• Journal of Integrative Natural Science
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• v.5 no.1
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• pp.22-26
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• 2012

Chemokine receptor antagonists have potential applications in field of drug discovery. Although the chemokine receptors are G-protein-coupled receptors, their cognate ligands are small proteins (8 to 12 kDa), and so inhibiting the ligand/receptor interaction has been challenging. In particular, CCR2 and CCR5 and their ligands have been implicated in the pathophysiology of a number of diseases, including rheumatoid arthritis and multiple sclerosis. Based on their roles in disease, they have been attractive targets for the pharmaceutical industry, targeting both CCR2 and CCR5 could be a useful strategy. Because of the importance of these receptors, providing information regarding the binding site is of prime importance. Herein, we report the comparison of CCR2 of CCR5 binding sites both sequentially as well as structurally. We also urged the importance of crucial residues in the binding site, to facilitate the development of dual antagonists targeting both the receptors. These results could also be useful for the design of novel and potent dual CCR2 and CCR5 antagonists using structure based drug design.

• IMMUNE NETWORK
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• v.16 no.3
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• pp.176-182
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• 2016

CCR3 is a chemokine receptor that mediates the accumulation of allergic inflammatory cells, including eosinophils and Th2 cells, at inflamed sites. The regulatory sequence of the CCR3 gene, contains two Runt-related transcription factor (RUNX) 1 sites and two PU.1 sites, in addition to a functional GATA site for transactivation of the CCR3 gene. In the present study, we examined the effects of the cis-acting elements of RUNX1 and PU.1 on transcription of the gene in EoL-1 eosinophilic cells and Jurkat T cells, both of which expressed functional surface CCR3 and these two transcription factors. Introduction of RUNX1 siRNA or PU.1 siRNA resulted in a modest decrease in CCR3 reporter activity in both cell types, compared with transfection of GATA-1 siRNA. Cotransfection of the two siRNAs led to inhibition in an additive manner. EMSA analysis showed that RUNX1, in particular, bound to its binding motifs. Mutagenesis analysis revealed that all point mutants lacking RUNX1- and PU.1-binding sites exhibited reduced reporter activities. These results suggest that RUNX1 and PU.1 participate in transcriptional regulation of the CCR3 gene.

• Journal of fish pathology
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• v.20 no.3
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• pp.299-306
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• 2007

Cysteine-cysteine chemokine receptor 9 (CCR9) homologue cDNA was isolated from olive flounder leukocyte cDNA library. Olive flounder CCR9 homologue consisted of 1709 bp encoding 367amino acid residues. When compared with other known CCR peptide sequences, the most conserved region of the olive flounder CCR9 peptide is the seven transmembranes. A phylogenetic analysis based on the deduced amino acid sequence showed the homologous relationship between the olive flounder CCR9 sequence and that of Mouse CCR9. The olive flounder CCR9 gene was predominantly expressed in the Peripheral blood leukocytes (PBLs), kidney, spleen, and gills.

• The Plant Pathology Journal
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• v.26 no.4
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• pp.380-385
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• 2010

Suppression subtractive hybridization was used to isolate wound-induced genes from soybean. One of the wound-induced genes, gmwi143 designated as GmCCR, showed high homology with genes encoding cinnamoyl-CoA reductase (CCR; EC 1.2.1.44). Deduced amino acid sequences encoded by GmCCR showed the highest identity (77%) with those of Acacia CCR. There are 2 CCR genes highly homologous to GmCCR in soybean genome based on Phytozome DB analysis. RNA expression of GmCCR was specifically induced by local and systemic wounding, drought, high salinity or by ultraviolet stress. Our study suggests that GmCCR may be involved in resistance mechanism during abiotic stresses in plants.

• The Journal of the Korea Contents Association
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• v.10 no.11
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• pp.371-379
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• 2010

This study analyzes relative efficiency analysis for universities or colleges of Chung Cheong regions using data envelopment analysis. The main results of this study can by summarized as follows. First, in case of efficiency for CCR, the number of efficient universities(CCR value is one) are five universities. and mean value of CCR for universities located in Chungbuk region was most high. Second, the number of efficient colleges(CCR value is one) are three colleges. and mean value of CCR for colleges located in Daejeon region was most high. Third, in case of efficiency for BCC, the number of efficient universities(BCC value is one) are nine universities. and mean value of BCC for universities located in Chungbuk region was most high. Fourth, the number of efficient colleges(BCC value is one) are seven colleges. and mean value of BCC for colleges located in Chungbuk region was most high.

• Journal of the Korean Society for Library and Information Science
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• v.47 no.3
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• pp.275-293
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• 2013

This study conducted comparative analysis of cataloging descriptions and rules in KCR 4 and CCR 2, as follows, for the purpose of seeking understanding of classical materials cataloging rules and networking of oriental historical data cataloging (bibliographical descriptions). First, to compare the general rules, the objects of descriptions and composition of descriptions, recording order, and punctuation and information source of descriptions were analyzed. As a result, KCR 4 is more detailed in terms of author role identifications and information source regulations and CCR2 is more detailed in terms of regulations related to printing and publications and serial publications. Second, to compare the details, the main titles and liability indications, edition details, publication details and format details, and note details. As a result, regarding the description of edition type and publication details, KCR4 has detailed regulations and CCR2 has characteristic summary in terms of note details.

