Publications by authors named "Alain Brunelle"

88 Publications

Time-of-Flight Secondary Ion Mass Spectrometry Imaging of Cross Sections from the Bacchanals Paintings of Nicolas Poussin.

Anal Chem 2021 03 4;93(10):4463-4471. Epub 2021 Mar 4.

Sorbonne Université, CNRS, Laboratoire d'Archéologie Moléculaire et Structurale, LAMS, 4 place Jussieu, 75005 Paris, France.

The two paintings Infant Bacchanals (Museo Nazionale d'Arte Antica, Palazzo Barberini, Rome, Italy) executed by Nicolas Poussin (Les Andelys, 1594-Rome, 1665) in around 1626 are thought to have been painted "a guazzo", which means either with a glue or with an egg binding medium. To date, this has never been confirmed through analysis. Dual-beam time-of-flight secondary ion mass spectrometry (TOF-SIMS), using a bismuth cluster liquid metal ion gun and an argon gas cluster ion beam, allows the mapping of organic and inorganic matter on paintings cross sections, with the possibility to acquire submicrometer-resolution mass spectrometry images of the sample, together with high mass resolution using a delayed extraction of secondary ions. The surfaces of cross sections from both paintings were prepared beforehand either by polishing or by microtome cutting and then cleaned with the gas cluster ion beam directly inside the vacuum chamber of the instrument. The nature of the binders in the two paintings was investigated by TOF-SIMS analyses. By considering the uneven physical properties of the heterogeneous analyzed surfaces, several high-resolution images were recorded with different instrument settings. The detection of lipids seems to point toward an oil-containing medium, rather than a glue-binding medium. An emulsion made of oil and glue is another hypothesis to be explored to better understand the artist's working methods in his early career.
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http://dx.doi.org/10.1021/acs.analchem.0c04471DOI Listing
March 2021

Multimodal Imaging Based on Vibrational Spectroscopies and Mass Spectrometry Imaging Applied to Biological Tissue: A Multiscale and Multiomics Review.

Anal Chem 2021 01 30;93(1):445-477. Epub 2020 Nov 30.

Institut de Chimie & Biologie des Membranes & des Nano-objets, CBMN UMR 5248, CNRS, Université de Bordeaux, 1 Allée Geoffroy Saint-Hilaire, 33600 Pessac, France.

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http://dx.doi.org/10.1021/acs.analchem.0c04595DOI Listing
January 2021

Narrow Aperture Detection Electrodes ICR Cell with Quadrupolar Ion Detection for FT-ICR MS at the Cyclotron Frequency.

J Am Soc Mass Spectrom 2020 Nov 5;31(11):2258-2269. Epub 2020 Oct 5.

Spectroswiss, EPFL Innovation Park, 1015 Lausanne, Switzerland.

Ion signal detection at the true (unperturbed) cyclotron frequency instead of the conventional reduced cyclotron frequency has remained a formidable challenge since the inception of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Recently, routine FT-ICR MS at the true cyclotron frequency has become a reality with the implementation of ICR cells with narrow aperture detection electrodes (NADEL). Here, we describe the development and implementation of the next generation of these cells, namely, a 2xNADEL ICR cell, which comprises four flat detect and four ∼45° cylindrical excite electrodes, enabling independent ion excitation and quadrupolar ion detection. The performance of the 2xNADEL ICR cell was evaluated on two commercial FT-ICR MS platforms, 10 T LTQ FT from Thermo Scientific and 9.4 T SolariX XR from Bruker Daltonics. The cells provided accurate mass measurements in the analyses of singly and multiply charged peptides (root-mean-square, RMS, mass error / of 90 ppb), proteins (/ = 200 ppb), and petroleum fractions (/ < 200 ppb). Due to the reduced influence of measured frequency on the space charge and external (trapping) electric fields, the 2xNADEL ICR cells exhibited stable performance in a wide range of trapping potentials (1-20 V). Similarly, in a 13 h rat brain MALDI imaging experiment, the RMS mass error did not exceed 600 ppb even for low signal-to-noise ratio analyte peaks. Notably, the same set of calibration constants was applicable to Fourier spectra in all pixels, reducing the need for recalibration at the individual pixel level. Overall, these results support further experimental development and fundamentals investigation of this promising technology.
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http://dx.doi.org/10.1021/jasms.0c00221DOI Listing
November 2020

Multimodal Imaging Mass Spectrometry to Identify Markers of Pulmonary Arterial Hypertension in Human Lung Tissue Using MALDI-ToF, ToF-SIMS, and Hybrid SIMS.

Anal Chem 2020 09 17;92(17):12079-12087. Epub 2020 Aug 17.

Université Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, 91198, Gif-sur-Yvette, France.

