Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain.ope

제주 사회 운동가들의 인식에 나타난 부속 공간의 정체성: 예멘 난민 옹호 운동을 사례로

학위논문(석사)--서울대학교 대학원 :사회과학대학 지리학과,2019. 8. 신혜란.This study investigates how the locality of an annexational space is reflected in the perceptions of social activists through the case of Jeju Island. Locality in this thesis refers to the sum total of the various relationships that spaces as well as actors create across time, which is very fluid, multilayered, political, and value-oriented (Moon, 2016). Recently, increasing attention has been paid to the concept of locality in social science fields and humanities. In the field of geography, locality has been one of the key concepts following the spatial restructuring in the Western capitalist countries in the 1970s. In previous studies, annexation has been used to mean incorporation of one region to another region or a country. For example, Tanji (2006) used the concept of annexation to refer to compulsory amalgamation of Okinawa to mainland Japan. In this thesis, the concept of annexation is expanded to imply the relations with the mainland from the local point of view. Therefore, I define an annexational space as a space which experienced annexation to the mainland, where the locality featuring dichotomy between the mainland and the area, with complex toward the mainland and loneliness lying behind the pride in local social movement. The emergence and progress of the local refugee movement in Jeju Island enables examination of the locality of an annexational space. Therefore, this study aims to reveal the dynamics of pro-Yemeni refugee movement in Jeju Island. This study aims to answer the following two research questions. (1) How is locality of Jeju Island as an annexational space reflected in the perceptions of local social activists? (2) What kinds of relationship with the mainland have formed the locality? In summary, the results of this study are as follows. Firstly, locality of Jeju Island was investigated by analysis of the local interpretation of the Yemeni refugee issue. Perceptions of refugees and interpretation of the refugee issue in Jeju civil society was different from the mainland. The dichotomous way of thinking between Yug-ji (mainland) and Jeju Island made the difference. Once an independent kingdom annexed into the state in the mainland Korea, Jeju Islanders referred to all other parts of the country as Yug-ji. In the perspective of the local activists, Yemeni refugee issue was an incident that revealed the mainland's perception of treating Jeju as its surroundings. Based on the dichotomy, Jeju Islanders showed complex toward mainland, being susceptible to ideas of mainlanders and being exclusive to mainlanders concurrently. They believed those who opposed the refugee acceptance were mainly from the mainland, and felt that Jeju residents who cared about this public opinion had become increasingly reluctant for accepting refugees. Activists were also sensitive to the public opinion and felt the need to respond. Second, in the process of the emergence of local refugee movement, locality of Jeju Island as an annexational space was exposed. Community culture was found in the solid local activist network, which is based on strong regional identity as Jeju Islanders and personal acquaintances. They built coalitions to support other organizations, and solidarity beyond political factions for local issues was easier because of this character. Local activists were confident in their ability to quickly assemble and cope with the problems themselves. They found the spirit of resistance from the local history, from uprisings in the feudal age to 4·3 Uprising. However, there is loneliness