A combined computational and experimental investigation of the [2Fe–2S] cluster in biotin synthase

Biotin synthase was the first example of what is now regarded as a distinctive enzyme class within the radical S-adenosylmethionine superfamily, the members of which use Fe/S clusters as the sulphur source in radical sulphur insertion reactions. The crystal structure showed that this enzyme contains a [2Fe–2S] cluster with a highly unusual arginine ligand, besides three normal cysteine ligands. However, the crystal structure is at such a low resolution that neither the exact coordination mode nor the role of this exceptional ligand has been elucidated yet, although it has been shown that it is not essential for enzyme activity. We have used quantum refinement of the crystal structure and combined quantum mechanical and molecular mechanical calculations to explore possible coordination modes and their influences on cluster properties. The investigations show that the protonation state of the arginine ligand has little influence on cluster geometry, so even a positively charged guanidinium moiety would be in close proximity to the iron atom. Nevertheless, the crystallised enzyme most probably contains a deprotonated (neutral) arginine coordinating via the NH group. Furthermore, the Fe···Fe distance seems to be independent of the coordination mode and is in perfect agreement with distances in other structurally characterised [2Fe–2S] clusters. The exceptionally large Fe···Fe distance found in the crystal structure could not be reproduced

Hyperbaric oxygen treatment and nephrotoxicity induced by gentamicin in rats

Abstract Background Nephrotoxicity is a significant adverse side effect of gentamicin. Previous preclinical studies showed that hyperbaric oxygen treatment (HBOT) may have beneficial effects by attenuating renal damage in rats subjected to renal injury. We evaluated the effect of HBOT on acute renal failure caused by gentamicin. Methods Thirty-six rats were divided into four groups. Gentamicin (150 mg/kg for 5 consecutive days) was administered in 30 rats, 10 rats received only gentamicin, 10 rats received 100% oxygen therapy on days 1-5 of the experiment, 10 received daily HBOT on days 1-5 of the experiment, and the remaining six served as a control group. On day 6, renal function tests and renal pathological examinations were performed. Results Body weight and biochemical parameters were similar in all groups except for higher plasma levels of calcium in the 100% oxygen group (P = 0.03). All the rats in the experimental group showed biochemical parameters compatible with renal failure (high serum levels of urea and creatinine). All the rats in the control group had normal renal function tests. Two rats from the HBOT group died on the fifth day of the experiment. All rats in the control group demonstrated normal renal morphology. All 28 intoxicated rats showed moderate to severe histopathological changes without significant differences between the groups. Conclusions Treatment of gentamicin-induced nephrotoxicity with either HBOT or 100% oxygen for 5 days had no beneficial renal effect. Mortality was observed only in the HBOT group

COVID-19 an Kölner Schulen: Eine differenzierte Übersicht der Schulentscheidungen im Gesundheitsamt der Stadt Köln bis zum Ende des Schuljahres 2019/2020

Im Epidemiologischen Bulletin 42/2020 werden die Herausforderungen, der Umgang und die Erfahrungen des Gesundheitsamts Kölns zwischen März und Juli 2020 im Umgang mit Schulen während der COVID-19-Pandemie vorgestellt. Die Autoren sehen zum jetzigen Zeitpunkt im Bereich der Schulen die differenzierte Einzelfallbearbeitung als ein hinreichend sicheres und angemessenes Instrument an. Ob bei kompletter Öffnung der Schulen, im Falle ansteigender Fallzahlen nach Ferienende, die personelle Ausstattung der Gesundheitsämter dieses Vorgehen ermöglichen kann, ist aus Perspektive der Autoren fraglich. Sie plädieren aber für den bestmöglichen Erhalt des Schulbetriebs, um möglichst vielen Schüler*innen eine angemessene Förderung zu bieten und die Bildungsgerechtigkeit zu erhalten