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Sample records for complex secondary metabolome

  1. Genome sequencing reveals complex secondary metabolome in themarine actinomycete Salinispora tropica

    Energy Technology Data Exchange (ETDEWEB)

    Udwary, Daniel W.; Zeigler, Lisa; Asolkar, Ratnakar; Singan,Vasanth; Lapidus, Alla; Fenical, William; Jensen, Paul R.; Moore, BradleyS.

    2007-05-01

    Recent fermentation studies have identified actinomycetes ofthe marine-dwelling genus Salinispora as prolific natural productproducers. To further evaluate their biosynthetic potential, we analyzedall identifiable secondary natural product gene clusters from therecently sequenced 5,184,724 bp S. tropica CNB-440 circular genome. Ouranalysis shows that biosynthetic potential meets or exceeds that shown byprevious Streptomyces genome sequences as well as other naturalproduct-producing actinomycetes. The S. tropica genome features ninepolyketide synthase systems of every known formally classified family,non-ribosomal peptide synthetases and several hybrid clusters. While afew clusters appear to encode molecules previously identified inStreptomyces species,the majority of the 15 biosynthetic loci are novel.Specific chemical information about putative and observed natural productmolecules is presented and discussed. In addition, our bioinformaticanalysis was critical for the structure elucidation of the novelpolyenemacrolactam salinilactam A. This study demonstrates the potentialfor genomic analysis to complement and strengthen traditional naturalproduct isolation studies and firmly establishes the genus Salinispora asa rich source of novel drug-like molecules.

  2. Metabolomics

    DEFF Research Database (Denmark)

    Kamstrup-Nielsen, Maja Hermann

    Metabolomics is the analysis of the whole metabolome and the focus in metabolomics studies is to measure as many metabolites as possible. The use of chemometrics in metabolomics studies is widespread, but there is a clear lack of validation in the developed models. The focus in this thesis has been...... how to properly handle complex metabolomics data, in order to achieve reliable and valid multivariate models. This has been illustrated by three case studies with examples of forecasting breast cancer and early detection of colorectal cancer based on data from nuclear magnetic resonance (NMR...... is a presentation of a core consistency diagnostic aiding in determining the number of components in a PARAFAC2 model. It is of great importance to validate especially PLS-DA models and if not done properly, the developed models might reveal spurious groupings. Furthermore, data from metabolomics studies contain...

  3. Chitosan and grape secondary metabolites: A proteomics and metabolomics approach

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    Bavaresco Luigi

    2017-01-01

    Full Text Available Chitosan is a polysaccharide obtained by deacetylation of chitin, and it is involved in defence mechanisms of plants toward diseases. In the present work, V. vinifera L. cv. Ortrugo, grafted on 420A rootstock was grown in pot and treated, at veraison, by 0.03% chitosan solution at cluster level. Just before the treatment (T0 and 24 hours (T1, 48 hours (T2, 72 hours (T3 and 10 days (T4 later, the concentration of stilbenic compounds was detected, and at T1 proteomics and metabolomics analyses were done. Proteomics relies on the analysis of the complete set of proteins existing in a given substrate, while metabolomics relies on the analyses of the complete set of metabolites in a given substrate. The treatment improved the stilbene concentration over the control at T1. Proteomic analysis showed that superoxide dismutase (SOD and phenylalanine ammonia-lyase (PAL were overexpressed in the treated grapes. SOD is known to be an enzyme active against reactive oxygen species (ROS while PAL is a key enzyme in the phenylpropanoids pathway. Metabolomics analysis highlighted the positive role of the treatment in improving the triperpenoid concentration (betulin, erythrodiol, uvaol, oleanolate; these compounds are known to be effective against microbes, insects and fungi.

  4. Deciphering the genome and secondary metabolome of the plant pathogen Fusarium culmorum

    NARCIS (Netherlands)

    Schmidt, R.L.; Durling, M.; de Jager, V.C.L.; Menezes, R. C.; Nordkvist, E.; Svatos, A.; Dubey, Mohit; Lauterbach, L.; Dikschat, J.S.; Karlsson, M.; Garbeva, P.V.

    2018-01-01

    Fusarium culmorum is one of the most important fungal plant pathogens that causes diseases on a wide diversity of cereal and non-cereal crops. We report herein for the first time the genome sequence of F. culmorum strain PV and its associated secondary metabolome that plays a role in the interaction

  5. Metabolomics methods for the synthetic biology of secondary metabolism

    NARCIS (Netherlands)

    Quoc-Thai Nguyen, [No Value; Merlo, Maria E.; Medema, Marnix H.; Jankevics, Andris; Breitling, Rainer; Takano, Eriko; Just, Wilhelm; Reiss, Thomas

    2012-01-01

    Many microbial secondary metabolites are of high biotechnological value for medicine, agriculture, and the food industry. Bacterial genome mining has revealed numerous novel secondary metabolite biosynthetic gene clusters, which encode the potential to synthesize a large diversity of compounds that

  6. Metabolomics

    DEFF Research Database (Denmark)

    Pedersen, Hans

    fusion where data from different platforms can be combined. Complex data are obtained when samples are analysed using NMR, fluorescence and GC-MS. Chemometrics methods which can be used to extract the relevant information from the obtained data are presented. Focus has been on principal component...... based on NMR data with RRV and known risk markers. The sensitivity and specificity values are 0.80 and 0.79, respectively, for a test set validated model. The second case study is based on plasma samples with verified colorectal cancer and three types of control samples analysed by fluorescence...

  7. Livestock metabolomics and the livestock metabolome: A systematic review.

    Science.gov (United States)

    Goldansaz, Seyed Ali; Guo, An Chi; Sajed, Tanvir; Steele, Michael A; Plastow, Graham S; Wishart, David S

    2017-01-01

    Metabolomics uses advanced analytical chemistry techniques to comprehensively measure large numbers of small molecule metabolites in cells, tissues and biofluids. The ability to rapidly detect and quantify hundreds or even thousands of metabolites within a single sample is helping scientists paint a far more complete picture of system-wide metabolism and biology. Metabolomics is also allowing researchers to focus on measuring the end-products of complex, hard-to-decipher genetic, epigenetic and environmental interactions. As a result, metabolomics has become an increasingly popular "omics" approach to assist with the robust phenotypic characterization of humans, crop plants and model organisms. Indeed, metabolomics is now routinely used in biomedical, nutritional and crop research. It is also being increasingly used in livestock research and livestock monitoring. The purpose of this systematic review is to quantitatively and objectively summarize the current status of livestock metabolomics and to identify emerging trends, preferred technologies and important gaps in the field. In conducting this review we also critically assessed the applications of livestock metabolomics in key areas such as animal health assessment, disease diagnosis, bioproduct characterization and biomarker discovery for highly desirable economic traits (i.e., feed efficiency, growth potential and milk production). A secondary goal of this critical review was to compile data on the known composition of the livestock metabolome (for 5 of the most common livestock species namely cattle, sheep, goats, horses and pigs). These data have been made available through an open access, comprehensive livestock metabolome database (LMDB, available at http://www.lmdb.ca). The LMDB should enable livestock researchers and producers to conduct more targeted metabolomic studies and to identify where further metabolome coverage is needed.

  8. Livestock metabolomics and the livestock metabolome: A systematic review

    Science.gov (United States)

    Guo, An Chi; Sajed, Tanvir; Steele, Michael A.; Plastow, Graham S.; Wishart, David S.

    2017-01-01

    Metabolomics uses advanced analytical chemistry techniques to comprehensively measure large numbers of small molecule metabolites in cells, tissues and biofluids. The ability to rapidly detect and quantify hundreds or even thousands of metabolites within a single sample is helping scientists paint a far more complete picture of system-wide metabolism and biology. Metabolomics is also allowing researchers to focus on measuring the end-products of complex, hard-to-decipher genetic, epigenetic and environmental interactions. As a result, metabolomics has become an increasingly popular “omics” approach to assist with the robust phenotypic characterization of humans, crop plants and model organisms. Indeed, metabolomics is now routinely used in biomedical, nutritional and crop research. It is also being increasingly used in livestock research and livestock monitoring. The purpose of this systematic review is to quantitatively and objectively summarize the current status of livestock metabolomics and to identify emerging trends, preferred technologies and important gaps in the field. In conducting this review we also critically assessed the applications of livestock metabolomics in key areas such as animal health assessment, disease diagnosis, bioproduct characterization and biomarker discovery for highly desirable economic traits (i.e., feed efficiency, growth potential and milk production). A secondary goal of this critical review was to compile data on the known composition of the livestock metabolome (for 5 of the most common livestock species namely cattle, sheep, goats, horses and pigs). These data have been made available through an open access, comprehensive livestock metabolome database (LMDB, available at http://www.lmdb.ca). The LMDB should enable livestock researchers and producers to conduct more targeted metabolomic studies and to identify where further metabolome coverage is needed. PMID:28531195

  9. Metabolome and proteome profiling of complex I deficiency induced by rotenone.

    Science.gov (United States)

    Gielisch, Ina; Meierhofer, David

    2015-01-02

    Complex I (CI; NADH dehydrogenase) deficiency causes mitochondrial diseases, including Leigh syndrome. A variety of clinical symptoms of CI deficiency are known, including neurodegeneration. Here, we report an integrative study combining liquid chromatography-mass spectrometry (LC-MS)-based metabolome and proteome profiling in CI deficient HeLa cells. We report a rapid LC-MS-based method for the relative quantification of targeted metabolome profiling with an additional layer of confidence by applying multiple reaction monitoring (MRM) ion ratios for further identity confirmation and robustness. The proteome was analyzed by label-free quantification (LFQ). More than 6000 protein groups were identified. Pathway and network analyses revealed that the respiratory chain was highly deregulated, with metabolites such as FMN, FAD, NAD(+), and ADP, direct players of the OXPHOS system, and metabolites of the TCA cycle decreased up to 100-fold. Synthesis of functional iron-sulfur clusters, which are of central importance for the electron transfer chain, and degradation products like bilirubin were also significantly reduced. Glutathione metabolism on the pathway level, as well as individual metabolite components such as NADPH, glutathione (GSH), and oxidized glutathione (GSSG), was downregulated. Overall, metabolome and proteome profiles in CI deficient cells correlated well, supporting our integrated approach.

  10. System-Level and Granger Network Analysis of Integrated Proteomic and Metabolomic Dynamics Identifies Key Points of Grape Berry Development at the Interface of Primary and Secondary Metabolism

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    Lei Wang

    2017-06-01

    Full Text Available Grapevine is a fruit crop with worldwide economic importance. The grape berry undergoes complex biochemical changes from fruit set until ripening. This ripening process and production processes define the wine quality. Thus, a thorough understanding of berry ripening is crucial for the prediction of wine quality. For a systemic analysis of grape berry development we applied mass spectrometry based platforms to analyse the metabolome and proteome of Early Campbell at 12 stages covering major developmental phases. Primary metabolites involved in central carbon metabolism, such as sugars, organic acids and amino acids together with various bioactive secondary metabolites like flavonols, flavan-3-ols and anthocyanins were annotated and quantified. At the same time, the proteomic analysis revealed the protein dynamics of the developing grape berries. Multivariate statistical analysis of the integrated metabolomic and proteomic dataset revealed the growth trajectory and corresponding metabolites and proteins contributing most to the specific developmental process. K-means clustering analysis revealed 12 highly specific clusters of co-regulated metabolites and proteins. Granger causality network analysis allowed for the identification of time-shift correlations between metabolite-metabolite, protein- protein and protein-metabolite pairs which is especially interesting for the understanding of developmental processes. The integration of metabolite and protein dynamics with their corresponding biochemical pathways revealed an energy-linked metabolism before veraison with high abundances of amino acids and accumulation of organic acids, followed by protein and secondary metabolite synthesis. Anthocyanins were strongly accumulated after veraison whereas other flavonoids were in higher abundance at early developmental stages and decreased during the grape berry developmental processes. A comparison of the anthocyanin profile of Early Campbell to other

  11. System-Level and Granger Network Analysis of Integrated Proteomic and Metabolomic Dynamics Identifies Key Points of Grape Berry Development at the Interface of Primary and Secondary Metabolism.

    Science.gov (United States)

    Wang, Lei; Sun, Xiaoliang; Weiszmann, Jakob; Weckwerth, Wolfram

    2017-01-01

    Grapevine is a fruit crop with worldwide economic importance. The grape berry undergoes complex biochemical changes from fruit set until ripening. This ripening process and production processes define the wine quality. Thus, a thorough understanding of berry ripening is crucial for the prediction of wine quality. For a systemic analysis of grape berry development we applied mass spectrometry based platforms to analyse the metabolome and proteome of Early Campbell at 12 stages covering major developmental phases. Primary metabolites involved in central carbon metabolism, such as sugars, organic acids and amino acids together with various bioactive secondary metabolites like flavonols, flavan-3-ols and anthocyanins were annotated and quantified. At the same time, the proteomic analysis revealed the protein dynamics of the developing grape berries. Multivariate statistical analysis of the integrated metabolomic and proteomic dataset revealed the growth trajectory and corresponding metabolites and proteins contributing most to the specific developmental process. K-means clustering analysis revealed 12 highly specific clusters of co-regulated metabolites and proteins. Granger causality network analysis allowed for the identification of time-shift correlations between metabolite-metabolite, protein- protein and protein-metabolite pairs which is especially interesting for the understanding of developmental processes. The integration of metabolite and protein dynamics with their corresponding biochemical pathways revealed an energy-linked metabolism before veraison with high abundances of amino acids and accumulation of organic acids, followed by protein and secondary metabolite synthesis. Anthocyanins were strongly accumulated after veraison whereas other flavonoids were in higher abundance at early developmental stages and decreased during the grape berry developmental processes. A comparison of the anthocyanin profile of Early Campbell to other cultivars revealed

  12. Metabolome-genome-wide association study dissects genetic architecture for generating natural variation in rice secondary metabolism

    Science.gov (United States)

    Matsuda, Fumio; Nakabayashi, Ryo; Yang, Zhigang; Okazaki, Yozo; Yonemaru, Jun-ichi; Ebana, Kaworu; Yano, Masahiro; Saito, Kazuki

    2015-01-01

    Plants produce structurally diverse secondary (specialized) metabolites to increase their fitness for survival under adverse environments. Several bioactive compounds for new drugs have been identified through screening of plant extracts. In this study, genome-wide association studies (GWAS) were conducted to investigate the genetic architecture behind the natural variation of rice secondary metabolites. GWAS using the metabolome data of 175 rice accessions successfully identified 323 associations among 143 single nucleotide polymorphisms (SNPs) and 89 metabolites. The data analysis highlighted that levels of many metabolites are tightly associated with a small number of strong quantitative trait loci (QTLs). The tight association may be a mechanism generating strains with distinct metabolic composition through the crossing of two different strains. The results indicate that one plant species produces more diverse phytochemicals than previously expected, and plants still contain many useful compounds for human applications. PMID:25267402

  13. Proteomic and Metabolomic Analyses Reveal Contrasting Anti-Inflammatory Effects of an Extract of Mucor Racemosus Secondary Metabolites Compared to Dexamethasone.

    Science.gov (United States)

    Meier, Samuel M; Muqaku, Besnik; Ullmann, Ronald; Bileck, Andrea; Kreutz, Dominique; Mader, Johanna C; Knasmüller, Siegfried; Gerner, Christopher

    2015-01-01

    Classical drug assays are often confined to single molecules and targeting single pathways. However, it is also desirable to investigate the effects of complex mixtures on complex systems such as living cells including the natural multitude of signalling pathways. Evidence based on herbal medicine has motivated us to investigate potential beneficial health effects of Mucor racemosus (M rac) extracts. Secondary metabolites of M rac were collected using a good-manufacturing process (GMP) approved production line and a validated manufacturing process, in order to obtain a stable product termed SyCircue (National Drug Code USA: 10424-102). Toxicological studies confirmed that this product does not contain mycotoxins and is non-genotoxic. Potential effects on inflammatory processes were investigated by treating stimulated cells with M rac extracts and the effects were compared to the standard anti-inflammatory drug dexamethasone on the levels of the proteome and metabolome. Using 2D-PAGE, slight anti-inflammatory effects were observed in primary white blood mononuclear cells, which were more pronounced in primary human umbilical vein endothelial cells (HUVECs). Proteome profiling based on nLC-MS/MS analysis of tryptic digests revealed inhibitory effects of M rac extracts on pro-inflammatory cytoplasmic mediators and secreted cytokines and chemokines in these endothelial cells. This finding was confirmed using targeted proteomics, here treatment of stimulated cells with M rac extracts down-regulated the secretion of IL-6, IL-8, CXCL5 and GROA significantly. Finally, the modulating effects of M rac on HUVECs were also confirmed on the level of the metabolome. Several metabolites displayed significant concentration changes upon treatment of inflammatory activated HUVECs with the M rac extract, including spermine and lysophosphatidylcholine acyl C18:0 and sphingomyelin C26:1, while the bulk of measured metabolites remained unaffected. Interestingly, the effects of M rac

  14. Effect of High-Carbohydrate Diet on Plasma Metabolome in Mice with Mitochondrial Respiratory Chain Complex III Deficiency

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    Jayasimman Rajendran

    2016-11-01

    Full Text Available Mitochondrial disorders cause energy failure and metabolic derangements. Metabolome profiling in patients and animal models may identify affected metabolic pathways and reveal new biomarkers of disease progression. Using liver metabolomics we have shown a starvation-like condition in a knock-in (Bcs1lc.232A>G mouse model of GRACILE syndrome, a neonatal lethal respiratory chain complex III dysfunction with hepatopathy. Here, we hypothesized that a high-carbohydrate diet (HCD, 60% dextrose will alleviate the hypoglycemia and promote survival of the sick mice. However, when fed HCD the homozygotes had shorter survival (mean ± SD, 29 ± 2.5 days, n = 21 than those on standard diet (33 ± 3.8 days, n = 30, and no improvement in hypoglycemia or liver glycogen depletion. We investigated the plasma metabolome of the HCD- and control diet-fed mice and found that several amino acids and urea cycle intermediates were increased, and arginine, carnitines, succinate, and purine catabolites decreased in the homozygotes. Despite reduced survival the increase in aromatic amino acids, an indicator of liver mitochondrial dysfunction, was normalized on HCD. Quantitative enrichment analysis revealed that glycine, serine and threonine metabolism, phenylalanine and tyrosine metabolism, and urea cycle were also partly normalized on HCD. This dietary intervention revealed an unexpected adverse effect of high-glucose diet in complex III deficiency, and suggests that plasma metabolomics is a valuable tool in evaluation of therapies in mitochondrial disorders.

  15. Real-life metabolomics data analysis: how to deal with complex data?

    NARCIS (Netherlands)

    Rubingh, C.M.

    2010-01-01

    Door de grote datasets die gegenereerd worden in metabolomics studies, in combinatie met de ingewikkelde studiedesigns die vaak nodig zijn om subtiele verschillen in metabolietprofielen te kunnen detecteren, zijn standaard multivariate technieken niet meer afdoende. Dit geldt voor alle fasen van de

  16. System-Level and Granger Network Analysis of Integrated Proteomic and Metabolomic Dynamics Identifies Key Points of Grape Berry Development at the Interface of Primary and Secondary Metabolism

    OpenAIRE

    Wang, Lei; Sun, Xiaoliang; Weiszmann, Jakob; Weckwerth, Wolfram

    2017-01-01

    Grapevine is a fruit crop with worldwide economic importance. The grape berry undergoes complex biochemical changes from fruit set until ripening. This ripening process and production processes define the wine quality. Thus, a thorough understanding of berry ripening is crucial for the prediction of wine quality. For a systemic analysis of grape berry development we applied mass spectrometry based platforms to analyse the metabolome and proteome of Early Campbell at 12 stages covering major d...

  17. Metabolomics: A Primer.

    Science.gov (United States)

    Liu, Xiaojing; Locasale, Jason W

    2017-04-01

    Metabolomics generates a profile of small molecules that are derived from cellular metabolism and can directly reflect the outcome of complex networks of biochemical reactions, thus providing insights into multiple aspects of cellular physiology. Technological advances have enabled rapid and increasingly expansive data acquisition with samples as small as single cells; however, substantial challenges in the field remain. In this primer we provide an overview of metabolomics, especially mass spectrometry (MS)-based metabolomics, which uses liquid chromatography (LC) for separation, and discuss its utilities and limitations. We identify and discuss several areas at the frontier of metabolomics. Our goal is to give the reader a sense of what might be accomplished when conducting a metabolomics experiment, now and in the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The food metabolome

    DEFF Research Database (Denmark)

    Scalbert, Augustin; Brennan, Lorraine; Manach, Claudine

    2014-01-01

    to the diet. By its very nature it represents a considerable and still largely unexploited source of novel dietary biomarkers that could be used to measure dietary exposures with a high level of detail and precision. Most dietary biomarkers currently have been identified on the basis of our knowledge of food......The food metabolome is defined as the part of the human metabolome directly derived from the digestion and biotransformation of foods and their constituents. With >25,000 compounds known in various foods, the food metabolome is extremely complex, with a composition varying widely according...... by the recent identification of novel biomarkers of intakes for fruit, vegetables, beverages, meats, or complex diets. Moreover, examples also show how the scrutiny of the food metabolome can lead to the discovery of bioactive molecules and dietary factors associated with diseases. However, researchers still...

  19. Metabolomics by Proton High-Resolution Magic-Angle-Spinning Nuclear Magnetic Resonance of Tomato Plants Treated with Two Secondary Metabolites Isolated from Trichoderma.

    Science.gov (United States)

    Mazzei, Pierluigi; Vinale, Francesco; Woo, Sheridan Lois; Pascale, Alberto; Lorito, Matteo; Piccolo, Alessandro

    2016-05-11

    Trichoderma fungi release 6-pentyl-2H-pyran-2-one (1) and harzianic acid (2) secondary metabolites to improve plant growth and health protection. We isolated metabolites 1 and 2 from Trichoderma strains, whose different concentrations were used to treat seeds of Solanum lycopersicum. The metabolic profile in the resulting 15 day old tomato leaves was studied by high-resolution magic-angle-spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy directly on the whole samples without any preliminary extraction. Principal component analysis (PCA) of HRMAS NMR showed significantly enhanced acetylcholine and γ-aminobutyric acid (GABA) content accompanied by variable amount of amino acids in samples treated with both Trichoderma secondary metabolites. Seed germination rates, seedling fresh weight, and the metabolome of tomato leaves were also dependent upon doses of metabolites 1 and 2 treatments. HRMAS NMR spectroscopy was proven to represent a rapid and reliable technique for evaluating specific changes in the metabolome of plant leaves and calibrating the best concentration of bioactive compounds required to stimulate plant growth.

  20. Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures

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    Vogel Hans J

    2008-01-01

    Full Text Available Abstract Background Opium poppy (Papaver somniferum produces a diverse array of bioactive benzylisoquinoline alkaloids and has emerged as a model system to study plant alkaloid metabolism. The plant is cultivated as the only commercial source of the narcotic analgesics morphine and codeine, but also produces many other alkaloids including the antimicrobial agent sanguinarine. Modulations in plant secondary metabolism as a result of environmental perturbations are often associated with the altered regulation of other metabolic pathways. As a key component of our functional genomics platform for opium poppy we have used proton nuclear magnetic resonance (1H NMR metabolomics to investigate the interplay between primary and secondary metabolism in cultured opium poppy cells treated with a fungal elicitor. Results Metabolite fingerprinting and compound-specific profiling showed the extensive reprogramming of primary metabolic pathways in association with the induction of alkaloid biosynthesis in response to elicitor treatment. Using Chenomx NMR Suite v. 4.6, a software package capable of identifying and quantifying individual compounds based on their respective signature spectra, the levels of 42 diverse metabolites were monitored over a 100-hour time course in control and elicitor-treated opium poppy cell cultures. Overall, detectable and dynamic changes in the metabolome of elicitor-treated cells, especially in cellular pools of carbohydrates, organic acids and non-protein amino acids were detected within 5 hours after elicitor treatment. The metabolome of control cultures also showed substantial modulations 80 hours after the start of the time course, particularly in the levels of amino acids and phospholipid pathway intermediates. Specific flux modulations were detected throughout primary metabolism, including glycolysis, the tricarboxylic acid cycle, nitrogen assimilation, phospholipid/fatty acid synthesis and the shikimate pathway, all of which

  1. Integration of metabolomics and proteomics in molecular plant physiology--coping with the complexity by data-dimensionality reduction.

    Science.gov (United States)

    Weckwerth, Wolfram

    2008-02-01

    In recent years, genomics has been extended to functional genomics. Toward the characterization of organisms or species on the genome level, changes on the metabolite and protein level have been shown to be essential to assign functions to genes and to describe the dynamic molecular phenotype. Gas chromatography (GC) and liquid chromatography coupled to mass spectrometry (GC- and LC-MS) are well suited for the fast and comprehensive analysis of ultracomplex metabolite samples. For the integration of metabolite profiles with quantitative protein profiles, a high throughput (HTP) shotgun proteomics approach using LC-MS and label-free quantification of unique proteins in a complex protein digest is described. Multivariate statistics are applied to examine sample pattern recognition based on data-dimensionality reduction and biomarker identification in plant systems biology. The integration of the data reveal multiple correlative biomarkers providing evidence for an increase of information in such holistic approaches. With computational simulation of metabolic networks and experimental measurements, it can be shown that biochemical regulation is reflected by metabolite network dynamics measured in a metabolomics approach. Examples in molecular plant physiology are presented to substantiate the integrative approach.

  2. Gut metabolome meets microbiome

    DEFF Research Database (Denmark)

    Lamichhane, Santosh; Sen, Partho; Dickens, Alex M

    2018-01-01

    It is well established that gut microbes and their metabolic products regulate host metabolism. The interactions between the host and its gut microbiota are highly dynamic and complex. In this review we present and discuss the metabolomic strategies to study the gut microbial ecosystem. We...... highlight the metabolic profiling approaches to study faecal samples aimed at deciphering the metabolic product derived from gut microbiota. We also discuss how metabolomics data can be integrated with metagenomics data derived from gut microbiota and how such approaches may lead to better understanding...

  3. Nanoparticle-Assisted Metabolomics

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    Bo Zhang

    2018-03-01

    Full Text Available Understanding and harnessing the interactions between nanoparticles and biological molecules is at the forefront of applications of nanotechnology to modern biology. Metabolomics has emerged as a prominent player in systems biology as a complement to genomics, transcriptomics and proteomics. Its focus is the systematic study of metabolite identities and concentration changes in living systems. Despite significant progress over the recent past, important challenges in metabolomics remain, such as the deconvolution of the spectra of complex mixtures with strong overlaps, the sensitive detection of metabolites at low abundance, unambiguous identification of known metabolites, structure determination of unknown metabolites and standardized sample preparation for quantitative comparisons. Recent research has demonstrated that some of these challenges can be substantially alleviated with the help of nanoscience. Nanoparticles in particular have found applications in various areas of bioanalytical chemistry and metabolomics. Their chemical surface properties and increased surface-to-volume ratio endows them with a broad range of binding affinities to biomacromolecules and metabolites. The specific interactions of nanoparticles with metabolites or biomacromolecules help, for example, simplify metabolomics spectra, improve the ionization efficiency for mass spectrometry or reveal relationships between spectral signals that belong to the same molecule. Lessons learned from nanoparticle-assisted metabolomics may also benefit other emerging areas, such as nanotoxicity and nanopharmaceutics.

  4. Complex regional pain syndrome related dystonia : exploratory metabolomics and therapeutic studies

    NARCIS (Netherlands)

    Plas, Anton Adriaan van der

    2013-01-01

    Dit proefschrift beschrijft de resultaten van aan aantal studies naar bewegingsstoornissen en pijn bij patiënten met complex regionaal pijnsyndroom (CRPS). Ten eerste werd het effect onderzocht van intrathecaal baclofen op verschillende pijnkwaliteiten bij CRPS-patiënten, de invloed bestudeerd van

  5. Metabolomics and bioanalysis of terpenoid derived secondary metabolites : Analysis of Cannabis sativa L. metabolite production and prenylases for cannabinoid production

    NARCIS (Netherlands)

    Muntendam, Remco

    2015-01-01

    Cannabinoid research has gained a renenewed interest by both the public and scientist. Focus is mainly directed to the medicinal activities, as reported for various cannabinoid structures. This thesis focusses on prenyl-derived secondary metabolites with main focus on cannabinoids. Firstly the

  6. Nutritional Metabolomics

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde

    strategy influences the patterns identified as important for the nutritional question under study. Therefore, in depth understanding of the study design and the specific effects of the analytical technology on the produced data is extremely important to achieve high quality data handling. Besides data......Metabolomics provides a holistic approach to investigate the perturbations in human metabolism with respect to a specific exposure. In nutritional metabolomics, the research question is generally related to the effect of a specific food intake on metabolic profiles commonly of plasma or urine....... Application of multiple analytical strategies may provide comprehensive information to reach a valid answer to these research questions. In this thesis, I investigated several analytical technologies and data handling strategies in order to evaluate their effects on the biological answer. In metabolomics, one...

  7. Computational RNA secondary structure design: empirical complexity and improved methods

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    Condon Anne

    2007-01-01

    Full Text Available Abstract Background We investigate the empirical complexity of the RNA secondary structure design problem, that is, the scaling of the typical difficulty of the design task for various classes of RNA structures as the size of the target structure is increased. The purpose of this work is to understand better the factors that make RNA structures hard to design for existing, high-performance algorithms. Such understanding provides the basis for improving the performance of one of the best algorithms for this problem, RNA-SSD, and for characterising its limitations. Results To gain insights into the practical complexity of the problem, we present a scaling analysis on random and biologically motivated structures using an improved version of the RNA-SSD algorithm, and also the RNAinverse algorithm from the Vienna package. Since primary structure constraints are relevant for designing RNA structures, we also investigate the correlation between the number and the location of the primary structure constraints when designing structures and the performance of the RNA-SSD algorithm. The scaling analysis on random and biologically motivated structures supports the hypothesis that the running time of both algorithms scales polynomially with the size of the structure. We also found that the algorithms are in general faster when constraints are placed only on paired bases in the structure. Furthermore, we prove that, according to the standard thermodynamic model, for some structures that the RNA-SSD algorithm was unable to design, there exists no sequence whose minimum free energy structure is the target structure. Conclusion Our analysis helps to better understand the strengths and limitations of both the RNA-SSD and RNAinverse algorithms, and suggests ways in which the performance of these algorithms can be further improved.

  8. The Human Urine Metabolome

    Science.gov (United States)

    Bouatra, Souhaila; Aziat, Farid; Mandal, Rupasri; Guo, An Chi; Wilson, Michael R.; Knox, Craig; Bjorndahl, Trent C.; Krishnamurthy, Ramanarayan; Saleem, Fozia; Liu, Philip; Dame, Zerihun T.; Poelzer, Jenna; Huynh, Jessica; Yallou, Faizath S.; Psychogios, Nick; Dong, Edison; Bogumil, Ralf; Roehring, Cornelia; Wishart, David S.

    2013-01-01

    Urine has long been a “favored” biofluid among metabolomics researchers. It is sterile, easy-to-obtain in large volumes, largely free from interfering proteins or lipids and chemically complex. However, this chemical complexity has also made urine a particularly difficult substrate to fully understand. As a biological waste material, urine typically contains metabolic breakdown products from a wide range of foods, drinks, drugs, environmental contaminants, endogenous waste metabolites and bacterial by-products. Many of these compounds are poorly characterized and poorly understood. In an effort to improve our understanding of this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide characterization of human urine. This involved both computer-aided literature mining and comprehensive, quantitative experimental assessment/validation. The experimental portion employed NMR spectroscopy, gas chromatography mass spectrometry (GC-MS), direct flow injection mass spectrometry (DFI/LC-MS/MS), inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) experiments performed on multiple human urine samples. This multi-platform metabolomic analysis allowed us to identify 445 and quantify 378 unique urine metabolites or metabolite species. The different analytical platforms were able to identify (quantify) a total of: 209 (209) by NMR, 179 (85) by GC-MS, 127 (127) by DFI/LC-MS/MS, 40 (40) by ICP-MS and 10 (10) by HPLC. Our use of multiple metabolomics platforms and technologies allowed us to identify several previously unknown urine metabolites and to substantially enhance the level of metabolome coverage. It also allowed us to critically assess the relative strengths and weaknesses of different platforms or technologies. The literature review led to the identification and annotation of another 2206 urinary compounds and was used to help guide the subsequent experimental studies. An online database containing

  9. Metabolomics and bioactive substances in plants

    DEFF Research Database (Denmark)

    Khakimov, Bekzod

    Metabolomic analysis of plants broadens understanding of how plants may benefit humans, animals and the environment, provide sustainable food and energy, and improve current agricultural, pharmacological and medicinal practices in order to bring about healthier and longer life. The quality...... and amount of the extractible biological information is largely determined by data acquisition, data processing and analysis methodologies of the plant metabolomics studies. This PhD study focused mainly on the development and implementation of new metabolomics methodologies for improved data acquisition...... and data processing. The study mainly concerned the three most commonly applied analytical techniques in plant metabolomics, GC-MS, LC-MS and NMR. In addition, advanced chemometrics methods e.g. PARAFAC2 and ASCA have been extensively used for development of complex metabolomics data processing...

  10. Secondary Teachers' Conception of Various Forms of Complex Numbers

    Science.gov (United States)

    Karakok, Gulden; Soto-Johnson, Hortensia; Dyben, Stephenie Anderson

    2015-01-01

    This study explores in-service high school mathematics teachers' conception of various forms of complex numbers and ways in which they transition between different representations of these forms. One 90-min interview was conducted with three high school mathematics teachers after they completed three professional development sessions, each 4 h, on…

  11. Probabilistic Principal Component Analysis for Metabolomic Data.

    LENUS (Irish Health Repository)

    Nyamundanda, Gift

    2010-11-23

    Abstract Background Data from metabolomic studies are typically complex and high-dimensional. Principal component analysis (PCA) is currently the most widely used statistical technique for analyzing metabolomic data. However, PCA is limited by the fact that it is not based on a statistical model. Results Here, probabilistic principal component analysis (PPCA) which addresses some of the limitations of PCA, is reviewed and extended. A novel extension of PPCA, called probabilistic principal component and covariates analysis (PPCCA), is introduced which provides a flexible approach to jointly model metabolomic data and additional covariate information. The use of a mixture of PPCA models for discovering the number of inherent groups in metabolomic data is demonstrated. The jackknife technique is employed to construct confidence intervals for estimated model parameters throughout. The optimal number of principal components is determined through the use of the Bayesian Information Criterion model selection tool, which is modified to address the high dimensionality of the data. Conclusions The methods presented are illustrated through an application to metabolomic data sets. Jointly modeling metabolomic data and covariates was successfully achieved and has the potential to provide deeper insight to the underlying data structure. Examination of confidence intervals for the model parameters, such as loadings, allows for principled and clear interpretation of the underlying data structure. A software package called MetabolAnalyze, freely available through the R statistical software, has been developed to facilitate implementation of the presented methods in the metabolomics field.

  12. Chemometric characterization of the hydrogen bonding complexes of secondary amides and aromatic hydrocarbons

    OpenAIRE

    Jović, Branislav; Nikolić, Aleksandar; Petrović, Slobodan

    2012-01-01

    The paper reports the results of the study of hydrogen bonding complexes between secondary amides and various aromatic hydrocarbons. The possibility of using chemometric methods was investigated in order to characterize N-H•••π hydrogen bonded complexes. Hierarchical clustering and Principal Component Analysis (PCA) have been applied on infrared spectroscopic and Taft parameters of 43 N-substituted amide complexes with different aromatic hydrocarbons. Results obtained in this report are...

  13. Informatics for Metabolomics.

    Science.gov (United States)

    Kusonmano, Kanthida; Vongsangnak, Wanwipa; Chumnanpuen, Pramote

    2016-01-01

    Metabolome profiling of biological systems has the powerful ability to provide the biological understanding of their metabolic functional states responding to the environmental factors or other perturbations. Tons of accumulative metabolomics data have thus been established since pre-metabolomics era. This is directly influenced by the high-throughput analytical techniques, especially mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based techniques. Continuously, the significant numbers of informatics techniques for data processing, statistical analysis, and data mining have been developed. The following tools and databases are advanced for the metabolomics society which provide the useful metabolomics information, e.g., the chemical structures, mass spectrum patterns for peak identification, metabolite profiles, biological functions, dynamic metabolite changes, and biochemical transformations of thousands of small molecules. In this chapter, we aim to introduce overall metabolomics studies from pre- to post-metabolomics era and their impact on society. Directing on post-metabolomics era, we provide a conceptual framework of informatics techniques for metabolomics and show useful examples of techniques, tools, and databases for metabolomics data analysis starting from preprocessing toward functional interpretation. Throughout the framework of informatics techniques for metabolomics provided, it can be further used as a scaffold for translational biomedical research which can thus lead to reveal new metabolite biomarkers, potential metabolic targets, or key metabolic pathways for future disease therapy.

  14. Metabolomics for laboratory diagnostics.

    Science.gov (United States)

    Bujak, Renata; Struck-Lewicka, Wiktoria; Markuszewski, Michał J; Kaliszan, Roman

    2015-09-10

    Metabolomics is an emerging approach in a systems biology field. Due to continuous development in advanced analytical techniques and in bioinformatics, metabolomics has been extensively applied as a novel, holistic diagnostic tool in clinical and biomedical studies. Metabolome's measurement, as a chemical reflection of a current phenotype of a particular biological system, is nowadays frequently implemented to understand pathophysiological processes involved in disease progression as well as to search for new diagnostic or prognostic biomarkers of various organism's disorders. In this review, we discussed the research strategies and analytical platforms commonly applied in the metabolomics studies. The applications of the metabolomics in laboratory diagnostics in the last 5 years were also reviewed according to the type of biological sample used in the metabolome's analysis. We also discussed some limitations and further improvements which should be considered taking in mind potential applications of metabolomic research and practice. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Microbial metabolomics in open microscale platforms

    Science.gov (United States)

    Barkal, Layla J.; Theberge, Ashleigh B.; Guo, Chun-Jun; Spraker, Joe; Rappert, Lucas; Berthier, Jean; Brakke, Kenneth A.; Wang, Clay C. C.; Beebe, David J.; Keller, Nancy P.; Berthier, Erwin

    2016-01-01

    The microbial secondary metabolome encompasses great synthetic diversity, empowering microbes to tune their chemical responses to changing microenvironments. Traditional metabolomics methods are ill-equipped to probe a wide variety of environments or environmental dynamics. Here we introduce a class of microscale culture platforms to analyse chemical diversity of fungal and bacterial secondary metabolomes. By leveraging stable biphasic interfaces to integrate microculture with small molecule isolation via liquid–liquid extraction, we enable metabolomics-scale analysis using mass spectrometry. This platform facilitates exploration of culture microenvironments (including rare media typically inaccessible using established methods), unusual organic solvents for metabolite isolation and microbial mutants. Utilizing Aspergillus, a fungal genus known for its rich secondary metabolism, we characterize the effects of culture geometry and growth matrix on secondary metabolism, highlighting the potential use of microscale systems to unlock unknown or cryptic secondary metabolites for natural products discovery. Finally, we demonstrate the potential for this class of microfluidic systems to study interkingdom communication between fungi and bacteria. PMID:26842393

  16. [Arterial hypertension and RU-486: a complex case of secondary hypertension].

    Science.gov (United States)

    Leone, Alessandra; Pisaneschi, Silvia; Montereggi, Francesco; Canu, Letizia; Corsini, Elisa; Mannelli, Massimo; Montereggi, Alessio

    2013-06-01

    Secondary hypertension accounts for 10-15% of all cases of hypertension, and early diagnosis with identification of its etiology can be challenging. In this scenario, therapeutic management of affected patients may be difficult. Hypercortisolism is one of the possible causes of secondary hypertension, but its low prevalence and atypical clinical symptoms can lead to a delayed diagnosis. The complex clinical presentation and potential complications need a close collaboration among different clinicians in order to plan optimal or new treatment protocols.

  17. Metabolomics and Epidemiology Working Group

    Science.gov (United States)

    The Metabolomics and Epidemiology (MetEpi) Working Group promotes metabolomics analyses in population-based studies, as well as advancement in the field of metabolomics for broader biomedical and public health research.

  18. Structure and reactivity of boron-ate complexes derived from primary and secondary boronic esters.

    Science.gov (United States)

    Feeney, Kathryn; Berionni, Guillaume; Mayr, Herbert; Aggarwal, Varinder K

    2015-06-05

    Boron-ate complexes derived from primary and secondary boronic esters and aryllithiums have been isolated, and the kinetics of their reactions with carbenium ions studied. The second-order rate constants have been used to derive nucleophilicity parameters for the boron-ate complexes, revealing that nucleophilicity increased with (i) electron-donating aromatics on boron, (ii) neopentyl glycol over pinacol boronic esters, and (iii) 12-crown-4 ether.

  19. Organisational simplification and secondary complexity in health services for adults with learning disabilities.

    Science.gov (United States)

    Heyman, Bob; Swain, John; Gillman, Maureen

    2004-01-01

    This paper explores the role of complexity and simplification in the delivery of health care for adults with learning disabilities, drawing upon qualitative data obtained in a study carried out in NE England. It is argued that the requirement to manage complex health needs with limited resources causes service providers to simplify, standardise and routinise care. Simplified service models may work well enough for the majority of clients, but can impede recognition of the needs of those whose characteristics are not congruent with an adopted model. The data were analysed in relation to the core category, identified through thematic analysis, of secondary complexity arising from organisational simplification. Organisational simplification generates secondary complexity when operational routines designed to make health complexity manageable cannot accommodate the needs of non-standard service users. Associated themes, namely the social context of services, power and control, communication skills, expertise and service inclusiveness and evaluation are explored in relation to the core category. The concept of secondary complexity resulting from organisational simplification may partly explain seemingly irrational health service provider behaviour.

  20. Jean’s instability in a complex plasma in presence of secondary electrons and nonthermal ions

    International Nuclear Information System (INIS)

    Sarkar, Susmita; Maity Saumyen

    2013-01-01

    In this paper we have investigated the effect of secondary electron emission and nonthermality of ion velocity distribution simultaneously on Jean’s instability in a complex plasma in presence of negatively charged dust grains. Primary and secondary electron temperatures are assumed to be equal. Thus plasma under consideration consists of Boltzmann distributed electrons, nonthermal ions and negatively charged dust grains. The dust grain component is modeled by continuity and momentum equations. From the linear dispersion relation we have calculated the real frequency and growth rate of the Jean’s mode. Numerically it is found that for lower values of the nonthermal parameter Jean’s instability is higher for higher secondary electron emission whereas the effect of secondary electron emission on Jean’s instability becomes insignificant for higher values of the nonthermal parameter. (author)

  1. Metabolomic Studies in Drosophila.

    Science.gov (United States)

    Cox, James E; Thummel, Carl S; Tennessen, Jason M

    2017-07-01

    Metabolomic analysis provides a powerful new tool for studies of Drosophila physiology. This approach allows investigators to detect thousands of chemical compounds in a single sample, representing the combined contributions of gene expression, enzyme activity, and environmental context. Metabolomics has been used for a wide range of studies in Drosophila , often providing new insights into gene function and metabolic state that could not be obtained using any other approach. In this review, we survey the uses of metabolomic analysis since its entry into the field. We also cover the major methods used for metabolomic studies in Drosophila and highlight new directions for future research. Copyright © 2017 by the Genetics Society of America.

  2. RNACompress: Grammar-based compression and informational complexity measurement of RNA secondary structure

    Directory of Open Access Journals (Sweden)

    Chen Chun

    2008-03-01

    Full Text Available Abstract Background With the rapid emergence of RNA databases and newly identified non-coding RNAs, an efficient compression algorithm for RNA sequence and structural information is needed for the storage and analysis of such data. Although several algorithms for compressing DNA sequences have been proposed, none of them are suitable for the compression of RNA sequences with their secondary structures simultaneously. This kind of compression not only facilitates the maintenance of RNA data, but also supplies a novel way to measure the informational complexity of RNA structural data, raising the possibility of studying the relationship between the functional activities of RNA structures and their complexities, as well as various structural properties of RNA based on compression. Results RNACompress employs an efficient grammar-based model to compress RNA sequences and their secondary structures. The main goals of this algorithm are two fold: (1 present a robust and effective way for RNA structural data compression; (2 design a suitable model to represent RNA secondary structure as well as derive the informational complexity of the structural data based on compression. Our extensive tests have shown that RNACompress achieves a universally better compression ratio compared with other sequence-specific or common text-specific compression algorithms, such as Gencompress, winrar and gzip. Moreover, a test of the activities of distinct GTP-binding RNAs (aptamers compared with their structural complexity shows that our defined informational complexity can be used to describe how complexity varies with activity. These results lead to an objective means of comparing the functional properties of heteropolymers from the information perspective. Conclusion A universal algorithm for the compression of RNA secondary structure as well as the evaluation of its informational complexity is discussed in this paper. We have developed RNACompress, as a useful tool

  3. Efficient SN2 fluorination of primary and secondary alkyl bromides by copper(I) fluoride complexes

    KAUST Repository

    Liu, Yanpin; Chen, Chaohuang; Li, Huaifeng; Huang, Kuo-Wei; Tan, Jianwei; Weng, Zhiqiang

    2013-01-01

    Copper(I) fluoride complexes ligated by phenanthroline derivatives have been synthesized and structurally characterized by X-ray crystallography. These complexes adopt as either ionic or neutral forms in the solid state, depending on the steric bulkiness of the substituent groups on the phenanthroline ligands. These complexes react with primary and secondary alkyl bromides to produce the corresponding alkyl fluorides in modest to good yields. This new method is compatible with a variety of important functional groups such as ether, thioether, amide, nitrile, methoxyl, hydroxyl, ketone, ester, and heterocycle moieties. © 2013 American Chemical Society.

  4. Chemometric characterization of the hydrogen bonding complexes of secondary amides and aromatic hydrocarbons

    Directory of Open Access Journals (Sweden)

    Jović Branislav

    2012-01-01

    Full Text Available The paper reports the results of the study of hydrogen bonding complexes between secondary amides and various aromatic hydrocarbons. The possibility of using chemometric methods was investigated in order to characterize N-H•••π hydrogen bonded complexes. Hierarchical clustering and Principal Component Analysis (PCA have been applied on infrared spectroscopic and Taft parameters of 43 N-substituted amide complexes with different aromatic hydrocarbons. Results obtained in this report are in good agreement with conclusions of other spectroscopic and thermodynamic analysis.

  5. Efficient SN2 fluorination of primary and secondary alkyl bromides by copper(I) fluoride complexes

    KAUST Repository

    Liu, Yanpin

    2013-11-11

    Copper(I) fluoride complexes ligated by phenanthroline derivatives have been synthesized and structurally characterized by X-ray crystallography. These complexes adopt as either ionic or neutral forms in the solid state, depending on the steric bulkiness of the substituent groups on the phenanthroline ligands. These complexes react with primary and secondary alkyl bromides to produce the corresponding alkyl fluorides in modest to good yields. This new method is compatible with a variety of important functional groups such as ether, thioether, amide, nitrile, methoxyl, hydroxyl, ketone, ester, and heterocycle moieties. © 2013 American Chemical Society.

  6. Metabolomics investigation of whey intake

    DEFF Research Database (Denmark)

    Stanstrup, Jan

    syndrome are complex disorders and are not caused by a high-calorie diet and low exercise level alone. The specific nature of the nutrients, independent of their caloric value, also play a role. The question is which. In the quest to answer this question the qualitative intake of protein is of special...... and prevention of the metabolic syndrome related to obesity and diabetes. In this thesis the effects of whey intake on the human metabolome was investigated using a metabolomics approach. We demonstrated that intake of whey causes a decreased rate of gastric emptying compared to other protein sources....... Therefore this thesis will also present and discuss state-of-the-art tools for computer-assisted compound identification, including: annotation of adducts and fragments, determination of the molecular ion, in silico fragmentation, retention time mapping between analytical systems and de novo retention time...

  7. Metabolomic Analysis of Complex Chinese Remedies: Examples of Induced Nephrotoxicity in the Mouse from a Series of Remedies Containing Aristolochic Acid

    Directory of Open Access Journals (Sweden)

    Dong-Ming Tsai

    2013-01-01

    Full Text Available Aristolochic acid nephropathy is caused by aristolochic acid (AA and AA-containing herbs. In traditional Chinese medicine, a principle called “Jun-Chen-Zou-Shi” may be utilized to construct a remedial herbal formula that attempts to mitigate the toxicity of the main ingredient. This study used Bu-Fei-A-Jiao-Tang (BFAJT to test if the compound remedy based on a principle of “Jun-Chen-Zou-Shi” can decrease the toxicity of AA-containing herbs. We compared the three toxicities of AA standard, Madouling (an Aristolochia herb, and a herbal formula BFAJT. AA standard was given for BALB/c mice at a dose of 5 mg/kg bw/day or 7.5 mg/kg bw/day for 10 days. Madouling and BFAJT were given at an equivalence of AA 0.5 mg/kg bw/day for 21 days. Nephrotoxicity was evaluated by metabolomics and histopathology. The urinary metabolomics profiles were characterized by 1H NMR spectroscopy. The spectral data was analyzed with partial least squares discriminant analysis, and the significant differential metabolites between groups were identified. The result showed different degrees of acute renal tubular injuries, and metabolomics analysis found that the kidney injuries were focused in proximal renal tubules. Both metabolomics and pathological studies revealed that AA standard, Madouling, and BFAJT were all nephrotoxicants. The compositions of the compound remedy did not diminish the nephrotoxicity caused by AA.

  8. Structured plant metabolomics for the simultaneous exploration of multiple factors.

    Science.gov (United States)

    Vasilev, Nikolay; Boccard, Julien; Lang, Gerhard; Grömping, Ulrike; Fischer, Rainer; Goepfert, Simon; Rudaz, Serge; Schillberg, Stefan

    2016-11-17

    Multiple factors act simultaneously on plants to establish complex interaction networks involving nutrients, elicitors and metabolites. Metabolomics offers a better understanding of complex biological systems, but evaluating the simultaneous impact of different parameters on metabolic pathways that have many components is a challenging task. We therefore developed a novel approach that combines experimental design, untargeted metabolic profiling based on multiple chromatography systems and ionization modes, and multiblock data analysis, facilitating the systematic analysis of metabolic changes in plants caused by different factors acting at the same time. Using this method, target geraniol compounds produced in transgenic tobacco cell cultures were grouped into clusters based on their response to different factors. We hypothesized that our novel approach may provide more robust data for process optimization in plant cell cultures producing any target secondary metabolite, based on the simultaneous exploration of multiple factors rather than varying one factor each time. The suitability of our approach was verified by confirming several previously reported examples of elicitor-metabolite crosstalk. However, unravelling all factor-metabolite networks remains challenging because it requires the identification of all biochemically significant metabolites in the metabolomics dataset.

  9. Palladium(II) complexes supported by a bidentate bis(secondary)phosphine linked by pyridine

    KAUST Repository

    Winston, Matthew S.; Bercaw, John E.

    2014-01-01

    A series of complexes of the type (PNP-H2)PdX2 (X=Cl, Br, I) have been synthesized, where PNP-H2 is a bis(secondary)phosphine ligand linked by a pyridine, 2,6-(2'-(Ph(H)P)(C6H4))2(C5H3N). Due to chirality at phosphorus, the parent ligand exists as a

  10. Metabolomics data normalization with EigenMS.

    Directory of Open Access Journals (Sweden)

    Yuliya V Karpievitch

    Full Text Available Liquid chromatography mass spectrometry has become one of the analytical platforms of choice for metabolomics studies. However, LC-MS metabolomics data can suffer from the effects of various systematic biases. These include batch effects, day-to-day variations in instrument performance, signal intensity loss due to time-dependent effects of the LC column performance, accumulation of contaminants in the MS ion source and MS sensitivity among others. In this study we aimed to test a singular value decomposition-based method, called EigenMS, for normalization of metabolomics data. We analyzed a clinical human dataset where LC-MS serum metabolomics data and physiological measurements were collected from thirty nine healthy subjects and forty with type 2 diabetes and applied EigenMS to detect and correct for any systematic bias. EigenMS works in several stages. First, EigenMS preserves the treatment group differences in the metabolomics data by estimating treatment effects with an ANOVA model (multiple fixed effects can be estimated. Singular value decomposition of the residuals matrix is then used to determine bias trends in the data. The number of bias trends is then estimated via a permutation test and the effects of the bias trends are eliminated. EigenMS removed bias of unknown complexity from the LC-MS metabolomics data, allowing for increased sensitivity in differential analysis. Moreover, normalized samples better correlated with both other normalized samples and corresponding physiological data, such as blood glucose level, glycated haemoglobin, exercise central augmentation pressure normalized to heart rate of 75, and total cholesterol. We were able to report 2578 discriminatory metabolite peaks in the normalized data (p<0.05 as compared to only 1840 metabolite signals in the raw data. Our results support the use of singular value decomposition-based normalization for metabolomics data.

  11. Partial Least Squares with Structured Output for Modelling the Metabolomics Data Obtained from Complex Experimental Designs: A Study into the Y-Block Coding

    Directory of Open Access Journals (Sweden)

    Yun Xu

    2016-10-01

    Full Text Available Partial least squares (PLS is one of the most commonly used supervised modelling approaches for analysing multivariate metabolomics data. PLS is typically employed as either a regression model (PLS-R or a classification model (PLS-DA. However, in metabolomics studies it is common to investigate multiple, potentially interacting, factors simultaneously following a specific experimental design. Such data often cannot be considered as a “pure” regression or a classification problem. Nevertheless, these data have often still been treated as a regression or classification problem and this could lead to ambiguous results. In this study, we investigated the feasibility of designing a hybrid target matrix Y that better reflects the experimental design than simple regression or binary class membership coding commonly used in PLS modelling. The new design of Y coding was based on the same principle used by structural modelling in machine learning techniques. Two real metabolomics datasets were used as examples to illustrate how the new Y coding can improve the interpretability of the PLS model compared to classic regression/classification coding.

  12. The Human Serum Metabolome

    Science.gov (United States)

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.

    2011-01-01

    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca. PMID:21359215

  13. Metabolomics in chemical ecology.

    Science.gov (United States)

    Kuhlisch, Constanze; Pohnert, Georg

    2015-07-01

    Chemical ecology elucidates the nature and role of natural products as mediators of organismal interactions. The emerging techniques that can be summarized under the concept of metabolomics provide new opportunities to study such environmentally relevant signaling molecules. Especially comparative tools in metabolomics enable the identification of compounds that are regulated during interaction situations and that might play a role as e.g. pheromones, allelochemicals or in induced and activated defenses. This approach helps overcoming limitations of traditional bioassay-guided structure elucidation approaches. But the power of metabolomics is not limited to the comparison of metabolic profiles of interacting partners. Especially the link to other -omics techniques helps to unravel not only the compounds in question but the entire biosynthetic and genetic re-wiring, required for an ecological response. This review comprehensively highlights successful applications of metabolomics in chemical ecology and discusses existing limitations of these novel techniques. It focuses on recent developments in comparative metabolomics and discusses the use of metabolomics in the systems biology of organismal interactions. It also outlines the potential of large metabolomics initiatives for model organisms in the field of chemical ecology.

  14. Metabolome analysis for discovering biomarkers of gastroenterological cancer.

    Science.gov (United States)

    Suzuki, Makoto; Nishiumi, Shin; Matsubara, Atsuki; Azuma, Takeshi; Yoshida, Masaru

    2014-09-01

    Improvements in analytical technologies have made it possible to rapidly determine the concentrations of thousands of metabolites in any biological sample, which has resulted in metabolome analysis being applied to various types of research, such as clinical, cell biology, and plant/food science studies. The metabolome represents all of the end products and by-products of the numerous complex metabolic pathways operating in a biological system. Thus, metabolome analysis allows one to survey the global changes in an organism's metabolic profile and gain a holistic understanding of the changes that occur in organisms during various biological processes, e.g., during disease development. In clinical metabolomic studies, there is a strong possibility that differences in the metabolic profiles of human specimens reflect disease-specific states. Recently, metabolome analysis of biofluids, e.g., blood, urine, or saliva, has been increasingly used for biomarker discovery and disease diagnosis. Mass spectrometry-based techniques have been extensively used for metabolome analysis because they exhibit high selectivity and sensitivity during the identification and quantification of metabolites. Here, we describe metabolome analysis using liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Furthermore, the findings of studies that attempted to discover biomarkers of gastroenterological cancer are also outlined. Finally, we discuss metabolome analysis-based disease diagnosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Environmental metabolomics: a SWOT analysis (strengths, weaknesses, opportunities, and threats).

    Science.gov (United States)

    Miller, Marion G

    2007-02-01

    Metabolomic approaches have the potential to make an exceptional contribution to understanding how chemicals and other environmental stressors can affect both human and environmental health. However, the application of metabolomics to environmental exposures, although getting underway, has not yet been extensively explored. This review will use a SWOT analysis model to discuss some of the strengths, weaknesses, opportunities, and threats that are apparent to an investigator venturing into this relatively new field. SWOT has been used extensively in business settings to uncover new outlooks and identify problems that would impede progress. The field of environmental metabolomics provides great opportunities for discovery, and this is recognized by a high level of interest in potential applications. However, understanding the biological consequence of environmental exposures can be confounded by inter- and intra-individual differences. Metabolomic profiles can yield a plethora of data, the interpretation of which is complex and still being evaluated and researched. The development of the field will depend on the availability of technologies for data handling and that permit ready access metabolomic databases. Understanding the relevance of metabolomic endpoints to organism health vs adaptation vs variation is an important step in understanding what constitutes a substantive environmental threat. Metabolomic applications in reproductive research are discussed. Overall, the development of a comprehensive mechanistic-based interpretation of metabolomic changes offers the possibility of providing information that will significantly contribute to the protection of human health and the environment.

  16. Formation of wood secondary cell wall may involve two type cellulose synthase complexes in Populus.

    Science.gov (United States)

    Xi, Wang; Song, Dongliang; Sun, Jiayan; Shen, Junhui; Li, Laigeng

    2017-03-01

    Cellulose biosynthesis is mediated by cellulose synthases (CesAs), which constitute into rosette-like cellulose synthase complexe (CSC) on the plasma membrane. Two types of CSCs in Arabidopsis are believed to be involved in cellulose synthesis in the primary cell wall and secondary cell walls, respectively. In this work, we found that the two type CSCs participated cellulose biosynthesis in differentiating xylem cells undergoing secondary cell wall thickening in Populus. During the cell wall thickening process, expression of one type CSC genes increased while expression of the other type CSC genes decreased. Suppression of different type CSC genes both affected the wall-thickening and disrupted the multilaminar structure of the secondary cell walls. When CesA7A was suppressed, crystalline cellulose content was reduced, which, however, showed an increase when CesA3D was suppressed. The CesA suppression also affected cellulose digestibility of the wood cell walls. The results suggest that two type CSCs are involved in coordinating the cellulose biosynthesis in formation of the multilaminar structure in Populus wood secondary cell walls.

  17. Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures

    OpenAIRE

    Zulak, Katherine G; Weljie, Aalim M; Vogel, Hans J; Facchini, Peter J

    2008-01-01

    Abstract Background Opium poppy (Papaver somniferum) produces a diverse array of bioactive benzylisoquinoline alkaloids and has emerged as a model system to study plant alkaloid metabolism. The plant is cultivated as the only commercial source of the narcotic analgesics morphine and codeine, but also produces many other alkaloids including the antimicrobial agent sanguinarine. Modulations in plant secondary metabolism as a result of environmental perturbations are often associated with the al...

  18. Metabolomic studies in pulmonology

    Directory of Open Access Journals (Sweden)

    R. R. Furina

    2015-01-01

    Full Text Available The review shows the results of metabolomic studies in pulmonology. The key idea of metabolomics is to detect specific biomarkers in a biological sample for the diagnosis of diseases of the bronchi and lung. Main methods for the separation and identification of volatile organic substances as biomarkers (gas chromatography, mass spectrometry, and nuclear magnetic resonance spectrometry used in metabolomics are given. A solid-phase microextraction method used to pre-prepare a sample is also covered. The results of laboratory tests for biomarkers for lung cancer, acute respiratory distress syndrome, chronic obstructive pulmonary disease, cystic fibrosis, chronic infections, and pulmonary tuberculosis are presented. In addition, emphasis is placed on the possibilities of metabolomics used in experimental medicine, including to the study of asthma. The information is of interest to both theorists and practitioners.

  19. Current metabolomics: technological advances.

    Science.gov (United States)

    Putri, Sastia P; Yamamoto, Shinya; Tsugawa, Hiroshi; Fukusaki, Eiichiro

    2013-07-01

    Metabolomics, the global quantitative assessment of metabolites in a biological system, has played a pivotal role in various fields of science in the post-genomic era. Metabolites are the result of the interaction of the system's genome with its environment and are not merely the end product of gene expression, but also form part of the regulatory system in an integrated manner. Therefore, metabolomics is often considered a powerful tool to provide an instantaneous snapshot of the physiology of a cell. The power of metabolomics lies on the acquisition of analytical data in which metabolites in a cellular system are quantified, and the extraction of the most meaningful elements of the data by using various data analysis tool. In this review, we discuss the latest development of analytical techniques and data analyses methods in metabolomics study. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. Metabolomics er fremtiden

    DEFF Research Database (Denmark)

    Pedersern, Birger

    2010-01-01

    Forskningen i fødevarer har fået et potent redskab i hånden. Metabolomics er vejen frem, mener professor Søren Balling Engelsen fra Københavns Universitet......Forskningen i fødevarer har fået et potent redskab i hånden. Metabolomics er vejen frem, mener professor Søren Balling Engelsen fra Københavns Universitet...

  1. Quality assurance of metabolomics.

    Science.gov (United States)

    Bouhifd, Mounir; Beger, Richard; Flynn, Thomas; Guo, Lining; Harris, Georgina; Hogberg, Helena; Kaddurah-Daouk, Rima; Kamp, Hennicke; Kleensang, Andre; Maertens, Alexandra; Odwin-DaCosta, Shelly; Pamies, David; Robertson, Donald; Smirnova, Lena; Sun, Jinchun; Zhao, Liang; Hartung, Thomas

    2015-01-01

    Metabolomics promises a holistic phenotypic characterization of biological responses to toxicants. This technology is based on advanced chemical analytical tools with reasonable throughput, including mass-spectroscopy and NMR. Quality assurance, however - from experimental design, sample preparation, metabolite identification, to bioinformatics data-mining - is urgently needed to assure both quality of metabolomics data and reproducibility of biological models. In contrast to microarray-based transcriptomics, where consensus on quality assurance and reporting standards has been fostered over the last two decades, quality assurance of metabolomics is only now emerging. Regulatory use in safety sciences, and even proper scientific use of these technologies, demand quality assurance. In an effort to promote this discussion, an expert workshop discussed the quality assurance needs of metabolomics. The goals for this workshop were 1) to consider the challenges associated with metabolomics as an emerging science, with an emphasis on its application in toxicology and 2) to identify the key issues to be addressed in order to establish and implement quality assurance procedures in metabolomics-based toxicology. Consensus has still to be achieved regarding best practices to make sure sound, useful, and relevant information is derived from these new tools.

  2. Palladium(II) complexes supported by a bidentate bis(secondary)phosphine linked by pyridine

    KAUST Repository

    Winston, Matthew S.

    2014-10-01

    A series of complexes of the type (PNP-H2)PdX2 (X=Cl, Br, I) have been synthesized, where PNP-H2 is a bis(secondary)phosphine ligand linked by a pyridine, 2,6-(2\\'-(Ph(H)P)(C6H4))2(C5H3N). Due to chirality at phosphorus, the parent ligand exists as a mixture of nearly equivalent rac and meso diastereomers non-interconverting at room temperature. When ligated to Pd(II) halides, however, the diastereomeric ratio is dependent upon the halide. The chloro, bromo, and iodo complexes have been characterized crystallographically. Conformationally similar meso diastereomers of each dihalide are roughly C s symmetric in the solid state, while the rac diastereomers (identified only for X=Br, I) show substantially different solid-state conformations. © 2014 Elsevier B.V.

  3. An overview of plant volatile metabolomics, sample treatment and reporting considerations with emphasis on mechanical damage and biological control of weeds.

    Science.gov (United States)

    Beck, John J; Smith, Lincoln; Baig, Nausheena

    2014-01-01

    The technology for the collection and analysis of plant-emitted volatiles for understanding chemical cues of plant-plant, plant-insect or plant-microbe interactions has increased over the years. Consequently, the in situ collection, analysis and identification of volatiles are considered integral to elucidation of complex plant communications. Due to the complexity and range of emissions the conditions for consistent emission of volatiles are difficult to standardise. To discuss: evaluation of emitted volatile metabolites as a means of screening potential target- and non-target weeds/plants for insect biological control agents; plant volatile metabolomics to analyse resultant data; importance of considering volatiles from damaged plants; and use of a database for reporting experimental conditions and results. Recent literature relating to plant volatiles and plant volatile metabolomics are summarised to provide a basic understanding of how metabolomics can be applied to the study of plant volatiles. An overview of plant secondary metabolites, plant volatile metabolomics, analysis of plant volatile metabolomics data and the subsequent input into a database, the roles of plant volatiles, volatile emission as a function of treatment, and the application of plant volatile metabolomics to biological control of invasive weeds. It is recommended that in addition to a non-damaged treatment, plants be damaged prior to collecting volatiles to provide the greatest diversity of odours. For the model system provided, optimal volatile emission occurred when the leaf was punctured with a needle. Results stored in a database should include basic environmental conditions or treatments. Copyright © 2013 John Wiley & Sons, Ltd.

  4. Linking metabolomics data to underlying metabolic regulation

    Directory of Open Access Journals (Sweden)

    Thomas eNägele

    2014-11-01

    Full Text Available The comprehensive experimental analysis of a metabolic constitution plays a central role in approaches of organismal systems biology.Quantifying the impact of a changing environment on the homeostasis of cellular metabolism has been the focus of numerous studies applying various metabolomics techniques. It has been proven that approaches which integrate different analytical techniques, e.g. LC-MS, GC-MS, CE-MS and H-NMR, can provide a comprehensive picture of a certain metabolic homeostasis. Identification of metabolic compounds and quantification of metabolite levels represent the groundwork for the analysis of regulatory strategies in cellular metabolism. This significantly promotes our current understanding of the molecular organization and regulation of cells, tissues and whole organisms.Nevertheless, it is demanding to elicit the pertinent information which is contained in metabolomics data sets.Based on the central dogma of molecular biology, metabolite levels and their fluctuations are the result of a directed flux of information from gene activation over transcription to translation and posttranslational modification.Hence, metabolomics data represent the summed output of a metabolic system comprising various levels of molecular organization.As a consequence, the inverse assignment of metabolomics data to underlying regulatory processes should yield information which-if deciphered correctly-provides comprehensive insight into a metabolic system.Yet, the deduction of regulatory principles is complex not only due to the high number of metabolic compounds, but also because of a high level of cellular compartmentalization and differentiation.Motivated by the question how metabolomics approaches can provide a representative view on regulatory biochemical processes, this article intends to present and discuss current metabolomics applications, strategies of data analysis and their limitations with respect to the interpretability in context of

  5. Differential network analysis reveals evolutionary complexity in secondary metabolism of Rauvolfia serpentina over Catharanthus roseus

    Directory of Open Access Journals (Sweden)

    Shivalika Pathania

    2016-08-01

    Full Text Available Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Towards these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These mechanisms may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of Rauvolfia serpentina, and key genes that contribute towards diversification of specific metabolites.

