The distribution of attention across issues is of fundamental importance to the political agenda and outputs of government. This article presents an issue-based theory of the diversity of governing agendas where the core functions of government—defense, international affairs, the economy, government operations, and the rule of law—are prioritized ahead of all other issues. It undertakes comparative analysis of issue diversity of the executive agenda of several European countries and the United States over the postwar period. The results offer strong evidence of the limiting effect of core issues—the economy, government operations, defense, and international affairs—on agenda diversity. This suggests not only that some issues receive more attention than others but also that some issues are attended to only at times when the agenda is more diverse. When core functions of government are high on the agenda, executives pursue a less diverse agenda—focusing the majority of their attention on fewer issues. Some issues are more equal than others in executive agenda setting.

The azanucleosides azacitidine and decitabine are currently used for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in patients not only eligible for intensive chemotherapy but are also being explored in other hematologic and solid cancers. Based on their capacity to interfere with the DNA methylation machinery, these drugs are also referred to as hypomethylating agents (HMAs). As DNA methylation contributes to epigenetic regulation, azanucleosides are further considered to be among the first true “epigenetic drugs” that have reached clinical application. However, intriguing new evidence suggests that DNA hypomethylation is not the only mechanism of action for these drugs. This review summarizes the experience from more than 10 years of clinical practice with azanucleosides and discusses their molecular actions, including several not related to DNA methylation. A particular focus is placed on possible causes of primary and acquired resistances to azanucleoside treatment. We highlight current limitations for the success and durability of azanucleoside-based therapy and illustrate that a better understanding of the molecular determinants of drug response holds great potential to overcome resistance.

Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis.

Abstract.A growing body of work has examined the relationship between media and politics from an agenda-setting perspective: Is attention for issues initiated by political elites with the media following suit, or is the reverse relation stronger? A long series of single-country studies has suggested a number of general agenda-setting patterns but these have never been confirmed in a comparative approach. In a comparative, longitudinal design including comparable media and politics evidence for seven European countries (Belgium, Denmark, France, Netherlands, Spain, Switzerland and the United Kingdom), this study highlights a number of generic patterns. Additionally, it shows how the political system matters. Overall, the media are a stronger inspirer of political action in countries with single-party governments compared to those with multiple-party governments for opposition parties. But, government parties are more reactive to media under multiparty governments.

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