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- 저자 : Hyeonjoo Lee (검색결과 16 건)
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SIRT3 deregulation is linked to mitochondrial dysfunction in Alzheimer's disease
Lee, Junghee,Kim, Yunha,Liu, Tian,Hwang, Yu Jin,Hyeon, Seung Jae,Im, Hyeonjoo,Lee, Kyungeun,Alvarez, Victor E.,McKee, Ann C.,Um, Soo‐,Jong,Hur, Manwook,Mook‐,Jung, Inhee,Kowall, Neil W.,Ry John Wiley and Sons Inc. 2018 Aging cell Vol.17 No.1
<P><B>Summary</B></P><P>Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD‐dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD. SIRT3 mRNA and protein levels were significantly decreased in AD cerebral cortex, and Ac‐p53 K320 was significantly increased in AD mitochondria. SIRT3 prevented p53‐induced mitochondrial dysfunction and neuronal damage in a deacetylase activity‐dependent manner. Notably, mitochondrially targeted p53 (mito‐p53) directly reduced mitochondria DNA‐encoded ND2 and ND4 gene expression resulting in increased reactive oxygen species (ROS) and reduced mitochondrial oxygen consumption. ND2 and ND4 gene expressions were significantly decreased in patients with AD. p53‐ChIP analysis verified the presence of p53‐binding elements in the human mitochondrial genome and increased p53 occupancy of mitochondrial DNA in AD. SIRT3 overexpression restored the expression of ND2 and ND4 and improved mitochondrial oxygen consumption by repressing mito‐p53 activity. Our results indicate that SIRT3 dysfunction leads to p53‐mediated mitochondrial and neuronal damage in AD. Therapeutic modulation of SIRT3 activity may ameliorate mitochondrial pathology and neurodegeneration in AD.</P>
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Lee, Junghee,Nguyen, Phuong T.,Shim, Hyun Soo,Hyeon, Seung Jae,Im, Hyeonjoo,Choi, Mi-Hyun,Chung, Sooyoung,Kowall, Neil W.,Lee, Sean Bong,Ryu, Hoon Elsevier 2019 Biochimica et biophysica acta. Molecular basis of Vol.1865 No.7
<P><B>Abstract</B></P> <P>Ewing's sarcoma (EWS) is a bone cancer arising predominantly in young children. <I>EWSR1</I> (<I>Ewing Sarcoma breakpoint region 1</I>/<I>EWS RNA binding protein 1</I>) gene is ubiquitously expressed in most cell types, indicating it has diverse roles in various cellular processes and organ development. Recently, several studies have shown that missense mutations of <I>EWSR1</I> genes are known to be associated with central nervous system disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Otherwise, EWSR1 plays epigenetic roles in gene expression, RNA processing, and cellular signal transduction. Interestingly, EWSR1 controls micro RNA (miRNA) levels via Drosha, leading to autophagy dysfunction and impaired dermal development. <I>Ewsr1</I> deficiency also leads to premature senescence of blood cells and gamete cells with a high rate of apoptosis due to the abnormal meiosis. Despite these roles of EWSR1 in various cellular functions, the exact mechanisms are not yet understood. In this context, the current review overviews a large body of evidence and discusses on what <I>EWSR1</I> genetic mutations are associated with brain diseases and on how EWSR1 modulates cellular function via the epigenetic pathway. This will provide a better understanding of bona fide roles of EWSR1 in aging and its association with brain disorders.</P> <P><B>Highlights</B></P> <P> <UL> <LI> EWSR1 (Ewing Sarcoma breakpoint region 1/EWS RNA binding protein 1) has diverse roles in various cellular processes. </LI> <LI> Missense mutations of <I>EWSR1</I> are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). </LI> <LI> EWSR1 deficiency also contributes to hematopoietic stem cell senescence. </LI> <LI> EWSR1 participates in mitochondria function and cellular energy homeostasis by modulating the stability of PGC-1α. </LI> <LI> EWSR1 deficiency deregulates dopaminergic signaling pathways by reducing TH activity and leads to motor dysfunction. </LI> </UL> </P>
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서비스 지향 아키텍처를 위한 컴포넌트기반 시스템의 서비스 식별