Pulmonary arterial hypertension (PAH) is a rare and deadly disease affecting roughly 15-60 people per million in Europe with a poorly understood pathology. There are currently no diagnostic tools for early detection nor does a curative treatment exist. The lipid composition of arteries in lung tissue samples from human PAH and control patients were investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) combined with time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging. Using random forests as an IMS data analysis technique, it was possible to identify the ion at / 885.6 as a marker of PAH in human lung tissue. The / 885.6 ion intensity was shown to be significantly higher around diseased arteries and was confirmed to be a diacylglycerophosphoinositol PI(C18:0/C20:4) via MS/MS using a novel hybrid SIMS instrument. The discovery of a potential biomarker opens up new research avenues which may finally lead to a better understanding of the PAH pathology and highlights the vital role IMS can play in modern biomedical research.
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http://dx.doi.org/10.1021/acs.analchem.0c02815DOI Listing
September 2020

Kidney Lipidomics by Mass Spectrometry Imaging: A Focus on the Glomerulus.

Int J Mol Sci 2019 Apr 1;20(7). Epub 2019 Apr 1.

Institut Mondor de Recherche Biomédicale, INSERM, U955 EQ21, 8, rue du Général Sarrail, 94010 Créteil, France.

Lipid disorders have been associated with glomerulopathies, a distinct type of renal pathologies, such as nephrotic syndrome. Global analyses targeting kidney lipids in this pathophysiologic context have been extensively performed, but most often regardless of the architectural and functional complexity of the kidney. The new developments in mass spectrometry imaging technologies have opened a promising field in localized lipidomic studies focused on this organ. In this article, we revisit the main works having employed the Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) technology, and the few reports on the use of TOF-Secondary Ion Mass Spectrometry (TOF-SIMS). We also present a first analysis of mouse kidney cortex sections by cluster TOF-SIMS. The latter represents a good option for high resolution lipid imaging when frozen unfixed histological samples are available. The advantages and drawbacks of this developing field are discussed.
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http://dx.doi.org/10.3390/ijms20071623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480965PMC
April 2019

Biosynthetic investigation of γ-lactones in Sextonia rubra wood using in situ TOF-SIMS MS/MS imaging to localize and characterize biosynthetic intermediates.

Sci Rep 2019 02 13;9(1):1928. Epub 2019 Feb 13.

CNRS UMR8172 EcoFoG, AgroParisTech, CIRAD, INRA, Université des Antilles, Université de Guyane, 97300, Cayenne, France.

Molecular analysis by parallel tandem mass spectrometry (MS/MS) imaging contributes to the in situ characterization of biosynthetic intermediates which is crucial for deciphering the metabolic pathways in living organisms. We report the first use of TOF-SIMS MS/MS imaging for the cellular localization and characterization of biosynthetic intermediates of bioactive γ-lactones rubrynolide and rubrenolide in the Amazonian tree Sextonia rubra (Lauraceae). Five γ-lactones, including previously reported rubrynolide and rubrenolide, were isolated using a conventional approach and their structural characterization and localization at a lateral resolution of ~400 nm was later achieved using TOF-SIMS MS/MS imaging analysis. 2D/3D MS imaging at subcellular level reveals that putative biosynthetic γ-lactones intermediates are localized in the same cell types (ray parenchyma cells and oil cells) as rubrynolide and rubrenolide. Consequently, a revised metabolic pathway of rubrynolide was proposed, which involves the reaction between 2-hydroxysuccinic acid and 3-oxotetradecanoic acid, contrary to previous studies suggesting a single polyketide precursor. Our results provide insights into plant metabolite production in wood tissues and, overall, demonstrate that combining high spatial resolution TOF-SIMS imaging and MS/MS structural characterization offers new opportunities for studying molecular and cellular biochemistry in plants.
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http://dx.doi.org/10.1038/s41598-018-37577-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374367PMC
February 2019

Internal Energy Distribution of Secondary Ions Under Argon and Bismuth Cluster Bombardments: "Soft" Versus "Hard" Desorption-Ionization Process.

J Am Soc Mass Spectrom 2019 Feb 12;30(2):321-328. Epub 2018 Nov 12.

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.

