• Molecules and Cells
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• v.25 no.4
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• pp.545-552
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• 2008

A hepadnaviruses replicates its DNA genome via reverse transcription of an RNA template (pregenomic RNA or pgRNA), which has a cap structure at the 5' end and a poly(A) tail at the 3' end. We have previously shown that the 5' cap is indispensable for encapsidation of the pgRNA. A speculative extension of the above finding is that the cap contributes to encapsidation via its interaction with the poly(A) tail, possibly involving eIF4E-eIF4G-PABP interaction. To test this hypothesis, poly(A)-less pgRNAs were generated via cleavage by a cis-acting hepatitis delta virus ribozyme sequence. We found that accumulation of the poly(A)-less pgRNA was markedly diminished, mostly likely due to its reduced stability. Importantly, however, the remaining poly(A)-less pgRNAs were nonetheless encapsidated and reverse transcribed normally when the reduced stability was taken account. Our finding clearly contradicts the notion that the poly(A) tail has any function in encapsidation and viral reverse transcription.

• Journal of Life Science
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• v.9 no.1
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• pp.76-83
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• 1999

Mammalial expression vectors containing GRP94, BiP, ERp72, and PDI, were introduced into FRTL5 cells. Transfected cells were selected by neomycin resistance for exogenously overexpressed proteins in the ER. The use of a reducible cross-linker, DSP, markedly improved the ability to detect noncovalent interactions of PDI, BiP and GRP94 with newly-synthesized thyroglobulin. Under normal conditions, GRP94 was found to associate transiently with early Tg folding intermediates, displaying interaction kinetics similar to those reported for another ER chaperones of BiP.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.380-387
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• 2017

The foamy viruses are currently considered essential for development as vectors for gene delivery. Previous studies demonstrated that prototype foamy virus (PFV) can infect and replicate prevalently in a variety of cell types for its exclusive replication strategy. However, the virus-host interaction, especially PFV-transportin3 (TNPO3), is still poorly understood. In our investigation of the role of TNPO3 in PFV infection, we found lower virus production in TNPO3 knockdown (KD) cells compared with wild-type 293T cells. PCR analysis revealed that viral DNAs were mostly altered to circular forms: both 1-long terminal repeat (1-LTR) and 2-LTR in TNPO3 KD cells. We therefore suggest that TNPO3 is required for successful PFV replication, at least at/after the nuclear entry step of viral DNA. These findings highlight the obscure mysteries of PFV-host interaction and the requirement of TNPO3 for productive infection of PFV in 293T cells.

• Genomics & Informatics
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• v.12 no.2
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• pp.64-70
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• 2014

Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.

• Journal of Preventive Medicine and Public Health
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• v.42 no.6
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• pp.360-370
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• 2009

Genetic factors clearly play a role in carcinogenesis, but migrant studies provide unequivocal evidence that environmental factors are critical in defining cancer risk. Therefore, one may expect that the lower availability of substrate for biochemical reactions leads to more genetic changes in enzyme function; for example, most studies have indicated the variant MTHFR genotype 677TT is related to biomarkers, such as homocysteine concentrations or global DNA methylation particularly in a low folate diet. The modification of a phenotype related to a genotype, particularly by dietary habits, could support the notion that some of inconsistencies in findings from molecular epidemiologic studies could be due to differences in the populations studied and unaccounted underlying characteristics mediating the relationship between genetic polymorphisms and the actual phenotypes. Given the evidence that diet can modify cancer risk, gene-diet interactions in cancer etiology would be anticipated. However, much of the evidence in this area comes from observational epidemiology, which limits the causal inference. Thus, the investigation of these interactions is essential to gain a full understanding of the impact of genetic variation on health outcomes. This report reviews current approaches to gene-diet interactions in epidemiological studies. Characteristics of gene and dietary factors are divided into four categories: one carbon metabolism-related gene polymorphisms and dietary factors including folate, vitamin B group and methionines; oxidative stress-related gene polymorphisms and antioxidant nutrients including vegetable and fruit intake; carcinogen-metabolizing gene polymorphisms and meat intake including heterocyclic amins and polycyclic aromatic hydrocarbon; and other gene-diet interactive effect on cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2745-2749
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• 2015

Objective: To study the PLCE1 gene rs2274223 polymorphism with regard to esophageal cancer and its interaction with diet, lifestyle, psychological and environmental factors in Southwest Shandong province. Materials and Methods: A case series study (case-case) was conducted. Questionnaire data were collected and 3 ml-5ml venous blood was drawn for DNA extraction among the qualified research subjects. PLCE1 gene polymorphism was detected after PCR amplification of DNA. SPSS 13.0 software was used for statistical analysis of the data. Results: The three genotypes A/A, A/G and G/G PLCE1 gene rs2274223 was 31, 16 and 4 cases, accounting for 60.8%, 31.4%, 0.08% respectively. The difference of three genotypes (AA/GA/GG) proportion between negative and positive family history of patients was statistically significant, ${\chi}^2=6.213$, p=0.045. There was no statistically significant relationship between PLCE1 gene rs2274223 polymorphism and smoking, drinking, ${\chi}^2=0.119$, p=0.998, and ${\chi}^2=1.727$, p=0.786. There was no linkage of the three rs2274223 PLCE1 gene genotypes (AA/GA/GG) proportion with eating fried, pickled, hot, mildew, overnight, smoked, excitant food, eat speed, salt taste or not (p>0.05). or with living environment pollution and nine risk factors of occupational exposure (p>0.05). There was no statistically significant difference in TS scores between different genotype of rs2274223 PLCE1 gene. Conclusions: The PLCE1 rs2274223 polymorphism has a relationship with family history of esophageal cancer, but does not have any significant association with age, gender, smoking, alcohol drinking, food hygiene, eating habits, living around the environment and occupation in cases.

