• Asian-Australasian Journal of Animal Sciences
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• 제31권9호
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• pp.1387-1392
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• 2018

Objective: In a nucleus breeding scheme, the sire of dam's pathway plays an important role in producing genetic improvement. Selection proportion is the key parameter for predicting selection intensity, through truncating the normal distribution. Semen sexing using flow cytometry reduces the number of vials of sperm that can be obtained from a proved bull. In addition, a lower fertility of this kind of sperm is expected because of the lower sperm dosage in sex sorted semen. Both of these factors could affect the selection proportion in the sire of dam's pathway ($p_{SD}$). Methods: In the current study, through a deterministic simulation, effect of utilizing sex sorted semen on selection ($p_{SD}$) was investigated in three different strategies including 1: continuous use of sex sorted semen in heifers (CS), 2: the use of sex sorted semen for the first two (S2) and 3: the first (S1) inseminations followed by conventional semen. Results: Results indicated that the use of sex sorted semen has a negative impact on the sire of dams (SD) pathway due to increase in selection proportion. Consequently selection intensity was decreased by 10.24 to 20.57, 6.38 to 8.87 and 3.76 to 6.25 percent in the CS, S2, and S1 strategies, respectively. Conclusion: Considering the low effect of sexed semen on genetic improvement in dam pathways, it is necessary to consider the joint effect of using sex sorted semen on the sire and dams pathway to estimate about the real effect of sexed semen on genetic improvement in a nucleus breeding scheme.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2157-2162
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• 2012

Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.

• Journal of Korean Neurosurgical Society
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• 제63권4호
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• pp.444-454
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• 2020

Objective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-α/IFN-β receptor/STAT and IFN-γ/IFN-γ receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-α and IFN-γ while no change on the hypoxia-inducible factor-1α and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/STAT signaling triggered by IFN-α and IFN-γ.

• KSBB Journal
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• 제29권4호
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• pp.244-249
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• 2014

Biosynthesis pathway of medium-chain-length (MCL) polyhydroxyalkanoates (PHA) from fatty acid ${\beta}$-oxidation pathway was constructed in recombinant Escherichia coli by introducing the Pseudomonas sp. 61-3 PHA synthase gene (phaC2) and the maoC genes from Pseudomonas putida, Sinorhizobium meliloti, and Ralstonia eutropha. The metabolic link between fatty acid ${\beta}$-oxidation pathway and PHA biosynthesis pathway was constructed by MaoC, which is homologous to P. aeruginosa (R)-specific enoyl-CoA hydratase (PhaJ1). When the E. coli W3110 strains expressing the phaC2 gene and one of the maoC genes from P. putida, Sinorhizobium meliloti, and Ralstonia eutropha were cultured in LB medium containing 2 g/L of sodium decanoate as a carbon source, MCL-PHA that mainly consists of 3-hydroxyhexanoate (3HHx), 3-hydroxyoctanoate (3HO) and 3-hydroxydecanoate (3HD), was produced. The monomer composition of PHA and PHA contents varied depending on MaoC employed for the production of PHA. The highest PHA content of 18.7 wt% was achieved in recombinant E. coli W3110 expressing the phaC2 gene and the P. putida maoC gene. These results suggest that MCL-PHA biosynthesis pathway can be constructed in recombinant E. coli strains from the b-oxidation pathway by employing MaoC able to supply (R)-3-hydroxyacyl-CoA, the substrate of PHA synthase.

