• Title/Summary/Keyword: life science domain

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Functional and Physiological Characteristic of RIPK and MLKL in TNF Signaling (TNF 신호전달에서 RIPK와 MLKL의 기능적 생리적 특성)

  • Park, Young-Hoon;Jeong, Mi Suk;Jang, Se Bok
    • Journal of Life Science
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    • v.26 no.7
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    • pp.868-874
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    • 2016
  • Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are members of the serine or threonine protein kinase superfamily that phosphorylates the hydroxyl group of serine or threonine through the highly conserved kinase region. The RIPK family plays a crucial role not only in inflammation and innate immunity, but also in mediating programmed cell death, such as apoptosis and necroptosis. The interaction between RIPK1 and other TNFR1-related proteins has been shown to assemble a signaling complex I that controls activation of the pro-survival transcription factor NF-κB upon binding of cytokines to TNF receptor 1 (TNFR1). Moreover, RIPK1 and RIPK3 interact through their RIP homotypic interaction motifs (RHIMs) to mediate programmed necrosis, which has long been considered an accidental and uncontrolled cell death form with morphological characteristics differing from those of apoptosis. Highly conserved sequences of RHIM in RIPK1 and RIPK3 were shown to regulate their binary interaction, leading to assembly of a cytosolic amyloid complex termed the “necrosome”. The necrosome also contains mixed lineage kinase domain-like protein (MLKL), which has been found recently to be a substrate of RIPK3 to mediate downstream signaling. This review provides an overview of the functional and physiological characteristics of RIPKs and MLKL in TNF signaling.

Cloning and Expression of Antifungal Protein (PR5) Genes from Hot Pepper (Capsicum annuum L.) (고추(Capsicum annuum)의 항균성 단백질(PR-5) 유전자의 클로닝과 발현 분석)

  • Park, Hae-Jin;Lee, Jung-Hoon;Yoon, Yong-Hwi;Kim, Hak-Yoon;Shin, Dong-Hyun;Lee, In-Jung;Kim, Dal-Ung;Kim, Kil-Ung
    • Journal of Life Science
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    • v.12 no.3
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    • pp.264-273
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    • 2002
  • We have isolated and artificially expressed three cDNA clones of Capsicum annuum PR5 genes for elucidating the antifungal activity against Phytophthora capsici which contracted a hot pepper root rot in field condition. Three divergent PR5 proteins from hot pepper were designated as CAPR5-1 and CAPR5-2 from susceptible cultivar (Subicho) as well as CAPR5-3 from resistant cultivar (CM331) in response to P. capsici. The cDNA similarity was found over 80% of identity among the three CAPR5s, and deduced amino acid sequence was characterized that all of CAPR5s contained 16 cysteine residues which possibly had a significant role in the structural formation. The result of genomic DNA blot showed that CAPR5-1 and CAPR5-2 existed as single copy in the Subicho genome. Three recombinant CPARs in E. coli were identified by SDS-PACE, and each expressed protein was treated on the PDA medium which contained cultured pathogens. Although three CAPR5 proteins did not affected the hyphal growth of Glomerella glycines and Colletotrichum fagenarium, CAPR5-1, CAPR5-2, and CAPR5-3 showed a specific antifungal activities against P. capsici.

IKKγ Facilitates the Activation of NF-κB by Hsp90 (Hsp90에 의한 NF-κB의 활성화를 촉진하는 IKKγ의 역할)

  • Lee, Jeong Ah;Kim, Dong Wan
    • Journal of Life Science
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    • v.32 no.3
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    • pp.241-248
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    • 2022
  • NF-κB acts as a critical transcription factor in inflammation and innate immunity, and it is also closely involved in cell survival and tumorigenesis via induction of anti-apoptotic genes. In these processes, NF-κB cooperates with multiple other signaling molecules and pathways, and although many studies have demonstrated that Hsp90 regulates NF-κB activity, the exact mechanism is unclear. In this study, we investigated the relationship between Hsp90 and IKKγ in the regulation of NF-κB using expression plasmids of IKK complex components. Wild-type and deletion mutants of IKKγ were expressed together with Hsp90, and the combined regulatory effect of Hsp90 and IKKγ on NF-κB activation was assayed. The results show that Hsp90 activates NF-κB by promoting the phosphorylation and degradation of IκBα and that activation of NF-κB by NIK and LPS was increased by Hsp90. IKKγ elevated the effect of Hsp90 on NF-κB activation by increasing phosphorylation and degradation of IκBα. The positive regulation on NF-κB by Hsp90 and IKKγ was also proved in analysis with IKKβ-EE, the constitutively active form of IKKβ. In experiments with the deletion mutants of IKKγ, the N-terminal IKKβ binding domain, C-terminal leucine zipper, and zinc finger domains of IKKγ were found not necessary for the positive regulation of NF-κB activity. Additionally, the expression of pro-inflammatory cytokines was synergistically elevated by Hsp90 and IKKγ. These results indicate that inhibiting the interaction between Hsp90 and IKKγ is a possible strategic method for controlling NF-κB and related diseases.

