Full-length genomic analysis of porcine G9P[23] and G9P[7] rotavirus strains isolated from pigs with diarrhea in South Korea

Kim, H.H.,Matthijnssens, J.,Kim, H.J.,Kwon, H.J.,Park, J.G.,Son, K.Y.,Ryu, E.H.,Kim, D.S.,Lee, W.S.,Kang, M.I.,Yang, D.K.,Hyun, B.H.,Park, S.I.,Park, S.J.,Cho, K.O. Elsevier Science 2012 INFECTION GENETICS AND EVOLUTION Vol.12 No.7

Group A rotaviruses (RVAs) are agents causing severe gastroenteritis in infants and young animals. G9 RVA strains are believed to have originated from pigs. However, this genotype has emerged as the fifth major human RVA genotype worldwide. To better understand the relationship between human and porcine RVA strains, complete RVA genome data are needed. For human RVA strains, the number of complete genome data have grown exponentially. However, there is still a lack of complete genome data on porcine RVA strains. Recently, G9 RVA strains have been identified as the third most important genotype in diarrheic pigs in South Korea in combinations with P[7] and P[23]. This study is the first report on complete genome analyses of 1 G9P[7] and 3 G9P[23] porcine RVA strains, resulting in the following genotype constellation: G9-P[7]/P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1. By comparisons of these genotype constellations, it was revealed that the Korean G9P[7] and G9P[23] RVA strains possessed a typical porcine RVA backbone, similar to other known porcine RVA strains. However, detailed phylogenetic analyses revealed the presence of intra-genotype reassortments among porcine RVA strains in South Korea. Thus, our data provide genetic information of G9 RVA strains increasingly detected in both humans and pigs, and will help to establish the role of pigs as a source or reservoir for novel human RVA strains.

A genetic variation in microRNA target site of <i>KRT81</i> gene is associated with survival in early-stage non-small-cell lung cancer

Lee, S. Y.,Choi, J. E.,Jeon, H. S.,Hong, M. J.,Choi, Y. Y.,Kang, H. G.,Yoo, S. S.,Lee, E. B.,Jeong, J. Y.,Lee, W. K.,Lee, J.,Cha, S. I.,Kim, C. H.,Kim, Y. T.,Jheon, S.,Son, J. W.,Park, J. Y. Oxford University Press 2015 ANNALS OF ONCOLOGY Vol.26 No.6

<P>In this study, <I>KRT81</I> rs3660G>C was associated with survival of patients with NSCLC after surgical resection. Mechanistic study suggested that the G-to-C change caused reduced binding efficiency of miRNA, leading to decreased translational repression, thereby increased <I>KRT81</I> expression. The <I>KRT81</I> rs3660G>C may be a useful prognostic biomarker in early-stage NSCLC patients.</P><P><B>Background</B></P><P>MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA–mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC).</P><P><B>Methods</B></P><P>Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (<I>n</I> = 479). <I>Renilla</I> luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs.</P><P><B>Results</B></P><P>Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, <I>KRT81</I> rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50–0.85; <I>P</I> = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of <I>KRT81</I> in tumor tissues.</P><P><B>Conclusion</B></P><P>The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.</P>

Effects of Dietary Levels of Glycine, Threonine and Protein on Threonine Efficiency and Threonine Dehydrogenase Activity in Hepatic Mitochondria of Chicks

Lee, C.W.,Cho, I.J.,Lee, Y.J.,Son, Y.S.,Kwak, I.,Ahn, Y.T.,Kim, S.C.,An, W.G. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.1

This study was carried out to evaluate the relationship between threonine (Thr) efficiency and Thr dehydrogenase (TDG) activity as an indicator of Thr oxidation on chicks fed with levels of diets (CP [17.5% and 21.5%] and Thr [3.8 and 4.7 g/100 g CP]; glycine [Gly][0.64% and 0.98%] and true digestible Thr [dThr] [0.45% and 0.60%]). Calculation of the Thr efficiency was based on N-balance data and an exponential N-utilization model, and TDG activity was determined as accumulation of aminoacetone and Gly during incubation of hepatic mitochondria. This study found that in the liver of chicks who received a diet containing up to 0.79% Thr (4.7 g Thr/100 g of CP) in the 17.5% CP diet, no significant (p>0.05) effect on TDG activity was observed. However, significantly (p = 0.014) increased TDG activity was observed with a diet containing 21.5% CP (4.7 g Thr/100 g of CP) and the efficiency of Thr utilization showed a significant (p = 0.001) decrease, indicating the end of the Thr limiting range. No significant (p>0.05) effect on the total TDG activity and accumulation of Gly was observed with addition of Gly to a diet containing 0.45% dThr. In addition, addition of Gly to a diet containing 0.60% dThr also did not result in a change in accumulation of Gly. Due to an increase in accumulation of aminoacetone, an elevated effect on total TDG activity was also observed. No significant (p>0.05) reduction in the efficiency of Thr utilization was observed after addition of Gly at the level of 0.45% dThr. However, significantly (p<0.001) reduced efficiency of Thr utilization was observed after addition of Gly at the level of 0.60% dThr. Collectively, we found that TDG was stimulated not only by addition of Thr and protein to the diet, but also by addition of Gly, and efficiency of Thr utilization was favorably affected by addition of Gly at the level near to the optimal Thr concentration. In addition, no metabolic requirement of Gly through the TDG pathway was observed with almost the same accumulation of Gly and a slight increase in TDG activity by addition of Gly. Thus, our findings suggest that determination of TDG activity and parameter of efficiency of Thr utilization may be useful for evaluation of dietary Thr level.