• 미생물과산업
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• 제25권1호
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• pp.2-9
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• 1999

A study was made on enzymes of carbohydrate metabolism in T. concretivorus grown with and without glucose. The present results show that T. concretivorus possesses high activities of pentose shunt pathway and related enzymes, glucokinase, G-6-P dehydrogenase, 6-PG dehydrogenase, and phosphoglucoisomerase, but low activities of enzymes unique to EMP(fructose-1,6-diphosphate aldolase). Although the synthesis of the latter enzymes remains largely unaffected by the growth enviroment, that of the former is stimulated by glucose. And the failure to detect ED pathway enzymes in cells grown in thiosulate or thiosulfate-glucose medium eliminates the ED pathway as a significant route of glucose catabolism in T.concretivorus. These results suggest that pentose shunt pathway performs an energetic role in glucose metabolism by T.concretivorus with EMP as a subway. The absence of ED pathway and the presence of pentose shunt pathway which is the major route of catabolism in T.concretivorus are similar to those of other obligately chemolitho-trophic thiobacilli. The G-6-P and 6-PG dehydrogenase are both NAD and NADP specific, but MAD predominant. However, the 3-PGAL dehydrogenase is only NAD specific. Since the specific activity of 3-PGAL generated from glucose is converted mainly into pyruvate which is channeled into the TCA cycle. All enzymes of the TCA cycle tested and NADH oxidase are detected in the cells of T.concretivorus grown in thiosulfate. The specific activities of fumarase and isocitrate dehydrogenase are high and others are low. The presence of two isocitrate dehydrogenase (NAD-and NADP-linked) may have important regulatory function for this organism. The activity of NAD-oxidase, which is implicated in the energy generating metabolism, was very high in the crude cell-free extract of T.concretivorus, recording 55.11 m.mu. mole/min/mg protein. This well coincides with the fact that activities of NAD-linked G-6-P dehydrogenase, 6-PG dehydrogenase and 3-PGAL dehydrogenase were high.

• 미생물학회지
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• 제11권1호
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• pp.1-18
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• 1973

A study was made on enzymes of carbohydrate metabolism in T. concretivorus grown with and without glucose. The present results show that T. concretivorus possesses high activities of pentose shunt pathway and related enzymes, glucokinase, G-6-P dehydrogenase, 6-PG dehydrogenase, and phosphoglucoisomerase, but low activities of enzymes unique to EMP(fructose-1, 6-diphosphate aldolase). Although the synthesis of the latter enzymes remains largely unaffected by the growth enviroment, that of the former is stimulated by glucose. And the failure to detect ED pathway enzymes in cells grown in thiosulate or thiosulfate-glucose medium eliminates the ED pathway as a significant route of glucose catabolism in T.concretivorus. These results suggest that pentose shunt pathway performs an energetic role in glucose metabolism by T.concretivorus with EMP as a subway. The absence of ED pathway and the presence of pentose shunt pathway which is the major route of catabolism in T.concretivorus are similar to those of other obligately chemolitho-trophic thiobacilli. The G-6-P and 6-PG dehydrogenase are both NAD and NADP specific, but MAD predominant. However, the 3-PGAL dehydrogenase is only NAD specific. Since the specific activity of 3-PGAL generated from glucose is converted mainly into pyruvate which is channeled into the TCA cycle. All enzymes of the TCA cycle tested and NADH oxidase are detected in the cells of T.concretivorus grown in thiosulfate. The specific activities of fumarase and isocitrate dehydrogenase are high and others are low. The presence of two isocitrate dehydrogenase (NAD-and NADP-linked) may have important regulatory function for this organism. The activity of NAD-oxidase, which is implicated in the energy generating metabolism, was very high in the crude cell-free extract of T.concretivorus, recording 55.11 m$\mu$ mole/min/mg protein. This well coincides with the fact that activities of NAD-linked G-6-P dehydrogenase, 6-PG dehydrogenase and 3-PGAL dehydrogenase were high.

• 한국균학회소식:학술대회논문집
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• 한국균학회 2018년도 춘계학술대회 및 임시총회
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• pp.11-11
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• 2018

