Inter-laboratory mass spectrometry dataset based on passive sampling of drinking water for non-target analysis

Non-target analysis (NTA) employing high-resolution mass spectrometry is a commonly applied approach for the detection of novel chemicals of emerging concern in complex environmental samples. NTA typically results in large and information-rich datasets that require computer aided (ideally automated) strategies for their processing and interpretation. Such strategies do however raise the challenge of reproducibility between and within different processing workflows. An effective strategy to mitigate such problems is the implementation of inter-laboratory studies (ILS) with the aim to evaluate different workflows and agree on harmonized/standardized quality control procedures. Here we present the data generated during such an ILS. This study was organized through the Norman Network and included 21 participants from 11 countries. A set of samples based on the passive sampling of drinking water pre and post treatment was shipped to all the participating laboratories for analysis, using one pre-defined method and one locally (i.e. in-house) developed method. The data generated represents a valuable resource (i.e. benchmark) for future developments of algorithms and workflows for NTA experiments

Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction.

Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondrial energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/β-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondrial ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondrial energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologies

Insights into the high-energy γ-ray emission of Markarian 501 from extensive multifrequency observations in the Fermi era

We report on the γ-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average Large Area Telescope (LAT) γ-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 ± 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of two), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 ± 0.14, and the softest one is 2.51 ± 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3 GeV. In this paper, we also present the first results from the 4.5 month long multifrequency campaign (2009 March 15-August 1) on Mrk 501, which included the Very Long Baseline Array (VLBA), Swift, RXTE, MAGIC, and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The extensive radio to TeV data set from this campaign provides us with the most detailed spectral energy distribution yet collected for this source during its relatively low activity. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton (SSC) model. In the framework of this model, we find that the dominant emission region is characterized by a size ≲0.1 pc (comparable within a factor of few to the size of the partially resolved VLBA core at 15-43 GHz), and that the total jet power (≃1044 erg s-1) constitutes only a small fraction (∼10-3) of the Eddington luminosity. The energy distribution of the freshly accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3 GeV-10 TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20 GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks. We find that the ultrarelativistic electrons and mildly relativistic protons within the blazar zone, if comparable in number, are in approximate energy equipartition, with their energy dominating the jet magnetic field energy by about two orders of magnitude. © 2011. The American Astronomical Society

Metodo di controllo della risposta da parte di animali da reddito alla somministrazione di una razione alimentare

Il presente trovato si riferisce ad un metodo (10) di controllo della risposta da parte di animali da reddito alla somministrazione di una razione alimentare, che si caratterizza per il fatto di comprendere le seguenti operazioni: - stabilire lungo un fronte di mangiatoia (11) due vicine serie di punti di campionamento (12, 13), una prima serie di punti di campionamento (12) raggiunti o raggiungibili da un animale, ed una seconda serie di punti di campionamento (13) non raggiunti o non raggiungibili da un animale, - per ciascuna di tali serie di punti di campionamento (12, 13) effettuare, su una razione distribuita, campionamenti ripetuti su gruppi (14, 15, 16, 17, 18, 19, 20, 21) di affiancati punti di campionamento, primi gruppi (14, 15, 16, 17) appartenenti a detta prima serie (12), e secondi gruppi (18, 19, 20, 21) appartenenti a detta seconda serie (13), - per ciascuna rilevazione in ciascun punto di campionamento, si rilevano i seguenti parametri: a) almeno un parametro relativo alla percentuale di alimento trattenuto o passante da un setaccio; b) lunghezza media geometrica della fibra contenuta nella razione; c) contenuto in proteina greggia; d) contenuto in Neutral Detergent Fiber, e) contenuto in Amido

Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction

Mitochondrial diseases impair oxidative phosphorylation and ATP production, while effective treatment is still lacking. Defective complex III is associated with ahighly variable clinical spectrum. We show that pyocyanin, a bacterial redox cycler, can replace the redox functions of complex III, acting as an electron shunt. Sub-muM pyocyanin was harmless, restored respiration and increased ATP production in fibroblasts from five patients harboring pathogenic mutations in TTC19, BCS1L or LYRM7, involved in assembly/stabilization of complex III. Pyocyanin normalized the mitochondrial membrane potential, and mildly increased ROS production and biogenesis. These in vitro effects were confirmed in both DrosophilaTTC19KO and in Danio rerioTTC19KD, as administration of low concentrations of pyocyanin significantly ameliorated movement proficiency. Importantly, daily administration of pyocyanin for two months was not toxic in control mice. Our results point to utilization of redox cyclers for therapy of complex III disorders

Integrated Exposure and Algal Ecotoxicological Assessments of Effluents from Secondary and Advanced-Tertiary Wastewater-Treatment Plants

The great concern over the environmental impact of wastewaters has led to the designing of advanced treatment processes to upgrade conventional treatment plants and achieve a significant reduction of contaminants in receiving waters. In the present study we combined chemical and ecotoxicological analyses, aiming to evaluate the reduction of toxicity effects associated with the removal of micropollutants and to define the contribution of the detected compounds to the overall toxicity of the mixtures in a series of wastewater effluents collected from a secondary treatment (OUT 2) and from a tertiary activated carbon treatment (OUT 3) plant. The target compounds were selected after a screening procedure among pharmaceuticals, musk fragrances, and trace metals. The classical algal growth inhibition test was conducted on the original effluent samples and on different fractions obtained by solid-phase extraction (SPE) treatment. A good accordance was found between the removal of toxicity (30%-80%) and organic compounds (70%-80%) after the tertiary treatment, suggesting its high efficiency to improve the wastewater quality. The discrepancy between the contribution to the overall toxicity of the nonadsorbable compounds (i.e., inorganic or very polar organic compounds) as experimentally measured by the SPE bioassays (18%-76%) and calculated by the concentration addition approach (>97%) could be mitigated by including the bioavailability correction in metal-toxicity modeling of wastewater mixtures. For the organic compounds, the toxic equivalency method enabled us to quantify the portion of toxicity explained by the detected chemicals in both OUT 2 (82%-104%) and OUT 3 (5%-57%), validating the selection of the target molecules. The applied integrating approach could be implemented by the inclusion of both additional target chemicals and toxicity endpoints. Environ Toxicol Chem 2022;00:1-16. (c) 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC