• Title/Summary/Keyword: Translational research

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Regulation of cellular functions of p53 by ubiquitination (유비퀴틴화에 의한 세포 내 p53의 기능 조절)

  • Jung, Jin-Hyuk;Lee, Joon-Young;Lee, Sun-Mi;Choe, Tae-Boo;An, Sung-Kwan
    • KSBB Journal
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    • v.24 no.3
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    • pp.217-226
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    • 2009
  • p53 undergoes various post-translational modifications, including phosphorylation, ubiquitination, sumoylation, acetylation, methylation, and poly(ADP-ribosyl)ation. Modification of p53 widely affects to various functions of p53. Acetylation and phosphorylation of p53 have been studied for regulating its transcriptional activity which is observed in various stress condition. Otherwise, ubiquitination of p53 by Mdm2 has been well-studied as a canonical ubiquitin-mediated proteasomal degradation pathway. Moreover several investigators have recently reported that ubiquitination of p53 modulates not only its proteasome-dependent degradation by poly-ubiquitination but also its localization and transcriptional activity by mono-ubiquitination which usually does not serve the proteasome dependent degradation. Here we review recent studies on the cellular functions of p53 regulated by post-translational modifications, particularly focusing on mechanisms of ubiquitination.

The Guideline of Diagnosis and Treatment of Attention-Deficit Hyperactivity Disorder: Developed by ADHD Translational Research Center (주의력결핍 과잉행동장애 진단 및 치료: ADHD 중개연구센터 가이드라인)

  • Lee, Sumin;Choi, Jae-Won;Kim, Kyoung-Min;Kim, Jun Won;Kim, Sooyeon;Kang, Taewoong;Kim, Johanna Inhyang;Lee, Young Sik;Kim, Bongseog;Han, Doug Hyun;Cheong, Jae Hoon;Lee, Soyoung Irene;Hyun, Gi Jung;Kim, Bung-Nyun
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.27 no.4
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    • pp.236-266
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    • 2016
  • Attention-deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric conditions. In 2007, the Korean Academy of child and Adolescent Psychiatry developed Korean ADHD practice parameter. Advances in the scientific evidence of ADHD caused practice parameter to be modified and updated. The present guidelines developed by ADHD translational research center summarize current literature for the treatment of ADHD in children and adults. This parameter includes the clinical evaluation for ADHD, comorbid conditions associated with ADHD, clinical feature and course, research on the etiology of the disorder, and psychopharmacological and non-pharmacological treatments for ADHD.

A Piezo-Driven Miniaturized XY Stage with Two Prismatic-Prismatic Joints Type Parallel Compliant Mechanism (2 개의 병진-병진 관절형 병렬 탄성 메커니즘을 갖는 압전구동 소형 XY 스테이지)

  • Choi, Kee-Bong;Lee, Jae Jong;Kim, Gee Hong;Lim, Hyung Jun
    • Journal of the Korean Society for Precision Engineering
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    • v.30 no.12
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    • pp.1281-1286
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    • 2013
  • In this paper, a miniaturized stage with two prismatic-prismatic joints (2-PP) type parallel compliant mechanism driven by piezo actuators is proposed. This stage consists of two layers which are a motion guide layer and an actuation layer. The motion guide layer has 2-PP type parallel compliant mechanism to guide two translational motions, whereas the actuation layer has two leverage type amplification mechanisms and two piezo actuators to generate forces. Since the volume of the stage is too small to mount displacement sensors, the piezo actuators embedding strain gauge sensors are chosen. With the strain gauge-embedded piezo actuators, a semi-control is implemented, which results in hysteresis compensation of the stage. As the results, the operating range of $30{\mu}m$, the resolution of 20 nm, and the bandwidth of 400 Hz in each axis were obtained in the experiments.

FIV Analysis for a Rod Supported by Springs at Both Ends

  • H. S. Kang;K. N. Song;Kim, H. K.;K. H. Yoon
    • Nuclear Engineering and Technology
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    • v.33 no.6
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    • pp.619-625
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    • 2001
  • An axial-flow-induced vibration model was proposed for a rod supported by two translational springs at both ends. For developing the model, a one-mode approximation was made based on the assumption that the first mode was dominant in vibration behavior of the single span rod. The first natural frequency and mode shape functions for the flow-induced vibration, called the FIV model were derived by using Lagrange's method. The vibration displacements at reactor conditions were calculated by the proposed model for the spring-supported rod and by the previous model for the simple-supported(55) rod. As a result, the vibration displacement for the spring-supported rod was larger than that of the 55 rod, and the discrepancy between both displacements became much larger as flow velocity increased. The vibration displacement for the spring-supported rod appeared to decrease with the increase of the spring constant. AS flow velocity increased, the increase rate of vibration displacement was calculated to go linearly up, and that of the rod having the short span length was larger than that of the rod having the long span length although the displacement value itself of the long span rod was larger than that of the short one.

