Differences in anti-malarial activity of 4-aminoalcohol quinoline enantiomers and investigation of the presumed underlying mechanism of action

International audienc

Clinical experience with medical hypnosis as an adjunctive therapy in heart surgery

Heart surgery patients are at high risk for psychological trauma and comorbid psychological disorders. Depression, anxiety, and post-traumatic stress disorders in this patient group are predictors of outcomes after cardiac surgery. Medical hypnosis is effective for non-pharmacologic prevention and treatment of psychological disorders and has been associated with improved health-related quality of life and better cardiovascular outcomes. This contribution makes note of evidence of the effectiveness of medical hypnosis in a discussion of the clinical experience with specific hypnotherapeutic tools and interventions from the perspective of the mental health team in one large cardiac center in Germany. Based on our experience, we encourage heart centers to educate their heart surgery care teams about the core concepts of medical hypnosis and to make hypnotherapeutic techniques available as an adjunctive therapy

A dynamic water channel affects O2_2 stability in [FeFe]-hydrogenases

[FeFe]-hydrogenases are capable of reducing protons at a high rate. However, molecular oxygen (O$_2$) induces the degradation of their catalytic cofactor, the H-cluster, which consists of a cubane [4Fe4S] subcluster (4Fe$_H$) and a unique diiron moiety (2Fe$_H$). Previous attempts to prevent O$_2$-induced damage have focused on enhancing the protein's sieving effect for O$_2$ by blocking the hydrophobic gas channels that connect the protein surface and the 2Fe$_H$. In this study, we aimed to block an O$_2$ diffusion pathway and shield 4Fe$_H$ instead. Molecular dynamics (MD) simulations identified a novel water channel (W$_H$) surrounding the H-cluster. As this hydrophilic path may be accessible for O$_2$ molecules we applied site-directed mutagenesis targeting amino acids along W$_H$ in proximity to 4Fe$_H$ to block O$_2$ diffusion. Protein film electrochemistry experiments demonstrate increased O$_2$ stabilities for variants G302S and S357T, and MD simulations based on high-resolution crystal structures confirmed an enhanced local sieving effect for O$_2$ in the environment of the 4Fe$_H$ in both cases. The results strongly suggest that, in wild type proteins, O$_2$ diffuses from the 4Fe$_H$ to the 2Fe$_H$. These results reveal new strategies for improving the O$_2$ stability of [FeFe]-hydrogenases by focusing on the O$_2$ diffusion network near the active site