• Title/Summary/Keyword: Network biology

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Algorithm for Predicting Functionally Equivalent Proteins from BLAST and HMMER Searches

  • Yu, Dong Su;Lee, Dae-Hee;Kim, Seong Keun;Lee, Choong Hoon;Song, Ju Yeon;Kong, Eun Bae;Kim, Jihyun F.
    • Journal of Microbiology and Biotechnology
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    • v.22 no.8
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    • pp.1054-1058
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    • 2012
  • In order to predict biologically significant attributes such as function from protein sequences, searching against large databases for homologous proteins is a common practice. In particular, BLAST and HMMER are widely used in a variety of biological fields. However, sequence-homologous proteins determined by BLAST and proteins having the same domains predicted by HMMER are not always functionally equivalent, even though their sequences are aligning with high similarity. Thus, accurate assignment of functionally equivalent proteins from aligned sequences remains a challenge in bioinformatics. We have developed the FEP-BH algorithm to predict functionally equivalent proteins from protein-protein pairs identified by BLAST and from protein-domain pairs predicted by HMMER. When examined against domain classes of the Pfam-A seed database, FEP-BH showed 71.53% accuracy, whereas BLAST and HMMER were 57.72% and 36.62%, respectively. We expect that the FEP-BH algorithm will be effective in predicting functionally equivalent proteins from BLAST and HMMER outputs and will also suit biologists who want to search out functionally equivalent proteins from among sequence-homologous proteins.

Immune Stimulating Efficacy of Soluble β-1,3-glucans (수용성 β-1,3-glucans의 면역 활성 효능에 대한 연구)

  • Shim, Jung-Hyun;Choi, Won-A;Kim, Jong-Wan;Lee, Hae-Sook;Baek, Tae-Woong;Cho, Min-Cheol;Lee, Kyung-Ae;Sang, Byung-Chan;Yoon, Do-Young
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.156-163
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    • 2003
  • Background: $\beta$-1,3-glucans are well known to enhance the immune reactions, resulting in antitumor, antibacterial, antiviral, anticoagulatory and wound healing activities. $\beta$-1, 3-glucans have various activities depending on molecular weight, degree of branching, conformation, water-solubility and intermolecular association. However, the $\beta$-1,3-glucan linked backbone structure is essential and $\beta$-D-glucopyranosyl units are required for immuno-potentiating activities. Result: In this study, we tested the immunophamacological activities of soluble $\beta$-1,3-glucans and confirmed the following activities: (1) $IFN-{\gamma}$ production in PBMCs in the presence or the absence of PHA, LPS, or IL-18; (2) induction of various cytokines in the spleen and thymus; (3) adjuvant effect on the antibody production; (4) nitrogen oxide synthesis in macrophages; (5) the cytotoxic and antitumor effects on cell lines and ICR mice. Conclusion: These results strongly suggested that $\beta$-1,3-glucans possessed various immuno-pharmacological activities.

The Stem Bark of Kalopanax pictus Exhibits Anti-inflammatory Effect through Heme Oxygenase-1 Induction and NF-${\kappa}B$ Suppression

  • Bang, Soo-Young;Park, Ga-Young;Park, Sun-Young;Kim, Ji-Hee;Lee, Yun-Kyoung;Lee, Sang-Joon;Kim, Young-Hee
    • IMMUNE NETWORK
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    • v.10 no.6
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    • pp.212-218
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    • 2010
  • Backgroud: The stem bark of Kalopanax pictus (KP) has been used in traditional medicine to treat rheumatoidal arthritis, neurotic pain and diabetes mellitus in China and Korea. In this study, the mechanism responsible for anti-inflammatory effects of KP was investigated. Methods: We examined the effects of KP on NO production, nitric oxide synthase (iNOS) and HO-1 expression, NF-${\kappa}B$, Nrf2 and MAPK activation in mouse peritoneal macrophages. Results: The aqueous extract of KP inhibited LPS-induced NO secretion as well as inducible iNOS expression, without affecting cell viability. KP suppressed LPS-induced NF-${\kappa}B$ activation, phosphorylation and degradation of $I{\kappa}B-{\alpha}$, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Furthermore, KP induced HO-1 expression and Nrf2 nuclear translocation. Conclusion: These results suggest that KP has the inhibitory effects on LPS-induced NO production in macrophages through NF-${\kappa}B$ suppression and HO-1 induction.

