6:2 FTOH의 치어, 성어 단계의 제브라피시 모델을 이용한 갑상선 교란 연구

학위논문(석사) -- 서울대학교대학원 : 보건대학원 환경보건학과, 2023. 2. 최경호.6:2 fluorotelomer alcohol (6:2 FTOH) is used as alternatives to PFOA, which is well known for toxicity effects. While there is a growing concern about the potential adverse health concerns of alternative PFASs, little is known about the thyroid disrupting effects in aquatic organisms. This study investigated adverse effects of 6:2 FTOH in thyroid system and possible mechanisms using embryo-larval and adult male zebrafish (Danio rerio). Five thyroid hormones (tT3, tT4, fT3, fT4, and TSH) and related gene expression were analyzed using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). 6:2 FTOH significantly decreased thyroid hormone levels in zebrafish larvae. Gene expressions associated with thyroid hormone regulation, synthesis, and transport (trh, trhr, tshβ, trα, trβ, tg, and ttr) were decreased. Gene expressions related to thyroid hormone metabolism (ugt1ab and sult1st5) were increased in an chemical exposed group. In adult zebrafish, 6:2 FTOH significantly increased tT3 and fT3 levels. Gene expression in adult male zebrafish liver resulted in decreased gene expression related to metabolism and transport of thyroid hormones (sult1st5, dio1, dio2, and ttr). This study demonstrates that 6:2 FTOH have a potential for thyroid hormone disruption by interfering regulation, synthesis, transport and metabolism of thyroid hormones. Further studies are needed to investigate the additional mode of action of thyroid hormone disruption and related health effects due to 6:2 FTOH.6:2 fluorotelomer alcohol (6:2 FTOH)은 유해성이 잘 알려진 PFOA를 대체하여 사용되는 신종 과불화화합물이다. 대체 과불화화합물의 잠재적 건강 악영향에 대한 우려가 커지고 있지만, 갑상선 교란 영향에 대한 연구가 매우 부족하다. 따라서, 본 연구에서는 제브라피시 (Danio rerio) 배아-치어와 수컷 성어를 이용하여 6:2 FTOH의 갑상선 교란 영향을 조사하였다. 본 연구에서는 enzyme-linked immunosorbent assay (ELISA)와 quantitative real-time polymerase chain reaction (qRT-PCR) 기법을 이용하여 다섯 종류의 갑상선 호르몬 (tT3, tT4, fT3, fT4 및 TSH)과 관련 유전자 발현을 분석하였다. 6:2 FTOH는 제브라피시 치어에서 통계적으로 유의한 수준으로 갑상선 호르몬 수치를 감소시켰다. 또한, 갑상선 호르몬 조절, 합성, 수송 관련 유전자 (trh, trhr, tshβ, trα, trβ, tg 및 ttr) 발현을 감소시켰다. 반면, 일부 농도 군에서 갑상선 호르몬 대사 관련 유전자 (ugt1ab 및 sult1st5) 발현을 증가시켰다. 6:2 FTOH는 제브라피시 성어에서 통계적으로 유의한 수준으로 tT3와 fT3 수치를 증가시켰고, 간에서 갑상선 호르몬 대사와 수송에 관련된 유전자 (sult1st5, dio1, dio2 및 ttr) 발현을 감소시켰다. 본 연구 결과는 6:2 FTOH가 갑상선 호르몬 조절, 합성, 수송 및 대사 기전을 방해하여 갑상선 교란 가능성이 있음을 시사한다. 6:2 FTOH로 인한 갑상선 교란 영향과 관련 건강 영향을 확인하기 위한 추가 연구가 필요할 것이다.1. Introduction 1 2. Materials and Methods 4 2.1. Chemicals 4 2.2. Zebrafish husbandry and experimental design 6 2.3. Thyroid hormone measurement 8 2.4. Gene expression analysis 9 2.5. Statistical analysis 16 3. Results 17 3.1. Thyroid hormone disruption in larval zebrafish 17 3.2. Thyroid hormone disruption in adult zebrafish 21 4. Discussion 27 5. Conclusion 30 References 31 Abstract in Korean 35석

