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3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression
Colorectal carcinoma (CRC) is a deadly cancer with an aggressive nature, and how CRC tumor cells manage to translocate and proliferate in a new tissue environment remains not fully understood. Recently, higher-order chromatin structures and spatial genome organization are increasingly implicated in diseases including cancer, but in-depth studies of three-dimensional genome (3D genome) of metastatic cancer are currently lacking, preventing the understanding of the roles of genome organization during metastasis. Here we perform multi-omics profiling of matched normal colon, primary tumor, lymph node metastasis, liver metastasis and normal liver tissue from CRC patients using Hi-C, ATAC-seq and RNA-seq technologies. We find that widespread alteration of 3D chromatin structure is accompanied by dysregulation of genes including SPP1 during the tumorigenesis or metastasis of CRC. Remarkably, the hierarchy of topological associating domain (TAD) changes dynamically, which challenges the traditional view that the TAD structure between tumor and normal tissue is conservative. In addition, we define compartment stability score to measure large-scale alteration in metastatic tumors. To integrate multi-omics data and recognize candidate genes driving cancer metastasis, a pipeline is developed based on Hi-C, RNA-seq and ATAC-seq data. And three candidate genes ARL4C, FLNA, and RGCC are validated to be associated with CRC cell migration and invasion using in vitro knockout experiments. Overall, these data resources and results offer new insights into the involvement of 3D genome in cancer metastasis.
Reply to: Creep deformation does not explain the Brumadinho disaster
Microstructure and permanent damage We understand the discussers’ line of thought, but a quantitative analysis of Fig. 1 in Reid et al.1 supports our conclusion that…
Mixed-layer lipidomes suggest offshore transport of energy-rich and essential lipids by cyclonic eddies
Mesoscale eddies are ubiquitous features in the ocean affecting the cycles of nutrients and carbon. Cyclonic eddies formed in Eastern Boundary Upwelling Systems can substantially modulate primary production by phytoplankton and the vertical and lateral export of organic carbon. However, the impact of eddy activity on the biochemical composition of eukaryotic phytoplankton, bacteria and archaea and associated consequences for carbon and energy flows are largely unknown. Here, we investigated the microbial lipidome in the surface ocean in and around a cyclonic eddy formed in the coastal upwelling system off Mauritania. We show that the eddy contained almost three times the amount of lipids compared to the surrounding open-ocean and coastal waters. The eddy lipid signature with energy-rich triacylglycerols and essential fatty acid-containing membrane lipids of eukaryotic phytoplankton origin was further significantly different from the ambient waters. Strong variability in lipid distributions within the eddy was related to differences in microbial community composition. Estimates indicate that in the Mauritanian upwelling area, as much as 9.7 ± 2.0 gigagrams of lipid carbon per year is delivered to the open ocean by coastal cyclonic eddies potentially fueling higher trophic levels and contributing to the maintenance of secondary productivity and carbon export offshore.
Tracing inclusivity at UNFCCC conferences through side events and interest group dynamics
Inclusivity and transparency are the foundations of procedural justice in climate governance. However, concerns persist around the influence of business interest groups at United Nations Framework Convention on Climate Change (UNFCCC) Conferences of Parties (COPs). COPs have increased in size and complexity, obscuring agendas and organizational relationships. Here we analyse the discourse and networks of actors at COP side events from 2003 to 2023 using machine learning-based topic modelling and social network analysis. We trace how discussions on energy, food and forests have evolved. Focusing on energy topics, we show that fossil fuel lobbyists gain COP access through developed-country business non-governmental organizations (NGOs) and developing-country governments. Their nominators focus on renewable energy and system approaches but are peripheral in the anti-fossil fuel discourse which grew from a collaborative network of environmental NGOs. Despite data availability challenges, systematically tracing the inclusivity of COP processes can uncover power dynamics at the highest levels of climate governance.
Power price stability and the insurance value of renewable technologies
To understand if renewables stabilize or destabilize electricity prices, we simulate European power markets as projected by the National Energy and Climate Plans for 2030 but replicating the historical variability in electricity demand, the prices of fossil fuels and weather. We propose a β-sensitivity metric, defined as the projected increase in the average annual price of electricity when the price of natural gas increases by 1 euro. We show that annual power prices spikes would be more moderate because the β-sensitivity would fall from 1.4 euros to 1 euro. Deployment of solar photovoltaic and wind technologies exceeding 30% of the 2030 target would lower it further, below 0.5 euros. Our framework shows that this stabilization of prices would produce social welfare gains, that is, we find an insurance value of renewables. Because market mechanisms do not internalize this value, we argue that it should be explicitly considered in energy policy decisions.
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