Publications by authors named "Philippe Schmitt-Kopplin"

308 Publications

Exploring the chemical space of white wine antioxidant capacity: A combined DPPH, EPR and FT-ICR-MS study.

Food Chem 2021 Mar 23;355:129566. Epub 2021 Mar 23.

Univ. Bourgogne Franche-Comté, AgroSup Dijon, PAM UMR A 02.102, Institut Universitaire de la Vigne et du Vin - Jules Guyot, F-21000 Dijon, France.

The chemical composition and functionality of molecular fractions associated with dry white wines oxidative stability remain poorly understood. In the present study, DPPH assay, electron paramagnetic resonance spectroscopy (EPR) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) were used to explore the chemical diversity associated with the antioxidant capacity (AC) of white wines. AC determined using the DPPH assay and EPR were complementary and enabled differentiation of wine samples into groups with low, medium, and high AC. Mass spectra variations associated with global DPPH- and EPR-derived indices enabled identification of 365 molecular markers correlated with samples with high AC, of which 32% were CHO compounds including phenolic and sugar derivatives, 20% were CHOS and 36% were CHONS compounds including cysteine-containing peptides. This study confirmed the importance of CHONS and CHOS compounds in the antioxidant metabolome of dry white wines. Knowledge about these compounds will enable better understanding of the oxidative stability of white wines and therefore aid in achieving optimum shelf life.
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http://dx.doi.org/10.1016/j.foodchem.2021.129566DOI Listing
March 2021

Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population.

Nat Commun 2021 03 11;12(1):1588. Epub 2021 Mar 11.

RG Adipocytes & Metabolism, Institute for Diabetes and Obesity, Helmholtz Center Munich, Neuherberg, Germany.

Adipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.
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http://dx.doi.org/10.1038/s41467-021-21826-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952576PMC
March 2021

IL-17 controls central nervous system autoimmunity through the intestinal microbiome.

Sci Immunol 2021 Feb;6(56)

Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Interleukin-17A- (IL-17A) and IL-17F-producing CD4 T helper cells (T17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). T17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, T17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which correlated with an altered composition of their gut microbiota. However, loss of IL-17A/F in T cells did not diminish their encephalitogenic capacity. Reconstitution of a wild-type-like intestinal microbiota or reintroduction of IL-17A specifically into the gut epithelium of IL-17A/F-deficient mice reestablished their susceptibility to EAE. Thus, our data demonstrated that IL-17A and IL-17F are not encephalitogenic mediators but rather modulators of intestinal homeostasis that indirectly alter CNS-directed autoimmunity.
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http://dx.doi.org/10.1126/sciimmunol.aaz6563DOI Listing
February 2021

Amplifying and Fine-Tuning Rsm sRNAs Expression and Stability to Optimize the Survival of in Nutrient-Poor Environments.

Microorganisms 2021 Jan 26;9(2). Epub 2021 Jan 26.

Aix Marseille Univ, CEA, CNRS, BIAM, Lab Microbial Ecology of the Rhizosphere (LEMiRE), F-13108 Saint-Paul-Lez-Durance, France.

In the beneficial plant root-associated strain NFM421, the GacS/GacA two-component system positively controls biofilm formation and the production of secondary metabolites through the synthesis of , and . Here, we evidenced the genetic amplification of Rsm sRNAs by the discovery of a novel 110-nt long sRNA encoding gene, , generated by the duplication of (formerly ). Like the others genes, its overexpression overrides the mutation. We explored the expression and the stability of , , and encoding genes under rich or nutrient-poor conditions, and showed that their amount is fine-tuned at the transcriptional and more interestingly at the post-transcriptional level. Unlike and , we noticed that the expression of and genes was exclusively GacA-dependent. The highest expression level and longest half-life for each sRNA were correlated with the highest ppGpp and cyclic-di-GMP levels and were recorded under nutrient-poor conditions. Together, these data support the view that the Rsm system in is likely linked to the stringent response, and seems to be required for bacterial adaptation to nutritional stress.
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http://dx.doi.org/10.3390/microorganisms9020250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911923PMC
January 2021

The fall, recovery, classification, and initial characterization of the Hamburg, Michigan H4 chondrite.

Meteorit Planet Sci 2020 Nov 27;55(11):2341-2359. Epub 2020 Oct 27.

Department of Earth Sciences University of Toronto 22 Russell St Toronto Ontario M5S 3B1 Canada.

The Hamburg meteorite fell on January 16, 2018, near Hamburg, Michigan, after a fireball event widely observed in the U.S. Midwest and in Ontario, Canada. Several fragments fell onto frozen surfaces of lakes and, thanks to weather radar data, were recovered days after the fall. The studied rock fragments show no or little signs of terrestrial weathering. Here, we present the initial results from an international consortium study to describe the fall, characterize the meteorite, and probe the collision history of Hamburg. About 1 kg of recovered meteorites was initially reported. Petrology, mineral chemistry, trace element and organic chemistry, and O and Cr isotopic compositions are characteristic of H4 chondrites. Cosmic ray exposure ages based on cosmogenic He, Ne, and Ar are ~12 Ma, and roughly agree with each other. Noble gas data as well as the cosmogenic Be concentration point to a small 40-60 cm diameter meteoroid. An Ar-Ar age of 4532 ± 24 Ma indicates no major impact event occurring later in its evolutionary history, consistent with data of other H4 chondrites. Microanalyses of phosphates with LA-ICPMS give an average Pb-Pb age of 4549 ± 36 Ma. This is in good agreement with the average SIMS Pb-Pb phosphate age of 4535.3 ± 9.5 Ma and U-Pb Concordia age of 4535 ± 10 Ma. The weighted average age of 4541.6 ± 9.5 Ma reflects the metamorphic phosphate crystallization age after parent body formation in the early solar system.
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http://dx.doi.org/10.1111/maps.13584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820957PMC
November 2020

Investigation of fennel protein extracts by shot-gun Fourier transform ion cyclotron resonance mass spectrometry.

