DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

“These Grandmas Drove Me Mad. It Was Brilliant!”—Promising Starting Points to Support Citizen Competence for Sustainable Consumption in Adults

The article addresses citizen competence for sustainable consumption in adults. It discusses whether it is possible to develop educational offerings for adults (being by nature short and isolated) that effectively promote this competence and whether it makes a difference if sustainable consumption is approached by focusing on good life (quality of life) and justice or by focusing on natural resources and environment (as is suggested by, e.g., environmental literacy approaches). Taking the case of energy policy, it presents an educational intervention (EdIn) developed, implemented, and investigated by the authors. In data-analysis, three approaches were adopted (methodological triangulation), one analysing the deliberations’ cognitive structure, one analysing the participants’ perception, one analysing the participants’ reaction (in terms of the knowledge/concepts and values/concerns they voiced). The results show, firstly, that the didactical design of EdIn was successful with a view to supporting citizen competence in participants. Secondly, they show that in adult civic education sustainable consumption should be approached by focusing on good life and justice. Thirdly, they indicate that people do not necessarily perceive themselves to be part of societal decision-making, leading from the question of the design and content of civic educational activities to the question of their necessity

Critical review: Grand challenges in assessing the adverse effects of contaminants of emerging concern on aquatic food webs

Much progress has been made in the past decades to understand the sources, transport, fate andbiological effects of contaminants of emerging concern (CECs) in aquatic ecosystems. Despitethese advancements, significant obstacles remain to comprehensively assess the environmentalrisks associated with the presence of CECs. Many of these obstacles center around theextrapolation of effects of single chemicals observed in the laboratory or effects observed inindividual organisms or species in the field to impacts of multiple stressors on aquatic food webs.In the current review, we identified five challenges that need to be addressed to advance studiesof CECs from singular exposure events to multi-species aquatic food web interactions: (i) moredetailed information on the complexity of mixtures of CECs in the aquatic environment; (ii)understanding sub-lethal effects of CECs on a wide range of aquatic organisms; (iii) ascertainingthe biological consequences of variable duration CEC exposures within and across generations inaquatic species; (iv) linkage of multiple stressors with CEC exposure in aquatic systems; and (v)documenting the trophic consequences of CEC exposure across aquatic food webs. We reviewthe current literature to demonstrate how these challenges can be addressed to fill knowledgegaps.Fil: Nilsen, Elena. United States Geological Survey; Estados UnidosFil: Smalling, Kelly L. United States Geological Survey; Estados UnidosFil: Ahrens, Lutz. Swedish University Of Agricultural Sciences; SueciaFil: Gros, Meritxell. Catalan Institute For Water Research; España. Swedish University Of Agricultural Sciences; SueciaFil: Miglioranza, Karina Silvia Beatriz. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Marinas. Laboratorio de Ecotoxicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Picó, Yolanda. Universidad de Valencia; EspañaFil: Schoenfuss, Heiko. St. Cloud State University; Estados Unido

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

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