基質小胞由来miR-125bは破骨細胞の形成を抑制する

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(歯学)Doctor of Philosophy in Dental Sciencedoctora

Initiation of breastfeeding within 120 minutes after birth is associated with breastfeeding at four months among Japanese women: A self-administered questionnaire survey

<p>Abstract</p> <p>Background</p> <p>The proportion of mothers in Japan who breastfeed exclusively has been low since the 1970s. The purpose of this study was to examine the association between the time of first breastfeed after birth and the proportion of mothers fully breastfeeding up to four months postpartum.</p> <p>Methods</p> <p>A survey was conducted using a self-administered questionnaire. The participants were 318 mothers who participated in a physical examination of their four month old infants in Nagasaki City, Japan in 2003.</p> <p>Results</p> <p>The time of first breastfeeding up to 120 minutes was significantly associated with the proportion of mothers fully breastfeeding during their stay in the clinic/hospital (p = 0.006), at one month (p = 0.004) and at four months after birth (p = 0.003). There was no significant difference in the proportion of full breastfeeding in mothers who first breastfed between the period of less 30 minutes after birth and that of between 31 and 120 minutes after birth. Logistic regression analysis indicated that the proportion of mothers who continued full breastfeeding at four months was significantly higher in those who breastfed their baby within 120 minutes compared with more than 120 minutes (OR 2.5, p = 0.01), but was not significantly different in those who breastfed within 30 minutes compared with more than 30 minutes (OR 1.8, p = 0.06). Early breastfeeding was affected by caesarean section, premature delivery and severe bleeding during delivery.</p> <p>Conclusion</p> <p>Commencement of early breastfeeding was associated with the proportion of mothers who fully breastfed their infants up to four months. Early breastfeeding, especially within two hours, is recommended for child and maternal health.</p

Visualization of spatiotemporal activation of Notch signaling: Live monitoring and significance in neural development

AbstractNotch signaling plays various key roles in cell fate determination during CNS development in a context-dependent fashion. However, its precise physiological role and the localization of its target cells remain unclear. To address this issue, we developed a new reporter system for assessing the RBP-J-mediated activation of Notch signaling target genes in living cells and tissues using a fluorescent protein Venus. Our reporter system revealed that Notch signaling is selectively activated in neurosphere-initiating multipotent neural stem cells in vitro and in radial glia in the embryonic forebrain in vivo. Furthermore, the activation of Notch signaling occurs during gliogenesis and is required in the early stage of astroglial development. Consistent with these findings, the persistent activation of Notch signaling inhibits the differentiation of GFAP-positive astrocytes. Thus, the development of our RBP-J-dependent live reporter system, which is activated upon Notch activation, together with a stage-dependent gain-of-function analysis allowed us to gain further insight into the complexity of Notch signaling in mammalian CNS development

The renin–angiotensin system promotes arrhythmogenic substrates and lethal arrhythmias in mice with non-ischaemic cardiomyopathy

[Aims]The progression of pathological left ventricular remodelling leads to cardiac dysfunction and contributes to the occurrence of malignant arrhythmias and sudden cardiac death. The underlying molecular mechanisms remain unclear, however. Our aim was to examine the role of the renin–angiotensin system (RAS) in the mechanism underlying arrhythmogenic cardiac remodelling using a transgenic mouse expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). This mouse model exhibits progressive cardiac dysfunction leading to lethal arrhythmias. [Methods and results]Subcutaneous administration of aliskiren, a direct renin inhibitor, significantly suppressed the progression of pathological cardiac remodelling and improved survival among dnNRSF-Tg mice while reducing arrhythmogenicity. Genetic deletion of the angiotensin type 1a receptor (AT1aR) similarly suppressed cardiac remodelling and sudden death. In optical mapping analyses, spontaneous ventricular tachycardia (VT) and fibrillation (VF) initiated by breakthrough-type excitations originating from focal activation sites and maintained by functional re-entry were observed in dnNRSF-Tg hearts. Under constant pacing, dnNRSF-Tg hearts exhibited markedly slowed conduction velocity, which likely contributes to the arrhythmogenic substrate. Aliskiren treatment increased conduction velocity and reduced the incidence of sustained VT. These effects were associated with suppression of cardiac fibrosis and restoration of connexin 43 expression in dnNRSF-Tg ventricles. [Conclusion]Renin inhibition or genetic deletion of AT1aR suppresses pathological cardiac remodelling that leads to the generation of substrates maintaining VT/VF and reduces the occurrence of sudden death in dnNRSF-Tg mice. These findings demonstrate the significant contribution of RAS activation to the progression of arrhythmogenic substrates

The Frizzled 3 gene is associated with methamphetamine psychosis in the Japanese population

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