Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects

Circulating microRNAs (miRNAs) are receiving attention as potential biomarkers of various diseases, including cancers, chronic obstructive pulmonary disease, and cardiovascular disease. However, it is unknown whether the levels of circulating miRNAs in a healthy subject might vary with external factors in daily life. In this study, we investigated whether cigarette smoking, a habit that has spread throughout the world and is a risk factor for various diseases, affects plasma miRNA profiles. We determined the profiles of 11 smokers and 7 non-smokers by TaqMan MicroRNA array analysis. A larger number of miRNAs were detected in smokers than in non-smokers, and the plasma levels of two-thirds of the detected miRNAs (43 miRNAs) were significantly higher in smokers than in non-smokers. A principal component analysis of the plasma miRNA profiles clearly separated smokers and non-smokers. Twenty-four of the miRNAs were previously reported to be potential biomarkers of disease, suggesting the possibility that smoking status might interfere with the diagnosis of disease. Interestingly, we found that quitting smoking altered the plasma miRNA profiles to resemble those of non-smokers. These results suggested that the differences in the plasma miRNA profiles between smokers and non-smokers could be attributed to cigarette smoking. In addition, we found that an acute exposure of ex-smokers to cigarette smoke (smoking one cigarette) did not cause a dramatic change in the plasma miRNA profile. In conclusion, we found that repeated cigarette smoking substantially alters the plasma miRNA profile, interfering with the diagnosis of disease or signaling potential smoking-related diseases. © 2013 Elsevier Inc

Identification of a novel intronic enhancer responsible for the transcriptional regulation of musashi1 in neural stem/progenitor cells

<p>Abstract</p> <p>Background</p> <p>The specific genetic regulation of neural primordial cell determination is of great interest in stem cell biology. The Musashi1 (Msi1) protein, which belongs to an evolutionarily conserved family of RNA-binding proteins, is a marker for neural stem/progenitor cells (NS/PCs) in the embryonic and post-natal central nervous system (CNS). Msi1 regulates the translation of its downstream targets, including <it>m-Numb </it>and <it>p21 </it>mRNAs. <it>In vitro </it>experiments using knockout mice have shown that Msi1 and its isoform Musashi2 (Msi2) keep NS/PCs in an undifferentiated and proliferative state. Msi1 is expressed not only in NS/PCs, but also in other somatic stem cells and in tumours. Based on previous findings, Msi1 is likely to be a key regulator for maintaining the characteristics of self-renewing stem cells. However, the mechanisms regulating <it>Msi1 </it>expression are not yet clear.</p> <p>Results</p> <p>To identify the DNA region affecting <it>Msi1 </it>transcription, we inserted the fusion gene <it>ffLuc</it>, comprised of the fluorescent <it>Venus </it>protein and firefly <it>Luciferase</it>, at the translation initiation site of the mouse <it>Msi1 </it>gene locus contained in a 184-kb bacterial artificial chromosome (BAC). Fluorescence and Luciferase activity, reflecting the <it>Msi1 </it>transcriptional activity, were observed in a stable BAC-carrying embryonic stem cell line when it was induced toward neural lineage differentiation by retinoic acid treatment. When neuronal differentiation was induced in embryoid body (EB)-derived neurosphere cells, reporter signals were detected in Msi1-positive NSCs and GFAP-positive astrocytes, but not in MAP2-positive neurons. By introducing deletions into the BAC reporter gene and conducting further reporter experiments using a minimized enhancer region, we identified a region, "D5E2," that is responsible for <it>Msi1 </it>transcription in NS/PCs.</p> <p>Conclusions</p> <p>A regulatory element for <it>Msi1 </it>transcription in NS/PCs is located in the sixth intron of the <it>Msi1 </it>gene. The 595-bp D5E2 intronic enhancer can transactivate <it>Msi1 </it>gene expression with cell-type specificity markedly similar to the endogenous Msi1 expression patterns.</p

精神疾患におけるマイクログリア由来ニューレグリン発現

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.博士（医学）・乙第1404号・平成29年6月28日Copyright © 2017 Elsevier Inc. All rights reserved

Electrochemical Polarization Part 1: Fundamentals and Corrosion

Polarization measurement is one of the major electrochemical methods used by electrochemists. The changes in current/potential with time at constant potential/current are investigated. The outcomes of these observations can be used to plot a current–potential curve. Therefore, it is important to understand the relationship between the three parameters: electrode potential, current, and time. In this paper, we described the fundamentals of the polarization, especially the current–potential curve (Butler–Volmer equation) and mass-transfer. In addition, the concept of polarization in corrosion reactions is explored

Electrochemical Polarization Part 2: Electrochemical Devices

In this paper, examples of polarization measurements with a battery, electric double-layer capacitor, and fuel cell are discussed. The analysis of the polarization of a real cell and analytical methodology are described. In battery section, the rate capability is examined in detail and the origin of the different rate properties is discussed. Charge/discharge tests and self-discharge measurements are performed in the electric double-layer capacitor. Detailed measurement conditions and data analysis methods are introduced in the fuel cell section. The contents indicated in each section are very useful for interpreting the obtained experimental data

Primary cerebral and cerebellar astrocytes display differential sensitivity to extracellular sodium with significant effects on apoptosis.

Central pontine myelinolysis is one of the idiopathic or iatrogenic brain dysfunction, and the most common cause is excessively rapid correction of chronic hyponatraemia. While myelin disruption is the main pathology, as the diagnostic name indicates, a previous study has reported that astrocyte death precedes the destruction of the myelin sheath after the rapid correction of chronic low Na+ levels, and interestingly, certain brain regions (cerebral cortex, hippocampus, etc.) are specifically damaged but not cerebellum. Here, using primary astrocyte cultures derived from rat cerebral cortex and cerebellum, we examined how extracellular Na+ alterations affect astrocyte death and whether the response is different between the two populations of astrocytes. Twice the amount of extracellular [Na+] and voltage-gated Na+ channel opening induced substantial apoptosis in both populations of astrocytes, while, in contrast, one half [Na+] prevented apoptosis in cerebellar astrocytes, in which the Na+–Ca2+ exchanger, NCX2, was highly expressed but not in cerebral astrocytes. Strikingly, the rapid correction of chronic one half [Na+] exposure significantly increased apoptosis in cerebellar astrocytes but not in cerebral astrocytes. These results indicate that extracellular [Na+] affects astrocyte apoptosis, and the response to alterations in [Na+] is dependent on the brain region from which the astrocyte is derived.博士（医学）・乙第1346号・平成26年12月3日Copyright © 2014 John Wiley & Sons, Ltd.identifier:Cell biochemistry and function Vol.32 No.4 p.395-400identifier:02636484identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2750identifier:Cell biochemistry and function, 32(4): 395-40