삼광벼의 키다리병 저항성 양적형질유전자좌 (QTL) mapping

강도유 전북대학교 일반대학원 2019 국내석사

Rice is an important food resource for more than half of the world's population and is the most commonly used grain. Bakanae disease has become a serious threat to almost all rice cultivation regions worldwide. The incidence of Bakanae disease is increasing due to temperature rise induced by global warming, and the advent of fungicide-resistant strains has rendered disease control difficult. The disease causes both qualitative and quantitative losses to the grains under the field conditions. In this study, quantitative trait locus (QTL) mapping was performed with F2 and F3 population derived from a cross between the susceptible variety, Junambyeo, and the resistant variety, Samgwangbyeo. A genetic map comprising 176 KASPmarkers and a derived CAPS (dCAPS) marker was constructed. The total genetic distance of the map was 2394.0 cM, and the average interval between markers was 14.5 cM. Bakanae disease bioassay of 188 F3 families derived from the F2 plants from the cross between Junambyeo and Samgwangbyeo was performed by in vitro seedling screening method. The mortality rates of the F3 families ranged from 0 to 100%, while that of Samgwangbyeo was 1.7% and that of Junambyeo was 83.3%. Based on the genetic map and the mortality rate data, QTL analysis was performed by composite interval mapping (CIM) method. A major QTL was detected at 29.2 cM on chromosome 9 with a logarithm of the odds (LOD) score of 60.3. This is a novel Bakanae disease resistance QTL which will be useful in breeding rice varieties resistant to Bakanae disease.

Computational approaches to discover disease-associated biomedical entities

김현진 Graduate School, Yonsei University 2016 국내박사

“True knowledge exists in knowing that you know nothing”. It is Socrates’s widely known quote describing the significance of “ignorance”. To paraphrase the Socrates’s quote: New and true biomedical associations exist in knowing that you know undiscovered biomedical associations. The paraphrased sentence indicates that discovering hidden associations is a starting point of identifying novel biomedical associations. For wellness and longevity, healthcare plan is indispensable and that’s the reason why study on disease is important. Therefore, we focused on disease-associated associations among many biomedical associations. Discovering novel disease-associated associations can provide ample information to disease research. As technology of computer-related has developed, the computational biology has influenced research on disease that analyzes biological data using computers and the related techniques have been advanced a lot. To find new and true disease-associated associations, we propose three novel computational approaches, each of which can discover hidden disease-gene, disease-disease, and disease-drug associations. First, GSEH takes gene expression heterogeneity to find genes related with the biological process of a disease. The gene expression heterogeneity denotes that samples in the same class may have dissimilar gene expression levels. In this study, we used collaborative filtering to calculate the degree of gene expression heterogeneity between classes and then scored the genes by the degree of gene expression heterogeneity to find “differentially predicted” genes. The concept of gene expression heterogeneity can be used as helpful information to find disease-associated genes. Second, we propose a new literature-based method LDDSim to measure disease-disease similarities. Because the LDDSim provides the similarities among diseases, we can know which disease has a high possibility to relate with a given disease. In addition to it, disease network using the disease similarities can be constructed with the LDDSim. Measuring similarities between diseases and building disease network is essential for disease treatment and disease function study. Lastly, we propose LDW which produces novel disease-drug associations and scores the associations on the distance between the drug and the disease. Many researches in LBD(Literature-Based Discovery) have been proposed since Dr. Swanson’s ABC model. Yet, fixed and finite text data sources and linking terms come to limits in producing novel knowledge. To get over the limitations, we utilize web crawl data as a new text data source and location name as a new linking term concept. Through the GSEH, we discovered more numerous disease-associated genes than other comparable methods. The genes prioritized by the GSEH are potentially of significance to biological processes of a disease and can provide insight into them. LDDSim found a larger number of answer disease pairs than other comparable methods and showed the lowest p-value. Moreover, LDDSim built a disease network with top-ranking disease pairs from our method. The disease network can help with insights into relationship between diseases. The top-ranking disease-drug associations generated by LDW and prioritized by the distance showed meaningful p-values. We also created a world disease map with our disease-location associations and manually checked the top-scoring diseases in the associations to assess the relatedness of the diseases and the locations of the associations. The three approaches have their own limitations, but they can find disease-related associations and provide additional information to facilitate disease research.