The emission/ionization process under massive argon cluster bombardment was investigated by measuring the internal energy distributions of a series of benzylpyridinium ions. Argon clusters with kinetic energies between 10 and 20 keV and cluster sizes ranging from 500 to 10,000 were used to establish the influence of their size, energy, and velocity on the internal energy distribution of the secondary ions. It is shown that the internal energy distribution of secondary ions principally depends on the energy per atom or the velocity of the cluster ion beam (E/n ∝ v). Under low energy per atom (E/n ˂ 10 eV), the mean internal energy and fragmentation yield increase rapidly with the incident energy of individual constituents. Beyond 10 eV/atom impact (up to 40 eV/atom), the internal energy reaches a plateau and remains constant. Results were compared with those generated from bismuth cluster impacts for which the mean internal energies correspond well to the plateau values for argon clusters. However, a significant difference was found between argon and bismuth clusters concerning the damage or disappearance cross section. A 20 times smaller disappearance cross section was measured under 20 keV Ar impact compared to 25 keV Bi bombardment, thus quantitatively showing the low damage effect of large argon clusters for almost the same molecular ion yield. Graphical Abstract ᅟ.
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http://dx.doi.org/10.1007/s13361-018-2090-zDOI Listing
February 2019

Abiotic synthesis of amino acids in the recesses of the oceanic lithosphere.

Nature 2018 12 7;564(7734):59-63. Epub 2018 Nov 7.

Synchrotron SOLEIL, Gif-sur-Yvette, France.

Abiotic hydrocarbons and carboxylic acids are known to be formed on Earth, notably during the hydrothermal alteration of mantle rocks. Although the abiotic formation of amino acids has been predicted both from experimental studies and thermodynamic calculations, its occurrence has not been demonstrated in terrestrial settings. Here, using a multimodal approach that combines high-resolution imaging techniques, we obtain evidence for the occurrence of aromatic amino acids formed abiotically and subsequently preserved at depth beneath the Atlantis Massif (Mid-Atlantic Ridge). These aromatic amino acids may have been formed through Friedel-Crafts reactions catalysed by an iron-rich saponite clay during a late alteration stage of the massif serpentinites. Demonstrating the potential of fluid-rock interactions in the oceanic lithosphere to generate amino acids abiotically gives credence to the hydrothermal theory for the origin of life, and may shed light on ancient metabolisms and the functioning of the present-day deep biosphere.
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http://dx.doi.org/10.1038/s41586-018-0684-zDOI Listing
December 2018

Tandem Mass Spectrometry Imaging and in Situ Characterization of Bioactive Wood Metabolites in Amazonian Tree Species Sextonia rubra.

Anal Chem 2018 06 8;90(12):7535-7543. Epub 2018 Jun 8.

Institut de Chimie des Substances Naturelles , CNRS UPR 2301, Univ. Paris-Sud, Université Paris-Saclay , Avenue de la Terrasse , 91198 Gif-sur-Yvette , France.

Driven by a necessity for confident molecular identification at high spatial resolution, a new time-of-flight secondary ion mass spectrometry (TOF-SIMS) tandem mass spectrometry (tandem MS) imaging instrument has been recently developed. In this paper, the superior MS/MS spectrometry and imaging capability of this new tool is shown for natural product study. For the first time, via in situ analysis of the bioactive metabolites rubrynolide and rubrenolide in Amazonian tree species Sextonia rubra (Lauraceae), we were able both to analyze and to image by tandem MS the molecular products of natural biosynthesis. Despite the low abundance of the metabolites in the wood sample(s), efficient MS/MS analysis of these γ-lactone compounds was achieved, providing high confidence in the identification and localization. In addition, tandem MS imaging minimized the mass interferences and revealed specific localization of these metabolites primarily in the ray parenchyma cells but also in certain oil cells and, further, revealed the presence of previously unidentified γ-lactone, paving the way for future studies in biosynthesis.
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http://dx.doi.org/10.1021/acs.analchem.8b01157DOI Listing
June 2018

Radial distribution of wood extractives in European larch Larix decidua by TOF-SIMS imaging.

Phytochemistry 2018 Jun 10;150:31-39. Epub 2018 Mar 10.

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France. Electronic address:

Wood extractives in the xylem of European larch Larix decidua were mapped by time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging, which allows the radial distribution of both mineral and lipophilic extractives in the xylem to be scrutinized with high spatial resolution for the first time. Results show that all the components are inhomogeneously distributed across the annual ring. Mineral nutrients including Na, K, Ca, and Cl ions exhibit no preferential localization between earlywood and latewood, whereas PO ion is exclusively present in the ray cells, indicating it may be related to acid phosphatase. Lipophilic extractives were found to be more abundant in the inner secondary xylem. Ion images with 400 nm spatial resolution reveal that fatty acids, triglycerides and phytosterols are co-localized principally in the earlywood within the first annual ring. Resin acids prove to be the main components in the resin canal of the secondary xylem and are distributed in the outer of it.
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http://dx.doi.org/10.1016/j.phytochem.2018.02.017DOI Listing
June 2018

Insights into the MALDI Process after Matrix Deposition by Sublimation Using 3D ToF-SIMS Imaging.

