Biocompatible, hyperbranched nanocarriers for the transport and release of copper ions

Core–shell and core–multishell nanocarriers were designed to transport copper ions into cells. Herein, we present their synthesis and physicochemical characterization and demonstrate the high influence of their architectures on the loading and release of copper. Their low toxicity may open a new way to balance the Cu-homeostasis in neurodegenerative diseases

Ethanol-guided behavior in Drosophila larvae

Chemosensory signals allow vertebrates and invertebrates not only to orient in its environment toward energy-rich food sources to maintain nutrition but also to avoid unpleasant or even poisonous substrates. Ethanol is a substance found in the natural environment of Drosophila melanogaster. Accordingly, D. melanogaster has evolved specific sensory systems, physiological adaptations, and associated behaviors at its larval and adult stage to perceive and process ethanol. To systematically analyze how D. melanogaster larvae respond to naturally occurring ethanol, we examined ethanol-induced behavior in great detail by reevaluating existing approaches and comparing them with new experiments. Using behavioral assays, we confirm that larvae are attracted to different concentrations of ethanol in their environment. This behavior is controlled by olfactory and other environmental cues. It is independent of previous exposure to ethanol in their food. Moreover, moderate, naturally occurring ethanol concentration of 4% results in increased larval fitness. On the contrary, higher concentrations of 10% and 20% ethanol, which rarely or never appear in nature, increase larval mortality. Finally, ethanol also serves as a positive teaching signal in learning and memory and updates valence associated with simultaneously processed odor information. Since information on how larvae perceive and process ethanol at the genetic and neuronal level is limited, the establishment of standardized assays described here is an important step towards their discovery

The origin of PM10, PM2.5 and NO2 background levels in Germany with focus on North Rhine-Westphalia

Air pollution is bad for human health and an international problem which is far from being solved. A large portion of the total PM10 and NO2 burden at, e.g., a street canyon, comes from background concentration. To analyse the origin of these background concentrations, simulations for PM10, PM2.5, and NO2 have been performed with the chemical transport model EURAD (EURopean Air pollution Dispersion model system) for the domain of North Rhine-Westfalia (NRW) with different groups of emission sources within NRW switched off. The results allow a better estimation of the kind of measures needed to meet the EU limit values for PM10 and NO2. Additionally, simulations for Germany with and without anthropogenic emissions in Germany have been performed to determine the contribution of transboundary transport to the background concentration in Germany. The model results show that the contribution of the different sources depends upon the area and constituent. 30 to 80% of the background concentration (annual mean) stems from transboundary transport of air pollutants. While at the conurbation Rhine-Ruhr industry is the main contributor for PM10 and PM2.5, and road traffic for NO2, in the rural areas the contribution of industry and road traffic has about the same magnitude for all constituents

T-cells of invasive candidiasis patients show patterns of T-cell-exhaustion suggesting checkpoint blockade as treatment option

Objective: Recent data imply that strengthening host immunity by checkpoint inhibition improves outcome in invasive fungal infections (IFI), particularly in candidiasis. Methods: To assess T-cell exhaustion in this context, we compared peripheral blood mononuclear cells (PBMCs) and serum samples of patients with invasive Candida albicans infection (IC, n = 21) to PBMCs or tumor-infiltrating lymphocytes (TILs) from cancer patients (n = 14) and PBMCs of healthy controls (n = 20). Type and differentiation of lymphocytes and expression of 29 immune-regulatory molecules were analyzed by flow cytometry. C. albicans specific responses were assessed by FluoroSpot (n = 8) and antibody measurement (n = 14). Results: Fractions and phenotypes of lymphocyte subsets in PBMCs of IC patients were similar compared to PBMCs of controls, while they were different in TILs. PBMCs of patients with IC showed increased expression of immune-checkpoint molecules. The pattern of upregulated molecules was similar to TILs, but not present in PBMCs of control cancer patients. Fractions of T-cells expressing PD-1 and TIGIT were higher in IC patients that died. FluoroSpot analysis showed a Candida-specific IFN-y or IL-2 response in 5/8 patients, enhanced by addition of nivolumab in vitro. Conclusions: Together with preclinical data and preliminary evidence of clinical efficacy in mucormycosis, our results support clinical evaluation of immune-checkpoint inhibition in IFI treatment. (C) 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved

Degradation of protein translation machinery by amino acid starvation-induced macroautophagy

<p>Macroautophagy is regarded as a nonspecific bulk degradation process of cytoplasmic material within the lysosome. However, the process has mainly been studied by nonspecific bulk degradation assays using radiolabeling. In the present study we monitor protein turnover and degradation by global, unbiased approaches relying on quantitative mass spectrometry-based proteomics. Macroautophagy is induced by rapamycin treatment, and by amino acid and glucose starvation in differentially, metabolically labeled cells. Protein dynamics are linked to image-based models of autophagosome turnover. Depending on the inducing stimulus, protein as well as organelle turnover differ. Amino acid starvation-induced macroautophagy leads to selective degradation of proteins important for protein translation. Thus, protein dynamics reflect cellular conditions in the respective treatment indicating stimulus-specific pathways in stress-induced macroautophagy.</p