Metabolomics applied to urine samples in childhood asthma; differentiation between asthma phenotypes and identification of relevant metabolites

Asthma is a heterogeneous disorder and one of the most common chronic childhood diseases. An improved characterization of asthma phenotypes would be invaluable for the understanding of the pathogenic mechanisms and the correct treatment of this disease. The aim of this pilot study was to explore the potential of metabolomics applied to urine samples in characterizing asthma, and to identify the most representative metabolites. Urine samples of 41 atopic asthmatic children (further subdivided in sub-groups according to the symptoms) and 12 age-matched controls were analyzed. Untargeted metabolic profiles were collected by LC-MS, and studied by multivariate analysis. The group of the asthmatics was differentiated by a model that proved to be uncorrelated with the chronic assumption of controller drugs by part of the patients. The distinct sub-groups were also appropriately modeled. Further investigations revealed a reduced excretion of urocanic acid, methyl-imidazoleacetic acid and of a metabolite resembling the structure of an Ile-Pro fragment in the asthmatics. The meaning of these findings was discussed and mainly correlated with the modulation of immunity in asthma. Metabolic profiles from urines have revealed the potential to characterize asthma and enabled the identification of metabolites which may have a role in the underlying inflammation.JRC.I.6-Systems toxicolog

Report on characterisation of New Psychoactive Substances (NPS)

The emergence of designer drugs as abused substances has seen a dramatic increase over the past few years. About 70 new psychoactive substances were discovered in 2012 and more than 80 in 2013. Customs and forensic laboratories are faced with a challenge in identifying the chemical structure of these new compounds. Their analytical controls based on infrared spectroscopy and gas chromatography-mass spectrometry allow the recognition of known substances already recorded in spectroscopic libraries. However the identification of new derivatives as well as new chemical structures requires highly sophisticated analytical techniques such as Nuclear Magnetic Resonance (NMR) and High Resolution Mass Spectrometry (HR-MS). The report introduces an analytical strategy allowing the characterisation of unknown compounds based on the experience of the JRC in the use of these techniques. These approaches have been tested in the laboratory of the Joint Research Centre (JRC) and the efficiency of the proposed approach has been successfully demonstrated on several study cases. The report gives an overview of the analytical strategies and modern laboratory techniques needed to perform a fast unambiguous identification and characterisation of unknown organic chemical substances such as New Psychoactive Substances (NPS).JRC.I.1-Chemical Assessment and Testin

New geological and tephrochronological data on the palaeontological site of the Senèze maar (Early Pleistocene, Massif Central, France)

The volcanic system of Senèze (Domeyrat, Haute-Loire) comprises a basanite flow, scoriae, a maar crater and phreatomagmatic products. New field research and detailed cartography clarify their geometry and geological relationships. The maar contains an important palaeontological site of the Early Pleistocene that yielded forty species of mammals attributed to the biozone MNQ 18 (of which it is the reference locality). The excavations undertaken between 2001 and 2006 recovered new fossils and documented their stratigraphic and geodynamic context. The fossiliferous site is located on the shore of the palaeolake and includes several lacustrine and slope deposits linked to the contemporaneous climatic changes which in turn produced a number of locally fossiliferous findspots which appear to be close in age. The discovery of ten tephras emitted by the Mont-Dore strato-volcano, situated 60 km to the NW allowed development of a remarkable tephrochronological framework. Because of the intense weathering of the tephras, their composition is determined by their mineralogical content (feldspars, brown amphiboles, brown and green diopside, titanite, apatite, zircon, biotite-phlogopite, Fe-Ti oxides) and the chemical composition of feldspars (anorthoclase, sodic sanidine and plagioclases). The study of these tephras reveals the importance of the contemporaneous (mainly trachytic) pyroclastic activity and confirms the polyphased deposition of the site. The 40Ar/39Ar laser dating of alkali feldspars from five tephras shows a relatively narrow range of age comprised between 2.09 and 2.21 \textpm 0.02 Ma (1σ, age relative to ACs-2 standard at 1.201 Ma). Senèze is thus confirmed as a key Early Pleistocene palaeontological site in Europe

The protective role of transferrin in Müller glial cells after iron-induced toxicity

PURPOSE: Transferrin (Tf) expression is enhanced by aging and inflammation in humans. We investigated the role of transferrin in glial protection. METHODS: We generated transgenic mice (Tg) carrying the complete human transferrin gene on a C57Bl/6J genetic background. We studied human (hTf) and mouse (mTf) transferrin localization in Tg and wild-type (WT) C57Bl/6J mice using immunochemistry with specific antibodies. Müller glial (MG) cells were cultured from explants and characterized using cellular retinaldehyde binding protein (CRALBP) and vimentin antibodies. They were further subcultured for study. We incubated cells with FeCl(3)-nitrilotriacetate to test for the iron-induced stress response; viability was determined by direct counting and measurement of lactate dehydrogenase (LDH) activity. Tf expression was determined by reverse transcriptase-quantitative PCR with human- or mouse-specific probes. hTf and mTf in the medium were assayed by ELISA or radioimmunoassay (RIA), respectively. RESULTS: mTf was mainly localized in retinal pigment epithelium and ganglion cell layers in retina sections of both mouse lines. hTf was abundant in MG cells. The distribution of mTf and hTf mRNA was consistent with these findings. mTf and hTf were secreted into the medium of MG cell primary cultures. Cells from Tg mice secreted hTf at a particularly high level. However, both WT and Tg cell cultures lose their ability to secrete Tf after a few passages. Tg MG cells secreting hTf were more resistant to iron-induced stress toxicity than those no longer secreted hTf. Similarly, exogenous human apo-Tf, but not human holo-Tf, conferred resistance to iron-induced stress on MG cells from WT mice. CONCLUSIONS: hTf localization in MG cells from Tg mice was reminiscent of that reported for aged human retina and age-related macular degeneration, both conditions associated with iron deposition. The role of hTf in protection against toxicity in Tg MG cells probably involves an adaptive mechanism developed in neural retina to control iron-induced stress

