• Title/Summary/Keyword: Negative regulation

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Regulation of the Edwardsiella tarda Hemolysin Gene and luxS by EthR

  • Fang, Wang;Zhang, Min;Hu, Yong-Hua;Zhang, Wei-wei;Sun, Li
    • Journal of Microbiology and Biotechnology
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    • v.19 no.8
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    • pp.765-773
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    • 2009
  • Edwardsiella tarda is a pathogen with a broad host range that includes human and animals. The E. tarda hemolysin (Eth) system, which comprises EthA and EthB, is a noted virulence element that is widely distributed in pathogenic isolates of E. tarda. Previous study has shown that the expression of ethB is regulated by iron, which suggests the possibility that the ferric uptake regulator (Fur) is involved in the regulation of ethB. The work presented in this report supports the previous findings and demonstrates that ethB expression was decreased under conditions when the E. tarda Fur ($Fur_{Et}$) was overproduced, and enhanced when $Fur_{Et}$ was inactivated. We also identified a second ethB regulator, EthR, which is a transcription regulator of the GntR family. EthR represses ethB expression by direct interaction with the ethB promoter region. In addition to ethB, EthR also modulates, but positively, luxS expression and AI-2 production by binding to the luxS promoter region. The expression of ethR itself is subject to negative autoregulation; interference with this regulation by overexpressing ethR during the process of infection caused (i) drastic changes in ethB and luxS expressions, (ii) vitiation in the tissue dissemination and survival ability of the bacterium, and (iii) significant attenuation of the overall bacterial virulence. These results not only provide new insights into the regulation mechanisms of the Eth hemolysin and LuxS/AI-2 quorum sensing systems but also highlight the importance of these systems in bacterial virulence.

TrkB Promotes Breast Cancer Metastasis via Suppression of Runx3 and Keap1 Expression

  • Kim, Min Soo;Lee, Won Sung;Jin, Wook
    • Molecules and Cells
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    • v.39 no.3
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    • pp.258-265
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    • 2016
  • In metastatic breast cancer, the acquisition of malignant traits has been associated with the increased rate of cell growth and division, mobility, resistance to chemotherapy, and invasiveness. While screening for the key regulators of cancer metastasis, we observed that neurotrophin receptor TrkB is frequently overexpressed in breast cancer patients and breast cancer cell lines. Additionally, we demonstrate that TrkB expression and clinical breast tumor pathological phenotypes show significant correlation. Moreover, TrkB expression was significantly upregulated in basal-like, claudin-low, and metaplastic breast cancers from a published microarray database and in patients with triple-negative breast cancer, which is associated with a higher risk of invasive recurrence. Interestingly, we identified a new TrkB-regulated functional network that is important for the tumorigenicity and metastasis of breast cancer. We demonstrated that TrkB plays a key role in regulation of the tumor suppressors Runx3 and Keap1. A markedly increased expression of Runx3 and Keap1 was observed upon knockdown of TrkB, treatment with a TrkB inhibitor, and in TrkB kinase dead mutants. Additionally, the inhibition of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces proliferation. These observations suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1 and that it is a promising target for future intervention strategies for preventing tumor metastasis and cancer chemoprevention.

Identification of Positive and Negative Regulatory Elements of the Human Cytochrome P4501A2 (CYP1A2) Gene

  • Chung, Injae;Jeong, Choonsik;Jung, Kihwa;Bresnick, Edward
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.81-81
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    • 1997
  • We previously demonstrated an enhancer-like positive regulatory element within a 259-bp sequence (-2352 to-2094 bp) of the human CYP1A2 gene in HepG2 cells. Three protein binding sites were identified by DNase I footprint analyses within the 259-bp sequence: protected region A PRA ( -2283 to-2243 bp), PRB (-2218 to-2187 bp), and PRC (-2124 to-2098 bp) (I. Chung and E. Bresnick, Mol. Pharmacol. 47, 677-685, 1995). In the present study, the functional significance of those protected regions was examined. Transfection experiments with deletion and substitution mutants defined the PRB and PRC as containing positive and negative regulatory elements, respectively. Human breast carcinoma MCF-7 cells were cotransfected with a hepatocyte nuclear factor-1 (HNF-1) expression vector and CYP1A2 promoter-or thymidine kinase promoter-luciferase remoter gene constructs. HNF-1, which contributes to the liver specificity of genes, enhanced reporter gene activity in a PRC sequence-dependent manner. These results suggested that PRC could exist bound to a repressor which was displaceable by other transcription factors such as HNF-1. Results obtained by transfection of HepG2 hepatoma cells with various PRB substitution mutant-luciferase gene fusion constructs indicated that the entire sequence of PRB was necessary for promoter activity. Consequently, the regulation of CYP1A3 expression is very complex, requiring a number of both positive and negative regulatory factors.

