• Title/Summary/Keyword: Double regulation

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Proper Regulation of the Cutoff System in Offshore Landfill Built on Clay Ground with Double Walls (점토지반에 이중벽체가 적용된 해상폐기물매립장의 적정 차수 기준)

  • Hwang, Woong-Ki;Kim, Hyang-Eun;Choi, Hoseong;Kim, Tae-Hyung
    • Journal of the Korean Geotechnical Society
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    • v.35 no.8
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    • pp.5-15
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    • 2019
  • This study was conducted to propose a reasonable requirement regulation of cutoff barriers composed of bottom layer and vertical barrier of offshore landfill for the prevention of contaminant leakage. The bottom layer was composed of impermeable clay layer; vertical walls were composed of double walls; outer wall was composed of steel sheet pile which registed against outer force; cutoff vertical barrier took the role of inner wall. Seepage-advection-dispersion numerical analysis was conducted using SEEP/W and CTRAN/W programs under steady and unsteady flows. The results showed that the values calculated under steady flow showed higher migration of pollutant than those of unsteady flow. The values calculated under steady flow are more valid from a design point of view. Under steady flow and the bottom clay layer and when the vertical barrier are homogeneous and completely well installed, respectively, the minimum required cutoff regulations for hydraulic conductivity, thickness, and embedded depth of the bottom clay layer and vertical barrier were suggested.

The Effect of Emotional Expressive Ambivalence on Interpersonal Stress :The Mediating Effect of Social Support and Cognitive Emotion Regulation Strategy (직장인의 정서표현 양가성이 대인관계 스트레스에 미치는 영향:사회적 지지와 인지적 정서조절전략의 매개효과)

  • Lee, Hyun-Joo;Chung, Eun-Jung
    • The Journal of the Korea Contents Association
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    • v.20 no.9
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    • pp.558-576
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    • 2020
  • The purpose of the research was to verify the mediating effect of social support and cognitive emotional regulation strategy when office worker's emotional expressive ambivalence influences on interpersonal stress. A survey was conducted with 422 office workers from August to September of 2018. SPSS, AMOS and Mplus were used for descriptive statistics, correlation analysis, verification of structural equation modeling and mediated effect. There was a partial mediating effect in emotional expressive ambivalence of self-defense model, a complete mediating effect in relational emotional expressive ambivalence model. In both self-defense and relational emotional expressive ambivalence model, double mediation effect of passing through support and cognitive emotional regulation strategy in the relationship between emotional expressive ambivalence and interpersonal stress was significant. This study sought ways to reduce interpersonal stress by increasing the level of perception of social support and using adaptive cognitive emotional control strategies for office workers.

Sp1 Decoy Oligodeoxynucleotides Inhibit Serum-induced Mesangial Cell Proliferation (Sp1 Decoy Oligodeoxynucleotides에 의한 사구체 혈관간세포 증식억제 효과)

  • Chae Young Mi;Kim Sung Young;Park Kwan Kyu;Chang Young Chae
    • KSBB Journal
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    • v.19 no.5
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    • pp.335-340
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    • 2004
  • Mesangial expansion caused by cell proliferation and glomerular extracellular matrix accumulation is one of the earliest renal abnormalties observed at the onset of hyperglycemia in diabetes mellitus. Transcription factor Sp1 is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation, and is assumed to play an essential role in mesangial expansion, transforming growth factor (TGF)-$\beta$1, plasminogen activator inhibitor (PAI)-1. We have generated a phosphorothioated double-stranded Sp1-decoy oligodeoxynucleotide that effectively blocks Sp1 binding to the promoter region for transcriptional regulation of TGF-$\beta$1 and PAI-1. The Sp1 decoy oligodeoxynucleotide suppressed transcription of these cytokines and proliferation of primary rat mesangial cells in response to serum stimulation. These results suggest that the Sp1 decoy oligodeoxynucleotide could bea powerful tool in preventing the pathogenesis of renal hypertrophy.

The Kinetic Investigation of D-Hydroxyisovalerate Dehydrogenase from Fusarium sambucinum

  • Lee, Chan;Goerisch, Helmut;Zocher, Rainer
    • BMB Reports
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    • v.33 no.3
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    • pp.228-233
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    • 2000
  • The steady-state investigation of the mechanism of Dhydroxyisovalerate dehydrogenase was performed in order to understand this type of kinetic patterns. The initial velocity was measured with various amounts of both substrates, NADPH and 2-ketoisovalerate. Double reciprocal plots gave patterns that conversed on or near the abscissa. Binding studies indicated that NADPH bound first to the enzyme. The product $NADP^+$ was found to be a competitive inhibitor with respect to NADPH at a constant concentration of 2-ketoisovalerate. However, it showed noncompetitive inhibition against 2-ketoisovalerate at a fixed amount of NADPH. Another product, D-hydroxyisovalerate, was a non-competitive inhibitor versus NADPH and 2-ketoisovalerate at constant levels of 2-ketoisovalerate and NADPH, respectively. These results were comparable with an ordered bi-bi mechanism, in which NADPH bound first to the enzyme, followed by the binding of 2- ketoisovalerate. $NADP^+$ is the last product to be released. The ordered reaction manner of D-hydroxyisovalerate dehydrogenase from 2-ketoisovalerate to D-hydroxyisovalerate allows the accurate regulation of valine metabolism and it may lead to the regulation of total biosynthesis of enniatins in the Fusarium species.

