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Hypoxia-induced SETX links replication stress with the unfolded protein response
YesTumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.SR, KBL, PV and MH were supported by a CRUK grant C5255/A23755 (awarded to E.M.H.). N.N. was supported by an MRC studentship (MC_ST_U16007). I. P.F. was supported by CRUK Oxford Centre Prize DPhil Studentship C38302/A12981. N.G. was supported by a Royal Society University Research fellowship. W.-C.C. was funded by CRUK grant 23969 (awarded to F.M.B.). S.F.E.-K. was supported by a Wellcome Trust Investigator Award (103844) and a Lister Institute of Preventative Medicine Fellowship (137661). J.G. was supported by a Jean Shanks Foundation/ Pathological Society of Great Britain and Ireland Clinical PhD Fellowship (JSPS CPhD 2018 01)
Consumer perceptions of monetary and non-monetary introductory promotions for new products
Little research has examined how consumers respond to sales promotions in new product categories. This article fills this gap by integrating research on reference prices with literature on sales promotions for new product categories. Existing research suggests that consumers respond more favourably to non-monetary promotions (e.g. extra free promotions) than monetary promotions (e.g. price discounts) because non-monetary promotions are framed as segregated gains rather than reduced losses. However, both kinds of promotions are widely used in practice, suggesting the importance of other contributory factors. With a consumer experiment on a national panel of consumers, this research demonstrates that extra free product promotions are most preferred for existing products, and introductory low-price promotions are preferred for innovative products. The moderating effect of a product's innovativeness is explained via a new relationship in the marketing literature, whereby perceived risk mediates the relationship between perceived innovativeness and a consumer's tendency to stockpile
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