Caspase-8 activation initiates apoptotic signaling cascades, and certain mutations in procasepase-8 have been reported to be associated with the progression and prognosis of different types of tumors. In this study, we have identified four novel mutations, which are highly correlated with chemotherapy resistance and poor prognosis of acute myeloid leukemia (AML) patients, within the P10 subunit of procaspase-8. These newly discovered mutations cause premature termination of translation, resulting in truncated procaspase-8 protein, which is incapable of forming dimer to initiate apoptosis signaling pathway. Further biochemical analysis reveals that the segment of P10 subunit of procaspase-8 consisting of three amino acid residues from L491 to F493 is crucial for the formation of procaspase-8 interdimer, and the aberration of this segment disrupts the dimerization and consequently precludes the activation of caspase-8 and downstream apoptotic signaling pathway. Therefore, the patients with AML who bear these types of P10 mutations were more likely to develop chemotherapy resistance due to impaired apoptotic signaling in cellular system, leading to significantly reduced overall survival (OS) as compared with patients carrying no such types of P10 mutations. Taken together, these newly identified P10 mutations in procaspase-8 could be used as novel biomarkers for predicting response and survival of chemotherapy-treated AML patients, as well as potential therapeutic targets for medical intervention in the future.
Purpose
The purpose of this paper is to see whether children’ regulatory fit/nonfit can moderate the implicit influence of in-game advertising.
Design/methodology/approach
An experiment was done with 418 children (aged 7–11) from three primary schools in a middle-size city in China that voluntarily took part in the experiment. Children were randomly allocated to the following four conditions: playing a game without any brands (a control group), playing the same game and exposed to a subtle in-game advertising (a test control group), playing the same branded game with regulatory fit (regulatory fit group) and playing the same branded game with regulatory nonfit (regulatory nonfit group).
Findings
The results first suggest exposure to in-game advertising makes children more likely to choose it afterward, despite most of them are not aware being exposed to it. The results further suggest children’s regulatory fit does not further increase children’s choice of the focal brand, suggesting linking the focal brand to fun and engaging game experiences is sufficient to influence their brand choice. However, children’s regulatory nonfit attenuates the implicit influence of in-game advertising.
Originality/value
By focusing on children’s game strategy, this research complements the extant literature that only focuses on advertising features and/or game character to document the implicit influence of in-game advertising. In addition, by focusing on regulatory fit/nonfit, this paper provides initial evidence how contextual factors such as children’s game strategy may help them cope with advertising influence built on affect transfer.
Two new V V complexes with the bromo-substituted hydrazones N'-(3-bromo-2-hydroxybenzylidene)-3-hydroxy-4-methoxybenzohydrazide (H 2 L 1), N'-(3-bromo-2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide (H 2 L 2), [VOL 1 (OCH 3)(CH 3 OH)] (1) and [VOL 2 (OCH 3)(CH 3 OH)] (2), were synthesized and structurally characterized by IR, UV-Vis and 1 H NMR spectroscopy, as well as single-crystal X-ray determination. The V atom in the mononuclear complexes are six-coordinated in octahedral geometry. The free hydrazones and the complexes were studied on their antibacterial activity on S. aureus, B. subtilis, E. coli and P. fluorescence, and antifungal activity on C. albicans and A. niger. The bromo groups of the hydrazone ligands may increase their antibacterial activity.
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