as a remote island and envy toward the mainland behind the pride. It has always been treated as a periphery, including social movements. A yearning for the center arose with these experiences and as an isolated island, it requires mainland help when it encounters limitations. Instead of asking for help from the mainland, Jeju activists argued that Yemeni refuge issue is a national one. It also dealt with the issue separately by interacting with the mainland refugee network. Implications of this research are as follows. First, this study investigated the locality of an annexational space through a specific case. It also contributed to the discussion of locality which has mainly investigated western capitalist societies by analyzing the case in Asia. Second, it discovered a close relationship between the locality and social movement. It is worth referring to the case of refugee movement in Jeju Island at a time when the localization of social movements is spreading.본 연구는 제주도의 난민 운동을 사례로 하여 부속공간(annexational space)의 정체성이 사회운동가들의 인식에서 어떻게 나타나는지 살펴본다. 본 논문에서 로컬리티(locality)는 오랜 시간에 걸쳐 시간뿐만 아니라 공간이 만들어내는 다양한 관계의 총합으로, 매우 유동적이고 다층적이며 정치적이고 가치 지향적(문재원, 2016)이다. 최근 사회과학과 인문학에서 로컬리티 개념에 대한 관심이 높아지고 있다. 지리학 분야에서 로컬리티는 1970년대 서구 자본주의 국가에서 나타난 공간 재편(spatial restructuring)을 설명하기 위해 등장한 개념으로 활발히 연구되어 왔다. 선행 연구에서 '병합(annexation)'은 한 지역을 다른 지역이나 국가에 통합시키는 것을 의미했다. 예를 들어, Tanji(2006)는 오키나와와 일본 본토의 강제 합병을 설명하기 위해 이 개념을 사용했다. 본 논문에서는 지역의 관점에서 본토와의 관계를 포함하도록 병합(annexation) 개념의 의미를 확장한다. 따라서 따라서 본 연구에서는 부속 공간(annexational space)을 본토와의 합병을 경험하였으며 본토와의 관계를 중심으로 하여 본토와 지역 사이 이분법적 사고와 본토에 대한 콤플렉스를 특징으로 하는 로컬리티가 형성된 공간으로 정의한다. 제주도의 지역 난민 운동의 출현은 부속공간의 로컬리티를 잘 나타내는 사례이다. 연구 질문은 다음 두 가지이다. (1) 부속 공간으로서의 제주의 로컬리티가 난민 옹호 운동에 참여한 지역 사회 운동가들의 인식에 어떻게 반영되었는가? (2) 본토와의 어떤 관계가 그 로컬리티를 형성하였는가? 본 연구의 결과는 다음과 같다. 첫째, 예멘 난민 문제에 대한 지역적 해석을 분석한 결과 제주도의 부속 공간으로서의 로컬리티가 드러났다. 제주 시민사회의 난민과 이슈에 대한 해석은 내륙 지역과 달랐는데, 육지(본토)와 제주도의 이분법적 사고방식이 차이를 만들었다. 지역 운동가들의 입장에서 보면 예멘 난민 문제는 제주를 주변으로 취급하는 본토의 인식을 드러낸 사건이었다. 이러한 이분법을 바탕으로 제주도민들은 본토인에 대한 생각에 민감하고 동시에 본토인에게 배타적인 등 본토에 대한 콤플렉스를 드러냈다. 그들은 난민 수용에 반대하는 사람들이 주로 내륙 출신이라고 믿었고, 이런 여론을 신경 쓰는 제주 주민들이 난민을 점차 꺼리게 되었다고 생각했다. 활동가들도 내륙의 여론에 민감해 이에 대응할 필요성을 느끼고 있었다. 둘째, 지역 난민 운동이 출현하는 과정에서도 부속 공간으로서의 로컬리티가 중요한 역할을 했다. 지역 사회 운동 네트워크 속에서 강한 공동체 문화를 발견할 수 있었다. 그들은 다른 조직을 지원하기 위해 연합체를 만들었고, 강력한 지역 정체성 때문에 지역 문제를 해결하기 위한 정파를 넘어선 연대가 보다 용이했다. 지역 운동가들은 지역 현안에 대해 지역 공동체 내부에서 신속하게 대처할 수 있는 능력에 대해 자부심을 가지고 있었다. 그러나 이러한 자부심 뒤에는 외딴 섬으로의 외로움과 본토에 대한 선망이 있었다. 제주도는 항상 사회 운동을 포함한 모든 분야에서 주변부로 취급되어 왔기 때문에 중심부에 대한 선망을 내면화해 왔다. 따라서 제주 활동가들은 본토에 도움을 요청하기보다는 예멘 난민 이슈가 국가적인 문제라고 주장함으로써 연대의 필요성을 제기했다. 또 본토 난민 네트워크와 교류하였으나 이 문제를 지역 내에서 처리하고자 하였다. 이 연구의 함의는 다음과 같다. 첫째, 본 연구는 특정 사례를 통해 부속 공간의 로컬리티를 살펴보았다. 또한 서구 자본주의 국가에 집중된 기존의 연구와 달리 아시아 지역을 사례로 로컬리티에 대해 논의하였다. 둘째, 로컬리티와 사회 운동 사이의 밀접한 관계를 발견했다. 사회운동의 로컬화가 확산되고 있는 상황에서 제주도의 난민 옹호 운동의 사례를 참고할 만하다.Chapter 1. Introduction 1 1.1. Research Background and Purpose 1 1.2. Research Subject and Methods 4 1.3. Structure of the Thesis 7 Chapter 2. Literature Review 9 2.1. Locality of an Annexational Space 9 2.2. Previous Literature on Social Movements and Refugee Movements 17 Chapter 3. Case Introduction 23 3.1. Geography and History of Jeju Island 23 3.2. Yemeni Refugee Influx in Jeju Island 27 Chapter 4. Local Interpretation of the Yemeni Refugee Issue 33 4.1. Jeju Islanders Perceptions on Yemeni Refugees 33 4.2. Dichotomy between Yug-ji (mainland) and Jeju Island. 37 4.3. Complex toward the Mainland. 42 Chapter 5. Pro-Yemeni Refugee Movement in an Annexational Space 49 5.1. The Emergence of Pro-Yemeni Refugee Movement: Community to Coalition 49 5.2. Loneliness behind the Pride 57 Chapter 6. Conclusion 65 Bibliography 68 Abstract in Korean 76Maste