한국 고등학생 영어학습자를 위한 과정중심 쓰기 수업과 수행평가의 통합

학위논문(석사)--서울대학교 대학원 :사범대학 외국어교육과(영어전공),2019. 8. 김진완.듣기, 말하기, 읽기, 쓰기 네 가지 언어 능력 중 쓰기가 고등사고능력을 요구하는 기술로 여겨져 쓰기 능력의 중요성이 부각되고 있다. 선행 연구들을 살펴보면, 다양한 측면에서 모국어 쓰기와 외국어 쓰기가 다르다는 점이 밝혀졌고, 외국어 학습자들이 능숙하게 영어로 쓰기를 하기 위해서는 영어로 글쓰는 방법을 배우는 것이 필수적이라는 사실을 알 수 있다. 역사적으로 쓰기를 가르치는 초기 방법은 결과중심 쓰기 접근법이었으며 과정중심 쓰기 접근법으로 옮겨가다가 이후에는 결과중심 쓰기 접근법과 과정중심 쓰기 접근법을 적절하게 혼합하여 적용하는 글쓰기 수업들이 등장하였다. 본 연구는 과정중심 쓰기 교수법을 수행평가와 통합하였을 때 한국 고등학생 영어학습자들에게 어떤 영향을 끼치는지에 대해 탐구했다. 영작문 수행평가는 학생들의 쓰기 능력을 평가하는 것이기 때문에 쓰기 과정뿐만 아니라 최종 쓰기 결과물에도 초점을 맞추어야 한다. 한국의 교육 시스템은 평가에 민감하게 반응하는 구조여서 과정중심 쓰기 수업을 영작문 수행평가와 통합하는 것이 학생들의 쓰기 수업 참여를 촉진할 것이고, 결과적으로 쓰기 능력을 향상시킬 것으로 기대되었다. 62명의 한국 고등학교 영어 학습자들을 대상으로 과정중심 쓰기 수업을 영작문 수행평가와 통합하여 10주 동안 쓰기 수업을 실시한 결과물과 학생들의 사전·사후 설문지, 그리고 교수자의 관찰 노트를 바탕으로 양적·질적 연구를 실시하였다. 연구 결과, 학생들은 쓰기 과정과 쓰기 결과물 모두에서 통계적으로 유의미한 발전을 보였다. 먼저 쓰기 결과물의 향상을 조사하기 위해 학생들이 실험 첫 주에 작성한 글과 마지막 주에 작성한 최종 쓰기 결과물을 비교했다. 학생들의 글이 길이가 길어지고 내용도 풍부해졌으며 유기적으로 구조화되었음을 확인할 수 있었다. 또한 다양한 표현을 통한 표현력 향상과 언어 사용의 측면도 발전을 보였다. 다음으로 쓰기 과정에서 학생들은 계획적인 글쓰기를 통해서 완성도 높은 1차 쓰기를 했고, 학생들 간 피드백을 통해 서로 간에 자율적인 학습이 있었으며 과정중심 쓰기 수업 속에서 지속적인 고쳐 쓰기를 하면서 스스로 글을 수정하는 능력을 길렀다. 쓰기 과정은 쓰기 결과물과 밀접하게 연관되어 있기 때문에 학생들은 최종 영작문 수행평가에서 더 높은 점수를 받을 수 있었다. 통계적인 결과에서는 하위 수준 그룹의 쓰기 결과물만이 향상된 것으로 나타났지만 쓰기 과정 속에서 나타난 쓰기 결과물들을 질적으로 분석해보니 상위 수준과 하위 수준 모두에게서 쓰기 능력 향상이 확인되었다. 특히 쓰기 유창성과 자기 수정 능력은 상위 수준 학습자 그룹이 하위 수준 학습자 그룹보다 눈에 띄는 발전을 보였다. 본 연구는 한국의 평가 중심 교육 시스템 속에서 학생들을 쓰기 수업에 더욱 적극적으로 참여시키기 위해서는 수업과 영작문 수행평가를 통합하는 것이 필수적이며 효과적인 쓰기 과정을 통한 쓰기 결과물 향상을 위해서는 과정중심 쓰기 수업이 필요하다는 것을 시사한다. 이러한 수업과 평가의 통합은 당대의 교육 정책에도 부합하는 것이라 할 수 있다. 결국 이번 연구는 다양하고 실행 가능한 쓰기 수업과 쓰기 평가의 통합적인 방법들이 논의되어야 할 필요성을 제기하는 것에 의의가 있다 하겠다.The importance of writing ability is highlighted, because among four language skills – listening, speaking, reading, and writing – writing skill is known to require higher order thinking. However, previous literatures have proved that L2 writing is different from L1 writing in many aspects, so it is essential for EFL learners to learn how to write in English in order to become proficient writers. Historically, product-oriented writing approach was the initial step to teach the way to write, moved to process-oriented writing approach, and then mixed them in some ways. With regard to the trend of writing approach, this exploratory study explored the influence of process-oriented writing instruction integrated with performance assessment on Korean high school EFL learners. Since performance assessment evaluates students writing ability, it should focus on not only writing process but also final writing product. Also, Korea is in the examination-driven education system, so it was expected that integrating process-oriented writing instruction with performance assessment would facilitate students involvement in writing, which results in development of writing ability. Sixty two Korean high school EFL learners writing products during 10 weeks writing classes, self-report pre- and post-questionnaire surveys, and instructors observation notes were collected and analyzed quantitatively and qualitatively. Results revealed that students have developed their writing in terms of both writing process and writing product. In order to investigate development in the aspect of writing product, students final writing written in the last week was compared with the first writing written in the first week. Statistically, they wrote significantly longer, with more thorough and substantive content, and organized their ideas more effectively. Through qualitative analyses, it was also proved that they used a variety of expressions and vocabulary, and better managed language use through process-oriented writing instruction integrated with performance assessment. In the aspect of writing process, students planned more, completed the