WorldWideScience

Sample records for based plant metabolomics

  1. Mass spectrometry-based plant metabolomics: Metabolite responses to abiotic stress.

    Science.gov (United States)

    Jorge, Tiago F; Rodrigues, João A; Caldana, Camila; Schmidt, Romy; van Dongen, Joost T; Thomas-Oates, Jane; António, Carla

    2016-09-01

    Metabolomics is one omics approach that can be 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 analysis of a wide range of chemical species with diverse physical properties, from ionic inorganic compounds to biochemically derived hydrophilic carbohydrates, organic and amino acids, and a range of hydrophobic lipid-related compounds. This complexitiy brings huge challenges to the analytical technologies employed in current plant metabolomics programs, and powerful analytical tools are required for the separation and characterization of this extremely high compound diversity present in biological sample matrices. The use of mass spectrometry (MS)-based analytical platforms to profile stress-responsive metabolites that allow some plants to adapt to adverse environmental conditions is fundamental in current plant biotechnology research programs for the understanding and development of stress-tolerant plants. In this review, we describe recent applications of metabolomics and emphasize its increasing application to study plant responses to environmental (stress-) factors, including drought, salt, low oxygen caused by waterlogging or flooding of the soil, temperature, light and oxidative stress (or a combination of them). Advances in understanding the global changes occurring in plant metabolism under specific abiotic stress conditions are fundamental to enhance plant fitness and increase stress tolerance. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:620-649, 2016. PMID:25589422

  2. 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 m

  3. MeRy-B, a metabolomic database and knowledge base for exploring plant primary metabolism.

    Science.gov (United States)

    Deborde, Catherine; Jacob, Daniel

    2014-01-01

    Plant primary metabolites are organic compounds that are common to all or most plant species and are essential for plant growth, development, and reproduction. They are intermediates and products of metabolism involved in photosynthesis and other biosynthetic processes. Primary metabolites belong to different compound families, mainly carbohydrates, organic acids, amino acids, nucleotides, fatty acids, steroids, or lipids. Until recently, unlike the Human Metabolome Database ( http://www.hmdb.ca ) dedicated to human metabolism, there was no centralized database or repository dedicated exclusively to the plant kingdom that contained information on metabolites and their concentrations in a detailed experimental context. MeRy-B is the first platform for plant (1)H-NMR metabolomic profiles (MeRy-B, http://bit.ly/meryb ), designed to provide a knowledge base of curated plant profiles and metabolites obtained by NMR, together with the corresponding experimental and analytical metadata. MeRy-B contains lists of plant metabolites, mostly primary metabolites and unknown compounds, with information about experimental conditions, the factors studied, and metabolite concentrations for 19 different plant species (Arabidopsis, broccoli, daphne, grape, maize, barrel clover, melon, Ostreococcus tauri, palm date, palm tree, peach, pine tree, eucalyptus, plantain rice, strawberry, sugar beet, tomato, vanilla), compiled from more than 2,300 annotated NMR profiles for various organs or tissues deposited by 30 different private or public contributors in September 2013. Currently, about half of the data deposited in MeRy-B is publicly available. In this chapter, readers will be shown how to (1) navigate through and retrieve data of publicly available projects on MeRy-B website; (2) visualize lists of experimentally identified metabolites and their concentrations in all plant species present in MeRy-B; (3) get primary metabolite list for a particular plant species in MeRy-B; and for a

  4. An overview of NMR-based metabolomics to identify secondary plant compounds involved in host plant resistance.

    Science.gov (United States)

    Leiss, Kirsten A; Choi, Young H; Verpoorte, Robert; Klinkhamer, Peter G L

    2011-06-01

    Secondary metabolites provide a potential source for the generation of host plant resistance and development of biopesticides. This is especially important in view of the rapid and vast spread of agricultural and horticultural pests worldwide. Multiple pests control tactics in the framework of an integrated pest management (IPM) programme are necessary. One important strategy of IPM is the use of chemical host plant resistance. Up to now the study of chemical host plant resistance has, for technical reasons, been restricted to the identification of single compounds applying specific chemical analyses adapted to the compound in question. In biological processes however, usually more than one compound is involved. Metabolomics allows the simultaneous detection of a wide range of compounds, providing an immediate image of the metabolome of a plant. One of the most universally used metabolomic approaches comprises nuclear magnetic resonance spectroscopy (NMR). It has been NMR which has been applied as a proof of principle to show that metabolomics can constitute a major advancement in the study of host plant resistance. Here we give an overview on the application of NMR to identify candidate compounds for host plant resistance. We focus on host plant resistance to western flower thrips (Frankliniella occidentalis) which has been used as a model for different plant species. PMID:21765818

  5. Plant bioassay to assess the effects of allelochemicals on the metabolome of the target species Aegilops geniculata by an NMR-based approach.

    Science.gov (United States)

    D'Abrosca, Brigida; Scognamiglio, Monica; Fiumano, Vittorio; Esposito, Assunta; Choi, Young Hae; Verpoorte, Robert; Fiorentino, Antonio

    2013-09-01

    A metabolomic-based approach for the study of allelopathic interactions in the Mediterranean area is proposed using Aegilops geniculata Roth (Poaceae), a Mediterranean herbaceous plant, as test species. Its metabolome has been elucidated by 1D and 2D NMR experiments. Hydroponic plant cultures of A. geniculata were treated with specific compounds of known allelopathic potential: catechol, coumarin, p-coumaric acid, p-hydroxybenzoic acid, ferulic acid and juglone. The metabolic variations due to the presence of allelochemicals have been analyzed and measured. All of the compounds showed the strongest effects at the highest concentration, with coumarin and juglone as the most active compounds, causing an increase of several metabolites. The metabolome changes in test plants confirmed the allelochemicals' reported modes of action. The results demonstrated that the proposed method is a promising tool. It can be applied to plant extracts, making it possible to evidence the metabolites responsible for the activity, as well as their mechanisms of action.

  6. Recent advances in plant metabolomics and greener pastures.

    Science.gov (United States)

    Sumner, Lloyd W

    2010-01-27

    Metabolomics is an extension of the omics concept and experimental approaches. However, is metabolomics just another trendy omics fashion perturbation or is metabolomics actually delivering novel content and value? This article highlights some recent advances that definitely support the role of plant metabolomics in the movement toward greener pastures.

  7. Metabolomics and bioactive substances in plants

    DEFF Research Database (Denmark)

    Khakimov, Bekzod

    (Analytical and Bioanalytical Chemistry, In Press, DOI: 10.1007/s00216-013-7341-z) outlines a novel GC-MS derivatization method using TMSCN for trimethylsilylation for improved analysis of complex biological mixtures . A review paper (Journal of Cereal Science, Accepted) written for the special issue......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 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...

  8. Mass spectrometry as a quantitative tool in plant metabolomics.

    Science.gov (United States)

    Jorge, Tiago F; Mata, Ana T; António, Carla

    2016-10-28

    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

  9. NMR-based milk metabolomics

    DEFF Research Database (Denmark)

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

    2013-01-01

    Milk is a key component in infant nutrition worldwide and, in the Western parts of the world, also in adult nutrition. Milk of bovine origin is both consumed fresh and processed into a variety of dairy products including cheese, fermented milk products, and infant formula. The nutritional quality...... 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...

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

    OpenAIRE

    Jun Hong; Litao Yang; Dabing Zhang; Jianxin Shi

    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 plan...

  11. NMR-Based Milk Metabolomics

    Directory of Open Access Journals (Sweden)

    Hanne C. Bertram

    2013-04-01

    Full Text Available Milk is a key component in infant nutrition worldwide and, in the Western parts of the world, also in adult nutrition. Milk of bovine origin is both consumed fresh and processed into a variety of dairy products including cheese, fermented milk products, and infant formula. The nutritional quality 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 the milk metabolite profiling with nutritional aspects, and applications which aim to link the milk metabolite profile to various technological qualities of milk. The metabolite profiling studies encompass the identification of novel metabolites, which potentially can be used as biomarkers or as bioactive 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 a better understanding of how milk composition is linked to nutritional or quality traits.

  12. NMR-Based Milk Metabolomics.

    Science.gov (United States)

    Sundekilde, Ulrik K; Larsen, Lotte B; Bertram, Hanne C

    2013-01-01

    Milk is a key component in infant nutrition worldwide and, in the Western parts of the world, also in adult nutrition. Milk of bovine origin is both consumed fresh and processed into a variety of dairy products including cheese, fermented milk products, and infant formula. The nutritional quality 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 the milk metabolite profiling with nutritional aspects, and applications which aim to link the milk metabolite profile to various technological qualities of milk. The metabolite profiling studies encompass the identification of novel metabolites, which potentially can be used as biomarkers or as bioactive 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 a better understanding of how milk composition is linked to nutritional or quality traits. PMID:24957988

  13. 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.

  14. 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

  15. 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.

  16. Time-resolved NMR metabolomics of plant cells based on a microfluidic chip.

    Science.gov (United States)

    Maisch, Jan; Kreppenhofer, Kristina; Büchler, Silke; Merle, Christian; Sobich, Shukhrat; Görling, Benjamin; Luy, Burkhard; Ahrens, Ralf; Guber, Andreas E; Nick, Peter

    2016-08-01

    The plant secondary metabolism generates numerous compounds harbouring pharmaceutical activity. In plants, these compounds are typically formed by different and specialised cell types that have to interact constituting a metabolic process chain. This interactivity impedes biotechnological production of secondary compounds, because cell differentiation is suppressed under the conditions of a batch bio-fermenter. We present a novel strategy to address this limitation using a biomimetic approach, where we simulate the situation in a real tissue by a microfluidic chamber system, where plant cells can be integrated into a process flow. We show that walled cells of the plant model tobacco BY-2 can be successfully cultivated in this system and that physiological parameters (such as cell viability, mitotic index and division synchrony) can be preserved over several days. The microfluidic design allows to resolve dynamic changes of specific metabolites over different stages of culture development. These results serve as proof-of-principle that a microfluidic organisation of cultivated plant cells can mimic the metabolic flows in a real plant tissue. PMID:27318870

  17. Time-resolved NMR metabolomics of plant cells based on a microfluidic chip.

    Science.gov (United States)

    Maisch, Jan; Kreppenhofer, Kristina; Büchler, Silke; Merle, Christian; Sobich, Shukhrat; Görling, Benjamin; Luy, Burkhard; Ahrens, Ralf; Guber, Andreas E; Nick, Peter

    2016-08-01

    The plant secondary metabolism generates numerous compounds harbouring pharmaceutical activity. In plants, these compounds are typically formed by different and specialised cell types that have to interact constituting a metabolic process chain. This interactivity impedes biotechnological production of secondary compounds, because cell differentiation is suppressed under the conditions of a batch bio-fermenter. We present a novel strategy to address this limitation using a biomimetic approach, where we simulate the situation in a real tissue by a microfluidic chamber system, where plant cells can be integrated into a process flow. We show that walled cells of the plant model tobacco BY-2 can be successfully cultivated in this system and that physiological parameters (such as cell viability, mitotic index and division synchrony) can be preserved over several days. The microfluidic design allows to resolve dynamic changes of specific metabolites over different stages of culture development. These results serve as proof-of-principle that a microfluidic organisation of cultivated plant cells can mimic the metabolic flows in a real plant tissue.

  18. An overview of NMR-based metabolomics to identify secondary plant compounds involved in host plant resistance

    OpenAIRE

    Leiss, Kirsten A.; Choi, Young H.; Verpoorte, Robert; Klinkhamer, Peter G. L.

    2010-01-01

    Secondary metabolites provide a potential source for the generation of host plant resistance and development of biopesticides. This is especially important in view of the rapid and vast spread of agricultural and horticultural pests worldwide. Multiple pests control tactics in the framework of an integrated pest management (IPM) programme are necessary. One important strategy of IPM is the use of chemical host plant resistance. Up to now the study of chemical host plant resistance has, for te...

  19. Metabolomics

    DEFF Research Database (Denmark)

    Pedersen, Hans

    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...... in metabolomics studies has been presented in the three case studies. In the first case study, plasma samples from healthy individuals have been analysed by NMR. Some have developed breast cancer later in life and these have been separated from healthy individuals by means of a properly validated PLS-DA model...... 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...

  20. Novel quantitative metabolomic approach for the study of stress responses of plant root metabolism.

    Science.gov (United States)

    Li, Kefeng; Wang, Xu; Pidatala, Venkataramana R; Chang, Chi-Peng; Cao, Xiaohong

    2014-12-01

    Quantitative metabolomics (qMetabolomics) is a powerful tool for understanding the intricate metabolic processes involved in plant abiotic stress responses. qMetabolomics is hindered by the limited coverage and high cost of isotopically labeled standards. In this study, we first selected 271 metabolites which might play important roles in abiotic stress responses as the targets and established a comprehensive LC-MS/MS based qMetabolomic method. We then developed a novel metabolic labeling method using E. coli-Saccharomyces cerevisiae two-step cultivation for the production of uniformly (13)C-labeled metabolites as internal standards. Finally, we applied the developed qMetabolomic method to investigate the influence of Pb stress on maize root metabolism. The absolute concentration of 226 metabolites in maize roots was accurately quantified in a single run within 30 min. Our study also revealed that glycolysis, purine, pyrimidine, and phospholipids were the main metabolic pathways in maize roots involved in Pb stress response. To our knowledge, this is the most comprehensive qMetabolomic method for plant metabolomics thus far. We developed a simple and inexpensive metabolic labeling method which dramatically expanded the availability of uniformly (13)C labeled metabolites. Our findings also provided new insights of maize metabolic responses to Pb stress.

  1. Metabolomic characteristics of Catharanthus roseus plants in time and space

    OpenAIRE

    Qifang, Pan

    2014-01-01

    The thesis aims at combining metabolomics with other methods to investigate the regulation of the TIA biosynthesis and how this is connected with other pathways and the plant’s physiology and development. It reviews the biosynthesis studies of Catharanthus roseus. An HPLC method is described for both precursors and alkaloids which was validated to analyze alkaloid contents in different organs, its relationship with leaf age and growth of C. roseus plants. A metabolomics investigation of C. ro...

  2. NMR-Based Milk Metabolomics

    OpenAIRE

    Bertram, Hanne C.; Larsen, Lotte B; Sundekilde, Ulrik K

    2013-01-01

    Milk is a key component in infant nutrition worldwide and, in the Western parts of the world, also in adult nutrition. Milk of bovine origin is both consumed fresh and processed into a variety of dairy products including cheese, fermented milk products, and infant formula. The nutritional quality 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 ...

  3. Fusion of mass spectrometry-based metabolomics data

    NARCIS (Netherlands)

    Smilde, A.K.; Werf, M.J. van der; Bijlsma, S.; Werff-van der Vat, B.J.C. van der; Jellema, R.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 biologi

  4. 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

  5. Plant metabolomics: from holistic hope, to hype, to hot topic

    NARCIS (Netherlands)

    Hall, R.D.

    2006-01-01

    In a short time, plant metabolomics has gone from being just an ambitious concept to being a rapidly growing, valuable technology applied in the stride to gain a more global picture of the molecular organization of multicellular organisms. The combination of improved analytical capabilities with new

  6. Liquid chromatography-quadrupole time of flight tandem mass spectrometry-based targeted metabolomic study for varietal discrimination of grapes according to plant sterols content.

    Science.gov (United States)

    Millán, Laura; Sampedro, M Carmen; Sánchez, Alicia; Delporte, Cédric; Van Antwerpen, Pierre; Goicolea, M Aranzazu; Barrio, Ramón J

    2016-07-01

    Grapevine and derived products are rich in a wide range of compounds and its quality mainly depends on its metabolites, as a result of viticulture practices. Plant sterols, also called phytosterols (PS), are secondary metabolites regarded as bioactive substance present in grape berries and other plant-based food. The present study deals with a metabolomic approach focusing on phytosterols family in six varieties of Rioja grapes (Cabernet Sauvignon, Tempranillo, Graciano, Garnacha, White Garnacha and Viura), in order to find significant differences among them. Liquid chromatography- mass spectrometry with a quadrupole-time of flight mass analyzer (LC-QTOF) was used to find as many metabolites as possible in the different grape berry fractions, and using statistics to help finding significant clustering of the metabolic profile of pulp, peel and seeds in relation to the variety. The best chromatographic and detection conditions were achieved by gas phase ionization via atmospheric pressure chemical ionization (APCI) in positive mode. Furthermore, analysis with electrospray (ESI) is also needed for phytosterol derivatives confirmation. Putative compounds of interest in the analyzed samples were found by an automated compound extraction algorithm (Molecular Feature Extraction, MFE) and an initial differential expression from the data was created with the aid of commercial software. Once the data were collected, the results were filtered, aligned and normalized, and evaluating applying one-way analysis of variance (ANOVA) with a 95% significance level. For sample class prediction, partial least square-discriminant analysis (PLS-DA) is used as a supervised pattern recognition method and excellent separation among the grape varieties is shown. An overall accuracy of 93.3% (pulp samples), 100.0% (peel) or 96.7% (seeds) in discriminating between grape varieties was achieved when comparing the different fractions. In general, 7 PS derivatives were identified with ID scores

  7. Bridging the gap between comprehensive extraction protocols in plant metabolomics studies and method validation.

    Science.gov (United States)

    Bijttebier, Sebastiaan; Van der Auwera, Anastasia; Foubert, Kenn; Voorspoels, Stefan; Pieters, Luc; Apers, Sandra

    2016-09-01

    It is vital to pay much attention to the design of extraction methods developed for plant metabolomics, as any non-extracted or converted metabolites will greatly affect the overall quality of the metabolomics study. Method validation is however often omitted in plant metabolome studies, as the well-established methodologies for classical targeted analyses such as recovery optimization cannot be strictly applied. The aim of the present study is to thoroughly evaluate state-of-the-art comprehensive extraction protocols for plant metabolomics with liquid chromatography-photodiode array-accurate mass mass spectrometry (LC-PDA-amMS) by bridging the gap with method validation. Validation of an extraction protocol in untargeted plant metabolomics should ideally be accomplished by validating the protocol for all possible outcomes, i.e. for all secondary metabolites potentially present in the plant. In an effort to approach this ideal validation scenario, two plant matrices were selected based on their wide versatility of phytochemicals: meadowsweet (Filipendula ulmaria) for its polyphenols content, and spicy paprika powder (from the genus Capsicum) for its apolar phytochemicals content (carotenoids, phytosterols, capsaicinoids). These matrices were extracted with comprehensive extraction protocols adapted from literature and analysed with a generic LC-PDA-amMS characterization platform that was previously validated for broad range phytochemical analysis. The performance of the comprehensive sample preparation protocols was assessed based on extraction efficiency, repeatability and intermediate precision and on ionization suppression/enhancement evaluation. The manuscript elaborates on the finding that none of the extraction methods allowed to exhaustively extract the metabolites. Furthermore, it is shown that depending on the extraction conditions enzymatic degradation mechanisms can occur. Investigation of the fractions obtained with the different extraction methods

  8. 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.

  9. Discrimination of conventional and organic white cabbage from a long-term field trial study using untargeted LC-MS-based metabolomics

    DEFF Research Database (Denmark)

    Mie, Axel; Laursen, Kristian Holst; Åberg, K. Magnus;

    2014-01-01

    The influence of organic and conventional farming practices on the content of single nutrients in plants is disputed in the scientific literature. Here, large-scale untargeted LC-MS-based metabolomics was used to compare the composition of white cabbage from organic and conventional agriculture, ...... cases. Thus, it was concluded that the investigated conventional and organic management practices have a systematic impact on the metabolome of white cabbage. This emphasizes the potential of untargeted metabolomics for authenticity testing of organic plant products....

  10. Field-based Metabolomics for Assessing Contaminated Surface Waters

    Science.gov (United States)

    Metabolomics is becoming well-established for studying chemical contaminant-induced alterations to normal biological function. For example, the literature contains a wealth of laboratory-based studies involving analysis of samples from organisms exposed to individual chemical tox...

  11. 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, no

  12. 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.

  13. A proposed framework for the description of plant metabolomics experiments and their results

    NARCIS (Netherlands)

    Jenkens, H.; Hardy, N.; Beckmann, M.; Draper, J.; Smith, A.R.; Taylor, J.; Fiehn, O.; Goodacre, R.; Bino, R.J.; Hall, R.D.; Kopka, J.; Lane, G.A.; Lange, B.M.; Liu, J.R.; Mendes, P.; Nikolau, B.J.; Oliver, S.G.; Paton, I.R.; Roessner-Tunali, U.; Saito, K.; Smedsgaard, J.; Sumner, L.W.; Wang, T.; Walsh, S.; Wurtele, E.S.; Kell, D.B.

    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 a

  14. 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 know...

  15. Are the metabolomic responses to folivory of closely related plant species linked to macroevolutionary and plant-folivore coevolutionary processes?

    Science.gov (United States)

    Rivas-Ubach, Albert; Hódar, José A; Sardans, Jordi; Kyle, Jennifer E; Kim, Young-Mo; Oravec, Michal; Urban, Otmar; Guenther, Alex; Peñuelas, Josep

    2016-07-01

    The debate whether the coevolution of plants and insects or macroevolutionary processes (phylogeny) is the main driver determining the arsenal of molecular defensive compounds of plants remains unresolved. Attacks by herbivorous insects affect not only the composition of defensive compounds in plants but also the entire metabolome. Metabolomes are the final products of genotypes and are constrained by macroevolutionary processes, so closely related species should have similar metabolomic compositions and may respond in similar ways to attacks by folivores. We analyzed the elemental compositions and metabolomes of needles from three closely related Pinus species with distant coevolutionary histories with the caterpillar of the processionary moth respond similarly to its attack. All pines had different metabolomes and metabolic responses to herbivorous attack. The metabolomic variation among the species and the responses to folivory reflected their macroevolutionary relationships, with P. pinaster having the most divergent metabolome. The concentrations of terpenes were in the attacked trees supporting the hypothesis that herbivores avoid plant individuals with higher concentrations. Our results suggest that macroevolutionary history plays important roles in the metabolomic responses of these pine species to folivory, but plant-insect coevolution probably constrains those responses. Combinations of different evolutionary factors and trade-offs are likely responsible for the different responses of each species to folivory, which is not necessarily exclusively linked to plant-insect coevolution. PMID:27386082

  16. MeRy-B: a web knowledgebase for the storage, visualization, analysis and annotation of plant NMR metabolomic profiles

    Directory of Open Access Journals (Sweden)

    Bernillon Stéphane

    2011-06-01

    Full Text Available Abstract Background Improvements in the techniques for metabolomics analyses and growing interest in metabolomic approaches are resulting in the generation of increasing numbers of metabolomic profiles. Platforms are required for profile management, as a function of experimental design, and for metabolite identification, to facilitate the mining of the corresponding data. Various databases have been created, including organism-specific knowledgebases and analytical technique-specific spectral databases. However, there is currently no platform meeting the requirements for both profile management and metabolite identification for nuclear magnetic resonance (NMR experiments. Description MeRy-B, the first platform for plant 1H-NMR metabolomic profiles, is designed (i to provide a knowledgebase of curated plant profiles and metabolites obtained by NMR, together with the corresponding experimental and analytical metadata, (ii for queries and visualization of the data, (iii to discriminate between profiles with spectrum visualization tools and statistical analysis, (iv to facilitate compound identification. It contains lists of plant metabolites and unknown compounds, with information about experimental conditions, the factors studied and metabolite concentrations for several plant species, compiled from more than one thousand annotated NMR profiles for various organs or tissues. Conclusion MeRy-B manages all the data generated by NMR-based plant metabolomics experiments, from description of the biological source to identification of the metabolites and determinations of their concentrations. It is the first database allowing the display and overlay of NMR metabolomic profiles selected through queries on data or metadata. MeRy-B is available from http://www.cbib.u-bordeaux2.fr/MERYB/index.php.

  17. Are the metabolomic responses to folivory of closely related plant species linked to macroevolutionary and plant-folivore coevolutionary processes?

    Energy Technology Data Exchange (ETDEWEB)

    Rivas Ubach, Albert; Hodar, Jose A.; Sardans, J.; Kyle, Jennifer E.; Kim, Young-Mo; Oravec, Michal; Urban, Otmar; Guenther, Alex B.; Penuelas, Josep

    2016-06-02

    The debate whether the coevolution of plants and insects or macroevolutionary processes (phylogeny) is the main driver determining the arsenal of molecular defensive compounds of plants remains unresolved. Attacks by herbivorous insects affect not only the composition of defensive compounds in plants but the entire metabolome (the set of molecular metabolites), including defensive compounds. Metabolomes are the final products of genotypes and are directly affected by macroevolutionary processes, so closely related species should have similar metabolomic compositions and may respond in similar ways to attacks by folivores. We analyzed the elemental compositions and metabolomes of needles from Pinus pinaster, P. nigra and P. sylvestris to determine if these closely related Pinus species with different coevolutionary histories with the caterpillars of the processionary moth respond similarly to attacks by this lepidopteran. All pines had different metabolomes and metabolic responses to herbivorous attack. The metabolomic variation among the pine species and the responses to folivory reflected their macroevolutionary relationships, with P. pinaster having the most divergent metabolome. The concentrations of phenolic metabolites were generally not higher in the attacked trees, which had lower concentrations of terpenes, suggesting that herbivores avoid individuals with high concentrations of terpenes. Our results suggest that macroevolutionary history plays important roles in the metabolomic responses of these pine species to folivory, but plant-insect coevolution probably constrains those responses. Combinations of different evolutionary factors and trade-offs are likely responsible for the different responses of each species to folivory, which is not necessarily exclusively linked to plant-insect coevolution.

  18. Metabolomics in Plants and Humans: Applications in the Prevention and Diagnosis of Diseases

    Directory of Open Access Journals (Sweden)

    Diego F. Gomez-Casati

    2013-01-01

    Full Text Available 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.

  19. NMR-based Metabolomics for Cancer Research

    Science.gov (United States)

    Metabolomics is considered as a complementary tool to other omics platforms to provide a snapshot of the cellular biochemistry and physiology taking place at any instant. Metabolmics approaches have been widely used to provide comprehensive and quantitative analyses of the metabo...

  20. 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 biochemic

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

    NARCIS (Netherlands)

    Macel, M.; Vos, de R.C.H.; Jansen, J.J.; Putten, van der W.H.; Dam, van N.M.

    2014-01-01

    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 co

  2. Discrimination of conventional and organic white cabbage from a long-term field trial study using untargeted LC-MS-based metabolomics

    DEFF Research Database (Denmark)

    Mie, Axel; Laursen, Kristian Holst; Åberg, K. Magnus;

    2014-01-01

    The influence of organic and conventional farming practices on the content of single nutrients in plants is disputed in the scientific literature. Here, large-scale untargeted LC-MS-based metabolomics was used to compare the composition of white cabbage from organic and conventional agriculture, ...... % of cases. Thus, it was concluded that the investigated conventional and organic management practices have a systematic impact on the metabolome of white cabbage. This emphasizes the potential of untargeted metabolomics for authenticity testing of organic plant products....

  3. Spatially-resolved in vivo plant metabolomics by laser ablation-based mass spectrometry imaging (MSI techniques: LDI-MSI and LAESI

    Directory of Open Access Journals (Sweden)

    Aleš eSvatoš

    2015-07-01

    Full Text Available This short review aims to summarize the current developments and applications of mass spectrometry-based methods for in situ profiling and imaging of plants with minimal or no sample pre-treatment or manipulation. Infrared-laser ablation electrospray ionization (LAESI and UV-laser desorption/ionization (LDI methods are reviewed. The underlying mechanisms of the ionization techniques - namely, laser ablation of biological samples and electrospray ionization - as well as variations of the LAESI ion source for specific targets of interest are described.

  4. Advances in metabolomic applications in plant genetics and breeding

    Science.gov (United States)

    Metabolomics is a systems biology discipline wherein abundances of endogenous metabolites from biological samples are identified and quantitatively measured across a large range of metabolites and/or a large number of samples. Since all developmental, physiological and response to the environment ph...

  5. Metabolomic characteristics of Catharanthus roseus plants in time and space

    NARCIS (Netherlands)

    Qifang, Pan; Qifang, Pan

    2014-01-01

    The thesis aims at combining metabolomics with other methods to investigate the regulation of the TIA biosynthesis and how this is connected with other pathways and the plant’s physiology and development. It reviews the biosynthesis studies of Catharanthus roseus. An HPLC method is described for bot

  6. Plant Metabolomics and Its Potential for Systems Biology Research: Background Concepts, Technology, and Methodology

    NARCIS (Netherlands)

    Allwood, J.W.; Vos, de C.H.; Moing, A.; Deborde, C.; Erban, A.; Kopka, J.; Goodacre, R.; Hall, R.D.

    2011-01-01

    The "metabolome" comprises the entire complement of small molecules in a plant or any other organism. It represents the ultimate phenotype of cells, deduced from the perturbation of gene expression and the modulation of protein function, as well as environmental cues. Extensive advances over the pas

  7. Discovery and validation of urinary exposure markers for different plant foods by untargeted metabolomics

    DEFF Research Database (Denmark)

    Andersen, Maj-Britt Schmidt; Kristensen, Mette; Manach, Claudine;

    2014-01-01

    While metabolomics is increasingly used to investigate the food metabolome and identify new markers of food exposure, limited attention has been given to the validation of such markers. The main objectives of the present study were to (1) discover potential food exposure markers (PEMs) for a range...... of plant foods in a study setting with a mixed dietary background and (2) validate PEMs found in a previous meal study. Three-day weighed dietary records and 24-h urine samples were collected three times during a 6-month parallel intervention study from 107 subjects randomized to two distinct dietary...... patterns. An untargeted UPLC-qTOF-MS metabolomics analysis was performed on the urine samples, and all features detected underwent strict data analyses, including an iterative paired t test and sensitivity and specificity analyses for foods. A total of 22 unique PEMs were identified that covered 7 out...

  8. NMR-based Metabolomics Applications in Biological and Environmental Science

    Science.gov (United States)

    As a complimentary tool to other omics platforms, metabolomics is increasingly being used bybiologists to study the dynamic response of biological systems (cells, tissues, or wholeorganisms) under diverse physiological or pathological conditions. Metabolomics deals with the quali...

  9. LC-MS based Metabolomics Analysis to Identify Potential Allelochemicals in Wedelia trilobata

    Directory of Open Access Journals (Sweden)

    Kamalrul Azlan Azizan

    2016-05-01

    Full Text Available Wedelia trilobata is a noxious invasive weed that has been widely cultivated as a decorative and groundcover plant. The plant has been reported to contain diverse bioactive compounds with a broad spectrum of biological activities including allelochemicals. Allelochemicals contribute to allelopathy interactions that suppress the growth and development of nearby plants. Several studies have reported the allelopathic potential of W. trilobata and its negative effects to crop plants. However, relatively little is known about the allelochemicals’ composition and how allelochemicals contribute to the allelopathic behavior of this plant. In order to prove allelopathy, the identification of the causative allelochemicals is required. The identification of potential allelochemicals that serve as biomarkers could be useful for assessing allelopathy interactions. In this study, a liquid chromatography (LC based metabolomics approach was applied to find biomarkers with allelopathic effects from W. trilobata. Ethanol and water were used to extract metabolites from the leaves of W. trilobata and analyzed using liquid chromatography coupled with quadrupole high-resolution time of flight mass spectrometry (LC-QTOF-MS. Using multivariate statistical analysis (MVA, we identified eight Rt-m/z pairs as candidate marker compounds for assessing allelopathy interactions of W. trilobata. The results highlight the application of metabolomics for understanding of the role of allelochemicals in allelopathy interactions of W. trilobata .

  10. Stable Isotope-Assisted Evaluation of Different Extraction Solvents for Untargeted Metabolomics of Plants

    Science.gov (United States)

    Doppler, Maria; Kluger, Bernhard; Bueschl, Christoph; Schneider, Christina; Krska, Rudolf; Delcambre, Sylvie; Hiller, Karsten; Lemmens, Marc; Schuhmacher, Rainer

    2016-01-01

    The evaluation of extraction protocols for untargeted metabolomics approaches is still difficult. We have applied a novel stable isotope-assisted workflow for untargeted LC-HRMS-based plant metabolomics , which allows for the first time every detected feature to be considered for method evaluation. The efficiency and complementarity of commonly used extraction solvents, namely 1 + 3 (v/v) mixtures of water and selected organic solvents (methanol, acetonitrile or methanol/acetonitrile 1 + 1 (v/v)), with and without the addition of 0.1% (v/v) formic acid were compared. Four different wheat organs were sampled, extracted and analysed by LC-HRMS. Data evaluation was performed with the in-house-developed MetExtract II software and R. With all tested solvents a total of 871 metabolites were extracted in ear, 785 in stem, 733 in leaf and 517 in root samples, respectively. Between 48% (stem) and 57% (ear) of the metabolites detected in a particular organ were found with all extraction mixtures, and 127 of 996 metabolites were consistently shared between all extraction agent/organ combinations. In aqueous methanol, acidification with formic acid led to pronounced pH dependency regarding the precision of metabolite abundance and the number of detectable metabolites, whereas extracts of acetonitrile-containing mixtures were less affected. Moreover, methanol and acetonitrile have been found to be complementary with respect to extraction efficiency. Interestingly, the beneficial properties of both solvents can be combined by the use of a water-methanol-acetonitrile mixture for global metabolite extraction instead of aqueous methanol or aqueous acetonitrile alone. PMID:27367667

  11. Stable Isotope-Assisted Evaluation of Different Extraction Solvents for Untargeted Metabolomics of Plants

    Directory of Open Access Journals (Sweden)

    Maria Doppler

    2016-06-01

    Full Text Available The evaluation of extraction protocols for untargeted metabolomics approaches is still difficult. We have applied a novel stable isotope-assisted workflow for untargeted LC-HRMS-based plant metabolomics , which allows for the first time every detected feature to be considered for method evaluation. The efficiency and complementarity of commonly used extraction solvents, namely 1 + 3 (v/v mixtures of water and selected organic solvents (methanol, acetonitrile or methanol/acetonitrile 1 + 1 (v/v, with and without the addition of 0.1% (v/v formic acid were compared. Four different wheat organs were sampled, extracted and analysed by LC-HRMS. Data evaluation was performed with the in-house-developed MetExtract II software and R. With all tested solvents a total of 871 metabolites were extracted in ear, 785 in stem, 733 in leaf and 517 in root samples, respectively. Between 48% (stem and 57% (ear of the metabolites detected in a particular organ were found with all extraction mixtures, and 127 of 996 metabolites were consistently shared between all extraction agent/organ combinations. In aqueous methanol, acidification with formic acid led to pronounced pH dependency regarding the precision of metabolite abundance and the number of detectable metabolites, whereas extracts of acetonitrile-containing mixtures were less affected. Moreover, methanol and acetonitrile have been found to be complementary with respect to extraction efficiency. Interestingly, the beneficial properties of both solvents can be combined by the use of a water-methanol-acetonitrile mixture for global metabolite extraction instead of aqueous methanol or aqueous acetonitrile alone.

  12. New frontiers in pharmaceutical analysis: A metabolomic approach to check batch compliance of complex products based on natural substances.

    Science.gov (United States)

    Mattoli, L; Burico, M; Fodaroni, G; Tamimi, S; Bedont, S; Traldi, P; Stocchero, M

    2016-07-15

    Natural substances, particularly medicinal plants and their extracts, are still today intended as source for new Active Pharmaceutical Ingredients (APIs). Alternatively they can be validly employed to prepare medicines, food supplements or medical devices. The most adopted analytical approach used to verify quality of natural substances like medicinal plants is based still today on the traditional quantitative determination of marker compounds and/or active ingredients, besides the acquisition of a fingerprint by TLC, NIR, HPLC, GC. Here a new analytical approach based on untargeted metabolomic fingerprinting by means of Mass Spectrometry (MS) to verify the quality of grinTuss adulti syrup, a complex products based on medicinal plants, is proposed. Recently, untargeted metabolomic has been successfully applied to assess quality of natural substances, plant extracts, as well as corresponding formulated products, being the complexity a resource but not necessarily a limit. The untargeted metabolomic fingerprinting includes the monitoring of the main constituents, giving weighted relevance to the most abundant ones, but also considering minor components, that might be notable in view of an integrated - often synergistic - effect on the biological system. Two different years of production were investigated. The collected samples were analyzed by Flow Injection ElectroSpray Ionization Mass Spectrometry Analysis (FIA-ESI-MS) and a suitable data processing procedure was developed to transform the MS spectra into robust fingerprints. Multivariate Statistical Process Control (MSPC) was applied in order to obtain multivariate control charts that were validated to prove the effectiveness of the proposed method. PMID:27155737

  13. 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.

  14. Metabolomics-based discovery of diagnostic biomarkers for onchocerciasis.

    Directory of Open Access Journals (Sweden)

    Judith R Denery

    Full Text Available BACKGROUND: Development of robust, sensitive, and reproducible diagnostic tests for understanding the epidemiology of neglected tropical diseases is an integral aspect of the success of worldwide control and elimination programs. In the treatment of onchocerciasis, clinical diagnostics that can function in an elimination scenario are non-existent and desperately needed. Due to its sensitivity and quantitative reproducibility, liquid chromatography-mass spectrometry (LC-MS based metabolomics is a powerful approach to this problem. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of an African sample set comprised of 73 serum and plasma samples revealed a set of 14 biomarkers that showed excellent discrimination between Onchocerca volvulus-positive and negative individuals by multivariate statistical analysis. Application of this biomarker set to an additional sample set from onchocerciasis endemic areas where long-term ivermectin treatment has been successful revealed that the biomarker set may also distinguish individuals with worms of compromised viability from those with active infection. Machine learning extended the utility of the biomarker set from a complex multivariate analysis to a binary format applicable for adaptation to a field-based diagnostic, validating the use of complex data mining tools applied to infectious disease biomarker discovery and diagnostic development. CONCLUSIONS/SIGNIFICANCE: An LC-MS metabolomics-based diagnostic has the potential to monitor the progression of onchocerciasis in both endemic and non-endemic geographic areas, as well as provide an essential tool to multinational programs in the ongoing fight against this neglected tropical disease. Ultimately this technology can be expanded for the diagnosis of other filarial and/or neglected tropical diseases.

  15. Nuclear magnetic resonance based metabolomics and liver diseases: Recent advances and future clinical applications.

    Science.gov (United States)

    Amathieu, Roland; Triba, Mohamed Nawfal; Goossens, Corentine; Bouchemal, Nadia; Nahon, Pierre; Savarin, Philippe; Le Moyec, Laurence

    2016-01-01

    Metabolomics is defined as the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. It is an "omics" technique that is situated downstream of genomics, transcriptomics and proteomics. Metabolomics is recognized as a promising technique in the field of systems biology for the evaluation of global metabolic changes. During the last decade, metabolomics approaches have become widely used in the study of liver diseases for the detection of early biomarkers and altered metabolic pathways. It is a powerful technique to improve our pathophysiological knowledge of various liver diseases. It can be a useful tool to help clinicians in the diagnostic process especially to distinguish malignant and non-malignant liver disease as well as to determine the etiology or severity of the liver disease. It can also assess therapeutic response or predict drug induced liver injury. Nevertheless, the usefulness of metabolomics is often not understood by clinicians, especially the concept of metabolomics profiling or fingerprinting. In the present work, after a concise description of the different techniques and processes used in metabolomics, we will review the main research on this subject by focusing specifically on in vitro proton nuclear magnetic resonance spectroscopy based metabolomics approaches in human studies. We will first consider the clinical point of view enlighten physicians on this new approach and emphasis its future use in clinical "routine".

  16. Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites

    Directory of Open Access Journals (Sweden)

    Miroslava Cuperlovic-Culf

    2016-09-01

    Full Text Available Fusarium head blight (FHB, primarily caused by Fusarium graminearum, is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum, such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

  17. Effect of acute stresses on zebra fish (Danio rerio) metabolome measured by NMR-based metabolomics.

    Science.gov (United States)

    Mushtaq, Mian Yahya; Marçal, Rosilene Moretti; Champagne, Danielle L; van der Kooy, Frank; Verpoorte, Robert; Choi, Young Hae

    2014-09-01

    We applied an acute stress model to zebra fish in order to measure the changes in the metabolome due to biological stress. This was done by submitting the fish to fifteen minutes of acute confinement (netting) stress, and then five minutes for the open field and light/dark field tests. A polar extract of the zebra fish was then subjected to (1)H nuclear magnetic spectroscopy. Multivariate data analysis of the spectra showed a clear separation associated to a wide range of metabolites between zebra fish that were submitted to open field and light/dark field tests. Alanine, taurine, adenosine, creatine, lactate, and histidine were high in zebra fish to which the light/dark field test was applied, regardless of stress, while acetate and isoleucine/lipids appeared to be higher in zebra fish exposed to the open field test. These results show that any change in the environment, even for a small period of time, has a noticeable physiological impact. This research provides an insight of how different mechanisms are activated under different environments to maintain the homeostasis of the body. It should also contribute to establish zebra fish as a model for metabolomics studies. PMID:25098933

  18. Untargeted Metabolomics of Tomato Plants after Root-Knot Nematode Infestation.

    Science.gov (United States)

    Eloh, Kodjo; Sasanelli, Nicola; Maxia, Andrea; Caboni, Pierluigi

    2016-07-27

    After 2 months from the infestation of tomato plants with the root-knot nematode (RKN) Meloidogyne incognita, we performed a gas chromatography-mass spectrometry untargeted fingerprint analysis for the identification of characteristic metabolites and biomarkers. Principal component analysis, and orthogonal projections to latent structures discriminant analysis suggested dramatic local changes of the plant metabolome. In the case of tomato leaves, β-alanine, phenylalanine, and melibiose were induced in response to RKN stimuli, while ribose, glycerol, myristic acid, and palmitic acid were reduced. For tomato stems, upregulated metabolites were ribose, sucrose, fructose, and glucose, while fumaric acid and glycine were downregulated. The variation in molecular strategies to the infestation of RKNs may play an important role in how Solanum lycopersicum and other plants adapt to nematode parasitic stress. PMID:27389052

  19. Improved batch correction in untargeted MS-based metabolomics

    NARCIS (Netherlands)

    Wehrens, Ron; Hageman, Jos A.; Eeuwijk, van Fred; Kooke, Rik; Flood, Pádraic J.; Wijnker, Erik; Keurentjes, Joost J.B.; Lommen, Arjen; Eekelen, van Henriëtte D.L.M.; Hall, Robert D.; Mumm, Roland; Vos, de Ric C.H.

    2016-01-01

    Introduction: Batch effects in large untargeted metabolomics experiments are almost unavoidable, especially when sensitive detection techniques like mass spectrometry (MS) are employed. In order to obtain peak intensities that are comparable across all batches, corrections need to be performed. S

  20. Genetic algorithm based two-mode clustering of metabolomics data

    NARCIS (Netherlands)

    Hageman, J.A.; Berg, R.A. van den; Westerhuis, J.A.; Werf, M.J. van der; 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 metho

  1. (1)H NMR based metabolomics approach to study the toxic effects of herbicide butachlor on goldfish (Carassius auratus).

    Science.gov (United States)

    Xu, Hua-Dong; Wang, Jun-Song; Li, Ming-Hui; Liu, Yan; Chen, Ting; Jia, Ai-Qun

    2015-02-01

    Butachlor, one of the most widely used herbicides in agriculture, has been reported with high ecotoxicity to aquatic plants and animals. In this study, a (1)H NMR based metabolomics approach combined with histopathological examination and biochemical assays was applied to comprehensively investigate the toxic effects of butachlor on four important organs (gill, brain, liver and kidney) of goldfish (Carassius auratus) for the first time. After 10 days' butachlor exposure at two dosages of 3.2 and 0.64 μmol/L, fish tissues (gill, brain, liver and kidney) and serum were collected. Histopathological inspection revealed severe impairment of gill filaments and obvious cellular edema in livers and kidneys. The increase of glutathione peroxidase (GSH-Px) activity in gill and methane dicarboxylic aldehyde (MDA) level in four tissues reflected the disturbance of antioxidative system in the intoxicated goldfish. Serum lactate dehydrogenase (LDH) activity and creatinine (CRE) level were increased in butachlor exposure groups, suggesting liver and kidney injuries induced by butachlor. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of NMR profiles disclosed metabolic changes that were related to the toxic effects of butachlor including oxidative stress, disorder of energy metabolism and amino acids metabolism, and disturbance of neurotransmitter balance in butachlor exposed goldfish. This integrated metabolomics approach provided a molecular basis underlying the toxicity of butachlor and demonstrated that metabolomics was a powerful and highly effective approach to elucidate the toxicity and underlying mechanisms of herbicides and pesticides, applicable for their risk assessment.

  2. NMR-based metabolomics of prostate cancer: a protagonist in clinical diagnostics.

    Science.gov (United States)

    Kumar, Deepak; Gupta, Ashish; Nath, Kavindra

    2016-06-01

    Advances in the application of NMR spectroscopy-based metabolomic profiling of prostate cancer comprises a potential tactic for understanding the impaired biochemical pathways arising due to a disease evolvement and progression. This technique involves qualitative and quantitative estimation of plethora of small molecular weight metabolites of body fluids or tissues using state-of-the-art chemometric methods delivering an important platform for translational research from basic to clinical, to reveal the pathophysiological snapshot in a single step. This review summarizes the present arrays and recent advancements in NMR-based metabolomics and a glimpse of currently used medical imaging tactics, with their role in clinical diagnosis of prostate cancer. PMID:26959614

  3. Post-acquisition filtering of salt cluster artefacts for LC-MS based human metabolomic studies.

    Science.gov (United States)

    McMillan, A; Renaud, J B; Gloor, G B; Reid, G; Sumarah, M W

    2016-01-01

    Liquid chromatography-high resolution mass spectrometry (LC-MS) has emerged as one of the most widely used platforms for untargeted metabolomics due to its unparalleled sensitivity and metabolite coverage. Despite its prevalence of use, the proportion of true metabolites identified in a given experiment compared to background contaminants and ionization-generated artefacts remains poorly understood. Salt clusters are well documented artefacts of electrospray ionization MS, recognized by their characteristically high mass defects (for this work simply generalized as the decimal numbers after the nominal mass). Exploiting this property, we developed a method to identify and remove salt clusters from LC-MS-based human metabolomics data using mass defect filtering. By comparing the complete set of endogenous metabolites in the human metabolome database to actual plasma, urine and stool samples, we demonstrate that up to 28.5 % of detected features are likely salt clusters. These clusters occur irrespective of ionization mode, column type, sweep gas and sample type, but can be easily removed post-acquisition using a set of R functions presented here. Our mass defect filter removes unwanted noise from LC-MS metabolomics datasets, while retaining true metabolites, and requires only a list of m/z and retention time values. Reducing the number of features prior to statistical analyses will result in more accurate multivariate modeling and differential feature selection, as well as decreased reporting of unknowns that often constitute the largest proportion of human metabolomics data. PMID:27606010

  4. Strategy for nuclear-magnetic-resonance-based metabolomics of human feces

    DEFF Research Database (Denmark)

    Lamichhane, Santosh; Yde, Christian Clement; Schmedes, Mette Søndergaard;

    2015-01-01

    Metabolomic analyses of fecal material are gaining increasing attention because the gut microbial ecology and activity have an impact on the human phenotype and regulate host metabolism. Sample preparation is a crucial step, and in this study we recommend a methodology for extraction and analysis...... of fresh feces by NMR-based metabolomics. The evaluation of extraction solvents showed that buffer extraction is a suitable approach to extract metabolic information in feces. So, the effects of weight-to-buffer (Wf:Vb) combinations and the effect of sonication and freeze-thaw cycles on the reproducibility...

  5. LC-MS-Based Metabolomic Investigation of Chemopreventive Phytochemical-Elicited Metabolic Events.

    Science.gov (United States)

    Wang, Lei; Yao, Dan; Chen, Chi

    2016-01-01

    Phytochemicals are under intensive investigation for their potential use as chemopreventive agents in blocking or suppressing carcinogenesis. Metabolic interactions between phytochemical and biological system play an important role in determining the efficacy and toxicity of chemopreventive phytochemicals. However, complexities of phytochemical biotransformation and intermediary metabolism pose challenges for studying phytochemical-elicited metabolic events. Metabolomics has become a highly effective technical platform to detect subtle changes in a complex metabolic system. Here, using green tea polyphenols as an example, we describe a workflow of LC-MS-based metabolomics study, covering the procedures and techniques in sample collection, preparation, LC-MS analysis, data analysis, and interpretation. PMID:26608291

  6. 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

  7. Discrimination of conventional and organic white cabbage from a long-term field trial study using untargeted LC-MS-based metabolomics.

    Science.gov (United States)

    Mie, Axel; Laursen, Kristian Holst; Åberg, K Magnus; Forshed, Jenny; Lindahl, Anna; Thorup-Kristensen, Kristian; Olsson, Marie; Knuthsen, Pia; Larsen, Erik Huusfeldt; Husted, Søren

    2014-05-01

    The influence of organic and conventional farming practices on the content of single nutrients in plants is disputed in the scientific literature. Here, large-scale untargeted LC-MS-based metabolomics was used to compare the composition of white cabbage from organic and conventional agriculture, measuring 1,600 compounds. Cabbage was sampled in 2 years from one conventional and two organic farming systems in a rigidly controlled long-term field trial in Denmark. Using Orthogonal Projection to Latent Structures-Discriminant Analysis (OPLS-DA), we found that the production system leaves a significant (p = 0.013) imprint in the white cabbage metabolome that is retained between production years. We externally validated this finding by predicting the production system of samples from one year using a classification model built on samples from the other year, with a correct classification in 83 % of cases. Thus, it was concluded that the investigated conventional and organic management practices have a systematic impact on the metabolome of white cabbage. This emphasizes the potential of untargeted metabolomics for authenticity testing of organic plant products. PMID:24618989

  8. 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.

  9. 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.

    Science.gov (United States)

    Marti, Guillaume; Schnee, Sylvain; Andrey, Yannis; Simoes-Pires, Claudia; Carrupt, Pierre-Alain; Wolfender, Jean-Luc; Gindro, Katia

    2014-01-01

    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. PMID:25197936

  10. Accurate mass error correction in liquid chromatography time-of-flight mass spectrometry based metabolomics

    NARCIS (Netherlands)

    Mihaleva, V.V.; Vorst, O.F.J.; Maliepaard, C.A.; Verhoeven, H.A.; Vos, de C.H.; Hall, R.D.; Ham, van R.C.H.J.

    2008-01-01

    Compound identification and annotation in (untargeted) metabolomics experiments based on accurate mass require the highest possible accuracy of the mass determination. Experimental LC/TOF-MS platforms equipped with a time-to-digital converter (TDC) give the best mass estimate for those mass signals

  11. NMR-based metabolomics for identification of α-amylase inhibitors in rowan berries (Sorbus spp.)

    DEFF Research Database (Denmark)

    Broholm, Sofie L.; Gramsbergen, Simone; Nyberg, Nils;

    Type 2 diabetes is a metabolic disorder estimated to affect millions of people all over the world.1 One way of reducing diabetes-related complications is to control postprandial glucose.2 Inhibition of the carbohydrate digestive enzyme α-amylase is a therapeutic target for maintaining low blood g...... a 1H-NMR method suitable for NMR-based metabolomics...