  6. Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus.

    Science.gov (United States)

    Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S

    2016-01-01

    Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites.

  7. Updates in metabolomics tools and resources: 2014-2015.

    Science.gov (United States)

    Misra, Biswapriya B; van der Hooft, Justin J J

    2016-01-01

    Data processing and interpretation represent the most challenging and time-consuming steps in high-throughput metabolomic experiments, regardless of the analytical platforms (MS or NMR spectroscopy based) used for data acquisition. Improved machinery in metabolomics generates increasingly complex datasets that create the need for more and better processing and analysis software and in silico approaches to understand the resulting data. However, a comprehensive source of information describing the utility of the most recently developed and released metabolomics resources--in the form of tools, software, and databases--is currently lacking. Thus, here we provide an overview of freely-available, and open-source, tools, algorithms, and frameworks to make both upcoming and established metabolomics researchers aware of the recent developments in an attempt to advance and facilitate data processing workflows in their metabolomics research. The major topics include tools and researches for data processing, data annotation, and data visualization in MS and NMR-based metabolomics. Most in this review described tools are dedicated to untargeted metabolomics workflows; however, some more specialist tools are described as well. All tools and resources described including their analytical and computational platform dependencies are summarized in an overview Table. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Clinical Metabolomics and Glaucoma.

    Science.gov (United States)

    Barbosa-Breda, João; Himmelreich, Uwe; Ghesquière, Bart; Rocha-Sousa, Amândio; Stalmans, Ingeborg

    2018-01-01

    Glaucoma is one of the leading causes of irreversible blindness worldwide. However, there are no biomarkers that accurately help clinicians perform an early diagnosis or detect patients with a high risk of progression. Metabolomics is the study of all metabolites in an organism, and it has the potential to provide a biomarker. This review summarizes the findings of metabolomics in glaucoma patients and explains why this field is promising for new research. We identified published studies that focused on metabolomics and ophthalmology. After providing an overview of metabolomics in ophthalmology, we focused on human glaucoma studies. Five studies have been conducted in glaucoma patients and all compared patients to healthy controls. Using mass spectrometry, significant differences were found in blood plasma in the metabolic pathways that involve palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors. For nuclear magnetic resonance spectroscopy, a high glutamine-glutamate/creatine ratio was found in the vitreous and lateral geniculate body; no differences were detected in the optic radiations, and a lower N-acetylaspartate/choline ratio was observed in the geniculocalcarine and striate areas. Metabolomics can move glaucoma care towards a personalized approach and provide new knowledge concerning the pathophysiology of glaucoma, which can lead to new therapeutic options. © 2017 S. Karger AG, Basel.

  9. Effect of glycine nitrogen on lettuce growth under soilless culture: a metabolomics approach to identify the main changes occurred in plant primary and secondary metabolism.

    Science.gov (United States)

    Yang, Xiao; Feng, Lei; Zhao, Li; Liu, Xiaosong; Hassani, Danial; Huang, Danfeng

    2018-01-01

    Lettuce is a significant source of antioxidants and bioactive compounds. Nitrate is a cardinal fertilizer in horticulture and influences vegetable yield and quality; however, the negative effects of nitrate on the biosynthesis of flavonoids require further study. It is expected that using fertilizers containing organic nitrogen (N) could promote the synthesis of health-promoting compounds. Lettuces were hydroponically cultured in media containing 9 mmol L -1 nitrate or 9 mmol L -1 glycine for 4 weeks. Primary and secondary metabolites were analyzed using gas chromatography/mass spectrometry (GC/MS) and ultra-performance liquid chromatography/ion mobility spectrometry/quadrupole time-of-flight mass spectrometry (UPLC/IMS/QTOF-MS). Data analysis revealed that 29 metabolites were significantly altered between nitrate and glycine treatments. Metabolites were tentatively identified by comparison with online databases, literature and standards and using collision cross-section values. Significant differences in flavonoid biosynthesis, phenolic biosynthesis and the tricarboxylic acid (TCA) cycle response were observed between N sources. Compared with nitrate, glycine promoted accumulation of glycosylated flavonoids (quercetin 3-glucoside, quercetin 3-(6″-malonyl-glucoside), luteolin 7-glucuronide, luteolin 7-glucoside), ascorbic acid and amino acids (l-valine, l-leucine, l-glutamine, asparagine, l-serine, l-ornithine, 4-aminobutanoic acid, l-phenylalanine) but reduced phenolic acids (dihydroxybenzoic acid hexose isomers 1 and 2, chicoric acid, chicoric acid isomer 1) and TCA intermediates (fumaric, malic, citric and succinic acids). The novel methodology applied in this study can be used to characterize metabolites in lettuce. Accumulation of glycosylated flavonoids, amino acids and ascorbic acid in response to glycine supply provides strong evidence supporting the idea that using amino acids as an N source alters the nutritional value of vegetable crops. © 2017

  10. Structure and properties of silver sulfate complexes derived from dipyridyl methylthio ligands with secondary donor site

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wen-Hua; Yan, Hao-Jie; Chen, Hui; Liu, Rui-Heng; Li, Ai-Min; Wang, Guo [Beijing Key Laboratory for Optical Materials and Photonic Devices, Department of Chemistry, Capital Normal University, Beijing 100048 (China); Wan, Chong-Qing, E-mail: wancq@cnu.edu.cn [Beijing Key Laboratory for Optical Materials and Photonic Devices, Department of Chemistry, Capital Normal University, Beijing 100048 (China); State Key Laboratory of Structural Chemistry in China, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China)

    2017-06-15

    Dipyridyl sulphide ligands 4-(pyridin-4-ylmethylthio)pyridine (abbreviated as L1) and 3-(pyridin-4-ylmethylthio)pyridine (abbreviated as L2) have been designed and used as μ-{sub N},{sub N}-bridging linkages to construct coordination polymers with free –S–CH{sub 2}– groups as secondary donor sites. By use solvent control method, coordination polymers ([Ag{sub 3}SO{sub 4}(L1){sub 3}](Cl)·4.5H{sub 2}O){sub ∞}(1), ([Ag{sub 2}SO{sub 4}(L1){sub 2}]·6H{sub 2}O·2CH{sub 3}OH){sub ∞}(2), ([Ag{sub 2}SO{sub 4}(L2){sub 2}]·H{sub 2}O){sub ∞}(3) and ([Ag{sub 4}(SO{sub 4}){sub 2}(L2){sub 4}]·5H{sub 2}O){sub ∞}(4) with different architectures were obtained. Complexes 1, 3 and 4 feature 1D channel with different sizes and structures. Complex 1 exhibits guest exchange by THF and 1,4-dioxane, and Hg{sup 2+} sorption ability from solution due to its relative larger channel and available bonding sites of –S– exposed to the channel region. All complexes have been characterized through single-crystal and powder X-ray diffraction (PXRD), FT-IR spectra, X-ray photoelectron spectroscopy (XPS), elemental and thermogravimetric analyses. The guest exchange and Hg{sup 2+} sorption were monitored and identified, and the structure-property relationship of coordination polymers 1–4 are discussed. - Graphical abstract: Coordination polymers of silver(I) sulfate with secondary donor sites are shown guest exchange property and Hg{sup 2+} absorb ability from solution. This work provides a new method to construct functional materials with potential application. - Highlights: • New example of constructing functional coordination polymer with secondary donor methylthio group. • Guest exchange and interesting Hg(II) absorb ability from solution are investigated. • New method to construct functional materials with potential application.

  11. The food metabolome: a window over dietary exposure.

    Science.gov (United States)

    Scalbert, Augustin; Brennan, Lorraine; Manach, Claudine; Andres-Lacueva, Cristina; Dragsted, Lars O; Draper, John; Rappaport, Stephen M; van der Hooft, Justin J J; Wishart, David S

    2014-06-01

    The food metabolome is defined as the part of the human metabolome directly derived from the digestion and biotransformation of foods and their constituents. With >25,000 compounds known in various foods, the food metabolome is extremely complex, with a composition varying widely according to the diet. By its very nature it represents a considerable and still largely unexploited source of novel dietary biomarkers that could be used to measure dietary exposures with a high level of detail and precision. Most dietary biomarkers currently have been identified on the basis of our knowledge of food compositions by using hypothesis-driven approaches. However, the rapid development of metabolomics resulting from the development of highly sensitive modern analytic instruments, the availability of metabolite databases, and progress in (bio)informatics has made agnostic approaches more attractive as shown by the recent identification of novel biomarkers of intakes for fruit, vegetables, beverages, meats, or complex diets. Moreover, examples also show how the scrutiny of the food metabolome can lead to the discovery of bioactive molecules and dietary factors associated with diseases. However, researchers still face hurdles, which slow progress and need to be resolved to bring this emerging field of research to maturity. These limits were discussed during the First International Workshop on the Food Metabolome held in Glasgow. Key recommendations made during the workshop included more coordination of efforts; development of new databases, software tools, and chemical libraries for the food metabolome; and shared repositories of metabolomic data. Once achieved, major progress can be expected toward a better understanding of the complex interactions between diet and human health. © 2014 American Society for Nutrition.

  12. THE INFLUENCE OF COMPLEX THERAPY ON THE INFLAMMATORY MARKERS OF PATIENTS WITH SECONDARY OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    I. A. Starodubtseva

    2015-01-01

    Full Text Available The aim of the study is to evaluate the efficacy of complex therapy of secondary osteoarthritis in patients with rheumatoid arthritis with the use of inhibitor of interleukin-1, including the dynamics of inflammatory markers.Materials and methods: 248 patients with secondary osteoarthritis in rheumatoid arthritis were involved in the trial. The participants were divided into 4 groups: patients of group I took inhibitor of interleukin-1 (diacerein in combination with laser therapy and methotrexate; inhibitor of interleukin-1 in complex with methotrexate took patients from group II; group 3 — laser therapy + methotrexate and patients of group IV took only methotrexate. The efficacy of therapy we estimated in 6 months.Results: The constructed model surfaces indicated the decreased levels of IL-1, COMP and DAS 28 in group 1 till 6,68±0,37 pg/ml (p<0,001, 16,92±0,8 ng/ml х 10² (p<0,001 и 2,06±1,19 (p<0,05 accordingly in comparison with groups III and IV. Also the model surfaces revealed the interdependency of all these indicators. The control group (IV reacted to the treatment by decreasing the indicators as well. However, the dynamics of the changes was significantly less. In patients of groups I and II the levels of ESR and CRP decreased to 13,95±0,52* (*p<0,001 and 10,97±0,43* (*p<0,001; 16,53±0,63* (*p<0,001 and 12,81±0,77* (*p<0,001 accordingly.Conclusions: In comparison analysis we noted statistical significant advantages (p<0,01 of the use of diacerein with methotrexate regarding the dynamic of IL-1 and COMP, ESR, CRP in patient’s serum, which is accompanied by the reduction of basic disease activity on DAS 28.

  13. A Review of Applications of Metabolomics in Cancer

    Directory of Open Access Journals (Sweden)

    Richard D. Beger

    2013-07-01

    Full Text Available Cancer is a devastating disease that alters the metabolism of a cell and the surrounding milieu. Metabolomics is a growing and powerful technology capable of detecting hundreds to thousands of metabolites in tissues and biofluids. The recent advances in metabolomics technologies have enabled a deeper investigation into the metabolism of cancer and a better understanding of how cancer cells use glycolysis, known as the “Warburg effect,” advantageously to produce the amino acids, nucleotides and lipids necessary for tumor proliferation and vascularization. Currently, metabolomics research is being used to discover diagnostic cancer biomarkers in the clinic, to better understand its complex heterogeneous nature, to discover pathways involved in cancer that could be used for new targets and to monitor metabolic biomarkers during therapeutic intervention. These metabolomics approaches may also provide clues to personalized cancer treatments by providing useful information to the clinician about the cancer patient’s response to medical interventions.

  14. Syntheses and characterizations of secondary Pb-O bonding supported Pb(II)-sulfonate complexes

    Science.gov (United States)

    Huang, Guo-Zhen; Zou, Xin; Zhu, Zhi-Biao; Deng, Zhao-Peng; Huo, Li-Hua; Gao, Shan

    2018-06-01

    The reaction of Pb(II) salts and mono- or disulfonates leads to the formation of eight new Pb(II)-mono/disulfonate complexes, [Pb(L1)(H2O)]2 (1), [Pb4(L2)2(AcO)2]n·5nH2O (2), [Pb(L3)(H2O)]2 (3), [Pb(HL4)(H2O)2]n·nH2O (4), [Pb(HL5)(H2O)2]n·2nH2O (5), [Pb(H2L6)(H2O)]n·nDMF·2nH2O (6), [Pb2(H3L7)4(H2O)6]·2H2O (7) and [Pb(H2L7)(H2O)]n·nH2O (8) (H2L1= 2-hydroxy-5-methyl-benzenesulfonic acid, H3L2= 2-hydroxyl-5-methyl- 1,3-benzenedisulfonic acid, H2L3= 2-hydroxy-5-nitro-benzenesulfonic acid, H3L4= 2-hydroxyl-5-bromo-1,3- benzenedisulfonic acid, H3L5= 2-hydroxyl-5-carboxyl-benzenesulfonic acid, H4L6= 2,5-dihydroxyl-3-carboxyl- benzenesulfonic acid, H4L7= 2,4-dihydroxyl-5-carboxyl-benzenesulfonic acid, DMF = N,N'-dimethyl-formamide, AcO- = acetate), which have been characterized by elemental analysis, IR, TG, PL, powder and single-crystal X-ray diffraction. In view of the primary Pb-O bonds, these eight complexes exhibit diverse dinuclear (1, 3 and 7), helical chain (4), wave-like chain (5), linear chain (6), zigzag chain (8) and layer structure (2), in which the Pb(II) cations present different hemi-directed geometries. Taking the secondary Pb-O bonds into account, chain structure for complex 7, layer motifs for complexes 1 and 3-6, as well as 3-D framework for complex 8 are observed with Pb(II) cations showing more intricate holo-directed geometries. The various coordination modes of these seven different mono/disulfonate anions are responsible for the formation of these multiple structures. Furthermore, the introduction of hydroxyl and carboxyl groups increases the coordination ability of sulfonate to the p-block metal cation. Luminescent analyses indicate that complex 7 presents purple emission at 395 nm at room temperature.

  15. Effect of secondary electron emission on Jean's instability in a complex plasma in the presence of nonthermal ions

    International Nuclear Information System (INIS)

    Sarkar, Susmita; Maity, Saumyen; Banerjee, Soumyajyoti

    2011-01-01

    In this paper, we have investigated the role of secondary electron emission on Jean's instability in a complex plasma in the presence of nonthermal ions. The equilibrium dust surface potential has been considered negative and hence primary and secondary electron temperatures are equal. Such plasma consists of three components: Boltzman distributed electrons, nonthermal ions and negatively charged inertial dust grains. From the linear dispersion relation, we have calculated the real frequency and growth rate of Jean's instability. Numerically, we have shown that for strong ion nonthermality Jean's mode is unstable. Growth of the instability reduces and the real part of the wave frequency increases with increasing secondary electron emission from dust grains. Hence, strong secondary electron emission suppresses Jean's instability in a complex plasma even when ion nonthermality is strong and equilibrium dust charge is negative.

  16. Analytical methods in untargeted metabolomics: state of the art in 2015

    Directory of Open Access Journals (Sweden)

    Arnald eAlonso

    2015-03-01

    Full Text Available Metabolomics comprises the methods and techniques that are used to measure the small molecule composition of biofluids and tissues, and is actually one of the most rapidly evolving research fields. The determination of the metabolomic profile –the metabolome- has multiple applications in many biological sciences, including the developing of new diagnostic tools in medicine. Recent technological advances in nuclear magnetic resonance (NMR and mass spectrometry (MS are significantly improving our capacity to obtain more data from each biological sample. Consequently, there is a need for fast and accurate statistical and bioinformatic tools that can deal with the complexity and volume of the data generated in metabolomic studies. In this review we provide an update of the most commonly used analytical methods in metabolomics, starting from raw data processing and ending with pathway analysis and biomarker identification. Finally, the integration of metabolomic profiles with molecular data from other high throughput biotechnologies is also reviewed.

  17. Stable isotope-resolved metabolomics and applications for drug development

    Science.gov (United States)

    Fan, Teresa W-M.; Lorkiewicz, Pawel; Sellers, Katherine; Moseley, Hunter N.B.; Higashi, Richard M.; Lane, Andrew N.

    2012-01-01

    Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response. In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality. PMID:22212615

  18. Metabolomics and Personalized Medicine.

    Science.gov (United States)

    Koen, Nadia; Du Preez, Ilse; Loots, Du Toit

    2016-01-01

    Current clinical practice strongly relies on the prognosis, diagnosis, and treatment of diseases using methods determined and averaged for the specific diseased cohort/population. Although this approach complies positively with most patients, misdiagnosis, treatment failure, relapse, and adverse drug effects are common occurrences in many individuals, which subsequently hamper the control and eradication of a number of diseases. These incidences can be explained by individual variation in the genome, transcriptome, proteome, and metabolome of a patient. Various "omics" approaches have investigated the influence of these factors on a molecular level, with the intention of developing personalized approaches to disease diagnosis and treatment. Metabolomics, the newest addition to the "omics" domain and the closest to the observed phenotype, reflects changes occurring at all molecular levels, as well as influences resulting from other internal and external factors. By comparing the metabolite profiles of two or more disease phenotypes, metabolomics can be applied to identify biomarkers related to the perturbation being investigated. These biomarkers can, in turn, be used to develop personalized prognostic, diagnostic, and treatment approaches, and can also be applied to the monitoring of disease progression, treatment efficacy, predisposition to drug-related side effects, and potential relapse. In this review, we discuss the contributions that metabolomics has made, and can potentially still make, towards the field of personalized medicine. © 2016 Elsevier Inc. All rights reserved.

  19. Single cell metabolomics

    NARCIS (Netherlands)

    Heinemann, Matthias; Zenobi, Renato

    Recent discoveries suggest that cells of a clonal population often display multiple metabolic phenotypes at the same time. Motivated by the success of mass spectrometry (MS) in the investigation of population-level metabolomics, the analytical community has initiated efforts towards MS-based single

  20. Effect of Weakly Nonthermal Ion Velocity Distribution on Jeans Instability in a Complex Plasma in Presence of Secondary Electrons

    International Nuclear Information System (INIS)

    Sarkar, S.; Maity, S.

    2013-01-01

    In this paper we have investigated the effect of weak nonthermality of ion velocity distribution on Jean’s instability in a complex plasma in presence of secondary electrons and negatively charged dust grains. The primary and secondary electron temperatures are assumed equal. Thus plasma under consideration consists of three components: Boltzman distributed electrons, non-thermal ions and negatively charged inertial dust grains. From the linear dispersion relation we have calculated the real frequency and growth rate of the Jean’s mode. Numerically we have found that secondary electron emission destabilizes Jean’s mode when ion nonthermality is weak. (author)

  1. metaMS: An open-source pipeline for GC–MS-based untargeted metabolomics

    NARCIS (Netherlands)

    Wehrens, H.R.M.J.; Weingart, G.; Mattivi, F.

    2014-01-01

    Untargeted metabolomics are rapidly becoming an important tool for studying complex biological samples. Gas chromatography–mass spectrometry (GC–MS) is the most widely used analytical technology for metabolomic analysis of compounds that are volatile or can be chemically derivatised into volatile

  2. Mass spectrometry-based metabolomics for tuberculosis meningitis.

    Science.gov (United States)

    Zhang, Peixu; Zhang, Weiguanliu; Lang, Yue; Qu, Yan; Chu, Fengna; Chen, Jiafeng; Cui, Li

    2018-04-18

    Tuberculosis meningitis (TBM) is a prevalent form of extra-pulmonary tuberculosis that causes substantial morbidity and mortality. Diagnosis of TBM is difficult because of the limited sensitivity of existing laboratory techniques. A metabolomics approach can be used to investigate the sets of metabolites of both bacteria and host, and has been used to clarify the mechanisms underlying disease development, and identify metabolic changes, leadings to improved methods for diagnosis, treatment, and prognostication. Mass spectrometry (MS) is a major analysis platform used in metabolomics, and MS-based metabolomics provides wide metabolite coverage, because of its high sensitivity, and is useful for the investigation of Mycobacterium tuberculosis (Mtb) and related diseases. It has been used to investigate TBM diagnosis; however, the processes involved in the MS-based metabolomics approach are complex and flexible, and often consist of several steps, and small changes in the methods used can have a huge impact on the final results. Here, the process of MS-based metabolomics is summarized and its applications in Mtb and Mtb-related diseases discussed. Moreover, the current status of TBM metabolomics is described. Copyright © 2018. Published by Elsevier B.V.

  3. NMR-based milk metabolomics

    DEFF Research Database (Denmark)

    Sundekilde, Ulrik; Larsen, Lotte Bach; Bertram, Hanne Christine S.

    2013-01-01

    and processing capabilities of bovine milk is closely associated to milk composition. Metabolomics is ideal in the study of the low-molecular-weight compounds in milk, and this review focuses on the recent nuclear magnetic resonance (NMR)-based metabolomics trends in milk research, including applications linking...... compounds. Furthermore, metabolomics applications elucidating how the differential regulated genes affects milk composition are also reported. This review will highlight the recent advances in NMR-based metabolomics on milk, as well as give a brief summary of when NMR spectroscopy can be useful for gaining...

  4. Prothrombin Complex Concentrate for Intracerebral Hemorrhage Secondary to Vitamin K Deficiency Bleeding in a 6-Week-Old Child.

    Science.gov (United States)

    Rech, Megan A; Wittekindt, Lindsay; Friedman, Samantha D; Kling, Kendall; Ubogy, David

    2015-12-01

    Four-factor prothrombin complex concentrate is approved for use of life-threatening bleeding secondary to vitamin K antagonism in adults. We describe the use of four-factor prothrombin complex concentrate for hemostasis in a 6-week-old child with life-threatening vitamin K dependent-bleeding who never received vitamin K prophylaxis at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Metabolomics for Quality and food security

    International Nuclear Information System (INIS)

    Diretto, Gianfranco

    2015-01-01

    By the term 'Metabolomics' means the discipline which allows you to determine the set of small molecules (metabolites) produced by an organism in a given time. The metabolomic analysis requires complex technological platforms that allow, in the first place, the separation (chromatography liquid or gaseous) of the different molecules and, subsequently, the identification of the same on the basis of characteristic ratio between their mass and charge (m / z). This study arises by estimates that, between climate change planned for the coming decades, there will also be quick increasing the concentration of Co2 in the atmosphere. In this context, it is essential to predict how these changes weather will impact on product quality plant at the base of our diet. [it

  6. Secondary Power Resources of the Fuel and Energy Complex in Ukraine

    Directory of Open Access Journals (Sweden)

    Shkrabets F.P.

    2016-04-01

    Full Text Available This article describes the types of secondary energy resources that occur during or as a result of mining or of technological processes at metallurgical, coke and chemical enterprises. The research of opportunities to use them directly at industrial enterprises, in case when an energy resource or the energy generated “is not a commodity” was carried out. To generate electricity from secondary sources, the use of diesel power plants and gas–turbine facilities was offered. The values ​​of investments in the construction of thermal power plants (TPP based on different types of secondary energy resources were calculated. Tentative capacities of power plants, which utilize the energy of secondary sources were also computed. The figures used for assessing the release and use of secondary energy resources were given. The necessity of using secondary sources of energy to reduce harmful effects on the environment was emphasized.

  7. Metabolomics in transfusion medicine.

    Science.gov (United States)

    Nemkov, Travis; Hansen, Kirk C; Dumont, Larry J; D'Alessandro, Angelo

    2016-04-01

    Biochemical investigations on the regulatory mechanisms of red blood cell (RBC) and platelet (PLT) metabolism have fostered a century of advances in the field of transfusion medicine. Owing to these advances, storage of RBCs and PLT concentrates has become a lifesaving practice in clinical and military settings. There, however, remains room for improvement, especially with regard to the introduction of novel storage and/or rejuvenation solutions, alternative cell processing strategies (e.g., pathogen inactivation technologies), and quality testing (e.g., evaluation of novel containers with alternative plasticizers). Recent advancements in mass spectrometry-based metabolomics and systems biology, the bioinformatics integration of omics data, promise to speed up the design and testing of innovative storage strategies developed to improve the quality, safety, and effectiveness of blood products. Here we review the currently available metabolomics technologies and briefly describe the routine workflow for transfusion medicine-relevant studies. The goal is to provide transfusion medicine experts with adequate tools to navigate through the otherwise overwhelming amount of metabolomics data burgeoning in the field during the past few years. Descriptive metabolomics data have represented the first step omics researchers have taken into the field of transfusion medicine. However, to up the ante, clinical and omics experts will need to merge their expertise to investigate correlative and mechanistic relationships among metabolic variables and transfusion-relevant variables, such as 24-hour in vivo recovery for transfused RBCs. Integration with systems biology models will potentially allow for in silico prediction of metabolic phenotypes, thus streamlining the design and testing of alternative storage strategies and/or solutions. © 2015 AABB.

  8. Metabolomic Analysis in Brain Research: Opportunities & Challenges

    Directory of Open Access Journals (Sweden)

    Catherine G Vasilopoulou

    2016-05-01

    Full Text Available Metabolism being a fundamental part of molecular physiology, elucidating the structure and regulation of metabolic pathways is crucial for obtaining a comprehensive perspective of cellular function and understanding the underlying mechanisms of its dysfunction(s. Therefore, quantifying an accurate metabolic network activity map under various physiological conditions is among the major objectives of systems biology in the context of many biological applications. Especially for CNS, metabolic network activity analysis can substantially enhance our knowledge about the complex structure of the mammalian brain and the mechanisms of neurological disorders, leading to the design of effective therapeutic treatments. Metabolomics has emerged as the high-throughput quantitative analysis of the concentration profile of small molecular weight metabolites, which act as reactants and products in metabolic reactions and as regulatory molecules of proteins participating in many biological processes. Thus, the metabolic profile provides a metabolic activity fingerprint, through the simultaneous analysis of tens to hundreds of molecules of pathophysiological and pharmacological interest. The application of metabolomics is at its standardization phase in general, and the challenges for paving a standardized procedure are even more pronounced in brain studies. In this review, we support the value of metabolomics in brain research. Moreover, we demonstrate the challenges of designing and setting up a reliable brain metabolomic study, which, among other parameters, has to take into consideration the sex differentiation and the complexity of brain physiology manifested in its regional variation. We finally propose ways to overcome these challenges and design a study that produces reproducible and consistent results.

  9. LUNAR DUST GRAIN CHARGING BY ELECTRON IMPACT: COMPLEX ROLE OF SECONDARY ELECTRON EMISSIONS IN SPACE ENVIRONMENTS

    International Nuclear Information System (INIS)

    Abbas, M. M.; Craven, P. D.; LeClair, A. C.; Spann, J. F.; Tankosic, D.

    2010-01-01

    Dust grains in various astrophysical environments are generally charged electrostatically by photoelectric emissions with radiation from nearby sources, or by electron/ion collisions by sticking or secondary electron emissions (SEEs). The high vacuum environment on the lunar surface leads to some unusual physical and dynamical phenomena involving dust grains with high adhesive characteristics, and levitation and transportation over long distances. Knowledge of the dust grain charges and equilibrium potentials is important for understanding a variety of physical and dynamical processes in the interstellar medium, and heliospheric, interplanetary/planetary, and lunar environments. It has been well recognized that the charging properties of individual micron-/submicron-size dust grains are expected to be substantially different from the corresponding values for bulk materials. In this paper, we present experimental results on the charging of individual 0.2-13 μm size dust grains selected from Apollo 11 and 17 dust samples, and spherical silica particles by exposing them to mono-energetic electron beams in the 10-200 eV energy range. The dust charging process by electron impact involving the SEEs discussed is found to be a complex charging phenomenon with strong particle size dependence. The measurements indicate substantial differences between the polarity and magnitude of the dust charging rates of individual small-size dust grains, and the measurements and model properties of corresponding bulk materials. A more comprehensive plan of measurements of the charging properties of individual dust grains for developing a database for realistic models of dust charging in astrophysical and lunar environments is in progress.

  10. Lunary Dust Grain Charging by Electron Impact: Complex Role of Secondary Electron Emissions in Space Environments

    Science.gov (United States)

    Abbas, M. M.; Tankosic, D.; Crave, P. D.; LeClair, A.; Spann, J. F.

    2010-01-01

    Dust grains in various astrophysical environments are generally charged electrostatically by photoelectric emissions with radiation from nearby sources, or by electron/ion collisions by sticking or secondary electron emissions (SEES). The high vacuum environment on the lunar surface leads to some unusual physical and dynamical phenomena involving dust grains with high adhesive characteristics, and levitation and transportation over long distances. Knowledge of the dust grain charges and equilibrium potentials is important for understanding a variety of physical and dynamical processes in the interstellar medium, and heliospheric, interplanetary/ planetary, and lunar environments. It has been well recognized that the charging properties of individual micron-/submicron-size dust grains are expected to be substantially different from the corresponding values for bulk materials. In this paper, we present experimental results on the charging of individual 0.2-13 m size dust grains selected from Apollo 11 and 17 dust samples, and spherical silica particles by exposing them to mono-energetic electron beams in the 10-200 eV energy range. The dust charging process by electron impact involving the SEES discussed is found to be a complex charging phenomenon with strong particle size dependence. The measurements indicate substantial differences between the polarity and magnitude of the dust charging rates of individual small-size dust grains, and the measurements and model properties of corresponding bulk materials. A more comprehensive plan of measurements of the charging properties of individual dust grains for developing a database for realistic models of dust charging in astrophysical and lunar environments is in progress.

  11. Integration of metabolomics data into metabolic networks.

    Science.gov (United States)

    Töpfer, Nadine; Kleessen, Sabrina; Nikoloski, Zoran

    2015-01-01

    Metabolite levels together with their corresponding metabolic fluxes are integrative outcomes of biochemical transformations and regulatory processes and they can be used to characterize the response of biological systems to genetic and/or environmental changes. However, while changes in transcript or to some extent protein levels can usually be traced back to one or several responsible genes, changes in fluxes and particularly changes in metabolite levels do not follow such rationale and are often the outcome of complex interactions of several components. The increasing quality and coverage of metabolomics technologies have fostered the development of computational approaches for integrating metabolic read-outs with large-scale models to predict the physiological state of a system. Constraint-based approaches, relying on the stoichiometry of the considered reactions, provide a modeling framework amenable to analyses of large-scale systems and to the integration of high-throughput data. Here we review the existing approaches that integrate metabolomics data in variants of constrained-based approaches to refine model reconstructions, to constrain flux predictions in metabolic models, and to relate network structural properties to metabolite levels. Finally, we discuss the challenges and perspectives in the developments of constraint-based modeling approaches driven by metabolomics data.

  12. A range of complex probabilistic models for RNA secondary structure prediction that includes the nearest-neighbor model and more.

    Science.gov (United States)

    Rivas, Elena; Lang, Raymond; Eddy, Sean R

    2012-02-01

    The standard approach for single-sequence RNA secondary structure prediction uses a nearest-neighbor thermodynamic model with several thousand experimentally determined energy parameters. An attractive alternative is to use statistical approaches with parameters estimated from growing databases of structural RNAs. Good results have been reported for discriminative statistical methods using complex nearest-neighbor models, including CONTRAfold, Simfold, and ContextFold. Little work has been reported on generative probabilistic models (stochastic context-free grammars [SCFGs]) of comparable complexity, although probabilistic models are generally easier to train and to use. To explore a range of probabilistic models of increasing complexity, and to directly compare probabilistic, thermodynamic, and discriminative approaches, we created TORNADO, a computational tool that can parse a wide spectrum of RNA grammar architectures (including the standard nearest-neighbor model and more) using a generalized super-grammar that can be parameterized with probabilities, energies, or arbitrary scores. By using TORNADO, we find that probabilistic nearest-neighbor models perform comparably to (but not significantly better than) discriminative methods. We find that complex statistical models are prone to overfitting RNA structure and that evaluations should use structurally nonhomologous training and test data sets. Overfitting has affected at least one published method (ContextFold). The most important barrier to improving statistical approaches for RNA secondary structure prediction is the lack of diversity of well-curated single-sequence RNA secondary structures in current RNA databases.

  13. ECONOMIC AND LEGAL ASPECTS OF MANAGEMENT OF WASTES AND SECONDARY MATERIAL RESOURCES (ON THE EXAMPLE OF CONSTRUCTION COMPLEX

    Directory of Open Access Journals (Sweden)

    Tskhovrebov Eduard Stanislavovich

    2018-05-01

    Full Text Available Subject: technical and economic processes and aspects of handling wastes and secondary material resources; stages of transition of anthropogenic object of environment to wastes and secondary material resources; technical possibility and economic feasibility of using secondary material resources as a secondary raw material for making products, providing energy, works, services. The problem of economy and rational use of material and power resources is relevant and significant within the limits of maintenance of a strategic course of Russia on innovative sustainable development. In this article, issues of actualization and harmonization of the regulatory and legal base in the field of management of wastes and secondary material resources are considered from the viewpoint of maintenance of minimization of waste formation and maximum use of secondary material resources in an industrial-economic cycle, provision of economic incentives for innovative activity in the given field. The actual multi-plan problem, chosen here as a topic of research, concerns regulations in management of wastes and secondary material resources in construction complex, in which economic, civil-law, ecological, social, industrial and legal relations are closely coordinated and define a subject of the present research. Production and consumption waste is a dangerous anthropogenic object of the environment but at the same time, it is a valuable secondary material resource. The non-use of wastes to be recycled as secondary raw materials for energy generation, production and, as a result, their increasing accumulation in the environment causes irreparable harm to natural objects and human health due to their dangerous properties. Research objectives: scientific and methodological substantiation of legal regulation, economic basis for formation of wastes and secondary material resources management system (on the example of construction complex and building materials industry

  14. Metabolomics as an emerging strategy for the investigation of yogurt components

    NARCIS (Netherlands)

    Settachaimongkon, S.; Valenberg, van H.J.F.; Smid, E.J.

    2017-01-01

    The advanced development in metabolomics allows discovery of a wide range of metabolites in complex biological systems including food matrices. This analytical approach provides opportunities to attain a global metabolite profile and discover potential biomarkers and various chemical contaminants

  15. Metabolomics of Genetically Modified Crops

    Directory of Open Access Journals (Sweden)

    Carolina Simó

    2014-10-01

    Full Text Available Metabolomic-based approaches are increasingly applied to analyse genetically modified organisms (GMOs making it possible to obtain broader and deeper information on the composition of GMOs compared to that obtained from traditional analytical approaches. The combination in metabolomics of advanced analytical methods and bioinformatics tools provides wide chemical compositional data that contributes to corroborate (or not the substantial equivalence and occurrence of unintended changes resulting from genetic transformation. This review provides insight into recent progress in metabolomics studies on transgenic crops focusing mainly in papers published in the last decade.

  16. Metabolomics of Genetically Modified Crops

    Science.gov (United States)

    Simó, Carolina; Ibáñez, Clara; Valdés, Alberto; Cifuentes, Alejandro; García-Cañas, Virginia

    2014-01-01

    Metabolomic-based approaches are increasingly applied to analyse genetically modified organisms (GMOs) making it possible to obtain broader and deeper information on the composition of GMOs compared to that obtained from traditional analytical approaches. The combination in metabolomics of advanced analytical methods and bioinformatics tools provides wide chemical compositional data that contributes to corroborate (or not) the substantial equivalence and occurrence of unintended changes resulting from genetic transformation. This review provides insight into recent progress in metabolomics studies on transgenic crops focusing mainly in papers published in the last decade. PMID:25334064

  17. Can NMR solve some significant challenges in metabolomics?

    Science.gov (United States)

    Gowda, G.A. Nagana; Raftery, Daniel

    2015-01-01

    The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact biospecimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory. PMID:26476597

  18. Can NMR solve some significant challenges in metabolomics?

    Science.gov (United States)

    Nagana Gowda, G. A.; Raftery, Daniel

    2015-11-01

    The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact bio-specimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory.

  19. Higher Order Inclusion Complexes and Secondary Interactions Studied by Global Analysis of Calorimetric Titrations

    DEFF Research Database (Denmark)

    Schönbeck, Jens Christian Sidney; Holm, René; Westh, Peter

    2012-01-01

    This paper investigates the use of isothermal titration calorimetry (ITC) as a tool for studying molecular systems in which weaker secondary interactions are present in addition to a dominant primary interaction. Such systems are challenging since the signal pertaining to the stronger primary......). The results are validated by a 13C NMR titration and negative controls with a bile salt with no secondary binding site (glycocholate) (K = 2.96 ± 0.01 × 103 M–1). The method proved useful for detailed analysis of ITC data and may strengthen its use as a tool for studying molecular systems by advanced binding...

  20. Methods to assess secondary volatile lipid oxidation products in complex food matrices

    DEFF Research Database (Denmark)

    Jacobsen, Charlotte; Yesiltas, Betül

    A range of different methods are available to determine secondary volatile lipid oxidation products. These methods include e.g. spectrophotometric determination of anisidine values and TBARS as well as GC based methods for determination of specific volatile oxidation products such as pentanal...... headspace methods on the same food matrices will be presented....

  1. The Caenorhabditis elegans RDE-10/RDE-11 complex regulates RNAi by promoting secondary siRNA amplification.

    Science.gov (United States)

    Zhang, Chi; Montgomery, Taiowa A; Fischer, Sylvia E J; Garcia, Susana M D A; Riedel, Christian G; Fahlgren, Noah; Sullivan, Christopher M; Carrington, James C; Ruvkun, Gary

    2012-05-22

    In nematodes, plants, and fungi, RNAi is remarkably potent and persistent due to the amplification of initial silencing signals by RNA-dependent RNA polymerases (RdRPs). In Caenorhabditis elegans (C. elegans), the interaction between the RNA-induced silencing complex (RISC) loaded with primary small interfering RNAs (siRNAs) and the target messenger RNA (mRNA) leads to the recruitment of RdRPs and synthesis of secondary siRNAs using the target mRNA as the template. The mechanism and genetic requirements for secondary siRNA accumulation are not well understood. From a forward genetic screen for C. elegans genes required for RNAi, we identified rde-10, and through proteomic analysis of RDE-10-interacting proteins, we identified a protein complex containing the new RNAi factor RDE-11, the known RNAi factors RSD-2 and ERGO-1, and other candidate RNAi factors. The RNAi defective genes rde-10 and rde-11 encode a novel protein and a RING-type zinc finger domain protein, respectively. Mutations in rde-10 and rde-11 genes cause dosage-sensitive RNAi deficiencies: these mutants are resistant to low dosage but sensitive to high dosage of double-stranded RNAs. We assessed the roles of rde-10, rde-11, and other dosage-sensitive RNAi-defective genes rsd-2, rsd-6, and haf-6 in both exogenous and endogenous small RNA pathways using high-throughput sequencing and qRT-PCR. These genes are required for the accumulation of secondary siRNAs in both exogenous and endogenous RNAi pathways. The RDE-10/RDE-11 complex is essential for the amplification of RNAi in C. elegans by promoting secondary siRNA accumulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Metabolomics Workbench (MetWB)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Metabolomics Program's Data Repository and Coordinating Center (DRCC), housed at the San Diego Supercomputer Center (SDSC), University of California, San Diego,...

  3. NMR-based metabolomics applications

    DEFF Research Database (Denmark)

    Iaccarino, Nunzia

    Metabolomics is the scientific discipline that identifies and quantifies endogenous and exogenous metabolites in different biological samples. Metabolites are crucial components of a biological system and they are highly informative about its functional state, due to their closeness to the organism...... focused on the analysis of various samples covering a wide range of fields, namely, food and nutraceutical sciences, cell metabolomics and medicine using a metabolomics approach. Indeed, the first part of the thesis describes two exploratory studies performed on Algerian extra virgin olive oil and apple...... juice from ancient Danish apple cultivars. Both studies revealed variety-related peculiarities that would have been difficult to detect by means of traditional analysis. The second part of the project includes four metabolomics studies performed on samples of biological origin. In particular, the first...

  4. The biology of plant metabolomics

    NARCIS (Netherlands)

    Hall, R.D.

    2011-01-01

    Following a general introduction, this book includes details of metabolomics of model species including Arabidopsis and tomato. Further chapters provide in-depth coverage of abiotic stress, data integration, systems biology, genetics, genomics, chemometrics and biostatisitcs. Applications of plant

  5. Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1-Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism.

    Science.gov (United States)

    Volovelsky, Oded; Cohen, Gili; Kenig, Ariel; Wasserman, Gilad; Dreazen, Avigail; Meyuhas, Oded; Silver, Justin; Naveh-Many, Tally

    2016-04-01

    Secondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6(p-/-) mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid-induced AKI. Uremic rpS6(p-/-) mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild-type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6. Copyright © 2016 by the American Society of Nephrology.

  6. Fast Swinnex Filtration (FSF): A fast and robust sampling and extraction method suitable for metabolomics analysis of cultures grown in complex media

    DEFF Research Database (Denmark)

    McCloskey, Douglas; Utrilla, Jose; Naviaux, Robert K.

    2015-01-01

    , we develop a fast-filtration method using pressuredriven Swinnex filters. We show that the method is fast enough to provide an accurate snapshot of intracellular metabolism, reduces matrix interference from the media to improve the number of compounds that can be detected, and is applicable...... to anaerobic and aerobic liquid cultures grown in a variety of culturing systems. Furthermore, we apply the fast filtration method to investigate differences in the absolute intracellular metabolite levels of anaerobic cultures grown in minimal and complex media....

  7. CAE Analysis of Secondary Shaft Systems in Great Five-axis Turning-Milling Complex CNC Machine

    Directory of Open Access Journals (Sweden)

    Chih-Chiang Hong

    2018-01-01

    Full Text Available The commercial computer aided engineering (CAE software is used to analyze the linear-static construction, stress and deformation for the secondary shaft systems in great five-axis turning-milling complex computer numerical control (CNC machine. It is convenient and always only three dimensional (3D graphic parts needed firstly prepared and further more detail used for the commercial CAE. It is desirable to predict a deformed position for the cut tool under external pressure loads in the working process of CNC machine. The linear results for static analysis of stresses, displacements in corresponding to the screw shaft locates at top, medium and bottom positions of the secondary shaft systems are obtained by using the simulation module of SOLIDWORKS®.

  8. Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (s)-fluoxetine, and N-desmethyldiltiazem.

    Science.gov (United States)

    Hanson, Kelsey L; VandenBrink, Brooke M; Babu, Kantipudi N; Allen, Kyle E; Nelson, Wendel L; Kunze, Kent L

    2010-06-01

    Three secondary amines desipramine (DES), (S)-fluoxetine [(S)-FLX], and N-desmethyldiltiazem (MA) undergo N-hydroxylation to the corresponding secondary hydroxylamines [N-hydroxydesipramine, (S)-N-hydroxyfluoxetine, and N-hydroxy-N-desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N-desmethyldesipramine, (S)-norfluoxetine, and N,N-didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine > primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N-dealkylation to N-hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [(S)-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N-methyl-d(3)-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N-demethylation to N-hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N-hydroxylation rather than N-dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation.

  9. Transition metal complexes bearing NHC ligands substituted with secondary polyfluoroalkyl groups

    Czech Academy of Sciences Publication Activity Database

    Kolaříková, V.; Šimůnek, O.; Rybáčková, M.; Cvačka, Josef; Březinová, Anna; Kvíčala, J.

    2015-01-01

    Roč. 44, č. 45 (2015), s. 19663-19673 ISSN 1477-9226 Institutional support: RVO:61388963 Keywords : complexes * catalysis * Suzuki-Miyaura coupling Subject RIV: CA - Inorganic Chemistry Impact factor: 4.177, year: 2015

  10. Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade.

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2018-01-28

    The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

  11. Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2018-01-01

    The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

  12. Metabolomics in Radiation-Induced Biological Dosimetry: A Mini-Review and a Polyamine Study

    Directory of Open Access Journals (Sweden)

    Changhyun Roh

    2018-05-01

    Full Text Available In this study, we elucidate that polyamine metabolite is a powerful biomarker to study post-radiation changes. Metabolomics in radiation biodosimetry, the application of a metabolomics analysis to the field of radiobiology, promises to increase the understanding of biological responses by ionizing radiation (IR. Radiation exposure triggers a complex network of molecular and cellular responses that impacts metabolic processes and alters the levels of metabolites. Such metabolites have potential as biomarkers for radiation dosimetry. Among metabolites, polyamine is one of many potential biomarkers to estimate radiation response. In addition, this review provides an opportunity for the understanding of a radiation metabolomics in biodosimetry and a polyamine case study.

  13. Metabolomics Society’s International Affiliations

    NARCIS (Netherlands)

    Roessner, U.; Rolin, D.; Rijswijk, van M.E.C.; Hall, R.D.; Hankemeier, T.

    2015-01-01

    In 2012 the Metabolomics Society established a more formal system for national and regional metabolomics initiatives, interest groups, societies and networks to become an International Affiliate of the Society. A number of groups (http://metabolomicssociety.org/international-affilia

  14. Role of metabolomics in TBI research

    Science.gov (United States)

    Wolahan, Stephanie M.; Hirt, Daniel; Braas, Daniel; Glenn, Thomas C.

    2016-01-01

    Synopsis Metabolomics is an important member of the omics community in that it defines which small molecules may be responsible for disease states. This article reviews the essential principles of metabolomics from specimen preparation, chemical analysis, and advanced statistical methods. Metabolomics in TBI has so far been underutilized. Future metabolomics based studies focused on the diagnoses, prognoses, and treatment effects, need to be conducted across all types of TBI. PMID:27637396

  15. ECMDB: The E. coli Metabolome Database

    OpenAIRE

    Guo, An Chi; Jewison, Timothy; Wilson, Michael; Liu, Yifeng; Knox, Craig; Djoumbou, Yannick; Lo, Patrick; Mandal, Rupasri; Krishnamurthy, Ram; Wishart, David S.

    2012-01-01

    The Escherichia coli Metabolome Database (ECMDB, http://www.ecmdb.ca) is a comprehensively annotated metabolomic database containing detailed information about the metabolome of E. coli (K-12). Modelled closely on the Human and Yeast Metabolome Databases, the ECMDB contains >2600 metabolites with links to ?1500 different genes and proteins, including enzymes and transporters. The information in the ECMDB has been collected from dozens of textbooks, journal articles and electronic databases. E...

  16. Targeting of the hydrophobic metabolome by pathogens.

    Science.gov (United States)

    Helms, J Bernd; Kaloyanova, Dora V; Strating, Jeroen R P; van Hellemond, Jaap J; van der Schaar, Hilde M; Tielens, Aloysius G M; van Kuppeveld, Frank J M; Brouwers, Jos F

    2015-05-01

    The hydrophobic molecules of the metabolome - also named the lipidome - constitute a major part of the entire metabolome. Novel technologies show the existence of a staggering number of individual lipid species, the biological functions of which are, with the exception of only a few lipid species, unknown. Much can be learned from pathogens that have evolved to take advantage of the complexity of the lipidome to escape the immune system of the host organism and to allow their survival and replication. Different types of pathogens target different lipids as shown in interaction maps, allowing visualization of differences between different types of pathogens. Bacterial and viral pathogens target predominantly structural and signaling lipids to alter the cellular phenotype of the host cell. Fungal and parasitic pathogens have complex lipidomes themselves and target predominantly the release of polyunsaturated fatty acids from the host cell lipidome, resulting in the generation of eicosanoids by either the host cell or the pathogen. Thus, whereas viruses and bacteria induce predominantly alterations in lipid metabolites at the host cell level, eukaryotic pathogens focus on interference with lipid metabolites affecting systemic inflammatory reactions that are part of the immune system. A better understanding of the interplay between host-pathogen interactions will not only help elucidate the fundamental role of lipid species in cellular physiology, but will also aid in the generation of novel therapeutic drugs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Viewbrics: Formative Assessment of Complex Skills with Video-Enhanced Rubrics (VER) in Dutch Secondary Education

    NARCIS (Netherlands)

    Rusman, Ellen; Nadolski, Rob; Boon, Jo; Ackermans, Kevin

    2016-01-01

    To learn complex skills, like collaboration, learners need to acquire a concrete and consistent mental model of what it means to master this skill. If learners know their current mastery level and know their targeted mastery level, they can better determine their subsequent learning activities.

  18. Metabolomics: the chemistry between ecology and genetics

    NARCIS (Netherlands)

    Macel, M.; Van Dam, N.M.; Keurentjes, J.J.B.

    2010-01-01

    Metabolomics is a fast developing field of comprehensive untargeted chemical analyses. It has many applications and can in principle be used on any organism without prior knowledge of the metabolome or genome. The amount of functional information that is acquired with metabolomics largely depends on

  19. Fungal community, Fusarium head blight complex and secondary metabolites associated with malting barley grains harvested in Umbria, central Italy.

    Science.gov (United States)

    Beccari, Giovanni; Senatore, Maria Teresa; Tini, Francesco; Sulyok, Michael; Covarelli, Lorenzo

    2018-05-20

    In recent years, due to the negative impact of toxigenic mycobiota and of the accumulation of their secondary metabolites in malting barley grains, monitoring the evolution of fungal communities in a certain cultivation area as well as detecting the different mycotoxins present in the raw material prior to malting and brewing processes have become increasingly important. In this study, a survey was carried out on malting barley samples collected after their harvest in the Umbria region (central Italy). Samples were analyzed to determine the composition of the fungal community, to identify the isolated Fusarium species, to quantify fungal secondary metabolites in the grains and to characterize the in vitro mycotoxigenic profile of a subset of the isolated Fusarium strains. The fungal community of barley grains was mainly composed of microorganisms belonging to the genus Alternaria (77%), followed by those belonging to the genus Fusarium (27%). The Fusarium head blight (FHB) complex was represented by nine species with the predominance of Fusarium poae (37%), followed by Fusarium avenaceum (23%), Fusarium graminearum (22%) and Fusarium tricinctum (7%). Secondary metabolites biosynthesized by Alternaria and Fusarium species were present in the analyzed grains. Among those biosynthesized by Fusarium species, nivalenol and enniatins were the most prevalent ones. Type A trichothecenes (T-2 and HT-2 toxins) as well as beauvericin were also present with a high incidence. Conversely, the number of samples contaminated with deoxynivalenol was low. Conjugated forms, such as deoxynivalenol-3-glucoside and HT-2-glucoside, were detected for the first time in malting barley grains cultivated in the surveyed area. In addition, strains of F. avenaceum and F. tricinctum showed the ability to biosynthesize in vitro high concentrations of enniatins. The analysis of fungal secondary metabolites, both in the grains and in vitro, revealed also the presence of other compounds, for which

  20. Long non-coding RNA discovery across the genus anopheles reveals conserved secondary structures within and beyond the Gambiae complex.

    Science.gov (United States)

    Jenkins, Adam M; Waterhouse, Robert M; Muskavitch, Marc A T

    2015-04-23

    Long non-coding RNAs (lncRNAs) have been defined as mRNA-like transcripts longer than 200 nucleotides that lack significant protein-coding potential, and many of them constitute scaffolds for ribonucleoprotein complexes with critical roles in epigenetic regulation. Various lncRNAs have been implicated in the modulation of chromatin structure, transcriptional and post-transcriptional gene regulation, and regulation of genomic stability in mammals, Caenorhabditis elegans, and Drosophila melanogaster. The purpose of this study is to identify the lncRNA landscape in the malaria vector An. gambiae and assess the evolutionary conservation of lncRNAs and their secondary structures across the Anopheles genus. Using deep RNA sequencing of multiple Anopheles gambiae life stages, we have identified 2,949 lncRNAs and more than 300 previously unannotated putative protein-coding genes. The lncRNAs exhibit differential expression profiles across life stages and adult genders. We find that across the genus Anopheles, lncRNAs display much lower sequence conservation than protein-coding genes. Additionally, we find that lncRNA secondary structure is highly conserved within the Gambiae complex, but diverges rapidly across the rest of the genus Anopheles. This study offers one of the first lncRNA secondary structure analyses in vector insects. Our description of lncRNAs in An. gambiae offers the most comprehensive genome-wide insights to date into lncRNAs in this vector mosquito, and defines a set of potential targets for the development of vector-based interventions that may further curb the human malaria burden in disease-endemic countries.

  1. The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

    Science.gov (United States)

    Serkova, Natalie J.; Standiford, Theodore J.

    2011-01-01

    Metabolomics, a science of systems biology, is the global assessment of endogenous metabolites within a biologic system and represents a “snapshot” reading of gene function, enzyme activity, and the physiological landscape. Metabolite detection, either individual or grouped as a metabolomic profile, is usually performed in cells, tissues, or biofluids by either nuclear magnetic resonance spectroscopy or mass spectrometry followed by sophisticated multivariate data analysis. Because loss of metabolic homeostasis is common in critical illness, the metabolome could have many applications, including biomarker and drug target identification. Metabolomics could also significantly advance our understanding of the complex pathophysiology of acute illnesses, such as sepsis and acute lung injury/acute respiratory distress syndrome. Despite this potential, the clinical community is largely unfamiliar with the field of metabolomics, including the methodologies involved, technical challenges, and, most importantly, clinical uses. Although there is evidence of successful preclinical applications, the clinical usefulness and application of metabolomics in critical illness is just beginning to emerge, the advancement of which hinges on linking metabolite data to known and validated clinically relevant indices. In addition, other important aspects, such as patient selection, sample collection, and processing, as well as the needed multivariate data analysis, have to be taken into consideration before this innovative approach to biomarker discovery can become a reliable tool in the intensive care unit. The purpose of this review is to begin to familiarize clinicians with the field of metabolomics and its application for biomarker discovery in critical illnesses such as sepsis. PMID:21680948

  2. An overview of renal metabolomics.

    Science.gov (United States)

    Kalim, Sahir; Rhee, Eugene P

    2017-01-01

    The high-throughput, high-resolution phenotyping enabled by metabolomics has been applied increasingly to a variety of questions in nephrology research. This article provides an overview of current metabolomics methodologies and nomenclature, citing specific considerations in sample preparation, metabolite measurement, and data analysis that investigators should understand when examining the literature or designing a study. Furthermore, we review several notable findings that have emerged in the literature that both highlight some of the limitations of current profiling approaches, as well as outline specific strengths unique to metabolomics. More specifically, we review data on the following: (i) tryptophan metabolites and chronic kidney disease onset, illustrating the interpretation of metabolite data in the context of established biochemical pathways; (ii) trimethylamine-N-oxide and cardiovascular disease in chronic kidney disease, illustrating the integration of exogenous and endogenous inputs to the blood metabolome; and (iii) renal mitochondrial function in diabetic kidney disease and acute kidney injury, illustrating the potential for rapid translation of metabolite data for diagnostic or therapeutic aims. Finally, we review future directions, including the need to better characterize interperson and intraperson variation in the metabolome, pool existing data sets to identify the most robust signals, and capitalize on the discovery potential of emerging nontargeted methods. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  3. Applied metabolomics in drug discovery.

    Science.gov (United States)

    Cuperlovic-Culf, M; Culf, A S

    2016-08-01

    The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs. This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads.

  4. Synthesis, spectroscopic, DFT calculations and biological activity studies of ruthenium carbonyl complexes with 2-picolinic acid and a secondary ligand

    Science.gov (United States)

    Shohayeb, Shahera M.; Mohamed, Rania G.; Moustafa, H.; El-Medani, Samir M.

    2016-09-01

    Thermal reaction of [Ru3(CO)12] with 2-picolinic acid (Hpic) in the absence and presence of a secondary ligand (pyridine, Py, bipyridine, Bipy, or thiourea, Tu) was investigated. Four complexes with molecular formulae: [Ru(CO)3(Hpic)], 1, [Ru2(CO)5(Hpic)(Py)], 2, [Ru2(CO)5(Hpic)(Tu)], 3 and [Ru2(CO)4(Hpic)(Bipy)], 4, were isolated. All complexes were characterized based on elemental analyses, IR, 1H NMR, magnetic studies, mass spectrometry and thermal analysis. The ligand and its complexes have been screened for antibacterial activities. Density Functional Theory (DFT) calculations at the B3LYP/6-311G (d,p)_ level of theory have been carried out to investigate the equilibrium geometry of the ligands. The optimized geometry parameters of the complexes were evaluated using B3LYP method and LANL2DZ basis set. The extent of natural charge population (core, valence and rydberg), exact electronic configuration, total Lewis and total non-Lewis are estimated and discussed in terms of natural bond orbitals (NBO) analysis.

  5. Deprotonation/protonation of coordinated secondary thioamide units of pincer ruthenium complexes: modulation of voltammetric and spectroscopic characterization of the pincer complexes.

    Science.gov (United States)

    Teratani, Takuya; Koizumi, Take-aki; Yamamoto, Takakazu; Tanaka, Koji; Kanbara, Takaki

    2011-09-21

    New pincer ruthenium complexes, [Ru(SCS)(tpy)]PF(6) (1) (SCS = 2,6-bis(benzylaminothiocarbonyl)phenyl), tpy = 2,2':6',2''-terpyridyl) and [Ru(SNS)(tpy)]PF(6) (2) (SNS = 2,5-bis(benzylaminothiocarbonyl)pyrrolyl), having κ(3)SCS and κ(3)SNS pincer ligands with two secondary thioamide units were synthesized by the reactions of [RuCl(3)(tpy)] with N,N'-dibenzyl-1,3-benzenedicarbothioamide (L1) and N,N'-dibenzyl-2,5-1H-pyrroledicarbothioamide (L2), respectively, and their chemical and electrochemical properties were elucidated. The structure of 1 was determined by X-ray crystallography. The complexes 1 and 2 showed a two-step deprotonation reaction by treatment with 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), and the addition of DBU led to a shift of the metal-centered redox couples to a lower potential by 720 and 550 mV, respectively. The di-deprotonated complexes were also studied by (1)H-NMR and UV-vis spectroscopy. The addition of methanesulfonic acid (MSA) to the di-deprotonated complexes enabled the recovery of 1 and 2, indicating that the thioamide moiety underwent a reversible deprotonation-protonation process, which resulted in regulating the redox potentials of the metal center. The Pourbaix diagram of 1 revealed that 1 underwent a one-proton/one-electron transfer process in the pH range of 5.83-10.35, and a two-proton/one-electron process at a pH of over 10.35, indicating that the deprotonation/protonation process of the complexes is related to proton-coupled electron transfer (PCET). This journal is © The Royal Society of Chemistry 2011

  6. Food metabolomics: from farm to human.

    Science.gov (United States)

    Kim, Sooah; Kim, Jungyeon; Yun, Eun Ju; Kim, Kyoung Heon

    2016-02-01

    Metabolomics, one of the latest components in the suite of systems biology, has been used to understand the metabolism and physiology of living systems, including microorganisms, plants, animals and humans. Food metabolomics can be defined as the application of metabolomics in food systems, including food resources, food processing and diet for humans. The study of food metabolomics has increased gradually in the recent years, because food systems are directly related to nutrition and human health. This review describes the recent trends and applications of metabolomics to food systems, from farm to human, including food resource production, industrial food processing and food intake by humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites

    Science.gov (United States)

    Studt, Lena; Niehaus, Eva-Maria; Espino, Jose J.; Huß, Kathleen; Michielse, Caroline B.; Albermann, Sabine; Wagner, Dominik; Bergner, Sonja V.; Connolly, Lanelle R.; Fischer, Andreas; Reuter, Gunter; Kleigrewe, Karin; Bald, Till; Wingfield, Brenda D.; Ophir, Ron; Freeman, Stanley; Hippler, Michael; Smith, Kristina M.; Brown, Daren W.; Proctor, Robert H.; Münsterkötter, Martin; Freitag, Michael; Humpf, Hans-Ulrich; Güldener, Ulrich; Tudzynski, Bettina

    2013-01-01

    The fungus Fusarium fujikuroi causes “bakanae” disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary success of F

  8. Radiation Metabolomics: Current Status and Future Directions

    Directory of Open Access Journals (Sweden)

    Smrithi eSugumaran Menon

    2016-02-01

    Full Text Available Human exposure to ionizing radiation disrupts normal metabolic processes in cells and organs by inducing complex biological responses that interfere with gene and protein expression. Conventional dosimetry, monitoring of prodromal symptoms and peripheral lymphocyte counts are of limited value as organ and tissue specific biomarkers for personnel exposed to radiation, particularly, weeks or months after exposure. Analysis of metabolites generated in known stress-responsive pathways by molecular profiling helps to predict the physiological status of an individual in response to environmental or genetic perturbations. Thus, a multi-metabolite profile obtained from a high resolution mass spectrometry-based metabolomics platform offers potential for identification of robust biomarkers to predict radiation toxicity of organs and tissues resulting from exposures to therapeutic or non-therapeutic ionizing radiation. Here, we review the status of radiation metabolomics and explore applications as a standalone technology, as well as its integration in systems biology, to facilitate a better understanding of the molecular basis of radiation response. Finally, we draw attention to the identification of specific pathways that can be targeted for the development of therapeutics to alleviate or mitigate harmful effects of radiation exposure.

  9. Recent Highlights of Metabolomics in Chinese Medicine Syndrome Research

    Directory of Open Access Journals (Sweden)

    Ai-hua Zhang

    2013-01-01

    Full Text Available Chinese medicine syndrome (CMS, “ZHENG” in Chinese is an understanding of the regularity of disease occurrence and development as well as a certain stage of a comprehensive response of patients with body condition. However, because of the complexity of CMS and the limitation of present investigation method, the research for deciphering the scientific basis and systematic features of CMS is difficult to go further. Metabolomics enables mapping of early biochemical changes in disease and hence provides an opportunity to develop predictive biomarkers. Moreover, its method and design resemble those of traditional Chinese medicine (TCM which focuses on human disease via the integrity of close relationship between body and syndromes. In the systemic context, metabolomics has a convergence with TCM syndrome; therefore it could provide useful tools for exploring essence of CMS disease, facilitating personalized TCM, and will help to in-depth understand CMS. The integration of the metabolomics and CMS aspects will give promise to bridge the gap between Chinese and Western medicine and help catch the traditional features of CMS. In this paper, particular attention will be paid to the past successes in applications of robust metabolomic approaches to contribute to low-molecular-weight metabolites (biomarkers discovery in CMS research and development.

  10. Carpal instabilities and secondary degenerative changes due to lesions of the radiocarpal ligament complex

    International Nuclear Information System (INIS)

    Stabler, A.; Berger, H.; Lissner, J.

    1990-01-01

    This paper reports on trauma, rheumatoid arthritis, calcium pyrophosphate dihydrate crystal deposition (CPDD), neurologic disease, and beta 2 -microglobulin-related amyloid deposits in patients undergoing chronic hemodialysis that can lead to distinct lesions of the radiocarpal ligament complex, causing rotational subluxation of the scaphoid and ulnar translocation of the carpus. The clinical and radiologic findings were analyzed in 35 patients, examined from 1985 to 1989. Degenerative changes in rotational subluxation of the scaphoid develop in three steps. First there is osteoarthritis at the styloid process, then the degeneration progresses into the central midcarpal joint, and finally it progresses to the ulnar midcarpal joint. Despite different etiologies of ligament failure, the radiologic features are very similar, because the mechanism of degeneration is identical in posttraumatic, inflammatory, neurogenic, CPDD, or beta 2 -microglobulin-related instability. However, there are some distinct radiologic differences in relation to the primary cause of the ligament defect

  11. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology.

    Science.gov (United States)

    Aretz, Ina; Meierhofer, David

    2016-04-27

    Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

  12. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology

    Directory of Open Access Journals (Sweden)

    Ina Aretz

    2016-04-01

    Full Text Available Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

  13. THE LESSONIA NIGRESCENS SPECIES COMPLEX (LAMINARIALES, PHAEOPHYCEAE) SHOWS STRICT PARAPATRY AND COMPLETE REPRODUCTIVE ISOLATION IN A SECONDARY CONTACT ZONE(1).

    Science.gov (United States)

    Tellier, Florence; Tapia, Javier; Faugeron, Sylvain; Destombe, Christophe; Valero, Myriam

    2011-08-01

    During secondary contact between phylogenetically closely related species (sibling species) having diverged in allopatry, the maintenance of species integrity depends on intrinsic and extrinsic reproductive barriers. In kelps (Phaeophyceae), the observations of hybrids in laboratory conditions suggest that reproductive isolation is incomplete. However, not all interspecific crosses are successful, and very few hybrids have been observed in nature, despite the co-occurrence of many kelp species in sympatry. This suggests that there are reproductive barriers that maintain species integrity. In this study, we characterized the fine genetic structure of a secondary contact zone to clarify the extent of reproductive isolation between two sister species. In Lessonia nigrescens Bory (Laminariales, Phaeophyta) species complex, two cryptic species have been recently found out from gene phylogenies, and-waiting for a formal taxonomic description-we used their geographic distribution to name them (northern and southern species). We studied 12 populations, distributed along 50 km of coastline, and employed two molecular approaches, assigning individuals to phylogenetic species according to a diagnostic mitochondrial marker (351 individuals analyzed) and quantifying interspecific gene flow with four microsatellite markers (248 individuals analyzed). No hybridization or introgression was revealed, indicating complete reproductive isolation in natural conditions. Unexpectedly, our study demonstrated that the two species were strictly segregated in space. This absence of co-occurrence along the contact zone can partially explain the lack of hybridization, raising new interesting questions as to the mechanisms that limit sympatry at small spatial scales. © 2011 Phycological Society of America.

  14. Postmodification of MOF-5 using secondary complex formation using 8- hydroxyquinoline (HOQ) for the development of visible light active photocatalysts

    Science.gov (United States)

    Thakare, Sanjay R.; Ramteke, Shruti M.

    2018-05-01

    A novel HOQ@MOF-5 compound photocatalyst was successfully constructed by interacting 8- Hydroxyquinoline with MOF-5 synthesized through a room temperature method. The secondary complex formation between the Zn cluster with 8-Hydroxyquinoline harnessed visible light and acted as a mediator to transfer photoinduced electrons to MOF-5 for enhancing the photocatalytic reaction rate with visible light. HOQ@MOF-5 was characterized by various spectroscopic techniques, such as XRD showing the crystalline nature of compound, UV-Visible spectroscopy showing the 2.54 eV band gap of HOQ@MOF-5 and morphological analysis tools, such as the nanoparticle nature of the compound with 9.561 nm particle size. The photocatalytic effect was estimated using the photocatalytic degradation of phenol as a representative organic pollutant under visible light irradiation. This work provides a new compound acting as source of electrons transfer for the development of efficient photocatalysts for remediation of environmental pollution.

