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Follicle Cell Death during Ovarian Atresia in the Rat (Rat난소폐쇄에서의 난포의 사망기전)

  • ;;A. J. W. Hsueh
    • Korean Journal of Animal Reproduction
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    • v.20 no.4
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    • pp.385-393
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    • 1997
  • 다세포 생물에서 몸의 효율적 생존을 위한 각 기관의 homeostasis는 세포 증식과 사망에 의해 조절된다. 따라서, apoptosis라 명명된 세포사망은 정교한 기전에 의한 능동적이고 자발적인 사망기전으로써 몸의 정상적 유지를 위한 필수적인 현상이다. 발생기 세포나 신경세포 또는 흉선세포 분화 동안 과다한 세포의 제거가 apoptosis의 대표적인 예이며, 각종 호르몬에 의해 그 기능이 조절되는 난소세포에서도 apoptosis가 활발히 일어난다. Rat난소에는 태어날 때 수십 만개의 난포를 지니고 있는데, 이 중 단지 1%만이 배란에 사용되어질 뿐이고 나머지는 모두 사망하게 된다. 이러한 난포사망은 난소의 적절한 세포 수를 유지하기 위한 필수적 과정이며, 인위적으로 apoptosis를 억제하는 유전자인 bcl-2를 과다 발현시키면 난소암이 발생하는 연구결과가 이를 입증해주고 있다. 이처럼 중요한 난포 사망기전은 apoptosis라는 개념이 정립되면서 최근 들어 점차 그 연구가 활발해지고 있다. Apoptosis의 특징 중 뚜렷한 점은 DNA가 일정한 간격으로(180∼200 bp)잘려지는 DNA fragmentation현상으로, 이를 이용하여 DNA3'-end 부위에 방사선동위원소를 label한 후 이를 전기영동으로 분리하면 apoptosis를 손쉽게 측정할 수 있다. 난소의 기능은 시상하부호르몬인 LH와 FSH 뿐만 아니라 난소에서 분비되는 각종 난소국부호르몬들에 의해 조절된다. 특정한 발육단계의 난포는 특정한 호르몬에 의해 그 기능을 조절 받는데, 이러한 난소기능 조절기작은 매우 복잡한 경로를 지니고 있다. 이러한 복잡한 기작으로 인해 초기 연구에서첨 생체 내에서 밝히려는 연구 시도는 어려움에 부딪치게 되었다. 생체내 실험은 난소가 다양한 발육단계의 난포를 동시에 지니고 있어 특정한 발육단계의 난포 사망기전을 연구하기 어렵다. 또한 난포는 생체 내에서 다양한 호르몬을 동시에 분비하기 때문에 특정한 난소국부호르몬이 사망기전에 미치는 영향을 조사하기 힘든 점이 있다. 최근 들어 난포체외배양이 다양하게 개발되면서, 이러한 어려운 점을 극복할 수 있게 되었다. 본 논문은 각 발육단계의 난포를 절단해 체외배양하면서, apoptosis DNA 절단 현상을 이용하여 각종 난소국부 호르몬들이 난포발육단계별로 사망기전에 미치는 영향을 요약해 보였다. 난포는 발육하면서 점차 복잡한 호르몬 경로를 생존을 위해 필요로 한다. Prevulatory난포생존에 필요한 난소국부호르몬들은 early antral 단계의 난포에서는 그 미치는 영향이 감소되다가 preantral단계의 난포에서는 영향을 전혀 미치지 못했다. 단지 예외는 cGMP처리로써, 세포내 cGMP수준을 일정하게 유지시켜주는 것이 난포발육단계에 무관하게 생존에 중요한 인자로, 장래 연구는 난포 세포내의 cGMP수준을 조절하는 기작을 규명하는데 있을 것이다.

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Immunoregulatory Mechanism of Polysaccharides from Natural Plant Resources (신기술 신소재/해외기술 - 천연소재 유래 다당체의 면역조절 기작)

