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Trend of In Silico Prediction Research Using Adverse Outcome Pathway (독성발현경로(Adverse Outcome Pathway)를 활용한 In Silico 예측기술 연구동향 분석)

  • Sujin Lee;Jongseo Park;Sunmi Kim;Myungwon Seo
    • Journal of Environmental Health Sciences
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    • v.50 no.2
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    • pp.113-124
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    • 2024
  • Background: The increasing need to minimize animal testing has sparked interest in alternative methods with more humane, cost-effective, and time-saving attributes. In particular, in silico-based computational toxicology is gaining prominence. Adverse outcome pathway (AOP) is a biological map depicting toxicological mechanisms, composed of molecular initiating events (MIEs), key events (KEs), and adverse outcomes (AOs). To understand toxicological mechanisms, predictive models are essential for AOP components in computational toxicology, including molecular structures. Objectives: This study reviewed the literature and investigated previous research cases related to AOP and in silico methodologies. We describe the results obtained from the analysis, including predictive techniques and approaches that can be used for future in silico-based alternative methods to animal testing using AOP. Methods: We analyzed in silico methods and databases used in the literature to identify trends in research on in silico prediction models. Results: We reviewed 26 studies related to AOP and in silico methodologies. The ToxCast/Tox21 database was commonly used for toxicity studies, and MIE was the most frequently used predictive factor among the AOP components. Machine learning was most widely used among prediction techniques, and various in silico methods, such as deep learning, molecular docking, and molecular dynamics, were also utilized. Conclusions: We analyzed the current research trends regarding in silico-based alternative methods for animal testing using AOPs. Developing predictive techniques that reflect toxicological mechanisms will be essential to replace animal testing with in silico methods. In the future, since the applicability of various predictive techniques is increasing, it will be necessary to continue monitoring the trend of predictive techniques and in silico-based approaches.

Molecular Epidemiological Characteristics of Vibrio Parahaemolyticus as Recently wilde-spreaded in Korea (최근 한국에서 유행하는 장염비브리오균의 분자 역학적 특성)

  • 김상숙;이희무;이중복
    • KSBB Journal
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    • v.18 no.6
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    • pp.522-528
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    • 2003
  • The purpose of this study is to inquire into molecular epidemiological characteristics of Vibrio parahaemolyticus. For this study, 120 strains(120 strains of Vibrio parahaemolyticus sampled from diarrhea patients) were examined and analyzed for biochemical characteristics, TDH (thermostable direct hemolysin) antibiotics sensitivity and detection of toxR, gyrE, tdh, and tds gents. G-S PCR (Group Specific Polymerase), PFGE (Pulsed-field Gel Electrophoriesis) methods were performed on the materials from patients were results. 1 Vibrio parahaemolyticus didn't grow in 0% density of NaCl, but the fact was found that those grew in 8% density of NaCl. 2. O:K serotypes of Vibrio parahaemolyticus was turned up in domestic patients was 17 types. Among those O3:K6 was the most, it was 68.3%. 3. In 18 kinds of antibiotic tests resistant against Ampicillin, Ticacillin was comparatively high. the case of resistant against Ampicillin, Ticacillin, Vancomycin at the multiple resistant was 52.5%. 4. Toxin gene tdh had only 109 strains among 120 ones isolated from patients held the genes of 199bp size, and 11 strains was negativity 5. In the test of Kanagawa toxic productivity, 107 strains among strains isolated from patients appeared to be positivity reaction 6. The strain that held trh toxin was only 3, and those among test strains had the genes of 250bp size and that had tdh, trh genes at a time were 3 strains, and TDH toxic productivity of those were 16 times, and it was weak. 7. Group Specific-PCR appeared to be useful in the confirmation of O3:K6 serotype interrelations. 8. Three strains which showed difference of 7 DNA sequence even in the same serotype were detected by the result of analyzing the regular gene, toxRS DNA sequence. These strains are differ from general strains which carry infection easily. 9. These mutual dose epidemiological relations were classified into smaller-parts through PFGE method. As a result of such classify, 3 findings were found. V. parahaemolyticus sampled from diarrhea patients were classified into 3 types. And third, the result obtained through PFGE method can be used as a useful tool in a point of molecular-epidemiological view.

