Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition

Ishikawa, T., Kitaura, Y., Kadota, Y. et al. Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition. Sci Rep 7, 39825 (2017). https://doi.org/10.1038/srep3982

Suplatast tosilate alleviates nasal symptoms through the suppression of nuclear factor of activated T-cells-mediated IL-9 gene expression in toluene-2,4-diisocyanate-sensitized rats

Histamine H1 receptor (H1R) gene is upregulated in patients with pollinosis; its expression level is highly correlated with the nasal symptom severity. Antihistamines are widely used as allergy treatments because they inhibit histamine signaling by blocking H1R or suppressing H1R signaling as inverse agonists. However, long-term treatment with antihistamines does not completely resolve toluene-2,4-diisocyanate (TDI)-induced nasal symptoms, although it can decrease H1R gene expression to the basal level, suggesting additional signaling is responsible for the pathogenesis of the allergic symptoms. Here, we show that treatment with suplatast tosilate in combination with antihistamines markedly alleviates nasal symptoms in TDI-sensitized rats. Suplatast suppressed TDI-induced upregulation of IL-9 gene expression. Suplatast also suppressed ionomycin/phorbol-12-myristate-13-acetate-induced upregulation of IL-2 gene expression in Jurkat cells, in which calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling is known to be involved. Immunoblot analysis demonstrated that suplatast inhibited binding of NFAT to DNA. Furthermore, suplatast suppressed ionomycin-induced IL-9 mRNA upregulation in RBL-2H3 cells, in which CN/NFAT signaling is also involved. These data suggest that suplatast suppressed NFAT-mediated IL-9 gene expression in TDI-sensitized rats and this might be the underlying mechanism of the therapeutic effects of combined therapy of suplatast with antihistamine

A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions.

Human pluripotent stem cells (hPSCs), including embryonic stem cells and induced pluripotent stem cells, are potentially useful in regenerative therapies for heart disease. For medical applications, clinical-grade cardiac cells must be produced from hPSCs in a defined, cost-effective manner. Cell-based screening led to the discovery of KY02111, a small molecule that promotes differentiation of hPSCs to cardiomyocytes. Although the direct target of KY02111 remains unknown, results of the present study suggest that KY02111 promotes differentiation by inhibiting WNT signaling in hPSCs but in a manner that is distinct from that of previously studied WNT inhibitors. Combined use of KY02111 and WNT signaling modulators produced robust cardiac differentiation of hPSCs in a xeno-free, defined medium, devoid of serum and any kind of recombinant cytokines and hormones, such as BMP4, Activin A, or insulin. The methodology has potential as a means for the practical production of human cardiomyocytes for regeneration therapies

On a unified double zeta function of Mordell--Tornheim type

We introduce the unified double zeta function of Mordell--Tornheim type and compute its values at non-positive integer points. We then discuss a possible generalization of the Kaneko--Zagier conjecture for all integer points.Comment: 13 page

What is the value added by caseworkers?

Includes bibliographical references. Title from cover. Also available via the InternetAvailable from British Library Document Supply Centre- DSC:3597. 9512(no 3825) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Excitatory and inhibitory 5-hydroxytryptamine (5-HT) receptors expressed in the isolated porcine uterine muscles

5-Hydroxytryptamine (5-HT) receptors mediating excitatory and inhibitory actions of 5-HT on contractility of uterine strips from non-pregnant pigs were characterized. Expression of 5-HT_<2A> and 5-HT_7 receptors was examined by molecular biological study. 5-HT-containing cells were observed immunohistochemically. In the spontaneously contracting uterine circular muscle layers, 5-HT caused inhibition of contractile activity. SB269970 (5-HT_7 receptor antagonist, 10 nM) shifted the concentration-inhibition curve of 5-HT to the right, but higher concentrations of SB269970 (100 nM-1 μM) changed the monophasic curve to a biphasic curve (mixture of excitatory and inhibitory responses to 5-HT). Addition of ketanserin (5-HT_2 receptor antagonist, 10 nM-1 μM) decreased the excitatory effects of 5-HT. 5-HT was less effective in inhibiting the spontaneous contraction in the longitudinal muscles. Ketanserin enhanced the inhibitory responses and SB269970 reversed the inhibitory responses to excitatory responses. In the presence of SB269970, α-methyl-5-HT was equipotent to 5-HT in increasing contractility of longitudinal muscle and ketanserin competitively inhibited the responses to α-methyl-5-HT (pK_d = 8.78). Muscle layer-dependent expression of both 5-HT_<2A> receptor and 5-HT_7 receptor mRNAs in the porcine uterine muscle layers was demonstrated by RT-PCR and real-time PCR. 5-HT immunoreactivity was detected only in uterine gland cells, which were localized near the uterine circular muscle layers. In the longitudinal and circular muscle layers with endometrium, compounds 48/80 and ketanserin did not change the spontaneous contractility, but SB269970 significantly increased the contractile activity of the circular muscle. In conclusion, excitatory 5-HT_<2A> and inhibitory 5-HT_7 are present in the uterus of non-pregnant pigs. Endogenous 5-HT containing cells are mainly present in uterine glands of the pig. The possible roles of 5-HT and its receptors in regulation of porcine uterine spontaneous contractility are discussed