• 한국통신학회논문지
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• 제29권5C호
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• pp.716-725
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• 2004

본 논문에서는 VHLS 광학판 기반의 새로운 다시점 3D 디스플레이 시스템을 제시하였다. 즉, VHLS 광학판을 체적 홀로그램의 각 다중화 기록 특성을 이용하여 다시점 영상의 방향벡터를 회절격자 형태로 기록한 일종의 광방향 변조기로 제작한 다음, 제작된 VHLS을 LCD 공간광변조기에 부착되어 패널에 입력되는 다시점의 스테레오 영상을 각 시점에 해당하는 특정방향으로 분리해 줌으로써 다시점 3D 디스플레이 시스템을 실현하였다. 또한, 본 논문에서는 VHLS 광학판의 원리와 특성을 분석한 다음 상용 포토폴리머를 이용하여 최적화된 4시점의 VHLS 광학판을 설계 제작하고 이를 이용하여 4시점의 스테레오스코픽 3D 디스플레이 시스템을 구현하였다. 그리고 적응적 변위 추정 알고리즘으로 합성된 4시점의 테스트 영상을 이용한 광학실험을 통해 VHLS 기반의 다시점 3D 디스플레이 시스템의 구현 가능성을 제시하였다.

• BMB Reports
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• 제49권5호
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• pp.245-246
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• 2016

The level and activity of critical regulatory proteins in cells are tightly controlled by several tiers of post-translational modifications. HIF-1α is maintained at low levels under normoxia conditions by the collaboration between PHD proteins and the VHL-containing E3 ubiquitin ligase complex. We recently identified a new physiologically relevant mechanism that regulates HIF-1α stability in the nucleus in response to cellular oxygen levels. This mechanism is based on the collaboration between the SET7/9 methyltransferase and the LSD1 demethylase. SET7/9 adds a methyl group to HIF-1α, which triggers degradation of the protein by the ubiquitin-proteasome system, whereas LSD1 removes the methyl group, leading to stabilization of HIF-1α under hypoxia conditions. In cells from knock-in mice with a mutation preventing HIF-1α methylation (Hif1α^KA/KA), HIF-1α levels were increased in both normoxic and hypoxic conditions. Hif1α^KA/KA knock-in mice displayed increased hematological parameters, such as red blood cell count and hemoglobin concentration. They also displayed pathological phenotypes; retinal and tumor-associated angiogenesis as well as tumor growth were increased in Hif1α^KA/KA knock-in mice. Certain human cancer cells exhibit mutations that cause defects in HIF-1α methylation. In summary, this newly identified methylation-based regulation of HIF-1α stability constitutes another layer of regulation that is independent of previously identified mechanisms.

• Genomics & Informatics
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• 제11권4호
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• pp.239-244
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• 2013

Somatic mutation is a major cause of cancer progression and varied responses of tumors against anticancer agents. Thus, we must obtain and characterize genome-wide mutational profiles in individual cancer subtypes. The Cancer Genome Atlas database includes large amounts of sequencing and omics data generated from diverse human cancer tissues. In the present study, we integrated and analyzed the exome sequencing data from ~3,000 tissue samples and summarized the major mutant genes in each of the diverse cancer subtypes and stages. Mutations were observed in most human genes (~23,000 genes) with low frequency from an analysis of 11 major cancer subtypes. The majority of tissue samples harbored 20-80 different mutant genes, on average. Lung cancer samples showed a greater number of mutations in diverse genes than other cancer subtypes. Only a few genes were mutated with over 5% frequency in tissue samples. Interestingly, mutation frequency was generally similar between non-metastatic and metastastic samples in most cancer subtypes. Among the 12 major mutations, the TP53, USH2A, TTN, and MUC16 genes were found to be frequent in most cancer types, while BRAF, FRG1B, PBRM1, and VHL showed lineage-specific mutation patterns. The present study provides a useful resource to understand the broad spectrum of mutation frequencies in various cancer types.

