비교유전체학을 이용한 선충의 서브텔로미어 진화와 표현형 변이 연구

학위논문(박사)--서울대학교 대학원 :자연과학대학 생명과학부,2020. 2. 이준호.CB4856 계통의 유전체를 N2의 표준 유전체와 비교하였다. CB4856 유전체는 Pacific Biosciences (PacBio) 사의 RSII 기법을 활용해 염기서열 분석을 진행하였고(80×, N50 리드 길이 11.8 kb), 이후 유전체 이어붙이기 과정을 거쳐 염색체에 가까운 수준(76 contigs, N50 contig 2.8 Mb)으로 완성할 수 있었다. 두 유전체를 비교한 결과 2,694개 유전자에서 구조 변이를 확인할 수 있었고 그 중 상당수는 염색체 바깥쪽에 몰려있었다. 염색체 끝에 인접한 서브텔로미어(subtelomere) 지역은 가장 구조 변이가 심각한 지역으로, 그 중에는 새롭게 서브텔로미어가 생겨난 곳도 있었다. 5번 염색체 오른쪽의 서브텔로미어 구조는 CB4856 계통의 조상에서 텔로미어(telomere) 손상이 일어났고, 텔로머레이즈(telomerase) 유전자가 분명 존재했음에도 그 대신 대안적 텔로미어 연장(Alternative Lengthening of telomeres)을 통해 손상이 회복됐으며, 이후 절단 유도 복제(break-induced replication)이 일어나면서 새롭게 서브텔로미어가 형성됐다는 것을 암시하고 있다. 본 연구는 구조 변이와 새로운 서브텔로미어를 포함한 상당한 유전체 변화가 한 종 내에서도 유지될 수 있고, 이러한 변화가 종 내의 유전다양성을 높일 수 있다는 것을 보여준다. 다음으로, 예쁜꼬마선충의 근연종이면서도 성별(암수한몸, 암컷, 수컷)과 행동(튜브 닉테이션)에서 확연한 차이를 보이는 Auanema freiburgensis와 Auanema sp. APS14 두 종의 유전체 초안 또한 본 연구에서 분석됐다. A. freiburgensis와 Auanema sp. APS14의 유전체는 각각 PacBio RSII (270×, N50 리드 길이 12.5 kb)와 Oxford Nanopore Technologies (ONT) 사의 MinION (113×, N50 리드 길이 3.6 kb)을 통해 염기서열 이 분석됐으며, 유전체 이어붙이기 결과 예쁜꼬마선충(~100 Mb)에 비해 유전체 크기 또한 상당히 작다는 것(각각 55 Mb와 69 Mb) 또한 확인되었다. 이 두 유전체는 어떻게 유전체 내에 생긴 변화가 새로운 형질의 진화에 영향을 줄 수 있었을지 이해하는 데에 기여할 수 있을 것으로 내다본다.Long-read sequencing technologies have contributed greatly to comparative genomics among species and can also be applied to study genomics within a species. In this study, to determine how substantial genomic changes are generated and tolerated within a species, a C. elegans strain, CB4856, was sequenced which is one of the most genetically divergent strains compared to the N2 reference strain. For this comparison, the Pacific Biosciences (PacBio) RSII platform (80×, N50 read length 11.8 kb) was used and de novo genome assembly were generated to the level of pseudochromosomes containing 76 contigs (N50 contig = 2.8 Mb). I identified structural variations that affected as many as 2,694 genes, most of which are at chromosome arms. Subtelomeric regions contained the most extensive genomic rearrangements, which even created new subtelomeres in some cases. The subtelomere structure of Chromosome VR implies that ancestral telomere damage was repaired by alternative lengthening of telomeres even in the presence of a functional telomerase gene and that a new subtelomere was formed by break-induced replication. My study demonstrates that substantial genomic changes including structural variations and new subtelomeres can be tolerated within a species, and that these changes may accumulate genetic diversity within a species. Secondly, I also assembled draft genomes of two C. elegans relative species, Auanema freiburgensis and Auanema sp. APS14, which have and a distinct reproductive (three genders; male, female, and hermaphrodite) and behavioral repertoire (tube-nictation). A. freiburgensis and Auanema sp. APS14 were sequenced using the PacBio RSII (270×, N50 read length 12.5 kb) and the Oxford Nanopore Technologies (ONT) MinION platforms (113×, N50 read length 3.6 kb), respectively, and their reads were assembled as smaller genomes (55 and 69 Mb, respectively) compared to that of C. elegans (~100 Mb). Comparative genomic studies of these genomes will help understand how genomic changes in close relative species affect evolution of novel traits.Chapter 1. Introduction 1 Long-read sequencing and de novo genome assembly 2 Caenorhabditis and Caenorhabditis elegans as a model system for comparative genomics 2 Repetitive nature of subtelomere and the trace of alternative lengthening of telomeres (ALT) in subtelomeric regions 3 Phenotypic diversity in the genus Auanema 4 Purposes of the study 6 Materials and Methods 7 Chapter II. De novo genome assembly of the CB4856 genome and subtelomere evolution via past ALT events in C. elegans 17 Part I. De novo genome assembly of the CB4856 genome and structural variants compared to the reference strain, N2 18 Long-read sequencing and de novo assembly of the CB4856 genome 18 Long-read sequencing identified new structural variations 19 Part II. Subtelomere evolution via past ALT events in C. elegans 21 Long-read sequencing revealed the hypervariable nature of subtelomeres 21 The structure of Chr VR subtelomere is unique, in consequence of past ALT and BIR events 21 New genes in the subtelomeric region 22 Chapter III. Phenotypic characterization of Korean nematodes and draft genome assembly of two Auanema species 24 Korean nematode collection 25 Phenotypic diversification in the genus Auanema 25 Highly contiguous genome assembly using two long-read sequencing technologies 26 Chapter IV. Discussion 28 Enrichment of genetic variations in chromosome arms and subtelomeres by background selection and error-prone recombination 29 New subtelomere formation by ALT and BIR 30 References 78 Abstract in Korean 87 Acknowledgement 88Docto