재난기록의 교육적 활용을 위한 감염병 지도(Map) 아카이브 방안에 대한 연구 : 코로나19 기록을 중심으로

최수희 韓國外國語大學校 大學院 2023 국내석사

본 연구는 시민들이 감염병 대유행으로 인한 재난 상황을 올바르게 이해하고 효율적으로 대응할 수 있도록 교육하기 위한 전략으로 감염병 지도(Map) 아카이브를 제안하고, 이를 통한 교육적 활용방안을 모색하는데 목적을 두고 있다. 감염병 재난은 사회적 소통과 교류가 활발해질수록 광범위하게 영향을 미치기 때문에 시민사회 구성원 모두가 해당 재난에 대한 기억을 공유하고 학습하는 일은 무엇보다 중요하다. 기록학적 관점에서 감염병 유행 과정에서 생산되는 기록은 성찰과 배움의 기회를 제공하는 매개체이다. 그러나 감염병 재난 기록은 다양한 출처와 유형을 갖고 생산이 되기 때문에 시민들이 기록에 쉽게 접근하는 것은 물론이고, 이를 분석하고 이해하는데 많은 어려움이 있다. 이러한 문제 아래, 연구자는 지도(Map) 형태의 아카이브가 감염병 재난 사건을 구조화함으로써 산발적으로 존재하는 다양한 기록을 체계적으로 연결하고 시민들이 이해하기 쉽게 서비스할 수 있다고 보고 연구를 진행하였다. 연구를 위해 지도(Map) 아카이브의 개념을 정리하고 그 필요성을 살펴보았다. 코로나19 사건을 대상으로 맥락 분석을 하고, 코로나19 전개 과정 동안 생산되는 기록을 살펴본 후 그 유형과 특징을 정리하였다. 그리고 Geographic information system(이하, GIS)를 활용한 재난정보 서비스와 재난 아카이브 사례를 선정하여 감염병 지도(Map) 아카이브에 필요한 요소들을 분석하였다. 연구를 토대로 감염병 지도(Map) 아카이브는 GIS 기능을 갖춘 공간정보플랫폼 Open API를 사용하여 설계할 것을 제안하였다. 그리고 아카이브의 필수 메뉴 요소로 ‘소장기록 검색’ 서비스, ‘지도(Map) 검색’ 서비스, ‘교육 공간’, ‘참여 공간’을 도출하였으며, 아카이브에 기록콘텐츠로 들어갈 컬렉션은 시기별, 테마별, 지역별, 출처별, 유형별 분류 등으로 구분·정리하였다. 다음으로 지도(Map) 기반 기록서비스의 구체적인 형태를 탐구하고, 교육적 활용방안으로는 ‘이용자 맞춤 교육 콘텐츠’ 개발과 ‘참여형 재난 교육 프로그램’을 개발할 것을 제안하였다. 본 논문에서 연구한 지도(Map) 아카이브는 아직 국내에서 상용화되지 않은 아카이브 형태로, 기록을 활용한 교육의 한 대안으로써 가능성을 보여주었다는데 의의가 있다. 특히 지도를 통해 다양한 정보를 제공하는 공간정보플랫폼은 재난 위기관리 도구로써 적극적으로 활용되고 있기에, 이와 결합하여 만든 감염병 지도(Map) 아카이브는 향후 시민들의 재난 인식에 많은 도움을 주는 등 다양한 가치 창출이 가능한 공간이 될 것이라 기대되고 있다. This study aims to propose an infectious disease map archives as a strategy for educating citizens to correctly understand and respond efficiently to disaster situations caused by an infectious disease pandemic, and to find ways to use it for education. Infectious disease disasters have a broader impact as social communication and exchange become more active, so it is more important than anything else for all members of civil society to share and learn about the memories of the disaster. From an archival perspective, records produced during the epidemic of infectious diseases are a medium that provides opportunities for reflection and learning. However, it is difficult for citizens to easily access, analyze, and understand the records. Because infectious disease disaster records are produced with various sources and types. Under these problems, I proceeded with research, believing that a map-type archives can systematically connect various records that exist sporadically by structuring infectious disease disaster events and provide services that are easy for citizens to understand. For research, I organized the concept of a map archive and examined its necessity. I conducted a contextual analysis of the Covid-19 incident, looked at the records produced during the Covid-19 outbreak, and organized the types and characteristics. And I selected cases of disaster information services and disaster archives using GIS and analyzed the elements necessary for an infectious disease map archive. Based on the research, I suggested that the infectious disease map archive be designed using the spatial information platform Open API with GIS function. And I derived ‘collection record search' service, ‘Map search' service, ‘educational space', and ‘participation space' as essential menu elements of the archive. Also, I classified and organized the collections to be included in the archives as contents by period, theme, region, source, and type. Next, I explored the specific form of map-based record service, and suggested developing 'user-customized educational contents' and 'participatory disaster education programs' as educational utilization plans. The Map archives studied in this paper is a form of archives that has not yet been commercialized in Korea, and has significance in that it showed potential as an alternative to education using records. In particular, since the geospatial information platform, which provides various information through maps, is actively used as a disaster risk management tool, the infectious disease map archives created in combination with it creates various values such as helping citizens to recognize disasters in the future. It is hoped that this will be a possible space.