  15. Peptaibol, secondary-metabolite, and hydrophobin pattern of commercial biocontrol agents formulated with species of the Trichoderma harzianum complex.

    Science.gov (United States)

    Degenkolb, Thomas; Fog Nielsen, Kristian; Dieckmann, Ralf; Branco-Rocha, Fabiano; Chaverri, Priscila; Samuels, Gary J; Thrane, Ulf; von Döhren, Hans; Vilcinskas, Andreas; Brückner, Hans

    2015-04-01

    The production of bioactive polypeptides (peptaibiotics) in vivo is a sophisticated adaptation strategy of both mycoparasitic and saprotrophic Trichoderma species for colonizing and defending their natural habitats. This feature is of major practical importance, as the detection of peptaibiotics in plant-protective Trichoderma species, which are successfully used against economically relevant bacterial and fungal plant pathogens, certainly contributes to a better understanding of these complex antagonistic interactions. We analyzed five commercial biocontrol agents (BCAs), namely Canna(®) , Trichosan(®) , Vitalin(®) , Promot(®) WP, and TrichoMax(®) , formulated with recently described species of the Trichoderma harzianum complex, viz. T. afroharzianum, T. simmonsii, and T. guizhouense. By using the well-established, HPLC/MS-based peptaibiomics approach, it could unequivocally be demonstrated that all of these formulations contained new and recurrent peptaibols, i.e., peptaibiotics carrying an acetylated N-terminus, the C-terminus of which is reduced to a 1,2-amino alcohol. Their chain lengths, including the amino alcohol, were 11, 14, and 18 residues, respectively. Peptaibols were also to be the dominating secondary metabolites in plate cultures of the four strains obtained from four of the Trichoderma- based BCAs, contributing 95% of the UHPLC-UV/VIS peak areas and 99% of the total ion count MS peak area from solid media. Furthermore, species-specific hydrophobins, as well as non-peptaibiotic secondary metabolites, were detected, the latter being known for their antifungal, siderophore, or plant-growth-promoting activities. Notably, none of the isolates produced low-molecular weight mycotoxins. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

  16. New approaches for metabolomics by mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Vertes, Akos [George Washington Univ., Washington, DC (United States)

    2017-07-10

    Small molecules constitute a large part of the world around us, including fossil and some renewable energy sources. Solar energy harvested by plants and bacteria is converted into energy rich small molecules on a massive scale. Some of the worst contaminants of the environment and compounds of interest for national security also fall in the category of small molecules. The development of large scale metabolomic analysis methods lags behind the state of the art established for genomics and proteomics. This is commonly attributed to the diversity of molecular classes included in a metabolome. Unlike nucleic acids and proteins, metabolites do not have standard building blocks, and, as a result, their molecular properties exhibit a wide spectrum. This impedes the development of dedicated separation and spectroscopic methods. Mass spectrometry (MS) is a strong contender in the quest for a quantitative analytical tool with extensive metabolite coverage. Although various MS-based techniques are emerging for metabolomics, many of these approaches include extensive sample preparation that make large scale studies resource intensive and slow. New ionization methods are redefining the range of analytical problems that can be solved using MS. This project developed new approaches for the direct analysis of small molecules in unprocessed samples, as well as pushed the limits of ultratrace analysis in volume limited complex samples. The projects resulted in techniques that enabled metabolomics investigations with enhanced molecular coverage, as well as the study of cellular response to stimuli on a single cell level. Effectively individual cells became reaction vessels, where we followed the response of a complex biological system to external perturbation. We established two new analytical platforms for the direct study of metabolic changes in cells and tissues following external perturbation. For this purpose we developed a novel technique, laser ablation electrospray

  17. Vitamins, metabolomics, and prostate cancer.

    Science.gov (United States)

    Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

    2017-06-01

    How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease. Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

  18. The metabolomics standards initiative (MSI)

    NARCIS (Netherlands)

    Fiehn, O.; Robertson, D.; Griffin, J.; Werf, M. van der; Nikolau, B.; Morrison, N.; Sumner, L.W.; Goodacre, R.; Hardy, N.W.; Taylor, C.; Fostel, J.; Kristal, B.; Kaddurah-Daouk, R.; Mendes, P.; Ommen, B. van; Lindon, J.C.; Sansone, S.-A.

    2007-01-01

    In 2005, the Metabolomics Standards Initiative has been formed. An outline and general introduction is provided to inform about the history, structure, working plan and intentions of this initiative. Comments on any of the suggested minimal reporting standards are welcome to be sent to the open

  19. Metabolomic and high-throughput sequencing analysis—modern approach for the assessment of biodeterioration of materials from historic buildings

    Science.gov (United States)

    Gutarowska, Beata; Celikkol-Aydin, Sukriye; Bonifay, Vincent; Otlewska, Anna; Aydin, Egemen; Oldham, Athenia L.; Brauer, Jonathan I.; Duncan, Kathleen E.; Adamiak, Justyna; Sunner, Jan A.; Beech, Iwona B.

    2015-01-01

    Preservation of cultural heritage is of paramount importance worldwide. Microbial colonization of construction materials, such as wood, brick, mortar, and stone in historic buildings can lead to severe deterioration. The aim of the present study was to give modern insight into the phylogenetic diversity and activated metabolic pathways of microbial communities colonized historic objects located in the former Auschwitz II–Birkenau concentration and extermination camp in Oświecim, Poland. For this purpose we combined molecular, microscopic and chemical methods. Selected specimens were examined using Field Emission Scanning Electron Microscopy (FESEM), metabolomic analysis and high-throughput Illumina sequencing. FESEM imaging revealed the presence of complex microbial communities comprising diatoms, fungi and bacteria, mainly cyanobacteria and actinobacteria, on sample surfaces. Microbial diversity of brick specimens appeared higher than that of the wood and was dominated by algae and cyanobacteria, while wood was mainly colonized by fungi. DNA sequences documented the presence of 15 bacterial phyla representing 99 genera including Halomonas, Halorhodospira, Salinisphaera, Salinibacterium, Rubrobacter, Streptomyces, Arthrobacter and nine fungal classes represented by 113 genera including Cladosporium, Acremonium, Alternaria, Engyodontium, Penicillium, Rhizopus, and Aureobasidium. Most of the identified sequences were characteristic of organisms implicated in deterioration of wood and brick. Metabolomic data indicated the activation of numerous metabolic pathways, including those regulating the production of primary and secondary metabolites, for example, metabolites associated with the production of antibiotics, organic acids and deterioration of organic compounds. The study demonstrated that a combination of electron microscopy imaging with metabolomic and genomic techniques allows to link the phylogenetic information and metabolic profiles of microbial

  20. Metabolomic and high-throughput sequencing analysis – modern approach for the assessment of biodeterioration of materials from historic buildings

    Directory of Open Access Journals (Sweden)

    Beata eGutarowska

    2015-09-01

    Full Text Available Preservation of cultural heritage is of paramount importance worldwide. Microbial colonization of construction materials, such as wood, brick, mortar and stone in historic buildings can lead to severe deterioration. The aim of the present study was to give modern insight into the phylogenetic diversity and activated metabolic pathways of microbial communities colonized historic objects located in the former Auschwitz II-Birkenau concentration and extermination camp in Oświęcim, Poland. For this purpose we combined molecular, microscopic and chemical methods. Selected specimens were examined using Field Emission Scanning Electron Microscopy (FESEM, metabolomic analysis and high-throughput Illumina sequencing. FESEM imaging revealed the presence of complex microbial communities comprising diatoms, fungi and bacteria, mainly cyanobacteria and actinobacteria, on sample surfaces. Microbial diversity of brick specimens appeared higher than that of the wood and was dominated by algae and cyanobacteria, while wood was mainly colonized by fungi. DNA sequences documented the presence of 15 bacterial phyla representing 99 genera including Halomonas, Halorhodospira, Salinisphaera, Salinibacterium, Rubrobacter, Streptomyces, Arthrobacter and 9 fungal classes represented by 113 genera including Cladosporium, Acremonium, Alternaria, Engyodontium, Penicillium, Rhizopus and Aureobasidium. Most of the identified sequences were characteristic of organisms implicated in deterioration of wood and brick. Metabolomic data indicated the activation of numerous metabolic pathways, including those regulating the production of primary and secondary metabolites, for example, metabolites associated with the production of antibiotics, organic acids and deterioration of organic compounds. The study demonstrated that a combination of electron microscopy imaging with metabolomic and genomic techniques allows to link the phylogenetic information and metabolic profiles of

  1. Metabolomic and high-throughput sequencing analysis-modern approach for the assessment of biodeterioration of materials from historic buildings.

    Science.gov (United States)

    Gutarowska, Beata; Celikkol-Aydin, Sukriye; Bonifay, Vincent; Otlewska, Anna; Aydin, Egemen; Oldham, Athenia L; Brauer, Jonathan I; Duncan, Kathleen E; Adamiak, Justyna; Sunner, Jan A; Beech, Iwona B

    2015-01-01

    Preservation of cultural heritage is of paramount importance worldwide. Microbial colonization of construction materials, such as wood, brick, mortar, and stone in historic buildings can lead to severe deterioration. The aim of the present study was to give modern insight into the phylogenetic diversity and activated metabolic pathways of microbial communities colonized historic objects located in the former Auschwitz II-Birkenau concentration and extermination camp in Oświecim, Poland. For this purpose we combined molecular, microscopic and chemical methods. Selected specimens were examined using Field Emission Scanning Electron Microscopy (FESEM), metabolomic analysis and high-throughput Illumina sequencing. FESEM imaging revealed the presence of complex microbial communities comprising diatoms, fungi and bacteria, mainly cyanobacteria and actinobacteria, on sample surfaces. Microbial diversity of brick specimens appeared higher than that of the wood and was dominated by algae and cyanobacteria, while wood was mainly colonized by fungi. DNA sequences documented the presence of 15 bacterial phyla representing 99 genera including Halomonas, Halorhodospira, Salinisphaera, Salinibacterium, Rubrobacter, Streptomyces, Arthrobacter and nine fungal classes represented by 113 genera including Cladosporium, Acremonium, Alternaria, Engyodontium, Penicillium, Rhizopus, and Aureobasidium. Most of the identified sequences were characteristic of organisms implicated in deterioration of wood and brick. Metabolomic data indicated the activation of numerous metabolic pathways, including those regulating the production of primary and secondary metabolites, for example, metabolites associated with the production of antibiotics, organic acids and deterioration of organic compounds. The study demonstrated that a combination of electron microscopy imaging with metabolomic and genomic techniques allows to link the phylogenetic information and metabolic profiles of microbial communities

  2. Can NMR solve some significant challenges in metabolomics?

    Science.gov (United States)

    Nagana Gowda, G A; Raftery, Daniel

    2015-11-01

    The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact bio-specimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. YMDB: the Yeast Metabolome Database

    Science.gov (United States)

    Jewison, Timothy; Knox, Craig; Neveu, Vanessa; Djoumbou, Yannick; Guo, An Chi; Lee, Jacqueline; Liu, Philip; Mandal, Rupasri; Krishnamurthy, Ram; Sinelnikov, Igor; Wilson, Michael; Wishart, David S.

    2012-01-01

    The Yeast Metabolome Database (YMDB, http://www.ymdb.ca) is a richly annotated ‘metabolomic’ database containing detailed information about the metabolome of Saccharomyces cerevisiae. Modeled closely after the Human Metabolome Database, the YMDB contains >2000 metabolites with links to 995 different genes/proteins, including enzymes and transporters. The information in YMDB has been gathered from hundreds of books, journal articles and electronic databases. In addition to its comprehensive literature-derived data, the YMDB also contains an extensive collection of experimental intracellular and extracellular metabolite concentration data compiled from detailed Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) metabolomic analyses performed in our lab. This is further supplemented with thousands of NMR and MS spectra collected on pure, reference yeast metabolites. Each metabolite entry in the YMDB contains an average of 80 separate data fields including comprehensive compound description, names and synonyms, structural information, physico-chemical data, reference NMR and MS spectra, intracellular/extracellular concentrations, growth conditions and substrates, pathway information, enzyme data, gene/protein sequence data, as well as numerous hyperlinks to images, references and other public databases. Extensive searching, relational querying and data browsing tools are also provided that support text, chemical structure, spectral, molecular weight and gene/protein sequence queries. Because of S. cervesiae's importance as a model organism for biologists and as a biofactory for industry, we believe this kind of database could have considerable appeal not only to metabolomics researchers, but also to yeast biologists, systems biologists, the industrial fermentation industry, as well as the beer, wine and spirit industry. PMID:22064855

  4. Metabolomics of Aspergillus fumigatus

    DEFF Research Database (Denmark)

    Frisvad, Jens Christian; Rank, Christian; Nielsen, Kristian Fog

    2009-01-01

    fumiquinazolines. We also tentatively detected sphingofungins in A. fumigatus Af293 and in an isolate of A. lentulus. The sphingofungins may have a similar role as the toxic fumonisins, found in A. niger. A further number of mycotoxins, including ochratoxin A, and other secondary metabolites have been reported...

  5. The next wave in metabolome analysis

    DEFF Research Database (Denmark)

    Nielsen, Jens; Oliver, S.

    2005-01-01

    The metabolome of a cell represents the amplification and integration of signals from other functional genomic levels, such as the transcriptome and the proteome. Although this makes metabolomics a useful tool for the high-throughput analysis of phenotypes, the lack of a direct connection...... to the genome makes it difficult to interpret metabolomic data. Nevertheless, functional genomics has produced examples of the use of metabolomics to elucidate the phenotypes of otherwise silent mutations. Despite several successes, we believe that future metabolomic studies must focus on the accurate...... measurement of the concentrations of unambiguously identified metabolites. The research community must develop databases of metabolite concentrations in cells that are grown in several well-defined conditions if metabolomic data are to be integrated meaningfully with data from the other levels of functional...

  6. Using next generation transcriptome sequencing to predict an ectomycorrhizal metabolome

    Directory of Open Access Journals (Sweden)

    Cseke Leland J

    2011-05-01

    Full Text Available Abstract Background Mycorrhizae, symbiotic interactions between soil fungi and tree roots, are ubiquitous in terrestrial ecosystems. The fungi contribute phosphorous, nitrogen and mobilized nutrients from organic matter in the soil and in return the fungus receives photosynthetically-derived carbohydrates. This union of plant and fungal metabolisms is the mycorrhizal metabolome. Understanding this symbiotic relationship at a molecular level provides important contributions to the understanding of forest ecosystems and global carbon cycling. Results We generated next generation short-read transcriptomic sequencing data from fully-formed ectomycorrhizae between Laccaria bicolor and aspen (Populus tremuloides roots. The transcriptomic data was used to identify statistically significantly expressed gene models using a bootstrap-style approach, and these expressed genes were mapped to specific metabolic pathways. Integration of expressed genes that code for metabolic enzymes and the set of expressed membrane transporters generates a predictive model of the ectomycorrhizal metabolome. The generated model of mycorrhizal metabolome predicts that the specific compounds glycine, glutamate, and allantoin are synthesized by L. bicolor and that these compounds or their metabolites may be used for the benefit of aspen in exchange for the photosynthetically-derived sugars fructose and glucose. Conclusions The analysis illustrates an approach to generate testable biological hypotheses to investigate the complex molecular interactions that drive ectomycorrhizal symbiosis. These models are consistent with experimental environmental data and provide insight into the molecular exchange processes for organisms in this complex ecosystem. The method used here for predicting metabolomic models of mycorrhizal systems from deep RNA sequencing data can be generalized and is broadly applicable to transcriptomic data derived from complex systems.

  7. Metabolomics Application in Maternal-Fetal Medicine

    OpenAIRE

    Fanos, Vassilios; Atzori, Luigi; Makarenko, Karina; Melis, Gian Benedetto; Ferrazzi, Enrico

    2013-01-01

    Metabolomics in maternal-fetal medicine is still an “embryonic” science. However, there is already an increasing interest in metabolome of normal and complicated pregnancies, and neonatal outcomes. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns are amniotic fluid, blood, plasma, cord blood, placenta, urine, and vaginal secretions. All published papers highlight the strong correlation between biomarkers found in these tissues and fetal malformations, prete...

  8. Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization

    Science.gov (United States)

    Adkins, Daniel E.; McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Vann, Robert E.; Clark, Shaunna L.; Souza, Renan P.; Crowley, James J.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.; Beardsley, Patrick M.

    2014-01-01

    Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In the present study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate < 0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4-guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent methamphetamine levels and, with the exception of the myo-inositol association, suggest a mechanism whereby strain-based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA-induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization. PMID:24034544

  9. NMR metabolomics of thrips (Frankliniella occidentalis) resistance in Senecio hybrids.

    Science.gov (United States)

    Leiss, Kirsten A; Choi, Young H; Abdel-Farid, Ibrahim B; Verpoorte, Robert; Klinkhamer, Peter G L

    2009-02-01

    Western flower thrips (Frankliniella occidentalis) has become a key insect pest of agricultural and horticultural crops worldwide. Little is known about host plant resistance to thrips. In this study, we investigated thrips resistance in F (2) hybrids of Senecio jacobaea and Senecio aquaticus. We identified thrips-resistant hybrids applying three different bioassays. Subsequently, we compared the metabolomic profiles of these hybrids applying nuclear magnetic resonance spectroscopy (NMR). The new developments of NMR facilitate a wide range coverage of the metabolome. This makes NMR especially suitable if there is no a priori knowledge of the compounds related to herbivore resistance and allows a holistic approach analyzing different chemical compounds simultaneously. We show that the metabolomes of thrips-resistant and -susceptible hybrids differed considerably. Thrips-resistant hybrids contained higher amounts of the pyrrolizidine alkaloids (PA), jacobine, and jaconine, especially in younger leaves. Also, a flavanoid, kaempferol glucoside, accumulated in the resistant plants. Both PAs and kaempferol are known for their inhibitory effect on herbivores. In resistant and susceptible F (2) hybrids, young leaves showed less thrips damage than old leaves. Consistent with the optimal plant defense theory, young leaves contained increased levels of primary metabolites such as sucrose, raffinose, and stachyose, but also accumulated jacaranone as a secondary plant defense compound. Our results prove NMR as a promising tool to identify different metabolites involved in herbivore resistance. It constitutes a significant advance in the study of plant-insect relationships, providing key information on the implementation of herbivore resistance breeding strategies in plants.

  10. Metabolomics in Toxicology and Preclinical Research

    Science.gov (United States)

    Ramirez, Tzutzuy; Daneshian, Mardas; Kamp, Hennicke; Bois, Frederic Y.; Clench, Malcolm R.; Coen, Muireann; Donley, Beth; Fischer, Steven M.; Ekman, Drew R.; Fabian, Eric; Guillou, Claude; Heuer, Joachim; Hogberg, Helena T.; Jungnickel, Harald; Keun, Hector C.; Krennrich, Gerhard; Krupp, Eckart; Luch, Andreas; Noor, Fozia; Peter, Erik; Riefke, Bjoern; Seymour, Mark; Skinner, Nigel; Smirnova, Lena; Verheij, Elwin; Wagner, Silvia; Hartung, Thomas; van Ravenzwaay, Bennard; Leist, Marcel

    2013-01-01

    Summary Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context. PMID:23665807

  11. Endocrinology Meets Metabolomics: Achievements, Pitfalls, and Challenges.

    Science.gov (United States)

    Tokarz, Janina; Haid, Mark; Cecil, Alexander; Prehn, Cornelia; Artati, Anna; Möller, Gabriele; Adamski, Jerzy

    2017-10-01

    The metabolome, although very dynamic, is sufficiently stable to provide specific quantitative traits related to health and disease. Metabolomics requires balanced use of state-of-the-art study design, chemical analytics, biostatistics, and bioinformatics to deliver meaningful answers to contemporary questions in human disease research. The technology is now frequently employed for biomarker discovery and for elucidating the mechanisms underlying endocrine-related diseases. Metabolomics has also enriched genome-wide association studies (GWAS) in this area by providing functional data. The contributions of rare genetic variants to metabolome variance and to the human phenotype have been underestimated until now. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Functional metabolomics reveals novel active products in the DHA metabolome

    Directory of Open Access Journals (Sweden)

    Masakazu eShinohara

    2012-04-01

    Full Text Available Endogenous mechanisms for successful resolution of an acute inflammatory response and the local return to homeostasis are of interest because excessive inflammation underlies many human diseases. In this review, we provide an update and overview of functional metabolomics that identified a new bioactive metabolome of docosahexaenoic acid (DHA. Systematic studies revealed that DHA was converted to DHEA-derived novel bioactive products as well as aspirin-triggered (AT forms of protectins. The new oxygenated DHEA derived products blocked PMN chemotaxis, reduced P-selectin expression and platelet-leukocyte adhesion, and showed organ protection in ischemia/reperfusion injury. These products activated cannabinoid receptor (CB2 receptor and not CB1 receptors. The AT-PD1 reduced neutrophil (PMN recruitment in murine peritonitis. With human cells, AT-PD1 decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. The recent findings reviewed here indicate that DHEA oxidative metabolism and aspirin-triggered conversion of DHA produce potent novel molecules with anti-inflammatory and organ-protective properties, opening the DHA metabolome functional roles.

  13. Understanding Plant Nitrogen Metabolism through Metabolomics and Computational Approaches

    Directory of Open Access Journals (Sweden)

    Perrin H. Beatty

    2016-10-01

    Full Text Available A comprehensive understanding of plant metabolism could provide a direct mechanism for improving nitrogen use efficiency (NUE in crops. One of the major barriers to achieving this outcome is our poor understanding of the complex metabolic networks, physiological factors, and signaling mechanisms that affect NUE in agricultural settings. However, an exciting collection of computational and experimental approaches has begun to elucidate whole-plant nitrogen usage and provides an avenue for connecting nitrogen-related phenotypes to genes. Herein, we describe how metabolomics, computational models of metabolism, and flux balance analysis have been harnessed to advance our understanding of plant nitrogen metabolism. We introduce a model describing the complex flow of nitrogen through crops in a real-world agricultural setting and describe how experimental metabolomics data, such as isotope labeling rates and analyses of nutrient uptake, can be used to refine these models. In summary, the metabolomics/computational approach offers an exciting mechanism for understanding NUE that may ultimately lead to more effective crop management and engineered plants with higher yields.

  14. Metabolomic Biomarkers in the Progression to Type 1 Diabetes

    DEFF Research Database (Denmark)

    Overgaard, Anne Julie; Kaur, Simranjeet; Pociot, Flemming

    2016-01-01

    diabetes has been studied using this technique, although in relatively small cohorts and at limited time points. Overall, three observations have been consistently reported; phospholipids at birth are lower in children developing type 1 diabetes early in childhood, methionine levels are lower in children......Metabolomics is the snapshot of all detectable metabolites and lipids in biological materials and has potential in reflecting genetic and environmental factors contributing to the development of complex diseases, such as type 1 diabetes. The progression to seroconversion to development of type 1...... at seroconversion, and triglycerides are increased at seroconversion and associated to microbiome diversity, indicating an association between the metabolome and microbiome in type 1 diabetes progression....

  15. Bridging the gap: basic metabolomics methods for natural product chemistry.

    Science.gov (United States)

    Jones, Oliver A H; Hügel, Helmut M

    2013-01-01

    Natural products and their derivatives often have potent physiological activities and therefore play important roles as both frontline treatments for many diseases and as the inspiration for chemically synthesized therapeutics. However, the detection and synthesis of new therapeutic compounds derived from, or inspired by natural compounds has declined in recent years due to the increased difficulty of identifying and isolating novel active compounds. A new strategy is therefore necessary to jumpstart this field of research. Metabolomics, including both targeted and global metabolite profiling strategies, has the potential to be instrumental in this effort since it allows a systematic study of complex mixtures (such as plant extracts) without the need for prior isolation of active ingredients (or mixtures thereof). Here we describe the basic steps for conducting metabolomics experiments and analyzing the results using some of the more commonly used analytical and statistical methodologies.

  16. Metabolomics window into diabetic complications.

    Science.gov (United States)

    Wu, Tao; Qiao, Shuxuan; Shi, Chenze; Wang, Shuya; Ji, Guang

    2018-03-01

    Diabetes has become a major global health problem. The elucidation of characteristic metabolic alterations during the diabetic progression is critical for better understanding its pathogenesis, and identifying potential biomarkers and drug targets. Metabolomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of diabetic complications. The present review provides an update on the application of metabolomics in diabetic complications, including diabetic coronary artery disease, diabetic nephropathy, diabetic retinopathy and diabetic neuropathy, and this review provides notes on the prevention and prediction of diabetic complications. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  17. Metabolomics techniques for nanotoxicity investigations.

    Science.gov (United States)

    Lv, Mengying; Huang, Wanqiu; Chen, Zhipeng; Jiang, Hulin; Chen, Jiaqing; Tian, Yuan; Zhang, Zunjian; Xu, Fengguo

    2015-01-01

    Nanomaterials are commonly defined as engineered structures with at least one dimension of 100 nm or less. Investigations of their potential toxicological impact on biological systems and the environment have yet to catch up with the rapid development of nanotechnology and extensive production of nanoparticles. High-throughput methods are necessary to assess the potential toxicity of nanoparticles. The omics techniques are well suited to evaluate toxicity in both in vitro and in vivo systems. Besides genomic, transcriptomic and proteomic profiling, metabolomics holds great promises for globally evaluating and understanding the molecular mechanism of nanoparticle-organism interaction. This manuscript presents a general overview of metabolomics techniques, summarizes its early application in nanotoxicology and finally discusses opportunities and challenges faced in nanotoxicology.

  18. Conventional and Advanced Separations in Mass Spectrometry-Based Metabolomics: Methodologies and Applications

    Energy Technology Data Exchange (ETDEWEB)

    Heyman, Heino M.; Zhang, Xing; Tang, Keqi; Baker, Erin Shammel; Metz, Thomas O.

    2016-02-16

    Metabolomics is the quantitative analysis of all metabolites in a given sample. Due to the chemical complexity of the metabolome, optimal separations are required for comprehensive identification and quantification of sample constituents. This chapter provides an overview of both conventional and advanced separations methods in practice for reducing the complexity of metabolite extracts delivered to the mass spectrometer detector, and covers gas chromatography (GC), liquid chromatography (LC), capillary electrophoresis (CE), supercritical fluid chromatography (SFC) and ion mobility spectrometry (IMS) separation techniques coupled with mass spectrometry (MS) as both uni-dimensional and as multi-dimensional approaches.

  19. Complex refractive indices in the near-ultraviolet spectral region of biogenic secondary organic aerosol aged with ammonia

    Energy Technology Data Exchange (ETDEWEB)

    Flores, J. M.; Washenfelder, Rebecca; Adler, Gabriela; Lee, H-J; Segev, Lior; Laskin, Julia; Laskin, Alexander; Nizkorodov, Sergey; Brown, Steven; Rudich, Yinon

    2014-05-14

    Atmospheric absorption by brown carbon aerosol may play an important role in global radiative forcing. Brown carbon arises from both primary and secondary sources, but the mechanisms and reactions for the latter are highly uncertain. One proposed mechanism is the reaction of ammonia or amino acids with carbonyl products in secondary organic aerosol (SOA). We generated SOA in situ by reacting biogenic alkenes (α-pinene, limonene, and α-humulene) with excess ozone, humidifying the resulting aerosol, and reacting the humidified aerosol with gaseous ammonia. We determined the complex refractive indices (RI) in the 360 – 420 nm range for these aerosols using broadband cavity enhanced spectroscopy (BBCES). The average real part (n) of the measured spectral range of the NH3-aged α-pinene SOA increased from n = 1.50 (±0.01) for the unreacted SOA to n = 1.57 (± 0.01) after a 1.5h exposure to 1.9 ppm NH3; whereas,the imaginary component (k) remained below k < 0.001 (± 0.002). For the limonene and α-humulene SOA the real part did not change significantly, and we observed a small change in the imaginary component of the RI. The imaginary component increased from k = 0.0 to an average k= 0.029 (± 0.021) for α-humulene SOA, and from k < 0.001 (± 0.002) to an average k = 0.032 (±0.019) for limonene SOA after a 1.5 h exposure to 1.3 and 1.9 ppm of NH3, respectively. Collected filter samples of the aged and unreacted α-pinene SOA and limonene SOA were analyzed off-line with nanospray desorption electrospray ionization high resolution mass spectrometry (nano-DESI/HR-MS), and in-situ with a Time-of-Fligh Aerosol Mass Spectrometer, confirming that the SOA reacted and that various nitrogen-containing reaction products formed. If we assume that NH3 aging reactions scale linearly with time and concentration, then a 1.5 h reaction with 1 ppm NH3 in the laboratory is equivalent to 24 h reaction with 63 ppbv NH3, indicating that the observed aerosol absorption will be limited

  20. Proteomics and Metabolomics: two emerging areas for legume improvement

    Directory of Open Access Journals (Sweden)

    Abirami eRamalingam

    2015-12-01

    Full Text Available The crop legumes such as chickpea, common bean, cowpea, peanut, pigeonpea, soybean, etc. are important source of nutrition and contribute to a significant amount of biological nitrogen fixation (>20 million tons of fixed nitrogen in agriculture. However, the production of legumes is constrained due to abiotic and biotic stresses. It is therefore imperative to understand the molecular mechanisms of plant response to different stresses and identify key candidate genes regulating tolerance which can be deployed in breeding programs. The information obtained from transcriptomics has facilitated the identification of candidate genes for the given trait of interest and utilizing them in crop breeding programs to improve stress tolerance. However, the mechanisms of stress tolerance are complex due to the influence of multi-genes and post-transcriptional regulations. Furthermore, stress conditions greatly affect gene expression which in turn causes modifications in the composition of plant proteomes and metabolomes. Therefore, functional genomics involving various proteomics and metabolomics approaches have been obligatory for understanding plant stress tolerance. These approaches have also been found useful to unravel different pathways related to plant and seed development as well as symbiosis. Proteome and metabolome profiling using high-throughput based systems have been extensively applied in the model legume species Medicago truncatula and Lotus japonicus, as well as in the model crop legume, soybean, to examine stress signalling pathways, cellular and developmental processes and nodule symbiosis. Moreover, the availability of protein reference maps as well as proteomics and metabolomics databases greatly support research and understanding of various biological processes in legumes. Protein-protein interaction techniques, particularly the yeast two-hybrid system have been advantageous for studying symbiosis and stress signalling in legumes. In

  1. A Plasma Metabolomic Signature of the Exfoliation Syndrome Involves Amino Acids, Acylcarnitines, and Polyamines.

    Science.gov (United States)

    Leruez, Stéphanie; Bresson, Thomas; Chao de la Barca, Juan M; Marill, Alexandre; de Saint Martin, Grégoire; Buisset, Adrien; Muller, Jeanne; Tessier, Lydie; Gadras, Cédric; Verny, Christophe; Amati-Bonneau, Patrizia; Lenaers, Guy; Gohier, Philippe; Bonneau, Dominique; Simard, Gilles; Milea, Dan; Procaccio, Vincent; Reynier, Pascal

    2018-02-01

    To determine the plasma metabolomic signature of the exfoliative syndrome (XFS), the most common cause worldwide of secondary open-angle glaucoma. We performed a targeted metabolomic study, using the standardized p180 Biocrates Absolute IDQ p180 kit with a QTRAP 5500 mass spectrometer, to compare the metabolomic profiles of plasma from individuals with XFS (n = 16), and an age- and sex-matched control group with cataract (n = 18). A total of 151 metabolites were detected correctly, 16 of which allowed for construction of an OPLS-DA model with a good predictive capability (Q2cum = 0.51) associated with a low risk of over-fitting (permQ2 = -0.48, CV-ANOVA P-value <0.001). The metabolites contributing the most to the signature were octanoyl-carnitine (C8) and decanoyl-carnitine (C10), the branched-chain amino acids (i.e., isoleucine, leucine, and valine), and tyrosine, all of which were at higher concentrations in the XFS group, whereas spermine and spermidine, together with their precursor acetyl-ornithine, were at lower concentrations than in the control group. We identified a significant metabolomic signature in the plasma of individuals with XFS. Paradoxically, this signature, characterized by lower concentrations of the neuroprotective spermine and spermidine polyamines than in controls, partially overlaps the plasma metabolomic profile associated with insulin resistance, despite the absence of evidence of insulin resistance in XFS.

  2. Arbuscular Mycorrhizal Fungi and Plant Chemical Defence: Effects of Colonisation on Aboveground and Belowground Metabolomes.

    Science.gov (United States)

    Hill, Elizabeth M; Robinson, Lynne A; Abdul-Sada, Ali; Vanbergen, Adam J; Hodge, Angela; Hartley, Sue E

    2018-02-01

    Arbuscular mycorrhizal fungal (AMF) colonisation of plant roots is one of the most ancient and widespread interactions in ecology, yet the systemic consequences for plant secondary chemistry remain unclear. We performed the first metabolomic investigation into the impact of AMF colonisation by Rhizophagus irregularis on the chemical defences, spanning above- and below-ground tissues, in its host-plant ragwort (Senecio jacobaea). We used a non-targeted metabolomics approach to profile, and where possible identify, compounds induced by AMF colonisation in both roots and shoots. Metabolomics analyses revealed that 33 compounds were significantly increased in the root tissue of AMF colonised plants, including seven blumenols, plant-derived compounds known to be associated with AMF colonisation. One of these was a novel structure conjugated with a malonyl-sugar and uronic acid moiety, hitherto an unreported combination. Such structural modifications of blumenols could be significant for their previously reported functional roles associated with the establishment and maintenance of AM colonisation. Pyrrolizidine alkaloids (PAs), key anti-herbivore defence compounds in ragwort, dominated the metabolomic profiles of root and shoot extracts. Analyses of the metabolomic profiles revealed an increase in four PAs in roots (but not shoots) of AMF colonised plants, with the potential to protect colonised plants from below-ground organisms.

  3. The future of metabolomics in ELIXIR

    Science.gov (United States)

    van Rijswijk, Merlijn; Beirnaert, Charlie; Caron, Christophe; Cascante, Marta; Dominguez, Victoria; Dunn, Warwick B.; Ebbels, Timothy M. D.; Giacomoni, Franck; Gonzalez-Beltran, Alejandra; Hankemeier, Thomas; Haug, Kenneth; Izquierdo-Garcia, Jose L.; Jimenez, Rafael C.; Jourdan, Fabien; Kale, Namrata; Klapa, Maria I.; Kohlbacher, Oliver; Koort, Kairi; Kultima, Kim; Le Corguillé, Gildas; Moreno, Pablo; Moschonas, Nicholas K.; Neumann, Steffen; O’Donovan, Claire; Reczko, Martin; Rocca-Serra, Philippe; Rosato, Antonio; Salek, Reza M.; Sansone, Susanna-Assunta; Satagopam, Venkata; Schober, Daniel; Shimmo, Ruth; Spicer, Rachel A.; Spjuth, Ola; Thévenot, Etienne A.; Viant, Mark R.; Weber, Ralf J. M.; Willighagen, Egon L.; Zanetti, Gianluigi; Steinbeck, Christoph

    2017-01-01

    Metabolomics, the youngest of the major omics technologies, is supported by an active community of researchers and infrastructure developers across Europe. To coordinate and focus efforts around infrastructure building for metabolomics within Europe, a workshop on the “Future of metabolomics in ELIXIR” was organised at Frankfurt Airport in Germany. This one-day strategic workshop involved representatives of ELIXIR Nodes, members of the PhenoMeNal consortium developing an e-infrastructure that supports workflow-based metabolomics analysis pipelines, and experts from the international metabolomics community. The workshop established metabolite identification as the critical area, where a maximal impact of computational metabolomics and data management on other fields could be achieved. In particular, the existing four ELIXIR Use Cases, where the metabolomics community - both industry and academia - would benefit most, and which could be exhaustively mapped onto the current five ELIXIR Platforms were discussed. This opinion article is a call for support for a new ELIXIR metabolomics Use Case, which aligns with and complements the existing and planned ELIXIR Platforms and Use Cases. PMID:29043062

  4. The future of metabolomics in ELIXIR.

    Science.gov (United States)

    van Rijswijk, Merlijn; Beirnaert, Charlie; Caron, Christophe; Cascante, Marta; Dominguez, Victoria; Dunn, Warwick B; Ebbels, Timothy M D; Giacomoni, Franck; Gonzalez-Beltran, Alejandra; Hankemeier, Thomas; Haug, Kenneth; Izquierdo-Garcia, Jose L; Jimenez, Rafael C; Jourdan, Fabien; Kale, Namrata; Klapa, Maria I; Kohlbacher, Oliver; Koort, Kairi; Kultima, Kim; Le Corguillé, Gildas; Moreno, Pablo; Moschonas, Nicholas K; Neumann, Steffen; O'Donovan, Claire; Reczko, Martin; Rocca-Serra, Philippe; Rosato, Antonio; Salek, Reza M; Sansone, Susanna-Assunta; Satagopam, Venkata; Schober, Daniel; Shimmo, Ruth; Spicer, Rachel A; Spjuth, Ola; Thévenot, Etienne A; Viant, Mark R; Weber, Ralf J M; Willighagen, Egon L; Zanetti, Gianluigi; Steinbeck, Christoph

    2017-01-01

    Metabolomics, the youngest of the major omics technologies, is supported by an active community of researchers and infrastructure developers across Europe. To coordinate and focus efforts around infrastructure building for metabolomics within Europe, a workshop on the "Future of metabolomics in ELIXIR" was organised at Frankfurt Airport in Germany. This one-day strategic workshop involved representatives of ELIXIR Nodes, members of the PhenoMeNal consortium developing an e-infrastructure that supports workflow-based metabolomics analysis pipelines, and experts from the international metabolomics community. The workshop established metabolite identification as the critical area, where a maximal impact of computational metabolomics and data management on other fields could be achieved. In particular, the existing four ELIXIR Use Cases, where the metabolomics community - both industry and academia - would benefit most, and which could be exhaustively mapped onto the current five ELIXIR Platforms were discussed. This opinion article is a call for support for a new ELIXIR metabolomics Use Case, which aligns with and complements the existing and planned ELIXIR Platforms and Use Cases.

  5. Symbiosis of chemometrics and metabolomics: past, present, and future

    NARCIS (Netherlands)

    van der Greef, J.; Smilde, A. K.

    2005-01-01

    Metabolomics is a growing area in the field of systems biology. Metabolomics has already a long history and also the connection of metabolomics with chemometrics goes back some time. This review discusses the symbiosis of metabolomics and chemometrics with emphasis on the medical domain, puts the

  6. A Metabolomic Perspective on Coeliac Disease

    Science.gov (United States)

    Calabrò, Antonio

    2014-01-01

    Metabolomics is an “omic” science that is now emerging with the purpose of elaborating a comprehensive analysis of the metabolome, which is the complete set of metabolites (i.e., small molecules intermediates) in an organism, tissue, cell, or biofluid. In the past decade, metabolomics has already proved to be useful for the characterization of several pathological conditions and offers promises as a clinical tool. A metabolomics investigation of coeliac disease (CD) revealed that a metabolic fingerprint for CD can be defined, which accounts for three different but complementary components: malabsorption, energy metabolism, and alterations in gut microflora and/or intestinal permeability. In this review, we will discuss the major advancements in metabolomics of CD, in particular with respect to the role of gut microbiome and energy metabolism. PMID:24665364

  7. Mass Spectrometry Strategies for Clinical Metabolomics and Lipidomics in Psychiatry, Neurology, and Neuro-Oncology

    Science.gov (United States)

    Wood, Paul L

    2014-01-01

    Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed. PMID:23842599

  8. Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs.

    Science.gov (United States)

    Shu, Yisong; Liu, Zhenli; Zhao, Siyu; Song, Zhiqian; He, Dan; Wang, Menglei; Zeng, Honglian; Lu, Cheng; Lu, Aiping; Liu, Yuanyan

    2017-08-01

    Traditional Chinese medicine (TCM) exerts its therapeutic effect in a holistic fashion with the synergistic function of multiple characteristic constituents. The holism philosophy of TCM is coincident with global and systematic theories of metabolomics. The proposed pseudotargeted metabolomics methodologies were employed for the establishment of reliable quality control markers for use in the screening strategy of TCMs. Pseudotargeted metabolomics integrates the advantages of both targeted and untargeted methods. In the present study, targeted metabolomics equipped with the gold standard RRLC-QqQ-MS method was employed for in vivo quantitative plasma pharmacochemistry study of characteristic prototypic constituents. Meanwhile, untargeted metabolomics using UHPLC-QE Orbitrap HRMS with better specificity and selectivity was employed for identification of untargeted metabolites in the complex plasma matrix. In all, 32 prototypic metabolites were quantitatively determined, and 66 biotransformed metabolites were convincingly identified after being orally administered with standard extracts of four labeled Citrus TCMs. The global absorption and metabolism process of complex TCMs was depicted in a systematic manner.

  9. Mass spectrometry strategies for clinical metabolomics and lipidomics in psychiatry, neurology, and neuro-oncology.

    Science.gov (United States)

    Wood, Paul L

    2014-01-01

    Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites. Conceptual and financial factors contribute to the generation of statistically under-powered clinical studies, whereas bioinformatics issues result in the publication of a large number of unidentified metabolites. The path forward in this field involves targeted metabolomics analyses of large control and patient populations to define both the normal range of a defined metabolite and the potential heterogeneity (eg, bimodal) in complex patient populations. This approach requires that metabolomics research groups, in addition to developing a number of analytical platforms, build sufficient chemistry resources to supply the analytical standards required for absolute metabolite quantitation. Examples of metabolomics evaluations of sulfur amino-acid metabolism in psychiatry, neurology, and neuro-oncology and of lipidomics in neurology will be reviewed.

  10. Create, run, share, publish, and reference your LC-MS, FIA-MS, GC-MS, and NMR data analysis workflows with the Workflow4Metabolomics 3.0 Galaxy online infrastructure for metabolomics.

    Science.gov (United States)

    Guitton, Yann; Tremblay-Franco, Marie; Le Corguillé, Gildas; Martin, Jean-François; Pétéra, Mélanie; Roger-Mele, Pierrick; Delabrière, Alexis; Goulitquer, Sophie; Monsoor, Misharl; Duperier, Christophe; Canlet, Cécile; Servien, Rémi; Tardivel, Patrick; Caron, Christophe; Giacomoni, Franck; Thévenot, Etienne A

    2017-12-01

    Metabolomics is a key approach in modern functional genomics and systems biology. Due to the complexity of metabolomics data, the variety of experimental designs, and the multiplicity of bioinformatics tools, providing experimenters with a simple and efficient resource to conduct comprehensive and rigorous analysis of their data is of utmost importance. In 2014, we launched the Workflow4Metabolomics (W4M; http://workflow4metabolomics.org) online infrastructure for metabolomics built on the Galaxy environment, which offers user-friendly features to build and run data analysis workflows including preprocessing, statistical analysis, and annotation steps. Here we present the new W4M 3.0 release, which contains twice as many tools as the first version, and provides two features which are, to our knowledge, unique among online resources. First, data from the four major metabolomics technologies (i.e., LC-MS, FIA-MS, GC-MS, and NMR) can be analyzed on a single platform. By using three studies in human physiology, alga evolution, and animal toxicology, we demonstrate how the 40 available tools can be easily combined to address biological issues. Second, the full analysis (including the workflow, the parameter values, the input data and output results) can be referenced with a permanent digital object identifier (DOI). Publication of data analyses is of major importance for robust and reproducible science. Furthermore, the publicly shared workflows are of high-value for e-learning and training. The Workflow4Metabolomics 3.0 e-infrastructure thus not only offers a unique online environment for analysis of data from the main metabolomics technologies, but it is also the first reference repository for metabolomics workflows. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Biomarker discovery in neurological diseases: a metabolomic approach

    Directory of Open Access Journals (Sweden)

    Afaf El-Ansary

    2009-12-01

    Full Text Available Afaf El-Ansary, Nouf Al-Afaleg, Yousra Al-YafaeeBiochemistry Department, Science College, King Saud University, Riyadh, Saudi ArabiaAbstract: Biomarkers are pharmacological and physiological measurements or specific biochemicals in the body that have a particular molecular feature that makes them useful for measuring the progress of disease or the effects of treatment. Due to the complexity of neurological disorders, it is very difficult to have perfect markers. Brain diseases require plenty of markers to reflect the metabolic impairment of different brain cells. The recent introduction of the metabolomic approach helps the study of neurological diseases based on profiling a multitude of biochemical components related to brain metabolism. This review is a trial to elucidate the possibility to use this approach to identify plasma metabolic markers related to neurological disorders. Previous trials using different metabolomic analyses including nuclear magnetic resonance spectroscopy, gas chromatography combined with mass spectrometry, liquid chromatography combined with mass spectrometry, and capillary electrophoresis will be traced.Keywords: metabolic biomarkers, neurological disorders. metabolome, nuclear magnetic resonance, mass spectrometry, chromatography

  12. Metabolomics for Biomarker Discovery: Moving to the Clinic

    Science.gov (United States)

    Zhang, Aihua; Sun, Hui; Yan, Guangli; Wang, Ping; Wang, Xijun

    2015-01-01

    To improve the clinical course of diseases, more accurate diagnostic and assessment methods are required as early as possible. In order to achieve this, metabolomics offers new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has become an important tool in clinical research and the diagnosis of human disease and has been applied to discovery and identification of the perturbed pathways. It provides a powerful approach to discover biomarkers in biological systems and offers a holistic approach with the promise to clinically enhance diagnostics. When carried out properly, it could provide insight into the understanding of the underlying mechanisms of diseases, help to identify patients at risk of disease, and predict the response to specific treatments. Currently, metabolomics has become an important tool in clinical research and the diagnosis of human disease and becomes a hot topic. This review will highlight the importance and benefit of metabolomics for identifying biomarkers that accurately screen potential biomarkers of diseases. PMID:26090402

  13. Functional Analysis of Metabolomics Data.

    Science.gov (United States)

    Chagoyen, Mónica; López-Ibáñez, Javier; Pazos, Florencio

    2016-01-01

    Metabolomics aims at characterizing the repertory of small chemical compounds in a biological sample. As it becomes more massive and larger sets of compounds are detected, a functional analysis is required to convert these raw lists of compounds into biological knowledge. The most common way of performing such analysis is "annotation enrichment analysis," also used in transcriptomics and proteomics. This approach extracts the annotations overrepresented in the set of chemical compounds arisen in a given experiment. Here, we describe the protocols for performing such analysis as well as for visualizing a set of compounds in different representations of the metabolic networks, in both cases using free accessible web tools.

  14. Interspecies interactions stimulate diversification of the Streptomyces coelicolor secreted metabolome.

    Science.gov (United States)

    Traxler, Matthew F; Watrous, Jeramie D; Alexandrov, Theodore; Dorrestein, Pieter C; Kolter, Roberto

    2013-08-20

    Soils host diverse microbial communities that include filamentous actinobacteria (actinomycetes). These bacteria have been a rich source of useful metabolites, including antimicrobials, antifungals, anticancer agents, siderophores, and immunosuppressants. While humans have long exploited these compounds for therapeutic purposes, the role these natural products may play in mediating interactions between actinomycetes has been difficult to ascertain. As an initial step toward understanding these chemical interactions at a systems level, we employed the emerging techniques of nanospray desorption electrospray ionization (NanoDESI) and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) imaging mass spectrometry to gain a global chemical view of the model bacterium Streptomyces coelicolor interacting with five other actinomycetes. In each interaction, the majority of secreted compounds associated with S. coelicolor colonies were unique, suggesting an idiosyncratic response from S. coelicolor. Spectral networking revealed a family of unknown compounds produced by S. coelicolor during several interactions. These compounds constitute an extended suite of at least 12 different desferrioxamines with acyl side chains of various lengths; their production was triggered by siderophores made by neighboring strains. Taken together, these results illustrate that chemical interactions between actinomycete bacteria exhibit high complexity and specificity and can drive differential secondary metabolite production. Actinomycetes, filamentous actinobacteria from the soil, are the deepest natural source of useful medicinal compounds, including antibiotics, antifungals, and anticancer agents. There is great interest in developing new strategies that increase the diversity of metabolites secreted by actinomycetes in the laboratory. Here we used several metabolomic approaches to examine the chemicals made by these bacteria when grown in pairwise coculture. We found that

  15. The characterization of secondary lithium-ion battery degradation when operating complex, ultra-high power pulsed loads

    Science.gov (United States)

    Wong, Derek N.

    The US Navy is actively developing all electric fleets, raising serious questions about what is required of onboard power supplies in order to properly power the ship's electrical systems. This is especially relevant when choosing a viable power source to drive high power propulsion and electric weapon systems in addition to the conventional loads deployed aboard these types of vessels. Especially when high pulsed power loads are supplied, the issue of maintaining power quality becomes important and increasingly complex. Conventionally, a vessel's electrical power is generated using gas turbine or diesel driven motor-generator sets that are very inefficient when they are used outside of their most efficient load condition. What this means is that if the generator is not being utilized continuously at its most efficient load capacity, the quality of the output power may also be effected and fall outside of the acceptable power quality limits imposed through military standards. As a solution to this potential problem, the Navy has proposed using electrochemical storage devices since they are able to buffer conventional generators when the load is operating below the generator's most efficient power level or able to efficiently augment a generator when the load is operating in excess of the generator's most efficient power rating. Specifically, the US Navy is interested in using commercial off-the-shelf (COTS) lithium-ion batteries within an intelligently controlled energy storage module that could act as either a prime power supply for on-board pulsed power systems or as a backup generator to other shipboard power systems. Due to the unique load profile of high-rate pulsed power systems, the implementation of lithium-ion batteries within these complex systems requires them to be operated at very high rates and the effects these things have on cell degradation has been an area of focus. There is very little published research into the effects that high power transient

  16. Metabolomics: beyond biomarkers and towards mechanisms

    Science.gov (United States)

    Johnson, Caroline H.; Ivanisevic, Julijana; Siuzdak, Gary

    2017-01-01

    Metabolomics, which is the profiling of metabolites in biofluids, cells and tissues, is routinely applied as a tool for biomarker discovery. Owing to innovative developments in informatics and analytical technologies, and the integration of orthogonal biological approaches, it is now possible to expand metabolomic analyses to understand the systems-level effects of metabolites. Moreover, because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases. PMID:26979502

  17. Metabolomics applied to the pancreatic islet.

    Science.gov (United States)

    Gooding, Jessica R; Jensen, Mette V; Newgard, Christopher B

    2016-01-01

    Metabolomics, the characterization of the set of small molecules in a biological system, is advancing research in multiple areas of islet biology. Measuring a breadth of metabolites simultaneously provides a broad perspective on metabolic changes as the islets respond dynamically to metabolic fuels, hormones, or environmental stressors. As a result, metabolomics has the potential to provide new mechanistic insights into islet physiology and pathophysiology. Here we summarize advances in our understanding of islet physiology and the etiologies of type-1 and type-2 diabetes gained from metabolomics studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Mathematical Modeling Approaches in Plant Metabolomics.

    Science.gov (United States)

    Fürtauer, Lisa; Weiszmann, Jakob; Weckwerth, Wolfram; Nägele, Thomas

    2018-01-01

    The experimental analysis of a plant metabolome typically results in a comprehensive and multidimensional data set. To interpret metabolomics data in the context of biochemical regulation and environmental fluctuation, various approaches of mathematical modeling have been developed and have proven useful. In this chapter, a general introduction to mathematical modeling is presented and discussed in context of plant metabolism. A particular focus is laid on the suitability of mathematical approaches to functionally integrate plant metabolomics data in a metabolic network and combine it with other biochemical or physiological parameters.

  19. Conventional and accelerated-solvent extractions of green tea (camellia sinensis) for metabolomics-based chemometrics.

    Science.gov (United States)

    Kellogg, Joshua J; Wallace, Emily D; Graf, Tyler N; Oberlies, Nicholas H; Cech, Nadja B

    2017-10-25

    Metabolomics has emerged as an important analytical technique for multiple applications. The value of information obtained from metabolomics analysis depends on the degree to which the entire metabolome is present and the reliability of sample treatment to ensure reproducibility across the study. The purpose of this study was to compare methods of preparing complex botanical extract samples prior to metabolomics profiling. Two extraction methodologies, accelerated solvent extraction and a conventional solvent maceration, were compared using commercial green tea [Camellia sinensis (L.) Kuntze (Theaceae)] products as a test case. The accelerated solvent protocol was first evaluated to ascertain critical factors influencing extraction using a D-optimal experimental design study. The accelerated solvent and conventional extraction methods yielded similar metabolite profiles for the green tea samples studied. The accelerated solvent extraction yielded higher total amounts of extracted catechins, was more reproducible, and required less active bench time to prepare the samples. This study demonstrates the effectiveness of accelerated solvent as an efficient methodology for metabolomics studies. Copyright © 2017. Published by Elsevier B.V.

  20. Using metabolomics to evaluate food intake

    DEFF Research Database (Denmark)

    Manach, Claudine; Brennan, Lorraine; Dragsted, Lars Ove

    2015-01-01

    Improving dietary assessment is essential for modern nutritional epidemiology. This chapter discusses the potential of metabolomics for the identification of new biomarkers of intake and presents the first candidate biomarkers discovered using this approach. It then describes the challenges...

  1. Metabolomics in Population-Based Research

    Science.gov (United States)

    Metabolomics is the study of small molecules of both endogenous and exogenous origin, such as metabolic substrates and their products, lipids, small peptides, vitamins and other protein cofactors generated by metabolism, which are downstream from genes.

  2. Proteomic and metabolomic approaches to biomarker discovery

    CERN Document Server

    Issaq, Haleem J

    2013-01-01

    Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

  3. Metabolomics Application in Maternal-Fetal Medicine

    Directory of Open Access Journals (Sweden)

    Vassilios Fanos

    2013-01-01

    Full Text Available Metabolomics in maternal-fetal medicine is still an “embryonic” science. However, there is already an increasing interest in metabolome of normal and complicated pregnancies, and neonatal outcomes. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns are amniotic fluid, blood, plasma, cord blood, placenta, urine, and vaginal secretions. All published papers highlight the strong correlation between biomarkers found in these tissues and fetal malformations, preterm delivery, premature rupture of membranes, gestational diabetes mellitus, preeclampsia, neonatal asphyxia, and hypoxic-ischemic encephalopathy. The aim of this review is to summarize and comment on original data available in relevant published works in order to emphasize the clinical potential of metabolomics in obstetrics in the immediate future.

  4. Bullying, "Cussing" and "Mucking About": Complexities in Tackling Homophobia in Three Secondary Schools in South London, UK

    Science.gov (United States)

    Warwick, Ian; Aggleton, Peter

    2014-01-01

    In countries such as the UK, schools have a responsibility to prevent all forms of bullying, including those related to sexual orientation. However, relatively little is known about how schools go about this work successfully. This study aimed to identify how three secondary schools in south London, England, were addressing homophobia. Three…

  5. Complex of primary and secondary parasitoids (Hymenoptera: Encyrtidae and Signiphoridae) of Hypogeoccoccus spp. mealybugs (Hemiptera: Pseudococcidae) in the New World

    Science.gov (United States)

    Parasitoids, both primary and secondary (hyperparasitoids), of Hypogeococcus spp. mealybugs (Hemiptera: Pseudococcidae) are reviewed to report results of the surveys in the New World conducted during 2009–2017 for perspective natural enemies of the Harrisia cactus mealybug, Hypogeococcus sp., which ...

  6. Metabolomic approach: postharvest storage stability of red radish (raphanus sativus l.)

    International Nuclear Information System (INIS)

    Jahangir, M.; Farid, J.B.A.

    2014-01-01

    Post harvest storage of vegetables at different temperature for consumption is commonly practiced that need standardization. Among vegetables, red radish (Raphanus sativus L.) is a well known and commonly consumed vegetable all over the world. Its bioactive or nutritional constituents include a wide range of metabolites including, glucosinolates, phenolics, amino acids, organic acids, and sugars. However, many of these metabolites are not stable and can easily be degraded or modified during storage. In order to investigate the metabolomic changes during post harvest storage, radish samples (intact roots and aerial parts) were subjected to four different storage temperatures above and below 0 degree C (20 degree C, 4 degree C, -20 degree C, and -80 degree C), for a maximum of 28 days. 1H-NMR and two-dimensional NMR spectra data resulting from the analysis of the different samples were subjected to principal component analysis (PCA) to investigate any possible metabolomic changes. A profound chemical alteration was observed in primary and secondary metabolites. Glucosinolates, phenylpropanoids, organic acids, amino acids, and sugars were found to be the discriminating metabolites for the storage effect. Initially, an increase in secondary metabolites (phenolics and glucosinolates) was observed, but levels of these compounds decreased in later stages, probably due to the breakdown of these products. Whereas late storage samples contained high amounts of amino acids (alanine, valine, threonine, (gama-amino-butyric acid / GABA)) and some glucosinolates (glucobrassicin, neoglucobrassicin). This phenomenon was pronounced at room temperature as compared to other storage temperatures. Interestingly even at lower and freezing temperatures metabolomic changes in these biological samples were observed. The least metabolomic changes were observed at samples stored at -80 degree C. While studying temperature dependent metabolomic changes, high levels of glucose, adenine, alanine

  7. Sample normalization methods in quantitative metabolomics.

    Science.gov (United States)

    Wu, Yiman; Li, Liang

    2016-01-22

    To reveal metabolomic changes caused by a biological event in quantitative metabolomics, it is critical to use an analytical tool that can perform accurate and precise quantification to examine the true concentration differences of individual metabolites found in different samples. A number of steps are involved in metabolomic analysis including pre-analytical work (e.g., sample collection and storage), analytical work (e.g., sample analysis) and data analysis (e.g., feature extraction and quantification). Each one of them can influence the quantitative results significantly and thus should be performed with great care. Among them, the total sample amount or concentration of metabolites can be significantly different from one sample to another. Thus, it is critical to reduce or eliminate the effect of total sample amount variation on quantification of individual metabolites. In this review, we describe the importance of sample normalization in the analytical workflow with a focus on mass spectrometry (MS)-based platforms, discuss a number of methods recently reported in the literature and comment on their applicability in real world metabolomics applications. Sample normalization has been sometimes ignored in metabolomics, partially due to the lack of a convenient means of performing sample normalization. We show that several methods are now available and sample normalization should be performed in quantitative metabolomics where the analyzed samples have significant variations in total sample amounts. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Simultaneous Pathoproteomic Evaluation of the Dystrophin-Glycoprotein Complex and Secondary Changes in the mdx-4cv Mouse Model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Sandra Murphy

    2015-06-01

    Full Text Available In skeletal muscle, the dystrophin-glycoprotein complex forms a membrane-associated assembly of relatively low abundance, making its detailed proteomic characterization in normal versus dystrophic tissues technically challenging. To overcome this analytical problem, we have enriched the muscle membrane fraction by a minimal differential centrifugation step followed by the comprehensive label-free mass spectrometric analysis of microsomal membrane preparations. This organelle proteomic approach successfully identified dystrophin and its binding partners in normal versus dystrophic hind limb muscles. The introduction of a simple pre-fractionation step enabled the simultaneous proteomic comparison of the reduction in the dystrophin-glycoprotein complex and secondary changes in the mdx-4cv mouse model of dystrophinopathy in a single analytical run. The proteomic screening of the microsomal fraction from dystrophic hind limb muscle identified the full-length dystrophin isoform Dp427 as the most drastically reduced protein in dystrophinopathy, demonstrating the remarkable analytical power of comparative muscle proteomics. Secondary pathoproteomic expression patterns were established for 281 proteins, including dystrophin-associated proteins and components involved in metabolism, signalling, contraction, ion-regulation, protein folding, the extracellular matrix and the cytoskeleton. Key findings were verified by immunoblotting. Increased levels of the sarcolemmal Na+/K+-ATPase in dystrophic leg muscles were also confirmed by immunofluorescence microscopy. Thus, the reduction of sample complexity in organelle-focused proteomics can be advantageous for the profiling of supramolecular protein complexes in highly intricate systems, such as skeletal muscle tissue.

  9. Comprehensive untargeted metabolomics of Lychnnophorinae subtribe (Asteraceae: Vernonieae) in a phylogenetic context.

    Science.gov (United States)

    Martucci, Maria Elvira Poleti; Loeuille, Benoit; Pirani, José Rubens; Gobbo-Neto, Leonardo

    2018-01-01

    Members of the subtribe Lychnophorinae occur mostly within the Cerrado domain of the Brazilian Central Plateau. The relationships between its 11 genera, as well as between Lychnophorinae and other subtribes belonging to the tribe Vernonieae, have recently been investigated upon a phylogeny based on molecular and morphological data. We report the use of a comprehensive untargeted metabolomics approach, combining HPLC-MS and GC-MS data, followed by multivariate analyses aiming to assess the congruence between metabolomics data and the phylogenetic hypothesis, as well as its potential as a chemotaxonomic tool. We analyzed 78 species by UHPLC-MS and GC-MS in both positive and negative ionization modes. The metabolic profiles obtained for these species were treated in MetAlign and in MSClust and the matrices generated were used in SIMCA for hierarchical cluster analyses, principal component analyses and orthogonal partial least square discriminant analysis. The results showed that metabolomic analyses are mostly congruent with the phylogenetic hypothesis especially at lower taxonomic levels (Lychnophora or Eremanthus). Our results confirm that data generated using metabolomics provide evidence for chemotaxonomical studies, especially for phylogenetic inference of the Lychnophorinae subtribe and insight into the evolution of the secondary metabolites of this group.

  10. Comprehensive untargeted metabolomics of Lychnnophorinae subtribe (Asteraceae: Vernonieae in a phylogenetic context.

    Directory of Open Access Journals (Sweden)

    Maria Elvira Poleti Martucci

    Full Text Available Members of the subtribe Lychnophorinae occur mostly within the Cerrado domain of the Brazilian Central Plateau. The relationships between its 11 genera, as well as between Lychnophorinae and other subtribes belonging to the tribe Vernonieae, have recently been investigated upon a phylogeny based on molecular and morphological data. We report the use of a comprehensive untargeted metabolomics approach, combining HPLC-MS and GC-MS data, followed by multivariate analyses aiming to assess the congruence between metabolomics data and the phylogenetic hypothesis, as well as its potential as a chemotaxonomic tool. We analyzed 78 species by UHPLC-MS and GC-MS in both positive and negative ionization modes. The metabolic profiles obtained for these species were treated in MetAlign and in MSClust and the matrices generated were used in SIMCA for hierarchical cluster analyses, principal component analyses and orthogonal partial least square discriminant analysis. The results showed that metabolomic analyses are mostly congruent with the phylogenetic hypothesis especially at lower taxonomic levels (Lychnophora or Eremanthus. Our results confirm that data generated using metabolomics provide evidence for chemotaxonomical studies, especially for phylogenetic inference of the Lychnophorinae subtribe and insight into the evolution of the secondary metabolites of this group.

  11. Comprehensive metabolomic profiling and incident cardiovascular disease: a systematic review

    Science.gov (United States)

    Background: Metabolomics is a promising tool of cardiovascular biomarker discovery. We systematically reviewed the literature on comprehensive metabolomic profiling in association with incident cardiovascular disease (CVD). Methods and Results: We searched MEDLINE and EMBASE from inception to Janua...

  12. Plant Metabolomics : the missiong link in functional genomics strategies

    NARCIS (Netherlands)

    Hall, R.D.; Beale, M.; Fiehn, O.; Hardy, N.; Summer, L.; Bino, R.

    2002-01-01

    After the establishment of technologies for high-throughput DNA sequencing (genomics), gene expression analysis (transcriptomics), and protein analysis (proteomics), the remaining functional genomics challenge is that of metabolomics. Metabolomics is the term coined for essentially comprehensive,

  13. The contribution of qualitative research in designing a complex intervention for secondary prevention of coronary heart disease in two different healthcare systems.

    LENUS (Irish Health Repository)

    Corrrigan, Mairead

    2006-01-01

    BACKGROUND: Developing complex interventions for testing in randomised controlled trials is of increasing importance in healthcare planning. There is a need for careful design of interventions for secondary prevention of coronary heart disease (CHD). It has been suggested that integrating qualitative research in the development of a complex intervention may contribute to optimising its design but there is limited evidence of this in practice. This study aims to examine the contribution of qualitative research in developing a complex intervention to improve the provision and uptake of secondary prevention of CHD within primary care in two different healthcare systems. METHODS: In four general practices, one rural and one urban, in Northern Ireland and the Republic of Ireland, patients with CHD were purposively selected. Four focus groups with patients (N = 23) and four with staff (N = 29) informed the development of the intervention by exploring how it could be tailored and integrated with current secondary prevention activities for CHD in the two healthcare settings. Following an exploratory trial the acceptability and feasibility of the intervention were discussed in four focus groups (17 patients) and 10 interviews (staff). The data were analysed using thematic analysis. RESULTS: Integrating qualitative research into the development of the intervention provided depth of information about the varying impact, between the two healthcare systems, of different funding and administrative arrangements, on their provision of secondary prevention and identified similar barriers of time constraints, training needs and poor patient motivation. The findings also highlighted the importance to patients of stress management, the need for which had been underestimated by the researchers. The qualitative evaluation provided depth of detail not found in evaluation questionnaires. It highlighted how the intervention needed to be more practical by minimising administration

  14. The contribution of qualitative research in designing a complex intervention for secondary prevention of coronary heart disease in two different healthcare systems

    Directory of Open Access Journals (Sweden)

    Leathem Claire S

    2006-07-01

    Full Text Available Abstract Background Developing complex interventions for testing in randomised controlled trials is of increasing importance in healthcare planning. There is a need for careful design of interventions for secondary prevention of coronary heart disease (CHD. It has been suggested that integrating qualitative research in the development of a complex intervention may contribute to optimising its design but there is limited evidence of this in practice. This study aims to examine the contribution of qualitative research in developing a complex intervention to improve the provision and uptake of secondary prevention of CHD within primary care in two different healthcare systems. Methods In four general practices, one rural and one urban, in Northern Ireland and the Republic of Ireland, patients with CHD were purposively selected. Four focus groups with patients (N = 23 and four with staff (N = 29 informed the development of the intervention by exploring how it could be tailored and integrated with current secondary prevention activities for CHD in the two healthcare settings. Following an exploratory trial the acceptability and feasibility of the intervention were discussed in four focus groups (17 patients and 10 interviews (staff. The data were analysed using thematic analysis. Results Integrating qualitative research into the development of the intervention provided depth of information about the varying impact, between the two healthcare systems, of different funding and administrative arrangements, on their provision of secondary prevention and identified similar barriers of time constraints, training needs and poor patient motivation. The findings also highlighted the importance to patients of stress management, the need for which had been underestimated by the researchers. The qualitative evaluation provided depth of detail not found in evaluation questionnaires. It highlighted how the intervention needed to be more practical by minimising

  15. The contribution of qualitative research in designing a complex intervention for secondary prevention of coronary heart disease in two different healthcare systems.

