オミクスデータに基づくラベルフリー代謝フラックス推定による肥満における肝臓グルコース代謝異常の解析

学位の種別: 課程博士審査委員会委員 : （主査）東京大学准教授 木立 尚孝, 東京大学教授 黒田 真也, 東京大学教授 角田 達彦, 東京大学客員准教授 齋藤 裕, 京都大学特定准教授 河岡 慎

Syntaxin 17 recruitment to mature autophagosomes is temporally regulated by PI4P accumulation

During macroautophagy, cytoplasmic constituents are engulfed by autophagosomes. Lysosomes fuse with closed autophagosomes but not with unclosed intermediate structures. This is achieved in part by the late recruitment of the autophagosomal SNARE syntaxin 17 (STX17) to mature autophagosomes. However, how STX17 recognizes autophagosome maturation is not known. Here, we show that this temporally regulated recruitment of STX17 depends on the positively charged C-terminal region of STX17. Consistent with this finding, mature autophagosomes are more negatively charged compared with unclosed intermediate structures. This electrostatic maturation of autophagosomes is likely driven by the accumulation of phosphatidylinositol 4-phosphate (PI4P) in the autophagosomal membrane. Accordingly, dephosphorylation of autophagosomal PI4P prevents the association of STX17 to autophagosomes. Furthermore, molecular dynamics simulations support PI4P-dependent membrane insertion of the transmembrane helices of STX17. Based on these findings, we propose a model in which STX17 recruitment to mature autophagosomes is temporally regulated by a PI4P-driven change in the surface charge of autophagosomes

Practical studies on the relationship between physical activity and life rhythm of young children.

本研究は, 広島大学附属幼稚園に在籍する幼児の身体活動と生活リズムの関連性を明らかにすることを目的とする。特に日内の身体活動量から幼児の生活リズム・体温変動における身体活動に関する視座を得ることを本研究の目的とする。 方法として, 幼稚園に在籍する5歳児34名の保護者に対し16項目の質問紙調査を行った。質問紙調査にて生活リズム評価の該当数を求め, 5項目以上該当する幼児を生活リズム未確立群, 0から2項目該当する幼児を生活リズム確立群とした。また, 対象児として抽出した24名の幼児の腰に2軸加速度計を装着し身体活動を測定した。加えて同対象者に耳式体温計を用い体温測定を行った。 結果から, 生活リズムが未確立である幼児は総じて身体活動を行う機会が少なく, 特に幼稚園降園後の遊びの様子として, 身体を動かして活発に遊ぶよりも静かに遊ぶ傾向が示された。生活リズムの違いによる体温の比較では, 生活リズムが確立されていない幼児は体温の上昇が遅い時刻に移行することが明らかとなった。このことから, 幼稚園の在園時間における運動遊びが, 一日を通して「動かせない身体」を持つ幼児の健康や身体発達に有効に働くことが示唆された

Inhibition of Streptococcus mutans Biofilm Formation by Streptococcus salivarius FruA▿

The oral microbial flora consists of many beneficial species of bacteria that are associated with a healthy condition and control the progression of oral disease. Cooperative interactions between oral streptococci and the pathogens play important roles in the development of dental biofilms in the oral cavity. To determine the roles of oral streptococci in multispecies biofilm development and the effects of the streptococci in biofilm formation, the active substances inhibiting Streptococcus mutans biofilm formation were purified from Streptococcus salivarius ATCC 9759 and HT9R culture supernatants using ion exchange and gel filtration chromatography. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry analysis was performed, and the results were compared to databases. The S. salivarius HT9R genome sequence was determined and used to indentify candidate proteins for inhibition. The candidates inhibiting biofilms were identified as S. salivarius fructosyltransferase (FTF) and exo-beta-d-fructosidase (FruA). The activity of the inhibitors was elevated in the presence of sucrose, and the inhibitory effects were dependent on the sucrose concentration in the biofilm formation assay medium. Purified and commercial FruA from Aspergillus niger (31.6% identity and 59.6% similarity to the amino acid sequence of FruA from S. salivarius HT9R) completely inhibited S. mutans GS-5 biofilm formation on saliva-coated polystyrene and hydroxyapatite surfaces. Inhibition was induced by decreasing polysaccharide production, which is dependent on sucrose digestion rather than fructan digestion. The data indicate that S. salivarius produces large quantities of FruA and that FruA alone may play an important role in multispecies microbial interactions for sucrose-dependent biofilm formation in the oral cavity

Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity

<p>Source codes and datasets for reproducing the results of the paper entitled "Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity".</p&gt

DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle

Abstract Each tissue has a dominant set of functional proteins required to mediate tissue-specific functions. Epigenetic modifications, transcription, and translational efficiency control tissue-dominant protein production. However, the coordination of these regulatory mechanisms to achieve such tissue-specific protein production remains unclear. Here, we analyzed the DNA methylome, transcriptome, and proteome in mouse liver and skeletal muscle. We found that DNA hypomethylation at promoter regions is globally associated with liver-dominant or skeletal muscle-dominant functional protein production within each tissue, as well as with genes encoding proteins involved in ubiquitous functions in both tissues. Thus, genes encoding liver-dominant proteins, such as those involved in glycolysis or gluconeogenesis, the urea cycle, complement and coagulation systems, enzymes of tryptophan metabolism, and cytochrome P450-related metabolism, were hypomethylated in the liver, whereas those encoding-skeletal muscle-dominant proteins, such as those involved in sarcomere organization, were hypomethylated in the skeletal muscle. Thus, DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins