탁물 집합의 차지 면적 평균과 편차, 표지 직물의 드럼 중심으로부터의 거리 평균과 편차, 드럼과 표지 직물의 속도 차 평균, 표지 직물의 출현 빈도가 추출되었다. 그리고 회귀분석 결과 표지 직물의 드럼 중심으로부터의 거리 평균, 표지 직물의 출현빈도가 세척성에 대한 회귀식의 영향이 큰 두 가지 독립변수로 나타났으며, 위 두 거동지수가 작을수록 세척성이 높은 것으로 나타났다. 이는 낙하와 같은 기계력이 큰 거동뿐 아니라 직물 간의 섞임, 마찰과 같은 상호작용이 활발할수록 세척성이 높다는 것을 의미한다.Fabric movements in a front-loading washer were analyzed and the correlation between fabric movements and detergency was investigated. With 3.25kg laundry load, 25% of maximum load, various fabric movements were induced with different drum rotating speed. Fabric movements were observed by macro and micro dimension and they were digitized and visualized. Finally, the influence of fabric movements on detergency was investigated. As for the macro fabric movements, the occupied area ratios by laundry loads in the washer were varied according to the drum rotating speed. As for the micro fabric movements, the movements of tracer fabric were divided into 12 movements. The tendency of micro fabric movements as well as the degree of interactions between fabrics at each rotating speed were investigated. The characteristics of macro and micro fabric movement also influenced on detergency and resulted in the maximum detergency at 46rpm. Among ten fabric movement indexes, five indexes (occupied area of laundry batch, maximum and minimum value ratio of occupied area of laundry batch, distance between the center of drum and tracer fabric, speed difference between drum and tracer fabric, appearance frequency of tracer fabric) came out to have a statistically significant correlation with detergency. Also, a regression equation of detergency was obtained with R2 value of 0.707 and p-value below 0.01. The two independent variables of the regression equation were average value of distance between center of the drum and tracer fabric and appearance frequency of tracer fabric, with an inverse correlation with detergency. Therefore, it was concluded that not only mechanical force like falling movement but also interactions between fabrics like abrasion and mixing were needed to improve detergency for practical laundry loads.목 차 I. 서론 01 II. 실험 09 1. 시료 09 2. 세탁기 11 3. 직물거동 분석 13 3.1. 세탁조건 13 3.2. 직물거동 촬영 17 3.3. 동영상 분석 19 4. 세척성 평가 22 4.1. 세탁조건 22 4.2. 세척성 측정 29 5. 통계 분석 31 III. 결과 및 고찰 32 1. 직물 거동 분석의 조건 32 2. 세탁회전속도에 따른 직물의 거동 37 2.1. 집합적 거동 39 2.2. 개별적 거동 44 3. 직물 거동이 세척성에 미치는 영향 52 3.1. 세탁회전속도에 따른 세척성과 세척의 균일성 52 3.2. 직물 거동의 수치화 56 3.3. 직물거동지수와 세척성의 상관관계 60 IV. 요약 및 결론 66 V. 참고문헌 69 부 록 I. 73 Abstract 80Maste