Enhancing the Anti-cancer Activity of Non-steroidal Anti-inflammatory Drug and Down-regulation of Cancer Stemness-related Markers in Human Cancer Cells by DAPT and MHY2245 (DAPT 및 MHY2245의 비스테로이드소염제(NSAID)의 항암 활성 증강 및 종양줄기세포관련 표지자 발현 감소 활성에 대한 분자적 기전)

  • Moon, Hyun-Jung;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.32 no.3
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    • pp.210-221
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    • 2022
  • This study investigated the mechanisms underlying the anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) in human cancer cells in combination with either N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, or MHY2245, a new synthetic sirtuin 1 inhibitor. The results showed both DAPT and MHY2245 as novel chemosensitizers of human colon cancer KM12 and human hepatocellular carcinoma SNU475 cells to NSAIDs involving celecoxib and 2, 5-dimethyl celecoxib. The NSAID-induced cytotoxicity of these cells was significantly increased by DAPT and MHY2245 in a cyclooxygenase-2 independent manner. In addition, DAPT and MHY2245 reduced levels of p62, Notch1 intracellular domain, and multiple cancer stemness (CS)-related markers including Notch1, CD44, CD133, octamer-binding transcription factor 4, mutated p53 and c-Myc. However, the level of activating transcription factor 4 (ATF4) was enhanced, probably indicating the down-regulation of multiple CS-related markers by DAPT or MHY2245-mediated autophagy induction. Moreover, the NSAID-mediated reduction of p62/nuclear factor erythroid-derived 2-like 2 and CS-related marker proteins and the up-regulation of C/EBP homologous protein (CHOP)/ATF4 were accelerated by DAPT and MHY2245. As such, the combination of NSAID and either DAPT or MHY2245 resulted in higher cytotoxicity than NSAID alone by accelerating the down-regulation of multiple CS-related markers and PARP activation, indicating that both inhibitors promote NSAID-mediated autophagic cell death, possibly through the CHOP/ATF4 pathway. In conclusion, either combination strategy may be useful for the effective treatment of human cancer cells expressing CS-related markers.

The Role of Ubiquitin-conjugating Enzymes as Therapeutic Targets in Cancer (암 치료 표적으로써 유비퀴틴 접합 효소 UBE2의 기능)

  • Seon Min Woo;Taeg Kyu Kwon
    • Journal of Life Science
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    • v.33 no.6
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    • pp.523-529
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    • 2023
  • Ubiquitination is a post-translational modification that is involved in the quality control of proteins and responsible for modulating a variety of cellular physiological processes. Protein ubiquitination and deubiquitination are reversible processes that regulate the stability of target substrates. The ubiquitin proteasome system (UPS) helps regulate tumor-promoting processes, such as DNA repair, cell cycle, apoptosis, metastasis, and angiogenesis. The UPS comprises a combination of ubiquitin, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin-ligase enzymes (E3), which complete the degradation of target proteins. Ubiquitin-conjugating enzymes (UBE2s) play an inter-mediate role in the UPS process by moving activated ubiquitin to target proteins through E3 ligases. UBE2s consist of 40 members and are classified according to conserved catalytic ubiquitin-conjugating (UBC) domain-flanking extensions in humans. Since UBE2s have specificity to substrates like E3 ligase, the significance of UBE2 has been accentuated in tumorigenesis. The dysregulation of multiple E2 enzymes and their critical roles in modulating oncogenic signaling pathways have been reported in several types of cancer. The elevation of UBE2 expression is correlated with a worse prognosis in cancer patients. In this review, we summarize the basic functions and regulatory mechanisms of UBE2s and suggest the possibility of their use as therapeutic targets for cancer.