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Sepsis Mortality in CIITA Deficient Mice is Associated with Excessive Release of High-mobility Group Box 1

  • Kim, Ji-Young;Kim, Ju-Hyun;Seo, Jae-Nam;Oh, Kwon-Ik
    • IMMUNE NETWORK
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    • v.8 no.2
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    • pp.39-45
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    • 2008
  • Background: Down regulation of major histocompatibility complex class II transactivator (CIITA) has been identified as a major factor of immunosuppression in sepsis and the level of CIITA expression inversely correlates with the degree of severity. However, it has not been fully elucidated whether the lower expression of CIITA is a cause of disease process or a just associated sign. Here we determined whether the CIITA deficiency decreased survival rate using murine sepsis model. Methods: Major histocompatibility complex class II (MHC-II) deficient, CIITA deficient and wild type B6 mice were subjected to cecal ligation puncture (CLP) surgery. CIITA and recombination activation gene (RAG)-1 double deficient mice were generated to test the role of lymphocytes in CIITA-associated sepsis progression. Results: Sepsis mortality was enhanced in CIITA deficient mice, not by impaired bacterial clearance resulted from CD4 T cell depletion, but hyper-inflammatory response such as excessive release of a pro-inflammatory cytokine, high-mobility group box 1 (HMGB1). Conclusion: Our results demonstrate that CIITA deficiency affects the course of sepsis via the unexpected function of CIITA, regulation of cytokine release.

Modulation of a Fungal Signaling by Hypovirus

  • Kim, Dae-Hyuk
    • The Plant Pathology Journal
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    • v.19 no.1
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    • pp.30-33
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    • 2003
  • The chestnut blight fungus, Cryphonectria parasitica, and its hypovirus aye a useful model system in the study of the mechanisms of hypoviral infection and its consequences, such as a biological control of fungal pathogens. Strains containing the double-stranded (ds) RNA viruses Cryphonectria hypovirus 1 show characteristic symptoms of hypovirulence and display hypovirulence-associated changes, such as reduced pigmentation, sporulation, laccase production, and oxalate accumulation. Interestingly, symptoms caused by hypoviral infection appear to be the result of aberrant expression of a number of specific genes in the hypovirulent strain. Several viral regulated fungal genes are identified as cutinase gene, Lac1, which encodes an extracellular laccase, Crp, which encodes an abundant tissue-specific cell-surface hydrophobin that mediates physical strength, and Mf2/1 and Mf2/2, which encode pheromone genes involved in poor sporulation in the presence of hypo-virus. Since the phenotypic changes in the fungal host are pleiotropic, although coordinated and specific, it has been suggested that the hypovirus disturbs one or several regulatory pathways (Nuss,1996). Accordingly, several studies have shown the implementation of a signal transduction pathway during viral symptom development. Although further studies are required, hypovirulence and its associated symptom development due to the hypoviral regulation of a fungal hetero-trimeric G-protein have been suggested. In addition, recent studies have shown the presence of a novel protein kinase gene cppk1 and its transcriptional upregulation by hypovirus. In this review, the presence of important components in signal transduction pathway, their putative biological function, and viral-specific regulation will be addressed.

The G115 standardized ginseng extract: an example for safety, efficacy, and quality of an herbal medicine

  • Bilia, Anna R.;Bergonzi, Maria C.
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.179-193
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    • 2020
  • Ginseng products on the market show high variability in their composition and overall quality. This becomes a challenge for both consumers and health-care professionals who are in search of high-quality, reliable ginseng products that have a proven safety and efficacy profile. The botanical extract standardization is of crucial importance in this context as it determines the reproducibility of the quality of the product that is essential for the evaluation of effectiveness and safety. This review focuses on the well-characterized and standardized ginseng extract, G115, which represents an excellent example of an herbal drug preparation with constant safety and efficacy within the herbal medicinal products. Over the many decades, extensive preclinical and clinical research has been conducted to evaluate the efficacy and safety of G115. In vitro and in vivo studies of G115 have shown pharmacological effects on physical performance, cognitive function, metabolism, and the immune system. Furthermore, a significant number of G115 clinical studies, most of them double-blind placebo-controlled, have reinforced the findings of preclinical evidence and proved the efficacy of this extract on blood glucose and lipid regulation, chronic obstructive pulmonary disease, energy, physical performance, and immune and cognitive functions. Clinical trials and 50 years of presence on the market are proof of a good safety profile of G115.