    Science.gov (United States)

    Corrrigan, Mairead; Cupples, Margaret E; Smith, Susan M; Byrne, Molly; Leathem, Claire S; Clerkin, Pauline; Murphy, Andrew W

    2006-07-18

    Developing complex interventions for testing in randomised controlled trials is of increasing importance in healthcare planning. There is a need for careful design of interventions for secondary prevention of coronary heart disease (CHD). It has been suggested that integrating qualitative research in the development of a complex intervention may contribute to optimising its design but there is limited evidence of this in practice. This study aims to examine the contribution of qualitative research in developing a complex intervention to improve the provision and uptake of secondary prevention of CHD within primary care in two different healthcare systems. In four general practices, one rural and one urban, in Northern Ireland and the Republic of Ireland, patients with CHD were purposively selected. Four focus groups with patients (N = 23) and four with staff (N = 29) informed the development of the intervention by exploring how it could be tailored and integrated with current secondary prevention activities for CHD in the two healthcare settings. Following an exploratory trial the acceptability and feasibility of the intervention were discussed in four focus groups (17 patients) and 10 interviews (staff). The data were analysed using thematic analysis. Integrating qualitative research into the development of the intervention provided depth of information about the varying impact, between the two healthcare systems, of different funding and administrative arrangements, on their provision of secondary prevention and identified similar barriers of time constraints, training needs and poor patient motivation. The findings also highlighted the importance to patients of stress management, the need for which had been underestimated by the researchers. The qualitative evaluation provided depth of detail not found in evaluation questionnaires. It highlighted how the intervention needed to be more practical by minimising administration, integrating role plays into behaviour

  16. Cultivar Diversity of Grape Skin Polyphenol Composition and Changes in Response to Drought Investigated by LC-MS Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Lucie Pinasseau

    2017-10-01

    Full Text Available Phenolic compounds represent a large family of plant secondary metabolites, essential for the quality of grape and wine and playing a major role in plant defense against biotic and abiotic stresses. Phenolic composition is genetically driven and greatly affected by environmental factors, including water stress. A major challenge for breeding of grapevine cultivars adapted to climate change and with high potential for wine-making is to dissect the complex plant metabolic response involved in adaptation mechanisms. A targeted metabolomics approach based on ultra high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QqQ-MS analysis in the Multiple Reaction Monitoring (MRM mode has been developed for high throughput profiling of the phenolic composition of grape skins. This method enables rapid, selective, and sensitive quantification of 96 phenolic compounds (anthocyanins, phenolic acids, stilbenoids, flavonols, dihydroflavonols, flavan-3-ol monomers, and oligomers…, and of the constitutive units of proanthocyanidins (i.e., condensed tannins, giving access to detailed polyphenol composition. It was applied on the skins of mature grape berries from a core-collection of 279 Vitis vinifera cultivars grown with or without watering to assess the genetic variation for polyphenol composition and its modulation by irrigation, in two successive vintages (2014–2015. Distribution of berry weights and δ13C values showed that non irrigated vines were subjected to a marked water stress in 2014 and to a very limited one in 2015. Metabolomics analysis of the polyphenol composition and chemometrics analysis of this data demonstrated an influence of water stress on the biosynthesis of different polyphenol classes and cultivar differences in metabolic response to water deficit. Correlation networks gave insight on the relationships between the different polyphenol metabolites and related biosynthetic pathways. They also

  17. Fusion of mass spectrometry-based metabolomics data

    NARCIS (Netherlands)

    Smilde, Age K.; van der Werf, Mariët J.; Bijlsma, Sabina; van der Werff-van der Vat, Bianca J. C.; Jellema, Renger H.

    2005-01-01

    A general method is presented for combining mass spectrometry-based metabolomics data. Such data are becoming more and more abundant, and proper tools for fusing these types of data sets are needed. Fusion of metabolomics data leads to a comprehensive view on the metabolome of an organism or

  18. Systematic Applications of Metabolomics in Metabolic Engineering

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    Robert A. Dromms

    2012-12-01

    Full Text Available The goals of metabolic engineering are well-served by the biological information provided by metabolomics: information on how the cell is currently using its biochemical resources is perhaps one of the best ways to inform strategies to engineer a cell to produce a target compound. Using the analysis of extracellular or intracellular levels of the target compound (or a few closely related molecules to drive metabolic engineering is quite common. However, there is surprisingly little systematic use of metabolomics datasets, which simultaneously measure hundreds of metabolites rather than just a few, for that same purpose. Here, we review the most common systematic approaches to integrating metabolite data with metabolic engineering, with emphasis on existing efforts to use whole-metabolome datasets. We then review some of the most common approaches for computational modeling of cell-wide metabolism, including constraint-based models, and discuss current computational approaches that explicitly use metabolomics data. We conclude with discussion of the broader potential of computational approaches that systematically use metabolomics data to drive metabolic engineering.

  19. Causal Genetic Variation Underlying Metabolome Differences.

    Science.gov (United States)

    Swain-Lenz, Devjanee; Nikolskiy, Igor; Cheng, Jiye; Sudarsanam, Priya; Nayler, Darcy; Staller, Max V; Cohen, Barak A

    2017-08-01

    An ongoing challenge in biology is to predict the phenotypes of individuals from their genotypes. Genetic variants that cause disease often change an individual's total metabolite profile, or metabolome. In light of our extensive knowledge of metabolic pathways, genetic variants that alter the metabolome may help predict novel phenotypes. To link genetic variants to changes in the metabolome, we studied natural variation in the yeast Saccharomyces cerevisiae We used an untargeted mass spectrometry method to identify dozens of metabolite Quantitative Trait Loci (mQTL), genomic regions containing genetic variation that control differences in metabolite levels between individuals. We mapped differences in urea cycle metabolites to genetic variation in specific genes known to regulate amino acid biosynthesis. Our functional assays reveal that genetic variation in two genes, AUA1 and ARG81 , cause the differences in the abundance of several urea cycle metabolites. Based on knowledge of the urea cycle, we predicted and then validated a new phenotype: sensitivity to a particular class of amino acid isomers. Our results are a proof-of-concept that untargeted mass spectrometry can reveal links between natural genetic variants and metabolome diversity. The interpretability of our results demonstrates the promise of using genetic variants underlying natural differences in the metabolome to predict novel phenotypes from genotype. Copyright © 2017 by the Genetics Society of America.

  20. Application of Metabolomics in Thyroid Cancer Research

    Directory of Open Access Journals (Sweden)

    Anna Wojakowska

    2015-01-01

    Full Text Available Thyroid cancer is the most common endocrine malignancy with four major types distinguished on the basis of histopathological features: papillary, follicular, medullary, and anaplastic. Classification of thyroid cancer is the primary step in the assessment of prognosis and selection of the treatment. However, in some cases, cytological and histological patterns are inconclusive; hence, classification based on histopathology could be supported by molecular biomarkers, including markers identified with the use of high-throughput “omics” techniques. Beside genomics, transcriptomics, and proteomics, metabolomic approach emerges as the most downstream attitude reflecting phenotypic changes and alterations in pathophysiological states of biological systems. Metabolomics using mass spectrometry and magnetic resonance spectroscopy techniques allows qualitative and quantitative profiling of small molecules present in biological systems. This approach can be applied to reveal metabolic differences between different types of thyroid cancer and to identify new potential candidates for molecular biomarkers. In this review, we consider current results concerning application of metabolomics in the field of thyroid cancer research. Recent studies show that metabolomics can provide significant information about the discrimination between different types of thyroid lesions. In the near future, one could expect a further progress in thyroid cancer metabolomics leading to development of molecular markers and improvement of the tumor types classification and diagnosis.

  1. NMR and MS Methods for Metabolomics.

    Science.gov (United States)

    Amberg, Alexander; Riefke, Björn; Schlotterbeck, Götz; Ross, Alfred; Senn, Hans; Dieterle, Frank; Keck, Matthias

    2017-01-01

    Metabolomics, also often referred as "metabolic profiling," is the systematic profiling of metabolites in biofluids or tissues of organisms and their temporal changes. In the last decade, metabolomics has become more and more popular in drug development, molecular medicine, and other biotechnology fields, since it profiles directly the phenotype and changes thereof in contrast to other "-omics" technologies. The increasing popularity of metabolomics has been possible only due to the enormous development in the technology and bioinformatics fields. In particular, the analytical technologies supporting metabolomics, i.e., NMR, UPLC-MS, and GC-MS, have evolved into sensitive and highly reproducible platforms allowing the determination of hundreds of metabolites in parallel. This chapter describes the best practices of metabolomics as seen today. All important steps of metabolic profiling in drug development and molecular medicine are described in great detail, starting from sample preparation to determining the measurement details of all analytical platforms, and finally to discussing the corresponding specific steps of data analysis.

  2. Secondary metabolite comparison of the species within the Heterobasidion annosum s.l. complex

    DEFF Research Database (Denmark)

    Hansson, David; Wubshet, Sileshi Gizachew; Olson, Åke

    2014-01-01

    The metabolite production of the five members of the fungal species complex Heterobasidion annosum s.l., i.e. H. annosum s.s., H. abietinum, H. parviporum, H. occidentale and H. irregulare, was analyzed by LC–HRMS. The five members are described to have differences in host preferences: H. annosum...

  3. High-Resolution Metabolomics: Review of the Field and Implications for Nursing Science and the Study of Preterm Birth.

    Science.gov (United States)

    Li, Shuzhao; Dunlop, Anne L; Jones, Dean P; Corwin, Elizabeth J

    2016-01-01

    Most complex health conditions do not have a single etiology but rather develop from exposure to multiple risk factors that interact to influence individual susceptibility. In this review, we discuss the emerging field of metabolomics as a means by which metabolic pathways underlying a disease etiology can be exposed and specific metabolites can be identified and linked, ultimately providing biomarkers for early detection of disease onset and new strategies for intervention. We present the theoretical foundation of metabolomics research, the current methods employed in its conduct, and the overlap of metabolomics research with other "omic" approaches. As an exemplar, we discuss the potential of metabolomics research in the context of deciphering the complex interactions of the maternal-fetal exposures that underlie the risk of preterm birth, a condition that accounts for substantial portions of infant morbidity and mortality and whose etiology and pathophysiology remain incompletely defined. We conclude by providing strategies for including metabolomics research in future nursing studies for the advancement of nursing science. © The Author(s) 2015.

  4. Impact of Soil Warming on the Plant Metabolome of Icelandic Grasslands

    Science.gov (United States)

    Gargallo-Garriga, Albert; Ayala-Roque, Marta; Granda, Victor; Sigurdsson, Bjarni D.; Leblans, Niki I. W.; Oravec, Michal; Urban, Otmar; Janssens, Ivan A.

    2017-01-01

    Climate change is stronger at high than at temperate and tropical latitudes. The natural geothermal conditions in southern Iceland provide an opportunity to study the impact of warming on plants, because of the geothermal bedrock channels that induce stable gradients of soil temperature. We studied two valleys, one where such gradients have been present for centuries (long-term treatment), and another where new gradients were created in 2008 after a shallow crustal earthquake (short-term treatment). We studied the impact of soil warming (0 to +15 °C) on the foliar metabolomes of two common plant species of high northern latitudes: Agrostis capillaris, a monocotyledon grass; and Ranunculus acris, a dicotyledonous herb, and evaluated the dependence of shifts in their metabolomes on the length of the warming treatment. The two species responded differently to warming, depending on the length of exposure. The grass metabolome clearly shifted at the site of long-term warming, but the herb metabolome did not. The main up-regulated compounds at the highest temperatures at the long-term site were saccharides and amino acids, both involved in heat-shock metabolic pathways. Moreover, some secondary metabolites, such as phenolic acids and terpenes, associated with a wide array of stresses, were also up-regulated. Most current climatic models predict an increase in annual average temperature between 2–8 °C over land masses in the Arctic towards the end of this century. The metabolomes of A. capillaris and R. acris shifted abruptly and nonlinearly to soil warming >5 °C above the control temperature for the coming decades. These results thus suggest that a slight warming increase may not imply substantial changes in plant function, but if the temperature rises more than 5 °C, warming may end up triggering metabolic pathways associated with heat stress in some plant species currently dominant in this region. PMID:28832555

  5. Sulfites and the wine metabolome.

    Science.gov (United States)

    Roullier-Gall, Chloé; Hemmler, Daniel; Gonsior, Michael; Li, Yan; Nikolantonaki, Maria; Aron, Alissa; Coelho, Christian; Gougeon, Régis D; Schmitt-Kopplin, Philippe

    2017-12-15

    In a context of societal concern about food preservation, the reduction of sulfite input plays a major role in the wine industry. To improve the understanding of the chemistry involved in the SO 2 protection, a series of bottle aged Chardonnay wines made from the same must, but with different concentrations of SO 2 added at pressing were analyzed by ultrahigh resolution mass spectrometry (FT-ICR-MS) and excitation emission matrix fluorescence (EEMF). Metabolic fingerprints from FT-ICR-MS data could discriminate wines according to the added concentration to the must but they also revealed chemistry-related differences according to the type of stopper, providing a wine metabolomics picture of the impact of distinct stopping strategies. Spearman rank correlation was applied to link the statistically modeled EEMF components (parallel factor analysis (PARAFAC)) and the exact mass information from FT-ICR-MS, and thus revealing the extent of sulfur-containing compounds which could show some correlation with fluorescence fingerprints. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Metabolomics: Definitions and Significance in Systems Biology.

    Science.gov (United States)

    Klassen, Aline; Faccio, Andréa Tedesco; Canuto, Gisele André Baptista; da Cruz, Pedro Luis Rocha; Ribeiro, Henrique Caracho; Tavares, Marina Franco Maggi; Sussulini, Alessandra

    2017-01-01

    Nowadays, there is a growing interest in deeply understanding biological mechanisms not only at the molecular level (biological components) but also the effects of an ongoing biological process in the organism as a whole (biological functionality), as established by the concept of systems biology. Within this context, metabolomics is one of the most powerful bioanalytical strategies that allow obtaining a picture of the metabolites of an organism in the course of a biological process, being considered as a phenotyping tool. Briefly, metabolomics approach consists in identifying and determining the set of metabolites (or specific metabolites) in biological samples (tissues, cells, fluids, or organisms) under normal conditions in comparison with altered states promoted by disease, drug treatment, dietary intervention, or environmental modulation. The aim of this chapter is to review the fundamentals and definitions used in the metabolomics field, as well as to emphasize its importance in systems biology and clinical studies.

  7. Microbiome, Metabolome and Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Ishfaq Ahmed

    2016-06-01

    Full Text Available Inflammatory Bowel Disease (IBD is a multifactorial disorder that conceptually occurs as a result of altered immune responses to commensal and/or pathogenic gut microbes in individuals most susceptible to the disease. During Crohn’s Disease (CD or Ulcerative Colitis (UC, two components of the human IBD, distinct stages define the disease onset, severity, progression and remission. Epigenetic, environmental (microbiome, metabolome and nutritional factors are important in IBD pathogenesis. While the dysbiotic microbiota has been proposed to play a role in disease pathogenesis, the data on IBD and diet are still less convincing. Nonetheless, studies are ongoing to examine the effect of pre/probiotics and/or FODMAP reduced diets on both the gut microbiome and its metabolome in an effort to define the healthy diet in patients with IBD. Knowledge of a unique metabolomic fingerprint in IBD could be useful for diagnosis, treatment and detection of disease pathogenesis.

  8. Metabolomics to Explore Impact of Dairy Intake

    Directory of Open Access Journals (Sweden)

    Hong Zheng

    2015-06-01

    Full Text Available Dairy products are an important component in the Western diet and represent a valuable source of nutrients for humans. However, a reliable dairy intake assessment in nutrition research is crucial to correctly elucidate the link between dairy intake and human health. Metabolomics is considered a potential tool for assessment of dietary intake instead of traditional methods, such as food frequency questionnaires, food records, and 24-h recalls. Metabolomics has been successfully applied to discriminate between consumption of different dairy products under different experimental conditions. Moreover, potential metabolites related to dairy intake were identified, although these metabolites need to be further validated in other intervention studies before they can be used as valid biomarkers of dairy consumption. Therefore, this review provides an overview of metabolomics for assessment of dairy intake in order to better clarify the role of dairy products in human nutrition and health.

  9. Blood transcriptomics and metabolomics for personalized medicine.

    Science.gov (United States)

    Li, Shuzhao; Todor, Andrei; Luo, Ruiyan

    2016-01-01

    Molecular analysis of blood samples is pivotal to clinical diagnosis and has been intensively investigated since the rise of systems biology. Recent developments have opened new opportunities to utilize transcriptomics and metabolomics for personalized and precision medicine. Efforts from human immunology have infused into this area exquisite characterizations of subpopulations of blood cells. It is now possible to infer from blood transcriptomics, with fine accuracy, the contribution of immune activation and of cell subpopulations. In parallel, high-resolution mass spectrometry has brought revolutionary analytical capability, detecting > 10,000 metabolites, together with environmental exposure, dietary intake, microbial activity, and pharmaceutical drugs. Thus, the re-examination of blood chemicals by metabolomics is in order. Transcriptomics and metabolomics can be integrated to provide a more comprehensive understanding of the human biological states. We will review these new data and methods and discuss how they can contribute to personalized medicine.

  10. A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers.

    Science.gov (United States)

    Vehof, Jelle; Hysi, Pirro G; Hammond, Christopher J

    2017-04-01

    To test the association between serum metabolites and dry eye disease (DED) using a hypothesis-free metabolomics approach. Cross-sectional association study. A total of 2819 subjects from the population-representative TwinsUK cohort in the United Kingdom, with a mean age of 57 years (range, 17-82 years). We tested associations between 222 known serum metabolites and DED. All subjects underwent nontargeted metabolomic analysis of plasma samples using gas and liquid chromatography in combination with mass spectrometry (Metabolon Inc., Durham, NC). Dry eye disease was defined from the validated Short Questionnaire for Dry Eye Syndrome (SQDES) as a previous diagnosis of DED by a clinician or "often" or "constant" symptoms of dryness and irritation. Analyses were performed with linear mixed effect models that included age, BMI, and sex as covariates, corrected for multiple testing. Primary outcome was DED as defined by the SQDES, and secondary outcomes were symptom score of DED and a clinical diagnosis of DED. Prevalence of DED as defined by the SQDES was 15.5% (n = 436). A strong and metabolome-wide significant association with DED was found with decreased levels of the metabolites androsterone sulfate (P = 0.00030) and epiandrosterone sulfate (P = 0.00036). Three other metabolites involved in androgen metabolism, 4-androsten-3beta,17beta-diol disulfate 1 and 2, and dehydroepiandrosterone sulfate, were the next most strongly associated of the 222 metabolites, but did not reach metabolome-wide significance. Dryness and irritation symptoms, as opposed to a clinical diagnosis, were particularly strongly associated with decreased androgen steroid metabolites, with all reaching metabolome-wide significance (androsterone sulfate, P = 0.000000029; epiandrosterone sulfate, P = 0.0000040; 4-androsten-3beta,17beta-diol disulfate 1, P = 0.000016; 4-androsten-3beta,17beta-diol disulfate 2, P = 0.000064; and dehydroepiandrosterone sulfate, P = 0.00011). Of these 5

  11. Studying the Differences of Bacterial Metabolome and Microbiome in the Colon between Landrace and Meihua Piglets

    Directory of Open Access Journals (Sweden)

    Shijuan Yan

    2017-09-01

    Full Text Available This study was conducted to compare the microbiome and metabolome differences in the colon lumen from two pig breeds with different genetic backgrounds. Fourteen weaned piglets at 30 days of age, including seven Landrace piglets (a lean-type pig breed with a fast growth rate and seven Meihua piglets (a fatty-type Chinese local pig breed with a slow growth rate, were fed the same diets for 35 days. Untargeted metabolomics analyses showed that a total of 401 metabolites differed between Landrace and Meihua. Seventy of these 401 metabolites were conclusively identified. Landrace accumulated more short-chain fatty acids (SCFAs and secondary bile acids in the colon lumen. Moreover, expression of the SCFAs transporter (solute carrier family 5 member 8, SLC5A8 and receptor (G protein-coupled receptor 41, GPR41 in the colon mucosa was higher, while the bile acids receptor (farnesoid X receptor, FXR had lower expression in Landrace compared to Meihua. The relative abundances of 8 genera and 16 species of bacteria differed significantly between Landrace and Meihua, and were closely related to the colonic concentrations of bile acids or SCFAs based on Pearson's correlation analysis. Collectively, our results demonstrate for the first time that there were differences in the colonic microbiome and metabolome between Meihua and Landrace piglets, with the most profound disparity in production of SCFAs and secondary bile acids.

  12. Towards the Fecal Metabolome Derived from Moderate Red Wine Intake

    Directory of Open Access Journals (Sweden)

    Ana Jiménez-Girón

    2014-12-01

    Full Text Available Dietary polyphenols, including red wine phenolic compounds, are extensively metabolized during their passage through the gastrointestinal tract; and their biological effects at the gut level (i.e., anti-inflammatory activity, microbiota modulation, interaction with cells, among others seem to be due more to their microbial-derived metabolites rather than to the original forms found in food. In an effort to improve our understanding of the biological effects that phenolic compounds exert at the gut level, this paper summarizes the changes observed in the human fecal metabolome after an intervention study consisting of a daily consumption of 250 mL of wine during four weeks by healthy volunteers (n = 33. It assembles data from two analytical approaches: (1 UPLC-ESI-MS/MS analysis of phenolic metabolites in fecal solutions (targeted analysis; and (2 UHPLC-TOF MS analysis of the fecal solutions (non-targeted analysis. Both approaches revealed statistically-significant changes in the concentration of several metabolites as a consequence of the wine intake. Similarity and complementarity between targeted and non-targeted approaches in the analysis of the fecal metabolome are discussed. Both strategies allowed the definition of a complex metabolic profile derived from wine intake. Likewise, the identification of endogenous markers could lead to new hypotheses to unravel the relationship between moderate wine consumption and the metabolic functionality of gut microbiota.

  13. Integration of metabolomics and transcriptomics in nanotoxicity studies.

    Science.gov (United States)

    Shin, Tae Hwan; Lee, Da Yeon; Lee, Hyeon-Seong; Park, Hyung Jin; Jin, Moon Suk; Paik, Man-Jeong; Manavalan, Balachandran; Mo, Jung-Soon; Lee, Gwang

    2018-01-01

    Biomedical research involving nanoparticles has produced useful products with medical applications. However, the potential toxicity of nanoparticles in biofluids, cells, tissues, and organisms is a major challenge. The '-omics' analyses provide molecular profiles of multifactorial biological systems instead of focusing on a single molecule. The 'omics' approaches are necessary to evaluate nanotoxicity because classical methods for the detection of nanotoxicity have limited ability in detecting miniscule variations within a cell and do not accurately reflect the actual levels of nanotoxicity. In addition, the 'omics' approaches allow analyses of in-depth changes and compensate for the differences associated with high-throughput technologies between actual nanotoxicity and results from traditional cytotoxic evaluations. However, compared with a single omics approach, integrated omics provides precise and sensitive information by integrating complex biological conditions. Thus, these technologies contribute to extended safety evaluations of nanotoxicity and allow the accurate diagnoses of diseases far earlier than was once possible in the nanotechnology era. Here, we review a novel approach for evaluating nanotoxicity by integrating metabolomics with metabolomic profiling and transcriptomics, which is termed "metabotranscriptomics". [BMB Reports 2018; 51(1): 14-20].

  14. MetaboAnalyst 3.0--making metabolomics more meaningful.

    Science.gov (United States)

    Xia, Jianguo; Sinelnikov, Igor V; Han, Beomsoo; Wishart, David S

    2015-07-01

    MetaboAnalyst (www.metaboanalyst.ca) is a web server designed to permit comprehensive metabolomic data analysis, visualization and interpretation. It supports a wide range of complex statistical calculations and high quality graphical rendering functions that require significant computational resources. First introduced in 2009, MetaboAnalyst has experienced more than a 50X growth in user traffic (>50 000 jobs processed each month). In order to keep up with the rapidly increasing computational demands and a growing number of requests to support translational and systems biology applications, we performed a substantial rewrite and major feature upgrade of the server. The result is MetaboAnalyst 3.0. By completely re-implementing the MetaboAnalyst suite using the latest web framework technologies, we have been able substantially improve its performance, capacity and user interactivity. Three new modules have also been added including: (i) a module for biomarker analysis based on the calculation of receiver operating characteristic curves; (ii) a module for sample size estimation and power analysis for improved planning of metabolomics studies and (iii) a module to support integrative pathway analysis for both genes and metabolites. In addition, popular features found in existing modules have been significantly enhanced by upgrading the graphical output, expanding the compound libraries and by adding support for more diverse organisms. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. A 'Foodomic' Approach for the Evaluation of Food Quality and its Impact on the Human Metabolome

    DEFF Research Database (Denmark)

    Trimigno, Alessia

    In recent years, omic sciences have been increasingly employed in a multitude of research fields thanks to their high-throughput capabilities and holistic approach. Among the omic sciences, metabolomics and foodomics have recently emerged in the investigation of food and nutrition and their relat......In recent years, omic sciences have been increasingly employed in a multitude of research fields thanks to their high-throughput capabilities and holistic approach. Among the omic sciences, metabolomics and foodomics have recently emerged in the investigation of food and nutrition...... and their relation to the individual health and wellness status (Chapter 1). The analytical platforms used are ideal for non-targeted analysis, due to their capability of detecting and identifying a large set of variables (or metabolites) in complex biological samples. The most employed metabolomics techniques...... carried out both in Italy and in Denmark, outlines the analytical pipeline of the foodomic approach and highlights the current challenges in the field (Chapter 2.3). The thesis traces the path of modern foodomics and metabolomics from the definition and description of food quality (Chapters 3 to 6...

  16. Impact of a western diet on the ovarian and serum metabolome.

    Science.gov (United States)

    Dhungana, Suraj; Carlson, James E; Pathmasiri, Wimal; McRitchie, Susan; Davis, Matt; Sumner, Susan; Appt, Susan E

    2016-10-01

    The objective of this investigation was to determine differences in the profiles of endogenous metabolites (metabolomics) among ovaries and serum derived from Old World nonhuman primates fed prudent or Western diets. A retrospective, observational study was done using archived ovarian tissue and serum from midlife cynomolgus monkeys (Macaca fasicularis). Targeted and broad spectrum metabolomics analysis was used to compare ovarian tissue and serum from monkeys that had been exposed to a prudent diet or a Western diet. Monkeys in the prudent diet group (n=13) were research naïve and had been exposed only to a commercial monkey chow diet (low in cholesterol and saturated fats, high in complex carbohydrates). Western diet monkeys (n=8) had consumed a diet that was high in cholesterol, saturated animal fats and soluble carbohydrates for 2 years prior to ovarian tissue and serum collection. Metabolomic analyses were done on extracts of homogenized ovary tissue samples, and extracts of serum. Targeted analysis was conducted using the Biocrates p180 kit and broad spectrum analysis was conducted using UPLC-TOF-MS, resulting in the detection of 3500 compound ions. Using metabolomics methods, which capture thousands of signals for metabolites, 64 metabolites were identified in serum and 47 metabolites were identified in ovarian tissue that differed by diet. Quantitative targeted analysis revealed 13 amino acids, 6 acrylcarnitines, and 2 biogenic amines that were significantly (pmetabolome, and demonstrated perturbation in carnitine, lipids/fatty acid, and amino acid metabolic pathways. Published by Elsevier Ireland Ltd.

  17. Metabolomic applications to decipher gut microbial metabolic influence in health and disease

    Directory of Open Access Journals (Sweden)

    Francois-Pierre eMartin

    2012-04-01

    Full Text Available Dietary preferences and nutrients composition have been shown to influence human and gut microbial metabolism, which ultimately has specific effects on health and diseases’ risk. Increasingly, results from molecular biology and microbiology demonstrate the key role of the gut microbiota metabolic interface to the overall mammalian host’s health status. There is therefore raising interest in nutrition research to characterize the molecular foundations of the gut microbial mammalian cross-talk at both physiological and biochemical pathway levels. Tackling these challenges can be achieved through systems biology approaches, such as metabolomics, to underpin the highly complex metabolic exchanges between diverse biological compartments, including organs, systemic biofluids and microbial symbionts. By the development of specific biomarkers for prediction of health and disease, metabolomics is increasingly used in clinical applications as regard to disease aetiology, diagnostic stratification and potentially mechanism of action of therapeutical and nutraceutical solutions. Surprisingly, an increasing number of metabolomics investigations in pre-clinical and clinical studies based on proton nuclear magnetic resonance (1H NMR spectroscopy and mass spectrometry (MS provided compelling evidence that system wide and organ-specific biochemical processes are under the influence of gut microbial metabolism. This review aims at describing recent applications of metabolomics in clinical fields where main objective is to discern the biochemical mechanisms under the influence of the gut microbiota, with insight into gastrointestinal health and diseases diagnostics and improvement of homeostasis metabolic regulation.

  18. Establishment of quantitative severity evaluation model for spinal cord injury by metabolomic fingerprinting.

    Directory of Open Access Journals (Sweden)

    Jin Peng

    Full Text Available Spinal cord injury (SCI is a devastating event with a limited hope for recovery and represents an enormous public health issue. It is crucial to understand the disturbances in the metabolic network after SCI to identify injury mechanisms and opportunities for treatment intervention. Through plasma 1H-nuclear magnetic resonance (NMR screening, we identified 15 metabolites that made up an "Eigen-metabolome" capable of distinguishing rats with severe SCI from healthy control rats. Forty enzymes regulated these 15 metabolites in the metabolic network. We also found that 16 metabolites regulated by 130 enzymes in the metabolic network impacted neurobehavioral recovery. Using the Eigen-metabolome, we established a linear discrimination model to cluster rats with severe and mild SCI and control rats into separate groups and identify the interactive relationships between metabolic biomarkers in the global metabolic network. We identified 10 clusters in the global metabolic network and defined them as distinct metabolic disturbance domains of SCI. Metabolic paths such as retinal, glycerophospholipid, arachidonic acid metabolism; NAD-NADPH conversion process, tyrosine metabolism, and cadaverine and putrescine metabolism were included. In summary, we presented a novel interdisciplinary method that integrates metabolomics and global metabolic network analysis to visualize metabolic network disturbances after SCI. Our study demonstrated the systems biological study paradigm that integration of 1H-NMR, metabolomics, and global metabolic network analysis is useful to visualize complex metabolic disturbances after severe SCI. Furthermore, our findings may provide a new quantitative injury severity evaluation model for clinical use.

  19. SWATHtoMRM: Development of High-Coverage Targeted Metabolomics Method Using SWATH Technology for Biomarker Discovery.

    Science.gov (United States)

    Zha, Haihong; Cai, Yuping; Yin, Yandong; Wang, Zhuozhong; Li, Kang; Zhu, Zheng-Jiang

    2018-03-20

    The complexity of metabolome presents a great analytical challenge for quantitative metabolite profiling, and restricts the application of metabolomics in biomarker discovery. Targeted metabolomics using multiple-reaction monitoring (MRM) technique has excellent capability for quantitative analysis, but suffers from the limited metabolite coverage. To address this challenge, we developed a new strategy, namely, SWATHtoMRM, which utilizes the broad coverage of SWATH-MS technology to develop high-coverage targeted metabolomics method. Specifically, SWATH-MS technique was first utilized to untargeted profile one pooled biological sample and to acquire the MS 2 spectra for all metabolites. Then, SWATHtoMRM was used to extract the large-scale MRM transitions for targeted analysis with coverage as high as 1000-2000 metabolites. Then, we demonstrated the advantages of SWATHtoMRM method in quantitative analysis such as coverage, reproducibility, sensitivity, and dynamic range. Finally, we applied our SWATHtoMRM approach to discover potential metabolite biomarkers for colorectal cancer (CRC) diagnosis. A high-coverage targeted metabolomics method with 1303 metabolites in one injection was developed to profile colorectal cancer tissues from CRC patients. A total of 20 potential metabolite biomarkers were discovered and validated for CRC diagnosis. In plasma samples from CRC patients, 17 out of 20 potential biomarkers were further validated to be associated with tumor resection, which may have a great potential in assessing the prognosis of CRC patients after tumor resection. Together, the SWATHtoMRM strategy provides a new way to develop high-coverage targeted metabolomics method, and facilitates the application of targeted metabolomics in disease biomarker discovery. The SWATHtoMRM program is freely available on the Internet ( http://www.zhulab.cn/software.php ).

  20. Evaluation of intensity drift correction strategies using MetaboDrift, a normalization tool for multi-batch metabolomics data.

    Science.gov (United States)

    Thonusin, Chanisa; IglayReger, Heidi B; Soni, Tanu; Rothberg, Amy E; Burant, Charles F; Evans, Charles R

    2017-11-10

    In recent years, mass spectrometry-based metabolomics has increasingly been applied to large-scale epidemiological studies of human subjects. However, the successful use of metabolomics in this context is subject to the challenge of detecting biologically significant effects despite substantial intensity drift that often occurs when data are acquired over a long period or in multiple batches. Numerous computational strategies and software tools have been developed to aid in correcting for intensity drift in metabolomics data, but most of these techniques are implemented using command-line driven software and custom scripts which are not accessible to all end users of metabolomics data. Further, it has not yet become routine practice to assess the quantitative accuracy of drift correction against techniques which enable true absolute quantitation such as isotope dilution mass spectrometry. We developed an Excel-based tool, MetaboDrift, to visually evaluate and correct for intensity drift in a multi-batch liquid chromatography - mass spectrometry (LC-MS) metabolomics dataset. The tool enables drift correction based on either quality control (QC) samples analyzed throughout the batches or using QC-sample independent methods. We applied MetaboDrift to an original set of clinical metabolomics data from a mixed-meal tolerance test (MMTT). The performance of the method was evaluated for multiple classes of metabolites by comparison with normalization using isotope-labeled internal standards. QC sample-based intensity drift correction significantly improved correlation with IS-normalized data, and resulted in detection of additional metabolites with significant physiological response to the MMTT. The relative merits of different QC-sample curve fitting strategies are discussed in the context of batch size and drift pattern complexity. Our drift correction tool offers a practical, simplified approach to drift correction and batch combination in large metabolomics studies

  1. RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites.

    Science.gov (United States)

    Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K; Mathé, Ewy A

    2018-02-22

    The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be

  2. COordination of Standards in MetabOlomicS (COSMOS): facilitating integrated metabolomics data access

    NARCIS (Netherlands)

    Salek, R.M.; Neumann, S.; Schober, D.; Hummel, J.; Billiau, K.; Kopka, J.; Correa, E.; Reijmers, T.; Rosato, A.; Tenori, L.; Turano, P.; Marin, S.; Deborde, C.; Jacob, D.; Rolin, D.; Dartigues, B.; Conesa, P.; Haug, K.; Rocca-Serra, P.; O’Hagan, S.; Hao, J.; Vliet, M. van; Sysi-Aho, M.; Ludwig, C.; Bouwman, J.; Cascante, M.; Ebbels, T.; Griffin, J.L.; Moing, A.; Nikolski, M.; Oresic, M.; Sansone, S.A.; Viant, M.R.; Goodacre, R.; Günther, U.L.; Hankemeier, T.; Luchinat, C.; Walther, D.; Steinbeck, C.

    2015-01-01

    Metabolomics has become a crucial phenotyping technique in a range of research fields including medicine, the life sciences, biotechnology and the environmental sciences. This necessitates the transfer of experimental information between research groups, as well as potentially to publishers and

  3. Metabolomics as a tool to identify biomarkers to predict and improve outcomes in reproductive medicine: a systematic review.

    Science.gov (United States)

    Bracewell-Milnes, Timothy; Saso, Srdjan; Abdalla, Hossam; Nikolau, Dimitrios; Norman-Taylor, Julian; Johnson, Mark; Holmes, Elaine; Thum, Meen-Yau

    2017-11-01

    Infertility is a complex disorder with significant medical, psychological and financial consequences for patients. With live-birth rates per cycle below 30% and a drive from the Human Fertilisation and Embryology Authority (HFEA) to encourage single embryo transfer, there is significant research in different areas aiming to improve success rates of fertility treatments. One such area is investigating the causes of infertility at a molecular level, and metabolomics techniques provide a platform for studying relevant biofluids in the reproductive tract. The aim of this systematic review is to examine the recent findings for the potential application of metabolomics to female reproduction, specifically to the metabolomics of follicular fluid (FF), embryo culture medium (ECM) and endometrial fluid. To our knowledge no other systematic review has investigated this topic. English peer-reviewed journals on PubMed, Science Direct, SciFinder, were systematically searched for studies investigating metabolomics and the female reproductive tract with no time restriction set for publications. Studies were assessed for quality using the risk of bias assessment and ROBIN-I. There were 21 studies that met the inclusion criteria and were included in the systematic review. Metabolomic studies have been employed for the compositional analysis of various biofluids in the female reproductive tract, including FF, ECM, blastocoele fluid and endometrial fluid. There is some weak evidence that metabolomics technologies studying ECM might be able to predict the viability of individual embryos and implantation rate better than standard embryo morphology, However these data were not supported by randomized the controlled trials (RCTs) which showed no evidence that using metabolomics is able to improve the most important reproductive outcomes, such as clinical pregnancy and live-birth rates. This systematic review provides guidance for future metabolomic studies on biofluids of the female

  4. Accurate, fully-automated NMR spectral profiling for metabolomics.

    Directory of Open Access Journals (Sweden)

    Siamak Ravanbakhsh

    Full Text Available Many diseases cause significant changes to the concentrations of small molecules (a.k.a. metabolites that appear in a person's biofluids, which means such diseases can often be readily detected from a person's "metabolic profile"-i.e., the list of concentrations of those metabolites. This information can be extracted from a biofluids Nuclear Magnetic Resonance (NMR spectrum. However, due to its complexity, NMR spectral profiling has remained manual, resulting in slow, expensive and error-prone procedures that have hindered clinical and industrial adoption of metabolomics via NMR. This paper presents a system, BAYESIL, which can quickly, accurately, and autonomously produce a person's metabolic profile. Given a 1D 1H NMR spectrum of a complex biofluid (specifically serum or cerebrospinal fluid, BAYESIL can automatically determine the metabolic profile. This requires first performing several spectral processing steps, then matching the resulting spectrum against a reference compound library, which contains the "signatures" of each relevant metabolite. BAYESIL views spectral matching as an inference problem within a probabilistic graphical model that rapidly approximates the most probable metabolic profile. Our extensive studies on a diverse set of complex mixtures including real biological samples (serum and CSF, defined mixtures and realistic computer generated spectra; involving > 50 compounds, show that BAYESIL can autonomously find the concentration of NMR-detectable metabolites accurately (~ 90% correct identification and ~ 10% quantification error, in less than 5 minutes on a single CPU. These results demonstrate that BAYESIL is the first fully-automatic publicly-accessible system that provides quantitative NMR spectral profiling effectively-with an accuracy on these biofluids that meets or exceeds the performance of trained experts. We anticipate this tool will usher in high-throughput metabolomics and enable a wealth of new applications of

  5. The exo-metabolome in filamentous fungi

    DEFF Research Database (Denmark)

    Thrane, Ulf; Andersen, Birgitte; Frisvad, Jens Christian

    2007-01-01

    Filamentous fungi are a diverse group of eukaryotic microorganisms that have a significant impact on human life as spoilers of food and feed by degradation and toxin production. They are also most useful as a source of bulk and fine chemicals and pharmaceuticals. This chapter focuses on the exo-metabolome...

  6. Metabolome analysis of Drosophila melanogaster during embryogenesis.

    Science.gov (United States)

    An, Phan Nguyen Thuy; Yamaguchi, Masamitsu; Bamba, Takeshi; Fukusaki, Eiichiro

    2014-01-01

    The Drosophila melanogaster embryo has been widely utilized as a model for genetics and developmental biology due to its small size, short generation time, and large brood size. Information on embryonic metabolism during developmental progression is important for further understanding the mechanisms of Drosophila embryogenesis. Therefore, the aim of this study is to assess the changes in embryos' metabolome that occur at different stages of the Drosophila embryonic development. Time course samples of Drosophila embryos were subjected to GC/MS-based metabolome analysis for profiling of low molecular weight hydrophilic metabolites, including sugars, amino acids, and organic acids. The results showed that the metabolic profiles of Drosophila embryo varied during the course of development and there was a strong correlation between the metabolome and different embryonic stages. Using the metabolome information, we were able to establish a prediction model for developmental stages of embryos starting from their high-resolution quantitative metabolite composition. Among the important metabolites revealed from our model, we suggest that different amino acids appear to play distinct roles in different developmental stages and an appropriate balance in trehalose-glucose ratio is crucial to supply the carbohydrate source for the development of Drosophila embryo.

  7. Circadian Metabolomics in Time and Space

    Directory of Open Access Journals (Sweden)

    Kenneth A. Dyar

    2017-07-01

    Full Text Available Circadian rhythms are widely known to govern human health and disease, but specific pathogenic mechanisms linking circadian disruption to metabolic diseases are just beginning to come to light. This is thanks in part to the development and application of various “omics”-based tools in biology and medicine. Current high-throughput technologies allow for the simultaneous monitoring of multiple dynamic cellular events over time, ranging from gene expression to metabolite abundance and sub-cellular localization. These fundamental temporal and spatial perspectives have allowed for a more comprehensive understanding of how various dynamic cellular events and biochemical processes are related in health and disease. With advances in technology, metabolomics has become a more routine “omics” approach for studying metabolism, and “circadian metabolomics” (i.e., studying the 24-h metabolome has recently been undertaken by several groups. To date, circadian metabolomes have been reported for human serum, saliva, breath, and urine, as well as tissues from several species under specific disease or mutagenesis conditions. Importantly, these studies have consistently revealed that 24-h rhythms are prevalent in almost every tissue and metabolic pathway. Furthermore, these circadian rhythms in tissue metabolism are ultimately linked to and directed by internal 24-h biological clocks. In this review, we will attempt to put these data-rich circadian metabolomics experiments into perspective to find out what they can tell us about metabolic health and disease, and what additional biomarker potential they may reveal.

  8. Metabolomics in the fight against malaria

    Directory of Open Access Journals (Sweden)

    Jorge L Salinas

    2014-08-01

    Full Text Available Metabolomics uses high-resolution mass spectrometry to provide a chemical fingerprint of thousands of metabolites present in cells, tissues or body fluids. Such metabolic phenotyping has been successfully used to study various biologic processes and disease states. High-resolution metabolomics can shed new light on the intricacies of host-parasite interactions in each stage of the Plasmodium life cycle and the downstream ramifications on the host’s metabolism, pathogenesis and disease. Such data can become integrated with other large datasets generated using top-down systems biology approaches and be utilised by computational biologists to develop and enhance models of malaria pathogenesis relevant for identifying new drug targets or intervention strategies. Here, we focus on the promise of metabolomics to complement systems biology approaches in the quest for novel interventions in the fight against malaria. We introduce the Malaria Host-Pathogen Interaction Center (MaHPIC, a new systems biology research coalition. A primary goal of the MaHPIC is to generate systems biology datasets relating to human and non-human primate (NHP malaria parasites and their hosts making these openly available from an online relational database. Metabolomic data from NHP infections and clinical malaria infections from around the world will comprise a unique global resource.

  9. Metabolomics studies in brain tissue: A review.

    Science.gov (United States)

    Gonzalez-Riano, Carolina; Garcia, Antonia; Barbas, Coral

    2016-10-25

    Brain is still an organ with a composition to be discovered but beyond that, mental disorders and especially all diseases that curse with dementia are devastating for the patient, the family and the society. Metabolomics can offer an alternative tool for unveiling new insights in the discovery of new treatments and biomarkers of mental disorders. Until now, most of metabolomic studies have been based on biofluids: serum/plasma or urine, because brain tissue accessibility is limited to animal models or post mortem studies, but even so it is crucial for understanding the pathological processes. Metabolomics studies of brain tissue imply several challenges due to sample extraction, along with brain heterogeneity, sample storage, and sample treatment for a wide coverage of metabolites with a wide range of concentrations of many lipophilic and some polar compounds. In this review, the current analytical practices for target and non-targeted metabolomics are described and discussed with emphasis on critical aspects: sample treatment (quenching, homogenization, filtration, centrifugation and extraction), analytical methods, as well as findings considering the used strategies. Besides that, the altered analytes in the different brain regions have been associated with their corresponding pathways to obtain a global overview of their dysregulation, trying to establish the link between altered biological pathways and pathophysiological conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Exploring the analysis of structured metabolomics data

    NARCIS (Netherlands)

    Verouden, M.P.H.; Westerhuis, J.A.; van der Werf, M.J.; Smilde, A.K.

    2009-01-01

    In metabolomics research a large number of metabolites are measured that reflect the cellular state under the experimental conditions studied. In many occasions the experiments are performed according to an experimental design to make sure that sufficient variation is induced in the metabolite

  11. Analysis of metabolomics data from twin families

    NARCIS (Netherlands)

    Draisma, Hermanus Henricus Maria

    2011-01-01

    Metabolomics is the comprehensive analysis of small molecules involved in metabolism, on the basis of samples that have been obtained from organisms in a given physiological state. Data obtained from measurements of trait levels in twin families can be used to elucidate the importance of genetic and

  12. Data-processing strategies for metabolomics studies

    NARCIS (Netherlands)

    Hendriks, M.M.W.B.; Eeuwijk, van F.A.; Jellema, R.H.; Westerhuis, J.A.; Reijmers, T.H.; Hoefsloot, H.C.J.; Smilde, A.K.

    2011-01-01

    Metabolomics studies aim at a better understanding of biochemical processes by studying relations between metabolites and between metabolites and other types of information (e.g., sensory and phenotypic features). The objectives of these studies are diverse, but the types of data generated and the

  13. Quantitative metabolomics based on gas chromatography mass spectrometry: Status and perspectives

    NARCIS (Netherlands)

    Koek, M.M.; Jellema, R.H.; Greef, J. van der; Tas, A.C.; Hankemeier, T.

    2011-01-01

    Metabolomics involves the unbiased quantitative and qualitative analysis of the complete set of metabolites present in cells, body fluids and tissues (the metabolome). By analyzing differences between metabolomes using biostatistics (multivariate data analysis; pattern recognition), metabolites

  14. Advancing the large-scale CCS database for metabolomics and lipidomics at the machine-learning era.

    Science.gov (United States)

    Zhou, Zhiwei; Tu, Jia; Zhu, Zheng-Jiang

    2018-02-01

    Metabolomics and lipidomics aim to comprehensively measure the dynamic changes of all metabolites and lipids that are present in biological systems. The use of ion mobility-mass spectrometry (IM-MS) for metabolomics and lipidomics has facilitated the separation and the identification of metabolites and lipids in complex biological samples. The collision cross-section (CCS) value derived from IM-MS is a valuable physiochemical property for the unambiguous identification of metabolites and lipids. However, CCS values obtained from experimental measurement and computational modeling are limited available, which significantly restricts the application of IM-MS. In this review, we will discuss the recently developed machine-learning based prediction approach, which could efficiently generate precise CCS databases in a large scale. We will also highlight the applications of CCS databases to support metabolomics and lipidomics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Complex Role of Secondary Electron Emissions in Dust Grain Charging in Space Environments: Measurements on Apollo 11 and 17 Dust Grains

    Science.gov (United States)

    Abbas, M. M.; Tankosic, D.; Spann, J. F.; LeClair, A. C.

    2010-01-01

    Dust grains in various astrophysical environments are generally charged electrostatically by photoelectric emissions with radiation from nearby sources, or by electron/ion collisions by sticking or secondary electron emissions. Knowledge of the dust grain charges and equilibrium potentials is important for understanding of a variety of physical and dynamical processes in the interstellar medium (ISM), and heliospheric, interplanetary, planetary, and lunar environments. The high vacuum environment on the lunar surface leads to some unusual physical and dynamical phenomena involving dust grains with high adhesive characteristics, and levitation and transportation over long distances. It has been well recognized that the charging properties of individual micron/submicron size dust grains are expected to be substantially different from the corresponding values for bulk materials and theoretical models. In this paper we present experimental results on charging of individual dust grains selected from Apollo 11 and Apollo 17 dust samples by exposing them to mono-energetic electron beams in the 10- 400 eV energy range. The charging rates of positively and negatively charged particles of approximately 0.2 to 13 microns diameters are discussed in terms of the secondary electron emission (SEE) process, which is found to be a complex charging process at electron energies as low as 10-25 eV, with strong particle size dependence. The measurements indicate substantial differences between dust charging properties of individual small size dust grains and of bulk materials.

  16. Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

    Directory of Open Access Journals (Sweden)

    Jeffrey G. Pelton

    2011-09-01

    Full Text Available Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately

  17. Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

    Science.gov (United States)

    Liu, Jia; Litt, Lawrence; Segal, Mark R.; Kelly, Mark J. S.; Pelton, Jeffrey G.; Kim, Myungwon

    2011-01-01

    Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing

  18. MeMo: a hybrid SQL/XML approach to metabolomic data management for functional genomics

    Directory of Open Access Journals (Sweden)

    Hardy Nigel

    2006-06-01

    Full Text Available Abstract Background The genome sequencing projects have shown our limited knowledge regarding gene function, e.g. S. cerevisiae has 5–6,000 genes of which nearly 1,000 have an uncertain function. Their gross influence on the behaviour of the cell can be observed using large-scale metabolomic studies. The metabolomic data produced need to be structured and annotated in a machine-usable form to facilitate the exploration of the hidden links between the genes and their functions. Description MeMo is a formal model for representing metabolomic data and the associated metadata. Two predominant platforms (SQL and XML are used to encode the model. MeMo has been implemented as a relational database using a hybrid approach combining the advantages of the two technologies. It represents a practical solution for handling the sheer volume and complexity of the metabolomic data effectively and efficiently. The MeMo model and the associated software are available at http://dbkgroup.org/memo/. Conclusion The maturity of relational database technology is used to support efficient data processing. The scalability and self-descriptiveness of XML are used to simplify the relational schema and facilitate the extensibility of the model necessitated by the creation of new experimental techniques. Special consideration is given to data integration issues as part of the systems biology agenda. MeMo has been physically integrated and cross-linked to related metabolomic and genomic databases. Semantic integration with other relevant databases has been supported through ontological annotation. Compatibility with other data formats is supported by automatic conversion.

  19. The metabolomic profile of umbilical cord blood in neonatal hypoxic ischaemic encephalopathy.

    Directory of Open Access Journals (Sweden)

    Brian H Walsh

    Full Text Available Hypoxic ischaemic encephalopathy (HIE in newborns can cause significant long-term neurological disability. The insult is a complex injury characterised by energy failure and disruption of cellular homeostasis, leading to mitochondrial damage. The importance of individual metabolic pathways, and their interaction in the disease process is not fully understood. The aim of this study was to describe and quantify the metabolomic profile of umbilical cord blood samples in a carefully defined population of full-term infants with HIE.The injury severity was defined using both the modified Sarnat score and continuous multichannel electroencephalogram. Using these classification systems, our population was divided into those with confirmed HIE (n = 31, asphyxiated infants without encephalopathy (n = 40 and matched controls (n = 71. All had umbilical cord blood drawn and biobanked at -80 °C within 3 hours of delivery. A combined direct injection and LC-MS/MS assay (AbsolutIDQ p180 kit, Biocrates Life Sciences AG, Innsbruck, Austria was used for the metabolomic analyses of the samples. Targeted metabolomic analysis showed a significant alteration between study groups in 29 metabolites from 3 distinct classes (Amino Acids, Acylcarnitines, and Glycerophospholipids. 9 of these metabolites were only significantly altered between neonates with Hypoxic ischaemic encephalopathy and matched controls, while 14 were significantly altered in both study groups. Multivariate Discriminant Analysis models developed showed clear multifactorial metabolite associations with both asphyxia and HIE. A logistic regression model using 5 metabolites clearly delineates severity of asphyxia and classifies HIE infants with AUC = 0.92. These data describe wide-spread disruption to not only energy pathways, but also nitrogen and lipid metabolism in both asphyxia and HIE.This study shows that a multi-platform targeted approach to metabolomic analyses using accurately phenotyped and

  20. Metabolomics of Clostridial Biofuel Production

    Energy Technology Data Exchange (ETDEWEB)

    Rabinowitz, Joshua D [Princeton Univ., NJ (United States); Aristilde, Ludmilla [Cornell Univ., Ithaca, NY (United States); Amador-Noguez, Daniel [Univ. of Wisconsin, Madison, WI (United States)

    2015-09-08

    Members of the genus Clostridium collectively have the ideal set of the metabolic capabilities for fermentative biofuel production: cellulose degradation, hydrogen production, and solvent excretion. No single organism, however, can effectively convert cellulose into biofuels. Here we developed, using metabolomics and isotope tracers, basic science knowledge of Clostridial metabolism of utility for future efforts to engineer such an organism. In glucose fermentation carried out by the biofuel producer Clostridium acetobutylicum, we observed a remarkably ordered series of metabolite concentration changes as the fermentation progressed from acidogenesis to solventogenesis. In general, high-energy compounds decreased while low-energy species increased during solventogenesis. These changes in metabolite concentrations were accompanied by large changes in intracellular metabolic fluxes, with pyruvate directed towards acetyl-CoA and solvents instead of oxaloacetate and amino acids. Thus, the solventogenic transition involves global remodeling of metabolism to redirect resources from biomass production into solvent production. In contrast to C. acetobutylicum, which is an avid fermenter, C. cellulolyticum metabolizes glucose only slowly. We find that glycolytic intermediate concentrations are radically different from fast fermenting organisms. Associated thermodynamic and isotope tracer analysis revealed that the full glycolytic pathway in C. cellulolyticum is reversible. This arises from changes in cofactor utilization for phosphofructokinase and an alternative pathway from phosphoenolpyruvate to pyruvate. The net effect is to increase the high-energy phosphate bond yield of glycolysis by 150% (from 2 to 5) at the expense of lower net flux. Thus, C. cellulolyticum prioritizes glycolytic energy efficiency over speed. Degradation of cellulose results in other sugars in addition to glucose. Simultaneous feeding of stable isotope-labeled glucose and unlabeled pentose sugars

  1. Emerging New Strategies for Successful Metabolite Identification in Metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Bingol, Ahmet K.; Bruschweiler-Li, Lei; Li, Dawei; Zhang, Bo; Xie, Mouzhe; Bruschweiler, Rafael

    2016-02-26

    NMR is a very powerful tool for the identification of known and unknown (or unnamed) metabolites in complex mixtures as encountered in metabolomics. Known compounds can be reliably identified using 2D NMR methods, such as 13C-1H HSQC, for which powerful web servers with databases are available for semi-automated analysis. For the identification of unknown compounds, new combinations of NMR with MS have been developed recently that make synergistic use of the mutual strengths of the two techniques. The use of chemical additives to the NMR tube, such as reactive agents, paramagnetic ions, or charged silica nanoparticles, permit the identification of metabolites with specific physical chemical properties. In the following sections, we give an overview of some of the recent advances in metabolite identification and discuss remaining challenges.

  2. Stoichiometric Correlation Analysis: Principles of Metabolic Functionality from Metabolomics Data

    Directory of Open Access Journals (Sweden)

    Kevin Schwahn

    2017-12-01

    Full Text Available Recent advances in metabolomics technologies have resulted in high-quality (time-resolved metabolic profiles with an increasing coverage of metabolic pathways. These data profiles represent read-outs from often non-linear dynamics of metabolic networks. Yet, metabolic profiles have largely been explored with regression-based approaches that only capture linear relationships, rendering it difficult to determine the extent to which the data reflect the underlying reaction rates and their couplings. Here we propose an approach termed Stoichiometric Correlation Analysis (SCA based on correlation between positive linear combinations of log-transformed metabolic profiles. The log-transformation is due to the evidence that metabolic networks can be modeled by mass action law and kinetics derived from it. Unlike the existing approaches which establish a relation between pairs of metabolites, SCA facilitates the discovery of higher-order dependence between more than two metabolites. By using a paradigmatic model of the tricarboxylic acid cycle we show that the higher-order dependence reflects the coupling of concentration of reactant complexes, capturing the subtle difference between the employed enzyme kinetics. Using time-resolved metabolic profiles from Arabidopsis thaliana and Escherichia coli, we show that SCA can be used to quantify the difference in coupling of reactant complexes, and hence, reaction rates, underlying the stringent response in these model organisms. By using SCA with data from natural variation of wild and domesticated wheat and tomato accession, we demonstrate that the domestication is accompanied by loss of such couplings, in these species. Therefore, application of SCA to metabolomics data from natural variation in wild and domesticated populations provides a mechanistic way to understanding domestication and its relation to metabolic networks.

  3. Chemometric and multivariate statistical analysis of time-of-flight secondary ion mass spectrometry spectra from complex Cu-Fe sulfides.

    Science.gov (United States)

    Kalegowda, Yogesh; Harmer, Sarah L

    2012-03-20

    Time-of-flight secondary ion mass spectrometry (TOF-SIMS) spectra of mineral samples are complex, comprised of large mass ranges and many peaks. Consequently, characterization and classification analysis of these systems is challenging. In this study, different chemometric and statistical data evaluation methods, based on monolayer sensitive TOF-SIMS data, have been tested for the characterization and classification of copper-iron sulfide minerals (chalcopyrite, chalcocite, bornite, and pyrite) at different flotation pulp conditions (feed, conditioned feed, and Eh modified). The complex mass spectral data sets were analyzed using the following chemometric and statistical techniques: principal component analysis (PCA); principal component-discriminant functional analysis (PC-DFA); soft independent modeling of class analogy (SIMCA); and k-Nearest Neighbor (k-NN) classification. PCA was found to be an important first step in multivariate analysis, providing insight into both the relative grouping of samples and the elemental/molecular basis for those groupings. For samples exposed to oxidative conditions (at Eh ~430 mV), each technique (PCA, PC-DFA, SIMCA, and k-NN) was found to produce excellent classification. For samples at reductive conditions (at Eh ~ -200 mV SHE), k-NN and SIMCA produced the most accurate classification. Phase identification of particles that contain the same elements but a different crystal structure in a mixed multimetal mineral system has been achieved.

  4. Binary similarity measures for fingerprint analysis of qualitative metabolomic profiles.

    Science.gov (United States)

    Rácz, Anita; Andrić, Filip; Bajusz, Dávid; Héberger, Károly

    2018-01-01

    Contemporary metabolomic fingerprinting is based on multiple spectrometric and chromatographic signals, used either alone or combined with structural and chemical information of metabolic markers at the qualitative and semiquantitative level. However, signal shifting, convolution, and matrix effects may compromise metabolomic patterns. Recent increase in the use of qualitative metabolomic data, described by the presence (1) or absence (0) of particular metabolites, demonstrates great potential in the field of metabolomic profiling and fingerprint analysis. The aim of this study is a comprehensive evaluation of binary similarity measures for the elucidation of patterns among samples of different botanical origin and various metabolomic profiles. Nine qualitative metabolomic data sets covering a wide range of natural products and metabolomic profiles were applied to assess 44 binary similarity measures for the fingerprinting of plant extracts and natural products. The measures were analyzed by the novel sum of ranking differences method (SRD), searching for the most promising candidates. Baroni-Urbani-Buser (BUB) and Hawkins-Dotson (HD) similarity coefficients were selected as the best measures by SRD and analysis of variance (ANOVA), while Dice (Di1), Yule, Russel-Rao, and Consonni-Todeschini 3 ranked the worst. ANOVA revealed that concordantly and intermediately symmetric similarity coefficients are better candidates for metabolomic fingerprinting than the asymmetric and correlation based ones. The fingerprint analysis based on the BUB and HD coefficients and qualitative metabolomic data performed equally well as the quantitative metabolomic profile analysis. Fingerprint analysis based on the qualitative metabolomic profiles and binary similarity measures proved to be a reliable way in finding the same/similar patterns in metabolomic data as that extracted from quantitative data.

  5. Secondary Hypertension

    Science.gov (United States)

    Secondary hypertension Overview Secondary hypertension (secondary high blood pressure) is high blood pressure that's caused by another medical condition. Secondary hypertension can be caused by conditions that affect your kidneys, ...

  6. Experimental Chagas disease-induced perturbations of the fecal microbiome and metabolome.

    Science.gov (United States)

    McCall, Laura-Isobel; Tripathi, Anupriya; Vargas, Fernando; Knight, Rob; Dorrestein, Pieter C; Siqueira-Neto, Jair L

    2018-03-01

    Trypanosoma cruzi parasites are the causative agents of Chagas disease. These parasites infect cardiac and gastrointestinal tissues, leading to local inflammation and tissue damage. Digestive Chagas disease is associated with perturbations in food absorption, intestinal traffic and defecation. However, the impact of T. cruzi infection on the gut microbiota and metabolome have yet to be characterized. In this study, we applied mass spectrometry-based metabolomics and 16S rRNA sequencing to profile infection-associated alterations in fecal bacterial composition and fecal metabolome through the acute-stage and into the chronic stage of infection, in a murine model of Chagas disease. We observed joint microbial and chemical perturbations associated with T. cruzi infection. These included alterations in conjugated linoleic acid (CLA) derivatives and in specific members of families Ruminococcaceae and Lachnospiraceae, as well as alterations in secondary bile acids and members of order Clostridiales. These results highlight the importance of multi-'omics' and poly-microbial studies in understanding parasitic diseases in general, and Chagas disease in particular.

  7. Metabolomics reveals variation and correlation among different tissues of olive (Olea europaea L.

    Directory of Open Access Journals (Sweden)

    Rao Guodong

    2017-09-01

    Full Text Available Metabolites in olives are associated with nutritional value and physiological properties. However, comprehensive information regarding the olive metabolome is limited. In this study, we identified 226 metabolites from three different tissues of olive using a non-targeted metabolomic profiling approach, of which 76 named metabolites were confirmed. Further statistical analysis revealed that these 76 metabolites covered different types of primary metabolism and some of the secondary metabolism pathways. One-way analysis of variance (ANOVA statistical assay was performed to calculate the variations within the detected metabolites, and levels of 65 metabolites were differentially expressed in different samples. Hierarchical cluster analysis (HCA dendrograms showed variations among different tissues that were similar to the metabolite profiles observed in new leaves and fruit. Additionally, 5776 metabolite-metabolite correlations were detected by a Pearson correlation coefficient approach. Screening of the calculated correlations revealed 3136, 3025, and 5184 were determined to metabolites and had significant correlations in three different combinations, respectively. This work provides the first comprehensive metabolomic of olive, which will provide new insights into understanding the olive metabolism, and potentially help advance studies in olive metabolic engineering.

  8. Gaharu, from the metabolomic aspect

    International Nuclear Information System (INIS)

    Chong Saw Peng; Ahsanulkhaliqin Abdul Wahab; Mohd Fajri Osman; Shyful Azizi Abdul Rahman; Khairuddin Abdul Rahim; Mat Rasol Awang

    2006-01-01

    Agarwood, one of the timber woody plant which has the similar response as grand fir toward external invasion and is able to produce oleoresin as the secondary metabolite from plant defense system to inhibit the invader and heal the wound. Species of agarwood found in Malaysia is known as Aquilaria malaccensis, and locally known as karas or depu. A. malaccensis is valuable due to its oleoresin (gaharu). Gaharu is a product produced in the secondary metabolic pathway known as terpenoid synthesis pathway. In order to switch on this pathway, the plant defense system need to be induced and lead to the octadecanoid pathway where the linolenic acid (LA) converts to jasmonic acid (JA). Jasmonic acid is the major key to switch the plant metabolic pathway from primary metabolic pathway to secondary metabolic pathway. To prove this hypothesis, some researches on molecular study such as gene expression and protein expression are conducted to identify key components, which will lead to the manipulation of the metabolic pathway. (Author)

  9. THE PAST, THE PRESENT AND THE FUTURE OF THE COMPREHENSIVE SECONDARY SCHOOL COMPLEX NO 2 IN BIAŁY BÓR IN THE COMMON EDUCATIONAL SPACE

    Directory of Open Access Journals (Sweden)

    Izabela Stelmasiak

    2017-04-01

    Full Text Available The phenomenon of globalization, cultural changes, increased migration processes lead Europe/ the World to a model of a global village. The feeling of national identity, the awareness of common and different features resulting from the history, origin and culture play an important role for its inhabitants. The reality of a multicultural society is a subject of research and postulates of intercultural pedagogy.The above issue refers also to Poland  which has been a multicultural country for century. Nowadays the following minority groups should be distinguished: Germans, Belarusians, Ukrainians, Russians, Czechs, Slovaks, Jews and Armenians. The ethnic minorities include: Romani people, Lemkos and Tatars, however Silesians and Kashubians are proposed minorities.The system changes of Poland after the year 1990 caused a change of legislation and ratifying international conventions which determined the legal frames and the scope of the activity of minority groups.Ukrainians have a special position in the Pomeranian region due to a migration action “Vistula” which was carried out in the year 1947 by communist authorities. At present 6.5 thousand people live in the north of the country, most of them in  districts of Człuchów (1.19 % and Szczecinek (1.12 % of the total number of inhabitants.Education, especially communicative competences in a language of ancestors are a leading purpose of teaching. Complexes of Secondary Schools in Biały Bór, Górów Iławiecki, Legnica, Przemyśl, Bartoszyce and Ukrainian classes in Banie Mazurskie and Bielsko Podlaskie realize bilingual teaching. Apart from didactical and educational activity these schools play a role of the centres of pension trustees of Ukrainian culture, the culture which they promote in social environment.The Taras Szewczenko Complex of Secondary Schools No2 in Biały Bór is a representative school in Pomerania. The fate of the school present symbolically the fate of

  10. Metabolomics to Decipher the Chemical Defense of Cereals against Fusarium graminearum and Deoxynivalenol Accumulation

    Directory of Open Access Journals (Sweden)

    Léa Gauthier

    2015-10-01

    Full Text Available Fusarium graminearum is the causal agent of Fusarium head blight (FHB and Gibberella ear rot (GER, two devastating diseases of wheat, barley, and maize. Furthermore, F. graminearum species can produce type B trichothecene mycotoxins that accumulate in grains. Use of FHB and GER resistant cultivars is one of the most promising strategies to reduce damage induced by F. graminearum. Combined with genetic approaches, metabolomic ones can provide powerful opportunities for plant breeding through the identification of resistant biomarker metabolites which have the advantage of integrating the genetic background and the influence of the environment. In the past decade, several metabolomics attempts have been made to decipher the chemical defense that cereals employ to counteract F. graminearum. By covering the major classes of metabolites that have been highlighted and addressing their potential role, this review demonstrates the complex and integrated network of events that cereals can orchestrate to resist to F. graminearum.

  11. Gut metabolome meets microbiome: A methodological perspective to understand the relationship between host and microbe.