  • Cho, Chang-Won
    • Bulletin of Food Technology
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    • v.26 no.3
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    • pp.178-187
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    • 2013
  • 분자단계에서 천연소재 유래 다당체는 면역 세포 표면(예, 대식세포)에 있는 한가지 또는 여러가지 수용체(${\beta}$-glucan 수용체, mannose 수용체, complement 수용체 3, Toll-like 수용체, scavenger 수용체)와 면역 반응을 시작하기 위하여 결합할 수 있고, 그 후에 신호전달을 위하여 cytokine과 second messenger($Ca^{2+}$, cAMP, cGMP, NO 등등)들을 생성한다. 그 결과로 선천면역과 적응면역을 유도하여 다양한 질환에 영향을 미친다. 추가적으로 다당체들의 면역조절은 신경내분비 체계의 조절과도 연관되어 있다. 최근 수많은 천연소재유래 다당체의 생리활성에 관한 연구가 진행되고 있다. 다양한 연구를 통해 정확한 약효, 낮은 독성과 부작용을 가진 일단의 다당체가 발견되어 현재 임상에서 암 치료에도 사용되고 있다. 이러한 사실들은 면역증진 다당체들이 항 종양치료를 위한 새로운 치료제로서 큰 시장을 개척할 수 있다는 가능성을 보여주고 있다. 이러한 사실에도 불구하고 현재 다당체에 대한 연구는 다음과 같은 취약점을 내포하고 있다. 첫째 다당체의 생리활성에 대한 정해진 비교기준이 없다. 특별히 임상 환경에서는 이러한 연구들이 중국, 일본, 한국과 일부 다른 동양국가들에 국한되어 있어 유럽이나 미국에서의 연구 자료가 결여되어있다. 둘째 현재 연구에 사용되고 있는 대다수의 천연소재 유래 다당체는 순수한 다당체가 아닌 천연 그대로의 것을 사용하고 있어 소재로부터 유래하는 다른 활성성분에 의해 쉽게 영향을 받을 수 있어 순수 다당체가 면역체계에 어떠한 역할을 수행하는지 진단하는데 어려움이 있다. 셋째 면역조절 경로에서 다당체의 정확한 신호전달 경로가 아직 정확하게 밝혀지지 않았고, 또한 동물과 임상실험에서 다당체가 작용하는 수용체 및 신호전달 경로에 대한 상반되는 결과가 발표되고 있기도 하다. 따라서 다당체의 면역조절활성에 대한 연구에 있어 다음과 같은 점들에 주목해야 할 필요가 있다. 첫째 다당체의 구조와 활성간의 상관관계를 밝혀야 할 것이다. 특히 다당체의 세부 구조 및 활성 부위를 밝혀낸다면 분자수준의 면역조절 기작을 명확히 하는데 도움을 줄 수 있을 것이다. 이러한 정보를 확보할 수 있다면 다당체의 구조를 변형시켜 활성을 증진시킬 수 있을 것이며, 또한 활성이 증가된 다당체를 합성하는 일도 가능해 질 것으로 예상된다. 마지막으로 ${\beta}$-glucan과 lentinan과 같은 정제된 다당체의 연구를 지속적으로 수행하여 효과적인 동물실험 및 임상실험 protocol을 확보하고 연구결과들에 대한 database를 구축해야 할 필요가 있다. 이러한 노력들이 성공적으로 수행된다면 천연소재유래 다당체들이 가까운 장래에 암 치료를 포함한 다양한 질병에 적용 가능한 새로운 면역조절제로 사용될 수 있을 것이다.

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Empirical Study on the Effects of Business Alliance capabilities needed for each stage of alliance lifecycle on Performance - Focused on the Moderating Effect of Partnership & Entrepreneurship Using Multi-Group Analysis - (비즈니스 제휴 단계별 역량이 성과에 미치는 영향에 관한 실증연구 - 다중집단분석에 의한 기업가정신과 파트너십의 조절효과를 중심으로 -)

  • Lee, In-Su;Roh, Jae-Whak;You, Yen-Yoo
    • International Commerce and Information Review
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    • v.16 no.3
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    • pp.431-463
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    • 2014
  • This paper analyzed the effect of the alliance capabilities needed for each stage of alliance lifecycle(search & negociation, contract, operation, evaluation/termination) according to the alliance life cycle of SMEs consulting firms on the performance, and the moderating effect of the partnership & entrepreneurship between the process capabilities and performance using the multi-group analysis The result shows that searching & operational capabilities have a positive impact on the customer & learning performance, not contracting and termination capabilities, and the partnership & entrepreneurship moderated between the process capabilities and alliance performance. This study shows that the operation stage in the alliance life cycle is the most important, in this process alliance partners show the higher partnership & entrepreneurship than any other stages.

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In Vitro and In Vivo Effects of Piceatannol and Resveratrol on Glucose Control and TLR4-NF-κB Pathway (피세아테놀과 레스베라트롤의 혈당조절 및 TLR4-NF-κB 경로 조절 작용)

  • Lee, Hee Jae;Lee, Hae-Jeung;Yang, Soo Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.2
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    • pp.267-272
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    • 2017
  • Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B ($NF-{\kappa}B$) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC ($50{\mu}M$) or RSV ($50{\mu}M$). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and $NF-{\kappa}B$ were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo.