이현주(Hyeonjoo Lee),최병주(Byoungju Choi),이정원(Jungwon Lee) 한국정보과학회 2008 정보과학회논문지 : 소프트웨어 및 응용 Vol.35 No.2
Today, businesses have to respond with flexibility and speed to ever-changing customer demand and market opportunities. Service-oriented architecture (SOA) is the best methodology for minimizing the complexity and the cost of enterprise-level infrastructure and for maximizing the productivity and the flexibility of an enterprise. Most of the enterprise-level SOA delivery strategies deal with the top-down approach, which organization has to define the business processes, to model business services, and to find the required services or to develop new services. However, a lot of peoples want to maximally reuse legacy component-based systems as well as to deliver SOA into their organizations. In this paper, we propose a bottom-up approach for identifying business services with proper granularity. It can improve the reusability and maintenance of services by considering not data I/O of components of legacy applications but GUI event patterns. Our proposed method is applied to MIS with 129 GUIs and 13 components. As a result, the variance of the coupling value of components is increased five times and three business services are distinctly exposed. It also provides a 49% improvement in reducing the relationship problems between services over a service identification method using only partitioning information of components. 서비스 지향 아키텍처(Service Oriented Architecture)는 기업 인프라의 복잡성 및 유지비용을 최소화하고, 기업의 생산성과 유연성을 극대화할 수 있는 것으로, 경영환경이 빠르게 급변하는 최근에 떠오른 이슈이다. 엔터프라이즈 수준에서 서비스 지향 아키텍처를 도입하는 전략은 조직의 비즈니스 프로세스를 정의하고 이에 필요한 서비스를 모델링하여, 필요한 서비스를 찾아내거나 개발하는 하향식 전략이 대부분이다. 그러나 대부분의 조직은 SOA를 도입하면서도 기존에 사용하던 컴포넌트 시스템을 최대한 재사용할 수 있기를 바라고 있다. 본 논문에서는 이미 개발된 컴포넌트 기반 시스템에서 입출력 데이타가 아닌 GUI 이벤트 정보를 이용하여 상향식 방법으로, 서비스 재사용성과 유지보수성을 고려하면서 비즈니스 서비스 모델에 적합한 크기의 서비스를 식별할 수 있는 방법을 제안한다. 본 논문에서 제안한 방법은 실제 129개의 GUI와 13개의 컴포넌트를 가진 경영정보시스템에 적용한 결과 기존의 컴포넌트를 기준으로 서비스를 식별하는 것보다 결합도가 5배정도로 약해지면서 3개의 서비스가 명확히 구분되었고, 식별 후 연관관계에 따른 문제점도 약 49%정도 줄어드는 것을 보였다.
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지리학자의 공공직 참여에 관한 연구 : 프랑스 사례를 중심으로
이현주(Hyeonjoo LEE),권용우(Yongwoo Kwon) 대한지리학회 2004 대한지리학회지 Vol.39 No.4
우리나라에서 지리학전공자들의 사회진출 영역이 한정되어 고용시장의 적체현상이 발생하는 까닭에 지리학의 활동영역을 확대시키는 노력의 일환으로 프랑스 지리학계의 사례를 통하여 지리학자의 공공직 진출의 가능성을 논의코자 본 연구를 실시하였다. 지리학은 고대부터 사상들의 분포관계와 지역특성에 대한 지식을 제공함으로써 효율적인 통치를 보좌하는 역할을 담당하였으며 영토의 확장과 관리를 위한 지역연구의 활용이 활발하여 유럽 국가들에서는 지리학자들의 정치참여를 독려하는 분위기였다. 한국에서도 최근 여러 차원의 사회진출이 확대되고 있는 실정이다. 프랑스 지리학계는 지리적 시각과 접근방법의 특성이 지리학자들의 공공직 진출을 용이하게 만드는 것으로 평가하고 있다. 특히 지역개발, 환경, 부문적 경제, 관광개발, 국제정치 분야 등이 지리학자들이 진출하기에 적절한 공공직 분야이다는 의견이다. 따라서 한국지리학계가 사회과학 전반적인 지식에 대해 개방적인 태도를 견지하며 지리학 특정분야의 전문지식 획득과 동시에 지리학 전반의 고른 지식을 배양하는 것이 공공직 참여를 확대할 수 있는 길이 될 것이다. It is generally found that geography majors’ progression in society has a very limited scope in Korea and this is one of the causes of lessening geographers’ job market. As an attempt to draw a solution to this problem, this paper, by a close examination of the French case, tries to discuss the possibility of geographers’ participation in the public sector. Geographers’ participation in political and social issues has long history. They acted as providers of geographical knowledge on human and physical features of the world and also as counsellors for effective administration and politics. French geographers evaluate that it is the characteristics of geography that enable geographers to progress into the public sector. They also perceive that such fields as regional development, environment, economy, tourism, international politics are possible ones for geographers.<br/> Some implications can be drawn from this case study to extend geographers’ participation in the public sector in Korea; it is required to sustain open mind to every field of social sciences, to improve specialized as well as generalized knowledge on geographical features, and to provide practical knowledge on spatial analysis and management.