Genetic diversity of the VP7, VP4 and VP6 genes of Korean porcine group C rotaviruses

Jeong, Y.J.,Matthijnssens, J.,Kim, D.S.,Kim, J.Y.,Alfajaro, M.M.,Park, J.G.,Hosmillo, M.,Son, K.Y.,Soliman, M.,Baek, Y.B.,Kwon, J.,Choi, J.S.,Kang, M.I.,Cho, K.O. Elsevier Scientific Pub. Co 2015 Veterinary microbiology Vol.176 No.1

Porcine group C rotaviruses (RVCs) are considered important pathogens due to their economic impact on pig industry and may also cross the host species barrier toward humans. Unlike RVA, however, genetic and phylogenetic data on RVCs from pigs and other host species are scarce. In the present study, full-length ORF sequences of 26 VP7, 9 VP4 and 9 VP6 genes of Korean porcine RVC strains were compared with those of other known RVC strains by phylogenetic analyses and pairwise identity frequency graphs. Applying the established 85% nucleotide identity cut-off value for RVC VP7 classification, the 26 Korean porcine RVC strains belonged to the G1, G3, G6 and G7 genotypes. Although more complete RVC VP4 sequences are warranted before a definitive cut-off value could be determined, a provisional 83% nucleotide cut-off value proposed for RVC VP4 classification resulted in 7 P-genotypes, 5 of which possessed porcine RVC strains. A 90% nucleotide cut-off value for VP6 divided RVC strains into 7 I-genotypes, 5 of which had porcine RVC strains. G/P/I-genotype comparisons suggested the occurrence of rather frequent reassortment events among Korean porcine RVC strains, and strong geographical differences in the distribution of RVC G-genotypes worldwide. Our data indicate that a large genetic diversity exists among porcine RVC strains. For the final genotype determination of each gene segment, more intensified epidemiological studies on animal and human RVC strains throughout the world are needed.

Genomic Common Data Model for Seamless Interoperation of Biomedical Data in Clinical Practice: Retrospective Study

Shin, Seo Jeong,You, Seng Chan,Park, Yu Rang,Roh, Jin,Kim, Jang-Hee,Haam, Seokjin,Reich, Christian G,Blacketer, Clair,Son, Dae-Soon,Oh, Seungbin,Park, Rae Woong JMIR Publications 2019 Journal of medical Internet research Vol.21 No.3