Analysis of Terms on Panel Descriptions of the Domain for Astronomy at the Gwacheon National Science Museum (국립과천과학관의 천문영역 패널 설명의 용어 분석)

  • Yun, Hye-Ryun;Sohn, Jungjoo
    • Journal of Science Education
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    • v.36 no.2
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    • pp.329-340
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    • 2012
  • The purpose of this study is to analyze the terms which were described in panels for astronomic article on exhibition at the Gwacheon National Science Museum, and to clarify that the terms were appropriate and easily understandable or not. In research, totally, 965 terms were collected in 52 panels(14 panels in planetarium, 17 panels in national history part, and 21 panels in traditional science part). All terms were categorized to 4types, as 1.Standard/Scientific terms, 2.Non-Standard/Scientific terms, 3.Standard/Non-Scientific terms, 4. Non-Standanrd/Non-Scientific casual words, based on 'Dictionary of Standard Korean' and 'Terminology of Astronomy'. And questionnaires survey was done to 24 in-service teachers at elementary school, middle school, and high school to clarify that the level of the terms are appropriate to students. The results of this study show that accurate scientific terms were 68.5%, and many of students had difficulty in understanding those scientific terms in the panels because of unfamiliarity. Therefore, in order to make students get more interest and better understanding, it is proposed to minimize scientific terms and to substitute them to casual terms which were related with practical life.

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Molecular Cloning and Characterization of a Large Subunit of Salmonella typhimurium Glutamate Synthase (GOGAT) Gene in Escherichia coli

  • Chung Tae-Wook;Lee Dong-Ick;Kim Dong-Soo;Jin Un-Ho;Park Chun;Kim Jong-Guk;Kim Min-Gon;Ha Sang-Do;Kim Keun-Sung;Lee Kyu-Ho;Kim Kwang-Yup;Chung Duck-Hwa;Kim Cheorl-Ho
    • Journal of Microbiology
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    • v.44 no.3
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    • pp.301-310
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    • 2006
  • Two pathways of ammonium assimilation and glutamate biosynthesis have been identified in microorganisms. One pathway involves the NADP-linked glutamate dehydrogenase, which catalyzes the amination of 2-oxoglutarate to form glutamate. An alternative pathway involves the combined activities of glutamine synthetase, which aminates glutamate to form glutamine, and glutamate synthase, which transfers the amide group of glutamine to 2-oxoglutarate to yield two molecules of glutamate. We have cloned the large subunit of the glutamate synthase (GOGAT) from Salmonella typhimurium by screening the expression of GOGAT and complementing the gene in E. coli GOGAT large subunit-deficient mutants. Three positive clones (named pUC19C12, pUC19C13 and pUC19C15) contained identical Sau3AI fragments, as determined by restriction mapping and Southern hybridization, and expressed GOGAT efficiently and constitutively using its own promoter in the heterologous host. The coding region expressed in Escherichia coli was about 170 kDa on SDS-PAGE. This gene spans 4,732 bases, contains an open reading frame of 4,458 nucleotides, and encodes a mature protein of 1,486 amino acid residues (Mr =166,208). The EMN-binding domain of GOGAT contains 12 glycine residues, and the 3Fe-4S cluster has 3 cysteine residues. The comparison of the translated amino acid sequence of the Salmonella GOGAT with sequences from other bacteria such as Escherichia coli, Salmonella enterica, Shigella flexneri, Yersinia pestis, Vibrio vulnificus and Pseudomonas aeruginosa shows sequence identity between 87 and 95%.