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이현주,이승헌 한국경제지리학회 2004 한국경제지리학회지 Vol.7 No.2
지역경제발전에 가장 큰 영향을 미치는 기업들의 환경을 분석하여 경기도 접경지역 내 경제공간의 특성을 밝히고자 본 연구를 실시하였다. 경기도 접경지역은 1990년대 이후 수도권 공간조직의 변화에 영향을 받아 기존의 군사적 기능 외 새로운 기능을 부여받고 있다. 수도권 핵심지역의 탈산업화와 주변지역에서의 산업화 추세가 경기도 외과지역인 접경지역에까지 영향을 미쳐 경기도 접경지역은 재래산업 위주의 비도시형 산업 집중공간, 영세기업의 생산공간으로 발전하고 있다. 접경지역의 가장 큰 흡인인자는 공장부지확보의 용이성과 저렴한 공업용지구입 조건이고 과거 입지지역에서의 기업 배출요인은 환경규제 정책에 의한 기업 환경기준 강화, 생활환경 보호와 관련된 민원과 공장 부지확장이다. 1990년대 이후에 입지한 기업조차도 남북경제협력의 영향이 매우 미미한 것으로 조사되는 등 전체적으로 접경지역에 기업을 입지시킨 이유가 적극적이고 진취적인 발전전략에 의하기보다는 소극적이고 방어적인 이유에 의한 입지결정이다. 지역환경에 대한 기업입지 만족도가 높지 않는 것으로 조사된다. 불만조건으로 노동력 부족의 문제와 지리적 격리성으로 인한 행정 및 고차서비스 부문과의 접근성 부족이 가장 부각된다. 현재 진행되는 수도권 경제구조의 변화양상이 경기도 접경지역의 성장에 긍정적인 영향만을 끼치는 것이 아님에 주목하고 지역의 내생적 성장 잠재력을 향상시키고 상대적 낙후성을 개선하는 방향으로 접경지역의 발전 방향을 정립하고 핵심적 역할을 담당할 기업의 입지환경을 조성하여야 한다. The purpose of this paper analyzes the characteristics of economic space in Gyeonggi border regions. Especially, this study focuses on understanding the environment enveloped the enterprises because today, largely influenced factor for regional economic development is enterprises. Since 1990's the change of the spacial organization in Korean Capital region has been inducing the functional transformation in Gyeonggi border regions so that new function - beyond military functions- is developed in these regions. By the disindustrialization in core region contributed to the industrialization in periphery, border regions are developed as a concentrated space of traditional industries and small size manufactural firms. The most important pull factor is facility for obtain a factory site and favorable condition of land price. Globally, the reasons to locate enterprise in these regions are found not in positive and progressive strategies but in passive and defensive strategies. Therefore few enterprise carried about influences of economic cooperation between North and South Korea at the moment of decision of their site. The survey reveal that enterprises didn't highly estimate the environment in border regions as their business activities. The first dissatisfied condition is insufficiency of labour and difficulty of access for administrative and high level services, due to geographical separation. Considering the recent tendency of spacial reorganization in Capital region is not always good for border regions, border regions have to employ a policy with the object of ameliorating regional business environments and growing up a potentiality of endogenous development.