Anal Chem 2018 02 17;90(3):1907-1914. Epub 2018 Jan 17.

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay , 91190 Gif-sur-Yvette, France.

Imaging mass spectrometry (IMS) has become a powerful tool to characterize the spatial distribution of biomolecules in thin tissue sections. In the case of matrix-assisted laser desorption ionization (MALDI) IMS, homogeneous matrix deposition is critical to produce high-quality ion images, and sublimation in particular has shown to be an excellent matrix deposition method for the imaging of lipids. Matrix deposition by sublimation is, however, a completely solvent-free system, which ought to prevent the mixing of matrix and analytes thought to be necessary for successful MALDI. Using 3D time-of-flight secondary ion imaging mass spectrometry, we have studied the matrix-tissue interface in 3D with high resolution to understand the MALDI process of lipids after matrix deposition by sublimation. There is a strong indication that diffusion is the process by which lipids migrate from the tissue to the matrix layer. We show that triacylglycerols and phospholipids have a delayed migratory trend as compared to diacylglycerols and monoacylglycerols, which is dependent on time and matrix thickness. Additional experiments show that a pure lipid's capacity to migrate into the matrix is dependent on its fluidity at room temperature. Furthermore, it is shown that cholesterol can only migrate in the presence of a (fluid) lipid and appears to fluidize lipids, which could explain its colocalization with the diacylglycerols and monoacylglycerols in the matrix.
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http://dx.doi.org/10.1021/acs.analchem.7b03993DOI Listing
February 2018

An Integrative Approach to Decipher the Chemical Antagonism between the Competing Endophytes Paraconiothyrium variabile and Bacillus subtilis.

J Nat Prod 2017 11 15;80(11):2863-2873. Epub 2017 Nov 15.

Unité Molécules de Communication et Adaptation des Micro-organismes (UMR 7245), Sorbonne Université, Muséum National d'Histoire Naturelle, CNRS , CP 54, 57 rue Cuvier, 75005 Paris, France.

An integrative approach combining traditional natural products chemistry, molecular networking, and mass spectrometry imaging has been undertaken to decipher the molecular dialogue between the fungus Paraconiothyrium variabile and the bacterium Bacillus subtilis, which were isolated as endophytes from the conifer Cephalotaxus harringtonia and are characterized by a strong and mutual antibiosis. From this study, we highlight that bacterial surfactins and a fungal tetronic acid are involved in such competition and that the fungus is able to hydrolyze surfactins to fight against the bacterial partner.
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http://dx.doi.org/10.1021/acs.jnatprod.6b01185DOI Listing
November 2017

Environmentally Friendly Procedure Based on Supercritical Fluid Chromatography and Tandem Mass Spectrometry Molecular Networking for the Discovery of Potent Antiviral Compounds from Euphorbia semiperfoliata.

J Nat Prod 2017 10 19;80(10):2620-2629. Epub 2017 Sep 19.

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, University of Paris-Saclay , 91198 Gif-sur-Yvette, France.

A supercritical fluid chromatography-based targeted purification procedure using tandem mass spectrometry and molecular networking was developed to analyze, annotate, and isolate secondary metabolites from complex plant extract mixture. This approach was applied for the targeted isolation of new antiviral diterpene esters from Euphorbia semiperfoliata whole plant extract. The analysis of bioactive fractions revealed that unknown diterpene esters, including jatrophane esters and phorbol esters, were present in the samples. The purification procedure using semipreparative supercritical fluid chromatography led to the isolation and identification of two new jatrophane esters (13 and 14) and one known (15) and three new 4-deoxyphorbol esters (16-18). The structure and absolute configuration of compound 16 were confirmed by X-ray crystallography. This compound was found to display antiviral activity against Chikungunya virus (EC = 0.45 μM), while compound 15 proved to be a potent and selective inhibitor of HIV-1 replication in a recombinant virus assay (EC = 13 nM). This study showed that a supercritical fluid chromatography-based protocol and molecular networking can facilitate and accelerate the discovery of bioactive small molecules by targeting molecules of interest, while minimizing the use of toxic solvents.
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http://dx.doi.org/10.1021/acs.jnatprod.7b00113DOI Listing
October 2017

Skin Penetration Enhancement by Natural Oils for Dihydroquercetin Delivery.

Molecules 2017 Sep 12;22(9). Epub 2017 Sep 12.

Department of Clinical Pharmacy, Lithuanian University of Health Sciences, Sukilėlių pr. 13, Kaunas 50166, Lithuania.