    Science.gov (United States)

    Lamichhane, Santosh; Sen, Partho; Dickens, Alex M; Orešič, Matej; Bertram, Hanne Christine

    2018-04-30

    It is well established that gut microbes and their metabolic products regulate host metabolism. The interactions between the host and its gut microbiota are highly dynamic and complex. In this review we present and discuss the metabolomic strategies to study the gut microbial ecosystem. We highlight the metabolic profiling approaches to study faecal samples aimed at deciphering the metabolic product derived from gut microbiota. We also discuss how metabolomics data can be integrated with metagenomics data derived from gut microbiota and how such approaches may lead to better understanding of the microbial functions. Finally, the emerging approaches of genome-scale metabolic modelling to study microbial co-metabolism and host-microbe interactions are highlighted. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Metabolomics to Decipher the Chemical Defense of Cereals against Fusarium graminearum and Deoxynivalenol Accumulation

    Science.gov (United States)

    Gauthier, Léa; Atanasova-Penichon, Vessela; Chéreau, Sylvain; Richard-Forget, Florence

    2015-01-01

    Fusarium graminearum is the causal agent of Fusarium head blight (FHB) and Gibberella ear rot (GER), two devastating diseases of wheat, barley, and maize. Furthermore, F. graminearum species can produce type B trichothecene mycotoxins that accumulate in grains. Use of FHB and GER resistant cultivars is one of the most promising strategies to reduce damage induced by F. graminearum. Combined with genetic approaches, metabolomic ones can provide powerful opportunities for plant breeding through the identification of resistant biomarker metabolites which have the advantage of integrating the genetic background and the influence of the environment. In the past decade, several metabolomics attempts have been made to decipher the chemical defense that cereals employ to counteract F. graminearum. By covering the major classes of metabolites that have been highlighted and addressing their potential role, this review demonstrates the complex and integrated network of events that cereals can orchestrate to resist to F. graminearum. PMID:26492237

  13. Integration of Plant Metabolomics Data with Metabolic Networks: Progresses and Challenges.

    Science.gov (United States)

    Töpfer, Nadine; Seaver, Samuel M D; Aharoni, Asaph

    2018-01-01

    In the last decade, plant genome-scale modeling has developed rapidly and modeling efforts have advanced from representing metabolic behavior of plant heterotrophic cell suspensions to studying the complex interplay of cell types, tissues, and organs. A crucial driving force for such developments is the availability and integration of "omics" data (e.g., transcriptomics, proteomics, and metabolomics) which enable the reconstruction, extraction, and application of context-specific metabolic networks. In this chapter, we demonstrate a workflow to integrate gas chromatography coupled to mass spectrometry (GC-MS)-based metabolomics data of tomato fruit pericarp (flesh) tissue, at five developmental stages, with a genome-scale reconstruction of tomato metabolism. This method allows for the extraction of context-specific networks reflecting changing activities of metabolic pathways throughout fruit development and maturation.

  14. Chemometrics applied to quality control and metabolomics for traditional Chinese medicines.

    Science.gov (United States)

    Liu, Shao; Liang, Yi-Zeng; Liu, Hai-Tao

    2016-03-15

    Traditional Chinese medicines (TCMs) bring a great challenge in quality control and evaluating the efficacy because of their complexity of chemical composition. Chemometric techniques provide a good opportunity for mining more useful chemical information from TCMs. Then, the application of chemometrics in the field of TCMs is spontaneous and necessary. This review focuses on the recent various important chemometrics tools for chromatographic fingerprinting, including peak alignment information features, baseline correction and applications of chemometrics in metabolomics and modernization of TCMs, including authentication and evaluation of the quality of TCMs, evaluating the efficacy of TCMs and essence of TCM syndrome. In the conclusions, the general trends and some recommendations for improving chromatographic metabolomics data analysis are provided. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Proteomics and metabolomics for mechanistic insights and biomarker discovery in cardiovascular disease.

    Science.gov (United States)

    Barallobre-Barreiro, Javier; Chung, Yuen-Li; Mayr, Manuel

    2013-08-01

    In the last decade, proteomics and metabolomics have contributed substantially to our understanding of cardiovascular diseases. The unbiased assessment of pathophysiological processes without a priori assumptions complements other molecular biology techniques that are currently used in a reductionist approach. In this review, we highlight some of the "omics" methods used to assess protein and metabolite changes in cardiovascular disease. A discrete biological function is very rarely attributed to a single molecule; more often it is the combined input of many proteins. In contrast to the reductionist approach, in which molecules are studied individually, "omics" platforms allow the study of more complex interactions in biological systems. Combining proteomics and metabolomics to quantify changes in metabolites and their corresponding enzymes will advance our understanding of pathophysiological mechanisms and aid the identification of novel biomarkers for cardiovascular disease. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  16. Metabolomic analysis of three Mollicute species.

    Directory of Open Access Journals (Sweden)

    Anna A Vanyushkina

    Full Text Available We present a systematic study of three bacterial species that belong to the class Mollicutes, the smallest and simplest bacteria, Spiroplasma melliferum, Mycoplasma gallisepticum, and Acholeplasma laidlawii. To understand the difference in the basic principles of metabolism regulation and adaptation to environmental conditions in the three species, we analyzed the metabolome of these bacteria. Metabolic pathways were reconstructed using the proteogenomic annotation data provided by our lab. The results of metabolome, proteome and genome profiling suggest a fundamental difference in the adaptation of the three closely related Mollicute species to stress conditions. As the transaldolase is not annotated in Mollicutes, we propose variants of the pentose phosphate pathway catalyzed by annotated enzymes for three species. For metabolite detection we employed high performance liquid chromatography coupled with mass spectrometry. We used liquid chromatography method - hydrophilic interaction chromatography with silica column - as it effectively separates highly polar cellular metabolites prior to their detection by mass spectrometer.

  17. Metabolomics Workbench: An international repository for metabolomics data and metadata, metabolite standards, protocols, tutorials and training, and analysis tools.

    Science.gov (United States)

    Sud, Manish; Fahy, Eoin; Cotter, Dawn; Azam, Kenan; Vadivelu, Ilango; Burant, Charles; Edison, Arthur; Fiehn, Oliver; Higashi, Richard; Nair, K Sreekumaran; Sumner, Susan; Subramaniam, Shankar

    2016-01-04

    The Metabolomics Workbench, available at www.metabolomicsworkbench.org, is a public repository for metabolomics metadata and experimental data spanning various species and experimental platforms, metabolite standards, metabolite structures, protocols, tutorials, and training material and other educational resources. It provides a computational platform to integrate, analyze, track, deposit and disseminate large volumes of heterogeneous data from a wide variety of metabolomics studies including mass spectrometry (MS) and nuclear magnetic resonance spectrometry (NMR) data spanning over 20 different species covering all the major taxonomic categories including humans and other mammals, plants, insects, invertebrates and microorganisms. Additionally, a number of protocols are provided for a range of metabolite classes, sample types, and both MS and NMR-based studies, along with a metabolite structure database. The metabolites characterized in the studies available on the Metabolomics Workbench are linked to chemical structures in the metabolite structure database to facilitate comparative analysis across studies. The Metabolomics Workbench, part of the data coordinating effort of the National Institute of Health (NIH) Common Fund's Metabolomics Program, provides data from the Common Fund's Metabolomics Resource Cores, metabolite standards, and analysis tools to the wider metabolomics community and seeks data depositions from metabolomics researchers across the world. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases

    Directory of Open Access Journals (Sweden)

    Jianhong Lu

    2017-08-01

    Full Text Available Coronary heart disease (CHD is a complex human disease associated with inflammation and oxidative stress. The underlying mechanisms and diagnostic biomarkers for the different types of CHD remain poorly defined. Metabolomics has been increasingly recognized as an enabling technique with the potential to identify key metabolomic features in an attempt to understand the pathophysiology and differentiate different stages of CHD. We performed comprehensive metabolomic analysis in human plasma from 28 human subjects with stable angina (SA, myocardial infarction (MI, and healthy control (HC. Subsequent analysis demonstrated a uniquely altered metabolic profile in these CHD: a total of 18, 37 and 36 differential metabolites were identified to distinguish SA from HC, MI from SA, and MI from HC groups respectively. Among these metabolites, glycerophospholipid (GPL metabolism emerged as the most significantly disturbed pathway. Next, we used a targeted metabolomic approach to systematically analyze GPL, oxidized phospholipid (oxPL, and downstream metabolites derived from polyunsaturated fatty acids (PUFAs, such as arachidonic acid and linoleic acid. Surprisingly, lipids associated with lipid peroxidation (LPO pathways including oxidized PL and isoprostanes, isomers of prostaglandins, were significantly elevated in plasma of MI patients comparing to HC and SA, consistent with the notion that oxidative stress-induced LPO is a prominent feature in CHD. Our studies using the state-of-the-art metabolomics help to understand the underlying biological mechanisms involved in the pathogenesis of CHD; LPO metabolites may serve as potential biomarkers to differentiation MI from SA and HC. Keywords: Metabolomics, Lipid peroxidation, Lipidomics, Myocardial infarction, Isoprostanes, Coronary heart disease (CHD

  19. Blood Transcriptomics and Metabolomics for Personalized Medicine

    Science.gov (United States)

    2015-10-31

    involved in rheumatoid arthritis . PLoS Comput Biol 2011;7. [100] Zhu J. Stitching together multiple data dimensions reveals interacting metabolomic...capability, detecting N10,000 metabo- lites, together with environmental exposure, dietary intake, microbial activity, and pharmaceutical drugs. Thus...research to clinical care has constantly seen huge disap- pointments. With the accumulation of detailed, information-rich data, human subjects start to

  20. Data fusion in metabolomic cancer diagnostics

    DEFF Research Database (Denmark)

    Bro, Rasmus; Nielsen, Hans Jørgen; Savorani, Francesco

    2013-01-01

    We have recently shown that fluorescence spectroscopy of plasma samples has promising abilities regarding early detection of colorectal cancer. In the present paper, these results were further developed by combining fluorescence with the biomarkers, CEA and TIMP-1 and traditional metabolomic meas...... measurements in the form of (1)H NMR spectroscopy. The results indicate that using an extensive profile established by combining such measurements together with the biomarkers is better than using single markers....

  1. Chemical Composition and Seasonality of Aromatic Mediterranean Plant Species by NMR-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Monica Scognamiglio

    2015-01-01

    Full Text Available An NMR-based metabolomic approach has been applied to analyse seven aromatic Mediterranean plant species used in traditional cuisine. Based on the ethnobotanical use of these plants, the approach has been employed in order to study the metabolic changes during different seasons. Primary and secondary metabolites have been detected and quantified. Flavonoids (apigenin, quercetin, and kaempferol derivatives and phenylpropanoid derivatives (e.g., chlorogenic and rosmarinic acid are the main identified polyphenols. The richness in these metabolites could explain the biological properties ascribed to these plant species.

  2. Chemical Composition and Seasonality of Aromatic Mediterranean Plant Species by NMR-Based Metabolomics.

    Science.gov (United States)

    Scognamiglio, Monica; D'Abrosca, Brigida; Esposito, Assunta; Fiorentino, Antonio

    2015-01-01

    An NMR-based metabolomic approach has been applied to analyse seven aromatic Mediterranean plant species used in traditional cuisine. Based on the ethnobotanical use of these plants, the approach has been employed in order to study the metabolic changes during different seasons. Primary and secondary metabolites have been detected and quantified. Flavonoids (apigenin, quercetin, and kaempferol derivatives) and phenylpropanoid derivatives (e.g., chlorogenic and rosmarinic acid) are the main identified polyphenols. The richness in these metabolites could explain the biological properties ascribed to these plant species.

  3. PAMDB: a comprehensive Pseudomonas aeruginosa metabolome database.

    Science.gov (United States)

    Huang, Weiliang; Brewer, Luke K; Jones, Jace W; Nguyen, Angela T; Marcu, Ana; Wishart, David S; Oglesby-Sherrouse, Amanda G; Kane, Maureen A; Wilks, Angela

    2018-01-04

    The Pseudomonas aeruginosaMetabolome Database (PAMDB, http://pseudomonas.umaryland.edu) is a searchable, richly annotated metabolite database specific to P. aeruginosa. P. aeruginosa is a soil organism and significant opportunistic pathogen that adapts to its environment through a versatile energy metabolism network. Furthermore, P. aeruginosa is a model organism for the study of biofilm formation, quorum sensing, and bioremediation processes, each of which are dependent on unique pathways and metabolites. The PAMDB is modelled on the Escherichia coli (ECMDB), yeast (YMDB) and human (HMDB) metabolome databases and contains >4370 metabolites and 938 pathways with links to over 1260 genes and proteins. The database information was compiled from electronic databases, journal articles and mass spectrometry (MS) metabolomic data obtained in our laboratories. For each metabolite entered, we provide detailed compound descriptions, names and synonyms, structural and physiochemical information, nuclear magnetic resonance (NMR) and MS spectra, enzymes and pathway information, as well as gene and protein sequences. The database allows extensive searching via chemical names, structure and molecular weight, together with gene, protein and pathway relationships. The PAMBD and its future iterations will provide a valuable resource to biologists, natural product chemists and clinicians in identifying active compounds, potential biomarkers and clinical diagnostics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Major-histocompatibility-complex-associated variation in secondary sexual traits of white-tailed deer (Odocoileus virginianus): evidence for good-genes advertisement.

    Science.gov (United States)

    Ditchkoff, S S; Lochmiller, R L; Masters, R E; Hoofer, S R; Van Den Bussche, R A

    2001-03-01

    Good-genes hypotheses predict that development of secondary sexual characters can be an honest advertisement of heritable male quality. We explored this hypothesis using a cervid model (adult, male white-tailed deer, Odocoileus virginianus) to determine whether antler development could provide an honest signal of a male's genetic quality and condition to adversaries. We compared antler, morphometric, hormonal, and parasitic data collected from hunter-harvested deer to characteristics of the Mhc-DRB (Odvi), the most widely studied gene of the major histocompatibility complex (MHC) in Artiodactyla. We detected associations between genetic characteristics at Odvi-DRB and antler development and body mass, suggesting that antler development and body mass may be associated with pathogen resistance in deer and thus may be an honest signal of genetic quality. We also detected associations between Odvi-DRB characteristics and serum testosterone during the breeding season, suggesting that certain MHC characteristics may help deer cope with stresses related to breeding activity. In addition, we observed a negative relationship between degree of antler development and overall abundance of abomasal helminths. Our observations provide support for the hypothesis that antler development in white-tailed deer is an honest signal of quality.

  5. A metabolomics study on human dietary intervention with apples

    DEFF Research Database (Denmark)

    Dragsted, L. O.; Kristensen, M.; Ravn-Haren, Gitte

    2009-01-01

    Metabolomics is a promising tool for searching out new biomarkers and the development of hypotheses in nutrition research. This chapter will describe the design of human dietary intervention studies where samples are collected for metabolomics analyses as well as the analytical issues and data...

  6. Plant metabolomics and its potential application for human nutrition

    NARCIS (Netherlands)

    Hall, R.D.; Brouwer, I.D.; Fitzgerald, M.A.

    2008-01-01

    With the growing interest in the use of metabolomic technologies for a wide range of biological targets, food applications related to nutrition and quality are rapidly emerging. Metabolomics offers us the opportunity to gain deeper insights into, and have better control of, the fundamental

  7. Untargeted Metabolomics Strategies—Challenges and Emerging Directions

    Science.gov (United States)

    Schrimpe-Rutledge, Alexandra C.; Codreanu, Simona G.; Sherrod, Stacy D.; McLean, John A.

    2016-12-01

    Metabolites are building blocks of cellular function. These species are involved in enzyme-catalyzed chemical reactions and are essential for cellular function. Upstream biological disruptions result in a series of metabolomic changes and, as such, the metabolome holds a wealth of information that is thought to be most predictive of phenotype. Uncovering this knowledge is a work in progress. The field of metabolomics is still maturing; the community has leveraged proteomics experience when applicable and developed a range of sample preparation and instrument methodology along with myriad data processing and analysis approaches. Research focuses have now shifted toward a fundamental understanding of the biology responsible for metabolomic changes. There are several types of metabolomics experiments including both targeted and untargeted analyses. While untargeted, hypothesis generating workflows exhibit many valuable attributes, challenges inherent to the approach remain. This Critical Insight comments on these challenges, focusing on the identification process of LC-MS-based untargeted metabolomics studies—specifically in mammalian systems. Biological interpretation of metabolomics data hinges on the ability to accurately identify metabolites. The range of confidence associated with identifications that is often overlooked is reviewed, and opportunities for advancing the metabolomics field are described.

  8. Gas chromatography mass spectrometry : key technology in metabolomics

    NARCIS (Netherlands)

    Koek, Maud Marijtje

    2009-01-01

    Metabolomics involves the unbiased quantitative and qualitative analysis of the complete set of metabolites present in cells, body fluids and tissues. Gas chromatography coupled to mass spectrometry (GC-MS) is very suitable for metabolomics analysis, as it combines high separation power with

  9. Metabolomics to study functional consequences in peroxisomal disorders

    NARCIS (Netherlands)

    Herzog, K.

    2017-01-01

    This thesis focusses on metabolomics approaches performed in cultured cells and blood samples from patients with peroxisomal disorders. By applying both targeted and untargeted metabolomics, the aim of these approaches was to study the functional consequences of the primary genetic defects causing

  10. Metabolomics for Undergraduates: Identification and Pathway Assignment of Mitochondrial Metabolites

    Science.gov (United States)

    Marques, Ana Patrícia; Serralheiro, Maria Luisa; Ferreira, António E. N.; Freire, Ana Ponces; Cordeiro, Carlos; Silva, Marta Sousa

    2016-01-01

    Metabolomics is a key discipline in systems biology, together with genomics, transcriptomics, and proteomics. In this omics cascade, the metabolome represents the biochemical products that arise from cellular processes and is often regarded as the final response of a biological system to environmental or genetic changes. The overall screening…

  11. Applications of Metabolomics in Agriculture

    NARCIS (Netherlands)

    Dixon, R.; Gang, D.R.; Charlton, A.J.; Fiehn, O.; Kuiper, H.A.; Reynolds, T.L.; Tjeerdema, R.S.; Jeffery, E.H.; German, J.B.; Ridley, W.P.; Seiber, J.N.

    2006-01-01

    Biological systems are exceedingly complex. The unraveling of the genome in plants and humans revealed fewer than the anticipated number of genes. Therefore, other processes such as the regulation of gene expression, the action of gene products, and the metabolic networks resulting from catalytic

  12. Mapping gas-phase organic reactivity and concomitant secondary organic aerosol formation: chemometric dimension reduction techniques for the deconvolution of complex atmospheric data sets

    Science.gov (United States)

    Wyche, K. P.; Monks, P. S.; Smallbone, K. L.; Hamilton, J. F.; Alfarra, M. R.; Rickard, A. R.; McFiggans, G. B.; Jenkin, M. E.; Bloss, W. J.; Ryan, A. C.; Hewitt, C. N.; MacKenzie, A. R.

    2015-07-01

    Highly non-linear dynamical systems, such as those found in atmospheric chemistry, necessitate hierarchical approaches to both experiment and modelling in order to ultimately identify and achieve fundamental process-understanding in the full open system. Atmospheric simulation chambers comprise an intermediate in complexity, between a classical laboratory experiment and the full, ambient system. As such, they can generate large volumes of difficult-to-interpret data. Here we describe and implement a chemometric dimension reduction methodology for the deconvolution and interpretation of complex gas- and particle-phase composition spectra. The methodology comprises principal component analysis (PCA), hierarchical cluster analysis (HCA) and positive least-squares discriminant analysis (PLS-DA). These methods are, for the first time, applied to simultaneous gas- and particle-phase composition data obtained from a comprehensive series of environmental simulation chamber experiments focused on biogenic volatile organic compound (BVOC) photooxidation and associated secondary organic aerosol (SOA) formation. We primarily investigated the biogenic SOA precursors isoprene, α-pinene, limonene, myrcene, linalool and β-caryophyllene. The chemometric analysis is used to classify the oxidation systems and resultant SOA according to the controlling chemistry and the products formed. Results show that "model" biogenic oxidative systems can be successfully separated and classified according to their oxidation products. Furthermore, a holistic view of results obtained across both the gas- and particle-phases shows the different SOA formation chemistry, initiating in the gas-phase, proceeding to govern the differences between the various BVOC SOA compositions. The results obtained are used to describe the particle composition in the context of the oxidised gas-phase matrix. An extension of the technique, which incorporates into the statistical models data from anthropogenic (i

  13. Tools for the functional interpretation of metabolomic experiments.

    Science.gov (United States)

    Chagoyen, Monica; Pazos, Florencio

    2013-11-01

    The so-called 'omics' approaches used in modern biology aim at massively characterizing the molecular repertories of living systems at different levels. Metabolomics is one of the last additions to the 'omics' family and it deals with the characterization of the set of metabolites in a given biological system. As metabolomic techniques become more massive and allow characterizing larger sets of metabolites, automatic methods for analyzing these sets in order to obtain meaningful biological information are required. Only recently the first tools specifically designed for this task in metabolomics appeared. They are based on approaches previously used in transcriptomics and other 'omics', such as annotation enrichment analysis. These, together with generic tools for metabolic analysis and visualization not specifically designed for metabolomics will for sure be in the toolbox of the researches doing metabolomic experiments in the near future.

  14. Metabolomics in Sepsis and Its Impact on Public Health.

    Science.gov (United States)

    Evangelatos, Nikolaos; Bauer, Pia; Reumann, Matthias; Satyamoorthy, Kapaettu; Lehrach, Hans; Brand, Angela

    2017-01-01

    Sepsis, with its often devastating consequences for patients and their families, remains a major public health concern that poses an increasing financial burden. Early resuscitation together with the elucidation of the biological pathways and pathophysiological mechanisms with the use of "-omics" technologies have started changing the clinical and research landscape in sepsis. Metabolomics (i.e., the study of the metabolome), an "-omics" technology further down in the "-omics" cascade between the genome and the phenome, could be particularly fruitful in sepsis research with the potential to alter the clinical practice. Apart from its benefit for the individual patient, metabolomics has an impact on public health that extends beyond its applications in medicine. In this review, we present recent developments in metabolomics research in sepsis, with a focus on pneumonia, and we discuss the impact of metabolomics on public health, with a focus on free/libre open source software. © 2018 S. Karger AG, Basel.

  15. New tools and resources in metabolomics: 2016-2017.

    Science.gov (United States)

    Misra, Biswapriya B

    2018-04-01

    Rapid advances in mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based platforms for metabolomics have led to an upsurge of data every single year. Newer high-throughput platforms, hyphenated technologies, miniaturization, and tool kits in data acquisition efforts in metabolomics have led to additional challenges in metabolomics data pre-processing, analysis, interpretation, and integration. Thanks to the informatics, statistics, and computational community, new resources continue to develop for metabolomics researchers. The purpose of this review is to provide a summary of the metabolomics tools, software, and databases that were developed or improved during 2016-2017, thus, enabling readers, developers, and researchers access to a succinct but thorough list of resources for further improvisation, implementation, and application in due course of time. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Compliance with minimum information guidelines in public metabolomics repositories.

    Science.gov (United States)

    Spicer, Rachel A; Salek, Reza; Steinbeck, Christoph

    2017-09-26

    The Metabolomics Standards Initiative (MSI) guidelines were first published in 2007. These guidelines provided reporting standards for all stages of metabolomics analysis: experimental design, biological context, chemical analysis and data processing. Since 2012, a series of public metabolomics databases and repositories, which accept the deposition of metabolomic datasets, have arisen. In this study, the compliance of 399 public data sets, from four major metabolomics data repositories, to the biological context MSI reporting standards was evaluated. None of the reporting standards were complied with in every publicly available study, although adherence rates varied greatly, from 0 to 97%. The plant minimum reporting standards were the most complied with and the microbial and in vitro were the least. Our results indicate the need for reassessment and revision of the existing MSI reporting standards.

  17. The Secondary Organic Aerosol Processor (SOAP v1.0) model: a unified model with different ranges of complexity based on the molecular surrogate approach

    Science.gov (United States)

    Couvidat, F.; Sartelet, K.

    2015-04-01

    In this paper the Secondary Organic Aerosol Processor (SOAP v1.0) model is presented. This model determines the partitioning of organic compounds between the gas and particle phases. It is designed to be modular with different user options depending on the computation time and the complexity required by the user. This model is based on the molecular surrogate approach, in which each surrogate compound is associated with a molecular structure to estimate some properties and parameters (hygroscopicity, absorption into the aqueous phase of particles, activity coefficients and phase separation). Each surrogate can be hydrophilic (condenses only into the aqueous phase of particles), hydrophobic (condenses only into the organic phases of particles) or both (condenses into both the aqueous and the organic phases of particles). Activity coefficients are computed with the UNIFAC (UNIversal Functional group Activity Coefficient; Fredenslund et al., 1975) thermodynamic model for short-range interactions and with the Aerosol Inorganic-Organic Mixtures Functional groups Activity Coefficients (AIOMFAC) parameterization for medium- and long-range interactions between electrolytes and organic compounds. Phase separation is determined by Gibbs energy minimization. The user can choose between an equilibrium representation and a dynamic representation of organic aerosols (OAs). In the equilibrium representation, compounds in the particle phase are assumed to be at equilibrium with the gas phase. However, recent studies show that the organic aerosol is not at equilibrium with the gas phase because the organic phases could be semi-solid (very viscous liquid phase). The condensation-evaporation of organic compounds could then be limited by the diffusion in the organic phases due to the high viscosity. An implicit dynamic representation of secondary organic aerosols (SOAs) is available in SOAP with OAs divided into layers, the first layer being at the center of the particle (slowly

  18. Metabolomic Profiles of a Midge (Procladius villosimanus, Kieffer Are Associated with Sediment Contamination in Urban Wetlands

    Directory of Open Access Journals (Sweden)

    Katherine J. Jeppe

    2017-12-01

    Full Text Available Metabolomic techniques are powerful tools for investigating organism-environment interactions. Metabolite profiles have the potential to identify exposure or toxicity before populations are disrupted and can provide useful information for environmental assessment. However, under complex environmental scenarios, metabolomic responses to exposure can be distorted by background and/or organismal variation. In the current study, we use LC-MS (liquid chromatography-mass spectrometry and GC-MS (gas chromatography-mass spectrometry to measure metabolites of the midge Procladius villosimanus inhabiting 21 urban wetlands. These metabolites were tested against common sediment contaminants using random forest models and metabolite enrichment analysis. Sediment contaminant concentrations in the field correlated with several P. villosimanus metabolites despite natural environmental and organismal variation. Furthermore, enrichment analysis indicated that metabolite sets implicated in stress responses were enriched, pointing to specific cellular functions affected by exposure. Methionine metabolism, sugar metabolism and glycerolipid metabolism associated with total petroleum hydrocarbon and metal concentrations, while mitochondrial electron transport and urea cycle sets associated only with bifenthrin. These results demonstrate the potential for metabolomics approaches to provide useful information in field-based environmental assessments.

  19. A review of blood sample handling and pre-processing for metabolomics studies.

    Science.gov (United States)

    Hernandes, Vinicius Veri; Barbas, Coral; Dudzik, Danuta

    2017-09-01

    Metabolomics has been found to be applicable to a wide range of clinical studies, bringing a new era for improving clinical diagnostics, early disease detection, therapy prediction and treatment efficiency monitoring. A major challenge in metabolomics, particularly untargeted studies, is the extremely diverse and complex nature of biological specimens. Despite great advances in the field there still exist fundamental needs for considering pre-analytical variability that can introduce bias to the subsequent analytical process and decrease the reliability of the results and moreover confound final research outcomes. Many researchers are mainly focused on the instrumental aspects of the biomarker discovery process, and sample related variables sometimes seem to be overlooked. To bridge the gap, critical information and standardized protocols regarding experimental design and sample handling and pre-processing are highly desired. Characterization of a range variation among sample collection methods is necessary to prevent results misinterpretation and to ensure that observed differences are not due to an experimental bias caused by inconsistencies in sample processing. Herein, a systematic discussion of pre-analytical variables affecting metabolomics studies based on blood derived samples is performed. Furthermore, we provide a set of recommendations concerning experimental design, collection, pre-processing procedures and storage conditions as a practical review that can guide and serve for the standardization of protocols and reduction of undesirable variation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Rice Bran Metabolome Contains Amino Acids, Vitamins & Cofactors, and Phytochemicals with Medicinal and Nutritional Properties.

    Science.gov (United States)

    Zarei, Iman; Brown, Dustin G; Nealon, Nora Jean; Ryan, Elizabeth P

    2017-12-01

    Rice bran is a functional food that has shown protection against major chronic diseases (e.g. obesity, diabetes, cardiovascular disease and cancer) in animals and humans, and these health effects have been associated with the presence of bioactive phytochemicals. Food metabolomics uses multiple chromatography and mass spectrometry platforms to detect and identify a diverse range of small molecules with high sensitivity and precision, and has not been completed for rice bran. This study utilized global, non-targeted metabolomics to identify small molecules in rice bran, and conducted a comprehensive search of peer-reviewed literature to determine bioactive compounds. Three U.S. rice varieties (Calrose, Dixiebelle, and Neptune), that have been used for human dietary intervention trials, were assessed herein for bioactive compounds that have disease control and prevention properties. The profiling of rice bran by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) identified 453 distinct phytochemicals, 209 of which were classified as amino acids, cofactors & vitamins, and secondary metabolites, and were further assessed for bioactivity. A scientific literature search revealed 65 compounds with health properties, 16 of which had not been previously identified in rice bran. This suite of amino acids, cofactors & vitamins, and secondary metabolites comprised 46% of the identified rice bran metabolome, which substantially enhanced our knowledge of health-promoting rice bran compounds provided during dietary supplementation. Rice bran metabolite profiling revealed a suite of biochemical molecules that can be further investigated and exploited for multiple nutritional therapies and medical food applications. These bioactive compounds may also be biomarkers of dietary rice bran intake. The medicinal compounds associated with rice bran can function as a network across metabolic pathways and this

  1. Multi-platform metabolomics and a genetic approach support the authentication of agarwood produced by Aquilaria crassna and Aquilaria malaccensis.

    Science.gov (United States)

    Nguyen, Huy Truong; Min, Jung-Eun; Long, Nguyen Phuoc; Thanh, Ma Chi; Le, Thi Hong Van; Lee, Jeongmi; Park, Jeong Hill; Kwon, Sung Won

    2017-08-05

    Agarwood, the resinous heartwood produced by some Aquilaria species such as Aquilaria crassna, Aquilaria malaccensis and Aquilaria sinensis, has been traditionally and widely used in medicine, incenses and especially perfumes. However, up to now, the authentication of agarwood has been largely based on morphological characteristics, a method which is prone to errors and lacks reproducibility. Hence, in this study, we applied metabolomics and a genetic approach to the authentication of two common agarwood chips, those produced by Aquilaria crassna and Aquilaria malaccensis. Primary metabolites, secondary metabolites and DNA markers of agarwood were authenticated by 1 H NMR metabolomics, GC-MS metabolomics and DNA-based techniques, respectively. The results indicated that agarwood chips could be classified accurately by all the methods illustrated in this study. Additionally, the pros and cons of each method are also discussed. To the best of our knowledge, our research is the first study detailing all the differences in the primary and secondary metabolites, as well as the DNA markers between the agarwood produced by these two species. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Phosphate stresses affect ionome and metabolome in tea plants.

    Science.gov (United States)

    Ding, Zhaotang; Jia, Sisi; Wang, Yu; Xiao, Jun; Zhang, Yinfei

    2017-11-01

    In order to study the response of tea plants to P stress, we conducted the ionomic and metabolomic analysis by ICP-OES, GC-MS and LC-MS. The results demonstrated that P was antagonistic with S, and was cooperative with Cu, Zn, Mn and Fe under P-deficiency. However, P was antagonistic with Mn, Fe and S, and was cooperative with Cu and Zn under P-excess. Moreover, P-deficiency or excess reduced the syntheses of flavonoids and phosphorylated metabolites. P-deficiency decreased the amount of glutamate and increased the content of glutamine, while P-excess decreased the content of glutamine. Besides, P-deficiency increased three organic acids and decreased three organic acids. P-excess increased the contents of malic acid, oxalic acid, ribonic acid and etc. involved in primary metabolism, but decreased the contents of p-coumaric acid, indoleacrylic acid, related to secondary metabolism. Furthermore, the contents of Mn and Zn were found to be positively related to the amounts of myricetin and quercetin, and the content of Mn to be positively related to the amount of arabinose. The results implied that the P stresses severely disturbed the metabolism of minerals and metabolites in tea plants, which influenced the yield and quality of tea. Copyright © 2017. Published by Elsevier Masson SAS.

  3. Fecal Metabolomics of Type 2 Diabetic Rats and Treatment with Gardenia jasminoides Ellis Based on Mass Spectrometry Technique.

    Science.gov (United States)

    Zhou, Yuan; Men, Lihui; Pi, Zifeng; Wei, Mengying; Song, Fengrui; Zhao, Chunfang; Liu, Zhiqiang

    2018-02-14

    Modern studies have indicated Gardenia jasminoides Ellis (G. jasminoides) showed positive effect in treating type 2 diabetes mellitus (T2DM). In this study, 60 streptozotocin-induced T2DM rats were divided into four groups: type 2 diabetes control group, geniposide-treated group, total iridoid glycosides-treated group, and crude extraction of gardenlae fructus-treated group. The other ten healthy rats were the healthy control group. During 12 weeks of treatment, rat's feces samples were collected for the metabolomics study based on mass spectrometry technique. On the basis of the fecal metabolomics method, 19 potential biomarkers were screened and their relative intensities in each group were compared. The results revealed G. jasminoides mainly regulated dysfunctions in phenylalanine metabolism, tryptophan metabolism, and secondary bile acid biosynthesis pathways induced by diabetes. The current study provides new insight for metabonomics methodology toward T2DM, and the results show that feces can preferably reflect the liver and intestines disorders.

  4. Metabolomics reveals the heterogeneous secretome of two entomopathogenic fungi to ex vivo cultured insect tissues.

    Directory of Open Access Journals (Sweden)

    Charissa de Bekker

    Full Text Available Fungal entomopathogens rely on cellular heterogeneity during the different stages of insect host infection. Their pathogenicity is exhibited through the secretion of secondary metabolites, which implies that the infection life history of this group of environmentally important fungi can be revealed using metabolomics. Here metabolomic analysis in combination with ex vivo insect tissue culturing shows that two generalist isolates of the genus Metarhizium and Beauveria, commonly used as biological pesticides, employ significantly different arrays of secondary metabolites during infectious and saprophytic growth. It also reveals that both fungi exhibit tissue specific strategies by a distinguishable metabolite secretion on the insect tissues tested in this study. In addition to showing the important heterogeneous nature of these two entomopathogens, this study also resulted in the discovery of several novel destruxins and beauverolides that have not been described before, most likely because previous surveys did not use insect tissues as a culturing system. While Beauveria secreted these cyclic depsipeptides when encountering live insect tissues, Metarhizium employed them primarily on dead tissue. This implies that, while these fungi employ comparable strategies when it comes to entomopathogenesis, there are most certainly significant differences at the molecular level that deserve to be studied.

  5. Revealing metabolomic variations in Cortex Moutan from different root parts using HPLC-MS method.

    Science.gov (United States)

    Xiao, Chaoni; Wu, Man; Chen, Yongyong; Zhang, Yajun; Zhao, Xinfeng; Zheng, Xiaohui

    2015-01-01

    The distribution of metabolites in the different root parts of Cortex Moutan (the root bark of Paeonia suffruticosa Andrews) is not well understood, therefore, scientific evidence is not available for quality assessment of Cortex Moutan. To reveal metabolomic variations in Cortex Moutan in order to gain deeper insights to enable quality control. Metabolomic variations in the different root parts of Cortex Moutan were characterised using high-performance liquid chromatography combined with mass spectrometry (HPLC-MS) and multivariate data analysis. The discriminating metabolites in different root parts were evaluated by the one-way analysis of variance and a fold change parameter. The metabolite profiles of Cortex Moutan were largely dominated by five primary and 41 secondary metabolites . Higher levels of malic acid, gallic acid and mudanoside-B were mainly observed in the second lateral roots, whereas dihydroxyacetophenone, benzoyloxypaeoniflorin, suffruticoside-A, kaempferol dihexoside, mudanpioside E and mudanpioside J accumulated in the first lateral and axial roots. The highest contents of paeonol, galloyloxypaeoniflorin and procyanidin B were detected in the axial roots. Accordingly, metabolite compositions of Cortex Moutan were found to vary among different root parts. The axial roots have higher quality than the lateral roots in Cortex Moutan due to the accumulation of bioactive secondary metabolites associated with plant physiology. These findings provided important scientific evidence for grading Cortex Moutan on the general market. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Metabolomic Tools to Assess the Chemistry and Bioactivity of Endophytic Aspergillus Strain.

    Science.gov (United States)

    Tawfike, Ahmed F; Tate, Rothwelle; Abbott, Gráinne; Young, Louise; Viegelmann, Christina; Schumacher, Marc; Diederich, Marc; Edrada-Ebel, RuAngelie

    2017-10-01

    Endophytic fungi associated with medicinal plants are a potential source of novel chemistry and biology that may find applications as pharmaceutical and agrochemical drugs. In this study, a combination of metabolomics and bioactivity-guided approaches were employed to isolate secondary metabolites with cytotoxicity against cancer cells from an endophytic Aspergillus aculeatus. The endophyte was isolated from the Egyptian medicinal plant Terminalia laxiflora and identified using molecular biological methods. Metabolomics and dereplication studies were accomplished by utilizing the MZmine software coupled with the universal Dictionary of Natural Products database. Metabolic profiling, with aid of multivariate data analysis, was performed at different stages of the growth curve to choose the optimized method suitable for up-scaling. The optimized culture method yielded a crude extract abundant with biologically-active secondary metabolites. Crude extracts were fractionated using different high-throughput chromatographic techniques. Purified compounds were identified by HR-ESI-MS, 1D- and 2D-NMR. This study introduced a new method of dereplication utilizing both high-resolution mass spectrometry and NMR spectroscopy. The metabolites were putatively identified by applying a chemotaxonomic filter. We also present a short review on the diverse chemistry of terrestrial endophytic strains of Aspergillus, which has become a part of our dereplication work and this will be of wide interest to those working in this field. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  7. Exploring natural variation of Pinus pinaster Aiton using metabolomics: Is it possible to identify the region of origin of a pine from its metabolites?

    Science.gov (United States)

    Meijón, Mónica; Feito, Isabel; Oravec, Michal; Delatorre, Carolina; Weckwerth, Wolfram; Majada, Juan; Valledor, Luis

    2016-02-01

    Natural variation of the metabolome of Pinus pinaster was studied to improve understanding of its role in the adaptation process and phenotypic diversity. The metabolomes of needles and the apical and basal section of buds were analysed in ten provenances of P. pinaster, selected from France, Spain and Morocco, grown in a common garden for 5 years. The employment of complementary mass spectrometry techniques (GC-MS and LC-Orbitrap-MS) together with bioinformatics tools allowed the reliable quantification of 2403 molecular masses. The analysis of the metabolome showed that differences were maintained across provenances and that the metabolites characteristic of each organ are mainly related to amino acid metabolism, while provenances were distinguishable essentially through secondary metabolism when organs were analysed independently. Integrative analyses of metabolome, environmental and growth data provided a comprehensive picture of adaptation plasticity in conifers. These analyses defined two major groups of plants, distinguished by secondary metabolism: that is, either Atlantic or Mediterranean provenance. Needles were the most sensitive organ, where strong correlations were found between flavonoids and the water regime of the geographic origin of the provenance. The data obtained point to genome specialization aimed at maximizing the drought stress resistance of trees depending on their origin. © 2016 John Wiley & Sons Ltd.

  8. Environmental metabolomics with data science for investigating ecosystem homeostasis.

    Science.gov (United States)

    Kikuchi, Jun; Ito, Kengo; Date, Yasuhiro

    2018-02-01

    A natural ecosystem can be viewed as the interconnections between complex metabolic reactions and environments. Humans, a part of these ecosystems, and their activities strongly affect the environments. To account for human effects within ecosystems, understanding what benefits humans receive by facilitating the maintenance of environmental homeostasis is important. This review describes recent applications of several NMR approaches to the evaluation of environmental homeostasis by metabolic profiling and data science. The basic NMR strategy used to evaluate homeostasis using big data collection is similar to that used in human health studies. Sophisticated metabolomic approaches (metabolic profiling) are widely reported in the literature. Further challenges include the analysis of complex macromolecular structures, and of the compositions and interactions of plant biomass, soil humic substances, and aqueous particulate organic matter. To support the study of these topics, we also discuss sample preparation techniques and solid-state NMR approaches. Because NMR approaches can produce a number of data with high reproducibility and inter-institution compatibility, further analysis of such data using machine learning approaches is often worthwhile. We also describe methods for data pretreatment in solid-state NMR and for environmental feature extraction from heterogeneously-measured spectroscopic data by machine learning approaches. Copyright © 2017. Published by Elsevier B.V.

  9. Challenges of metabolomics in human gut microbiota research.

    Science.gov (United States)

    Smirnov, Kirill S; Maier, Tanja V; Walker, Alesia; Heinzmann, Silke S; Forcisi, Sara; Martinez, Inés; Walter, Jens; Schmitt-Kopplin, Philippe

    2016-08-01

    The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond

    Directory of Open Access Journals (Sweden)

    Jumpei Washio

    2016-06-01

    Full Text Available Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the ‘Warburg effect’. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.

  11. Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond.

    Science.gov (United States)

    Washio, Jumpei; Takahashi, Nobuhiro

    2016-06-02

    Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the 'Warburg effect'. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.

  12. LC-MS based Metabolomics

    DEFF Research Database (Denmark)

    Magdenoska, Olivera

    . The analytical tools applied for analysis of intracellular metabolites should be capable to cope with the large number of metabolites to be analyzed and the complex matrix in the samples. Therefore the combination of separation and detection techniques is commonly applied for analysis of intracellular........ In the studies conducted during this Ph.D. the developed method was used to understand how the genetic manipulations in various organisms, influence the levels of their intracellular metabolites. The method development was divided into three steps: i) optimization of the MS detection, ii) establishment...... of the MS detection aimed to determine multiple reaction monitoring (MRM) transitions of the analytes and to increase the sensitivity by testing different ion-source parameters and collision energies. This resulted in optimized detection of more than 50 intracellular metabolites. During the optimization...

  13. Metabolomics, a promising approach to translational research in cardiology

    Directory of Open Access Journals (Sweden)

    Martino Deidda

    2015-12-01

    In this article, we will provide a description of metabolomics in comparison with other, better known “omics” disciplines such as genomics and proteomics. In addition, we will review the current rationale for the implementation of metabolomics in cardiology, its basic methodology and the available data from human studies in this discipline. The topics covered will delineate the importance of being able to use the metabolomic information to understand the mechanisms of diseases from the perspective of systems biology, and as a non-invasive approach to the diagnosis, grading and treatment of cardiovascular diseases.

  14. Introduction to metabolomics and its applications in ophthalmology

    Science.gov (United States)

    Tan, S Z; Begley, P; Mullard, G; Hollywood, K A; Bishop, P N

    2016-01-01

    Metabolomics is the study of endogenous and exogenous metabolites in biological systems, which aims to provide comparative semi-quantitative information about all metabolites in the system. Metabolomics is an emerging and potentially powerful tool in ophthalmology research. It is therefore important for health professionals and researchers involved in the speciality to understand the basic principles of metabolomics experiments. This article provides an overview of the experimental workflow and examples of its use in ophthalmology research from the study of disease metabolism and pathogenesis to identification of biomarkers. PMID:26987591

  15. The Human Blood Metabolome-Transcriptome Interface

    Science.gov (United States)

    Schramm, Katharina; Adamski, Jerzy; Gieger, Christian; Herder, Christian; Carstensen, Maren; Peters, Annette; Rathmann, Wolfgang; Roden, Michael; Strauch, Konstantin; Suhre, Karsten; Kastenmüller, Gabi; Prokisch, Holger; Theis, Fabian J.

    2015-01-01

    Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the ‘human blood metabolome-transcriptome interface’ (BMTI). Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease. PMID:26086077

  16. The Human Blood Metabolome-Transcriptome Interface.

    Directory of Open Access Journals (Sweden)

    Jörg Bartel

    2015-06-01

    Full Text Available Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the 'human blood metabolome-transcriptome interface' (BMTI. Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease.

  17. Long-term fertilization determines different metabolomic profiles and responses in saplings of three rainforest tree species with different adult canopy position.

    Directory of Open Access Journals (Sweden)

    Albert Gargallo-Garriga

    Full Text Available Tropical rainforests are frequently limited by soil nutrient availability. However, the response of the metabolic phenotypic plasticity of trees to an increase of soil nutrient availabilities is poorly understood. We expected that increases in the ability of a nutrient that limits some plant processes should be detected by corresponding changes in plant metabolome profile related to such processes.We studied the foliar metabolome of saplings of three abundant tree species in a 15 year field NPK fertilization experiment in a Panamanian rainforest. The largest differences were among species and explained 75% of overall metabolome variation. The saplings of the large canopy species, Tetragastris panamensis, had the lowest concentrations of all identified amino acids and the highest concentrations of most identified secondary compounds. The saplings of the "mid canopy" species, Alseis blackiana, had the highest concentrations of amino acids coming from the biosynthesis pathways of glycerate-3P, oxaloacetate and α-ketoglutarate, and the saplings of the low canopy species, Heisteria concinna, had the highest concentrations of amino acids coming from the pyruvate synthesis pathways.The changes in metabolome provided strong evidence that different nutrients limit different species in different ways. With increasing P availability, the two canopy species shifted their metabolome towards larger investment in protection mechanisms, whereas with increasing N availability, the sub-canopy species increased its primary metabolism. The results highlighted the proportional distinct use of different nutrients by different species and the resulting different metabolome profiles in this high diversity community are consistent with the ecological niche theory.

  18. The MetabolomeExpress Project: enabling web-based processing, analysis and transparent dissemination of GC/MS metabolomics datasets

    Directory of Open Access Journals (Sweden)

    Carroll Adam J

    2010-07-01

    Full Text Available Abstract Background Standardization of analytical approaches and reporting methods via community-wide collaboration can work synergistically with web-tool development to result in rapid community-driven expansion of online data repositories suitable for data mining and meta-analysis. In metabolomics, the inter-laboratory reproducibility of gas-chromatography/mass-spectrometry (GC/MS makes it an obvious target for such development. While a number of web-tools offer access to datasets and/or tools for raw data processing and statistical analysis, none of these systems are currently set up to act as a public repository by easily accepting, processing and presenting publicly submitted GC/MS metabolomics datasets for public re-analysis. Description Here, we present MetabolomeExpress, a new File Transfer Protocol (FTP server and web-tool for the online storage, processing, visualisation and statistical re-analysis of publicly submitted GC/MS metabolomics datasets. Users may search a quality-controlled database of metabolite response statistics from publicly submitted datasets by a number of parameters (eg. metabolite, species, organ/biofluid etc.. Users may also perform meta-analysis comparisons of multiple independent experiments or re-analyse public primary datasets via user-friendly tools for t-test, principal components analysis, hierarchical cluster analysis and correlation analysis. They may interact with chromatograms, mass spectra and peak detection results via an integrated raw data viewer. Researchers who register for a free account may upload (via FTP their own data to the server for online processing via a novel raw data processing pipeline. Conclusions MetabolomeExpress https://www.metabolome-express.org provides a new opportunity for the general metabolomics community to transparently present online the raw and processed GC/MS data underlying their metabolomics publications. Transparent sharing of these data will allow researchers to

  19. ROMANCE: A new software tool to improve data robustness and feature identification in CE-MS metabolomics.

    Science.gov (United States)

    González-Ruiz, Víctor; Gagnebin, Yoric; Drouin, Nicolas; Codesido, Santiago; Rudaz, Serge; Schappler, Julie

    2018-05-01

    The use of capillary electrophoresis coupled to mass spectrometry (CE-MS) in metabolomics remains an oddity compared to the widely adopted use of liquid chromatography. This technique is traditionally regarded as lacking the reproducibility to adequately identify metabolites by their migration times. The major reason is the variability of the velocity of the background electrolyte, mainly coming from shifts in the magnitude of the electroosmotic flow and from the suction caused by electrospray interfaces. The use of the effective electrophoretic mobility is one solution to overcome this issue as it is a characteristic feature of each compound. To date, such an approach has not been applied to metabolomics due to the complexity and size of CE-MS data obtained in such studies. In this paper, ROMANCE (RObust Metabolomic Analysis with Normalized CE) is introduced as a new software for CE-MS-based metabolomics. It allows the automated conversion of batches of CE-MS files with minimal user intervention. ROMANCE converts the x-axis of each MS file from the time into the effective mobility scale and the resulting files are already pseudo-aligned, present normalized peak areas and improved reproducibility, and can eventually follow existing metabolomic workflows. The software was developed in Scala, so it is multi-platform and computationally-efficient. It is available for download under a CC license. In this work, the versatility of ROMANCE was demonstrated by using data obtained in the same and in different laboratories, as well as its application to the analysis of human plasma samples. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Comparative analysis of targeted metabolomics: dominance-based rough set approach versus orthogonal partial least square-discriminant analysis.

    Science.gov (United States)

    Blasco, H; Błaszczyński, J; Billaut, J C; Nadal-Desbarats, L; Pradat, P F; Devos, D; Moreau, C; Andres, C R; Emond, P; Corcia, P; Słowiński, R

    2015-02-01

    Metabolomics is an emerging field that includes ascertaining a metabolic profile from a combination of small molecules, and which has health applications. Metabolomic methods are currently applied to discover diagnostic biomarkers and to identify pathophysiological pathways involved in pathology. However, metabolomic data are complex and are usually analyzed by statistical methods. Although the methods have been widely described, most have not been either standardized or validated. Data analysis is the foundation of a robust methodology, so new mathematical methods need to be developed to assess and complement current methods. We therefore applied, for the first time, the dominance-based rough set approach (DRSA) to metabolomics data; we also assessed the complementarity of this method with standard statistical methods. Some attributes were transformed in a way allowing us to discover global and local monotonic relationships between condition and decision attributes. We used previously published metabolomics data (18 variables) for amyotrophic lateral sclerosis (ALS) and non-ALS patients. Principal Component Analysis (PCA) and Orthogonal Partial Least Square-Discriminant Analysis (OPLS-DA) allowed satisfactory discrimination (72.7%) between ALS and non-ALS patients. Some discriminant metabolites were identified: acetate, acetone, pyruvate and glutamine. The concentrations of acetate and pyruvate were also identified by univariate analysis as significantly different between ALS and non-ALS patients. DRSA correctly classified 68.7% of the cases and established rules involving some of the metabolites highlighted by OPLS-DA (acetate and acetone). Some rules identified potential biomarkers not revealed by OPLS-DA (beta-hydroxybutyrate). We also found a large number of common discriminating metabolites after Bayesian confirmation measures, particularly acetate, pyruvate, acetone and ascorbate, consistent with the pathophysiological pathways involved in ALS. DRSA provides

  1. Organic complexation and translocation of ferric iron in podzols of the Negro River watershed. Separation of secondary Fe species from Al species

    Science.gov (United States)

    Fritsch, E.; Allard, Th.; Benedetti, M. F.; Bardy, M.; do Nascimento, N. R.; Li, Y.; Calas, G.

    2009-04-01

    The development of podzols in lateritic landscapes of the upper Amazon basin contributes to the exportation of organic carbon and associated metals in the black waters of the Negro River watershed. We have investigated the distribution of Fe III in the clay-size fraction of eight organic-rich horizons of waterlogged plateau podzols, to unravel the weathering conditions and mechanisms that control its transfer to the rivers. The speciation and amount of Fe III stored in residual mineral phases of laterites, or bound to organic compounds of weakly and well-expressed podzols, were determined by electron paramagnetic resonance spectroscopy combined with chemical analyses. Reducing conditions restrict the production of organo-Fe complexes in the subsoil B-horizons of waterlogged podzols and most of the Fe 2+ released from the dissolution of Fe-oxides is exported to the rivers via the perched groundwater. However, significant amounts of diluted Fe III bound to organic ligands (Fe IIIOM) and nano Fe-oxides are produced at the margin of the depression in the topsoil A horizons of weakly expressed podzols due to shorter periods of anoxia. The downward translocation of organically bound metals from topsoil A to subsoil B-horizons of podzols occurs in shorter distances for Fe than it does for Al. This separation of secondary Fe species from Al species is attributed to the physical fractionation of their organic carriers in texture contrasted B-horizons of podzols, as well as to the effect of pH on metal speciation in soil solutions and metal binding onto soil organic ligands (mostly for Al). This leads us to consider the topsoil A horizons of weakly expressed podzols, as well as the subsoil Bh horizon of better-expressed ones, as the main sources for the transfer of Fe IIIOM to the rivers. The concentration of Fe IIIOM rises from soil sources to river colloids, suggesting drastic biogeochemical changes in more oxygenated black waters of the Negro River watershed. The

  2. Global species delimitation and phylogeography of the circumtropical ‘sexy shrimp’ Thor amboinensis reveals a cryptic species complex and secondary contact in the Indo-West Pacific

    KAUST Repository

    Titus, Benjamin M.

    2018-04-27

    Aim The “sexy shrimp” Thor amboinensis is currently considered a single circumtropical species. However, the tropical oceans are partitioned by hard and soft barriers to dispersal, providing ample opportunity for allopatric speciation. Herein, we test the null hypothesis that T. amboinensis is a single global species, reconstruct its global biogeographical history, and comment on population‐level patterns throughout the Tropical Western Atlantic. Location Coral reefs in all tropical oceans. Methods Specimens of Thor amboinensis were obtained through field collection and museum holdings. We used one mitochondrial (COI) and two nuclear (NaK, enolase) gene fragments for global species delimitation and phylogenetic analyses (n = 83 individuals, 30 sample localities), while phylogeographical reconstruction in the TWA was based on COI only (n = 303 individuals, 10 sample localities). Results We found evidence for at least five cryptic lineages (9%–22% COI pairwise sequence divergence): four in the Indo‐West Pacific and one in the Tropical Western Atlantic. Phylogenetic reconstruction revealed that endemic lineages from Japan and the South Central Pacific are more closely related to the Tropical Western Atlantic lineage than to a co‐occurring lineage that is widespread throughout the Indo‐West Pacific. Concatenated and species tree phylogenetic analyses differ in the placement of an endemic Red Sea lineage and suggest alternate dispersal pathways into the Atlantic. Phylogeographical reconstruction throughout the Tropical Western Atlantic reveals little genetic structure over more than 3,000 km. Main conclusions Thor amboinensis is a species complex that has undergone a series of allopatric speciation events and whose members are in secondary contact in the Indo‐West Pacific. Nuclear‐ and mitochondrial‐ gene phylogenies show evidence of introgression between lineages inferred to have been separated more than 20 Ma. Phylogenetic discordance between

  3. Relationships between drought, heat and air humidity responses revealed by transcriptome-metabolome co-analysis.

    Science.gov (United States)

    Georgii, Elisabeth; Jin, Ming; Zhao, Jin; Kanawati, Basem; Schmitt-Kopplin, Philippe; Albert, Andreas; Winkler, J Barbro; Schäffner, Anton R

    2017-07-10

    may respond with different extent to individual stress components. Their contrasting behavior in response to temperature stress highlights that the protein folding machinery effectively shields the metabolism from stress. Disentangling the complex relationships between transcriptome and metabolome in response to stress is an enormous challenge. As demonstrated by case studies with supporting evidence from additional data, the large dataset provided in this study may assist in determining linked genetic and metabolic features as candidates for future mechanistic analyses.

  4. Knowns and unknowns in metabolomics identified by multidimensional NMR and hybrid MS/NMR methods

    Energy Technology Data Exchange (ETDEWEB)

    Bingol, Kerem; Brüschweiler, Rafael

    2017-02-01

    Metabolomics continues to make rapid progress through the development of new and better methods and their applications to gain insight into the metabolism of a wide range of different biological systems from a systems biology perspective. Customization of NMR databases and search tools allows the faster and more accurate identification of known metabolites, whereas the identification of unknowns, without a need for extensive purification, requires new strategies to integrate NMR with mass spectrometry, cheminformatics, and computational methods. For some applications, the use of covalent and non-covalent attachments in the form of labeled tags or nanoparticles can significantly reduce the complexity of these tasks.

  5. Microbial metabolomics with gas chromatography/mass spectrometry

    NARCIS (Netherlands)

    Koek, M.M.; Muilwijk, B.; Werf, M.J. van der; Hankemeier, T.

    2006-01-01

    An analytical method was set up suitable for the analysis of microbial metabolomes, consisting of an oximation and silylation derivatization reaction and subsequent analysis by gas chromatography coupled to mass spectrometry. Microbial matrixes contain many compounds that potentially interfere with

  6. Impact of Intestinal Microbiota on Intestinal Luminal Metabolome

    Science.gov (United States)

    Matsumoto, Mitsuharu; Kibe, Ryoko; Ooga, Takushi; Aiba, Yuji; Kurihara, Shin; Sawaki, Emiko; Koga, Yasuhiro; Benno, Yoshimi

    2012-01-01

    Low–molecular-weight metabolites produced by intestinal microbiota play a direct role in health and disease. In this study, we analyzed the colonic luminal metabolome using capillary electrophoresis mass spectrometry with time-of-flight (CE-TOFMS) —a novel technique for analyzing and differentially displaying metabolic profiles— in order to clarify the metabolite profiles in the intestinal lumen. CE-TOFMS identified 179 metabolites from the colonic luminal metabolome and 48 metabolites were present in significantly higher concentrations and/or incidence in the germ-free (GF) mice than in the Ex-GF mice (p metabolome and a comprehensive understanding of intestinal luminal metabolome is critical for clarifying host-intestinal bacterial interactions. PMID:22724057

  7. Sparse Mbplsr for Metabolomics Data and Biomarker Discovery

    DEFF Research Database (Denmark)

    Karaman, İbrahim

    2014-01-01

    the link between high throughput metabolomics data generated on different analytical platforms, discover important metabolites deriving from the digestion processes in the gut, and automate metabolic pathway discovery from mass spectrometry. PLS (partial least squares) based chemometric methods were...

  8. International NMR-based Environmental Metabolomics Intercomparison Exercise

    Science.gov (United States)

    Several fundamental requirements must be met so that NMR-based metabolomics and the related technique of metabonomics can be formally adopted into environmental monitoring and chemical risk assessment. Here we report an intercomparison exercise which has evaluated the effectivene...

  9. Spectral Relative Standard Deviation: A Practical Benchmark in Metabolomics

    Science.gov (United States)

    Metabolomics datasets, by definition, comprise of measurements of large numbers of metabolites. Both technical (analytical) and biological factors will induce variation within these measurements that is not consistent across all metabolites. Consequently, criteria are required to...

  10. NMR-based metabolomic profiling of overweight adolescents

    DEFF Research Database (Denmark)

    Zheng, Hong; Yde, Christian C; Arnberg, Karina

    2014-01-01

    The plasma and urine metabolome of 192 overweight 12-15-year-old adolescents (BMI of 25.4 ± 2.3 kg/m(2)) were examined in order to elucidate gender, pubertal development measured as Tanner stage, physical activity measured as number of steps taken daily, and intra-/interindividual differences...... and the metabolome could be identified. The present study for the first time provides comprehensive information about associations between the metabolome and gender, pubertal development, and physical activity in overweight adolescents, which is an important subject group to approach in the prevention of obesity...... affecting the metabolome detected by proton NMR spectroscopy. Higher urinary excretion of citrate, creatinine, hippurate, and phenylacetylglutamine and higher plasma level of phosphatidylcholine and unsaturated lipid were found for girls compared with boys. The results suggest that gender differences...

  11. Human gut microbes impact host serum metabolome and insulin sensitivity

    DEFF Research Database (Denmark)

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn

    2016-01-01

    Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individ......Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin......-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus...

  12. Metabolomic profiling of Green Frogs exposed to Mixed Pesticides

    Data.gov (United States)

    U.S. Environmental Protection Agency — GC/MS data from the metabolomic profiling of green frog livers after exposure to pesticides and their mixtures. This dataset is associated with the following...

  13. Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure.

    Science.gov (United States)

    McClay, Joseph L; Adkins, Daniel E; Vunck, Sarah A; Batman, Angela M; Vann, Robert E; Clark, Shaunna L; Beardsley, Patrick M; van den Oord, Edwin J C G

    2013-04-01

    Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate ( p = 4.4 × 10 -5 , q = 0.013), tryptophan ( p = 7.0 × 10 -4 , q = 0.035) and 2-hydroxyglutarate ( p = 1.1 × 10 -4 , q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate ( p = 3.8 × 10 -7 ). Associations specific to repeated (5 day) MA exposure included phosphocholine ( p = 4.0 × 10 -4 , q = 0.087) and ergothioneine ( p = 3.0 × 10 -4 , q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects.

  14. The impact of ambient air pollution on the human blood metabolome.

    Science.gov (United States)

    Vlaanderen, J J; Janssen, N A; Hoek, G; Keski-Rahkonen, P; Barupal, D K; Cassee, F R; Gosens, I; Strak, M; Steenhof, M; Lan, Q; Brunekreef, B; Scalbert, A; Vermeulen, R C H

    2017-07-01

    Biological perturbations caused by air pollution might be reflected in the compounds present in blood originating from air pollutants and endogenous metabolites influenced by air pollution (defined here as part of the blood metabolome). We aimed to assess the perturbation of the blood metabolome in response to short term exposure to air pollution. We exposed 31 healthy volunteers to ambient air pollution for 5h. We measured exposure to particulate matter, particle number concentrations, absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and particulate matter oxidative potential. We collected blood from the participants 2h before and 2 and 18h after exposure. We employed untargeted metabolite profiling to monitor 3873 metabolic features in 493 blood samples from these volunteers. We assessed lung function using spirometry and six acute phase proteins in peripheral blood. We assessed the association of the metabolic features with the measured air pollutants and with health markers that we previously observed to be associated with air pollution in this study. We observed 89 robust associations between air pollutants and metabolic features two hours after exposure and 118 robust associations 18h after exposure. Some of the metabolic features that were associated with air pollutants were also associated with acute health effects, especially changes in forced expiratory volume in 1s. We successfully identified tyrosine, guanosine, and hypoxanthine among the associated features. Bioinformatics approach Mummichog predicted enriched pathway activity in eight pathways, among which tyrosine metabolism. This study demonstrates for the first time the application of untargeted metabolite profiling to assess the impact of air pollution on the blood metabolome. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Metabolomic NMR fingerprinting: an exploratory and predictive tool

    OpenAIRE

    Lauri, Ilaria

    2014-01-01

    Metabolomics is the comprehensive assessment of low molecular weight organic metabolites within biological system. The identification and characterization of several chemical species, or metabolic fingerprinting, is an emergent approach in metabolomics field that provides a valuable “snapshot” of metabolic profiles. This approach is finding an increasing number of applications in many areas including cancer research, drug discovery and food science. The combined use of NMR spectroscopy, data ...

  16. Metabolomics approach for discovering disease biomarkers and understanding metabolic pathway

    Directory of Open Access Journals (Sweden)

    Jeeyoun Jung

    2011-12-01

    Full Text Available Metabolomics, the multi-targeted analysis of endogenous metabolites from biological samples, can be efficiently applied to screen disease biomarkers and investigate pathophysiological processes. Metabolites change rapidly in response to physiological perturbations, making them the closest link to disease phenotypes. This study explored the role of metabolomics in gaining mechanistic insight into disease processes and in searching for novel biomarkers of human diseases

  17. Metabolomics and Metabolic Diseases: Where Do We Stand?

    Science.gov (United States)

    Newgard, Christopher B

    2017-01-10

    Metabolomics, or the comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms, has undergone a rapid technological evolution in the past two decades. These advances have led to the application of metabolomics to defining predictive biomarkers for incident cardiometabolic diseases and, increasingly, as a blueprint for understanding those diseases' pathophysiologic mechanisms. Progress in this area and challenges for the future are reviewed here. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Pediatric obesity: could metabolomics be a useful tool?

    OpenAIRE

    Angelica Dessì; Vassilios Fanos

    2013-01-01

    Pediatric obesity represents an important health issue. In recent years applications of metabolomics have led to evaluation of responses to the various nutrients (nutrigenomics), in particular to lipids, in diseases such as obesity and diabetes. The experimental data and the studies in pediatrics  that evaluated the metabolic condition in infant obesity are presented. It is thus to be hoped that future progress in connection with this new technique, together with a metabolomic study of mother...

  19. Linking diet to acne metabolomics, inflammation, and comedogenesis: an update

    Directory of Open Access Journals (Sweden)

    Melnik BC

    2015-07-01

    Full Text Available Bodo C Melnik Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Germany Abstract: Acne vulgaris, an epidemic inflammatory skin disease of adolescence, is closely related to Western diet. Three major food classes that promote acne are: 1 hyperglycemic carbohydrates, 2 milk and dairy products, 3 saturated fats including trans-fats and deficient ω-3 polyunsaturated fatty acids (PUFAs. Diet-induced insulin/insulin-like growth factor (IGF-1-signaling is superimposed on elevated IGF-1 levels during puberty, thereby unmasking the impact of aberrant nutrigenomics on sebaceous gland homeostasis. Western diet provides abundant branched-chain amino acids (BCAAs, glutamine, and palmitic acid. Insulin and IGF-1 suppress the activity of the metabolic transcription factor forkhead box O1 (FoxO1. Insulin, IGF-1, BCAAs, glutamine, and palmitate activate the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1, the key regulator of anabolism and lipogenesis. FoxO1 is a negative coregulator of androgen receptor, peroxisome proliferator-activated receptor-γ (PPARγ, liver X receptor-α, and sterol response element binding protein-1c (SREBP-1c, crucial transcription factors of sebaceous lipogenesis. mTORC1 stimulates the expression of PPARγ and SREBP-1c, promoting sebum production. SREBP-1c upregulates stearoyl-CoA- and Δ6-desaturase, enhancing the proportion of monounsaturated fatty acids in sebum triglycerides. Diet-mediated aberrations in sebum quantity (hyperseborrhea and composition (dysseborrhea promote Propionibacterium acnes overgrowth and biofilm formation with overexpression of the virulence factor triglyceride lipase increasing follicular levels of free palmitate and oleate. Free palmitate functions as a “danger signal,” stimulating toll-like receptor-2-mediated inflammasome activation with interleukin-1β release, Th17 differentiation, and interleukin-17-mediated keratinocyte

  20. Ultrasound: a subexploited tool for sample preparation in metabolomics.

    Science.gov (United States)

    Luque de Castro, M D; Delgado-Povedano, M M

    2014-01-02

    Metabolomics, one of the most recently emerged "omics", has taken advantage of ultrasound (US) to improve sample preparation (SP) steps. The metabolomics-US assisted SP step binomial has experienced a dissimilar development that has depended on the area (vegetal or animal) and the SP step. Thus, vegetal metabolomics and US assisted leaching has received the greater attention (encompassing subdisciplines such as metallomics, xenometabolomics and, mainly, lipidomics), but also liquid-liquid extraction and (bio)chemical reactions in metabolomics have taken advantage of US energy. Also clinical and animal samples have benefited from US assisted SP in metabolomics studies but in a lesser extension. The main effects of US have been shortening of the time required for the given step, and/or increase of its efficiency or availability for automation; nevertheless, attention paid to potential degradation caused by US has been scant or nil. Achievements and weak points of the metabolomics-US assisted SP step binomial are discussed and possible solutions to the present shortcomings are exposed. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Quality assurance procedures for mass spectrometry untargeted metabolomics. a review.

