• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1107-1112
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• 2009

The aim of this study is to develop and synthesize $5-HT_{1A}$ receptor imaging agents with WAY-100635 moiety and $^{99m}Tc(CO)_3$ core. WAY-100635 is commonly known as $5-HT_{1A}$ antagonist and its labeled compound ([$^{11}C$] WAY-100635) has been used as effective radioligand for imaging brain $5-HT_{1A}$ receptors with PET(Positron Emission Tomography). However, there are several restrictions in using a radioisotope of C-11 and requires for more effective radioisotopes and ligands. In order to produce a structure most similar to WAY-100635, WAY-100635 derivatives containing a cysteine chelator were designed and confirmed by using in silico (Hyperchem). The novel compounds (7a, 7b, 7c) were prepared in five or 7 steps with yields of 16%, 36% and 42%, respectively and radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+}$. The labeling yield was 99% for all the newly synthesized compounds. [$^{99m}Tc(CO)_3$]- WAY-100635 derivatives show a neutral charge which were confirmed by paper electrophoresis.

• Genomics & Informatics
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• v.13 no.2
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• pp.53-59
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• 2015

In developing countries threat of cholera is a significant health concern whenever water purification and sewage disposal systems are inadequate. Vibrio cholerae is one of the responsible bacteria involved in cholera disease. The complete genome sequence of V. cholerae deciphers the presence of various genes and hypothetical proteins whose function are not yet understood. Hence analyzing and annotating the structure and function of hypothetical proteins is important for understanding the V. cholerae. V. cholerae O139 is the most common and pathogenic bacterial strain among various V. cholerae strains. In this study sequence of six hypothetical proteins of V. cholerae O139 has been annotated from NCBI. Various computational tools and databases have been used to determine domain family, protein-protein interaction, solubility of protein, ligand binding sites etc. The three dimensional structure of two proteins were modeled and their ligand binding sites were identified. We have found domains and families of only one protein. The analysis revealed that these proteins might have antibiotic resistance activity, DNA breaking-rejoining activity, integrase enzyme activity, restriction endonuclease, etc. Structural prediction of these proteins and detection of binding sites from this study would indicate a potential target aiding docking studies for therapeutic designing against cholera.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.67.1-67.15
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• 2023

Background: Feline immunodeficiency virus (FIV) causes an acquired immunodeficiency-like syndrome in cats. FIV is latent. No effective treatment has been developed for treatment the infected cats. The first and second generations non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment, nevirapine (NVP) and efavirenz (EFV), and rilpivirine (RPV), were used to investigate the potential of NNRTIs for treatment of FIV infection. Objective: This study aims to use experimental and in silico approaches to investigate the potential of NNRTIs, NVP, EFV, and RPV, for inhibition of FIV reverse transcriptase (FIV-RT). Methods: The FIV-RT and human immunodeficiency virus reverse transcriptase (HIV-RT) were expressed and purified using chromatography approaches. The purified proteins were used to determine the IC₅₀ values with NVP, EFV, and RPV. Surface plasmon resonance (SPR) analysis was used to calculate the binding affinities of NNRTIs to HIV-RT and FIV-RT. The molecular docking and molecular dynamic simulations were used to demonstrate the mechanism of FIV-RT and HIV-RT with first and second generation NNRTI complexes. Results: The IC₅₀ values of NNRTIs NVP, EFV, and RPV against FIV-RT were in comparable ranges to HIV-RT. The SPR analysis showed that NVP, EFV, and RPV could bind to both enzymes. Computational calculation also supports that these NNRTIs can bind with both FIV-RT and HIV-RT. Conclusions: Our results suggest the first and second generation NNRTIs (NVP, EFV, and RPV) could inhibit both FIV-RT and HIV-RT.

• Journal of Life Science
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• v.31 no.10
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• pp.913-921
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• 2021

Limb-girdle muscular dystrophy (LGMD) which is characterized by progressive muscle weakening of the hip and shoulder shows both dominant and recessive inheritances with many pathogenic genes including TTN. This study performed to identify genetic causes of a male patient with late onset (45 years old) autosomal recessive LGMD and atrial flutter. By application of the whole exome sequencing, we identified bi-allelic variants of TTN gene in the patient. One allele had a single missense variant of [c.24124G>T (p.V8042F)], while the other allele consisted of three missense variants of [c.29222G>C (p.R9741P) + c.67490A>G (p.H22497R) + c.75376C>T (p.R25126C)]. The p.V8042F allele was transmitted from his mother, while the other haplotype allele was putatively transmitted from his father. His two unaffected sons had only the p.R9741P. These variants have been not reported or rarely reported in the public human genome databases (1,000 Genome, gnomAD, and KRGDB). Most variants were located in the highly conserved immunoglobulin or fibronectin domains and were predicted to be pathogenic by the in silico analyses. The TTN giant protein plays a key role in muscle assembly, force transmission at the Z-line, and maintenance of resting tension in the I-band. In conclusion, we think that these bi-allelic compound heterozygous mutations may play a role as the genetic causes of the LGMD phenotype.

