• 제목/요약/키워드: cross-regulation

검색결과 211건 처리시간 0.028초

Regulation of vascular smooth muscle phenotype by cross-regulation of krüppel-like factors

  • Ha, Jung Min;Yun, Sung Ji;Jin, Seo Yeon;Lee, Hye Sun;Kim, Sun Ja;Shin, Hwa Kyoung;Bae, Sun Sik
    • The Korean Journal of Physiology and Pharmacology
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    • 제21권1호
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    • pp.37-44
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    • 2017
  • Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that $kr{\ddot{u}}ppel$-like factor 8 (KLF8) is essential for tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with $TNF{\alpha}$ significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by $TNF{\alpha}$ stimulation in an ERK-dependent manner. The promoter region of KLF8 contained putative Sp1, KLF4, and $NF{\kappa}B$ binding sites. Myocardin significantly enhanced the promoter activity of KLF4 and KLF8. The ectopic expression of KLF4 strongly enhanced the promoter activity of KLF8. Moreover, silencing of Akt1 significantly attenuated the promoter activity of KLF8; conversely, the overexpression of Akt1 significantly enhanced the promoter activity of KLF8. The promoter activity of SMA, $SM22{\alpha}$, and KLF8 was significantly elevated in the contractile phenotype of VSMCs. The ectopic expression of KLF8 markedly enhanced the expression of SMA and $SM22{\alpha}$ concomitant with morphological changes. The overexpression of KLF8 stimulated the promoter activity of SMA. Stimulation of VSMCs with $TNF{\alpha}$ enhanced the expression of KLF5, and the promoter activity of KLF5 was markedly suppressed by KLF8 ectopic expression. Finally, the overexpression of KLF5 suppressed the promoter activity of SMA and $SM22{\alpha}$, thereby reduced the contractility in response to the stimulation of angiotensin II. These results suggest that cross-regulation of KLF family of transcription factors plays an essential role in the VSMC phenotype.

승객 이명감 기준을 만족하는 고속철도 터널 최소 단면적에 대한 연구 (A STUDY ON THE MINIMUM CROSS-SECTIONAL AREA OF HIGH-SPEED RAILWAY TUNNEL SATISFYING PASSENGER EAR DISCOMFORT CRITERIA)

  • 권현빈
    • 한국전산유체공학회지
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    • 제20권3호
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    • pp.62-69
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    • 2015
  • Pressure change inside cabin as well as in tunnel has been calculated to assess the passenger pressure comfort of high-speed train. $C-STA^{TM}$, a CFD program based on axi-symmetric Navier-Stokes equation and Roe's FDS has been used to simulate the pressure change in tunnel during a high-speed train passing through it. To present the relative motion between the train and the tunnel, a modified patched grid scheme based on the structured grid system has been employed. The simulation program has been validated by comparing the simulation results with field measurements. Extensive parametric study has been conducted for various train speed, tunnel cross-sectional area and tunnel length to the pressure change in cabin. KTX-Sancheon(KTX2) high-speed train has been chosen for simulation and the train speed have been varied from 200 km/h to 375 km/h. The tunnel length has been varied from 300 m to 7.5 km and tunnel area from $50m^2$ to $120m^2$. Total 504 simulations have been conducted varying the parameters. Based on the database produced from the parametric simulations, minimum tunnel cross-sectional area has been surveyed for various train speeds based on Korean regulation on pressure change in cabin.

Fine Tuning and Cross-talking of TGF-β Signal by Inhibitory Smads

  • Park, Seok-Hee
    • BMB Reports
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    • 제38권1호
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    • pp.9-16
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    • 2005
  • Transforming Growth Factor (TGF)-$\beta$ family, including TGF-$\beta$, bone morphorgenic protein (BMP), and activn, plays an important role in essential cellular functions such as proliferation, differentiation, apoptosis, tissue remodeling, angiognesis, immune responses, and cell adhesions. TGF-$\beta$ predominantly transmits the signals through serine/threonine receptor kinases and cytoplasmic proteins called Smads. Since the discovery of TGF-$\beta$ in the early 1980s, the dysregulation of TGF-$\beta$/Smad signaling has been implicated in the pathogenesis of human diseases. Among signal transducers in TGF-$\beta$/Smad signaling, inhibitory Smads (I-Smads), Smad6 and Smad7, act as major negative regulators forming autoinhibitory feedback loops and mediate the cross-talking with other signaling pathways. Expressions of I-Smads are mainly regulated on the transcriptional levels and post-translational protein degradations and their intracellular levels are tightly controlled to maintain the homeostatic balances. However, abnormal levels of I-Smads in the pathological conditions elicit the altered TGF-$\beta$ signaling in cells, eventually causing TGF-$\beta$-related human diseases. Thus, exploring the molecular mechanisms about the regulations of I-Smads may provide the therapeutic clues for human diseases induced by the abnormal TGF-$\beta$ signaling.