Food Res Int 2021 Jan 30;139:109919. Epub 2020 Nov 30.

Dipartimento di Scienze Agrarie, degli Alimenti e dell'Ambiente, Università degli Studi di Foggia, Via Napoli, 25, 71122 Foggia, Italy. Electronic address:

A rapid shot-gun method by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is proposed for the characterization of fennel proteins. After enzymatic digestion with trypsin, few microliters of extract were analyzed by direct infusion in positive ion mode. A custom-made non-redundant fennel-specific proteome database was derived from the well-known NCBI database; additional proteins belonging to recognized allergenic sources (celery, carrot, parsley, birch, and mugwort) were also included in our database, since patients hypersensitive to these plants could also suffer from fennel allergy. The peptide sequence of each protein from that derived list was theoretically sequenced to produce calculated m/z lists of possible m/z ions after tryptic digestions. Then, by using a home-made Matlab algorithm, those lists were matched with the experimental FT-ICR mass spectrum of the fennel peptide mixture. Finally, Peptide Mass Fingerprint searches confirmed the presence of the matched proteins inside the fennel extract with a total of 70 proteins (61 fennel specific and 9 allergenic proteins).
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http://dx.doi.org/10.1016/j.foodres.2020.109919DOI Listing
January 2021

Influence of the UV/HO Advanced Oxidation Process on Dissolved Organic Matter and the Connection between Elemental Composition and Disinfection Byproduct Formation.

Environ Sci Technol 2020 12 12;54(23):14964-14973. Epub 2020 Nov 12.

Department of Civil and Environmental Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon 000, Hong Kong SAR.

The UV/HO process is a promising advanced oxidation process (AOP) for micropollutant abatement in drinking water treatment and water reuse plants. However, during micropollutant degradation by the AOP, dissolved organic matter (DOM) and the disinfection byproduct (DBP) formation potential may also be altered. This study investigated the influence of the UV/HO AOP on the elemental composition and DBP formation potential of two DOM isolates by using ultrahigh-resolution mass spectrometry (UHRMS). After the AOP, 629 new chemical formulas with an increased degree of oxidation and decreased aromaticity were obtained. Such alterations led to the formation of 226 unknown DBPs with decreased aromaticity indices (AI) in the subsequent 3-day chlorination. Links between the unknown DBPs and the corresponding precursors in DOM were visualized by network computational analysis. The analysis gave three zones in the van Krevelen diagram based on the possibility of the CHO formulas located in each zone to link to the corresponding DBPs. A further investigation with two model compounds reconfirmed the hydroxylation and ring cleavage of DOM by HO attack during the AOP and the influence on DBP formation. These results obtained from UHRMS build the connection between the elemental composition of DOM and the formation potential of DBPs.
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http://dx.doi.org/10.1021/acs.est.0c03220DOI Listing
December 2020

Sulfate Alters the Competition Among Microbiome Members of Sediments Chronically Exposed to Asphalt.

Front Microbiol 2020 29;11:556793. Epub 2020 Sep 29.

Research Unit Comparative Microbiome Analysis, Helmholtz Zentrum München, Helmholtz Association of German Research Centers, Neuherberg, Germany.

Sulfate-reducing microorganisms (SRMs) often compete with methanogens for common substrates. Due to thermodynamic reasons, SRMs should outcompete methanogens in the presence of sulfate. However, many studies have documented coexistence of these microbial groups in natural environments, suggesting that thermodynamics alone cannot explain the interactions among them. In this study, we investigated how SRMs compete with the established methanogenic communities in sediment from a long-term, electron acceptor-depleted, asphalt-exposed ecosystem and how they affect the composition of the organic material. We hypothesized that, upon addition of sulfate, SRMs (i) outcompete the methanogenic communities and (ii) markedly contribute to transformations of the organic material. We sampled sediments from the test and proximate control sites under anoxic conditions and incubated them in seawater medium with or without sulfate. Abundance and activity pattern of SRMs and methanogens, as well as the total prokaryotic community, were followed for 6 weeks by using qPCR targeting selected marker genes. Some of these genes were also subjected to amplicon sequencing to assess potential shifts in diversity patterns. Alterations of the organic material in the microcosms were determined by mass spectrometry. Our results indicate that the competition of SRMs with methanogens upon sulfate addition strongly depends on the environment studied and the starting microbiome composition. In the asphalt-free sediments (control), the availability of easily degradable organic material (mainly plant-derived) allows SRMs to use a larger variety of substrates, reducing interspecies competition with methanogens. In contrast, the abundant presence of recalcitrant compounds in the asphalt-exposed sediment was associated with a strong competition between SRMs and methanogens, ultimately detrimental for the latter. Our data underpin the importance of the quality of bioavailable organic materials in anoxic environments as a driver for microbial community structure and function.
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http://dx.doi.org/10.3389/fmicb.2020.556793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550536PMC
September 2020

Unraveling the chemodiversity of halogenated disinfection by-products formed during drinking water treatment using target and non-target screening tools.

J Hazard Mater 2021 01 15;401:123681. Epub 2020 Aug 15.

Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences (SLU), Box 7050, SE-750 07, Uppsala, Sweden.

To date, there is no analytical approach available that allows the full identification and characterization of highly complex disinfection by-product (DBP) mixtures. This study aimed at investigating the chemodiversity of drinking water halogenated DBPs using diverse analytical tools: measurement of adsorbable organic halogen (AOX) and mass spectrometry (MS)-based target and non-target analytical workflows. Water was sampled before and after chemical disinfection (chlorine or chloramine) at four drinking water treatment plants in Sweden. The target analysis had the highest sensitivity, although it could only partially explain the AOX formed in the disinfected waters. Non-target Fourier transform ion cyclotron resonance (FT-ICR) MS analysis indicated that only up to 19 Cl and/or Br-CHO formulae were common to all disinfected waters. Unexpectedly, a high diversity of halogenated DBPs (presumed halogenated polyphenolic and highly unsaturated compounds) was found in chloraminated surface water, comparable to that found in chlorinated surface water. Overall, up to 86 DBPs (including isobaric species) were tentatively identified using liquid chromatography (LC)-Orbitrap MS. Although further work is needed to confirm their identity and assess their relevance in terms of toxicity, they can be used to design suspect lists to improve the characterization of disinfected water halogenated mixtures.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123681DOI Listing
January 2021

Water-Based Extraction of Bioactive Principles from Blackcurrant Leaves and : A Comparative Study.

Foods 2020 Oct 16;9(10). Epub 2020 Oct 16.

IBMM, University of Montpellier, CNRS, ENSCM, 34093 Montpellier, France.

The water-based extraction of bioactive components from flavonoid-rich medicinal plants is a key step that should be better investigated. This is especially true when dealing with easy-to-use home-made conditions of extractions, which are known to be a bottleneck in the course for a better control and optimization of the daily uptake of active components from medicinal plants. In this work, the water-based extraction of Blackcurrant () leaves (BC) and (CA) known to have complementary pharmacological properties, was studied and compared with a previous work performed on the extraction of Hawthorn ( HAW). Various extraction modes in water (infusion, percolation, maceration, ultrasounds, microwaves) were compared for the extraction of bioactive principles contained in BC and CA in terms of extraction yield, of amount of flavonoids, phenolic compounds, and proanthocyanidin oligomers, and of UHPLC profiles of the extracted compounds. The qualitative and quantitative aspects of the extraction, in addition to the kinetic of extraction, were studied. The optimized easy-to-use-at-home extraction protocol developed for HAW was found very efficient to easily extract bioactive components from BC and CA plants. UHPLC-ESI-MS and high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) were also implemented to get more qualitative information on the specific and common chemical compositions of the three plants (including HAW). Their antihyaluronidase, antioxidant, and antihypertensive activities were also determined and compared, demonstrating similar activities as the reference compound for some of these plants.
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http://dx.doi.org/10.3390/foods9101478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602794PMC
October 2020

Disturbed gut microbiota and bile homeostasis in -infected mice contributes to metabolic dysregulation and growth impairment.

Sci Transl Med 2020 10;12(565)

Institute of Medical Microbiology, RWTH University Hospital, 52074 Aachen, Germany.

Although infection with the human enteropathogen causes self-limited diarrhea in adults, infant populations in endemic areas experience persistent pathogen carriage in the absence of diarrhea. The persistence of this protozoan parasite in infants has been associated with reduced weight gain and linear growth (height-for-age). The mechanisms that support persistent infection and determine the different disease outcomes in the infant host are incompletely understood. Using a neonatal mouse model of persistent infection, we demonstrate that induced bile secretion and used the bile constituent phosphatidylcholine as a substrate for parasite growth. In addition, we show that infection altered the enteric microbiota composition, leading to enhanced bile acid deconjugation and increased expression of fibroblast growth factor 15. This resulted in elevated energy expenditure and dysregulated lipid metabolism with reduced adipose tissue, body weight gain, and growth in the infected mice. Our results indicate that this enteropathogen's modulation of bile acid metabolism and lipid metabolism in the neonatal mouse host led to an altered body composition, suggesting how infection could contribute to growth restriction in infants in endemic areas.
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http://dx.doi.org/10.1126/scitranslmed.aay7019DOI Listing
October 2020

Ragweed plants grown under elevated CO levels produce pollen which elicit stronger allergic lung inflammation.

Allergy 2020 Oct 9. Epub 2020 Oct 9.

Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Zentrum München, Munich, Germany.

Background: Common ragweed has been spreading as a neophyte in Europe. Elevated CO levels, a hallmark of global climate change, have been shown to increase ragweed pollen production, but their effects on pollen allergenicity remain to be elucidated.

Methods: Ragweed was grown in climate-controlled chambers under normal (380 ppm, control) or elevated (700 ppm, based on RCP4.5 scenario) CO levels. Aqueous pollen extracts (RWE) from control- or CO -pollen were administered in vivo in a mouse model for allergic disease (daily for 3-11 days, n = 5) and employed in human in vitro systems of nasal epithelial cells (HNECs), monocyte-derived dendritic cells (DCs), and HNEC-DC co-cultures. Additionally, adjuvant factors and metabolites in control- and CO -RWE were investigated using ELISA and untargeted metabolomics.