Archvillin C-Terminus-Binding Proteins in Human Skeletal Muscle

  • Chang, Goo-Rak
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.207-212
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    • 2010
  • Archivillin, a muscle-specific isoform of supervillin, is a component of the costameric cytoskeleton of muscle cells. The purpose of this study was to determine which protein in the skeletal muscle collaborates with archvillin C-terminus. For this purpose, a yeast two-hybrid screening of human skeletal muscle cDNA library was performed using the C-terminal region of archvillin as bait. This study shows that seven human skeletal muscle proteins, namely, nebulin, xeplin, archvillin, GAPDH, TOX4, PITRM1, and YME1L1 interact with archvillin C-terminus. Especially, xeplin is a newly discovered protein interacts with archvillin C-terminus. These results indicate that archvillin C-terminus acts as a bridge between nebulin and xeplin at costameres. Archvillin C-terminal region interacts with nebulin C-terminal region at Z-discs and interacts with xeplin at the vicinity of sarcolemma. I propose that these interactions may contribute to formation of costameric structure and muscle contraction.

Fabrication and Characterization of Self-Aligned Recessed Channel SOI NMOSFEGs

  • Lee, Jong-Ho
    • Journal of Electrical Engineering and information Science
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    • v.2 no.4
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    • pp.106-110
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    • 1997
  • A new SOI NMOSFET with a 'LOCOS-like' shape self-aligned polysilicon gate formed on the recessed channel region has been fabricated by a mix-and-match technology. For the first time, a new scheme for implementing self-alignment in both source/drain and gate structure in recessed channel device fabrication was tried. Symmetric source/drain doping profile was obtained and highly symmetric electrical characteristics were observed. Drain current measured from 0.3${\mu}{\textrm}{m}$ SOI devices with V\ulcorner of 0.77V and Tox=7.6nm is 360$mutextrm{A}$/${\mu}{\textrm}{m}$ at V\ulcorner\ulcorner=3.5V and V\ulcorner=2.5V. Improved breakdown characteristics were obtained and the BV\ulcorner\ulcorner\ulcorner(the drain voltage for 1 nA/${\mu}{\textrm}{m}$ of I\ulcorner at V=\ulcorner\ulcorner=0V) of the device with L\ulcorner\ulcorner=0.3${\mu}{\textrm}{m}$ under the floating body condition was as high as 3.7 V. Problems for the new scheme are also addressed and more advanced device structure based on the proposed scheme is proposed to solve the problems.

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염료 또는 피염물로부터 발암성 아민의 검출

  • 오세화;강명녀
    • Textile Coloration and Finishing
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    • v.7 no.4
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    • pp.113-115
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    • 1995
  • 환경오염이 건강에 미치는 영향에 대한 관심이 높아지면서 서유럽 국가들, 특히 독일에서는 섬유, 가죽, 옷 등 일용제품에 환경마크(ECO-Label)를 부착하려는 경향이 있다. 환경마크는 소비자들에게 그들이 구입한 제품들이 환경오염을 일으키지 않으며, 또 사용시 몸에 해롭지 않다는 것을 보증하기 위한 것으로서, 여러 관련 협회, 연구기관 또는 컨설팅 회사가 각각의 유해 물질에 대해서 정한 표준과 허용 한계치에 기초하여 주어진다. 이러한 환경마크들 중에서 eco-tex, Gut, Oeko-Tex Standard 100, TOX PROOF, EU environmental symbol 등이 있으며, 이 외에도 더욱 많은 환경마크들이 특히 독일에서 경쟁적으로 생겨나고 있다. 이들 중에서 가장 잘 알려져 있고 널리 사용되고 있는 것은 'Oeko-Tex Standard 100'으로서 서유럽 12개 국가들이 참여하며 각국을 대표하는 연구기관들로 구성된 '국제 섬유 환경학 연구 실험 기구(Int'l Association for Research and Testing in the field of Textile Ecology)'에 의해 주어진다.

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Fine-Tuned ProtBERT for Toxic Protein Classification (ProtBERT를 활용한 독성 단백질 분류)

  • Ahn, Sung-Yoon;Lee, Sang-Woong
    • Proceedings of the Korean Society of Computer Information Conference
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    • 2022.07a
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    • pp.673-674
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    • 2022
  • 살아있는 유기체에 의해 분비되는 독소는 대부분의 경우 인간에게 유해하다. 가령 여름철 날것이나 오래된 음식에서 쉽게 식중독에 걸릴 수 있는데, 이는 주로 Clorustidium Botulinum이 만들어낸 보툴리눔 독소가 원인이다. 유기체에 의해 생성된 모든 독소는 단백질이며 이는 아미노산 서열로 나타낼 수 있다. 이를 통해 생물정보학 분야의 많은 연구자들이 많은 머신러닝 기술을 통해 단백질의 독성을 예측할 수 있었다. 최근 몇 년 동안 SVM를 사용하는 BTXpred와 CNN을 사용하는 ToxDL과 같은 모델이 각각 박테리아와 동물 독소의 독성을 예측하기 위해 제안되었다. 시대가 변함에 따라 BERT와 같은 성능이 더욱 뛰어난 모델이 시퀀스 분류를 위해 도입되었다. 본 논문은 독성 단백질을 분류를 위해 ProtBERT를 사용할 경우 이의 성능을 보여주고자 한다.

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Genetic Characteristics and Virulence Factors of Pandemic Vibrio parahaemolyticus Isolated in South Korea and Japan (한국과 일본에서 유행하는 장염비브리오의 병원성 인자와 유전자의 특성)

  • Hong, Seuk-Won;Moon, Ji-Young;Lee, Bok-Kwon;Kim, Yung-Bu
    • Journal of Life Science
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    • v.17 no.3 s.83
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    • pp.386-395
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    • 2007
  • A total of 27 strains of Vibrio parahaemolyticus (18 strains isolated from Korea and 9 strains from Japan) were serotyped and examined for biochemical characteristics, antimicrobial susceptibility patterns, cytotoxicity assay, thermostable direct hemolysin (TDH) production and molecular epidemiology. Using polymerase chain reaction (PCR) method and DNA probe hybridization method, the strains were tested for toxR, tdh, trh and ORF 8 genes. The V. parahaemolyticus isolated from patients were belonged to 8 different serotypes : O3:K6, O1:K38, O3:K57, O4:K9, O4:Kl2, O4:K68, O5:Kl5 and O6:K46. Urease-positive strain possessed the trh gene, and conversely, urease-negative strains lacked the gene, indicating that urease production by V. parahemolyticus strains strongly correlates with the possession of the trh gene. Most strains showed multiple resistant to more than three antibiotics and the antibiogram could be classified into 6 group (I to VI). All of the O3:K6 strains isolated in South Korea and Japan producted TDH at high levels. The TDH titers ranged between 256 and 2.048, and the average titer was 1009. To distinguish the new and increasingly common V. parahaemolyticus strains from clinical isolates, ORF 8 is a useful genetic marker. After Southern hybridization, the HindIII restriction fragment patterns of the tdh gene were grouped one type, respectively. One type showed two bands one of which was 4.3kb and the other was 11.5kb in size. Variation between the O3:K6 serotype are minor when compared to the differences seen with the non O3:K6 strains. The migration patterns of Not I -digested of the total DNA of the O3:K6 strains were similar, and only slight variations were observed between the serotypes. By contrast, the O3:K6 strains and non O3:K6 had markedly different profiles. In conclusion, Random amplified polymorphic DNA (RAPD) profile using appropriate primers was an effective epidemiological marker.

Single and 28-day repeated dose toxicity studies of botulinum toxin type A in mice and rats (마우스 및 랫드에서 botulinum toxin type A의 단회 및 28일 반복투여 독성시험)