NLRC4 Inflammasome-Mediated Regulation of Eosinophilic Functions

  • Ilgin Akkaya;Ece Oylumlu;Irem Ozel;Goksu Uzel;Lubeyne Durmus;Ceren Ciraci
    • IMMUNE NETWORK
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    • v.21 no.6
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    • pp.42.1-42.20
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    • 2021
  • Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

Evaluation of Environmental Factors to Determine the Distribution of Functional Feeding Groups of Benthic Macroinvertebrates Using an Artificial Neural Network

  • Park, Young-Seuk;Lek, Sovan;Chon, Tae-Soo;Verdonschot, Piet F.M.
    • Journal of Ecology and Environment
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    • v.31 no.3
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    • pp.233-241
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    • 2008
  • Functional feeding groups (FFGs) of benthic macroinvertebrates are guilds of invertebrate taxa that obtain food in similar ways, regardless of their taxonomic affinities. They can represent a heterogeneous assemblage of benthic fauna and may indicate disturbances of their habitats. The proportion of different groups can change in response to disturbances that affect the food base of the system, thereby offering a means of assessing disruption of ecosystem functioning. In this study, we used benthic macroinvertebrate communities collected at 650 sites of 23 different water types in the province of Overijssel, The Netherlands. Physical and chemical environmental factors were measured at each sampling site. Each taxon was assigned to its corresponding FFG based on its food resources. A multilayer perceptron (MLP) using a backpropagation algorithm, a supervised artificial neural network, was applied to evaluate the influence of environmental variables to the FFGs of benthic macroinvertebrates through a sensitivity analysis. In the evaluation of input variables, the sensitivity analysis with partial derivatives demonstrates the relative importance of influential environmental variables on the FFG, showing that different variables influence the FFG in various ways. Collector-filterers and shredders were mainly influenced by $Ca^{2+}$ and width of the streams, and scrapers were influenced mostly with $Ca^{2+}$ and depth, and predators were by depth and pH. $Ca^{2+}$ and depth displayed relatively high influence on all four FFGs, while some variables such as pH, %gravel, %silt, and %bank affected specific groups. This approach can help to characterize community structure and to ecologically assess target ecosystems.

Mapping Knowledge Structure of Science and Technology Based on University Research Domain Analysis (대학의 연구 영역 분석을 통한 과학 기술 분야의 지식 구조 매핑에 관한 연구)

  • Chung, Young-Mee;Han, Ji-Yeon
    • Journal of the Korean Society for information Management
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    • v.26 no.2
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    • pp.195-210
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    • 2009
  • This study explores knowledge structures of science and technology disciplines using a cocitation analysis of journal subject categories with the publication data of a science & technology oriented university in Korea. References cited in the articles published by the faculty of the university were analyzed to produce MDS maps and network centralities. For the whole university research domain, six clusters were created including clusters of Biology related subjects, Medicine related subjects, Chemistry plus Engineering subjects, and multidisciplinary sciences plus other subjects of multidisciplinary nature. It was found that subjects of multidisciplinary nature and Biology related subjects function as central nodes in knowledge communication network in science and technology. Same analysis procedure was applied to two natural science disciplines and another two engineering disciplines to present knowledge structures of the departmental research domains.

v-Crk Induces Rac-dependent Membrane Ruffling and Cell Migration in CAS-deficient Embryonic Fibroblasts

  • Sung, Bong Hwan;Yeo, Myoung Gu;Oh, Hye Jin;Song, Woo Keun
    • Molecules and Cells
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    • v.25 no.1
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    • pp.131-137
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    • 2008
  • Crk-associated substrate (CAS) is a focal adhesion protein that is involved in integrin signaling and cell migration. CAS deficiency reduces the migration and spreading of cells, both of which are processes mediated by Rac activation. We examined the functions of v-Crk, the oncogene product of the CT10 virus p47gag-crk, which affects cell migration and spreading, membrane ruffling, and Rac activation in CAS-deficient mouse embryonic fibroblasts (CAS-/- MEFs). CAS-/- MEFs showed less spreading than did CAS+/+ MEFs, but spreading was recovered in mutant cells that expressed v-Crk (CAS-/-v-Crk MEF). We observed that the reduction in spreading was linked to the formation of membrane ruffles, which were accompanied by Rac activation. In CAS-/- MEFs, Rac activity was significantly reduced, and Rac was not localized to the membrane. In contrast, Rac was active and localized to the membrane in CAS-/-v-Crk MEFs. Lamellipodia protrusion and ruffle retraction velocities were both reduced in CAS-/- MEFs, but not in CAS-/-v-Crk MEFs. We also found that microinjection of anti-gag antibodies inhibited the migration of CAS-/-v-Crk MEFs. These findings indicate that v-Crk controls cell migration and membrane dynamics by activating Rac in CAS-deficient MEFs.