• Molecules and Cells
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• v.28 no.2
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• pp.111-117
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• 2009

The CHRM3 gene is a member of the muscarinic acetylcholine receptor family that plays important roles in the regulation of fundamental physiological functions. The evolutionary mechanism of exon-acquisition and alternative splicing of the CHRM3 gene in relation to transposable elements (TEs) were analyzed using experimental approaches and in silico analysis. Five different transcript variants (T1, T2, T3, T3-1, and T4) derived from three distinct promoter regions (T1: L1HS, T2, T4: original, T3, T3-1: THE1C) were identified. A placenta (T1) and testis (T3 and T3-1)-dominated expression pattern appeared to be controlled by different TEs (L1HS and THE1C) that were integrated into the common ancestor genome during primate evolution. Remarkably, the T1 transcript was formed by the integration event of the human specific L1HS element. Among the 12 different brain regions, the brain stem, olfactory region, and cerebellum showed decreased expression patterns. Evolutionary analysis of splicing sites and alternative splicing suggested that the exon-acquisition event was determined by a selection and conservation mechanism. Furthermore, continuous integration events of transposable elements could produce lineage specific alternative transcripts by providing novel promoters and splicing sites. Taken together, exon-acquisition and alternative splicing events of CHRM3 genes were shown to have occurred through the continuous integration of transposable elements following conservation.

• International Journal of Advanced Culture Technology
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• v.6 no.4
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• pp.275-283
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• 2018

Cancer show distinct pattern of gene expression when it is compared to normal. This difference results malignant characteristic of cancer. Many cancer drugs are targeting this difference so that it can selectively kill cancer cells. One of the recent demand for personalized treating cancer is retrieving normal tissue from a patient so that the gene expression difference between cancer and normal be assessed. However, in most clinical situation it is hard to retrieve normal tissue from a patient. This is because biopsy of normal tissues may cause damage to the organ function or a risk of infection or side effect what a patient to take. Thus, there is a challenge to estimate normal cell's gene expression where cancers are originated from without taking additional biopsy. In this paper, we propose in-silico based prediction of normal cell's gene expression from gene expression data of a tumor sample. We call this challenge as reverting the cancer into normal. We divided this challenge into two parts. The first part is making a generator that is able to fool a pretrained discriminator. Pretrained discriminator is from the training of public data (9,601 cancers, 7,240 normals) which shows 0.997 of accuracy to discriminate if a given gene expression pattern is cancer or normal. Deceiving this pretrained discriminator means our method is capable of generating very normal-like gene expression data. The second part of the challenge is to address whether generated normal is similar to true reverse form of the input cancer data. We used, cycle-consistent adversarial networks to approach our challenges, since this network is capable of translating one domain to the other while maintaining original domain's feature and at the same time adding the new domain's feature. We evaluated that, if we put cancer data into a cycle-consistent adversarial network, it could retain most of the information from the input (cancer) and at the same time change the data into normal. We also evaluated if this generated gene expression of normal tissue would be the biological reverse form of the gene expression of cancer used as an input.

• Composites Research
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• v.37 no.2
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• pp.132-138
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• 2024

In this study, a molecular dynamics simulation study was performed to investigate the size-dependent electroelastic properties of single-walled boron nitride nanotubes(BNNT). To describe the elasticity and polarization of BNNT under mechanical loading, the Tersoff potential model and rigid ion approximation were adopted. For the prediction of piezoelectric constants and Young's modulus of BNNTs, piezoelectric constitutive equations based on the Maxwell's equation were used to calculate the strain-electric displacement and strain-stress relationships. It was found that the piezoelectric constants of BNNTs gradually decreases as the radius of the tubes increases showing a nonnegligible size effect. On the other hand, the elastic constants of the BNNTs showed opposites trends according to the equivalent geometrical assumption of the tubular structures. To establish the structure-property relationships, localized configurational change of the primarily bonded B-N bonded topology was investigated in detail to elucidate the BNNT curvature dependent elasticity.

• Journal of Life Science
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• v.30 no.10
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• pp.886-895
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• 2020

The development of novel peptide antibiotics with potent antimicrobial activity and anti-inflammatory activity is urgently needed. In a previous work, we performed an in-silico analysis of the Papilio xuthus transcriptome to identify putative antimicrobial peptides and identified several candidates. In this study, we investigated the antibacterial and anti-inflammatory activities of papiliocin 3, which was selected bioinformatically based on its physicochemical properties against bacteria and mouse macrophage Raw264.7 cells. Papiliocin 3 showed antibacterial activities against E. coli and S. aureus without inducing hemolysis and decreased the nitric oxide production of the lipopolysaccharide-induced Raw264.7 cells. Moreover, ELISA and Western blot analysis revealed that papiliocin 3 reduced the expression levels of pro-inflammatory enzymes, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E₂ (PGE₂). In addition, we examined whether papiliocin 3 could inhibit the expression of pro-inflammatory cytokines (interleukin-6 and interleukin-1β) in LPS-induced Raw264.7 cells. We found that papiliocin 3 markedly reduced the expression level of cytokines through the regulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling. We also confirmed that papiliocin 3 binds to bacterial cell membranes via a specific interaction with lipopolysaccharides. Collectively, these findings suggest that papiliocin 3 could be a promising molecule for development as a novel peptide antibiotic.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.2
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• pp.125-132
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• 2006

Objective: In the previous study, we complied the differentially expressed genes during early folliculogenesis. Objective of the present study was to identify downstream target genes of transcription factors (TFs) using bioinformatics for selecting the target TFs among the gene lists for further functional analysis. Materials & Methods: By using bioinformatics tools, constituent domains were identified from database searches using Gene Ontology, MGI, and Entrez Gene. Downstream target proteins/genes of each TF were identified from database searches using TF database ($TRANSFAC^{(R)}$ 6.0) and eukaryotic promoter database (EPD). Results: DNA binding and trans-activation domains of all TFs listed previously were identified, and the list of downstream target proteins/genes was obtained from searches of TF database and promoter database. Based on the known function of identified downstream genes and the domains, 3 (HNF4, PPARg, and TBX2) out of 26 TFs were selected for further functional analysis. The genes of wee1-like protein kinase and p21WAF1 (cdk inhibitor) were identified as potential downstream target genes of HNF4 and TBX2, respectively. PPARg, through protein-protein interaction with other protein partners, acts as a transcription regulator of genes of EGFR, p21WAF1, cycD1, p53, and VEGF. Among the selected 3 TFs, further study is in progress for HNF4 and TBX2, since wee1-like protein kinase and cdk inhibitor may involved in regulating maturation promoting factor (MPF) activity during early folliculogenesis. Conclusions: Approach used in the present study, in silico analysis of downstream target genes, was useful for analyzing list of TFs obtained from high-throughput cDNA microarray study. To verify its binding and functions of the selected TFs in early folliculogenesis, EMSA and further relevant characterizations are under investigation.

• Journal of Life Science
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• v.27 no.10
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• pp.1215-1224
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• 2017

Until now, various oncogenic pathways were idenfied. The accumulation of DNA mutation induces genomic instability in the cell, and it makes cancer. The development of bioinformatics and genomics, to find the precise and reliable biomarker is available. This biomarker could be applied the early-dignosis, prediction and convalescence of cancer. Recently, Transposable elements (TEs) have been attracted as the regulator of genes, because they occupy a half of human genome, and the cause of various diseases. TEs induce DNA mutation, as well as the regulation of gene expression, that makes to cancer development. So, we confirmed the relationship between TEs and colon cancer, and provided the clue for colon cancer biomarker. First, we confirmed long interspersed nuclear element-1 (LINE-1), Alu, and long terminal repeats (LTRs) and their relationship to colon cancer. Because these elements have large composition and enormous effect to the human genome. Interestingly, colon cancer specific patterns were detected, such as the hypomethylation of LINE-1, LINE-1 insertion in the APC gene, hypo- or hypermethylation of Alu, and isoform derived from LTR insertion. Moreover, hypomethylation of LINE-1 in proto-oncogene is used as the biomarker of colon cancer metastasis, and MLH1 mutation induced by Alu is detected in familial or hereditary colon cancer. The genes, effected by TEs, were analyzed their expression patterns by in silico analysis. Then, we provided tissue- and gender-specific expression patterns. This information can provide reliable cancer biomarker, and apply to prediction and diagnosis of colon cancer.