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Bacterial Stringent Signal Directs Virulence and Survival in Vibrio cholerae.

  • Oh, Young Taek;Kim, Hwa Young;Yoon, Sang Sun
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.10a
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    • pp.8-8
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    • 2019
  • The stringent response (SR) is characterized as a bacterial defense mechanism in response to various growth-inhibiting stresses. It is activated by accumulation of a small nucleotide regulator, (p)ppGpp, and induces global changes in bacterial transcription and translation. Recent work from our group has shown that (p)ppGpp plays a critical role in virulence and survival in Vibrio cholerae. The genes, relA and relV, are involved in the production of (p)ppGpp, while the spoT gene encodes an enzyme that hydrolyzes it in V. cholerae. A mutant strain defective in (p)ppGpp production (i.e. ${\Delta}relA{\Delta}relV{\Delta}spoT$ mutant) lost the ability to produce cholera toxin (CT) and lost their viability due to uncontrolled production of organic acids, when grown with extra glucose. In contrast, the ${\Delta}relA{\Delta}spoT$ mutant, a (p)ppGpp overproducer strain, produced enhanced level of CT and exhibited better growth in glucose supplemented media via glucose metabolic switch from organic fermentation to acetoin, a neutral fermentation end product, fermentation. These findings indicates that (p)ppGpp, in addition to its well-known role as a SR mediator, positively regulates CT production and maintenance of growth fitness in V. cholerae. This implicates SR as a promising drug target, inhibition of which may possibly downregulate V. cholerae virulence and survival fitness. Therefore, we screened a chemical library and identified a compound that induces medium acidification (termed iMAC) and thereby loss of wild type V. cholerae viability under glucose-rich conditions. Further, we present a potential mechanism by which the compound inhibits (p)ppGpp accumulation. Together, these results indicate that iMAC treatment causes V. cholerae cells to produce significantly less (p)ppGpp, an important regulator of the bacterial virulence and survival response, and further suggesting that it has a therapeutic potential to be developed as a novel antibacterial agent against cholera.

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A meta-analysis on advantages of peripheral nerve block post-total knee arthroplasty

  • You, Di;Qin, Lu;Li, Kai;Li, Di;Zhao, Guoqing;Li, Longyun
    • The Korean Journal of Pain
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    • v.34 no.3
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    • pp.271-287
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    • 2021
  • Background: Postoperative pain management is crucial for patients undergoing total knee arthroplasty (TKA). There have been many recent clinical trials on post-TKA peripheral nerve block; however, they have reported inconsistent findings. In this meta-analysis, we aimed to comprehensively analyze studies on post-TKA analgesia to provide evidence-based clinical suggestions. Methods: We performed a computer-based query of PubMed, Embase, the Cochrane Library, and the Web of Science to retrieve related articles using neurothe following search terms: nerve block, nerve blockade, chemodenervation, chemical neurolysis, peridural block, epidural anesthesia, extradural anesthesia, total knee arthroplasty, total knee replacement, partial knee replacement, and others. After quality evaluation and data extraction, we analyzed the complications, visual analogue scale (VAS) score, patient satisfaction, perioperative opioid dosage, and rehabilitation indices. Evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: We included 16 randomized controlled trials involving 981 patients (511 receiving peripheral nerve block and 470 receiving epidural block) in the final analysis. Compared with an epidural block, a peripheral nerve block significantly reduced complications. There were no significant between-group differences in the postoperative VAS score, patient satisfaction, perioperative opioid dosage, and rehabilitation indices. Conclusions: Our findings demonstrate that the peripheral nerve block is superior to the epidural block in reducing complications without compromising the analgesic effect and patient satisfaction. Therefore, a peripheral nerve block is a safe and effective postoperative analgesic method with encouraging clinical prospects.