Identification of Differentially Expressed Genes in Ducks in Response to Avian Influenza A Virus Infections

  • Ndimukaga, Marc;Won, Kyunghye;Truong, Anh Duc;Song, Ki-Duk
    • Korean Journal of Poultry Science
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    • v.47 no.1
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    • pp.9-19
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    • 2020
  • Avian influenza (AI) viruses are highly contagious viruses that infect many bird species and are zoonotic. Ducks are resistant to the deadly and highly pathogenic avian influenza virus (HPAIV) and remain asymptomatic to the low pathogenic avian influenza virus (LPAIV). In this study, we identified common differentially expressed genes (DEGs) after a reanalysis of previous transcriptomic data for the HPAIV and LPAIV infected duck lung cells. Microarray datasets from a previous study were reanalyzed to identify common target genes from DEGs and their biological functions. A total of 731 and 439 DEGs were identified in HPAIV- and LPAIV-infected duck lung cells, respectively. Of these, 227 genes were common to cells infected with both viruses, in which 193 genes were upregulated and 34 genes were downregulated. Functional annotation of common DEGs revealed that translation related gene ontology (GO) terms were enriched, including ribosome, protein metabolism, and gene expression. REACTOME analyses also identified pathways for protein and RNA metabolism as well as for tissue repair, including collagen biosynthesis and modification, suggesting that AIVs may evade the host defense system by suppressing host translation machinery or may be suppressed before being exported to the cytosol for translation. AIV infection also increased collagen synthesis, showing that tissue lesions by virus infection may be mediated by this pathway. Further studies should focus on these genes to clarify their roles in AIV pathogenesis and their possible use in AIV therapeutics.

The Effects of Output Sector Munificence and Dynamism on Distribution Channel Performances: Moderating Effects of Integration (수요부문 풍요성과 동태성이 유통경로 성과에 미치는 영향: 수직적 통합의 조절효과)

  • Kim, Sang-Deok;Oh, Se-Jo
    • Journal of Distribution Research
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    • v.11 no.1
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    • pp.1-20
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    • 2006
  • In these days of severe changes in the environment and economic slump, it is indispensable for firms to cope with the environment effectively. This study is an attempt to investigate the mechanisms through which output sector munificence and dynamism affect distribution channel performances, such as, satisfaction, trust, and commitment. Especially, this study focus on moderating effects on distribution channel integration that has not been investigated in the past. For the purpose of empirical testing, 70 corporate channels, 120 contractual channels, and 100 conventional marketing channels have been selected and analyzed. According to the result from moderated regression analysis, munificence strengthens distribution channel performances, while dynamism weakens them. And integration reinforces the effects.

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A Difference Analysis Among Nationality, Gender and Age Regarding Environmentally Conscious Behavior (친환경 행동에 대한 국가, 성별, 연령 차이분석)

  • Yoon, Sung-Wook;Yang, Yeon-Jo
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.8
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    • pp.5089-5095
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    • 2015
  • The study seeks to determine how much environmentally conscious behaviors vary depending on the nationality, gender and age. For its purpose, this study suggests hypotheses that Korean and American consumers, who are culturally different from each other, show differences from each other in environmentally conscious behaviors. An interaction effect is also expected between gender and age. With regard to environmentally conscious behavior. Meanwhile, the study tried to examine whether personal values have any mediating effect on the behaviors. The findings of this study can be summarized as follows. Environmentally conscious behaviors by American consumers were more significant than those by Korean consumers. And men were more positive in making environmentally conscious behaviors than women were. In addition, there were interaction effects between nationality and gender, and nationality and age. Furthermore, personal values, depending on age, were found to have moderating effects on environmentally conscious behaviors.

CLK3 is a Novel Negative Regulator of NF-κB Signaling (NF-κB 신호경로에서 CLK3의 새로운 음성 조절자로서의 기능)