Combination therapy with 7-O-succinyl macrolactin A tromethamine salt and temozolomide against glioblastoma

학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과, 2018. 2. 김재용.7-O-succinyl macrolactin A has shown anti-inflammatory, anti-angiogenesis, and anti-metastatic effects. It also exhibits strong suppression of tumor growth. In our previous study, we assessed the anti-neoplastic effects of 7-O-succinyl macrolactin A tromethamine salt (SMA salt) on a glioma cell line. Moreover, according to our data, SMA salt might be contributed to the inhibitory effects on migration and invasion, as well as a cytotoxic effect on the glioblastoma cell lines. In the present study, we investigated the anti-tumor effects of combination therapy with SMA salt and temozolomide (TMZ) in glioblastoma cell lines. The combination therapy affected cell viability significantly, decreasing in glioblastoma cell lines. In cell migration assays, combination therapy showed more inhibitory effects than TMZ in these cell lines. The tumor volume was significantly decreased in the combination group compared with both TMZ and control groups by using the orthotopic mouse model. The effects of combination therapy with SMA salt and TMZ attributed to the inhibition of migration, invasion activities and anti-tumor effects. SMA salt could be one of the promising candidates for combination therapy in clinical settings.Introduction 1 Materials and methods 4 Results 9 Disccussion 13 Reference 18 국문 초록 29Docto

동물매개중재활동에 참여 중인 개의 동물복지 평가를 위한 코티졸 측정

학위논문 (석사)-- 서울대학교 대학원 : 수의과대학 수의학과, 2018. 2. 이항.Although quality standards and hazard management for human subjects in animal-assisted interventions (AAIs) have been examined for years, only limited number of studies have explored the welfare state of involving animals. To set animal welfare standards for AAIs involving animals, studies on the stress level of the animals in on-the-job activities are needed. This study examined cortisol levels of the four AAI dogs to compare the stress level in different kinds of activities in the SAAA for children by volunteers with pets. To compare the stress level of AAI dogs according to the characteristics of the participants, the four dogs which have activities with three groups of intellectual disabilities (autistic adult, adult with intellectual disability, and youth with intellectual disabilities) were examined in AKCAAT. Although no significant changes in stress were observed in the saliva cortisol as physiological indicator, the activities demanding stronger human-animal relationships were noted to increase their stress, especially in young and inexperienced dogs. The finding of this study can give the insights for monitoring stress levels in AAI animals and setting the AAI animal welfare guideline in Korea.1. Introduction 1 2. Materials and Methods 7 2.1. Handlers and AAI dogs 7 2.1.1. AAS, LAPS Questionnaire 8 2.2. AAI design 14 2.2.1. SAAA 14 2.2.2. AKCAAT 15 2.3. Salivary sample collection 19 2.4. Sample analysis 23 2.5. Statistical analysis 23 3. Results 24 3.1. SAAA 24 3.2. AKCAAT 25 4. Discussion 30 5. Conclusion and animal welfare implications 41 5.1. Acknowledgments 41 5.2. Conflict of interest 41 6. References 42 7. Appendix 51 국문초록 53Maste