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LSD1-S112A exacerbates the pathogenesis of CSE/LPS-induced chronic obstructive pulmonary disease in mice

  • Jeong, Jiyeong;Oh, Chaeyoon;Kim, Jiwon;Yoo, Chul-Gyu;Kim, Keun Il
    • BMB Reports
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    • v.54 no.10
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    • pp.522-527
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    • 2021
  • Lysine-specific demethylase 1 (LSD1) is an epigenetic regulator that modulates the chromatin status, contributing to gene activation or repression. The post-translational modification of LSD1 is critical for the regulation of many of its biological processes. Phosphorylation of serine 112 of LSD1 by protein kinase C alpha (PKCα) is crucial for regulating inflammation, but its physiological significance is not fully understood. This study aimed to investigate the role of Lsd1-S112A, a phosphorylation defective mutant, in the cigarette smoke extract/LPS-induced chronic obstructive pulmonary disease (COPD) model using Lsd1SA/SA mice and to explore the potential mechanism underpinning the development of COPD. We found that Lsd1SA/SA mice exhibited increased susceptibility to CSE/LPS-induced COPD, including high inflammatory cell influx into the bronchoalveolar lavage fluid and airspace enlargement. Additionally, the high gene expression associated with the inflammatory response and oxidative stress was observed in cells and mice containing Lsd1-S112A. Similar results were obtained from the mouse embryonic fibroblasts exposed to a PKCα inhibitor, Go6976. Thus, the lack of LSD1 phosphorylation exacerbates CSE/LPS-induced COPD by elevating inflammation and oxidative stress.

Surface pressure measurements in translating tornado-like vortices

  • Kassab, Aya;Jubayer, Chowdhury;Ashrafi, Arash;Hangan, Horia
    • Wind and Structures
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    • v.33 no.6
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    • pp.447-462
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    • 2021
  • High spatial and temporal surface pressure measurements were carried out in the state-of-the-art tornado simulator, the Wind Engineering, Energy and Environment (WindEEE) Dome, to explore the characteristics of stationary and translating tornado-like vortices (TLV) for a wide range of swirl ratios (S=0.21 to 1.03). The translational speed of the TLV and the surface roughness were varied to examine their effects on tornado ground pressures, wandering, and vortex structure. It was found that wandering is more pronounced at low swirl ratios and has a substantial effect on the peak pressure magnitude for stationary TLV (error percentage ≤ 35%). A new method for removing wandering was proposed which is applicable for a wide range of swirl ratios. For translating TLV, the near-surface part lagged behind the top of the vortex, resulting in a tilt of the tornado vertical axis at higher translating speeds. Also, a veering motion of the tornado base towards the left of the direction of the translation was observed. Wandering was less pronounced for higher translation speeds. Increasing the surface roughness caused an analogous effect as lowering the swirl ratio.

A new method for determining the effective length factor of columns in partially braced frames on elastic supports

  • Adel Slimani;Toufik Belaid;Messaoud Saidani;Fatiha Ammari;Redouane Adman
    • Structural Engineering and Mechanics
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    • v.85 no.6
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    • pp.825-835
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    • 2023
  • The effective buckling length factor is an important parameter in the elastic buckling analysis of steel structures. The present article aims at developing a new method that allows the determination of the buckling factor values for frames. The novelty of the method is that it considers the interaction between the bracing and the elastic supports for asymmetrical frames in particular. The approach consists in isolating a critical column within the frame and evaluating the rotational and translational stiffness of its restraints to obtain the critical buckling load. This can be achieved by introducing, through a dimensionless parameter 𝜙i, the effects of coupling between the axial loading and bending stiffness of the columns, on the classical stability functions. Subsequently, comparative, and parametric studies conducted on several frames are presented for assessing the influence of geometry, loading, bracing, and support conditions of the frame columns on the value of the effective buckling length factor K. The results show that the formulas recommended by different approaches can give rather inaccurate values of K, especially in the case of asymmetric frames. The expressions used refer solely to local stiffness distributions, and not to the overall behavior of the structure.

Beneficial Effect of Korea Red Ginseng on Halitosis; Attenuation of H2S Induced Inflammatory Mediators and cystathionine γ-lyase Expression (고려홍삼의 구강악취 억제기능; H2S 생성에 따른 염증매개 유전자 및 cystathionine γ-lyase의 약화기능)

  • Choi, Ki-Seok;Lee, So-Jung;Lee, Jeong-Sang;Hong, Kyung-Sook;Kim, Jeong-Gon;Kim, Yoon-Jae;Hahm, Ki-Baik
    • Journal of Ginseng Research
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    • v.33 no.4
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    • pp.367-377
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    • 2009
  • Halitosis is a generally accepted marker of diseases in the oral cavity and of systemic and gastrointestinal disorders. Based on these authors' previous findings (that (1) there is a close association between H. pylori infection and halitosis; (2) Korea red ginseng may suppress the colonization of H. pylori, fight H. pylori-induced cytotoxicity, and impose significant anti-inflammatory actions in patients with chronic gastritis; and (3) H. pylori infection is linked with the generation of significant levels of volatile sulfur compounds (VSCs), and the levels of VSCs correlate significantly with H. pylori-associated mucosal damages), in the current study, the authors documented the molecular mechanisms of Korea red ginseng's efficacy in ameliorating halitosis. When the RAW 264.7 cells were treated with the $H_2S$ releasing compound NaHS, the mRNA expression of cystathionine ${\gamma}$-lyase (CSE), IL-6, COX-2, and iNOS were more significantly induced compared with the vehicle-treated group. The cytoskeletal components of ezrin's and moesin's mRNA expressions were elevated by NaHS treatment accompanied by the activation of MAPK, p38, and ERK. Korea red ginseng pretreatment reduced both the NaHS-induced CSE expression and the proinflammatory genes (e.g., IL-6, COX-2, and iNOS) in a concentration-dependent manner. The ERM expression and the phosphorylation of p38 were also significantly reduced by Korea-red-ginseng pretreatment. Overall, Korea red ginseng pretreatment imposed significant anti-inflammatory effects through the downregulation of the NaHS-triggered proinflammatory gene expression, CSE, and ERM mRNA expression. Korea red ginseng could thus be said to be a key remedy of halitosis and to be effective in relieving gastric inflammation.

Inferring Transcriptional Interactions and Regulator Activities from Experimental Data

  • Wang, Rui-Sheng;Zhang, Xiang-Sun;Chen, Luonan
    • Molecules and Cells
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    • v.24 no.3
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    • pp.307-315
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    • 2007
  • Gene regulation is a fundamental process in biological systems, where transcription factors (TFs) play crucial roles. Inferring transcriptional interactions between TFs and their target genes has utmost importance for understanding the complex regulatory mechanisms in cellular systems. On one hand, with the rapid progress of various high-throughput experiment techniques, more and more biological data become available, which makes it possible to quantitatively study gene regulation in a systematic manner. On the other hand, transcription regulation is a complex biological process mediated by many events such as post-translational modifications, degradation, and competitive binding of multiple TFs. In this review, with a particular emphasis on computational methods, we report the recent advances of the research topics related to transcriptional regulatory networks, including how to infer transcriptional interactions, reveal combinatorial regulation mechanisms, and reconstruct TF activity profiles.

Isocitrate dehydrogenase mutations: new opportunities for translational research

  • Keum, Young-Sam;Choi, Bu Young
    • BMB Reports
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    • v.48 no.5
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    • pp.266-270
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    • 2015
  • Over the last decade, comprehensive genome-wide sequencing studies have enabled us to find out unexpected genetic alterations of metabolism in cancer. An example is the identification of arginine missense mutations of isocitrate dehydrogenases-1 and -2 (IDH1/2) in glioma, acute myeloid leukemia (AML), chondrosarcomas, and cholangiocarcinoma. These alterations are closely associated with the production of a new stereospecific metabolite, (R)-2-hydroxyglutarate (R-2HG). A large number of follow-up studies have been performed to address the molecular mechanisms of IDH1/2 mutations underlying how these events contribute to malignant transformation. In the meanwhile, the development of selective mutant IDH1/2 chemical inhibitors is being actively pursued in the scientific community and pharmaceutical industry. The present review article briefly discusses the important findings that highlight the molecular mechanisms of IDH1/2 mutations in cancer and provides a current status for development of selective mutant IDH1/2 chemical inhibitors. [BMB Reports 2015; 48(5): 266-270]