Sonic hedgehog (Shh) is a secreted morphogen crucial for cell fate decision, cellular proliferation, and patterning during vertebrate development. The intracellular Shh signalling is transduced by Smoothened (Smo), a seven-transmembrane spanning protein that belongs to the G-protein coupled receptor family. Among four families of Gα α α α subunits, Gα α α α i has been thought to be responsible for transducing Shh signalling, while several lines of evidence indicated that other signalling pathways may be involved. We found that the G12 family of heterotrimeric G proteins and the small GTPase RhoA are involved in Shh/Smo-mediated cellular responses, including stimulation of target gene promoter and inhibition of neurite outgrowth of neuroblastoma cells. We also found that the G12/RhoA pathway is responsible for Smo-induced nuclear import of GLI3 which is thought to transduce Shh signals to nucleus. Furthermore, misexpression of a G12-specific GTPase-activating protein in rat neural tubes leads to pertubation of motor neurone and interneurone development, mimicking the effects of decreased Shh signalling. These results show that Shh signalling is mediated in part by activating G12 family coupled signalling pathways. The participation of RhoA, a pivotal molecular switch in many signal transduction pathways, may help explain how Shh can trigger a variety of cellular responses.
Spherically propagating laminar and turbulent flames were studied using iso-octane / air mixtures with and without dilution. The main purpose of this study is to clarify the influence of thermo-diffusive effects on the turbulent flames. In order to examine the thermo-diffusive effects solely by separating them from the effects of flame stretch, turbulent burning velocities were compared at constant flame stretch factors. The mean flame stretch factor acting on turbulent flame front may be represented by the turbulence Karlovitz number. Thus, turbulent explosions were carried out at fixed turbulence Karlovitz numbers. The ratio of turbulent burning velocity to unstretched laminar burning velocity increased with the equivalence ratio for non-diluted mixtures at fixed turbulence Karlovitz numbers. And this ratio for CO2 diluted mixtures was larger than N2 diluted mixtures. The Markstein number that denotes the sensitivity of the flame to thermo-diffusive effects depends on the equivalence ratio and diluents of the mixture. The ratio of turbulent burning velocity to unstretched laminar one increased with decreasing Markstein number. Especially, it changed stepwise around Markstein number of zero. However, the burning velocity ratios did not increase with increasing mixture pressure although the Markstein number decreased with pressure.
Repair of superficial damage to gastrointestinal mucosa occurs by a process called restitution. Goblet cells reside throughout the length of the intestine and are responsible for the production of mucus. However, a kinetic analysis of goblet cell dynamics of small intestine in restitution has hitherto not been reported. The aim of the present study was to investigate the role of goblet cells in the process of restitution of rat small intestine subjected to ischemia and ischemia-reperfusion injury, and therefore intestinal epithelium from rats subjected to both ischemia and ischemia-reperfusion was studied. Detachment of enterocytes was observed after 5-min of reperfusion. After 20-30 minutes of reperfusion, the denuded villous tips were covered with goblet cells. Within 75 min of reperfusion the epithelium restitution was complete. On the other hand, restitution was not observed in ischemia group. These data suggest that goblet cells may play an important role in restitution after ischemia-reperfusion injury.
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