Effect of hepatic steatosis on native T1 mapping of 3T magnetic resonance imaging in the assessment of T1 values for patients with non-alcoholic fatty liver disease

안지현 Graduate School, Yonsei University 2021 국내박사

Objectives: This study investigated whether T1 values in native T1 mapping of 3T magnetic resonance imaging (MRI) of the liver were affected by the fatty component. Materials and Methods: This prospective study involved 340 participants from a population-based cohort study between May 8, 2018 and August 8, 2019. Data obtained included: (1) hepatic stiffness according to magnetic resonance elastography (MRE); (2) T1 value according to T1 mapping; (3) fat fraction and iron concentration from multi-echo Dixon; and (4) clinical indices of hepatic steatosis including body mass index, waist circumference, history of diabetes, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and triglycerides. The correlations between T1 value and fat fraction, and between T1 value and liver stiffness were assessed using Pearson’s correlation coefficient. The independent two-sample t-test was used to evaluate the differences in T1 values according to the presence or absence of hepatic steatosis, and the one-way analysis of variance was used to evaluate the difference in T1 value by grading of hepatic steatosis according to MRI-based proton density fat fraction (PDFF). In addition, univariate and multivariate linear regression analyses were performed to determine whether other variables influenced the T1 value. Results: T1 value showed a positive correlation with the fat fraction obtained from PDFF (r=0.615, P < 0.001) and with the liver stiffness obtained from MRE (r=0.370, P < 0.001). Regardless of the evaluation method, the T1 value was significantly increased in subjects with hepatic steatosis (P < 0.001). When comparing hepatic steatosis grades based on MRI-PDFF, the mean T1 values were significantly different in all grades, and the T1 value tended to increase as the grade increased (P < 0.001, P for trend < 0.001). On multiple linear regression analysis, the T1 value was influenced by MRI-PDFF, calculated liver iron concentration, liver stiffness, and serum aspartate aminotransferase level. Conclusion: The T1 value obtained by current T1 mapping of 3T MRI was affected by the liver fat component and several other factors such as liver stiffness, iron concentration, and inflammation. 목적: 이 연구는 3T 자기공명영상에서 native T1 mapping의 T1 이완시간이 지방 성분에 의해 영향을 받는지 조사하고자 하였다. 재료 및 방법 : 이 전향적 연구에는 인구 기반 코호트로부터 2018년 5월 8일부터 2019년 8월 8일까지 340명의 참가자가 참여하였고, 참가자들로부터 다음과 같은 데이터를 획득하였다:(1) 자기공명탄성영상을 통한 간의 강성도; (2) T1 mapping을 통한 T1 이완시간; (3) 자기공명영상 기반 양성자 밀도 지방분율(MRI-PDFF); (4) 체질량지수, 허리둘레, 당뇨 과거력, 아스파르테이트아미노전달효소, 알라닌아미노전달효소, 감마글루타밀전달효소, 트리글리세라이드를 활용한 간 지방증 지표들. Pearson의 상관계수 분석을 통해 간의 강성도 및 지방 분율과 T1 이완시간 간의 상관성을 평가하였다. 독립표본 t-검정을 이용하여 지방간 여부에 따른 T1 이완시간의 차이를 평가하였고, MRI-PDFF 수치를 이용한 지방간 등급에 따른 T1 이완시간의 차이는 일원배치분산분석을 통해 평가하였다. 추가적으로, T1 이완시간에 영향을 미치는 변수들을 알아보기 위해 다중 선형회귀분석을 시행하였다. 결과 : T1 이완시간은 MRI-PDFF와 양의 상관관계를 보였고(r=0.615, P < 0.001), 자기공명탄성영상을 통해 획득한 간의 강성도와 양의 상관관계를 보였다 (r=0.370, P < 0.001). 지방간의 평가 방법의 종류에 관계없이 지방간이 있는 경우에 T1 이완시간이 유의하게 증가하였다 (P < 0.001). MRI-PDFF를 기반으로 하여 지방간 등급을 나누어 비교하였을 때, 평균 T1 이완시간은 등급별로 차이가 있었으며 등급이 증가할수록 T1 이완시간이 증가하는 경향을 보였다 (P < 0.001, P for trend < 0.001). 다중 선형회귀분석에서 MRI-PDFF, 간의 철 성분, 간의 강성도, 그리고 아스파르테이트아미노전달효소가 T1 이완시간에 영향을 미치는 것으로 나타났다. 결론 : 3T 자기공명영상장치에서 현재의 T1 mapping을 통해 획득한 T1 이완시간은 간의 지방 성분 및 간의 강성도, 간의 철 성분, 염증과 같은 요인들의 영향을 받는다.

