In many cancers, high proliferation rates correlate with elevation of rRNA and tRNA levels, and nucleolar hypertrophy. However, the underlying mechanisms linking increased nucleolar transcription and tumorigenesis are only minimally understood. Here we show that IMP dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for
de novo
guanine nucleotide biosynthesis, is overexpressed in the highly lethal brain cancer, glioblastoma (GBM). This leads to increased rRNA and tRNA synthesis, stabilization of the nucleolar GTP-binding protein, Nucleostemin, and enlarged, malformed nucleoli. Pharmacological or genetic inactivation of IMPDH2 in GBM reverses these effects and inhibits cell proliferation, whereas untransformed glia cells are unaffected by similar IMPDH2 perturbations. Impairment of IMPDH2 activity triggers nucleolar stress and growth arrest of GBM cells even in the absence of functional p53. Our results reveal that upregulation of IMPDH2 is a prerequisite for aberrant nucleolar function and increased anabolic processes in GBM, which constitutes a primary event in gliomagenesis.
In this paper, we propose a tabletop system for affecting our perception of satiety and controlling energy intakes by controlling a size of a projected image around the food. We hypothesized that ambiguous perception of satiety can be applied to control our food intake. Given that estimating portion size is often a relative judgment, apparent food volume is assessed according to the size of neighboring objects such as many cutleries. Especially, the effect of the size of dish on food intake has been debated. Based on the knowledge, we constructed a tabletop system which projects virtual dishes around the food on it, in order to change the assessed apparent food volume interactively. Our results suggest that the size of virtual dish change the perception of satiety and the amount of food consumption.
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