A collaboratively derived international research agenda on legislative science advice

© 2019, The Author(s). The quantity and complexity of scientific and technological information provided to policymakers have been on the rise for decades. Yet little is known about how to provide science advice to legislatures, even though scientific information is widely acknowledged as valuable for decision-making in many policy domains. We asked academics, science advisers, and policymakers from both developed and developing nations to identify, review and refine, and then rank the most pressing research questions on legislative science advice (LSA). Experts generally agree that the state of evidence is poor, especially regarding developing and lower-middle income countries. Many fundamental questions about science advice processes remain unanswered and are of great interest: whether legislative use of scientific evidence improves the implementation and outcome of social programs and policies; under what conditions legislators and staff seek out scientific information or use what is presented to them; and how different communication channels affect informational trust and use. Environment and health are the highest priority policy domains for the field. The context-specific nature of many of the submitted questions—whether to policy issues, institutions, or locations—suggests one of the significant challenges is aggregating generalizable evidence on LSA practices. Understanding these research needs represents a first step in advancing a global agenda for LSA research

Position Paper on Water, Energy, Food and Ecosystem (WEFE) Nexus and Sustainable development Goals (SDGs)

The EU and the international community is realising that the Water, Energy, Food and Ecosystem components are interlinked and require a joint planning in order to meet the daunting global challenges related to Water, Energy and Food security and maintaining the ecosystem health and in this way, reach the SDGs. If not dealt with, the world will not be able to meet the demand for water, energy and food in a not too far future and, in any case, in a not sustainable way. The strain on the ecosystems resulting from unsustainable single-sector planning will lead to increasing poverty, inequality and instability. The Nexus approach is fully aligned with and supportive of the EU Consensus on Development. Key elements of the Consensus will require collaborative efforts across sectors in ways that can be supported/implemented by a Nexus approach. In this way, transparent and accountable decision-making, involving the civil society is key and common to the European Consensus on Development and the Nexus approach. The Nexus approach will support the implementation of the SDG in particular SDG 2 (Food), SDG 6 (Water) and SDG 7 (Energy), but most SDGs have elements that link to food, water and energy in one or other way, and will benefit from a Nexus approach. The SDGs are designed to be cross-cutting and be implemented together, which is also reflected in a WEFE Nexus approach. A Nexus approach offers a sustainable way of addressing the effects of Climate Change and increase resilience. The WEFE Nexus has in it the main drivers of climate change (water, energy and food security) and the main affected sectors (water and the environment). Decisions around policy, infrastructure, … developed based on the WEFE Nexus assessments will be suitable as elements of climate change mitigation and adaptation. In fact, it is difficult to imagine solutions to the climate change issue that are not built on a form of Nexus approach. The Nexus approach is being implemented around the world, as examples in the literature demonstrate. These examples together with more examples from EU and member state development cooperation will help build experience that can be consolidated and become an important contribution to a Toolkit for WEFE Nexus Implementation. From the expert discussions, it appears that because of the novelty of the approach, a Toolkit will be an important element in getting the Nexus approach widely used. This should build on experiences from practical examples of NEXUS projects or similar inter-sectorial collaboration projects; and, there are already policy, regulation and practical experience to allow institutions and countries to start applying the Nexus concept.JRC.D.2-Water and Marine Resource

N/C interactions are dispensable for normal in vivo functioning of the androgen receptor in male mice

The androgen receptor (AR) plays a central role in the development and maintenance of the male phenotype. The binding of androgens to the receptor induces interactions between the carboxyterminal ligand-binding domain and the highly conserved 23FQNLF27 motif in the aminoterminal domain. The role of these so-called N/C interactions in AR functioning is debated. In vitro assays show that mutating the AR in the 23FQNLF27 motif (called ARNoC) attenuates the AR transactivation of reporter genes, has no effect on ligand binding, but does affect protein-protein interactions with several AR coregulators. To test the in vivo relevance of the N/C interaction, we analyzed the consequences of the genomic introduction of the ARNoC mutation in mice. Surprisingly, the ARNoC/Y mice show a normal male development, with unaffected male anogenital distance and normal accessory sex glands, male circulating androgen levels, body composition, and fertility. The responsiveness of androgen target genes in kidney, prostate, and testes was also unaffected. We thus conclude that the N/C interactions in the AR are not essential for the development of a male phenotype under normal physiological conditions

The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation

Whereas dimerization of the DNA-binding domain of the androgen receptor (AR) plays an evident role in recognizing bipartite response elements, the contribution of the dimerization of the ligand-binding domain (LBD) to the correct functioning of the AR remains unclear. Here, we describe a mouse model with disrupted dimerization of the AR LBD (AR(Lmon/Y)). The disruptive effect of the mutation is demonstrated by the feminized phenotype, absence of male accessory sex glands, and strongly affected spermatogenesis, despite high circulating levels of testosterone. Testosterone replacement studies in orchidectomized mice demonstrate that androgen-regulated transcriptomes in AR(Lmon/Y) mice are completely lost. The mutated AR still translocates to the nucleus and binds chromatin, but does not bind to specific AR binding sites. In vitro studies reveal that the mutation in the LBD dimer interface also affects other AR functions such as DNA binding, ligand binding, and co-regulator binding. In conclusion, LBD dimerization is crucial for the development of AR-dependent tissues through its role in transcriptional regulation in vivo. Our findings identify AR LBD dimerization as a possible target for AR inhibition