• Journal of Korean Neurosurgical Society
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• 제65권1호
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• pp.4-12
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• 2022

Objective : We reported the differentially methylated genes in patients with subarachnoid hemorrhage (SAH) using bioinformatics analyses to explore the biological characteristics of the development of delayed cerebral ischemia (DCI). Methods : DNA methylation profiles obtained from 40 SAH patients from an epigenome-wide association study were analyzed. Functional enrichment analysis, protein-protein interaction (PPI) network, and module analyses were carried out. Results : A total of 13 patients (32.5%) experienced DCI during the follow-up. In total, we categorized the genes into the two groups of hypermethylation (n=910) and hypomethylation (n=870). The hypermethylated genes referred to biological processes of organic cyclic compound biosynthesis, nucleobase-containing compound biosynthesis, heterocycle biosynthesis, aromatic compound biosynthesis and cellular nitrogen compound biosynthesis. The hypomethylated genes referred to biological processes of carbohydrate metabolism, the regulation of cell size, and the detection of a stimulus, and molecular functions of amylase activity, and hydrolase activity. Based on PPI network and module analysis, three hypermethylation modules were mainly associated with antigen-processing, Golgi-to-ER retrograde transport, and G alpha (i) signaling events, and two hypomethylation modules were associated with post-translational protein phosphorylation and the regulation of natural killer cell chemotaxis. VHL, KIF3A, KIFAP3, RACGAP1, and OPRM1 were identified as hub genes for hypermethylation, and ALB and IL5 as hub genes for hypomethylation. Conclusion : This study provided novel insights into DCI pathogenesis following SAH. Differently methylated hub genes can be useful biomarkers for the accurate DCI diagnosis.

• Animal Bioscience
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• 제35권8호
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• pp.1121-1128
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• 2022

Objective: This study aimed to identify the genetic diversity and population structure of Mongolian horse populations according to the province of residence (Khentii, KTP; Uvs, USP; Omnogovi and Dundgovi, GOP; Khovsgol, KGP) using 14 microsatellite (MS) markers. Methods: A total of 269 whole blood samples were obtained from the four populations (KTP, USP, GOP, KGP) geographically distinct provinces. Multiplex polymerase chain reaction (PCR) was conducted using 14 MS markers (AHT4, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG6, HTG7, and VHL20), as recommended by the International Society for Animal Genetics. Capillary electrophoresis was conducted using the amplified PCR products, alleles were determined. Alleles were used for statistical analysis of genetic variability, Nei's DA genetic distance, principal coordinate analysis (PCoA), factorial corresponding analysis (FCA), and population structure. Results: On average, the number of alleles, expected heterozygosity (H_Exp), observed heterozygosity (H_Obs), and polymorphic information content among all populations were 11.43, 0.772, 0.757, and 0.737, respectively. In the PCoA and FCA, GOP, and KGP were genetically distinct from other populations, and the KTP and USP showed a close relationship. The two clusters identified using Nei's DA genetic distance analysis and population structure highlighted the presence of structurally clear genetic separation. Conclusion: Overall, the results of this study suggest that genetic diversity between KTP and USP was low, and that between GOP and KGP was high. It is thought that these results will help in the effective preservation and improvement of Mongolian horses through genetic diversity analysis and phylogenetic relationships.

• Animal Bioscience
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• 제34권9호
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• pp.1460-1465
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• 2021

Objective: The study aimed to evaluate the diversity of donkey populations by comparing with the diversity of Thoroughbred and Jeju Halla horses; identified breeding backgrounds can contribute to management and conservation of donkeys in South Korea. Methods: A total of 100 horse (50 Thoroughbreds and 50 Jeju Halla horses) and 79 donkeys samples were genotyped with 15 microsatellite markers (AHT4, AHT5, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG10, LEX3, and VHL20), to identify genetic diversity and relationships among horses and donkeys. Results: The observed number of alleles per locus ranged from 1 (ASB17, HMS1) to 14 (AHT5), with a mean value of 4.87, 8.00, and 5.87 in Thoroughbreds, Jeju Halla horses, and donkeys, respectively. Of the 15 markers, AHT4, AHT5, ASB23, CA425, HMS2, HMS3, HTG4, HTG10, and LEX3 loci had relatively high polymorphism information content (PIC) values (PIC>0.5) in these three populations. Mean levels of genetic variation were H_E = 0.6721 and H_O = 0.6600 in Thoroughbreds, H_E = 0.7898 and H_O = 0.7100 in Jeju Halla horses, and H_E = 0.5635 and H_O = 0.4861 in donkeys. Of the 15 loci in donkeys, three loci had negative inbreeding coefficients (FIS), with a moderate mean FIS (0.138). The FIS estimate for the HTG4 marker was highest (0.531) and HMS6 marker was lowest (-0.001). The total probability of exclusion value of 15 microsatellite loci was 0.9996 in donkeys. Conclusion: Genetic cluster analysis showed that the genetic relationship among 79 donkeys was generally consistent with pedigree records. Among the three breeds, donkeys and Thoroughbred horses formed clearly different groups, but the group of Jeju Halla horses overlapped with that of Thoroughbred horses, suggesting that the loci would be suitable for donkey parentage testing. Therefore, the results of this study are a valid tool for genetic study and conservation of donkeys.