  12. 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 rele

  13. Recent Advances in the Application of Metabolomics to Studies of Biogenic Volatile Organic Compounds (BVOC Produced by Plant

    Directory of Open Access Journals (Sweden)

    Yoko Iijima

    2014-08-01

    Full Text Available In many plants, biogenic volatile organic compounds (BVOCs are produced as specialized metabolites that contribute to the characteristics of each plant. The varieties and composition of BVOCs are chemically diverse by plant species and the circumstances in which the plants grow, and also influenced by herbivory damage and pathogen infection. Plant-produced BVOCs are receptive to many organisms, from microorganisms to human, as both airborne attractants and repellants. In addition, it is known that some BVOCs act as signals to prime a plant for the defense response in plant-to-plant communications. The compositional profiles of BVOCs can, thus, have profound influences in the physiological and ecological aspects of living organisms. Apart from that, some of them are commercially valuable as aroma/flavor compounds for human. Metabolomic technologies have recently revealed new insights in biological systems through metabolic dynamics. Here, the recent advances in metabolomics technologies focusing on plant-produced BVOC analyses are overviewed. Their application markedly improves our knowledge of the role of BVOCs in chemosystematics, ecological influences, and aroma research, as well as being useful to prove the biosynthetic mechanisms of BVOCs.

  14. 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

    2016-01-01

    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. PMID:26467476

  15. A novel approach for LC-MS/MS-based chiral metabolomics fingerprinting and chiral metabolomics extraction using a pair of enantiomers of chiral derivatization reagents.

    Science.gov (United States)

    Takayama, Takahiro; Mochizuki, Toshiki; Todoroki, Kenichiro; Min, Jun Zhe; Mizuno, Hajime; Inoue, Koichi; Akatsu, Hiroyasu; Noge, Ichiro; Toyo'oka, Toshimasa

    2015-10-22

    Chiral metabolites are found in a wide variety of living organisms and some of them are understood to be physiologically active compounds and biomarkers. However, the overall analysis of chiral metabolomics is quite difficult due to the high number of metabolites, the significant diversity in their physicochemical properties, and concentration range from metabolite-to-metabolite. To solve this difficulty, we developed a novel approach for chiral metabolomics fingerprinting and chiral metabolomics extraction, which is based on the labeling of a pair of enantiomers of chiral derivatization reagents (i.e., DMT-(S,R)-Pro-OSu and DMT-3(S,R)-Apy) and precursor ion scan chromatography of the derivatives. The multivariate statistics is also required for this strategy. The proposed procedures were evaluated by the detection of a diagnostic marker (i.e., d-lactic acid) using the saliva of diabetic patients. This method was used for the determination of biomarker candidates of chiral amines and carboxyls in Alzheimer's disease (AD) brain homogenates. As the results, l-phenylalanine (L-Phe) and l-lactic acid (L-LA) were identified as the decreased and increased biomarker candidates in the AD brain, respectively. Therefore, the proposed approach seems to be helpful for the determination of non-target chiral metabolomics possessing amines and carboxyls. PMID:26526912

  16. Waste materials derived bio-effectors used as growth promoters for strawberry plants. An agronomic and metabolomic study

    Science.gov (United States)

    Vasileva, Brankica; Chami, Ziad Al; De Pascali, Sandra; Cavoski, Ivana; Fanizzi, Francesco Paolo

    2015-04-01

    Recently, a novel concept of bio-effectors has emerged to describe a group of products that are able to improve plant performance more than fertilizers. In this study, three different agro-industrial residues, i.e. brewers' spent grain (BSG), fennel processing residues (FPR) and lemon processing residues (LPR) were chosen as potential bio-effectors. A greenhouse soilless pot experiment was conducted on strawberry plants (Fragaria x ananassa var. Festival) in order to study the effect of BSG, FPR and LPR water extracts, at different concentrations, on plant growth and fruit quality. Their effect was compared with humic-like substances as a positive/reference control (Ctrl+) and with Hoagland solution as a negative control (Ctrl-). Agronomic parameters and the nutrient uptake were measured on shoots, roots and fruits. Metabolomic profiling tests were carried out on leaves, roots and fruit juices through the NMR technique. Plants treated with the FPR extract showed better vegetative growth, while plants treated with the BSG extract gave higher yield and better fruit size. Metabolomic profiling showed that fruits and roots of plants treated with FPR and LPR extracts had higher concentrations of sucrose, malate and acetate, while BSG treated plants had higher concentrations of citrate and β-glucose. In conclusion, according to the results achieved, the bio-effectors used in this study promote plant growth and fruit quality regardless of their nutritional content. Keywords: bio-effectors, agro-industrial waste, nuclear magnetic resonance (NMR), strawberry, growth promotion, fruit quality.

  17. Toward the comprehensive understanding of the gut ecosystem via metabolomics-based integrated omics approach.

    Science.gov (United States)

    Aw, Wanping; Fukuda, Shinji

    2015-01-01

    Recent advances in DNA sequencing and mass spectrometry technologies have allowed us to collect more data on microbiome and metabolome to assess the influence of the gut microbiota on human health at a whole-systems level. Major advances in metagenomics and metabolomics technologies have shown that the gut microbiota contributes to host overall health status to a large extent. As such, the gut microbiota is often likened to a measurable and functional organ consisting of prokaryotic cells, which creates the unique gut ecosystem together with the host eukaryotic cells. In this review, we discuss in detail the relationship between gut microbiota and its metabolites like choline, bile acids, phenols, and short-chain fatty acids in the host health and etiopathogenesis of various pathological states such as multiple sclerosis, autism, obesity, diabetes, and chronic kidney disease. By integrating metagenomic and metabolomic information on a systems biology-wide approach, we would be better able to understand this interplay between gut microbiome and host metabolism. Integration of the microbiome, metatranscriptome, and metabolome information will pave the way toward an improved holistic understanding of the complex mammalian superorganism. Through the modeling of metabolic interactions between lifestyle, diet, and microbiota, integrated omics-based understanding of the gut ecosystem is the new avenue, providing exciting novel therapeutic approaches for optimal host health. PMID:25338280

  18. NMR-based metabolomics in human disease diagnosis: Applications, limitations, and recommendations

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2013-04-03

    Metabolomics is a dynamic and emerging research field, similar to proteomics, transcriptomics and genomics in affording global understanding of biological systems. It is particularly useful in functional genomic studies in which metabolism is thought to be perturbed. Metabolomics provides a snapshot of the metabolic dynamics that reflect the response of living systems to both pathophysiological stimuli and/or genetic modification. Because this approach makes possible the examination of interactions between an organism and its diet or environment, it is particularly useful for identifying biomarkers of disease processes that involve the environment. For example, the interaction of a high fat diet with cardiovascular disease can be studied via such a metabolomics approach by modeling the interaction between genes and diet. The high reproducibility of NMR-based techniques gives this method a number of advantages over other analytical techniques in large-scale and long-term metabolomic studies, such as epidemiological studies. This approach has been used to study a wide range of diseases, through the examination of biofluids, including blood plasma/serum, urine, blister fluid, saliva and semen, as well as tissue extracts and intact tissue biopsies. However, complicating the use of NMR spectroscopy in biomarker discovery is the fact that numerous variables can effect metabolic composition including, fasting, stress, drug administration, diet, gender, age, physical activity, life style and the subject\\'s health condition. To minimize the influence of these variations in the datasets, all experimental conditions including sample collection, storage, preparation as well as NMR spectroscopic parameters and data analysis should be optimized carefully and conducted in an identical manner as described by the local standard operating protocol. This review highlights the potential applications of NMR-based metabolomics studies and gives some recommendations to improve sample

  19. Metabolomics-Based Screening of Biofilm-Inhibitory Compounds against Pseudomonas aeruginosa from Burdock Leaf

    Directory of Open Access Journals (Sweden)

    Zaixiang Lou

    2015-09-01

    Full Text Available Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg·mL−1. Then, the chemical composition of burdock leaf fraction was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS and 11 active compounds (chlorogenic acid, caffeic acid, p-coumaric acid, quercetin, ursolic acid, rutin, cynarin, luteolin, crocin, benzoic acid, and Tenacissoside I were identified. Lastly, UPLC-MS analysis was employed to obtain the metabolic fingerprints of burdock leaf fractions before and after inhibiting the biofilm of Pseudomonas aeruginosa. The metabolic fingerprints were transformed to data, analyzed with PLS-DA (partial least squares discriminant analysis and the peaks whose area was significantly changed were found out. Thus, 81 compounds were screened as potential anti-biofilm ingredients. Among them, rutin, ursolic acid, caffeic acid, p-coumaric acid and quercetin were identified and confirmed as the main anti-biofilm compounds in burdock leaf. The study provided basic anti-biofilm profile data for the compounds in burdock leaf, as well as provided a convenient method for fast screening of anti-biofilm compounds from natural plants.

  20. Metabolomics-Based Screening of Biofilm-Inhibitory Compounds against Pseudomonas aeruginosa from Burdock Leaf.

    Science.gov (United States)

    Lou, Zaixiang; Tang, Yuxia; Song, Xinyi; Wang, Hongxin

    2015-01-01

    Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg·mL(-1). Then, the chemical composition of burdock leaf fraction was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and 11 active compounds (chlorogenic acid, caffeic acid, p-coumaric acid, quercetin, ursolic acid, rutin, cynarin, luteolin, crocin, benzoic acid, and Tenacissoside I) were identified. Lastly, UPLC-MS analysis was employed to obtain the metabolic fingerprints of burdock leaf fractions before and after inhibiting the biofilm of Pseudomonas aeruginosa. The metabolic fingerprints were transformed to data, analyzed with PLS-DA (partial least squares discriminant analysis) and the peaks whose area was significantly changed were found out. Thus, 81 compounds were screened as potential anti-biofilm ingredients. Among them, rutin, ursolic acid, caffeic acid, p-coumaric acid and quercetin were identified and confirmed as the main anti-biofilm compounds in burdock leaf. The study provided basic anti-biofilm profile data for the compounds in burdock leaf, as well as provided a convenient method for fast screening of anti-biofilm compounds from natural plants. PMID:26370951

  1. Nutri-metabolomics: subtle serum metabolic differences in healthy subjects by NMR-based metabolomics after a short-term nutritional intervention with two tomato sauces.

    Science.gov (United States)

    Bondia-Pons, Isabel; Cañellas, Nicolau; Abete, Itziar; Rodríguez, Miguel Ángel; Perez-Cornago, Aurora; Navas-Carretero, Santiago; Zulet, M Ángeles; Correig, Xavier; Martínez, J Alfredo

    2013-12-01

    Postgenomics research and development is witnessing novel intersections of omics data intensive technology and applications in health and personalized nutrition. Chief among these is the nascent field of nutri-metabolomics that harnesses metabolomics platforms to discern person-to-person variations in nutritional responses. To this end, differences in the origin and ripening stage of fruits might have a strong impact on their phytochemical composition, and consequently, on their potential nutri-metabolomics effects on health. The objective of the present study was to evaluate the effects of a 4-week cross-over nutritional intervention on the metabolic status of 24 young healthy subjects. The intervention was carried out with two tomato sauces differing in their natural lycopene content, which was achieved by using tomatoes harvested at different times. Blood samples were drawn from each subject before and after each intervention period. Aqueous and lipid extracts from serum samples were analyzed by 1H-NMR metabolic profiling combined with analysis of variance simultaneous component analysis (ASCA) and multilevel simultaneous component analysis (MSCA). These methods allowed the interpretation of the variation induced by the main factors of the study design (sauce treatment and time). The levels of creatine, creatinine, leucine, choline, methionine, and acetate in aqueous extracts were increased after the intervention with the high-lycopene content sauce, while those of ascorbic acid, lactate, pyruvate, isoleucine, alanine were increased after the normal-lycopene content sauce. In conclusion, NMR-based metabolomics of aqueous and lipid extracts allowed the detection of different metabolic changes after the nutritional intervention. This outcome might partly be due to the different ripening state of the fruits used in production of the tomato sauces. The findings presented herein collectively attest to the emergence of the field of nutri-metabolomics as a novel

  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. Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

    DEFF Research Database (Denmark)

    Huang, Sijia; Chong, Nicole; Lewis, Nathan;

    2016-01-01

    .993. Moreover, important metabolic pathways, such as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate pathway, are revealed as critical biological pathways for early diagnosis of breast cancer. Conclusions: We have successfully developed a new type of pathway-based model to study....... Methods: We propose that higher-order functional representation of metabolomics data, such as pathway-based metabolomic features, can be used as robust biomarkers for breast cancer. Towards this, we have developed a new computational method that uses personalized pathway dysregulation scores for disease...... diagnosis. We applied this method to predict breast cancer occurrence, in combination with correlation feature selection (CFS) and classification methods. Results: The resulting all-stage and early-stage diagnosis models are highly accurate in two sets of testing blood samples, with average AUCs (Area Under...

  4. NMR-based stable isotope resolved metabolomics in systems biochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Teresa W-M. [University of Louisville, Department of Chemistry (United States); Lane, Andrew N., E-mail: anlane01@louisville.edu [University of Louisville, Center for Regulatory Environmental Analytical Metabolomics (United States)

    2011-04-15

    An important goal of metabolomics is to characterize the changes in metabolic networks in cells or various tissues of an organism in response to external perturbations or pathologies. The profiling of metabolites and their steady state concentrations does not directly provide information regarding the architecture and fluxes through metabolic networks. This requires tracer approaches. NMR is especially powerful as it can be used not only to identify and quantify metabolites in an unfractionated mixture such as biofluids or crude cell/tissue extracts, but also determine the positional isotopomer distributions of metabolites derived from a precursor enriched in stable isotopes such as {sup 13}C and {sup 15}N via metabolic transformations. In this article we demonstrate the application of a variety of 2-D NMR editing experiments to define the positional isotopomers of compounds present in polar and non-polar extracts of human lung cancer cells grown in either [U-{sup 13}C]-glucose or [U-{sup 13}C,{sup 15}N]-glutamine as source tracers. The information provided by such experiments enabled unambiguous reconstruction of metabolic pathways, which is the foundation for further metabolic flux modeling.

  5. Metabolomics-Based Screening of Biofilm-Inhibitory Compounds against Pseudomonas aeruginosa from Burdock Leaf

    OpenAIRE

    Zaixiang Lou; Yuxia Tang; Xinyi Song; Hongxin Wang

    2015-01-01

    Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg·mL−1. Then, the chemical composition of burdock leaf fraction was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and 11 active compounds (chlorogenic acid, caffeic acid, p-coumaric acid, quercetin, ursolic aci...

  6. Metabolome based reaction graphs of M. tuberculosis and M. leprae: a comparative network analysis.

    Directory of Open Access Journals (Sweden)

    Ketki D Verkhedkar

    Full Text Available BACKGROUND: Several types of networks, such as transcriptional, metabolic or protein-protein interaction networks of various organisms have been constructed, that have provided a variety of insights into metabolism and regulation. Here, we seek to exploit the reaction-based networks of three organisms for comparative genomics. We use concepts from spectral graph theory to systematically determine how differences in basic metabolism of organisms are reflected at the systems level and in the overall topological structures of their metabolic networks. METHODOLOGY/PRINCIPAL FINDINGS: Metabolome-based reaction networks of Mycobacterium tuberculosis, Mycobacterium leprae and Escherichia coli have been constructed based on the KEGG LIGAND database, followed by graph spectral analysis of the network to identify hubs as well as the sub-clustering of reactions. The shortest and alternate paths in the reaction networks have also been examined. Sub-cluster profiling demonstrates that reactions of the mycolic acid pathway in mycobacteria form a tightly connected sub-cluster. Identification of hubs reveals reactions involving glutamate to be central to mycobacterial metabolism, and pyruvate to be at the centre of the E. coli metabolome. The analysis of shortest paths between reactions has revealed several paths that are shorter than well established pathways. CONCLUSIONS: We conclude that severe downsizing of the leprae genome has not significantly altered the global structure of its reaction network but has reduced the total number of alternate paths between its reactions while keeping the shortest paths between them intact. The hubs in the mycobacterial networks that are absent in the human metabolome can be explored as potential drug targets. This work demonstrates the usefulness of constructing metabolome based networks of organisms and the feasibility of their analyses through graph spectral methods. The insights obtained from such studies provide a

  7. Shotgun metabolomic approach based on mass spectrometry for hepatic mitochondria of mice under arsenic exposure.

    Science.gov (United States)

    García-Sevillano, M A; García-Barrera, T; Navarro, F; Montero-Lobato, Z; Gómez-Ariza, J L

    2015-04-01

    Mass spectrometry (MS)-based toxicometabolomics requires analytical approaches for obtaining unbiased metabolic profiles. The present work explores the general application of direct infusion MS using a high mass resolution analyzer (a hybrid systems triple quadrupole-time-of-flight) and a complementary gas chromatography-MS analysis to mitochondria extracts from mouse hepatic cells, emphasizing on mitochondria isolation from hepatic cells with a commercial kit, sample treatment after cell lysis, comprehensive metabolomic analysis and pattern recognition from metabolic profiles. Finally, the metabolomic platform was successfully checked on a case-study based on the exposure experiment of mice Mus musculus to inorganic arsenic during 12 days. Endogenous metabolites alterations were recognized by partial least squares-discriminant analysis. Subsequently, metabolites were identified by combining MS/MS analysis and metabolomics databases. This work reports for the first time the effects of As-exposure on hepatic mitochondria metabolic pathways based on MS, and reveals disturbances in Krebs cycle, β-oxidation pathway, amino acids degradation and perturbations in creatine levels. This non-target analysis provides extensive metabolic information from mitochondrial organelle, which could be applied to toxicology, pharmacology and clinical studies.

  8. The fungal leaf endophyte Paraconiothyrium variabile specifically metabolizes the host-plant metabolome for its own benefit.

    Science.gov (United States)

    Tian, Yuan; Amand, Séverine; Buisson, Didier; Kunz, Caroline; Hachette, François; Dupont, Joëlle; Nay, Bastien; Prado, Soizic

    2014-12-01

    Fungal endophytes live inside plant tissues and some have been found to provide benefits to their host. Nevertheless, their ecological impact is not adequately understood. Considering the fact that endophytes are continuously interacting with their hosts, it is conceivable that both partners have substantial influence on each other's metabolic processes. In this context, we have investigated the action of the endophytic fungus Paraconiothyrium variabile, isolated from the leaves of Cephalotaxus harringtonia, on the secondary metabolome of the host-plant. The alteration of the leaf compounds by the fungus was monitored through metabolomic approaches followed by structural characterization of the altered products. Out of more than a thousand molecules present in the crude extract of the plant leaf, we have observed a specific biotransformation of glycosylated flavonoids by the endophyte. In all cases it led to the production of the corresponding aglycone via deglycosylation. The deglycosylated flavonoids turned out to display significant beneficial effects on the hyphal growth of germinated spores. Our finding, along with the known allelopathic role of flavonoids, illustrates the chemical cooperation underlying the mutualistic relationship between the plant and the endophyte. PMID:25446235

  9. Mass spectrometry-based metabolomics: applications to biomarker and metabolic pathway research.

    Science.gov (United States)

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

    2016-01-01

    Mass spectrometry-based metabolomics has become increasingly popular in molecular medicine. High-definition mass spectrometry (MS), coupled with pattern recognition methods, have been carried out to obtain comprehensive metabolite profiling and metabolic pathway of large biological datasets. This sets the scene for a new and powerful diagnostic approach. Analysis of the key metabolites in body fluids has become an important part of improving disease diagnosis. With technological advances in analytical techniques, the ability to measure low-molecular-weight metabolites in bio-samples provides a powerful platform for identifying metabolites that are uniquely correlated with a specific human disease. MS-based metabolomics can lead to enhanced understanding of disease mechanisms and to new diagnostic markers and has a strong potential to contribute to improving early diagnosis of diseases. This review will highlight the importance and benefit with certain characteristic examples of MS-metabolomics for identifying metabolic pathways and metabolites that accurately screen for potential diagnostic biomarkers of diseases. PMID:25739660

  10. [A novel metabolomic data scaling method based on K-L divergence].

    Science.gov (United States)

    Deng, Ling-Li; Cheng, Kian-Kai; Shen, Gui-Ping; Zhou, Ling; Liu, Xin-Zhuo; Dong, Ji-Yang; Chen, Zhong

    2014-10-01

    A new scaling method in the current study based on Kullback-Leibler (K-L) divergence is proposed for NMR metabolomic data. The proposed method (called K-L scaling) is a supervised scaling method as group information is incorporated in the scaling procedure. Notably, K-L divergence measures the difference between two different datasets by their probability distributions, it can be used for the analysis of data that either follows Gaussian or non-Gaussian distributions. In K-L scaling, all variables were first standardized to unit variance, then their variance was adjusted using Kullback-Leibler divergence to highlight the significant variables. K-L scaling can tell effectively the difference in spectral data points between two experimental groups, and then enhances the weights of biological-relevant variables, and at the same time reduces the weight of noise and uninformative variables. The developed method was applied to a H-NMR metabolomic dataset acquired from human urine. Analysis results of the dataset showed that this new scaling method is efficient in suppressing the contribution of noise in the resulting multivariate model In addition, it can increase the weights of important variables, and improve the interpretability and predictability of subsequent principal component regression (PCR) and partial least squares discriminant analysis (PLS-DA). Furthermore, the scaling method facilitated the identification of metabolic signatures. The current result suggested that the developed K-L scaling method may become a useful alternative for the preprocessing of NMR-based metabolomic data.

  11. PLS-Based and Regularization-Based Methods for the Selection of Relevant Variables in Non-targeted Metabolomics Data.

    Science.gov (United States)

    Bujak, Renata; Daghir-Wojtkowiak, Emilia; Kaliszan, Roman; Markuszewski, Michał J

    2016-01-01

    Non-targeted metabolomics constitutes a part of the systems biology and aims at determining numerous metabolites in complex biological samples. Datasets obtained in the non-targeted metabolomics studies are high-dimensional due to sensitivity of mass spectrometry-based detection methods as well as complexity of biological matrices. Therefore, a 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). The orthogonal projections to latent structures-discriminant analysis (OPLS-DA) without and with multiple testing correction as well as the least absolute shrinkage and selection operator (LASSO) with bootstrapping, were tested and compared. For the RH study, OPLS-DA model built without multiple testing correction selected 46 and 218 variables based on the VIP criteria using Pareto and UV scaling, respectively. For the PH study, 217 and 320 variables were selected based on the VIP criteria using Pareto and UV scaling, respectively. In the RH study, OPLS-DA model built after correcting for multiple testing, selected 4 and 19 variables as in terms of Pareto and UV scaling, respectively. For the PH study, 14 and 18 variables were selected based on the VIP criteria in terms of Pareto and UV scaling, respectively. In the RH and PH study, the LASSO selected 14 and 4 variables with reproducibility between 99.3 and 100%, respectively. In the light of PLS-based models, the larger the search space the higher the probability of developing models that fit the training data well with simultaneous poor predictive performance on the validation set. The LASSO offers potential improvements over standard linear regression due to the presence of the constrain, which promotes sparse solutions. This paper is the first one to date

  12. Electronic Nose and Exhaled Breath NMR-based Metabolomics Applications in Airways Disease.

    Science.gov (United States)

    Santini, Giuseppe; Mores, Nadia; Penas, Andreu; Capuano, Rosamaria; Mondino, Chiara; Trové, Andrea; Macagno, Francesco; Zini, Gina; Cattani, Paola; Martinelli, Eugenio; Motta, Andrea; Macis, Giuseppe; Ciabattoni, Giovanni; Montuschi, Paolo

    2016-01-01

    Breathomics, the multidimensional molecular analysis of exhaled breath, includes analysis of exhaled breath with gas-chromatography/mass spectrometry (GC/MS) and electronic noses (e-noses), and metabolomics of exhaled breath condensate (EBC), a non-invasive technique which provides information on the composition of airway lining fluid, generally by high-resolution nuclear magnetic resonance (NMR) spectroscopy or MS methods. Metabolomics is the identification and quantification of small molecular weight metabolites in a biofluid. Specific profiles of volatile compounds in exhaled breath and metabolites in EBC (breathprints) are potentially useful surrogate markers of inflammatory respiratory diseases. Electronic noses (e-noses) are artificial sensor systems, usually consisting of chemical cross-reactive sensor arrays for characterization of patterns of breath volatile compounds, and algorithms for breathprints classification. E-noses are handheld, portable, and provide real-time data. E-nose breathprints can reflect respiratory inflammation. E-noses and NMR-based metabolomics of EBC can distinguish patients with respiratory diseases such as asthma, COPD, and lung cancer, or diseases with a clinically relevant respiratory component including cystic fibrosis and primary ciliary dyskinesia, and healthy individuals. Breathomics has also been reported to identify patients affected by different types of respiratory diseases. Patterns of breath volatile compounds detected by e-nose and EBC metabolic profiles have been associated with asthma phenotypes. In combination with other -omics platforms, breathomics might provide a molecular approach to respiratory disease phenotyping and a molecular basis to tailored pharmacotherapeutic strategies. Breathomics might also contribute to identify new surrogate markers of respiratory inflammation, thus, facilitating drug discovery. Validation in newly recruited, prospective independent cohorts is essential for development of e

  13. Review of sample preparation strategies for MS-based metabolomic studies in industrial biotechnology.

    Science.gov (United States)

    Causon, Tim J; Hann, Stephan

    2016-09-28

    Fermentation and cell culture biotechnology in the form of so-called "cell factories" now play an increasingly significant role in production of both large (e.g. proteins, biopharmaceuticals) and small organic molecules for a wide variety of applications. However, associated metabolic engineering optimisation processes relying on genetic modification of organisms used in cell factories, or alteration of production conditions remain a challenging undertaking for improving the final yield and quality of cell factory products. In addition to genomic, transcriptomic and proteomic workflows, analytical metabolomics continues to play a critical role in studying detailed aspects of critical pathways (e.g. via targeted quantification of metabolites), identification of biosynthetic intermediates, and also for phenotype differentiation and the elucidation of previously unknown pathways (e.g. via non-targeted strategies). However, the diversity of primary and secondary metabolites and the broad concentration ranges encompassed during typical biotechnological processes means that simultaneous extraction and robust analytical determination of all parts of interest of the metabolome is effectively impossible. As the integration of metabolome data with transcriptome and proteome data is an essential goal of both targeted and non-targeted methods addressing production optimisation goals, additional sample preparation steps beyond necessary sampling, quenching and extraction protocols including clean-up, analyte enrichment, and derivatisation are important considerations for some classes of metabolites, especially those present in low concentrations or exhibiting poor stability. This contribution critically assesses the potential of current sample preparation strategies applied in metabolomic studies of industrially-relevant cell factory organisms using mass spectrometry-based platforms primarily coupled to liquid-phase sample introduction (i.e. flow injection, liquid

  14. Advances in high-resolution mass spectrometry based on metabolomics studies for food--a review.

    Science.gov (United States)

    Rubert, Josep; Zachariasova, Milena; Hajslova, Jana

    2015-01-01

    Food authenticity becomes a necessity for global food policies, since food placed in the market without fail has to be authentic. It has always been a challenge, since in the past minor components, called also markers, have been mainly monitored by chromatographic methods in order to authenticate the food. Nevertheless, nowadays, advanced analytical methods have allowed food fingerprints to be achieved. At the same time they have been also combined with chemometrics, which uses statistical methods in order to verify food and to provide maximum information by analysing chemical data. These sophisticated methods based on different separation techniques or stand alone have been recently coupled to high-resolution mass spectrometry (HRMS) in order to verify the authenticity of food. The new generation of HRMS detectors have experienced significant advances in resolving power, sensitivity, robustness, extended dynamic range, easier mass calibration and tandem mass capabilities, making HRMS more attractive and useful to the food metabolomics community, therefore becoming a reliable tool for food authenticity. The purpose of this review is to summarise and describe the most recent metabolomics approaches in the area of food metabolomics, and to discuss the strengths and drawbacks of the HRMS analytical platforms combined with chemometrics. PMID:26365870

  15. Advances in high-resolution mass spectrometry based on metabolomics studies for food--a review.

    Science.gov (United States)

    Rubert, Josep; Zachariasova, Milena; Hajslova, Jana

    2015-01-01

    Food authenticity becomes a necessity for global food policies, since food placed in the market without fail has to be authentic. It has always been a challenge, since in the past minor components, called also markers, have been mainly monitored by chromatographic methods in order to authenticate the food. Nevertheless, nowadays, advanced analytical methods have allowed food fingerprints to be achieved. At the same time they have been also combined with chemometrics, which uses statistical methods in order to verify food and to provide maximum information by analysing chemical data. These sophisticated methods based on different separation techniques or stand alone have been recently coupled to high-resolution mass spectrometry (HRMS) in order to verify the authenticity of food. The new generation of HRMS detectors have experienced significant advances in resolving power, sensitivity, robustness, extended dynamic range, easier mass calibration and tandem mass capabilities, making HRMS more attractive and useful to the food metabolomics community, therefore becoming a reliable tool for food authenticity. The purpose of this review is to summarise and describe the most recent metabolomics approaches in the area of food metabolomics, and to discuss the strengths and drawbacks of the HRMS analytical platforms combined with chemometrics.

  16. GC-MS-Based Metabolome and Metabolite Regulation in Serum-Resistant Streptococcus agalactiae.

    Science.gov (United States)

    Wang, Zhe; Li, Min-Yi; Peng, Bo; Cheng, Zhi-Xue; Li, Hui; Peng, Xuan-Xian

    2016-07-01

    Streptococcus agalactiae causes severe systemic infections in human and fish. In the present study, we established a pathogen-plasma interaction model by which we explored how S. agalactiae evaded serum-mediated killing. We found that S. agalactiae grew faster in the presence of yellow grouper plasma than in the absence of the plasma, indicating S. agalactiae evolved a way of evading the fish immune system. To determine the events underlying this phenotype, we applied GC-MS-based metabolomics approaches to identify differential metabolomes between S. agalactiae cultured with and without yellow grouper plasma. Through bioinformatics analysis, decreased malic acid and increased adenosine were identified as the most crucial metabolites that distinguish the two groups. Meanwhile, they presented with decreased TCA cycle and elevated purine metabolism, respectively. Finally, exogenous malic acid and adenosine were used to reprogram the plasma-resistant metabolome, leading to elevated and decreased susceptibility to the plasma, respectively. Therefore, our findings reveal for the first time that S. agalactiae utilizes a metabolic trick to respond to plasma killing as a result of serum resistance, which may be reverted or enhanced by exogenous malic acid and adenosine, respectively, suggesting that the metabolic trick can be regulated by metabolites. PMID:27251450

  17. Applications of NMR-based metabolomics in biological and environmental research

    Science.gov (United States)

    As a complimentary tool to other omics platforms, metabolomics is increasingly being used by biologists to study the dynamic response of biological systems (cells, tissues, or whole organisms) under diverse physiological or pathological conditions. Metabolomics deals with the qu...

  18. 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

  19. Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias

    Science.gov (United States)

    Imperlini, Esther; Santorelli, Lucia; Orrù, Stefania; Scolamiero, Emanuela; Ruoppolo, Margherita

    2016-01-01

    Organic acidemias (OAs) are inherited metabolic disorders caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders result in the accumulation of mono-, di-, or tricarboxylic acids, generally referred to as organic acids. The OA outcomes can involve different organs and/or systems. Some OA disorders are easily managed if promptly diagnosed and treated, whereas, in others cases, such as propionate metabolism-related OAs (propionic acidemia, PA; methylmalonic acidemia, MMA), neither diet, vitamin therapy, nor liver transplantation appears to prevent multiorgan impairment. Here, we review the recent developments in dissecting molecular bases of OAs by using integration of mass spectrometry- (MS-) based metabolomic and proteomic strategies. MS-based techniques have facilitated the rapid and economical evaluation of a broad spectrum of metabolites in various body fluids, also collected in small samples, like dried blood spots. This approach has enabled the timely diagnosis of OAs, thereby facilitating early therapeutic intervention. Besides providing an overview of MS-based approaches most frequently used to study the molecular mechanisms underlying OA pathophysiology, we discuss the principal challenges of metabolomic and proteomic applications to OAs.

  20. 2-Hydrazinoquinoline as a Derivatization Agent for LC-MS-Based Metabolomic Investigation of Diabetic Ketoacidosis

    Directory of Open Access Journals (Sweden)

    Chi Chen

    2013-10-01

    Full Text Available Short-chain carboxylic acids, aldehydes and ketones are products and regulators of many important metabolic pathways. Their levels in biofluids and tissues reflect the status of specific metabolic reactions, the homeostasis of the whole metabolic system and the wellbeing of a biological entity. In this study, the use of 2-hydrazinoquinoline (HQ as a novel derivatization agent was explored and optimized for simultaneous liquid chromatography-mass spectrometry (LC-MS analysis of carboxylic acids, aldehydes and ketones in biological samples. The formation of carboxylic acid derivative is attributed to the esterification reaction between HQ and a carboxyl group, while the production of aldehyde and ketone derivatives is through the formation of Schiff bases between HQ and a carbonyl group. The compatibility of HQ with biological samples was demonstrated by derivatizing urine, serum and liver extract samples. Using this HQ-based approach, the kinetics of type 1 diabetes-induced metabolic changes was characterized by the LC-MS-based metabolomic analysis of urine samples from streptozotocin (STZ-treated mice. Subsequently, carboxylic acid, aldehyde and ketone metabolites associated with STZ-elicited disruption of nutrient and energy metabolism were conveniently identified and elucidated. Overall, HQ derivatization of carboxylic acids, aldehydes and ketones could serve as a useful tool for the LC-MS-based metabolomic investigation of endogenous metabolism.

  1. Bio-effectors from waste materials as growth promoters for tomato plants, an agronomic and metabolomic study

    Science.gov (United States)

    Abou Chehade, Lara; Chami, Ziad Al; De Pascali, Sandra; Cavoski, Ivana; Fanizzi, Francesco Paolo

    2015-04-01

    In organic farming, where nutrient management is constrained and sustainability is claimed, bio-effectors pave their way. Considering selected bio-effectors, this study integrates metabolomics to agronomy in depicting induced relevant phenomena. Extracts of three agro-industrial wastes (Lemon processing residues, Fennel processing residues and Brewer's spent grain) are being investigated as sources of bio-effectors for the third trial consequently. Corresponding individual and mixture aqueous extracts are assessed for their synergistic and/or single agronomic and qualitative performances on soil-grown tomato, compared to both a control and humic acid treatments. A metabolomic profiling of tomato fruits via the Proton Nuclear Magnetic Resonance (NMR) spectroscopy, as holistic indicator of fruit quality and extract-induced responses, complements crop productivity and organoleptic/nutritional qualitative analyses. Results are expected to show mainly an enhancement of the fruit qualitative traits, and to confirm partly the previous results of better crop productivity and metabolism enhancement. Waste-derived bio-effectors could be, accordingly, demonstrated as potential candidates of plant-enhancing substances. Keywords: bio-effectors, organic farming, agro-industrial wastes, nuclear magnetic resonance (NMR), tomato.

  2. MetaDB a Data Processing Workflow in Untargeted MS-Based Metabolomics Experiments.

    Science.gov (United States)

    Franceschi, Pietro; Mylonas, Roman; Shahaf, Nir; Scholz, Matthias; Arapitsas, Panagiotis; Masuero, Domenico; Weingart, Georg; Carlin, Silvia; Vrhovsek, Urska; Mattivi, Fulvio; Wehrens, Ron

    2014-01-01

    Due to their sensitivity and speed, mass-spectrometry based analytical technologies are widely used to in metabolomics to characterize biological phenomena. To address issues like metadata organization, quality assessment, data processing, data storage, and, finally, submission to public repositories, bioinformatic pipelines of a non-interactive nature are often employed, complementing the interactive software used for initial inspection and visualization of the data. These pipelines often are created as open-source software allowing the complete and exhaustive documentation of each step, ensuring the reproducibility of the analysis of extensive and often expensive experiments. In this paper, we will review the major steps which constitute such a data processing pipeline, discussing them in the context of an open-source software for untargeted MS-based metabolomics experiments recently developed at our institute. The software has been developed by integrating our metaMS R package with a user-friendly web-based application written in Grails. MetaMS takes care of data pre-processing and annotation, while the interface deals with the creation of the sample lists, the organization of the data storage, and the generation of survey plots for quality assessment. Experimental and biological metadata are stored in the ISA-Tab format making the proposed pipeline fully integrated with the Metabolights framework.

  3. NMR-Based Metabolomic Analysis of Huanglongbing-Asymptomatic and -Symptomatic Citrus Trees.

    Science.gov (United States)

    Freitas, Deisy dos Santos; Carlos, Eduardo Fermino; Gil, Márcia Cristina Soares de Souza; Vieira, Luiz Gonzaga Esteves; Alcantara, Glaucia Braz

    2015-09-01

    Huanglongbing (HLB) is one of the most severe diseases that affects citrus trees worldwide and is associated with the yet uncultured bacteria Candidatus Liberibacter spp. To assess the metabolomic differences between HLB-asymptomatic and -symptomatic tissues, extracts from leaf and root samples taken from a uniform 6-year-old commercial orchard of Valencia trees were subjected to nuclear magnetic resonance (NMR) and chemometrics. The results show that the symptomatic trees had higher sucrose content in their leaves and no variation in their roots. In addition, proline betaine and malate were detected in smaller amounts in the HLB-affected symptomatic leaves. The changes in metabolic processes of the plant in response to HLB are corroborated by the relationship between the bacterial levels and the metabolic profiles.

  4. (1)H nuclear magnetic resonance-based metabolomics study of earthworm Perionyx excavatus in vermifiltration process.

    Science.gov (United States)

    Wang, Lei; Huang, Xulei; Laserna, Anna Karen Carrasco; Li, Sam Fong Yau

    2016-10-01

    In this study, (1)H nuclear magnetic resonance (NMR)-based metabolomics approach was used to characterize the metabolic response of the earthworm Perionyx excavatus in continuous vermifiltration for two months under hydraulic loading rates of 1m(3)m(-2)d(-1) (VF1) and 1.5m(3)m(-2)d(-1) (VF1.5). Both VF1 and VF1.5 showed higher removal of chemical oxygen demand and total nitrogen than the biofilter without earthworms. Principal component analysis of the NMR spectra of earthworm metabolites showed significant separations between those not subjected to wastewater filtration (control) and VF1 or VF1.5. Temporal variations of earthworm biomass, and the identified metabolites that are significantly different between control, VF1 and VF1.5 revealed that worms underwent increasing metabolic activity within 20days in VF1 and 14days in VF1.5, then decreasing metabolic activity. The use of NMR-based metabolomics in monitoring earthworm metabolism was demonstrated to be a novel approach in studying engineered vermifiltration systems. PMID:27469092

  5. (1)H nuclear magnetic resonance-based metabolomics study of earthworm Perionyx excavatus in vermifiltration process.

    Science.gov (United States)

    Wang, Lei; Huang, Xulei; Laserna, Anna Karen Carrasco; Li, Sam Fong Yau

    2016-10-01

    In this study, (1)H nuclear magnetic resonance (NMR)-based metabolomics approach was used to characterize the metabolic response of the earthworm Perionyx excavatus in continuous vermifiltration for two months under hydraulic loading rates of 1m(3)m(-2)d(-1) (VF1) and 1.5m(3)m(-2)d(-1) (VF1.5). Both VF1 and VF1.5 showed higher removal of chemical oxygen demand and total nitrogen than the biofilter without earthworms. Principal component analysis of the NMR spectra of earthworm metabolites showed significant separations between those not subjected to wastewater filtration (control) and VF1 or VF1.5. Temporal variations of earthworm biomass, and the identified metabolites that are significantly different between control, VF1 and VF1.5 revealed that worms underwent increasing metabolic activity within 20days in VF1 and 14days in VF1.5, then decreasing metabolic activity. The use of NMR-based metabolomics in monitoring earthworm metabolism was demonstrated to be a novel approach in studying engineered vermifiltration systems.

  6. MetaDB a Data Processing Workflow in Untargeted MS-Based Metabolomics Experiments

    Directory of Open Access Journals (Sweden)

    Pietro eFranceschi

    2014-12-01

    Full Text Available Due to their sensitivity and speed, mass-spectrometry based analytical technologies are widely used to in metabolomics to characterize biological phenomena. To address issues like metadata organization, quality assessment, data processing, data storage and, finally, submission to public repositories, bioinformatic pipelines of a non-interactive nature are often employed, complementing the interactive software used for initial inspection and visualization of the data. These pipelines often are created as open-source software allowing the complete and exhaustive documentation of each step, ensuring the reproducibility of the analysis of extensive and often expensive experiments.In this paper we will review the major steps which constitute such a data processing pipeline, discussing them in the context of open source software for untargeted Liquid Chromatography Mass Spectrometry (LC-MS and Gas Chromatography Mass Spectrometry (GC-MS metabolomics experiments recently developed at our institute. The software has been developed by integrating our metaMS R package with a user-friendly web based application written in Grails. MetaMS takes care of data pre-processing and annotation, while the interface deals with the creation of the sample lists, the organization of the data storage and the generation of survey plots for quality assessment. Experimental and biological metadata are stored in the ISA-Tab format making the proposed pipeline fully integrated with the Metabolights framework.

  7. Enabling Metabolomics Based Biomarker Discovery Studies Using Molecular Phenotyping of Exosome-Like Vesicles.

    Directory of Open Access Journals (Sweden)

    Tatiana Altadill

    Full Text Available Identification of sensitive and specific biomarkers with clinical and translational utility will require smart experimental strategies that would augment expanding the breadth and depth of molecular measurements within the constraints of currently available technologies. Exosomes represent an information rich matrix to discern novel disease mechanisms that are thought to contribute to pathologies such as dementia and cancer. Although proteomics and transcriptomic studies have been reported using Exosomes-Like Vesicles (ELVs from different sources, exosomal metabolome characterization and its modulation in health and disease remains to be elucidated. Here we describe methodologies for UPLC-ESI-MS based small molecule profiling of ELVs from human plasma and cell culture media. In this study, we present evidence that indeed ELVs carry a rich metabolome that could not only augment the discovery of low abundance biomarkers but may also help explain the molecular basis of disease progression. This approach could be easily translated to other studies seeking to develop predictive biomarkers that can subsequently be used with simplified targeted approaches.

  8. Application of NMR-based metabolomics to the study of gut microbiota in obesity.

    Science.gov (United States)

    Calvani, Riccardo; Brasili, Elisa; Praticò, Giulia; Sciubba, Fabio; Roselli, Marianna; Finamore, Alberto; Marini, Federico; Marzetti, Emanuele; Miccheli, Alfredo

    2014-01-01

    Lifestyle habits, host gene repertoire, and alterations in the intestinal microbiota concur to the development of obesity. A great deal of research has recently been focused on investigating the role gut microbiota plays in the pathogenesis of metabolic dysfunctions and increased adiposity. Altered microbiota can affect host physiology through several pathways, including enhanced energy harvest, and perturbations in immunity, metabolic signaling, and inflammatory pathways. A broad range of "omics" technologies is now available to help decipher the interactions between the host and the gut microbiota at detailed genetic and functional levels. In particular, metabolomics--the comprehensive analysis of metabolite composition of biological fluids and tissues--could provide breakthrough insights into the links among the gut microbiota, host genetic repertoire, and diet during the development and progression of obesity. Here, we briefly review the most insightful findings on the involvement of gut microbiota in the pathogenesis of obesity. We also discuss how metabolomic approaches based on nuclear magnetic resonance spectroscopy could help understand the activity of gut microbiota in relation to obesity, and assess the effects of gut microbiota modulation in the treatment of this condition.

  9. Overexpression of ORCA3 and G10H in Catharanthus roseus Plants Regulated Alkaloid Biosynthesis and Metabolism Revealed by NMR-Metabolomics

    Science.gov (United States)

    Pan, Qifang; Wang, Quan; Yuan, Fang; Xing, Shihai; Zhao, Jingya; Choi, Young Hae; Verpoorte, Robert; Tian, Yuesheng; Wang, Guofeng; Tang, Kexuan

    2012-01-01

    In order to improve the production of the anticancer dimeric indole alkaloids in Catharanthuse roseus, much research has been dedicated to culturing cell lines, hairy roots, and efforts to elucidate the regulation of the monoterpenoid indole alkaloid (MIA) biosynthesis. In this study, the ORCA3 (Octadecanoid-derivative Responsive Catharanthus AP2-domain) gene alone or integrated with the G10H (geraniol 10-hydroxylase) gene were first introduced into C. roseus plants. Transgenic C. roseus plants overexpressing ORCA3 alone (OR lines), or co-overexpressing G10H and ORCA3 (GO lines) were obtained by genetic modification. ORCA3 overexpression induced an increase of AS, TDC, STR and D4H transcripts but did not affect CRMYC2 and G10H transcription. G10H transcripts showed a significant increase under G10H and ORCA3 co-overexpression. ORCA3 and G10H overexpression significantly increased the accumulation of strictosidine, vindoline, catharanthine and ajmalicine but had limited effects on anhydrovinblastine and vinblastine levels. NMR-based metabolomics confirmed the higher accumulation of monomeric indole alkaloids in OR and GO lines. Multivariate data analysis of 1H NMR spectra showed change of amino acid, organic acid, sugar and phenylpropanoid levels in both OR and GO lines compared to the controls. The result indicated that enhancement of MIA biosynthesis by ORCA3 and G10H overexpression might affect other metabolic pathways in the plant metabolism of C. roseus. PMID:22916202

  10. Overexpression of ORCA3 and G10H in Catharanthus roseus plants regulated alkaloid biosynthesis and metabolism revealed by NMR-metabolomics.

    Directory of Open Access Journals (Sweden)

    Qifang Pan

    Full Text Available In order to improve the production of the anticancer dimeric indole alkaloids in Catharanthuse roseus, much research has been dedicated to culturing cell lines, hairy roots, and efforts to elucidate the regulation of the monoterpenoid indole alkaloid (MIA biosynthesis. In this study, the ORCA3 (Octadecanoid-derivative Responsive Catharanthus AP2-domain gene alone or integrated with the G10H (geraniol 10-hydroxylase gene were first introduced into C. roseus plants. Transgenic C. roseus plants overexpressing ORCA3 alone (OR lines, or co-overexpressing G10H and ORCA3 (GO lines were obtained by genetic modification. ORCA3 overexpression induced an increase of AS, TDC, STR and D4H transcripts but did not affect CRMYC2 and G10H transcription. G10H transcripts showed a significant increase under G10H and ORCA3 co-overexpression. ORCA3 and G10H overexpression significantly increased the accumulation of strictosidine, vindoline, catharanthine and ajmalicine but had limited effects on anhydrovinblastine and vinblastine levels. NMR-based metabolomics confirmed the higher accumulation of monomeric indole alkaloids in OR and GO lines. Multivariate data analysis of (1H NMR spectra showed change of amino acid, organic acid, sugar and phenylpropanoid levels in both OR and GO lines compared to the controls. The result indicated that enhancement of MIA biosynthesis by ORCA3 and G10H overexpression might affect other metabolic pathways in the plant metabolism of C. roseus.

  11. Applications of Fourier Transform Ion Cyclotron Resonance (FT-ICR) and Orbitrap Based High Resolution Mass Spectrometry in Metabolomics and Lipidomics

    Science.gov (United States)

    Ghaste, Manoj; Mistrik, Robert; Shulaev, Vladimir

    2016-01-01

    Metabolomics, along with other “omics” approaches, is rapidly becoming one of the major approaches aimed at understanding the organization and dynamics of metabolic networks. Mass spectrometry is often a technique of choice for metabolomics studies due to its high sensitivity, reproducibility and wide dynamic range. High resolution mass spectrometry (HRMS) is a widely practiced technique in analytical and bioanalytical sciences. It offers exceptionally high resolution and the highest degree of structural confirmation. Many metabolomics studies have been conducted using HRMS over the past decade. In this review, we will explore the latest developments in Fourier transform mass spectrometry (FTMS) and Orbitrap based metabolomics technology, its advantages and drawbacks for using in metabolomics and lipidomics studies, and development of novel approaches for processing HRMS data. PMID:27231903

  12. Rice suspension cultured cells are evaluated as a model system to study salt responsive networks in plants using a combined proteomic and metabolomic profiling approach.

    Science.gov (United States)

    Liu, Dawei; Ford, Kristina L; Roessner, Ute; Natera, Siria; Cassin, Andrew M; Patterson, John H; Bacic, Antony

    2013-06-01

    Salinity is one of the major abiotic stresses affecting plant productivity but surprisingly, a thorough understanding of the salt-responsive networks responsible for sustaining growth and maintaining crop yield remains a significant challenge. Rice suspension culture cells (SCCs), a single cell type, were evaluated as a model system as they provide a ready source of a homogenous cell type and avoid the complications of multicellular tissue types in planta. A combination of growth performance, and transcriptional analyses using known salt-induced genes was performed on control and 100 mM NaCl cultured cells to validate the biological system. Protein profiling was conducted using both DIGE- and iTRAQ-based proteomics approaches. In total, 106 proteins were identified in DIGE experiments and 521 proteins in iTRAQ experiments with 58 proteins common to both approaches. Metabolomic analysis provided insights into both developmental changes and salt-induced changes of rice SCCs at the metabolite level; 134 known metabolites were identified, including 30 amines and amides, 40 organic acids, 40 sugars, sugar acids and sugar alcohols, 21 fatty acids and sterols, and 3 miscellaneous compounds. Our results from proteomic and metabolomic studies indicate that the salt-responsive networks of rice SCCs are extremely complex and share some similarities with thee cellular responses observed in planta. For instance, carbohydrate and energy metabolism pathways, redox signaling pathways, auxin/indole-3-acetic acid pathways and biosynthesis pathways for osmoprotectants are all salt responsive in SCCs enabling cells to maintain cellular function under stress condition. These data are discussed in the context of our understanding of in planta salt-responses. PMID:23661342

  13. 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.

  14. UPLC/Q-TOF MS-based metabolomics and qRT-PCR in enzyme gene screening with key role in triterpenoid saponin biosynthesis of Polygala tenuifolia.

    Directory of Open Access Journals (Sweden)

    Fusheng Zhang

    Full Text Available The dried root of Polygala tenuifolia, named Radix Polygalae, is a well-known traditional Chinese medicine. Triterpenoid saponins are some of the most important components of Radix Polygalae extracts and are widely studied because of their valuable pharmacological properties. However, the relationship between gene expression and triterpenoid saponin biosynthesis in P. tenuifolia is unclear.In this study, ultra-performance liquid chromatography (UPLC coupled with quadrupole time-of-flight mass spectrometry (Q-TOF MS-based metabolomic analysis was performed to identify and quantify the different chemical constituents of the roots, stems, leaves, and seeds of P. tenuifolia. A total of 22 marker compounds (VIP>1 were explored, and significant differences in all 7 triterpenoid saponins among the different tissues were found. We also observed an efficient reference gene GAPDH for different tissues in this plant and determined the expression level of some genes in the triterpenoid saponin biosynthetic pathway. Results showed that MVA pathway has more important functions in the triterpenoid saponin biosynthesis of P. tenuifolia. The expression levels of squalene synthase (SQS, squalene monooxygenase (SQE, and beta-amyrin synthase (β-AS were highly correlated with the peak area intensity of triterpenoid saponins compared with data from UPLC/Q-TOF MS-based metabolomic analysis.This finding suggested that a combination of UPLC/Q-TOF MS-based metabolomics and gene expression analysis can effectively elucidate the mechanism of triterpenoid saponin biosynthesis and can provide useful information on gene discovery. These findings can serve as a reference for using the overexpression of genes encoding for SQS, SQE, and/or β-AS to increase the triterpenoid saponin production of P. tenuifolia.

