Soluble mannose receptor induces proinflammatory macrophage activation and metaflammation

Proinflammatory activation of macrophages in metabolic tissues is critically important in the induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor (sMR) plays a direct functional role in both macrophage activation and metaflammation. We show that sMR binds CD45 on macrophages and inhibits its phosphatase activity, leading to an Src/Akt/ NF-kappa B-mediated cellular reprogramming toward an inflammatory phenotype both in vitro and in vivo. Remarkably, increased serum sMR levels were observed in obese mice and humans and directly correlated with body weight. Importantly, enhanced sMR levels increase serum proinflammatory cytokines, activate tissue macrophages, and promote insulin resistance. Altogether, our results reveal sMR as regulator of proinflammatory macrophage activation, which could constitute a therapeutic target for metaflammation and other hyperinflammatory diseases.Diabetes mellitus: pathophysiological changes and therap

Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

BACKGROUND: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. METHODS: In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. RESULTS: Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. CONCLUSIONS: Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity

Messung des dynamischen Strukturfaktors von Aluminium mit unelastischer Roentgenstreuung Korrelations- und Bandstruktureffekte

SIGLEAvailable from TIB Hannover: DW 5728 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Adaptive indirectly cooled monochromator crystals at HASYLAB

The high-heat-load monochromator, based on the HASYLAB (Hamburger Synchrotronstrahlungslabor) `Torii' design, has been used successfully for 2 years at the BW2 wiggler beamline. The bowing of the reflecting surface induced by the heat load and water pressure is compensated mechanically. This is achieved by mounting the specially shaped crystal in a bending mechanism and by heat transfer from the directly water-cooled crystal. We present the latest step in the development of this design. The piezoceramic-driven actuators are replaced by actuators based on the thermal expansion of copper rods. The direct water cooling of the crystal is replaced by a safer indirect water-cooling scheme. Characterization results of the crystal are presented. The Si(111) rocking-curve width at 9.5 keV was measured to be 8.3 arcsec under 500 W heat load