Targeting homologous recombination and telomerase in Barrett’s adenocarcinoma: Impact on telomere maintenance, genomic instability, and tumor growth

Homologous recombination (HR), a mechanism to accurately repair DNA in normal cells, is deregulated in cancer. Elevated/deregulated HR is implicated in genomic instability and telomere maintenance, which are critical lifelines of cancer cells. We have previously shown that HR activity is elevated and significantly contributes to genomic instability in BAC. The purpose of this study was to evaluate therapeutic potential of HR inhibition, alone and in combination with telomerase inhibition, in BAC. We demonstrate that telomerase inhibition in BAC cells increases HR activity, RAD51 expression, and association of RAD51 to telomeres. Suppression of HR leads to shorter telomeres as well as markedly reduced genomic instability in BAC cells over time. Combination of HR suppression (whether transgenic or chemical) with telomerase inhibition, causes a significant increase in telomere attrition and apoptotic death in all BAC cell lines tested, relative to either treatment alone. A subset of treated cells also stain positive for β-galactosidase, indicating senescence. The combined treatment is also associated with decline in S-phase and a strong G2/M arrest, indicating massive telomere attrition. In a subcutaneous tumor model, the combined treatment resulted in the smallest tumors, which were even smaller (P=0.001) than those resulted from either treatment alone. Even the tumors removed from these mice had significantly reduced telomeres and evidence of apoptosis. We therefore conclude that although telomeres are elongated by telomerase, elevated RAD51/HR assist in their maintenance/stabilization in BAC cells. Telomerase inhibitor prevents telomere elongation but induces RAD51/HR, which contribute to telomere maintenance/stabilization and prevention of apoptosis, reducing the efficacy of treatment. Combining HR inhibition with telomerase, makes telomeres more vulnerable to degradation and significantly increases/expedites their attrition, leading to apoptosis. We therefore demonstrate that a therapy, targeting HR and telomerase, has potential to prevent both the tumor growth and genomic evolution in BAC

Fractional composition and evolution of residual oil from coal of Early Permian Shanxi Formation (P1s), Ordos Basin (China)

Abstract To explore the residual oil contents and its fractional compositions changes with thermal stress, experiment of a whole coal sample from lower Permian Shanxi formation (P1sh) of Ordos Basin (China) was conducted in the grain-based micro-scale sealed vessel to explore the residual oil contents, fractional compositions and evolution at different temperatures and maturities. The residual oil of Shanxi coal reach the maximum at Ro=0.92% which was only 47.87 mg/g TOC. In oil window, the residual oil of Shanxi coal is mainly composed of asphaltenes, aromatics and resins with less saturates, showing lower oil prospective. In wet and dry gas windows, the residual oil becomes lower due to oil expulsion and cracking into gases. The main fractional compositions of residual oil are mainly aromatics and resins, which are gas-prone and can be the source of coal-bed methane at higher maturity stages

Extracting Raft Aquaculture Areas from Remote Sensing Images via an Improved U-Net with a PSE Structure

Remote sensing has become a primary technology for monitoring raft aquaculture products. However, due to the complexity of the marine aquaculture environment, the boundaries of the raft aquaculture areas in remote sensing images are often blurred, which will result in ‘adhesion’ phenomenon in the raft aquaculture areas extraction. The fully convolutional network (FCN) based methods have made great progress in the field of remote sensing in recent years. In this paper, we proposed an FCN-based end-to-end raft aquaculture areas extraction model (which is called UPS-Net) to overcome the ‘adhesion’ phenomenon. The UPS-Net contains an improved U-Net and a PSE structure. The improved U-Net can simultaneously capture boundary and contextual information of raft aquaculture areas from remote sensing images. The PSE structure can adaptively fuse the boundary and contextual information to reduce the ‘adhesion’ phenomenon. We selected laver raft aquaculture areas in eastern Lianyungang in China as the research region to verify the effectiveness of our model. The experimental results show that compared with several state-of-the-art models, the proposed UPS-Net model performs better at extracting raft aquaculture areas and can significantly reduce the ‘adhesion’ phenomenon