  15. A novel serum metabolomics-based diagnostic approach for colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Shin Nishiumi

    Full Text Available BACKGROUND: To improve the quality of life of colorectal cancer patients, it is important to establish new screening methods for early diagnosis of colorectal cancer. METHODOLOGY/PRINCIPAL FINDINGS: We performed serum metabolome analysis using gas-chromatography/mass-spectrometry (GC/MS. First, the accuracy of our GC/MS-based serum metabolomic analytical method was evaluated by calculating the RSD% values of serum levels of various metabolites. Second, the intra-day (morning, daytime, and night and inter-day (among 3 days variances of serum metabolite levels were examined. Then, serum metabolite levels were compared between colorectal cancer patients (N = 60; N = 12 for each stage from 0 to 4 and age- and sex-matched healthy volunteers (N = 60 as a training set. The metabolites whose levels displayed significant changes were subjected to multiple logistic regression analysis using the stepwise variable selection method, and a colorectal cancer prediction model was established. The prediction model was composed of 2-hydroxybutyrate, aspartic acid, kynurenine, and cystamine, and its AUC, sensitivity, specificity, and accuracy were 0.9097, 85.0%, 85.0%, and 85.0%, respectively, according to the training set data. In contrast, the sensitivity, specificity, and accuracy of CEA were 35.0%, 96.7%, and 65.8%, respectively, and those of CA19-9 were 16.7%, 100%, and 58.3%, respectively. The validity of the prediction model was confirmed using colorectal cancer patients (N = 59 and healthy volunteers (N = 63 as a validation set. At the validation set, the sensitivity, specificity, and accuracy of the prediction model were 83.1%, 81.0%, and 82.0%, respectively, and these values were almost the same as those obtained with the training set. In addition, the model displayed high sensitivity for detecting stage 0-2 colorectal cancer (82.8%. CONCLUSIONS/SIGNIFICANCE: Our prediction model established via GC/MS-based serum metabolomic analysis

  16. 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 co

  17. Effect of the environment on the secondary metabolic profile of Tithonia diversifolia: a model for environmental metabolomics of plants

    Science.gov (United States)

    Sampaio, Bruno Leite; Edrada-Ebel, Ruangelie; da Costa, Fernando Batista

    2016-07-01

    Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant’s metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts.

  18. Effect of the environment on the secondary metabolic profile of Tithonia diversifolia: a model for environmental metabolomics of plants

    Science.gov (United States)

    Sampaio, Bruno Leite; Edrada-Ebel, RuAngelie; Da Costa, Fernando Batista

    2016-01-01

    Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant’s metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts. PMID:27383265

  19. Evaluation of dried blood spots as sample matrix for gas chromatography/mass spectrometry based metabolomic profiling.

    Science.gov (United States)

    Kong, Sing Teang; Lin, Hai-Shu; Ching, Jianhong; Ho, Paul C

    2011-06-01

    We propose using dried blood spots (DBS) as sample matrix for gas chromatography/mass spectrometry (GC/MS) based metabolomic profiling for the benefits of higher sample stability, more convenient sample acquisition with DBS, higher analyte separation power, and more readily biomarker identification with GC/MS. To establish this proposition, the metabolomic profiles generated from DBS were compared with that obtained from the conventional whole blood and plasma matrixes and also with dried plasma spots (DPS) as another covariate control. Our findings indicated that whole blood produced the most number of detectable markers (866), whereas DPS yielded the least number (614). DBS and plasma matrix, on the other hand, produced the most similar numbers of detectable (695 vs 749) and identifiable markers (137 vs 147, matching with Fiehn library). From the analysis of the DBS and plasma metabolomic profiles, it was concluded that when l-lysine 2, iminodiacetic acid 2, dl-threo-beta-hydroxyaspartic acid, citric acid, or adenosine-5-monophosphate 2 are not involved as markers, DBS could be a suitable substitute for plasma for metabolomic profiling.

  20. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Um, So Young [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Park, Jung Hyun [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Chung, Myeon Woo [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Kim, Kyu-Bong [College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Kim, Seon Hwa [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Choi, Ki Hwan, E-mail: hyokwa11@korea.kr [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Lee, Hwa Jeong, E-mail: hwalee@ewha.ac.kr [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer NMR based metabolomics - gastric damage by indomethacin. Black-Right-Pointing-Pointer Pattern recognition analysis was performed to biomarkers of gastric damage. Black-Right-Pointing-Pointer 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. Black-Right-Pointing-Pointer The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the {sup 1}H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg{sup -1}) or co-administration with cimetidine (100 mg kg{sup -1}), which protects against GI damage. The {sup 1}H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg{sup -1}) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by

  1. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    International Nuclear Information System (INIS)

    Highlights: ► NMR based metabolomics – gastric damage by indomethacin. ► Pattern recognition analysis was performed to biomarkers of gastric damage. ► 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. ► The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the 1H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg−1) or co-administration with cimetidine (100 mg kg−1), which protects against GI damage. The 1H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg−1) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a NMR based metabolomics approach.

  2. Distinguishing Ontario ginseng landraces and ginseng species using NMR-based metabolomics.

    Science.gov (United States)

    Yuk, Jimmy; McIntyre, Kristina L; Fischer, Christian; Hicks, Joshua; Colson, Kimberly L; Lui, Ed; Brown, Dan; Arnason, John T

    2013-05-01

    The use of (1)H-NMR-based metabolomics to distinguish and identify unique markers of five Ontario ginseng (Panax quinquefolius L.) landraces and two ginseng species (P. quinquefolius and P. ginseng) was evaluated. Three landraces (2, 3, and 5) were distinguished from one another in the principal component analysis (PCA) scores plot. Further analysis was conducted and specific discriminating metabolites from the PCA loadings were determined. Landraces 3 and 5 were distinguishable on the basis of a decreased NMR intensity in the methyl ginsenoside region, indicating decreased overall ginsenoside levels. In addition, landrace 5 was separated by an increased amount of sucrose relative to the rest of the landraces. Landrace 2 was separated from the rest of the landraces by the increased level of ginsenoside R(b1). The Ontario P. quinquefolius was also compared with Asian P. ginseng by PCA, and clear separation between the two groups was detected in the PCA scores plot. The PCA loadings plot and a t-test NMR difference plot were able to identify an increased level of maltose and a decreased level of sucrose in the Asian ginseng compared with the Ontario ginseng. An overall decrease of ginsenoside content, especially ginsenoside R(b1), was also detected in the Asian ginseng's metabolic profile. This study demonstrates the potential of NMR-based metabolomics as a powerful high-throughput technique in distinguishing various closely related ginseng landraces and its ability to identify metabolic differences from Ontario and Asian ginseng. The results from this study will allow better understanding for quality assessment, species authentication, and the potential for developing a fully automated method for quality control. PMID:23250379

  3. Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

    Science.gov (United States)

    Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.; Collins, Carl C.; Wolfrum, Edward J.; Broeckling, Corey D.; Prenni, Jessica E.; Jahn, Courtney E.

    2016-01-01

    Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end products of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p sorghum. Taken together, this study demonstrates the integration of metabolomics with morpho-physiological datasets to elucidate links between plant metabolism, growth, and architecture. PMID:27462319

  4. IDEOM : an Excel interface for analysis of LC-MS-based metabolomics data

    NARCIS (Netherlands)

    Creek, Darren J.; Jankevics, Andris; Burgess, Karl E. V.; Breitling, Rainer; Barrett, Michael P.; Wren, Jonathan

    2012-01-01

    The application of emerging metabolomics technologies to the comprehensive investigation of cellular biochemistry has been limited by bottlenecks in data processing, particularly noise filtering and metabolite identification. IDEOM provides a user-friendly data processing application that automates

  5. Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

    Science.gov (United States)

    Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.; Collins, Carl C.; Wolfrum, Edward J.; Broeckling, Corey D.; Prenni, Jessica E.; Jahn, Courtney E.

    2016-01-01

    Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end products of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho

  6. Non-Targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.; Collins, Carl C.; Wolfrum, Edward J.; Broeckling, Corey D.; Prenni, Jessica E.; Jahn, Courtney E.

    2016-07-01

    Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end products of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho

  7. Metabolomic profile in pancreatic cancer patients: a consensus-based approach to identify highly discriminating metabolites

    OpenAIRE

    Di Gangi, Iole Maria; Mazza, Tommaso; Fontana, Andrea; Copetti, Massimiliano; Fusilli, Caterina; Ippolito, Antonio; Mattivi, Fulvio; Latiano, Anna; Andriulli, Angelo; Vrhovsek, Urska; Pazienza, Valerio

    2016-01-01

    Purpose pancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer' patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer. Experimental Design Two targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate m...

  8. Data preprocessing method for liquid chromatography-mass spectrometry based metabolomics.

    Science.gov (United States)

    Wei, Xiaoli; Shi, Xue; Kim, Seongho; Zhang, Li; Patrick, Jeffrey S; Binkley, Joe; McClain, Craig; Zhang, Xiang

    2012-09-18

    A set of data preprocessing algorithms for peak detection and peak list alignment are reported for analysis of liquid chromatography-mass spectrometry (LC-MS)-based metabolomics data. For spectrum deconvolution, peak picking is achieved at the selected ion chromatogram (XIC) level. To estimate and remove the noise in XICs, each XIC is first segmented into several peak groups based on the continuity of scan number, and the noise level is estimated by all the XIC signals, except the regions potentially with presence of metabolite ion peaks. After removing noise, the peaks of molecular ions are detected using both the first and the second derivatives, followed by an efficient exponentially modified Gaussian-based peak deconvolution method for peak fitting. A two-stage alignment algorithm is also developed, where the retention times of all peaks are first transferred into the z-score domain and the peaks are aligned based on the measure of their mixture scores after retention time correction using a partial linear regression. Analysis of a set of spike-in LC-MS data from three groups of samples containing 16 metabolite standards mixed with metabolite extract from mouse livers demonstrates that the developed data preprocessing method performs better than two of the existing popular data analysis packages, MZmine2.6 and XCMS(2), for peak picking, peak list alignment, and quantification.

  9. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

    Science.gov (United States)

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies. PMID:27507964

  10. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health

    Science.gov (United States)

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies. PMID:27507964

  11. Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: A review.

    OpenAIRE

    Roux, Aurélie; Lison, Dominique; Junot, Christophe; Heillier, Jean-François

    2011-01-01

    International audience The metabolome is the set of small molecular mass organic compounds found in a given biological media. It includes all organic substances naturally occurring from the metabolism of the studied living organism, except biological polymers, but also xenobiotics and their biotransformation products. The metabolic fingerprints of biofluids obtained by mass spectrometry (MS) or nuclear magnetic resonance (NMR)-based methods contain a few hundreds to thousands of signals re...

  12. Mass Spectrometry-Based Quantitative Metabolomics Revealed a Distinct Lipid Profile in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Yun Yen

    2013-04-01

    Full Text Available Breast cancer accounts for the largest number of newly diagnosed cases in female cancer patients. Although mammography is a powerful screening tool, about 20% of breast cancer cases cannot be detected by this method. New diagnostic biomarkers for breast cancer are necessary. Here, we used a mass spectrometry-based quantitative metabolomics method to analyze plasma samples from 55 breast cancer patients and 25 healthy controls. A number of 30 patients and 20 age-matched healthy controls were used as a training dataset to establish a diagnostic model and to identify potential biomarkers. The remaining samples were used as a validation dataset to evaluate the predictive accuracy for the established model. Distinct separation was obtained from an orthogonal partial least squares-discriminant analysis (OPLS-DA model with good prediction accuracy. Based on this analysis, 39 differentiating metabolites were identified, including significantly lower levels of lysophosphatidylcholines and higher levels of sphingomyelins in the plasma samples obtained from breast cancer patients compared with healthy controls. Using logical regression, a diagnostic equation based on three metabolites (lysoPC a C16:0, PC ae C42:5 and PC aa C34:2 successfully differentiated breast cancer patients from healthy controls, with a sensitivity of 98.1% and a specificity of 96.0%.

  13. An UPLC-MS-based metabolomics investigation on the anti-fatigue effect of salidroside in mice.

    Science.gov (United States)

    Ma, Chaoyang; Hu, Liming; Tao, Guanjun; Lv, Wenping; Wang, Hongxin

    2015-02-01

    An ultra-performance liquid chromatography-quadrupole time-of-flight-based metabolomic approach was developed to study influence of salidroside, an anti-fatigue ingredient from Rhoiola rosea, on urinary metabolic profiling of rats to a single dose of 180 mg/kg per day. Unsupervised principal component analysis (PCA) and supervised orthogonal pre-projection to latent structures discriminate analysis (OPLS-DA) on metabolite profiling revealed obvious differentiation between the salidroside treated groups and controls in both positive and negative ion modes. Eleven urinary metabolites contributing to the differentiation were identified as anti-fatigue biomarkers: N-acetylserotonin, 2-Methoxyestrone 3-glucuronide, Taurine, Melatonin, Sorbitol, Geranyl diphosphate, Z-nucleotide, Cortisone, Dihydrocortisol, Sebacic acid, Pregnenolone sulfate. The physiological significance of these biomarkers is discussed. The work showed that metabolomics is a powerful tool in studying the anti-fatigue effects of natural compound salidroside on multiple targets in vivo. PMID:25543286

  14. Evaluation of Pacific white shrimp (Litopenaeus vannamei health during a superintensive aquaculture growout using NMR-based metabolomics.

    Directory of Open Access Journals (Sweden)

    Tracey B Schock

    Full Text Available Success of the shrimp aquaculture industry requires technological advances that increase production and environmental sustainability. Indoor, superintensive, aquaculture systems are being developed that permit year-round production of farmed shrimp at high densities. These systems are intended to overcome problems of disease susceptibility and of water quality issues from waste products, by operating as essentially closed systems that promote beneficial microbial communities (biofloc. The resulting biofloc can assimilate and detoxify wastes, may provide nutrition for the farmed organisms resulting in improved growth, and may aid in reducing disease initiated from external sources. Nuclear magnetic resonance (NMR-based metabolomic techniques were used to assess shrimp health during a full growout cycle from the nursery phase through harvest in a minimal-exchange, superintensive, biofloc system. Aberrant shrimp metabolomes were detected from a spike in total ammonia nitrogen in the nursery, from a reduced feeding period that was a consequence of surface scum build-up in the raceway, and from the stocking transition from the nursery to the growout raceway. The biochemical changes in the shrimp that were induced by the stressors were essential for survival and included nitrogen detoxification and energy conservation mechanisms. Inosine and trehalose may be general biomarkers of stress in Litopenaeus vannamei. This study demonstrates one aspect of the practicality of using NMR-based metabolomics to enhance the aquaculture industry by providing physiological insight into common environmental stresses that may limit growth or better explain reduced survival and production.

  15. NMR-based microbial metabolomics and the temperature-dependent coral pathogen Vibrio coralliilyticus.

    Science.gov (United States)

    Boroujerdi, Arezue F B; Vizcaino, Maria I; Meyers, Alexander; Pollock, Elizabeth C; Huynh, Sara Lien; Schock, Tracey B; Morris, Pamela J; Bearden, Daniel W

    2009-10-15

    Coral bleaching occurs when the symbioses between coral animals and their zooxanthellae is disrupted, either as part of a natural cycle or as the result of unusual events. The bacterium Vibrio coralliilyticus (type strain ATCC BAA-450) has been linked to coral disease globally (for example in the Mediterranean, Red Sea, Indian Ocean, and Great Barrier Reef) and like many other Vibrio species exhibits a temperature-dependent pathogenicity. The temperature-dependence of V. corallillyticus in regard to its metabolome was investigated. Nuclear magnetic resonance (NMR) spectra were obtained of methanol-water extracts of intracellula rmetabolites (endometabolome) from multiple samples of the bacteria cultured into late stationary phase at 27 degrees C (virulent form) and 24 degrees C (avirulent form). The spectra were subjected to principal components analysis (PCA), and significant temperature-based separations in PC1, PC2, and PC3 dimensions were observed. Betaine, succinate, and glutamate were identified as metabolites that caused the greatest temperature-based separations in the PC scores plots. With increasing temperature, betaine was shown to be down regulated, while succinate and glutamate were up regulated.

  16. Application of (1)H NMR-based serum metabolomic studies for monitoring female patients with rheumatoid arthritis.

    Science.gov (United States)

    Zabek, Adam; Swierkot, Jerzy; Malak, Anna; Zawadzka, Iga; Deja, Stanisław; Bogunia-Kubik, Katarzyna; Mlynarz, Piotr

    2016-01-01

    Rheumatoid arthritis is a chronic autoimmune-based inflammatory disease that leads to progressive joint degeneration, disability, and an increased risk of cardiovascular complications, which is the main cause of mortality in this population of patients. Although several biomarkers are routinely used in the management of rheumatoid arthritis, there is a high demand for novel biomarkers to further improve the early diagnosis of rheumatoid arthritis, stratification of patients, and the prediction of a better response to a specific therapy. In this study, the metabolomics approach was used to provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy. The results indicated that twelve metabolites were important for the discrimination of healthy control and rheumatoid arthritis. Notably, valine, isoleucine, lactate, alanine, creatinine, GPC  APC and histidine relative levels were lower in rheumatoid arthritis, whereas 3-hydroxyisobutyrate, acetate, NAC, acetoacetate and acetone relative levels were higher. Simultaneously, the analysis of the concentration of metabolites in rheumatoid arthritis and 3 months after induction treatment revealed that L1, 3-hydroxyisobutyrate, lysine, L5, acetoacetate, creatine, GPC+APC, histidine and phenylalanine were elevated in RA, whereas leucine, acetate, betaine and formate were lower. Additionally, metabolomics tools were employed to discriminate between patients with different IL-17A genotypes. Metabolomics may provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy in rheumatoid arthritis.

  17. Application of (1)H NMR-based serum metabolomic studies for monitoring female patients with rheumatoid arthritis.

    Science.gov (United States)

    Zabek, Adam; Swierkot, Jerzy; Malak, Anna; Zawadzka, Iga; Deja, Stanisław; Bogunia-Kubik, Katarzyna; Mlynarz, Piotr

    2016-01-01

    Rheumatoid arthritis is a chronic autoimmune-based inflammatory disease that leads to progressive joint degeneration, disability, and an increased risk of cardiovascular complications, which is the main cause of mortality in this population of patients. Although several biomarkers are routinely used in the management of rheumatoid arthritis, there is a high demand for novel biomarkers to further improve the early diagnosis of rheumatoid arthritis, stratification of patients, and the prediction of a better response to a specific therapy. In this study, the metabolomics approach was used to provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy. The results indicated that twelve metabolites were important for the discrimination of healthy control and rheumatoid arthritis. Notably, valine, isoleucine, lactate, alanine, creatinine, GPC  APC and histidine relative levels were lower in rheumatoid arthritis, whereas 3-hydroxyisobutyrate, acetate, NAC, acetoacetate and acetone relative levels were higher. Simultaneously, the analysis of the concentration of metabolites in rheumatoid arthritis and 3 months after induction treatment revealed that L1, 3-hydroxyisobutyrate, lysine, L5, acetoacetate, creatine, GPC+APC, histidine and phenylalanine were elevated in RA, whereas leucine, acetate, betaine and formate were lower. Additionally, metabolomics tools were employed to discriminate between patients with different IL-17A genotypes. Metabolomics may provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy in rheumatoid arthritis. PMID:26476882

  18. Evidence of vintage effects on grape wines using 1H NMR-based metabolomic study.

    Science.gov (United States)

    Lee, Jang-Eun; Hwang, Geum-Sook; Van Den Berg, Frans; Lee, Cherl-Ho; Hong, Young-Shick

    2009-08-19

    The chemical composition of grape wines varies with grape variety, environmental factors of climate and soil, and bacterial strains, which can each affect the wine quality. Using (1)H NMR analysis coupled with multivariate statistical data sets, we investigated the effects of grape vintage on metabolic profiles of wine and the relationship between wine metabolites and meteorological data. Principal component analysis (PCA) showed a clear differentiation between Meoru wines that were vinified with the same yeast strain and Meoru grapes harvested from the same vineyard but with a different vintage. The metabolites contributing to the differentiation were identified as 2,3-butandiol, lactic acid, alanine, proline, gamma-aminobutyric acid (GABA), choline, and polyphenols, by complementary PCA loading plot. Markedly higher levels of proline, lactic acid and polyphenols were observed in the 2006 vintage wines compared to those of 2007 vintage, showing excellent agreement with the meteorological data that the sun-exposed time and rainfall in 2006 were approximately two times more and four times less, respectively, than those in 2007. These results revealed the important role of climate during ripening period in the chemical compositions of the grape. This study highlights the reliability of NMR-based metabolomic data by integration with meteorological data in characterizing wine or grape.

  19. Objective Definition of Monofloral and Polyfloral Honeys Based on NMR Metabolomic Profiling.

    Science.gov (United States)

    Schievano, Elisabetta; Finotello, Claudia; Uddin, Jalal; Mammi, Stefano; Piana, Lucia

    2016-05-11

    In this paper, a remarkably precise, simple, and objective definition of monofloral and polyfloral honey based on NMR metabolomics is proposed. The spectra of organic extracts of 983 samples of 16 botanical origins were used to derive one-versus-all OPLS-DA classification models. The predictive components of the statistical models reveal not only the principal but also the secondary floral origins present in a sample of honey, a novel feature with respect to the methods present in the literature that are able to confirm the authenticity of monofloral honeys but not to characterize a mixture of honey types. This result descends from the peculiar features of the chloroform spectra that show diagnostic resonances for almost each botanical origin, making these NMR spectra suitable fingerprints. The reliability of the method was tested with an additional 120 samples, and the class assignments were compared with those obtained by traditional analysis. The two approaches are in excellent agreement in identifying the floral species present in honeys and in the botanical classification. Therefore, this NMR method may prove to be a valid solution to the huge limitations of traditional classification, which is very demanding and complex. PMID:27086991

  20. [Comparison between Astragalus membranaceus var. mongholicus and Hedysarum polybotrys based on ITS sequences and metabolomics].

    Science.gov (United States)

    Jiao, Mei-li; Li, Zhen-yu; Zhang, Fu-sheng; Qin, Xue-mei

    2015-12-01

    Astragalus membranaceus var. mongholicus and Hedysarum polybotrys belong to different genera, but have similar drug efficacy in traditional Chinese medicine theory, and H. polybotrys was used as the legal A. membranaceus var. mongholicus previously. In this study, similarities and differences between them were analyzed via their ITS/ITS2 fragments information. The ITS (internal transcribed spacer) regions were amplified using polymerase chain reaction and then sequenced in two-way. The alignment lengths of ITS regions were 616 bp, in which 508 loci were consistent, and 103 loci were different, accounting for 82.47% and 16.72% of the total ITS nucleotides in length, respectively. As genotype determines phenotype, 1HNMR-based metabolomic approach was further used to reveal the chemical similarities and differences between them. Thirty-four metabolites were identified in the 1H NMR spectra, and twenty-seven metabolites were the common components. Amino acids, carbohydrates and other primary metabolites were similar, while a large difference existed in the flavonoids and astragalosides. This study suggests that A. membranaceus var. mongholicus and H. polybotrys show similarities and differences from molecular and chemical perspectives, which has laid a foundation for elucidating the effective material basis of drug with similar efficacy and resources utilization. PMID:27169287

  1. Discrimination of the geographical origin of beef by (1)H NMR-based metabolomics.

    Science.gov (United States)

    Jung, Youngae; Lee, Jueun; Kwon, Joseph; Lee, Kwang-Sik; Ryu, Do Hyun; Hwang, Geum-Sook

    2010-10-13

    The geographical origin of beef is of increasing interest to consumers and producers due to "mad cow" disease and the implementation of the Free Trade Agreement (FTA). In this study, (1)H NMR spectroscopy coupled with multivariate statistical analyses was used to differentiate the geographical origin of beef samples. Principal component analysis (PCA) and orthogonal projection to latent structure-discriminant analysis (OPLS-DA) showed significant separation between extracts of beef originating from four countries: Australia, Korea, New Zealand, and the United States. The major metabolites responsible for differentiation in OPLS-DA loading plots were succinate and various amino acids including isoleucine, leucine, methionine, tyrosine, and valine. A one-way ANOVA was performed to statistically certify the difference in metabolite levels. The data suggest that NMR-based metabolomics is an efficient method to distinguish fingerprinting difference between raw beef samples, and several metabolites including various amino acids and succinate can be possible biomarkers for discriminating the geographical origin of beef. PMID:20831251

  2. NMR based serum metabolomics reveals a distinctive signature in patients with Lupus Nephritis

    Science.gov (United States)

    Guleria, Anupam; Pratap, Avadhesh; Dubey, Durgesh; Rawat, Atul; Chaurasia, Smriti; Sukesh, Edavalath; Phatak, Sanat; Ajmani, Sajal; Kumar, Umesh; Khetrapal, Chunni Lal; Bacon, Paul; Misra, Ramnath; Kumar, Dinesh

    2016-01-01

    Management of patient with Lupus Nephritis (LN) continues to remain a challenge for the treating physicians because of considerable morbidity and even mortality. The search of biomarkers in serum and urine is a focus of researchers to unravel new targets for therapy. In the present study, the utility of NMR-based serum metabolomics has been evaluated for the first time in discriminating LN patients from non-nephritis lupus patients (SLE) and further to get new insights into the underlying disease processes for better clinical management. Metabolic profiling of sera obtained from 22 SLE patients, 40 LN patients and 30 healthy controls (HC) were performed using high resolution 1D 1H-CPMG and diffusion edited NMR spectra to identify the potential molecular biomarkers. Using multivariate analysis, we could distinguish SLE and LN patients from HC and LN from SLE patients. Compared to SLE patients, the LN patients had increased serum levels of lipid metabolites (including LDL/VLDL lipoproteins), creatinine and decreased levels of acetate. Our results revealed that metabolic markers especially lipids and acetate derived from NMR spectroscopy has high sensitivity and specificity to distinguish LN among SLE patients and has the potential to be a useful adjunctive tool in diagnosis and clinical management of LN. PMID:27739464

  3. (1)H NMR-based metabolomic approach for understanding the fermentation behaviors of wine yeast strains.

    Science.gov (United States)

    Son, Hong-Seok; Hwang, Geum-Sook; Kim, Ki Myong; Kim, Eun-Young; van den Berg, Frans; Park, Won-Mok; Lee, Cherl-Ho; Hong, Young-Shick

    2009-02-01

    (1)H NMR spectroscopy coupled with multivariate statistical analysis was used for the first time to investigate metabolic changes in musts during alcoholic fermentation and wines during aging. Three Saccharomyces cerevisiae yeast strains (RC-212, KIV-1116, and KUBY-501) were also evaluated for their impacts on the metabolic changes in must and wine. Pattern recognition (PR) methods, including PCA, PLS-DA, and OPLS-DA scores plots, showed clear differences for metabolites among musts or wines for each fermentation stage up to 6 months. Metabolites responsible for the differentiation were identified as valine, 2,3-butanediol (2,3-BD), pyruvate, succinate, proline, citrate, glycerol, malate, tartarate, glucose, N-methylnicotinic acid (NMNA), and polyphenol compounds. PCA scores plots showed continuous movements away from days 1 to 8 in all musts for all yeast strains, indicating continuous and active fermentation. During alcoholic fermentation, the highest levels of 2,3-BD, succinate, and glycerol were found in musts with the KIV-1116 strain, which showed the fastest fermentation or highest fermentative activity of the three strains, whereas the KUBY-501 strain showed the slowest fermentative activity. This study highlights the applicability of NMR-based metabolomics for monitoring wine fermentation and evaluating the fermentative characteristics of yeast strains.

  4. Metabolomics for Quality and food security

    International Nuclear Information System (INIS)

    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.

  5. Metabolomics of genetically modified crops.

    Science.gov (United States)

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

    2014-10-20

    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.

  6. Comparison of Fruits of Forsythia suspensa at Two Different Maturation Stages by NMR-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Jinping Jia

    2015-05-01

    Full Text Available Forsythiae Fructus (FF, the dried fruit of Forsythia suspensa, has been widely used as a heat-clearing and detoxifying herbal medicine in China. Green FF (GF and ripe FF (RF are fruits of Forsythia suspensa at different maturity stages collected about a month apart. FF undergoes a complex series of physical and biochemical changes during fruit ripening. However, the clinical uses of GF and RF have not been distinguished to date. In order to comprehensively compare the chemical compositions of GF and RF, NMR-based metabolomics coupled with HPLC and UV spectrophotometry methods were adopted in this study. Furthermore, the in vitro antioxidant and antibacterial activities of 50% methanol extracts of GF and RF were also evaluated. A total of 27 metabolites were identified based on NMR data, and eight of them were found to be different between the GF and RF groups. The GF group contained higher levels of forsythoside A, forsythoside C, cornoside, rutin, phillyrin and gallic acid and lower levels of rengyol and β-glucose compared with the RF group. The antioxidant activity of GF was higher than that of RF, but no significant difference was observed between the antibacterial activities of GF and RF. Given our results showing their distinct chemical compositions, we propose that NMR-based metabolic profiling can be used to discriminate between GF and RF. Differences in the chemical and biological activities of GF and RF, as well as their clinical efficacies in traditional Chinese medicine should be systematically investigated in future studies.

  7. 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.

  8. 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. PMID:26476597

  9. Elucidating induced plant defenses: the use of targeted metabolomics as a bridge from elicitation to response

    Science.gov (United States)

    Dynamic plant defense responses to biotic attack involve the perception of specific biochemical elicitors associated with the offending agent, activation of signaling cascades, and the production of small molecules with complex protective roles. Chemical analyses are essential empirical tools for el...

  10. 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

    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...... the fact that lower levels of total carbon were found in ant-hosting plants. The increased levels of total nitrogen, amino acids, fatty acids and caffeine and the decreased total carbon were consistent with changes observed in plants grown with an increased supply of nitrogen-containing nutrients. The up...

  11. An untargeted metabolomics approach to contaminant analysis. Pinpointing potential unknown compounds

    NARCIS (Netherlands)

    Lommen, A.; Weg, van der G.; Engelen, M.C.; Bor, G.; Hoogenboom, L.A.P.; Nielen, M.W.F.

    2007-01-01

    This study deals with an automated data analysis strategy to pinpoint potential unknown compounds in full scan mass spectrometry (MS) experiments. Three examples of an untargeted metabolomics approach to contaminant analysis are given. By comparing a plant-oil based hormone cocktail to 90 plant oil

  12. 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.

  13. Computational approaches for systems metabolomics.

    Science.gov (United States)

    Krumsiek, Jan; Bartel, Jörg; Theis, Fabian J

    2016-06-01

    Systems genetics is defined as the simultaneous assessment and analysis of multi-omics datasets. In the past few years, metabolomics has been established as a robust tool describing an important functional layer in this approach. The metabolome of a biological system represents an integrated state of genetic and environmental factors and has been referred to as a 'link between genotype and phenotype'. In this review, we summarize recent progresses in statistical analysis methods for metabolomics data in combination with other omics layers. We put a special focus on complex, multivariate statistical approaches as well as pathway-based and network-based analysis methods. Moreover, we outline current challenges and pitfalls of metabolomics-focused multi-omics analyses and discuss future steps for the field.

  14. 1H NMR- based metabolomics approaches as non- invasive tools for diagnosis of endometriosis

    Directory of Open Access Journals (Sweden)

    Negar Ghazi

    2016-01-01

    Full Text Available Background: So far, non-invasive diagnostic approaches such as ultrasound, magnetic resonance imaging, or blood tests do not have sufficient diagnostic power for endometriosis disease. Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. Objective: The present study focuses on the identification of predictive biomarkers in serum by pattern recognition techniques and uses partial least square discriminant analysis, multi-layer feed forward artificial neural networks (ANNs and quadratic discriminant analysis (QDA modeling tools for the early diagnosis of endometriosis in a minimally invasive manner by 1H- NMR based metabolomics. Materials and Methods: This prospective cohort study was done in Pasteur Institute, Iran in June 2013. Serum samples of 31 infertile women with endometriosis (stage II and III who confirmed by diagnostic laparoscopy and 15 normal women were collected and analyzed by nuclear magnetic resonance spectroscopy. The model was built by using partial least square discriminant analysis, QDA, and ANNs to determine classifier metabolites for early prediction risk of disease. Results: The levels of 2- methoxyestron, 2-methoxy estradiol, dehydroepiandrostion androstendione, aldosterone, and deoxy corticosterone were enhanced significantly in infertile group. While cholesterol and primary bile acids levels were decreased. QDA model showed significant difference between two study groups. Positive and negative predict value levels obtained about 71% and 78%, respectively. ANNs provided also criteria for detection of endometriosis. Conclusion: The QDA and ANNs modeling can be used as computational tools in noninvasive diagnose of endometriosis. However, the model designed by QDA methods is more efficient compared to ANNs in diagnosis of endometriosis patients.

  15. Assessment of clam ruditapes philippinarum as Heavy metal bioindicators using NMR-based metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaoli; Zhang, Linbao; You, Liping [Key Laboratory of Coastal Zone Environment Processes, CAS, Shandong Provincial Key Laboratory of Coastal Zone Environment Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai (China); The Graduate School of Chinese Academy of Sciences, Beijing (China); Yu, Junbao; Cong, Ming; Wang, Qing; Li, Fei; Li, Lianzhen; Zhao, Jianmin; Li, Chenghua; Wu, Huifeng [Key Laboratory of Coastal Zone Environment Processes, CAS, Shandong Provincial Key Laboratory of Coastal Zone Environment Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai (China)

    2011-08-15

    There are mainly distributed three pedigrees (White, Liangdao Red, and Zebra) of Manila clam Ruditapes philippinarum in Yantai population along the Bohai marine and coast. However, the biological differences to environmental stressors have been ignored in toxicology studies, which could lead to the distortion of biological interpretations of toxicological effects induced by environmental contaminants. In this study, we applied a system biology approach, metabolomics to compare the metabolic profiles in digestive gland from three pedigrees of clam and characterize and compare the metabolic responses induced by mercury in clam digestive gland tissues to determine a sensitive pedigree of clam as a preferable bioindicator for metal pollution monitoring and toxicology research. The most abundant metabolites, respectively, included branched-chain amino acids, alanine, and arginine in White samples, glutamate, dimethylglycine, and glycine in Zebra clams and acetylcholine, betaine, glucose, and glycogen in Liangdao Red clams. After 48 h exposure of 20 {mu}g L{sup -1} Hg{sup 2+}, the metabolic profiles from the three pedigrees of clams showed differentially significant changes in alanine, glutamate, succinate, taurine, hypotaurine, glycine, arginine, glucose, etc. Our findings indicate the toxicological effects of mercury exposure in Manila clams including the neurotoxicity, disturbances in energetic metabolisms and osmoregulation in the digestive glands and suggest that Liangdao Red pedigree of clam could be a preferable bioindicator for the metal pollution monitoring based on the more sensitive classes of metabolic changes from digestive glands compared with other two (White and Zebra) pedigrees of clams. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. Metabolomics of Genetically Modified Crops

    OpenAIRE

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

    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 resul...

  17. Nuclear magnetic resonance-based metabolomics reveals that dairy protein fractions affect urinary urea excretion differently in overweight adolescents

    DEFF Research Database (Denmark)

    Zheng, Hong; Yde, Christian C.; Dalsgaard, Trine K.;

    2015-01-01

    was investigated by using NMR-based urine metabolomics. Overweight adolescents (n = 192; age = 12–15 years; BMI = 25.4 ± 2.3 kg/m2) were randomly assigned to 1 L/day of casein (citrate content: 3.27 mol/L), whey (citrate content: 0.04 mol/L), skim milk, or water for 12 weeks. A significant increase in the urinary...

  18. Nutritional Metabolomics

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde

    of the crucial steps is data preprocessing, which is particularly cumbersome for complex liquid chromatography mass spectrometry (LC-MS) data. Accordingly, in PAPER I, different LC-MS data preprocessing tools, MarkerLynx, MZmine, XCMS and a customised method (spectral binning and chromatographic collapsing) were...... and alignment algorithms, such that each has pros and cons. Thus, the use of more than one software tool and/or the use of several parameter settings during data preprocessing are likely to decrease the risk of failing to detect features (potential marker candidates) in untargeted metabolomics. On the other...... hand, customised methods lead to many false positives and negatives. Data preprocessing is followed by data analysis. In metabolomics, large amount of complex data characterise few samples, thus data analysis becomes a critical step as well. Principal component analysis (PCA) is useful for exploratory...

  19. NMR-based metabolomics approach to study the toxicity of lambda-cyhalothrin to goldfish (Carassius auratus)

    International Nuclear Information System (INIS)

    Highlights: •A goldfish model was established to investigate the toxicity of lambda-cyhalothrin (LCT) exposure on multiple organs. •NMR based metabolomics approach were firstly used to provide a global view of the toxicity of LCT. •LCT induced neurotransmitters and osmoregulatory imbalances, oxidative stress, energy and amino acid metabolic disorders. •Glutamate–glutamine–GABA axis as a potential target for LCT toxicity was first found. -- Abstract: In this study, a 1H nuclear magnetic resonance (NMR) based metabolomics approach was applied to investigate the toxicity of lambda-cyhalothrin (LCT) in goldfish (Carassius auratus). LCT showed tissue-specific damage to gill, heart, liver and kidney tissues of goldfish. NMR profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) was developed to discern metabolite changes occurring after one week LCT exposure in brain, heart and kidney tissues of goldfish. LCT exposure influenced levels of many metabolites (e.g., leucine, isoleucine and valine in brain and kidney; lactate in brain, heart and kidney; alanine in brain and kidney; choline in brain, heart and kidney; taurine in brain, heart and kidney; N-acetylaspartate in brain; myo-inositol in brain; phosphocreatine in brain and heart; 2-oxoglutarate in brain; cis-aconitate in brain, and etc.), and broke the balance of neurotransmitters and osmoregulators, evoked oxidative stress, disturbed metabolisms of energy and amino acids. The implication of glutamate–glutamine–gamma-aminobutyric axis in LCT induced toxicity was demonstrated for the first time. Our findings demonstrated the applicability and potential of metabolomics approach for the elucidation of toxicological effects of pesticides and the underlying mechanisms, and the discovery of biomarkers for pesticide pollution in aquatic environment

  20. NMR-based metabolomics approach to study the toxicity of lambda-cyhalothrin to goldfish (Carassius auratus)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Minghui [State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009 (China); Wang, Junsong, E-mail: wang.junsong@gmail.com [Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Nanjing 210094 (China); Lu, Zhaoguang; Wei, Dandan; Yang, Minghua [State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009 (China); Kong, Lingyi, E-mail: cpu_lykong@126.com [State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009 (China)

    2014-01-15

    Highlights: •A goldfish model was established to investigate the toxicity of lambda-cyhalothrin (LCT) exposure on multiple organs. •NMR based metabolomics approach were firstly used to provide a global view of the toxicity of LCT. •LCT induced neurotransmitters and osmoregulatory imbalances, oxidative stress, energy and amino acid metabolic disorders. •Glutamate–glutamine–GABA axis as a potential target for LCT toxicity was first found. -- Abstract: In this study, a {sup 1}H nuclear magnetic resonance (NMR) based metabolomics approach was applied to investigate the toxicity of lambda-cyhalothrin (LCT) in goldfish (Carassius auratus). LCT showed tissue-specific damage to gill, heart, liver and kidney tissues of goldfish. NMR profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) was developed to discern metabolite changes occurring after one week LCT exposure in brain, heart and kidney tissues of goldfish. LCT exposure influenced levels of many metabolites (e.g., leucine, isoleucine and valine in brain and kidney; lactate in brain, heart and kidney; alanine in brain and kidney; choline in brain, heart and kidney; taurine in brain, heart and kidney; N-acetylaspartate in brain; myo-inositol in brain; phosphocreatine in brain and heart; 2-oxoglutarate in brain; cis-aconitate in brain, and etc.), and broke the balance of neurotransmitters and osmoregulators, evoked oxidative stress, disturbed metabolisms of energy and amino acids. The implication of glutamate–glutamine–gamma-aminobutyric axis in LCT induced toxicity was demonstrated for the first time. Our findings demonstrated the applicability and potential of metabolomics approach for the elucidation of toxicological effects of pesticides and the underlying mechanisms, and the discovery of biomarkers for pesticide pollution in aquatic environment.

  1. Transcriptome and metabolome analysis of plant sulphate starvation and resupply provides novel information on transcriptional regulation of metabolism associated with sulphur, nitrogen and phosphorus nutritional responses in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Monika eBielecka

    2015-01-01

    Full Text Available Sulphur is an essential macronutrient for plant growth and development. Reaching a thorough understanding of the molecular basis for changes in plant metabolism depending on the sulphur-nutritional status at the systems level will advance our basic knowledge and help target future crop improvement. Although the transcriptional responses induced by sulphate starvation have been studied in the past, knowledge of the regulation of sulphur metabolism is still fragmentary. This work focuses on the discovery of candidates for regulatory genes such as transcription factors (TFs using ‘omics technologies. For this purpose a short term sulphate-starvation / re-supply approach was used. ATH1 microarray studies and metabolite determinations yielded 21 TFs which responded more than 2-fold at the transcriptional level to sulphate starvation. Categorization by response behaviors under sulphate-starvation / re-supply and other nutrient starvations such as nitrate and phosphate allowed determination of whether the TF genes are specific for or common between distinct mineral nutrient depletions. Extending this co-behavior analysis to the whole transcriptome data set enabled prediction of putative downstream genes. Additionally, combinations of transcriptome and metabolome data allowed identification of relationships between TFs and downstream responses, namely, expression changes in biosynthetic genes and subsequent metabolic responses. Effect chains on glucosinolate and polyamine biosynthesis are discussed in detail. The knowledge gained from this study provides a blueprint for an integrated analysis of transcriptomics and metabolomics and application for the identification of uncharacterized genes.

  2. Identification of Altered Metabolomic Profiles Following a Panchakarma-based Ayurvedic Intervention in Healthy Subjects: The Self-Directed Biological Transformation Initiative (SBTI).

    Science.gov (United States)

    Peterson, Christine Tara; Lucas, Joseph; John-Williams, Lisa St; Thompson, J Will; Moseley, M Arthur; Patel, Sheila; Peterson, Scott N; Porter, Valencia; Schadt, Eric E; Mills, Paul J; Tanzi, Rudolph E; Doraiswamy, P Murali; Chopra, Deepak

    2016-01-01

    The effects of integrative medicine practices such as meditation and Ayurveda on human physiology are not fully understood. The aim of this study was to identify altered metabolomic profiles following an Ayurveda-based intervention. In the experimental group, 65 healthy male and female subjects participated in a 6-day Panchakarma-based Ayurvedic intervention which included herbs, vegetarian diet, meditation, yoga, and massage. A set of 12 plasma phosphatidylcholines decreased (adjusted p metabolomic alterations may reflect a Panchakarma-induced modulation of metabotypes. Panchakarma promoted statistically significant changes in plasma levels of phosphatidylcholines, sphingomyelins and others in just 6 days. Forthcoming studies that integrate metabolomics with genomic, microbiome and physiological parameters may facilitate a broader systems-level understanding and mechanistic insights into these integrative practices that are employed to promote health and well-being. PMID:27611967

  3. Mass spectra-based framework for automated structural elucidation of metabolome data to explore phytochemical diversity

    Directory of Open Access Journals (Sweden)

    Fumio eMatsuda

    2011-08-01

    Full Text Available A novel framework for automated elucidation of metabolite structures in liquid chromatography-mass spectrometer (LC-MS metabolome data was constructed by integrating databases. High-resolution tandem mass spectra data automatically acquired from each metabolite signal were used for database searches. Three distinct databases, KNApSAcK, ReSpect, and the PRIMe standard compound database, were employed for the structural elucidation. The outputs were retrieved using the CAS metabolite identifier for identification and putative annotation. A simple metabolite ontology system was also introduced to attain putative characterization of the metabolite signals. The automated method was applied for the metabolome data sets obtained from the rosette leaves of 20 Arabidopsis accessions. Phenotypic variations in novel Arabidopsis metabolites among these accessions could be investigated using this method.

  4. NMR-based metabolomic studies on the toxicological effects of cadmium and copper on green mussels Perna viridis

    Energy Technology Data Exchange (ETDEWEB)

    Wu Huifeng [Section of Marine Ecology and Biotechnology, Division of Life Science, Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon (Hong Kong); Wang Wenxiong, E-mail: wwang@ust.hk [Section of Marine Ecology and Biotechnology, Division of Life Science, Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon (Hong Kong)

    2010-11-15

    Traditional toxicology studies have focused on selected biomarkers to characterize the biological stress induced by metals in marine organisms. In this study, a system biology tool, metabolomics, was applied to the marine mussel Perna viridis to investigate changes in the metabolic profiles of soft tissue as a response to copper (Cu) and cadmium (Cd), both as single metal and as a mixture. The major metabolite changes corresponding to metal exposure are related to amino acids, osmolytes, and energy metabolites. Following metal exposure for 1 week, there was a significant increase in the levels of branched chain amino acids, histidine, glutamate, glutamine, hypotaurine, dimethylglycine, arginine and ATP/ADP. For the Cu + Cd co-exposed mussels, the levels of lactate, branched chain amino acid, succinate, and NAD increased, whereas the levels of glucose, glycogen, and ATP/ADP decreased, indicating a different metabolic profile for the single metal exposure groups. After 2 weeks of exposure, the mussels showed acclimatization to Cd exposure based on the recovery of some metabolites. However, the metabolic profile induced by the metal mixture was very similar to that from Cu exposure, suggesting that Cu dominantly induced the metabolic disturbances. Both Cu and Cd may lead to neurotoxicity, disturbances in energy metabolism, and osmoregulation changes. These results demonstrate the high applicability and reliability of NMR-based metabolomics in interpreting the toxicological mechanisms of metals using global metabolic biomarkers.

  5. (1)H NMR-based metabolomics of Daphnia magna responses after sub-lethal exposure to triclosan, carbamazepine and ibuprofen.

    Science.gov (United States)

    Kovacevic, Vera; Simpson, André J; Simpson, Myrna J

    2016-09-01

    Pharmaceuticals and personal care products are a class of emerging contaminants that are present in wastewater effluents, surface water, and groundwater around the world. There is a need to determine rapid and reliable bioindicators of exposure and the toxic mode of action of these contaminants to aquatic organisms. (1)H nuclear magnetic resonance (NMR)-based metabolomics in combination with multivariate statistical analysis was used to determine the metabolic profile of Daphnia magna after exposure to a range of sub-lethal concentrations of triclosan (6.25-100μg/L), carbamazepine (1.75-14mg/L) and ibuprofen (1.75-14mg/L) for 48h. Sub-lethal triclosan exposure suggested a general oxidative stress condition and the branched-chain amino acids, glutamine, glutamate, and methionine emerged as potential bioindicators. The aromatic amino acids, serine, glycine and alanine are potential bioindicators for sub-lethal carbamazepine exposure that may have altered energy metabolism. The potential bioindicators for sub-lethal ibuprofen exposure are serine, methionine, lysine, arginine and leucine, which showed a concentration-dependent response. The differences in the metabolic changes were related to the dissimilar modes of toxicity of triclosan, carbamazepine and ibuprofen. (1)H NMR-based metabolomics gave an improved understanding of how these emerging contaminants impact the keystone species D. magna. PMID:26809854

  6. Recommendations and Standardization of Biomarker Quantification Using NMR-based Metabolomics with Particular Focus on Urinary Analysis

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2016-01-08

    NMR-based metabolomics has shown considerable promise in disease diagnosis and biomarker discovery because it allows one to non-destructively identify and quantify large numbers of novel metabolite biomarkers in both biofluids and tissues. Indeed, precise metabolite quantification is a necessary prerequisite to move any chemical biomarker or biomarker panel from the lab into the clinic. Among the many biofluids (urine, serum, plasma, cerebrospinal fluid and saliva) commonly used for disease diagnosis and prognosis, urine has several advantages. It is abundant, sterile, easily obtained, needs little sample preparation and does not require any invasive medical procedures for collection. Furthermore, urine captures and concentrates many “unwanted” or “undesirable” compounds throughout the body, thereby providing a rich source of potentially useful disease biomarkers. However, the incredible variation in urine chemical concentrations due to effects such as gender, age, diet, life style, health conditions, and physical activity make the analysis of urine and the identification of useful urinary biomarkers by NMR quite challenging. In this review, we discuss a number of the most significant issues regarding NMR-based urinary metabolomics with a specific emphasis on metabolite quantification for disease biomarker applications. We also propose a number of data collection and instrumental recommendations regarding NMR pulse sequences, acceptable acquisition parameter ranges, relaxation effects on quantitation, proper handling of instrumental differences, as well as recommendations regarding sample preparation and biomarker assessment.

  7. 1H nuclear magnetic resonance-based metabolomics reveals sex-specific metabolic changes of gastrodin intervention in rats

    Institute of Scientific and Technical Information of China (English)

    Xin Li; Yuan-Wei Jia; Jun-Song Wang; Ming-Hua Yang; Kelvin D G Wang; Ling-Yi Kong

    2014-01-01

    Objective:To explore1H nuclear magnetic resonance-based metabolomics on sex-specific metabolic changes of gastrodin intervention in rats.Methods:In this research,1HNMR-based metabolomics was used for the first time to investigate metabolic changes following chronic intervention with gastrodin in rats.Results:24 endogenous metabolites were identified.Body weight, daily diet and the total volume of urine in in each day of each rat were measured synchronously.Modifications in12 metabolites were observed following gastrodin intervention, indicating gastrodin-induced alterations in carbohydrate and energy metabolism.Interestingly, these metabolic changes were not totally identical in female and male rats.Some metabolic changes arising from gastrodin intervention showed sexual dimorphism includingLDL/VLDL and lactate which were on the decrease in the female but on the increase in the male, together with arginine/ornithine, creatine, and glycerol which were on the increase in the female but on the decrease in the male.While the decrease in pyruvate, succinate and glutamate was only shown in the male and the increase in valine,α-ketoglutarate, glycine and glucose was only in the female. Conclusions:This research shows the sex-specific metabolic response toGAS intervention, weatherGAS is a healthy dietary supplement for the male merits further investigation.

  8. ~1H nuclear magnetic resonance-based metabolomics reveals sex-specific metabolic changes of gastrodin intervention in rats

    Institute of Scientific and Technical Information of China (English)

    Xin; Li; Yuan-Wei; Jia; Jun-Song; Wang; Ming-Hua; Yang; Kelvin; D.G.Wang; Ling-Yi; Kong

    2014-01-01

    Objective:To explore~1H nuclear magnetic resonance-based metabolomics on sex-specific metabolic changes of gastrodin intervention in rats.Methods:In this research,~1H NMR-based metabolomics was used for the first time to investigate metabolic changes following chronic intervention with gastrodin in rats.Results:24 endogenous metabolites were identified.Body weight.daily diet and the total volume of urine in in each day of each rat were measured synchronously.Modifications in 12 metabolites were observsd following gastrodin intervention,indicating gastrodin-induced alterations in carbohydrate and energy metabolism.Interestingly,these metabolic changes were not totally identical in female and male rats.Some metabolic changes arising from gastrodin intervention showed sexual dimorphism including LDL/VLDL and lactate which were on the decrease in the female but on the increase in the male,together with arginine/ornithine,creatine,and glycerol which were on the increase in the female but on the decrease in the male.While the decrease in pyruvate,succinate and glutamate was only shown in the male and the increase in valine,α-ketoglutarate and glucose was only in the female.Conclusions:This resesrch shows the sex-specific metabolic response to GAS intervention,weather GAS is a healthy dietary supplement for the male merits further investigation

  9. Role of Metabolomics in Traumatic Brain Injury Research.

    Science.gov (United States)

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

    2016-10-01

    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, to advanced statistical methods. Metabolomics in traumatic brain injury 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 traumatic brain injury. PMID:27637396

  10. Discovering Regulated Metabolite Families in Untargeted Metabolomics Studies.

    Science.gov (United States)

    Treutler, Hendrik; Tsugawa, Hiroshi; Porzel, Andrea; Gorzolka, Karin; Tissier, Alain; Neumann, Steffen; Balcke, Gerd Ulrich

    2016-08-16

    The identification of metabolites by mass spectrometry constitutes a major bottleneck which considerably limits the throughput of metabolomics studies in biomedical or plant research. Here, we present a novel approach to analyze metabolomics data from untargeted, data-independent LC-MS/MS measurements. By integrated analysis of MS(1) abundances and MS/MS spectra, the identification of regulated metabolite families is achieved. This approach offers a global view on metabolic regulation in comparative metabolomics. We implemented our approach in the web application "MetFamily", which is freely available at http://msbi.ipb-halle.de/MetFamily/ . MetFamily provides a dynamic link between the patterns based on MS(1)-signal intensity and the corresponding structural similarity at the MS/MS level. Structurally related metabolites are annotated as metabolite families based on a hierarchical cluster analysis of measured MS/MS spectra. Joint examination with principal component analysis of MS(1) patterns, where this annotation is preserved in the loadings, facilitates the interpretation of comparative metabolomics data at the level of metabolite families. As a proof of concept, we identified two trichome-specific metabolite families from wild-type tomato Solanum habrochaites LA1777 in a fully unsupervised manner and validated our findings based on earlier publications and with NMR. PMID:27452369

  11. Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study.

