地域子育て支援センターにおける親支援のあり方 : 広島市東区子育て支援センターと京都市総合子育て支援センター「こどもみらい館」を事例として

departmental bulletin pape

<地域研究>横浜市関内地区における​まちなか居住の実態と魅力の要因に関する研究

departmental bulletin pape

A Humanistic Education Study and an Educational Issue at present : Concerning the study on facilitate for children of no attendance by humanistic support

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STRONG ANTIBODY REACTION AGAINST GLYCOSPHINGOLIPIDS INJECTED IN LIPOSOMEEMBEDDED FORMS IN β3GN-T5 KNOCKOUT MICE

2011-08It is known that mutant mice of the β-1,3-N-acetylglucosaminyltransferase gene (β3Gn-T5) respond well to T-cell dependent and independent antigens. Here, we examined the effectiveness of anti-ganglioside antibody generation by immunization of β3Gn-T5 mutant mice with liposome-embedded glycosphingolipids such as GD1a and GT1b. Consequently, the mutant mice showed a more efficient generation of anti-GD1a or anti-GT1b antibodies than wild-type mice in an enzyme-linked immunosorbent assay using sera during immunization. Thus, the β3Gn-T5 deficient mutant mice proved more responsive than wild-type mice to not only protein antigens, but also to carbohydrates in glycolipids. Furthermore, about 50% of monoclonal antibodies generated using splenocytes of the immunized mutant mice were of the IgG class. Besides general high responsiveness to proteins and glycolipids, it could be expected that the mutant mice of β3Gn-T5 would be useful in the generation of monoclonal antibodies towards lacto-/neolacto-series glycolipids, since these mutants lack lacto-/neolacto-series glycolipids. In fact, they showed a good serum response in immuno-fluorescence assay with cultured living cells when immunized by glycolipids extracted from ovarian cancer cell lines. These results suggested that β3Gn-T5 mutant mice are useful for the generation of anti-glycolipid antigens with lacto-/neolacto-core structures expressed in cancer cells.departmental bulletin pape

Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci

<div><p>Long non-coding RNAs are a new class of non-coding RNAs that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Nearly 90% of the phenotype-associated single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific <i>cis</i>-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs. We explored sequence and structure based attributes of these lncRNAs, and also predicted the structural effects of mapped SNPs within them. We also identified lncRNAs in IBD and T1D that are under recent positive selection. Our analysis identified putative lncRNA secondary structure-disruptive SNPs within and in close proximity (+/−5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable information that could be potentially useful for future structure-function studies on lncRNAs.</p></div

Schematic outline of the analysis pipeline.

<p>The summary of the steps involved in this study. All human lncRNAs (sense exonic, sense non-exonic, antisense and intergenic) located within and in close proximity (5 kb up/downstream) of the IBD and T1D candidate genes were identified. Based on the above described workflow, we predicted potential lncRNA secondary structure-disruptive GWAS SNPs within the IBD and T1D loci-associated lncRNAs. cis-eQTL signals were identified for these lncRNAs and linkage disequilibrium analysis was also explored for selected SNPs. We exploited HapMap data to identify candidate lncRNAs under recent positive selection.</p

Mapped lncRNA intervals within IBD and T1D susceptibility loci genes.

<p>Categorization of the genomic association of the lncRNAs to the IBD and T1D loci-associated genes, as sense exonic (A), sense non-exonic (B), antisense (C), and intergenic (D).</p

Common structure-disruptive SNPs within IBD and T1D loci-associated lncRNAs.

<p>Four SNPs common between an IBD and T1D loci-associated antisense lncRNA were in close proximity of a protein coding gene <i>HORMAD2</i>, which has been implicated in both IBD and T1D and three other T1D candidate genes <i>MTMR3</i> (protein coding gene), <i>CTA-85E5.10</i> (processed transcript), <i>CNN2P1</i> (pseudogene). Two SNPs rs3757247 and rs597325 were located within lncRNA <i>NONHSAG044354</i> and a protein coding gene <i>BACH2</i> and a pseudogene <i>RP3-453I5.2</i>. SNP rs602662 was found to be present within antisense lncRNA <i>NONHSAG026183</i> and protein coding gene <i>FUT2</i>. Strand is displayed in brackets for lncRNAs and their-associated IBD/T1D candidate genes.</p

IBD and T1D candidate gene associated lncRNAs.

<p>IBD and T1D candidate gene associated lncRNAs located in and around the (+/−) 5 kb up/downstream of start and end site of each candidate gene. Number of exonic/non-exonic, antisense lncRNAs are described for both IBD and T1D.</p

<i>cis</i>-eQTLs and gene-SNP associations for rs3757247 and rs597325 with <i>BACH2</i> candidate gene.

<p>(A) The gene SNP association for rs3757247 and <i>BACH2</i> candidate gene in whole blood. (B, C, D) The gene SNP association for rs597325 and <i>BACH2</i> in colon transverse, brain cortex and cell line fibroblasts. The gene SNP associations are calculated using linear regression model using Genotype Tissue Expression Portal (GTEx) in the selected tissues with more than 80 samples using a <i>cis</i> window of +/−1 MB around the transcription start site (TSS) at significance level of 0.05. For each gene SNP association plot, p-values are displayed at the bottom.</p