first draft based on planning, learned from others during peer feedback, and built self-revising ability during repeated revising in the process-oriented writing instruction. Writing process linked closely to writing product, and thus students could end up gaining better scores in the final performance assessment. However, there was discrepancy according to proficiency levels, high and low. Although statistical results proved development in writing product for low proficiency group only, qualitative analyses on writing products through process-oriented writing demonstrated writing development for both high and low proficiency groups. Moreover, especially high proficiency group students displayed outstanding self-revising ability with better writing fluency. The present study suggests that process-oriented writing instruction be necessary for Korean high school EFL students to develop writing product during effective writing process. In order to encourage students involvement in the writing instruction, integrating instruction with performance assessment is essential in the examination-driven education system of Korea, and the integration of instruction and assessment corresponds to the contemporary educational policy. Consequently, this urges EFL writing practitioners to begin discussing various feasible methods to integrate writing instruction with writing assessment into educational practice.CHAPTER 1. INTRODUCTION 1 1.1. The Need and Purpose of the study 1 1.2. Research Questions 9 1.3. Organization of the Thesis 10 CHAPTER 2. LITERATURE REVIEW 12 2.1. L2 Writing Approaches 12 2.1.1. Product-Oriented Writing Approach 13 2.1.2. Process-Oriented Writing Approach 16 2.2. Integrating Product and Process Approach 19 2.3. Studies on Process-Oriented Writing Assessment 22 2.3.1. Process-Oriented Writing Assessment in ESL Context 22 2.3.2. Process-Oriented Writing Assessment in EFL Context 24 CHAPTER 3. METHODOLOGY 31 3.1. Participants 31 3.2. Materials 33 3.2.1. Pre-Questionnaire and Post-Questionnaire 33 3.2.2. Writing Prompt 35 3.3. Procedures 36 3.4. Data Analysis 41 Chapter 4. RESULTS AND DISCUSSION 45 4.1. Development in Writing Product through PIPA 45 4.1.1. Development in Overall Writing Quality 46 4.1.2. Development in Writing Product 50 4.1.2.1. Writing Development in Fluency 50 4.1.2.2. Writing Development in Content and Organization 52 4.1.2.3. Writing Development in Vocabulary and Language Use 66 4.2. Development in Writing Process through PIPA 75 4.2.1. Development in the First Process-Oriented Writing 75 4.2.2. Development in the Second Process-Oriented Writing as Performance Assessment 81 4.2.2.1. From Planning to the Second Draft 82 4.2.2.2. From the Second Draft to the Third Draft 94 4.3. Different Writing Development according to Proficiency Groups 102 4.3.1. Different Development in Writing Product according to Proficiency Groups 102 4.3.1.1. High Proficiency Group 104 4.3.1.2. Low Proficiency Group 106 4.3.1.3. Comparison between Proficiency Groups 108 4.3.2. Different Development in Writing Process according to Proficiency Groups 114 4.3.2.1. High Proficiency Group 114 4.3.2.2. Low Proficiency Group 122 4.3.2.3. Comparison between Proficiency Groups 132 CHAPTER 5. CONCLUSION 138 5.1. Summary of Major findings 138 5.2. Pedagogical Implications 142 5.3. Limitations and Suggestions 145 REFERENCES 148 APPENDICES 156 Appendix A: A Sample of Class Observation Notes 156 Appendix B: Preliminary Questionnaire 157 Appendix C: Post Questionnaire 160 Appendix D: Diagnostic Assessment (First Writing) 163 Appendix E: Writing Worksheets during Process-Oriented Writing Instruction 164 Appendix F: Performance Assessment (Final Writing) 168 Appendix G: Performance Assessment Criteria 169 Appendix H: Scoring Rubric 171 ABSTRACT IN KOREAN 173Maste