Results: In vivo, CO -RWE induced stronger allergic lung inflammation compared to control-RWE, as indicated by lung inflammatory cell infiltrate and mediators, mucus hypersecretion, and serum total IgE. In vitro, HNECs stimulated with RWE increased indistinctively the production of pro-inflammatory cytokines (IL-8, IL-1β, and IL-6). In contrast, supernatants from CO -RWE-stimulated HNECs, compared to control-RWE-stimulated HNECS, significantly increased TNF and decreased IL-10 production in DCs. Comparable results were obtained by stimulating DCs directly with RWEs. The metabolome analysis revealed differential expression of secondary plant metabolites in control- vs CO -RWE. Mixes of these metabolites elicited similar responses in DCs as compared to respective RWEs.

Conclusion: Our results indicate that elevated ambient CO levels elicit a stronger RWE-induced allergic response in vivo and in vitro and that RWE increased allergenicity depends on the interplay of multiple metabolites.
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http://dx.doi.org/10.1111/all.14618DOI Listing
October 2020

Decomposing the molecular complexity of brewing.

NPJ Sci Food 2020 20;4:11. Epub 2020 Aug 20.

Chair of Analytical Food Chemistry, Technical University of Munich, Freising, Germany.

The compositional space of a set of 120 diverse beer samples was profiled by rapid flow-injection analysis (FIA) Fourier transform ion cyclotron mass spectrometry (FTICR-MS). By the unrivaled mass resolution, it was possible to uncover and assign compositional information to thousands of yet unknown metabolites in the beer matrix. The application of several statistical models enabled the assignment of different molecular pattern to certain beer attributes such as the beer type, the way of adding hops and the grain used. The dedicated van Krevelen diagrams and mass difference networks displayed the structural connectivity of the annotated sum formulae. Thereby it was possible to provide a base of knowledge of the beer metabolome far above database-dependent annotations. Typical metabolic signatures for beer types, which reflect differences in ingredients and ways of brewing, could be extracted. Besides, the complexity of isomeric compounds, initially profiled as single mass values in fast FIA-FTICR-MS, was resolved by selective UHPLC-ToF-MS analysis. Thereby structural hypotheses based on FTICR's sum formulae could be confirmed. Benzoxazinoid hexosides deriving from the wheat's secondary metabolism were uncovered as suitable marker substances for the use of whole wheat grains, in contrast to merely wheat starch or barley. Furthermore, it was possible to describe Hydroxymethoxybenzoxazinone(HMBOA)-hexosesulfate as a hitherto unknown phytoanticipin derivative in wheat containing beers. These findings raise the potential of ultrahigh resolution mass spectrometry for rapid quality control and inspection purposes as well as deep metabolic profiling, profound search for distinct hidden metabolites and classification of archeological beer samples.
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http://dx.doi.org/10.1038/s41538-020-00070-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441322PMC
August 2020

An Enhanced Isotopic Fine Structure Method for Exact Mass Analysis in Discovery Metabolomics: FIA-CASI-FTMS.

J Am Soc Mass Spectrom 2020 Oct 11;31(10):2025-2034. Epub 2020 Sep 11.

Helmholtz Center Munich, Analytical BioGeoChemistry, Munich 85764, Germany.

A major bottleneck in metabolomics is the annotation of a molecular formula as a first step to a tentative structure assignment of known and unknown metabolites. The direct observation of an isotopic fine structure (IFS) provides the ability to confidently assign an unknown's molecular formula out of a complex mass spectrum. However, the majority of mass spectrometers deployed for metabolomic studies do not have sufficient resolving power and high-fidelity isotope ratios in the mass range of interest to determine molecular formulas from IFS data. To increase the number of unknowns for which IFS can be determined, a segmented "boxcar" approach using a selection quadrupole as a broadband mass filter is used. In this longer, enhanced dynamic range discovery experiment, selected ions in a specific mass range are accumulated before detection by the analyzer cell. The mass filter window is then moved across the entire mass range resulting in a composite mass spectrum covering the / range of interest for phenomics research. The effectiveness of the FIA-CASI-FTMS workflow utilizing IFS for molecular formula assignment is realized with the implementation of the dynamically harmonized cell, which distinguishes the approach from other segmented workflows because of the analytical properties of the cell. The discovery approach was applied to a human plasma sample to confidently assign an unknown molecular formula as part of the quest to illuminate its metabolic "dark matter" via high-fidelity IFS ratio determinations. The FIA-CASI-FTMS workflow showed a 2.6-fold increase in both matching with the Human Metabolome Database and an increase in the IFS pattern.
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http://dx.doi.org/10.1021/jasms.0c00047DOI Listing
October 2020

Comprehensive Vitamer Profiling of Folate Mono- and Polyglutamates in Baker's Yeast () as a Function of Different Sample Preparation Procedures.

Metabolites 2020 Jul 23;10(8). Epub 2020 Jul 23.

Chair of Analytical Food Chemistry, Technical University of Munich, 85354 Freising-Weihenstephan, Germany.