    Science.gov (United States)

    Dudzik, Danuta; Barbas-Bernardos, Cecilia; García, Antonia; Barbas, Coral

    2018-01-05

    Untargeted metabolomics, as a global approach, has already proven its great potential and capabilities for the investigation of health and disease, as well as the wide applicability for other research areas. Although great progress has been made on the feasibility of metabolomics experiments, there are still some challenges that should be faced and that includes all sources of fluctuations and bias affecting every step involved in multiplatform untargeted metabolomics studies. The identification and reduction of the main sources of unwanted variation regarding the pre-analytical, analytical and post-analytical phase of metabolomics experiments is essential to ensure high data quality. Nowadays, there is still a lack of information regarding harmonized guidelines for quality assurance as those available for targeted analysis. In this review, sources of variations to be considered and minimized along with methodologies and strategies for monitoring and improvement the quality of the results are discussed. The given information is based on evidences from different groups among our own experiences and recommendations for each stage of the metabolomics workflow. The comprehensive overview with tools presented here might serve other researchers interested in monitoring, controlling and improving the reliability of their findings by implementation of good experimental quality practices in the untargeted metabolomics study. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. SECIMTools: a suite of metabolomics data analysis tools.

    Science.gov (United States)

    Kirpich, Alexander S; Ibarra, Miguel; Moskalenko, Oleksandr; Fear, Justin M; Gerken, Joseph; Mi, Xinlei; Ashrafi, Ali; Morse, Alison M; McIntyre, Lauren M

    2018-04-20

    Metabolomics has the promise to transform the area of personalized medicine with the rapid development of high throughput technology for untargeted analysis of metabolites. Open access, easy to use, analytic tools that are broadly accessible to the biological community need to be developed. While technology used in metabolomics varies, most metabolomics studies have a set of features identified. Galaxy is an open access platform that enables scientists at all levels to interact with big data. Galaxy promotes reproducibility by saving histories and enabling the sharing workflows among scientists. SECIMTools (SouthEast Center for Integrated Metabolomics) is a set of Python applications that are available both as standalone tools and wrapped for use in Galaxy. The suite includes a comprehensive set of quality control metrics (retention time window evaluation and various peak evaluation tools), visualization techniques (hierarchical cluster heatmap, principal component analysis, modular modularity clustering), basic statistical analysis methods (partial least squares - discriminant analysis, analysis of variance, t-test, Kruskal-Wallis non-parametric test), advanced classification methods (random forest, support vector machines), and advanced variable selection tools (least absolute shrinkage and selection operator LASSO and Elastic Net). SECIMTools leverages the Galaxy platform and enables integrated workflows for metabolomics data analysis made from building blocks designed for easy use and interpretability. Standard data formats and a set of utilities allow arbitrary linkages between tools to encourage novel workflow designs. The Galaxy framework enables future data integration for metabolomics studies with other omics data.

  3. Metabolomics through the lens of precision cardiovascular medicine.

    Science.gov (United States)

    Lam, Sin Man; Wang, Yuan; Li, Bowen; Du, Jie; Shui, Guanghou

    2017-03-20

    Metabolomics, which targets at the extensive characterization and quantitation of global metabolites from both endogenous and exogenous sources, has emerged as a novel technological avenue to advance the field of precision medicine principally driven by genomics-oriented approaches. In particular, metabolomics has revealed the cardinal roles that the environment exerts in driving the progression of major diseases threatening public health. Herein, the existent and potential applications of metabolomics in two key areas of precision cardiovascular medicine will be critically discussed: 1) the use of metabolomics in unveiling novel disease biomarkers and pathological pathways; 2) the contribution of metabolomics in cardiovascular drug development. Major issues concerning the statistical handling of big data generated by metabolomics, as well as its interpretation, will be briefly addressed. Finally, the need for integration of various omics branches and adopting a multi-omics approach to precision medicine will be discussed. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  4. Metabolome Integrated Analysis of High-Temperature Response in Pinus radiata

    Directory of Open Access Journals (Sweden)

    Mónica Escandón

    2018-04-01

    Full Text Available The integrative omics approach is crucial to identify the molecular mechanisms underlying high-temperature response in non-model species. Based on future scenarios of heat increase, Pinus radiata plants were exposed to a temperature of 40°C for a period of 5 days, including recovered plants (30 days after last exposure to 40°C in the analysis. The analysis of the metabolome using complementary mass spectrometry techniques (GC-MS and LC-Orbitrap-MS allowed the reliable quantification of 2,287 metabolites. The analysis of identified metabolites and highlighter metabolic pathways across heat time exposure reveal the dynamism of the metabolome in relation to high-temperature response in P. radiata, identifying the existence of a turning point (on day 3 at which P. radiata plants changed from an initial stress response program (shorter-term response to an acclimation one (longer-term response. Furthermore, the integration of metabolome and physiological measurements, which cover from the photosynthetic state to hormonal profile, suggests a complex metabolic pathway interaction network related to heat-stress response. Cytokinins (CKs, fatty acid metabolism and flavonoid and terpenoid biosynthesis were revealed as the most important pathways involved in heat-stress response in P. radiata, with zeatin riboside (ZR and isopentenyl adenosine (iPA as the key hormones coordinating these multiple and complex interactions. On the other hand, the integrative approach allowed elucidation of crucial metabolic mechanisms involved in heat response in P. radiata, as well as the identification of thermotolerance metabolic biomarkers (L-phenylalanine, hexadecanoic acid, and dihydromyricetin, crucial metabolites which can reschedule the metabolic strategy to adapt to high temperature.

  5. The Lipopolysaccharide-Induced Metabolome Signature in Arabidopsis thaliana Reveals Dynamic Reprogramming of Phytoalexin and Phytoanticipin Pathways

    Science.gov (United States)

    Finnegan, Tarryn; Steenkamp, Paul A.; Piater, Lizelle A.

    2016-01-01

    Lipopolysaccharides (LPSs), as MAMP molecules, trigger the activation of signal transduction pathways involved in defence. Currently, plant metabolomics is providing new dimensions into understanding the intracellular adaptive responses to external stimuli. The effect of LPS on the metabolomes of Arabidopsis thaliana cells and leaf tissue was investigated over a 24 h period. Cellular metabolites and those secreted into the medium were extracted with methanol and liquid chromatography coupled to mass spectrometry was used for quantitative and qualitative analyses. Multivariate statistical data analyses were used to extract interpretable information from the generated multidimensional LC-MS data. The results show that LPS perception triggered differential changes in the metabolomes of cells and leaves, leading to variation in the biosynthesis of specialised secondary metabolites. Time-dependent changes in metabolite profiles were observed and biomarkers associated with the LPS-induced response were tentatively identified. These include the phytohormones salicylic acid and jasmonic acid, and also the associated methyl esters and sugar conjugates. The induced defensive state resulted in increases in indole—and other glucosinolates, indole derivatives, camalexin as well as cinnamic acid derivatives and other phenylpropanoids. These annotated metabolites indicate dynamic reprogramming of metabolic pathways that are functionally related towards creating an enhanced defensive capacity. The results reveal new insights into the mode of action of LPS as an activator of plant innate immunity, broadens knowledge about the defence metabolite pathways involved in Arabidopsis responses to LPS, and identifies specialised metabolites of functional importance that can be employed to enhance immunity against pathogen infection. PMID:27656890

  6. Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis

    Science.gov (United States)

    Vingara, Lisa K.; Yu, Hui Jing; Wagshul, Mark E.; Serafin, Dana; Christodoulou, Christopher; Pelczer, István; Krupp, Lauren B.; Maletić-Savatić, Mirjana

    2013-01-01

    Proton magnetic resonance spectroscopy (1H-MRS) is capable of noninvasively detecting metabolic changes that occur in the brain tissue in vivo. Its clinical utility has been limited so far, however, by analytic methods that focus on independently evaluated metabolites and require prior knowledge about which metabolites to examine. Here, we applied advanced computational methodologies from the field of metabolomics, specifically partial least squares discriminant analysis and orthogonal partial least squares, to in vivo 1H-MRS from frontal lobe white matter of 27 patients with relapsing–remitting multiple sclerosis (RRMS) and 14 healthy controls. We chose RRMS, a chronic demyelinating disorder of the central nervous system, because its complex pathology and variable disease course make the need for reliable biomarkers of disease progression more pressing. We show that in vivo MRS data, when analyzed by multivariate statistical methods, can provide reliable, distinct profiles of MRS-detectable metabolites in different patient populations. Specifically, we find that brain tissue in RRMS patients deviates significantly in its metabolic profile from that of healthy controls, even though it appears normal by standard MRI techniques. We also identify, using statistical means, the metabolic signatures of certain clinical features common in RRMS, such as disability score, cognitive impairments, and response to stress. This approach to human in vivo MRS data should promote understanding of the specific metabolic changes accompanying disease pathogenesis, and could provide biomarkers of disease progression that would be useful in clinical trials. PMID:23751863

  7. PLS-based and regularization-based methods for the selection of relevant variables in non-targeted metabolomics data

    Directory of Open Access Journals (Sweden)

    Renata Bujak

    2016-07-01

    Full Text Available Non-targeted metabolomics constitutes a part of systems biology and aims to determine many metabolites in complex biological samples. Datasets obtained in non-targeted metabolomics studies are multivariate and high-dimensional due to the sensitivity of mass spectrometry-based detection methods as well as complexity of biological matrices. Proper selection of variables which contribute into group classification is a crucial step, especially in metabolomics studies which are focused on searching for disease biomarker candidates. In the present study, three different statistical approaches were tested using two metabolomics datasets (RH and PH study. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA without and with multiple testing correction as well as least absolute shrinkage and selection operator (LASSO were tested and compared. For the RH study, OPLS-DA model built without multiple testing correction, selected 46 and 218 variables based on VIP criteria using Pareto and UV scaling, respectively. In the case of the PH study, 217 and 320 variables were selected based on VIP criteria using Pareto and UV scaling, respectively. In the RH study, OPLS-DA model built with multiple testing correction, selected 4 and 19 variables as statistically significant in terms of Pareto and UV scaling, respectively. For PH study, 14 and 18 variables were selected based on VIP criteria in terms of Pareto and UV scaling, respectively. Additionally, the concept and fundaments of the least absolute shrinkage and selection operator (LASSO with bootstrap procedure evaluating reproducibility of results, was demonstrated. In the RH and PH study, the LASSO selected 14 and 4 variables with reproducibility between 99.3% and 100%. However, apart from the popularity of PLS-DA and OPLS-DA methods in metabolomics, it should be highlighted that they do not control type I or type II error, but only arbitrarily establish a cut-off value for PLS-DA loadings

  8. Metabolomic and Transcriptomic Comparison of Solid-State and Submerged Fermentation of Penicillium expansum KACC 40815.

    Science.gov (United States)

    Kim, Hyang Yeon; Heo, Do Yeon; Park, Hye Min; Singh, Digar; Lee, Choong Hwan

    2016-01-01

    Penicillium spp. are known to harbor a wide array of secondary metabolites with cryptic bioactivities. However, the metabolomics of these species is not well-understood in terms of different fermentation models and conditions. The present study involved metabolomics profiling and transcriptomic analysis of Penicillium expansum 40815 under solid-state fermentation (SSF) and submerged fermentation (SmF). Metabolite profiling was carried out using ultra-performance liquid chromatography quadruple time-of-flight mass spectrometry with multivariate analysis, followed by transcriptomic analyses of differentially expressed genes. In principal component analysis, the metabolite profiling data was studied under different experimental sets, including SSF and SmF. The significantly different metabolites such as polyketide metabolites (agonodepside B, rotiorin, verrucosidin, and ochrephilone) and corresponding gene transcripts (polyketide synthase, aromatic prenyltransferase, and terpenoid synthase) were primarily detected under SmF conditions. In contrast, the meroterpenoid compounds (andrastin A and C) and their genes transcripts were exclusively detected under SSF conditions. We demonstrated that the metabolite production and its corresponding gene expression levels in P. expansum 40815 were significantly influenced by the varying growth parameters and the immediate environment. This study further provides a foundation to produce specific metabolites by regulating fermentation conditions.

  9. Cardioprotective and Metabolomic Profiling of Selected Medicinal Plants against Oxidative Stress

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    Nadia Afsheen

    2018-01-01

    Full Text Available In this research work, the antioxidant and metabolomic profiling of seven selected medicinally important herbs including Rauvolfia serpentina, Terminalia arjuna, Coriandrum sativum, Elettaria cardamom, Piper nigrum, Allium sativum, and Crataegus oxyacantha was performed. The in vivo cardioprotective potential of these medicinal plants was evaluated against surgically induced oxidative stress through left anterior descending coronary artery ligation (LADCA in dogs. The antioxidant profiling of these plants was done through DPPH and DNA protection assay. The C. oxyacantha and T. arjuna showed maximum antioxidant potential, while the E. cardamom showed poor antioxidative strength even at its high concentration. Different concentrations of extracts of the said plants exhibited the protection of plasmid DNA against H2O2 damage as compared to the plasmid DNA merely treated with H2O2. The metabolomic profiling through LC-MS analysis of these antioxidants revealed the presence of active secondary metabolites responsible for their antioxidant potential. During in vivo analysis, blood samples of all treatment groups were drawn at different time intervals to analyze the cardiac and hemodynamic parameters. The results depicted that the group pretreated with HC4 significantly sustained the level of CK-MB, SGOT, and LDH as well as hemodynamic parameters near to normal. The histopathological examination also confirmed the cardioprotective potential of HC4. Thus, the HC4 being safe and inexpensive cardioprotective herbal combination could be considered as an alternate of synthetic drugs.

  10. Cardioprotective and Metabolomic Profiling of Selected Medicinal Plants against Oxidative Stress

    Science.gov (United States)

    Afsheen, Nadia; Jahan, Nazish; Ijaz, Misbah; Manzoor, Asad; Khan, Khalid Mahmood; Hina, Saman

    2018-01-01

    In this research work, the antioxidant and metabolomic profiling of seven selected medicinally important herbs including Rauvolfia serpentina, Terminalia arjuna, Coriandrum sativum, Elettaria cardamom, Piper nigrum, Allium sativum, and Crataegus oxyacantha was performed. The in vivo cardioprotective potential of these medicinal plants was evaluated against surgically induced oxidative stress through left anterior descending coronary artery ligation (LADCA) in dogs. The antioxidant profiling of these plants was done through DPPH and DNA protection assay. The C. oxyacantha and T. arjuna showed maximum antioxidant potential, while the E. cardamom showed poor antioxidative strength even at its high concentration. Different concentrations of extracts of the said plants exhibited the protection of plasmid DNA against H2O2 damage as compared to the plasmid DNA merely treated with H2O2. The metabolomic profiling through LC-MS analysis of these antioxidants revealed the presence of active secondary metabolites responsible for their antioxidant potential. During in vivo analysis, blood samples of all treatment groups were drawn at different time intervals to analyze the cardiac and hemodynamic parameters. The results depicted that the group pretreated with HC4 significantly sustained the level of CK-MB, SGOT, and LDH as well as hemodynamic parameters near to normal. The histopathological examination also confirmed the cardioprotective potential of HC4. Thus, the HC4 being safe and inexpensive cardioprotective herbal combination could be considered as an alternate of synthetic drugs. PMID:29576858

  11. A metabolomic approach to the study of wine micro-oxygenation.

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    Panagiotis Arapitsas

    Full Text Available Wine micro-oxygenation is a globally used treatment and its effects were studied here by analysing by untargeted LC-MS the wine metabolomic fingerprint. Eight different procedural variations, marked by the addition of oxygen (four levels and iron (two levels were applied to Sangiovese wine, before and after malolactic fermentation. Data analysis using supervised and unsupervised multivariate methods highlighted some known candidate biomarkers, together with a number of metabolites which had never previously been considered as possible biomarkers for wine micro-oxygenation. Various pigments and tannins were identified among the known candidate biomarkers. Additional new information was obtained suggesting a correlation between oxygen doses and metal contents and changes in the concentration of primary metabolites such as arginine, proline, tryptophan and raffinose, and secondary metabolites such as succinic acid and xanthine. Based on these findings, new hypotheses regarding the formation and reactivity of wine pigment during micro-oxygenation have been proposed. This experiment highlights the feasibility of using unbiased, untargeted metabolomic fingerprinting to improve our understanding of wine chemistry.

  12. A Metabolomic Approach to the Study of Wine Micro-Oxygenation

    Science.gov (United States)

    Arapitsas, Panagiotis; Scholz, Matthias; Vrhovsek, Urska; Di Blasi, Stefano; Biondi Bartolini, Alessandra; Masuero, Domenico; Perenzoni, Daniele; Rigo, Adelio; Mattivi, Fulvio

    2012-01-01

    Wine micro-oxygenation is a globally used treatment and its effects were studied here by analysing by untargeted LC-MS the wine metabolomic fingerprint. Eight different procedural variations, marked by the addition of oxygen (four levels) and iron (two levels) were applied to Sangiovese wine, before and after malolactic fermentation. Data analysis using supervised and unsupervised multivariate methods highlighted some known candidate biomarkers, together with a number of metabolites which had never previously been considered as possible biomarkers for wine micro-oxygenation. Various pigments and tannins were identified among the known candidate biomarkers. Additional new information was obtained suggesting a correlation between oxygen doses and metal contents and changes in the concentration of primary metabolites such as arginine, proline, tryptophan and raffinose, and secondary metabolites such as succinic acid and xanthine. Based on these findings, new hypotheses regarding the formation and reactivity of wine pigment during micro-oxygenation have been proposed. This experiment highlights the feasibility of using unbiased, untargeted metabolomic fingerprinting to improve our understanding of wine chemistry. PMID:22662221

  13. Metabolomic profiling reveals deep chemical divergence between two morphotypes of the zoanthid Parazoanthus axinellae

    Science.gov (United States)

    Cachet, Nadja; Genta-Jouve, Grégory; Ivanisevic, Julijana; Chevaldonné, Pierre; Sinniger, Frédéric; Culioli, Gérald; Pérez, Thierry; Thomas, Olivier P.

    2015-01-01

    Metabolomics has recently proven its usefulness as complementary tool to traditional morphological and genetic analyses for the classification of marine invertebrates. Among the metabolite-rich cnidarian order Zoantharia, Parazoanthus is a polyphyletic genus whose systematics and phylogeny remain controversial. Within this genus, one of the most studied species, Parazoanthus axinellae is prominent in rocky shallow waters of the Mediterranean Sea and the NE Atlantic Ocean. Although different morphotypes can easily be distinguished, only one species is recognized to date. Here, a metabolomic profiling approach has been used to assess the chemical diversity of two main Mediterranean morphotypes, the “slender” and “stocky” forms of P. axinellae. Targeted profiling of their major secondary metabolites revealed a significant chemical divergence between the morphotypes. While zoanthoxanthin alkaloids and ecdysteroids are abundant in both morphs, the “slender” morphotype is characterized by the presence of additional and bioactive 3,5-disubstituted hydantoin derivatives named parazoanthines. The absence of these specific compounds in the “stocky” morphotype was confirmed by spatial and temporal monitoring over an annual cycle. Moreover, specimens of the “slender” morphotype are also the only ones found as epibionts of several sponge species, particularly Cymbaxinella damicornis thus suggesting a putative ecological link. PMID:25655432

  14. Bio-effectors from waste materials as growth promoters, an agronomic and metabolomic study

    Science.gov (United States)

    Alwanney, Deaa; Chami, Ziad Al; Angelica De Pascali, Sandra; Cavoski, Ivana; Fanizzi, Francesco Paolo

    2014-05-01

    Nowadays, improving plant performance by providing growth promoters is a main concern of the organic agriculture. As a consequence of increased food demands, more efficient and alternatives of the current plant nutrition strategies are becoming urgent. Recently, a novel concept "bio-effectors" raised on to describe a group of products that are able to improve plant performance and do not belong to fertilizers or pesticides. Agro-Food processing residues are promising materials as bio-effector. Three plant-derived materials: brewers' spent grain (BSG), fennel processing residues (FPR) and lemon processing residues (LPR) were chosen as bio-effector candidates. Plant-derived materials were characterized in term of total macro and micronutrients content. Green extraction methodology and solvent choice (aqueous; ethanol; and aqueous: ethanol mixture 1:1) was based on the extraction yield as main factor. Optimum extracts, to be used on the tomato test plant, were determined using phytotoxicity test (seed germination test) as main constraint. Thereafter, selected extracts were characterized and secondary metabolites profiling were detected by NMR technique. Selected extracts were applied on tomato in a growth chamber at different doses in comparison to humic-like substances as positive control (Ctrl+) and to a Hoagland solution as negative control (Ctrl-). At the end of the experiment, agronomical parameters were determined and NMR-metabolomic profiling were conducted on tomato seedlings. Results are summarized as follow: (i) raw showed an interesting content, either at nutritional or biological level; (ii) aqueous extraction resulted higher yield than other used solvent; (iii) at high extraction ratio (1:25 for BSG; 1:100 for FPR; and 1:200 for LPR) aqueous extracts were not phytotoxic on the tomato test plant; (iv) all aqueous extract are differently rich in nutrients, aminoacids, sugars and low molecular weight molecules; (v) all extract exhibited a growth promotion at

  15. Effects of a prolonged standardized diet on normalizing the human metabolome123

    OpenAIRE

    Winnike, Jason H; Busby, Marjorie G; Watkins, Paul B; O'Connell, Thomas M

    2009-01-01

    Background: Although the effects of acute dietary interventions on the human metabolome have been studied, the extent to which the metabolome can be normalized by extended dietary standardization has not yet been examined.

  16. Understanding Aquatic Rhizosphere Processes Through Metabolomics and Metagenomics Approach

    Science.gov (United States)

    Lee, Yong Jian; Mynampati, Kalyan; Drautz, Daniela; Arumugam, Krithika; Williams, Rohan; Schuster, Stephan; Kjelleberg, Staffan; Swarup, Sanjay

    2013-04-01

    The aquatic rhizosphere is a region around the roots of aquatic plants. Many studies focusing on terrestrial rhizosphere have led to a good understanding of the interactions between the roots, its exudates and its associated rhizobacteria. The rhizosphere of free-floating roots, however, is a different habitat that poses several additional challenges, including rapid diffusion rates of signals and nutrient molecules, which are further influenced by the hydrodynamic forces. These can lead to rapid diffusion and complicates the studying of diffusible factors from both plant and/or rhizobacterial origins. These plant systems are being increasingly used for self purification of water bodies to provide sustainable solution. A better understanding of these processes will help in improving their performance for ecological engineering of freshwater systems. The same principles can also be used to improve the yield of hydroponic cultures. Novel toolsets and approaches are needed to investigate the processes occurring in the aquatic rhizosphere. We are interested in understanding the interaction between root exudates and the complex microbial communities that are associated with the roots, using a systems biology approach involving metabolomics and metagenomics. With this aim, we have developed a RhizoFlowCell (RFC) system that provides a controlled study of aquatic plants, observed the root biofilms, collect root exudates and subject the rhizosphere system to changes in various chemical or physical perturbations. As proof of concept, we have used RFC to test the response of root exudation patterns of Pandanus amaryllifolius after exposure to the pollutant naphthalene. Complexity of root exudates in the aquatic rhizosphere was captured using this device and analysed using LC-qTOF-MS. The highly complex metabolomic profile allowed us to study the dynamics of the response of roots to varying levels of naphthalene. The metabolic profile changed within 5mins after spiking with

  17. [Secondary hypertension].

    Science.gov (United States)

    Yoshida, Yuichi; Shibata, Hirotaka

    2015-11-01

    Hypertension is a common disease and a crucial predisposing factor of cardiovascular diseases. Approximately 10% of hypertensive patients are secondary hypertension, a pathogenetic factor of which can be identified. Secondary hypertension consists of endocrine, renal, and other diseases. Primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperthyroidism, and hypothyroidism result in endocrine hypertension. Renal parenchymal hypertension and renovascular hypertension result in renal hypertension. Other diseases such as obstructive sleep apnea syndrome are also very prevalent in secondary hypertension. It is very crucial to find and treat secondary hypertension at earlier stages since most secondary hypertension is curable or can be dramatically improved by specific treatment. One should keep in mind that screening of secondary hypertension should be done at least once in a daily clinical practice.

  18. Vitamin D prenatal programming of childhood metabolomics profiles at age 3 y.

    Science.gov (United States)

    Blighe, Kevin; Chawes, Bo L; Kelly, Rachel S; Mirzakhani, Hooman; McGeachie, Michael; Litonjua, Augusto A; Weiss, Scott T; Lasky-Su, Jessica A

    2017-10-01

    Background: Vitamin D deficiency is implicated in a range of common complex diseases that may be prevented by gestational vitamin D repletion. Understanding the metabolic mechanisms related to in utero vitamin D exposure may therefore shed light on complex disease susceptibility. Objective: The goal was to analyze the programming role of in utero vitamin D exposure on children's metabolomics profiles. Design: First, unsupervised clustering was done with plasma metabolomics profiles from a case-control subset of 245 children aged 3 y with and without asthma from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), in which pregnant women were randomly assigned to vitamin D supplementation or placebo. Thereafter, we analyzed the influence of maternal pre- and postsupplement vitamin D concentrations on cluster membership. Finally, we used the metabolites driving the clustering of children to identify the dominant metabolic pathways that were influential in each cluster. Results: We identified 3 clusters of children characterized by 1 ) high concentrations of fatty acids and amines and low maternal postsupplement vitamin D (mean ± SD; 27.5 ± 11.0 ng/mL), 2 ) high concentrations of amines, moderate concentrations of fatty acids, and normal maternal postsupplement vitamin D (34.0 ± 14.1 ng/mL), and 3 ) low concentrations of fatty acids, amines, and normal maternal postsupplement vitamin D (35.2 ± 15.9 ng/mL). Adjusting for sample storage time, maternal age and education, and both child asthma and vitamin D concentration at age 3 y did not modify the association between maternal postsupplement vitamin D and cluster membership ( P = 0.0014). Maternal presupplement vitamin D did not influence cluster membership, whereas the combination of pre- and postsupplement concentrations did ( P = 0.03). Conclusions: Young children can be clustered into distinct biologically meaningful groups by their metabolomics profiles. The clusters differed in concentrations of

  19. Towards Polypharmacokinetics: Pharmacokinetics of Multicomponent Drugs and Herbal Medicines Using a Metabolomics Approach

    Directory of Open Access Journals (Sweden)

    Ke Lan

    2013-01-01

    Full Text Available Determination of pharmacokinetics (PKs of multicomponent pharmaceuticals and/or nutraceuticals (polypharmacokinetics, poly-PKs is difficult due to the vast number of compounds present in natural products, their various concentrations across a wide range, complexity of their interactions, as well as their complex degradation dynamics in vivo. Metabolomics coupled with multivariate statistical tools that focus on the comprehensive analysis of small molecules in biofluids is a viable approach to address the challenges of poly-PK. This paper discusses recent advances in the characterization of poly-PK and the metabolism of multicomponent xenobiotic agents, such as compound drugs, dietary supplements, and herbal medicines, using metabolomics strategy. We propose a research framework that integrates the dynamic concentration profile of bioavailable xenobiotic molecules that result from in vivo absorption and hepatic and gut bacterial metabolism, as well as the human metabolic response profile. This framework will address the bottleneck problem in the pharmacological evaluation of multicomponent pharmaceuticals and nutraceuticals, leading to the direct elucidation of the pharmacological and molecular mechanisms of these compounds.

  20. Decoding the dynamics of cellular metabolism and the action of 3-bromopyruvate and 2-deoxyglucose using pulsed stable isotope-resolved metabolomics.

    Science.gov (United States)

    Pietzke, Matthias; Zasada, Christin; Mudrich, Susann; Kempa, Stefan

    2014-01-01

    Cellular metabolism is highly dynamic and continuously adjusts to the physiological program of the cell. The regulation of metabolism appears at all biological levels: (post-) transcriptional, (post-) translational, and allosteric. This regulatory information is expressed in the metabolome, but in a complex manner. To decode such complex information, new methods are needed in order to facilitate dynamic metabolic characterization at high resolution. Here, we describe pulsed stable isotope-resolved metabolomics (pSIRM) as a tool for the dynamic metabolic characterization of cellular metabolism. We have adapted gas chromatography-coupled mass spectrometric methods for metabolomic profiling and stable isotope-resolved metabolomics. In addition, we have improved robustness and reproducibility and implemented a strategy for the absolute quantification of metabolites. By way of examples, we have applied this methodology to characterize central carbon metabolism of a panel of cancer cell lines and to determine the mode of metabolic inhibition of glycolytic inhibitors in times ranging from minutes to hours. Using pSIRM, we observed that 2-deoxyglucose is a metabolic inhibitor, but does not directly act on the glycolytic cascade.

  1. Methodological aspects for metabolome visualization and characterization: a metabolomic evaluation of the 24 h evolution of human urine after cocoa powder consumption.

    Science.gov (United States)

    Llorach-Asunción, R; Jauregui, O; Urpi-Sarda, M; Andres-Lacueva, C

    2010-01-20

    The LC-MS based metabolomics studies are characterized by the capacity to produce a large and complex dataset being mandatory to use the appropriate tools to recover and to interpret as maximum information as possible. In this context, a combined partial least square discriminat analysis (PLS-DA) and two-way hierarchical clustering (two-way HCA) using Bonferroni correction as filter is proposed to improve analysis in human urinary metabolome modifications in a nutritional intervention context. After overnight fasting, 10 subjects consumed cocoa powder with milk. Urine samples were collected before the ingestion product and at 0-6, 6-12, 12-24 h after test-meal consumption and analysed by LC-Q-ToF. The PLS-DA analysis showed a clear pattern related to the differences between before consumption period and the other three periods revealing relevant mass features in this separation, however, a weaker association between mass features and the three periods after cocoa consumption was observed. On the other hand, two-way HCA showed a separation of four urine time periods and point out the mass features associated with the corresponding urine times. The correlation matrix revealed complex relations between the mass features that could be used for metabolite identifications and to infer the possible metabolite origin. The reported results prove that combining visualization strategies would be an excellent way to produce new bioinformatic applications that help the scientific community to unravel the complex relations between the consumption of phytochemicals and their expected effects on health.

  2. Metabolomic markers of fatigue: Association between circulating metabolome and fatigue in women with chronic widespread pain.

    Science.gov (United States)

    Freidin, Maxim B; Wells, Helena R R; Potter, Tilly; Livshits, Gregory; Menni, Cristina; Williams, Frances M K

    2018-02-01

    Fatigue is a sensation of unbearable tiredness that frequently accompanies chronic widespread musculoskeletal pain (CWP) and inflammatory joint disease. Its mechanisms are poorly understood and there is a lack of effective biomarkers for diagnosis and onset prediction. We studied the circulating metabolome in a population sample characterised for CWP to identify biomarkers showing specificity for fatigue. Untargeted metabolomic profiling was conducted on fasting plasma and serum samples of 1106 females with and without CWP from the TwinsUK cohort. Linear mixed-effects models accounting for covariates were used to determine relationships between fatigue and metabolites. Receiver operating curve (ROC)-analysis was used to determine predictive value of metabolites for fatigue. While no association between fatigue and metabolites was identified in twins without CWP (n=711), in participants with CWP (n=395), levels of eicosapentaenoate (EPA) ω-3 fatty acid were significantly reduced in those with fatigue (β=-0.452±0.116; p=1.2×10 -4 ). A significant association between fatigue and two other metabolites also emerged when BMI was excluded from the model: 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF), and C-glycosyltryptophan (p=1.5×10 -4 and p=3.1×10 -4 , respectively). ROC analysis has identified a combination of 15 circulating metabolites with good predictive potential for fatigue in CWP (AUC=75%; 95% CI 69-80%). The results of this agnostic metabolomics screening show that fatigue is metabolically distinct from CWP, and is associated with a decrease in circulating levels of EPA. Our panel of circulating metabolites provides the starting point for a diagnostic test for fatigue in CWP. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Serum metabolome and lipidome changes in adult patients with primary dengue infection.

    Directory of Open Access Journals (Sweden)

    Liang Cui

    Full Text Available Dengue virus (DENV is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis.Systems level characterization of serum metabolome and lipidome of adult DF patients at early febrile, defervescence, and convalescent stages of DENV infection was performed using liquid chromatography- and gas chromatography-mass spectrometry. The tractability of following metabolite and lipid changes in a relatively large sample size (n = 44 across three prominent infection stages allowed the identification of critical physiologic changes that coincided with the different stages. Sixty differential metabolites were identified in our metabolomics analysis and the main metabolite classes were free fatty acids, acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic pathways included fatty acid biosynthesis and β-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers.DENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes, thus preventing the host from development of pathologies by excessive

  4. Atmo-metabolomics: a new measurement approach for investigating aerosol composition and ecosystem functioning.

    Science.gov (United States)

    Rivas-Ubach, A.; Liu, Y.; Sardans, J.; Tfaily, M. M.; Kim, Y. M.; Bourrianne, E.; Paša-Tolić, L.; Penuelas, J.; Guenther, A. B.

    2016-12-01

    Aerosols play crucial roles in the processes controlling the composition of the atmosphere and the functioning of ecosystems. Gaining a deeper understanding of the chemical composition of aerosols is one of the major challenges for atmospheric and climate scientists and is beginning to be recognized as important for ecological research. Better comprehension of aerosol chemistry can potentially provide valuable information on atmospheric processes such as oxidation of organics and the production of cloud condensation nuclei as well as provide an approximation of the general status of an ecosystem through the measurement of certain stress biomarkers. In this study, we describe an efficient aerosol sampling method, the metabolite extraction and the analytical procedures for the chemical characterization of aerosols, namely, the atmo-metabolome. We used mass spectrometry (MS) coupled to liquid chromatography (LC-MS), gas chromatography (GC-MS) and Fourier transform ion cyclotron resonance (FT-ICR-MS) to characterize the atmo-metabolome of two marked seasons; spring and summer. Our sampling and extraction methods demonstrated to be suitable for aerosol chemical characterization with any of the analytical platforms used in this study. The atmo-metabolome between spring and summer showed overall statistically differences. We identified several metabolites that can be attributed to pollen and other plant-related aerosols. Spring aerosols exhibit higher concentrations of metabolites linked to higher plant activity while summer samples had higher concentrations of metabolites that may reflect certain oxidative stresses in primary producers. Moreover, the elemental composition of aerosols showed clear different between seasons. Summer aerosols were generally higher in molecular weight and with higher O/C ratios, indicating higher oxidation levels and condensation of compounds relative to spring. Our method represents an advanced approach for characterizing the composition of

  5. A Conversation on Data Mining Strategies in LC-MS Untargeted Metabolomics: Pre-Processing and Pre-Treatment Steps

    Directory of Open Access Journals (Sweden)

    Fidele Tugizimana

    2016-11-01

    Full Text Available Untargeted metabolomic studies generate information-rich, high-dimensional, and complex datasets that remain challenging to handle and fully exploit. Despite the remarkable progress in the development of tools and algorithms, the “exhaustive” extraction of information from these metabolomic datasets is still a non-trivial undertaking. A conversation on data mining strategies for a maximal information extraction from metabolomic data is needed. Using a liquid chromatography-mass spectrometry (LC-MS-based untargeted metabolomic dataset, this study explored the influence of collection parameters in the data pre-processing step, scaling and data transformation on the statistical models generated, and feature selection, thereafter. Data obtained in positive mode generated from a LC-MS-based untargeted metabolomic study (sorghum plants responding dynamically to infection by a fungal pathogen were used. Raw data were pre-processed with MarkerLynxTM software (Waters Corporation, Manchester, UK. Here, two parameters were varied: the intensity threshold (50–100 counts and the mass tolerance (0.005–0.01 Da. After the pre-processing, the datasets were imported into SIMCA (Umetrics, Umea, Sweden for more data cleaning and statistical modeling. In addition, different scaling (unit variance, Pareto, etc. and data transformation (log and power methods were explored. The results showed that the pre-processing parameters (or algorithms influence the output dataset with regard to the number of defined features. Furthermore, the study demonstrates that the pre-treatment of data prior to statistical modeling affects the subspace approximation outcome: e.g., the amount of variation in X-data that the model can explain and predict. The pre-processing and pre-treatment steps subsequently influence the number of statistically significant extracted/selected features (variables. Thus, as informed by the results, to maximize the value of untargeted metabolomic data

  6. Metabolomics of Small Numbers of Cells: Metabolomic Profiling of 100, 1000, and 10000 Human Breast Cancer Cells.

    Science.gov (United States)

    Luo, Xian; Li, Liang

    2017-11-07

    In cellular metabolomics, it is desirable to carry out metabolomic profiling using a small number of cells in order to save time and cost. In some applications (e.g., working with circulating tumor cells in blood), only a limited number of cells are available for analysis. In this report, we describe a method based on high-performance chemical isotope labeling (CIL) nanoflow liquid chromatography mass spectrometry (nanoLC-MS) for high-coverage metabolomic analysis of small numbers of cells (i.e., ≤10000 cells). As an example, 12 C-/ 13 C-dansyl labeling of the metabolites in lysates of 100, 1000, and 10000 MCF-7 breast cancer cells was carried out using a new labeling protocol tailored to handle small amounts of metabolites. Chemical-vapor-assisted ionization in a captivespray interface was optimized for improving metabolite ionization and increasing robustness of nanoLC-MS. Compared to microflow LC-MS, the nanoflow system provided much improved metabolite detectability with a significantly reduced sample amount required for analysis. Experimental duplicate analyses of biological triplicates resulted in the detection of 1620 ± 148, 2091 ± 89 and 2402 ± 80 (n = 6) peak pairs or metabolites in the amine/phenol submetabolome from the 12 C-/ 13 C-dansyl labeled lysates of 100, 1000, and 10000 cells, respectively. About 63-69% of these peak pairs could be either identified using dansyl labeled standard library or mass-matched to chemical structures in human metabolome databases. We envisage the routine applications of this method for high-coverage quantitative cellular metabolomics using a starting material of 10000 cells. Even for analyzing 100 or 1000 cells, although the metabolomic coverage is reduced from the maximal coverage, this method can still detect thousands of metabolites, allowing the analysis of a large fraction of the metabolome and focused analysis of the detectable metabolites.

  7. Secondary Evaluations.

    Science.gov (United States)

    Cook, Thomas D.

    Secondary evaluations, in which an investigator takes a body of evaluation data collected by a primary evaluation researcher and examines the data to see if the original conclusions about the program correspond with his own, are discussed. The different kinds of secondary evaluations and the advantages and disadvantages of each are pointed out,…

  8. Stability Constants of Mixed Ligand Complexes of Transition Metal(II Ions with Salicylidene-4-methoxyaniline as Primary Ligand and 5-Bromosalicylidene-4-nitroaniline as Secondary Ligand

    Directory of Open Access Journals (Sweden)

    N. G. Nadkarni

    2011-01-01

    Full Text Available Binary and ternary complexes of the type M-Y and M-X-Y [M = Mn(II, Ni(II, Cu(II and Zn(II; X = salicylidene-4-methoxyaniline and Y=5-bromosalicylidene-4-nitroaniline] have been examined pH-metrically at 27±0.5 °C and at constant ionic strength, μ= 0.1 M (KCl in 75 : 25(v/v 1,4-dioxne-water medium. The stability constants for binary (M-Y and ternary (M-X-Y systems were calculated. The relative stability (Δ log KT values of the ternary complexes with corresponding binary complexes for all the metal(II ions in the present study found to be negative indicating that ternary 1:1:1 (M-X-Y complexes are less stable than binary 1:1 (M-Y complexes. In the ternary system studied, the order of stability constants of mixed ligand complexes with respect to the metal ions was found to be Cu(II > NI(II > Mn(II > Zn(II; which is same as in the corresponding binary (M-Y systems.

  9. LC-MS-BASED METABOLOMICS OF XENOBIOTIC-INDUCED TOXICITIES

    Directory of Open Access Journals (Sweden)

    Chi Chen

    2013-01-01

    Full Text Available Xenobiotic exposure, especially high-dose or repeated exposure of xenobiotics, can elicit detrimental effects on biological systems through diverse mechanisms. Changes in metabolic systems, including formation of reactive metabolites and disruption of endogenous metabolism, are not only the common consequences of toxic xenobiotic exposure, but in many cases are the major causes behind development of xenobiotic-induced toxicities (XIT. Therefore, examining the metabolic events associated with XIT generates mechanistic insights into the initiation and progression of XIT, and provides guidance for prevention and treatment. Traditional bioanalytical platforms that target only a few suspected metabolites are capable of validating the expected outcomes of xenobiotic exposure. However, these approaches lack the capacity to define global changes and to identify unexpected events in the metabolic system. Recent developments in high-throughput metabolomics have dramatically expanded the scope and potential of metabolite analysis. Among all analytical techniques adopted for metabolomics, liquid chromatography-mass spectrometry (LC-MS has been most widely used for metabolomic investigations of XIT due to its versatility and sensitivity in metabolite analysis. In this review, technical platform of LC-MS-based metabolomics, including experimental model, sample preparation, instrumentation, and data analysis, are discussed. Applications of LC-MS-based metabolomics in exploratory and hypothesis-driven investigations of XIT are illustrated by case studies of xenobiotic metabolism and endogenous metabolism associated with xenobiotic exposure.

  10. [Development of Plant Metabolomics and Medicinal Plant Genomics].

    Science.gov (United States)

    Saito, Kazuki

    2018-01-01

     A variety of chemicals produced by plants, often referred to as 'phytochemicals', have been used as medicines, food, fuels and industrial raw materials. Recent advances in the study of genomics and metabolomics in plant science have accelerated our understanding of the mechanisms, regulation and evolution of the biosynthesis of specialized plant products. We can now address such questions as how the metabolomic diversity of plants is originated at the levels of genome, and how we should apply this knowledge to drug discovery, industry and agriculture. Our research group has focused on metabolomics-based functional genomics over the last 15 years and we have developed a new research area called 'Phytochemical Genomics'. In this review, the development of a research platform for plant metabolomics is discussed first, to provide a better understanding of the chemical diversity of plants. Then, representative applications of metabolomics to functional genomics in a model plant, Arabidopsis thaliana, are described. The extension of integrated multi-omics analyses to non-model specialized plants, e.g., medicinal plants, is presented, including the identification of novel genes, metabolites and networks for the biosynthesis of flavonoids, alkaloids, sulfur-containing metabolites and terpenoids. Further, functional genomics studies on a variety of medicinal plants is presented. I also discuss future trends in pharmacognosy and related sciences.

  11. Metabolomics for functional genomics, systems biology, and biotechnology.

    Science.gov (United States)

    Saito, Kazuki; Matsuda, Fumio

    2010-01-01

    Metabolomics now plays a significant role in fundamental plant biology and applied biotechnology. Plants collectively produce a huge array of chemicals, far more than are produced by most other organisms; hence, metabolomics is of great importance in plant biology. Although substantial improvements have been made in the field of metabolomics, the uniform annotation of metabolite signals in databases and informatics through international standardization efforts remains a challenge, as does the development of new fields such as fluxome analysis and single cell analysis. The principle of transcript and metabolite cooccurrence, particularly transcriptome coexpression network analysis, is a powerful tool for decoding the function of genes in Arabidopsis thaliana. This strategy can now be used for the identification of genes involved in specific pathways in crops and medicinal plants. Metabolomics has gained importance in biotechnology applications, as exemplified by quantitative loci analysis, prediction of food quality, and evaluation of genetically modified crops. Systems biology driven by metabolome data will aid in deciphering the secrets of plant cell systems and their application to biotechnology.

  12. Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction.

    Science.gov (United States)

    Boiteau, Rene M; Hoyt, David W; Nicora, Carrie D; Kinmonth-Schultz, Hannah A; Ward, Joy K; Bingol, Kerem

    2018-01-17

    We introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS²), and NMR into a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter out the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture, and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana . The NMR/MS² approach is well suited to the discovery of new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases.

  13. Novel chemistry of invasive plants: exotic species have more unique metabolomic profiles than native congeners.

    Science.gov (United States)

    Macel, Mirka; de Vos, Ric C H; Jansen, Jeroen J; van der Putten, Wim H; van Dam, Nicole M

    2014-07-01

    It is often assumed that exotic plants can become invasive when they possess novel secondary chemistry compared with native plants in the introduced range. Using untargeted metabolomic fingerprinting, we compared a broad range of metabolites of six successful exotic plant species and their native congeners of the family Asteraceae. Our results showed that plant chemistry is highly species-specific and diverse among both exotic and native species. Nonetheless, the exotic species had on average a higher total number of metabolites and more species-unique metabolites compared with their native congeners. Herbivory led to an overall increase in metabolites in all plant species. Generalist herbivore performance was lower on most of the exotic species compared with the native species. We conclude that high chemical diversity and large phytochemical uniqueness of the exotic species could be indicative of biological invasion potential.

  14. Tissue Multiplatform-Based Metabolomics/Metabonomics for Enhanced Metabolome Coverage.

    Science.gov (United States)

    Vorkas, Panagiotis A; Abellona U, M R; Li, Jia V

    2018-01-01

    The use of tissue as a matrix to elucidate disease pathology or explore intervention comes with several advantages. It allows investigation of the target alteration directly at the focal location and facilitates the detection of molecules that could become elusive after secretion into biofluids. However, tissue metabolomics/metabonomics comes with challenges not encountered in biofluid analyses. Furthermore, tissue heterogeneity does not allow for tissue aliquoting. Here we describe a multiplatform, multi-method workflow which enables metabolic profiling analysis of tissue samples, while it can deliver enhanced metabolome coverage. After applying a dual consecutive extraction (organic followed by aqueous), tissue extracts are analyzed by reversed-phase (RP-) and hydrophilic interaction liquid chromatography (HILIC-) ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) and nuclear magnetic resonance (NMR) spectroscopy. This pipeline incorporates the required quality control features, enhances versatility, allows provisional aliquoting of tissue extracts for future guided analyses, expands the range of metabolites robustly detected, and supports data integration. It has been successfully employed for the analysis of a wide range of tissue types.

  15. Diurnal effects of anoxia on the metabolome of the seagrass Zostera marina

    DEFF Research Database (Denmark)

    Hasler-Sheetal, Harald; Holmer, Marianne; Weckwerth, Wolfram

    2014-01-01

    Environmental metabolomics has become interesting in marine ecological studies. One example is the revealing of new insights in stress response of Zostera marina. This is essential to understand how, at which level and to what extend aquatic plants adapt, tolerate and react to environmental...... stressors. We exposed Z. marina to water column anoxia and assessed the diurnal metabolomic response by GC-TOF-MS based metabolomics identifying 109 known and 217 unknown metabolites. During day time photosynthetic oxygen production prevents severe effects of anoxia on the metabolome (complete set of small...... the applicability of metabolomics to assess environmental stress responses of Zostera marina....

  16. Metabolomics in plants and humans: applications in the prevention and diagnosis of diseases.

    Science.gov (United States)

    Gomez-Casati, Diego F; Zanor, Maria I; Busi, María V

    2013-01-01

    In the recent years, there has been an increase in the number of metabolomic approaches used, in parallel with proteomic and functional genomic studies. The wide variety of chemical types of metabolites available has also accelerated the use of different techniques in the investigation of the metabolome. At present, metabolomics is applied to investigate several human diseases, to improve their diagnosis and prevention, and to design better therapeutic strategies. In addition, metabolomic studies are also being carried out in areas such as toxicology and pharmacology, crop breeding, and plant biotechnology. In this review, we emphasize the use and application of metabolomics in human diseases and plant research to improve human health.

  17. Deconstructing the pig sex metabolome: Targeted metabolomics in heavy pigs revealed sexual dimorphisms in plasma biomarkers and metabolic pathways.

    Science.gov (United States)

    Bovo, S; Mazzoni, G; Calò, D G; Galimberti, G; Fanelli, F; Mezzullo, M; Schiavo, G; Scotti, E; Manisi, A; Samoré, A B; Bertolini, F; Trevisi, P; Bosi, P; Dall'Olio, S; Pagotto, U; Fontanesi, L

    2015-12-01

    Metabolomics has opened new possibilities to investigate metabolic differences among animals. In this study, we applied a targeted metabolomic approach to deconstruct the pig sex metabolome as defined by castrated males and entire gilts. Plasma from 545 performance-tested Italian Large White pigs (172 castrated males and 373 females) sampled at about 160 kg live weight were analyzed for 186 metabolites using the Biocrates AbsoluteIDQ p180 Kit. After filtering, 132 metabolites (20 AA, 11 biogenic amines, 1 hexose, 13 acylcarnitines, 11 sphingomyelins, 67 phosphatidylcholines, and 9 lysophosphatidylcholines) were retained for further analyses. The multivariate approach of the sparse partial least squares discriminant analysis was applied, together with a specifically designed statistical pipeline, that included a permutation test and a 10 cross-fold validation procedure that produced stability and effect size statistics for each metabolite. Using this approach, we identified 85 biomarkers (with metabolites from all analyzed chemical families) that contributed to the differences between the 2 groups of pigs ( metabolic shift in castrated males toward energy storage and lipid production. Similar general patterns were observed for most sphingomyelins, phosphatidylcholines, and lysophosphatidylcholines. Metabolomic pathway analysis and pathway enrichment identified several differences between the 2 sexes. This metabolomic overview opened new clues on the biochemical mechanisms underlying sexual dimorphism that, on one hand, might explain differences in terms of economic traits between castrated male pigs and entire gilts and, on the other hand, could strengthen the pig as a model to define metabolic mechanisms related to fat deposition.

  18. A Latitudinal Metabolome of the Atlantic Ocean

    Science.gov (United States)

    Johnson, W.; Kido Soule, M. C.; Longnecker, K.; Kujawinski, E. B.

    2016-02-01

    Microbial consortia function via the exchange and transformation of small organic molecules or metabolites. These metabolites make up a pool of rapidly cycling organic matter in the ocean that is challenging to characterize due to its low concentrations. We seek to determine the distribution of these molecules and the factors that shape their abundance and flux. Through measurements of the abundance of a core set of metabolites, including nucleic acids, amino acids, sugars, vitamins, and signaling molecules, we gain a real-time snapshot of microbial activity. We used a targeted metabolomics technique to profile metabolite abundance in particulate and dissolved organic matter extracts collected from a 14,000 km transect running from 38˚S to 55˚N in the Western Atlantic Ocean. This extensive dataset is the first of its kind in the Atlantic Ocean and allows us to explore connections among metabolites as well as latitudinal trends in metabolite abundance. We found changes in the intracellular abundance of certain metabolites between low and high nutrient regions and a wide distribution of certain dissolved vitamins in the surface ocean. These measurements give us baseline data on the distribution of these metabolites and allow us to extend our understanding of microbial community activity in different regions of the ocean.

  19. Genetic basis of metabolome variation in yeast.

    Directory of Open Access Journals (Sweden)

    Jeffrey S Breunig

    2014-03-01

    Full Text Available Metabolism, the conversion of nutrients into usable energy and biochemical building blocks, is an essential feature of all cells. The genetic factors responsible for inter-individual metabolic variability remain poorly understood. To investigate genetic causes of metabolome variation, we measured the concentrations of 74 metabolites across ~ 100 segregants from a Saccharomyces cerevisiae cross by liquid chromatography-tandem mass spectrometry. We found 52 quantitative trait loci for 34 metabolites. These included linkages due to overt changes in metabolic genes, e.g., linking pyrimidine intermediates to the deletion of ura3. They also included linkages not directly related to metabolic enzymes, such as those for five central carbon metabolites to ira2, a Ras/PKA pathway regulator, and for the metabolites, S-adenosyl-methionine and S-adenosyl-homocysteine to slt2, a MAP kinase involved in cell wall integrity. The variant of ira2 that elevates metabolite levels also increases glucose uptake and ethanol secretion. These results highlight specific examples of genetic variability, including in genes without prior known metabolic regulatory function, that impact yeast metabolism.

  20. Mass spectrometry as a quantitative tool in plant metabolomics

    Science.gov (United States)

    Jorge, Tiago F.; Mata, Ana T.

    2016-01-01

    Metabolomics is a research field used to acquire comprehensive information on the composition of a metabolite pool to provide a functional screen of the cellular state. Studies of the plant metabolome include the analysis of a wide range of chemical species with very diverse physico-chemical properties, and therefore powerful analytical tools are required for the separation, characterization and quantification of this vast compound diversity present in plant matrices. In this review, challenges in the use of mass spectrometry (MS) as a quantitative tool in plant metabolomics experiments are discussed, and important criteria for the development and validation of MS-based analytical methods provided. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644967

  1. Plant Metabolomics: An Indispensable System Biology Tool for Plant Science

    Science.gov (United States)

    Hong, Jun; Yang, Litao; Zhang, Dabing; Shi, Jianxin

    2016-01-01

    As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality. PMID:27258266

  2. Plant Metabolomics: An Indispensable System Biology Tool for Plant Science

    Directory of Open Access Journals (Sweden)

    Jun Hong

    2016-06-01

    Full Text Available As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality.

  3. A primer to nutritional metabolomics by NMR spectroscopy and chemometrics

    DEFF Research Database (Denmark)

    Savorani, Francesco; Rasmussen, Morten Arendt; Mikkelsen, Mette Skau

    2013-01-01

    This paper outlines the advantages and disadvantages of using high throughput NMR metabolomics for nutritional studies with emphasis on the workflow and data analytical methods for generation of new knowledge. The paper describes one-by-one the major research activities in the interdisciplinary...... metabolomics platform and highlights the opportunities that NMR spectra can provide in future nutrition studies. Three areas are emphasized: (1) NMR as an unbiased and non-destructive platform for providing an overview of the metabolome under investigation, (2) NMR for providing versatile information and data...... structures for multivariate pattern recognition methods and (3) NMR for providing a unique fingerprint of the lipoprotein status of the subject. For the first time in history, by combining NMR spectroscopy and chemometrics we are able to perform inductive nutritional research as a complement to the deductive...

  4. Metabolomics in epidemiology: from metabolite concentrations to integrative reaction networks.

    Science.gov (United States)

    Fearnley, Liam G; Inouye, Michael

    2016-10-01

    Metabolomics is becoming feasible for population-scale studies of human disease. In this review, we survey epidemiological studies that leverage metabolomics and multi-omics to gain insight into disease mechanisms. We outline key practical, technological and analytical limitations while also highlighting recent successes in integrating these data. The use of multi-omics to infer reaction rates is discussed as a potential future direction for metabolomics research, as a means of identifying biomarkers as well as inferring causality. Furthermore, we highlight established analysis approaches as well as simulation-based methods currently used in single- and multi-cell levels in systems biology. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

  5. The effects of gliadin on urine metabolome in mice

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Zhang, Li; Frandsen, Henrik Lauritz

    Gliadin, a proline-rich protein of gluten, is thought to modulate the gut microbiota and affect the intestinal permeability and immune system. However, little is known about the long-term effects of gliadin on the host and microbial metabolism. To study this, we compared the urine metabolome of two...... groups of mice, which were on a high fat diet with and without gliadin, respectively, for 23 weeks. Using liquid chromatography mass-spectrometry (MS) followed by multivariate analyses we were able to show a clear separation of the two groups of mice based on their urine metabolome. Discriminating...... in the gliadin mice. Also, Maillard reaction products and β-oxidized tocopherols were observed in higher levels in the urine of gliadin mice, suggesting increased oxidative stress in the gliadin mice. Indisputably, gliadin affected the urine metabolome. However, the mechanisms behind the observed metabolite...

  6. Metabolic changes in serum metabolome in response to a meal.

    Science.gov (United States)

    Shrestha, Aahana; Müllner, Elisabeth; Poutanen, Kaisa; Mykkänen, Hannu; Moazzami, Ali A

    2017-03-01

    The change in serum metabolic response from fasting state to postprandial state provides novel insights into the impact of a single meal on human metabolism. Therefore, this study explored changes in serum metabolite profile after a single meal. Nineteen healthy postmenopausal women with normal glucose tolerance participated in the study. They received a meal consisting of refined wheat bread (50 g carbohydrates, 9 g protein, 4.2 g fat and 2.7 g dietary fibre), 40 g cucumber and 300 mL noncaloric orange drink. Blood samples were collected at fasting and five postprandial time points. Metabolic profile was measured by nuclear magnetic resonance and targeted liquid chromatography-mass spectrometry. Changes over time were assessed with multivariate models and ANOVA, with baseline as control. The metabolomic analyses demonstrated alterations in phospholipids, amino acids and their breakdown products, glycolytic products, acylcarnitines and ketone bodies after a single meal. More specifically, phosphatidylcholines, lysophosphatidylcholines and citrate displayed an overall declining pattern, while leucine, isoleucine, methionine and succinate increased initially but declined thereafter. A sharp decline in acylcarnitines and ketone bodies and increase in glycolytic products postprandially suggest a switch in the body's energy source from β-oxidation to glycolysis. Moreover, individuals with relatively high postprandial insulin responses generated a higher postprandial leucine responses compared to participants with lower insulin responses. The study demonstrated complex changes from catabolic to anabolic metabolism after a meal and indicated that the extent of postprandial responses is different between individuals with high and low insulin response.

  7. Reconstruction of food webs in biological soil crusts using metabolomics.

    Science.gov (United States)

    Baran, Richard; Brodie, Eoin L.; Mayberry-Lewis, Jazmine; Nunes Da Rocha, Ulisses; Bowen, Benjamin P.; Karaoz, Ulas; Cadillo-Quiroz, Hinsby; Garcia-Pichel, Ferran; Northen, Trent R.

    2015-04-01

    Biological soil crusts (BSCs) are communities of organisms inhabiting the upper layer of soil in arid environments. BSCs persist in a dessicated dormant state for extended periods of time and experience pulsed periods of activity facilitated by infrequent rainfall. Microcoleus vaginatus, a non-diazotrophic filamentous cyanobacterium, is the key primary producer in BSCs in the Colorado Plateau and is an early pioneer in colonizing arid environments. Over decades, BSCs proceed through developmental stages with increasing complexity of constituent microorganisms and macroscopic properties. Metabolic interactions among BSC microorganisms probably play a key role in determining the community dynamics and cycling of carbon and nitrogen. However, these metabolic interactions have not been studied systematically. Towards this goal, exometabolomic analysis was performed using liquid chromatography coupled to tandem mass spectrometry on biological soil crust pore water and spent media of key soil bacterial isolates. Comparison of spent vs. fresh media was used to determine uptake or release of metabolites by specific microbes. To link pore water experiments with isolate studies, metabolite extracts of authentic soil were used as supplements for isolate exometabolomic profiling. Our soil metabolomics methods detected hundreds of metabolites from soils including many novel compounds. Overall, Microcoleus vaginatus was found to release and utilize a broad range of metabolites. Many of these metabolites were also taken up by heterotrophs but there were surprisingly few metabolites uptaken by all isolates. This points to a competition for a small set of central metabolites and specialization of individual heterotrophs towards a diverse pool of available organic nutrients. Overall, these data suggest that understanding the substrate specialization of biological soil crust bacteria can help link community structure to nutrient cycling.

  8. Association between the metabolome and low bone mineral density in Taiwanese women determined by (1)H NMR spectroscopy.

    Science.gov (United States)

    You, Ying-Shu; Lin, Ching-Yu; Liang, Hao-Jan; Lee, Shen-Hung; Tsai, Keh-Sung; Chiou, Jeng-Min; Chen, Yen-Ching; Tsao, Chwen-Keng; Chen, Jen-Hau

    2014-01-01

    Osteoporosis is related to the alteration of specific circulating metabolites. However, previous studies on only a few metabolites inadequately explain the pathogenesis of this complex syndrome. To date, no study has related the metabolome to bone mineral density (BMD), which would provide an overview of metabolism status and may be useful in clinical practice. This cross-sectional study involved 601 healthy Taiwanese women aged 40 to 55 years recruited from MJ Health Management Institution between 2009 and 2010. Participants were classified according to high (2nd tertile plus 3rd tertile) and low (1st tertile) BMD groups. The plasma metabolome was evaluated by proton nuclear magnetic resonance spectroscopy ((1) H NMR). Principal components analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and logistic regression analysis were used to assess the association between the metabolome and BMD. The high and low BMD groups could be differentiated by PLS-DA but not PCA in postmenopausal women (Q(2)  = 0.05, ppermutation  = 0.04). Among postmenopausal women, elevated glutamine was significantly associated with low BMD (adjusted odds ratio [AOR] = 5.10); meanwhile, elevated lactate (AOR = 0.55), acetone (AOR = 0.51), lipids (AOR = 0.04), and very low-density lipoprotein (AOR = 0.49) protected against low BMD. To the best of our knowledge, this study is the first to identify a group of metabolites for characterizing low BMD in postmenopausal women using a (1) H NMR-based metabolomic approach. The metabolic profile may be useful for predicting the risk of osteoporosis in postmenopausal women at an early age. © 2014 American Society for Bone and Mineral Research.

  9. Untargeted metabolomics studies employing NMR and LC-MS reveal metabolic coupling between Nanoarcheum equitans and its archaeal host Ignicoccus hospitalis.

    Science.gov (United States)

    Hamerly, Timothy; Tripet, Brian P; Tigges, Michelle; Giannone, Richard J; Wurch, Louie; Hettich, Robert L; Podar, Mircea; Copié, Valerie; Bothner, Brian

    2015-08-01

    Interspecies interactions are the basis of microbial community formation and infectious diseases. Systems biology enables the construction of complex models describing such interactions, leading to a better understanding of disease states and communities. However, before interactions between complex organisms can be understood, metabolic and energetic implications of simpler real-world host-microbe systems must be worked out. To this effect, untargeted metabolomics experiments were conducted and integrated with proteomics data to characterize key molecular-level interactions between two hyperthermophilic microbial species, both of which have reduced genomes. Metabolic changes and transfer of metabolites between the archaea Ignicoccus hospitalis and Nanoarcheum equitans were investigated using integrated LC-MS and NMR metabolomics. The study of such a system is challenging, as no genetic tools are available, growth in the laboratory is challenging, and mechanisms by which they interact are unknown. Together with information about relative enzyme levels obtained from shotgun proteomics, the metabolomics data provided useful insights into metabolic pathways and cellular networks of I. hospitalis that are impacted by the presence of N. equitans , including arginine, isoleucine, and CTP biosynthesis. On the organismal level, the data indicate that N. equitans exploits metabolites generated by I. hospitalis to satisfy its own metabolic needs. This finding is based on N. equitans 's consumption of a significant fraction of the metabolite pool in I. hospitalis that cannot solely be attributed to increased biomass production for N. equitans . Combining LC-MS and NMR metabolomics datasets improved coverage of the metabolome and enhanced the identification and quantitation of cellular metabolites.

  10. Mass spectrometric based approaches in urine metabolomics and biomarker discovery.

    Science.gov (United States)

    Khamis, Mona M; Adamko, Darryl J; El-Aneed, Anas

    2017-03-01

    Urine metabolomics has recently emerged as a prominent field for the discovery of non-invasive biomarkers that can detect subtle metabolic discrepancies in response to a specific disease or therapeutic intervention. Urine, compared to other biofluids, is characterized by its ease of collection, richness in metabolites and its ability to reflect imbalances of all biochemical pathways within the body. Following urine collection for metabolomic analysis, samples must be immediately frozen to quench any biogenic and/or non-biogenic chemical reactions. According to the aim of the experiment; sample preparation can vary from simple procedures such as filtration to more specific extraction protocols such as liquid-liquid extraction. Due to the lack of comprehensive studies on urine metabolome stability, higher storage temperatures (i.e. 4°C) and repetitive freeze-thaw cycles should be avoided. To date, among all analytical techniques, mass spectrometry (MS) provides the best sensitivity, selectivity and identification capabilities to analyze the majority of the metabolite composition in the urine. Combined with the qualitative and quantitative capabilities of MS, and due to the continuous improvements in its related technologies (i.e. ultra high-performance liquid chromatography [UPLC] and hydrophilic interaction liquid chromatography [HILIC]), liquid chromatography (LC)-MS is unequivocally the most utilized and the most informative analytical tool employed in urine metabolomics. Furthermore, differential isotope tagging techniques has provided a solution to ion suppression from urine matrix thus allowing for quantitative analysis. In addition to LC-MS, other MS-based technologies have been utilized in urine metabolomics. These include direct injection (infusion)-MS, capillary electrophoresis-MS and gas chromatography-MS. In this article, the current progresses of different MS-based techniques in exploring the urine metabolome as well as the recent findings in providing

  11. Medicinal Plants: A Public Resource for Metabolomics and Hypothesis Development

    Directory of Open Access Journals (Sweden)

    Eve Syrkin Wurtele

    2012-11-01

    Full Text Available Specialized compounds from photosynthetic organisms serve as rich resources for drug development. From aspirin to atropine, plant-derived natural products have had a profound impact on human health. Technological advances provide new opportunities to access these natural products in a metabolic context. Here, we describe a database and platform for storing, visualizing and statistically analyzing metabolomics data from fourteen medicinal plant species. The metabolomes and associated transcriptomes (RNAseq for each plant species, gathered from up to twenty tissue/organ samples that have experienced varied growth conditions and developmental histories, were analyzed in parallel. Three case studies illustrate different ways that the data can be integrally used to generate testable hypotheses concerning the biochemistry, phylogeny and natural product diversity of medicinal plants. Deep metabolomics analysis of Camptotheca acuminata exemplifies how such data can be used to inform metabolic understanding of natural product chemical diversity and begin to formulate hypotheses about their biogenesis. Metabolomics data from Prunella vulgaris, a species that contains a wide range of antioxidant, antiviral, tumoricidal and anti-inflammatory constituents, provide a case study of obtaining biosystematic and developmental fingerprint information from metabolite accumulation data in a little studied species. Digitalis purpurea, well known as a source of cardiac glycosides, is used to illustrate how integrating metabolomics and transcriptomics data can lead to identification of candidate genes encoding biosynthetic enzymes in the cardiac glycoside pathway. Medicinal Plant Metabolomics Resource (MPM [1] provides a framework for generating experimentally testable hypotheses about the metabolic networks that lead to the generation of specialized compounds, identifying genes that control their biosynthesis and establishing a basis for modeling metabolism in less

  12. Metabolomic biosignature differentiates melancholic depressive patients from healthy controls.

    Science.gov (United States)

    Liu, Yashu; Yieh, Lynn; Yang, Tao; Drinkenburg, Wilhelmus; Peeters, Pieter; Steckler, Thomas; Narayan, Vaibhav A; Wittenberg, Gayle; Ye, Jieping

    2016-08-23

    Major depressive disorder (MDD) is a heterogeneous disease at the level of clinical symptoms, and this heterogeneity is likely reflected at the level of biology. Two clinical subtypes within MDD that have garnered interest are "melancholic depression" and "anxious depression". Metabolomics enables us to characterize hundreds of small molecules that comprise the metabolome, and recent work suggests the blood metabolome may be able to inform treatment decisions for MDD, however work is at an early stage. Here we examine a metabolomics data set to (1) test whether clinically homogenous MDD subtypes are also more biologically homogeneous, and hence more predictiable, (2) devise a robust machine learning framework that preserves biological meaning, and (3) describe the metabolomic biosignature for melancholic depression. With the proposed computational system we achieves around 80 % classification accuracy, sensitivity and specificity for melancholic depression, but only ~72 % for anxious depression or MDD, suggesting the blood metabolome contains more information about melancholic depression.. We develop an ensemble feature selection framework (EFSF) in which features are first clustered, and learning then takes place on the cluster centroids, retaining information about correlated features during the feature selection process rather than discarding them as most machine learning methods will do. Analysis of the most discriminative feature clusters revealed differences in metabolic classes such as amino acids and lipids as well as pathways studied extensively in MDD such as the activation of cortisol in chronic stress. We find the greater clinical homogeneity does indeed lead to better prediction based on biological measurements in the case of melancholic depression. Melancholic depression is shown to be associated with changes in amino acids, catecholamines, lipids, stress hormones, and immune-related metabolites. The proposed computational framework can be adapted

  13. Metabolomics of dates (Phoenix dactylifera) reveals a highly dynamic ripening process accounting for major variation in fruit composition.