    Science.gov (United States)

    Stenson, Martin; Pedersen, Anders; Hasselblom, Sverker; Nilsson-Ehle, Herman; Karlsson, Bengt Göran; Pinto, Rui; Andersson, Per-Ola

    2016-08-01

    The prognosis for diffuse large B-cell lymphoma (DLBCL) patients with early relapse or refractory disease is dismal. To determine if clinical outcome correlated to diverse serum metabolomic profiles, we used (1)H nuclear magnetic resonance (NMR) spectroscopy and compared two groups of DLBCL patients treated with immunochemotherapy: i) refractory/early relapse (REF/REL; n=27) and ii) long-term progression-free (CURED; n = 60). A supervised multivariate analysis showed a separation between the groups. Among discriminating metabolites higher in the REF/REL group were the amino acids lysine and arginine, the degradation product cadaverine and a compound in oxidative stress (2-hydroxybutyrate). In contrast, the amino acids aspartate, valine and ornithine, and a metabolite in the glutathione cycle, pyroglutamate, were higher in CURED patients. Together, our data indicate that NMR-based serum metabolomics can identify a signature for DLBCL patients with high-risk of failing immunochemotherapy, prompting for larger validating studies which could lead to more individualized treatment of this disease. PMID:26887805

  12. NMR-based metabolomics approach to study the toxicity of lambda-cyhalothrin to goldfish (Carassius auratus).

    Science.gov (United States)

    Li, Minghui; Wang, Junsong; Lu, Zhaoguang; Wei, Dandan; Yang, Minghua; Kong, Lingyi

    2014-01-01

    In this study, a (1)H nuclear magnetic resonance (NMR) based metabolomics approach was applied to investigate the toxicity of lambda-cyhalothrin (LCT) in goldfish (Carassius auratus). LCT showed tissue-specific damage to gill, heart, liver and kidney tissues of goldfish. NMR profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) was developed to discern metabolite changes occurring after one week LCT exposure in brain, heart and kidney tissues of goldfish. LCT exposure influenced levels of many metabolites (e.g., leucine, isoleucine and valine in brain and kidney; lactate in brain, heart and kidney; alanine in brain and kidney; choline in brain, heart and kidney; taurine in brain, heart and kidney; N-acetylaspartate in brain; myo-inositol in brain; phosphocreatine in brain and heart; 2-oxoglutarate in brain; cis-aconitate in brain, and etc.), and broke the balance of neurotransmitters and osmoregulators, evoked oxidative stress, disturbed metabolisms of energy and amino acids. The implication of glutamate-glutamine-gamma-aminobutyric axis in LCT induced toxicity was demonstrated for the first time. Our findings demonstrated the applicability and potential of metabolomics approach for the elucidation of toxicological effects of pesticides and the underlying mechanisms, and the discovery of biomarkers for pesticide pollution in aquatic environment. PMID:24291083

  13. Metabolomic-Based Study of the Leafy Gall, the Ecological Niche of the Phytopathogen Rhodococcus fascians, as a Potential Source of Bioactive Compounds

    Directory of Open Access Journals (Sweden)

    Pierre Duez

    2013-06-01

    Full Text Available Leafy gall is a plant hyperplasia induced upon Rhodococcus fascians infection. Previously, by genomic and transcriptomic analysis, it has been reported that, at the early stage of symptom development, both primary and secondary metabolisms are modified. The present study is based on the hypothesis that fully developed leafy gall, could represent a potential source of new bioactive compounds. Therefore, non-targeted metabolomic analysis of aqueous and chloroform extracts of leafy gall and non-infected tobacco was carried out by 1H-NMR coupled to principal component analysis (PCA and orthogonal projections to latent structures-discriminant analysis (OPLS-DA. Polar metabolite profiling reflects modifications mainly in the primary metabolites and in some polyphenolics. In contrast, main modifications occurring in non-polar metabolites concern secondary metabolites, and gas chromatography and mass spectrometry (GC-MS evidenced alterations in diterpenoids family. Analysis of crude extracts of leafy galls and non-infected tobacco leaves exhibited a distinct antiproliferative activity against all four tested human cancer cell lines. A bio-guided fractionation of chloroformic crude extract yield to semi-purified fractions, which inhibited proliferation of glioblastoma U373 cells with IC50 between 14.0 and 2.4 µg/mL. Discussion is focused on the consequence of these metabolic changes, with respect to plant defense mechanisms following infection. Considering the promising role of diterpenoid family as bioactive compounds, leafy gall may rather be a propitious source for drug discovery.

  14. 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.

  15. Integrative drug efficacy assessment of Danggui and European Danggui using NMR-based metabolomics.

    Science.gov (United States)

    Zhang, Zheng-Zheng; Fan, Ma-Li; Hao, Xia; Qin, Xue-Mei; Li, Zhen-Yu

    2016-02-20

    Danggui (DG) is a commonly used herbal drug in traditional Chinese medicine, and usually adulterated with European Danggui (EDG) due to the increasing demand. In present study, global metabolic profiling with NMR coupled with integrative drug efficacy evaluation methods was performed to compare and discover underlying blood-enriching regulation mechanisms of DG and EDG on blood deficiency rats induced by acetyl phenylhydrazine (APH). Totally, the contents of 12 key metabolites in serum and 4 in urine of DG group, 7 in serum and 4 in urine of EDG group were significantly reversed in comparison with model group. DG was more effective than EDG as revealed by the relative distance, efficacy index and similarity analysis. The metabolism pathways analysis showed that the better effect of DG maybe related with the regulatory effect on valine, leucine and isoleucine biosynthesis, synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, as well as nicotinate and nicotinamide metabolism. The results presented here showed that metabolomic coupled with efficacy index and similarity analysis made it possible to disclose the subtle biological difference between DG and EDG, which highlight the potential of metabolomic approach to quantitatively compare the pharmacological effect of the herbal drugs. PMID:26686769

  16. 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.

  17. {sup 1}H NMR-based metabolomics of time-dependent responses of Eisenia fetida to sub-lethal phenanthrene exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lankadurai, Brian P.; Wolfe, David M.; Simpson, Andre J. [Department of Chemistry, University of Toronto, 1265 Military Trail, Toronto, Ontario M1C 1A4 Canada (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Chemistry, University of Toronto, 1265 Military Trail, Toronto, Ontario M1C 1A4 Canada (Canada)

    2011-10-15

    {sup 1}H NMR-based metabolomics was used to examine the response of the earthworm Eisenia fetida after exposure to sub-lethal concentrations of phenanthrene over time. Earthworms were exposed to 0.025 mg/cm{sup 2} of phenanthrene (1/64th of the LC{sub 50}) via contact tests over four days. Earthworm tissues were extracted using a mixture of chloroform, methanol and water, resulting in polar and non-polar fractions that were analyzed by {sup 1}H NMR after one, two, three and four days. NMR-based metabolomic analyses revealed heightened E. fetida responses with longer phenanthrene exposure times. Amino acids alanine and glutamate, the sugar maltose, the lipids cholesterol and phosphatidylcholine emerged as potential indicators of phenanthrene exposure. The conversion of succinate to fumarate in the Krebs cycle was also interrupted by phenanthrene. Therefore, this study shows that NMR-based metabolomics is a powerful tool for elucidating time-dependent relationships in addition to the mode of toxicity of phenanthrene in earthworm exposure studies. - Highlights: > NMR-based earthworm metabolomic analysis of the mode of action of phenanthrene is presented. > The earthworm species E. fetida were exposed to sub-lethal phenanthrene concentrations. > Both polar and non-polar metabolites of E. fetida tissue extracts were analyzed by {sup 1}H NMR. > Longer phenanthrene exposure times resulted in heightened earthworm responses. > An interruption of the Krebs cycle was also observed due to phenanthrene exposure. - {sup 1}H NMR metabolomics is used to determine the relationship between phenanthrene exposure and the metabolic response of the earthworm E. fetida over time and also to elucidate the phenanthrene mode of toxicity.

  18. Discrimination of Citrus reticulata Blanco and Citrus reticulata 'Chachi' by gas chromatograph-mass spectrometry based metabolomics approach.

    Science.gov (United States)

    Duan, Li; Guo, Long; Dou, Li-Li; Zhou, Chang-Lin; Xu, Feng-Guo; Zheng, Guo-Dong; Li, Ping; Liu, E-Hu

    2016-12-01

    Citri Reticulatae Pericarpium, mainly including the pericarp of Citrus reticulata Blanco and the pericarp of Citrus reticulata 'Chachi', has been consumed daily as food and dietary supplement for centuries. In this study, GC-MS based metabolomics was employed to compare comprehensively the volatile constituents in Citrus reticulata Blanco and Citrus reticulata 'Chachi'. Principal component analysis and orthogonal partial least squares discrimination analysis indicated that samples could be distinguished effectively from one another. Fifteen metabolites were finally identified for use as chemical markers in discrimination of Citri Reticulatae Pericarpium samples. The antimicrobial activity against Gram-negative and Gram-positive bacteria of the volatile oil from Citrus reticulata Blanco and Citrus reticulata 'Chachi' was investigated preliminarily. PMID:27374515

  19. Metabolomics-based prediction models of yeast strains for screening of metabolites contributing to ethanol stress tolerance

    Science.gov (United States)

    Hashim, Z.; Fukusaki, E.

    2016-06-01

    The increased demand for clean, sustainable and renewable energy resources has driven the development of various microbial systems to produce biofuels. One of such systems is the ethanol-producing yeast. Although yeast produces ethanol naturally using its native pathways, production yield is low and requires improvement for commercial biofuel production. Moreover, ethanol is toxic to yeast and thus ethanol tolerance should be improved to further enhance ethanol production. In this study, we employed metabolomics-based strategy using 30 single-gene deleted yeast strains to construct multivariate models for ethanol tolerance and screen metabolites that relate to ethanol sensitivity/tolerance. The information obtained from this study can be used as an input for strain improvement via metabolic engineering.

  20. A metabolomic study in oats (Avena sativa) highlights a drought tolerance mechanism based upon salicylate signalling pathways and the modulation of carbon, antioxidant and photo-oxidative metabolism.

    Science.gov (United States)

    Sánchez-Martín, Javier; Heald, Jim; Kingston-Smith, Alison; Winters, Ana; Rubiales, Diego; Sanz, Mariluz; Mur, Luis A J; Prats, Elena

    2015-07-01

    Although a wealth of information is available on the induction of one or several drought-related responses in different species, little is known of how their timing, modulation and crucially integration influence drought tolerance. Based upon metabolomic changes in oat (Avena sativa L.), we have defined key processes involved in drought tolerance. During a time course of increasing water deficit, metabolites from leaf samples were profiled using direct infusion-electrospray mass spectroscopy (DI-ESI-MS) and high-performance liquid chromatography (HPLC) ESI-MS/MS and analysed using principal component analysis (PCA) and discriminant function analysis (DFA). The involvement of metabolite pathways was confirmed through targeted assays of key metabolites and physiological experiments. We demonstrate an early accumulation of salicylic acid (SA) influencing stomatal opening, photorespiration and antioxidant defences before any change in the relative water content. These changes are likely to maintain plant water status, with any photoinhibitory effect being counteracted by an efficient antioxidant capacity, thereby representing an integrated mechanism of drought tolerance in oats. We also discuss these changes in relation to those engaged at later points, consequence of the different water status in susceptible and resistant genotypes.

  1. 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease.

    Directory of Open Access Journals (Sweden)

    Jingjing Xu

    Full Text Available Wilson's disease (WD, also known as hepatoleticular degeneration (HLD, is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established.A combination of 1HNMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the urine and blood serum samples collected from the copper-laden rat model of WD with PA treatment.Copper accumulation in the copper-laden rats is associated with increased lactate, creatinine, valine and leucine, as well as decreased levels of glucose and taurine in the blood serum. There were also significant changes in p-hydroxyphenylacetate (p-HPA, creatinine, alpha-ketoglutarate (α-KG, dimethylamine, N-acetylglutamate (NAG, N-acetylglycoprotein (NAC in the urine of these rats. Notably, the changes in p-HPA, glucose, lactate, taurine, valine, leucine, and NAG were found reversed following PA treatment. Nevertheless, there were no changes for dimethylamine, α-KG, and NAC as a result of the treatment. Compared with the controls, the concentrations of hippurate, formate, alanine, and lactate were changed when PA was applied and this is probably due to its side effect. A tool named SMPDB (Small Molecule Pathway Database is introduced to identify the metabolic pathway influenced by the copper-laden diet.The study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the molecular

  2. Metabolomics in food science.

    Science.gov (United States)

    Cevallos-Cevallos, Juan Manuel; Reyes-De-Corcuera, José Ignacio

    2012-01-01

    Metabolomics, the newest member of the omics techniques, has become an important tool in agriculture, pharmacy, and environmental sciences. Advances in compound extraction, separation, detection, identification, and data analysis have allowed metabolomics applications in food sciences including food processing, quality, and safety. This chapter discusses recent advances and applications of metabolomics in food science.

  3. 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

  4. Metabolomics techniques in nanotoxicology studies.

    Science.gov (United States)

    Schnackenberg, Laura K; Sun, Jinchun; Beger, Richard D

    2012-01-01

    The rapid growth in the development of nanoparticles for uses in a variety of applications including targeted drug delivery, cancer therapy, imaging, and as biological sensors has led to questions about potential toxicity of such particles to humans. High-throughput methods are necessary to evaluate the potential toxicity of nanoparticles. The omics technologies are particularly well suited to evaluate toxicity in both in vitro and in vivo systems. Metabolomics, specifically, can rapidly screen for biomarkers related to predefined pathways or processes in biofluids and tissues. Specifically, oxidative stress has been implicated as a potential mechanism of toxicity in nanoparticles and is generally difficult to measure by conventional methods. Furthermore, metabolomics can provide mechanistic insight into nanotoxicity. This chapter focuses on the application of both LC/MS and NMR-based metabolomics approaches to study the potential toxicity of nanoparticles.

  5. [Anti-depressive mechanism of Fufang Chaigui prescription based on neuroendocrine hormone and metabolomic correlation analysis].

    Science.gov (United States)

    Chen, Lei; Liu, Huan; Chen, Jian-li; Gao, Xiao-xia; Zhou, Yu-zhi; Tian, Jun-sheng; Qin, Xue-mei

    2015-10-01

    To elucidate the anti-depressive effect of Fufang Chaigui prescription and its mechanism and investigate its effect on neuroendocrine hormone, rats were included into a chronic unpredictable mild stress (CUMS) model for 28 d, and drugs were administered at the same time. During the period, rats' behaviors were observed and the blood was collected by using ELISA to determine representative hormone concentrations of HPAA, HPTA and HPGA. The changes in endogenous metabolites were analyzed by using H NMR metabolomics to seek the potential biomarkers. Results showed Fufang Chaigui prescription could improve the behaviors of CUMS rats obviously, increase contents of ACTH, CORT, T₃and decrease contents of TSH and TESTO and regulate the levels of lactate, α-glucose, choline, N-acetylglycoprotein, trimethylamine oxide and leucine to get closer to the contents of control group. The results of correlation analysis indicated that HPTA was associated with glycometabolism, amino acid metabolism and choline metabolism. And HPAA was related to glycometabolism and amino acid metabolism. However, HPGA was only correlated with glycometabolism. In conclusion, Fufang Chaigui prescription could show an obvious anti-depressive effect and its underlying mechanism might involve regulations of neuroendocrine function and pathways of glycometabolism, amino acid metabolism and choline metabolism. PMID:27062831

  6. Metabolic Profiling of Human Benign and Malignant Pulmonary Nodules Using Mass Spectrometry-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Choon Nam Ong

    2013-07-01

    Full Text Available Solitary pulmonary nodule (SPN or coin lesion is a mass in the lung and can be commonly found in chest X-rays or computerized tomography (CT scans. However, despite the advancement of imaging technologies, it is still difficult to distinguish malignant cancer from benign SPNs. Here we investigated the metabolic profiling of patients with benign and malignant pulmonary nodules. A combination of gas chromatography/mass spectrometry (GC/MS and liquid chromatography/mass spectrometry (LC/MS was used to profile the plasma metabolites in 17 patients with malignant SPNs, 15 patients with benign SPNs and 20 healthy controls. The metabolic profiles were assayed using OPLS-DA, and further analyzed to identify marker metabolites related to diseases. Both GC/MS- and LC/MS-derived models showed clear discriminations in metabolic profiles among three groups. It was found that 63 metabolites (12 from GC/MS, 51 from LC/MS contributed to the differences. Of these, 48 metabolites showed same change trend in both malignant and benign SPNs as compared with healthy controls, indicating some common pathways including inflammation and oxidative injury shared by two diseases. In contrast, 14 metabolites constituted distinct profiles that differentiated malignant from benign SPNs, which might be a unique biochemical feature associated with lung cancer. Overall, our data suggested that integration of two highly sensitive and complementary metabolomics platforms could enable a comprehensive metabolic profiling and assist in discrimination malignant from benign SPNs.

  7. Pea Fiber and Wheat Bran Fiber Show Distinct Metabolic Profiles in Rats as Investigated by a 1H NMR-Based Metabolomic Approach

    OpenAIRE

    Guangmang Liu; Liang Xiao; Tingting Fang; Yimin Cai; Gang Jia; Hua Zhao; Jing Wang; Xiaoling Chen; Caimei Wu

    2014-01-01

    This study aimed to examine the effect of pea fiber (PF) and wheat bran fiber (WF) supplementation in rat metabolism. Rats were assigned randomly to one of three dietary groups and were given a basal diet containing 15% PF, 15% WF, or no supplemental fiber. Urine and plasma samples were analyzed by NMR-based metabolomics. PF significantly increased the plasma levels of 3-hydroxybutyrate, and myo-inositol as well as the urine levels of alanine, hydroxyphenylacetate, phenylacetyglycine, and α-k...

  8. Gas chromatography-mass spectrometry based metabolomic approach for optimization and toxicity evaluation of earthworm sub-lethal responses to carbofuran.

    Science.gov (United States)

    Mudiam, Mohana Krishna Reddy; Ch, Ratnasekhar; Saxena, Prem Narain

    2013-01-01

    Despite recent advances in understanding mechanism of toxicity, the development of biomarkers (biochemicals that vary significantly with exposure to chemicals) for pesticides and environmental contaminants exposure is still a challenging task. Carbofuran is one of the most commonly used pesticides in agriculture and said to be most toxic carbamate pesticide. It is necessary to identify the biochemicals that can vary significantly after carbofuran exposure on earthworms which will help to assess the soil ecotoxicity. Initially, we have optimized the extraction conditions which are suitable for high-throughput gas chromatography mass spectrometry (GC-MS) based metabolomics for the tissue of earthworm, Metaphire posthuma. Upon evaluation of five different extraction solvent systems, 80% methanol was found to have good extraction efficiency based on the yields of metabolites, multivariate analysis, total number of peaks and reproducibility of metabolites. Later the toxicity evaluation was performed to characterize the tissue specific metabolomic perturbation of earthworm, Metaphire posthuma after exposure to carbofuran at three different concentration levels (0.15, 0.3 and 0.6 mg/kg of soil). Seventeen metabolites, contributing to the best classification performance of highest dose dependent carbofuran exposed earthworms from healthy controls were identified. This study suggests that GC-MS based metabolomic approach was precise and sensitive to measure the earthworm responses to carbofuran exposure in soil, and can be used as a promising tool for environmental eco-toxicological studies.

  9. Gas chromatography-mass spectrometry based metabolomic approach for optimization and toxicity evaluation of earthworm sub-lethal responses to carbofuran.

    Directory of Open Access Journals (Sweden)

    Mohana Krishna Reddy Mudiam

    Full Text Available Despite recent advances in understanding mechanism of toxicity, the development of biomarkers (biochemicals that vary significantly with exposure to chemicals for pesticides and environmental contaminants exposure is still a challenging task. Carbofuran is one of the most commonly used pesticides in agriculture and said to be most toxic carbamate pesticide. It is necessary to identify the biochemicals that can vary significantly after carbofuran exposure on earthworms which will help to assess the soil ecotoxicity. Initially, we have optimized the extraction conditions which are suitable for high-throughput gas chromatography mass spectrometry (GC-MS based metabolomics for the tissue of earthworm, Metaphire posthuma. Upon evaluation of five different extraction solvent systems, 80% methanol was found to have good extraction efficiency based on the yields of metabolites, multivariate analysis, total number of peaks and reproducibility of metabolites. Later the toxicity evaluation was performed to characterize the tissue specific metabolomic perturbation of earthworm, Metaphire posthuma after exposure to carbofuran at three different concentration levels (0.15, 0.3 and 0.6 mg/kg of soil. Seventeen metabolites, contributing to the best classification performance of highest dose dependent carbofuran exposed earthworms from healthy controls were identified. This study suggests that GC-MS based metabolomic approach was precise and sensitive to measure the earthworm responses to carbofuran exposure in soil, and can be used as a promising tool for environmental eco-toxicological studies.

  10. 1H NMR-Based Metabolomic Analysis of Sub-Lethal Perfluorooctane Sulfonate Exposure to the Earthworm, Eisenia fetida, in Soil.

    Science.gov (United States)

    Lankadurai, Brian P; Furdui, Vasile I; Reiner, Eric J; Simpson, André J; Simpson, Myrna J

    2013-01-01

    1H NMR-based metabolomics was used to measure the response of Eisenia fetida earthworms after exposure to sub-lethal concentrations of perfluorooctane sulfonate (PFOS) in soil. Earthworms were exposed to a range of PFOS concentrations (five, 10, 25, 50, 100 or 150 mg/kg) for two, seven and fourteen days. Earthworm tissues were extracted and analyzed by 1H NMR. Multivariate statistical analysis of the metabolic response of E. fetida to PFOS exposure identified time-dependent responses that were comprised of two separate modes of action: a non-polar narcosis type mechanism after two days of exposure and increased fatty acid oxidation after seven and fourteen days of exposure. Univariate statistical analysis revealed that 2-hexyl-5-ethyl-3-furansulfonate (HEFS), betaine, leucine, arginine, glutamate, maltose and ATP are potential indicators of PFOS exposure, as the concentrations of these metabolites fluctuated significantly. Overall, NMR-based metabolomic analysis suggests elevated fatty acid oxidation, disruption in energy metabolism and biological membrane structure and a possible interruption of ATP synthesis. These conclusions obtained from analysis of the metabolic profile in response to sub-lethal PFOS exposure indicates that NMR-based metabolomics is an excellent discovery tool when the mode of action (MOA) of contaminants is not clearly defined. PMID:24958147

  11. 1H NMR-Based Metabolomic Analysis of Sub-Lethal Perfluorooctane Sulfonate Exposure to the Earthworm, Eisenia fetida, in Soil

    Directory of Open Access Journals (Sweden)

    Myrna J. Simpson

    2013-08-01

    Full Text Available 1H NMR-based metabolomics was used to measure the response of Eisenia fetida earthworms after exposure to sub-lethal concentrations of perfluorooctane sulfonate (PFOS in soil. Earthworms were exposed to a range of PFOS concentrations (five, 10, 25, 50, 100 or 150 mg/kg for two, seven and fourteen days. Earthworm tissues were extracted and analyzed by 1H NMR. Multivariate statistical analysis of the metabolic response of E. fetida to PFOS exposure identified time-dependent responses that were comprised of two separate modes of action: a non-polar narcosis type mechanism after two days of exposure and increased fatty acid oxidation after seven and fourteen days of exposure. Univariate statistical analysis revealed that 2-hexyl-5-ethyl-3-furansulfonate (HEFS, betaine, leucine, arginine, glutamate, maltose and ATP are potential indicators of PFOS exposure, as the concentrations of these metabolites fluctuated significantly. Overall, NMR-based metabolomic analysis suggests elevated fatty acid oxidation, disruption in energy metabolism and biological membrane structure and a possible interruption of ATP synthesis. These conclusions obtained from analysis of the metabolic profile in response to sub-lethal PFOS exposure indicates that NMR-based metabolomics is an excellent discovery tool when the mode of action (MOA of contaminants is not clearly defined.

  12. Model-based peak alignment of metabolomic profiling from comprehensive two-dimensional gas chromatography mass spectrometry

    Directory of Open Access Journals (Sweden)

    Jeong Jaesik

    2012-02-01

    Full Text Available Abstract Background Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC/TOF-MS has been used for metabolite profiling in metabolomics. However, there is still much experimental variation to be controlled including both within-experiment and between-experiment variation. For efficient analysis, an ideal peak alignment method to deal with such variations is in great need. Results Using experimental data of a mixture of metabolite standards, we demonstrated that our method has better performance than other existing method which is not model-based. We then applied our method to the data generated from the plasma of a rat, which also demonstrates good performance of our model. Conclusions We developed a model-based peak alignment method to process both homogeneous and heterogeneous experimental data. The unique feature of our method is the only model-based peak alignment method coupled with metabolite identification in an unified framework. Through the comparison with other existing method, we demonstrated that our method has better performance. Data are available at http://stage.louisville.edu/faculty/x0zhan17/software/software-development/mspa. The R source codes are available at http://www.biostat.iupui.edu/~ChangyuShen/CodesPeakAlignment.zip. Trial Registration 2136949528613691

  13. LC-MS based Metabolomics Analysis to Identify Potential Allelochemicals in Wedelia trilobata

    OpenAIRE

    Kamalrul Azlan Azizan; Sarah Ibrahim; Nurul Haizun Abdul Ghani; Mohammad Firdaus Nawawi

    2016-01-01

    Wedelia trilobata is a noxious invasive weed that has been widely cultivated as a decorative and groundcover plant. The plant has been reported to contain diverse bioactive compounds with a broad spectrum of biological activities including allelochemicals. Allelochemicals contribute to allelopathy interactions that suppress the growth and development of nearby plants. Several studies have reported the allelopathic potential of W. trilobata and its negative effects to crop plants. However, rel...

  14. Recent Advances in the Application of Metabolomics to Studies of Biogenic Volatile Organic Compounds (BVOC) Produced by Plant

    OpenAIRE

    Yoko Iijima

    2014-01-01

    In many plants, biogenic volatile organic compounds (BVOCs) are produced as specialized metabolites that contribute to the characteristics of each plant. The varieties and composition of BVOCs are chemically diverse by plant species and the circumstances in which the plants grow, and also influenced by herbivory damage and pathogen infection. Plant-produced BVOCs are receptive to many organisms, from microorganisms to human, as both airborne attractants and repellants. In addition, it is know...

  15. 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.

  16. Improving the quality of biomarker candidates in untargeted metabolomics via peak table-based alignment of comprehensive two-dimensional gas chromatography-mass spectrometry data.

    Science.gov (United States)

    Bean, Heather D; Hill, Jane E; Dimandja, Jean-Marie D

    2015-05-15

    The potential of high-resolution analytical technologies like GC×GC/TOF MS in untargeted metabolomics and biomarker discovery has been limited by the development of fully automated software that can efficiently align and extract information from multiple chromatographic data sets. In this work we report the first investigation on a peak-by-peak basis of the chromatographic factors that impact GC×GC data alignment. A representative set of 16 compounds of different chromatographic characteristics were followed through the alignment of 63 GC×GC chromatograms. We found that varying the mass spectral match parameter had a significant influence on the alignment for poorly-resolved peaks, especially those at the extremes of the detector linear range, and no influence on well-chromatographed peaks. Therefore, optimized chromatography is required for proper GC×GC data alignment. Based on these observations, a workflow is presented for the conservative selection of biomarker candidates from untargeted metabolomics analyses. PMID:25857541

  17. ¹H-NMR and MS based metabolomics study of the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet.

    Science.gov (United States)

    Li, Ze-Yun; Ding, Li-Li; Li, Jin-Mei; Xu, Bao-Li; Yang, Li; Bi, Kai-Shun; Wang, Zheng-Tao

    2015-01-01

    Curcumin, a principle bioactive component of Curcuma longa L, is well known for its anti-hyperlipidemia effect. However, no holistic metabolic information of curcumin on hyperlipidemia models has been revealed, which may provide us an insight into the underlying mechanism. In the present work, NMR and MS based metabolomics was conducted to investigate the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet (HFD) feeding for 12 weeks. The HFD induced animals were orally administered with curcumin (40, 80 mg/kg) or lovastatin (30 mg/kg, positive control) once a day during the inducing period. Serum biochemistry assay of TC, TG, LDL-c, and HDL-c was conducted and proved that treatment of curcumin or lovastatin can significantly improve the lipid profiles. Subsequently, metabolomics analysis was carried out for urine samples. Orthogonal Partial Least Squares-Discriminant analysis (OPLS-DA) was employed to investigate the anti-hyperlipidemia effect of curcumin and to detect related potential biomarkers. Totally, 35 biomarkers were identified, including 31 by NMR and nine by MS (five by both). It turned out that curcumin treatment can partially recover the metabolism disorders induced by HFD, with the following metabolic pathways involved: TCA cycle, glycolysis and gluconeogenesis, synthesis of ketone bodies and cholesterol, ketogenesis of branched chain amino acid, choline metabolism, and fatty acid metabolism. Besides, NMR and MS based metabolomics proved to be powerful tools in investigating pharmacodynamics effect of natural products and underlying mechanisms.

  18. ¹H-NMR and MS based metabolomics study of the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet.

    Directory of Open Access Journals (Sweden)

    Ze-Yun Li

    Full Text Available Curcumin, a principle bioactive component of Curcuma longa L, is well known for its anti-hyperlipidemia effect. However, no holistic metabolic information of curcumin on hyperlipidemia models has been revealed, which may provide us an insight into the underlying mechanism. In the present work, NMR and MS based metabolomics was conducted to investigate the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet (HFD feeding for 12 weeks. The HFD induced animals were orally administered with curcumin (40, 80 mg/kg or lovastatin (30 mg/kg, positive control once a day during the inducing period. Serum biochemistry assay of TC, TG, LDL-c, and HDL-c was conducted and proved that treatment of curcumin or lovastatin can significantly improve the lipid profiles. Subsequently, metabolomics analysis was carried out for urine samples. Orthogonal Partial Least Squares-Discriminant analysis (OPLS-DA was employed to investigate the anti-hyperlipidemia effect of curcumin and to detect related potential biomarkers. Totally, 35 biomarkers were identified, including 31 by NMR and nine by MS (five by both. It turned out that curcumin treatment can partially recover the metabolism disorders induced by HFD, with the following metabolic pathways involved: TCA cycle, glycolysis and gluconeogenesis, synthesis of ketone bodies and cholesterol, ketogenesis of branched chain amino acid, choline metabolism, and fatty acid metabolism. Besides, NMR and MS based metabolomics proved to be powerful tools in investigating pharmacodynamics effect of natural products and underlying mechanisms.

  19. Global mass spectrometry based metabolomics profiling of erythrocytes infected with Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Theodore R Sana

    data acquisition. Untargeted and targeted data mining workflows, when used together to perform pathway-inferred metabolomics, have the benefit of obviating MS/MS confirmation for every detected compound.

  20. A potential tool for diagnosis of male infertility: Plasma metabolomics based on GC-MS.

    Science.gov (United States)

    Zhou, Xinyi; Wang, Yang; Yun, Yonghuan; Xia, Zian; Lu, Hongmei; Luo, Jiekun; Liang, Yizeng

    2016-01-15

    Male infertility has become an important public health problem worldwide. Nowadays the diagnosis of male infertility frequently depends on the results of semen quality or requires more invasive surgical intervention. Therefore, it is necessary to develop a novel approach for early diagnosis of male infertility. According to the presence or absence of normal sexual function, the male infertility is classified into two phenotypes, erectile dysfunction (ED) and semen abnormalities (SA). The aim of this study was to investigate the GC-MS plasma profiles of infertile male having erectile dysfunction (ED) and having semen abnormalities (SA) and discover the potential biomarkers. The plasma samples from healthy controls (HC) (n=61) and infertility patients with ED (n=26) or with SA (n=44) were analyzed by gas chromatography-mass spectrometry (GC-MS) for discrimination and screening potential biomarkers. The partial least squares-discriminant analysis (PLS-DA) was performed on GC-MS dataset. The results showed that HC could be discriminated from infertile cases having SA (AUC=86.96%, sensitivity=78.69%, specificity=84.09%, accuracy=80.95%) and infertile cases having ED (AUC=94.33%, sensitivity=80.33%, specificity=100%, accuracy=87.36%). Some potential biomarkers were successfully discovered by two commonly used variable selection methods, variable importance on projection (VIP) and original coefficients of PLS-DA (β). 1,5-Anhydro-sorbitol and α-hydroxyisovaleric acid were identified as the potential biomarkers for distinguishing HC from the male infertility patients. Meanwhile, lactate, glutamate and cholesterol were the found to be the important variables to distinguish between patients with erectile dysfunction from those with semen abnormalities. The plasma metabolomics may be developed as a novel approach for fast, noninvasive, and acceptable diagnosis and characterization of male infertility.

  1. Feasibility Study of NMR Based Serum Metabolomic Profiling to Animal Health Monitoring: A Case Study on Iron Storage Disease in Captive Sumatran Rhinoceros (Dicerorhinus sumatrensis).

    Science.gov (United States)

    Watanabe, Miki; Roth, Terri L; Bauer, Stuart J; Lane, Adam; Romick-Rosendale, Lindsey E

    2016-01-01

    A variety of wildlife species maintained in captivity are susceptible to iron storage disease (ISD), or hemochromatosis, a disease resulting from the deposition of excess iron into insoluble iron clusters in soft tissue. Sumatran rhinoceros (Dicerorhinus sumatrensis) is one of the rhinoceros species that has evolutionarily adapted to a low-iron diet and is susceptible to iron overload. Hemosiderosis is reported at necropsy in many African black and Sumatran rhinoceroses but only a small number of animals reportedly die from hemochromatosis. The underlying cause and reasons for differences in susceptibility to hemochromatosis within the taxon remains unclear. Although serum ferritin concentrations have been useful in monitoring the progression of ISD in many species, there is some question regarding their value in diagnosing hemochromatosis in the Sumatran rhino. To investigate the metabolic changes during the development of hemochromatosis and possibly increase our understanding of its progression and individual susceptibility differences, the serum metabolome from a Sumatran rhinoceros was investigated by nuclear magnetic resonance (NMR)-based metabolomics. The study involved samples from female rhinoceros at the Cincinnati Zoo (n = 3), including two animals that died from liver failure caused by ISD, and the Sungai Dusun Rhinoceros Conservation Centre in Peninsular Malaysia (n = 4). Principal component analysis was performed to visually and statistically compare the metabolic profiles of the healthy animals. The results indicated that significant differences were present between the animals at the zoo and the animals in the conservation center. A comparison of the 43 serum metabolomes of three zoo rhinoceros showed two distinct groupings, healthy (n = 30) and unhealthy (n = 13). A total of eighteen altered metabolites were identified in healthy versus unhealthy samples. Results strongly suggest that NMR-based metabolomics is a valuable tool for animal health

  2. [Exploring the mechanism of rhizoma coptidis in treating type II diabetes mellitus based on metabolomics by gas chromatography-mass spectrometry].

    Science.gov (United States)

    Wang, Jing; Yuan, Zimin; Kong, Hongwei; Li, Yong; Lu, Xin; Xu, Guowang

    2012-01-01

    Metabolomics was used to explore the mechanism of Rhizoma coptidis in treating type II diabetes mellitus. The rat model of type II diabetes mellitus was constructed by an injection of streptozocin (40 mg/kg), along with diets of fat emulsion. The rats were divided into four groups, the control group, the model group, the Rhizoma coptidis group (10 g/kg) and the metformin group (0.08 g/kg). After the treatment for 30 d, blood samples were collected to test biomedical indexes, and 24 h urine samples were collected for the metabolomics experiment. In the Rhizoma coptidis group, fasting blood glucose (FBG), total cholesterol (TC) and total plasma triglycerides (TG) were significantly decreased by 59.26%, 58.66% and 42.18%, respectively, compared with those in the model group. Based on gas chromatography-mass spectrometry, a urinary metabolomics method was used to study the mechanism of Rhizoma coptidis in treating diabetes mellitus. Based on the principal component analysis, it was found that the model group and control group were separated into two different clusters. The Rhizoma coptidis group was located between the model group and the control group, closer to the control group. Twelve significantly changed metabolites of diabetes mellitus were detected and identified, including 4-methyl phenol, benzoic acid, aminomalonic acid, and so on. After diabetic rats were administered with Rhizoma coptidis, 7 metabolites were significantly changed, and L-ascorbic acid and aminomalonic acid which related with the oxidative stress were significantly regulated to normal. The pharmacological results showed that Rhizoma coptidis could display anti-hyperglycemic and anti-hyperlipidemic effects. The Rhizoma coptidis had antioxidation function in preventing the occurrence of complications with diabetes mellitus to some extent. The work illustrates that the metabolomics method is a useful tool to study the treatment mechanism of traditional Chinese medicine.

  3. LC/MS-based metabolomics strategy to assess the amelioration effects of ginseng total saponins on memory deficiency induced by simulated microgravity.

    Science.gov (United States)

    Feng, Li; Yue, Xiao-Fei; Chen, Yi-Xi; Liu, Xin-Min; Wang, Li-Sha; Cao, Fang-Rui; Wang, Qiong; Liao, Yong-Hong; Pan, Rui-le; Chang, Qi

    2016-06-01

    Microgravity-induced memory deficiency seriously affects learning and memory ability of the astronaut during spaceflight, with few effective countermeasures. Panax ginseng C. A. Mey. has been used as a nootropic herb for thousands of years in Asian countries. Saponins are recognized as its major active components. Previous studies have shown that ginseng saponins offer protection against memory deficits caused by various factors. Nevertheless, the underlying mechanisms of their nootropic effects are still largely unknown. In this study, we evaluated the memory-improving effects of ginseng total saponins (GTS) on simulated microgravity hindlimb-unloaded rats using a metabolomics approach. After being exposed to a 7-days hindlimb unloading (HU), variations of plasmatic and hippocampal metabolic profiles of rats with and without GTS intervention were examined by a liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics method. Subsequently, 8 hippocampal neurotransmitters were determined using a LC-MS/MS method. Finally, a LC-MS/MS based targeted metabolomics was performed to validate biomarkers found in the untargeted analysis. Besides, to support the metabolomics results, passive avoidance (PA) test, Nissl staining, and plasmatic corticosterone (CORT) levels determination were performed. The results showed that HU could lead to variations of 7 neurotransmitters and significantly different plasmatic and hippocampal metabolic profiles. GTS could restore most of the imbalanced neurotransmitters, especially glutamic acid and acetylcholine, and correct the levels of various disturbed learning and memory relevant biomarkers such as asparagine, phenylalanine, tyrosine, tryptophan, and choline. In addition, GTS could markedly ameliorate HU-induced memory deficiency, protect hippocampal neurons from damage, and down-regulate elevated CORT levels. In conclusion, GTS exhibits memory-improving effects mainly through regulating the metabolism of amino acids

  4. Toxicological effects induced by cadmium in gills of Manila clam ruditapes philippinarum using NMR-based metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Linbao; Liu, Xiaoli; You, Liping; Zhou, Di [Key Laboratory of Coastal Zone Environment Processes, CAS, Shandong Provincial Key Laboratory of Coastal Zone Environment Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai (China); The Graduate School of Chinese Academy of Sciences, Beijing (China); Yu, Junbao; Zhao, Jianmin; Wu, Huifeng [Key Laboratory of Coastal Zone Environment Processes, CAS, Shandong Provincial Key Laboratory of Coastal Zone Environment Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai (China); Feng, Jianghua [Department of Electronic Science, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen (China)

    2011-11-15

    Cadmium (Cd) has become an important heavy metal contaminant in the sediment and seawater along the Bohai Sea and been of great ecological risk due to its toxic effects to marine organisms. In this work, the toxicological effects caused by environmentally relevant concentrations (10 and 40 {mu}g L{sup -1}) of Cd were studied in the gill tissues of Manila clam Ruditapes philippinarum after exposure for 24, 48, and 96 h. Both low (10 {mu}g L{sup -1}) and high (40 {mu}g L{sup -1}) doses of Cd caused the disturbances in energy metabolism and osmotic regulation and neurotoxicity based on the metabolic biomarkers such as succinate, alanine, branched chain amino acids, betaine, hypotaurine, and glutamate in clam gills after 24 h of exposure. However, the recovery of toxicological effects of Cd after exposure for 96 h was obviously observed in clam to Cd exposures. Overall, these results indicated that NMR-based metabolomics was applicable to elucidate the toxicological effects of heavy metal contaminants in the marine bioindicator. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Clinical impact of human breast milk metabolomics.

    Science.gov (United States)

    Cesare Marincola, Flaminia; Dessì, Angelica; Corbu, Sara; Reali, Alessandra; Fanos, Vassilios

    2015-12-01

    Metabolomics is a research field concerned with the analysis of metabolome, the complete set of metabolites in a given cell, tissue, or biological sample. Being able to provide a molecular snapshot of biological systems, metabolomics has emerged as a functional methodology in a wide range of research areas such as toxicology, pharmacology, food technology, nutrition, microbial biotechnology, systems biology, and plant biotechnology. In this review, we emphasize the applications of metabolomics in investigating the human breast milk (HBM) metabolome. HBM is the recommended source of nutrition for infants since it contains the optimal balance of nutrients for developing babies, and it provides a range of benefits for growth, immunity, and development. The molecular mechanisms beyond the inter- and intra-variability of HBM that make its composition unique are yet to be well-characterized. Although still in its infancy, the study of HBM metabolome has already proven itself to be of great value in providing insights into this biochemical variability in relation to mother phenotype, diet, disease, and lifestyle. The results of these investigations lay the foundation for further developments useful to identify normal and aberrant biochemical changes as well as to develop strategies to promote healthy infant feeding practices.

  6. Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High Performance Liquid Chromatography-Mass Spectrometry-based Experimental and Computational Pipeline.

    Science.gov (United States)

    Ranninger, Christina; Rurik, Marc; Limonciel, Alice; Ruzek, Silke; Reischl, Roland; Wilmes, Anja; Jennings, Paul; Hewitt, Philip; Dekant, Wolfgang; Kohlbacher, Oliver; Huber, Christian G

    2015-07-31

    Untargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the replacement of expensive and laborious animal models. Here we describe a long term repeat dose nephrotoxicity study conducted on the human renal proximal tubular epithelial cell line, RPTEC/TERT1, treated with 10 and 35 μmol·liter(-1) of chloroacetaldehyde, a metabolite of the anti-cancer drug ifosfamide. Our study outlines the establishment of an automated and easy to use untargeted metabolomics workflow for HPLC-high resolution mass spectrometry data. Automated data analysis workflows based on open source software (OpenMS, KNIME) enabled a comprehensive and reproducible analysis of the complex and voluminous metabolomics data produced by the profiling approach. Time- and concentration-dependent responses were clearly evident in the metabolomic profiles. To obtain a more comprehensive picture of the mode of action, transcriptomics and proteomics data were also integrated. For toxicity profiling of chloroacetaldehyde, 428 and 317 metabolite features were detectable in positive and negative modes, respectively, after stringent removal of chemical noise and unstable signals. Changes upon treatment were explored using principal component analysis, and statistically significant differences were identified using linear models for microarray assays. The analysis revealed toxic effects only for the treatment with 35 μmol·liter(-1) for 3 and 14 days. The most regulated metabolites were glutathione and metabolites related to the oxidative stress response of the cells. These findings are corroborated by proteomics and transcriptomics data, which show, among other things, an activation of the Nrf2 and ATF4 pathways. PMID:26055719

  7. (1)H NMR based metabolomics approach to study the toxic effects of dichlorvos on goldfish (Carassius auratus).

    Science.gov (United States)

    Liu, Yan; Chen, Ting; Li, Ming-Hui; Xu, Hua-Dong; Jia, Ai-Qun; Zhang, Jian-Fa; Wang, Jun-Song

    2015-11-01

    Dichlorvos (DDVP), one of the most widely used organophosphorus pesticides (OPs), has caused serious pollution in environment. In this study, (1)H nuclear magnetic resonance (NMR) based metabolomics approach combined with histopathological and immunohistochemical examination, and biochemical assays were used to investigate toxicities of DDVP on goldfish (Carassius auratus). After 10 days' exposure of DDVP at three dosages of 5.18, 2.59 and 1.73 mg/L, goldfish tissues (gill, brain, liver and kidney) and serum were collected. Histopathology revealed severe impairment of gills, livers and kidneys, and immunohistochemistry disclosed glial fibrillary acidic protein (GFAP) positive reactive astrocytes in brains. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles disclosed that DDVP influenced many metabolites (glutamate, aspartate, acetylcholine, 4-aminobutyrate, glutathione, AMP and lactate in brain; glutathione, glucose, histamine in liver; BCAAs, AMP, aspartate, glutamate, riboflavin in kidney) dose-dependently, involved with imbalance of neurotransmitters, oxidative stress, and disorders of energy and amino acid metabolism. Several self-protection mechanisms concerning glutamate degradation and glutathione (GSH) redox system were found in DDVP intoxicated goldfish. PMID:26210017

  8. Development of urinary pseudotargeted LC-MS-based metabolomics method and its application in hepatocellular carcinoma biomarker discovery.

    Science.gov (United States)

    Shao, Yaping; Zhu, Bin; Zheng, Ruiyin; Zhao, Xinjie; Yin, Peiyuan; Lu, Xin; Jiao, Binghua; Xu, Guowang; Yao, Zhenzhen

    2015-02-01

    Hepatocellular carcinoma (HCC) is one of the pestilent malignancies leading to cancer-related death. Discovering effective biomarkers for HCC diagnosis is an urgent demand. To identify potential metabolite biomarkers, we developed a urinary pseudotargeted method based on liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (LC-QTRAP MS). Compared with nontargeted method, the pseudotargeted method can achieve better data quality, which benefits differential metabolites discovery. The established method was applied to cirrhosis (CIR) and HCC investigation. It was found that urinary nucleosides, bile acids, citric acid, and several amino acids were significantly changed in liver disease groups compared with the controls, featuring the dysregulation of purine metabolism, energy metabolism, and amino metabolism in liver diseases. Furthermore, some metabolites such as cyclic adenosine monophosphate, glutamine, and short- and medium-chain acylcarnitines were the differential metabolites of HCC and CIR. On the basis of binary logistic regression, butyrylcarnitine (carnitine C4:0) and hydantoin-5-propionic acid were defined as combinational markers to distinguish HCC from CIR. The area under curve was 0.786 and 0.773 for discovery stage and validation stage samples, respectively. These data show that the established pseudotargeted method is a complementary one of targeted and nontargeted methods for metabolomics study.

  9. Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models.

    Science.gov (United States)

    Schultz, Luise; Zurich, Marie-Gabrielle; Culot, Maxime; da Costa, Anaelle; Landry, Christophe; Bellwon, Patricia; Kristl, Theresa; Hörmann, Katrin; Ruzek, Silke; Aiche, Stephan; Reinert, Knut; Bielow, Chris; Gosselet, Fabien; Cecchelli, Romeo; Huber, Christian G; Schroeder, Olaf H-U; Gramowski-Voss, Alexandra; Weiss, Dieter G; Bal-Price, Anna

    2015-12-25

    The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that covered the major biological, pharmacological and neuro-toxicological responses. Furthermore, four drugs (diazepam, cyclosporine A, chlorpromazine and amiodarone) were tested more in depth as representatives of different classes of neurotoxicants, inducing toxicity through different pathways of toxicity. The developed in vitro BBB model allowed detection of toxic effects at the level of BBB and evaluation of drug transport through the barrier for predicting free brain concentrations of the studied drugs. The measurement of neuronal electrical activity was found to be a sensitive tool to predict the neuroactivity and neurotoxicity of drugs after acute exposure. The histotypic 3D re-aggregating brain cell cultures, containing all brain cell types, were found to be well suited for OMICs analyses after both acute and long term treatment. The obtained data suggest that an in vitro ITS based on the information obtained from BBB studies and combined with metabolomics, proteomics and neuronal electrical activity measurements performed in stable in vitro neuronal cell culture systems, has high potential to improve current in vitro drug-induced neurotoxicity evaluation.

  10. Cancer Metabolomics and the Human Metabolome Database

    Directory of Open Access Journals (Sweden)

    David S. Wishart

    2016-03-01

    Full Text Available The application of metabolomics towards cancer research has led to a renewed appreciation of metabolism in cancer development and progression. It has also led to the discovery of metabolite cancer biomarkers and the identification of a number of novel cancer causing metabolites. The rapid growth of metabolomics in cancer research is also leading to challenges. In particular, with so many cancer-associate metabolites being identified, it is often difficult to keep track of which compounds are associated with which cancers. It is also challenging to track down information on the specific pathways that particular metabolites, drugs or drug metabolites may be affecting. Even more frustrating are the difficulties associated with identifying metabolites from NMR or MS spectra. Fortunately, a number of metabolomics databases are emerging that are designed to address these challenges. One such database is the Human Metabolome Database (HMDB. The HMDB is currently the world’s largest and most comprehensive, organism-specific metabolomics database. It contains more than 40,000 metabolite entries, thousands of metabolite concentrations, >700 metabolic and disease-associated pathways, as well as information on dozens of cancer biomarkers. This review is intended to provide a brief summary of the HMDB and to offer some guidance on how it can be used in metabolomic studies of cancer.

  11. Metabolomic Heterogeneity of Pulmonary Arterial Hypertension

    OpenAIRE

    Zhao, Yidan; Peng, Jenny; Lu, Catherine; Hsin, Michael; Mura, Marco; Wu, Licun; Chu, Lei; Zamel, Ricardo; Machuca, Tiago; Waddell, Thomas; Liu, Mingyao; Keshavjee, Shaf; Granton, John; de Perrot, Marc

    2014-01-01

    Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of ...

  12. Cell-based metabolomics for assessing chemical exposure and toxicity of environmental surface waters (presentation)

    Science.gov (United States)

    Introduction: Waste water treatment plants (WWTPs), concentrated animal feeding operations (CAFOs), mining activities, and agricultural operations release contaminants that negatively affect surface water quality. Traditional methods using live animals (e.g. fish) to monitor/as...

  13. Cell-based Metabolomics for Assessing Chemical Exposure and Toxicity of Environmental Surface Waters

    Science.gov (United States)

    Waste water treatment plants (WWTPs), concentrated animal feeding operations (CAFOs), mining activities, and agricultural operations release contaminants that negatively affect surface water quality. Traditional methods using live animals/fish to monitor/assess contaminant exposu...

