国際環境条約の有効性に関する研究 : 環境面と経済面に対する定量的研究

早大学位記番号:新6726早稲田大

Extensive Structural Variations Between Mitochondrial Genomes of CMS and Normal Peppers (Capsicum Annuum L.) Revealed by Complete Nucleotide Sequencing

Cytoplasmic male sterility (CMS) is an inability to produce functional pollen that is caused by mutation of the mitochondrial genome. Comparative analyses of mitochondrial genomes of lines with and without CMS in several species have revealed structural differences between genomes, including extensive rearrangements caused by recombination. However, the mitochondrial genome structure and the DNA rearrangements that may be related to CMS have not been characterized in Capsicum spp. Results: We obtained the complete mitochondrial genome sequences of the pepper CMS line FS4401 (507,452 bp) and the fertile line Jeju (511,530 bp). Comparative analysis between mitochondrial genomes of peppers and tobacco that are included in Solanaceae revealed extensive DNA rearrangements and poor conservation in non-coding DNA. In comparison between pepper lines, FS4401 and Jeju mitochondrial DNAs contained the same complement of protein coding genes except for one additional copy of an atp6 gene (psi atp6-2) in FS4401. In terms of genome structure, we found eighteen syntenic blocks in the two mitochondrial genomes, which have been rearranged in each genome. By contrast, sequences between syntenic blocks, which were specific to each line, accounted for 30,380 and 17,847 bp in FS4401 and Jeju, respectively. The previously-reported CMS candidate genes, orf507 and psi atp6-2, were located on the edges of the largest sequence segments that were specific to FS4401. In this region, large number of small sequence segments which were absent or found on different locations in Jeju mitochondrial genome were combined together. The incorporation of repeats and overlapping of connected sequence segments by a few nucleotides implied that extensive rearrangements by homologous recombination might be involved in evolution of this region. Further analysis using mtDNA pairs from other plant species revealed common features of DNA regions around CMS-associated genes. Conclusions: Although large portion of sequence context was shared by mitochondrial genomes of CMS and male-fertile pepper lines, extensive genome rearrangements were detected. CMS candidate genes located on the edges of highly-rearranged CMS-specific DNA regions and near to repeat sequences. These characteristics were detected among CMS-associated genes in other species, implying a common mechanism might be involved in the evolution of CMS-associated genes.Golden Seed ProjectMinistry of Agriculture, Food and Rural Affairs (MAFRA)Ministry of Oceans and Fisheries (MOF)Rural Development Administration (RDA)Korea Forest Service (KFS)Vegetable Breeding Research Center through the R&D Convergence Center Support Program, Ministry of Agriculture, Food and Rural Affairs (MAFRA) Republic of Korea 710001-07Molecular Bioscience

Interdependence of manufacturing industry between Korea and ASEAN-5 countries : Asian International Input-Output analysis

The purpose of this study is to analyze the interdependence of the manufacturing industry between South South Korea and ASEAN-5 countries. To conduct an international analysis for the manufacturing industries, an interregional input-output (IRIO) model is applied. The Asian International Input-Output Table (AIIO) provided by IDE-JETRO (2017) is employed and the spillover effects of manufacturing industry are compared in terms of inducement production, value added and backward/forward linkages. The results indicate that the production inducement outcome between Malaysia and South Korea and the effect of forward and backward linkage industry are high, and the dependence on industry is high. On the other hand, in terms of decomposition of value added exports to ASEAN from South South Korea in the manufacturing sector; Vietnam, Singapore, and Indonesia are the states where South South Korea's domestic value-added exports are high. The result shows that South South Korea is necessary to diversify economic cooperation between East Asian and ASEAN member states

Anti-lipoapoptotic effect of Artemisia capillaris extract on free fatty acids-induced HepG2 cells

BACKGROUND: Artemisia capillaris (AC) has been recognized as one of the promising candidates for hepatoprotective, hypoglycemic, hypolipidemic, antiobesitic and anti-inflammatory therapeutic effectiveness. This study evaluated the inherent mechanism and anti-apoptotic activity of 30% ethanol extract of AC (AC extract) 100 μg/ml on free fatty acids (FFAs)-induced HepG2 cellular steatosis and lipoapoptosis. METHODS: Hepatic steatosis was induced by culturing HepG2 cells with a FFAs mixture (oleic and palmitic acid at the proportion of 2:1) for 24 h, thus ultimately giving rise to lipoapoptosis. Cell viability and lipid accumulation were detected by MTT assay and Oil Red O staining method respectively and Caspase-3, −9, Bax, Bcl-2, p-JNK and PUMA were measured for lipoapoptosis after 24 hours. RESULTS: AC extract significantly improved the FFAs-induced steatosis without cytotoxicity and Caspase-3, −9, Bax and Bcl-2 were modulated profitably to HepG2 cells after AC treatment. In addition, AC extract inhibited the activation of c-Jun NH(2) terminal kinase (JNK) and PUMA, which mechanism is related to non-alcoholic steatohepatitis (NASH). CONCLUSIONS: Combined together, AC extract exerted an obvious hypolipidemic and anti-apoptotic effect, indicating that AC extract might have potential therapeutic herb against NASH

