식물 특이적인 DNA 탈메틸화 효소를 이용하여 DNA 메틸화 수준을 파악함으로써 후성대립유전자를 탐지

학위논문 (석사)-- 서울대학교 대학원 : 식물생산과학부, 2015. 2. 허진회.DNA methylation is one of the crucial epigenetic factors to control gene expression in plants and mammals. Aberrant changes in DNA methylation often lead to the formation of epialleles in plants, and the epimutants that harbor such epialleles sometimes display stable transgenerational inheritance. Therefore, DNA methylation analysis is required to detect epialleles. However, conventional DNA methylation analyses sometimes are not sufficient to detect epialleles. Here we report a novel DNA methylation analysis method combining both 5-methylcytosine (5mC) excision activity of plant-specific DNA demethylase DEMETER (DME) protein and a quantitative real-time PCR (qRT-PCR) technique. Because DME induces a nick in a sequence non-specific manner at the position where 5mC is present, heavily methylated targets cannot be PCR-amplified due to a number of DNA strand breaks, whereas unmethylated or less methylated regions can be easily amplified. We demonstrate the feasibility of DME-qPCR by successfully distinguishing between wild type and two epialleles, fwa and Cnr, derived from Arabidopsis and tomato, respectively. This novel method has versatility over other enzyme-based tools, and at the same time, may overcome several problems that current DNA methylation analysis principles have – such as pretreatment and intrinsic technical bias.ABSTRACT i CONTENTS iii LIST OF TABLES v LIST OF FIGURES vi LIST OF BBREVIATIONS viii INTRODUCTION 1 LITERATURE REVIEWS 4 1. Plant epigenome 2. Principles of DNA methylation analysis 3. Epialleles and epimutants 4. Plant-specific DNA demethylase MATERIAL AND METHODS 11 Purification of DNA demethylase, DEMETER (DME) Preparation of in vitro-methylated plasmids Plant materials Cleaved Amplified Polymorphic Sequences (CAPS) Analysis Bisulfite Sequencing Preparation of quantitative real-time PCR templates Analysis of DNA methylation using quantitative real-time PCR RESULTS 17 CCGG methylation was detected by using DME, not McrBC Proportion of CG-methylated pUC19 plasmids in total plasmid templates was measured by quantitative PCR after DME treatment DME-qPCR distinguished epialleles from wild type alleles DME-qPCR showed difference between hypermethylated wild type allele and hypomethylated fwa allele in F2 population from Arabidopsis DISCUSSION 31 REFERENCES 34 ABSTRACT IN KOREAN 41Maste

정신증의 기능 저하를 반영하는 정신병리학적 요인 탐색 연구

학위논문(석사) -- 서울대학교대학원 : 자연과학대학 뇌인지과학과, 2023. 2. 권준수.Objectives: It is important to properly evaluate and treat the decline in daily function commonly observed in psychosis as it affects the individual's adaptive life. However, there are barriers to visiting a hospital due to negative social perceptions and prejudice against psychosis, so even if psychosis is suspected, it is difficult to be immediately evaluated by a professional. Therefore, it is necessary to actively utilize a self-report evaluation tool. Considering the characteristics of psychosis, not only the symptoms but also functional decline preemptively appears before conversion to a disease, so a self-report tool that can identify the dynamics between symptoms and function is needed. However, these tools have not been developed so far, and exploratory studies to identify the symptom factors related to functions that must be conducted prior to the development of these tools are also insufficient. Therefore, the purpose of this study is to explore factors related to functional decline using symptom-related self-report questionnaires. Methods: We administered 9 self-report questionnaires to evaluate symptom-related factors and a global assessment of functioning (GAF) to 143 patients with first-episode psychosis, 125 subjects with clinical high-risk for psychosis, and 118 healthy controls. A machine learning approach was used to identify the factors of various symptom-related domains that differentiate functional decline based on the GAF scores. A random forest algorithm was used to build a model to classify factors related to functional decline. Based on this, ABC analysis was used to derive the final key factors related to functional decline. Results: In the questionnaires of 5 symptom-related domains, 15 items appeared as major factors in distinguishing functional deterioration. The selected factors are as follows; The Positive and Negative Affect Scale 1, 5, 8, 14, and Beck Depression Inventory 15. Symptom Checklist 2, 5, 12, 14, 15, 17, 20, 21, and Mood Survey 2, and Affect Intensity Measure 39. In order to evaluate the performance of how well major symptom-related factors classify functional decline, one of the representative evaluation indicators, balance accuracy, was found to be 0.808. This value indicates moderate or very good performance. In other words, the agreement between the real functional decline group and the functional decline group predicted by the model as key factors reached 80.8%, confirming that the selected symptom-related factors are important factors explaining functional decline. Conclusions: In this study, we identified key self-reported psychopathological factors related to symptoms that may reflect to functional decline at each stage of the course of psychosis, from healthy controls to patients with schizophrenia. It was also confirmed that these factors discriminated functional differences between subjects with psychosis and healthy controls. The results can be seen as the basis for developing a self-report evaluation tool related to psychosis in the future and laying the foundation for constructing a questionnaire.목적: 정신증에서 일반적으로 관찰되는 일상에서의 기능 저하는 개인의 적응적 삶에 영향을 주어 적절히 평가하고 치료하는 것이 중요하다. 그러나 많은 사람들이 정신증에 대한 부정적인 사회 인식과 편견으로 병원 방문의 장벽이 있어 설사 정신증이 의심되더라도 바로 전문가적 평가를 받기에는 어려움이 있기 때문에 자가보고식 도구가 적극적으로 활용될 필요가 있다. 정신증의 특성상 질환으로 전환되기 전부터 증상 발현 뿐만 아니라 기능 저하 역시 선제적으로 나타나기 때문에 증상과 기능 간의 역동을 파악할 수 있는 자가보고 도구가 필요하지만 현재까지 개발되지 않았고, 이러한 도구 개발에 앞서 선행적으로 실시되어야 하는 기능과 관련된 증상 요인이 무엇인지 규명하는 탐색적 연구 역시 불충분한 상태이다. 따라서 증상 관련 자가보고 설문을 이용하여 기능 저하와 관련되어 있는 요인을 탐색해 보는 것이 본 연구의 목적이다. 방법: 143명의 첫 발병 정신증 환자와 125명의 임상적 정신증 고위험군, 정상 대조군 118명을 대상으로 9가지의 증상 관련 요인을 평가하는 자가보고 설문과 전반적 기능 평가 척도 (GAF)를 시행하였다. GAF 점수 기반의 기능 저하를 구분해주는 다양한 증상 관련 도메인의 요인이 무엇인지 규명하기 위해 기계학습 방법을 이용하였다. 랜덤 포레스트 알고리즘을 사용하여 기능 저하와 관련된 요인들을 분류하는 모델을 구축하였고, ABC 분석을 통해 최종 기능 관련 핵심 요인들을 도출해냈다. 결과: 5가지 증상 관련 도메인의 설문에서 15가지 문항들이 기능적 저하를 구분하는 주요 요인들로 나타났다. 해당하는 요인은 다음과 같다. 정적 정서 및 부적 정서 척도 1, 5, 8, 14번 문항. 벡 우울 척도의 15번 문항. 간이 정신 진단 검사 2, 5, 12, 14, 15, 17, 20, 21번 문항. 기분 질문지의 2번 문항과 정서 강도 척도 39번 문항. 주요한 증상 관련 요인들이 기능 저하를 얼만큼 잘 분류해냈는지 성능을 평가하기 위해 대표 평가 지표 중 하나인 균형 정확도를 측정한 결과 0.808로 나타났고, 이는 성능 기준에 따라 중간이나 아주 좋은 수준의 값을 의미한다. 즉, 실제로 기능이 저하된 그룹과 모델을 통해 핵심 요인들로 예측한 기능 저하 그룹 간의 일치도가 80.8%에 달하여, 선택된 증상 관련 요인들이 기능 저하를 설명해주는 중요한 요인임을 확인하였다. 결론: 본 연구에서는 정상 대조군부터 조현병 환자까지의 기능 저하를 반영할 수 있는 증상 관련 핵심 자가보고 요인이 무엇인지 규명했으며, 이러한 요인들이 정신증을 보이는 대상자와 정상 대조군 간의 기능적 차이를 구분해내는 것을 확인하였다. 해당 결과는 추후 정신증 관련 자가보고식 평가 도구를 개발하는 데에 바탕이 되어 설문을 구성하기 위한 초석을 쌓았다고 볼 수 있다.Chapter 1. Introduction 1 1.1. Study Background 1 1.2. Aim of the Research 3 Chapter 2. Methods 4 2.1. Participants 4 2.2. Measures 5 2.3. Statistical Analysis 11 2.4. Model Building and Performance Assessment 12 Chapter 3. Results 17 3.1. Demographic and clinical characteristics 17 3.2. Psychopathological characteristics 17 3.3. Model for exploring factors of functional decline 21 Chapter 4. Discussion 36 Chapter 5. Conclusion 42 References 45 Appendix 52 Abstract in Korean 67석

Direction of Development for Ulsan’s Whale Sightseeing

본 연구는 울산 관광 산업의 현황 및 문제점을 살펴보고 이와 관련하여 고래관광산업의 발전 방향 및 전략을 제안하고자 하였다. 본 연구는 상공회의소의 서비스산업육성보고서 및 관광산업육성 보고서에 기초하여 단계별 연계형 고래관광을 제안하였다. 또한 포지셔닝 및 촉진 전략을 제시하고 저녁시간 대 휴식 공간 및 프로그램의 개발의 필요성을 제시하였다

Reconstruction of a Severely Damaged Cartilaginous Septum with a Bypass L-Strut Graft using Costal Cartilage

Objectives Reconstruction of a weakened septal cartilage is a key procedure for the correction of deformed noses. However, when septal mucoperichondrium dissection is technically challenging, reconstruction of the lower two-thirds of the nose should be performed bypassing the damaged septal cartilage and mucosa. This article summarizes our experience with treating patients with severely damaged septal cartilage with bypass L-strut graft using costal cartilage. Methods We retrospectively reviewed 26 patients who underwent rhinoplasty using bypass L-strut graft. Autologous costal cartilage was used for creating L-strut in two different ways: (1) by fashioning the L-shaped graft as one unit using the sixth rib cartilage and (2) by integrating a dorsal strut with a columellar strut using slices of the seventh rib cartilage. The caudal strut is fixated to the anterior nasal spine; the dorsal L-strut is placed on the nasal dorsum with no fixation to the nasal bone. Medical records were assessed for demographic, clinical, and treatment information. Results One-piece-type L-strut graft was used for 11 patients and integrated-type L-strut graft was used for 15 patients. No statistical differences were found in postoperative aesthetic outcomes between the two groups. The postoperative assessment of surgical outcomes was excellent in 10 patients, good in 10, fair in 6, and poor in none. Functionally, all 26 patients experienced improvements in nasal breathing. Conclusion Bypass L-strut graft using costal cartilage is a useful surgical maneuver of septal reconstruction in particular nasal deformity when the creation of the septal mucoperichondrial pocket is difficult or better to be avoided