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This comment piece seeks to remind readers of the urgency and importance of adaptation to climate change in the European Union, note significant recent policy developments, and highlight some of the opportunities that one particular aspect of EU policy, the new Mission on Adaptation, affords communities and policy makers to identify and develop more transformative actions. It offers initial suggestions for how social scientists might engage with these opportunities between now and 2030, but also stresses the need to consider them realistically in the context of the contemporary EU political landscape. [ABSTRACT FROM AUTHOR]

Cancers arise through the acquisition of oncogenic mutations and grow by clonal expansion1,2. Here we reveal that most mutagenic DNA lesions are not resolved into a mutated DNA base pair within a single cell cycle. Instead, DNA lesions segregate, unrepaired, into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterize this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multiallelic and combinatorial genetic diversity. The phasing of lesions enables accurate measurement of strand-biased repair processes, quantification of oncogenic selection and fine mapping of sister-chromatid-exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes. Mutagenic lesions such as those that give rise to cancer frequently segregate—unrepaired—during cell division, resulting in phasing of multiple alleles across generations of daughter cells and consequent tumour heterogeneity. [ABSTRACT FROM AUTHOR]

Noncoding regulatory variants play a central role in the genetics of human diseases and in evolution. Here we measure allele-specific transcription factor binding occupancy of three liver-specific transcription factors between crosses of two inbred mouse strains to elucidate the regulatory mechanisms underlying transcription factor binding variations in mammals. Our results highlight the pre-eminence of cis-acting variants on transcription factor occupancy divergence. Transcription factor binding differences linked to cis-acting variants generally exhibit additive inheritance, while those linked to trans-acting variants are most often dominantly inherited. Cis-acting variants lead to local coordination of transcription factor occupancies that decay with distance; distal coordination is also observed and may be modulated by long-range chromatin contacts. Our results reveal the regulatory mechanisms that interplay to drive transcription factor occupancy, chromatin state, and gene expression in complex mammalian cell states. [ABSTRACT FROM AUTHOR]

The international climate regime represented by the United Nations Framework Convention on Climate Change has been widely critiqued. However, 'new' dynamic forms of climate governing are appearing in alternative domains, producing a more polycentric pattern. Some analysts believe that the new forms will fill gaps in the existing regime, but this optimism is based on untested assumptions about their diffusion and performance. The advent of polycentric governance offers new opportunities for climate action, but it is too early to judge whether hopes about the effectiveness of emerging forms of climate governance are well founded. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the authors discuss reports on mainstreaming climate change into European Union sectoral policies.

Follicular helper (TFH) cells provide crucial signals to germinal center B cells undergoing somatic hypermutation and selection that results in affinity maturation. Tight control of TFH numbers maintains self tolerance. We describe a population of Foxp3+Blimp-1+CD4+ T cells constituting 10-25% of the CXCR5highPD-1highCD4+ T cells found in the germinal center after immunization with protein antigens. These follicular regulatory T (TFR) cells share phenotypic characteristics with TFH and conventional Foxp3+ regulatory T (Treg) cells yet are distinct from both. Similar to TFH cells, TFR cell development depends on Bcl-6, SLAM-associated protein (SAP), CD28 and B cells; however, TFR cells originate from thymic-derived Foxp3+ precursors, not naive or TFH cells. TFR cells are suppressive in vitro and limit TFH cell and germinal center B cell numbers in vivo. In the absence of TFR cells, an outgrowth of non-antigen-specific B cells in germinal centers leads to fewer antigen-specific cells. Thus, the TFH differentiation pathway is co-opted by Treg cells to control the germinal center response. [ABSTRACT FROM AUTHOR]

Climate policy is a relatively young and dynamic area of public policy making. However, its development has attracted far more attention than the results it delivers in practice, which of course are the concern of policy evaluators. This article attempts to provide the first systematic cataloging of the emerging patterns of policy evaluation undertaken in different parts of the European Union. Theories of policy evaluation suggest that these evaluation practices should acknowledge the inherent complexity of climate policy making, be reflexive by questioning official policy goals, and be participatory. A meta-analysis of 259 climate policy evaluations suggests that current practice engages with some but not all of these issues. This article concludes by analyzing the implications of this finding for those in the academic and practitioner community who are keen to understand the extent to which climate policy evaluation is delivering on its promises. [ABSTRACT FROM AUTHOR]

Climate change is widely recognised as a ‘wicked’ policy problem. Agreeing and implementing governance responses is proving extremely difficult. Policy makers in many jurisdictions now emphasise their ambition to govern using the best available evidence. One obvious source of such evidence is the evaluations of the performance of existing policies. But to what extent do these evaluations provide insights into the difficult dilemmas that governors typically encounter? We address this question by reviewing the content of 262 evaluation studies of European climate policies in the light of six kinds of dilemma found in the governance literature. We are interested in what these studies say about the performance of European climate policies and in their capacity to inform evidence-based policy-making. We find that the evaluations do arrive at common findings: that climate change is framed as a problem of market and/or state failure; that voluntary measures tend to be ineffective; that market-based instruments tend to be regressive; that EU-level policies have driven climate policies in the latecomer EU Member States; and that lack of monitoring and weak enforcement are major obstacles to effective policy implementation. However, we also conclude that the evidence base these studies represent is surprisingly weak for such a high profile area. There is too little systematic climate policy evaluation work in the EU to support systematic evidence-based policy making. This reduces the scope for sound policy making in the short run and is a constraint to policy learning in the longer term. [ABSTRACT FROM AUTHOR]