Critical Exponents of the pure and random-field Ising models

We show that current estimates of the critical exponents of the three-dimensional random-field Ising model are in agreement with the exponents of the pure Ising system in dimension 3 - theta where theta is the exponent that governs the hyperscaling violation in the random case.Comment: 9 pages, 4 encapsulated Postscript figures, REVTeX 3.

Calcul de stabilité des berges d'un canal : Application au réseau de canaux de la Sèvre Niortaise

Les berges de la Sèvre Niortaise sont régulièrement endommagées par des glissements circulaires. Des chantiers de restauration utilisant des soutènements par pieux, des géotextiles et des plantations ont déjà été réalisés. L'étendue des dégradations étant importante, l'optimisation des travaux est devenue nécessaire. Ainsi, nous travaillons à la réalisation d'un outil de prédiction des évolutions topographiques du canal et des berges. Celui-ci sert à la proposition de solutions de restauration. Le paramétrage du modèle s'appuie sur des essais mécaniques réalisés sur des échantillons de sol prélevés in situ. Une berge située à Damvix (85) a été modélisée. Cette étude a permis de déterminer la géométrie des surfaces de rupture potentielles et de tester l'influence des différents facteurs déstabilisants

Systematic analytical characterization of new psychoactive substances: A case study

AbstractNew psychoactive substances (NPS) are synthesized compounds that are not usually covered by European and/or international laws. With a slight alteration in the chemical structure of existing illegal substances registered in the European Union (EU), these NPS circumvent existing controls and are thus referred to as “legal highs”. They are becoming increasingly available and can easily be purchased through both the internet and other means (smart shops). Thus, it is essential that the identification of NPS keeps up with this rapidly evolving market.In this case study, the Belgian Customs authorities apprehended a parcel, originating from China, containing two samples, declared as being “white pigments”. For routine identification, the Belgian Customs Laboratory first analysed both samples by gas-chromatography mass-spectrometry and Fourier-Transform Infrared spectroscopy. The information obtained by these techniques is essential and can give an indication of the chemical structure of an unknown substance but not the complete identification of its structure. To bridge this gap, scientific and technical support is ensured by the Joint Research Centre (JRC) to the European Commission Directorate General for Taxation and Customs Unions (DG TAXUD) and the Customs Laboratory European Network (CLEN) through an Administrative Arrangement for fast recognition of NPS and identification of unknown chemicals. The samples were sent to the JRC for a complete characterization using advanced techniques and chemoinformatic tools.The aim of this study was also to encourage the development of a science-based policy driven approach on NPS.These samples were fully characterized and identified as 5F-AMB and PX-3 using 1H and 13C nuclear magnetic resonance (NMR), high-resolution tandem mass-spectrometry (HR-MS/MS) and Raman spectroscopy. A chemoinformatic platform was used to manage, unify analytical data from multiple techniques and instruments, and combine it with chemical and structural information

In vitro cannabinoid receptor activity, metabolism, and detection in seized samples of CH-PIATA, a new indole-3-acetamide synthetic cannabinoid

The rapidly evolving synthetic cannabinoid receptor agonist (SCRA) market poses significant challenges for forensic scientists. Since the enactment of a generic ban in China, a variety of new compounds have emerged capable of evading the legislation by carrying new structural features. One recent example of a SCRA with new linker and head moieties is CH-PIATA (CH-PIACA, CHX-PIATA, CHX-PIACA). CH-PIATA bears an additional methylene spacer in the linker moiety between the indole core and the traditional carbonyl component of the linker. This study describes detections in 2022 of this new SCRA in the United States, Belgium, and Scottish prisons. CH-PIATA was detected once in a seized powder by Belgian customs and 12 times in Scottish prisons in infused papers or resin. The metabolites of CH-PIATA were investigated via in vitro human liver microsome (HLM) incubations and eight metabolites were identified, dominated by oxidative biotransformations. A blood sample from the United States was confirmed to contain a mixture of SCRAs including CH-PIATA via presence of the parent and at least five of the metabolites identified from HLM incubations. Furthermore, this paper evaluates the intrinsic in vitro cannabinoid 1 and 2 (CB1 and CB2) receptor activation potential of CH-PIATA reference material and the powder seized by Belgian customs by means of & beta;-arrestin 2 recruitment assays. Both the reference and the seized powder showed a weak activity at both CB receptors with signs of antagonism found. Based on these results, the expected harm potential of this newly emerging substance remains limited