Hydroxyzine Induces Cell Death in Triple-Negative Breast Cancer Cells via Mitochondrial Superoxide and Modulation of Jak2/STAT3 Signaling

  • Shakya, Rajina;Park, Gyu Hwan;Joo, Sang Hoon;Shim, Jung-Hyun;Choi, Joon-Seok
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.585-592
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    • 2022
  • Treatment of triple-negative breast cancer (TNBC) has been limited due to the lack of molecular targets. In this study, we evaluated the cytotoxicity of hydroxyzine, a histamine H1 receptor antagonist in human triple-negative breast cancer BT-20 and HCC-70 cells. Hydroxyzine inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay showed that hydroxyzine induced apoptosis. The hydroxyzine-induced apoptosis was accompanied down-regulation of cyclins and CDKs, as well as the generation of reactive oxygen species (ROS) without cell cycle arrest. The effect of hydroxyzine on the induction of ROS and apoptosis on TNBC cells was prevented by pre-treatment with ROS scavengers, N-acetyl cysteine or Mito-TEMPO, a mitochondria-targeted antioxidant, indicating that an increase in the generation of ROS mediated the apoptosis induced by hydroxyzine. Western blot analysis showed that hydroxyzine-induced apoptosis was through down-regulation of the phosphorylation of JAK2 and STAT3 by hydroxyzine treatment. In addition, hydroxyzine induced the phosphorylation of JNK and p38 MAPK. Our results indicate that hydroxyzine induced apoptosis via mitochondrial superoxide generation and the suppression of JAK2/STAT3 signaling.

Identification of Protein Phosphatase 4 Inhibitory Protein That Plays an Indispensable Role in DNA Damage Response

  • Park, Jaehong;Lee, Jihye;Lee, Dong-Hyun
    • Molecules and Cells
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    • v.42 no.7
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    • pp.546-556
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    • 2019
  • Protein phosphatase 4 (PP4) is a crucial protein complex that plays an important role in DNA damage response (DDR), including DNA repair, cell cycle arrest and apoptosis. Despite the significance of PP4, the mechanism by which PP4 is regulated remains to be elucidated. Here, we identified a novel PP4 inhibitor, protein phosphatase 4 inhibitory protein (PP4IP) and elucidated its cellular functions. PP4IP-knockout cells were generated using the CRISPR/Cas9 system, and the phosphorylation status of PP4 substrates (H2AX, KAP1, and RPA2) was analyzed. Then we investigated that how PP4IP affects the cellular functions of PP4 by immunoprecipitation, immunofluorescence, and DNA double-strand break (DSB) repair assays. PP4IP interacts with PP4 complex, which is affected by DNA damage and cell cycle progression and decreases the dephosphorylational activity of PP4. Both overexpression and depletion of PP4IP impairs DSB repairs and sensitizes cells to genotoxic stress, suggesting timely inhibition of PP4 to be indispensable for cells in responding to DNA damage. Our results identify a novel inhibitor of PP4 that inhibits PP4-mediated cellular functions and establish the physiological importance of this regulation. In addition, PP4IP might be developed as potential therapeutic reagents for targeting tumors particularly with high level of PP4C expression.

Expression of the Floral Repressor miRNA156 is Positively Regulated by the AGAMOUS-like Proteins AGL15 and AGL18

  • Serivichyaswat, Phanu;Ryu, Hak-Seung;Kim, Wanhui;Kim, Soonkap;Chung, Kyung Sook;Kim, Jae Joon;Ahn, Ji Hoon
    • Molecules and Cells
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    • v.38 no.3
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    • pp.259-266
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    • 2015
  • The regulation of flowering time has crucial implications for plant fitness. MicroRNA156 (miR156) represses the floral transition in Arabidopsis thaliana, but the mechanisms regulating its transcription remain unclear. Here, we show that two AGAMOUS-like proteins, AGL15 and AGL18, act as positive regulators of the expression of MIR156. Small RNA northern blot analysis revealed a significant decrease in the levels of mature miR156 in agl15 agl18 double mutants, but not in the single mutants, suggesting that AGL15 and AGL18 co-regulate miR156 expression. Histochemical analysis further indicated that the double mutants showed a reduction in MIR156 promoter strength. The double mutants also showed reduced abundance of pri-miR156a and pri-miR156c, two of the primary transcripts from MIR156 genes. Electrophoretic mobility shift assays demonstrated that AGL15 directly associated with the CArG motifs in the MIR156a/c promoters. AGL18 did not show binding affinity to the CArG motifs, but pull-down and yeast two-hybrid assays showed that AGL18 forms a heterodimer with AGL15. GFP reporter assays and bimolecular fluorescence complementation (BiFC) showed that AGL15 and AGL18 co-localize in the nucleus and confirmed their in vivo interaction. Overexpression of miR156 did not affect the levels of AGL15 and AGL18 transcripts. Taking these data together, we present a model for the transcriptional regulation of MIR156. In this model, AGL15 and AGL18 may form a complex along with other proteins, and bind to the CArG motifs of the promoters of MIR156 to activate the MIR156 expression.