『源氏物語』と歌ことば表現-連想と変容-

早大学位記番号:新8064早稲田大

“Spring without the Lady who planted the flower” in the chapter Maboroshi of “The Tale of Genji” : Based on Yamabuki and the missing Women

departmental bulletin pape

A non-carboxylating pentose bisphosphate pathway in halophilic archaea

Bacteria and Eucarya utilize the non-oxidative pentose phosphate pathway to direct the ribose moieties of nucleosides to central carbon metabolism. Many archaea do not possess this pathway, and instead, Thermococcales utilize a pentose bisphosphate pathway involving ribose-1, 5-bisphosphate (R15P) isomerase and ribulose-1, 5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco). Intriguingly, multiple genomes from halophilic archaea seem only to harbor R15P isomerase, and do not harbor Rubisco. In this study, we identify a previously unrecognized nucleoside degradation pathway in halophilic archaea, composed of guanosine phosphorylase, ATP-dependent ribose-1-phosphate kinase, R15P isomerase, RuBP phosphatase, ribulose-1-phosphate aldolase, and glycolaldehyde reductase. The pathway converts the ribose moiety of guanosine to dihydroxyacetone phosphate and ethylene glycol. Although the metabolic route from guanosine to RuBP via R15P is similar to that of the pentose bisphosphate pathway in Thermococcales, the downstream route does not utilize Rubisco and is unique to halophilic archaea

Binding of 14-3-3β but not 14-3-3σ controls the cytoplasmic localization of CDC25B: Binding site preferences of 14-3-3 subtypes and the subcellular localization of CDC25B

The dual specificity phosphatase CDC25B positively controls the G2-M transition by activating CDK1/cyclin B. The binding of 14-3-3 to CDC25B has been shown to regulate the subcellular redistribution of CDC25B from the nucleus to the cytoplasm and may be correlated with the G2 checkpoint. We used a FLAG-tagged version of CDC25B to study the differences among the binding sites for the 14-3-3 subtypes, 14-3-3β, 14-3-3ε and 14-3-3σ, and the relationship between subtype binding and the subcellular localization of CDC25B. All three subtypes were found to bind to CDC25B. Site-directed mutagenesis studies revealed that 14-3-3β bound exclusively near serine-309 of CDC25B1, which is within a potential consensus motif for 14-3-3 binding. By contrast, 14-3-3σ bound preferentially to a site around serine-216, and the presence of serine-137 and -309 enhanced the binding. In addition to these binding-site differences, we found that the binding of 14-3-3β drove CDC25B to the cytoplasm and that mutation of serine-309 to alanine completely abolished the cytoplasmic localization of CDC25B. However, co-expression of 14-3-3σ and CDC25B did not affect the subeellular localization of CDC25B. Furthermore, serine-309 of CDC25B was sufficient to produce its cytoplasmic distribution with co-expression of 14-3-3β, even when other putative 14-3-3 binding sites were mutated. 14-3-3ε resembled 14-3-3β with regard to its binding to CDC25B and the control of CDC25B subcellujar localization. The results of the present study indicite that two 14-3-3 subtypes can control the subcellular localization of CDC25B by binding to a specific site and that 14-3-3σ has effects on CDC25B other than the control of its subcellular localization

Transcriptional Activation of Low-Density Lipoprotein Receptor Gene by DJ-1 and Effect of DJ-1 on Cholesterol Homeostasis

DJ-1 is a novel oncogene and also causative gene for familial Parkinson’s disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone and mitochondrial regulation. For transcriptional regulation, DJ-1 acts as a coactivator that binds to various transcription factors, resulting in stimulation or repression of the expression of their target genes. In this study, we found the low-density lipoprotein receptor (LDLR) gene is a transcriptional target gene for DJ-1. Reduced expression of LDLR mRNA and protein was observed in DJ-1-knockdown cells and DJ-1-knockout mice and this occurred at the transcription level. Reporter gene assays using various deletion and point mutations of the LDLR promoter showed that DJ-1 stimulated promoter activity by binding to the sterol regulatory element (SRE) with sterol regulatory element binding protein (SREBP) and that stimulating activity of DJ-1 toward LDLR promoter activity was enhanced by oxidation of DJ-1. Chromatin immunoprecipitation, gel-mobility shift and co-immunoprecipitation assays showed that DJ-1 made a complex with SREBP on the SRE. Furthermore, it was found that serum LDL cholesterol level was increased in DJ-1-knockout male, but not female, mice and that the increased serum LDL cholesterol level in DJ-1-knockout male mice was cancelled by administration with estrogen, suggesting that estrogen compensates the increased level of serum LDL cholesterol in DJ-1-knockout female mice. This is the first report that DJ-1 participates in metabolism of fatty acid synthesis through transcriptional regulation of the LDLR gene

The relationship between taste threshold change and serum zinc level in cancer patients treated with anticancer drugs <Original Articles>

化学療法の有害事象のうち味覚障害は発生頻度の高い有害事象である.味覚と血清亜鉛値との関連については以前から指摘されているが,抗がん剤投与後の味覚変化に血清亜鉛値が影響していることを示した報告は少ない.本研究の目的は,抗がん剤投与後のがん患者の味覚閾値と血清亜鉛値を測定し,両者の関連性を検証することである.60名のがん患者の抗がん剤投与前,抗がん剤投与後3日と投与後6日に味覚と血清亜鉛値,血清銅値を測定した. 抗がん剤投与後の味覚の変化は,塩味で時間経過による有意差を認めた(p<0.01).血清亜鉛値でも時間経過による有意差を認めた(p<0.01).味覚と血清亜鉛値との関係では,抗がん剤投与後3日において,血清亜鉛値と塩味の感度に負の相関を認め(r =- 0.402,p<0.01),血清亜鉛値が低い時,塩味の感度が鈍麻したことが示された.一方,血清銅値と味覚感度には相関を認めなかった.抗がん剤投与後の味覚感度,特に塩味の鈍麻については血清亜鉛値との関連が示された.Taste disorder is one of the most frequent side effects of chemotherapy. A relationship between serum zinc level and taste sensitivity has been pointed out in previous reports, but there have only been a few reports showing the effect of serum zinc level on taste sensitivity after anticancer drug administration. The purpose of this study was to examine the serum zinc levels and taste thresholds of cancer patients treated with anticancer drugs and to determine whether they are related. Taste thresholds and levels of serum trace elements (zinc and copper) were measured in 60 cancer patients before administration of anticancer drugs and on the three and six days after administration. There were significant differences in the salt threshold with elapse of time after chemotherapy (p<0.01). There were also significant differences in the serum zinc level with elapse of time after chemotherapy (p<0.01). There was a significant relationship between low salt sensitivity and change in serum zinc value (r = -0.402, p<0.01). Although there was no significant relationship between serum copper value and taste sensitivity, there was a relationship between salt sensitivity and serum zinc value