Cell type-specific proteome labeling by genetic code expansion

의과대학/석사Analyzing gene expression of specific cells in a living organism is crucial in understanding complex biological systems. It has not been possible, however, to isolate the proteome of specific cells in vertebrates. Recently, advance in genetic code expansion has provided a new potential direction in achieving this aim. By using the tool of genetic code expansion, I expanded the genetic code of mammalian cells by introducing the pyrrolysyl-tRNA synthetase (PylRS)/tRNAPyl system of Methanosarcina mazei, a methane-producing genus of archaea. Although the amber (UAG) codon is a stop codon to most of organisms, Methanosarcina uses it as a sense codon that encodes pyrrolysine (Pyl), the 22nd amino acid. Unlike eukaryotes where the amber codon is recognized by eukaryotic release factor 1 (eRF1) which helps the termination of mRNA translation, Methanosarcina expresses the tRNA (tRNAPyl) whose anticodon recognizes the amber codon. PylRS esterifies tRNAPyl and Pyl, generating the Pyl-tRNAPyl that site-specifically incorporates Pyl into the growing polypeptides during mRNA translation. In this thesis, I expressed PylRS and tRNAPyl in mammalian cells and showed that the M. mazei PylRS/tRNAPyl system is functional in mammalian cells and orthogonal to endogenous tRNAs and tRNA synthetases. I also showed that the anticodon of tRNAPyl can be changed to recognize other stop and sense codons without compromising their compatibility with PylRS and Pyl. Furthermore, I showed that Pyl-derivatives containing bio-orthogonal functional group such as alkyne can be site-specifically incorporated into the endogenous proteome only when the genetic code was expanded by the PylRS/tRNAPyl system. By using azide-alkyne cycloaddition, the de novo proteome of genetic code-expanded cells could be specifically visualized. The results of this thesis show a promising direction for a new technique to isolate the proteome of a specific cell type from a living animal.ope

Comparative Ultrastructures of the Fertilized Egg Envelopes in Nothobranchius foerschi and Nothobranchius rachovii, Nothobranchiidae, Teleostei

In the case of genus Nothobranchius, Nothobranchiidae, the morphology of fertilized eggs and ultrastructures of fertilized egg envelopes have been reported in only two fishes. Therefore it is hard for sure to these morphological characteristics show genus specificity because of lower research samples. So, we studied the morphology of fertilized egg, and compared the ultrastructures of outer surface, micropyle, and section of fertilized egg envelopes under the light and electron microscopes from the other two species, Nothobranchius foerschi and Nothobranchius rachovii, Nothobranchiidae to find out whether these structures have the species specificity or not. Both fertilized eggs were spherical, demersal and adhesive, and have a large oil droplet. The adhesive whip-like structures were distributed on the outer surface of egg envelope, and a micropyle located on the animal pole. The fertilized egg envelope consisted of two distinct layers: an outer electron-dense layer with adhesive structures and an inner lamellae layer in both species. The external shapes of fertilized egg and ultrastuctures of outer surface, micropyle, and section of fertilized egg envelope have same structure including results before. Our data indicate that these morphological characteristics of fertilized egg and fertilized egg envelope show genus Nothobranchius specificity.ope

An increased chloride level in hypochloremia is associated with decreased mortality in patients with severe sepsis or septic shock

Only a few observational studies investigated the association between hypochloremia and mortality in critically ill patients, and these studies included small number of septic patients. Also, no study has evaluated the effect of an increase in chloride (Cl-) concentration in hypochloremia on the mortality. A total of 843 Korean septic patients were divided into three groups based on their baseline Cl- level, and Cox analyses were performed to evaluate the 28-day mortality. Moreover, the change in Cl- level (ΔCl) from baseline to 24, 48, or 72 hour was determined, and Cox analyses were also conducted to evaluate the relationship of ΔCl with mortality. 301 (35.7%) patients were hypochloremic (Cl-  110 mEq/L). During the follow-up period, 119 (14.1%) patients died. Hypochloremia was significantly associated with an increased mortality after adjusting for several variables, but an 1 mEq/L increase of ΔCl within 24 hour in patients with hypochloremia was significantly related to a decreased mortality. Caution might be required in severe septic patients with hypochloremia considering their increased mortality rate. However, an increased Cl- concentration might decrease the mortality rate of such patients.ope

An Imported Case of Brucella melitensis Infection in South Korea

Brucellosis is a zoonotic infection that is usually transmitted from cattle to humans through ingestion of animal milk, direct contact with animal parts, or inhalation of aerosolized particles. In Korea, brucellosis seem to be transmitted through close contact with blood, fetus, urine, and placenta of domestic cow that has been infected by Brucella abortus, or inhalation of B. arbortus while examining or slaughtering cow. Brucella melitensis infection is rare in Korea and there have been no reported cases of B. melitensis originating from other countries until now. This report details a case of complicated brucellosis with infective spondylitis in a 48-year-old male construction worker recently returned from Iraq. Infection with B. melitensis was confirmed using 16s rRNA sequencing and omp31 gene analysis. The patient was successfully treated using a combination of rifampin, doxycycline, and streptomycin, in accordance with WHO guidelines. This is the first reported case of complicated brucellosis with infective spondylitis in Korea caused by B. melitensis originating from Iraq.ope