To investigate the effects of protein malnutrition on a normal growth trajectory, we radiographed Rattus norvegicus from 22 d (weaning) and continuing past adult size. We took measurements from longitudinal radiographs of rats fed a control diet and littermates fed an isocaloric low protein experimental diet. A Gompertz model was fit to each individual rat for body weight and 22 measurements of the craniofacial skeleton, producing parameters that described the rate and timing of growth. We tested for differences in these parameters due to diet, sex and litter with a mixed-model three-way ANOVA. Allometric analysis examined the scaling relationships between and within various regions of the skull. For most measurements, final sizes predicted by the model were not significantly different between rats fed the two diets, although the differences in final measurements showed small, but significant differences in growth between rats in the two diet groups. The instantaneous initial rate of growth, maximum rate of growth and deceleration of growth were significantly higher in the control rats for every measurement. Rats fed the low protein diet grew for a significantly longer period of time. The shape of the neurocranium was relatively conserved between diet groups; however, rats fed the low protein diet had shorter and relatively wider skulls than the controls. These results suggest that functional demands of the viscerocranium were greater after birth, and that growth in this area was faster. The viscerocranium reached functional adult proportions earlier and was therefore more susceptible to epigenetic perturbations such as dietary protein level. Protein malnutrition did not affect many aspects of adult size, but strongly altered the growth trajectory to achieve that size.

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Cyclin-dependent kinase inhibitor p27, a critical determinant for cell cycle progression, is an important regulation target of mitogenic signals during arterial injury. In this study, we show in rat aortic smooth muscle cells that PDGF-BB down-regulated p27 protein and mRNA in an ERK-dependent mechanism. Inhibition of ERK, but not other subtypes of the mitogen-activated protein kinase family, prevented the reduction of p27 protein and mRNA. Conversely, direct activation of ERK via adenovirus-mediated expression of a constitutively active form of MEK led to a reduction of p27 protein and mRNA, further supporting the central role of ERK in regulation of p27 expression. Rapamycin, which potently inhibited PDGF-induced activation of p70 S6 kinase as well as proliferation of smooth muscle cells, did not alter the expression of p27. To delineate the molecular mechanism underlying the p27 down-regulation, we examined the effect of PDGF-BB on p27 promoter activity as well as mRNA stability. Stimulation with PDGF-BB significantly shortened the half-life of p27 mRNA without affecting its promoter activity. To further understand the PDGF-stimulated p27 mRNA turnover, we inserted the 5-and/or 3-untranslated regions of p27 cDNA into a non-PDGF-responsive luciferase gene. Only those chimeric genes that contained the 3-untranslated region responded to PDGF-BB with reduced expression. Moreover, inhibition of ERK completely prevented the effect of PDGF on the chimera expression. In summary, our data suggest that p27 is down-regulated by PDGF-BB in vascular smooth muscle cells through an ERK-dependent posttranscriptional mechanism.

Often compared with the Gold Rush, the marijuana industry is already a multibillion-dollar phenomenon and is expected to generate 22 billion dollars in sales in the United States by 2020. Two years have passed since the legalization of recreational marijuana begun in Colorado. This unprecedented change has created numerous business opportunities as well as legal and operational challenges for the hospitality and tourism industry. This article explores the legalization of recreational marijuana in terms of the tourism industry in Colorado and identifies several challenges found in the current marijuana-related literature in the context of hospitality and tourism research. We also present several research areas that could help hospitality and tourism researchers explore and contribute to the body of knowledge of this emerging market by using Colorado as a focal point. Future research on marijuana tourism is of great importance in that the rapid rise of this niche market creates the pressing challenges and promising opportunities for destinations. Such knowledge will only increase in importance as marijuana tourism continues to evolve as a special interest tourism segment.