국내 주가지수선물시장의 수익률, 변동성, 거래량과 주문량에 대한 기술적 분석

학위논문(석사)--서울대학교 대학원 :경영학과 경영학전공,2000.Maste

Manta형 무인잠수정의 호버링

Abstract The Unmanned Undersea Vehicle(UUV) which was called Manta-type Unmanned Undersea Vehicle(Manta UUV) had taken the shape of manta. Manta UUV was proposed by Bae et al.(2008). Manta UUV is based on the same design concept as Manta Test Vehicle(MTV), which was originally built and studied by the Naval Undersea Warfare Center(NUWC) in the USA. Effects due to hovering thrusters attached Manta UUV of large angle of attack are measured from model experiment in circulating water channel. Characteristics of various motions are evaluate to apply mathematical model for numerical simulation based on Bae et al.(2009a). Numerical simulation is carried out to calculate hovering motion due to only hovering thruster, lateral motion due to only current, composite motion due to both hovering thruster and current. Lateral motion due to current is calculated to apply velocity variables, which are defined as relative velocity due to angle of current, to mathematical model, and hovering motion due to hovering thruster is calculated to apply results of model experiment to mathematical model.목 차 Abstract 1. 서언 1 2. Manta UUV의 명세 및 좌표계 2 2.1 Manta UUV의 명세 2 2.2 좌표계 4 3. 호버링 스러스터의 성능에 관한 모형실험 5 3.1 실험 장치 5 3.1.1 회류수조 5 3.1.2 3분력계 6 3.1.3 서보시스템 7 3.1.4 모형선 10 3.2 실험 결과 14 4. 호버링 운동의 수치 시뮬레이션 18 4.1 대각도 받음각을 갖는 6자유도 운동 수학모델 18 4.2 유체력미계수 등 23 4.3 수치 시뮬레이션 결과 25 4.3.1 호버링 스러스터에 의한 수직이동 25 4.3.2 호버링 스러스터에 의한 심도변경 28 4.3.3 수직이동에 미치는 조류의 영향 30 4.3.4 심도변경에 미치는 조류의 영향 34 5. 결 론 36 참 고 문 헌 3

(A)Study on product development methodology in reverse supply chain

학위논문(석사)--서울대학교 대학원 :산업공학과,2005.Maste

미생물에 의한 isobutyric acid로부터 D-(-)-β-hydroxyisobutyrbutyric acid from isobytyric acid

Maste

Biodegradable, oxidation-resistant, and highly sensitive MXene/PEDOT:PSS wearable piezoresistive pressure sensor for human motion monitoring

웨어러블 센서는 사용자의 생체 신호를 정확하고 빠르게 모니터링할 수 있는 잠재력 을 가지고 있다. 이는 전자-피부, 생체 의학, 인간-기계 인터페이스등 다양한 분야에서 광 범위하게 활용되어 왔다. 그러나 이러한 광범위한 사용은 전자 폐기물로 인한 환경문제 를 야기한다. 이 문제를 해결하기 위해 다양한 생분해성 생체 고분자가 유연한 센서 및 웨어러블 장치의 설계에 사용되었다. 하지만 기존의 많은 생분해성 센서는 낮은 전기 전 도성, 낮은 민감도, 안정성 제한 등의 한계를 지니고 있다. 이러한 한계를 해결하기 위해 본 연구에서는 Ti3C2Tx MXene, Poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS)으로 코팅된 생분해성 셀룰로오스 종이 압력 센서를 개발하였다. MXene/PEDOT:PSS으로 코팅된 셀룰로오스 종이 압저항식 압력 센서는 광범위한 압력 범 위(0~40 kPa)에서 고감도(19.21 kPa-1)를 나타내고 낮은 압력 및 높은 압력에 대한 선형성, 높은 안정성(1400 cycles) 및 산화 안정성(>22 days)을 가진다. 또한 PEDOT:PSS와의 결합 으로 인하여 MXene의 산화에 대한 저항과 안정성을 향상시킨다. 제작된 압저항식 압력 센서는 미세 및 큰 굴곡, 성대 진동, 관절의 움직임과 같은 다양한 동작을 감지하여 인간 움직임 감지에서 뛰어난 성능을 보여준다. 개발된 압저항식 압력 센서는 인간-기계 인터 페이스, 로봇 공학, 전자 피부 및 웨어러블 센서를 포함한 미세 하거나 큰 압력 감지를 위한 다양한 분야에 응용될 것으로 기대된다.|Wearable sensors possess the potential to accurately and rapidly monitor users' physiological signals, finding extensive applications in diverse fields such as electronic skin, biomedical engineering, and human-machine interfaces. However, their widespread use has raised concerns about environmental issues caused by electronic waste. To address this challenge, various biodegradable biopolymers have been employed in the design of flexible sensors and wearable devices. Despite these advances, many existing biodegradable sensors face limitations such as low electrical conductivity, reduced sensitivity, and stability constraints. In this study, a biodegradable cellulose paper sensor coated with Ti3C2Tx MXene and poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS) was developed to overcome these challenges. The MXene/PEDOT:PSS-coated cellulose paper piezoresistive pressure sensor demonstrates high sensitivity (19.21 kPa⁻¹) across a wide pressure range (0–40 kPa), excellent linearity at low and high pressures, robust stability (1400 cycles), and improved oxidation resistance (>22 days), owing to the stabilizing effect of PEDOT:PSS on MXene. Moreover, the sensor exhibits outstanding performance in human-motion monitoring by detecting various subtle and vigorous movements, such as joint flexions, vocal cord vibrations, and bending motions. The developed piezoresistive pressure sensor is expected to find applications in diverse fields, such as human-machine interfaces(HMI), robotics, electronic skin(e-skin), and wearable sensors, enabling precise and reliable detection of both minute and intense pressures. Keywords : Pressure sensor, Piezoresistive sensor, Biodegradability, MXene, PEDOT:PSSMaste