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HyeonJoo Cheon,Young-Seok Woo,Ji Young Lee,Hee Sook Kim,Hyun Jin Kim,Sungwon Cho,Nam Hee Won,Jeongwon Sohn 생화학분자생물학회 2007 Experimental and molecular medicine Vol.39 No.4
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a proto-typic halogenated aromatic hydrocarbon (HAH), is part of its toxic effects appears to be derived from its ability to induce TNF-α production. However, the sig-naling pathway of TCDD that leads to TNF-α ex-pression has not been elucidated. In this study, we in-vestigated the signaling mechanism of TCD-induced TNF-α expression in PMA-differentiated THP-1 macrophages. TCDD induced both mRNA and protein expression of TNF-α in a dose- and time-dependent manner. αreceptor (AhR) inhibitor, prevented the TCDD-induced expression of TNF-α at both mRNA and protein levels. Genistein, a protein tyrosine kinase (PTK) inhibitor, and PD153035, an EGFR inhibitor, also blocked the in-crease of TNF-α expression by TCDD, indicating the role of EGFR in TCDD-induced TNF-α expression. On the other hand, P2, a c-Src specific inhibitor, did not affect TCDD-induced TNF-α expression. EGFR phos-treatment. TCDD-induced EGFR activation was AhR-dependent since co-treatment with α-NF pre-vented it. ERK was found to be a downstream efector of EGFR activation in the signaling pathway leading to TNF-α production after TCDD stimulation. Activation of ERK was observed from 30 min after TCDD treatment. PD98059, an inhibitor of the MEK-ERK path-way, completely prevented the TNF-α mRNA and pro-tein expression induced by TCDD, whereas inhibitors EGFR inhibitor, as well as α-NF significantly reduced ERK phosphorylation, suggesting that ERK activation by TCDD was mediated by both EGFR and AhR. These results indicate that TNF-α production by TCDD in dif-ferentiated THP-1 macrophages is AhR-dependent and involves activation of EGFR and ERK, but not c-Src, JNK, nor p38 MAPK. A signaling pathway is pro-posed where TCDD induces sequential activation of AhR, EGFR and ERK, leading to the increased ex-pression of TNF-α.
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Lee, Jiwon,Seul, Hyeonjoo,Jeong, Jae Kyeong Elsevier 2018 JOURNAL OF ALLOYS AND COMPOUNDS Vol.741 No.-
<P><B>Abstract</B></P> <P>In this study, we evaluated the structural, chemical, and electrical properties of ternary alloy aluminum yttrium oxide (Al<SUB>2-x</SUB>Y<SUB>x</SUB>O<SUB>3</SUB>) films prepared by employing a low-cost spin-cast technique. Al<SUB>2-x</SUB>Y<SUB>x</SUB>O<SUB>3</SUB> films annealed at 400 °C were found to possess smooth and excellent insulating characteristics compared to their binary Al<SUB>2</SUB>O<SUB>3</SUB> or Y<SUB>2</SUB>O<SUB>3</SUB> film counterparts. This superior performance of the Al<SUB>2-x</SUB>Y<SUB>x</SUB>O<SUB>3</SUB> films as a gate insulator can be explained based on structure stabilization from the cation alloying mixing effect. The amorphous indium zinc oxide (<I>a</I>-IZO) thin-film transistor (TFT) with the ternary alloy Al<SUB>0.45</SUB>Y<SUB>1.55</SUB>O<SUB>3</SUB> film exhibited a high mobility of 52.9 cm<SUP>2</SUP>/V, a low subthreshold gate swing of 0.19 V/decade, a threshold voltage of −0.51 V, a high <I>I</I> <SUB> <I>ON/OFF</I> </SUB> ratio of 4 × 10<SUP>6</SUP>, and good hysteresis-free stability, suggesting that the solution-based Al<SUB>0.45</SUB>Y<SUB>1.55</SUB>O<SUB>3</SUB> dielectric film is an attractive candidate as a gate dielectric for high-performance and low-cost <I>a</I>-IZO TFTs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Novel ternary alloy Al<SUB>2-x</SUB>Y<SUB>x</SUB>O<SUB>3</SUB> dielectric films were prepared by low-cost spin coating. </LI> <LI> The Al<SUB>2-x</SUB>Y<SUB>x</SUB>O<SUB>3</SUB> films show the good insulating and high permittivity. </LI> <LI> The a-IZO transistors with a Al<SUB>2-x</SUB>Y<SUB>x</SUB>O<SUB>3</SUB> gate dielectric exhibited the promising performance. </LI> </UL> </P>
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