• Nutrition Research and Practice
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• v.10 no.1
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• pp.115-124
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• 2016

BACKGROUND/OBJECTIVES: This is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction. SUBJECTS/METHODS: The experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > $23kg/m^2$) compared to the normality, and in women with low BMR (< 1426.3 kcal/day) compared to high BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P < $1{\times}10^{-4}$). Surveys to estimate energy intake using 24-h recall method for three days and questionnaires for family history, a medical examination, and physical activities were conducted. RESULTS: We found that two NRG3 gene SNPs in the 10q23.1 chromosomal region were highly associated with BMR (rs10786764; $P=8.0{\times}10^{-7}$, rs1040675; $2.3{\times}10^{-6}$) and BMI (rs10786764; $P=2.5{\times}10^{-5}$, rs10786764; $6.57{\times}10^{-5}$). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P < $10{\times}10^{-4}$. Five new loci associated with BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P < $1{\times}10^{-4}$). In the questionnaire investigation, significant differences were found in the number of starvation periods per week, family history of stomach cancer, coffee intake, and trial of weight control in each group. CONCLUSION: We discovered several common BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate.

• Journal of Plant Biotechnology
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• v.2 no.1
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• pp.43-49
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• 2000

An efficient and reliable Agrobacterium transformation procedure based on TDZ (thidiazuron)-induced organogenesis was established and applied to six Brazilian eggp1ant varieties. Optimum transgenic plants recovery was achieved upon the study of the following parameters affecting transformation efficiency, using F-100 variety as a model: i) explant source; ii) pre-culture period; iii) physical state of the pre-culture medium and iv) coculture conditions. The highest frequency of kanamycin-resistant calli derived from leaf explants (5%) was obtained without a pre-culture period and co-cultivation for 24 h in liquid medium followed by five days on solid RM (regeneration medium). For cotyledon explants, best results were achieved upon a pre-culture of 24 h in liquid RM and a co-cultivation period of 24 h in liquid RM followed by three days in solid RM, resulting in a transformation Sequency of 22.7%. Kanamycin-resistant organogenic calli were also obtained from cultivars Emb, Preta Comprida, Round nose Shaded, Campineira and Florida Market. The expression pattern of an epidermis-specific promoter was studied using transformants expressing a chimaeric construct comprised by the promoter Atgrp-5 transcriptionally fused to the coding region of the gus gene. The expression pattern was similar to that previously observed in tobacco and Arabidopsis thaliana, with preferential expression at the epidermis and the stem phloem. These results support the idea that the Atgrp-5 promoter can be used to drive defense genes in these tissues, which are sites of pathogen interaction and spread, in programs for the genetic improvement of eggplant.

• Journal of The Korean Society of Agricultural Engineers
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• v.57 no.3
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• pp.9-19
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• 2015

Internal air temperature of greenhouse is an important variable that can be influenced by the complex interaction between outside weather and greenhouse inside climate. This paper focuses on a data-based model approach to predict internal air temperature of the greenhouse. External air temperature, solar radiation, wind speed and wind direction were measured next to an experimental greenhouse supported by the Electronics and Telecommunications Research Institute and used as input variables for the model. Internal air temperature was measured at the center of three sections of the greenhouse and used as an output variable. The proposed model consisted of a transfer function including the four input variables and tested the prediction accuracy according to the sampling interval of the input variables, the orders of model polynomials and the time delay variable. As a result, a second-order model was suitable to predict the internal air temperature having the predictable time of 20-30 minutes and average errors of less than ${\pm}1K$. Afterwards mechanistic interpretation was conducted based on the energy balance equation, and it was found that the resulting model was considered physically acceptable and satisfied the physical reality of the heat transfer phenomena in a greenhouse. The proposed data-based model approach is applicable to any input variables and is expected to be useful for predicting complex greenhouse microclimate involving environmental control systems.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.10
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• pp.1496-1511
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• 2015

The study aimed to compare the necrotic enteritis (NE)-induced transcriptome differences between the spleens of Marek's disease resistant chicken line 6.3 and susceptible line 7.2 co-infected with Eimeria maxima/Clostridium perfringens using RNA-Seq. Total RNA from the spleens of two chicken lines were used to make libraries, generating 42,736,296 and 42,617,720 usable reads, which were assembled into groups of 29,897 and 29,833 mRNA genes, respectively. The transcriptome changes were investigated using the differentially expressed genes (DEGs) package, which indicated 3,255, 2,468 and 2,234 DEGs of line 6.3, line 7.2, and comparison between two lines, respectively (fold change ${\geq}2$, p<0.01). The transcription levels of 14 genes identified were further examined using qRT-PCR. The results of qRT-PCR were consistent with the RNA-seq data. All of the DEGs were analysed using gene ontology terms, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the DEGs in each term were found to be more highly expressed in line 6.3 than in line 7.2. RNA-seq analysis indicated 139 immune related genes, 44 CD molecular genes and 150 cytokines genes which were differentially expressed among chicken lines 6.3 and 7.2 (fold change ${\geq}2$, p<0.01). Novel mRNA analysis indicated 15,518 novel genes, for which the expression was shown to be higher in line 6.3 than in line 7.2 including some immune-related targets. These findings will help to understand host-pathogen interaction in the spleen and elucidate the mechanism of host genetic control of NE, and provide basis for future studies that can lead to the development of marker-based selection of highly disease-resistant chickens.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7089-7095
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• 2015