Two Flexible Loops in Subtilisin-like Thermophilic Protease, Thermicin, from Thermoanaerobacter yonseiensis

  • Jang, Hyeung-Jin;Lee, Chang-Hun;Lee, Weon-Tae;Kim, Yu-Sam
    • BMB Reports
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    • v.35 no.5
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    • pp.498-507
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    • 2002
  • A gene that encodes a thermostable protease, coined thermicin, has been isolated from Thermoanaerobacter yonseiensis that is expressed and characterized in E. coli.. In order to elucidate the molecular characteristics on thermostability of the enzyme, molecular modeling and mutagenesis technology were applied. In the modeling structure, the structural core, including the active site, was well conserved; whereas, the two loop regions were unique when compared to thermitase. The mutant enzyme with the small loop deleted (D190-I196), based on modeling structural information, showed identical enzyme activity. However, when the large loop was deleted (P233-P244), a little lower $K_m$ and even a lower kcat was found. This indicates that the large loop could influence catalytic activity. However, the unfolding temperature ($T_m$), which was determined by a differential-scanning calorimetry for the mutant enzyme deleted the small loop, was $96^{\circ}C$. This is $14^{\circ}C$ lower than that for the parent thermicin. These results suggest that the small loop may play a role in maintaining the proper folding of the enzyme at high temperatures, whereas the large loop might be related to catalysis.

Methionine Analogue Probes Functionally Important Residues in Active Site of Methionyl-tRNA Synthetase

  • Jo, Yeong-Joon;Lee, Sang-Won;Jo, Myung-Kyun;Lee, Jee-Woo;Kang, Mee-Kyoung;Yoon, Jeong-Hyeok;Kim, Sung-Hoon
    • BMB Reports
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    • v.32 no.6
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    • pp.547-553
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    • 1999
  • Aminoacyl-tRNA synthetases are essential enzymes catalyzing the attachment of specific amino acids to cognate tRNAs. In the present work, the substrate analogue L-methionine hydroxamate was used to identify functional residues located in the active site of the E. coli methionyl-tRNA synthetase (MetRS). This compound inhibited bacteria, yeast, and human MetRS activities to a similar degree, suggesting a conserved active site structure and mechanism between MetRSs of different phylogenetic domains. Mutants of the E. coli MetRS resistant to methionine hydroxamate were also isolated. These mutants contained a substitution either at T10, Y15, or Y94. These residues are highly conserved among the different MetRSs and the mutants showed decreased aminoacylation activity, suggesting their functional and structural significances. The putative roles of these residues are discussed on a structural basis.

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Plant development and defense signal network research

  • Paek, Kyung-Hee
    • Proceedings of the Korean Society of Plant Biotechnology Conference
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    • 2005.11a
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    • pp.81-83
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    • 2005
  • The Plant Signaling Network Research Center (SigNet) is a government-funded (by Korea's Ministry of Science and Technology (MOST)/ Korea Science and Engineering Foundation (KOSEF)) research center established at the School of Life Sciences and Biotechnology of Korea University in 2003. The SigNet conducts plant biological studies, especially in the field of developmental and defense biology. The research purpose of SigNet is dissection and analysis of plant development and defense signaling network through multiscientific approaches. Knowledge acquired from SigNet research scientists will provide new integrated view of understanding and potential application of plant development and defense mechanism. The other important mission of the SigNet is nurturing Center of Excellence for future outstanding research scientists of Korea. The SigNet will continue to expend every effort to achieve the goals for the future. Through passionate research endeavor of each laboratory and partnerships within inside and outside laboratories, we will continue to develop world-leading plant research group and to educate new generations of innovative researchers. As the SigNet looks toward the future, the SigNet will try to achieve its mission of research, education and service to the community. And the defense response research of our lab will be presented at later part.

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