Parkinson’s disease (PD) is characterized by a progressive and selective loss of dopamine-producing neurons in the substanti... Parkinson’s disease (PD) is characterized by a progressive and selective loss of dopamine-producing neurons in the substantia nigra. Several mutations of human genes including the E3 ubiquitin ligase, PARKIN, has been implicated in this characteristic cell death of the disease. However, it has been still mystery which cell death mechanisms are involved in the initiation and progression of dopaminergic cell loss in PD. In out recent paper, we made a discovery that poly(ADP-ribose) polymerase 1 (PARP1) activation downstream of accumulation of a parkin substrate, AIMP2, contributes to selective loss of dopamine neurons in mice and that this degeneration can be rescued by PARP1 deletion or inactivation with a highly potent and brain-permeable inhibitor. Finally, I would like to present and share some preliminary results testing potential association of PARP1-dependent cell death in other PD-related mouse models and human parkinson’s disease.

인간대상 연구와 실험동물 연구의 윤리와 제도적 이슈 ○ 인간대상 연구 (research involving human subjects) - IRB심의 대상구분... 인간대상 연구와 실험동물 연구의 윤리와 제도적 이슈 ○ 인간대상 연구 (research involving human subjects) - IRB심의 대상구분과 인간대상연구 수행시 유의사항 (생명윤리법과 약사법) ○ 실험동물 연구 (research involving animal subjects) - 실험동물 복지제도 소개(동물보호법/실험동물복지법) - 연구계획서 작성과 3R 원칙 □ 연사 약력 - 생명윤리학 박사 / 수의학 박사 - 대한의사협회 중앙윤리심의위원 - 식약처 중앙약사심의위원 - CITI-KOREA 프로그램디렉터 - 가톨릭중앙의료원 연구윤리사무국장 - 삼성의료원 기관윤리심의사무국장 - 대한기관윤리심의기구협의회 이사 - 연구분야 : 생명과학 연구윤리, 임상시험윤리, 실험동물복지 □ 주관기관 : 연구윤리정보센터 (CRE), https://www.cre.or.kr/

The specificity of proteases for the residue and length of substrates is a key to understanding regulatory mechanism, but lit... The specificity of proteases for the residue and length of substrates is a key to understanding regulatory mechanism, but little is known about the length selectivity. Crystallographic, functional and single-molecule techniques have been employed to uncover how aminopeptidase PepS only adopts substrates with certain lengths. Substrate length selectivity imposed by the substrate binding hole is a key in the regulation of the catalytic activity along with residue specificity and active-site repositioning.

Whi3 is a G1/S regulator and known to inhibit G1 CDK activity. It was first described as a cell-size control gene in a set of... Whi3 is a G1/S regulator and known to inhibit G1 CDK activity. It was first described as a cell-size control gene in a set of cell division cycle mutants in Saccharomyces cerevisiae. Dysfunction or deletion of Whi3 leads to abnormal cell cycle control and morphogenesis. Whi3 contains two conserved and interesting domains: a RRM domain which binds a large set of mRNAs, and a polyQ tract, which promotes protein aggregation. Although it is evident that these functions of Whi3 are tightly linked to many cellular functions such as cell cycle control or cell polarization, the basis, precise mechanisms and the role of Whi3 remain unknown. This thesis addresses some of the questions about the roles of Whi3 in cell functionality. How is cell cycle progression controlled through Whi3? What are the functions of the RRM and polyQ tract in Whi3 for the timing variability in cell cycle? How do the transcripts bound to Whi3 localize and why is it important for cell cycle control or cell polarization? Are there any other cellular function that are modulated by Whi3? The studies presented in this thesis demonstrate an unprecedented role for stabilization of G1 cyclin mRNA through Whi3 aggregation, as well as clustering of G1 cyclin mRNA. We also reveal novel functions of Whi3 aggregation and RNA binding in cell polarization, especially in polarized cell growth, morphogenesis and actin polarization. In this thesis, many novel microscopic, biochemical and bioinformatical techniques are described using Ashbya gossypii, which is a multinucleated and filamentous fungus. Ashbya is a powerful system to study timing variability in cell cycle and cell polarization due to multiple nuclear division in a common cytoplasm and the frequent maintenance and establishment of cell polarity in a cell regardless of cell cycle. Overall, this thesis describes new and multiple roles of Whi3 for cell cycle control and cell polarization.

The intracellular signaling mediator TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (D... The intracellular signaling mediator TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). We now report that DC-specific deletion of TRAF6 (TRAF6ΔDC) results, quite unexpectedly, in loss of mucosal tolerance, characterized by spontaneous rise in lamina propria Th2 cells, and development of eosinophilic enteritis and fibrosis of the small intestine. Loss of TRAF6ΔDC mucosal tolerance requires the presence of commensal microbiota in a manner that appears independent of the MyD88 pathway. Further, TRAF6ΔDC mice exhibit decreased regulatory T cell (Treg) numbers in the small intestine, and diminished induction of iTregs in response to model antigen. Finally, we demonstrate that aberrant Th2-associated responses in TRAF6ΔDC mice can be mitigated via restoration of Treg activity. Collectively, our findings reveal a novel role for TRAF6 in directing DC maintenance of intestinal immune tolerance through balanced induction of Tregs versus Th2 immunity.