N'-[(2-Hydroxy-1-naphthyl)methylene]arylhydrazides as Potent HIF-2α Inhibitors (N'-[(2-Hydroxy-1-naphthyl)methylene]arylhydrazide 화합물의 HIF-2α 저해 활성)

  • Lee, Hyosung
    • Journal of the Korea Convergence Society
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    • v.13 no.1
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    • pp.161-166
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    • 2022
  • HIF-2α is a transcription factor activated mainly in hypoxic condition known to play crucial roles in a wide variety of pathophysiological events including cancer, metabolic syndrome, arthritis etc. In this context, a number of N'-aryl isonicotinolyhydrazides, in which known pharmacophores are included, have been selected from commercial chemical library and tested for the inhibitory activities targeting HIF-2α in cultured HTB94 cell. HRE-luciferase and HIF-2α were introduced into the cell by transfection and adenoviri infection, respectively and the reporter gene assay discovered the potency of 2-hydroxy-1-naphthyl structure. Accordingly, the scaffold has been adjusted based on this structure and subjected to anti-HIF-2α activity test, identifying 2 compounds as HIF-2α inhibitors. The activities were confirmed by false positive test. This study has been performed via the convergence of biology and chemistry and the results may be useful for discovering novel inhibitors and HIF-2α biology studies, and contribute to the development of therapeutic agents.

Effects of Light Quality of a Light-Emitting Diode (LED) on Carbohydrate, Protein, and Lipid Contents of Tetraselmis suecica and T. tetrathele (발광다이오드(LED) 파장에 따른 Tetraselmis suecica와 T. tetrathele의 탄수화물, 단백질 및 지질 함량에 미치는 영향)

  • Kyong Ha Han;Seok Jin Oh
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.29 no.1
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    • pp.36-43
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    • 2023
  • To establish a culture system with enhanced cellular nutrition, we investigated the effects of light quality (blue, 450 nm; yellow, 590 nm; and red, 630 nm) of a light-emitting diode (LED) on the biochemical composition of Tetraselmis suecica and T. tetrathele. The protein content of both species was higher (42-69%) than the content of other biochemical substances under all wavelengths. Carbohydrate, protein, and lipid contents were higher under the yellow wavelength, which showed a low growth rate, than those under other wavelengths. The contents of all biochemical substances were low under the red wavelength, which showed a high growth rate. These results indicated that protein synthesis occurs in response to decreased cell division rate, while lipid and carbohydrate synthesis occurs owing to altered chemical composition and enzymatic activity. Therefore, we suggested a two-phase LED culture system, which emitted red LED during the early-middle exponential phase and yellow LED during the late exponential and stationary phases, to increase the yield of useful biochemical substances of T. suecica and T. tetrathele.

Exploring the Potential of Natural Products as FoxO1 Inhibitors: an In Silico Approach

  • Anugya Gupta;Rajesh Haldhar;Vipul Agarwal;Dharmendra Singh Rajput;Kyung-Soo Chun;Sang Beom Han;Vinit Raj;Sangkil Lee
    • Biomolecules & Therapeutics
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    • v.32 no.3
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    • pp.390-398
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    • 2024
  • FoxO1, a member of the Forkhead transcription factor family subgroup O (FoxO), is expressed in a range of cell types and is crucial for various pathophysiological processes, such as apoptosis and inflammation. While FoxO1's roles in multiple diseases have been recognized, the target has remained largely unexplored due to the absence of cost-effective and efficient inhibitors. Therefore, there is a need for natural FoxO1 inhibitors with minimal adverse effects. In this study, docking, MMGBSA, and ADMET analyses were performed to identify natural compounds that exhibit strong binding affinity to FoxO1. The top candidates were then subjected to molecular dynamics (MD) simulations. A natural product library was screened for interaction with FoxO1 (PDB ID-3CO6) using the Glide module of the Schrödinger suite. In silico ADMET profiling was conducted using SwissADME and pkCSM web servers. Binding free energies of the selected compounds were assessed with the Prime-MMGBSA module, while the dynamics of the top hits were analyzed using the Desmond module of the Schrödinger suite. Several natural products demonstrated high docking scores with FoxO1, indicating their potential as FoxO1 inhibitors. Specifically, the docking scores of neochlorogenic acid and fraxin were both below -6.0. These compounds also exhibit favorable drug-like properties, and a 25 ns MD study revealed a stable interaction between fraxin and FoxO1. Our findings highlight the potential of various natural products, particularly fraxin, as effective FoxO1 inhibitors with strong binding affinity, dynamic stability, and suitable ADMET profiles.

