Intercomparison Experiment of Water-Insoluble Carbonaceous Particles in Snow in a High-Mountain Environment (1598 m a.s.l.)

The harmonization of sampling, sample preparation and laboratory analysis methods to detect carbon compounds in snow requires detailed documentation of those methods and their uncertainties. Moreover, intercomparison experiments are needed to reveal differences and quantify the uncertainties further. Here, we document our sampling, filtering, and analysis protocols used in the intercomparison experiment from three laboratories to detect water-insoluble carbon in seasonal surface snow in the high-mountain environment at Kolm Saigurn (47.067842° N, 12.98394° E, alt 1598 m a.s.l.), Austria. The participating laboratories were TU Wien (Austria), the University of Florence (Italy), and the Finnish Meteorological Institute (Finland). For the carbon analysis, the NIOSH5040 and EUSAAR2 protocols of the OCEC thermal-optical method were used. The median of the measured concentrations of total carbon (TC) was 323 ppb, organic carbon (OC) 308 ppb, and elemental carbon (EC) 16 ppb. The methods and protocols used in this experiment did not reveal large differences between the laboratories, and the TC, OC, and EC values of four inter-comparison locations, five meters apart, did not show meter-scale horizontal variability in surface snow. The results suggest that the presented methods are applicable for future research and monitoring of carbonaceous particles in snow. Moreover, a recommendation on the key parameters that an intercomparison experiment participant should be asked for is presented to help future investigations on carbonaceous particles in snow. The work contributes to the harmonization of the methods for measuring the snow chemistry of seasonal snow deposited on the ground

Discovery of a Novel, Isothiazolonaphthoquinone-Based Small Molecule Activator of FOXO Nuclear-Cytoplasmic Shuttling

FOXO factors are tumour suppressor proteins commonly inactivated in human tumours by posttranslational modifications. Furthermore, genetic variation within the FOXO3a gene is consistently associated with human longevity. Therefore, the pharmacological activation of FOXO proteins is considered as an attractive therapeutic approach to treat cancer and age-related diseases. In order to identify agents capable of activating FOXOs, we tested a collection of small chemical compounds using image-based high content screening technology. Here, we report the discovery of LOM612 (compound 1a), a newly synthesized isothiazolonaphthoquinone as a potent FOXO relocator. Compound 1a induces nuclear translocation of a FOXO3a reporter protein as well as endogenous FOXO3a and FOXO1 in U2OS cells in a dose-dependent manner. This activity does not affect the subcellular localization of other cellular proteins including NFkB or inhibit CRM1-mediated nuclear export. Furthermore, compound 1a shows a potent antiproliferative effect in human cancer cell lines

Lymphatic and Blood Endothelial Extracellular Vesicles: A Story Yet to Be Written

Extracellular vesicles (EVs), such as exosomes, microvesicles, and apoptotic bodies, are cell-derived, lipid bilayer-enclosed particles mediating intercellular communication and are therefore vital for transmitting a plethora of biological signals. The vascular endothelium substantially contributes to the circulating particulate secretome, targeting important signaling pathways that affect blood cells and regulate adaptation and plasticity of endothelial cells in a paracrine manner. Different molecular signatures and functional properties of endothelial cells reflect their heterogeneity among different vascular beds and drive current research to understand varying physiological and pathological effects of blood and lymphatic endothelial EVs. Endothelial EVs have been linked to the development and progression of various vascular diseases, thus having the potential to serve as biomarkers and clinical treatment targets. This review aims to provide a brief overview of the human vasculature, the biology of extracellular vesicles, and the current knowledge of endothelium-derived EVs, including their potential role as biomarkers in disease development

Aortic Development and Anomalies

Development of the aorta takes place during the third week of gestation. It is a complex process that can lead to a variety of congenital variants and pathological anomalies. In diagnostic and interventional radiology, knowledge of aortic abnormalities and variant branching sequence is crucially important. This article gives a systematic overview of anatomical variability of the aorta