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The Internet Design Framework for Improvement of Users' Positive Emotions

  • Wu, Chunmao;Li, Xuefei;Dong, Cui
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.16 no.8
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    • pp.2720-2735
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    • 2022
  • This study proposes an internet design framework for users to improve their positive emotions when they are in a negative mood. First, the literature review focuses on the definition of emotion, positive emotional design in internet experiences, and emotion regulation. Second, in order to construct an internet design framework that improves positive emotion, this paper adopts a qualitative analysis method to analyze 70 collected studies in the area of regulating emotion and stimulating positive emotions. Additionally, bibliometrics and statistics are conducted to summarize the framework and strategies. Third, two cases of internet design are presented: (a) Internet design that improves users' positive emotions is examined under the background of extreme rainstorm as an example; an applet service design is provided by case study; (b) in the context of COVID-19, we developed an Internet of things interactive design that improves users' positive emotions. Fourth, the internet design framework and the results of the case studies are analyzed and discussed. Finally, an internet design framework is proposed to improve users' positive emotions when they are in a negative mood, which includes the Detachment-empathy framework, External-protection framework, Ability-strengthen framework, Perspective-transformation framework, and Macro-cognitive framework. The framework can help designers to generate design ideas accurately and quickly when users are in a negative mood, to improve subjective well-being, and contribute to the development of internet experience design.

The Moderating Effects of Emotional Support, Facilitative Relationship in the Relation between Father and Mother's Emotional Abuse and Difficulties in Emotion Regulation (아동기 부·모의 정서적 학대 경험과 성인기 정서조절곤란의 관계에서 정서적 지지, 촉진적 관계의 조절 효과)

  • Park, Won-Ju
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.7
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    • pp.255-264
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    • 2019
  • This study aimed to examine the moderating effects of emotional support and facilitative relationship in the relation of emotional abuse and difficulties in emotion regulation. This research suggests therapeutic methods for reducing the negative effects of emotional abuse. Data about emotional abuse, difficulties in emotion regulation, emotional support, and relationship inventory were collected by online survey from 336 adults in South Korea. To test moderation effects, multiple regression analyses entering emotional abuse, emotional support(facilitative relationship) and their interaction terms were hierarchically conducted. Emotional abuse increased difficulties in emotion regulation. Moderating effects of emotional support and facilitative relationship were found in the relation between father's emotional abuse and difficulties in emotion regulation. But Moderating effects of emotional support and facilitative relationship were not found in the relation between mother's emotional abuse and difficulties in emotion regulation. The different effects of father's emotional abuse and mother's, the effects of adult's positive relationship, and clinical implications of these findings were discussed.

Single-Inductor Multiple-Output DC-DC Converter with Negative Feedback Selection Circuit (부궤환 선택회로를 갖는 단일 인덕터 다중 출력 직류-직류 변환기)

  • Gong, Jung-Chul;Roh, Yong-Seong;Moon, Young-Jin;Choi, Woo-Seok;Yoo, Chang-Sik
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.48 no.12
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    • pp.23-30
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    • 2011
  • This paper presents a Single-Inductor Multiple-Output (SIMO) DC-DC Converter with a negative feedback selection circuit to improve a regulation property at light load and to generate independent multiple outputs. The conventional SIMO DC-DC converter with a fixed negative feedback circuit cannot regulate correctly at light load. The SIMO DC-DC converter with the proposed negative feedback selection circuit has been designed in 0.35um 2-poly 3-metal BCDMOS. This converter is dual output boost converter with the 1.5V input and 2.5V, 3.0V output. The power conversion efficiency varies from 59% at 10mA loads to 85% at 50mA loads.

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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    • v.23 no.2
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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.