Natural oils are commonly used in topical pharmaceutical formulations as emulsifiers, stabilizers or solubility enhancers. They are presented as safe and inert components, mainly used for formulation purposes. It is confirmed that natural oils can affect the skin penetration of various substances. Fatty acids are mainly responsible for this effect. Current understanding lacks reliable scientific data on penetration of natural oils into the skin and their skin penetration enhancement potential. In the current study, fatty acid content analysis was used to determine the principal fatty acids in soybean, olive, avocado, sea-buckthorn pulp, raspberry seed and coconut oils. Time of flight secondary ion mass spectrometry bioimaging was used to determine the distribution of these fatty acids in human skin ex vivo after application of the oils. Skin penetration enhancement ratios were determined for a perspective antioxidant compound dihydroquercetin. The results demonstrated skin penetration of fatty acids from all oils tested. Only soybean and olive oils significantly increased the skin distribution of dihydroquercetin and can be used as skin penetration enhancers. However, no correlation can be determined between the fatty acids' composition and skin penetration enhancement using currently available methodological approaches. This indicates that potential chemical penetration enhancement should be evaluated during formulation of topically applied products containing natural oils.
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http://dx.doi.org/10.3390/molecules22091536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151382PMC
September 2017

Dual Beam Depth Profiling and Imaging with Argon and Bismuth Clusters of Prenylated Stilbenes on Glandular Trichomes of Macaranga vedeliana.

Anal Chem 2017 09 22;89(17):9247-9252. Epub 2017 Aug 22.

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-Saclay , Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.

Using a time-of-flight secondary ion mass spectrometer equipped with an argon cluster ion for sputtering and a bismuth liquid metal ion source for analysis, both surfaces of leaves and fruits of Macaranga vedeliana, an endemic New Caledonian species, have been for the first time analyzed by a dual beam depth profiling. To prevent in-vacuum evaporation of the liquid content of the small glandular trichomes covering fruits and leaves surfaces and also to be able to analyze their liquid content while preventing any sublimation of the latter, the samples were kept frozen during the whole experiment using a nitrogen cooled sample holder. Thus, it was possible to demonstrate that vedelianin, an active metabolite of the family of prenylated stilbenes named schweinfurthins, is only located in these glandular trichomes.
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http://dx.doi.org/10.1021/acs.analchem.7b02020DOI Listing
September 2017

Structural Characterisation of Acetogenins from Annona muricata by Supercritical Fluid Chromatography Coupled to High-Resolution Tandem Mass Spectrometry.

Phytochem Anal 2017 Nov 19;28(6):512-520. Epub 2017 Jun 19.

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-Saclay, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.

Introduction: Acetogenins are plant polyketides known to be cytotoxic and proposed as antitumor candidates. They are also suspected to be alimentary neurotoxins. Their occurrence as complex mixtures renders their dereplication and structural identification difficult using liquid chromatography coupled to tandem mass spectrometry and efforts are required to improve the methodology.

Objective: To develop a supercritical fluid chromatography (SFC) high-resolution tandem mass spectrometry method, involving lithium post-column cationisation, for the structural characterisation of Annonaceous acetogenins in crude extracts.

Methodology: The seeds of Annona muricata L. were extracted with methanol. Supercritical fluid chromatography of the extract, using a 2-ethylpyridine stationary phase column, was monitored using a high-resolution quadrupole time-of-flight mass spectrometer. Lithium iodide was added post-column in the make-up solvent. For comparison, the same extract was analysed using high-pressure liquid chromatography coupled to the same mass spectrometer, with a column based on solid core particles.

Results: Sensitivity was similar for both HPLC and SFC approaches. Retention behaviour and fragmentation pathways of three different isomer groups are described. A previously unknown group of acetogenins was also evidenced for the first time.

Conclusion: The use of SFC-MS/MS allows the reduction of the time of analysis, of environmental impact and an increase in the chromatographic resolution, compared to liquid chromatography. This new methodology enlightened a new group of acetogenins, isomers of montanacin-D. Copyright © 2017 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pca.2700DOI Listing
November 2017

Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients.

Sci Rep 2017 04 24;7:46658. Epub 2017 Apr 24.

Inserm, Unité 1193, Villejuif, F-94800, France.

Nonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients. Then, metabolism dysregulations were investigated in both patients and murine models. Alterations of elongase and desaturase activities were observed along the fatty acid synthesis pathway. The decreased activity of the desaturase FADS1 appeared as a bottleneck, leading upstream to an accumulation of fatty acids and downstream to a deficiency of long-chain fatty acids resulting to impaired phospholipid synthesis. In NASH, mass spectrometry imaging on tissue section revealed the spreading into the hepatic parenchyma of selectively accumulated fatty acids. Such lipids constituted a highly toxic mixture to human hepatocytes. In conclusion, this study characterized a specific and sensitive lipid signature of NASH and positioned FADS1 as a significant player in accumulating toxic lipids during NASH progression.
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http://dx.doi.org/10.1038/srep46658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402394PMC
April 2017

Fatty acids penetration into human skin ex vivo: A TOF-SIMS analysis approach.

