A functional analysis of 180 cancer cell lines reveals conserved intrinsic metabolic programs.

Cancer cells reprogram their metabolism to support growth and invasion. While previous work has highlighted how single altered reactions and pathways can drive tumorigenesis, it remains unclear how individual changes propagate at the network level and eventually determine global metabolic activity. To characterize the metabolic lifestyle of cancer cells across pathways and genotypes, we profiled the intracellular metabolome of 180 pan-cancer cell lines grown in identical conditions. For each cell line, we estimated activity for 49 pathways spanning the entirety of the metabolic network. Upon clustering, we discovered a convergence into only two major metabolic types. These were functionally confirmed by 13 C-flux analysis, lipidomics, and analysis of sensitivity to perturbations. They revealed that the major differences in cancers are associated with lipid, TCA cycle, and carbohydrate metabolism. Thorough integration of these types with multiomics highlighted little association with genetic alterations but a strong association with markers of epithelial-mesenchymal transition. Our analysis indicates that in absence of variations imposed by the microenvironment, cancer cells adopt distinct metabolic programs which serve as vulnerabilities for therapy.

The alternative analog plasticizer BPS displays similar phenotypic and metabolomic responses to BPA in HepG2 and INS-1E cells.

Bisphenols A (BPA) and S (BPS) are endocrine-disrupting chemicals that affect energy metabolism, leading to impairment of glucose and lipid homeostasis. We aimed at identifying metabolic pathways regulated by both compounds in human liver cells and rat pancreatic ß-cells that could impair energy homeostasis regulation. We assessed the effects on growth, proliferation, and viability of hepatocarcinoma (HepG2) and insulinoma (INS-1E) cells exposed to either BPA or BPS in a full range concentration between 0.001 and 100 µM. Both the dose and duration of exposure caused a differential response on growth and viability of both cells. Effects were more pronounced on HepG2, as these cells exhibited non-linear dose-responses following exposure to xenobiotics. For INS-1E, effect was observed only at the highest concentration. In addition, we profiled their intracellular state by untargeted metabolomics at 24, 48, and 72 h of exposure. This analysis revealed time- and dose-dependently molecular changes for HepG2 and INS-1E that were similar between BPA and BPS. Both increased levels of inflammatory mediators, such as metabolites pertaining to linolenic and linoleic acid metabolic pathway. In summary, this study shows that BPS also disrupts molecular functions in cells that regulate energy homeostasis, displaying similar but less pronounced responses than BPA.

Intermediary organisations in collaborative environmental governance: evidence of the EU-funded LIFE sub-programme for the environment (LIFE-ENV).

In the framework of the collaborative environmental governance and specifically of network concepts, this study makes an exploratory analysis of the EU-funded LIFE sub-programme for the Environment (LIFE-ENV) and its priority area Environment and Resource Efficiency focused on the role of networks and in particular of intermediary organizations by using Social Network Analysis (SNA). More specifically, by investigating the evolving pattern of key statistics (density, clustering coefficient, betweenness and degree centrality) related to bipartite (organisations and projects) and dynamic (eleven years) networks, we identified 3003 organisations and 1006 projects and studied how they operate by forming new relations and reorganising existing connections. Results evidence that the LIFE-ENV attests a structural coherence and a stable structure over time and it is characterised by four different structures of network components, namely isolated coordinating beneficiary, isolated components, small components and giant components. Moreover, the LIFE-ENV is not a cohesive network, due to low values of both density and clustering coefficient. Based on betweenness centrality and degree centrality measures, the LIFE-ENV sub-programme has facilitated the emergence of 4855 intermediary organisations, which equals 29.5% of the total number of coordinating and associate beneficiaries involved in the programme in the eleven years considered. Transnational cooperation in the LIFE-ENV sub-programme is characterised by a different intensity of relations: some countries (i.e. Italy, Spain and Belgium) implement transnational cooperation with multiple European countries in both the North and South of Europe, while others tend to cluster with countries in the same geographical area, and lastly East European countries have limited participation in transnational cooperation. Our analysis supports the hypothesis of a declining collective action in the LIFE-ENV sub-programme.

Bioeconomy perception by future stakeholders: Hearing from European forestry students.

This article provides useful information for universities offering forestry programs and facing the growing demand for bioeconomy education. An explorative survey on bioeconomy perception among 1400 students enrolled in 29 universities across nine European countries offering forestry programs was performed. The data have been elaborated via descriptive statistics and cluster analysis. Around 70% of respondents have heard about the bioeconomy, mainly through university courses. Students perceive forestry as the most important sector for bioeconomy; however, the extent of perceived importance of forestry varies between countries, most significantly across groups of countries along a North-South European axis. Although differences across bachelor and master programs are less pronounced, they shed light on how bioeconomy is addressed by university programs and the level of student satisfaction with this. These differences and particularities are relevant for potential development routes towards comprehensive bioeconomy curricula at European forestry universities with a forestry focus.