Toxicity of Volatile Methylated Species of Bismuth, Arsenic, Tin, and Mercury in Mammalian Cells In Vitro

The biochemical transformation of mercury, tin, arsenic and bismuth through formation of volatile alkylated species performs a fundamental role in determining the environmental processing of these elements. While the toxicity of inorganic forms of most of these compounds are well documented (e.g., arsenic, mercury) and some of them are of relatively low toxicity (e.g., tin, bismuth), the more lipid-soluble organometals can be highly toxic. In the present study we investigated the cyto- and genotoxicity of five volatile metal(loid) compounds: trimethylbismuth, dimethylarsenic iodide, trimethylarsine, tetramethyltin, and dimethylmercury. As far as we know, this is the first study investigating the toxicity of volatile metal(loid) compounds in vitro. Our results showed that dimethylmercury was most toxic to all three used cell lines (CHO-9 cells, CaCo, Hep-G2) followed by dimethylarsenic iodide. Tetramethyltin was the least toxic compound; however, the toxicity was also dependend upon the cell type. Human colon cells (CaCo) were most susceptible to the toxicity of the volatile compounds compared to the other cell lines. We conclude from our study that volatile metal(loid) compounds can be toxic to mammalian cells already at very low concentrations but the toxicity depends upon the metal(loid) species and the exposed cell type

Joint analysis of resident complaints, meteorological, acoustic, and ground motion data to establish a robust annoyance evaluation of wind turbine emissions

In order to advance the expansion of onshore wind energy, wind turbines (WTs) must be erected in often complex terrain. The orography and the associated meteorological conditions, as well as the complex propagation of sound and ground motion waves can lead to increased annoyance of residents. Here a joint investigation of residential noise reports, meteorological, acoustic and ground motion data together with operational parameters of a wind farm in southern Germany is presented, with the objective to assess the annoyance of residents affected by WT emissions. Once strongly annoyed residents had been identified, simultaneous measurements were conducted over a 2-month period while residents used a noise reporting app to document their annoyance. A combination of the data shows that WT-related signals can be detected by acoustic and ground motion measurements in the vicinity of the WTs and, to a lesser extent, at the residential sites. In addition, background noise can be identified well. The app data indicates higher complaint rates in the early morning, evening and night hours. Changes in rotation rate seem to be the cause of annoyance as well as high rotation rates. These findings can be used to adjust WT operation in order to decrease immissions

Geruchsintensive Stoffe: Grundlagen, Bewertung und Markierung

Odours from substances at the workplace are often strong, unpleasant and perceptible even at concentrations below the valid MAK values. “Odour-associated symptoms” such as nausea and headaches may develop as a result of a special processing of neurophysiological signals, a specific neuroanatomical connectivity and the evolutionary significance of olfaction. These effects cannot be taken into consideration for the derivation of a MAK value because they occur only in isolated cases. Substances at the workplace that are associated with these kinds of effects are designated in the List of MAK and BAT Values with a corresponding footnote. This article presents the scientific background and the specific procedure used for applying the footnote. By stimulating specialized odour receptors, odours are perceptible even at very low concentrations. After crossing only a few synaptic junctions, the odour information reaches regions of the brain such as the limbic system, the vegetative nuclei of the hypothalamus and the reticular formation. Odours, particularly unpleasant ones, are often perceived as a sign of danger based on individual experiences and evolutionary developments. However, individual responses differ considerably and this variation cannot be explained adequately by physiological mechanisms. Therefore, in order to have the potential of inducing “odour-associated symptoms”, the workplace substances in question must have a low odour threshold and an unpleasant odour quality. The methods used to identify these odour characteristics are quite heterogeneous and have not been standardized. Different sources were used to determine the odour characteristics of the 43 workplace substances from the List of MAK and BAT Values that potentially met these criteria. After the data were checked for plausibility, 23 of the substances were designated with the footnote following a systematic evaluation

Rebound growth of BRAF mutant pediatric glioma cells after MAPKi withdrawal is associated with MAPK reactivation and secretion of microglia-recruiting cytokines

INTRODUCTION: Patients with pediatric low-grade gliomas (pLGGs), the most common primary brain tumors in children, can often benefit from MAPK inhibitor (MAPKi) treatment. However, rapid tumor regrowth, also referred to as rebound growth, may occur once treatment is stopped, constituting a significant clinical challenge. METHODS: Four patient-derived pediatric glioma models were investigated to model rebound growth in vitro based on viable cell counts in response to MAPKi treatment and withdrawal. A multi-omics dataset (RNA sequencing and LC-MS/MS based phospho-/proteomics) was generated to investigate possible rebound-driving mechanisms. Following in vitro validation, putative rebound-driving mechanisms were validated in vivo using the BT-40 orthotopic xenograft model. RESULTS: Of the tested models, only a BRAFV600E-driven model (BT-40, with additional CDKN2A/Bdel) showed rebound growth upon MAPKi withdrawal. Using this model, we identified a rapid reactivation of the MAPK pathway upon MAPKi withdrawal in vitro, also confirmed in vivo. Furthermore, transient overactivation of key MAPK molecules at transcriptional (e.g. FOS) and phosphorylation (e.g. pMEK) levels, was observed in vitro. Additionally, we detected increased expression and secretion of cytokines (CCL2, CX3CL1, CXCL10 and CCL7) upon MAPKi treatment, maintained during early withdrawal. While increased cytokine expression did not have tumor cell intrinsic effects, presence of these cytokines in conditioned media led to increased attraction of microglia cells in vitro. CONCLUSION: Taken together, these data indicate rapid MAPK reactivation upon MAPKi withdrawal as a tumor cell intrinsic rebound-driving mechanism. Furthermore, increased secretion of microglia-recruiting cytokines may play a role in treatment response and rebound growth upon withdrawal, warranting further evaluation

Lidar technology for the German offshore test site "alpha ventus"-Joint project in measurement development

This paper describes the content of the joint research project "Development of LiDAR measurement techniques for the German offshore test site" and its first results. The objective is to develop reliable and standardised remote sensing techniques for various new applications in the wind energy community and to support other RAVE1 projects at the German offshore test site "alpha ventus". The first measurement campaign dealt with the comparison of wind parameters measured by common anemometry in a height of up to 103 m and LiDAR data measured up to 220 m height. The first results show very good agreement when the two techniques are compared as to wind speed, wind direction and power curve determination at a 5 MW wind turbine. The status of the development of a wind field scanner for nacelle-based LiDAR measurements is described and an outlook to the forthcoming work is given