    Science.gov (United States)

    Diboun, Ilhame; Mathew, Sweety; Al-Rayyashi, Maryam; Elrayess, Mohamed; Torres, Maria; Halama, Anna; Méret, Michaël; Mohney, Robert P; Karoly, Edward D; Malek, Joel; Suhre, Karsten

    2015-12-16

    Dates are tropical fruits with appreciable nutritional value. Previous attempts at global metabolic characterization of the date metabolome were constrained by small sample size and limited geographical sampling. In this study, two independent large cohorts of mature dates exhibiting substantial diversity in origin, varieties and fruit processing conditions were measured by metabolomics techniques in order to identify major determinants of the fruit metabolome. Multivariate analysis revealed a first principal component (PC1) significantly associated with the dates' countries of production. The availability of a smaller dataset featuring immature dates from different development stages served to build a model of the ripening process in dates, which helped reveal a strong ripening signature in PC1. Analysis revealed enrichment in the dry type of dates amongst fruits with early ripening profiles at one end of PC1 as oppose to an overrepresentation of the soft type of dates with late ripening profiles at the other end of PC1. Dry dates are typical to the North African region whilst soft dates are more popular in the Gulf region, which partly explains the observed association between PC1 and geography. Analysis of the loading values, expressing metabolite correlation levels with PC1, revealed enrichment patterns of a comprehensive range of metabolite classes along PC1. Three distinct metabolic phases corresponding to known stages of date ripening were observed: An early phase enriched in regulatory hormones, amines and polyamines, energy production, tannins, sucrose and anti-oxidant activity, a second phase with on-going phenylpropanoid secondary metabolism, gene expression and phospholipid metabolism and a late phase with marked sugar dehydration activity and degradation reactions leading to increased volatile synthesis. These data indicate the importance of date ripening as a main driver of variation in the date metabolome responsible for their diverse nutritional and

  14. Overview of the taxonomy and of the major secondary metabolites and their biological activities related to human health of the Laurencia complex (Ceramiales, Rhodophyta from Brazil

    Directory of Open Access Journals (Sweden)

    Mutue T. Fujii

    2011-04-01

    Full Text Available In Brazil, the Laurencia complex is represented by twenty taxa: Laurencia s.s. with twelve species, Palisada with four species (including Chondrophycus furcatus now that the proposal of its transference to Palisada is in process, and Osmundea and Yuzurua with two species each. The majority of the Brazilian species of the Laurencia complex have been phylogenetically analyzed by 54 rbcL sequences, including five other Rhodomelacean species as outgroups. The analysis showed that the Laurencia complex is monophyletic with high posterior probability value. The complex was separated into five clades, corresponding to the genera: Chondrophycus, Laurencia, Osmundea, Palisada, and Yuzurua. A bibliographical survey of the terpenoids produced by Brazilian species showed that only six species of Laurencia and five of Palisada (including C. furcatcus have been submitted to chemical analysis with 48 terpenoids (47 sesquiterpenes and one triterpene isolated. No diterpenes were found. Of the total, 23 sesquiterpenes belong to the bisabolane class and eighteen to the chamigrene type, whose biochemical precursor is bisabolane, two are derived from lauranes and four are triquinols. Despite the considerable number of known terpenes and their ecological and pharmacological importance, few experimental biological studies have been performed. In this review, only bioactivities related to human health were considered.

  15. Secondary Headaches

    Science.gov (United States)

    ... in the medical history or examination to suggest secondary headache. Headache can be caused by general medical conditions such as severe hypertension, or by conditions that affect the brain and ...

  16. Systematic analysis of the polyphenol metabolome using the Phenol-Explorer database.

    Science.gov (United States)

    Rothwell, Joseph A; Urpi-Sarda, Mireia; Boto-Ordoñez, Maria; Llorach, Rafael; Farran-Codina, Andreu; Barupal, Dinesh Kumar; Neveu, Vanessa; Manach, Claudine; Andres-Lacueva, Cristina; Scalbert, Augustin

    2016-01-01

    The Phenol-Explorer web database details 383 polyphenol metabolites identified in human and animal biofluids from 221 publications. Here, we exploit these data to characterize and visualize the polyphenol metabolome, the set of all metabolites derived from phenolic food components. Qualitative and quantitative data on 383 polyphenol metabolites as described in 424 human and animal intervention studies were systematically analyzed. Of these metabolites, 301 were identified without prior enzymatic hydrolysis of biofluids, and included glucuronide and sulfate esters, glycosides, aglycones, and O-methyl ethers. Around one-third of these compounds are also known as food constituents and corresponded to polyphenols absorbed without further metabolism. Many ring-cleavage metabolites formed by gut microbiota were noted, mostly derived from hydroxycinnamates, flavanols, and flavonols. Median maximum plasma concentrations (C(max)) of all human metabolites were 0.09 and 0.32 μM when consumed from foods or dietary supplements, respectively. Median time to reach maximum plasma concentration in humans (T(max)) was 2.18 h. These data show the complexity of the polyphenol metabolome and the need to take into account biotransformations to understand in vivo bioactivities and the role of dietary polyphenols in health and disease. © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics

    Directory of Open Access Journals (Sweden)

    Massobrio Marco

    2009-05-01

    Full Text Available Abstract The assessment of oocyte quality in human in vitro fertilization (IVF is getting increasing attention from embryologists. Oocyte selection and the identification of the best oocytes, in fact, would help to limit embryo overproduction and to improve the results of oocyte cryostorage programs. Follicular fluid (FF is easily available during oocyte pick-up and theorically represents an optimal source on non-invasive biochemical predictors of oocyte quality. Unfortunately, however, the studies aiming to find a good molecular predictor of oocyte quality in FF were not able to identify substances that could be used as reliable markers of oocyte competence to fertilization, embryo development and pregnancy. In the last years, a well definite trend toward passing from the research of single molecular markers to more complex techniques that study all metabolites of FF has been observed. The metabolomic approach is a powerful tool to study biochemical predictors of oocyte quality in FF, but its application in this area is still at the beginning. This review provides an overview of the current knowledge about the biochemical predictors of oocyte quality in FF, describing both the results coming from studies on single biochemical markers and those deriving from the most recent studies of metabolomics

  18. The Use of Functional Genomics in Conjunction with Metabolomics for Mycobacterium tuberculosis Research

    Science.gov (United States)

    Swanepoel, Conrad C.

    2014-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a fatal infectious disease, resulting in 1.4 million deaths globally per annum. Over the past three decades, genomic studies have been conducted in an attempt to elucidate the functionality of the genome of the pathogen. However, many aspects of this complex genome remain largely unexplored, as approaches like genomics, proteomics, and transcriptomics have failed to characterize them successfully. In turn, metabolomics, which is relatively new to the “omics” revolution, has shown great potential for investigating biological systems or their modifications. Furthermore, when these data are interpreted in combination with previously acquired genomics, proteomics and transcriptomics data, using what is termed a systems biology approach, a more holistic understanding of these systems can be achieved. In this review we discuss how metabolomics has contributed so far to characterizing TB, with emphasis on the resulting improved elucidation of M. tuberculosis in terms of (1) metabolism, (2) growth and replication, (3) pathogenicity, and (4) drug resistance, from the perspective of systems biology. PMID:24771957

  19. The Use of Functional Genomics in Conjunction with Metabolomics for Mycobacterium tuberculosis Research

    Directory of Open Access Journals (Sweden)

    Conrad C. Swanepoel

    2014-01-01

    Full Text Available Tuberculosis (TB, caused by Mycobacterium tuberculosis, is a fatal infectious disease, resulting in 1.4 million deaths globally per annum. Over the past three decades, genomic studies have been conducted in an attempt to elucidate the functionality of the genome of the pathogen. However, many aspects of this complex genome remain largely unexplored, as approaches like genomics, proteomics, and transcriptomics have failed to characterize them successfully. In turn, metabolomics, which is relatively new to the “omics” revolution, has shown great potential for investigating biological systems or their modifications. Furthermore, when these data are interpreted in combination with previously acquired genomics, proteomics and transcriptomics data, using what is termed a systems biology approach, a more holistic understanding of these systems can be achieved. In this review we discuss how metabolomics has contributed so far to characterizing TB, with emphasis on the resulting improved elucidation of M. tuberculosis in terms of (1 metabolism, (2 growth and replication, (3 pathogenicity, and (4 drug resistance, from the perspective of systems biology.

  20. Heavy metal tolerance in plants: Role of transcriptomics, proteomics, metabolomics and ionomics

    Directory of Open Access Journals (Sweden)

    Samiksha eSingh

    2016-02-01

    Full Text Available Heavy metal contamination of soil and water causing toxicity/stress has become one important constraint to crop productivity and quality. This situation has further worsened by the increasing population growth and inherent food demand. It have been reported in several studies that counterbalancing toxicity, due to heavy metal requires complex mechanisms at molecular, biochemical, physiological, cellular, tissue and whole plant level, which might manifest in terms of improved crop productivity. Recent advances in various disciplines of biological sciences such as metabolomics, transcriptomics, proteomics etc. have assisted in the characterization of metabolites, transcription factors, stress-inducible proteins involved in heavy metal tolerance, which in turn can be utilized for generating heavy metal tolerant crops. This review summarizes various tolerance strategies of plants under heavy metal toxicity, covering the role of metabolites (metabolomics, trace elements (ionomics, transcription factors (transcriptomics, various stress-inducible proteins (proteomics as well as the role of plant hormones. We also provide a glance at strategies adopted by metal accumulating plants also known as metallophytes.

  1. Comparing Wild American Grapes with Vitis vinifera: A Metabolomics Study of Grape Composition.

    Science.gov (United States)

    Narduzzi, Luca; Stanstrup, Jan; Mattivi, Fulvio

    2015-08-05

    We analyzed via untargeted UHPLC-ESI-Q-TOF-MS the metabolome of the berry tissues (skin, pulp, seeds) of some American Vitis species (Vitis cinerea, Vitis californica, Vitis arizonica), together with four interspecific hybrids, and seven Vitis vinifera cultivars, aiming to find differences in the metabolomes of the American Vitis sp. versus Vitis vinifera. Apart from the known differences, that is, more complex content of anthocyanins and stilbenoids in the American grapes, we observed higher procyanidin accumulation (tens to hundreds of times) in the vinifera skin and seeds in comparison to American berries, and we confirmed this result via phloroglucinolysis. In the American grapes considered, we did not detect the accumulation of pleasing aroma precursors (terpenoids, glycosides), whereas they are common in vinifera grapes. We also found accumulation of hydrolyzable tannins and their precursors in the skin of the wild American grapes, which has never been reported earlier in any of the species under investigation. Such information is needed to improve the design of new breeding programs, lowering the risk of retaining undesirable characteristics in the chemical phenotype of the offspring.

  2. Heavy Metal Tolerance in Plants: Role of Transcriptomics, Proteomics, Metabolomics, and Ionomics

    Science.gov (United States)

    Singh, Samiksha; Parihar, Parul; Singh, Rachana; Singh, Vijay P.; Prasad, Sheo M.

    2016-01-01

    Heavy metal contamination of soil and water causing toxicity/stress has become one important constraint to crop productivity and quality. This situation has further worsened by the increasing population growth and inherent food demand. It has been reported in several studies that counterbalancing toxicity due to heavy metal requires complex mechanisms at molecular, biochemical, physiological, cellular, tissue, and whole plant level, which might manifest in terms of improved crop productivity. Recent advances in various disciplines of biological sciences such as metabolomics, transcriptomics, proteomics, etc., have assisted in the characterization of metabolites, transcription factors, and stress-inducible proteins involved in heavy metal tolerance, which in turn can be utilized for generating heavy metal-tolerant crops. This review summarizes various tolerance strategies of plants under heavy metal toxicity covering the role of metabolites (metabolomics), trace elements (ionomics), transcription factors (transcriptomics), various stress-inducible proteins (proteomics) as well as the role of plant hormones. We also provide a glance of some strategies adopted by metal-accumulating plants, also known as “metallophytes.” PMID:26904030

  3. The potential biomarkers of drug addiction: proteomic and metabolomics challenges.

    Science.gov (United States)

    Wang, Lv; Wu, Ning; Zhao, Tai-Yun; Li, Jin

    2016-07-28

    Drug addiction places a significant burden on society and individuals. Proteomics and metabolomics approaches pave the road for searching potential biomarkers to assist the diagnosis and treatment. This review summarized putative drug addiction-related biomarkers in proteomics and metabolomics studies and discussed challenges and prospects in future studies. Alterations of several hundred proteins and metabolites were reported when exposure to abused drug, which enriched in energy metabolism, oxidative stress response, protein modification and degradation, synaptic function and neurotrasmission, etc. Hsp70, peroxiredoxin-6 and α- and β-synuclein, as well as n-methylserotonin and purine metabolites, were promising as potential biomarker for drug addiction.

  4. Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2014-11-21

    The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily stored and can be collected by simple, noninvasive techniques. Moreover, given its chemical complexity, urine is particularly rich in potential disease biomarkers. This makes it an ideal biofluid for detecting or monitoring disease processes. Among the metabolomic tools available for urine analysis, NMR spectroscopy has proven to be particularly well-suited, because the technique is highly reproducible and requires minimal sample handling. As it permits the identification and quantification of a wide range of compounds, independent of their chemical properties, NMR spectroscopy has been frequently used to detect or discover disease fingerprints and biomarkers in urine. Although protocols for NMR data acquisition and processing have been standardized, no consensus on protocols for urine sample selection, collection, storage and preparation in NMR-based metabolomic studies have been developed. This lack of consensus may be leading to spurious biomarkers being reported and may account for a general lack of reproducibility between laboratories. Here, we review a large number of published studies on NMR-based urine metabolic profiling with the aim of identifying key variables that may affect the results of metabolomics studies. From this survey, we identify a number of issues that require either standardization or careful accounting in experimental design and provide some recommendations for urine collection, sample preparation and data acquisition.

  5. Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review.

    Science.gov (United States)

    Emwas, Abdul-Hamid; Luchinat, Claudio; Turano, Paola; Tenori, Leonardo; Roy, Raja; Salek, Reza M; Ryan, Danielle; Merzaban, Jasmeen S; Kaddurah-Daouk, Rima; Zeri, Ana Carolina; Nagana Gowda, G A; Raftery, Daniel; Wang, Yulan; Brennan, Lorraine; Wishart, David S

    The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily stored and can be collected by simple, noninvasive techniques. Moreover, given its chemical complexity, urine is particularly rich in potential disease biomarkers. This makes it an ideal biofluid for detecting or monitoring disease processes. Among the metabolomic tools available for urine analysis, NMR spectroscopy has proven to be particularly well-suited, because the technique is highly reproducible and requires minimal sample handling. As it permits the identification and quantification of a wide range of compounds, independent of their chemical properties, NMR spectroscopy has been frequently used to detect or discover disease fingerprints and biomarkers in urine. Although protocols for NMR data acquisition and processing have been standardized, no consensus on protocols for urine sample selection, collection, storage and preparation in NMR-based metabolomic studies have been developed. This lack of consensus may be leading to spurious biomarkers being reported and may account for a general lack of reproducibility between laboratories. Here, we review a large number of published studies on NMR-based urine metabolic profiling with the aim of identifying key variables that may affect the results of metabolomics studies. From this survey, we identify a number of issues that require either standardization or careful accounting in experimental design and provide some recommendations for urine collection, sample preparation and data acquisition.

  6. Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review

    KAUST Repository

    Emwas, Abdul-Hamid M.; Luchinat, Claudio; Turano, Paola; Tenori, Leonardo; Roy, Raja; Salek, Reza M.; Ryan, Danielle; Merzaban, Jasmeen; Kaddurah-Daouk, Rima; Zeri, Ana Carolina; Nagana Gowda, G. A.; Raftery, Daniel; Wang, Yulan; Brennan, Lorraine; Wishart, David S.

    2014-01-01

    The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily stored and can be collected by simple, noninvasive techniques. Moreover, given its chemical complexity, urine is particularly rich in potential disease biomarkers. This makes it an ideal biofluid for detecting or monitoring disease processes. Among the metabolomic tools available for urine analysis, NMR spectroscopy has proven to be particularly well-suited, because the technique is highly reproducible and requires minimal sample handling. As it permits the identification and quantification of a wide range of compounds, independent of their chemical properties, NMR spectroscopy has been frequently used to detect or discover disease fingerprints and biomarkers in urine. Although protocols for NMR data acquisition and processing have been standardized, no consensus on protocols for urine sample selection, collection, storage and preparation in NMR-based metabolomic studies have been developed. This lack of consensus may be leading to spurious biomarkers being reported and may account for a general lack of reproducibility between laboratories. Here, we review a large number of published studies on NMR-based urine metabolic profiling with the aim of identifying key variables that may affect the results of metabolomics studies. From this survey, we identify a number of issues that require either standardization or careful accounting in experimental design and provide some recommendations for urine collection, sample preparation and data acquisition.

  7. Application of metabolomics to toxicology of drugs of abuse: A mini review of metabolomics approach to acute and chronic toxicity studies.

    Science.gov (United States)

    Zaitsu, Kei; Hayashi, Yumi; Kusano, Maiko; Tsuchihashi, Hitoshi; Ishii, Akira

    2016-02-01

    Metabolomics has been widely applied to toxicological fields, especially to elucidate the mechanism of action of toxicity. In this review, metabolomics application with focus on the studies of chronic and acute toxicities of drugs of abuse like stimulants, opioids and the recently-distributed designer drugs will be presented in addition to an outline of basic analytical techniques used in metabolomics. Limitation of metabolomics studies and future perspectives will be also provided. Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  8. Phytotoxic activity against Bromus tectorum for secondary metabolites of a seed-pathogenic Fusarium strain belonging to the F. tricinctum species complex.

    Science.gov (United States)

    Masi, Marco; Meyer, Susan; Pescitelli, Gennaro; Cimmino, Alessio; Clement, Suzette; Peacock, Beth; Evidente, Antonio

    2017-12-01

    The winter annual grass Bromus tectorum (cheatgrass) has become highly invasive in semiarid ecosystems of western North America. In these areas, a natural phenomenon, complete cheatgrass stand failure ('die-off'), is apparently caused by a complex interaction among soilborne fungal pathogens. Several Fusarium strains belonging to the Fusarium tricinctum species complex were isolated from these soils and found to be pathogenic on B. tectorum seeds. One of these strains was produced in cheatgrass seed culture to evaluate its ability to produce phytotoxins. Six metabolites were isolated and identified by spectroscopic methods (essentially 1D and 2D NMR and ESIMS) as acuminatopyrone (1), blumenol A (2), chlamydosporol (3), isochlamydosporol (4), ergosterol (5) and 4-hydroxybenzaldehyde (6). Upon testing against B. tectorum in a seedling bioassay, (6) the coleoptile and radicle length of cheatgrass seedlings were significantly reduced. Compounds 1 and 2 showed moderate activity, while 3-5 were not significantly different from the control.

  9. A LC-MS metabolomics approach to investigate the effect of raw apple intake in the rat plasma metabolome

    DEFF Research Database (Denmark)

    Rago, Daniela; Kristensen, Mette; Gürdeniz, Gözde

    2013-01-01

    Fruit and vegetable consumption has been associated with several health benefits; however the mechanisms are largely unknown at the biochemical level. Our research aims to investigate whether plasma metabolome profiling can reflect biological effects after feeding rats with raw apple by using...... an untargeted UPLC–ESI– TOF–MS based metabolomics approach in both positive and negative mode. Eighty young male rats were randomised into groups receiving daily 0, 5 or 10 g fresh apple slices, respectively, for 13 weeks. During weeks 3–6 some of the animals were receiving 4 mg/ml 1,2-dimethylhydrazine...

  10. The Development of Metabolomic Sampling Procedures for Pichia pastoris, and Baseline Metabolome Data

    Science.gov (United States)

    Tredwell, Gregory D.; Edwards-Jones, Bryn; Leak, David J.; Bundy, Jacob G.

    2011-01-01

    Metabolic profiling is increasingly being used to investigate a diverse range of biological questions. Due to the rapid turnover of intracellular metabolites it is important to have reliable, reproducible techniques for sampling and sample treatment. Through the use of non-targeted analytical techniques such as NMR and GC-MS we have performed a comprehensive quantitative investigation of sampling techniques for Pichia pastoris. It was clear that quenching metabolism using solutions based on the standard cold methanol protocol caused some metabolite losses from P. pastoris cells. However, these were at a low level, with the NMR results indicating metabolite increases in the quenching solution below 5% of their intracellular level for 75% of metabolites identified; while the GC-MS results suggest a slightly higher level with increases below 15% of their intracellular values. There were subtle differences between the four quenching solutions investigated but broadly, they all gave similar results. Total culture extraction of cells + broth using high cell density cultures typical of P. pastoris fermentations, was an efficient sampling technique for NMR analysis and provided a gold standard of intracellular metabolite levels; however, salts in the media affected the GC-MS analysis. Furthermore, there was no benefit in including an additional washing step in the quenching process, as the results were essentially identical to those obtained just by a single centrifugation step. We have identified the major high-concentration metabolites found in both the extra- and intracellular locations of P. pastoris cultures by NMR spectroscopy and GC-MS. This has provided us with a baseline metabolome for P. pastoris for future studies. The P. pastoris metabolome is significantly different from that of Saccharomyces cerevisiae, with the most notable difference being the production of high concentrations of arabitol by P. pastoris. PMID:21283710

  11. The Muscle Metabolome Differs between Healthy and Frail Older Adults

    NARCIS (Netherlands)

    Fazelzadeh, P.; Hangelbroek, R.W.J.; Tieland, M.; de Groot, C.P.G.M.; Verdijk, L.B.; van Loon, L.J.C.; Smilde, A.K.; Alves, R.D.A.M.; Vervoort, J.; Müller, M.; van Duynhoven, J.P.M.; Boekschoten, M.V.

    2016-01-01

    Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy

  12. Bagged K-means clustering of metabolome data

    NARCIS (Netherlands)

    Hageman, J. A.; van den Berg, R. A.; Westerhuis, J. A.; Hoefsloot, H. C. J.; Smilde, A. K.

    2006-01-01

    Clustering of metabolomics data can be hampered by noise originating from biological variation, physical sampling error and analytical error. Using data analysis methods which are not specially suited for dealing with noisy data will yield sub optimal solutions. Bootstrap aggregating (bagging) is a

  13. Application of Metabolomics to Study Effects of Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Paulina Samczuk

    2018-01-01

    Full Text Available Bariatric surgery was born in the 1950s at the University of Minnesota. From this time, it continues to evolve and, by the same token, gives new or better possibilities to treat not only obesity but also associated comorbidities. Metabolomics is also a relatively young science discipline, and similarly, it shows great potential for the comprehensive study of the dynamic alterations of the metabolome. It has been widely used in medicine, biology studies, biomarker discovery, and prognostic evaluations. Currently, several dozen metabolomics studies were performed to study the effects of bariatric surgery. LC-MS and NMR are the most frequently used techniques to study main effects of RYGB or SG. Research has yield many interesting results involving not only clinical parameters but also molecular modulations. Detected changes pertain to amino acid, lipids, carbohydrates, or gut microbiota alterations. It proves that including bariatric surgery to metabolic surgery is warranted. However, many molecular modulations after those procedures remain unexplained. Therefore, application of metabolomics to study this field seems to be a proper solution. New findings can suggest new directions of surgery technics modifications, contribute to broadening knowledge about obesity and diseases related to it, and perhaps develop nonsurgical methods of treatment in the future.

  14. CLOSTAT alters the serum metabolome of Holstein Steer Calves

    Science.gov (United States)

    Probiotics are gaining increased interest in calf feeding operations as some producers seek novel, non-antibiotic technologies to improve health and performance. Therefore, the objective of this study was to evaluate changes in serum metabolomic compounds of Holstein steer calves supplemented with C...

  15. Metabolomic Responses of Guard Cells and Mesophyll Cells to Bicarbonate

    Science.gov (United States)

    Misra, Biswapriya B.; de Armas, Evaldo; Tong, Zhaohui; Chen, Sixue

    2015-01-01

    Anthropogenic CO2 presently at 400 ppm is expected to reach 550 ppm in 2050, an increment expected to affect plant growth and productivity. Paired stomatal guard cells (GCs) are the gate-way for water, CO2, and pathogen, while mesophyll cells (MCs) represent the bulk cell-type of green leaves mainly for photosynthesis. We used the two different cell types, i.e., GCs and MCs from canola (Brassica napus) to profile metabolomic changes upon increased CO2 through supplementation with bicarbonate (HCO3 -). Two metabolomics platforms enabled quantification of 268 metabolites in a time-course study to reveal short-term responses. The HCO3 - responsive metabolomes of the cell types differed in their responsiveness. The MCs demonstrated increased amino acids, phenylpropanoids, redox metabolites, auxins and cytokinins, all of which were decreased in GCs in response to HCO3 -. In addition, the GCs showed differential increases of primary C-metabolites, N-metabolites (e.g., purines and amino acids), and defense-responsive pathways (e.g., alkaloids, phenolics, and flavonoids) as compared to the MCs, indicating differential C/N homeostasis in the cell-types. The metabolomics results provide insights into plant responses and crop productivity under future climatic changes where elevated CO2 conditions are to take center-stage. PMID:26641455

  16. Sample preparation procedures utilized in microbial metabolomics: An overview.

    Science.gov (United States)

    Patejko, Małgorzata; Jacyna, Julia; Markuszewski, Michał J

    2017-02-01

    Bacteria are remarkably diverse in terms of their size, structure and biochemical properties. Due to this fact, it is hard to develop a universal method for handling bacteria cultures during metabolomic analysis. The choice of suitable processing methods constitutes a key element in any analysis, because only appropriate selection of procedures may provide accurate results, leading to reliable conclusions. Because of that, every analytical experiment concerning bacteria requires individually and very carefully planned research methodology. Although every study varies in terms of sample preparation, there are few general steps to follow while planning experiment, like sampling, separation of cells from growth medium, stopping their metabolism and extraction. As a result of extraction, all intracellular metabolites should be washed out from cell environment. What is more, extraction method utilized cannot cause any chemical decomposition or degradation of the metabolome. Furthermore, chosen extraction method should correlate with analytical technique, so it will not disturb or prolong following sample preparation steps. For those reasons, we observe a need to summarize sample preparation procedures currently utilized in microbial metabolomic studies. In the presented overview, papers concerning analysis of extra- and intracellular metabolites, published over the last decade, have been discussed. Presented work gives some basic guidelines that might be useful while planning experiments in microbial metabolomics. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. High-resolution metabolomics of occupational exposure to trichloroethylene

    NARCIS (Netherlands)

    Walker, Douglas I; Uppal, Karan; Zhang, Luoping; Vermeulen, Roel; Smith, Martyn; Hu, Wei; Purdue, Mark P; Tang, Xiaojiang; Reiss, Boris; Kim, Sungkyoon; Li, Laiyu; Huang, Hanlin; Pennell, Kurt D; Jones, Dean P; Rothman, Nathaniel; Lan, Qing

    2016-01-01

    BACKGROUND: Occupational exposure to trichloroethylene (TCE) has been linked to adverse health outcomes including non-Hodgkin's lymphoma and kidney and liver cancer; however, TCE's mode of action for development of these diseases in humans is not well understood. METHODS: Non-targeted metabolomics

  18. Growth of Malignant Non-CNS Tumors Alters Brain Metabolome

    Science.gov (United States)

    Kovalchuk, Anna; Nersisyan, Lilit; Mandal, Rupasri; Wishart, David; Mancini, Maria; Sidransky, David; Kolb, Bryan; Kovalchuk, Olga

    2018-01-01

    Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as “tumor brain.” Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID:29515623

  19. Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis.

    NARCIS (Netherlands)

    Darghouth, D.; Koehl, B.; Heilier, J.F.; Madalinski, G.; Bovee, P.H.; Bosman, G.J.C.G.M.; Delaunay, J.; Junot, C.; Romeo, P.H.

    2011-01-01

    Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent cations, associated with mutations in the Rh-associated glycoprotein gene. We assessed the red blood cell metabolome of 4 patients with this

  20. Validation of Metabolomic, Diagnostic, and Prognostic Classifiers of Lung Cancer

    Science.gov (United States)

    2016-10-01

    information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this...Additionally, global metabolomic profiling will allow us to interrogate whether the military have unique exposures that may be related to lung cancer

  1. Effect of sleep deprivation on the human metabolome

    NARCIS (Netherlands)

    S.K. Davies (Sarah); J.E. Ang (Joo Ern); V.L. Revell (Victoria); B. Holmes (Ben); A. Mann (Anuska); F.P. Robertson (Francesca); N. Cui (Nanyi); B. Middleton (Benita); K. Ackermann (Katrin); M.H. Kayser (Manfred); A.E. Thumser (Alfred); P. Raynaud (Philippe); D.J. Skene (Debra)

    2014-01-01

    textabstractSleep restriction and circadian clock disruption are associated with metabolic disorders such as obesity, insulin resistance, and diabetes. The metabolic pathways involved in human sleep, however, have yet to be investigatedwith the use of a metabolomics approach. Here we have used

  2. Metabolomics: Insulin Resistance and Type 2 Diabetes Mellitus

    Science.gov (United States)

    Type 2 diabetes mellitus (T2DM) develops over many years, providing an opportunity to consider early prognostic tools that guide interventions to thwart disease. Advancements in analytical chemistry enable quantitation of hundreds of metabolites in biofluids and tissues (metabolomics), providing in...

  3. Genetic algorithm based two-mode clustering of metabolomics data

    NARCIS (Netherlands)

    Hageman, J.A.; van den Berg, R.A.; Westerhuis, J.A.; van der Werf, M.J.; Smilde, A.K.

    2008-01-01

    Metabolomics and other omics tools are generally characterized by large data sets with many variables obtained under different environmental conditions. Clustering methods and more specifically two-mode clustering methods are excellent tools for analyzing this type of data. Two-mode clustering

  4. Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach

    OpenAIRE

    Romero-Ibarguengoitia, Maria Elena; Vadillo-Ortega, Felipe; Caballero, Augusto Enrique; Ibarra-González, Isabel; Herrera-Rosas, Arturo; Serratos-Canales, María Fabiola; León-Hernández, Mireya; González-Chávez, Antonio; Mummidi, Srinivas; Duggirala, Ravindranath; López-Alvarenga, Juan Carlos

    2018-01-01

    Background: Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines woul...

  5. Women with preterm birth have a distinct cervicovaginal metabolome.

    Science.gov (United States)

    Ghartey, Jeny; Bastek, Jamie A; Brown, Amy G; Anglim, Laura; Elovitz, Michal A

    2015-06-01

    Metabolomics has the potential to reveal novel pathways involved in the pathogenesis of preterm birth (PTB). The objective of this study was to investigate whether the cervicovaginal (CV) metabolome was different in asymptomatic women destined to have a PTB compared with term birth. A nested case-control study was performed using CV fluid collected from a larger prospective cohort. The CV fluid was collected between 20-24 weeks (V1) and 24-28 weeks (V2). The metabolome was compared between women with a spontaneous PTB (n = 10) to women who delivered at term (n = 10). Samples were extracted and prepared for analysis using a standard extraction solvent method. Global biochemical profiles were determined using gas chromatography/mass spectrometry and ultra-performance liquid chromatography/tandem mass spectrometry. An ANOVA was used to detect differences in biochemical compounds between the groups. A false discovery rate was estimated to account for multiple comparisons. A total of 313 biochemicals were identified in CV fluid. Eighty-two biochemicals were different in the CV fluid at V1 in those destined to have a PTB compared with term birth, whereas 48 were different at V2. Amino acid, carbohydrate, and peptide metabolites were distinct between women with and without PTB. These data suggest that the CV space is metabolically active during pregnancy. Changes in the CV metabolome may be observed weeks, if not months, prior to any clinical symptoms. Understanding the CV metabolome may hold promise for unraveling the pathogenesis of PTB and may provide novel biomarkers to identify women most at risk. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. MetaFIND: A feature analysis tool for metabolomics data

    Directory of Open Access Journals (Sweden)

    Cunningham Pádraig

    2008-11-01

    Full Text Available Abstract Background Metabolomics, or metabonomics, refers to the quantitative analysis of all metabolites present within a biological sample and is generally carried out using NMR spectroscopy or Mass Spectrometry. Such analysis produces a set of peaks, or features, indicative of the metabolic composition of the sample and may be used as a basis for sample classification. Feature selection may be employed to improve classification accuracy or aid model explanation by establishing a subset of class discriminating features. Factors such as experimental noise, choice of technique and threshold selection may adversely affect the set of selected features retrieved. Furthermore, the high dimensionality and multi-collinearity inherent within metabolomics data may exacerbate discrepancies between the set of features retrieved and those required to provide a complete explanation of metabolite signatures. Given these issues, the latter in particular, we present the MetaFIND application for 'post-feature selection' correlation analysis of metabolomics data. Results In our evaluation we show how MetaFIND may be used to elucidate metabolite signatures from the set of features selected by diverse techniques over two metabolomics datasets. Importantly, we also show how MetaFIND may augment standard feature selection and aid the discovery of additional significant features, including those which represent novel class discriminating metabolites. MetaFIND also supports the discovery of higher level metabolite correlations. Conclusion Standard feature selection techniques may fail to capture the full set of relevant features in the case of high dimensional, multi-collinear metabolomics data. We show that the MetaFIND 'post-feature selection' analysis tool may aid metabolite signature elucidation, feature discovery and inference of metabolic correlations.

  7. Metabolomics-Driven Nutraceutical Evaluation of Diverse Green Tea Cultivars

    Science.gov (United States)

    Ida, Megumi; Kosaka, Reia; Miura, Daisuke; Wariishi, Hiroyuki; Maeda-Yamamoto, Mari; Nesumi, Atsushi; Saito, Takeshi; Kanda, Tomomasa; Yamada, Koji; Tachibana, Hirofumi

    2011-01-01

    Background Green tea has various health promotion effects. Although there are numerous tea cultivars, little is known about the differences in their nutraceutical properties. Metabolic profiling techniques can provide information on the relationship between the metabolome and factors such as phenotype or quality. Here, we performed metabolomic analyses to explore the relationship between the metabolome and health-promoting attributes (bioactivity) of diverse Japanese green tea cultivars. Methodology/Principal Findings We investigated the ability of leaf extracts from 43 Japanese green tea cultivars to inhibit thrombin-induced phosphorylation of myosin regulatory light chain (MRLC) in human umbilical vein endothelial cells (HUVECs). This thrombin-induced phosphorylation is a potential hallmark of vascular endothelial dysfunction. Among the tested cultivars, Cha Chuukanbohon Nou-6 (Nou-6) and Sunrouge (SR) strongly inhibited MRLC phosphorylation. To evaluate the bioactivity of green tea cultivars using a metabolomics approach, the metabolite profiles of all tea extracts were determined by high-performance liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analyses, principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA), revealed differences among green tea cultivars with respect to their ability to inhibit MRLC phosphorylation. In the SR cultivar, polyphenols were associated with its unique metabolic profile and its bioactivity. In addition, using partial least-squares (PLS) regression analysis, we succeeded in constructing a reliable bioactivity-prediction model to predict the inhibitory effect of tea cultivars based on their metabolome. This model was based on certain identified metabolites that were associated with bioactivity. When added to an extract from the non-bioactive cultivar Yabukita, several metabolites enriched in SR were able to transform the extract into a bioactive extract

  8. Comparison of Salt Tolerance in Soja Based on Metabolomics of Seedling Roots

    Directory of Open Access Journals (Sweden)

    Mingxia Li

    2017-06-01

    Full Text Available Soybean is an important economic crop that is continually threatened by abiotic stresses, especially salt stress. Wild soybean is an important germplasm resource for the breeding of cultivated soybean. The root system plays a very important role in plant salt tolerance. To explore the salt tolerance-related mechanisms among Soja, we have demonstrated the seedling roots' growth and metabolomics in wild soybean, semi-wild soybean, and cultivated soybean under two types of salt stress by using gas chromatography-mass spectrometry. We characterized 47 kinds of differential metabolites under neutral salt stress, and isoleucine, serine, l-allothreonine, glutamic acid, phenylalanine, asparagines, aspartic acid, pentadecanoic acid, lignoceric acid, oleic acid, galactose, tagatose, d-arabitol, dihydroxyacetone, 3-hydroxybutyric acid, and glucuronic acid increased significantly in the roots of wild soybean seedlings. However, these metabolites were suppressed in semi-wild and cultivated soybeans. Amino acid, fatty acid, sugars, and organic acid synthesis and the secondary metabolism of antioxidants increased significantly in the roots of wild soybean seedling. Under alkaline salt stress, wild soybean contained significantly higher amounts of proline, glutamic acid, aspartic acid, l-allothreonine, isoleucine, serine, alanine, arachidic acid, oleic acid, cis-gondoic acid, fumaric acid, l-malic acid, citric acid, malonic acid, gluconic acid, 5-methoxytryptamine, salicylic acid, and fluorene than semi-wild and cultivated soybeans. Our study demonstrated that carbon and nitrogen metabolism, and the tricarboxylic acid (TCA cycle and receiver operating characteristics (especially the metabolism of phenolic substances of the seedling roots were important to resisting salt stress and showed a regular decreasing trend from wild soybean to cultivated soybean. The metabolomics's changes were critical factors in the evolution of salt tolerance among Soja. This study

  9. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

    Energy Technology Data Exchange (ETDEWEB)

    Snijders, Antoine M.; Langley, Sasha A.; Kim, Young-Mo; Brislawn, Colin J.; Noecker, Cecilia; Zink, Erika M.; Fansler, Sarah J.; Casey, Cameron P.; Miller, Darla R.; Huang, Yurong; Karpen, Gary H.; Celniker, Susan E.; Brown, James B.; Borenstein, Elhanan; Jansson, Janet K.; Metz, Thomas O.; Mao, Jian-Hua

    2016-11-28

    Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut.We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts themicrobiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.

  10. TARGETED, LCMS-BASED METABOLOMICS FOR QUANTITATIVE MEASUREMENT OF NAD+ METABOLITES

    Directory of Open Access Journals (Sweden)

    Samuel AJ Trammell

    2013-01-01

    Full Text Available Nicotinamide adenine dinucleotide (NAD+ is a coenzyme for hydride transfer reactions and a substrate for sirtuins and other NAD+-consuming enzymes. The abundance of NAD+, NAD+ biosynthetic intermediates, and related nucleotides reflects the metabolic state of cells and tissues. High performance liquid chromatography (HPLC followed by ultraviolet-visible (UV-Vis spectroscopic analysis of NAD+ metabolites does not offer the specificity and sensitivity necessary for robust quantification of complex samples. Thus, we developed a targeted, quantitative assay of the NAD+ metabolome with the use of HPLC coupled to mass spectrometry. Here we discuss NAD+ metabolism as well as the technical challenges required for reliable quantification of the NAD+ metabolites. The new method incorporates new separations and improves upon a previously published method that suffered from the problem of ionization suppression for particular compounds.

  11. The Lipopolysaccharide-Induced Metabolome Signature in Arabidopsis thaliana Reveals Dynamic Reprogramming of Phytoalexin and Phytoanticipin Pathways.

    Directory of Open Access Journals (Sweden)

    Tarryn Finnegan

    Full Text Available Lipopolysaccharides (LPSs, as MAMP molecules, trigger the activation of signal transduction pathways involved in defence. Currently, plant metabolomics is providing new dimensions into understanding the intracellular adaptive responses to external stimuli. The effect of LPS on the metabolomes of Arabidopsis thaliana cells and leaf tissue was investigated over a 24 h period. Cellular metabolites and those secreted into the medium were extracted with methanol and liquid chromatography coupled to mass spectrometry was used for quantitative and qualitative analyses. Multivariate statistical data analyses were used to extract interpretable information from the generated multidimensional LC-MS data. The results show that LPS perception triggered differential changes in the metabolomes of cells and leaves, leading to variation in the biosynthesis of specialised secondary metabolites. Time-dependent changes in metabolite profiles were observed and biomarkers associated with the LPS-induced response were tentatively identified. These include the phytohormones salicylic acid and jasmonic acid, and also the associated methyl esters and sugar conjugates. The induced defensive state resulted in increases in indole-and other glucosinolates, indole derivatives, camalexin as well as cinnamic acid derivatives and other phenylpropanoids. These annotated metabolites indicate dynamic reprogramming of metabolic pathways that are functionally related towards creating an enhanced defensive capacity. The results reveal new insights into the mode of action of LPS as an activator of plant innate immunity, broadens knowledge about the defence metabolite pathways involved in Arabidopsis responses to LPS, and identifies specialised metabolites of functional importance that can be employed to enhance immunity against pathogen infection.

  12. Complexity, adaptations and variations in the secondary insemination system of female Dermanyssina mites (Acari: Anactinothrichida: Gamasida): the case of Afrocypholaelaps africana.

    Science.gov (United States)

    Di Palma, A; Seeman, O D; Alberti, G

    2017-07-01

    Gamasine mites, mainly of the taxon Dermanyssina, possess a secondarily evolved insemination system (sperm access system), of which there are two, generally recognized, structurally different types, the laelapid- and the phytoseiid-type. The ultrastructure of the female sperm access system in Afrocypholaelaps africana is described. It consists of paired insemination pores, opening between the bases of legs three and four, and paired cuticle-lined tubules that converge into a large, sack-like spermatheca, remarkably cuticle-lined as well. The entire spermatheca and part of the tubules are embedded in a peculiar syncytial tissue where numerous sperm cells are present. The general organization of this insemination system is of the laelapid-type. However, it presents striking structural differences, compared with the systems described in Varroa destructor and Hattena cometis, the other gamasine mites having a laelapid-type system studied ultrastructurally until now. The functional morphology, complexity and variations of the sperm access system in Dermanyssina are discussed and correlated with the evolutionary biology of the group.

  13. NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

    Science.gov (United States)

    Liu, Haiyan; Tayyari, Fariba; Edison, Arthur S; Su, Zhihua; Gu, Liwei

    2016-08-01

    A (1)H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using (1)H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D (1)H-(13)C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and α-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, α-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Advances in computational metabolomics and databases deepen the understanding of metabolisms.

    Science.gov (United States)

    Tsugawa, Hiroshi

    2018-01-29

    Mass spectrometry (MS)-based metabolomics is the popular platform for metabolome analyses. Computational techniques for the processing of MS raw data, for example, feature detection, peak alignment, and the exclusion of false-positive peaks, have been established. The next stage of untargeted metabolomics would be to decipher the mass fragmentation of small molecules for the global identification of human-, animal-, plant-, and microbiota metabolomes, resulting in a deeper understanding of metabolisms. This review is an update on the latest computational metabolomics including known/expected structure databases, chemical ontology classifications, and mass spectrometry cheminformatics for the interpretation of mass fragmentations and for the elucidation of unknown metabolites. The importance of metabolome 'databases' and 'repositories' is also discussed because novel biological discoveries are often attributable to the accumulation of data, to relational databases, and to their statistics. Lastly, a practical guide for metabolite annotations is presented as the summary of this review. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Impacts of endophyte infection of ryegrass on rhizosphere metabolome and microbial community

    DEFF Research Database (Denmark)

    Wakelin, S.; Harrison, Scott James; Mander, C.

    2015-01-01

    37, within a genetically uniform breeding line of perennial ryegrass (Lolium perenne cv. Samson 11104) on the rhizosphere metabolome and the composition of the fungal, bacterial, and Pseudomonas communities. There were strong differences in the rhizosphere metabolomes between infested and non......-infested ryegrass strains (P=0.06). These were attributed to shifts in various n-alkane hydrocarbon compounds. The endophyte-associated alteration in rhizosphere metabolome was linked to changes in the total bacterial (P

  16. Analysis of sequential hair segments reflects changes in the metabolome across the trimesters of pregnancy

    DEFF Research Database (Denmark)

    Delplancke, Thibaut D J; de Seymour, Jamie V; Tong, Chao

    2018-01-01

    The hair metabolome has been recognized as a valuable source of information in pregnancy research, as it provides stable metabolite information that could assist with studying biomarkers or metabolic mechanisms of pregnancy and its complications. We tested the hypothesis that hair segments could...... mellitus (p metabolome during pregnancy, as well as highlight the potential of the maternal hair metabolome to differentiate pregnancy complications from healthy pregnancies....

  17. Targeted metabolomics profiles are strongly correlated with nutritional patterns in women

    OpenAIRE

    Menni, Cristina; Zhai, Guangju; MacGregor, Alexander; Prehn, Cornelia; Römisch-Margl, Werner; Suhre, Karsten; Adamski, Jerzy; Cassidy, Aedin; Illig, Thomas; Spector, Tim D.; Valdes, Ana M.

    2013-01-01

    Nutrition plays an important role in human metabolism and health. Metabolomics is a promising tool for clinical, genetic and nutritional studies. A key question is to what extent metabolomic profiles reflect nutritional patterns in an epidemiological setting. We assessed the relationship between metabolomic profiles and nutritional intake in women from a large cross-sectional community study. Food frequency questionnaires (FFQs) were applied to 1,003 women from the TwinsUK cohort with targete...

  18. Linking diet to acne metabolomics, inflammation, and comedogenesis: an update

    Science.gov (United States)

    Melnik, Bodo C

    2015-01-01

    Acne vulgaris, an epidemic inflammatory skin disease of adolescence, is closely related to Western diet. Three major food classes that promote acne are: 1) hyperglycemic carbohydrates, 2) milk and dairy products, 3) saturated fats including trans-fats and deficient ω-3 polyunsaturated fatty acids (PUFAs). Diet-induced insulin/insulin-like growth factor (IGF-1)-signaling is superimposed on elevated IGF-1 levels during puberty, thereby unmasking the impact of aberrant nutrigenomics on sebaceous gland homeostasis. Western diet provides abundant branched-chain amino acids (BCAAs), glutamine, and palmitic acid. Insulin and IGF-1 suppress the activity of the metabolic transcription factor forkhead box O1 (FoxO1). Insulin, IGF-1, BCAAs, glutamine, and palmitate activate the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the key regulator of anabolism and lipogenesis. FoxO1 is a negative coregulator of androgen receptor, peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor-α, and sterol response element binding protein-1c (SREBP-1c), crucial transcription factors of sebaceous lipogenesis. mTORC1 stimulates the expression of PPARγ and SREBP-1c, promoting sebum production. SREBP-1c upregulates stearoyl-CoA- and Δ6-desaturase, enhancing the proportion of monounsaturated fatty acids in sebum triglycerides. Diet-mediated aberrations in sebum quantity (hyperseborrhea) and composition (dysseborrhea) promote Propionibacterium acnes overgrowth and biofilm formation with overexpression of the virulence factor triglyceride lipase increasing follicular levels of free palmitate and oleate. Free palmitate functions as a “danger signal,” stimulating toll-like receptor-2-mediated inflammasome activation with interleukin-1β release, Th17 differentiation, and interleukin-17-mediated keratinocyte proliferation. Oleate stimulates P. acnes adhesion, keratinocyte proliferation, and comedogenesis via interleukin-1α release. Thus, diet

  19. Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

    Science.gov (United States)

    Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

    2017-03-20

    As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

  20. Metabolomics reveals biotic and abiotic elicitor effects on the soft coral Sarcophyton ehrenbergi terpenoid content.

    Science.gov (United States)

    Farag, Mohamed A; Al-Mahdy, Dalia A; Meyer, Achim; Westphal, Hildegard; Wessjohann, Ludger A

    2017-04-05

    The effects of six biotic and abiotic elicitors, i.e. MeJA (methyl jasmonate), SA (salicylic acid), ZnCl 2 , glutathione and β-glucan BG (fungal elicitor), and wounding, on the secondary metabolite accumulation in the soft coral Sarcophyton ehrenbergi were assessed. Upon elicitation, metabolites were extracted and analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Except for MeJA, no differences in photosynthetic efficiency were observed after treatments, suggesting the absence of a remarkable stress on primary production. Chemometric analyses of UPLC-MS data showed clear segregation of SA and ZnCl 2 elicited samples at 24 and 48 h post elicitation. Levels of acetylated diterpene and sterol viz., sarcophytonolide I and cholesteryl acetate, was increased in ZnCl 2 and SA groups, respectively, suggesting an activation of specific acetyl transferases. Post elicitation, sarcophytonolide I level increased 132 and 17-folds at 48 h in 0.1 mM SA and 1 mM ZnCl 2 groups, respectively. Interestingly, decrease in sarcophine, a major diterpene was observed only in response to ZnCl 2 , whereas no change was observed in sesquiterpene content following treatments. To the best of our knowledge, this study provides the first documentation for elicitation effects on a soft corals secondary metabolome and suggests that SA could be applied to increase diterpenoid levels in corals.

  1. Effect of Genotype and Environment on Salvia miltiorrhiza Roots Using LC/MS-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Qi Zhao

    2016-03-01

    Full Text Available Salvia miltiorrhiza (S. miltiorrhiza Bunge is broadly used as herbal medicine for the clinical treatments of cardiovascular and cerebrovascular diseases. Despite its commercial and medicinal values, few systematic studies on the metabolome of S. miltiorrhiza roots have been carried out so far. We systematically described the metabolic profiles of S. miltiorrhiza using high pressure liquid chromatography mass spectrometry (LC/MS in conjunction with multivariate statistical analyses, aimed at monitoring their biological variations of secondary metabolites related to three locations and four S. miltiorrhiza genotypes. A total of 40 bioactive constituents were putatively annotated in S. miltiorrhiza root samples. This study found that both the same S. miltiorrhiza genotype growing at three different locations and four S. miltiorrhiza genotypes growing at the same location had significant metabonomic differences identified by the principal component analysis (PCA approach. By using orthogonal projection to latent structure with discriminant analysis (OPLS-DA, 16 and 14 secondary metabolites can be used as potential location-specific and genotype-specific markers in S. miltiorrhiza, respectively. The specificity of LC/MS profiles offered a powerful tool to discriminate S. miltiorrhiza samples according to genotypes or locations.

  2. Metabolomics as a Tool to Investigate Abiotic Stress Tolerance in Plants

    Directory of Open Access Journals (Sweden)

    Aurelio Gómez-Cadenas

    2013-03-01

    Full Text Available Metabolites reflect the integration of gene expression, protein interaction and other different regulatory processes and are therefore closer to the phenotype than mRNA transcripts or proteins alone. Amongst all –omics technologies, metabolomics is the most transversal and can be applied to different organisms with little or no modifications. It has been successfully applied to the study of molecular phenotypes of plants in response to abiotic stress in order to find particular patterns associated to stress tolerance. These studies have highlighted the essential involvement of primary metabolites: sugars, amino acids and Krebs cycle intermediates as direct markers of photosynthetic dysfunction as well as effectors of osmotic readjustment. On the contrary, secondary metabolites are more specific of genera and species and respond to particular stress conditions as antioxidants, Reactive Oxygen Species (ROS scavengers, coenzymes, UV and excess radiation screen and also as regulatory molecules. In addition, the induction of secondary metabolites by several abiotic stress conditions could also be an effective mechanism of cross-protection against biotic threats, providing a link between abiotic and biotic stress responses. Moreover, the presence/absence and relative accumulation of certain metabolites along with gene expression data provides accurate markers (mQTL or MWAS for tolerant crop selection in breeding programs.

  3. Study of Leaf Metabolome Modifications Induced by UV-C Radiations in Representative Vitis, Cissus and Cannabis Species by LC-MS Based Metabolomics and Antioxidant Assays

    Directory of Open Access Journals (Sweden)

    Guillaume Marti

    2014-09-01

    Full Text Available UV-C radiation is known to induce metabolic modifications in plants, particularly to secondary metabolite biosynthesis. To assess these modifications from a global and untargeted perspective, the effects of the UV-C radiation of the leaves of three different model plant species, Cissus antarctica Vent. (Vitaceae, Vitis vinifera L. (Vitaceae and Cannabis sativa L. (Cannabaceae, were evaluated by an LC-HRMS-based metabolomic approach. The approach enabled the detection of significant metabolite modifications in the three species studied. For all species, clear modifications of phenylpropanoid metabolism were detected that led to an increased level of stilbene derivatives. Interestingly, resveratrol and piceid levels were strongly induced by the UV-C treatment of C. antarctica leaves. In contrast, both flavonoids and stilbene polymers were upregulated in UV-C-treated Vitis leaves. In Cannabis, important changes in cinnamic acid amides and stilbene-related compounds were also detected. Overall, our results highlighted phytoalexin induction upon UV-C radiation. To evaluate whether UV-C stress radiation could enhance the biosynthesis of bioactive compounds, the antioxidant activity of extracts from control and UV-C-treated leaves was measured. The results showed increased antioxidant activity in UV-C-treated V. vinifera extracts.

  4. Metabolomic imaging of prostate cancer with magnetic resonance spectroscopy and mass spectrometry

    International Nuclear Information System (INIS)

    Spur, Eva-Margarete; Decelle, Emily A.; Cheng, Leo L.

    2013-01-01

    Metabolomic imaging of prostate cancer (PCa) aims to improve in vivo imaging capability so that PCa tumors can be localized noninvasively to guide biopsy and evaluated for aggressiveness prior to prostatectomy, as well as to assess and monitor PCa growth in patients with asymptomatic PCa newly diagnosed by biopsy. Metabolomics studies global variations of metabolites with which malignancy conditions can be evaluated by profiling the entire measurable metabolome, instead of focusing only on certain metabolites or isolated metabolic pathways. At present, PCa metabolomics is mainly studied by magnetic resonance spectroscopy (MRS) and mass spectrometry (MS). With MRS imaging, the anatomic image, obtained from magnetic resonance imaging, is mapped with values of disease condition-specific metabolomic profiles calculated from MRS of each location. For example, imaging of removed whole prostates has demonstrated the ability of metabolomic profiles to differentiate cancerous foci from histologically benign regions. Additionally, MS metabolomic imaging of prostate biopsies has uncovered metabolomic expression patterns that could discriminate between PCa and benign tissue. Metabolomic imaging offers the potential to identify cancer lesions to guide prostate biopsy and evaluate PCa aggressiveness noninvasively in vivo, or ex vivo to increase the power of pathology analysis. Potentially, this imaging ability could be applied not only to PCa, but also to different tissues and organs to evaluate other human malignancies and metabolic diseases. (orig.)

  5. Metabolomic imaging of prostate cancer with magnetic resonance spectroscopy and mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Spur, Eva-Margarete [Massachusetts General Hospital, Harvard Medical School, Department of Pathology, Boston, MA (United States); Massachusetts General Hospital, Harvard Medical School, Department of Radiology, Boston, MA (United States); Charite Universitaetsmedizin, Berlin (Germany); Decelle, Emily A.; Cheng, Leo L. [Massachusetts General Hospital, Harvard Medical School, Department of Pathology, Boston, MA (United States); Massachusetts General Hospital, Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2013-07-15

    Metabolomic imaging of prostate cancer (PCa) aims to improve in vivo imaging capability so that PCa tumors can be localized noninvasively to guide biopsy and evaluated for aggressiveness prior to prostatectomy, as well as to assess and monitor PCa growth in patients with asymptomatic PCa newly diagnosed by biopsy. Metabolomics studies global variations of metabolites with which malignancy conditions can be evaluated by profiling the entire measurable metabolome, instead of focusing only on certain metabolites or isolated metabolic pathways. At present, PCa metabolomics is mainly studied by magnetic resonance spectroscopy (MRS) and mass spectrometry (MS). With MRS imaging, the anatomic image, obtained from magnetic resonance imaging, is mapped with values of disease condition-specific metabolomic profiles calculated from MRS of each location. For example, imaging of removed whole prostates has demonstrated the ability of metabolomic profiles to differentiate cancerous foci from histologically benign regions. Additionally, MS metabolomic imaging of prostate biopsies has uncovered metabolomic expression patterns that could discriminate between PCa and benign tissue. Metabolomic imaging offers the potential to identify cancer lesions to guide prostate biopsy and evaluate PCa aggressiveness noninvasively in vivo, or ex vivo to increase the power of pathology analysis. Potentially, this imaging ability could be applied not only to PCa, but also to different tissues and organs to evaluate other human malignancies and metabolic diseases. (orig.)

  6. The Recent Developments in Sample Preparation for Mass Spectrometry-Based Metabolomics.

    Science.gov (United States)

    Gong, Zhi-Gang; Hu, Jing; Wu, Xi; Xu, Yong-Jiang

    2017-07-04

    Metabolomics is a critical member in systems biology. Although great progress has been achieved in metabolomics, there are still some problems in sample preparation, data processing and data interpretation. In this review, we intend to explore the roles, challenges and trends in sample preparation for mass spectrometry- (MS-) based metabolomics. The newly emerged sample preparation methods were also critically examined, including laser microdissection, in vivo sampling, dried blood spot, microwave, ultrasound and enzyme-assisted extraction, as well as microextraction techniques. Finally, we provide some conclusions and perspectives for sample preparation in MS-based metabolomics.

  7. Metabolomics enables precision medicine: "A White Paper, Community Perspective".

    Science.gov (United States)

    Beger, Richard D; Dunn, Warwick; Schmidt, Michael A; Gross, Steven S; Kirwan, Jennifer A; Cascante, Marta; Brennan, Lorraine; Wishart, David S; Oresic, Matej; Hankemeier, Thomas; Broadhurst, David I; Lane, Andrew N; Suhre, Karsten; Kastenmüller, Gabi; Sumner, Susan J; Thiele, Ines; Fiehn, Oliver; Kaddurah-Daouk, Rima

    Metabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or "-omics" level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person's metabolic state provides a close representation of that individual's overall health status. This metabolic state reflects what has been encoded by the genome, and modified by diet, environmental factors, and the gut microbiome. The metabolic profile provides a quantifiable readout of biochemical state from normal physiology to diverse pathophysiologies in a manner that is often not obvious from gene expression analyses. Today, clinicians capture only a very small part of the information contained in the metabolome, as they routinely measure only a narrow set of blood chemistry analytes to assess health and disease states. Examples include measuring glucose to monitor diabetes, measuring cholesterol and high density lipoprotein/low density lipoprotein ratio to assess cardiovascular health, BUN and creatinine for renal disorders, and measuring a panel of metabolites to diagnose potential inborn errors of metabolism in neonates. We anticipate that the narrow range of chemical analyses in current use by the medical community today will be replaced in the future by analyses that reveal a far more comprehensive metabolic signature. This signature is expected to describe global biochemical aberrations that reflect patterns of variance in states of wellness, more accurately describe specific diseases and their progression, and greatly aid in differential diagnosis. Such future metabolic signatures will: (1) provide predictive, prognostic, diagnostic, and surrogate markers of diverse disease states; (2) inform on underlying molecular mechanisms of diseases; (3) allow for sub-classification of diseases, and

  8. Secondary osteoporosis.

    Science.gov (United States)

    Gennari, C; Martini, G; Nuti, R

    1998-06-01

    Generalized osteoporosis currently represents a heterogeneous group of conditions with many different causes and pathogenetic mechanisms, that often are variably associated. The term "secondary" is applied to all patients with osteoporosis in whom the identifiable causal factors are other than menopause and aging. In this heterogeneous group of conditions, produced by many different pathogenetic mechanisms, a negative bone balance may be variably associated with low, normal or increased bone remodeling states. A consistent group of secondary osteoporosis is related to endocrinological or iatrogenic causes. Exogenous hypercortisolism may be considered an important risk factor for secondary osteoporosis in the community, and probably glucocorticoid-induced osteoporosis is the most common type of secondary osteoporosis. Supraphysiological doses of corticosteroids cause two abnormalities in bone metabolism: a relative increase in bone resorption, and a relative reduction in bone formation. Bone loss, mostly of trabecular bone, with its resultant fractures is the most incapacitating consequence of osteoporosis. The estimated incidence of fractures in patients prescribed corticosteroid is 30% to 50%. Osteoporosis is considered one of the potentially serious side effects of heparin therapy. The occurrence of heparin-induced osteoporosis appeared to be strictly related to the length of treatment (over 4-5 months), and the dosage (15,000 U or more daily), but the pathogenesis is poorly understood. It has been suggested that heparin could cause an increase in bone resorption by increasing the number of differentiated osteoclasts, and by enhancing the activity of individual osteoclasts. Hyperthyroidism is frequently associated with loss of trabecular and cortical bone; the enhanced bone turnover that develops in thyrotoxicosis is characterized by an increase in the number of osteoclasts and resorption sites, and an increase in the ratio of resorptive to formative bone

  9. A robust and versatile mass spectrometry platform for comprehensive assessment of the thiol redox metabolome

    Directory of Open Access Journals (Sweden)

    T.R. Sutton

    2018-06-01

    Full Text Available Several diseases are associated with perturbations in redox signaling and aberrant hydrogen sulfide metabolism, and numerous analytical methods exist for the measurement of the sulfur-containing species affected. However, uncertainty remains about their concentrations and speciation in cells/biofluids, perhaps in part due to differences in sample processing and detection principles. Using ultrahigh-performance liquid chromatography in combination with electrospray-ionization tandem mass spectrometry we here outline a specific and sensitive platform for the simultaneous measurement of 12 analytes, including total and free thiols, their disulfides and sulfide in complex biological matrices such as blood, saliva and urine. Total assay run time is < 10 min, enabling high-throughput analysis. Enhanced sensitivity and avoidance of artifactual thiol oxidation is achieved by taking advantage of the rapid reaction of sulfhydryl groups with N-ethylmaleimide. We optimized the analytical procedure for detection and separation conditions, linearity and precision including three stable isotope labelled standards. Its versatility for future more comprehensive coverage of the thiol redox metabolome was demonstrated by implementing additional analytes such as methanethiol, N-acetylcysteine, and coenzyme A. Apparent plasma sulfide concentrations were found to vary substantially with sample pretreatment and nature of the alkylating agent. In addition to protein binding in the form of mixed disulfides (S-thiolation a significant fraction of aminothiols and sulfide appears to be also non-covalently associated with proteins. Methodological accuracy was tested by comparing the plasma redox status of 10 healthy human volunteers to a well-established protocol optimized for reduced/oxidized glutathione. In a proof-of-principle study a deeper analysis of the thiol redox metabolome including free reduced/oxidized as well as bound thiols and sulfide was performed

  10. Hierarchical cluster analysis of technical replicates to identify interferents in untargeted mass spectrometry metabolomics.

    Science.gov (United States)

    Caesar, Lindsay K; Kvalheim, Olav M; Cech, Nadja B

    2018-08-27

    Mass spectral data sets often contain experimental artefacts, and data filtering prior to statistical analysis is crucial to extract reliable information. This is particularly true in untargeted metabolomics analyses, where the analyte(s) of interest are not known a priori. It is often assumed that chemical interferents (i.e. solvent contaminants such as plasticizers) are consistent across samples, and can be removed by background subtraction from blank injections. On the contrary, it is shown here that chemical contaminants may vary in abundance across each injection, potentially leading to their misidentification as relevant sample components. With this metabolomics study, we demonstrate the effectiveness of hierarchical cluster analysis (HCA) of replicate injections (technical replicates) as a methodology to identify chemical interferents and reduce their contaminating contribution to metabolomics models. Pools of metabolites with varying complexity were prepared from the botanical Angelica keiskei Koidzumi and spiked with known metabolites. Each set of pools was analyzed in triplicate and at multiple concentrations using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). Before filtering, HCA failed to cluster replicates in the data sets. To identify contaminant peaks, we developed a filtering process that evaluated the relative peak area variance of each variable within triplicate injections. These interferent peaks were found across all samples, but did not show consistent peak area from injection to injection, even when evaluating the same chemical sample. This filtering process identified 128 ions that appear to originate from the UPLC-MS system. Data sets collected for a high number of pools with comparatively simple chemical composition were highly influenced by these chemical interferents, as were samples that were analyzed at a low concentration. When chemical interferent masses were removed, technical replicates clustered in

  11. Metabolome analysis - mass spectrometry and microbial primary metabolites

    DEFF Research Database (Denmark)

    Højer-Pedersen, Jesper Juul

    2008-01-01

    , and therefore sample preparation is critical for metabolome analysis. The three major steps in sample preparation for metabolite analysis are sampling, extraction and concentration. These three steps were evaluated for the yeast Saccharomyces cerevisiae with primary focus on analysis of a large number...... of metabolites by one method. The results highlighted that there were discrepancies between different methods. To increase the throughput of cultivation, S. cerevisiae was grown in microtitier plates (MTPs), and the growth was found to be comparable with cultivations in shake flasks. The carbon source was either...... a theoretical metabolome. This showed that in combination with the specificity of MS up to 84% of the metabolites can be identified in a high-accuracy ESI-spectrum. A total of 66 metabolites were systematically analyzed by positive and negative ESI-MS/MS with the aim of initiating a spectral library for ESI...

  12. PROM and Labour Effects on Urinary Metabolome: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Alessandra Meloni

    2018-01-01

    Full Text Available Since pathologies and complications occurring during pregnancy and/or during labour may cause adverse outcomes for both newborns and mothers, there is a growing interest in metabolomic applications on pregnancy investigation. In fact, metabolomics has proved to be an efficient strategy for the description of several perinatal conditions. In particular, this study focuses on premature rupture of membranes (PROM in pregnancy at term. For this project, urine samples were collected at three different clinical conditions: out of labour before PROM occurrence (Ph1, out of labour with PROM (Ph2, and during labour with PROM (Ph3. GC-MS analysis, followed by univariate and multivariate statistical analysis, was able to discriminate among the different classes, highlighting the metabolites most involved in the discrimination.