Cryphonectria parasitica, chestnut blight fungus, has a characteristic of decreasing pathogenicity when infected with Cryphonectria hypovirus 1. C. parasitica is known to be one of the most representative model systems used to observe the interaction between viruses, plants and fungi. The mitogen-activated protein kinase (MAPK) pathway, which is well conserved in various organisms ranging from yeast to humans, functions in relaying phosphorylation-dependent signals within MAPK cascades to diverse cellular functions involved in the regulation of pheromone, cell wall integrity, and osmotolerance in filamentous fungi. Several genes in the MAPK pathway were revealed to be regulated by hypovirus, or to be involved in pathogenicity in C. parasitica. Among these pathways, the CWI pathway has aroused interest because CpBck1, an ortholog of yeast Bck1 (a CWI MAPKKK), was previously reported to be involved in cell wall integrity and sectorization. Interestingly, sporadic sectorization was observed in the CpBck1 mutant and sectored phenotypes were stably inherited in the progeny that were successively transferred from sectored mycelia. In this study, we analyzed the biological function of CpSlt2, downstream gene of CpBck1, to confirm whether the sectorization phenomenon occurred in the specific single gene or cell wall integrity (CWI) pathway. As results, the CpSlt2-null mutant exhibited marked changes in colonial growth, near absence of conidiation and aerial hyphae, abnormal pigmentation, CWI-related phenotypic defects, and dramatically impaired virulence. As cultivation of the mutant strains progressed, the majority of the colonies showed sporadic sectorization and mycelia from the sectored area stably maintained the sectored phenotype. These results suggest that the unique sectorization is CWI pathway-specific, though the components in the same CWI pathway have common and specific functions.

• Genomics & Informatics
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• 제12권4호
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• pp.195-202
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• 2014

Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, $52.2{\pm}8.9years$ ; body mass index, $24.6{\pm}3.2kg/m^2$). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < $5{\times}10^{-6}$), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < $1.38{\times}10^{-7}$, Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

• 한국컴퓨터정보학회논문지
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• 제18권5호
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• pp.95-102
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• 2013

생명체 내에서 나타나는 네트워크 중 하나인 대사 경로는 화합물의 상호 관계를 그래프를 통해 표현된다. 대사 경로는 본질적인 복잡성 때문에 대사 경로 내의 흐름을 한 눈에 알 수 있도록 가시화하여 보여 주는 도구가 반드시 필요하다. 이러한 가시화 도구의 경우 노드수가 증가할수록 에지 교차가 기하급수적으로 증가하는 문제가 있다. 따라서 유전체 수준의 대사 경로를 연구하기 위해서는 대사 경로 그래프 레이아웃 상에 나타나는 에지 교차를 줄이는 것이 시각화의 매우 중요한 부분이다. 본 논문은 생물학에서의 대사 경로에 대한 시각화를 위한 2-계층을 이용한 대사 경로 레이아웃 알고리즘을 제안한다. 대사 경로의 구조적 특징을 고려하여 대사 경로 그래프에 존재하는 주요 컴포넌트인 환형 컴포넌트 또는 연결성 높은 노드를 찾아 상위 계층에 레이아웃 하고 나머지 부분그래프는 하위 계층에 레이아웃 한다. 제안한 대사 경로 레이아웃 알고리즘은 유연성 있는 대사 경로 분석의 기초가 된다.

• 한국컴퓨터정보학회논문지
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• 제18권6호
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• pp.71-79
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• 2013

화합물의 상호 관계를 그래프를 통해 표현하는 대사 경로는 본질적인 복잡성 때문에 대사 경로 내의 흐름을 한눈에 알 수 있도록 가시화하여 보여 주는 도구가 반드시 필요하다. 또한 유전체 수준의 대사 경로를 연구하기 위해서는 대사 경로 그래프 레이아웃 상에 나타나는 에지 교차를 줄이는 것이 시각화의 매우 중요한 부분이다. 본 논문은 생물학에서의 대사 경로에 대한 시각화를 위한 3-계층을 이용한 대사 경로 레이아웃 알고리즘을 제안한다. 대사경로의 구조적 특징을 고려하여 노드수가 증가하여도 에지 교차가 기하급수적으로 증가하는 문제를 해결하기 위하여 연결성 높은 노드와 환형 컴포넌트를 중앙계층에 위치시키고 나머지 부분 그래프를 상위와 하위 계층에 레이아웃 하도록 한다. 실험을 통해 에지 교차수가 줄어듦을 확인할 수 있다.