Consideration on the Contents of the Electromagnetism Domain in the 2022 Revised Elementary School Science Curriculum (2022 개정 초등학교 과학과 교육과정의 전자기 영역 내용 구성에서 고려해야 할 것)

  • Cheong, Yong Wook;Yoon, Hye-Gyoung
    • Journal of Korean Elementary Science Education
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    • v.41 no.2
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    • pp.186-198
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    • 2022
  • With the science curriculum about to be revised in 2022, this study aimed to guide curriculum revision by addressing suggested approaches to the electromagnetism education in elementary school science curriculum. The core concepts of electromagnetism are "electric field" and "magnetic field" as a medium of force, but the current curriculum does not properly describe the core concepts of electromagnetism. Mechanics and electromagnetism should be linked in elementary schools to form science curriculum based on core concepts to solve this problem. Additionally, the nine aspects of technology extracted in this study offer various educational contexts to match the development of engineering technology based on electromagnetism. However, the current curriculum does not comprise these various contexts and focuses on the limited content of electric circuits using light bulbs. Therefore, it is necessary to expand the scope of the curriculum to better mirror real-life technology. Through the use of more diverse materials and contexts, the scope and level of STS education as well as conceptual learning could be expanded. Finally, in the case of electric circuit learning, various issues such as difficulty in connecting electric circuits and electric field concepts, representativeness of electric circuit, students' learning difficulty, and phenomena-oriented learning should be considered.

Microbial Community of the Arctic Soil from the Glacier Foreland of Midtre Lovénbreen in Svalbard by Metagenome Analysis (북극 스발바르 군도 중앙로벤 빙하 해안 지역의 토양 시료 내 메타지놈 기반 미생물 군집분석)

  • Seok, Yoon Ji;Song, Eun-Ji;Cha, In-Tae;Lee, Hyunjin;Roh, Seong Woon;Jung, Ji Young;Lee, Yoo Kyung;Nam, Young-Do;Seo, Myung-Ji
    • Microbiology and Biotechnology Letters
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    • v.44 no.2
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    • pp.171-179
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    • 2016
  • Recent succession of soil microorganisms and vegetation has occurred in the glacier foreland, because of glacier thawing. In this study, whole microbial communities, including bacteria, archaea, and eukaryotes, from the glacier foreland of Midtre Lovénbreen in Svalbard were analyzed by metagenome sequencing, using the Ion Torrent Personal Genome Machine (PGM) platform. Soil samples were collected from two research sites (ML4 and ML7), with different exposure times, from the ice. A total of 2,798,108 and 1,691,859 reads were utilized for microbial community analysis based on the metagenomic sequences of ML4 and ML7, respectively. The relative abundance of microbial communities at the domain level showed a high proportion of bacteria (about 86−87%), whereas archaeal and eukaryotic communities were poorly represented by less than 1%. The remaining 12% of the sequences were found to be unclassified. Predominant bacterial groups included Proteobacteria (40.3% from ML4 and 43.3% from ML7) and Actinobacteria (22.9% and 24.9%). Major groups of Archaea included Euryarchaeota (84.4% and 81.1%), followed by Crenarchaeota (10.6% and 13.1%). In the case of eukaryotes, both ML4 and ML7 samples showed Ascomycota (33.8% and 45.0%) as the major group. These findings suggest that metagenome analysis using the Ion Torrent PGM platform could be suitably applied to analyze whole microbial community structures, providing a basis for assessing the relative importance of predominant groups of bacterial, archaeal, and eukaryotic microbial communities in the Arctic glacier foreland of Midtre Lovénbreen, with high resolution.

Analysis of Science and E-book Application for Universal Design for Learning for Students with Disabilities (장애학생을 위한 초등학교 과학과 e-book의 보편적 학습설계 적용 분석)

  • Lee, Okin
    • The Journal of the Convergence on Culture Technology
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    • v.6 no.4
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    • pp.9-14
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    • 2020
  • This study examined whether the integrated education science and resource e-book developed for students with disabilities were properly implemented in terms of universal design for learning. For analysis, "Teaching and learning materials for inclusive education of students with disabilities: grade 3~6 sciences", which were instructional adaptation, were selected for students with disabilities who are unable to learn the contents of general textbooks for the 3rd to 6th grade of the elementary school science course in the 2015 revised curriculum. The science grades are composed of 40 units, including basic science inquiry, matter, life, kinetic and energy, earth and universe. The content analysis standard was based on detailed items of 9 definitions according to the 3 principles of UDL presented in CAST (2018). As a result of the study, the strategy network was the largest among the UDL principles. As for the domain of the science curriculum, the kinetic and energy was the most common. As UDL detailed items, informations presentation suitable for learners was most frequent in cognitive network. Various ways of searching for data, was most frequent in strategies network. Diverse materials optimized difficulty of contents was most frequent in affective network.