• Animal Bioscience
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• 제35권4호
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• pp.527-532
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• 2022

Objective: In this study, we aimed to investigate the recent changes such as allele frequencies and total probability of exclusion (PE) in Thoroughbred horses in Korea using short tandem repeat (STR) parentage panels between 2006 and 2016. Methods: The genotype was provided for 5,988 horse samples with 15 microsatellite markers (AHT4, AHT5, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG10, LEX3 and VHL20). Results: In our study, the observed number of alleles per locus ranged from 3 (HMS1) to 9 (ASB17) in 2006 and 4 (HMS1) to 9 (ASB2) in 2016, with a mean value of 6.28 and 6.40, respectively. Of the 15 markers, HMS2, HTG4, and CA425 loci had relatively low polymorphism information content (<0.5000) in the Thoroughbred population. Mean levels of genetic variation in 2006 and 2016 were observed heterozygosity (H_O) = 0.708, and expected heterozygosity (H_E) = 0.685, as well as and H_O = 0.699 and H_E = 0.682, respectively. The PE was calculated for each group based on the allele frequencies of 14 or 15 STRs. The 2006 survey analyzed that PE was 0.9998, but it increased to 0.9999 in 2016 after the HMS2 marker was added in 2011. The current STR panel is still a powerful tool for parentage verification that contributes to the maintenance of integrity in the Thoroughbred population. Conclusion: The current STR panel is still a powerful tool for parentage verification that contributes to the maintenance of integrity in the Thoroughbred horses. However, continuous monitoring genetic variability is necessary.

• 생명과학회지
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• 제17권5호
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• pp.699-705
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• 2007

말 6개 품종 192두를 대상으로 17개의 microsatellite DNA marker를 이용하여 유전자(DNA)형을 분석하여 비교한 결과 제주마에서 각 marker별로 대립유전자의 수는 5-10개(평균 7.35개)로 분포하였고 제주마에서 관찰된 대립유전자는 총 125개가 관찰되어 평균 좌위 당 7.35개로서 몽고마의 130개(평균 7.65개)보다는 낮은 수치였다. 또한 AHT5 marker에서 대립유전자 P, ASB23 marker에서 대립유전자 Q와 R, CA425 marker에서 대립유전자 H, HMS3 marker에서 대립유전자 S, HTG10 marker에서 대립유전자 J, LEX3 marker에서 대립유전자 J 등 6개 marker에서 7개의 특이 대립유전자가 관찰되었다. 관찰된 이형접합성(observed heterozygosity)과 기대된 이형접합성(expected heterozygosity)은 각각 0.429-0.905(평균 0.703)와 0.387-0.841(평균 0.702)로 관찰되었고 다량정보량(PIC)은 0.354(HTG6)-0.816(LEX3)로서 평균 0.659로 나타났으며 17개 marker중 AHT4, AHT5, CA425, HMS2, HMS3, HTG10, LEX3, VHL20 marker 등이 다량정보량(PIC) 0.7 이상을 나타내었다. 17개 marker에 대한 전체 부권부정율(친부마 혹은 친모마 하나의 유전자형을 알고 있을 경우)을 제주마에 적용 시 99.99%로 나타났다. 말 6개 품종별로 분석하였을 때 평균 대립유전자의 수는 7.64개(몽고마)-4.23개(미니츄어 말)로 분포하였고 17개 marker 전체에서는 153개의 대립유전자가 검출되었다. 품종별로 분석한 결과 기대된 이형접합성(expected heterozygosity)과 관찰된 이형접합성(observed heterozygosity)은 각각 0.7950$\pm$0.0141(몽고마)-0.6751$\pm$0.0378(미니츄어 말), 0.7135$\pm$0.0180(제주경주마)-0.5621$\pm$0.0401(미니츄어 말)로 나타났다. 말 6개 품종을 17개 microsatellite marker로 분석한 결과 몽고마, 제주마, 제주경주마 등의 순으로 높은 유전적 다양성을 보였다. 제주마와 가장 가까운 유전적 유연 관계를 나타낸 집단은 몽고마로서 Da genetic distance에서 0.1517로 나타났고, 제주경주마와는 0.2628의 유전적 거리를 보였다.