  • Jeon, Tae-Won;Kim, Ji-Young;Hyun, Sun-Hee;Kim, Nam-Hee;Lee, Sang-Kyu;Kim, Chun-Hwa;Woo, Hee-Dong;Yang, Gi-Hyeok;Jung, Hyun-Ho;Jeong, Tae-Cheon
    • Korean Journal of Veterinary Research
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    • v.43 no.1
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    • pp.57-66
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    • 2003
  • Single and 28-day repeated dose toxicity studies of botulimnn toxin type A were carried out in ICR mice and Sprague-Dawley rats, respectively. In the single dose toxicity study, botulinwn toxin was injected intraperitoneally to male and female mice at a single dose of 40, 59, 89 133 and 200 ng/10 ml saline/kg. All animals died from 59 ng/kg group. Some clinical signs, such as decrease in locomotor activity, dyspnea, prone position and ptosis, were observed in most of both sexes from 59 ng/kg group, but no signs were seen in all animals at 40 ng/kg group. The results showed that the median lethal dose of botulinum toxin might be in the range of 40-59 ng/kg in both sexes. In the repeated dose toxicity study, the test material was administered intradermally for 28 days at doses of 0 (vehicle-treated control), 1.25, 2.5, 5.0 and $10.0ng/head/50{\mu}{\ell}$ saline in male and female rats. No test material-related changes were noted in survivals, clinical signs, food and water consumptions and gross finding in any group. Botulinum toxin treatment significantly decreased the body weight gain rate in male of 5.0 ng/head group and over and in female of 10.0 ng/head group compared to vehicle-treated control. One or more relative organ weights (i.e., spleen, thymus, liver and kidney) were increased significantly from 5.0 ng/head group compared to vehicle-treated control in both sexes. Serum biochemistry revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase, total protein and albumin in male, and increases in AST and ALT and decreases in $K^+$ and $Cl^-$ in female without dose-pendent manners. In the histopathological study, physical stimulation by needle caused slight inflammations of dennis. In addition, botulinum toxin treatment induced denervation of nerve cell and disuse of muscle, resulting in atrophy of skeletal muscle in both sexes from 2.5 ng/head group. When the antibodies to toxin were determined in all animals, a significant increase in serum antibodies was observed from 5.0 ng/head group. The results showed that the NOAEL of botulinum toxin might be 1.25 ng/head for 28-day repeated dose toxicity in rats.

Toxic Effects of Metal Plating Wastewater on Daphnia magna and Euglena agilis (Daphnia magna와 Euglena agilis를 이용한 도금폐수 독성평가)

  • Lee, Junga;Park, Da Kyung
    • Korean Journal of Environmental Biology
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    • v.34 no.2
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    • pp.116-123
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    • 2016
  • The ecotoxicity tests for metal plating wastewater were conducted using Daphnia magna (D. magna) and Euglena agilis (E. agilis). Evaluation for sources of toxicity was performed by 1) Correlation analysis between the concentration of individual metals in the metal plating wastewater and the toxic effects on D. magna, 2) Toxicant identification evaluation methods including graduated pH method, EDTA procedure and sodium thiosulfate procedure, 3) Comparison of toxic effect value ($EC_{50}$ or $LC_{50}$) of individual metal on D. magna and it's concentration in the metal plating wastewater. To evaluate the possibility of E. agilis, a Korean domestic organism, as a test model organism for metal plating waste water, E. agilis toxicity test was also assessed using on-line euglena ecotoxicity system (E-Tox system). Based on toxicant characterization test using D. magna, it was expected that SS, oxidants and heavy metals are responsible for toxicity of metal plating waste water. Especially Cu, Hg, and Ag were the major cationic metals that caused toxicity. E. agilis is less sensitive than D. magna based on the $EC_{50}$ value however it shows prompt response to toxic test substances. E. agilis shows even a significant effect on the cell swimming velocity within 2 min to toxic metal plating wastewater. Our study demonstrates that E. agilis test can be a putative ecotoxicity test for assessing the quality of metal plating waste water.

Molecular Detection of Virulence Factors in Carbapenem-Resistant Pseudomonas aeruginosa Isolated from a Tertiary Hospital in Daejeon (대전지역의 3차 병원에서 분리된 Carbapenem 내성 Pseudomonas aeruginosa의 병독성 인자 검출)

  • Cho, Hye Hyun
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.3
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    • pp.301-308
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    • 2019
  • The emergence and spread of multidrug resistant (MDR) Pseudomonas aeruginosa is a critical problem worldwide. The pathogenesis of P. aeruginosa is due partly to the production of several cell-associated and extracellular virulence factors. This study examined the distribution of virulence factors and antimicrobial resistance patterns of carbapenem-resistant P. aeruginosa (CRPA) isolated from a tertiary hospital in Daejeon, Korea. Antimicrobial susceptibility testing was performed using the disk diffusion method, and PCR and DNA sequencing were performed to determine for the presence of virulence genes. In addition, the sequence type (ST) of MDR P. aeruginosa was investigated by multilocus sequence typing (MLST). Among 32 CRPA isolates, 14 (43.8%) were MDR and the major ST was ST235 (10 isolates, 71.4%). All isolates were positive for the presence of virulence genes and the most prevalent virulence genes were toxA, plcN, and phzM (100%). All isolates carried at least eight or more different virulence genes and nine (28.1%) isolates had 15 virulence genes. The presence of the exoU gene was detected in 71.4% of the MDR P. aeruginosa isolates. These results indicate that the presence of the exoU gene can be a predictive marker for the persistence of MDR P. aeruginosa isolates.