Folates are a group of B vitamins playing an important role in many metabolic processes such as methylation reactions, nucleotide synthesis or oxidation and reduction processes. However, humans are not able to synthesize folates de novo and thus rely on external sources thereof. Baker's yeast () has been shown to produce high amounts of this vitamin but extensive identification of its folate metabolism is still lacking. Therefore, we optimized and compared different sample preparation and purification procedures applying solid phase extraction (SPE). Strong anion exchange (SAX), C18 and hydrophilic-lipophilic-balanced (HLB) materials were tested for their applicability in future metabolomics studies. SAX turned out to be the preferred material for the quantitative purification of folates. Qualification of several folate vitamers was achieved by ultra-high pressure liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-ToF-MS) measurements and quantification was performed by liquid chromatography tandem mass spectrometry (LC-MS/MS) applying stable isotope dilution assays (SIDAs). The oxidation product -pyrazino-triazine (MeFox) was included into the SIDA method for total folate determination and validation. Applying the best protocol (SAX) in regard to folate recovery, we analyzed 32 different vitamers in different polyglutamate states up to nonaglutamates, of which we could further identify 26 vitamers based on tandem-MS (MS) spectra. Total folate quantification revealed differences in formyl folate contents depending on the cartridge chemistry used for purification. These are supposedly a result of interconversion reactions occurring during sample preparation due to variation in pH adjustments for the different purification protocols. The occurrence of interconversion and oxidation reactions should be taken into consideration in sample preparation procedures for metabolomics analyses with a focus on folates.
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http://dx.doi.org/10.3390/metabo10080301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464241PMC
July 2020

Bio-Protection as an Alternative to Sulphites: Impact on Chemical and Microbial Characteristics of Red Wines.

Front Microbiol 2020 16;11:1308. Epub 2020 Jun 16.

UMR Procédés Alimentaires et Microbiologiques, Université de Bourgogne Franche-Comté/AgroSup Dijon, Equipe VAlMiS (Vin, Aliment, Microbiologie, Stress), Institut Universitaire de la Vigne et du Vin Jules Guyot, Dijon, France.

In wine, one method of limiting the addition of sulphites, a harmful and allergenic agent, is bio-protection. This practice consists of the early addition of microorganisms on grape must before fermentation. Non- yeasts have been proposed as an interesting alternative to sulphite addition. However, scientific data proving the effectiveness of bio-protection remains sparse. This study provides the first analysis of the chemical and microbiological effects of a strain inoculated at the beginning of the red winemaking process in three wineries as an alternative to sulphiting. Like sulphiting, bio-protection effectively limited the growth of spoilage microbiota and had no influence on the phenolic compounds protecting musts and wine from oxidation. The bio-protection had no effect on the volatile compounds and the sensory differences were dependent on the experimental sites. However, a non-targeted metabolomic analysis by FTICR-MS highlighted a bio-protection signature.
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http://dx.doi.org/10.3389/fmicb.2020.01308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308991PMC
June 2020

Reduced mitochondrial resilience enables non-canonical induction of apoptosis after TNF receptor signaling in virus-infected hepatocytes.

J Hepatol 2020 12 26;73(6):1347-1359. Epub 2020 Jun 26.

Institute of Molecular Immunology and Experimental Oncology, University Hospital München rechts der Isar; Technical University of Munich, Munich, Germany.

Background & Aims: Selective elimination of virus-infected hepatocytes occurs through virus-specific CD8 T cells recognizing peptide-loaded MHC molecules. Herein, we report that virus-infected hepatocytes are also selectively eliminated through a cell-autonomous mechanism.

Methods: We generated recombinant adenoviruses and genetically modified mouse models to identify the molecular mechanisms determining TNF-induced hepatocyte apoptosis in vivo and used in vivo bioluminescence imaging, immunohistochemistry, immunoblot analysis, RNAseq/proteome/phosphoproteome analyses, bioinformatic analyses, mitochondrial function tests.

Results: We found that TNF precisely eliminated only virus-infected hepatocytes independently of local inflammation and activation of immune sensory receptors. TNF receptor I was equally relevant for NF-kB activation in healthy and infected hepatocytes, but selectively mediated apoptosis in infected hepatocytes. Caspase 8 activation downstream of TNF receptor signaling was dispensable for apoptosis in virus-infected hepatocytes, indicating an unknown non-canonical cell-intrinsic pathway promoting apoptosis in hepatocytes. We identified a unique state of mitochondrial vulnerability in virus-infected hepatocytes as the cause for this non-canonical induction of apoptosis through TNF. Mitochondria from virus-infected hepatocytes showed normal biophysical and bioenergetic functions but were characterized by reduced resilience to calcium challenge. In the presence of unchanged TNF-induced signaling, reactive oxygen species-mediated calcium release from the endoplasmic reticulum caused mitochondrial permeability transition and apoptosis, which identified a link between extrinsic death receptor signaling and cell-intrinsic mitochondrial-mediated caspase activation.

Conclusion: Our findings reveal a novel concept in immune surveillance by identifying a cell-autonomous defense mechanism that selectively eliminates virus-infected hepatocytes through mitochondrial permeability transition.

Lay Summary: The liver is known for its unique immune functions. Herein, we identify a novel mechanism by which virus-infected hepatocytes can selectively eliminate themselves through reduced mitochondrial resilience to calcium challenge.
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http://dx.doi.org/10.1016/j.jhep.2020.06.026DOI Listing
December 2020

Cultivar- and Wood Area-Dependent Metabolomic Fingerprints of Grapevine Infected by Botryosphaeria Dieback.

Phytopathology 2020 Nov 6;110(11):1821-1837. Epub 2020 Oct 6.

Agroécologie, AgroSup Dijon, CNRS, INRAE, Univ. Bourgogne, Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.