Biointerphases 2017 03 2;12(1):011003. Epub 2017 Mar 2.

Department of Clinical Pharmacy, Lithuanian University of Health Sciences, Sukilėlių pr. 13, 50166 Kaunas, Lithuania.

Linoleic, oleic, palmitoleic, palmitic, and stearic fatty acids (FAs) are commonly used in dermatological formulations. They differ by their structure, presence in the skin, and mode of application in pharmaceuticals and cosmetics compounding. These FAs are also known as chemical penetration enhancers, but their mechanisms of penetration enhancement and effect on barrier characteristics of the skin require additional study. In this study, the authors conducted an ex vivo analysis of the distribution of lipid components in the epidermis and dermis of human skin after applying individual FAs. The goal was to elucidate possible mechanisms of penetration enhancement and FA effects on barrier characteristics of the skin. FA penetration studies were conducted ex vivo on human skin and time-of-flight secondary ion mass spectrometry (TOF-SIMS) bioimaging analysis was performed to visualize and analyze distribution of FAs in skin sections. The current study demonstrated that TOF-SIMS imaging was effective in visualizing the distribution of linoleic, oleic, palmitoleic, palmitic, and stearic acid in the human skin ex vivo after the skin penetration experiment of individual FAs. The integration of the obtained TOF-SIMS images allowed a semiquantitative comparison of the effects induced by individual FA applications on the human skin ex vivo. FAs showed varying abilities to penetrate the skin and disorder the FAs within the skin, based on their structures and physicochemical properties. Linoleic acid penetrated the skin and changed the distribution of all the analyzed FAs. Skin treatment with palmitoleic or oleic acid increased the amounts of singular FAs in the skin. Penetration of saturated FAs was low, but it increased the detected amounts of linoleic acid in both skin layers. The results indicate that application of FAs on the skin surface induce redistribution of native FAs not only in the stratum corneum layer of epidermis but also in the lipid content of full epidermis and dermis layers. The results indicate that topically applied pharmaceutical products should be evaluated for potential chemical penetration enhancement and lipid component redistribution effects during formulation.
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http://dx.doi.org/10.1116/1.4977941DOI Listing
March 2017

High mass and spatial resolution mass spectrometry imaging of Nicolas Poussin painting cross section by cluster TOF-SIMS.

J Mass Spectrom 2016 Dec;51(12):1196-1210

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-Saclay, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging using cluster primary ion beams is used for the identification of the pigments in the painting of Rebecca and Eliezer at the Well by Nicolas Poussin. The combination of the high mass resolution of the technique with a sub-micrometer spatial resolution offered by a delayed extraction of the secondary ions, together with the possibility to simultaneously identifying both minerals and organics, has proved to be the method of choice for the study of the stratigraphy of a paint cross section. The chemical compositions of small grains are shown with the help of a thorough processing of the data, with images of specific ions, mass spectra extracted from small regions of interest, and profiles drawn along the different painting layers. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/jms.3885DOI Listing
December 2016

Mapping Dicorynia guianensis Amsh. wood constituents by submicron resolution cluster-TOF-SIMS imaging.

J Mass Spectrom 2016 Jun;51(6):412-23

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-Saclay, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.

The preparation of tropical wood surface sections for time-of-flight secondary ion mass spectrometry imaging is described, and the use of delayed extraction of secondary ions and its interest for the analysis of vegetal surface are shown. The method has been applied to the study by time-of-flight secondary ion mass spectrometry imaging with a resolution of less than one micron of a tropical wood species, Dicorynia guianensis, which is one of the most exploited wood in French Guiana for its durable heartwood. The heartwood of this species exhibits an economical importance, but its production is not controlled in forestry. Results show an increase of tryptamine from the transition zone and a concomitant decrease of inorganic ions and starch fragment ions. These experiments lead to a better understanding of the heartwood formation and the origin of the natural durability of D. guianensis. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/jms.3762DOI Listing
June 2016

Validation data for the quantification of the Annonaceous acetogenin annonacin in Rat brain by UPLC-MS/MS.

Data Brief 2016 Jun 4;7:1633-8. Epub 2016 May 4.

Laboratoire de Pharmacognosie, BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, UFR Pharmacie, 5 rue J.-B. Clément, 92290 Châtenay-Malabry, France.

