Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Transformatives Regieren in Zeiten der Krisenpermanenz - ein Essay

Unser Alltag ist von Veränderungen und Transformationen geprägt. Krisen verdeutlichen dies in unterschiedlicher Art und zwingen politische Akteure, ihr Handlungsrepertoire anzupassen. Dieses Essay führt das Konzept des Transformativen Regierens im Sinne eines wandelbedingten Politikmanagements ein und stellt vier Spielarten dieses Regierungsstils vor: Anpassen, Kuratieren, Priorisieren und Tauschen. Resilienz als Ressource in Transformationszeiten nimmt dabei eine zentrale Rolle ein, denn sie erlaubt es, widerstandsfähig zu sein. Als inhaltlicher Anknüpfungspunkt für Transformatives Regieren dient die bisherige Arbeit der seit 2021 in Deutschland amtierenden Ampel-Regierung und ihr Umgang mit Krisen. Dabei wird ein Dilemma deutlich: Transformationsprozesse sind stets mit vielfältigen Kosten in allen Politikbereichen verbunden. Die daraus resultierenden Verteilungsfragen beantwortet die Ampel-Regierung bisher diffus und unvollständig. Dabei stehen die Regierungsparteien vor der Herausforderung, dass sie durch die jüngsten Krisen auf jeweils eigene Weise zu ideologischen Neuausrichtungen gezwungen wurden. Die Wirkungskraft der Resilienz steckt allerdings nicht in der veränderten ideologischen Ausrichtung der Parteien, sondern in ihrem kommunikativen Interaktionspotential.Our daily lives are shaped by changes and transformations. This is highlighted by several crises which force political actors to govern transformatively. This essay introduces the concept of transformative governance as the political management of change and presents four different modes: adaptation, guidance, prioritisation and exchange. Within transformative governance, resilience constitutes an important resouce enabling actors to act resistantly. The concept is developed with regard to the current "traffic light coalition" government in Germany, a Social Democrat, Green and Liberal coalition government elected in 2021, and how it deals with several crises. The results show that transformative processes are always linked to diverse costs in all policy areas. So far, the resulting questions regarding the distribution of goods are only answered in a diffuse and incomplete way. In this context, the governing parties currently face the challenge that the recent crises have forced them into ideological realignments. However, the effective power of resilience does not lie in the parties' changed ideological orientation, but in their communicative interaction potential

Transformation durch Policy-Lernen: Die Krise als Chance des Wandels

Plümer S. Transformation durch Policy-Lernen: Die Krise als Chance des Wandels. In: Korte K-R, Richter P, von Schuckmann A, eds. Regieren in der Transformationsgesellschaft. Impulse aus Sicht der Regierungsforschung. Studien der NRW School of Governance. Wiesbaden: Springer Fachmedien Wiesbaden; 2023: 13-26