  13. PROM and Labour Effects on Urinary Metabolome: A Pilot Study

    Science.gov (United States)

    Meloni, Alessandra; Palmas, Francesco; Mereu, Rossella; Deiana, Sara Francesca; Fais, Maria Francesca; Mussap, Michele; Ragusa, Antonio; Pintus, Roberta; Fanos, Vassilios; Melis, Gian Benedetto

    2018-01-01

    Since pathologies and complications occurring during pregnancy and/or during labour may cause adverse outcomes for both newborns and mothers, there is a growing interest in metabolomic applications on pregnancy investigation. In fact, metabolomics has proved to be an efficient strategy for the description of several perinatal conditions. In particular, this study focuses on premature rupture of membranes (PROM) in pregnancy at term. For this project, urine samples were collected at three different clinical conditions: out of labour before PROM occurrence (Ph1), out of labour with PROM (Ph2), and during labour with PROM (Ph3). GC-MS analysis, followed by univariate and multivariate statistical analysis, was able to discriminate among the different classes, highlighting the metabolites most involved in the discrimination. PMID:29511388

  14. Computational Approaches for Integrative Analysis of the Metabolome and Microbiome

    Directory of Open Access Journals (Sweden)

    Jasmine Chong

    2017-11-01

    Full Text Available The study of the microbiome, the totality of all microbes inhabiting the host or an environmental niche, has experienced exponential growth over the past few years. The microbiome contributes functional genes and metabolites, and is an important factor for maintaining health. In this context, metabolomics is increasingly applied to complement sequencing-based approaches (marker genes or shotgun metagenomics to enable resolution of microbiome-conferred functionalities associated with health. However, analyzing the resulting multi-omics data remains a significant challenge in current microbiome studies. In this review, we provide an overview of different computational approaches that have been used in recent years for integrative analysis of metabolome and microbiome data, ranging from statistical correlation analysis to metabolic network-based modeling approaches. Throughout the process, we strive to present a unified conceptual framework for multi-omics integration and interpretation, as well as point out potential future directions.

  15. Secondary osteoporosis.

    Science.gov (United States)

    Boyle, I T

    1993-10-01

    Osteoporosis with attendant increased fracture risk is a common complication of many other diseases. Indeed, almost all chronic diseases make some impact on life-style, usually by restricting physical activity and hence reducing the anabolic effect of exercise and gravitational strains on the skeleton. Restricted appetite and modified gastrointestinal tract function is another commonplace finding that has an impact on bone nutrition and synthesis, as on other systems. Sex hormone status is of particular importance for the maintenance of the normal skeleton, and the postmenopausal woman is at particular risk for most causes of secondary osteoporosis. In dealing with secondary osteoporosis in the hypo-oestrogenic woman, the question of giving hormone replacement therapy in addition to other disease-specific therapy should always be considered, as, for example, in a young amenorrhoeic woman with Crohn's disease. Similarly, in hypogonadal men the administration of testosterone is useful for bone conservation. The wider availability of bone densitometry ought to make us more aware of the presence of osteoporosis in the many disease states discussed above. This is particularly important as the life span of such patients is now increased by improved management of the underlying disease process in many instances. Even in steroid-induced osteoporosis--one of the commonest and most severe forms of osteoporosis--we now have some effective therapy in the form of the bisphosphonates and other anti-bone-resorbing drug classes. The possibility of prophylaxis against secondary osteoporosis has therefore become a possibility, although the very long-term effects of such drug regimens are still unknown. In some situations, such as thyrotoxicosis, Cushing's syndrome and immobilization, spontaneous resolution of at least part of the osteoporosis is possible after cure of the underlying problem. The shorter the existence of the basic problem, the more successful the restoration of the

  16. Media and growth conditions for induction of secondary metabolite production

    DEFF Research Database (Denmark)

    Frisvad, Jens Christian

    2012-01-01

    -defined media are suited for biochemical studies, but in order to get chemical diversity expressed in filamentous fungi, sources rich in amino acids, vitamins, and trace metals have to be added, such as yeast extract and oatmeal. A battery of solid agar media is recommended for exploration of chemical diversity...... as agar plug samples are easily analyzed to get an optimal representation of the qualitative secondary metabolome. Standard incubation for a week at 25°C in darkness is recommended, but optimal conditions have to be modified depending on the ecology and physiology of different filamentous fungi....

  17. Examining Practice in Secondary Visual Arts Education

    Science.gov (United States)

    Mitchell, Donna Mathewson

    2015-01-01

    Teaching in secondary visual arts classrooms is complex and challenging work. While it is implicated in much research, the complexity of the lived experience of secondary visual arts teaching has rarely been the subject of sustained and synthesized research. In this paper, the potential of practice as a concept to examine and represent secondary…

  18. Metabolomic biomarkers in serum and urine in women with preeclampsia

    OpenAIRE

    Austdal, Marie; Skråstad, Ragnhild; Gundersen, Astrid; Austgulen, Rigmor; Iversen, Ann-Charlotte; Bathen, Tone Frost

    2014-01-01

    Objective To explore the potential of magnetic resonance (MR) metabolomics for study of preeclampsia, for improved phenotyping and elucidating potential clues to etiology and pathogenesis. Methods Urine and serum samples from pregnant women with preeclampsia (n = 10), normal pregnancies (n = 10) and non-pregnant women (n = 10) matched by age and gestational age were analyzed with MR spectroscopy and subjected to multivariate analysis. Metabolites were then quantified and compared ...

  19. NMR metabolomics for assessment of exercise effects with mouse biofluids

    Energy Technology Data Exchange (ETDEWEB)

    Le Moyec, Laurence; Mille-Hamard, Laurence; Breuneval, Carole; Petot, Helene; Billat, Veronique L. [Universite Evry Val d' Essonne, UBIAE INSERM U902, Evry Cedex (France); Triba, Mohamed N. [Universite Paris 13, CSPBAT UMR 7244, Bobigny (France)

    2012-08-15

    Exercise modulates the metabolome in urine or blood as demonstrated previously for humans and animal models. Using nuclear magnetic resonance (NMR) metabolomics, the present study compares the metabolic consequences of an exhaustive exercise at peak velocity (Vp) and at critical velocity (Vc) on mice. Since small-volume samples (blood and urine) were collected, dilution was necessary to acquire NMR spectra. Consequently, specific processing methods were applied before statistical analysis. According to the type of exercise (control group, Vp group and Vc group), 26 male mice were divided into three groups. Mice were sacrificed 2 h after the end of exercise, and urine and blood samples were drawn from each mouse. Proton NMR spectra were acquired with urine and deproteinized blood. The NMR data were aligned with the icoshift method and normalised using the probabilistic quotient method. Finally, data were analysed with the orthogonal projection of latent-structure analysis. The spectra obtained with deproteinized blood can neither discriminate the control mice from exercised mice nor discriminate according to the duration of the exercise. With urine samples, a significant statistical model can be estimated when comparing the control mice to both groups, Vc and Vp. The best model is obtained according to the exercise duration with all mice. Taking into account the spectral regions having the highest correlations, the discriminant metabolites are allantoin, inosine and branched-chain amino acids. In conclusion, metabolomic profiles assessed with NMR are highly dependent on the exercise. These results show that urine samples are more informative than blood samples and that the duration of the exercise is a more important parameter to influence the metabolomic status than the exercise velocity. (orig.)

  20. Metabolomics to unveil and understand phenotypic diversity between pathogen populations.

    Directory of Open Access Journals (Sweden)

    Ruben t'Kindt

    Full Text Available Leishmaniasis is a debilitating disease caused by the parasite Leishmania. There is extensive clinical polymorphism, including variable responsiveness to treatment. We study Leishmania donovani parasites isolated from visceral leishmaniasis patients in Nepal that responded differently to antimonial treatment due to differing intrinsic drug sensitivity of the parasites. Here, we present a proof-of-principle study in which we applied a metabolomics pipeline specifically developed for L. donovani to characterize the global metabolic differences between antimonial-sensitive and antimonial-resistant L. donovani isolates. Clones of drug-sensitive and drug-resistant parasite isolates from clinical samples were cultured in vitro and harvested for metabolomics analysis. The relative abundance of 340 metabolites was determined by ZIC-HILIC chromatography coupled to LTQ-Orbitrap mass spectrometry. Our measurements cover approximately 20% of the predicted core metabolome of Leishmania and additionally detected a large number of lipids. Drug-sensitive and drug-resistant parasites showed distinct metabolic profiles, and unsupervised clustering and principal component analysis clearly distinguished the two phenotypes. For 100 metabolites, the detected intensity differed more than three-fold between the 2 phenotypes. Many of these were in specific areas of lipid metabolism, suggesting that the membrane composition of the drug-resistant parasites is extensively modified. Untargeted metabolomics has been applied on clinical Leishmania isolates to uncover major metabolic differences between drug-sensitive and drug-resistant isolates. The identified major differences provide novel insights into the mechanisms involved in resistance to antimonial drugs, and facilitate investigations using targeted approaches to unravel the key changes mediating drug resistance.

  1. An untargeted metabolomic assessment of cocoa beans during fermentation

    OpenAIRE

    Mayorga Gross, Ana Lucía; Quirós Guerrero, Luis Manuel; Fourny, G.; Vaillant Barka, Fabrice

    2016-01-01

    Fermentation is a critical step in the processing of high quality cocoa; however, the biochemistry behind is still not well understood at a molecular level. In this research, using a non-targeted approach, the main metabolomic changes that occur throughout the fermentation process were explored. Genetically undefined cocoa varieties from Trinidad and Tobago (n = 3), Costa Rica (n = 1) and one clone IMC-67 (n = 3) were subjected to spontaneous fermentation using farm-based and pilot plant cont...

  2. A Combined Metabolomic and Proteomic Analysis of Gestational Diabetes Mellitus

    OpenAIRE

    Hajduk, Joanna; Klupczynska, Agnieszka; Dereziński, Paweł; Matysiak, Jan; Kokot, Piotr; Nowak, Dorota; Gajęcka, Marzena; Nowak-Markwitz, Ewa; Kokot, Zenon

    2015-01-01

    The aim of this pilot study was to apply a novel combined metabolomic and proteomic approach in analysis of gestational diabetes mellitus. The investigation was performed with plasma samples derived from pregnant women with diagnosed gestational diabetes mellitus (n = 18) and a matched control group (n = 13). The mass spectrometry-based analyses allowed to determine 42 free amino acids and low molecular-weight peptide profiles. Different expressions of several peptides and altered amino acid ...

  3. Identifying biomarkers for asthma diagnosis using targeted metabolomics approaches.

    Science.gov (United States)

    Checkley, William; Deza, Maria P; Klawitter, Jost; Romero, Karina M; Klawitter, Jelena; Pollard, Suzanne L; Wise, Robert A; Christians, Uwe; Hansel, Nadia N

    2016-12-01

    The diagnosis of asthma in children is challenging and relies on a combination of clinical factors and biomarkers including methacholine challenge, lung function, bronchodilator responsiveness, and presence of airway inflammation. No single test is diagnostic. We sought to identify a pattern of inflammatory biomarkers that was unique to asthma using a targeted metabolomics approach combined with data science methods. We conducted a nested case-control study of 100 children living in a peri-urban community in Lima, Peru. We defined cases as children with current asthma, and controls as children with no prior history of asthma and normal lung function. We further categorized enrollment following a factorial design to enroll equal numbers of children as either overweight or not. We obtained a fasting venous blood sample to characterize a comprehensive panel of targeted markers using a metabolomics approach based on high performance liquid chromatography-mass spectrometry. A statistical comparison of targeted metabolites between children with asthma (n = 50) and healthy controls (n = 49) revealed distinct patterns in relative concentrations of several metabolites: children with asthma had approximately 40-50% lower relative concentrations of ascorbic acid, 2-isopropylmalic acid, shikimate-3-phosphate, and 6-phospho-d-gluconate when compared to children without asthma, and 70% lower relative concentrations of reduced glutathione (all p  13 077 normalized counts/second and betaine ≤ 16 47 121 normalized counts/second). By using a metabolomics approach applied to serum, we were able to discriminate between children with and without asthma by revealing different metabolic patterns. These results suggest that serum metabolomics may represent a diagnostic tool for asthma and may be helpful for distinguishing asthma phenotypes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. What Have Metabolomics Approaches Taught Us About Type 2 Diabetes?

    DEFF Research Database (Denmark)

    Gonzalez-Franquesa, Alba; Burkart, Alison M; Isganaitis, Elvira

    2016-01-01

    Type 2 diabetes (T2D) is increasing worldwide, making identification of biomarkers for detection, staging, and effective prevention strategies an especially critical scientific and medical goal. Fortunately, advances in metabolomics techniques, together with improvements in bioinformatics....... Conversely, tricarboxylic acid cycle intermediates, betaine, and other metabolites decrease. Future studies will be required to fully integrate these and other findings into our understanding of diabetes pathophysiology and to identify biomarkers of disease risk, stage, and responsiveness to specific...

  5. Diagnosis of acute and chronic enteric fever using metabolomics

    OpenAIRE

    Näsström, Elin

    2017-01-01

    Enteric (or typhoid) fever is a systemic infection mainly caused by Salmonella Typhi and Salmonella Paratyphi A. The disease is common in areas with poor water quality and insufficient sanitation. Humans are the only reservoir for transmission of the disease. The presence of asymptomatic chronic carriers is a complicating factor for the transmission. There are major limitations regarding the current diagnostic methods both for acute infection and chronic carriage. Metabolomics is a methodolog...

  6. Metabolome of human gut microbiome is predictive of host dysbiosis.

    Science.gov (United States)

    Larsen, Peter E; Dai, Yang

    2015-01-01

    Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome's interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome. Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome-host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.

  7. NMR-based metabolomics of mammalian cell and tissue cultures

    International Nuclear Information System (INIS)

    Aranibar, Nelly; Borys, Michael; Mackin, Nancy A.; Ly, Van; Abu-Absi, Nicholas; Abu-Absi, Susan; Niemitz, Matthias; Schilling, Bernhard; Li, Zheng Jian; Brock, Barry; Russell, Reb J.; Tymiak, Adrienne; Reily, Michael D.

    2011-01-01

    NMR spectroscopy was used to evaluate growth media and the cellular metabolome in two systems of interest to biomedical research. The first of these was a Chinese hamster ovary cell line engineered to express a recombinant protein. Here, NMR spectroscopy and a quantum mechanical total line shape analysis were utilized to quantify 30 metabolites such as amino acids, Krebs cycle intermediates, activated sugars, cofactors, and others in both media and cell extracts. The impact of bioreactor scale and addition of anti-apoptotic agents to the media on the extracellular and intracellular metabolome indicated changes in metabolic pathways of energy utilization. These results shed light into culture parameters that can be manipulated to optimize growth and protein production. Second, metabolomic analysis was performed on the superfusion media in a common model used for drug metabolism and toxicology studies, in vitro liver slices. In this study, it is demonstrated that two of the 48 standard media components, choline and histidine are depleted at a faster rate than many other nutrients. Augmenting the starting media with extra choline and histidine improves the long-term liver slice viability as measured by higher tissues levels of lactate dehydrogenase (LDH), glutathione and ATP, as well as lower LDH levels in the media at time points out to 94 h after initiation of incubation. In both models, media components and cellular metabolites are measured over time and correlated with currently accepted endpoint measures.

  8. Impact of red meat consumption on the metabolome of rats.

    Science.gov (United States)

    Jakobsen, Louise M A; Yde, Christian C; Van Hecke, Thomas; Jessen, Randi; Young, Jette F; De Smet, Stefaan; Bertram, Hanne Christine

    2017-03-01

    The scope of the present study was to investigate the effects of red versus white meat intake on the metabolome of rats. Twenty-four male Sprague-Dawley rats were randomly assigned to 15 days of ad libitum feeding of one of four experimental diets: (i) lean chicken, (ii) chicken with lard, (iii) lean beef, and (iv) beef with lard. Urine, feces, plasma, and colon tissue samples were analyzed using 1 H NMR-based metabolomics and real-time PCR was performed on colon tissue to examine the expression of specific genes. Urinary excretion of acetate and anserine was higher after chicken intake, while carnosine, fumarate, and trimethylamine N-oxide excretion were higher after beef intake. In colon tissue, higher choline levels and lower lipid levels were found after intake of chicken compared to beef. Expression of the apc gene was higher in response to the lean chicken and beef with lard diets. Correlation analysis revealed that intestinal apc gene expression was correlated with fecal lactate content (R 2 = 0.65). This study is the first to identify specific differences in the metabolome related to the intake of red and white meat. These differences may reflect perturbations in endogenous metabolism that can be linked to the proposed harmful effects associated with intake of red meat. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Nutritional impact on the plasma metabolome of rats.

    Science.gov (United States)

    Mellert, W; Kapp, M; Strauss, V; Wiemer, J; Kamp, H; Walk, T; Looser, R; Prokoudine, A; Fabian, E; Krennrich, G; Herold, M; van Ravenzwaay, B

    2011-11-30

    Metabolite profiling (metabolomics) elucidates changes in biochemical pathways under various conditions, e.g., different nutrition scenarios or compound administration. BASF and metanomics have obtained plasma metabolic profiles of approximately 500 compounds (agrochemicals, chemicals and pharmaceuticals) from 28-day rat studies. With these profiles the establishment of a database (MetaMap(®)Tox) containing specific metabolic patterns associated with many toxicological modes of action was achieved. To evaluate confounding factors influencing metabolome patterns, the effect of fasting vs. non-fasting prior to blood sampling, the influence of high caloric diet and caloric restriction as well as the administration of corn oil and olive oil was studied for its influence on the metabolome. All mentioned treatments had distinct effects: triacylglycerol, phospholipids and their degradation product levels (fatty acids, glycerol, lysophosphatidylcholine) were often altered depending on the nutritional status. Also some amino acid and related compounds were changed. Some metabolites derived from food (e.g. alpha-tocopherol, ascorbic acid, beta-sitosterol, campesterol) were biomarkers related to food consumption, whereas others indicated a changed energy metabolism (e.g. hydroxybutyrate, pyruvate). Strikingly, there was a profound difference in the metabolite responses to diet restriction in male and female rats. Consequently, when evaluating the metabolic profile of a compound, the effect of nutritional status should be taken into account. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. The Time Is Right to Focus on Model Organism Metabolomes

    Directory of Open Access Journals (Sweden)

    Arthur S. Edison

    2016-02-01

    Full Text Available Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research.

  11. A Combined Metabolomic and Proteomic Analysis of Gestational Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Joanna Hajduk

    2015-12-01

    Full Text Available The aim of this pilot study was to apply a novel combined metabolomic and proteomic approach in analysis of gestational diabetes mellitus. The investigation was performed with plasma samples derived from pregnant women with diagnosed gestational diabetes mellitus (n = 18 and a matched control group (n = 13. The mass spectrometry-based analyses allowed to determine 42 free amino acids and low molecular-weight peptide profiles. Different expressions of several peptides and altered amino acid profiles were observed in the analyzed groups. The combination of proteomic and metabolomic data allowed obtaining the model with a high discriminatory power, where amino acids ethanolamine, l-citrulline, l-asparagine, and peptide ions with m/z 1488.59; 4111.89 and 2913.15 had the highest contribution to the model. The sensitivity (94.44% and specificity (84.62%, as well as the total group membership classification value (90.32% calculated from the post hoc classification matrix of a joint model were the highest when compared with a single analysis of either amino acid levels or peptide ion intensities. The obtained results indicated a high potential of integration of proteomic and metabolomics analysis regardless the sample size. This promising approach together with clinical evaluation of the subjects can also be used in the study of other diseases.

  12. Metabolomics as a promising tool for early osteoarthritis diagnosis

    Directory of Open Access Journals (Sweden)

    E.B. de Sousa

    2017-09-01

    Full Text Available Osteoarthritis (OA is the main cause of disability worldwide, due to progressive articular cartilage loss and degeneration. According to recent research, OA is more than just a degenerative disease due to some metabolic components associated to its pathogenesis. However, no biomarker has been identified to detect this disease at early stages or to track its development. Metabolomics is an emerging field and has the potential to detect many metabolites in a single spectrum using high resolution nuclear magnetic resonance (NMR techniques or mass spectrometry (MS. NMR is a reproducible and reliable non-destructive analytical method. On the other hand, MS has a lower detection limit and is more destructive, but it is more sensitive. NMR and MS are useful for biological fluids, such as urine, blood plasma, serum, or synovial fluid, and have been used for metabolic profiling in dogs, mice, sheep, and humans. Thus, many metabolites have been listed as possibly associated to OA pathogenesis. The goal of this review is to provide an overview of the studies in animal models and humans, regarding the use of metabolomics as a tool for early osteoarthritis diagnosis. The concept of osteoarthritis as a metabolic disease and the importance of detecting a biomarker for its early diagnosis are highlighted. Then, some studies in plasma and synovial tissues are shown, and finally the application of metabolomics in the evaluation of synovial fluid is described.

  13. Metabolomics in cancer biomarker discovery: current trends and future perspectives.

    Science.gov (United States)

    Armitage, Emily G; Barbas, Coral

    2014-01-01

    Cancer is one of the most devastating human diseases that causes a vast number of mortalities worldwide each year. Cancer research is one of the largest fields in the life sciences and despite many astounding breakthroughs and contributions over the past few decades, there is still a considerable amount to unveil on the function of cancer. It is well known that cancer metabolism differs from that of normal tissue and an important hypothesis published in the 1950s by Otto Warburg proposed that cancer cells rely on anaerobic metabolism as the source for energy, even under physiological oxygen levels. Following this, cancer central carbon metabolism has been researched extensively and beyond respiration, cancer has been found to involve a wide range of metabolic processes, and many more are still to be unveiled. Studying cancer through metabolomics could reveal new biomarkers for cancer that could be useful for its future prognosis, diagnosis and therapy. Metabolomics is becoming an increasingly popular tool in the life sciences since it is a relatively fast and accurate technique that can be applied with either a particular focus or in a global manner to reveal new knowledge about biological systems. There have been many examples of its application to reveal potential biomarkers in different cancers that have employed a range of different analytical platforms. In this review, approaches in metabolomics that have been employed in cancer biomarker discovery are discussed and some of the most noteworthy research in the field is highlighted. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Metabolomics as a tool in the identification of dietary biomarkers.

    Science.gov (United States)

    Gibbons, Helena; Brennan, Lorraine

    2017-02-01

    Current dietary assessment methods including FFQ, 24-h recalls and weighed food diaries are associated with many measurement errors. In an attempt to overcome some of these errors, dietary biomarkers have emerged as a complementary approach to these traditional methods. Metabolomics has developed as a key technology for the identification of new dietary biomarkers and to date, metabolomic-based approaches have led to the identification of a number of putative biomarkers. The three approaches generally employed when using metabolomics in dietary biomarker discovery are: (i) acute interventions where participants consume specific amounts of a test food, (ii) cohort studies where metabolic profiles are compared between consumers and non-consumers of a specific food and (iii) the analysis of dietary patterns and metabolic profiles to identify nutritypes and biomarkers. The present review critiques the current literature in terms of the approaches used for dietary biomarker discovery and gives a detailed overview of the currently proposed biomarkers, highlighting steps needed for their full validation. Furthermore, the present review also evaluates areas such as current databases and software tools, which are needed to advance the interpretation of results and therefore enhance the utility of dietary biomarkers in nutrition research.

  15. Fusing metabolomics data sets with heterogeneous measurement errors

    Science.gov (United States)

    Waaijenborg, Sandra; Korobko, Oksana; Willems van Dijk, Ko; Lips, Mirjam; Hankemeier, Thomas; Wilderjans, Tom F.; Smilde, Age K.

    2018-01-01

    Combining different metabolomics platforms can contribute significantly to the discovery of complementary processes expressed under different conditions. However, analysing the fused data might be hampered by the difference in their quality. In metabolomics data, one often observes that measurement errors increase with increasing measurement level and that different platforms have different measurement error variance. In this paper we compare three different approaches to correct for the measurement error heterogeneity, by transformation of the raw data, by weighted filtering before modelling and by a modelling approach using a weighted sum of residuals. For an illustration of these different approaches we analyse data from healthy obese and diabetic obese individuals, obtained from two metabolomics platforms. Concluding, the filtering and modelling approaches that both estimate a model of the measurement error did not outperform the data transformation approaches for this application. This is probably due to the limited difference in measurement error and the fact that estimation of measurement error models is unstable due to the small number of repeats available. A transformation of the data improves the classification of the two groups. PMID:29698490

  16. NMR-based metabolomics of mammalian cell and tissue cultures

    Energy Technology Data Exchange (ETDEWEB)

    Aranibar, Nelly; Borys, Michael; Mackin, Nancy A.; Ly, Van; Abu-Absi, Nicholas; Abu-Absi, Susan [Bristol-Myers Squibb Company (United States); Niemitz, Matthias [PERCH Solutions Ltd. (Finland); Schilling, Bernhard; Li, Zheng Jian; Brock, Barry; Russell, Reb J.; Tymiak, Adrienne; Reily, Michael D., E-mail: michael.reily@bms.com [Bristol-Myers Squibb Company (United States)

    2011-04-15

    NMR spectroscopy was used to evaluate growth media and the cellular metabolome in two systems of interest to biomedical research. The first of these was a Chinese hamster ovary cell line engineered to express a recombinant protein. Here, NMR spectroscopy and a quantum mechanical total line shape analysis were utilized to quantify 30 metabolites such as amino acids, Krebs cycle intermediates, activated sugars, cofactors, and others in both media and cell extracts. The impact of bioreactor scale and addition of anti-apoptotic agents to the media on the extracellular and intracellular metabolome indicated changes in metabolic pathways of energy utilization. These results shed light into culture parameters that can be manipulated to optimize growth and protein production. Second, metabolomic analysis was performed on the superfusion media in a common model used for drug metabolism and toxicology studies, in vitro liver slices. In this study, it is demonstrated that two of the 48 standard media components, choline and histidine are depleted at a faster rate than many other nutrients. Augmenting the starting media with extra choline and histidine improves the long-term liver slice viability as measured by higher tissues levels of lactate dehydrogenase (LDH), glutathione and ATP, as well as lower LDH levels in the media at time points out to 94 h after initiation of incubation. In both models, media components and cellular metabolites are measured over time and correlated with currently accepted endpoint measures.

  17. Challenges of inversely estimating Jacobian from metabolomics data

    Directory of Open Access Journals (Sweden)

    Xiaoliang eSun

    2015-11-01

    Full Text Available Inferring dynamics of metabolic networks directly from metabolomics data provides a promising way to elucidate the underlying mechanisms of biological systems, as reported in our previous studies [1-3] by a differential Jacobian approach. The Jacobian is solved from an over-determined system of equations as JC + CJT = -2D, called Lyapunov Equation in its generic form , where J is the Jacobian, C is the covariance matrix of metabolomics data and D is the fluctuation matrix. Lyapunov Equation can be further simplified as the linear form Ax = b. Frequently, this linear equation system is ill-conditioned, i.e., a small variation in the right side b results in a big change in the solution x, thus making the solution unstable and error-prone. At the same time, inaccurate estimation of covariance matrix and uncertainties in the fluctuation matrix bring biases to the solution x. Here, we firstly reviewed common approaches to circumvent the ill-conditioned problems, including total least squares, Tikhonov regularization and truncated singular value decomposition. Then we benchmarked these methods on several in-silico kinetic models with small to large perturbations on the covariance and fluctuation matrices. The results identified that the accuracy of the reverse Jacobian is mainly dependent on the condition number of A, the perturbation amplitude of C and the stiffness of the kinetic models. Our research contributes a systematical comparison of methods to inversely solve Jacobian from metabolomics data.

  18. Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows.

    Science.gov (United States)

    Imhasly, Sandro; Naegeli, Hanspeter; Baumann, Sven; von Bergen, Martin; Luch, Andreas; Jungnickel, Harald; Potratz, Sarah; Gerspach, Christian

    2014-06-02

    Hepatic lipidosis or fatty liver disease is a major metabolic disorder of high-producing dairy cows that compromises animal performance and, hence, causes heavy economic losses worldwide. This syndrome, occurring during the critical transition from gestation to early lactation, leads to an impaired health status, decreased milk yield, reduced fertility and shortened lifetime. Because the prevailing clinical chemistry parameters indicate advanced liver damage independently of the underlying disease, currently, hepatic lipidosis can only be ascertained by liver biopsy. We hypothesized that the condition of fatty liver disease may be accompanied by an altered profile of endogenous metabolites in the blood of affected animals. To identify potential small-molecule biomarkers as a novel diagnostic alternative, the serum samples of diseased dairy cows were subjected to a targeted metabolomics screen by triple quadrupole mass spectrometry. A subsequent multivariate test involving principal component and linear discriminant analyses yielded 29 metabolites (amino acids, phosphatidylcholines and sphingomyelines) that, in conjunction, were able to distinguish between dairy cows with no hepatic lipidosis and those displaying different stages of the disorder. This proof-of-concept study indicates that metabolomic profiles, including both amino acids and lipids, distinguish hepatic lipidosis from other peripartal disorders and, hence, provide a promising new tool for the diagnosis of hepatic lipidosis. By generating insights into the molecular pathogenesis of hepatic lipidosis, metabolomics studies may also facilitate the prevention of this syndrome.

  19. HMDB 3.0--The Human Metabolome Database in 2013.

    Science.gov (United States)

    Wishart, David S; Jewison, Timothy; Guo, An Chi; Wilson, Michael; Knox, Craig; Liu, Yifeng; Djoumbou, Yannick; Mandal, Rupasri; Aziat, Farid; Dong, Edison; Bouatra, Souhaila; Sinelnikov, Igor; Arndt, David; Xia, Jianguo; Liu, Philip; Yallou, Faizath; Bjorndahl, Trent; Perez-Pineiro, Rolando; Eisner, Roman; Allen, Felicity; Neveu, Vanessa; Greiner, Russ; Scalbert, Augustin

    2013-01-01

    The Human Metabolome Database (HMDB) (www.hmdb.ca) is a resource dedicated to providing scientists with the most current and comprehensive coverage of the human metabolome. Since its first release in 2007, the HMDB has been used to facilitate research for nearly 1000 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 3.0) has been significantly expanded and enhanced over the 2009 release (version 2.0). In particular, the number of annotated metabolite entries has grown from 6500 to more than 40,000 (a 600% increase). This enormous expansion is a result of the inclusion of both 'detected' metabolites (those with measured concentrations or experimental confirmation of their existence) and 'expected' metabolites (those for which biochemical pathways are known or human intake/exposure is frequent but the compound has yet to be detected in the body). The latest release also has greatly increased the number of metabolites with biofluid or tissue concentration data, the number of compounds with reference spectra and the number of data fields per entry. In addition to this expansion in data quantity, new database visualization tools and new data content have been added or enhanced. These include better spectral viewing tools, more powerful chemical substructure searches, an improved chemical taxonomy and better, more interactive pathway maps. This article describes these enhancements to the HMDB, which was previously featured in the 2009 NAR Database Issue. (Note to referees, HMDB 3.0 will go live on 18 September 2012.).

  20. Salivary microbiota and metabolome associated with celiac disease.

    Science.gov (United States)

    Francavilla, Ruggiero; Ercolini, Danilo; Piccolo, Maria; Vannini, Lucia; Siragusa, Sonya; De Filippis, Francesca; De Pasquale, Ilaria; Di Cagno, Raffaella; Di Toma, Michele; Gozzi, Giorgia; Serrazanetti, Diana I; De Angelis, Maria; Gobbetti, Marco

    2014-06-01

    This study aimed to investigate the salivary microbiota and metabolome of 13 children with celiac disease (CD) under a gluten-free diet (treated celiac disease [T-CD]). The same number of healthy children (HC) was used as controls. The salivary microbiota was analyzed by an integrated approach using culture-dependent and -independent methods. Metabolome analysis was carried out by gas chromatography-mass spectrometry-solid-phase microextraction. Compared to HC, the number of some cultivable bacterial groups (e.g., total anaerobes) significantly (P endodontalis, and Prevotella nanceiensis), together with the smallest amount of Actinobacteria. T-CD children were also characterized by decreased levels of some Actinomyces species, Atopobium species, and Corynebacterium durum. Rothia mucilaginosa was the only Actinobacteria species found at the highest level in T-CD children. As shown by multivariate statistical analyses, the levels of organic volatile compounds markedly differentiated T-CD children. Some compounds (e.g., ethyl-acetate, nonanal, and 2-hexanone) were found to be associated with T-CD children. Correlations (false discovery rate [FDR], oral dysbiosis that could affect the oral metabolome.

  1. Metabolome of human gut microbiome is predictive of host dysbiosis

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Peter E.; Dai, Yang

    2015-09-14

    Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.

  2. A proteomic approach to investigating gene cluster expression and secondary metabolite functionality in Aspergillus fumigatus.

    OpenAIRE

    Owens, RA; Hammel, S; Sheridan, KJ; Jones, GW; Doyle, S

    2014-01-01

    A combined proteomics and metabolomics approach was utilised to advance the identification and characterisation of secondary metabolites in Aspergillus fumigatus. Here, implementation of a shotgun proteomic strategy led to the identification of non-redundant mycelial proteins (n = 414) from A. fumigatus including proteins typically under-represented in 2-D proteome maps: proteins with multiple transmembrane regions, hydrophobic proteins and proteins with extremes of molecular mass and pI. Ind...

  3. MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Nakayasu, Ernesto S.; Nicora, Carrie D.; Sims, Amy C.; Burnum-Johnson, Kristin E.; Kim, Young-Mo; Kyle, Jennifer E.; Matzke, Melissa M.; Shukla, Anil K.; Chu, Rosalie K.; Schepmoes, Athena A.; Jacobs, Jon M.; Baric, Ralph S.; Webb-Robertson, Bobbie-Jo; Smith, Richard D.; Metz, Thomas O.; Chia, Nicholas

    2016-05-03

    ABSTRACT

    Integrative multi-omics analyses can empower more effective investigation and complete understanding of complex biological systems. Despite recent advances in a range of omics analyses, multi-omic measurements of the same sample are still challenging and current methods have not been well evaluated in terms of reproducibility and broad applicability. Here we adapted a solvent-based method, widely applied for extracting lipids and metabolites, to add proteomics to mass spectrometry-based multi-omics measurements. Themetabolite,protein, andlipidextraction (MPLEx) protocol proved to be robust and applicable to a diverse set of sample types, including cell cultures, microbial communities, and tissues. To illustrate the utility of this protocol, an integrative multi-omics analysis was performed using a lung epithelial cell line infected with Middle East respiratory syndrome coronavirus, which showed the impact of this virus on the host glycolytic pathway and also suggested a role for lipids during infection. The MPLEx method is a simple, fast, and robust protocol that can be applied for integrative multi-omic measurements from diverse sample types (e.g., environmental,in vitro, and clinical).

    IMPORTANCEIn systems biology studies, the integration of multiple omics measurements (i.e., genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has been shown to provide a more complete and informative view of biological pathways. Thus, the prospect of extracting different types of molecules (e.g., DNAs, RNAs, proteins, and metabolites) and performing multiple omics measurements on single samples is very attractive, but such studies are challenging due to the fact that the extraction conditions differ according to the molecule type. Here, we adapted an organic solvent-based extraction method that demonstrated

  4. Metabolomic and proteomic analysis of D-lactate-producing Lactobacillus delbrueckii under various fermentation conditions.

    Science.gov (United States)

    Liang, Shaoxiong; Gao, Dacheng; Liu, Huanhuan; Wang, Cheng; Wen, Jianping

    2018-05-28

    As an important feedstock monomer for the production of biodegradable stereo-complex poly-lactic acid polymer, D-lactate has attracted much attention. To improve D-lactate production by microorganisms such as Lactobacillus delbrueckii, various fermentation conditions were performed, such as the employment of anaerobic fermentation, the utilization of more suitable neutralizing agents, and exploitation of alternative nitrogen sources. The highest D-lactate titer could reach 133 g/L under the optimally combined fermentation condition, increased by 70.5% compared with the control. To decipher the potential mechanisms of D-lactate overproduction, the time-series response of intracellular metabolism to different fermentation conditions was investigated by GC-MS and LC-MS/MS-based metabolomic analysis. Then the metabolomic datasets were subjected to weighted correlation network analysis (WGCNA), and nine distinct metabolic modules and eight hub metabolites were identified to be specifically associated with D-lactate production. Moreover, a quantitative iTRAQ-LC-MS/MS proteomic approach was employed to further analyze the change of intracellular metabolism under the combined fermentation condition, identifying 97 up-regulated and 42 down-regulated proteins compared with the control. The in-depth analysis elucidated how the key factors exerted influence on D-lactate biosynthesis. The results revealed that glycolysis and pentose phosphate pathways, transport of glucose, amino acids and peptides, amino acid metabolism, peptide hydrolysis, synthesis of nucleotides and proteins, and cell division were all strengthened, while ATP consumption for exporting proton, cell damage, metabolic burden caused by stress response, and bypass of pyruvate were decreased under the combined condition. These might be the main reasons for significantly improved D-lactate production. These findings provide the first omics view of cell growth and D-lactate overproduction in L. delbrueckii, which

  5. Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication.

    Science.gov (United States)

    Shender, Victoria O; Pavlyukov, Marat S; Ziganshin, Rustam H; Arapidi, Georgij P; Kovalchuk, Sergey I; Anikanov, Nikolay A; Altukhov, Ilya A; Alexeev, Dmitry G; Butenko, Ivan O; Shavarda, Alexey L; Khomyakova, Elena B; Evtushenko, Evgeniy; Ashrafyan, Lev A; Antonova, Irina B; Kuznetcov, Igor N; Gorbachev, Alexey Yu; Shakhparonov, Mikhail I; Govorun, Vadim M

    2014-12-01

    Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Metabolomics study of human urinary metabolome modifications after intake of almond (Prunus dulcis (Mill.) D.A. Webb) skin polyphenols.

    Science.gov (United States)

    Llorach, Rafael; Garrido, Ignacio; Monagas, Maria; Urpi-Sarda, Mireia; Tulipani, Sara; Bartolome, Begona; Andres-Lacueva, Cristina

    2010-11-05

    Almond, as a part of the nut family, is an important source of biological compounds, and specifically, almond skins have been considered an important source of polyphenols, including flavan-3-ols and flavonols. Polyphenol metabolism may produce several classes of metabolites that could often be more biologically active than their dietary precursor and could also become a robust new biomarker of almond polyphenol intake. In order to study urinary metabolome modifications during the 24 h after a single dose of almond skin extract, 24 volunteers (n = 24), who followed a polyphenol-free diet for 48 h before and during the study, ingested a dietary supplement of almond skin phenolic compounds (n = 12) or a placebo (n = 12). Urine samples were collected before ((-2)-0 h) and after (0-2 h, 2-6 h, 6-10 h, and 10-24 h) the intake and were analyzed by liquid chromatography-mass spectrometry (LC-q-TOF) and multivariate statistical analysis (principal component analysis (PCA) and orthogonal projection to latent structures (OPLS)). Putative identification of relevant biomarkers revealed a total of 34 metabolites associated with the single dose of almond extract, including host and, in particular, microbiota metabolites. As far as we know, this is the first time that conjugates of hydroxyphenylvaleric, hydroxyphenylpropionic, and hydroxyphenylacetic acids have been identified in human samples after the consumption of flavan-3-ols through a metabolomic approach. The results showed that this non-targeted approach could provide new intake biomarkers, contributing to the development of the food metabolome as an important part of the human urinary metabolome.

  7. Comprehensive transcriptome analyses correlated with untargeted metabolome reveal differentially expressed pathways in response to cell wall alterations.

    Science.gov (United States)

    Reem, Nathan T; Chen, Han-Yi; Hur, Manhoi; Zhao, Xuefeng; Wurtele, Eve Syrkin; Li, Xu; Li, Ling; Zabotina, Olga

    2018-03-01

    This research provides new insights into plant response to cell wall perturbations through correlation of transcriptome and metabolome datasets obtained from transgenic plants expressing cell wall-modifying enzymes. Plants respond to changes in their cell walls in order to protect themselves from pathogens and other stresses. Cell wall modifications in Arabidopsis thaliana have profound effects on gene expression and defense response, but the cell signaling mechanisms underlying these responses are not well understood. Three transgenic Arabidopsis lines, two with reduced cell wall acetylation (AnAXE and AnRAE) and one with reduced feruloylation (AnFAE), were used in this study to investigate the plant responses to cell wall modifications. RNA-Seq in combination with untargeted metabolome was employed to assess differential gene expression and metabolite abundance. RNA-Seq results were correlated with metabolite abundances to determine the pathways involved in response to cell wall modifications introduced in each line. The resulting pathway enrichments revealed the deacetylation events in AnAXE and AnRAE plants induced similar responses, notably, upregulation of aromatic amino acid biosynthesis and changes in regulation of primary metabolic pathways that supply substrates to specialized metabolism, particularly those related to defense responses. In contrast, genes and metabolites of lipid biosynthetic pathways and peroxidases involved in lignin polymerization were downregulated in AnFAE plants. These results elucidate how primary metabolism responds to extracellular stimuli. Combining the transcriptomics and metabolomics datasets increased the power of pathway prediction, and demonstrated the complexity of pathways involved in cell wall-mediated signaling.

  8. Pasture Feeding Changes the Bovine Rumen and Milk Metabolome

    Directory of Open Access Journals (Sweden)

    Tom F. O’Callaghan

    2018-04-01

    Full Text Available The purpose of this study was to examine the effects of two pasture feeding systems—perennial ryegrass (GRS and perennial ryegrass and white clover (CLV—and an indoor total mixed ration (TMR system on the (a rumen microbiome; (b rumen fluid and milk metabolome; and (c to assess the potential to distinguish milk from different feeding systems by their respective metabolomes. Rumen fluid was collected from nine rumen cannulated cows under the different feeding systems in early, mid and late lactation, and raw milk samples were collected from ten non-cannulated cows in mid-lactation from each of the feeding systems. The microbiota present in rumen liquid and solid portions were analysed using 16S rRNA gene sequencing, while 1H-NMR untargeted metabolomic analysis was performed on rumen fluid and raw milk samples. The rumen microbiota composition was not found to be significantly altered by any feeding system in this study, likely as a result of a shortened adaptation period (two weeks’ exposure time. In contrast, feeding system had a significant effect on both the rumen and milk metabolome. Increased concentrations of volatile fatty acids including acetic acid, an important source of energy for the cow, were detected in the rumen of TMR and CLV-fed cows. Pasture feeding resulted in significantly higher concentrations of isoacids in the rumen. The ruminal fluids of both CLV and GRS-fed cows were found to have increased concentrations of p-cresol, a product of microbiome metabolism. CLV feeding resulted in increased rumen concentrations of formate, a substrate compound for methanogenesis. The TMR feeding resulted in significantly higher rumen choline content, which contributes to animal health and milk production, and succinate, a product of carbohydrate metabolism. Milk and rumen-fluids were shown to have varying levels of dimethyl sulfone in each feeding system, which was found to be an important compound for distinguishing between the diets

  9. Secondary reconstruction of maxillofacial trauma.

    Science.gov (United States)

    Castro-Núñez, Jaime; Van Sickels, Joseph E

    2017-08-01

    Craniomaxillofacial trauma is one of the most complex clinical conditions in contemporary maxillofacial surgery. Vital structures and possible functional and esthetic sequelae are important considerations following this type of trauma and intervention. Despite the best efforts of the primary surgery, there are a group of patients that will have poor outcomes requiring secondary reconstruction to restore form and function. The purpose of this study is to review current concepts on secondary reconstruction to the maxillofacial complex. The evaluation of a posttraumatic patient for a secondary reconstruction must include an assessment of the different subunits of the upper face, middle face, and lower face. Virtual surgical planning and surgical guides represent the most important innovations in secondary reconstruction over the past few years. Intraoperative navigational surgery/computed-assisted navigation is used in complex cases. Facial asymmetry can be corrected or significantly improved by segmentation of the computerized tomography dataset and mirroring of the unaffected side by means of virtual surgical planning. Navigational surgery/computed-assisted navigation allows for a more precise surgical correction when secondary reconstruction involves the replacement of extensive anatomical areas. The use of technology can result in custom-made replacements and prebent plates, which are more stable and resistant to fracture because of metal fatigue. Careful perioperative evaluation is the key to positive outcomes of secondary reconstruction after trauma. The advent of technological tools has played a capital role in helping the surgical team perform a given treatment plan in a more precise and predictable manner.

  10. Metagenomic and metabolomic analysis of the toxic effects of trichloroacetamide-induced gut microbiome and urine metabolome perturbations in mice.

    Science.gov (United States)

    Zhang, Yan; Zhao, Fuzheng; Deng, Yongfeng; Zhao, Yanping; Ren, Hongqiang

    2015-04-03

    Disinfection byproducts (DBPs) in drinking water have been linked to various diseases, including colon, colorectal, rectal, and bladder cancer. Trichloroacetamide (TCAcAm) is an emerging nitrogenous DBP, and our previous study found that TCAcAm could induce some changes associated with host-gut microbiota co-metabolism. In this study, we used an integrated approach combining metagenomics, based on high-throughput sequencing, and metabolomics, based on nuclear magnetic resonance (NMR), to evaluate the toxic effects of TCAcAm exposure on the gut microbiome and urine metabolome. High-throughput sequencing revealed that the gut microbiome's composition and function were significantly altered after TCAcAm exposure for 90 days in Mus musculus mice. In addition, metabolomic analysis showed that a number of gut microbiota-related metabolites were dramatically perturbed in the urine of the mice. These results may provide novel insight into evaluating the health risk of environmental pollutants as well as revealing the potential mechanism of TCAcAm's toxic effects.

  11. The metabolome and transcriptome of the interaction between Ustilago maydis and Fusarium verticillioides in vitro

    Science.gov (United States)

    The metabolome and transcriptome of the maize-infecting fungi Ustilago maydis and Fusarium verticillioides were analyzed as the two fungi interact. Both fungi were grown for seven days in liquid medium alone or together in order to study how this interaction changes their metabolomic and transcripto...

  12. Current trends and future requirements for the mass spectrometric investigation of microbial, mammalian and plant metabolomes

    International Nuclear Information System (INIS)

    Dunn, Warwick B

    2008-01-01

    The functional levels of biological cells or organisms can be separated into the genome, transcriptome, proteome and metabolome. Of these the metabolome offers specific advantages to the investigation of the phenotype of biological systems. The investigation of the metabolome (metabolomics) has only recently appeared as a mainstream scientific discipline and is currently developing rapidly for the study of microbial, plant and mammalian metabolomes. The metabolome pipeline or workflow encompasses the processes of sample collection and preparation, collection of analytical data, raw data pre-processing, data analysis and data storage. Of these processes the collection of analytical data will be discussed in this review with specific interest shown in the application of mass spectrometry in the metabolomics pipeline. The current developments in mass spectrometry platforms (GC–MS, LC–MS, DIMS and imaging MS) and applications of specific interest will be highlighted. The current limitations of these platforms and applications will be discussed with areas requiring further development also highlighted. These include the detectable coverage of the metabolome, the identification of metabolites and the process of converting raw data to biological knowledge. (review article)

  13. Impacts on the metabolome of down-regulating polyphenol oxidase in transgenic potato tubers

    Science.gov (United States)

    Tubers of potato (Solanum tuberosum L. cv. Estima) genetically modified (GM) to reduce polyphenol oxidase (PPO) activity and enzymatic discolouration were assessed for changes in the metabolome using Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography (GC)-MS. Metabolome changes ...

  14. Introducing Undergraduate Students to Metabolomics Using a NMR-Based Analysis of Coffee Beans

    Science.gov (United States)

    Sandusky, Peter Olaf

    2017-01-01

    Metabolomics applies multivariate statistical analysis to sets of high-resolution spectra taken over a population of biologically derived samples. The objective is to distinguish subpopulations within the overall sample population, and possibly also to identify biomarkers. While metabolomics has become part of the standard analytical toolbox in…

  15. Biomarkers for predicting type 2 diabetes development — Can metabolomics improve on existing biomarkers?

    DEFF Research Database (Denmark)

    Savolainen, Otto; Fagerberg, Björn; Lind, Mads Vendelbo

    2017-01-01

    resistance (HOMA), smoking, serum adiponectin)) alone, and in combination with metabolomics had the largest areas under the curve (AUC) (0.794 (95% confidence interval [0.738–0.850]) and 0.808 [0.749–0.867] respectively), with the standalone metabolomics model based on nine fasting plasma markers having...

  16. Standard reporting requirements for biological samples in metabolomics experiments: Microbial and in vitro biology experiments

    NARCIS (Netherlands)

    Werf, M.J. van der; Takors, R.; Smedsgaard, J.; Nielsen, J.; Ferenci, T.; Portais, J.C.; Wittmann, C.; Hooks, M.; Tomassini, A.; Oldiges, M.; Fostel, J.; Sauer, U.

    2007-01-01

    With the increasing use of metabolomics as a means to study a large number of different biological research questions, there is a need for a minimal set of reporting standards that allow the scientific community to evaluate, understand, repeat, compare and re-investigate metabolomics studies. Here

  17. Metabolite Profiling in the Pursuit of Biomarkers for IVF Outcome: The Case for Metabolomics Studies

    Directory of Open Access Journals (Sweden)

    C. McRae

    2013-01-01

    Full Text Available Background. This paper presents the literature on biomarkers of in vitro fertilisation (IVF outcome, demonstrating the progression of these studies towards metabolite profiling, specifically metabolomics. The need for more, and improved, metabolomics studies in the field of assisted conception is discussed. Methods. Searches were performed on ISI Web of Knowledge SM for literature associated with biomarkers of oocyte and embryo quality, and biomarkers of IVF outcome in embryo culture medium, follicular fluid (FF, and blood plasma in female mammals. Results. Metabolomics in the field of female reproduction is still in its infancy. Metabolomics investigations of embryo culture medium for embryo selection have been the most common, but only within the last five years. Only in 2012 has the first metabolomics investigation of FF for biomarkers of oocyte quality been reported. The only metabolomics studies of human blood plasma in this context have been aimed at identifying women with polycystic ovary syndrome (PCOS. Conclusions. Metabolomics is becoming more established in the field of assisted conception, but the studies performed so far have been preliminary and not all potential applications have yet been explored. With further improved metabolomics studies, the possibility of identifying a method for predicting IVF outcome may become a reality.

  18. The future of metabolomics in ELIXIR [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Merlijn van Rijswijk

    2017-09-01

    Full Text Available Metabolomics, the youngest of the major omics technologies, is supported by an active community of researchers and infrastructure developers across Europe. To coordinate and focus efforts around infrastructure building for metabolomics within Europe, a workshop on the “Future of metabolomics in ELIXIR” was organised at Frankfurt Airport in Germany. This one-day strategic workshop involved representatives of ELIXIR Nodes, members of the PhenoMeNal consortium developing an e-infrastructure that supports workflow-based metabolomics analysis pipelines, and experts from the international metabolomics community. The workshop established metabolite identification as the critical area, where a maximal impact of computational metabolomics and data management on other fields could be achieved. In particular, the existing four ELIXIR Use Cases, where the metabolomics community - both industry and academia - would benefit most, and which could be exhaustively mapped onto the current five ELIXIR Platforms were discussed. This opinion article is a call for support for a new ELIXIR metabolomics Use Case, which aligns with and complements the existing and planned ELIXIR Platforms and Use Cases.

  19. The future of metabolomics in ELIXIR [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Merlijn van Rijswijk

    2017-10-01

    Full Text Available Metabolomics, the youngest of the major omics technologies, is supported by an active community of researchers and infrastructure developers across Europe. To coordinate and focus efforts around infrastructure building for metabolomics within Europe, a workshop on the “Future of metabolomics in ELIXIR” was organised at Frankfurt Airport in Germany. This one-day strategic workshop involved representatives of ELIXIR Nodes, members of the PhenoMeNal consortium developing an e-infrastructure that supports workflow-based metabolomics analysis pipelines, and experts from the international metabolomics community. The workshop established metabolite identification as the critical area, where a maximal impact of computational metabolomics and data management on other fields could be achieved. In particular, the existing four ELIXIR Use Cases, where the metabolomics community - both industry and academia - would benefit most, and which could be exhaustively mapped onto the current five ELIXIR Platforms were discussed. This opinion article is a call for support for a new ELIXIR metabolomics Use Case, which aligns with and complements the existing and planned ELIXIR Platforms and Use Cases.

  20. A proposed framework for the description of plant metabolomics experiments and their results

    DEFF Research Database (Denmark)

    Jenkins, H.; Hardy, N.; Beckmann, M-

    2004-01-01

    The study of the metabolite complement of biological samples, known as metabolomics, is creating large amounts of data, and support for handling these data sets is required to facilitate meaningful analyses that will answer biological questions. We present a data model for plant metabolomics known...

  1. Metabolomic profiling of rapid cold hardening and cold shock in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Overgaard, Johannes; Malmendal, Anders; Sørensen, Jesper

    2007-01-01

    study used untargeted (1)H NMR metabolomic profiling to examine the metabolomic response in Drosophila melanogaster during the 72 h following RCH and cold shock treatment. These findings are discussed in relation to the costs and benefits of RCH that are measured in terms of survival and reproductive...

  2. Bacterial Impact on the Gut Metabolome

    DEFF Research Database (Denmark)

    Sulek, Karolina; Wilcks, Andrea; Licht, Tine Rask

    During the last decade, it has become evident that the complex ecosystem of mi-crobes inhabiting the human gut plays an important role for human health. An in-creasing number of publications have shown that the composition and activity of our intestinal microbiota affects a number of different so...

  3. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

    Science.gov (United States)

    Theriot, Casey M.; Koenigsknecht, Mark J.; Carlson, Paul E.; Hatton, Gabrielle E.; Nelson, Adam M.; Li, Bo; Huffnagle, Gary B.; Li, Jun; Young, Vincent B.

    2014-01-01

    Antibiotics can have significant and long lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids, and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including primary bile acid taurocholate for germination, and carbon sources mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth. PMID:24445449

  4. Are ant feces nutrients for plants? A metabolomics approach to elucidate the nutritional effects on plants hosting weaver ants

    DEFF Research Database (Denmark)

    Vidkjær, Nanna Hjort; Wollenweber, Bernd; Gislum, René

    2015-01-01

    Weaver ants (genus Oecophylla) are tropical carnivorous ant species living in high numbers in the canopies of trees. The ants excrete copious amounts of fecal matter on leaf surfaces, and these feces may provide nutrients to host trees. This hypothesis is supported by studies of ant......-plant interactions involving other ant species that have demonstrated the transfer of nutrients from ants to plants. In this 7-months study, a GC–MS-based metabolomics approach along with an analysis of total nitrogen and carbon levels was used to study metabolic changes in ant-hosting Coffea arabica plants compared...... with control plants. The results showed elevated levels of total nitrogen, amino acids, fatty acids, caffeine, and secondary metabolites of the phenylpropanoid pathway in leaves from ant-hosting plants. Minor effects were observed for sugars, whereas little or no effect was observed for organic acids, despite...

  5. Associations of Nasopharyngeal Metabolome and Microbiome with Severity among Infants with Bronchiolitis. A Multiomic Analysis.

    Science.gov (United States)

    Stewart, Christopher J; Mansbach, Jonathan M; Wong, Matthew C; Ajami, Nadim J; Petrosino, Joseph F; Camargo, Carlos A; Hasegawa, Kohei

    2017-10-01

    Bronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about the mechanisms linking airway microbes and host response to disease severity. To determine the relations among the nasopharyngeal airway metabolome profiles, microbiome profiles, and severity in infants with bronchiolitis. We conducted a multicenter prospective cohort study of infants (age metabolomic and metagenomic (16S ribosomal RNA gene and whole-genome shotgun sequencing) approaches to 144 nasopharyngeal airway samples collected within 24 hours of hospitalization, we determined metabolome and microbiome profiles and their association with higher severity, defined by the use of positive pressure ventilation (i.e., continuous positive airway pressure and/or intubation). Nasopharyngeal airway metabolome profiles significantly differed by bronchiolitis severity (P metabolomics to predict bronchiolitis severity and better understand microbe-host interaction.

  6. The application of skin metabolomics in the context of transdermal drug delivery.

    Science.gov (United States)

    Li, Jinling; Xu, Weitong; Liang, Yibiao; Wang, Hui

    2017-04-01

    Metabolomics is a powerful emerging tool for the identification of biomarkers and the exploration of metabolic pathways in a high-throughput manner. As an administration site for percutaneous absorption, the skin has a variety of metabolic enzymes, except other than hepar. However, technologies to fully detect dermal metabolites remain lacking. Skin metabolomics studies have mainly focused on the regulation of dermal metabolites by drugs or on the metabolism of drugs themselves. Skin metabolomics techniques include collection and preparation of skin samples, data collection, data processing and analysis. Furthermore, studying dermal metabolic effects via metabolomics can provide novel explanations for the pathogenesis of some dermatoses and unique insights for designing targeted prodrugs, promoting drug absorption and controlling drug concentration. This paper reviews current progress in the field of skin metabolomics, with a specific focus on dermal drug delivery systems and dermatosis. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  7. Metabolomics reveals mycoplasma contamination interferes with the metabolism of PANC-1 cells.

    Science.gov (United States)

    Yu, Tao; Wang, Yongtao; Zhang, Huizhen; Johnson, Caroline H; Jiang, Yiming; Li, Xiangjun; Wu, Zeming; Liu, Tian; Krausz, Kristopher W; Yu, Aiming; Gonzalez, Frank J; Huang, Min; Bi, Huichang

    2016-06-01

    Mycoplasma contamination is a common problem in cell culture and can alter cellular functions. Since cell metabolism is either directly or indirectly involved in every aspect of cell function, it is important to detect changes to the cellular metabolome after mycoplasma infection. In this study, liquid chromatography mass spectrometry (LC/MS)-based metabolomics was used to investigate the effect of mycoplasma contamination on the cellular metabolism of human pancreatic carcinoma cells (PANC-1). Multivariate analysis demonstrated that mycoplasma contamination induced significant metabolic changes in PANC-1 cells. Twenty-three metabolites were identified and found to be involved in arginine and purine metabolism and energy supply. This study demonstrates that mycoplasma contamination significantly alters cellular metabolite levels, confirming the compelling need for routine checking of cell cultures for mycoplasma contamination, particularly when used for metabolomics studies. Graphical abstract Metabolomics reveals mycoplasma contamination changes the metabolome of PANC-1 cells.

  8. Profiling the metabolome changes caused by cranberry procyanidins in plasma of female rats using (1) H NMR and UHPLC-Q-Orbitrap-HRMS global metabolomics approaches.

    Science.gov (United States)

    Liu, Haiyan; Garrett, Timothy J; Tayyari, Fariba; Gu, Liwei

    2015-11-01

    The objective was to investigate the metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) using (1) H NMR and UHPLC-Q-Orbitrap-HRMS metabolomics approaches, and to identify the contributing metabolites. Twenty-four female Sprague-Dawley rats were randomly separated into two groups and administered PPCP or partially purified apple procyanidins (PPAP) for three times using a 250 mg extracts/kg body weight dose. Plasma was collected 6 h after the last gavage and analyzed using (1) H NMR and UHPLC-Q-Orbitrap-HRMS. No metabolome difference was observed using (1) H NMR metabolomics approach. However, LC-HRMS metabolomics data show that metabolome in the plasma of female rats administered PPCP differed from those gavaged with PPAP. Eleven metabolites were tentatively identified from a total of 36 discriminant metabolic features based on accurate masses and/or product ion spectra. PPCP caused a greater increase of exogenous metabolites including p-hydroxybenzoic acid, phenol, phenol-sulphate, catechol sulphate, 3, 4-dihydroxyphenylvaleric acid, and 4'-O-methyl-(-)-epicatechin-3'-O-beta-glucuronide in rat plasma. Furthermore, the plasma level of O-methyl-(-)-epicatechin-O-glucuronide, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5-(hydroxyphenyl)-ϒ-valerolactone-O-sulphate, 4-hydroxydiphenylamine, and peonidin-3-O-hexose were higher in female rats administered with PPAP. The metabolome changes caused by cranberry procyanidins were revealed using an UHPLC-Q-Orbitrap-HRMS global metabolomics approach. Exogenous and microbial metabolites were the major identified discriminate biomarkers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Profiling the Metabolome Changes Caused by Cranberry Procyanidins in Plasma of Female Rats using 1H NMR and UHPLC-Q-Orbitrap-HRMS Global Metabolomics Approaches

    Science.gov (United States)

    Liu, Haiyan; Garrett, Timothy J.; Tayyari, Fariba; Gu, Liwei

    2015-01-01

    Scope The objective was to investigate the metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) using 1H NMR and UHPLC-Q-Orbitrap-HRMS metabolomics approaches, and to identify the contributing metabolites. Methods and results Twenty four female Sprague-Dawley rats were randomly separated into two groups and administered PPCP or partially purified apple procyanidins (PPAP) for 3 times using a 250 mg extracts/kg body weight dose. Plasma were collected six hours after the last gavage and analyzed using 1H NMR and UHPLC-Q-Orbitrap-HRMS. No metabolome difference was observed using 1H NMR metabolomics approach. However, LC-HRMS metabolomics data show that metabolome in plasma of female rats administered PPCP differed from those gavaged with PPAP. Eleven metabolites were tentatively identified from a total of 36 discriminant metabolic features based on accurate masses and/or product ion spectra. PPCP caused a greater increase of exogenous metabolites including p-hydroxybenzoic acid, phenol, phenol-sulfate, catechol sulphate, 3, 4-dihydroxyphenylvaleric acid, and 4′-O-methyl-(−)-epicatechin-3′-O-beta-glucuronide in rat plasma. Furthermore, the plasma level of O-methyl-(−)-epicatechin-O-glucuronide, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5-(hydroxyphenyl)-γ-valerolactone-O-sulphate, 4-hydroxydiphenylamine, and peonidin-3-O-hexose were higher in female rats administered with PPAP. Conclusion The metabolome changes caused by cranberry procyanidins were revealed using an UHPLC-Q-Orbitrap-HRMS global metabolomics approach. Exogenous and microbial metabolites were the major identified discriminate biomarkers. PMID:26264887

  10. ESI-LC-MS based-metabolomics data of mangosteen (Garcinia mangostana Linn. fruit pericarp, aril and seed at different ripening stages

    Directory of Open Access Journals (Sweden)

    Siti Farah Mamat

    2018-04-01

    Full Text Available Fruit ripening is a complex phenomenon involving a series of biochemical, physiological and organoleptic changes. Ripening process in mangosteen (Garcinia mangostana Linn. is unique of which the fruit will only ripen properly if harvested during its middle stage (emergence of purple/pink colour but not earlier (green stage. The knowledge on the molecular mechanism and regulation behind this phenomenon is still limited. Hence, electrospray ionization liquid chromatography mass spectrometry (ESI-LC-MS based metabolomics analysis was applied to determine the metabolome of mangosteen ripening. Specifically, mangosteen pericarp, aril and seed were collected at four different ripening stages (stage 0: green, stage 2: yellowish with pink patches, stage 4: brownish red and stage 6: dark purple and subjected to metabolite profiling analysis. The data provided in this article have been deposited to the EMBL-EBI MetaboLights database (DOI: 10.1093/nar/gks1004. PubMed PMID: 23109552 with the identifier MTBLS595. The complete dataset can be accessed here https://www.ebi.ac.uk/metabolights/MTBLS595. Keywords: Ripening, Garcinia mangostana Linn., Metabolomics, ESI-LC-MS

  11. Combining two-dimensional gel electrophoresis and metabolomic data in support of dry-season survival in the two main species of the malarial mosquito Anopheles gambiae

    Directory of Open Access Journals (Sweden)

    Hidalgo K.

    2015-12-01

    Full Text Available In dry savannahs of West-Africa, the malarial mosquitoes of the Anopheles gambiae sensu stricto complex annually survive the harsh desiccating conditions of the dry season. However, the physiological and biochemical mechanisms underlying how these mosquitoes survive such desiccating conditions are still undefined, and controversial. In this context, we provide the first work examining both proteomic and metabolomic changes in the two molecular forms of A. gambiae s.s (M and S forms experimentally exposed to the rainy and dry season conditions as they experience in the field. Protein abundances of the mosquitoes were measured using a two-dimensional fluorescence difference gel electrophoresis (2D DIGE coupled with a matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF and tandem mass spectrometry (MS for protein identification. These assays were conducted by Applied Biomics (http://www.appliedbiomics.com, Applied Biomics, Inc. Hayward, CA, USA, and the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org via the PRIDE partner repository with the dataset identifier PXD000294. The metabolomic analysis was conducted using both Acquity UPLC® system (for amino acid identification, and a gas-chromatography-mass spectrometry platform (for sugars identification. Metabolomic fingerprintings were assessed in the University of Rennes 1, UMR CNRS 6553 EcoBio (France. A detailed interpretation of the obtained data can be found in Hidalgo et al. (2014 [1] (Journal of Insect Physiology (2014.

  12. The Chemistry of Plant–Microbe Interactions in the Rhizosphere and the Potential for Metabolomics to Reveal Signaling Related to Defense Priming and Induced Systemic Resistance

    Science.gov (United States)

    Mhlongo, Msizi I.; Piater, Lizelle A.; Madala, Ntakadzeni E.; Labuschagne, Nico; Dubery, Ian A.

    2018-01-01

    Plant roots communicate with microbes in a sophisticated manner through chemical communication within the rhizosphere, thereby leading to biofilm formation of beneficial microbes and, in the case of plant growth-promoting rhizomicrobes/-bacteria (PGPR), resulting in priming of defense, or induced resistance in the plant host. The knowledge of plant–plant and plant–microbe interactions have been greatly extended over recent years; however, the chemical communication leading to priming is far from being well understood. Furthermore, linkage between below- and above-ground plant physiological processes adds to the complexity. In metabolomics studies, the main aim is to profile and annotate all exo- and endo-metabolites in a biological system that drive and participate in physiological processes. Recent advances in this field has enabled researchers to analyze 100s of compounds in one sample over a short time period. Here, from a metabolomics viewpoint, we review the interactions within the rhizosphere and subsequent above-ground ‘signalomics’, and emphasize the contributions that mass spectrometric-based metabolomic approaches can bring to the study of plant-beneficial – and priming events. PMID:29479360

  13. Metabolomic analysis of the selection response of Drosophila melanogaster to environmental stress: are there links to gene expression and phenotypic traits?

    Science.gov (United States)

    Malmendal, Anders; Sørensen, Jesper Givskov; Overgaard, Johannes; Holmstrup, Martin; Nielsen, Niels Chr.; Loeschcke, Volker

    2013-05-01

    We investigated the global metabolite response to artificial selection for tolerance to stressful conditions such as cold, heat, starvation, and desiccation, and for longevity in Drosophila melanogaster. Our findings were compared to data from other levels of biological organization, including gene expression, physiological traits, and organismal stress tolerance phenotype. Overall, we found that selection for environmental stress tolerance changes the metabolomic 1H NMR fingerprint largely in a similar manner independent of the trait selected for, indicating that experimental evolution led to a general stress selection response at the metabolomic level. Integrative analyses across data sets showed little similarity when general correlations between selection effects at the level of the metabolome and gene expression were compared. This is likely due to the fact that the changes caused by these selection regimes were rather mild and/or that the dominating determinants for gene expression and metabolite levels were different. However, expression of a number of genes was correlated with the metabolite data. Many of the identified genes were general stress response genes that are down-regulated in response to selection for some of the stresses in this study. Overall, the results illu