  14. Comparative UPLC-QTOF-MS-based metabolomics and bioactivities analyses of Garcinia oblongifolia.

    Science.gov (United States)

    Li, Ping; AnandhiSenthilkumar, Harini; Wu, Shi-biao; Liu, Bo; Guo, Zhi-yong; Fata, Jimmie E; Kennelly, Edward J; Long, Chun-lin

    2016-02-01

    Garcinia oblongifolia Champ. ex Benth. (Clusiaceae) is a well-known medicinal plant from southern China, with edible fruits. However, the phytochemistry and bioactivity of the different plant parts of G. oblongifolia have not been studied extensively. Comparative metabolic profiling and bioactivities of the leaf, branch, and fruit of G. oblongifolia were investigated. A total of 40 compounds such as biflavonoids, xanthones, and benzophenones were identified using UPLC-QTOF-MS and MS(E), including 15 compounds reported for the first time from this species. Heatmap analyses found that benzophenones, xanthones, and biflavonoids were predominately found in branches, with benzophenones present in relatively high concentrations in all three plant parts. Xanthones were found to have limited distribution in fruit while biflavonoids were present at only low levels in leaves. In addition, the cytotoxic (MCF-7 breast cancer cell line) and antioxidant (ABTS and DPPH chemical tests) activities of the crude extracts of G. oblongifolia indicate that the branch extract exhibits greater bioactivity than either the leaf or the fruit extracts. Orthogonal partial least squares discriminate analysis was used to find 12 marker compounds, mainly xanthones, from the branches, including well-known antioxidants and cytotoxic agents. These G. oblongifolia results revealed that the variation in metabolite profiles can be correlated to the differences in bioactivity of the three plant parts investigated. This UPLC-QTOF-MS strategy can be useful to identify bioactive constituents expressed differentially in the various plant parts of a single species. PMID:26773895

  15. Transcriptomic and metabolomic analysis of Yukon Thellungiella plants grown in cabinets and their natural habitat show phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Guevara David R

    2012-10-01

    Full Text Available Abstract Background Thellungiella salsuginea is an important model plant due to its natural tolerance to abiotic stresses including salt, cold, and water deficits. Microarray and metabolite profiling have shown that Thellungiella undergoes stress-responsive changes in transcript and organic solute abundance when grown under controlled environmental conditions. However, few reports assess the capacity of plants to display stress-responsive traits in natural habitats where concurrent stresses are the norm. Results To determine whether stress-responsive changes observed in cabinet-grown plants are recapitulated in the field, we analyzed leaf transcript and metabolic profiles of Thellungiella growing in its native Yukon habitat during two years of contrasting meteorological conditions. We found 673 genes showing differential expression between field and unstressed, chamber-grown plants. There were comparatively few overlaps between genes expressed under field and cabinet treatment-specific conditions. Only 20 of 99 drought-responsive genes were expressed both in the field during a year of low precipitation and in plants subjected to drought treatments in cabinets. There was also a general pattern of lower abundance among metabolites found in field plants relative to control or stress-treated plants in growth cabinets. Nutrient availability may explain some of the observed differences. For example, proline accumulated to high levels in cold and salt-stressed cabinet-grown plants but proline content was, by comparison, negligible in plants at a saline Yukon field site. We show that proline accumulated in a stress-responsive manner in Thellungiella plants salinized in growth cabinets and in salt-stressed seedlings when nitrogen was provided at 1.0 mM. In seedlings grown on 0.1 mM nitrogen medium, the proline content was low while carbohydrates increased. The relatively higher content of sugar-like compounds in field plants and seedlings on low nitrogen

  16. Metabolomics across the globe

    NARCIS (Netherlands)

    Summer, L.W.; Hall, R.D.

    2013-01-01

    This article highlights some of the larger and more recent metabolomics activities which are funded and organised at local (mostly national) level. While being just a snap-shot, and far from exhaustive, the details clearly illustrate the extent to which metabolomics has already become established an

  17. The food metabolome

    DEFF Research Database (Denmark)

    Scalbert, Augustin; Brennan, Lorraine; Manach, Claudine;

    2014-01-01

    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......; 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.......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...

  18. UHPLC/Q-TOFMS-based plasma metabolomics of polycystic ovary syndrome patients with and without insulin resistance.

    Science.gov (United States)

    Chen, Ya-Xiao; Zhang, Xiao-Jing; Huang, Jia; Zhou, Shu-Jun; Liu, Fang; Jiang, Lin-Lin; Chen, Meiwan; Jian-Bo, Wan; Yang, Dong-Zi

    2016-03-20

    Polycystic ovary syndrome (PCOS), characterized with menstrual irregularities, hyperandrogenism and ovulatory abnormalities, is usually companied with insulin resistance (IR) and accounts for one of the most prevalent reproductive dysfunction of premenopausal women. Despite accumulating investigations, diagnostic standards of this pathological condition remain obscure. The aim of present study is to characterize the plasma metabolic characteristics of PCOS patients with and without IR, and subsequently identify the potential biomarkers for the diagnosis of PCOS and its IR complication. A total of 59 plasma samples from eligible healthy controls (CON, n=19), PCOS patients without IR (non-IR PCOS, n=19) and PCOS patients with IR (IR PCOS, n=21) were profiled by an ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOFMS) followed by multivariate statistical analysis. Compared to the healthy controls, significant decrease in the levels of phosphocholines (PCs) and lyso PC (18:2), and increase in trilauric glyceride level were observed in the plasma of IR PCOS. Meanwhile, the significant increase in the levels of saturated fatty acids (palmitic acid and stearic acid) and decanoylcarnitine, and decrease in PC (36:2) and PS (36:0) were found in non-IR PCOS patients. Trilauric glyceride and decanoylcarnitine were identified as the potential biomarkers with the highest sensitivity and specificity for the diagnosis of PCOS patients with and without IR, respectively. Furthermore, based on these alterations of metabolites, MetPA network pathway analysis suggested a profound involvement of the abnormalities of glycerophospholipid, glycerolipid and fatty acid metabolisms in the pathogenesis of PCOS and IR complications. Collectively, LC-MS-based metabolomics provides a promising strategy for complementary diagnosis of PCOS and its IR complication and offers a new insight to understand their pathogenesis mechanisms. PMID:26808063

  19. GC-MS-based metabolomic study on the antidepressant-like effects of diterpene ginkgolides in mouse hippocampus.

    Science.gov (United States)

    Liang, Zihong; Bai, Shunjie; Shen, Peng; Hu, Qingchuan; Wang, Xingfa; Dong, Meixue; Wang, Wei; Li, Juan; Cheng, Ke; Zhang, Shuxiao; Zou, Dezhi; Han, Yu; Wang, Haiyang; Xie, Peng

    2016-11-01

    Ginkgo biloba extract (GBE), including EGb-761, have been suggested to have antidepressant activity based on previous behavioral and biochemical analyses. However, because GBE contain many constituents, the mechanisms underlying this suggested antidepressant activity are unclear. Here, we investigated the antidepressant-like effects of diterpene ginkgolides (DG), an important class of constituents in GBE, and studied their effects in the mouse hippocampus using a GC-MS-based metabolomics approach. Mice were randomly divided into five groups and injected daily until testing with 0.9% NaCl solution, one of three doses of DG (4.06, 12.18, and 36.54mg/kg), or venlafaxine. Sucrose preference (SPT) and tail suspension (TST) tests were then performed to evaluate depressive-like behaviors in mice. DG (12.18 and 36.54mg/kg) and venlafaxine (VLX) administration significantly increased hedonic behavior in mice in the SPT. DG (12.18mg/kg) treatment also shortened immobility time in the TST, suggestive of antidepressant-like effects. Significant differences in the metabolic profile in the DG (12.18mg/kg) compared with the control or VLX group indicative of an antidepressant-like effect were observed using multivariate analysis. Eighteen differential hippocampal metabolites were identified that discriminated the DG (12.18mg/kg) and control groups. These biochemical changes involved neurotransmitter metabolism, oxidative stress, glutathione metabolism, lipid metabolism, energy metabolism, and kynurenic acid, providing clues to the therapeutic mechanisms of DG. Thus, this study showed that DG has antidepressant-like activities in mice and shed light on the biological mechanisms underlying the effects of diterpene ginkgolides on behavior, providing an important drug candidate for the treatment of depression. PMID:27498146

  20. GC-MS-based metabolomic study on the antidepressant-like effects of diterpene ginkgolides in mouse hippocampus.

    Science.gov (United States)

    Liang, Zihong; Bai, Shunjie; Shen, Peng; Hu, Qingchuan; Wang, Xingfa; Dong, Meixue; Wang, Wei; Li, Juan; Cheng, Ke; Zhang, Shuxiao; Zou, Dezhi; Han, Yu; Wang, Haiyang; Xie, Peng

    2016-11-01

    Ginkgo biloba extract (GBE), including EGb-761, have been suggested to have antidepressant activity based on previous behavioral and biochemical analyses. However, because GBE contain many constituents, the mechanisms underlying this suggested antidepressant activity are unclear. Here, we investigated the antidepressant-like effects of diterpene ginkgolides (DG), an important class of constituents in GBE, and studied their effects in the mouse hippocampus using a GC-MS-based metabolomics approach. Mice were randomly divided into five groups and injected daily until testing with 0.9% NaCl solution, one of three doses of DG (4.06, 12.18, and 36.54mg/kg), or venlafaxine. Sucrose preference (SPT) and tail suspension (TST) tests were then performed to evaluate depressive-like behaviors in mice. DG (12.18 and 36.54mg/kg) and venlafaxine (VLX) administration significantly increased hedonic behavior in mice in the SPT. DG (12.18mg/kg) treatment also shortened immobility time in the TST, suggestive of antidepressant-like effects. Significant differences in the metabolic profile in the DG (12.18mg/kg) compared with the control or VLX group indicative of an antidepressant-like effect were observed using multivariate analysis. Eighteen differential hippocampal metabolites were identified that discriminated the DG (12.18mg/kg) and control groups. These biochemical changes involved neurotransmitter metabolism, oxidative stress, glutathione metabolism, lipid metabolism, energy metabolism, and kynurenic acid, providing clues to the therapeutic mechanisms of DG. Thus, this study showed that DG has antidepressant-like activities in mice and shed light on the biological mechanisms underlying the effects of diterpene ginkgolides on behavior, providing an important drug candidate for the treatment of depression.

  1. The Time Is Right to Focus on Model Organism Metabolomes

    Science.gov (United States)

    Edison, Arthur S.; Hall, Robert D.; Junot, Christophe; Karp, Peter D.; Kurland, Irwin J.; Mistrik, Robert; Reed, Laura K.; Saito, Kazuki; Salek, Reza M.; Steinbeck, Christoph; Sumner, Lloyd W.; Viant, Mark R.

    2016-01-01

    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. PMID:26891337

  2. 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.

  3. Comparative effects of dexamethasone and bergenin on chronic bronchitis and their anti-inflammatory mechanisms based on NMR metabolomics.

    Science.gov (United States)

    Ren, Xiaolei; Ma, Shuangshuang; Wang, Juan; Tian, Simin; Fu, Xiaorui; Liu, Xinfeng; Li, Zhongfeng; Zhao, Baosheng; Wang, Xueyong

    2016-05-24

    In order to compare the effect of dexamethasone and bergenin on chronic bronchitis and to reveal their anti-inflammatory mechanisms, (1)H NMR-based metabolomics was performed to explore the potential biomarkers of the disease and study the therapeutic mechanisms of the drugs. In this study, 40 Sprague-Dawley male rats were randomly divided into 4 groups, namely control, model, dexamethasone and bergenin groups, with 10 rats in each group. Except for the control group, rats from the other three groups were exposed to tobacco smoke for 1 h d(-1) for 28 days. During the modeling, dexamethasone (0.2 mg kg(-1)) and bergenin (87 mg kg(-1)) were administered orally to dexamethasone or bergenin rats 3 h after exposure every day. On the other hand, control and model rats were intragastrically administered water. According to the results of morphometric analysis of the airway epithelium and the count of white blood cells in the bronchoalveolar lavage fluid (BALF), dexamethasone and bergenin could suppress the infiltration of inflammatory cells, inhibit the secretion of mucus, and reduce white blood cells in BALF. Serum samples from the rats' orbits were collected every week. The metabolic profiles of sera were analyzed by multivariate statistical analyses, including PCA, PLS-DA and OPLS-DA models, and 18 metabolites were identified. The dynamic fluctuations of these biomarkers in sera from different groups were detected. The results suggested that the anti-inflammatory mechanism of dexamethasone may be associated with BCAA metabolism and glycolysis while bergenin could change BCAA metabolism, glycine, serine and threonine metabolism, and glycolysis to treat chronic bronchitis. PMID:27098339

  4. 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.

  5. From numbers to a biological sense: How the strategy chosen for metabolomics data treatment may affect final results. A practical example based on urine fingerprints obtained by LC-MS.

    Science.gov (United States)

    Godzien, Joanna; Ciborowski, Michal; Angulo, Santiago; Barbas, Coral

    2013-10-01

    Application of high-throughput technologies in metabolomics studies increases the quantity of data obtained, which in turn imposes several problems during data analysis. Correctly and clearly addressed biological question and comprehensive knowledge about data structure and properties are definitely necessary to select proper chemometric tools. However, there is a broad range of chemometric tools available for use with metabolomics data, which makes this choice challenging. Precisely performed data treatment enables valuable extraction of information and its proper interpretation. The effect of an error made at an early stage will be enhanced throughout the later stages, which in combination with other errors made at each step can accumulate and significantly affect the data interpretation. Moreover, adequate application of these tools may help not only to detect, but sometimes also to correct, biological, analytical, or methodological errors, which may affect truthfulness of obtained results. This report presents steps and tools used for LC-MS based metabolomics data extraction, reduction, and visualization. Following such steps as data reprocessing, data pretreatment, data treatment, and data revision, authors want to show how to extract valuable information and how to avoid misinterpretation of results obtained. The purpose of this work was to emphasize problematic characteristics of metabolomics data and the necessity for their attentive and precise treatment. The dataset used to illustrate metabolomics data properties and to illustrate major data treatment challenges was obtained utilizing an animal model of control and diabetic rats, both with and without rosemary treatment. Urine samples were fingerprinted employing LC-QTOF-MS. PMID:23775708

  6. NMR-based metabolomics and hyphenated NMR techniques – a perfect match in natural products research

    DEFF Research Database (Denmark)

    Vinther, Joachim Møllesøe; Wubshet, Sileshi Gizachew; Stærk, Dan

    2015-01-01

    Ethnopharmacology is one of the world’s fastest-growing scientific disciplines encompassing a diverse range of subjects. It links natural sciences research on medicinal, aromatic and toxic plants with socio-cultural studies and has often been associated with the development of new drugs....... The Editors of Ethnopharmacology have assembled an international team of renowned contributors to provide a critical synthesis of the substantial body of new knowledge and evidence on the subject that has emerged over the past decade. Divided into three parts, the book begins with an overview of the subject...... therapeutics across a range of conditions including CNS disorders, cancer, bone and joint health and parasitic diseases. The final part is devoted to regional perspectives covering all continents, providing a state-of-the –art assessment of the status of ethnopharmacological research globally....

  7. 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.

  8. Cell-based Metabolomics for Monitoring Ecological Impacts of Environmental Surface Waters

    Science.gov (United States)

    Numerous surface waters are adversely impacted by contaminants released from sources such as WWfPs, CAFOs, mining activities, and agricultural operations. Ideally, an assessment strategy for these applications would include both chemical identification and effects-based monitorin...

  9. 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.

  10. Pattern Recognition and Pathway Analysis with Genetic Algorithms in Mass Spectrometry Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Wei Zou

    2009-04-01

    Full Text Available A robust and complete workflow for metabolic profiling and data mining was described in detail. Three independent and complementary analytical techniques for metabolic profiling were applied: hydrophilic interaction chromatography (HILIC–LC–ESI–MS, reversed-phase liquid chromatography (RP–LC–ESI–MS, and gas chromatography (GC–TOF–MS all coupled to mass spectrometry (MS. Unsupervised methods, such as principle component analysis (PCA and clustering, and supervised methods, such as classification and PCA-DA (discriminatory analysis were used for data mining. Genetic Algorithms (GA, a multivariate approach, was probed for selection of the smallest subsets of potentially discriminative predictors. From thousands of peaks found in total, small subsets selected by GA were considered as highly potential predictors allowing discrimination among groups. It was found that small groups of potential top predictors selected with PCA-DA and GA are different and unique. Annotated GC–TOF–MS data generated identified feature metabolites. Metabolites putatively detected with LC–ESI–MS profiling require further elemental composition assignment with accurate mass measurement by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS and structure elucidation by nuclear magnetic resonance spectroscopy (NMR. GA was also used to generate correlated networks for pathway analysis. Several case studies, comprising groups of plant samples bearing different genotypes and groups of samples of human origin, namely patients and healthy volunteers’ urine samples, demonstrated that such a workflow combining comprehensive metabolic profiling and advanced data mining techniques provides a powerful approach for pattern recognition and biomarker discovery

  11. 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...

  12. Fecal metabolome of the Hadza hunter-gatherers: a host-microbiome integrative view.

    Science.gov (United States)

    Turroni, Silvia; Fiori, Jessica; Rampelli, Simone; Schnorr, Stephanie L; Consolandi, Clarissa; Barone, Monica; Biagi, Elena; Fanelli, Flaminia; Mezzullo, Marco; Crittenden, Alyssa N; Henry, Amanda G; Brigidi, Patrizia; Candela, Marco

    2016-01-01

    The recent characterization of the gut microbiome of traditional rural and foraging societies allowed us to appreciate the essential co-adaptive role of the microbiome in complementing our physiology, opening up significant questions on how the microbiota changes that have occurred in industrialized urban populations may have altered the microbiota-host co-metabolic network, contributing to the growing list of Western diseases. Here, we applied a targeted metabolomics approach to profile the fecal metabolome of the Hadza of Tanzania, one of the world's few remaining foraging populations, and compared them to the profiles of urban living Italians, as representative of people in the post-industrialized West. Data analysis shows that during the rainy season, when the diet is primarily plant-based, Hadza are characterized by a distinctive enrichment in hexoses, glycerophospholipids, sphingolipids, and acylcarnitines, while deplete in the most common natural amino acids and derivatives. Complementary to the documented unique metagenomic features of their gut microbiome, our findings on the Hadza metabolome lend support to the notion of an alternate microbiome configuration befitting of a nomadic forager lifestyle, which helps maintain metabolic homeostasis through an overall scarcity of inflammatory factors, which are instead highly represented in the Italian metabolome. PMID:27624970

  13. Fecal metabolome of the Hadza hunter-gatherers: a host-microbiome integrative view

    Science.gov (United States)

    Turroni, Silvia; Fiori, Jessica; Rampelli, Simone; Schnorr, Stephanie L.; Consolandi, Clarissa; Barone, Monica; Biagi, Elena; Fanelli, Flaminia; Mezzullo, Marco; Crittenden, Alyssa N.; Henry, Amanda G.; Brigidi, Patrizia; Candela, Marco

    2016-01-01

    The recent characterization of the gut microbiome of traditional rural and foraging societies allowed us to appreciate the essential co-adaptive role of the microbiome in complementing our physiology, opening up significant questions on how the microbiota changes that have occurred in industrialized urban populations may have altered the microbiota-host co-metabolic network, contributing to the growing list of Western diseases. Here, we applied a targeted metabolomics approach to profile the fecal metabolome of the Hadza of Tanzania, one of the world’s few remaining foraging populations, and compared them to the profiles of urban living Italians, as representative of people in the post-industrialized West. Data analysis shows that during the rainy season, when the diet is primarily plant-based, Hadza are characterized by a distinctive enrichment in hexoses, glycerophospholipids, sphingolipids, and acylcarnitines, while deplete in the most common natural amino acids and derivatives. Complementary to the documented unique metagenomic features of their gut microbiome, our findings on the Hadza metabolome lend support to the notion of an alternate microbiome configuration befitting of a nomadic forager lifestyle, which helps maintain metabolic homeostasis through an overall scarcity of inflammatory factors, which are instead highly represented in the Italian metabolome. PMID:27624970

  14. Navigating the Human Metabolome for Biomarker Identification and Design of Pharmaceutical Molecules

    Directory of Open Access Journals (Sweden)

    Irene Kouskoumvekaki

    2011-01-01

    Full Text Available Metabolomics is a rapidly evolving discipline that involves the systematic study of endogenous small molecules that characterize the metabolic pathways of biological systems. The study of metabolism at a global level has the potential to contribute significantly to biomedical research, clinical medical practice, as well as drug discovery. In this paper, we present the most up-to-date metabolite and metabolic pathway resources, and we summarize the statistical, and machine-learning tools used for the analysis of data from clinical metabolomics. Through specific applications on cancer, diabetes, neurological and other diseases, we demonstrate how these tools can facilitate diagnosis and identification of potential biomarkers for use within disease diagnosis. Additionally, we discuss the increasing importance of the integration of metabolomics data in drug discovery. On a case-study based on the Human Metabolome Database (HMDB and the Chinese Natural Product Database (CNPD, we demonstrate the close relatedness of the two data sets of compounds, and we further illustrate how structural similarity with human metabolites could assist in the design of novel pharmaceuticals and the elucidation of the molecular mechanisms of medicinal plants.

  15. Mass spectrometry–based metabolomics, analysis of metabolite-protein interactions, and imaging

    Science.gov (United States)

    Lee, Do Yup; Bowen, Benjamin P.; Northen, Trent R.

    2010-01-01

    Our understanding of biology has been greatly improved through recent developments in mass spectrometry, which is providing detailed information on protein and metabolite composition as well as protein-metabolite interactions. The high sensitivity and resolution of mass spectrometry achieved with liquid or gas chromatography allows for detection and quantification of hundreds to thousands of molecules in a single measurement. Where homogenization-based sample preparation and extraction methods result in a loss of spatial information, mass spectrometry imaging technologies provide the in situ distribution profiles of metabolites and proteins within tissues. Mass spectrometry–based analysis of metabolite abundance, protein-metabolite interactions, and spatial distribution of compounds facilitates the high-throughput screening of biochemical reactions, the reconstruction of metabolic networks, biomarker discovery, determination of tissue compositions, and functional annotation of both proteins and metabolites. PMID:20701590

  16. Back tracing environmental toxicants in animal-derived food chain based on food metabolomics

    OpenAIRE

    Engel, Erwan; Ratel, Jérémy; Planche, Christelle

    2013-01-01

    Food-producing animals are exposed to toxic micropollutants via their environment and feeds. These micropollutants represent a chemical human health hazard because they are capable of entering the animals and being transferred to edible tissues 1 . Most current approaches to assessing contamination levels in foods are based on high performance analytical methods designed to determine the concentration of targeted micropollutant residues present down to trace levels in the food. Alternative...

  17. Bisphenol A alters n-6 fatty acid composition and decreases antioxidant enzyme levels in rat testes: a LC-QTOF-based metabolomics study.

    Directory of Open Access Journals (Sweden)

    Minjian Chen

    Full Text Available BACKGROUND: Male reproductive toxicity induced by exposure to bisphenol A (BPA has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. METHODOLOGY/PRINCIPAL FINDINGS: Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA and arachidonic acid (AA were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px as well as catalase (CAT also showed a decreasing trend in BPA treated group. CONCLUSIONS/SIGNIFICANCE: BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity.

  18. Application of a novel metabolomic approach based on atmospheric pressure photoionization mass spectrometry using flow injection analysis for the study of Alzheimer's disease.

    Science.gov (United States)

    González-Domínguez, Raúl; García-Barrera, Tamara; Gómez-Ariza, José Luis

    2015-01-01

    The use of atmospheric pressure photoionization is not widespread in metabolomics, despite its considerable potential for the simultaneous analysis of compounds with diverse polarities. This work considers the development of a novel analytical approach based on flow injection analysis and atmospheric pressure photoionization mass spectrometry for rapid metabolic screening of serum samples. Several experimental parameters were optimized, such as type of dopant, flow injection solvent, and their flows, given that a careful selection of these variables is mandatory for a comprehensive analysis of metabolites. Toluene and methanol were the most suitable dopant and flow injection solvent, respectively. Moreover, analysis in negative mode required higher solvent and dopant flows (100 µl min(-1) and 40 µl min(-1), respectively) compared to positive mode (50 µl min(-1) and 20 µl min(-1)). Then, the optimized approach was used to elucidate metabolic alterations associated with Alzheimer's disease. Thereby, results confirm the increase of diacylglycerols, ceramides, ceramide-1-phosphate and free fatty acids, indicating membrane destabilization processes, and reduction of fatty acid amides and several neurotransmitters related to impairments in neuronal transmission, among others. Therefore, it could be concluded that this metabolomic tool presents a great potential for analysis of biological samples, considering its high-throughput screening capability, fast analysis and comprehensive metabolite coverage.

  19. Discovery, screening and evaluation of a plasma biomarker panel for subjects with psychological suboptimal health state using 1H-NMR-based metabolomics profiles

    Science.gov (United States)

    Tian, Jun-sheng; Xia, Xiao-tao; Wu, Yan-fei; Zhao, Lei; Xiang, Huan; Du, Guan-hua; Zhang, Xiang; Qin, Xue-mei

    2016-01-01

    Individuals in the state of psychological suboptimal health keep increasing, only scales and questionnaires were used to diagnose in clinic under current conditions, and symptoms of high reliability and accuracy are destitute. Therefore, the noninvasive and precise laboratory diagnostic methods are needed. This study aimed to develop an objective method through screen potential biomarkers or a biomarker panel to facilitate the diagnosis in clinic using plasma metabolomics. Profiles were based on H-nuclear magnetic resonance (1H-NMR) metabolomics techniques combing with multivariate statistical analysis. Furthermore, methods of correlation analysis with Metaboanalyst 3.0 for selecting a biomarker panel, traditional Chinese medicine (TCM) drug intervention for validating the close relations between the biomarker panel and the state and the receiver operating characteristic curves (ROC curves) analysis for evaluation of clinical diagnosis ability were carried out. 9 endogenous metabolites containing trimethylamine oxide (TMAO), glutamine, N-acetyl-glycoproteins, citrate, tyrosine, phenylalanine, isoleucine, valine and glucose were identified and considered as potential biomarkers. Then a biomarker panel consisting of phenylalanine, glutamine, tyrosine, citrate, N-acetyl-glycoproteins and TMAO was selected, which exhibited the highest area under the curve (AUC = 0.971). This study provided critical insight into the pathological mechanism of psychological suboptimal health and would supply a novel and valuable diagnostic method. PMID:27650680

  20. 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.

  1. Untargeted Metabolomics Strategies—Challenges and Emerging Directions

    Science.gov (United States)

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

    2016-09-01

    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.

  2. 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. PMID:17269710

  3. COnsortium of METabolomics Studies (COMETS)

    Science.gov (United States)

    The COnsortium of METabolomics Studies (COMETS) is an extramural-intramural partnership that promotes collaboration among prospective cohort studies that follow participants for a range of outcomes and perform metabolomic profiling of individuals.

  4. Systematic Applications of Metabolomics in Metabolic Engineering

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Xenobiotic metabolomics: major impact on the metabolome.

    Science.gov (United States)

    Johnson, Caroline H; Patterson, Andrew D; Idle, Jeffrey R; Gonzalez, Frank J

    2012-01-01

    Xenobiotics are encountered by humans on a daily basis and include drugs, environmental pollutants, cosmetics, and even components of the diet. These chemicals undergo metabolism and detoxication to produce numerous metabolites, some of which have the potential to cause unintended effects such as toxicity. They can also block the action of enzymes or receptors used for endogenous metabolism or affect the efficacy and/or bioavailability of a coadministered drug. Therefore, it is essential to determine the full metabolic effects that these chemicals have on the body. Metabolomics, the comprehensive analysis of small molecules in a biofluid, can reveal biologically relevant perturbations that result from xenobiotic exposure. This review discusses the impact that genetic, environmental, and gut microflora variation has on the metabolome, and how these variables may interact, positively and negatively, with xenobiotic metabolism.

  7. Metabolic model-based integration of microbiome taxonomic and metabolomic profiles elucidates mechanistic links between ecological and metabolic variation

    Energy Technology Data Exchange (ETDEWEB)

    Noecker, Cecilia; Eng, Alexander; Srinivasan, Sujatha; Theriot , Casey M.; Young, VIncent B.; Jansson, Janet K.; Fredricks, David N.; Borenstein, Elhanan A.

    2016-01-19

    Multiple molecular assays now enable high-throughput profiling of the ecology, metabolic capacity, and activity of the human microbiome. However, to date analyses of such multi-meta-omic data typically focus on statistical associations, often ignoring extensive prior knowledge of the mechanisms linking these various facets of the microbiome. Here we introduce a comprehensive framework to systematically link variation in metabolomic data with community composition by utilizing taxonomic, genomic, and metabolic information. Specifically, we integrate available and inferred genomic data, metabolic network modeling, and a method for predicting community-wide metabolite turnover to estimate the biosynthetic and degradation potential of a given community. Our framework then compares variation in predicted metabolic potential with variation in measured metabolites' abundances to evaluate whether community composition can explain observed shifts in the community metabolome, and to identify key taxa and genes contributors. Focusing on two independent vaginal microbiome datasets, each pairing 16S community profiling with large-scale metabolomics, we demonstrate that our framework successfully recapitulates observed variation in 37% of metabolites. Well-predicted metabolite variation tends to result from disease-associated metabolism. We further identify several disease-enriched species that significantly contribute to these predictions. Interestingly, our analysis also detects metabolites for which predicted variation negatively correlates with measured variation, suggesting environmental control points of community metabolism. Applying this framework to gut microbiome datasets reveals similar trends,including prediction of bile acid metabolite shifts. This framework is an important first step towards a system-level multi-omic integration and an improved mechanistic understanding of the microbiome activity and dynamics in health and disease.

  8. Potential of human saliva for nuclear magnetic resonance-based metabolomics and for health-related biomarker identification

    DEFF Research Database (Denmark)

    Bertram, Hanne Christine; Eggers, Nina; Eller, Nanna

    2009-01-01

    In the present study, the ability of (1)H nuclear magnetic resonance (NMR) for metabolic profiling of human saliva samples was investigated. High-resolution (1)H NMR spectra were obtained, and signals were assigned to various metabolites mainly representing small organic acids and amino acids....... In addition, the use of human saliva for metabolomic studies was evaluated, and multivariate data analysis revealed that the 92 morning and night samples from 46 subjects could be discriminated with a predictability of 85%. The diurnal effect on the salivary metabolite profile were ascribed to changes...

  9. Metabolomic heterogeneity of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yidan Zhao

    Full Text Available Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH, the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.

  10. GC-MS Based Plasma Metabolomics for Identification of Candidate Biomarkers for Hepatocellular Carcinoma in Egyptian Cohort.

    Directory of Open Access Journals (Sweden)

    Mohammad R Nezami Ranjbar

    Full Text Available This study evaluates changes in metabolite levels in hepatocellular carcinoma (HCC cases vs. patients with liver cirrhosis by analysis of human blood plasma using gas chromatography coupled with mass spectrometry (GC-MS. Untargeted metabolomic analysis of plasma samples from participants recruited in Egypt was performed using two GC-MS platforms: a GC coupled to single quadruple mass spectrometer (GC-qMS and a GC coupled to a time-of-flight mass spectrometer (GC-TOFMS. Analytes that showed statistically significant changes in ion intensities were selected using ANOVA models. These analytes and other candidates selected from related studies were further evaluated by targeted analysis in plasma samples from the same participants as in the untargeted metabolomic analysis. The targeted analysis was performed using the GC-qMS in selected ion monitoring (SIM mode. The method confirmed significant changes in the levels of glutamic acid, citric acid, lactic acid, valine, isoleucine, leucine, alpha tocopherol, cholesterol, and sorbose in HCC cases vs. patients with liver cirrhosis. Specifically, our findings indicate up-regulation of metabolites involved in branched-chain amino acid (BCAA metabolism. Although BCAAs are increasingly used as a treatment for cancer cachexia, others have shown that BCAA supplementation caused significant enhancement of tumor growth via activation of mTOR/AKT pathway, which is consistent with our results that BCAAs are up-regulated in HCC.

  11. Capillary electrophoresis-mass spectrometry-based metabolome analysis of serum and saliva from neurodegenerative dementia patients.

    Science.gov (United States)

    Tsuruoka, Mayuko; Hara, Junko; Hirayama, Akiyoshi; Sugimoto, Masahiro; Soga, Tomoyoshi; Shankle, William R; Tomita, Masaru

    2013-10-01

    Despite increasing global prevalence, the precise pathogenesis and terms for objective diagnosis of neurodegenerative dementias remain controversial, and comprehensive understanding of the disease remains lacking. Here, we conducted metabolomic analysis of serum and saliva obtained from patients with neurodegenerative dementias (n = 10), including Alzheimer's disease, frontotemporal lobe dementia, and Lewy body disease, as well as from age-matched healthy controls (n = 9). Using CE-TOF-MS, six metabolites in serum (β-alanine, creatinine, hydroxyproline, glutamine, iso-citrate, and cytidine) and two in saliva (arginine and tyrosine) were significantly different between dementias and controls. Using multivariate analysis, serum was confirmed as a more efficient biological fluid for diagnosis compared to saliva; additionally, 45 metabolites in total were identified as candidate markers that could discriminate at least one pair of diagnostic groups from the healthy control group. These metabolites possibly provide an objective method for diagnosing dementia-type by multiphase screening. Moreover, diagnostic-type-dependent differences were observed in several tricarboxylic acid cycle compounds detected in serum, indicating that some pathways in glucose metabolism may be altered in dementia patients. This pilot study revealed novel alterations in metabolomic profiles between various neurodegenerative dementias, which would contribute to etiological investigations.

  12. 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

  13. 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

  14. NMR-based metabolomic profiling of overweight adolescents – an elucidation of the effects of inter-/intra-individual differences, gender, pubertal development and physical activity

    DEFF Research Database (Denmark)

    Zheng, Hong; Yde, Christian Clement; 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...... in the metabolome are being commenced already in childhood. The relationship between Tanner stage and the metabolome showed that pubertal development stage was positively related to urinary creatinine excretion and negatively related to urinary citrate content. No relations between physical activity...... 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...

  15. From models to crop species: caveats and solutions for translational metabolomics

    Directory of Open Access Journals (Sweden)

    Takayuki eTohge

    2011-10-01

    Full Text Available Although plant metabolomics is largely carried out on Arabidopsis it is essentially genome-independent, and thus potentially applicable to a wide range of species. However, transfer of between species, or even between different tissues of the same species, is not facile. This is because the reliability of protocols for harvesting, handling and analysis depends on the biological features and chemical composition of the plant tissue. In parallel with the diversification of model species it is important to establish good handling and analytic practice, in order to augment computational comparisons between tissues and species. LC-MS-based metabolomics is one of the powerful approaches for metabolite profiling. By using a combination of different extraction methods, separation columns and ion detection, a very wide range of metabolites can be analysed. However, its application requires careful attention to exclude potential pitfalls, including artifactual changes in metabolite levels during sample preparation and analytic errors due to ion-suppression. Here we provide case studies with two different LC-MS-based metabolomics platforms and four species (Arabidopsis thaliana, Chlamydomonas reinhardtii, Solanum lycopersicum and Oryza sativa that illustrate how such dangers can be detected and circumvented.

  16. The bases of plant introduction

    OpenAIRE

    Karpun Yu N

    2004-01-01

    The main problems of plintroduction are presented as theses. The plants introduction is suggested to regard as process of their cultivation, which has several stages: the mobilization of plant's material, primary test, sec- ond test. The basic terms are offered: introduction point, introduction search, collection number, introduction situation, etc. The peculiarities of plants introduction process are presented. The relationship between native flora and introduction plants are con...

  17. Vitroprocines, new antibiotics against Acinetobacter baumannii, discovered from marine Vibrio sp. QWI-06 using mass-spectrometry-based metabolomics approach

    Science.gov (United States)

    Liaw, Chih-Chuang; Chen, Pei-Chin; Shih, Chao-Jen; Tseng, Sung-Pin; Lai, Ying-Mi; Hsu, Chi-Hsin; Dorrestein, Pieter C.; Yang, Yu-Liang

    2015-08-01

    A robust and convenient research strategy integrating state-of-the-art analytical techniques is needed to efficiently discover novel compounds from marine microbial resources. In this study, we identified a series of amino-polyketide derivatives, vitroprocines A-J, from the marine bacterium Vibrio sp. QWI-06 by an integrated approach using imaging mass spectroscopy and molecular networking, as well as conventional bioactivity-guided fractionation and isolation. The structure-activity relationship of vitroprocines against Acinetobacter baumannii is proposed. In addition, feeding experiments with 13C-labeled precursors indicated that a pyridoxal 5‧-phosphate-dependent mechanism is involved in the biosynthesis of vitroprocines. Elucidation of amino-polyketide derivatives from a species of marine bacteria for the first time demonstrates the potential of this integrated metabolomics approach to uncover marine bacterial biodiversity.

  18. A signal filtering method for improved quantification and noise discrimination in fourier transform ion cyclotron resonance mass spectrometry-based metabolomics data.

    Science.gov (United States)

    Payne, Tristan G; Southam, Andrew D; Arvanitis, Theodoros N; Viant, Mark R

    2009-06-01

    Direct-infusion electrospray-ionization Fourier transform ion cyclotron resonance mass spectrometry (DI ESI FT-ICR MS) is increasingly being utilized in metabolomics, including the high sensitivity selected ion monitoring (SIM)-stitching approach. Accurate signal quantification and the discrimination of real signals from noise remain major challenges for this approach, with both adversely affected by factors including ion suppression during electrospray, ion-ion interactions in the detector cell, and thermally-induced white noise. This is particularly problematic for complex mixture analysis where hundreds of metabolites are present near the noise level. Here we address relative signal quantification and noise discrimination issues in SIM-stitched DI ESI FT-ICR MS-based metabolomics. Using liver tissue, we first optimized the number of scans (n) acquired per SIM window to address the balance between quantification accuracy versus acquisition time (and thus sample throughput); a minimum of n = 5 is recommended. Secondly, we characterized and computationally-corrected an effect whereby an ion's intensity is dependent upon its location within a SIM window, exhibiting a 3-fold higher intensity at the high m/z end. This resulted in significantly improved quantification accuracy. Finally, we thoroughly characterized a three-stage filter to discriminate noise from real signals, which comprised a signal-to-noise-ratio (SNR) hard threshold, then a "replicate" filter (retaining only peaks in r-out-of-3 replicate analyses), and then a "sample" filter (retaining only peaks in >s% of biological samples). We document the benefits of three-stage filtering versus one- and two-stage filters, and show the importance of selecting filter parameters that balance the confidence that a signal is real versus the total number of peaks detected.

  19. Metallomics and NMR-based metabolomics of Chlorella sp. reveal the synergistic role of copper and cadmium in multi-metal toxicity and oxidative stress.

    Science.gov (United States)

    Zhang, Wenlin; Tan, Nicole G J; Fu, Baohui; Li, Sam F Y

    2015-03-01

    Industrial wastewaters often contain high levels of metal mixtures, in which metal mixtures may have synergistic or antagonistic effects on aquatic organisms. A combination of metallomics and nuclear magnetic resonance spectroscopy (NMR)-based metabolomics was employed to understand the consequences of multi-metal systems (Cu, Cd, Pb) on freshwater microalgae. Morphological characterization, cell viability and chlorophyll a determination of metal-spiked Chlorella sp. suggested synergistic effects of Cu and Cd on growth inhibition and toxicity. While Pb has no apparent effect on Chlorella sp. metabolome, a substantial decrease of sucrose, amino acid content and glycerophospholipid precursors in Cu-spiked microalgae revealed Cu-induced oxidative stress. Addition of Cd to Cu-spiked cultures induced more drastic metabolic perturbations, hence we confirmed that Cu and Cd synergistically influenced photosynthesis inhibition, oxidative stress and membrane degradation. Total elemental analysis revealed a significant decrease in K, and an increase in Na, Mg, Zn and Mn concentrations in Cu-spiked cultures. This indicated that Cu is more toxic to Chlorella sp. as compared to Cd or Pb, and the combination of Cu and Cd has a strong synergistic effect on Chlorella sp. oxidative stress induction. Oxidative stress is confirmed by liquid chromatography tandem mass spectrometry analysis, which demonstrated a drastic decrease in the GSH/GSSG ratio solely in Cu-spiked cultures. Interestingly, we observed Cu-facilitated Cd and Pb bioconcentration in Chlorella sp. The absence of phytochelatins and an increment of extracellular polymeric substances (EPS) yields in Cu-spiked cultures suggested that the mode of bioconcentration of Cd and Pb is through adsorption of free metals onto the algal EPS rather than intracellular chelation to phytochelatins.

  20. Metabolomic changes of Brassica rapa under biotic stress

    NARCIS (Netherlands)

    Abdel-Farid Ali, Ibrahim Bayoumi

    2009-01-01

    It has been shown by this thesis that plant metabolomics is a promising tool for studying the interaction between B. rapa and pathogenic fungi. It gives a picture of the plant metabolites during the interaction. Brassica rapa has many defense related compounds such as glucosinolates, IAA, phenylprop

  1. Metabolomics Research Group 2011 Study

    OpenAIRE

    Asara, J. M.; Tolstikov, V.V.; Aronov, P.; Kesler, B.; Shulaev, V.; Turck, C. W.; Wikoff, W R

    2011-01-01

    The ABRF Metabolomics Research Group (MRG) was formed in 2009 and aims to educate research scientists and resource facilities in the analytical approaches and management of data resulting from comprehensive metabolite studies and to promote the science and standardization of metabolomic analyses for a variety of applications. Last year the MRG conducted a ‘Survey Study’ on the current use of metabolomics technologies and procedures in core facilities. This year the MRG is organizing a ‘Resear...

  2. Plant-based remediation processes

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Dharmendra Kumar (ed.) [Belgian Nuclear Research Centre (SCK.CEN), Mol (Belgium). Radiological Impact and Performance Assessment Division

    2013-11-01

    A valuable source of information for scientists in the field of environmental pollution and remediation. Describes the latest biotechnological methods for the treatment of contaminated soils. Includes case studies and protocols. Phytoremediation is an emerging technology that employs higher plants for the clean-up of contaminated environments. Basic and applied research have unequivocally demonstrated that selected plant species possess the genetic potential to accumulate, degrade, metabolize and immobilize a wide range of contaminants. The main focus of this volume is on the recent advances of technologies using green plants for remediation of various metals and metalloids. Topics include biomonitoring of heavy metal pollution, amendments of higher uptake of toxic metals, transport of heavy metals in plants, and toxicity mechanisms. Further chapters discuss agro-technological methods for minimizing pollution while improving soil quality, transgenic approaches to heavy metal remediation and present protocols for metal remediation via in vitro root cultures.

  3. Growing pioneer plants for a lunar base

    Science.gov (United States)

    Kozyrovska, N. O.; Lutvynenko, T. L.; Korniichuk, O. S.; Kovalchuk, M. V.; Voznyuk, T. M.; Kononuchenko, O.; Zaetz, I.; Rogutskyy, I. S.; Mytrokhyn, O. V.; Mashkovska, S. P.; Foing, B. H.; Kordyum, V. A.

    A precursory scenario of cultivating the first plants in a lunar greenhouse was elaborated in frames of a conceptual study to grow plants for a permanently manned lunar base. A prototype plant growth system represents an ornamental plant Tagetes patula L. for growing in a lunar rock anorthosite as a substrate. Microbial community anticipated to be in use to support a growth and development of the plant in a substrate of low bioavailability and provide an acceptable growth and blossoming of T. patula under growth limiting conditions.

  4. Metabolic regulation of trisporic acid on Blakeslea trispora revealed by a GC-MS-based metabolomic approach.

    Directory of Open Access Journals (Sweden)

    Jie Sun

    Full Text Available The zygomycete Blakeslea trispora is used commercially as natural source of â-carotene. Trisporic acid (TA is secreted from the mycelium of B. trispora during mating between heterothallic strains and is considered as a mediator of the regulation of mating processes and an enhancer of carotene biosynthesis. Gas chromatography-mass spectrometry and multivariate analysis were employed to investigate TA-associated intracellular biochemical changes in B. trispora. By principal component analysis, the differential metabolites discriminating the control groups from the TA-treated groups were found, which were also confirmed by the subsequent hierarchical cluster analysis. The results indicate that TA is a global regulator and its main effects at the metabolic level are reflected on the content changes in several fatty acids, carbohydrates, and amino acids. The carbon metabolism and fatty acids synthesis are sensitive to TA addition. Glycerol, glutamine, and ã-aminobutyrate might play important roles in the regulation of TA. Complemented by two-dimensional electrophoresis, the results indicate that the actions of TA at the metabolic level involve multiple metabolic processes, such as glycolysis and the bypass of the classical tricarboxylic acid cycle. These results reveal that the metabolomics strategy is a powerful tool to gain insight into the mechanism of a microorganism's cellular response to signal inducers at the metabolic level.

  5. NMR-Based Metabolomic Profiling of Overweight Adolescents: An Elucidation of the Effects of Inter-/Intraindividual Differences, Gender, and Pubertal Development

    Directory of Open Access Journals (Sweden)

    Hong Zheng

    2014-01-01

    Full Text Available The plasma and urine metabolome of 192 overweight 12–15-year-old adolescents (BMI of 25.4 ± 2.3 kg/m2 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 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 in the metabolome are being commenced already in childhood. The relationship between Tanner stage and the metabolome showed that pubertal development stage was positively related to urinary creatinine excretion and negatively related to urinary citrate content. No relations between physical activity 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 and life-style related diseases. While this study is preliminary, these results may have the potential to translate into clinical applicability upon further investigations; if biomarkers for Tanner stage can be established, these might be used for identification of individuals susceptible to an early pubertal development.

  6. Metabolomics in the Rhizosphere: Tapping into Belowground Chemical Communication.

    Science.gov (United States)

    van Dam, Nicole M; Bouwmeester, Harro J

    2016-03-01

    The rhizosphere is densely populated with a variety of organisms. Interactions between roots and rhizosphere community members are mostly achieved via chemical communication. Root exudates contain an array of primary and secondary plant metabolites that can attract, deter, or kill belowground insect herbivores, nematodes, and microbes, and inhibit competing plants. Metabolomics of root exudates can potentially help us to better understand this chemical dialogue. The main limitations are the proper sampling of the exudate, the sensitivity of the metabolomics platforms, and the multivariate data analysis to identify causal relations. Novel technologies may help to generate a spatially explicit metabolome of the root and its exudates at a scale that is relevant for the rhizosphere community.

  7. Metabolomics and Atherosclerosis

    OpenAIRE

    Sascha N Goonewardena; Prevette, Lisa E.; Desai, Ankit A

    2010-01-01

    Metabolites reflect the dynamic processes underlying cellular homeostasis. Recent advances in analytical chemistry and molecular biology have set the stage for metabolite profiling to help us understand complex molecular processes and physiology. Metabolomics is the comparative analysis of metabolite flux and how it relates to biological phenotypes. As an intermediate phenotype, metabolite signatures capture a unique aspect of cellular dynamics that is not typically interrogated, providing a ...

  8. Gas Chromatography Time-Of-Flight Mass Spectrometry (GC-TOF-MS)-Based Metabolomics for Comparison of Caffeinated and Decaffeinated Coffee and Its Implications for Alzheimer’s Disease

    Science.gov (United States)

    Chang, Kai Lun; Ho, Paul C.

    2014-01-01

    Findings from epidemiology, preclinical and clinical studies indicate that consumption of coffee could have beneficial effects against dementia and Alzheimer’s disease (AD). The benefits appear to come from caffeinated coffee, but not decaffeinated coffee or pure caffeine itself. Therefore, the objective of this study was to use metabolomics approach to delineate the discriminant metabolites between caffeinated and decaffeinated coffee, which could have contributed to the observed therapeutic benefits. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics approach was employed to characterize the metabolic differences between caffeinated and decaffeinated coffee. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed distinct separation between the two types of coffee (cumulative Q2 = 0.998). A total of 69 discriminant metabolites were identified based on the OPLS-DA model, with 37 and 32 metabolites detected to be higher in caffeinated and decaffeinated coffee, respectively. These metabolites include several benzoate and cinnamate-derived phenolic compounds, organic acids, sugar, fatty acids, and amino acids. Our study successfully established GC-TOF-MS based metabolomics approach as a highly robust tool in discriminant analysis between caffeinated and decaffeinated coffee samples. Discriminant metabolites identified in this study are biologically relevant and provide valuable insights into therapeutic research of coffee against AD. Our data also hint at possible involvement of gut microbial metabolism to enhance therapeutic potential of coffee components, which represents an interesting area for future research. PMID:25098597

  9. Microbial metabolomics : Toward a platform with full metabolome coverage

    NARCIS (Netherlands)

    Werf, M.J.v.d.; Overkamp, K.M.; Muilwijk, B.; Coulier, L.; Hankemeier, T.

    2007-01-01

    Achieving metabolome data with satisfactory coverage is a formidable challenge in metabolomics because metabolites are a chemically highly diverse group of compounds. Here we present a strategy for the development of an advanced analytical platform that allows the comprehensive analysis of microbial

  10. NMR-based Metabolomics in Aquatic Organisms:Progress%基于核磁共振的代谢组学技术在水产动物中的应用

    Institute of Scientific and Technical Information of China (English)

    邵铱娜; 李成华

    2014-01-01

    This report briefly introduces the concept of metabolomics, its detection techniques and the advantage of NMR-based metabolomics. Also, summarized are the basic procedure for aquatic sample pretreatment and data analysis for NMR-based metabolomics, as well as its research advancements in water environment pollution, aquaculture and integration of different techniques.%介绍了代谢组学的概念、分析技术以及核磁共振代谢组学的优势,探讨了水产动物核磁共振代谢组学样品处理和数据分析;重点综述了核磁共振代谢组学在水产动物水环境污染、水产养殖以及不同技术整合方面的研究现状,以进一步促进核磁共振代谢组学在水产动物中的运用。

  11. NMR-Based Metabolomic Investigations on the Differential Responses in Adductor Muscles from Two Pedigrees of Manila Clam Ruditapes philippinarum to Cadmium and Zinc

    Directory of Open Access Journals (Sweden)

    Junbao Yu

    2011-09-01

    Full Text Available Manila clam Ruditapes philippinarum is one of the most important economic species in shellfishery in China due to its wide geographic distribution and high tolerance to environmental changes (e.g., salinity, temperature. In addition, Manila clam is a good biomonitor/bioindicator in “Mussel Watch Programs” and marine environmental toxicology. However, there are several pedigrees of R. philippinarum distributed in the marine environment in China. No attention has been paid to the biological differences between various pedigrees of Manila clams, which may introduce undesirable biological variation in toxicology studies. In this study, we applied NMR-based metabolomics to detect the biological differences in two main pedigrees (White and Zebra of R. philippinarum and their differential responses to heavy metal exposures (Cadmium and Zinc using adductor muscle as a target tissue to define one sensitive pedigree of R. philippinarum as biomonitor for heavy metals. Our results indicated that there were significant metabolic differences in adductor muscle tissues between White and Zebra clams, including higher levels of alanine, glutamine, hypotaurine, phosphocholine and homarine in White clam muscles and higher levels of branched chain amino acids (valine, leucine and isoleucine, succinate and 4-aminobutyrate in Zebra clam muscles, respectively. Differential metabolic responses to heavy metals between White and Zebra clams were also found. Overall, we concluded that White pedigree of clam could be a preferable bioindicator/biomonitor in marine toxicology studies and for marine heavy metals based on the relatively high sensitivity to heavy metals.

  12. Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue – a GC-TOFMS based metabolomics study

    Directory of Open Access Journals (Sweden)

    Budczies Jan

    2012-07-01

    Full Text Available Abstract Background Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far. Results A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79% were significantly changed between cancer and normal tissues (p80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%. Conclusions For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.

  13. Comparative metabolomics in Glycine max and Glycine soja under salt stress to reveal the phenotypes of their offspring.

    Science.gov (United States)

    Lu, Yonghai; Lam, Honming; Pi, Erxu; Zhan, Qinglei; Tsai, Sauna; Wang, Chunmei; Kwan, Yiuwa; Ngai, Saiming

    2013-09-11

    Metabolomics is developing as an important functional genomics tool for understanding plant systems' response to genetic and environmental changes. Here, we characterized the metabolic changes of cultivated soybean C08 (Glycine max L. Merr) and wild soybean W05 (Glycine soja Sieb.et Zucc.) under salt stress using MS-based metabolomics, in order to reveal the phenotypes of their eight hybrid offspring (9H0086, 9H0124, 9H0391, 9H0736, 9H0380, 9H0400, 9H0434, and 9H0590). Total small molecule extracts of soybean seedling leaves were profiled by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-Fourier transform mass spectrometry (LC-FT/MS). We found that wild soybean contained higher amounts of disaccharides, sugar alcohols, and acetylated amino acids than cultivated soybean, but with lower amounts of monosaccharides, carboxylic acids, and unsaturated fatty acids. Further investigations demonstrated that the ability of soybean to tolerate salt was mainly based on synthesis of compatible solutes, induction of reactive oxygen species (ROS) scavengers, cell membrane modifications, and induction of plant hormones. On the basis of metabolic phenotype, the salt-tolerance abilities of 9H0086, 9H0124, 9H0391, 9H0736, 9H0380, 9H0400, 9H0434, and 9H0590 were discriminated. Our results demonstrated that MS-based metabolomics provides a fast and powerful approach to discriminate the salt-tolerance characteristics of soybeans.

  14. Model-based explanation of plant knowledge

    Energy Technology Data Exchange (ETDEWEB)

    Huuskonen, P.J. [VTT Electronics, Oulu (Finland). Embedded Software

    1997-12-31

    This thesis deals with computer explanation of knowledge related to design and operation of industrial plants. The needs for explanation are motivated through case studies and literature reviews. A general framework for analysing plant explanations is presented. Prototypes demonstrate key mechanisms for implementing parts of the framework. Power plants, steel mills, paper factories, and high energy physics control systems are studied to set requirements for explanation. The main problems are seen to be either lack or abundance of information. Design knowledge in particular is found missing at plants. Support systems and automation should be enhanced with ways to explain plant knowledge to the plant staff. A framework is formulated for analysing explanations of plant knowledge. It consists of three parts: 1. a typology of explanation, organised by the class of knowledge (factual, functional, or strategic) and by the target of explanation (processes, automation, or support systems), 2. an identification of explanation tasks generic for the plant domain, and 3. an identification of essential model types for explanation (structural, behavioural, functional, and teleological). The tasks use the models to create the explanations of the given classes. Key mechanisms are discussed to implement the generic explanation tasks. Knowledge representations based on objects and their relations form a vocabulary to model and present plant knowledge. A particular class of models, means-end models, are used to explain plant knowledge. Explanations are generated through searches in the models. Hypertext is adopted to communicate explanations over dialogue based on context. The results are demonstrated in prototypes. The VICE prototype explains the reasoning of an expert system for diagnosis of rotating machines at power plants. The Justifier prototype explains design knowledge obtained from an object-oriented plant design tool. Enhanced access mechanisms into on-line documentation are

  15. FPGA-Based Plant Protection System

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Hee; Ha, Jae Hong; Kim, Hang Bae [KEPCO E and C, Daejeon (Korea, Republic of)

    2011-08-15

    This paper relates to a plant protection system which detects non-permissible conditions and determines initiation of protective actions for nuclear power plants (NPPs). Conventional plant protection systems were designed based on analog technologies. It is well known that existing protection systems for NPPs contain many components which are becoming obsolete at an increasing rate. Nowadays maintenance and repair for analog-based plant protection systems may be difficult as analog parts become obsolete or difficult to obtain. Accordingly, as an alternative to the analog technology, the digitalisation of the plant protection system was required. Recently digital plant protection systems which include programmable logic controllers (PLCs) and/or computers have been introduced. However PLC or computer-based plant protection systems use an operating system and application software, and so they may result in a common mode failure when a problem occurs in the operating system or application software. Field Programmable Gate Arrays (FPGAs) are highlighted as an alternative to conventional protection or control systems. The paper presents the design of a four-channel plant protection system whose protection functions are implemented in FPGAs without any central processing unit or operating system.

  16. Pea fiber and wheat bran fiber show distinct metabolic profiles in rats as investigated by a 1H NMR-based metabolomic approach.

    Science.gov (United States)

    Liu, Guangmang; Xiao, Liang; Fang, Tingting; Cai, Yimin; Jia, Gang; Zhao, Hua; Wang, Jing; Chen, Xiaoling; Wu, Caimei

    2014-01-01

    This study aimed to examine the effect of pea fiber (PF) and wheat bran fiber (WF) supplementation in rat metabolism. Rats were assigned randomly to one of three dietary groups and were given a basal diet containing 15% PF, 15% WF, or no supplemental fiber. Urine and plasma samples were analyzed by NMR-based metabolomics. PF significantly increased the plasma levels of 3-hydroxybutyrate, and myo-inositol as well as the urine levels of alanine, hydroxyphenylacetate, phenylacetyglycine, and α-ketoglutarate. However, PF significantly decreased the plasma levels of isoleucine, leucine, lactate, and pyruvate as well as the urine levels of allantoin, bile acids, and trigonelline. WF significantly increased the plasma levels of acetone, isobutyrate, lactate, myo-inositol, and lipids as well as the urine levels of alanine, lactate, dimethylglycine, N-methylniconamide, and α-ketoglutarate. However, WF significantly decreased the plasma levels of amino acids, and glucose as well as the urine levels of acetate, allantoin, citrate, creatine, hippurate, hydroxyphenylacetate, and trigonelline. Results suggest that PF and WF exposure can promote antioxidant activity and can exhibit common systemic metabolic changes, including lipid metabolism, energy metabolism, glycogenolysis and glycolysis metabolism, protein biosynthesis, and gut microbiota metabolism. PF can also decrease bile acid metabolism. These findings indicate that different fiber diet may cause differences in the biofluid profile in rats.

  17. Pea fiber and wheat bran fiber show distinct metabolic profiles in rats as investigated by a 1H NMR-based metabolomic approach.

    Directory of Open Access Journals (Sweden)

    Guangmang Liu

    Full Text Available This study aimed to examine the effect of pea fiber (PF and wheat bran fiber (WF supplementation in rat metabolism. Rats were assigned randomly to one of three dietary groups and were given a basal diet containing 15% PF, 15% WF, or no supplemental fiber. Urine and plasma samples were analyzed by NMR-based metabolomics. PF significantly increased the plasma levels of 3-hydroxybutyrate, and myo-inositol as well as the urine levels of alanine, hydroxyphenylacetate, phenylacetyglycine, and α-ketoglutarate. However, PF significantly decreased the plasma levels of isoleucine, leucine, lactate, and pyruvate as well as the urine levels of allantoin, bile acids, and trigonelline. WF significantly increased the plasma levels of acetone, isobutyrate, lactate, myo-inositol, and lipids as well as the urine levels of alanine, lactate, dimethylglycine, N-methylniconamide, and α-ketoglutarate. However, WF significantly decreased the plasma levels of amino acids, and glucose as well as the urine levels of acetate, allantoin, citrate, creatine, hippurate, hydroxyphenylacetate, and trigonelline. Results suggest that PF and WF exposure can promote antioxidant activity and can exhibit common systemic metabolic changes, including lipid metabolism, energy metabolism, glycogenolysis and glycolysis metabolism, protein biosynthesis, and gut microbiota metabolism. PF can also decrease bile acid metabolism. These findings indicate that different fiber diet may cause differences in the biofluid profile in rats.

  18. Automated resolution of chromatographic signals by independent component analysis-orthogonal signal deconvolution in comprehensive gas chromatography/mass spectrometry-based metabolomics.

    Science.gov (United States)

    Domingo-Almenara, Xavier; Perera, Alexandre; Ramírez, Noelia; Brezmes, Jesus

    2016-07-01

    Comprehensive gas chromatography-mass spectrometry (GC×GC-MS) provides a different perspective in metabolomics profiling of samples. However, algorithms for GC×GC-MS data processing are needed in order to automatically process the data and extract the purest information about the compounds appearing in complex biological samples. This study shows the capability of independent component analysis-orthogonal signal deconvolution (ICA-OSD), an algorithm based on blind source separation and distributed in an R package called osd, to extract the spectra of the compounds appearing in GC×GC-MS chromatograms in an automated manner. We studied the performance of ICA-OSD by the quantification of 38 metabolites through a set of 20 Jurkat cell samples analyzed by GC×GC-MS. The quantification by ICA-OSD was compared with a supervised quantification by selective ions, and most of the R(2) coefficients of determination were in good agreement (R(2)>0.90) while up to 24 cases exhibited an excellent linear relation (R(2)>0.95). We concluded that ICA-OSD can be used to resolve co-eluted compounds in GC×GC-MS.

  19. Integrating candidate metabolites and biochemical factors to elucidate the action mechanism of Xue-sai-tong injection based on (1)H NMR metabolomics.

    Science.gov (United States)

    Jiang, Miaomiao; Zhao, Xiaoping; Wang, Linli; Xu, Lei; Zhang, Yan; Li, Zheng

    2016-07-15

    A strategy of integrating candidate metabolites with crucial biochemical factors was proposed in this study to discover relevant biological functions for interpreting the action mechanism of Traditional Chinese Medicines (TCM). This approach was applied to Xue-Sai-Tong injection (XST) to reveal the action mechanism based on the metabolic response in an ischemia/reperfusion (I/R) rat model by analyzing NMR profile. Partial least squares discriminate analysis (PLS-DA) was used to compare metabolic profiles of serum samples and revealed nine metabolites altered by I/R injury could be restored to normal status (sham-operated group) under the therapy of XST. The pathway enrichment analysis suggested the metabolic changes were mainly involved in pyruvate metabolism, glycolysis, and citrate cycle. The functional roles of the candidate metabolites were further identified by Pearson correlation analysis with the key biochemical factors in serum. The results indicated pyruvate, succinate, acetate and lysine showed significant associations with the oxidative stress factors. Elevated level of pyruvate was found as an essential metabolic response for the major effect of XST against I/R injury by enhancing glycolysis and overcoming the induced reactive oxygen species (ROS). This metabolomics approach provides a better understanding of the mechanisms of TCM and helps to develop a holistic view of TCM efficacy. PMID:26862062

  20. Investigation on the antidepressant effect of sea buckthorn seed oil through the GC-MS-based metabolomics approach coupled with multivariate analysis.

    Science.gov (United States)

    Tian, Jun-sheng; Liu, Cai-chun; Xiang, Huan; Zheng, Xiao-fen; Peng, Guo-jiang; Zhang, Xiang; Du, Guan-hua; Qin, Xue-mei

    2015-11-01

    Depression is one of the prevalent and serious mental disorders and the number of depressed patients has been on the rise globally during the recent decades. Sea buckthorn seed oil from traditional Chinese medicine (TCM) is edible and has been widely used for treatment of different diseases for a long time. However, there are few published reports on the antidepressant effect of sea buckthorn seed oil. With the objective of finding potential biomarkers of the therapeutic response of sea buckthorn seed oil in chronic unpredictable mild stress (CUMS) rats, urine metabolomics based on gas chromatography-mass spectrometry (GC-MS) coupled with multivariate analysis was applied. In this study, we discovered a higher level of pimelic acid as well as palmitic acid and a lower level of suberic acid, citrate, phthalic acid, cinnamic acid and Sumiki's acid in urine of rats exposed to CUMS procedures after sea buckthorn seed oil was administered. These changes of metabolites are involved in energy metabolism, fatty acid metabolism and other metabolic pathways as well as in the synthesis of neurotransmitters and it is helpful to facilitate the efficacy evaluation and mechanism elucidating the effect of sea buckthorn seed oil for depression management.

  1. Profiling of Altered Metabolomic States in Nicotiana tabacum Cells Induced by Priming Agents

    Science.gov (United States)

    Mhlongo, Msizi I.; Steenkamp, Paul A.; Piater, Lizelle A.; Madala, Ntakadzeni E.; Dubery, Ian A.

    2016-01-01

    Metabolomics has developed into a valuable tool for advancing our understanding of plant metabolism. Plant innate immune defenses can be activated and enhanced so that, subsequent to being pre-sensitized, plants are able to launch a stronger and faster defense response upon exposure to pathogenic microorganisms, a phenomenon known as priming. Here, three contrasting chemical activators, namely acibenzolar-S-methyl, azelaic acid and riboflavin, were used to induce a primed state in Nicotiana tabacum cells. Identified biomarkers were then compared to responses induced by three phytohormones—abscisic acid, methyljasmonate, and salicylic acid. Altered metabolomes were studied using a metabolite fingerprinting approach based on liquid chromatography and mass spectrometry. Multivariate data models indicated that these inducers cause time-dependent metabolic perturbations in the cultured cells and revealed biomarkers of which the levels are affected by these agents. A total of 34 metabolites were annotated from the mass spectral data and online databases. Venn diagrams were used to identify common biomarkers as well as those unique to a specific agent. Results implicate 20 cinnamic acid derivatives conjugated to (i) quinic acid (chlorogenic acids), (ii) tyramine, (iii) polyamines, or (iv) glucose as discriminatory biomarkers of priming in tobacco cells. Functional roles for most of these metabolites in plant defense responses could thus be proposed. Metabolites induced by the activators belong to the early phenylpropanoid pathway, which indicates that different stimuli can activate similar pathways but with different metabolite fingerprints. Possible linkages to phytohormone-dependent pathways at a metabolomic level were indicated in the case of cells treated with salicylic acid and methyljasmonate. The results contribute to a better understanding of the priming phenomenon and advance our knowledge of cinnamic acid derivatives as versatile defense metabolites. PMID

  2. New progress of metabolomics based on research of drug%基于药物研究的代谢组学技术新进展

    Institute of Scientific and Technical Information of China (English)

    闾红燕; 王坚; 黄绳武

    2013-01-01

    近年来代谢组学成为药物研究领域中一个重要且有价值的工具,完善代谢组学技术和方法已成为目前研究的热点,文章针对近年来其技术和方法上的整合创新及其在药物研究中的应用作出评述,提出其今后发展方向.%Metabolomics has become an important and a valuable tool in drug research area in recent years. How to complete the techniques and methods of metabolomics has become the focus of the present study. This paper will summarize the innovative of metabolomics techniques and methods and the application of pharmaceutical research, put forward the development direction in the future.

  3. A Rough Guide to Metabolite Identification Using High Resolution Liquid Chromatography Mass Spectrometry in Metabolomic Profiling in Metazoans

    Directory of Open Access Journals (Sweden)

    David G Watson

    2013-01-01

    Full Text Available Compound identification in mass spectrometry based metabolomics can be a problem but sometimes the problem seems to be presented in an over complicated way. The current review focuses on metazoans where the range of metabolites is more restricted than for example in plants. The focus is on liquid chromatography with high resolution mass spectrometry where it is proposed that most of the problems in compound identification relate to structural isomers rather than to isobaric compounds. Thus many of the problems faced relate to separation of isomers, which is usually required even if fragmentation is used to support structural identification. Many papers report the use of MS/MS or MS2 as an adjunct to the identification of known metabolites but there a few examples in metabolomics studies of metazoans of complete structure elucidation of novel metabolites or metabolites where no authentic standards are available for comparison.

  4. Taking Metabolomics to the Field: A Pilot Study in a Great Lakes Area of Concern (AOC)

    Science.gov (United States)

    Measurement of changes in endogenous metabolites via 1H-NMR-based metabolomics has shown great potential for assessing organisms exposed to environmental pollutants, and thus could aid the efforts of risk assessors. However, to date, the application of metabolomics to ecologi...

  5. Metabolomics in diabetic complications.

    Science.gov (United States)

    Filla, Laura A; Edwards, James L

    2016-04-01

    With a global prevalence of 9%, diabetes is the direct cause of millions of deaths each year and is quickly becoming a health crisis. Major long-term complications of diabetes arise from persistent oxidative stress and dysfunction in multiple metabolic pathways. The most serious complications involve vascular damage and include cardiovascular disease as well as microvascular disorders such as nephropathy, neuropathy, and retinopathy. Current clinical analyses like glycated hemoglobin and plasma glucose measurements hold some value as prognostic indicators of the severity of complications, but investigations into the underlying pathophysiology are still lacking. Advancements in biotechnology hold the key to uncovering new pathways and establishing therapeutic targets. Metabolomics, the study of small endogenous molecules, is a powerful toolset for studying pathophysiological processes and has been used to elucidate metabolic signatures of diabetes in various biological systems. Current challenges in the field involve correlating these biomarkers to specific complications to provide a better prediction of future risk and disease progression. This review will highlight the progress that has been made in the field of metabolomics including technological advancements, the identification of potential biomarkers, and metabolic pathways relevant to macro- and microvascular diabetic complications.

  6. Lunar base agriculture: Soils for plant growth

    Science.gov (United States)

    Ming, Douglas W. (Editor); Henninger, Donald L. (Editor)

    1989-01-01

    This work provides information on research and experimentation concerning various aspects of food production in space and particularly on the moon. Options for human settlement of the moon and Mars and strategies for a lunar base are discussed. The lunar environment, including the mineralogical and chemical properties of lunar regolith are investigated and chemical and physical considerations for a lunar-derived soil are considered. It is noted that biological considerations for such a soil include controlled-environment crop production, both hydroponic and lunar regolith-based; microorganisms and the growth of higher plants in lunar-derived soils; and the role of microbes to condition lunar regolith for plant cultivation. Current research in the controlled ecological life support system (CELSS) project is presented in detail and future research areas, such as the growth of higher research plants in CELSS are considered. Optimum plant and microbiological considerations for lunar derived soils are examined.

  7. Model-Based Power Plant Master Control

    Energy Technology Data Exchange (ETDEWEB)

    Boman, Katarina; Thomas, Jean; Funkquist, Jonas

    2010-08-15

    The main goal of the project has been to evaluate the potential of a coordinated master control for a solid fuel power plant in terms of tracking capability, stability and robustness. The control strategy has been model-based predictive control (MPC) and the plant used in the case study has been the Vattenfall power plant Idbaecken in Nykoeping. A dynamic plant model based on nonlinear physical models was used to imitate the true plant in MATLAB/SIMULINK simulations. The basis for this model was already developed in previous Vattenfall internal projects, along with a simulation model of the existing control implementation with traditional PID controllers. The existing PID control is used as a reference performance, and it has been thoroughly studied and tuned in these previous Vattenfall internal projects. A turbine model was developed with characteristics based on the results of steady-state simulations of the plant using the software EBSILON. Using the derived model as a representative for the actual process, an MPC control strategy was developed using linearization and gain-scheduling. The control signal constraints (rate of change) and constraints on outputs were implemented to comply with plant constraints. After tuning the MPC control parameters, a number of simulation scenarios were performed to compare the MPC strategy with the existing PID control structure. The simulation scenarios also included cases highlighting the robustness properties of the MPC strategy. From the study, the main conclusions are: - The proposed Master MPC controller shows excellent set-point tracking performance even though the plant has strong interactions and non-linearity, and the controls and their rate of change are bounded. - The proposed Master MPC controller is robust, stable in the presence of disturbances and parameter variations. Even though the current study only considered a very small number of the possible disturbances and modelling errors, the considered cases are

  8. Urine-based Metabolomics with Fish: Use of Repeat Sampling (of an individual) to Non-lethally Assess Temporal Effects of Contaminants

    Science.gov (United States)

    Environmental metabolomics is a rapidly developing field for assessing the global metabolite profiles of tissues and/or biofluids from ecologically relevant organisms to identify biomarkers of exposure to various stressors, elucidate a chemical’s mode(s)-of-action, and decipher t...

  9. 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,...

  10. Optimizing the plant-based diet.

    Science.gov (United States)

    Mann, J I

    2000-09-01

    Any attempt to optimize a plant-based diet necessitates an identification of the features of the diet which confer benefit as well as any which may be associated with detrimental effects. The former task is more difficult than might be assumed as there is no doubt that some of the apparent health benefits observed amongst vegetarians are a consequence of environmental determinants of health which characterize groups of people who choose vegetarian diets, rather than dietary practices. This review will consider the major health benefits of plant-based diets, the specific foods or nutrients which confer the benefits as far as can be ascertained from present knowledge, potential nutrient deficiencies associated with a plant-based diet and nutritional strategies that can be employed to prevent any such deficiencies. PMID:24398280

  11. NMR-based metabolomics to determine acute inhalation effects of nano- and fine-sized ZnO particles in the rat lung.

    Science.gov (United States)

    Lee, Sheng-Han; Wang, Ting-Yi; Hong, Jia-Huei; Cheng, Tsun-Jen; Lin, Ching-Yu

    2016-09-01

    Zinc oxide (ZnO) particles induce acute occupational inhalation illness in humans and rats. However, the possible molecular mechanisms of ZnO particles on the respiratory system remain unclear. In this study, metabolic responses of the respiratory system of rats inhaled ZnO particles were investigated by a nuclear magnetic resonance (NMR)-based metabolomic approach. Male Sprague-Dawley rats were treated with a series of doses of nano-sized (35 nm) or fine-sized (250 nm) ZnO particles. The corresponding control groups inhaled filtered air. After 24 h, bronchoalveolar lavage fluid (BALF) and lung tissues were collected, extracted and prepared for (1)H and J-resolved NMR analysis, followed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). PCA and PLSDA models from analysis of BALF and hydrophilic lung NMR spectra demonstrated that dose response trends were restricted to the 250 nm ZnO particle exposure group and were not observed in the 35 nm ZnO particle exposure group. Increased isoleucine and valine, as well as decreased acetate, trimethylamine n-oxide, taurine, glycine, formate, ascorbate and glycerophosphocholine, were recorded in the BALF of rats treated with moderate and high dose 250 nm ZnO exposures. Decreases in taurine and glucose, as well as an increase of phosphorylcholine-containing lipids and fatty acyl chains, were detected in the lung tissues from 250 nm ZnO-treated rats. These metabolic changes may be associated with cell anti-oxidation, energy metabolism, DNA damage and membrane stability. We also concluded that a metabolic approach provides more complete measurements and suggests potential molecular mechanisms of adverse effects. PMID:27245357

  12. Metabolomics Analysis of Health Functions of Physalis Pubescens L. using by Ultra-performance Liquid Chromatography/Electrospray Ionization Quadruple Time-of-Flight Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    Hang Chu; Hui Sun; Guang-Li Yan; Ai-Hua Zhang; Chang Liu; Hui Dong; Xiang-Cai Meng; Xi-Jun Wang

    2015-01-01

    Herbal medicines may benefit from metabolomics studies, and applying metabolomics may provide answers about which herbal interventions may be effective for individuals, which metabolic processes are triggered, and the subsequent chemical pathways of activity. Physalis pubescens L (PPL) is an herbal fruit for one year living plant and has been developed into healthy function’s food. However, the mechanisms of health functions are still unclear. To comprehensively and holistically assess its anti-fatigue and antioxidant effects, a novel integrative metabolomics approach was applied. In this study, we present metabolomics analysis applying ultra performance liquid chromatography coupled to quadrupole with time-of-flight mass spectrometry (UPLC-Q/TOF-MS) to determine metabolite alterations after oral administration PPL to rats. Fifteen metabolites in urine were identified as potential biomarkers. Pattern analysis of the UPLC-Q/TOF-MS data disclosed that PPL could relieve fatigue rats by ameliorating the disturbance in amino acids metabolism and energy metabolism, alleviating the oxidative stress from reactive oxygen species and the inflammatory damage, and recovering the destructed regulation. Based on these results, we demonstrated that PPL is a promising source of natural anti-fatigue and antioxidants material for use in functional foods and medicines.

  13. Metabolomics Analysis of Health Functions of Physalis Pubescens L. using by Ultra-performance Liquid Chromatography/Electrospray Ionization Quadruple Time-of-Flight Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Hang Chu

    2015-07-01

    Full Text Available Herbal medicines may benefit from metabolomics studies, and applying metabolomics may provide answers about which herbal interventions may be effective for individuals, which metabolic processes are triggered, and the subsequent chemical pathways of activity. Physalis pubescens L (PPL is an herbal fruit for one year living plant and has been developed into healthy function's food. However, the mechanisms of health functions are still unclear. To comprehensively and holistically assess its anti-fatigue and antioxidant effects, a novel integrative metabolomics approach was applied. In this study, we present metabolomics analysis applying ultra performance liquid chromatography coupled to quadrupole with time-of-flight mass spectrometry (UPLC-Q/TOF-MS to determine metabolite alterations after oral administration PPL to rats. Fifteen metabolites in urine were identified as potential biomarkers. Pattern analysis of the UPLC-Q/TOF-MS data disclosed that PPL could relieve fatigue rats by ameliorating the disturbance in amino acids metabolism and energy metabolism, alleviating the oxidative stress from reactive oxygen species and the inflammatory damage, and recovering the destructed regulation. Based on these results, we demonstrated that PPL is a promising source of natural anti-fatigue and antioxidants material for use in functional foods and medicines.

  14. A 1H NMR-based metabolomics approach to evaluate the geographical authenticity of herbal medicine and its application in building a model effectively assessing the mixing proportion of intentional admixtures: A case study of Panax ginseng: Metabolomics for the authenticity of herbal medicine.

    Science.gov (United States)

    Nguyen, Huy Truong; Lee, Dong-Kyu; Choi, Young-Geun; Min, Jung-Eun; Yoon, Sang Jun; Yu, Yun-Hyun; Lim, Johan; Lee, Jeongmi; Kwon, Sung Won; Park, Jeong Hill

    2016-05-30

    Ginseng, the root of Panax ginseng has long been the subject of adulteration, especially regarding its origins. Here, 60 ginseng samples from Korea and China initially displayed similar genetic makeup when investigated by DNA-based technique with 23 chloroplast intergenic space regions. Hence, (1)H NMR-based metabolomics with orthogonal projections on the latent structure-discrimination analysis (OPLS-DA) were applied and successfully distinguished between samples from two countries using seven primary metabolites as discrimination markers. Furthermore, to recreate adulteration in reality, 21 mixed samples of numerous Korea/China ratios were tested with the newly built OPLS-DA model. The results showed satisfactory separation according to the proportion of mixing. Finally, a procedure for assessing mixing proportion of intentionally blended samples that achieved good predictability (adjusted R(2)=0.8343) was constructed, thus verifying its promising application to quality control of herbal foods by pointing out the possible mixing ratio of falsified samples. PMID:26942336

  15. A 1H NMR-based metabolomics approach to evaluate the geographical authenticity of herbal medicine and its application in building a model effectively assessing the mixing proportion of intentional admixtures: A case study of Panax ginseng: Metabolomics for the authenticity of herbal medicine.

    Science.gov (United States)

    Nguyen, Huy Truong; Lee, Dong-Kyu; Choi, Young-Geun; Min, Jung-Eun; Yoon, Sang Jun; Yu, Yun-Hyun; Lim, Johan; Lee, Jeongmi; Kwon, Sung Won; Park, Jeong Hill

    2016-05-30

    Ginseng, the root of Panax ginseng has long been the subject of adulteration, especially regarding its origins. Here, 60 ginseng samples from Korea and China initially displayed similar genetic makeup when investigated by DNA-based technique with 23 chloroplast intergenic space regions. Hence, (1)H NMR-based metabolomics with orthogonal projections on the latent structure-discrimination analysis (OPLS-DA) were applied and successfully distinguished between samples from two countries using seven primary metabolites as discrimination markers. Furthermore, to recreate adulteration in reality, 21 mixed samples of numerous Korea/China ratios were tested with the newly built OPLS-DA model. The results showed satisfactory separation according to the proportion of mixing. Finally, a procedure for assessing mixing proportion of intentionally blended samples that achieved good predictability (adjusted R(2)=0.8343) was constructed, thus verifying its promising application to quality control of herbal foods by pointing out the possible mixing ratio of falsified samples.

  16. Hazard identification based on plant functional modelling

    International Nuclear Information System (INIS)

    A major objective of the present work is to provide means for representing a process plant as a socio-technical system, so as to allow hazard identification at a high level. The method includes technical, human and organisational aspects and is intended to be used for plant level hazard identification so as to identify critical areas and the need for further analysis using existing methods. The first part of the method is the preparation of a plant functional model where a set of plant functions link together hardware, software, operations, work organisation and other safety related aspects of the plant. The basic principle of the functional modelling is that any aspect of the plant can be represented by an object (in the sense that this term is used in computer science) based upon an Intent (or goal); associated with each Intent are Methods, by which the Intent is realized, and Constraints, which limit the Intent. The Methods and Constraints can themselves be treated as objects and decomposed into lower-level Intents (hence the procedure is known as functional decomposition) so giving rise to a hierarchical, object-oriented structure. The plant level hazard identification is carried out on the plant functional model using the Concept Hazard Analysis method. In this, the user will be supported by checklists and keywords and the analysis is structured by pre-defined worksheets. The preparation of the plant functional model and the performance of the hazard identification can be carried out manually or with computer support. (au) (4 tabs., 10 ills., 7 refs.)

  17. Plant-Based Vaccines: Production and Challenges

    Directory of Open Access Journals (Sweden)

    Erna Laere

    2016-01-01

    Full Text Available Plant-based vaccine technologies involve the integration of the desired genes encoding the antigen protein for specific disease into the genome of plant tissues by various methods. Agrobacterium-mediated gene transfer and transformation via genetically modified plant virus are the common methods that have been used to produce effective vaccines. Nevertheless, with the advancement of science and technology, new approaches have been developed to increase the efficiency of former methods such as biolistic, electroporation, agroinfiltration, sonication, and polyethylene glycol treatment. Even though plant-based vaccines provide many benefits to the vaccine industry, there are still challenges that limit the rate of successful production of these third-generation vaccines. Even with all the limitations, continuous efforts are still ongoing in order to produce efficient vaccine for many human and animals related diseases owing to its great potentials. This paper reviews the existing conventional methods as well as the development efforts by researchers in order to improve the production of plant-based vaccines. Several challenges encountered during and after the production process were also discussed.

  18. Metabolomics technologies applied to the identification of compounds in plants : a liquid chromatography-mass spectrometry - nuclear magnetic resonance perspective over the tomato fruit

    NARCIS (Netherlands)

    Moco, S.I.A.

    2007-01-01

    A new era of plant biochemistry at the systems level is emerging in which the detailed description of biochemical phenomena, at the cellular level, is important for a better understanding of physiological, developmental, and biomolecular processes in plants. This emerging field is oriented towards t

  19. Plant viral vectors based on tobamoviruses.

    Science.gov (United States)

    Yusibov, V; Shivprasad, S; Turpen, T H; Dawson, W; Koprowski, H

    1999-01-01

    The potential of plant virus-based transient expression vectors is substantial. One objective is the production of large quantities of foreign peptides or proteins. At least one commercial group (Biosource Technologies) is producing large quantities of product in the field, has built factories to process truck-loads of material and soon expects to market virus-generated products. In the laboratory, large amounts of protein have been produced for structural or biochemical analyses. An important aspect of producing large amounts of a protein or peptide is to make the product easily purifiable. This has been done by attaching peptides or proteins to easily purified units such as virion particles or by exporting proteins to the apoplast so that purification begins with a highly enriched product. For plant molecular biology, virus-based vectors have been useful in identifying previously unknown genes by overexpression or silencing or by expression in different genotypes. Also, foreign peptides fused to virions are being used as immunogens for development of antisera for experimental use or as injected or edible vaccines for medical use. As with liposomes and microcapsules, plant cells and plant viruses are also expected to provide natural protection for the passage of antigen through the gastrointestinal tract. Perhaps the greatest advantage of plant virus-based transient expression vectors is their host, plants. For the production of large amounts of commercial products, plants are one of the most economical and productive sources of biomass. They also present the advantages of lack of contamination with animal pathogens, relative ease of genetic manipulation and the presence eukaryotic protein modification machinery.

  20. Plant viral vectors based on tobamoviruses.

    Science.gov (United States)

    Yusibov, V; Shivprasad, S; Turpen, T H; Dawson, W; Koprowski, H

    1999-01-01

    The potential of plant virus-based transient expression vectors is substantial. One objective is the production of large quantities of foreign peptides or proteins. At least one commercial group (Biosource Technologies) is producing large quantities of product in the field, has built factories to process truck-loads of material and soon expects to market virus-generated products. In the laboratory, large amounts of protein have been produced for structural or biochemical analyses. An important aspect of producing large amounts of a protein or peptide is to make the product easily purifiable. This has been done by attaching peptides or proteins to easily purified units such as virion particles or by exporting proteins to the apoplast so that purification begins with a highly enriched product. For plant molecular biology, virus-based vectors have been useful in identifying previously unknown genes by overexpression or silencing or by expression in different genotypes. Also, foreign peptides fused to virions are being used as immunogens for development of antisera for experimental use or as injected or edible vaccines for medical use. As with liposomes and microcapsules, plant cells and plant viruses are also expected to provide natural protection for the passage of antigen through the gastrointestinal tract. Perhaps the greatest advantage of plant virus-based transient expression vectors is their host, plants. For the production of large amounts of commercial products, plants are one of the most economical and productive sources of biomass. They also present the advantages of lack of contamination with animal pathogens, relative ease of genetic manipulation and the presence eukaryotic protein modification machinery. PMID:10394716

  1. 基于核磁共振波谱的盐芥盐胁迫代谢组学分析%NMR spectroscopy based metabolomic analysis of Thellungiella salsuginea under salt stress

    Institute of Scientific and Technical Information of China (English)

    王新宇; 王丽华; 于萍; 李楠; 吴惠丰; 阎秀峰

    2012-01-01

    Soil salinity is a critical environmental problem that disrupts plant metabolic homeostasis and requires adjustment of metabolic pathways in plant cells, a process that is usually referred to as acclimation. Metabolomics technologies have made significant contributions to the study of plant stress biology through identification of different compounds, such as signaling molecules and metabolic by-products in response to stress conditions, as well as small molecules involved in the plant acclimation processes. Thellungiella salsuginea is a close relative of Arabidopsis thaliana. It has been proposed as an ideal model for studying molecular mechanisms of salinity tolerance in plants because of its ' extremophile' characteristics manifested by extreme tolerance to high salt conditions. To obtain a better understanding of the molecular mechanisms underlying the response of T. salsuginea to salt stress, an Nuclear Magnetic Resonance ( NMR) -based metabolic profiling approach was used to profile metabolite changes in T. salsuginea after treatment with 150 mmol/L or 300 mmol/L NaCl for 24 h. In general, metabolomic studies should be designed to detect as many metabolites as possible in an organism, and a solvent that can extract a diverse group of metabolites should be employed. In our experiments, metabolites were extracted from the leaf tissues using a solvent system of methanol/water (1/1 ) , known to extract many different metabolites. H-NMR spectroscopy of samples from control, 150 mmol/L and 300 mmol/L NaCl treatment was performed separately. Spectral data were analyzed and interpreted using multivariate statistical analyses. Overall, the original NMR spectra were dominated by one of the organic acids, malate (8 2. 38 and 2. 68) , which is a T. salsuginea metabolite to maintain the osmotic balance in the cells and was approx. 10-100 times higher than other metabolites found in the H-NMR spectra. Principal components analysis ( PCA) was used in this work for the

  2. Topsoil depth substantially influences the responses to drought of the foliar metabolomes of Mediterranean forests

    Energy Technology Data Exchange (ETDEWEB)

    Rivas-Ubach, Albert; Barbeta, Adria; Sardans, J.; Guenther, Alex B.; Ogaya, R.; Oravec, Michal; Urban, Otmar; Penuelas, Josep

    2016-06-07

    Soils provide physical support, water, and nutrients to terrestrial plants. Upper soil layers are crucial for forest dynamics, especially under drought conditions, because many biological processes occur there and provide support, water and nutrients to terrestrial plants. We postulated that tree size and overall plant function manifested in the metabolome composition, the total set of metabolites, were dependent on the depth of upper soil layers and on water availability. We sampled leaves for stoichiometric and metabolomic analyses once per season from differently sized Quercus ilex trees under natural and experimental drought conditions as projected for the coming decades. Different sized trees had different metabolomes and plots with shallower soils had smaller trees. Soil moisture of the upper soil did not explain the tree size and smaller trees did not show higher concentrations of biomarker metabolites related to drought stress. However, the impact of drought treatment on metabolomes was higher in smaller trees in shallower soils. Our results suggested that tree size was more dependent on the depth of the upper soil layers, which indirectly affect the metabolomes of the trees, than on the moisture content of the upper soil layers. Metabolomic profiling of Q. ilex supported the premise that water availability in the upper soil layers was not necessarily correlated with tree size. The higher impact of drought on trees growing in shallower soils nevertheless indicates a higher vulnerability of small trees to the future increase in frequency, intensity, and duration of drought projected for the Mediterranean Basin and other areas. Metabolomics has proven to be an excellent tool detecting significant metabolic changes among differently sized individuals of the same species and it improves our understanding of the connection between plant metabolomes and environmental variables such as soil depth and moisture content.

  3. MetaboLights: towards a new COSMOS of metabolomics data management.

    Science.gov (United States)

    Steinbeck, Christoph; Conesa, Pablo; Haug, Kenneth; Mahendraker, Tejasvi; Williams, Mark; Maguire, Eamonn; Rocca-Serra, Philippe; Sansone, Susanna-Assunta; Salek, Reza M; Griffin, Julian L

    2012-10-01

    Exciting funding initiatives are emerging in Europe and the US for metabolomics data production, storage, dissemination and analysis. This is based on a rich ecosystem of resources around the world, which has been build during the past ten years, including but not limited to resources such as MassBank in Japan and the Human Metabolome Database in Canada. Now, the European Bioinformatics Institute has launched MetaboLights, a database for metabolomics experiments and the associated metadata (http://www.ebi.ac.uk/metabolights). It is the first comprehensive, cross-species, cross-platform metabolomics database maintained by one of the major open access data providers in molecular biology. In October, the European COSMOS consortium will start its work on Metabolomics data standardization, publication and dissemination workflows. The NIH in the US is establishing 6-8 metabolomics services cores as well as a national metabolomics repository. This communication reports about MetaboLights as a new resource for Metabolomics research, summarises the related developments and outlines how they may consolidate the knowledge management in this third large omics field next to proteomics and genomics.

  4. A Market-Based Virtual Power Plant

    DEFF Research Database (Denmark)

    You, Shi; Træholt, Chresten; Poulsen, Bjarne

    2009-01-01

    The fast growing penetration of Distributed Energy Resources (DER) and the continuing trend towards a more liberalized electricity market requires more efficient energy management strategies to handle both emerging technical and economic issues. In this paper, a market-based Virtual Power Plant...

  5. 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.

  6. 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. PMID:27074779

  7. NMR-Based Metabolomic Study on Isatis tinctoria: Comparison of Different Accessions, Harvesting Dates, and the Effect of Repeated Harvesting.

    Science.gov (United States)

    Guldbrandsen, Niels; Kostidis, Sarantos; Schäfer, Hartmut; De Mieri, Maria; Spraul, Manfred; Skaltsounis, Alexios-Leandros; Mikros, Emmanuel; Hamburger, Matthias

    2015-05-22

    Isatis tinctoria is an ancient dye and medicinal plant with potent anti-inflammatory and antiallergic properties. Metabolic differences were investigated by NMR spectroscopy of accessions from different origins that were grown under identical conditions on experimental plots. For these accessions, metabolite profiles at different harvesting dates were analyzed, and single and repeatedly harvested plants were compared. Leaf samples were shock-frozen in liquid N2 immediately after being harvested, freeze-dried, and cryomilled prior to extraction. Extracts were prepared by pressurized liquid extraction with ethyl acetate and 70% aqueous methanol. NMR spectra were analyzed using a combination of different methods of multivariate data analysis such as principal component analysis (PCA), canonical analysis (CA), and k-nearest neighbor concept (k-NN). Accessions and harvesting dates were well separated in the PCA/CA/k-NN analysis in both extracts. Pairwise statistical total correlation spectroscopy (STOCSY) revealed unsaturated fatty acids, porphyrins, carbohydrates, indole derivatives, isoprenoids, phenylpropanoids, and minor aromatic compounds as the cause of these differences. In addition, the metabolite profile was affected by the repeated harvest regime, causing a decrease of 1,5-anhydroglucitol, sucrose, unsaturated fatty acids, porphyrins, isoprenoids, and a flavonoid. PMID:25946005

  8. Non-target effects of GM potato : an eco-metabolomics approach

    NARCIS (Netherlands)

    Plischke, Andreas

    2013-01-01

    In this thesis, patterns of variation in plant metabolomes and insect communities were described in GM and non-GM potato plants in both laboratory and field experiments. Differences between plant genotypes in insect abundances were small when compared to year-to-year differences, location effects an

  9. Transcriptome and metabolome analysis of plant sulphate starvation and resupply provides novel information on transcriptional regulation of metabolism associated with sulphur, nitrogen and phosphorus nutritional responses in Arabidopsis.

    OpenAIRE

    Monika eBielecka; Mutsumi eWatanabe; Wolf Rüdiger Scheible; Rosa eMorcuende; Malcolm John Hawkesford; Holger eHesse; Rainer eHoefgen

    2015-01-01

    Sulphur is an essential macronutrient for plant growth and development. Reaching a thorough understanding of the molecular basis for changes in plant metabolism depending on the sulphur-nutritional status at the systems level will advance our basic knowledge and help target future crop improvement. Although the transcriptional responses induced by sulphate starvation have been studied in the past, knowledge of the regulation of sulphur metabolism is still fragmentary. This work focuses on the...

  10. Transcriptome and metabolome analysis of plant sulfate starvation and resupply provides novel information on transcriptional regulation of metabolism associated with sulfur, nitrogen and phosphorus nutritional responses in Arabidopsis

    OpenAIRE

    Bielecka, Monika; Watanabe, Mutsumi; Morcuende, Rosa; Scheible, Wolf-Rüdiger; Hawkesford, Malcolm J.; Hesse, Holger; Hoefgen, Rainer

    2015-01-01

    Sulfur is an essential macronutrient for plant growth and development. Reaching a thorough understanding of the molecular basis for changes in plant metabolism depending on the sulfur-nutritional status at the systems level will advance our basic knowledge and help target future crop improvement. Although the transcriptional responses induced by sulfate starvation have been studied in the past, knowledge of the regulation of sulfur metabolism is still fragmentary. This work focuses on the dis...

  11. Metabolome analysis - mass spectrometry and microbial primary metabolites

    DEFF Research Database (Denmark)

    Højer-Pedersen, Jesper Juul

    2008-01-01

    . Statistical analysis of the footprinting data revealed discriminating ions, which could be assigned using the in silico metabolome. By this approach metabolic footprinting can advance from a classification method that is used to derive biological information based on guilt-by-association, to a tool...... 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...... for databases that contain metabolite specific information, which will speed up the identification of profiled metabolites. To address the capabilities of electrospray ionization (ESI)-MS in detecting the metabolome of S. cerevisiae, the in silico metabolome of this organism was used as a template to present...

  12. Using NMR-Based Metabolomics to Evaluate Postprandial Urinary Responses Following Consumption of Minimally Processed Wheat Bran or Wheat Aleurone by Men and Women

    OpenAIRE

    Ramandeep Garg; Lorraine Brennan; Price, Ruth K.; Wallace, Julie M.W.; Strain, J. J.; Gibney, Mike J.; Shewry, Peter R.; Ward, Jane L.; Lalit Garg; Welch, Robert W.

    2016-01-01

    Wheat bran, and especially wheat aleurone fraction, are concentrated sources of a wide range of components which may contribute to the health benefits associated with higher consumption of whole-grain foods. This study used NMR metabolomics to evaluate urine samples from baseline at one and two hours postprandially, following the consumption of minimally processed bran, aleurone or control by 14 participants (7 Females; 7 Males) in a randomized crossover trial. The methodology discriminated b...

  13. Linking field-based metabolomics and chemical analyses to identify contaminants of emerging concern in the Great Lakes ecosystem

    Science.gov (United States)

    Although research has focused on remediating ecological impacts of environmental contaminants on the Great Lakes and other aquatic ecosystems, there exists a continuing need for additional biologically-based tools for monitoring success. Profiling of endogenous metabolites (i.e....

  14. Effect of a traditional Chinese medicine prescription Quzhuotongbi decoction on hyperuricemia model rats studied by using serum metabolomics based on gas chromatography-mass spectrometry.

    Science.gov (United States)

    Chen, Jiao; Zhou, Jia; Wei, Shuangshuang; Xie, Zhijun; Wen, Chengping; Xu, Guowang

    2016-07-15

    Morbidity of hyperuricemia has constantly increased in population in decades, and hyperuricemia has proved to be an important risk factor for gout, cardiovascular diseases and others. Many urate-lowering drugs have unfavorable side effects and drug interactions. Quzhuotongbi decoction (QZTBD) is an empirical traditional Chinese medicine prescription for clinical therapy of hyperuricemia without serious adverse effects. In the study, we investigated the effects of QZTBD on urate and other metabolites in the sera of hyperuricemia model rats. Hyperuricemia model was established by orally administering yeast extract paste, and allopurinol served as a positive control drug. Serum metabolomics was performed by using a gas chromatography-mass spectrometry (GC-MS) method. Student's t-test and the principal component analysis (PCA) were employed to find the metabolic perturbations in hyperuricemia model rats. The levels of urate, lactate, pyruvate and ornithine were significantly increased, and xanthine, glyconic acids (ribonate, galactonate), amino acids (aspartate, proline, glutamine, serine, pyroglutamate, glutamate) and glucose were down-regulated greatly in the model rats. It demonstrated that nucleotide metabolism, amino acid metabolism and glycolytic pathway were disturbed by yeast administration. An orthogonal signal correction-partial least-squares discriminant analysis (OSC-PLS DA) was performed to assess the effects of yeast administering and drug treatment. 11 significantly distinctive metabolites among four groups were defined according to the variable importance for project values (VIP>1) and univariate ANOVA (p value<0.05). As compared to the model rats, the serum uric acid levels were lowered markedly under the treatment of allopurinol or QZTBD. Aspartate and glutamine involved in purine metabolism, were raised to normal level as well. The different influences on xanthine, glutamate pyroglutamate and galactonate suggested there were different mechanisms of

  15. Preprocessing of NMR metabolomics data.

    Science.gov (United States)

    Euceda, Leslie R; Giskeødegård, Guro F; Bathen, Tone F

    2015-05-01

    Metabolomics involves the large scale analysis of metabolites and thus, provides information regarding cellular processes in a biological sample. Independently of the analytical technique used, a vast amount of data is always acquired when carrying out metabolomics studies; this results in complex datasets with large amounts of variables. This type of data requires multivariate statistical analysis for its proper biological interpretation. Prior to multivariate analysis, preprocessing of the data must be carried out to remove unwanted variation such as instrumental or experimental artifacts. This review aims to outline the steps in the preprocessing of NMR metabolomics data and describe some of the methods to perform these. Since using different preprocessing methods may produce different results, it is important that an appropriate pipeline exists for the selection of the optimal combination of methods in the preprocessing workflow.

  16. Overexpression of ORCA3 and G10H in Catharanthus roseus Plants Regulated Alkaloid Biosynthesis and Metabolism Revealed by NMR-Metabolomics

    OpenAIRE

    Qifang Pan; Quan Wang; Fang Yuan; Shihai Xing; Jingya Zhao; Young Hae Choi; Robert Verpoorte; Yuesheng Tian; Guofeng Wang; Kexuan Tang

    2012-01-01

    In order to improve the production of the anticancer dimeric indole alkaloids in Catharanthuse roseus, much research has been dedicated to culturing cell lines, hairy roots, and efforts to elucidate the regulation of the monoterpenoid indole alkaloid (MIA) biosynthesis. In this study, the ORCA3 (Octadecanoid-derivative Responsive Catharanthus AP2-domain) gene alone or integrated with the G10H (geraniol 10-hydroxylase) gene were first introduced into C. roseus plants. Transgenic C. roseus plan...

  17. Quality classification of Spanish olive oils by untargeted gas chromatography coupled to hybrid quadrupole-time of flight mass spectrometry with atmospheric pressure chemical ionization and metabolomics-based statistical approach.

    Science.gov (United States)

    Sales, C; Cervera, M I; Gil, R; Portolés, T; Pitarch, E; Beltran, J

    2017-02-01

    The novel atmospheric pressure chemical ionization (APCI) source has been used in combination with gas chromatography (GC) coupled to hybrid quadrupole time-of-flight (QTOF) mass spectrometry (MS) for determination of volatile components of olive oil, enhancing its potential for classification of olive oil samples according to their quality using a metabolomics-based approach. The full-spectrum acquisition has allowed the detection of volatile organic compounds (VOCs) in olive oil samples, including Extra Virgin, Virgin and Lampante qualities. A dynamic headspace extraction with cartridge solvent elution was applied. The metabolomics strategy consisted of three different steps: a full mass spectral alignment of GC-MS data using MzMine 2.0, a multivariate analysis using Ez-Info and the creation of the statistical model with combinations of responses for molecular fragments. The model was finally validated using blind samples, obtaining an accuracy in oil classification of 70%, taking the official established method, "PANEL TEST", as reference. PMID:27596432

  18. Investigation on biochemical compositional changes during the microbial fermentation process of Fu brick tea by LC-MS based metabolomics.

    Science.gov (United States)

    Xu, Jie; Hu, Feng-Lin; Wang, Wei; Wan, Xiao-Chun; Bao, Guan-Hu

    2015-11-01

    Fu brick tea (FBT) is a unique post-fermented tea product which is fermented with fungi during the manufacturing process. In this study, we investigated the biochemical compositional changes occurring during the microbial fermentation process (MFP) of FBT based on non-targeted LC-MS, which was a comprehensive and unbiased methodology. Our data analysis took a two-phase approach: (1) comparison of FBT with other tea products using PCA analysis to exhibit the characteristic effect of MFP on the formation of Fu brick tea and (2) comparison of tea samples throughout the MFP of FBT to elucidate the possible key metabolic pathways produced by the fungi. Non-targeted LC-MS analysis clearly distinguished FBT with other tea samples and highlighted some interesting metabolic pathways during the MFP including B ring fission catechin. Our study demonstrated that those fungi had a significant influence on the biochemical profiles in the FBT and consequently contributed to its unique quality.

  19. NMR-based metabolomic investigation of bioactivity of chemical constituents in black raspberry (Rubus occidentalis L.) fruit extracts.

    Science.gov (United States)

    Paudel, Liladhar; Wyzgoski, Faith J; Giusti, M Monica; Johnson, Jodee L; Rinaldi, Peter L; Scheerens, Joseph C; Chanon, Ann M; Bomser, Joshua A; Miller, A Raymond; Hardy, James K; Reese, R Neil

    2014-02-26

    Black raspberry (Rubus occidentalis L.) (BR) fruit extracts with differing compound profiles have shown variable antiproliferative activities against HT-29 colon cancer cell lines. This study used partial least-squares (PLS) regression analysis to develop a high-resolution (1)H NMR-based multivariate statistical model for discerning the biological activity of BR constituents. This model identified specific bioactive compounds and ascertained their relative contribution against cancer cell proliferation. Cyanidin 3-rutinoside and cyanidin 3-xylosylrutinoside were the predominant contributors to the extract bioactivity, but salicylic acid derivatives (e.g., salicylic acid glucosyl ester), quercetin 3-glucoside, quercetin 3-rutinoside, p-coumaric acid, epicatechin, methyl ellagic acid derivatives (e.g., methyl ellagic acetyl pentose), and citric acid derivatives also contributed significantly to the antiproliferative activity of the berry extracts. This approach enabled the identification of new bioactive components in BR fruits and demonstrates the utility of the method for assessing chemopreventive compounds in foods and food products.

