• Molecules and Cells
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• 제43권6호
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• pp.551-571
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• 2020

Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein's biological functions in dopamine-based neurogenesis.

• BMB Reports
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• 제44권6호
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• pp.405-409
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• 2011

The present study demonstrated that valproic acid (VPA) transcriptionally regulates human GM3 synthase (hST3Gal V), which catalyzes ganglioside GM3 biosynthesis in ARPE-19 human retinal pigment epithelial cells. For this, we characterized the promoter region of the hST3Gal V gene. Functional analysis of the 5'-flanking region of the hST3Gal V gene revealed that the -177 to -83 region functions as the VPA-inducible promoter and that the CREB/ATF binding site at -143 is crucial for VPA-induced expression of hST3Gal V in ARPE-19 cells. In addition, the transcriptional activity of hST3Gal V induced by VPA in ARPE-19 cells was inhibited by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. In summary, our results identified the core promoter region in the hST3Gal V promoter and for the first time demonstrated that ATF2 binding to the CREB/ATF binding site at -143 is essential for transcriptional activation of hST3Gal V in VPA-induced ARPE-19 cells.

• Molecules and Cells
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• 제42권11호
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• pp.739-746
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• 2019

Significant knowledge about the pathophysiology of Alzheimer's disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and APOE4-encoding apolipoprotein E4 (ApoE4) is strongly associated with these cases. As an apolipoprotein, the function of ApoE in brain cholesterol transport has been extensively studied and widely appreciated. Development of new technologies such as human-induced pluripotent stem cells (hiPSCs) and CRISPR-Cas9 genome editing tools have enabled us to develop human brain model systems in vitro and readily manipulate genomic information. In the context of these advances, recent studies provide strong evidence that abnormal cholesterol metabolism by ApoE4 could be linked to AD-associated pathology. In this review, we discuss novel discoveries in brain cholesterol dysregulation by ApoE4. We further elaborate cell type-specific roles in cholesterol regulation of four major brain cell types, neurons, astrocytes, microglia, and oligodendrocytes, and how its dysregulation can be linked to AD pathology.

• 한국방사선학회논문지
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• 제7권6호
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• pp.433-439
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• 2013

본 연구에서는 집속형 초음파를 이용하는 뇌 질환 치료의 연구를 위한 인체 두부 유사 팬텀을 개발하였다. 문헌 연구를 통하여 피부 조직, 두개골, 뇌 조직의 음향학적 및 물리적 특성을 조사하였으며 근사한 값을 가지는 적합한 각 조직 대체 물질을 제시하였다. 피부 조직의 경우 글리세롤 기반 연부 조직 유사 팬텀의 성분비를 조정하여 실제 조직과 유사한 음향학적 특성을 가지도록 하였으며 고분자 합성수지의 음향학적 특성을 측정하여 두개골 유사 물질로써의 적합성을 평가하였다. 뇌 조직은 투명한 egg white 팬텀을 이용하여 집속형 초음파의 가열 특성을 확인할 수 있도록 하였다. 또한 뇌 질환 치료 프로토콜 개발을 위한 시험 조사가 가능하도록 대체 물질들을 결합한 두부 유사 팬텀을 제작하였고 제작된 팬텀의 유효성 및 활용성 평가를 위해 초음파 조사 조건에 따른 팬텀의 변성을 관찰하였다.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.149-157
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• 2017

The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of $interleukin-1{\beta}$ and tumor necrosis $factor-{\alpha}$ at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.

• International Journal of Stem Cells
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• 제16권4호
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• pp.415-424
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• 2023

Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo. Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals. After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.

• 한국동물학회:학술대회논문집
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• 한국동물학회 2001년도 한국생물과학협회 학술발표대회
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• pp.214.2-215
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• 2001

No Abstract, See Full Text

• 한국지능시스템학회논문지
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• 제18권2호
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• pp.251-256
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• 2008

많은 연구자들은 여러 개의 채널을 가진 Electroencephalogram(EEG) 신호를 기반으로 한 사람의 감정인식을 위해 두뇌와 컴퓨터의 인터페이스에 관한 연구를 하고 있다. EEG 신호를 이용한 연구들은 주로 의학 분야와 심리학의 영역에서 간질이나 발작 등을 알아내고 거짓말 탐지기로써의 역할로 많이 사용되어져 왔다. 최근에는 사람의 두뇌와 컴퓨터 간의 인터페이스에 관한 연구들이 뇌파를 이용한 로봇의 제어하거나 게임을 하는 등의 여러 가지 공학적인 접근으로써 많은 연구가 진행되고 있다. 특히, EEG 신호를 통해서 두뇌를 연구하는 분야에서 EEG 신호의 잡음을 제거해서 보다 정확한 신호를 추출하는 연구에도 많이 중점을 두고 있다. 본 논문에서는 사람의 감정에 따른 EEG 신호를 측정하고 측정된 EEG 신호를 5개 부분의 주파수 영역으로 분류하였다. 영역별로 분류된 EEG 신호들은 전체영역에 대한 상대적인 비율의 값으로 계산하게 된다. 그 값들은 Bayesian Networks를 통해서 현재 어떠한 감정을 나타내는지 확률 값으로 나타낸다. 그 결과 값에 따라 사람의 감정은 아바타로 표현하게 된다.

• 제어로봇시스템학회:학술대회논문집
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• 제어로봇시스템학회 2001년도 ICCAS
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• pp.154.1-154
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• 2001

The paper describes a new type of robot called "artificial liferobot" which is able to learn, make decisions, and behave by itself based on a brain-type computing technique called "artificial brain". The artificial liferobot has self-learning ability from the environment by the interactions between human being and it. The artificial brain makes the artificial liferobot to behave by itself with its intensions like living things as human being. We briefly introduce one attempt of our researches for developing cognitive and behavioral intelligent artificial liferobot in out laboratory. One of our purposes is the development of the artificial liferobot, which plays an Important role in taking care of elderly and infirm people in a rapidly aging society.

• 한국HCI학회논문지
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• 제12권4호
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• pp.75-80
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• 2017

최근 인지과학의 활발한 연구와 기술의 발달로 인해 사회과학분야에서 정신생리학적 연구를 통한 뇌의 다양한 측정과 정교한 분석 기법이 개발 되었다. 그러나 뇌파를 이용한 뉴미디어활용에 관한 연구는 장비들을 장착하는 과정에서의 한계점으로 인해 진행되지 못하였다. 이러한 문제를 극복하고자, 가상현실장비를 착용한 상태에서도 전 영역의 뇌파측정이 가능한 캡을 디자인하고 활용방법을 제안한다.