Cxcl12 evolution – subfunctionalization of a ligand through altered interaction with the chemokine receptor

The active migration of primordial germ cells (PGCs) from their site of specification towards their target is a valuable model for investigating directed cell migration within the complex environment of the developing embryo. In several vertebrates, PGC migration is guided by Cxcl12, a member of the chemokine superfamily. Interestingly, two distinct Cxcl12 paralogs are expressed in zebrafish embryos and contribute to the chemotattractive landscape. Although this offers versatility in the use of chemokine signals, it also requires a mechanism through which migrating cells prioritize the relevant cues that they encounter. Here, we show that PGCs respond preferentially to one of the paralogs and define the molecular basis for this biased behavior. We find that a single amino acid exchange switches the relative affinity of the Cxcl12 ligands for one of the duplicated Cxcr4 receptors, thereby determining the functional specialization of each chemokine that elicits a distinct function in a distinct process. This scenario represents an example of protein subfunctionalization – the specialization of two gene copies to perform complementary functions following gene duplication – which in this case is based on receptor-ligand interaction. Such specialization increases the complexity and flexibility of chemokine signaling in controlling concurrent developmental processes

Protestant perspectives on end of life care

This book examines the ethics of end of life care, focusing on the kinds of decisions that are commonly made in clinical practice. Specific attention is paid to the intensification of treatment for terminal symptoms, particularly pain relief, and the withdrawal and withholding of care, particularly life-saving or life-prolonging medical care. The book is structured into three sections. The first section contains essays examining end of life care from the perspective of moral theory and theology. The second sets out various conceptual terms and distinctions relevant to decision-making at the end of life. The third section contains chapters that focus on substantive ethical issues. This format not only provides for a comprehensive analysis of the ethical issues that arise in the context of end of life care but allows readers to effectively trace the philosophical, theological and conceptual underpinnings that inform their specific interests. This work will be of interest to scholars working in the area as well as clinicians, specialists and healthcare professionals who encounter these issues in the course of their practice

Evaluation komplexer Interventionen am Beispiel des Nationalen Aktionsplans für Menschen mit Seltenen Erkrankungen

Dörries M. Evaluation komplexer Interventionen am Beispiel des Nationalen Aktionsplans für Menschen mit Seltenen Erkrankungen. Bielefeld: Universität Bielefeld; 2022

Ethisches Urteilen in moderierten Fallbesprechungen. Eine Interpretation von Leitfäden für ethische Fallbesprechungen

Die moderne Biomedizin birgt zahlreiche moralische Herausforderungen und Dilemmata, die in pluralen Gesellschaften nicht immer einvernehmlich gelöst werden können. Dennoch müssen auf individueller, institutioneller und gesellschaftlicher Ebene Entscheidungen getroffen und Regelungen gefunden werden. Hierbei sind verschiedene, häufig miteinander in Konflikt stehende ethische Normen, Werte, Ideale und Interessen zu berücksichtigen. Wie in solchen Spannungsfeldern angemessene Entscheidungen gefunden werden können, ist bisher weder in der Praxis noch in der Theorie ausreichend geklärt. Dieser Band versammelt Beiträge verschiedener Disziplinen zu der Frage, wie ethische Entscheidungen in der Medizin und im Gesundheitswesen in einer gut begründeten Art und Weise getroffen werden können. Sie schlagen eine Brücke zwischen ethischer Theoriebildung und konkreter Entscheidungsfindung in der Praxis. Neben Beiträgen zu philosophischen Grundlagen ethischer Entscheidungen und zur Anwendung verschiedener Ethiktheorien auf einen klinischen Einzelfall werden Beiträge zu relevanten Entscheidungskontexten und -instrumenten der klinischen Praxis sowie der biomedizinischen Forschung und Politik geleiste

Metabolic footprint analysis uncovers strain specific overflow metabolism and D-isoleucine production of Staphylococcus aureus COL and HG001.

During infection processes, Staphylococcus aureus is able to survive within the host and to invade tissues and cells. For studying the interaction between the pathogenic bacterium and the host cell, the bacterial growth behaviour and its metabolic adaptation to the host cell environment provides first basic information. In the present study, we therefore cultivated S. aureus COL and HG001 in the eukaryotic cell culture medium RPMI 1640 and analyzed the extracellular metabolic uptake and secretion patterns of both commonly used laboratory strains. Extracellular accumulation of D-isoleucine was detected starting during exponential growth of COL and HG001 in RPMI medium. This non-canonical D-amino acid is known to play a regulatory role in adaptation processes. Moreover, individual uptake of glucose, accumulation of acetate, further overflow metabolites, and intermediates of the branched-chain amino acid metabolism constitute unique metabolic footprints. Altogether these time-resolved footprint analyses give first metabolic insights into staphylococcal growth behaviour in a culture medium used for infection related studies

Innovationsförderung der Krankenkassen

Greiner W, Dörries M, Leppert F. Sanfter Druck - Innovationsförderung der Krankenkassen. f&w führen und wirtschaften im Krankenhaus. 2013;1/2013:36-38

Digitalisierung im Gesundheitswesen: hochwertige und effizientere Versorgung

Dörries M, Gensorowsky D, Greiner W. Digitalisierung im Gesundheitswesen: hochwertige und effizientere Versorgung. Wirtschaftsdienst. 2017;97(10):687-703

Growth curves, extracellular metabolites and the statistical separation of <i>S. aureus</i> COL and HG001.

<p>(<b>A</b>) Growth curves of COL (blue line) and HG001 (red line) in RPMI medium are presented. Data are shown as mean values ± SD of quadruplicate samples. (<b>B</b>) Time-resolved extracellular metabolite concentrations (mmol/l) of COL and HG001 were visualized with MeV as color coded chart. Absent or low concentrated metabolites are displayed in blue, whereas increasing concentration turns into orange coloration. Concentrations greater than 0.5 mmol/l are colored in orange. Changes of yet unknown metabolites are displayed based on relative concentrations. Metabolites are arranged by hierarchical cluster analysis. Displayed are the mean values of concentrations of 4 biological replicates. (<b>C</b>) Principal component analysis of the exometabolome data of <i>S. aureus</i> COL (blue points) and HG001 (red points) of ten sampling time points. Single values of 4 biological replicates are displayed. The arrow indicates the starting and end points of the time-resolved exometabolome data. The percentages of variance are 97.407 for component 1 and 1.899 for component 2.</p