Leaving no one behind - understanding environmental inequality in Europe.

The European Union aims to deliver a healthy environment to its citizens, with significant progress achieved in tackling key environmental stressors in recent decades. At the same time, significant risks to health remain from air, soil and water pollution, noise, chemicals and the impacts of climate change. High quality environments - such as urban areas rich in green and blue spaces - offer significant benefits to health. The unequal distribution of these risks and benefits across society, whereby socially disadvantages groups are more likely to live in poorer environmental conditions, contributes to health inequity across Europe.The European Environment Agency (EEA) is exploring how environmental risks and benefits are distributed across society. Recent evidence produced by EEA indicated that poorer European regions are more likely to be exposed to environmental health hazards at levels that negatively affect health. At country level, the disproportionate exposure of lower socio-economic groups to air pollution, noise and high temperatures is seen in urban areas. We also see inequality in terms of who generates pollution and who suffers the consequences. While poorer countries are likely to be worse affected by climate change, high incomes are linked to high carbon footprints across Europe. Quality environments offer benefits to health, in particular in urban areas, and can contribute to reducing health inequalities. Environmental inequality also plays out across generations, whereby future generations will have to tackle environmental degradation resulting from the activities of past and current populations, such as the accumulation of persistent chemicals in the environment, biodiversity loss and climate change.New opportunities exist to explore the complex linkages between environmental quality, socio-economic status, and health and well-being. These include combining existing data from across these domains with data from new sources, such as citizen science initiatives, smart phones, social media and satellite observation data. Knowledge that integrates the social and environmental domains and explores the drivers behind environmental health inequity is crucial to supporting implementation of the United Nations (UN) 2030 Agenda for Sustainable Development, in particular the pledge of leaving no one behind.

Identification of the Privileged Position in the Imidazo[1,2-a]pyridine Ring of Phosphonocarboxylates for Development of Rab Geranylgeranyl Transferase (RGGT) Inhibitors.

Members of the Rab GTPase family are master regulators of vesicle trafficking. When disregulated, they are associated with a number of pathological states. The inhibition of RGGT, an enzyme responsible for post-translational geranylgeranylation of Rab GTPases represents one way to control the activity of these proteins. Because the number of molecules modulating RGGT is limited, we combined molecular modeling with biological assays to ascertain how modifications of phosphonocarboxylates, the first reported RGGT inhibitors, rationally improve understanding of their structure-activity relationship. We have identified the privileged position in the core scaffold of the imidazo[1,2-a]pyridine ring, which can be modified without compromising compounds' potency. Thus modified compounds are micromolar inhibitors of Rab11A prenylation, simultaneously being inactive against Rap1A/Rap1B modification, with the ability to inhibit proliferation of the HeLa cancer cell line. These findings were rationalized by molecular docking, which recognized interaction of phosphonic and carboxylic groups as decisive in phosphonocarboxylate localization in the RGGT binding site.