Botryosphaeria dieback is one of the most significant grapevine trunk diseases that affects the sustainability of the vineyards and provokes economic losses. The causal agents, Botryosphaeriaceae species, live in and colonize the wood of the perennial organs causing wood necrosis. Diseased vines show foliar symptoms, chlorosis, or apoplexy, associated to a characteristic brown stripe under the bark. According to the susceptibility of the cultivars, specific proteins such as PR-proteins and other defense-related proteins are accumulated in the brown stripe compared with the healthy woody tissues. In this study, we enhanced the characterization of the brown stripe and the healthy wood by obtaining a metabolite profiling for the three cultivars Chardonnay, Gewurztraminer, and Mourvèdre to deeper understand the interaction between the Botryosphaeria dieback pathogens and grapevine. The study confirmed a specific pattern according to the cultivar and revealed significant differences between the brown stripe and the healthy wood, especially for phytochemical and lipid compounds. This is the first time that such chemical discrimination was made and that lipids were so remarkably highlighted in the interaction of Botryosphaeriaceae species and grapevine. Their role in the disease development is discussed.
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http://dx.doi.org/10.1094/PHYTO-02-20-0055-RDOI Listing
November 2020

Antioxidant activity from inactivated yeast: Expanding knowledge beyond the glutathione-related oxidative stability of wine.

Food Chem 2020 Apr 30;325:126941. Epub 2020 Apr 30.

Univ. Bourgogne Franche-Comté, AgroSup Dijon, PAM UMR A 02.102, Institut Universitaire de la Vigne et du Vin - Jules Guyot, F-21000 Dijon, France.

Maintaining wine oxidative stability during barrel ageing and shelf life storage remains a challenge. This study evaluated the antioxidant activities of soluble extracts from seven enological yeast derivatives (YDs) with increased glutathione (GSH) enrichment. YDs enriched in GSH appeared on average 3.3 times more efficient at quenching radical species than YDs not enriched in GSH. The lack of correlation (Spearman correlation ρ = 0.46) between the GSH concentration released from YDs and their radical scavenging activity shed light on other non-GSH compounds present. After 4-methyl-1,2-benzoquinone derivatization, UHPLC-Q-ToF MS analyses specifically identified 52 nucleophiles potentially representing an extensive molecular nucleophilic fingerprint of YDs. The comparative analysis of YD chemical oxidation conditions revealed that the nucleophilic molecular fingerprint of the YD was strongly correlated to its antiradical activity. The proposed strategy shows that nucleophiles co-accumulated with GSH during the enrichment of YDs are responsible for their antioxidant activities.
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http://dx.doi.org/10.1016/j.foodchem.2020.126941DOI Listing
April 2020

Influence of regionality and maturation time on the chemical fingerprint of whisky.

Food Chem 2020 Apr 3;323:126748. Epub 2020 Apr 3.

Comprehensive Foodomics Platform, Chair of Analytical Food Chemistry, Technische Universität München, Freising, Germany; Research Unit Analytical BioGeoChemistry, Department of Environmental Sciences, Helmholtz Zentrum München, Neuherberg, Germany. Electronic address:

Understanding the chemical composition of whisky and the impact of each step in the manufacturing process provides a basis for responding to the challenges of producing high quality spirits. In this study, the objective was to discriminate whiskies according to their geographical origin and authenticate the maturation time in cask based on the non-volatile profiles. The combination of FT-ICR-MS and chemometrics allowed the distinction of whiskies from four geographical origins in Scotland (Highlands, Lowlands, Speyside and Islay). Statistical modeling was also used to discriminate whiskies according to the maturation time in cask and reveal chemical markers associated with the ageing regardless of the origin or the production process. Interestingly, the flow of transfer of compounds from wood barrels to distillates is not constant and homogeneous over the maturation time. The largest transfer of compounds from the barrel to the whisky was observed around twelve years of maturation.
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http://dx.doi.org/10.1016/j.foodchem.2020.126748DOI Listing
April 2020

Reading From the Crystal Ball: The Laws of Moore and Kurzweil Applied to Mass Spectrometry in Food Analysis.

Front Nutr 2020 28;7. Epub 2020 Feb 28.

Analytical Food Chemistry, Technical University of Munich, Freising, Germany.

Predictions about the future knowledge of the "complete" food metabolome may be assayed based on the laws of Moore and Kurzweil, who foresee a technological development on exponential behavior. The application of these laws allows us to extrapolate and predict roughly when each single metabolite in foods could be (1) known, (2) detectable, and (3) identifiable. To avoid huge additional uncertainties, we restrict the range of metabolites to those in unprocessed foods. From current metabolite databases and their coverage over time, the conservative number of all considered food metabolites can be estimated to be 500,000, predicting them being known by around 2025. Assuming these laws and extrapolating the current developments in chromatography and mass spectrometry technology, the year 2032 can be estimated, when single molecule detection will be possible in "routine" mass spectrometry. A possible forecast for the identification of all food metabolites, however, is much more difficult and estimated at the earliest in 2041 as the year when this may be achieved. However, the real prediction uncertainty is extreme and is discussed in the essay presented here.
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http://dx.doi.org/10.3389/fnut.2020.00009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058551PMC
February 2020

Advanced identification of global bioactivity hotspots via screening of the metabolic fingerprint of entire ecosystems.

Sci Rep 2020 Jan 28;10(1):1319. Epub 2020 Jan 28.

Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, D-85764, Germany.