  20. Analysis of the correlation between dipeptides and taste differences among soy sauces by using metabolomics-based component profiling.

    Science.gov (United States)

    Yamamoto, Shinya; Shiga, Kazuki; Kodama, Yukako; Imamura, Miho; Uchida, Riichiro; Obata, Akio; Bamba, Takeshi; Fukusaki, Eiichiro

    2014-07-01

    Characterizing the relationships between the components and taste differences among soy sauces can help evaluate and improve the quality of soy sauces. Although previous studies have reported that certain taste-active dipeptides, the relationships between taste differences and dipeptides of soy sauces are unknown. Therefore, our objective in this study was to investigate the correlations between the dipeptides and the taste differences among soy sauces. To analyze the dipeptides, we constructed an analytical method using liquid chromatography/tandem mass spectrometry (LC/MS/MS) in multiple reaction monitoring mode. Based on this method, we detected 237 dipeptides, the largest number ever detected in soy sauce research. Next, orthogonal projections to latent structures regressions were performed. The data matrix of components, including dipeptides and other low-molecular-weight hydrophilic components obtained from gas chromatography/mass spectrometry (GC/MS), served as explanatory variables (366 in total), whereas a sensory data matrix obtained using quantitative descriptive analysis served as the response variable. The accuracy of models for the sweetness and saltiness differences constructed using the LC/MS/MS and GC/MS data matrix were higher than did models constructed using only the GC/MS data matrix. As a result of investigation of the correlation between the dipeptides and taste differences among soy sauces by using variable importance in the projection (VIP) score, many dipeptides showed the high correlation with taste differences. Specifically, Ile-Gln, Pro-Lys, Ile-Glu, Thr-Phe, and Leu-Gln showed the high VIP score on sweet differences. This study is the first report that reveals the correlations between the dipeptides and taste differences among soy sauces.

  1. Alterations of the exo- and endometabolite profiles in breast cancer cell lines: A mass spectrometry-based metabolomics approach.

    Science.gov (United States)

    Willmann, Lucas; Schlimpert, Manuel; Hirschfeld, Marc; Erbes, Thalia; Neubauer, Hans; Stickeler, Elmar; Kammerer, Bernd

    2016-06-21

    In recent years, knowledge about metabolite changes which are characteristic for the physiologic state of cancer cells has been acquired by liquid chromatography coupled to mass spectrometry. Distinct molecularly characterized breast cancer cell lines provide an unbiased and standardized in vitro tumor model reflecting the heterogeneity of the disease. Tandem mass spectrometry is a widely applied analytical platform and highly sensitive technique for analysis of complex biological samples. Endo- and exometabolite analysis of the breast cancer cell lines MDA-MB-231, -453 and BT-474 as well as the breast epithelial cell line MCF-10A has been performed using two different analytical platforms: UPLC-ESI-Q-TOF based on a scheduled precursor list has been applied for highlighting of significant differences between cell lines and HPLC-ESI-QqQ using multiple reaction monitoring has been utilized for a targeted approach focusing on RNA metabolism and interconnected pathways, respectively. Statistical analysis enabled a clear discrimination of the breast epithelial from the breast cancer cell lines. As an effect of oxidative stress, a decreased GSH/GSSG ratio has been detected in breast cancer cell lines. The triple negative breast cancer cell line MDA-MB-231 showed an elevation in nicotinamide, 1-ribosyl-nicotinamide and NAD+ reflecting the increased energy demand in triple negative breast cancer, which has a more aggressive clinical course than other forms of breast cancer. Obtained distinct metabolite pattern could be correlated with distinct molecular characteristics of breast cancer cells. Results and methodology of this preliminary in vitro study could be transferred to in vivo studies with breast cancer patients. PMID:27188315

  2. Plant-based Rasayana drugs from Ayurveda.

    Science.gov (United States)

    Balasubramani, Subramani Paranthaman; Venkatasubramanian, Padma; Kukkupuni, Subrahmanya Kumar; Patwardhan, Bhushan

    2011-02-01

    Rasayana tantra is one of the eight specialties of Ayurveda. It is a specialized practice in the form of rejuvenative recipes, dietary regimen, special health promoting behaviour and drugs. Properly administered Rasayana can bestow the human being with several benefits like longevity, memory, intelligence, freedom from diseases, youthful age, excellence of luster, complexion and voice, optimum strength of physique and sense organs, respectability and brilliance. Various types of plant based Rasayana recipes are mentioned in Ayurveda. Review of the current literature available on Rasayanas indicates that anti-oxidant and immunomodulation are the most studied activities of the Rasayana drugs. Querying in Pubmed database on Rasayanas reveals that single plants as well as poly herbal formulations have been researched on. This article reviews the basics of Rasayana therapy and the published research on different Rasayana drugs for specific health conditions. It also provides the possible directions for future research. PMID:21390573

  3. Biological variation of Vanilla planifolia leaf metabolome.

    Science.gov (United States)

    Palama, Tony Lionel; Fock, Isabelle; Choi, Young Hae; Verpoorte, Robert; Kodja, Hippolyte

    2010-04-01

    The metabolomic analysis of Vanilla planifolia leaves collected at different developmental stages was carried out using (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate data analysis in order to evaluate their variation. Ontogenic changes of the metabolome were considered since leaves of different ages were collected at two different times of the day and in two different seasons. Principal component analysis (PCA) and partial least square modeling discriminate analysis (PLS-DA) of (1)H NMR data provided a clear separation according to leaf age, time of the day and season of collection. Young leaves were found to have higher levels of glucose, bis[4-(beta-D-glucopyranosyloxy)-benzyl]-2-isopropyltartrate (glucoside A) and bis[4-(beta-D-glucopyranosyloxy)-benzyl]-2-(2-butyl)-tartrate (glucoside B), whereas older leaves had more sucrose, acetic acid, homocitric acid and malic acid. Results obtained from PLS-DA analysis showed that leaves collected in March 2008 had higher levels of glucosides A and B as compared to those collected in August 2007. However, the relative standard deviation (RSD) exhibited by the individual values of glucosides A and B showed that those compounds vary more according to their developmental stage (50%) than to the time of day or the season in which they were collected (19%). Although morphological variations of the V. planifolia accessions were observed, no clear separation of the accessions was determined from the analysis of the NMR spectra. The results obtained in this study, show that this method based on the use of (1)H NMR spectroscopy in combination with multivariate analysis has a great potential for further applications in the study of vanilla leaf metabolome.

  4. Mass appeal : metabolite identification in mass spectrometry-focused untargeted metabolomics

    NARCIS (Netherlands)

    Dunn, Warwick B.; Erban, Alexander; Weber, Ralf J.M.; Creek, Darren J.; Brown, Marie; Breitling, Rainer; Hankemeier, Thomas; Goodacre, Royston; Neumann, Steffen; Kopka, Joachim; Viant, Mark R.

    2013-01-01

    Metabolomics has advanced significantly in the past 10 years with important developments related to hardware, software and methodologies and an increasing complexity of applications. In discovery-based investigations, applying untargeted analytical methods, thousands of metabolites can be detected w

  5. 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.

  6. Metabolomic assessment of induced and activated chemical defence in the invasive red alga Gracilaria vermiculophylla.

    Science.gov (United States)

    Nylund, Göran M; Weinberger, Florian; Rempt, Martin; Pohnert, Georg

    2011-01-01

    In comparison with terrestrial plants the mechanistic knowledge of chemical defences is poor for marine macroalgae. This restricts our understanding in the chemically mediated interactions that take place between algae and other organisms. Technical advances such as metabolomics, however, enable new approaches towards the characterisation of the chemically mediated interactions of organisms with their environment. We address defence responses in the red alga Gracilaria vermiculophylla using mass spectrometry based metabolomics in combination with bioassays. Being invasive in the north Atlantic this alga is likely to possess chemical defences according to the prediction that well-defended exotics are most likely to become successful invaders in systems dominated by generalist grazers, such as marine macroalgal communities. We investigated the effect of intense herbivore feeding and simulated herbivory by mechanical wounding of the algae. Both processes led to similar changes in the metabolic profile. Feeding experiments with the generalist isopod grazer Idotea baltica showed that mechanical wounding caused a significant increase in grazer resistance. Structure elucidation of the metabolites of which some were up-regulated more than 100 times in the wounded tissue, revealed known and novel eicosanoids as major components. Among these were prostaglandins, hydroxylated fatty acids and arachidonic acid derived conjugated lactones. Bioassays with pure metabolites showed that these eicosanoids are part of the innate defence system of macroalgae, similarly to animal systems. In accordance with an induced defence mechanism application of extracts from wounded tissue caused a significant increase in grazer resistance and the up-regulation of other pathways than in the activated defence. Thus, this study suggests that G. vermiculophylla chemically deters herbivory by two lines of defence, a rapid wound-activated process followed by a slower inducible defence. By unravelling

  7. Metabolic pathway engineering based on metabolomics confers acetic and formic acid tolerance to a recombinant xylose-fermenting strain of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Ishii Jun

    2011-01-01

    Full Text Available Abstract Background The development of novel yeast strains with increased tolerance toward inhibitors in lignocellulosic hydrolysates is highly desirable for the production of bio-ethanol. Weak organic acids such as acetic and formic acids are necessarily released during the pretreatment (i.e. solubilization and hydrolysis of lignocelluloses, which negatively affect microbial growth and ethanol production. However, since the mode of toxicity is complicated, genetic engineering strategies addressing yeast tolerance to weak organic acids have been rare. Thus, enhanced basic research is expected to identify target genes for improved weak acid tolerance. Results In this study, the effect of acetic acid on xylose fermentation was analyzed by examining metabolite profiles in a recombinant xylose-fermenting strain of Saccharomyces cerevisiae. Metabolome analysis revealed that metabolites involved in the non-oxidative pentose phosphate pathway (PPP [e.g. sedoheptulose-7-phosphate, ribulose-5-phosphate, ribose-5-phosphate and erythrose-4-phosphate] were significantly accumulated by the addition of acetate, indicating the possibility that acetic acid slows down the flux of the pathway. Accordingly, a gene encoding a PPP-related enzyme, transaldolase or transketolase, was overexpressed in the xylose-fermenting yeast, which successfully conferred increased ethanol productivity in the presence of acetic and formic acid. Conclusions Our metabolomic approach revealed one of the molecular events underlying the response to acetic acid and focuses attention on the non-oxidative PPP as a target for metabolic engineering. An important challenge for metabolic engineering is identification of gene targets that have material importance. This study has demonstrated that metabolomics is a powerful tool to develop rational strategies to confer tolerance to stress through genetic engineering.

  8. 基于代谢组学的杀菌剂作用机理研究%Study on Antifungal Modes-of-Action Based on Metabolomics

    Institute of Scientific and Technical Information of China (English)

    陈溪; 纪明山

    2013-01-01

    Metabolomics had so far been a valuable high-throughput screening tool for bioactive substances, and it was widely applied to life science and showed a promising perspective. The concept, empirical method, analytical method, data processing, application of metabolomics was summarized, and its potentials in biology, medicine, pesticide sphere were prospected. In this foundation, the development direction through the studies on antifungal metabolomics was rised. Through high-throughput screening and data processing as device, metabolic fingerprint library was established, and a method which can quickly screen unknown modes-of-action antifungal was set up. Metabolomics has important future trends in new drug research, drug toxicology analysis and assessment, and it might be a important breakthrough in pesticide study.%目前代谢组学是生物活性物质高效筛选的重要工具,在生命科学领域得到了越来越广泛的应用并展现出良好的前景.综述了代谢组学的概念、实验方法、分析方法、数据处理以及在生物、医药领域的应用及农药学领域的研究前景.并在此基础上,提出了利用代谢组学研究杀菌剂作用机理可能的发展方向.以高通量检测和数据处理为手段,建立代谢指纹图谱库,创建一个可以快速筛查未知杀菌剂作用机理的方法,在新型农药的研制、毒理学分析、安全评价等领域具有广阔的前景,将成为农药现代研究的一个重要突破口.

  9. Toxic Markers of Matrine Determined Using 1H-NMR-Based Metabolomics in Cultured Cells In Vitro and Rats In Vivo

    Directory of Open Access Journals (Sweden)

    Zhonghuang Li

    2015-01-01

    Full Text Available Matrine is one of the main bioactive alkaloids of Sophora flavescens Aiton, which has been widely used to treat various diseases in China. These diseases include viral hepatitis, liver fibrosis, cardiac arrhythmia, skin diseases, and tumors. However, matrine is also the main toxic compound of this herb, and the available biomarkers are not reliable in detecting or quantifying matrine risk. Metabolomics is a powerful tool used to identify early toxicity biomarkers that are specific indicators of damage to biosystems. This study aimed to find the potential biomarkers of the matrine-induced toxic effects in rats and HepG2 cells. The toxicological effects of rats induced by matrine could be derived from the elevated taurine and trimethylamine N-oxide levels and the depletion in hippurate and tricarboxylic acid cycle intermediates, such as 2-oxoglutarate, citrate, and succinate in the urine. Cell metabolomics revealed that the levels of alanine, choline, glutathione, lactate, phosphocholine, and cholesterol showed dose-dependent decreases, whereas the levels of taurine, fatty acid, and unsaturated fatty acid showed dose-dependent increases. Overall, a significant perturbation of metabolites in response to high dose of matrine was observed both in vivo and in vitro, and the selected metabolites particularly represent an attractive marker for matrine-induced toxicity.

  10. Toxic Markers of Matrine Determined Using (1) H-NMR-Based Metabolomics in Cultured Cells In Vitro and Rats In Vivo.

    Science.gov (United States)

    Li, Zhonghuang; Zheng, Liang; Shi, Jian; Zhang, Guiyu; Lu, Linlin; Zhu, Lijun; Zhang, Jiajie; Liu, Zhongqiu

    2015-01-01

    Matrine is one of the main bioactive alkaloids of Sophora flavescens Aiton, which has been widely used to treat various diseases in China. These diseases include viral hepatitis, liver fibrosis, cardiac arrhythmia, skin diseases, and tumors. However, matrine is also the main toxic compound of this herb, and the available biomarkers are not reliable in detecting or quantifying matrine risk. Metabolomics is a powerful tool used to identify early toxicity biomarkers that are specific indicators of damage to biosystems. This study aimed to find the potential biomarkers of the matrine-induced toxic effects in rats and HepG2 cells. The toxicological effects of rats induced by matrine could be derived from the elevated taurine and trimethylamine N-oxide levels and the depletion in hippurate and tricarboxylic acid cycle intermediates, such as 2-oxoglutarate, citrate, and succinate in the urine. Cell metabolomics revealed that the levels of alanine, choline, glutathione, lactate, phosphocholine, and cholesterol showed dose-dependent decreases, whereas the levels of taurine, fatty acid, and unsaturated fatty acid showed dose-dependent increases. Overall, a significant perturbation of metabolites in response to high dose of matrine was observed both in vivo and in vitro, and the selected metabolites particularly represent an attractive marker for matrine-induced toxicity.

  11. Comparison of fresh, dried and stir-frying gingers in decoction with blood stasis syndrome in rats based on a GC-TOF/MS metabolomics approach.

    Science.gov (United States)

    Han, YanQuan; Li, YuXin; Wang, YongZhong; Gao, JiaRong; Xia, LunZhu; Hong, Yan

    2016-09-10

    In China, ginger (Zingiberofficinale Rosc.) and its processed products, such as dried ginger and stir-frying ginger are commonly applied in traditional Chinese medicine (TCM). The paper presents the research on the effects of fresh ginger, dried ginger and stir-frying ginger extracts in blood stasis syndrome. First, a blood stasis syndrome rats model was established and then the hemorheological and blood coagulation activities were analyzed. Third, a sensitive, simple, and valid gas chromatography combined with time-of-flight mass spectrometry (GC-TOF/MS) method was established to compare the metabolic fingerprint coupled with multivariate analysis. The total 27 metabolites (16 in serum and 11 in urine) were identified and contributed to the blood stasis progress. These metabolites mainly involve six metabolism pathways in different impact-value. The altered efficacy index and metabolites can be regulated to normal levels by fresh ginger (FG), dried ginger (DG) and stir-frying ginger (SG). FG is the most effective as shown by the efficacy index, similarity analysis and peak intensity. The result presented here shows that metabolomics equipped with efficacy index makes it possible to study the blood stasis syndrome and to compare the effect and metabolites in fresh, dried and stir-frying gingers. The metabolomics approach can be recommended to study the pharmacological effect and mechanism of herbal drugs. PMID:27454085

  12. Effect of storage time on metabolite profile and alpha-glucosidase inhibitory activity of Cosmos caudatus leaves – GCMS based metabolomics approach

    Directory of Open Access Journals (Sweden)

    Neda Javadi

    2015-09-01

    Full Text Available Cosmos caudatus, which is a commonly consumed vegetable in Malaysia, is locally known as “Ulam Raja”. It is a local Malaysian herb traditionally used as a food and medicinal herb to treat several maladies. Its bioactive or nutritional constituents consist of a wide range of metabolites, including glucosinolates, phenolics, amino acids, organic acids, and sugars. However, many of these metabolites are not stable and easily degraded or modified during storage. In order to investigate the metabolomics changes occurring during post-harvest storage, C. caudatus samples were subjected to seven different storage times (0 hours, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 12 hours at room temperature. As the model experiment, the metabolites identified by gas chromatography-mass spectrometry (GC-MS were correlated with α-glucosidase inhibitory activity analyzed with multivariate data analysis (MVDA to find out the variation among samples and metabolites contributing to the activity. Orthogonal partial least squares (OPLS analysis was applied to investigate the metabolomics changes. A profound chemical alteration, both in primary and secondary metabolites, was observed. The α-tocopherol, catechin, cyclohexen-1-carboxylic acid, benzoic acid, myo-inositol, stigmasterol, and lycopene compounds were found to be the discriminating metabolites at early storage; however, sugars such as sucrose, α-d-galactopyranose, and turanose were detected, which was attributed to the discriminating metabolites for late storage. The result shows that the MVDA method is a promising technique to identify biomarker compounds relative to storage at different times.

  13. Using NMR-Based Metabolomics to Evaluate Postprandial Urinary Responses Following Consumption of Minimally Processed Wheat Bran or Wheat Aleurone by Men and Women

    Directory of Open Access Journals (Sweden)

    Ramandeep Garg

    2016-02-01

    Full Text Available Wheat bran, and especially wheat aleurone fraction, are concentrated sources of a wide range of components which may contribute to the health benefits associated with higher consumption of whole-grain foods. This study used NMR metabolomics to evaluate urine samples from baseline at one and two hours postprandially, following the consumption of minimally processed bran, aleurone or control by 14 participants (7 Females; 7 Males in a randomized crossover trial. The methodology discriminated between the urinary responses of control, and bran and aleurone, but not between the two fractions. Compared to control, consumption of aleurone or bran led to significantly and substantially higher urinary concentrations of lactate, alanine, N-acetylaspartate acid and N-acetylaspartylglutamate and significantly and substantially lower urinary betaine concentrations at one and two hours postprandially. There were sex related differences in urinary metabolite profiles with generally higher hippurate and citrate and lower betaine in females compared to males. Overall, this postprandial study suggests that acute consumption of bran or aleurone is associated with a number of physiological effects that may impact on energy metabolism and which are consistent with longer term human and animal metabolomic studies that used whole-grain wheat diets or wheat fractions.

  14. Using NMR-Based Metabolomics to Evaluate Postprandial Urinary Responses Following Consumption of Minimally Processed Wheat Bran or Wheat Aleurone by Men and Women.

    Science.gov (United States)

    Garg, Ramandeep; Brennan, Lorraine; Price, Ruth K; Wallace, Julie M W; Strain, J J; Gibney, Mike J; Shewry, Peter R; Ward, Jane L; Garg, Lalit; Welch, Robert W

    2016-02-01

    Wheat bran, and especially wheat aleurone fraction, are concentrated sources of a wide range of components which may contribute to the health benefits associated with higher consumption of whole-grain foods. This study used NMR metabolomics to evaluate urine samples from baseline at one and two hours postprandially, following the consumption of minimally processed bran, aleurone or control by 14 participants (7 Females; 7 Males) in a randomized crossover trial. The methodology discriminated between the urinary responses of control, and bran and aleurone, but not between the two fractions. Compared to control, consumption of aleurone or bran led to significantly and substantially higher urinary concentrations of lactate, alanine, N-acetylaspartate acid and N-acetylaspartylglutamate and significantly and substantially lower urinary betaine concentrations at one and two hours postprandially. There were sex related differences in urinary metabolite profiles with generally higher hippurate and citrate and lower betaine in females compared to males. Overall, this postprandial study suggests that acute consumption of bran or aleurone is associated with a number of physiological effects that may impact on energy metabolism and which are consistent with longer term human and animal metabolomic studies that used whole-grain wheat diets or wheat fractions.

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

    OpenAIRE

    Salek, RM; Neumann, S. (Stefan); Schober, D.; Hummel, J; Billiau, K.; Kopka, J.; E. Correa; Reijmers, T; Rosato, A.; Tenori, L.; P.Turano; Marin, S. (Sara); Deborde, C.; Jacob, D.; Rolin, D

    2015-01-01

    International audience 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 funders. After the initial efforts of the metabolomics standards initiative, minimum reporting standards were proposed which included the concepts for metabolomics databases. ...

  16. Metabolomic approach for improving ethanol stress tolerance in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ohta, Erika; Nakayama, Yasumune; Mukai, Yukio; Bamba, Takeshi; Fukusaki, Eiichiro

    2016-04-01

    The budding yeast Saccharomyces cerevisiae is widely used for brewing and ethanol production. The ethanol sensitivity of yeast cells is still a serious problem during ethanol fermentation, and a variety of genetic approaches (e.g., random mutant screening under selective pressure of ethanol) have been developed to improve ethanol tolerance. In this study, we developed a strategy for improving ethanol tolerance of yeast cells based on metabolomics as a high-resolution quantitative phenotypic analysis. We performed gas chromatography-mass spectrometry analysis to identify and quantify 36 compounds on 14 mutant strains including knockout strains for transcription factor and metabolic enzyme genes. A strong relation between metabolome of these mutants and their ethanol tolerance was observed. Data mining of the metabolomic analysis showed that several compounds (such as trehalose, valine, inositol and proline) contributed highly to ethanol tolerance. Our approach successfully detected well-known ethanol stress related metabolites such as trehalose and proline thus, to further prove our strategy, we focused on valine and inositol as the most promising target metabolites in our study. Our results show that simultaneous deletion of LEU4 and LEU9 (leading to accumulation of valine) or INM1 and INM2 (leading to reduction of inositol) significantly enhanced ethanol tolerance. This study shows the potential of the metabolomic approach to identify target genes for strain improvement of S. cerevisiae with higher ethanol tolerance.

  17. Xenobiotics Produce Distinct Metabolomic Responses in Zebrafish Larvae (Danio rerio).

    Science.gov (United States)

    Huang, Susie S Y; Benskin, Jonathan P; Chandramouli, Bharat; Butler, Heather; Helbing, Caren C; Cosgrove, John R

    2016-06-21

    Sensitive and quantitative protocols for characterizing low-dose effects are needed to meet the demands of 21st century chemical hazard assessment. To test the hypothesis that xenobiotic exposure at environmentally relevant concentrations produces specific biochemical fingerprints in organisms, metabolomic perturbations in zebrafish (Danio rerio) embryo/larvae were measured following 24 h exposures to 13 individual chemicals covering a wide range of contaminant classes. Measured metabolites (208 in total) included amino acids, biogenic amines, fatty acids, bile acids, sugars, and lipids. The 96-120 h post-fertilization developmental stage was the most appropriate model for detecting xenobiotic-induced metabolomic perturbations. Metabolomic fingerprints were largely chemical- and dose-specific and were reproducible in multiple exposures over a 16-month period. Furthermore, chemical-specific responses were detected in the presence of an effluent matrix; importantly, in the absence of morphological response. In addition to improving sensitivity for detecting biological responses to low-level xenobiotic exposures, these data can aid the classification of novel contaminants based on the similarity of metabolomic responses to well-characterized "model" compounds. This approach is clearly of use for rapid, sensitive, and specific analyses of chemical effect on organisms, and can supplement existing methods, such as the Zebrafish Embryo Toxicity assay (OECD TG236), with molecular-level information. PMID:27232715

  18. Metabolomic variation of brassica rapa var. rapa (var. raapstelen) and raphanus sativus l. at different developmental stages

    International Nuclear Information System (INIS)

    Brassica rapa (var. raapstelen) and Raphanus sativus (red radish) are being used as food and fodder while also known as model in recent plant research due to the diversity of metabolites as well as genetic resemblance to Arabidopsis. This study explains the change in metabolites (amino acids, organic acids, chlorophyll, carotenoids, tocopherols, ascorbic acid, sucrose, phenylpropanoids and glucosinolates) during plant development. In present study the metabolomic variation in relation to plant growth has been evaluated, for Brassica rapa (var. raapstelen) and red radish (Raphanus sativus) at three different developmental stages. A non-targeted and targeted metabolomic approach by NMR and HPLC in combination with Principal component analysis (PCA) of the data was used to identify phytochemicals being influenced by plant growth. The results lead to the better understanding of metabolic changes during plant development and show the importance of plant age with respect to the metabolomic profile of vegetables. (author)

  19. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    OpenAIRE

    2015-01-01

    Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top...

  20. 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

    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

  1. Visualization of Multivariate Metabolomic Data

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jun; CAO Bei; ZHENG Tian; LIU Lin-sheng; GUO Sheng; DUAN Jin-ao; AA Ji-ye; WANG Guang-ji; ZHANG Feng-yi; GU Rong-rong; WANG Xin-wen; ZHAO Chun-yan; LI Meng-jie; SHI Jian

    2011-01-01

    Objective Although principal components analysis profiles greatly facilitate the visualization and interpretation of the multivariate data,the quantitative concepts in both scores plot and loading plot are rather obscure.This article introduced three profiles that assisted the better understanding of metabolomic data.Methods The discriminatory profile,heat map,and statistic profile were developed to visualize the multivariate data obtained from high-throughput GC-TOF-MS analysis.Results The discriminatory profile and heat map obviously showed the discriminatory metabolites between the two groups,while the statistic profile showed the potential markers of statistic significance.Conclusion The three types of profiles greatly facilitate our understanding of the metabolomic data and the identification of the potential markers.

  2. GC-TOF/MS-based metabolomic strategy for combined toxicity effects of deoxynivalenol and zearalenone on murine macrophage ANA-1 cells.

    Science.gov (United States)

    Ji, Jian; Zhu, Pei; Pi, Fuwei; Sun, Chao; Jiang, Hui; Sun, Jiadi; Wang, Xiumei; Zhang, Yinzhi; Sun, Xiulan

    2016-09-15

    The actual health risk from exposure to combined mycotoxins is unknown, and few studies have focused on changes to cellular biological systems (e.g., metabolomics) caused by combined mycotoxic effects. To evaluate the combined mycotoxic effects of deoxynivalenol (DON) and zearalenone (ZEN) on the level of cellular biological systems, gas chromatographic, time-of-flight mass spectroscopy (GC-TOF/MS) of the complete murine macrophage ANA-1 cell metabolome was implemented in this study. Using optimized chromatography and mass spectrometry parameters, the metabolites detected by GC-TOF/MS were identified and processed using multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection on latent-structures discriminant analysis (OPLS-DA). The metabolite sets were screened for further pathway analysis under rules of t-test (P) value  1, and similarity value > 500. The mainly interfered metabolism pathways were categorized into two dominant types: amino acid metabolism and glycometabolism. Four metabolites, palmitic acid, 1-monopalmitin, ribose-5-phosphate and 2-deoxy-D-galactose, occur only under combined "DON + ZEN" treatment, indicating abnormal metabolism in ANA-1 cells. The metabolic state of ANA-1 cells under induction by combined "DON + ZEN" illustrates that DON may inhibit the estrogenic effects of ZEN. Thus, the combined effect of "DON + ZEN" may exacerbate toxicity in the pentose phosphate pathway, while palmitic acid metabolism is likely a new pathway effected by the combination, "DON + ZEN." PMID:27530666

  3. Evaluation of extracts of Piper sarmentosum for accelerated stability by metabolomic fingerprint profiling

    Directory of Open Access Journals (Sweden)

    K Hussain

    2009-01-01

    Full Text Available Unlike pharmaceuticals, precise stability assessment of herbal products is challenging because of their complex nature. A new trend in natural products is that the extract is considered active as a whole whether active constituents are known or not. Hence, the stability of all the constituents must be taken into account, which is possible by analyzing metabolomic fingerprint profiles. Therefore, present study aimed to evaluate ethanol extracts of fruit of Piper sarmentosum, an important medicinal plant, for accelerated stability using metabolomic fingerprint profiling. The extract was exposed to three storage conditions of different temperature and humidity and analyzed at 0, 1, 2, 4 and 6 months by Fourier transform infrared (FTIR spectroscopy and high performance thin layer chromatography (HPTLC to get metabolomic fingerprints. FTIR fingerprints in combination with chemometrics indicated the changes in metabolomics, stirring with the passage of time at all storage conditions. Visual inspection of HPTLC densitograms revealed metabolomic changes in the extracts stored for 6 months at 60 °C and 85% relative humidity. The results of the study indicate that the products made from this plant ought to be stored at room temperature, below 30 °C and 45% relative humidity, and excessive heating must be avoided during manufacturing process. Moreover, the method may be used by natural product industry as a tool of identification, classification and discrimination (ICD.

  4. Metabolomics in the Rhizosphere

    NARCIS (Netherlands)

    Dam, van Nicole M.; Bouwmeester, Harro J.

    2016-01-01

    The rhizosphere is densely populated with a variety of organisms. Interactions between roots and rhizosphere community members are mostly achieved via chemical communication. Root exudates contain an array of primary and secondary plant metabolites that can attract, deter, or kill belowground ins

  5. Global GPP based on Plant Functional Types

    Science.gov (United States)

    Veroustraete, Frank; Balzarolo, Manuela

    2016-04-01

    Vegetation variables like Gross Primary productivity (GPP) and the Normalized Difference Vegetation Index (NDVI) are key variables in vegetation carbon exchange studies. Field measurements of the NDVI are time consuming due to landscape heterogeneity across time. Typically a sampling protocol adopted during field campaigns is based on the VALERI protocol in that case toe estimate LAI. Field campaign GPP or NDVI measurements can be scaled up to using in-situ FLUXNET radiation raster maps. Regression analysis can then be applied to construct transfer functions for the determination of GPP raster maps raster imagery from Normalized Difference Vegetation Index (NDVI) raster maps derived from in-situ FLUXNET radiation raster maps. Subsequently, in the VALERI approach the scaling up of raster maps is performed by aggregation of high resolution in-situ FLUXNET radiation raster maps data into high resolution raster maps and subsequently aggregating these to 1x1 km MODIS NDVI raster maps by calculating average NDVI values for the low resolution data. The up-scaled 1x1 km pixels are then used to validate the MODIS GPP and NVI products. Hence up scaling based on in-situ FLUXNET radiation measurements are not a luxury for large and heterogeneous sites. Therefore this paper tackles the problem of up scaling using in-situ FLUXNET radiation measurements. Key Words: FLUXNET, GPP, Plant Functional Types, Up-scaling

  6. 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 tions/benefits-o

  7. Symbiosis of chemometrics and metabolomics: Past, present, and future

    NARCIS (Netherlands)

    Greef, J. van der; 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 co

  8. The yeast metabolome addressed by electrospray ionization mass spectrometry: Initiation of a mass spectral library and its applications for metabolic footprinting by direct infusion mass spectrometry

    DEFF Research Database (Denmark)

    Højer-Pedersen, Jesper Juul; Smedsgaard, Jørn; Nielsen, Jens

    2008-01-01

    , which could be assigned using the in silico metabolome. By this approach metabolic footprinting can advance from a classification method that is used to derive biological information based on guilt-by-association, to a tool for extraction of metabolic differences, which can guide new targeted biological...... for ionization of microbial metabolites without any previous derivatization needed. To address the capabilities of ESI-MS in detecting the metabolome of Saccharomyces cerevisiae, the in silico metabolome of this organism was used as a template to present a theoretical metabolome. This showed that in combination...

  9. 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.

  10. Image-Based Modeling of Plants and Trees

    CERN Document Server

    Kang, Sing Bang

    2009-01-01

    Plants and trees are among the most complex natural objects. Much work has been done attempting to model them, with varying degrees of success. In this book, we review the various approaches in computer graphics, which we categorize as rule-based, image-based, and sketch-based methods. We describe our approaches for modeling plants and trees using images. Image-based approaches have the distinct advantage that the resulting model inherits the realistic shape and complexity of a real plant or tree. We use different techniques for modeling plants (with relatively large leaves) and trees (with re

  11. Metabolomic phenotyping of af cloned pig model

    DEFF Research Database (Denmark)

    Clausen, Morten Rahr; Christensen, Kirstine Lykke; Hedemann, Mette Skou;

    2011-01-01

    Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes...... and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal...... outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n...

  12. MetaboLights: An Open-Access Database Repository for Metabolomics Data.

    Science.gov (United States)

    Kale, Namrata S; Haug, Kenneth; Conesa, Pablo; Jayseelan, Kalaivani; Moreno, Pablo; Rocca-Serra, Philippe; Nainala, Venkata Chandrasekhar; Spicer, Rachel A; Williams, Mark; Li, Xuefei; Salek, Reza M; Griffin, Julian L; Steinbeck, Christoph

    2016-01-01

    MetaboLights is the first general purpose, open-access database repository for cross-platform and cross-species metabolomics research at the European Bioinformatics Institute (EMBL-EBI). Based upon the open-source ISA framework, MetaboLights provides Metabolomics Standard Initiative (MSI) compliant metadata and raw experimental data associated with metabolomics experiments. Users can upload their study datasets into the MetaboLights Repository. These studies are then automatically assigned a stable and unique identifier (e.g., MTBLS1) that can be used for publication reference. The MetaboLights Reference Layer associates metabolites with metabolomics studies in the archive and is extensively annotated with data fields such as structural and chemical information, NMR and MS spectra, target species, metabolic pathways, and reactions. The database is manually curated with no specific release schedules. MetaboLights is also recommended by journals for metabolomics data deposition. This unit provides a guide to using MetaboLights, downloading experimental data, and depositing metabolomics datasets using user-friendly submission tools. PMID:27010336

  13. Fast Visual Modeling for Plant Based on Real Images

    Institute of Scientific and Technical Information of China (English)

    LI Yun-feng; ZHU Qing-sheng; CAO Yu-kun; LIU Yin-bin; HE Xi-ping

    2004-01-01

    Structures of natural plants are complex and difficult to model. This paper proposes a fast visual modeling for plants based on a small set of images, and establishes a reasonable plant model.Based on knowledge about growth patterns of the plant, image segmentation and 3D reconstruction are first performed to construct the plant skeleton (trunk and major branches), from which the remainder of the plant grows. Then the system produces the realistic plant model images based on image synthesis and validation. It is unnecessary to acquire the complex structure (such as the complex production rules of L-systems). The method provides a high degree of control over the final shape by image validation,resulting in realistic reconstruction.

  14. Fast Construction of Plant Architectural Models Based on Substructure Decomposition

    Institute of Scientific and Technical Information of China (English)

    YAN HongPing (严红平); Philippe de Reffye; PAN ChunHong (潘春洪); HU BaoGang (胡包钢)

    2003-01-01

    Plant structure, representing the physical link among different organs, includes many similar substructures. In this paper, a new method is presented to construct plant architectural models of most plant species. The plant structure is decomposed into a stem, a set of lateral substructures and a terminal substructure, which is called substructure decomposition; then based on substructure decomposition, the plant structures are expressed in an iterative way; and further the derivative formula is employed to compute the number of organs in plant structures to get the geometrical sizes of 3D plant organs by borrowing Hydraulic Model. Using 3D organs, a substructure library is built. Based on the substructures stored in substructure library, one can construct 3D plant structure according to certain topological and geometrical rules. The experiments with different plant species are included in this paper to demonstrate the validity of the new method for constructing plant structures. The experimental results show that the approach follows botanical knowledge with high efficiency in constructing plant structures of most plant species. In addition,this method enables users to check the detail information of plant structure.

  15. Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

    Science.gov (United States)

    Xiao, Man; Du, Guankui; Zhong, Guobing; Yan, Dongjing; Zeng, Huazong; Cai, Wangwei

    2016-01-01

    Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD) activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx) mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C)- and C3H fava beans-treated (C3H-FB) mice, and G6PDx-control (G6PDx-C)- and G6PDx fava beans-treated (G6PDx-FB) mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

  16. Identification of Ornamental Plant Functioned as Medicinal Plant Based on Redundant Discrete Wavelet Transformation

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2013-03-01

    Full Text Available Human has a duty to preserve the nature. One of the examples is preserving the ornamental plant. Huge economic value of plant trading, escalating esthetical value of one space and medicine efficacy that contained in a plant are some positive values from this plant. However, only few people know about its medicine efficacy. Considering the easiness to obtain and the medicine efficacy, this plant should be an initial treatment of a simple disease or option towards chemical based medicines. In order to let people get acquaint, we need a system that can proper identify this plant. Therefore, we propose to build a system based on Redundant Discrete Wavelet Transformation (RDWT through its leaf. Since its character is translation invariant that able to produce some robust features to identify ornamental plant. This system was successfully resulting 95.83% of correct classification rate.

  17. Jasmonate-mediated stomatal closure under elevated CO2 revealed by time-resolved metabolomics

    Science.gov (United States)

    Foliar stomatal movements are critical for regulating plant water status and gas exchange. Elevated carbon dioxide (CO2) concentrations are known to induce stomatal closure. However, current knowledge on CO2 signal transduction in stomatal guard cells is limited. Here we report the metabolomic respo...

  18. Metagenomics, Metatranscriptomics, and Metabolomics Approaches for Microbiome Analysis

    OpenAIRE

    Vanessa Aguiar-Pulido; Wenrui Huang; Victoria Suarez-Ulloa; Trevor Cickovski; Kalai Mathee; Giri Narasimhan

    2016-01-01

    Microbiomes are ubiquitous and are found in the ocean, the soil, and in/on other living organisms. Changes in the microbiome can impact the health of the environmental niche in which they reside. In order to learn more about these communities, different approaches based on data from multiple omics have been pursued. Metagenomics produces a taxonomical profile of the sample, metatranscriptomics helps us to obtain a functional profile, and metabolomics completes the picture by determining which...

  19. Mass spectrometry for high-throughput metabolomics analysis of urine

    OpenAIRE

    Abdelrazig, Salah M.A.

    2015-01-01

    Direct electrospray ionisation-mass spectrometry (direct ESI-MS), by omitting the chromatographic step, has great potential for application as a high-throughput approach for untargeted urine metabolomics analysis compared to liquid chromatography-mass spectrometry (LC-MS). The rapid development and technical innovations revealed in the field of ambient ionisation MS such as nanoelectrospray ionisation (nanoESI) chip-based infusion and liquid extraction surface analysis mass spectrometry (LESA...

  20. Biomarkers of Whale Shark Health: A Metabolomic Approach

    OpenAIRE

    Alistair D M Dove; Johannes Leisen; Manshui Zhou; Byrne, Jonathan J; Krista Lim-Hing; Webb, Harry D.; Leslie Gelbaum; Viant, Mark R.; Julia Kubanek; Facundo M Fernández

    2012-01-01

    In a search for biomarkers of health in whale sharks and as exploration of metabolomics as a modern tool for understanding animal physiology, the metabolite composition of serum in six whale sharks (Rhincodon typus) from an aquarium collection was explored using (1)H nuclear magnetic resonance (NMR) spectroscopy and direct analysis in real time (DART) mass spectrometry (MS). Principal components analysis (PCA) of spectral data showed that individual animals could be resolved based on the meta...

  1. Cytoplasmic genetic variation and extensive cytonuclear interactions influence natural variation in the metabolome

    DEFF Research Database (Denmark)

    Joseph, Bindu; Corwin, Jason A.; Li, Baohua;

    2013-01-01

    affects phenotypic variation. This showed that the cytoplasmic variation had effects similar to, if not larger than, the largest individual nuclear locus. Inclusion of cytoplasmic variation into the genetic model greatly increased the explained phenotypic variation. Cytoplasmic genetic variation was a...... central hub in the epistatic network controlling the plant metabolome. This epistatic influence manifested such that the cytoplasmic background could alter or hide pairwise epistasis between nuclear loci. Thus, cytoplasmic genetic variation plays a central role in controlling natural variation in...... metabolomic networks. This suggests that cytoplasmic genomes must be included in any future analysis of natural variation....

  2. The research on Virtual Plants Growth Based on DLA Model

    Science.gov (United States)

    Zou, YunLan; Chai, Bencheng

    This article summarizes the separated Evolutionary Algorithm in fractal algorithm of Diffusion Limited Aggregation model (i.e. DLA model) and put forward the virtual plant growth realization in computer based on DLA model. The method is carried out in the VB6.0 environment to achieve and verify the plant growth based on DLA model.

  3. Proteomics and Metabolomics of Arabidopsis Responses to Perturbation of Glucosinolate Biosynthesis

    Institute of Scientific and Technical Information of China (English)

    Ya-zhou Chen; Qiu-Ying Pang; Yan He; Ning Zhu; Isabel Branstrom; Xiu-Feng Yan; Sixue Chen

    2012-01-01

    To understand plant molecular networks of glucosinolate metabolism,perturbation of aliphatic glucosinolate biosynthesis was established using inducible RNA interference (RNAi) in Arabidopsis.Two RNAi lines were chosen for examining global protein and metabolite changes using complementary proteomics and metabolomics approaches.Proteins involved in metabolism including photosynthesis and hormone metabolism,protein binding,energy,stress,and defense showed marked responses to glucosinolate perturbation.In parallel,metabolomics revealed major changes in the levels of amino acids,carbohydrates,peptides,and hormones.The metabolomics data were correlated with the proteomics results and revealed intimate molecular connections between cellular pathways/processes and glucosinolate metabolism.This study has provided an unprecedented view of the molecular networks of glucosinolate metabolism and laid a foundation towards rationale glucosinolate engineering for enhanced defense and quality.

  4. Ultrahigh-Performance Liquid Chromatography-High-Resolution Quadrupole Time-of-Flight Mass Spectrometry Based Metabolomics Reveals Key Differences between Brachiaria decumbens and B. brizantha, Two Similar Pastures with Different Toxicities.

    Science.gov (United States)

    Pérez, Andy J; Hussain, Syeda M; Pecio, Łukasz; Kowalczyk, Mariusz; Herling, Valdo R; Stochmal, Anna

    2016-06-01

    Several species of Brachiaria (Poaceae) currently cover extensive grazing areas in Brazil, providing valuable source of feed for a large cattle population. However, numerous cases of toxicity outbreaks in livestock have raised concerns on safety of using these plants, especially B. decumbens. In this study, chemometric analysis of ultrahigh-performance liquid chromatography-high-resolution quadrupole time-of-flight mass spectrometry (UHPLC-HR-QTOF-MS) data has for the first time uncovered qualitative and quantitative differences between metabolomes of toxic B. decumbens and nontoxic B. brizantha. The steroidal saponin protoneodioscin was established as the main biomarker for B. decumbens when compared to B. brizantha, and therefore the key explanation for their phytochemical differentiation. Quantification of protodioscin in both plants showed no significant differences; consequently, the idea that this compound is solely responsible for toxicity outbreaks must be discarded. Instead, we propose that the added occurrence of its stereoisomer, protoneodioscin, in B. decumbens, can be considered as the probable cause of these events. Interestingly, the greatest concentrations of saponins for both species were reached during winter (B. decumbens = 53.6 ± 5.1 mg·g(-1) dry weight (D.W.); B. brizantha = 25.0 ± 1.9 mg·g(-1) D.W.) and spring (B. decumbens = 49.4 ± 5.0 mg·g(-1) D.W.; B. brizantha = 27.9 ± 1.4 mg·g(-1) D.W.), although in the case of B. decumbens these values do not vary significantly among seasons. PMID:27192362

  5. Field-deployed Metabolomics for Assessing Waters Impacted by Point and Non-Point Sources of Contamination

    Science.gov (United States)

    Metabolomics is becoming well-established for studying chemical contaminant-induced alterations to normal biological function. For example, the literature contains a wealth of laboratory-based studies involving analysis of samples from organisms exposed to individual chemical tox...

  6. Field-deployed Metabolomics for Assessing Surface Waters Impacted by Point and Non-Point Sources of Contamination

    Science.gov (United States)

    Metabolomics has become well-established for studying chemical contaminant-induced alterations to normal biological function. For example, the literature contains a wealth of laboratory-based studies involving analysis of samples from organisms exposed to individual chemical toxi...

  7. Use of Rhizosphere Metabolomics to Investigate Exudation of Phenolics by Arabidopsis Roots

    Science.gov (United States)

    Lee, Yong Jian; Rai, Amit; Reuben, Sheela; Nesati, Victor; Almeida, Reinaldo; Swarup, Sanjay

    2013-04-01

    and anthocyanin metabolites. We describe here the metabolites present in the root exudates using high resolution accurate mass (HRAM) metabolomics approach. Using this approach, biased rhizosphere for another class of PGPR strains can now be created. In this case, lignin- and anthocyanin- utilizing strains will be selectively preferred. We have set up a platform to perform metabolomics of exudates at the root surface. This has allowed us to use the liquid extraction surface analysis (LESA) system using a Thermo Velos Pro Orbitrap-MS to identify differences in exudate profiles along the root system of Arabidopsis. This platform enables direct sampling and measurement from plant roots grown aeroponically. As the metabolites are extracted from root surface and directly injected into the mass spectrometer, there is minimal loss of sample in this process. This method will now allow us to further dissect rhizosphere properties from places such as young root apex, as well as from the more mature base of roots. Taken together, these resources of altered rhizosphere, nutrient utilization pathways in microbes and surface analysis technology will help in extending our understanding of the processes in the plant rhizosphere.

  8. The prediction of the LWR plant accident based on the measured plant data

    International Nuclear Information System (INIS)

    In case of accident affecting a nuclear reactor, it is essential to anticipate the possible development of the situation to efficiently succeed in emergency response actions, i.e. firstly to be early warned, to get sufficient information on the plant: and as far as possible. The ASTRID (Assessment of Source Term for Emergency Response based on Installation Data) project consists in developing a methodology: of expertise to; structure the work of technical teams and to facilitate cross competence communications among EP players and a qualified computer tool that could be commonly used by the European countries to reliably predict source term in case of an accident in a light water reactor, using the information available on the plant. In many accident conditions the team of analysts may be located far away from the plant experiencing the accident and their decision making is based on the on-line plant data transmitted into the crisis centre in an interval of 30 - 600 seconds. The plant condition has to be diagnosed based on this information, In the ASTRID project the plant status diagnostics has been studied for the European reactor types including BWR, PWR and VVER plants. The directly measured plant data may be used for estimations of the break size from the primary system and its locations. The break size prediction may be based on the pressurizer level, reactor vessel level, primary pressure and steam generator level in the case of the steam generator tube rupture. In the ASTRID project the break predictions concept was developed and its validity for different plant types and is presented in the paper, when the plant data has been created with the plant specific thermohydraulic simulation model. The tracking simulator attempts to follow the plant behavior on-line based on the measured plant data for the main process parameters and most important boundary conditions. When the plant state tracking fails, the plant may be experiencing an accident, and the tracking

  9. [Plant Spectral Discrimination Based on Phenological Features].

    Science.gov (United States)

    Zhang, Lei; Zhao, Jian-long; Jia, Kun; Li, Xiao-song

    2015-10-01

    Spectral analysis plays a significant role onplant characteristic identification and mechanism recognition, there were many papers published on the aspects of absorption features in the spectra of chlorophyll and moisture, spectral analysis onvegetation red edge effect, spectra profile feature extraction, spectra profile conversion, vegetation leaf structure and chemical composition impacts on the spectra in past years. However, fewer researches issued on spectral changes caused by plant seasonal changes of life form, chlorophyll, leaf area index. This paper studied on spectral observation of 11 plants of various life form, plant leaf structure and its size, phenological characteristics, they include deciduous forest with broad vertical leaf, needle leaf evergreen forest, needle leaf deciduous forest, deciduous forest with broadflat leaf, high shrub with big leaf, high shrub with little leaf, deciduous forest with broad little leaf, short shrub, meadow, steppe and grass. Field spectral data were observed with SVC-HR768 (Spectra Vista company, USA), the band width covers 350-2 500 nm, spectral resolution reaches 1-4 nm. The features of NDVI, spectral maximum absorption depth in green band, and spectral maximum absorption depth in red band were measured after continuum removal processing, the mean, amplitude and gradient of these features on seasonal change profile were analyzed, meanwhile, separability research on plant spectral feature of growth period and maturation period were compared. The paper presents a calculation method of separability of vegetation spectra which consider feature spatial distances. This index is carried on analysis of the vegetation discrimination. The results show that: the spectral features during plant growth period are easier to distinguish than them during maturation period. With the same features comparison, plant separability of growth period is 3 points higher than it during maturation period. The overall separabilityof vegetation

  10. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics.

    Science.gov (United States)

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-01-01

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP. PMID:27338465

  11. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics

    Science.gov (United States)

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-01-01

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP. PMID:27338465

  12. Possible Future SOFC - ST Based Power Plants

    DEFF Research Database (Denmark)

    Rokni, Masoud; Scappin, Fabio

    2009-01-01

    Hybrid systems consisting Solid Oxide Fuel Cell (SOFC) on the top of a Steam Turbine (ST) are investigated. The plants are fired by natural gas. A desulfurization reactor removes the sulfur content in the NG while a pre-reformer break down the heavier hydrocarbons. The pre-treated fuel enters...

  13. 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

  14. 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.

  15. A Combined Metabolomic and Proteomic Analysis of Gestational Diabetes Mellitus.

    Science.gov (United States)

    Hajduk, Joanna; Klupczynska, Agnieszka; Dereziński, Paweł; Matysiak, Jan; Kokot, Piotr; Nowak, Dorota M; Gajęcka, Marzena; Nowak-Markwitz, Ewa; Kokot, Zenon J

    2015-12-16

    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.

  16. An exome array study of the plasma metabolome

    Science.gov (United States)

    Rhee, Eugene P.; Yang, Qiong; Yu, Bing; Liu, Xuan; Cheng, Susan; Deik, Amy; Pierce, Kerry A.; Bullock, Kevin; Ho, Jennifer E.; Levy, Daniel; Florez, Jose C.; Kathiresan, Sek; Larson, Martin G.; Vasan, Ramachandran S.; Clish, Clary B.; Wang, Thomas J.; Boerwinkle, Eric; O'Donnell, Christopher J.; Gerszten, Robert E.

