Zur naturwissenschaftlich-technischen Friedens- und Konfliktforschung: Aktuelle Herausforderungen und Bewertung der Empfehlungen des Wissenschaftsrats

Die besorgniserregende Aufkündigung des INF-Vertrags, der wiederholte Einsatz von Chemiewaffen in Syrien, kontroverse Diskussionen über die Einführung autonomer Waffensysteme oder zunehmende Cyber-Bedrohungen prägen das aktuelle politische Weltgeschehen. Besonders in einer Zeit, in der nukleare, biologische und chemische Abrüstung- und Rüstungskontrollmaßnahmen vor großen Herausforderungen stehen und gleichzeitig neue Technologien veränderte Anforderungen an diese Kontrollmechanismen mit sich bringen, gewinnt die naturwissenschaftlich-technische Friedensforschung enorm an Bedeutung. Sie beschäftigt sich auf der Grundlage von Erkenntnissen aus verschiedenen Naturwissenschaften und technischen Fachrichtungen (z. B. Physik, Chemie, Biologie, Informatik) mit der Rolle naturwissenschaftlicher und technischer Möglichkeiten im Kontext von Krieg und Frieden sowie Rüstung und Abrüstung. Sie unterstützt die politischen Prozesse der Kriegsprävention, der Abrüstung und der Vertrauensbildung mit Analysen der Eigenschaften und Folgen neuer Waffenarten und Technologien. Aus dieser Forschung werden Vorschläge für die Begrenzung neuer Waffenentwicklungen ebenso entwickelt wie technische Lösungen für eine verbesserte Rüstungskontrolle. Dieser Artikel benennt aktuelle Herausforderungen der naturwissenschaftlich-technischen Friedensforschung und geht dabei auch auf die aktuellen Empfehlungen des Wissenschaftsrats zur Weiterentwicklung der Friedens- und Konfliktforschung aus dem Jahr 2019 ein

Phosphorylation of CRN2 by CK2 regulates F-actin and Arp2/3 interaction and inhibits cell migration

CRN2 (synonyms: coronin 1C, coronin 3) functions in the re-organization of the actin network and is implicated in cellular processes like protrusion formation, secretion, migration and invasion. We demonstrate that CRN2 is a binding partner and substrate of protein kinase CK2, which phosphorylates CRN2 at S463 in its C-terminal coiled coil domain. Phosphomimetic S463D CRN2 loses the wild-type CRN2 ability to inhibit actin polymerization, to bundle F-actin, and to bind to the Arp2/3 complex. As a consequence, S463D mutant CRN2 changes the morphology of the F-actin network in the front of lamellipodia. Our data imply that CK2-dependent phosphorylation of CRN2 is involved in the modulation of the local morphology of complex actin structures and thereby inhibits cell migration

The Vinculin-ΔIn20/21 Mouse: Characteristics of a Constitutive, Actin-Binding Deficient Splice Variant of Vinculin

BACKGROUND: The cytoskeletal adaptor protein vinculin plays a fundamental role in cell contact regulation and affects central aspects of cell motility, which are essential to both embryonal development and tissue homeostasis. Functional regulation of this evolutionarily conserved and ubiquitously expressed protein is dominated by a high-affinity, autoinhibitory head-to-tail interaction that spatially restricts ligand interactions to cell adhesion sites and, furthermore, limits the residency time of vinculin at these sites. To date, no mutants of the vinculin protein have been characterized in animal models. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigate vinculin-DeltaEx20, a splice variant of the protein lacking the 68 amino acids encoded by exon 20 of the vinculin gene VCL. Vinculin-DeltaEx20 was found to be expressed alongside with wild type protein in a knock-in mouse model with a deletion of introns 20 and 21 (VCL-DeltaIn20/21 allele) and shows defective head-to-tail interaction. Homozygous VCL-DeltaIn20/21 embryos die around embryonal day E12.5 showing cranial neural tube defects and exencephaly. In mouse embryonic fibroblasts and upon ectopic expression, vinculin-DeltaEx20 reveals characteristics of constitutive head binding activity. Interestingly, the impact of vinculin-DeltaEx20 on cell contact induction and stabilization, a hallmark of the vinculin head domain, is only moderate, thus allowing invasion and motility of cells in three-dimensional collagen matrices. Lacking both F-actin interaction sites of the tail, the vinculin-DeltaEx20 variant unveils vinculin's dynamic binding to cell adhesions independent of a cytoskeletal association, and thus differs from head-to-tail binding deficient mutants such as vinculin-T12, in which activated F-actin binding locks the protein variant to cell contact sites. CONCLUSIONS/SIGNIFICANCE: Vinculin-DeltaEx20 is an active variant supporting adhesion site stabilization without an enhanced mechanical coupling. Its presence in a transgenic animal reveals the potential of splice variants in the vinculin gene to alter vinculin function in vivo. Correct control of vinculin is necessary for embryonic development

A clinical trial alert tool to recruit large patient samples and assess selection bias in general practice research

Background: Many research projects in general practice face problems when recruiting patients, often resulting in low recruitment rates and an unknown selection bias, thus limiting their value for health services research. The objective of the study is to evaluate the recruitment performance of the practice staff in 25 participating general practices when using a clinical trial alert (CTA) tool. Methods: The CTA tool was developed for an osteoporosis survey of patients at risk for osteoporosis and fractures. The tool used data from electronic patient records (EPRs) to automatically identify the population at risk (net sample), to apply eligibility criteria, to contact eligible patients, to enrol and survey at least 200 patients per practice. The effects of the CTA intervention were evaluated on the basis of recruitment efficiency and selection bias. Results: The CTA tool identified a net sample of 16,067 patients (range 162 to 1,316 per practice), of which the practice staff reviewed 5,161 (32%) cases for eligibility. They excluded 3,248 patients and contacted 1,913 patients. Of these, 1,526 patients (range 4 to 202 per practice) were successfully enrolled and surveyed. This made up 9% of the net sample and 80% of the patients contacted. Men and older patients were underrepresented in the study population. Conclusion: Although the recruitment target was unreachable for most practices, the practice staff in the participating practices used the CTA tool successfully to identify, document and survey a large patient sample. The tool also helped the research team to precisely determine a slight selection bias