Charting Aberrant Inflammatory and Fibrotic Signals in the Pathologic Landscape of Interstitial Lung Diseases with Single Cell RNA-seq

이세윤 서울대학교 대학원 2025 국내박사

Interstitial lung diseases (ILDs) represent a diverse group of pulmonary disorders characterized by chronic inflammation and progressive fibrosis, leading to impaired respiratory function. To uncover the cellular and molecular mechanisms underlying ILD, we performed single-cell and single-nucleus RNA sequencing on lung tissue and matched peripheral blood mononuclear cells (PBMCs) from 12 ILD patients, integrating these data with healthy lung references. The uniformly processed dataset, comprising 137,000 cells across 35 transcriptomic samples, revealed 45 fine-grained cell states that define the pathologic landscape of ILD. Using a comparative framework of healthy and diseased samples, I identified novel disease-specific epithelial cell states, including ICAM1+ alveolar type 1 (AT1) and type 2 (AT2) cells. These inflammatory epithelial populations were enriched for tumor necrosis factor-alpha signaling and inflammatory response pathways. In contrast, aberrant basaloid cells displayed signatures linked to extracellular matrix remodeling, epithelial-to-mesenchymal transition, and fibrosis, suggesting distinct fibrotic roles. Differential abundance analysis further highlighted an enrichment of inflammatory myeloid cells, including monocyte-derived macrophages and a previously uncharacterized subset of MMP19+ alveolar macrophages. Cell-cell interaction analysis revealed robust signaling between AT2 ICAM1+ cells and MMP19+ macrophages via the IL1B-CXCL2 axis, implicating this pathway as a key driver of alveolar damage and fibrosis. Matched PBMC and tissue joint-analyses unveiled systemic immune dysregulation in ILD patients, characterized by elevated cytotoxic lymphoid cell populations and a pronounced cytotoxic-naive imbalance, particularly within lymphoid cells. Leveraging these systemic immune profiles, I devised an 11-gene diagnostic panel that bridges monocyte and macrophage activity, demonstrating strong predictive power for ILD severity. This gene panel distinguished stable from progressive IPF patients, underscoring its clinical potential as a biomarker for fibrosis progression. This study provides a comprehensive atlas of the cellular and molecular landscape of ILD, illuminating inflammatory and fibrotic mechanisms driving disease progression. By uncovering novel disease-associated cell states, immune-epithelial interactions, and a robust diagnostic tool, this work lays the foundation for therapeutic and prognostic advancements in ILD. 간질성 폐 질환(ILD)은 염증과 섬유화를 특징으로 하는 다양한 폐 질환군으로, 호흡 부전으로 이어질 수 있는 심각한 질병이다. 본 연구에서는 ILD에서 세포 동태를 분석하기 위해 단일 세포 전사체 시퀀싱 (scRNA-seq)을 사용하여 환자 폐 조직 샘플을 분석하고, 이를 건강한 폐 데이터를 기반으로 한 참조 데이터와 통합하였다. 이를 통해 ICAM1을 발현하는 새로운 질병 특이적 폐포 유형 1(AT1) 및 유형 2(AT2) 염증 세포 상태를 확인하였으며, 이러한 세포들은 염증 반응 경로 및 TNF-α 신호 전달과 밀접한 관련이 있음을 발견했다. 반면, 섬유화와 상피-간엽 전이와 연관된 ECM 리모델링과 관련된 유전자 시그니처를 보여주는 기형적 기저 세포가 ILD에서 중요한 역할을 하는 것으로 나타났다. 세포 아형 구성비율 분석(differential abundance analysis)을 통해 섬유화 관련 대식세포, 염증성 섬유아세포 및 새로운 대식세포 아형의 현저한 증가를 발견했고, 세포 간 상호작용 분석을 통해 AT2 ICAM1+ 세포와 MMP19+ 대식세포 간의 강력한 신호 전달이 IL1B 및 CXCL2-CXCR2 축을 통해 매개되어 폐 손상과 섬유화 진행에 중요한 역할을 할 수 있음을 확인했다. 또한, 혈액의 세포 독성 NK 세포가 폐포 상피 세포와 상호작용할 가능성도 발견하여, 전신 면역 활성화가 폐 염증에 영향을 미칠 수 있음을 보고했다. 본 연구는 ILD에서 염증성 및 섬유화 세포 상태에 대한 포괄적인 세포 및 분자 지도를 제공하며, 질병 진행에 기여하는 염증성 미세환경을 겨냥한 치료 전략에 대한 새로운 타겟을 제시한다.

