A mouse bone marrow stromal cell line, TBR-B, shows inducible expression of smooth muscle-specific genes

AbstractWe established an in vitro culture system which mimicked the differentiation pathway of smooth muscle cell, using TBR-B, a bone marrow stromal cell line derived from transgenic mice harboring temperature-sensitive SV40 large T-antigen gene. TBR-B cells have the potential to express smooth muscle-specific genes including h1-calponin, h-caldesmon, SM22α and α-actin, only after cultured in the differentiation medium for 2 weeks. The differentiation state of TBR-B was well controlled by using different culture medium. Using this cell line, we also found that ascorbic acid is a potent factor inducing the expression of h1-calponin and α-actin. TBR-B cells will serve as a useful tool for elucidating the regulatory mechanisms of smooth muscle-specific gene expression, and for identifying compounds that regulate the differentiation state of vascular smooth muscle cells

Orexin neurons suppress narcolepsy via 2 distinct efferent pathways

13301甲第4185号博士（医学）金沢大学博士論文本文Full 以下に掲載：The Journal of Clinical Investigation 124(2) pp.604-616 2014. The Journal of Clinical Investigation. 共著者：長谷川 恵美, 柳沢 正史, 櫻井 武, 三枝 理

中枢概日時計のニューロンタイプ特異的な神経生理学的解析

科学研究費助成事業 研究成果報告書：若手研究(B)2016-2017課題番号 : 16K1900

High Incubation Investment of Females Paired to Attractive Males in Barn Swallows

Differential parental investment is the sexual selection process in which females that have acquired an attractive male invest relatively more in his offspring than females that are paired to an unattractive male. However, it is often difficult to distinguish between differential parental investment and compensation for a decrease in parental investment by an attractive mate. Using Barn Swallows Hirundo rustica gutturalis, in which males rarely participate in incubation, we investigated differential incubation investment of females. We made the following four observations: (1) Females participate in 94% of total nest attentiveness (time that eggs were incubated). (2) Female nest attentiveness was positively correlated with the ornamentation of their mates, the size of white spots in the tail, which is a measure of male attractiveness in this population. (3) Male nest attentiveness was not related to male ornaments. (4) Total nest attentiveness was positively correlated with the size of white spots in the tail. These results are consistent with differential parental investment, but not with compensation for a decrease in parental investment by a mate. Therefore, we conclude that female Barn Swallows that have acquired an attractive male invest differentially in incubation

Fine-tuning circadian rhythms: The importance of Bmal1 expression in the ventral forebrain

Although, the suprachiasmatic nucleus (SCN) of the hypothalamus acts as the central clock in mammals, the circadian expression of clock genes has been demonstrated not only in the SCN, but also in peripheral tissues and brain regions outside the SCN. However, the physiological roles of extra-SCN circadian clocks in the brain remain largely elusive. In response, we generated Nkx2.1-Bmal1-/- mice in which Bmal1, an essential clock component, was genetically deleted specifically in the ventral forebrain, including the preoptic area, nucleus of the diagonal band, and most of the hypothalamus except the SCN. In these mice, as expected, PER2::LUC oscillation was drastically attenuated in the explants of mediobasal hypothalamus, whereas it was maintained in those of the SCN. Although, Nkx2.1-Bmal1-/- mice were rhythmic and nocturnal, they showed altered patterns of locomotor activity during the night in a 12:12-h light:dark cycle and during subjective night in constant darkness. Control mice were more active during the first half than the second half of the dark phase or subjective night, whereas Nkx2.1-Bmal1-/- mice showed the opposite pattern of locomotor activity. Temporal patterns of sleep-wakefulness and feeding also changed accordingly. Such results suggest that along with mechanisms in the SCN, local Bmal1-dependent clocks in the ventral forebrain are critical for generating precise temporal patterns of circadian behaviors. © 2017 Mieda, Hasegawa, Kessaris and Sakurai

Orexin neurons suppress narcolepsy via 2 distinct efferent pathways

The loss of orexin neurons in humans is associated with the sleep disorder narcolepsy, which is characterized by excessive daytime sleepiness and cataplexy. Mice lacking orexin peptides, orexin neurons, or orexin receptors recapitulate human narcolepsy phenotypes, further highlighting a critical role for orexin signaling in the maintenance of wakefulness. Despite the known role of orexin neurons in narcolepsy, the precise neural mechanisms downstream of these neurons remain unknown. We found that targeted restoration of orexin receptor expression in the dorsal raphe (DR) and in the locus coeruleus (LC) of mice lacking orexin receptors inhibited cataplexy-like episodes and pathological fragmentation of wakefulness (i.e., sleepiness), respectively. The suppression of cataplexy-like episodes correlated with the number of serotonergic neurons restored with orexin receptor expression in the DR, while the consolidation of fragmented wakefulness correlated with the number of noradrenergic neurons restored in the LC. Furthermore, pharmacogenetic activation of these neurons using designer receptor exclusively activated by designer drug (DREADD) technology ameliorated narcolepsy in mice lacking orexin neurons. These results suggest that DR serotonergic and LC noradrenergic neurons play differential roles in orexin neuron-dependent regulation of sleep/wakefulness and highlight a pharmacogenetic approach for the amelioration of narcolepsy. © Copyright 2014 American Society for Clinical Investigation

On the Nature of AX J2049.6+2939 and AX J2050.0+2914

AX J2049.6+2939 is a compact X-ray source in the vicinity of the southern blow-up region of the Cygnus Loop supernova remnant (Miyata et al. 1998a). This source was the brightest X-ray source inside the Cygnus Loop observed during the ASCA survey project. The X-ray spectrum was well fitted by a power-law function with a photon index of $-2.1 \pm 0.1$. Short-term timing analysis was performed and no coherent pulsation was found. Follow-up observations with ASCA have revealed a large variation in X-ray intensity by a factor of $\simeq$ 50, whereas the spectral shape did not change within the statistical uncertainties. In the second ASCA observation, we found another X-ray source, AX J2050.0+2941, at the north east of AX J2049.6+2939. During the three ASCA observations, the X-ray intensity of AX J2050.0+2941 varied by a factor of $\simeq$4. No coherent pulsations could be found for AX J2050.0+2941. We have performed optical photometric and spectroscopic observations in the vicinity of AX J2049.6+2939 at the Kitt Peak National Observatory (KPNO). As a result, all objects brighter than $B$-band magnitude of 22 in the error box can be identified with normal stars. Combined with the X-ray results and the fact that there are no radio counterparts, AX J2049.6+2939 is not likely to be either an ordinary rotation-powered pulsar or an AGN. The nature of AX J2049.6+2939 is still unclear and further observations over a wide energy band are strongly required. As to AX J2050.0+2941, the long-term X-ray variability and the radio counterpart suggests that it is an AGN.Comment: 23 pages, 4 figures, Accepted for publication by Astrophysical Journa