ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair

To recognize DNA adducts, nucleotide excision repair (NER) deploys the XPC sensor, which detects damage-induced helical distortions, followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place in chromatin where DNA is tightly wrapped around histones. Here, we describe how the histone methyltransferase ASH1L, once activated by MRG15, helps XPC and TFIIH to navigate through chromatin and induce global-genome NER hotspots. Upon UV irradiation, ASH1L adds H3K4me3 all over the genome (except in active gene promoters), thus priming chromatin for XPC relocations from native to damaged DNA. The ASH1L-MRG15 complex further recruits the histone chaperone FACT to DNA lesions. In the absence of ASH1L, MRG15 or FACT, XPC is misplaced and persists on damaged DNA without being able to deliver the lesions to TFIIH. We conclude that ASH1L-MRG15 makes damage verifiable by the NER machinery through the sequential deposition of H3K4me3 and FACT

Understanding the long-term policy influence strategies of the tobacco industry:two contemporary case studies

Objective: This paper explores transnational tobacco companies’ (TTCs) long-term policy influence strategies using two case studies, harm reduction and illicit tobacco, to identify lessons for the tobacco control movement and wider efforts to address the commercial determinants of health.Methods: Evidence from a broad combination of sources including leaked documents and findings from over two decades of TTC monitoring were reviewed for each case study and categorised using the Policy Dystopia Model, focusing on the primary discursive strategy and key instrumental (action-based) strategies used.Results: In both case studies, TTCs seek to advance their interests by engaging primarily in reputation management, coalition management and information management strategies over the long-term to propagate their over-riding discursive strategy—‘we’ve changed, we are part of the solution’—despite clear evidence from both case studies that this is not the case. These strategies are globally coordinated and attempt primarily to reshape norms towards TTC involvement in tobacco control policy and delivery. Findings also suggest that industry denormalisation and the advent of Article 5.3 have led to the TTCs growing use of increasingly complex and opaque ‘webs of influence’.Conclusions: The tobacco control community must develop its own proactive long-term strategies which should include industry denormalisation, new ways to fund research that reduce industry control, and improved transparency measures for research and policy. These findings, including TTC adaptations to Article 5.3, also indicate the need for more structural solutions, addressing corporate power and the underlying political and economic system. These lessons can be applied to other unhealthy commodity industries

ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair

To recognize DNA adducts, nucleotide excision repair (NER) deploys the XPC sensor, which detects damage-induced helical distortions, followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place in chromatin where DNA is tightly wrapped around histones. Here, we describe how the histone methyltransferase ASH1L, once activated by MRG15, helps XPC and TFIIH to navigate through chromatin and induce global-genome NER hotspots. Upon UV irradiation, ASH1L adds H3K4me3 all over the genome (except in active gene promoters), thus priming chromatin for XPC relocations from native to damaged DNA. The ASH1L-MRG15 complex further recruits the histone chaperone FACT to DNA lesions. In the absence of ASH1L, MRG15 or FACT, XPC is misplaced and persists on damaged DNA without being able to deliver the lesions to TFIIH. We conclude that ASH1L-MRG15 makes damage verifiable by the NER machinery through the sequential deposition of H3K4me3 and FACT.ISSN:2041-172

Understanding the long-term policy influence strategies of the tobacco industry: two contemporary case studies.

OBJECTIVE: This paper explores transnational tobacco companies' (TTCs) long-term policy influence strategies using two case studies, harm reduction and illicit tobacco, to identify lessons for the tobacco control movement and wider efforts to address the commercial determinants of health. METHODS: Evidence from a broad combination of sources including leaked documents and findings from over two decades of TTC monitoring were reviewed for each case study and categorised using the Policy Dystopia Model, focusing on the primary discursive strategy and key instrumental (action-based) strategies used. RESULTS: In both case studies, TTCs seek to advance their interests by engaging primarily in reputation management, coalition management and information management strategies over the long-term to propagate their over-riding discursive strategy-'we've changed, we are part of the solution'-despite clear evidence from both case studies that this is not the case. These strategies are globally coordinated and attempt primarily to reshape norms towards TTC involvement in tobacco control policy and delivery. Findings also suggest that industry denormalisation and the advent of Article 5.3 have led to the TTCs growing use of increasingly complex and opaque 'webs of influence'. CONCLUSIONS: The tobacco control community must develop its own proactive long-term strategies which should include industry denormalisation, new ways to fund research that reduce industry control, and improved transparency measures for research and policy. These findings, including TTC adaptations to Article 5.3, also indicate the need for more structural solutions, addressing corporate power and the underlying political and economic system. These lessons can be applied to other unhealthy commodity industries

Association between self-reported sleep duration and dietary quality in European adolescents

Evidence has grown supporting the role for short sleep duration as an independent risk factor for weight gain and obesity. The purpose of the present study was to examine the relationship between sleep duration and dietary quality in European adolescents. The sample consisted of 1522 adolescents (aged 12.5-17.5 years) participating in the European multi-centre cross-sectional 'Healthy Lifestyle in Europe by Nutrition in Adolescence' study. Sleep duration was estimated by a self-reported questionnaire. Dietary intake was assessed by two 24 h recalls. The Diet Quality Index for Adolescents with Meal index (DQI-AM) was used to calculate overall dietary quality, considering the components dietary equilibrium, dietary diversity, dietary quality and a meal index. An average sleep duration of >= 9 h was classified as optimal, between 8 and 9 h as borderline insufficient and <8 h as insufficient. Sleep duration and the DQI-AM score were positively associated (beta = 0.027, r 0.130, P < 0.001). Adolescents with insufficient (62.05 (SD 14.18)) and borderline insufficient sleep (64.25 (SD 12.87)) scored lower on the DQI-AM than adolescents with an optimal sleep duration (64.57 (SD 12.39)) (P < 0.001; P = 0.018). The present study demonstrated in European adolescents that short sleep duration was associated with a lower dietary quality. This supports the hypothesis that the health consequences of insufficient sleep may be mediated by the relationship of insufficient sleep to poor dietary quality

Association between self-reported sleep duration and dietary quality in European adolescents

Evidence has grown supporting the role for short sleep duration as an independent risk factor for weight gain and obesity. The purpose of the present study was to examine the relationship between sleep duration and dietary quality in European adolescents. The sample consisted of 1522 adolescents (aged 12.5-17.5 years) participating in the European multi-centre cross-sectional ‘Healthy Lifestyle in Europe by Nutrition in Adolescence’ study. Sleep duration was estimated by a self-reported questionnaire. Dietary intake was assessed by two 24 h recalls. The Diet Quality Index for Adolescents with Meal index (DQI-AM) was used to calculate overall dietary quality, considering the components dietary equilibrium, dietary diversity, dietary quality and a meal index. An average sleep duration of ≥ 9 h was classified as optimal, between 8 and 9 h as borderline insufficient and < 8 h as insufficient. Sleep duration and the DQI-AM score were positively associated (β = 0.027, r 0.130, P< 0.001). Adolescents with insufficient (62.05 (sd 14.18)) and borderline insufficient sleep (64.25 (sd 12.87)) scored lower on the DQI-AM than adolescents with an optimal sleep duration (64.57 (sd 12.39)) (P< 0.001; P= 0.018). The present study demonstrated in European adolescents that short sleep duration was associated with a lower dietary quality. This supports the hypothesis that the health consequences of insufficient sleep may be mediated by the relationship of insufficient sleep to poor dietary quality.status: publishe