The Impact of Omnichannel Shopping Experience and Channel Integration on Customer Retention: Empirical Evidence from China

  • WANG, Junbin;JIANG, Xinyu
    • The Journal of Asian Finance, Economics and Business
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    • 제9권2호
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    • pp.229-242
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    • 2022
  • Creating a new retailing environment to meet the seamless experience requirements of consumers is a challenge for Omnichannel-related businesses. Based on the "appraisal-emotion-response" chain, the purpose of this research is to explore the psychological mechanism of omnichannel integration influencing customer retention and the moderating effect of customer showrooming experience. This research uses a structural equation model in partial least square software to analyze a two-stage survey (Study 1: n = 210; Study 2: n = 342) conducted in China. The results show that channel control experience has three dimensions: perceived channel attribute familiarity, channel type matching, and cross-channel access convenience; consistent interactive experience has two dimensions: information cross-channel consistency and cross-channel service support. Furthermore, both channel control experience and consistent interactive experience are favorable for customer retention through increased customer satisfaction (transactional and retailer satisfaction). Finally, customer showrooming experience positively moderates the relationship between consistent interactive experience and customer satisfaction. This research proposes a self-regulation process model to explain how omnichannel integration enhances consumers' experience, finally leading to consumer retention. The findings contribute to the omnichannel retail business literature and provide management implications for Asian retailers to implement an omnichannel business strategy.

Determinants of Circulating Soluble Leptin Receptor and Free Leptin Index in Indonesian Pre-Pubertal Obese Male Children: A Preliminary CrossSectional Study

  • Hendarto, Aryono;Nagrani, Dimple G.;Meiliana, Anna;Sastroasmoro, Sudigdo;Sjarif, Damayanti R.
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제23권2호
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    • pp.163-173
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    • 2020
  • Purpose: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children. Methods: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5-9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI. Results: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak. Conclusion: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

Identification and Validation of Four Novel Promoters for Gene Engineering with Broad Suitability across Species

  • Wang, Cai-Yun;Liu, Li-Cheng;Wu, Ying-Cai;Zhang, Yi-Xuan
    • Journal of Microbiology and Biotechnology
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    • 제31권8호
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    • pp.1154-1162
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    • 2021
  • The transcriptional capacities of target genes are strongly influenced by promoters, whereas few studies have focused on the development of robust, high-performance and cross-species promoters for wide application in different bacteria. In this work, four novel promoters (Pk.rtufB, Pk.r1, Pk.r2, and Pk.r3) were predicted from Ketogulonicigenium robustum and their inconsistency in the -10 and -35 region nucleotide sequences indicated they were different promoters. Their activities were evaluated by using green fluorescent protein (gfp) as a reporter in different species of bacteria, including K. vulgare SPU B805, Pseudomonas putida KT2440, Paracoccus denitrificans PD1222, Bacillus licheniformis and Raoultella ornithinolytica, due to their importance in metabolic engineering. Our results showed that the four promoters had different activities, with Pk.r1 showing the strongest activity in almost all of the experimental bacteria. By comparison with the commonly used promoters of E. coli (tufB, lac, lacUV5), K. vulgare (Psdh, Psndh) and P. putida KT2440 (JE111411), the four promoters showed significant differences due to only 12.62% nucleotide similarities, and relatively higher ability in regulating target gene expression. Further validation experiments confirmed their ability in initiating the target minCD cassette because of the shape changes under the promoter regulation. The overexpression of sorbose dehydrogenase and cytochrome c551 by Pk.r1 and Pk.r2 resulted in a 22.75% enhancement of 2-KGA yield, indicating their potential for practical application in metabolic engineering. This study demonstrates an example of applying bioinformatics to find new biological components for gene operation and provides four novel promoters with broad suitability, which enriches the usable range of promoters to realize accurate regulation in different genetic backgrounds.

Cross-talk between STAT6 and Ras/MAPK Pathway for the IL-4-mediated T Cell Survival

  • So, Eui-Young;Jang, Ji-Young;Lee, Choong-Eun
    • BMB Reports
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    • 제34권6호
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    • pp.578-583
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    • 2001
  • As a prototypic Thl vs Th2 cytokine, IFN-$\gamma$ and IL-4 activate distinct STAT proteins, STAT1 and STATE, respectively. In cytokine-producing Jurkat T cells, IL-4 is effectively rescued from cell death that is induced by dexamethasone, but IFN-$\gamma$ failed to do so. Since the Ras/MAPK pathway is known to play an important role in cytokine-induced cell survival, we investigated the mechanism of T cell survival through the analysis of functional cross-talk between Ras/MAPK and distinct STAT proteins that are activated by IL-4 and IFN-$\gamma$. Although IL-4 and IFN-$\gamma$ each induced the activation of STATE and STATI. in Jurkat T cells, respectively, only IL-4 was capable of inducing MAPK. Along with tyrosine kinase inhibitors, MEK/MAPK inhibitors also caused a significant suppression of the IL-4-induced STATE activity. This suggests a positive regulation of STATE by MAPK during IL-4 signal transduction. Furthermore, transfection studies with dominant active (da) vs dominant negative (dn) Ras revealed that daRas, but not dnRas, selectively up-regulated the expression and activity of STATE with a concomitant increase in MAPK activity. These results, therefore, suggest that there is a functional cross-talk between the Ras/MAPK and Jak/STAT6 pathways, which may have a role in the IL-4-induced T cell survival.