3D ventilation-weighted and ventilation flow capacity-weighted maps using 3D ultrashort echo-time MRI

Lee, Seokwon Sungkyunkwan University 2025 국내박사

Advanced neuroimaging protocol for neurodegenerative diseases

지수연 서울대학교 대학원 2023 국내박사

Magnetic Resonance Imaging (MRI) has provided unprecedented methodologies for non-invasive in-vivo assessment of 3-dimensional brain structure for several decades. With the flexibility of generating various contrasts with high resolution, MRI provides the most effective way to diagnose brain disorders. However, despite the exquisite anatomic details provided by the multiple routinely acquired contrast-weighted images, currently MRI is mainly utilized as means of differential diagnosis for neurodegenerative diseases. This is because the structural changes such as atrophy occurs long time after the onset of the disease. In recent years, several advanced MRI techniques that is sensitive to early stage of neurodegenerative diseases have been developed, demonstrating promising results for non-invasive diagnoses and study of the pathophysiology of diseases using MRI. In particular, neuromelanin-weighted MRI and susceptibility imaging have revealed great potentials. While these advanced MRI for neurodegenerative diseases bear great potential to substitute the current PET-based diagnosis with radiation exposure, widespread application of the advanced methods is hindered due to the additional scan time needed and the generalization limitations of each methods. In this work, a novel advanced MRI protocol is developed by 1) developing a new MRI data acquisition sequence which reduces the imaging time of clinical contrast-weighted images, which are routinely acquired for differential diagnosis with other diseases such as tumor, 2) overcoming the generalization limitation of neuromelanin-weighted MRI to scanner differences, and 3) by overcoming the generalization limitation of deep learning-based quantitative susceptibility mapping to different resolution data. The novel neuromelanin-weighted MRI and quantitative susceptibility mapping data can be acquired within the clinical limit of scan time thanks to the reduction of routine image scan time by 1). The proposed protocol may provide a cornerstone for MRI based non-invasive diagnosis of early stage neurodegenerative diseases. This may have a large clinical implication since the current image-based diagnosis of neurodegenerative diseases relies on PET with radiation exposure. Keywords : Magnetic Resonance Imaging (MRI), Neurodegenerative, Parkinson’s Disease (PD), Neuromelanin (NM), Quantitative susceptibility mapping (QSM) 자기 공명 영상 (MRI)은 수십 년 동안 3 차원 뇌 구조의 비 침습적인 생체 내 평가를 위한 전례 없는 방법론을 제공하였다. 고해상도로 다양한 대비를 생성할 수 있는 유연성을 갖춘 MRI는 뇌 장애를 진단하는 가장 효과적인 방법을 제공한다. 그러나, 다수의 명암 강조 이미지에 의해 제공되는 정교한 해부학적 세부 사항에도 불구 하 고, 신경 퇴행성 질환에서 현재 MRI는 주로 감별 진단의 수단으로 사용되고 있다. 이것은 위축과 같은 구조 변화가 발병 후 장기간에 걸쳐 발생하기 때문이다. 최근 몇 년 동안 신경 퇴행성 질환의 초기 단계에 민감한 고급 MRI 기술이 개발되었으며 MRI를 사용한 비 침습적 진단과 질병의 병태 생리학 연구에 유망한 결과가 나타나고 있다. 특히 뉴로멜라닌 강조 MRI와 자화율 이미징은 큰 가능성을 보이고 있다. 신경 퇴행성 질환에 대한 이러한 고급 MRI는 방사능 노출의 위험이 있는 현재의 PET 기반 진단을 대체할 수 있는 잠재력이 많지만, 필요한 추가 스캔 시간과 각 방법의 일반화 제한으로 인해 광범위한 적용이 제한되어 있는 상황이다. 이 논문 에서는 신경퇴행성질환을 위한 새로운 고급 MRI 프로토콜을 개발하기 위해 다음과 같은 과정을 거친다. 1) 종양과 같은 다른 질병과의 감별 진단을 위해 일상적으로 얻는 임상적 명암 강조 영상의 이미징 시간을 단축하는 새로운 MRI 데이터 획득 시퀀스를 개발한다. 2) 뉴로멜라닌 강조 MRI의 스캐너 간 차이에 대 한 일반화를 위한 영상법 개발한다. 마지막으로 3) 학습 기반 정량적 자화율 매핑의 다른 해상도 데이터에 대한 일반화의 제한을 극복하는 재구성 파이프라인을 개발한다. 새로운 뉴로멜라닌 강조 MRI 및 정량적 자화율 매핑 데이터는 1)에서 감별진단을 위해 얻는 영상의 스캔 시간을 단축하였기 때문에 스캔 시간의 임상 한계 내에서 얻을 수 있다. 제안된 프로토콜은 초기 단계의 신경 퇴행성 질환의 MRI 기반 비 침습적 진단의 기초를 제공할 가능성이 있다. 신경 퇴행성 질환의 현재 이미지 기반 진단은 방사선 노출과 함께 PET에 의존하기 때문에 이는 큰 임상적 의미를 가질 수 있다. Keywords : 자기공명영상법, 신경퇴행성 질병, 파킨슨씨 병, 뉴로멜라닌, 정량적자화율 매핑