• Journal of Life Science
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• v.28 no.4
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• pp.488-495
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• 2018

The p53 gene plays a critical role in the transcriptional regulation of cellular response to stress, DNA damage, hypoxia, and tumor development. Keeping in mind the recently discovered manifold physiological functions of p53, its involvement in the regulation of cancer is not surprising. In about 50% of all human cancers, inactivation of p53's protein function occurs either through mutations in the gene itself or defects in the mechanisms that activate it. This disorder plays a crucial role in tumor evolution by allowing the evasion of a p53-dependent response. Many recent studies have focused on directly targeting p53 mutants by identifying selective, small molecular compounds to deplete them or to restore their tumor-suppressive function. These small molecules should effectively regulate various interactions while maintaining good drug-like properties. Among them, the discovery of the key p53-negative regulator, MDM2, has led to the design of new small molecule inhibitors that block the interaction between p53 and MDM2. Some of these small molecule compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, more personalized anti-carcinogenic medicines. Here, we review the structural and functional consequences of wild type and mutant p53 as well as the development of therapeutic agents that directly target this gene, and compounds that inhibit the interaction between it and MDM2.

• Journal of the Korean Institute of Intelligent Systems
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• v.22 no.2
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• pp.192-197
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• 2012

With the advent of DNA microarray technologies, researches for disease diagnosis has been actively in progress. In typical experiments using microarray data, problems such as the large number of genes and the relatively small number of samples, the inherent measurement noise and the heterogeneity across different samples are the cause of the performance decrease. To overcome these problems, a new method using functional modules (e.g. signaling pathways) used as markers was proposed. They use the method using an activity of pathway summarizing values of a member gene's expression values. It showed better classification performance than the existing methods based on individual genes. The activity calculation, however, used in the method has some drawbacks such as a correlation between individual genes and each phenotype is ignored and characteristics of individual genes are removed. In this paper, we propose a method based on the ensemble classifier. It makes weak classifiers based on feature vectors using subsets of genes in selected pathways, and then infers the final classification result by combining the results of each weak classifier. In this process, we improved the performance by minimize the search space through a filtering process using gene-gene interaction information and the mRMR filter. We applied the proposed method to a classifying the lung cancer, it showed competitive classification performance compared to existing methods.

• The Plant Pathology Journal
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• v.30 no.4
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• pp.375-383
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• 2014

Fungi tolerate exposure to various abiotic stresses, including cytotoxic compounds and fungicides, via their ATP-driven efflux pumps belonging to ATP-binding cassette (ABC) transporters. To clarify the molecular basis of interaction between the fungus and various abiotic stresses including fungicides, we constructed a cDNA library from germinated conidia of Colletotrichum acutatum, a major anthracnose pathogen of pepper (Capsicum annum L.). Over 1,000 cDNA clones were sequenced, of which single clone exhibited significant nucleotide sequence homology to ABC transporter genes. We isolated three fosmid clones containing the C. acutatum ABC1 (CaABC1) gene in full-length from genomic DNA library screening. The CaABC1 gene consists of 4,059 bp transcript, predicting a 1,353-aa protein. The gene contains the typical ABC signature and Walker A and B motifs. The 5'-flanking region contains a CAAT motif, a TATA box, and a Kozak region. Phylogenetic and structural analysis suggested that the CaABC1 is a typical ABC transporter gene highly conserved in various fungal species, as well as in Chromista, Metazoans, and Viridiplantae. We also found that CaABC1 was up-regulated during conidiation and a minimal medium condition. Moreover, CaABC1 was induced in iprobenfos, kresoxim-methyl, thiophanate-methyl, and hygromycin B. These results demonstrate that CaABC1 is necessary for conidiation, abiotic stress, and various fungicide resistances. These results will provide the basis for further study on the function of ABC transporter genes in C. acutatum.

• Journal of Society of Preventive Korean Medicine
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• v.14 no.2
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• pp.1-12
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• 2010

The individual differences in disease development and susceptibility have been researched primarily on the subject of genes, environment or the interaction between genes and the environment respectively. However, there have been limitations in explaining complex diseases, and the differences in health and diseases in monozygotic and dizygotic twins. Fortunately, thanks to active research on the relationship between genes and the environment, and epigenetics, there has been much progress in the understanding of body's reactions and changes. Epigenetics is referred to as a study of gene expression through the interactions of DNA methylation, chromatin's histone and the change of structure in tail, RNA editing without any change in DNA sequence. In this paper, we introduce the basic concepts and mechanisms of epigenetics. The result of the epigenetics is heritable ; can regulate gene expressions ; is reversible ; and has many variable forms depending on cell types. The influences of epigenetics occur throughout life, but it is mainly determined in utero during early pregnancies. Diseases occur or the risk rises if these influences continue after birth until adult life when problems occur in excess/lack of nutrition, environmental plasticity, or already inputted data. Therefore, there is a need for change and innovation, especially in interest and investment in health education for young women near pregnancies and correct treatment of epigenetic-related diseases.