• The Journal of the Korea Contents Association
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• v.17 no.1
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• pp.201-212
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• 2017

This study presented the new evaluation index which can evaluate the discrimination of DEA models. To evaluate the discrimination of DEA models, data were analyzed using importance index as suggested in previous study and the coefficient of variation as suggested in this study for the discrimination evaluation. This study selected the CCR-DEA, BCC-DEA, entropy, bootstrap, super efficiency, and cross efficiency DEA model for the discrimination evaluation and accomplished empirical analysis. In order to grasp the rank correlation of the models, this study implemented the rank correlation analysis between the efficiency of CCR model and BCC model and entropy, bootstrap, super efficiency, and efficiency of the cross efficiency model. The obtained results of this study are as follows. First, the discrimination rank of models using the importance index and the coefficient of variation was shown to be identical. Therefore, the coefficient of variation can be used the discrimination evaluation index of DEA model. Second, the discrimination of the super efficiency model was found to be the highest rank among 4 models according to the analysis of this present study. Third, the highest rank correlation with CCR model was the super efficiency model. In addition, the super efficiency model was found to be the highest rank correlation with BCC model.

• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3429-3443
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• 2013

Chemokine receptor (CCR2) is a G protein-coupled receptor that contains seven transmembrane helices. Recent pharmaceutical research has focused on the antagonism of CCR2 and candidate drugs are currently undergoing clinical studies for the treatment of diseases like arthritis, multiple sclerosis, and type 2 diabetes. In this study, we analyzed the time dependent behavior of CCR2 docked with a potent 4-azetidinyl-1-aryl-cyclohexane (4AAC) derivative using molecular dynamics simulations (MDS) for 20 nanoseconds (ns). Homology modeling of CCR2 was performed and the 4AAC derivative was docked into this binding site. The docked model of selected conformations was then utilized to study the dynamic behavior of the 4AAC enzyme complexes inside lipid membrane. MDS of CCR2-16b of 4AAC complexes allowed us to refine the system since binding of an inhibitor to a receptor is a dynamic process and identify stable structures and better binding modes. Structure activity relationships (SAR) for 4AAC derivatives were investigated and reasons for the activities were determined. Probable binding pose for some CCR2 antagonists were determined from the perspectives of binding site. Initial modeling showed that Tyr49, Trp98, Ser101, Glu291, and additional residues are crucial for 4AAC binding, but MDS analysis showed that Ser101 may not be vital. 4AAC moved away from Ser101 and the hydrogen bonding between 4AAC and Ser101 vanished. The results of this study provide useful information regarding the structure-based drug design of CCR2 antagonists and additionally suggest key residues for further study by mutagenesis.

• Journal of Integrative Natural Science
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• v.6 no.3
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• pp.163-169
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• 2013

The chemokine receptor CCR1 a GPCR super family protein contains seven transmembrane domains. It plays an important role in rheumatoid arthritis, organ transplant rejection, Alzheimer's disease and also causes inflammation. Because of its role in disease processes, antagonism of CCR1 became an attractive therapeutic target. In the current study, we have taken a novel series of recently reported CCR1 antagonist of 1-(4-Phenylpiperazin-1-yl_-2-(1H-Pyrazol-1-yl) ethanone derivatives and performed a HQSAR analysis. The model was developed with Atom (A) and bond (B) parameters and with different set of atom counts to improve the model. The results of HQSAR showed good predictive ability in terms of $r^2$ (0.904) and $q^2$ (0.590) with 0.710 as standard error of prediction and 0.344 as standard error of estimate. The contribution map depicted the atom contribution in inhibitory effect. Compound-14 which was reported to be a highly active compound showed positive atom contribution in three R groups ($R^3$. $R^{5a}$ and $R^{2b}$) in inhibitory effect, which could be the reason why this compound is highly active compound whereas, the lowest active compound-6 showed negative contribution to inhibitory effect.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.29-37
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• 2003

Background: CC chemokine receptor (CCR) 7 and cognate CCR7 ligands, CCL21 (formerly secondary lymphoid tissue chemokine [SLC]) and CCL19 (formerly Epstein-Barr virus-induced molecule 1 ligand chemokine [ELC]), were known to establish microenvironment for the initiation of immune responses in secondary lymphoid tissue. As described previously, coadministration of DNA vaccine with CCR7 ligand-encoding plasmid DNA elicited enhanced humoral and cellular immunity via increasing the number of dendritic cells (DC) in secondary lymphoid tissue. The author hypothesized here that CCR7 ligand DNA could effectively expand memory CD4+ T cells to protect from viral infection likely via increasing DC number. Methods: To evaluate the effect of CCR7 ligand DNA on the expansion of memory CD4+ T cells, DO11.10.BALB/c transgenic (Tg)-mice, which have highly frequent ovalbumin $(OVA)_{323-339}$ peptide-specific CD4+ T cells, were used. Tg-mice were previously injected with CCR7 ligand DNA, then immunized with $OVA_{323-339}$ peptide plus complete Freund's adjuvant. Subsequently, memory CD4+ T cells in peripheral blood lymphocytes (PBL) were analyzed by FACS analysis for memory phenotype ($CD44^{high}$ and CD62 $L^{low}$) at memory stage. Memory CD4+ T cells recruited into inflammatory site induced with OVA-expressing virus were also analyzed. Finally, the protective efficacy against viral infection was evaluated. Results: CCR7 ligand DNA-treated Tg-mice showed more expanded $CD44^{high}$ memory CD4+ T cells in PBL than control vector-treated animals. The increased number of memory CD4+ T cells recruited into inflammatory site was also observed in CCR7 ligand DNA-treated Tg-mice. Such effectively expanded memory CD4+ T cell population increased the protective immunity against virulent viral infection. Conclusion: These results document that CCR7 and its cognate ligands play an important role in intracellular infection through establishing optimal memory T cell. Moreover, CCR7 ligand could be useful as modulator in DNA vaccination against viral infection as well as cancer.