가와사끼병 환아의 혈청 프로테옴 지도 비교

백승연 연세대학교 대학원 2003 국내석사

가와사끼병은 1967년 일본의 Tomisaku Kawasaki에 의해 처음 보고 되었으며 주로 5세 이하의 소아에서 호발하는 전신성 혈관염으로 후천성 심장 질환의 중요한 원인으로 생각되고 있다. 현재까지 감염에 의한 가능성이 많이 제시되고 있으나 아직까지도 그 원인 및 병리생태가 밝혀지지 않은 질환이다. 최근 단백질을 양적 및 질적으로 측정하는 학문인 프로테오믹스(proteomics)가 대두되고 있고, 이에 필요한 고해상도 이차원 전기영동과 mass spectrometry 등의 방법의 개발로 여러 질환의 원인 및 병태 생리를 찾고자 하는 노력이 있어왔다. 이에 본 연구에서는 가와사끼병 환자의 급성기 혈청으로 이차원 전기영동을 시행하여 얻은 프로테옴 지도를 통하여 가와사끼병의 원인 및 병태 생리를 찾을 수 있는 기초자료를 얻고자 하였다. 2000년 1월부터 2001년 7월까지 연세대학교 의과대학 부속 세브 스병원 소아과에 내원하여 임상적으로 전형적인 가와사끼병으로 진단받은 급성기 환아 5명과 발열을 주소로 내원하여 상기도 감염으로 진단받은 환아 5명을 대상으로 하였다. 환자의 혈청을 수집하여 실험 직전까지 -70℃에 얼렸다가 해동시킨 후, 재수화 (rehydration)하여 polyacrylamide gel에서 이차원 전기영동을 시행하였다. 염색법으로 silver staining method를 이용하였고, GS-800 Calibrated Imaging Densitometer를 이용하여 스캐닝한 후, PDQuest를 사용하여 단백스폿을 양적으로 측정하여 프로테옴 지도를 구하였다. 혈청 프로테옴 지도를 비교한 결과, 가와사끼병 환자군의 혈청에서 15개의 의미있는 단백스폿의 변화가 발견되었고, 모든 경우에서 상기도 감염 대조군에 비해 감소 소견을 나타내었다. 이 중에서 분자량 91.8 kDa, 등전점 5.77의 단백스폿과 분자량 92.4 kDa, 등전점 5.85의 단백스폿은 각각 유사한 분자량과 등전점을 갖는 알부민의 일부로 사료되며, 분자량 76.1 kDa, 등전점 4.80의 단백스폿, 분자량 75.0 kDa, 등전점 4.70의 단백스폿 및 분자량 74.4 kDa, 등전점 4.70의 단백스폿은 α-1-antitrypsin의 일부로 사료된다. 프로테오믹스를 이용한 단백스폿들의 성분이나 유용성을 더 정확하게 알아보기 위해서 더 많은 연구가 필요할 것으로 생각되며, 앞으로 electrospray ionization mass spectrometry (ESI-MS) 또는 matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS) 등과 SWISS-PROT (Swiss Institute of Bioinformatics, Geneva, Switzerland) 등을 이용한 방법으로 단백의 규명 및 특성을 파악하는 연구가 뒤따라야 할 것으로 생각된다. Kawasaki disease, first reported by Tomisaku Kawasaki in 1967, is a kind of systemic vasculitis usually observed in children under 5 years of age and also known as the leading cause of pediatric acquired heart disease. Though there have been some evidences suggesting infection as the cause, the exact pathophysiology of Kawasaki disease is still not completely understood. Many efforts were made to study the etiology and pathogenesis of several diseases after the field of proteomics had been introduced. Proteomics, the study of quality and quantity of proteins, has developed dramatically after