Accuracy Assessment and Classification of Surface Contaminants of Stone Cultural Heritages Using Hyperspectral Image - Focusing on Stone Buddhas in Four Directions at Gulbulsa Temple Site, Gyeongju - (초분광 영상을 활용한 석조문화재 표면오염물 분류 및 정확도 평가 - 경주 굴불사지 석조사면불상을 중심으로 -)

  • Ahn, Yu Bin;Yoo, Ji Hyun;Choie, Myoungju;Lee, Myeong Seong
    • Journal of Conservation Science
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    • v.36 no.2
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    • pp.73-81
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    • 2020
  • Considering the difficulties associated with the creation of deterioration maps for stone cultural heritages, quantitative determination of chemical and biological contaminants in them is still challenging. Hyperspectral image analysis has been proposed to overcome this drawback. In this study, hyperspectral imaging was performed on Stone Buddhas Temple in Four Directions at Gulbulsa Temple Site(Treasure 121), and several surface contaminants were observed. Based on the color and shape, these chemical and biological contaminants were classified into ten categories. Additionally, a method for establishing each class as a reference image was suggested. Simultaneously, with the help of Spectral Angle Mapper algorithm, two classification methods were used to classify the surface contaminants. Method A focused on the region of interest, while method B involved the application of the spectral library prepared from the image. Comparison of the classified images with the reference image revealed that the accuracies and kappa coefficients of methods A and B were 52.07% and 63.61%, and 0.43 and 0.55, respectively. Additionally, misclassified pixels were distributed in the same contamination series.

Quantitative Analysis of X-Ray Fluorescence for Understanding the Effect of Elevated Temperatures on Cement Pastes (XRF (X-ray fluorescence)를 활용한 고온환경에 노출된 시멘트 페이스트 분석의 이해)

  • Kil-Song Jeon;Young-Sun Heo
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.27 no.6
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    • pp.130-137
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    • 2023
  • By using XRF (X-ray fluorescence), this study investigates the variation of chemical properties in cement pastes at elevated temperatures. High-temperature conditions were prepared by using an electric furnace, planning a total of 11 target temperatures ranging from room temperature to 1000 ℃. A standard library of geo-quant basic was applied for the analysis of 12 elements in cement paste, including Ca, Si, Al, Fe, S, Mg, Ti, Sr, P, Mn, Zn and K. The results revealed that, as the temperature increased, the proportion of each element in the cement paste also increased. With the exception of a few elements present in extremely low amounts in the cement pastes, the variation in the composition ratio of most elements exhibited a strong correlation with temperature, with an R-squared value exceeding 0.98. In this study, cement pastes exposed to normal and high-temperature environments were compared. The authors established that the reasons for the different results in this comparison can be explained from the same perspective as when comparing raw cement with cement paste. Furthermore, this study discussed the potentially most dominant parameter when investigating the properties of cement paste using XRF.

Ttrosine Hydroxylase in Japanese Medaka (Oryzias latipes): cDNA Cloning and Molecular Monitoring of TH Gene Expression As a Biomarker (송사리 Tyrosine Hydroxylase: cDNA 클로닝 및 생물지표로서의 TH 유전자 발현의 분자생물학적 추적)