<P><B>Background</B></P><P>Clinical sequencing data should be shared in order to achieve the sufficient scale and diversity required to provide strong evidence for improving patient care. A distributed research network allows researchers to share this evidence rather than the patient-level data across centers, thereby avoiding privacy issues. The Observational Medical Outcomes Partnership (OMOP) common data model (CDM) used in distributed research networks has low coverage of sequencing data and does not reflect the latest trends of precision medicine.</P><P><B>Objective</B></P><P>The aim of this study was to develop and evaluate the feasibility of a genomic CDM (G-CDM), as an extension of the OMOP-CDM, for application of genomic data in clinical practice.</P><P><B>Methods</B></P><P>Existing genomic data models and sequencing reports were reviewed to extend the OMOP-CDM to cover genomic data. The Human Genome Organisation Gene Nomenclature Committee and Human Genome Variation Society nomenclature were adopted to standardize the terminology in the model. Sequencing data of 114 and 1060 patients with lung cancer were obtained from the Ajou University School of Medicine database of Ajou University Hospital and The Cancer Genome Atlas, respectively, which were transformed to a format appropriate for the G-CDM. The data were compared with respect to gene name, variant type, and actionable mutations.</P><P><B>Results</B></P><P>The G-CDM was extended into four tables linked to tables of the OMOP-CDM. Upon comparison with The Cancer Genome Atlas data, a clinically actionable mutation, p.Leu858Arg, in the <I>EGFR</I> gene was 6.64 times more frequent in the Ajou University School of Medicine database, while the p.Gly12Xaa mutation in the <I>KRAS</I> gene was 2.02 times more frequent in The Cancer Genome Atlas dataset. The data-exploring tool GeneProfiler was further developed to conduct descriptive analyses automatically using the G-CDM, which provides the proportions of genes, variant types, and actionable mutations. GeneProfiler also allows for querying the specific gene name and Human Genome Variation Society nomenclature to calculate the proportion of patients with a given mutation.</P><P><B>Conclusions</B></P><P>We developed the G-CDM for effective integration of genomic data with standardized clinical data, allowing for data sharing across institutes. The feasibility of the G-CDM was validated by assessing the differences in data characteristics between two different genomic databases through the proposed data-exploring tool GeneProfiler. The G-CDM may facilitate analyses of interoperating clinical and genomic datasets across multiple institutions, minimizing privacy issues and enabling researchers to better understand the characteristics of patients and promote personalized medicine in clinical practice.</P>

FABRICATION AND ELECTRICAL PROPERTIES OF PZT-PVDF 0-3 TYPE COMPOSITE FILM

Son, Y. H.,Kweon, S. Y.,Kim, S. J.,Kim, Y. M.,Hong, T. W.,Lee, Y. G. Taylor Francis 2007 Integrated ferroelectrics Vol.88 No.1

<P> A film speaker was fabricated with 0-3 type piezoelectric composite. The 0-3 type composite was developed to incorporate the advantages of both ceramic and polymer. The pastes of PZT-PVDF composite were made with various mixing ratio. The paste was printed by conventional screen-printing method on ITO (Indium Tin Oxide) bottom electrode which was deposited on PET (polyethylene terephthalate) polymer film. The prepared composite film was about 80 μm in thickness. After printing the top-electrode of silver-paste, 4 kV/mm of DC field was applied at 120°C for an hour to align the electric dipole in the 0-3 composite film. The piezoelectric charge constant of d33 was increased with increasing the PZT weight percent. The maximum value was 24 pC/N at 70 wt% of PZT. But the piezoelectric voltage constant of g33 had the maximum value about 32 mV · m/N at 65 wt% of PZT. The SPL (Sound Pressure Level) of the speaker fabricated with the 65:35 composite film was tested at various driving voltages of 1 ∼ 100Vrms. The SPL was saturated at the driving voltage of 70Vrms and the value was about 68 dB at 1 kHz.</P>

Pinoresinol-4,4'-di-O-β-d-glucoside from Valeriana officinalis root stimulates calcium mobilization and chemotactic migration of mouse embryo fibroblasts

Do, K.H.,Choi, Y.W.,Kim, E.K.,Yun, S.J.,Kim, M.S.,Lee, S.Y.,Ha, J.M.,Kim, J.H.,Kim, C.D.,Son, B.G.,Kang, J.S.,Khan, I.A.,Bae, S.S. G. Fischer 2009 Phytomedicine Vol.16 No.6

Lignans are major constituents of plant extracts and have important pharmacological effects on mammalian cells. Here we showed that pinoresinol-4,4'-di-O-β-d-glucoside (PDG) from Valeriana officinalis induced calcium mobilization and cell migration through the activation of lysophosphatidic acid (LPA) receptor subtypes. Stimulation of mouse embryo fibroblast (MEF) cells with 10μM PDG resulted in strong stimulation of MEF cell migration and the EC<SUB>50</SUB> was about 2μM. Pretreatment with pertussis toxin (PTX), an inhibitor of G<SUB>i</SUB> protein, completely blocked PDG-induced cell migration demonstrating that PDG evokes MEF cell migration through the activation of the G<SUB>i</SUB>-coupled receptor. Furthermore, pretreatment of MEF cells with Ki16425 (10μM), which is a selective antagonist for LPA<SUB>1</SUB> and LPA<SUB>3</SUB> receptors, completely blocked PDG-induced cell migration. Likewise, PDG strongly induced calcium mobilization, which was also blocked by Ki16425 in a dose-dependent manner. Prior occupation of the LPA receptor with LPA itself completely blocked PDG-induced calcium mobilization. Finally, PDG-induced MEF cell migration was attenuated by pretreatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor such as LY294002. Cells lacking downstream mediator of PI3K such as Akt1 and Akt2 (DKO cells) showed loss of PDG-induced migration. Re-expression of Akt1 (but not Akt2) completely restored PDG-induced DKO cell migration. Given these results, we conclude that PDG is a strong inducer of cell migration. We suggest that the pharmacological action of PDG may occur through the activation of an LPA receptor whereby activation of PI3K/Akt signaling pathway mediates PDG-induced MEF cell migration.