  • Byeol-Eun, Jeon;Chan-Seong, Kwon;Ji-Eun, Lee;Ye-Lin, Woo;Sang-Woo, Kim
    • Journal of Life Science
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    • v.32 no.11
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    • pp.833-840
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    • 2022
  • Chronic inflammation has been shown to be closely associated with tumor development and progression. Nuclear factor kappa B (NF-κB) is composed of a family of five transcription factors. NF-κB signaling plays a crucial role in the inflammatory response and is often found to be dysregulated in various types of cancer, making it an attractive target in cancer therapeutics. In this study, CDC-like kinase 3 (CLK3) was identified as a novel kinase that regulates the NF-κB signaling pathway. Our data demonstrate that CLK3 inhibits the canonical and non-canonical NF-κB pathways. Luciferase assays following the transient or stable expression of CLK3 indicated that this kinase inhibited NF-κB activation mediated by Tumor necrosis factor-alpha (TNFα) and Phorbol 12-myristate 13-acetate (PMA), which are known to activate NF-κB signaling via the canonical pathway. Consistent with data on the ectopic expression of CLK3, CLK3 knockdown using shRNA constructs increased NF-κB activity 1.5-fold upon stimulation with TNFα in HEK293 cells compared with the control cells. Additionally, overexpression of CLK3 suppressed the activation of this signaling pathway induced by NF-κB-inducing kinase (NIK) or CD40, which are well-established activators of the non-canonical pathway. To further examine the negative impact of CLK3 on NF-κB signaling, we performed Western blotting following the TNFα treatment to directly identify the molecular components of the NF-κB pathway that are affected by this kinase. Our results revealed that CLK3 mitigated the phosphorylation/activation of transforming growth factor-α-activated kinase 1 (TAK1), inhibitor of NF-κB kinase alpha/beta (IKKα/α), NF-κB p65 (RelA), NF-κB inhibitor alpha (IκBα), and Extracellular signal-regulated kinase 1/2-Mitogen-activated protein kinase (ERK1/2-MAPK), suggesting that CLK3 inhibits both the NF-κB and MAPK signaling activated by TNFα exposure. Further studies are required to elucidate the mechanism by which CLK3 inhibits the canonical and non-canonical NF-κB pathways. Collectively, these findings reveal CLK3 as a novel negative regulator of NF-κB signaling.

Anti-inflammatory effect of a mixture of Astragalus membranaceus and Lithospermum erythrorhizon extracts by inhibition of MAPK and NF-κB signaling pathways in RAW264.7 cells (RAW264.7 대식세포에서 MAPK 및 NF-κB 신호전달 경로 억제를 통한 황기 및 지치 복합물의 항염증 효과)

  • Choi, Doo Jin;Kim, Geum Soog;Choi, Bo-Ram;Lee, Young-Seob;Han, Kyung Sook;Lee, Dong-Sung;Lee, Dae Young
    • Journal of Applied Biological Chemistry
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    • v.63 no.4
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    • pp.421-428
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    • 2020
  • This study investigated a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extracts (ALM16), exerts anti-inflammatory effects in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells, and its underlying mechanism. ALM16 was prepared by mixing AM and LE extracts in a ratio of 7:3 (w/w). Cytotoxicity of ALM16 in RAW264.7 cells was not shown up to 200 ㎍/mL of ALM16. The results of this study showed that ALM16 does-dependently inhibits the production of nitric oxide, prostaglandin E2 and pro-inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) in LPS-induced RAW264.7 cells. ALM16 not only markedly reduced the protein expression levels of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 cells, but also inhibited the nuclear translocation and DNA-binding activity of nuclear factor-kappa B (NF-κB). In addition, ALM16 specifically inhibited the phosphorylation of c-Jun N-terminal kinase and extracellular signal-regulated kinases in LPS-stimulated RAW264.7 cells. In conclusion, these results suggest that ALM16 may exert anti-inflammatory effect by modulating mitogen-activated protein kinase and NF-κB signaling pathways.

Adolescents' Self-control and Big Five Personality Types Affecting Maladaptive and Adaptive Computer Game Use State (청소년의 Big Five 성격 유형과 자기 조절 성향이 게임 과용, 선용 행태에 미치는 영향)

  • Kim, YoungBerm;Lee, SangHo
    • Journal of Korea Society of Industrial Information Systems
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    • v.24 no.4
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    • pp.65-77
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    • 2019
  • Adolescents reach the game-use states of adaptive and maladaptive by the absorption to computer game. Authors claimed that the two states are commonly related with the time of game-use, and the degree of them are distinctive according to adolescent individuals, specifically their self-control propensity. Authors proposed a conceptual research model that Big Five personality types predict their self-control which moderates the relationships from game use-time to the maladaptive and adaptive states. The data to test its validity and reliability had been sampled 999 Korean students in elementary school, middle school, and high school. Resultingly, the openness and conscientiousness of the adolescents affected positively on the self-control, which moderated negatively the relationship from the game use time to the maladaptive use state, but the positive moderation on the relationships from game use time to adpative state was not significant. These results mean that we could apply teenager's Big Five personality type and their self-control traits as a tool for preventing teens from the overuse state like addiction.