• Title/Summary/Keyword: factors to Activate

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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.

Habitat Restoration Initiative for Endangered Species Parnassius bremeri (Lepidoptera: Papilionidae) in Korea (멸종위기종 붉은점모시나비의 서식지 복원구상)

  • Kim, Do-Sung;Park, Seong-Joon;Shin, Young-Kyu;Park, Doo-Sang
    • Journal of the Korean Institute of Landscape Architecture
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    • v.39 no.6
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    • pp.98-109
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    • 2011
  • Habitat restoration initiative is an important factor for the on-site preservation of butterflies. A new habitat necessitates the investigation of the ecology of the butterfly, the landscape of the habitat, the work process, and a cost analysis. In this study, these factors were analyzed through1) re-consideration of the secured results from three years of field work, and 2) a habitat area estimation conducted according to the presence or absence of larvae and adults via a Parnassius bremeri Bremer survey. The investigation of the natural habitat, done for both larvae and adult butterflies found in South Korea, suggested that multiple patches with a minimum size exceeding $300m^2$ and with an average size of about $1,600m^2$were required for survival of this butterfly. Therefore, more than five patches should be considered for butterfly habitat and patches should have similarity to the present habitat environment with transplantation plans for diet plants and honeydew plants. In addition, to activate the migration of the butterfly, cutting down trees that are obstacles to migration, minimizing the distance between patches and the addition of a stepping patch are also required. A patch connectivity analysis showed that patches should be located within 300m of neighboring patches, as the migration of the butterfly will fail if it is more than 600m. Additionally, more than $10,000m^2$ for a single patch or a patch network composed more than five patches over $1,600m^2$ in size were recommended, with a total patch size of $8,000m^2$. Additionally, neighboring multiple patch networks are more desirable than a single habitat in the event a cyclic habitat pattern arises. In this study, we suggest a habitat restoration and optimal prerequisites for a butterfly habitat. It is expected that this research will lead to the creation of a good model for the restoration of butterfly species.

A cluster analysis of the audit result on quality management system in architectural design and engineering firms (설계 및 엔지니어링분야의 품질경영시스템 심사결과에 대한 유형분석)

  • Bae Dae-kwon;Kim Soo-Yoo;Kim Jae-Jun
    • Korean Journal of Construction Engineering and Management
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    • v.6 no.2 s.24
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    • pp.120-128
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    • 2005
  • ISO 9001, the quality management system issued by the International Organization for Standardization, is being used by architectural design and engineering firms in order to strengthen the capability of business activities through the implementation of the international and advanced quality management systems. However, there have been significant problems in stable implementation and settlement of ISO 9001 in construction industry, which seem to be caused by key employees' lack of proper recognition and comprehension. The purpose of this research, accordingly, is to find and analyze nonconformity results which were found when the third party registrars audited the conformity of companies' quality management systems for ISO 9001 certification especially in architectural design and engineering firms. For this purpose this research was conducted by a cluster analysis of 647 audit reports out of representative 15 architectural design and engineering firms that have been audited periodically from 1997 to 2003 by the third party registrars. The analysis showed that the most frequent problems were generated in the areas of $\ulcorner$Design and Development$\lrcorner$ , $\ulcorner$production and Service Provision$\lrcorner$ , and $\ulcorner$General requirements$\lrcorner$ of the quality management system. The following, the areas of $\ulcorner$Monitoring and Measurement$\lrcorner$ and $\ulcorner$purchasing$\lrcorner$ were also analyzed as main factors which caused frequent nonconformity results. This research also shows that the corrective actions for nonconformity results are closely connected with the whole management activities in architectural design and engineering firms. Consequently, corrective actions for disposition of nonconformities should be implemented more specifically in order to settle and activate the quality management systems in architectural design and engineering firms.