A Case of Inflammatory Metastatic Carcinoma of the Breast

Cho, C. G Korean Dermatological Association 1998 Annals of Dermatology Vol.10 No.1

A novel imidazopyridine derivative, HS-106, induces apoptosis of breast cancer cells and represses angiogenesis by targeting the PI3K/mTOR pathway

Li, G.Y.,Jung, K.H.,Lee, H.,Son, M.K.,Seo, J.,Hong, S.W.,Jeong, Y.,Hong, S.,Hong, S.S. Elsevier Science Ireland 2013 Cancer letters Vol.329 No.1

Abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is an essential step for the formation and growth of tumors in humans. HS-106 is an imidazopyridine derivative that inhibits the kinase activity of PI3K by binding to the ATP-binding cleft. We found that this compound suppressed breast cancer cell proliferation and induced apoptosis by specifically inhibiting the activity of target proteins in the PI3K/Akt/mTOR signaling pathway. Cell cycle analysis revealed that treatment with HS-106 resulted in cell cycle arrest at the G<SUB>2</SUB>/M phase due to up-regulation of p-cdc25 and down-regulation of cyclin B1. Also, HS-106 induced apoptosis by increasing the levels of cleaved caspase-3 and cleaved PARP. In addition, chromatin condensation and apoptotic bodies were detected in HS-106-treated breast cancer cells. Furthermore, HS-106 decreased the expression of hypoxia-inducible factor 1α (HIF-1α), and inhibited tube formation and migration of human umbilical vein endothelial cells (HUVECs) in vitro and blood vessel formation in an in vivo Matrigel plug assay. These results show that HS-106 may be an effective novel therapeutic candidate in clinical trials as a potential treatment for human breast cancers or other advanced malignancies with aberrant PI3K/Akt/mTOR signaling.

Yorkshire 수퇘지의 경제형질 및 선발지수에 대한 검정종료월 보정계수 개발

이정규,황선숙,손창준,박중양 한국동물자원과학회 2001 한국축산학회지 Vol.43 No.4

The present study was undertaken to evaluate environmental effects on average daily gain(ADG), backfat thickness and feed/gain and selection index and thereby to derive correction factors for above traits and index, using 5,048 Yorkshire boars that had been performance-tested from January, 1993, through December, 1999, at the Korea Swine Test Station. The results obtained were as follows; Each test year and month was called according to the last day of the performance test. 1. Effects of test year and test month were significant(P$lt;0.01) in all the traits that had been included in the present study. 2. The ADG and selection index increased each year, whereas backfat thickness decreased. Feed/gain, albeit significantly affected by the test year, did not exhibit any apparent temporal trend. 3. The ADG was greatest between March and June(942.45∼955.89g); backfat thickness was lowest during August, September and November(1.302∼1.314㎝); feed/gain was lowest during March, April and June(2.261∼2.272); and the selection index also was superior during March, April and June(225.07∼226.69) to those during the rest of the year. 4. The selected ratio was estimated to range from 0.782 for April to 0.801 for July when the traits and selection index were adjusted in an additive mode, whereas in a multiplicative adjustment mode, it ranged from 0.733(February) to 0.808(July). 5. By the additive mode analysis, the test month-adjusted ADG ranged from 885.79g(December) to 900.33g(August); backfat thickness from 1.332㎝(April) to 1.339(July and December); feed/gain from 2.320(April) to 2.346(September and October); and selection index from 216.94(October) to 219.09(March). 6. By the multiplicative mode analysis, the adjusted ADG ranged from 886.58g(December) to 903.65g(August); backfat thickness from 1.332㎝(April) to 1.339(July, September and December); feed/gain from 2.320(April) to 2.348(October); and selection index from 217.03(October) to 219.15(March). 7. Rank correlation coefficients between unadjusted and adjusted values were satisfactorily high in all the examined traits and index; they, after multiplicative and additive adjustments, respectively, were 0.903 and 0.900 in ADG, 0.987 and 0.987 in backfat thickness, 0.970 and 0.971 in feed/gain and 0.935 and 0.936 in selection index. 8. The rank correlation coefficient was 1.000 between the selection index which had been calculated using the additive mode-adjusted ADG, backfat thickness and feed/gain and that which had been one-step-adjusted by the additive mode.