MiR-133b Acts as a Tumor Suppressor and Negatively Regulates TBPL1 in Colorectal Cancer Cells

  • Xiang, Kai-Min;Li, Xiao-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3767-3772
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    • 2014
  • Introduction: MicroRNAs have emerged as post-transcriptional regulators that are critically involved in tumorigenesis. This study was designed to explore the effect of miRNA 133b on the proliferation and expression of TBPL1 in colon cancer cells. Methods: Human colon cancer SW-620 cells and human colon adenocarcinoma HT-29 cells were cultured. MiRNA 133b mimcs, miRNA 133b inhibitors, siRNA for TBPL1 and scrambled control were synthesized and transfected into cells. MiR-133b levels in cells and CRC tumor tissue was measured by real-time PCR. TBPL1 mRNA was detected by RT-PCR. Cell proliferation was studied with MTT assay. Western blotting was applied to detect TBPL1 protein levels. Luciferase assays were conducted using a pGL3-promoter vector cloned with full length of 3'UTR of human TBPL1 or 3'UTR with mutant sequence of miR-133b target site in order to confirm if the putative binding site is responsible for the negative regulation of TBPL1 by miR-133b. Results: Real time PCR results showed that miRNA 133b was lower in CRC tissue than that in adjacent tissue. After miR-133b transfection, its level was elevated till 48h, accompanied by lower proliferation in both SW-620 and HT-29 cells. According to that listed in http://www.targetscan.org, the 3'-UTR of TBPL1 mRNA (NM_004865) contains one putative binding site of miR-133b. This site was confirmed to be responsible for the negative regulation by miR-133b with luciferase assay. Further, Western blotting and immunohistochemistry both indicated a higher TBPL1 protein expression level in CRC tissue. Finally, a siRNA for TBPL1 transfection obviously slowed down the cell proliferation in both SW-620 and HT-29 cells. Conclusion: MiR-133b might act as a tumor suppressor and negatively regulate TBPL1 in CRC.

Temporal and Spatial Regulation of Cell Cycle Genes during Maize Sex Determination (옥수수 성 결정에 있어서 세포주기 유전자들의 시간적, 공간적 조절)

  • Lee, Jung-Ro;Kim, Jong-Cheol
    • Journal of Life Science
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    • v.16 no.5
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    • pp.828-833
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    • 2006
  • Maize (Zea mays L.) pistil cell death and stamen cell arrest are pivotal process on the sex determination, which diverges from bisexual state of floral meristem to unisexual state in staminate or pistillate floret. We investigated the temporal and spatial distribution of cell cycle gene expression during maize sex determination. The positive regulatory genes of cell cycle, cyclin A, cyclin B, cyclin dependent kinase (CDK) and Mad2 were highly expressed in the developing pistil and stamen but the expression was disappeared in the dying pistil and arresting stamens. In contrast, the negative regulatory genes of cell cycle, Wee1 and CDK inhibitor (CKI) were expressed in the arresting stamens in the wild-type ear and tasselseed2 mutant tassel, however, these genes were not detected in dying pistil although the cyclin B gene expression was disappeared. These results suggest that both the pistil cell death and stamen cell arrest process in maize sex determination are involved in cell cycle regulation, but the different expression patterns of negative regulatory cell cycle genes in the arresting stamens and aborting pistils suggest that the two processes may have distinctive modes of action.

The Macroeconomic Analysis: the Main Results of Estimation of Monetary Indicators on the Materials of Russia, the Countries of the Commonwealth of Independent States (CIS) and North-East Asia

  • Vyborova, Elena Nikolaevna
    • East Asian Journal of Business Economics (EAJBE)
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    • v.7 no.3
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    • pp.13-48
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    • 2019
  • Purpose - This study is to analyze the monetary indicators and the key macroeconomic indicators and to assess the effectiveness of state regulation on its basis. The analysis of monetary aggregates of Russian Federation, CIS, the countries of leading countries of North-East Asia at the present stage of development. Research design and methodology - The volume of data on Russia was analyzed from the 1995 to the 2018. The data from the 1950 to the 2019 were estimated on China. The data from the 1980 to the 2018 were estimated on Japan. On South Korea - since the 1960 to the 2018. On Republic of Belarus - since the 2003 to the 2018. On Tajikistan - from the 2008 to 2017. On Kazakhstan - from the 1994 to the 2018. On Kyrgyzstan - from the 2002 to the 2018. On Armenia - from the 2003 to the 2018. Results - Hypothesis 1: In Russian Federation, the monetary stock has a stable tendency to grow. The volume of money stock of Russia and the analyzed countries is much determined by external debt, GDP, the export, the import, and the international reserves. Hypothesis 2: The growth of money supply does not always give a positive effect in the development of the country, as well as a significant increase in the amount of money stock does not always lead to negative consequences. The monetary stock should be commensurate with the macroeconomic indicators of the state. Conclusions - The growth of the monetary stock does not always give a positive effect in the development of the country, as well as a significant increase in the amount of monetary stock not always lead to negative consequences.