two-dimensional electrophoresis(high resolution) and mass spectrometry were brought in use. In this study, we tried to find a way to evaluate the etiology and pathogenesis of Kawasaki disease by analyzing the serum proteome maps of children in the acute stage of the disease. We studied 10 patients admitted to the pediatric department of Yonsei Severance Hospital from January 2000 to July 2001. Half were clinically diagnosed as typical Kawasaki disease and the rest whose main presenting symptom was fever, as upper respiratory infection. Sera collected from the patients were frozen to -70℃. They were melted and rehydrated later for isoelectric focusing method using polyacrylamide gel and two dimensional electrophoresis. The gel were stained by silver method and scanned with GS-800 Calibrated Imaging Densitometer. PDQuest was used to quantify protein and draw proteome maps. Analysing serum proteome maps, changes of protein spots were observed in 15 sites in the children with Kawasaki disease. The signals were all significantly decreased compared to those of the control group. The spots included a protein spot of molecular weight of 91.8kDa and isoelectric point 5.77 and a spot with 92.4kDa and isoelectric point 5.85 which are suspected as parts of albumin protein. Also, a spot of 76.1kDa and isoelectric point 4.80, a spot with 75.0kDa and isoelectric point 4.70, and a spot with 74.4kDa and isoelectric point 4.70 which are thought to be parts of α-1-antitrypsin. More studies would have to be performed to define and to understand the functions of protein spots detected in electrophoresis of sera of patients with Kawasaki disease. Further evaluations using methods such as electrospray ionization mass spectrometry (ESI-MS), matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS) or SWISS-PROT (Swiss Institute of Bioinformatics, Geneva, Switzerland) are expected to provide us with more information about those protein spots observed.

Mapping Forest Host Species Distributions and Understanding their Effects on Forecasts of Disease Spread