JBASE: Joint Bayesian Analysis of Subphenotypes and Epistasis

Motivation: Rapid advances in genotyping and genome-wide association studies have enabled the discovery of many new genotype–phenotype associations at the resolution of individual markers. However, these associations explain only a small proportion of theoretically estimated heritability of most diseases. In this work, we propose an integrative mixture model called JBASE: joint Bayesian analysis of subphenotypes and epistasis. JBASE explores two major reasons of missing heritability: interactions between genetic variants, a phenomenon known as epistasis and phenotypic heterogeneity, addressed via subphenotyping. Results: Our extensive simulations in a wide range of scenarios repeatedly demonstrate that JBASE can identify true underlying subphenotypes, including their associated variants and their interactions, with high precision. In the presence of phenotypic heterogeneity, JBASE has higher Power and lower Type 1 Error than five state-of-the-art approaches. We applied our method to a sample of individuals from Mexico with Type 2 diabetes and discovered two novel epistatic modules, including two loci each, that define two subphenotypes characterized by differences in body mass index and waist-to-hip ratio. We successfully replicated these subphenotypes and epistatic modules in an independent dataset from Mexico genotyped with a different platform. Availability and implementation: JBASE is implemented in Cþþ, supported on Linux and is available at http://www.cs.toronto.edu/goldenberg/JBASE/jbase.tar.gz. The genotype data underlying this study are available upon approval by the ethics review board of the Medical Centre Siglo XXI.No sponso

Sensitization to Aeroallergens in Korean Children: A Population-based Study in 2010

We performed this study to assess the prevalence of sensitization to aeroallergens and to analyze the difference between prevalence rates according to children's ages and residential areas. In this nationwide cross-sectional study, first grade students of 45 elementary schools and 40 middle schools were randomly selected, and skin prick tests were performed for 18 inhalant allergens between October and November 2010. Of 7,829 analyzed subjects, 3,753 (47.9%) were sensitized to at least one aeroallergen. Sensitization to Dermatophagoides farinae was found to be the most prevalent in elementary schoolchildren (32.4%), followed by Dermatophagoides pteronyssinus, Tyrophagus putrescentiae, Japanese hop, and oak. In middle schoolchildren, D. pteronyssinus yielded the highest prevalence (42.7%), followed by D. farinae, T. putrescentiae, Japanese hop, and cat. In middle schoolchildren, the sensitization rate to aeroallergens in metropolitan, urban, and rural areas was 57.2%, 54.3%, and 49.8%, respectively (P = 0.019). In this age group, the sensitization rate in low, middle, high, and very high income groups was 53.8%, 51.8%, 59.0%, and 59.6%, respectively (P = 0.002). In conclusion, the sensitization rate is 47.9% and house dust mite is the most prevalent allergen in the pediatric population in Korea. The rate is higher in metropolitan areas and the highest income group than in rural areas and low income groups

Homozygote CRIM1 variant is associated with thiopurine-induced neutropenia in leukemic patients with both wildtype NUDT15 and TPMT

Abstract Background NUDT15 and TPMT variants are strong genetic determinants of thiopurine-induced hematological toxicity that results in therapeutic failure in pediatric acute lymphoblastic leukemia (ALL). However, many patients with both wild-type (WT) NUDT15 and TPMT still suffer from thiopurine toxicity and therapeutic failure. Methods Whole-exome sequencing was done for discovery (N = 244) and replication (N = 76) cohorts. Age- and sex-adjusted multiple regression analyses of both WT patients were performed to identify (p < 0.01, N = 188 for discovery) and validate (p < 0.05, N = 52 for replication) candidate variants for the tolerated last-cycle 6-mercaptopurine (6-MP) dose intensity percentage (DIP). Both independent and additive effects of the candidate variants on well-known NUDT15 and TPMT were evaluated by multigene prediction models. Results Among the 12 candidate variants from the discovery phase, the rs3821169 variant of the gene encoding Cysteine-Rich Transmembrane BMP Regulator 1 (CRIM1) was successfully replicated (p < 0.05). It showed high interethnic variability with an impressively high allele frequency in East Asians (T = 0.255) compared to Africans (0.001), Americans (0.02), Europeans (0.009), and South Asians (0.05). Homozygote carriers of the CRIM1 rs3821169 variant (N = 12, 5%) showed significantly lower last-cycle 6-MP DIPs in the discovery, replication, and combined cohorts (p = 0.025, 0.013, and 0.001, respectively). The traditional two-gene model (NUDT15 and TPMT) for predicting 6-MP DIP < 25% was outperformed by the three-gene model that included CRIM1, in terms of the area under the receiver operating characteristic curve (0.734 vs. 0.665), prediction accuracy (0.759 vs. 0.756), sensitivity (0.636 vs. 0.523), positive predictive value (0.315 vs. 0.288), and negative predictive value (0.931 vs. 0.913). Conclusions The CRIM1 rs3821169 variant is suggested to be an independent and/or additive genetic determinant of thiopurine toxicity beyond NUDT15 and TPMT in pediatric ALL

Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients

Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients