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Purpose: Retinoblastoma, a childhood cancer, is most frequently caused by bi-allelic inactivation of RB1 gene. However, other oncogenic mutations such as MYCN amplification can induce retinoblastoma with proficient RB1. Previously, we established RB1-proficient MYCN-overexpressing retinoblastoma models both in human organoids and chicken. Here, we investigate the regulatory events in MYCN-induced retinoblastoma carcinogenesis based on the model in chicken. Methods: MYCN transformed retinal cells in culture were obtained from in vivo MYCN electroporated chicken embryo retina. The expression profiles were analysed by RNA sequencing. Chemical treatments, qRT-PCR, flow cytometry, immunohisto- and immunocytochemistry and western blot were applied to study the properties and function of these cells. Results: The expression profile of MYCN-transformed retinal cells in culture showed cone photoreceptor progenitor signature and robustly increased levels of E2Fs. This expression profile was consistently observed in long-term culture. Chemical treatments confirmed RB1 proficiency in these cells. The cells were insensitive to p53 activation but inhibition of E2f efficiently induced cell cycle arrest followed by apoptosis. Conclusion: In conclusion, with proficient RB1, MYCN-induced high level of E2F expression dysregulates the cell cycle and contributes to retinoblastoma carcinogenesis. The increased level of E2f renders the cells to adopt a similar mechanistic phenotype to a RB1-deficient tumour. [ABSTRACT FROM AUTHOR]

Abstract: A multi-element quartz shock gauge (MEQSG) with seven active sensing elements has been used to characterize impact loading. The measuring principle is based on the Sandia quartz gauge (SQG) criteria. Gas shock tube tests of the MEQSG have been conducted for uniform planar shock loading. The experimental results confirm the universal response of the seven active sensing elements of the MEQSG. Of particular interest is the application of the MEQSG to sense the direct “ejected matter” (ejecta) shock loading. Data show the total measured ejecta mass, which is in agreement with the predetermined mass. These results demonstrate that the MEQSG can be applied to sense unknown non-uniform spatial loading distribution. [Copyright &y& Elsevier]