신경병증성 통증 모델의 뇌섬엽에서 rapamycin이 mTOR 신호전달에 미치는 영향

Injury of peripheral nerves can trigger neuropathic pain, producing allodynia and hyperalgesia via peripheral and central sensitization. Neuropathic pain is related to physiological changes in the primary afferent nerves, including spinal cord and brain. Recent studies have focused on the role of the insular cortex in neuropathic pain. Because the insular cortex is thought to store pain-related memories, translational regulation in this structure may reveal novel targets for controlling chronic pain. In neurons, many proteins that are involved in the inducement of synaptic activity and the expression of synaptic plasticity are converged at synapses especially. Signaling via mammalian target of rapamycin (mTOR), which is known to control mRNA translation and influence synaptic plasticity, may be involved in the development of chronic pain. The activity of mTOR and its downstream effectors have been detected in peripheral and central regions including pain transmission. mTOR has been studied at the spinal level in neuropathic pain, but its role in the insular cortex under these conditions remains elusive. Therefore, this study was conducted to determine the role of mTOR signaling in neuropathic pain and to assess the potential therapeutic effects of rapamycin, an inhibitor of mTOR, in the insular cortex of rats with neuropathic pain. Mechanical allodynia was assessed in adult male Sprague-Dawley rats after neuropathic surgery and following microinjections of rapamycin in the insular cortex on post-operative days 3 and 7. To evaluate the effective pain prevention of pre-administration with rapamycin in the insular cortex, the animals were microinjected rapamycin into the insular cortex before nerve injury. Rapamycin reduced mechanical allodynia and downregulated the expression of mTOR signaling pathway, postsynaptic density protein 95 and N-methyl-D-aspartate receptor, thereby inhibiting neuropathic pain-induced synaptic plasticity. Finally, pre-microinjection of rapamycin effectively alleviated development mechanical allodynia but failed to the down regulated mTOR signaling pathway. These findings suggest that mTOR signaling in the insular cortex may be a critical molecular mechanism modulating neuropathic pain.open박

Data-driven Industry Classification and Convergence Analysis

MasterConvergence between industries is blurring the boundaries of existing industry classification systems. Predefined industry classification systems are static compared to the fast moving business environment. And man made structure and classification have subjective nature. For that reason, industry classification systems have limitation in grouping homogeneous company groups. To meet this challenge, data driven industry classification based on company business portfolio is implemented by network analysis and topic modeling method.이 연구는 실시간으로 변화하는 비즈니스 환경을 반영하기 위해 기업들의 비즈니스 포트폴리오 데이터를 기반으로 산업군을 분류하는 것을 목표로 한다. 개체간의 연결을 기반으로 하는 네트워크 과학 관점에서 유사한 기업 군집을 도출하고 토픽 모델링을 통해 도출된 군집에서 기업의 산업군을 분류하고 산업간의 융합 패턴을 분석하고자 한다

Composition comprisin Creb3L1/CrebA protein or polynucleotide encoding the CrebA/CREB3L1 for the prevention or treatment of neurodegenerative disease

본 발명은 CrebA/CREB3L1 단백질 또는 이를 암호화하는 폴리뉴클레오티드를 유효성분으로 함유하는 퇴행성뇌질환의 예방 또는 치료용 약학적 조성물에 관한 것으로, 구체적으로 CrebA/CREB3L1단백질은 Machado-Joseph disease의 MJDtr-78Q 단백질 독성으로 유발된 수상돌기의 GOP기능장애 및 원형질막 소실을 회복시키고, C4da 신경세포 수상돌기의 소실을 억제하며, 수상돌기 가지의 형태를 회복시키고, polyQ 독성으로 저해된 소포매개수송, 막구조화, 지질합성과 CrebA이 강하게 연관되어 있는 것을 확인하였으며, 사람유래 HEK293T 세포주에서 CREB3L1 및 세포막 수송과 관련된 Sec13 및 Sec23A의 발현이 polyQ독성에 의해 감소하는 것을 확인함으로써, 본 발명의 CrebA/CREB3L1 단백질 및 이를 암호화하는 뉴클레오티드는 퇴행성뇌질환의 예방 또는 치료용 조성물로써 유용하게 사용될 수 있다.CrebA/CREB3L1(cAMP-response element-binding protein/cAMP-response element-binding protein 3 like 1)단백질 또는 이를 암호화 하는 폴리뉴클레오티드를 유효성분으로 함유하는 퇴행성뇌질환의 예방 또는 치료용 약학적 조성물로서,상기 퇴행성뇌질환은 척수운동소뇌실증 1, 2, 6, 7 및 17형(spinocerebellar ataxias(SCA) types 1, 2, 6, 7 and 17), 마차도-조셉 질환(Machado-Joseph disease, MJD/SCA3), 헌팅턴병(Huntington's disease), 치상핵적핵담창구 시상하핵 위축증(dentatorubral pallidoluysian atrophy, DRPLA), X-연관 척수성 근육위축증 1(spinal and bulbar muscular atrophy, X-linked 1, SMAX1/SBMA), 및 근위축성측삭경화증(amyotrophic lateral sclerosis)으로 구성된 군으로부터 선택된 것인 약학적 조성물

Screening platform for assessing cellular and behavioral defects in Drosophila Melanogaster

For screening drugs or molecules that can modify disease pathophysiology of human disease or conduct drug screening, the use of appropriate in vivo model with low expenditure suitable for large-scale screening is essential. Drosophila Melanogaster, whose genome contain orthologs for 75% of human disease-related genes, offers a quantitative screening platform for assessing both cellular and behavioral defects that are thought to be representative of human diseases like Parkinson’s disease(PD), Huntington’s disease(HD) or amyotrophic lateral sclerosis(ALS). Here, we present the low cost screening analysis platform available for measuring cellular and behavioral defects in Drosophila. This platform can be adapted for the use of therapeutic target discovery process as an economic and powerful in vivo screening tool for the researchers