Kruskamp, Nicholas Frederick North Carolina State University ProQuest Dissertat 2022 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Emerging infectious diseases of trees are a type of biotic invasion that pose a dire threat to the world’s forest ecosystems. In temperate forest environments, tree diseases exacerbate the severity and frequency of other, naturally occurring disturbances. This leads to cascading and complex disturbance interactions that reduce biodiversity, alter carbon flux, and potentially change ecosystem state. The severity of these impacts is expected to worsen under future scenarios of climate change. Land managers, however, currently lack tools capable of forecasting infectious diseases to enact management actions that could slow or stop spread. In this dissertation, the research objectives were driven by the desire to improve mapping forest tree species across geographically broad landscapes, and examine how their use in ecological modeling can better inform land managers. In the first study, I explore how species distribution modeling choices related to the use of field observations, environmental and remote sensing covariates, and spatial dependence in machine learning models impact the accuracy of emerging infectious disease host tree species maps. Our results show that the use of spatial dependence in species distribution mapping can significantly improve their accuracy over heterogeneous landscapes. We also demonstrate how combining disparate field observations can improve mapping accuracy. In the second study, I test the sensitivity of a spatially explicit ecological forecasting model of pathogen spread to the choice of modeling scale resolution and landscape configuration. Here, we find that near-term forecasting was relatively reliable for up to three years of simulation in the scales examined, but that different measures of disagreement are more sensitive than others to scale and landscape configuration. The results of this work improve our ability to make informed decisions when mapping forest tree species, and elucidate the effects of scale when using forecasting models to predict future scenarios of disease spread. Ultimately, this work provides land managers with improved tools and understanding to better manage emerging infectious diseases.

Inflammatory TH17 Responses to Infection with Mycobacterium avium Subspecies Paratuberculosis (Map) in Cattle and Their Potential Role in the Development of Johne’S Disease

DeKuiper, Justin Lee Michigan State University ProQuest Dissertations & 2019 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic inflammatory gastrointestinal disease of ruminants known as Johne’s disease (JD). MAP primarily colonizes the ileum of ruminants, leading to reduced nutrient absorption, chronic diarrhea, and eventually death. The percentage of dairy operations infected MAP in the US may have risen to as much as 91% from earlier reports of 68%. In correspondence, an estimated dairy industry loss has increased from $200 million to $1.5 billion was due to JD. Control of JD is difficult largely due to insensitive diagnostic tools, a long subclinical stage of infection, and lack of effective vaccines. Correlates of protection are lacking in model systems of JD and the sources of inflammation due to JD are not well characterized. Inside macrophages, MAP survives and replicates. Monocyte-derived macrophages (MDMs), peripheral blood mononuclear cells (PBMCs), and various T-cells interact with MAP. Commonly studied immune responses, such as the Th1/Th2 paradigm, do not adequately explain host responses to MAP. The major remaining knowledge gaps in MAP immunopathogenesis include key inflammatory responders in the ileum, and how naive T-cell responsive choice (Th1, Th2, Th17) is influenced. A potential role for non-classical immune responses to MAP, such as that mediated by Th17 cells, has been suggested. Indeed, MAP antigens induce mRNAs encoding the cytokines IL-23 and IL-17A in bovine PBMCs. IL-23 and IL-17A production are both associated with Th17-like immune responses. Th17 cells are also defined by surface expression of the IL-23 receptor (IL-23R). The mean relative percent (MRP) of T cell subtypes expressing IL-23R was determined by flow cytometry and indicated an increase in mean relative percent (MRP) of T cells (CD4+, CD8+, and TCR1+) in peripheral blood mononuclear cells (PBMCs) of JD+ cows with high and low expression of IL-23R (IL-23RHigh and IL-23RLow) when compared to JD- cows. Although MAP stimulates PBMCs to secrete IL-17A in-vitro, there were no differences in IL-17A levels between subclinical JD+ and JD- cows when analyzed by ELISA. Plasma with low JD+ score values had significantly more IL-17A when compared to plasma with high JD+ score values, establishing a moderate correlation between JD+ score and IL-17A. However, overall plasma from JD+ cows had significantly less IL-17A than plasma from JD- cows. Unlike IL-17A, IL-23 was greater in plasma from JD+ cows than in JD- cows. Evaluating the relationship that MAP is having on APCs and CD3+ in relation to Th17 cytokines (IL-23, IL-17A, IL-17F, IL-22, IL-27) as well as Th1 cytokine IFNγ, CD3+ were stimulated with MAP in the presence of APCs (MDMs or B cells) or alone and evaluated by RT-qPCR. MAP stimulation significantly increased production of mRNA encoding Th17 cytokines and IFNγ in CD3+ T cells regardless of APCs. However, the presence of MDMs significantly increase the quantity of mRNA. Lastly, we observed that αβ T cells (mostly CD4+) are responsible for production of Th17 cytokines as an early response to MAP in the absence of APCs. Our data suggests that Th17-like cells may indeed play a role in early immune responses to MAP infection and development or control of JD. Understanding the influences and potential novel mechanisms of an inflammatory pathway during MAP infection could be exploited for treatment, prevention, or diagnosis of JD.