Glucokinase (GK) is a monomeric allosteric enzyme and plays a pivotal role in blood glucose homeostasis. GK is regulated by g... Glucokinase (GK) is a monomeric allosteric enzyme and plays a pivotal role in blood glucose homeostasis. GK is regulated by glucokinase regulatory protein (GKRP), and indirectly by allosteric effectors of GKRP. Despite their critical roles, the molecular basis for the allosteric regulation mechanism of GK by GKRP remains unclear. We determined the crystal structure of Xenopus GK and GKRP complex in the presence of fructose-6-phosphate at 2.9Å. GKRP binds to a super-open conformation of GK mainly through hydrophobic interaction, inhibiting the GK activity by locking a small domain of GK. We demonstrate the molecular mechanism for the modulation of GK activity by allosteric effectors of GKRP. Importantly, GKRP releases GK in a sigmoidal manner in response to glucose concentration by restricting a structural rearrangement of the GK small domain via a single ion pair. We find that GKRP acts as an allosteric switch for GK in blood glucose control by the liver.

○ 연구부정행위 중 이공계 연구자들이 특히 주의해야 할 사항(표절, 자기표절) ○ 이공계의 연구결과 발표 시 저자 결정(부당한 논... ○ 연구부정행위 중 이공계 연구자들이 특히 주의해야 할 사항(표절, 자기표절) ○ 이공계의 연구결과 발표 시 저자 결정(부당한 논문저자 표시) □ 연사 약력 - U. of Illinois 미국, 분석화학 Ph. D - U. of California-Berkely 화학과 박사 후 연구원 - 연세대학교 화학과 교수 - 연세대학교 연구처/산학협력단 정책부처장/정책부단장 - 연구분야 : 전기분석화학, 바이오센서 및 바이오 칩 등 □ 주관기관 : 연구윤리정보센터 (CRE), https://www.cre.or.kr/

Arrestins interact with G-protein-coupled receptors (GPCRs) to block interaction with G proteins and initiate G-protein-indep... Arrestins interact with G-protein-coupled receptors (GPCRs) to block interaction with G proteins and initiate G-protein-independent signalling. Arrestins have a bi-lobed structure that is stabilized by a long carboxy-terminal tail (C-tail), and displacement of the C-tail by receptor-attached phosphates activates arrestins for binding active GPCRs. Structures of the inactive state of arrestin are available, but it is not known how C-tail displacement activates arrestin for receptor coupling. Here we present a 3.0 Å crystal structure of the bovine arrestin-1 splice variant p44, in which the activation step is mimicked by C-tail truncation. The structure of this pre-activated arrestin is profoundly different from the basal state and gives insight into the activation mechanism. p44 displays breakage of the central polar core and other interlobe hydrogen-bond networks, leading to a ∼21° rotation of the two lobes as compared to basal arrestin-1. Rearrangements in key receptor-binding loops in the central crest region include the finger loop, loop 139 (refs 8, 10, 11) and the sequence Asp 296-Asn 305 (or gate loop), here identified as controlling the polar core. We verified the role of these conformational alterations in arrestin activation and receptor binding by site-directed fluorescence spectroscopy. The data indicate a mechanism for arrestin activation in which C-tail displacement releases critical central-crest loops from restricted to extended receptor-interacting conformations. In parallel, increased flexibility between the two lobes facilitates a proper fitting of arrestin to the active receptor surface. Our results provide a snapshot of an arrestin ready to bind the active receptor, and give an insight into the role of naturally occurring truncated arrestins in the visual system.

○ 중복게재의 개념과 유형 및 윤리문제 ○ 사례를 활용한 중복게재의 판단기준 ○ 중복게재에 대한 질의 및 응답 ○ 일상... ○ 중복게재의 개념과 유형 및 윤리문제 ○ 사례를 활용한 중복게재의 판단기준 ○ 중복게재에 대한 질의 및 응답 ○ 일상의 문제에 대해 토론하며 바람직한 해결방안 도출 □ 연사 약력 서울교육대학교 윤리교육과 학사 서울대학교 대학원 윤리교육과 석사 서울대학교 대학원 윤리교육과 박사 미국 The University of Illinois at Chicago(UIC) 교환교수 서울교육대학교 윤리교육과 교수 한국저작권위원회 표절위원회 위원 서울대, 전남대 등의 연구진실성검증을 위한 본조사위원 활동 □ 주관기관 : 연구윤리정보센터 (CRE), https://www.cre.or.kr/

본 세미나는 연구원들의 출판윤리 의식을 함양하고, 바른 논문 인용법을 알고 이를 실천하도록 하는데 목적을 둔다. 참여자들은 연구... 본 세미나는 연구원들의 출판윤리 의식을 함양하고, 바른 논문 인용법을 알고 이를 실천하도록 하는데 목적을 둔다. 참여자들은 연구윤리와 관련된 주제 중 출판 윤리와 관련된 딜레마를 접하고 자신의 입장과 그 이유들을 제시한 후, 강의자 및 다른 연구원들과의 토론을 통해 출판 윤리의 중요성을 인식할 수 있는 기회를 갖는다. 또한 강의자가 제시하는 구체적인 사례를 통해 올바른 논문 인용법을 알며, 참여자들이 연구 상황에서 실제적으로 접하는 문제들을 서로 나누고, 바람직한 해결방안을 찾도록 하는데 세미나의 주안점을 둔다. ○ 출판윤리와 관련된 딜레마에 대한 자신의 입장과 이유 제시 ○ 토론을 통해 출판 윤리의 중요성을 인식할 수 있는 기회 제공 ○ 구체적 사례를 통해 올바른 논문 인용법 습득 ○ 일상의 문제에 대해 토론하며 바람직한 해결방안 도출 □ 연사 약력 서울교육대학교 윤리교육과 학사 서울대학교 대학원 윤리교육과 석사 미국 The University of Georgia, Social Science Education, Ph.D. 경인교육대학교 윤리교육과 부교수 한국윤리학회 총무이사 연구분야: 연구윤리, 정보윤리, 도덕․인성교육 □ 주관기관 : 연구윤리정보센터 (CRE), https://www.cre.or.kr/