• International Journal of Oral Biology
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• 제34권4호
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• pp.205-213
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• 2009

The mechanisms underlying the actions of the antioxidants upon reactive oxygen species (ROS) generation by NADPH oxidase complex have remained uncertain. In this study, we investigated NADPH oxidase activity and the role of antioxidant enzymes upon the generation of ROS during hypoxic stress. ROS generation was found to increase in the mouse kidney under hypoxic stress in a time-dependent manner. Moreover, we found in MCT cells that hypoxia-induced hydrogen peroxide production was decreased by NAC pretreatment. We further analyzed HIF-$1{\alpha}$, PHD2 and VHL expression in the NAC-pretreated MCT cells and assessed the response of antioxidant enzymes at the transcriptional and translational levels. SOD3 and Prdx2 were significantly increased during hypoxia in the mouse kidney. We also confirmed in hypoxic $Prdx2^{-/-}$ and SOD3 transgenic mice that erythropoietin (EPO) is transcriptionally regulated by HIF-$1{\alpha}$. In addition, although EPO protein was found to be expressed in a HIF-$1{\alpha}$ independent manner in three mouse lines, its activity differed markedly between normal and $Prdx2^{-/-}$/SOD3 transgenic mice during hypoxic stress. In conclusion, our current results indicate that NADPH oxidase-mediated ROS generation is associated with hypoxic stress in the mouse kidney and that SOD3 and Prdx2 cooperate to regulate cellular redox reactions during hypoxia.

• Molecules and Cells
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• 제38권6호
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• pp.528-534
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• 2015

Hypoxia-inducible factor (HIF) is a key regulator of tumor growth and angiogenesis. Recent studies have shown that, BIX01294, a G9a histone methyltransferase (HMT)-specific inhibitor, induces apoptosis and inhibits the proliferation, migration, and invasion of cancer cells. However, not many studies have investigated whether inhibition of G9a HMT can modulate HIF-$1{\alpha}$ stability and angiogenesis. Here, we show that BIX01294 dose-dependently decreases levels of HIF-$1{\alpha}$ in HepG2 human hepatocellular carcinoma cells. The half-life of HIF-$1{\alpha}$, expression of proline hydroxylase 2 (PHD2), hydroxylated HIF-$1{\alpha}$ and von Hippel-Lindau protein (pVHL) under hypoxic conditions were decreased by BIX01294. The mRNA expression and secretion of vascular endothelial growth factor (VEGF) were also significantly reduced by BIX01294 under hypoxic conditions in HepG2 cells. BIX01294 remarkably decreased angiogenic activity induced by VEGF in vitro, ex vivo, and in vivo, as demonstrated by assays using human umbilical vein endothelial cells (HUVECs), mouse aortic rings, and chick chorioallantoic membranes (CAMs), respectively. Furthermore, BIX01294 suppressed VEGF-induced matrix metalloproteinase 2 (MMP2) activity and inhibited VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), focal adhesion kinase (FAK), and paxillin in HUVECs. In addition, BIX01294 inhibited VEGF-induced formation of actin cytoskeletal stress fibers. In conclusion, we demonstrated that BIX01294 inhibits HIF-$1{\alpha}$ stability and VEGF-induced angiogenesis through the VEGFR-2 signaling pathway and actin cytoskeletal remodeling, indicating a promising approach for developing novel therapeutics to stop tumor progression.