Strain differences between C57BL/6 and SWV mice in time of palate closure and induction of palatal slit and cleft palate

Palatal slit, which occurs spontaneously in C57BL/6 (C57BL) mice, is increased in frequency among C57BL fetuses from dams treated with triamcinolone acetonide, but is not induced in SWV fetuses. On the other hand, C57BL is more resistant than SWV to cleft palate induction by triamcinolone. Using these C57BL and SWV mice, the relation of palate stage and chronological age was examined from 1 P.M. on day 14 to 9 A.M. on day 16 in untreated embryos, and the condition of the palate after triamcinolone treatment on day 12 was examined at 9 A.M. on day 16. In untreated embryos, horizontalization and fusion of the palatal shelves occurred earlier in C57BL than in SWV embryos, but fusion of the primary palate with the secondary palate occurred later. After triamcinolone treatment, the development of the palate was delayed in both C57BL and SWV embryos. These results suggest that the times of normal palate closure are related to the differences between C57BL and SWV mice in their susceptibilities to palatal slit and cleft palate induction and that triamcinolone produces palatal slit and cleft palate by delaying palate closure.     

Occurrence of cleft palate, palatal slit, and fetal death in mice treated with a glucocorticoid: an embryo transfer experiment

SWV and C57BL/6 (C57BL) mice were treated subcutaneously with triamcinolone acetonide in a single dose of 2.5 mg/kg on day 12 of pregnancy (vaginal plug = day 0), and the palate of their fetuses was examined at term. Cleft palate was seen in some SWV and C57BL fetuses; its frequency was significantly higher in the former. Closer examination revealed palatal slit in some C57BL, but in no SWV fetuses. In addition, fetal mortality was significantly increased in SWV, but not in C57BL, exposed to triamcinolone. These strain differences in cleft palate, palatal slit, and fetal mortality were investigated by embryo transfer. The results showed that, in cleft palate induction, the effects of uterine environment were more important than those of fetal genotype. On the other hand, after transfer, palatal slit still occurred in C57BL but not in SWV fetuses; thus, in palatal slit occurrence, the fetal genotype played a more important role than the uterine environment. Accordingly, it is suggested that the nature of the participation of fetal genotype and uterine environment in palatal slit occurrence is different from that in cleft palate induction. In regard to fetal mortality, embryo transfer procedures influenced it in SWV dams and the effect of triamcinolone could not be detected after embryo transfer.     

Onset of the constrictive effect of indomethacin on the ductus arteriosus in fetal rats.

The time of onset of the constrictive effect of indomethacin on the ductus arteriosus (DA) in fetal rats was assessed by measurement of the caliber of the DA after maternal treatment with indomethacin on days 19-21 of gestation. The day following overnight mating was regarded as day 0 of gestation. Observation was performed by direct exposure of the DA by hand shaving of intact frozen fetuses. On days 20 and 21, the DA was significantly constricted 3 h after maternal treatment with 1 mg/kg of indomethacin. When the DA was examined at 19 1/2 and 19 2/3 days of gestation (3 h after indomethacin exposure), it was significantly constricted at 19 2/3 days but not at 19 1/2 days. Higher doses of indomethacin (10 and 100 mg/kg) induced a significant constriction of the DA at day 19 1/2, but not at the beginning of the same day (1.00 a.m.). These results suggest that the onset of the susceptibility of the DA to the constrictive effect of indomethacin occurs in the first half of day 19 of gestation.     

Unique T Cells with Unconventional Cytokine Profiles Induced in the Livers of Mice during Schistosoma mansoni Infection

During infection with Schistosoma, serious hepatic disorders are induced in the host. The liver possesses unique immune systems composed of specialized cells that differ from those of other immune competent organs or tissues. Host immune responses change dramatically during Schistosoma mansoni infection; in the early phase, Th1-related responses are induced, whereas during the late phase Th2 reactions dominate. Here, we describe unique T cell populations induced in the liver of mice during the period between Th1- and Th2-phases, which we term the transition phase. During this phase, varieties of immune cells including T lymphocytes increase in the liver. Subsets of CD4⁺ T cells exhibit unique cytokine production profiles, simultaneously producing both IFN-γ and IL-13 or both IFN-γ and IL-4. Furthermore, cells triply positive for IFN-γ, IL-13 and IL-4 also expand in the S. mansoni-infected liver. The induction of these unique cell populations does not occur in the spleen, indicating it is a phenomenon specific to the liver. In single hepatic CD4⁺ T cells showing the unique cytokine profiles, both T-bet and GATA-3 are expressed. Thus, our studies show that S. mansoni infection triggers the induction of hepatic T cell subsets with unique cytokine profiles.     

Regulation of active and quiescent somatic stem cells by Notch signaling

Somatic stem/progenitor cells actively proliferate and give rise to different types of mature cells (active state) in embryonic tissues while they are mostly dormant (quiescent state) in many adult tissues. Notch signaling is known to regulate both active and quiescent states of somatic stem cells, but how it regulates these different states is unknown. Recent studies revealed that the Notch effector Hes1 is expressed differently during the active and quiescent states during neurogenesis and myogenesis: high in the quiescent state and oscillatory in the active state. When the Hes1 expression level is high, both Ascl1 and MyoD expression are continuously suppressed. By contrast, when Hes1 expression oscillates, it periodically represses expression of the neurogenic factor Ascl1 and the myogenic factor MyoD, thereby driving Ascl1 and MyoD oscillations. High levels of Hes1 and the resultant Ascl1 suppression promote the quiescent state of neural stem cells, while Hes1 oscillation-dependent Ascl1 oscillations regulate their active state. Similarly, in satellite cells of muscles, known adult muscle stem cells, high levels of Hes1 and the resultant MyoD suppression seem to promote their quiescent state, while Hes1 oscillation-dependent MyoD oscillations activate their proliferation and differentiation. Therefore, the expression dynamics of Hes1 is a key regulatory mechanism of generating and maintaining active/quiescent stem cell states.     

Unprecedented olefin-dependent histidine-kinase inhibitory of zerumbone ring-opening material

Zerumbone ring-opening derivative, 4 (10E/10Z=3/2), inhibited autophosphorylation of the essential histidine-kinase YycG existing in Bacillus subtilis constituting a two-component system (TCS). Generation of 4E-form could be regulated chemically using the difference from the ring-opening reactivity of the precursor forming of 4 and pure 4E was isolated. The stereoisomer, 4E, showed main inhibition activity of autophosphorylation of YycG (IC(50)=63.5 microM).