Clinical evidence shows that dual inhibition of kinases as well angiogenesis provides ideal therapeutic option in the treatment of medullary thyroid carcinoma (MTC) than inhibiting either of these with the events separately. Although treatment with dual inhibitors has shown good clinical responses in patients with MTC, it has been associated with serious side effects. Some inhibitors are active agents for both angiogenesis or kinase activity. Owing to narrow therapeutic window of established inhibitors, the present study aims to identify high affinity dual inhibitors targeting RET and VEGFR2 respectively for kinase and angiogenesis activity. Established inhibitors like Vandetanib, Cabozantinib, Motesanib, PP121, RAF265 and Sunitinib served as query parent compounds for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. All the parent inhibitors and respective similar compounds were docked against RET and VEGFR2 in order to retrieve high affinity compounds with these two proteins. AGN-PC-0CUK9P PubCID: 59320403 a compound related to PPI21 showed almost equal affinity for RET and VEGFR2 and unlike other screened compounds with no apparent bias for either of the receptors. Further, AGNPC- 0CUK9P demonstrated appreciable interaction with both RET and VEGFR2 and superior kinase activity in addition to showed optimal ADMET properties and pharmacophore features. From our in silico investigation we suggest AGN-PC-0CUK9P as a superior dual inhibitor targeting RET and VEGFR2 with high efficacy which should be proposed for pharmacodynamic and pharmacokinetic studies for improved treatment of MTC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3805-3808
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• 2013

Background: Osteosarcomas have many established risk factors, both genetic and environmental, but by themselves these explain only part of the total cancer incidence. Bisphenol A (BPA) is an environmental estrogen associated with risk of several kinds of tumour. The lysyl oxidase gene (LOX) may also contribute to risk of tumours including osteosarcomas. Here, we investigated possible interactions of BPA and a LOX polymorphism on the risk of osteosarcoma. Method: The present hospital-based case-control study included 106 cancer patients and 112 controls from a Chinese population. Internal burden of BPA exposure was assessed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) method. Genotypes were determined using PCR-RFLP methods. Results: Compared with those in low BPA exposure group, subjects with BPA more than or equal to median value had significant increased risk of osteosarcoma among subjects who carried GC or CC genotypes. A significant interaction with BPA level and the -22G/C polymorphism was observed for osteosarcoma overall, osteosarcoma affecting knee and osteosarcoma affecting hip, as $P_{forinteraction}$ = 0.036 for osteosarcoma overall; $P_{forinteraction}$ = 0.024 for osteosarcoma affecting knee; and $P_{forinteraction}$ = 0.017 for osteosarcoma affecting hip. Conclusions: The results suggest that BPA exposure interacts with the -22G/C polymorphism of the LOX gene to increase the risk of osteosarcoma.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.141-149
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• 2015

"G protein-coupled receptor 40" (GPR40), a receptor for long-chain fatty acids, mediates the stimulation of glucose-induced insulin secretion. We examined the profiles of differential gene expression in GPR40-activated cells treated with linoleic acid, and finally predicted the integral pathways of the cellular mechanism of GPR40-mediated insulinotropic effects. After constructing a GPR40-overexpressing stable cell line (RIN-40) from the rat pancreatic ${\beta}$-cell line RIN-5f, we determined the gene expression profiles of RIN-5f and RIN-40. In total, 1004 genes, the expression of which was altered at least twofold, were selected in RIN-5f versus RIN-40. Moreover, the differential genetic profiles were investigated in RIN-40 cells treated with $30{\mu}M$ linoleic acid, which resulted in selection of 93 genes in RIN-40 versus RIN-40 treated with linoleic acid. Based on the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG, http://www.genome.jp/kegg/), sets of genes induced differentially by treatment with linoleic acid in RIN-40 cells were found to be related to mitogen-activated protein (MAP) kinase- and neuroactive ligand-receptor interaction pathways. A gene ontology (GO) study revealed that more than 30% of the genes were associated with signal transduction and cell proliferation. Thus, this study elucidated a gene expression pattern relevant to the signal pathways that are regulated by GPR40 activation during the acute period. Together, these findings increase our mechanistic understanding of endogenous molecules associated with GPR40 function, and provide information useful for identification of a target for the management of type 2 diabetes mellitus.

• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.155-164
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• 2006

Great inter-variability in drug response and adverse drug reactions is related to inter-variability of drug bioavailability, drug interaction and patient's disease and physyological state that cause change in absorption, distribution, metabolism and excretion of drugs. However, these alone do not sufficiently predict and explain inter-variability in drug response. In recent studies, it is reported that inter-variability in drug response and adverse drug reactions may largely resulted from genetically determined differences in drug absoption, distribution, metabolism and drug target proteins. Especially, the major human drug-metabolizing enzymes such as CYP450, N-acetyl tranferase, thiopurine S-methyl transferase, glutathione S-transferase are identified as the major gene variants that cause inter-individual variability in drug's response and adverse drug reactions. These variations may have most significant implications for those drugs that have narrow therapeutic index and serious adverse drug reactions. Therefore, the genetic variation such as polymorphisms in drug metabolizing enzymes can affect the response of individuals to drugs that are used in the treatment of depression, psychosis, cancer, cardiovascular disorders, ulcer and gastrointestinal disorders, pain and epilepsy, among others. This review describes the pharmacogenomics of the drug metabolizing enzymes associated with the drug response and its clinical applications.

• Journal of Sericultural and Entomological Science
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• v.4
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• pp.63-68
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• 1965

This treatise was carried out to study the hereditary phenomenon of silk lousiness and the interaction of genes related with silk lousiness. It was also studied how to improve the silk lousiness of general raw silk by refining process because the selective process was found as unsatisfactory method. The conclusions reached were as follows. A. Conclusions related with genetic problem. 1. The decreased effects of the lousiness were 11 % in the F$_1$ hybrids. 2. Lousiness was considered to inherit as the incomplete dominance. 3. The effects of the lousiness gene were additive, and the lousiness of raw silk might be influenced by more than two genes. 4. The quantitative characters of cocoons were not genetically correlated with the occurrence of lousiness. 5. Lousiness could not be said to occur more in the heavy-cocoon strains. 6. The microscopic lousiness test of this paper showed the same result of the international exforiation test. B. Conclusions related with lousiness improvement. 1. Raw silk was able to be refined by the employment of 0.2% cationic softener solution for 30 minutes at 95$^{\circ}C$, supressing the occurrence of lousiness. 2. Anionic chemical softener was not available for silk refining process. 3. The above cationic softener refining prosess did not cause any physical defect for the silk fiber. 4. Soap refining process caused silk lousiness easily.

• Journal of Korean Neurosurgical Society
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• v.61 no.1
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• pp.66-74
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• 2018

Objective : The aim of this study was to identify the susceptibility genes responsible for lumbar spondylosis (LS) in Korean patients. Methods : Data from 1427 subjects were made available for radiographic grading and genome wide association studies (GWAS) analysis. Lateral lumbar spine radiographs were obtained and the various degrees of degenerative change were semi-quantitatively scored. A pilot GWAS was performed using the AffymetrixGenome-Wide Human single-nucleotide polymorphisms (SNPs), 500K array. A total of 352228 SNPs were analyzed and the association between the SNPs and case-control status was analyzed by stepwise logistic regression analyses. Results : The top 100 SNPs with a cutoff p-value of less than $3.7{\times}10^{-4}$ were selected for joint space narrowing, while a cutoff p-value of $6.0{\times}10^{-4}$ was applied to osteophytes and the Kellgren-Lawrence (K-L) osteoarthritis grade. The SNPs with the strongest effect on disc space narrowing, osteophytes, and K-L grade were serine incorporator 1 (rs155467, odds ratio [OR]=17.58, $p=1.6{\times}10^{-4}$), stromal interaction molecule 2 (STIM1, rs210781, OR=5.53, $p=5{\times}10^{-4}$), and transient receptor potential cation channel, subfamily C (rs11224760, OR=3.99, $p=4.8{\times}10^{-4}$), respectively. Leucine-rich repeat-containing G protein-coupled receptor 4 was significantly associated with both disc space narrowing and osteophytes (rs1979400, OR=2.01, $p=1.1{\times}10^{-4}$ for disc space narrowing, OR=1.79, $p=3{\times}10^{-4}$ for osteophytes), while zinc finger and BTB domain containing 7C was significantly and negatively associated with both osteophytes and a K-L grade >2 (rs12457004,OR=0.25, $p=5.8{\times}10^{-4}$ and OR=0.27, $p=5.3{\times}10^{-4}$, respectively). Conclusion : We identified SNPs that potentially contribute to the pathogenesis of LS. This is the first report of a GWAS in an Asian population.