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Epigenetic regulation of long noncoding RNA UCA1 by SATB1 in breast cancer

  • Lee, Jong-Joo;Kim, Mikyoung;Kim, Hyoung-Pyo
    • BMB Reports
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    • 제49권10호
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    • pp.578-583
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    • 2016
  • Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated DNA-binding protein that functions as a chromatin organizer. SATB1 is highly expressed in aggressive breast cancer cells and promotes growth and metastasis by reprograming gene expression. Through genome-wide cross-examination of gene expression and histone methylation, we identified SATB1 target genes for which expression is associated with altered epigenetic marks. Among the identified genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was upregulated by SATB1 depletion. Upregulation of UCA1 coincided with increased H3K4 trimethylation (H3K4me3) levels and decreased H3K27 trimethylation (H3K27me3) levels. Our study showed that SATB1 binds to the upstream region of UCA1 in vivo, and that its promoter activity increases with SATB1 depletion. Furthermore, simultaneous depletion of SATB1 and UCA1 potentiated suppression of tumor growth and cell survival. Thus, SATB1 repressed the expression of oncogenic UCA1, suppressing growth and survival of breast cancer cells.

침출수 이동 해석을 통한 석탄재 처분방식의 평가 (Evaluation of Fly Ash Disposal Methods by Analysis of Leachate Migration)

  • 이상일
    • 물과 미래
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    • 제25권4호
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    • pp.61-73
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    • 1992
  • 폐기물 처분장으로부터 인간생활 환경으로까지 침출수가 어떤 방향과 속도로 유출될 것인가하는 것은 많은 사람의 관심의 대상이며, 어떤 처분장 설계가 관련 규제법을 효과적으로 만족시키고 있는가를 알아야 할 필요가 있다. 침출수이동에 관한 해석방법을 제심함에 있어, 화력발전의 결과로 생기는 석탄재의 폐기 방식중 두 가지 대표적인 방식인 매립방식과 연못방식에 대한 평가를 예시하였다. 관련 규제법으로는 "100/100 룰", 즉, 처분장으로부터 100ft(30.5cm) 떨어진 곳까지 침출수가 도달하는데 100년이상 걸려야 한다는 제약조건을 적용하였다. 수치해석에 의한 지하수 유동방정식의 해는 압력수두 분포와 유동량(flux)에 관한 정보를 제시하여 주었으며, 유적선(pathline)의 해석은 침출수 이동 경로와 시간에 관한 예측을 가능케 하였다.을 가능케 하였다.

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Regulation of Gene Expression for Amino Acid Biosynthesis in the Yeast, Sacchromyces cerevisiae

  • Lea, Ho Zoo
    • 한국동물학회:학술대회논문집
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    • 한국동물학회 1995년도 한국생물과학협회 학술발표대회
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    • pp.82-82
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    • 1995
  • Regulation of enzyme synthesis by transcriptional and translational control systems provides rather stable adaptation to change of amino acid level in the growth medium, while manipulation of enzyme activity through endproduct feedback inhibition represents rather short-term and reversible ways of adjusting metabolic fluctuation of amino acid level. Various control mechanisms interplay to regulate genes encoding enzymes for amino acid biosynthesis in the yeast, Sacchromyces cerevisiae. When amino acids are in short supply, genes under a cross-pathway regulatory mechanism Or general amino acid control (general control) increase their action, in which Gcn4p is the major positive regulator of gene expression. When cells are cultured in minimal medium, basal level expression is also regulated by supplementary control elements, where inorganic phosphate level is additionally involved. Most of amino acid biosynthetic genes are also regulated by the level of endproduct of the pathway. This pathway-specific regulatory mechanism is called specific amino acid control (specific controD, under which gene expression is reduced when endproduct is present in the medium. Derepression of a gene through general control can be usually overridden by repression through specific control, where the endproduct level of that particular pathway is high and not limiting. In this presentation, regulatory factors for basal level expression and general control of yeast amino acid biosynthesis will be discussed, m addition to pathway-specific repression patterns and interaction between CrOSS- and specific-control mechanisms. Preliminary results are also presented from the investigation of the cloned genes in the threonine biosynthetic pathway of the yeast. yeast.

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