Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity

We performed a genetic screen in mice to identify candidate genes that are associated with leukaemogenesis in the context of Trp53 heterozygosity. To do this we generated Trp53 heterozygous mice carrying the T2/Onc transposon and SB11 transposase alleles to allow transposon-mediated insertional mutagenesis to occur. From the resulting leukaemias/lymphomas that developed in these mice, we identified nine loci that are potentially associated with tumour formation in the context of Trp53 heterozygosity, including AB041803 and the Jun dimerization protein 2 (Jdp2). We show that Jdp2 transcriptionally regulates the Trp53 promoter, via an atypical AP-1 site, and that Jdp2 expression negatively regulates Trp53 expression levels. This study is the first to identify a genetic mechanism for tumour formation in the context of Trp53 heterozygosity

Permafrost degradation increases risk and large future costs of infrastructure on the Third Pole

Abstract The damage to infrastructure caused by near-surface permafrost degradation is directly related to the well-being of 10 million people and the sustainable development on the Qinghai-Tibet Plateau, the Third Pole of the Earth. Here we identify the economic damage caused by permafrost degradation to infrastructure on the Qinghai-Tibet Plateau by integrating data-driven projection, multihazard index, and lifespan replacement model. We found that additional cost of approximately $6.31 billion will be needed to maintain the service function of current infrastructure under the historical scenario (SSP245) by 2090. While 20.9$1.32 billion relative to the 2 °C target of Paris Agreement. These findings highlight the importance of mitigating global warming and of investment in the adaptation and maintenance of infrastructure on the Qinghai-Tibet Plateau, which has a sparse population but is a climate hotspot