Natural products (NP) are a valuable drug resource. However, NP-inspired drug leads are declining, among other reasons due to high re-discovery rates. We developed a conceptual framework using the metabolic fingerprint of entire ecosystems (MeE) to facilitate the discovery of global bioactivity hotspots. We assessed the MeE of 305 sites of diverse aquatic ecosystems, worldwide. All samples were tested for antiviral effects against the human immunodeficiency virus (HIV), followed by a comprehensive screening for cell-modulatory activity by High-Content Screening (HCS). We discovered a very strong HIV-1 inhibition mainly in samples taken from fjords with a strong terrestrial input. Multivariate data integration demonstrated an association of a set of polyphenols with specific biological alterations (endoplasmic reticulum, lysosomes, and NFkB) caused by these samples. Moreover, we found strong HIV-1 inhibition in one unrelated oceanic sample closely matching to HIV-1-inhibitory drugs on a cytological and a chemical level. Taken together, we demonstrate that even without physical purification, a sophisticated strategy of differential filtering, correlation analysis, and multivariate statistics can be employed to guide chemical analysis, to improve de-replication, and to identify ecosystems with promising characteristics as sources for NP discovery.
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http://dx.doi.org/10.1038/s41598-020-57709-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987164PMC
January 2020

GTP Cyclohydrolase 1/Tetrahydrobiopterin Counteract Ferroptosis through Lipid Remodeling.

ACS Cent Sci 2020 Jan 27;6(1):41-53. Epub 2019 Dec 27.

Institute of Molecular Toxicology and Pharmacology, Genetics and Cellular Engineering Group, HelmholtzZentrum Muenchen, Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany.

Ferroptosis is an iron-dependent form of regulated cell death linking iron, lipid, and glutathione levels to degenerative processes and tumor suppression. By performing a genome-wide activation screen, we identified a cohort of genes antagonizing ferroptotic cell death, including GTP cyclohydrolase-1 (GCH1) and its metabolic derivatives tetrahydrobiopterin/dihydrobiopterin (BH/BH). Synthesis of BH/BH by GCH1-expressing cells caused lipid remodeling, suppressing ferroptosis by selectively preventing depletion of phospholipids with two polyunsaturated fatty acyl tails. GCH1 expression level in cancer cell lines stratified susceptibility to ferroptosis, in accordance with its expression in human tumor samples. The GCH1-BH-phospholipid axis acts as a master regulator of ferroptosis resistance, controlling endogenous production of the antioxidant BH, abundance of CoQ, and peroxidation of unusual phospholipids with two polyunsaturated fatty acyl tails. This demonstrates a unique mechanism of ferroptosis protection that is independent of the GPX4/glutathione system.
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http://dx.doi.org/10.1021/acscentsci.9b01063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978838PMC
January 2020

Contribution of ketone/aldehyde-containing compounds to the composition and optical properties of Suwannee River fulvic acid revealed by ultrahigh resolution mass spectrometry and deuterium labeling.

Anal Bioanal Chem 2020 Feb 16;412(6):1441-1451. Epub 2020 Jan 16.

Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.

A prior method of mass labeling ketone-/aldehyde-containing species in natural dissolved organic matter (DOM) is further developed and applied. This application involved the treatment of Suwannee River fulvic acid (SRFA) with increasing concentrations of sodium borodeuteride (NaBD), followed by detection of reduced species via negative mode electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FTICR MS). The extent of reduction, as determined by ESI FTICR MS, resulting from increasing concentrations of NaBD correlated well with changes in the absorption and emission spectra of the corresponding untreated and borodeuteride-reduced samples, providing evidence that ketone/aldehyde functional groups contribute substantially to the bulk optical properties of SRFA. Furthermore, the differences in the reactivity and abundance of ketone-/aldehyde-containing species for various regions in Van Krevelen plots were revealed, thus showing how this mass labeling method can be used to provide more detailed structural information about components within complex DOM samples than that provided by the determination and analysis of molecular formulae alone. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-019-02377-xDOI Listing
February 2020

Preferential Sorption of Tannins at Aluminum Oxide Affects the Electron Exchange Capacities of Dissolved and Sorbed Humic Acid Fractions.

Environ Sci Technol 2020 02 22;54(3):1837-1847. Epub 2020 Jan 22.

Environmental Mineralogy and Chemistry, Center for Applied Geosciences , University of Tübingen , Hölderlinstr. 12 , D-72074 Tübingen , Germany.

Natural organic matter and humic substances (HS) in soils and sediments participate in numerous biogeochemical processes. Sorption to redox-inert aluminum oxide (AlO) was recently found to affect the redox properties of HS both in sorbed and dissolved state. With this study, we aim to decipher the molecular basis for these observations by applying Fourier transform ion cyclotron resonance mass spectrometry (FT-ICRMS) and mediated electrochemical analysis to Elliott soil, Pahokee peat, and Suwannee river humic acid (HA) samples before and after sorption to polar AlO and a nonpolar sorbent (DAX-8 resin). The FT-ICRMS data provided evidence of preferential sorption of specific HA fractions, primarily tannin-like compounds, to AlO. These oxygen-rich compounds bear a high density of redox-active functional groups, and their adsorption leads to a depletion of electron exchange capacity in dissolved HAs and enrichment of HAs adsorbed at AlO. Sorption of HAs to DAX-8 was less selective and caused only slight changes in electron exchange capacities of dissolved and sorbed HA fractions. By combining FT-ICRMS and electrochemical approaches, our findings suggest that a selective sorption of oxygen-rich compounds in HA fractions to mineral oxides is a decisive factor for the different redox properties of dissolved and sorbed HA fractions.
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http://dx.doi.org/10.1021/acs.est.9b04733DOI Listing
February 2020

Quantification of manganous ions in wine by NMR relaxometry.

Talanta 2020 Mar 15;209:120561. Epub 2019 Nov 15.