  • Shin, Sung-Woo;Kim, Jung-Sang;Chon, Tae-Soo;Lee, Sung-Kyu;Koh, Sung-Cheol
    • Environmental Analysis Health and Toxicology
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    • v.15 no.4
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    • pp.131-137
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    • 2000
  • The release of hazardous waste materials into the environment poses serious risks in humans and ecosystems. The risk assessment of environmental pollutants including hazardous chemicals requires a comprehensive measurement of hazard and exposure of the chemicals that can be achieved by toxicity evaluation using a biological system such as biomarkers. In this report we have tried to develop a biomarker used to elucidate a molecular basis of, and to monitor abnormal behaviors caused by diazinon in Japanese medaka (Oryzias latipes) as a model organism. First, an attempt was made to clone tyrosine hydroxylase gene from Japanese medaka that would be a candidate for a biomarker for neuronal modulations and behaviors. For monitoring experiments at behavioral and molecular biological levels, the fish were treated under different sublethal conditions of diazinon and their behavioral responses were observed . In this study we have successfully cloned a partial TH gene from the medaka fish through PCR screening of an ovary cDNA library. DNA sequencing analysis revealed that the amplified fragment was 327 bp encoding 109 amino acids. Comparing the DNA sequence of medaka TH with other species, TH gene revealed the DNA sequence was completely identical to that of rat TH. In the RT-PCR, 330 Up of mRNA was consistently amplified in all the treated samples including control There were no significant differences in the TH expression level regardless of treating concentrations (1∼5,000 ppb) and time (0∼48 hr) The reason appeared to be that RT-PCR was not performed using through a quantitative analysis normalized against an actin gene expression. Organ or tissue - specific detection of TH activity and mRNA as biomarkers will be a useful monitoring tool for neurobehavioral changes in fish influenced by toxic chemicals. Furthermore, quantitative analysis of locomotive patterns and its correlation with the neurochemical and molecular data would be highly useful in measuring toxicity and hazard ofvarious environmental pollutants.

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A Fast Search Algorithm for Raman Spectrum using Singular Value Decomposition (특이값 분해를 이용한 라만 스펙트럼 고속 탐색 알고리즘)

  • Seo, Yu-Gyung;Baek, Sung-June;Ko, Dae-Young;Park, Jun-Kyu;Park, Aaron
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.12
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    • pp.8455-8461
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    • 2015
  • In this paper, we propose new search algorithms using SVD(Singular Value Decomposition) for fast search of Raman spectrum. In the proposed algorithms, small number of the eigen vectors obtained by SVD are chosen in accordance with their respective significance to achieve computation reduction. By introducing pilot test, we exclude large number of data from search and then, we apply partial distance search(PDS) for further computation reduction. We prepared 14,032 kinds of chemical Raman spectrum as the library for comparisons. Experiments were carried out with 7 methods, that is Full Search, PDS, 1DMPS modified MPS for applying to 1-dimensional space data with PDS(1DMPS+PDS), 1DMPS with PDS by using descending sorted variance of data(1DMPS Sort with Variance+PDS), 250-dimensional components of the SVD with PDS(250SVD+PDS) and proposed algorithms, PSP and PSSP. For exact comparison of computations, we compared the number of multiplications and additions required for each method. According to the experiments, PSSP algorithm shows 64.8% computation reduction when compared with 250SVD+PDS while PSP shows 157% computation reduction.

Volatile Aromatic Components of Ginger(Zingiber officinalis Roscoe) Rhizomes and Japanese Spice Bush(Lindera obtusiloba BL) (생강과 생강나무의 향기성분조성 비교)

  • 문형인;이재학
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.42 no.1
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    • pp.7-13
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    • 1997
  • The composition and chemical structures of same individual components of essential oils from ginger flavor plants were estimated by gas chromatography and gas chromatography-mass spetrometric analysis with the aid of NBS and Wiley library and RI indice searches. Through gas chromatography and gas chromatography /mass spetrometry analysis of 43, 41, 32 essential oil components from flowers, leaves and stems from Lindera obstusiloba., respectively were identified, among which sabinene, $\beta$-myrcene, ι-limonene, phelandrene, ${\gamma}$-selinene, $\alpha$-terpinene, 2, 4a, 5, 6, 7, 8, 9, 9a -octahydro benzocycloheptane, $\delta$-cadinene, ${\gamma}$-terpinene, (Z) -3-hexen-1-ol acetate, ${\gamma}$-elemene, l-boreneol, $\delta$-guaiene, ledene, cis-3-hexanal, elemol, $\alpha$-chamigrene, $\beta$-endesmol: 9-octadecanal, 1-(1, 5-diMe-4-hexenyl)-4-Me. benzene were estimated to be major components.

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