Annonaceous acetogenins (AAGs) are environmental neurotoxins from the fruit pulp of several Annonaceae species, whose consumption was linked to the occurrence of sporadic atypical Parkinsonism with dementia. The quantification of the prototypical AAG annonacin in Rat brain homogenates was performed by UPLC-MS/MS in selected reaction monitoring (SRM) mode, using a triple quadrupole mass analyzer. A natural analog of annonacin was used as an internal standard. Analyzed data set of the analytical validation of this method is presented, including stability of the samples, extraction recovery and matrix effect, supporting the results described in the article "Quantification of the environmental neurotoxin annonacin in Rat brain by UPLC-MS/MS" N. Bonneau, I. Schmitz-Afonso, D. Touboul, A. Brunelle, P. Champy (2016) [1].
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http://dx.doi.org/10.1016/j.dib.2016.04.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866534PMC
June 2016

Quantification of the environmental neurotoxin annonacin in Rat brain by UPLC-MS/MS.

Toxicon 2016 Aug 4;118:129-33. Epub 2016 Apr 4.

Laboratoire de Pharmacognosie, BioCIS, Univ. Paris-Sud, CNRS, Université Paris-Saclay, UFR Pharmacie, 5 rue J.-B. Clément, 92290, Châtenay-Malabry, France. Electronic address:

The Annonaceous acetogenin annonacin is an environmental neurotoxin identified in the pulp of several fruits of the Annonaceae family, whose consumption was linked to the occurrence of sporadic atypical Parkinsonism with dementia. A method for its quantification in Rat brain homogenates by UPLC-MS/MS in selected reaction monitoring (SRM) mode was developed and validated. This method was applied to the quantitation of annonacin in Rat brain after intravenous (0.5 mg/kg) and oral (10 mg/kg, 100 mg/kg) administration.
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http://dx.doi.org/10.1016/j.toxicon.2016.03.015DOI Listing
August 2016

What more can TOF-SIMS bring than other MS imaging methods?

Bioanalysis 2016 19;8(5):367-9. Epub 2016 Feb 19.

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, Avenue de la Terrasse 91198, Gif-sur-Yvette, France.

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http://dx.doi.org/10.4155/bio.16.11DOI Listing
December 2016

Method development for quantification of the environmental neurotoxin annonacin in Rat plasma by UPLC-MS/MS and application to a pharmacokinetic study.

J Chromatogr B Analyt Technol Biomed Life Sci 2015 Nov 30;1004:46-52. Epub 2015 Sep 30.

Laboratoire de Pharmacognosie-Chimie des Substances Naturelles, UMR-BioCIS, CNRS, University Paris-Sud, Université Paris-Saclay, 5 rue Jean-Baptiste Clément, 9290, Châtenay-Malabry, France. Electronic address:

Annonacin is an environmental neurotoxin identified in the pulp of several fruits of the Annonaceae family (for example in Annona muricata, Asimina triloba), whose consumption was linked with the occurrence of sporadic atypical Parkinsonism with dementia. Pharmacokinetic parameters of this molecule are unknown. A method for its quantification in Rat plasma was developed, using its analogue annonacinone as an internal standard. Extraction from plasma was performed using ethylacetate with a good recovery. Quantification was performed by UPLC-MS/MS in SRM mode, based on the loss of the γ-methyl-γ-lactone (-112amu) from the sodium-cationized species [M+Na](+) of both annonacin and internal standard. The limit of quantification was 0.25ng/mL. Despite strong matrix effects, a good linearity was obtained over two distinct ranges 0.25-10ng/mL and 10-100ng/mL. The intra- and inter-day precisions (RSD) were lower than 10%, while accuracy was within ±10%. This method was applied to a pharmacokinetic study in the Rat. After oral administration of 10mg/kg annonacin, a Cmax of 7.9±1.5ng/mL was reached at Tmax 0.25h; T1/2 was 4.8±0.7h and apparent distribution volume was 387.9±64.6L. The bioavailability of annonacin was estimated to be 3.2±0.3% of the ingested dose.
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http://dx.doi.org/10.1016/j.jchromb.2015.09.039DOI Listing
November 2015

Time-of-flight secondary ion mass spectrometry imaging of biological samples with delayed extraction for high mass and high spatial resolutions.

Rapid Commun Mass Spectrom 2015 Jul;29(13):1187-95

Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Université Paris-Sud, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.

Rationale: In Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS), pulsed and focused primary ion beams enable mass spectrometry imaging, a method which is particularly useful to map various small molecules such as lipids at the surface of biological samples. When using TOF-SIMS instruments, the focusing modes of the primary ion beam delivered by liquid metal ion guns can provide either a mass resolution of several thousand or a sub-µm lateral resolution, but the combination of both is generally not possible.

Methods: With a TOF-SIMS setup, a delayed extraction applied to secondary ions has been studied extensively on rat cerebellum sections in order to compensate for the effect of long primary ion bunches.