Univ. Bourgogne Franche-Comté, Agrosup Dijon, UMR PAM A02.102, 1 Esplanade Erasme, 21000, Dijon, France.

Proton relaxation in model and real wines is investigated for the first time by fast field cycling NMR relaxometry. The relaxation mechanism unambiguously originates form proton interaction with paramagnetic ions naturally present in wines. Profiles of a white Chardonnay wine from Burgundy, a red Medoc, and model wines are well reproduced by Solomon-Bloembergen-Morgan equations. Relaxation is primarily governed by interactions with Mn. A straightforward model-independent quantification of the manganese ion concentration (down to few tens of μg/L) is proposed.
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http://dx.doi.org/10.1016/j.talanta.2019.120561DOI Listing
March 2020

A chemical and microbial characterization of selected mud volcanoes in Trinidad reveals pathogens introduced by surface water and rain water.

Sci Total Environ 2020 Mar 13;707:136087. Epub 2019 Dec 13.

GFZ German Research Centre for Geosciences, Section Geomicrobiology, 14473 Potsdam, Germany; University of Potsdam, Institute of Geosciences, 14476 Potsdam, Germany.

Terrestrial mud volcanoes are unique structures driven by tectonic pressure and fluids from the deep subsurface. These structures are mainly found in active tectonic zones, such as the area near the Los Bajos Fault in Trinidad. Here we report a chemical and microbiological characterization of three mud volcanoes, which included analyses of multiple liquid and solid samples from the mud volcanoes. Our study confirms previous suggestions that at least some of the mud volcano fluids are a mixture of deeper salt-rich water and surficial/precipitation water. No apparent water quality differences were found between sampling sites north and south of a major geological fault line. Microbiological analyses revealed diverse communities, both aerobic and anaerobic, including sulfate reducers, methanogens, carbon dioxide fixing and denitrifying bacteria. Several identified species were halophilic and likely derived from the deeper salt-rich subsurface water, while we also cultivated pathogenic species from the Vibrionaceae, Enterobacteriaceae, Shewanellaceae, and Clostridiaceae. These microorganisms were likely introduced into the mud volcano fluids both from surface water or shallow ground-water, and perhaps to a more minor degree by rain water. The identified pathogens are a major health concern that needs to be addressed.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136087DOI Listing
March 2020

Integrative Metabolomic and Metallomic Analysis in a Case-Control Cohort With Parkinson's Disease.

Front Aging Neurosci 2019 6;11:331. Epub 2019 Dec 6.

Analytische BioGeoChemie, Helmholtz Zentrum München, Neuherberg, Germany.

Parkinson's disease (PD) is a neurodegenerative disease with a complex etiology. Several factors are known to contribute to the disease onset and its progression. However, the complete underlying mechanisms are still escaping our understanding. To evaluate possible correlations between metabolites and metallomic data, in this research, we combined a control study measured using two different platforms. For the different data sources, we applied a Block Sparse Partial Least Square Discriminant Analysis (Block-sPLS-DA) model that allows for proving their relation, which in turn uncovers alternative influencing factors that remain hidden otherwise. We found two groups of variables that trace a strong relationship between metallomic and metabolomic parameters for disease development. The results confirmed that the redox active metals iron (Fe) and copper (Cu) together with fatty acids are the major influencing factors for the PD. Additionally, the metabolic waste product p-cresol sulfate and the trace element nickel (Ni) showed up as potentially important factors in PD. In summary, the data integration of different types of measurements emphasized the results of both stand-alone measurements providing a new comprehensive set of information and interactions, on PD disease, between different variables sources.
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http://dx.doi.org/10.3389/fnagi.2019.00331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908950PMC
December 2019

Molecular differences between water column and sediment pore water SPE-DOM in ten Swedish boreal lakes.

Water Res 2020 Mar 22;170:115320. Epub 2019 Nov 22.

Helmholtz Zentrum Munich, German Research Center for Environmental Health, Research Unit Analytical Biogeochemistry (BGC), Ingolstädter Landstraße 1, P. O. Box 1129, D-85758, Neuherberg, Germany. Electronic address:

Boreal lakes are considered hot spots of dissolved organic matter (DOM) processing within the global carbon cycle. This study has used FT-ICR mass spectrometry and comprehensive data evaluation to assess the molecular differences of SPE-DOM between lake column water SPE-DOM and sedimentary pore water SPE-DOM in 10 Swedish boreal lakes of the Malingsbo area, which were selected for their large diversity of physicochemical and morphological characteristics. While lake column water is well mixed and fairly oxygenated, sedimentary pore water is subject to depletion of oxygen and to confinement of molecules. Robust trends were deduced from molecular compositions present in all compartments and in all 10 lakes ("common compositions") with recognition of relative abundance. Sedimentary pore water SPE-DOM featured higher proportions of heteroatoms N and S, higher average H/C ratios in presence of higher DBE/C ratios, and higher average oxygenation than lake column water SPE-DOM. These trends were observed in all lakes except Ljustjärn, which is a ground water fed kettle lake with an unique lake biogeochemistry. Analogous trends were also observed in case of single or a few lakes and operated also for compounds present solely in either lake column water or sedimentary pore water. Unique compounds detected in either compartments and/or in a few lakes showed higher molecular diversity than the "common compositions". Processing of DOM molecules in sediments included selective preservation for polyphenolic compounds and microbial resynthesis of selected molecules of considerable diversity.
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http://dx.doi.org/10.1016/j.watres.2019.115320DOI Listing
March 2020