Results: The use of a delayed extraction has been proven to be an efficient solution leading to unique features, i.e. a mass resolution up to 10000 at m/z 385.4 combined with a lateral resolution of about 400 nm. Simulations of ion trajectories confirm the experimental determination of optimal delayed extraction and allow understanding of the behavior of ions as a function of their mass-to-charge ratio.

Conclusions: Although the use of a delayed extraction has been well known for many years and is very popular in MALDI, it is much less used in TOF-SIMS. Its full characterization now enables secondary ion images to be recorded in a single run with a submicron spatial resolution and with a mass resolution of several thousand. This improvement is very useful when analyzing lipids on tissue sections, or rare, precious, or very small size samples.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033000PMC
http://dx.doi.org/10.1002/rcm.7210DOI Listing
July 2015

Quantification of tocopherols and tocotrienols in soybean oil by supercritical-fluid chromatography coupled to high-resolution mass spectrometry.

Anal Bioanal Chem 2015 Jul 31;407(17):5133-42. Epub 2015 Mar 31.

Institut de Chimie des Substances Naturelles, UPR2301, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.

For the most effective analytical strategies, development and validation include optimization of such analytical variables as resolution, detectability, sensitivity, simplicity, cost effectiveness, flexibility, and speed. However, other aspects concerning operator safety and environmental impact are not considered at the same level. The result has been many unintended negative effects of analytical methods developed to investigate different kinds of sample, especially hydrophobic compounds that generate a large amount of chemical waste and have a strong negative environmental impact. In this context, quantification of tocopherols and tocotrienols, i.e. the vitamin E family, is usually achieved by normal-phase liquid chromatography using large volumes of toxic organic solvents, or reversed-phase liquid chromatography using a high percentage of methanol for elution. We propose here a "greener" analytical strategy, including the hyphenation of supercritical-fluid chromatography, using CO2 and ethanol as mobile phase, NH2 as stationary phase, and mass spectrometry for the detection and quantification of vitamin E congeners in soybean oil. An atmospheric-pressure photoionization (APPI) source seemed significantly more sensitive and robust than electrospray or atmospheric-pressure chemical ionization (APCI). This method led to shortened analysis time (less than 5 min) and was revealed to be as sensitive as more traditional approaches, with limits of detection and quantification in the tens of μg L(-1).
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http://dx.doi.org/10.1007/s00216-015-8604-7DOI Listing
July 2015

Biomedical studies by TOF-SIMS imaging.

Biointerphases 2014 Mar 11;10(1):018901. Epub 2014 Mar 11.

Institut de Chimie des Substances Naturelles, UPR2301, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.

Imaging by secondary ion mass spectrometry coupled to time-of-flight mass analysis (TOF-SIMS) is a method of which the applications have greatly increased since 10 years. Taking advantage of the development of cluster ion sources, TOF-SIMS offers images of molecular ions at a micrometer lateral resolution or slightly below and does not require complex sample preparation. Although TOF-SIMS has been primarily dedicated to surface analysis of inorganic or polymeric samples, several groups have successfully demonstrated that TOF-SIMS imaging is also perfectly suited for mapping organic compounds, such as drugs or lipids, directly on tissue sections from animals or from human biopsies. This minireview will enlighten some of these developments in the field of biomedical applications.
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http://dx.doi.org/10.1116/1.4901511DOI Listing
March 2014

Determination of ionization energies of a monoterpene series by atmospheric pressure photoionization using tunable vacuum ultraviolet synchrotron radiation.

Eur J Mass Spectrom (Chichester) 2014 ;20(5):403-7

Monoterpenes are the main class of biogenic volatile organic compounds. They promptly react with oxygen and nitrogen species, leading to the formation of secondary aerosols. The determination of their physicochemical properties, such as their ionization energies (IEs), is crucial to understand better their reactivity. We previously introduced a modified atmospheric pressure photoionization source coupled to a tunable vacuum ultraviolet source at the SOLEIL synchrotron radiation facility. Here, this set-up is employed to determine IEs of ten monoterpenes with a good precision (±50 meV) and a small sample consumption limited to 10 μg.
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http://dx.doi.org/10.1255/ejms.1291DOI Listing
May 2015

Mass spectrometry imaging of biological tissue: an approach for multicenter studies.

Anal Bioanal Chem 2015 Mar 10;407(8):2329-35. Epub 2015 Jan 10.

Institute of Inorganic and Analytical Chemistry, Justus Liebig University, Schubertstrasse 60, Bldg. 16, 35392, Giessen, Germany,

Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDI-Fourier transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common data format (imzML) and a public data repository can contribute to more reliability and transparency of MS imaging studies.
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http://dx.doi.org/10.1007/s00216-014-8410-7DOI Listing
March 2015