    2016-01-01

    The study of rare variants may enhance our understanding of the genetic determinants of the metabolome. Here, we analyze the association between 217 plasma metabolites and exome variants on the Illumina HumanExome Beadchip in 2,076 participants in the Framingham Heart Study, with replication in 1,528 participants of the Atherosclerosis Risk in Communities Study. We identify an association between GMPS and xanthosine using single variant analysis and associations between HAL and histidine, PAH and phenylalanine, and UPB1 and ureidopropionate using gene-based tests (P<5 × 10−8 in meta-analysis), highlighting novel coding variants that may underlie inborn errors of metabolism. Further, we show how an examination of variants across the spectrum of allele frequency highlights independent association signals at select loci and generates a more integrated view of metabolite heritability. These studies build on prior metabolomics genome wide association studies to provide a more complete picture of the genetic architecture of the plasma metabolome. PMID:27453504

  17. Systems Analysis Of Advanced Coal-Based Power Plants

    Science.gov (United States)

    Ferrall, Joseph F.; Jennings, Charles N.; Pappano, Alfred W.

    1988-01-01

    Report presents appraisal of integrated coal-gasification/fuel-cell power plants. Based on study comparing fuel-cell technologies with each other and with coal-based alternatives and recommends most promising ones for research and development. Evaluates capital cost, cost of electricity, fuel consumption, and conformance with environmental standards. Analyzes sensitivity of cost of electricity to changes in fuel cost, to economic assumptions, and to level of technology. Recommends further evaluation of integrated coal-gasification/fuel-cell integrated coal-gasification/combined-cycle, and pulverized-coal-fired plants. Concludes with appendixes detailing plant-performance models, subsystem-performance parameters, performance goals, cost bases, plant-cost data sheets, and plant sensitivity to fuel-cell performance.

  18. Discrimination of Three Panax Species Based on Differences in Volatile Organic Compounds Using a Static Headspace GC-MS-Based Metabolomics Approach.

    Science.gov (United States)

    Chen, Xiao-Jia; Qiu, Jian-Feng; Wang, Yi-Tao; Wan, Jian-Bo

    2016-01-01

    Panax ginseng (Asian ginseng), Panax quinquefolium (American ginseng) and Panax notoginseng (notoginseng) are highly valuable tonic herbs derived from the Panax genus that have similar morphological appearances and odors but different pharmacological activities and clinical indications. Thus, the authentication of these three Panax species is crucial for ensuring the quality, safety and efficacy of medication. In the present study, a static headspace gas chromatography - mass spectrometry (GC-MS) followed by a multivariate statistical analysis was developed to globally characterize the volatile organic compound (VOC) profiles in P. ginseng, P. quinquefolium, and P. notoginseng, and subsequently to discover differentiating chemical markers. Under the optimized conditions, the headspace VOCs of a total of 49 batches of Panax herbs derived from the three Panax species were profiled, and the dataset of sample code, [Formula: see text]-m/z pair and ion intensity was processed by unsupervised principal component analysis (PCA) and by supervised partial least squared discriminant analysis (PLS-DA) to comprehensively compare the chemical differences in Panax across the species. The results demonstrated that Panax herbs derived from three species possess obviously diverse chemical characteristics of VOCs, PCA, and PLS-DA. According to their VOC profiles, 49 tested samples could be clearly differentiated according to species. Chemomarker 1, 2, and 4 might be used as unique chemical markers of P. ginseng, P. notoginseng and P. quinquefolium, respectively. Our findings indicate that static headspace GC-MS-based VOC profiling, combined with multivariate statistical analysis, provide a reliable tool to discriminate between the three Panax species and to identify their differentiation markers, which will be helpful for ensuring their quality, safety and efficacy.

  19. Genetic manipulation of putrescine biosynthesis reprograms the cellular transcriptome and the metabolome

    OpenAIRE

    Page, Andrew F.; Cseke, Leland J.; Minocha, Rakesh; Turlapati, Swathi A.; Podila, Gopi K.; Ulanov, Alexander; Li, Zhong; Minocha, Subhash C.

    2016-01-01

    Background With the increasing interest in metabolic engineering of plants using genetic manipulation and gene editing technologies to enhance growth, nutritional value and environmental adaptation, a major concern is the potential of undesirable broad and distant effects of manipulating the target gene or metabolic step in the resulting plant. A comprehensive transcriptomic and metabolomic analysis of the product may shed some useful light in this regard. The present study used these two tec...

  20. Knowledge based system for fouling assessment of power plant boiler

    International Nuclear Information System (INIS)

    The paper presents the design of an expert system for fouling assessment in power plant boilers. It is an on-line expert system based on selected criteria for the fouling assessment. Using criteria for fouling assessment based on 'clean' and 'not-clean' radiation heat flux measurements, the diagnostic variable are defined for the boiler heat transfer surface. The development of the prototype knowledge-based system for fouling assessment in power plants boiler comprise the integrations of the elements including knowledge base, inference procedure and prototype configuration. Demonstration of the prototype knowledge-based system for fouling assessment was performed on the Sines power plant. It is a 300 MW coal fired power plant. 12 fields are used with 3 on each side of boiler

  1. 基于NMR代谢组学技术对山药化学成分的研究%Studies on chemical constituents of the yam by 1HNMR-based metabolomics

    Institute of Scientific and Technical Information of China (English)

    张敏; 焦宏; 郭捷

    2014-01-01

    试验采用基于NMR代谢组学的技术,分别对生山药饮片、麸炒山药及食用山药的化学成分进行了研究,检测出30多种化合物,包括腺苷、胆碱、多种氨基酸、有机酸及糖类等物质,其中有14种是3种山药的共有成分。另外,对引起生山药与麸炒山药、食用山药与药用山药差异的化学成分进行了指认,初步了解了炮制对山药化学成分的影响及山药药材与食材的差异。%The studies on chemical constituents of dried yam slices, bran fried yam and edible yam were carried out re-spectively by means of 1HNMR-based metabolomics. Over thirty compounds including adenosine, choline, amino acids, organic acids, sugars and other substances were detected, of which fourteen were common components in three kinds of yams. Their respective characteristic chemical compositions were indicated. Effect of processing on the chemical compo-nents of yam and the differences between edible yam and dried yam slices, bran fried yam were reviewed.

  2. ECMDB: the E. coli Metabolome Database.

    Science.gov (United States)

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

    2013-01-01

    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. Each metabolite entry in the ECMDB contains an average of 75 separate data fields, including comprehensive compound descriptions, names and synonyms, chemical taxonomy, compound structural and physicochemical data, bacterial growth conditions and substrates, reactions, pathway information, enzyme data, gene/protein sequence data and numerous hyperlinks to images, references and other public databases. The ECMDB also includes an extensive collection of intracellular metabolite concentration data compiled from our own work as well as other published metabolomic studies. This information is further supplemented with thousands of fully assigned reference nuclear magnetic resonance and mass spectrometry spectra obtained from pure E. coli metabolites that we (and others) have collected. 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 E. coli'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 molecular biologists, systems biologists and individuals in the biotechnology industry.

  3. OPTIMAS-DW: A comprehensive transcriptomics, metabolomics, ionomics, proteomics and phenomics data resource for maize

    Directory of Open Access Journals (Sweden)

    Colmsee Christian

    2012-12-01

    Full Text Available Abstract Background Maize is a major crop plant, grown for human and animal nutrition, as well as a renewable resource for bioenergy. When looking at the problems of limited fossil fuels, the growth of the world’s population or the world’s climate change, it is important to find ways to increase the yield and biomass of maize and to study how it reacts to specific abiotic and biotic stress situations. Within the OPTIMAS systems biology project maize plants were grown under a large set of controlled stress conditions, phenotypically characterised and plant material was harvested to analyse the effect of specific environmental conditions or developmental stages. Transcriptomic, metabolomic, ionomic and proteomic parameters were measured from the same plant material allowing the comparison of results across different omics domains. A data warehouse was developed to store experimental data as well as analysis results of the performed experiments. Description The OPTIMAS Data Warehouse (OPTIMAS-DW is a comprehensive data collection for maize and integrates data from different data domains such as transcriptomics, metabolomics, ionomics, proteomics and phenomics. Within the OPTIMAS project, a 44K oligo chip was designed and annotated to describe the functions of the selected unigenes. Several treatment- and plant growth stage experiments were performed and measured data were filled into data templates and imported into the data warehouse by a Java based import tool. A web interface allows users to browse through all stored experiment data in OPTIMAS-DW including all data domains. Furthermore, the user can filter the data to extract information of particular interest. All data can be exported into different file formats for further data analysis and visualisation. The data analysis integrates data from different data domains and enables the user to find answers to different systems biology questions. Finally, maize specific pathway information is

  4. Automated production of plant-based vaccines and pharmaceuticals.

    Science.gov (United States)

    Wirz, Holger; Sauer-Budge, Alexis F; Briggs, John; Sharpe, Aaron; Shu, Sudong; Sharon, Andre

    2012-12-01

    A fully automated "factory" was developed that uses tobacco plants to produce large quantities of vaccines and other therapeutic biologics within weeks. This first-of-a-kind factory takes advantage of a plant viral vector technology to produce specific proteins within the leaves of rapidly growing plant biomass. The factory's custom-designed robotic machines plant seeds, nurture the growing plants, introduce a viral vector that directs the plant to produce a target protein, and harvest the biomass once the target protein has accumulated in the plants-all in compliance with Food and Drug Administration (FDA) guidelines (e.g., current Good Manufacturing Practices). The factory was designed to be time, cost, and space efficient. The plants are grown in custom multiplant trays. Robots ride up and down a track, servicing the plants and delivering the trays from the lighted, irrigated growth modules to each processing station as needed. Using preprogrammed robots and processing equipment eliminates the need for human contact, preventing potential contamination of the process and economizing the operation. To quickly produce large quantities of protein-based medicines, we transformed a laboratory-based biological process and scaled it into an industrial process. This enables quick, safe, and cost-effective vaccine production that would be required in case of a pandemic.

  5. Metabolomics continues to flourish: highlights from the 2014 Metabolomics Society Conference

    NARCIS (Netherlands)

    Roessner, U.; Hall, R.D.

    2014-01-01

    The Metabolomics Society has now been organising its annual meetings for 10 years! The 10th annual conference returned, in June, to Tsuruoka, Japan where the very first meeting was also held in 2005—just shortly after our society had been formally established and our journal Metabolomics had brought

  6. Supporting plant operation through computer-based procedures

    International Nuclear Information System (INIS)

    Digital Systems are becoming more important in controlling and monitoring nuclear power plant operations. The capabilities of these systems provide additional functions as well as support operators in making decisions and avoiding errors. Regarding Operation Support Systems, an important way of taking advantage of these features is using computer-based procedures (CBPs) tools that enhance the plant operation. Integrating digital systems in analogue controls at nuclear power plants in operation becomes an extra challenge, in contrast to the integration of Digital Control Systems in new nuclear power plants. Considering the potential advantages of using this technology, Tecnatom has designed and developed a CBP platform taking currently operating nuclear power plants as its design basis. The result is a powerful tool which combines the advantages of CBPs and the conventional analogue control systems minimizing negative effects during plant operation and integrating operation aid-systems to support operators. (authors)

  7. Cyclotron-based effects on plant gravitropism

    Science.gov (United States)

    Kordyum, E.; Sobol, M.; Kalinina, Ia.; Bogatina, N.; Kondrachuk, A.

    Primary roots exhibit positive gravitropism and grow in the direction of the gravitational vector, while shoots respond negatively and grow opposite to the gravitational vector. We first demonstrated that the use of a weak combined magnetic field (CMF), which is comprised of a permanent magnetic field and an alternating magnetic field with the frequency resonance of the cyclotron frequency of calcium ions, can change root gravitropism from a positive direction to negative direction. Two-day-old cress seedlings were gravistimulated in a chamber that was placed into a μ-metal shield where this CMF was created. Using this "new model" of a root gravitropic response, we have studied some of its components including the movement of amyloplasts-statoliths in root cap statocytes and the distribution of Ca 2+ ions in the distal elongation zone during gravistimulation. Unlike results from the control, amyloplasts did not sediment in the distal part of a statocyte, and more Ca 2+ accumulation was observed in the upper side of a gravistimulated root for seedlings treated with the CMF. For plants treated with the CMF, it appears that a root gravitropic reaction occurs by a normal physiological process resulting in root bending although in the opposite direction. These results support the hypothesis that both the amyloplasts in the root cap statocytes and calcium are important signaling components in plant gravitropism.

  8. Metabolomics Analysis of Health Functions of Physalis Pubescens L. using by Ultra-performance Liquid Chromatography/Electrospray Ionization Quadruple Time-of-Flight Mass Spectrometry

    OpenAIRE

    Hang Chu; Hui Sun; Guang-Li Yan; Ai-Hua Zhang; Chang Liu; Hui Dong; Xiang-Cai Meng; Xi-Jun Wang

    2015-01-01

    Herbal medicines may benefit from metabolomics studies, and applying metabolomics may provide answers about which herbal interventions may be effective for individuals, which metabolic processes are triggered, and the subsequent chemical pathways of activity. Physalis pubescens L (PPL) is an herbal fruit for one year living plant and has been developed into healthy function's food. However, the mechanisms of health functions are still unclear. To comprehensively and holistically assess its an...

  9. Tools and databases of the KOMICS web portal for preprocessing, mining, and dissemination of metabolomics data.

    Science.gov (United States)

    Sakurai, Nozomu; Ara, Takeshi; Enomoto, Mitsuo; Motegi, Takeshi; Morishita, Yoshihiko; Kurabayashi, Atsushi; Iijima, Yoko; Ogata, Yoshiyuki; Nakajima, Daisuke; Suzuki, Hideyuki; Shibata, Daisuke

    2014-01-01

    A metabolome--the collection of comprehensive quantitative data on metabolites in an organism--has been increasingly utilized for applications such as data-intensive systems biology, disease diagnostics, biomarker discovery, and assessment of food quality. A considerable number of tools and databases have been developed to date for the analysis of data generated by various combinations of chromatography and mass spectrometry. We report here a web portal named KOMICS (The Kazusa Metabolomics Portal), where the tools and databases that we developed are available for free to academic users. KOMICS includes the tools and databases for preprocessing, mining, visualization, and publication of metabolomics data. Improvements in the annotation of unknown metabolites and dissemination of comprehensive metabolomic data are the primary aims behind the development of this portal. For this purpose, PowerGet and FragmentAlign include a manual curation function for the results of metabolite feature alignments. A metadata-specific wiki-based database, Metabolonote, functions as a hub of web resources related to the submitters' work. This feature is expected to increase citation of the submitters' work, thereby promoting data publication. As an example of the practical use of KOMICS, a workflow for a study on Jatropha curcas is presented. The tools and databases available at KOMICS should contribute to enhanced production, interpretation, and utilization of metabolomic Big Data.

  10. Tools and databases of the KOMICS web portal for preprocessing, mining, and dissemination of metabolomics data.

    Science.gov (United States)

    Sakurai, Nozomu; Ara, Takeshi; Enomoto, Mitsuo; Motegi, Takeshi; Morishita, Yoshihiko; Kurabayashi, Atsushi; Iijima, Yoko; Ogata, Yoshiyuki; Nakajima, Daisuke; Suzuki, Hideyuki; Shibata, Daisuke

    2014-01-01

    A metabolome--the collection of comprehensive quantitative data on metabolites in an organism--has been increasingly utilized for applications such as data-intensive systems biology, disease diagnostics, biomarker discovery, and assessment of food quality. A considerable number of tools and databases have been developed to date for the analysis of data generated by various combinations of chromatography and mass spectrometry. We report here a web portal named KOMICS (The Kazusa Metabolomics Portal), where the tools and databases that we developed are available for free to academic users. KOMICS includes the tools and databases for preprocessing, mining, visualization, and publication of metabolomics data. Improvements in the annotation of unknown metabolites and dissemination of comprehensive metabolomic data are the primary aims behind the development of this portal. For this purpose, PowerGet and FragmentAlign include a manual curation function for the results of metabolite feature alignments. A metadata-specific wiki-based database, Metabolonote, functions as a hub of web resources related to the submitters' work. This feature is expected to increase citation of the submitters' work, thereby promoting data publication. As an example of the practical use of KOMICS, a workflow for a study on Jatropha curcas is presented. The tools and databases available at KOMICS should contribute to enhanced production, interpretation, and utilization of metabolomic Big Data. PMID:24949426

  11. Green systems biology - From single genomes, proteomes and metabolomes to ecosystems research and biotechnology.

    Science.gov (United States)

    Weckwerth, Wolfram

    2011-12-10

    biochemical networks up to whole species populations. This process relies on the development of new technologies for the analysis of molecular data, especially genomics, metabolomics and proteomics data. The ambitious aim of these non-targeted 'omic' technologies is to extend our understanding beyond the analysis of separated parts of the system, in contrast to traditional reductionistic hypothesis-driven approaches. The consequent integration of genotyping, pheno/morphotyping and the analysis of the molecular phenotype using metabolomics, proteomics and transcriptomics will reveal a novel understanding of plant metabolism and its interaction with the environment. The analysis of single model systems - plants, fungi, animals and bacteria - will finally emerge in the analysis of populations of plants and other organisms and their adaptation to the ecological niche. In parallel, this novel understanding of ecophysiology will translate into knowledge-based approaches in crop plant biotechnology and marker- or genome-assisted breeding approaches. In this review the foundations of green systems biology are described and applications in ecosystems research are presented. Knowledge exchange of ecosystems research and green biotechnology merging into green systems biology is anticipated based on the principles of natural variation, biodiversity and the genotype-phenotype environment relationship as the fundamental drivers of ecology and evolution. PMID:21802534

  12. Color and Edge Histograms Based Medicinal Plants' Image Retrieval

    Directory of Open Access Journals (Sweden)

    Basavaraj S. Anami

    2012-08-01

    Full Text Available In this paper, we propose a methodology for color and edge histogram based medicinal plants image retrieval. The medicinal plants are divided into herbs, shrubs and trees. The medicinal plants are used in ayurvedic medicines. Manual identification of medicinal plants requires a priori knowledge. Automatic recognition of medicinal plants is useful. We have considered medicinal plant species, such as Papaya, Neem, Tulasi and Aloevera are considered for identification and retrieval. The color histograms are obtained in RGB, HSV and YCbCr color spaces. The number of valleys and peaks in the color histograms are used as features. But, these features alone are not helpful in discriminating plant images, since majority plant images are green in color. We have used edge and edge direction histograms in the work to get edges in the stem and leafy parts. Finally, these features are used in retrieval of medicinal plant images. Absolute distance, Euclidean distance and mean square error, similarity distance measures are deployed in the work. The results show an average retrieval efficiency of 94% and 98% for edge and edge direction features respectively.

  13. Metabolomic phenotyping of a cloned pig model

    Directory of Open Access Journals (Sweden)

    Callesen Henrik

    2011-08-01

    Full Text Available Abstract Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5 was for the first time elucidated by nuclear magnetic resonance (NMR-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n = 6 by multivariate data analysis, which revealed differences in the metabolic phenotypes. Plasma lactate was higher for cloned vs control pigs, while multiple metabolites were altered in the bile. However a lower inter-individual variability for cloned pigs compared with control pigs could not be established. Conclusions From the present study we conclude that cloned and normal outbred pigs are phenotypically different. However, it cannot be concluded that the use of cloned animals will reduce the inter-individual variation in intervention studies, though this is based on a limited number of animals.

  14. Metal-based nanotoxicity and detoxification pathways in higher plants.

    Science.gov (United States)

    Ma, Chuanxin; White, Jason C; Dhankher, Om Parkash; Xing, Baoshan

    2015-06-16

    The potential risks from metal-based nanoparticles (NPs) in the environment have increased with the rapidly rising demand for and use of nanoenabled consumer products. Plant's central roles in ecosystem function and food chain integrity ensure intimate contact with water and soil systems, both of which are considered sinks for NPs accumulation. In this review, we document phytotoxicity caused by metal-based NPs exposure at physiological, biochemical, and molecular levels. Although the exact mechanisms of plant defense against nanotoxicity are unclear, several relevant studies have been recently published. Possible detoxification pathways that might enable plant resistance to oxidative stress and facilitate NPs detoxification are reviewed herein. Given the importance of understanding the effects and implications of metal-based NPs on plants, future research should focus on the following: (1) addressing key knowledge gaps in understanding molecular and biochemical responses of plants to NPs stress through global transcriptome, proteome, and metablome assays; (2) designing long-term experiments under field conditions at realistic exposure concentrations to investigate the impact of metal-based NPs on edible crops and the resulting implications to the food chain and to human health; and (3) establishing an impact assessment to evaluate the effects of metal-based NPs on plants with regard to ecosystem structure and function.

  15. Metabolomics analysis of colorectal cancer based on GC-TOF-MS%基于GC-TOF-MS的结直肠癌代谢组学差异分析

    Institute of Scientific and Technical Information of China (English)

    于斐; 刘少壮; 仲明惟; 黄鑫; 焦杰; 胡三元; 于文滨

    2016-01-01

    Objective To explore the metabolic differences of cancer tissues,adjacent mucosa and normal mucosa in patients with colorectal cancer (CRC).Methods A total of 25 CRC patients were selected and the 3 kinds of tissues were taken from each patient.Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)platform was used for metabolomics analysis.The tissues were compared among each other,and principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA)were used to analyze the data.Differential me-tabolites were mapped in the KEGG database to search for the related metabolic pathways.Results Compared with the normal mucosa,47 metabolites were found different (P<0.05,q<0.05)in cancer tissues,and galactose metabolism, pentose phosphate pathway,glutamate and glutamine metabolism,glutamate,alanine and aspartate metabolism changed significantly (P<0.05).In the adjacent mucosa,3 metabolites were found different (P<0.05,q<0.05),and galac-tose metabolism changed significantly (P<0.05).A total of 34 metabolites were found different (P<0.05,q<0.05) between the cancer tissues and the adjacent mucosa,and pentose phosphate pathway,glutamate and glutamine metabo-lism,glutamate,alanine and aspartate metabolism changed significantly (P<0.05).Conclusion The glucose metab-olism and amino acid metabolism are changed in CRC tissues.%目的:探讨结直肠癌(CRC)患者癌组织、癌旁黏膜及正常黏膜的代谢差异。方法选取25例CRC患者,分别取癌组织、癌旁黏膜和正常黏膜各1份,采用气相色谱-飞行时间-质谱(GC-TOF-MS)分析平台对组织样本进行代谢组学检测,3种组织间相互比较并采用主成分分析和正交偏最小二乘判别分析对数据建模,分析差异代谢物并在KEGG数据库中映射,找出相关代谢通路。结果与正常黏膜相比,癌组织中有47种差异代谢物(P<0.05,q<0.05),其半乳糖代谢、磷酸戊糖途径

  16. Knowledge based diagnostics in nuclear power plants

    International Nuclear Information System (INIS)

    In the paper to be given a special process diagnostic system (PDS) will be presented, taking into account corresponding user experiences. It must be seen the result of a long term work on computerized process surveillance and control on NPP; it includes a model based system for noise analysis of mechanical vibrations, which has been enhanced by using of knowledge based technique (expert systems). The paper will discuss the process diagnostic frame concept and emphasize the vibration analysis expertsystem RADEX, with the parts modelling (building a knowledge base), man-machine communication aspects, implementation. (author). 5 refs, 5 figs

  17. Plasma metabolomics combined with lipidomics profiling reveals the potential antipyretic mechanisms of Qingkailing injection in a rat model.

    Science.gov (United States)

    Qin, Lingling; Zhang, Zhixin; Guo, Mingxing; Zhang, Qingqing; Wang, Qing; Lu, Zhiwei; Zhao, Huizhen; Liu, Yuehong; Fu, Shuang; Wang, Meiling; Gao, Xiaoyan

    2016-07-25

    Qingkailing injection (QKLI) has a notable antipyretic effect and is widely used in China as a clinical emergency medicine. To elucidate the pharmacological action thoroughly, following the investigation of the urine metabolome and hypothalamus metabolome, plasma metabolomics combined with lipidomics profiling of the QKLI antipyretic effect in a rat model is described in this paper. Compared with pure metabolomics profiling, this non-targeted plasma metabolomics combined with lipidomics profiling based on ultra-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS) could be used for a large-scale detection of features in plasma samples. The results showed that 15 metabolites at the 1 h time point and 19 metabolites at the 2 h time point after QKLI administration were associated with the antipyretic effect of QKLI, including amino acid, phosphatidylcholine and lysophosphatidylcholine. The metabolism pathway analysis revealed that the potential biomarkers, which were important for the antipyretic mechanism of QKLI, were closely responsible for correcting the perturbed pathways of amino acid metabolism and lipid metabolism. In conclusion, the use of complementary UPLC Q-TOF/MS based metabolomics and lipidomics allows for the discovery of new potential plasma biomarkers in the QKLI antipyretic process and the associated pathways, and aided in advancing the understanding of the holism and synergism of the Chinese drug. PMID:27208622

  18. Multimedia-based Medicinal Plants Sustainability Management System

    CERN Document Server

    Omogbadegun, Zacchaeus; Ayo, Charles; Mbarika, Victor; Omoregbe, Nicholas; Otofia, Efe; Chieze, Frank

    2011-01-01

    Medicinal plants are increasingly recognized worldwide as an alternative source of efficacious and inexpensive medications to synthetic chemo-therapeutic compound. Rapid declining wild stocks of medicinal plants accompanied by adulteration and species substitutions reduce their efficacy, quality and safety. Consequently, the low accessibility to and non-affordability of orthodox medicine costs by rural dwellers to be healthy and economically productive further threaten their life expectancy. Finding comprehensive information on medicinal plants of conservation concern at a global level has been difficult. This has created a gap between computing technologies' promises and expectations in the healing process under complementary and alternative medicine. This paper presents the design and implementation of a Multimedia-based Medicinal Plants Sustainability Management System addressing these concerns. Medicinal plants' details for designing the system were collected through semi-structured interviews and databas...

  19. The volatile metabolome of grapevine roots: first insights into the metabolic response upon phylloxera attack.

    Science.gov (United States)

    Lawo, Nora C; Weingart, Georg J F; Schuhmacher, Rainer; Forneck, Astrid

    2011-09-01

    Many plant species respond to herbivore attack by an increased formation of volatile organic compounds. In this preliminary study we analysed the volatile metabolome of grapevine roots [Teleki 5C (Vitis berlandieri Planch. × Vitis riparia Michx.)] with the aim to gain insight into the interaction between phylloxera (Daktulosphaira vitifoliae Fitch; Hemiptera: Phylloxeridae) and grapevine roots. In the first part of the study, headspace solid phase microextraction (HS-SPME) coupled to gas chromatography - mass spectrometry (GC-MS) was used to detect and identify volatile metabolites in uninfested and phylloxera-infested root tips of the grapevine rootstock Teleki 5C. Based on the comparison of deconvoluted mass spectra with spectra databases as well as experimentally derived retention indices with literature values, 38 metabolites were identified, which belong to the major classes of plant volatiles including C6-compounds, terpenes (including modified terpenes), aromatic compounds, alcohols and n-alkanes. Based on these identified metabolites, changes in root volatiles were investigated and resulted in metabolite profiles caused by phylloxera infestation. Our preliminary data indicate that defence related pathways such as the mevalonate and/or alternative isopentenyl pyrophosphate-, the lipoxygenase- (LOX) as well as the phenylpropanoid pathway are affected in root galls as a response to phylloxera attack. PMID:21764593

  20. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

    Directory of Open Access Journals (Sweden)

    Katarzyna Bozek

    2014-05-01

    Full Text Available Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

  1. Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid

    Science.gov (United States)

    Ruan, Zheng; Yang, Yuhui; Zhou, Yan; Wen, Yanmei; Ding, Sheng; Liu, Gang; Wu, Xin; Deng, Zeyuan; Assaad, Houssein; Wu, Guoyao

    2016-01-01

    This study was conducted to investigate effects of chlorogenic acid (CGA) supplementation on serum and hepatic metabolomes in rats. Rats received daily intragastric administration of either CGA (60 mg/kg body weight) or distilled water (control) for 4 weeks. Growth performance, serum biochemical profiles, and hepatic morphology were measured. Additionally, serum and liver tissue extracts were analyzed for metabolomes by high-resolution 1H nuclear magnetic resonance-based metabolomics and multivariate statistics. CGA did not affect rat growth performance, serum biochemical profiles, or hepatic morphology. However, supplementation with CGA decreased serum concentrations of lactate, pyruvate, succinate, citrate, β-hydroxybutyrate and acetoacetate, while increasing serum concentrations of glycine and hepatic concentrations of glutathione. These results suggest that CGA supplementation results in perturbation of energy and amino acid metabolism in rats. We suggest that glycine and glutathione in serum may be useful biomarkers for biological properties of CGA on nitrogen metabolism in vivo. PMID:24927697

  2. Maintenance of Ni-based alloy at PWR plant

    International Nuclear Information System (INIS)

    Kansai Electric owns 11 PWR plants. At our PWR plants, we are taking various preventive maintenance measures on Ni-based alloy according to the prediction of possible trouble while past trouble occurred at overseas plants due to Primary Water Stress Corrosion Cracking (PWSCC) being considered. In addition, we are making an effort to put new maintenance techniques into practical use by conducting demonstration tests to confirm their applicability to actual plants. We have replaced reactor vessel heads at 7 plants with new ones. At the other 4 plants, we took, measures to reduce the temperature of reactor vessel head top to delay the timing of PWSCC occurrence. We are carrying out the constant load tests to predict the timing of PWSCC occurrence at these 4 plants. It is planned to conduct non-destructive inspections at an appropriate timing based on the result of the prediction. Based on the prediction of the timing of PWSCC occurrence at bottom-mounted instrumentation (BMI), we have developed water jet peening (WJP) technique to reduce residual stress and applied the technique to our plants successively. Meanwhile, a technique to cut and eliminate cracking has been developed. In addition, capping technique, which covers overall the concerned nozzle on the outer surface of the reactor vessel, has been also established. For alloy 132/82 weld metal for the connection, we are conducting ultrasonic inspection at our plants successively. In order to prepare against PWSCC occurrence, we have also established a technique to replace the entire section of concerned short piping with new one. (author)

  3. Training in metabolomics research. I. Designing the experiment, collecting and extracting samples and generating metabolomics data.

    Science.gov (United States)

    Barnes, Stephen; Benton, H Paul; Casazza, Krista; Cooper, Sara J; Cui, Xiangqin; Du, Xiuxia; Engler, Jeffrey; Kabarowski, Janusz H; Li, Shuzhao; Pathmasiri, Wimal; Prasain, Jeevan K; Renfrow, Matthew B; Tiwari, Hemant K

    2016-07-01

    The study of metabolism has had a long history. Metabolomics, a systems biology discipline representing analysis of known and unknown pathways of metabolism, has grown tremendously over the past 20 years. Because of its comprehensive nature, metabolomics requires careful consideration of the question(s) being asked, the scale needed to answer the question(s), collection and storage of the sample specimens, methods for extraction of the metabolites from biological matrices, the analytical method(s) to be employed and the quality control of the analyses, how collected data are correlated, the statistical methods to determine metabolites undergoing significant change, putative identification of metabolites and the use of stable isotopes to aid in verifying metabolite identity and establishing pathway connections and fluxes. The National Institutes of Health Common Fund Metabolomics Program was established in 2012 to stimulate interest in the approaches and technologies of metabolomics. To deliver one of the program's goals, the University of Alabama at Birmingham has hosted an annual 4-day short course in metabolomics for faculty, postdoctoral fellows and graduate students from national and international institutions. This paper is the first part of a summary of the training materials presented in the course to be used as a resource for all those embarking on metabolomics research. The complete set of training materials including slide sets and videos can be viewed at http://www.uab.edu/proteomics/metabolomics/workshop/workshop_june_2015.php. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27434804

  4. Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xu-Hua Xu; Yue Huang; Gang Wang; Sheng-Di Chen

    2012-01-01

    Although the pathogenesis of Alzheimer's disease (AD) is still not fully understood,it is acknowledged that intervention should be made at the early stage.Therefore,identifying biomarkers for the clinical diagnosis is critical.Metabolomics,a novel "omics",uses methods based on low-molecular-weight molecules,with high-throughput evaluation of a large number of metabolites that may lead to the identification of new disease-specific biomarkers and the elucidation of pathophysiological mechanisms.This review discusses metabolomics investigations of AD and potential future developments in this field.

  5. Obesity and Asthma: Microbiome-Metabolome Interactions.

    Science.gov (United States)

    Shore, Stephanie A; Cho, Youngji

    2016-05-01

    Obesity is a risk factor for asthma, but obese subjects with asthma respond poorly to standard asthma drugs. Obesity also alters gut bacterial community structure. Obesity-related changes in gut bacteria contribute to weight gain and other obesity-related conditions, including insulin resistance and systemic inflammation. Here, we review the rationale for the hypothesis that obesity-related changes in gut bacteria may also play a role in obesity-related asthma. The metabolomes of the liver, serum, urine, and adipose tissue are altered in obesity. Gut bacteria produce a large number of metabolites, which can reach the blood and circulate to other organs, and gut bacteria-derived metabolites have been shown to contribute to disease processes outside the gastrointestinal tract, including cardiovascular disease. Here, we describe the potential roles for two such classes of metabolites in obesity-related asthma: short-chain fatty acids and bile acids. Greater understanding of the role of microbiota in obesity-related asthma could lead to novel microbiota-based treatments for these hard-to-treat patients. PMID:26949916

  6. Toxicity of a plant based mosquito repellent/killer

    OpenAIRE

    Singh, Bhoopendra; Singh, Prakash Raj; Mohanty, Manoj Kumar

    2012-01-01

    The mission to make humans less attractive to mosquitoes has fuelled decades of scientific research on mosquito behaviour and control. The search for the perfect topical insect repellent/killer continues. This analysis was conducted to review and explore the scientific information on toxicity produced by the ingredients/contents of a herbal product. In this process of systemic review the following methodology was applied. By doing a MEDLINE search with key words of selected plants, plant base...

  7. 基于核磁和质谱分析技术的代谢组学在癌症诊断中的应用%Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry-based Metabolomics for Cancer Diagnosis

    Institute of Scientific and Technical Information of China (English)

    顾海巍; 亓云鹏; 许柠; 丁健桦; 安艳波; 陈焕文

    2012-01-01

    In this review, we aim to introduce a relatively new approach, metabolomics, and explore its potential for cancer diagnosis. We will briefly introduce the concept of metabolomics and its rela?tionship with other omics studies in systems biology for cancer detection. The field of metabolomics focuses on the parallel measurement of hundreds of small molecule metabolites in biological samples such as blood, urine, and biopsied tissue. Since metabolite levels are sensitive to subtle changes in the pathological status, metabolomics promises novel avenues for early cancer detection and a better understanding of cancer processes. In fact, many previous metabolomics studies have clearly demons?trated the promises of metabolomics not only for the diagnosis of various kinds of cancer, but also for therapeutic monitoring as well as for drug development. In addition, in this review we will discuss the challenges and future directions for developing metabolomics methods towards clinical applications for cancer diagnosis.%本文对近年来用于癌症诊断的新方法——代谢组学及其在该领域内的应用进行了简要介绍.代谢组学通过定性与定量测量生物样本(血液、尿液、组织等)中数以千计的小分子代谢物,可灵敏地反映代谢组中与病理状态有关的细微变化,从而可为癌症的早期诊断及更好地理解癌变过程提供一种新颖的思路.本文还讨论了代谢组学与系统生物学中其它一些组学在癌症检测上的关联,介绍了一些用代谢组学进行不同癌症的诊断、治疗监测以及药物开发的前期研究工作,并探讨了用于临床癌症诊断的代谢组学方法所面临的机遇、挑战与未来发展方向.

  8. New Candidates for Plant-Based Repellents Against Aedes aegypti.

    Science.gov (United States)

    Misni, Norashiqin; Nor, Zurainee Mohamed; Ahmad, Rohani

    2016-06-01

    Based on an ethnobotanical study on use for plant species against mosquito bites in the Kota Tinggi District, Johor State, Malaysia, 3 plants selected for study, Citrus aurantifolia (leaves), Citrus grandis (fruit peel), and Alpinia galanga (rhizome), were extracted using hydrodistillation to produce essential oils. These essential oils were then formulated as a lotion using a microencapsulation process and then tested for their repellent effect against Aedes aegypti. N,N-diethyl-m-toluamide (deet) was also prepared in the same formulation and tested for repellency as controls. Four commercial plant-based repellent (KAPS(®), MozAway(®), BioZ Natural(®), and Mosiquard(®)) also were incorporated in the bioassay for comparison purposes. Bioassays revealed that at 20% concentration all repellent formulations demonstrated complete protection for 2 h and >90% for 4 h post-application. The A. galanga-based formulation provided the greatest level of protection (98.91%), which extended for 4 h post-application and was not significantly different from deet at similar concentration. When compared with commercial plant-based repellents (KAPS(®), MozAway(®), and BioZ Natural(®)), the 3 lotion formulations showed significantly better protection against Ae. aegypti bites, providing >90% protection for 4 h. In conclusion, our 3 plant-based lotion formulations provided acceptable levels of protection against host-seeking Ae. aegypti and should be developed. PMID:27280349

  9. Fault Diagnosis Strategies for SOFC-Based Power Generation Plants.

    Science.gov (United States)

    Costamagna, Paola; De Giorgi, Andrea; Gotelli, Alberto; Magistri, Loredana; Moser, Gabriele; Sciaccaluga, Emanuele; Trucco, Andrea

    2016-08-22

    The success of distributed power generation by plants based on solid oxide fuel cells (SOFCs) is hindered by reliability problems that can be mitigated through an effective fault detection and isolation (FDI) system. However, the numerous operating conditions under which such plants can operate and the random size of the possible faults make identifying damaged plant components starting from the physical variables measured in the plant very difficult. In this context, we assess two classical FDI strategies (model-based with fault signature matrix and data-driven with statistical classification) and the combination of them. For this assessment, a quantitative model of the SOFC-based plant, which is able to simulate regular and faulty conditions, is used. Moreover, a hybrid approach based on the random forest (RF) classification method is introduced to address the discrimination of regular and faulty situations due to its practical advantages. Working with a common dataset, the FDI performances obtained using the aforementioned strategies, with different sets of monitored variables, are observed and compared. We conclude that the hybrid FDI strategy, realized by combining a model-based scheme with a statistical classifier, outperforms the other strategies. In addition, the inclusion of two physical variables that should be measured inside the SOFCs can significantly improve the FDI performance, despite the actual difficulty in performing such measurements.

  10. Fault Diagnosis Strategies for SOFC-Based Power Generation Plants

    Directory of Open Access Journals (Sweden)

    Paola Costamagna

    2016-08-01

    Full Text Available The success of distributed power generation by plants based on solid oxide fuel cells (SOFCs is hindered by reliability problems that can be mitigated through an effective fault detection and isolation (FDI system. However, the numerous operating conditions under which such plants can operate and the random size of the possible faults make identifying damaged plant components starting from the physical variables measured in the plant very difficult. In this context, we assess two classical FDI strategies (model-based with fault signature matrix and data-driven with statistical classification and the combination of them. For this assessment, a quantitative model of the SOFC-based plant, which is able to simulate regular and faulty conditions, is used. Moreover, a hybrid approach based on the random forest (RF classification method is introduced to address the discrimination of regular and faulty situations due to its practical advantages. Working with a common dataset, the FDI performances obtained using the aforementioned strategies, with different sets of monitored variables, are observed and compared. We conclude that the hybrid FDI strategy, realized by combining a model-based scheme with a statistical classifier, outperforms the other strategies. In addition, the inclusion of two physical variables that should be measured inside the SOFCs can significantly improve the FDI performance, despite the actual difficulty in performing such measurements.

  11. Fault Diagnosis Strategies for SOFC-Based Power Generation Plants

    Science.gov (United States)

    Costamagna, Paola; De Giorgi, Andrea; Gotelli, Alberto; Magistri, Loredana; Moser, Gabriele; Sciaccaluga, Emanuele; Trucco, Andrea

    2016-01-01

    The success of distributed power generation by plants based on solid oxide fuel cells (SOFCs) is hindered by reliability problems that can be mitigated through an effective fault detection and isolation (FDI) system. However, the numerous operating conditions under which such plants can operate and the random size of the possible faults make identifying damaged plant components starting from the physical variables measured in the plant very difficult. In this context, we assess two classical FDI strategies (model-based with fault signature matrix and data-driven with statistical classification) and the combination of them. For this assessment, a quantitative model of the SOFC-based plant, which is able to simulate regular and faulty conditions, is used. Moreover, a hybrid approach based on the random forest (RF) classification method is introduced to address the discrimination of regular and faulty situations due to its practical advantages. Working with a common dataset, the FDI performances obtained using the aforementioned strategies, with different sets of monitored variables, are observed and compared. We conclude that the hybrid FDI strategy, realized by combining a model-based scheme with a statistical classifier, outperforms the other strategies. In addition, the inclusion of two physical variables that should be measured inside the SOFCs can significantly improve the FDI performance, despite the actual difficulty in performing such measurements. PMID:27556472

  12. [Frost-resistance of subtropical evergreen woody plants: an evaluation based on plant functional traits].

    Science.gov (United States)

    Xu, Yi-Lu; Yang, Xiao-Dong; Xu, Yue; Xie, Yi-Ming; Wang, Liang-Yan; Yan, En-Rong

    2012-12-01

    Evaluating the frost-resistance of evergreen woody plants is of significance in guiding the species selection in forest management in subtropical region. In this paper, an investigation was made on the functional traits (including specific leaf area, stem wood density, leaf area, leaf dry matter content, leaf relative electrical conductance, and twig wood density) of 64 common evergreen broad-leaved and coniferous woody plant species in the Ningbo region of Zhejiang Province, East China, after a severe snowstorm in early 2008, aimed to select the evergreen woody plants with high ability of freeze-tolerance, and to establish a related evaluation system. By using a hierarchy analysis approach, the weight values of the functional traits of each species were determined, and an index system for evaluating the plants tolerance ability against freeze and mechanical damage was established. Based on this system, 23 evergreen plant species with high tolerance ability against freeze and mechanical damage, such as Cyclobalanopsis gilva, Cyclobalanopsis nubium, Neolitsea aurata, and Vacciniuim mandarinorum, were selected. In the meantime, on the basis of the ordering with each of the functional traits, the ordering of the tolerance ability of the 64 plant species against freeze and mechanical damage was made, and a list for the frost-resistance ability of the subtropical evergreen woody plant species in Ningbo region was constituted. PMID:23479868

  13. Metabolomics for the Authentication of Natural Extracts Used in Flavors and Fragrances: the Case Study of Violet Leaf Absolutes from Viola odorata.

    Science.gov (United States)

    Saint-Lary, Laure; Roy, Céline; Paris, Jean-Philippe; Martin, Jean-François; Thomas, Olivier P; Fernandez, Xavier

    2016-06-01

    Natural extracts used in fine fragrances (alcoholic perfumes) are rare and precious. As such, they represent an interesting target for fraudulent practices called adulterations. Absolutes, important materials used in the creation of perfumes, are obtained by organic solvent extraction of raw plant materials. Because the nonvolatile part of these natural extracts is not normalized and scarcely reported, highlighting potential adulterations present in this fraction appears highly challenging. For the first time, we investigated the use of nontargeted UHPLC-ToFMS metabolomics for this purpose, considering Viola odorata l., a plant largely used in the perfume industry, as a model. Significant differences in the metabolic fingerprints of the violet leaf absolutes were evidenced according to geographical locations, and/or adulterations. Additionally, markers of the geographical origin were detected through their molecular weight/most probable molecular formula and retention time, while adulterations were statistically validated. In this study, we thus clearly demonstrated the efficiency of UHPLC-ToFMS-based metabolomics in accelerating both the identification of the origin of raw materials as well as the search for potential adulterations in absolutes, natural products of high added value. PMID:27135901

  14. (1)H NMR studies distinguish the water soluble metabolomic profiles of untransformed and RAS-transformed cells.

    Science.gov (United States)

    Marks, Vered; Munoz, Anisleidys; Rai, Priyamvada; Walls, Jamie D

    2016-01-01

    Metabolomic profiling is an increasingly important method for identifying potential biomarkers in cancer cells with a view towards improved diagnosis and treatment. Nuclear magnetic resonance (NMR) provides a potentially noninvasive means to accurately characterize differences in the metabolomic profiles of cells. In this work, we use (1)H NMR to measure the metabolomic profiles of water soluble metabolites extracted from isogenic control and oncogenic HRAS-, KRAS-, and NRAS-transduced BEAS2B lung epithelial cells to determine the robustness of NMR metabolomic profiling in detecting differences between the transformed cells and their untransformed counterparts as well as differences among the RAS-transformed cells. Unique metabolomic signatures between control and RAS-transformed cell lines as well as among the three RAS isoform-transformed lines were found by applying principal component analysis to the NMR data. This study provides a proof of principle demonstration that NMR-based metabolomic profiling can robustly distinguish untransformed and RAS-transformed cells as well as cells transformed with different RAS oncogenic isoforms. Thus, our data may potentially provide new diagnostic signatures for RAS-transformed cells. PMID:27330862

  15. mzGroupAnalyzer--predicting pathways and novel chemical structures from untargeted high-throughput metabolomics data.

    Directory of Open Access Journals (Sweden)

    Hannes Doerfler

    Full Text Available The metabolome is a highly dynamic entity and the final readout of the genotype x environment x phenotype (GxExP relationship of an organism. Monitoring metabolite dynamics over time thus theoretically encrypts the whole range of possible chemical and biochemical transformations of small molecules involved in metabolism. The bottleneck is, however, the sheer number of unidentified structures in these samples. This represents the next challenge for metabolomics technology and is comparable with genome sequencing 30 years ago. At the same time it is impossible to handle the amount of data involved in a metabolomics analysis manually. Algorithms are therefore imperative to allow for automated m/z feature extraction and subsequent structure or pathway assignment. Here we provide an automated pathway inference strategy comprising measurements of metabolome time series using LC- MS with high resolution and high mass accuracy. An algorithm was developed, called mzGroupAnalyzer, to automatically explore the metabolome for the detection of metabolite transformations caused by biochemical or chemical modifications. Pathways are extracted directly from the data and putative novel structures can be identified. The detected m/z features can be mapped on a van Krevelen diagram according to their H/C and O/C ratios for pattern recognition and to visualize oxidative processes and biochemical transformations. This method was applied to Arabidopsis thaliana treated simultaneously with cold and high light. Due to a protective antioxidant response the plants turn from green to purple color via the accumulation of flavonoid structures. The detection of potential biochemical pathways resulted in 15 putatively new compounds involved in the flavonoid-pathway. These compounds were further validated by product ion spectra from the same data. The mzGroupAnalyzer is implemented in the graphical user interface (GUI of the metabolomics toolbox COVAIN (Sun & Weckwerth, 2012

  16. 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.

  17. Microbiome, Metabolome and Inflammatory Bowel Disease.

    Science.gov (United States)

    Ahmed, Ishfaq; Roy, Badal C; Khan, Salman A; Septer, Seth; Umar, Shahid

    2016-01-01

    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. PMID:27681914

  18. [Metabolomics analysis of taxadiene producing yeasts].

    Science.gov (United States)

    Yan, Huifang; Ding, Mingzhu; Yuan, Yingjin

    2014-02-01

    In order to study the inherent difference among terpenes producing yeasts from the point of metabolomics, we selected taxadiene producing yeasts as the model system. The changes of cellular metabolites during fermentation log phase of artificial functional yeasts were determined using metabolomics methods. The results represented that compared to W303-1A as a blank control, the metabolites in glycolysis, tricarboxylic acid cycle (TCA) cycle and several amino acids were influenced. And due to the changes of metabolites, the growth of cells was inhibited to a certain extent. Among the metabolites identified, citric acid content in taxadiene producing yeasts changed the most, the decreasing amplitude reached 90% or more. Therefore, citric acid can be a marker metabolite for the future study of artificial functional yeasts. The metabolomics analysis of taxadiene producing yeasts can provide more information in further studies on optimization of terpenes production in heterologous chassis.

  19. Microbiome, Metabolome and Inflammatory Bowel Disease

    Science.gov (United States)

    Ahmed, Ishfaq; Roy, Badal C.; Khan, Salman A.; Septer, Seth; Umar, Shahid

    2016-01-01

    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. PMID:27681914

  20. 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.

  1. Fracture mechanics based life assessment in petrochemical plants

    International Nuclear Information System (INIS)

    The increasing use of thick walled pressure vessels in petrochemical plants operating at high pressure under severe service conditions could lead to catastrophic failure. In the Malaysian Institute for Nuclear Technology Research (MINT), initial efforts are underway to apply fracture mechanics approach for assessment of significance of defects detected during periodic in service inspection (ISI) of industrial plants. This paper outlines the integrity management strategy based on fracture mechanics and proposes a new procedure for life assessment of petrochemical plants based on ASME Boiler and Pressure Vessel Code, Section XI, BSI PD 6493:1991, BSI 6539:1994, BSI Standard 7910:1999 and API 579:2000. Essential relevant data required for the assessment is listed. Several methods available for determination of fracture toughness are reviewed with limitations in their application to petrochemical plants. A new non destructive method for determination of fracture toughness based on hardness testing and normalized key roughness curve is given. Results of fracture mechanics based life assessment conducted for 100 mm thick ammonia converter of Ni r o steel and 70 mm thick plat forming reactor vessel of ASTM A 38 7 grade B steel in operational fertilizer and petroleum refining plants are presented. (Author)

  2. Metabolomics for in situ environmental monitoring of surface waters impacted by contaminants from both point and non-point sources

    Science.gov (United States)

    We investigated the efficacy of metabolomics for field-monitoring of fish exposed to waste water treatment plant (WWTP) effluents and non-point sources of chemical contamination. Lab-reared male fathead minnows (Pimephales promelas, FHM) were held in mobile monitoring units and e...

  3. NMR and pattern recognition methods in metabolomics: From data acquisition to biomarker discovery: A review

    Energy Technology Data Exchange (ETDEWEB)

    Smolinska, Agnieszka, E-mail: A.Smolinska@science.ru.nl [Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen (Netherlands); Blanchet, Lionel [Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen (Netherlands); Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Buydens, Lutgarde M.C.; Wijmenga, Sybren S. [Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen (Netherlands)

    2012-10-31

    Highlights: Black-Right-Pointing-Pointer Procedures for acquisition of different biofluids by NMR. Black-Right-Pointing-Pointer Recent developments in metabolic profiling of different biofluids by NMR are presented. Black-Right-Pointing-Pointer The crucial steps involved in data preprocessing and multivariate chemometric analysis are reviewed. Black-Right-Pointing-Pointer Emphasis is given on recent findings on Multiple Sclerosis via NMR and pattern recognition methods. - Abstract: Metabolomics is the discipline where endogenous and exogenous metabolites are assessed, identified and quantified in different biological samples. Metabolites are crucial components of biological system and highly informative about its functional state, due to their closeness to functional endpoints and to the organism's phenotypes. Nuclear Magnetic Resonance (NMR) spectroscopy, next to Mass Spectrometry (MS), is one of the main metabolomics analytical platforms. The technological developments in the field of NMR spectroscopy have enabled the identification and quantitative measurement of the many metabolites in a single sample of biofluids in a non-targeted and non-destructive manner. Combination of NMR spectra of biofluids and pattern recognition methods has driven forward the application of metabolomics in the field of biomarker discovery. The importance of metabolomics in diagnostics, e.g. in identifying biomarkers or defining pathological status, has been growing exponentially as evidenced by the number of published papers. In this review, we describe the developments in data acquisition and multivariate analysis of NMR-based metabolomics data, with particular emphasis on the metabolomics of Cerebrospinal Fluid (CSF) and biomarker discovery in Multiple Sclerosis (MScl).

  4. MetabR: an R script for linear model analysis of quantitative metabolomic data

    Directory of Open Access Journals (Sweden)

    Ernest Ben

    2012-10-01

    Full Text Available Abstract Background Metabolomics is an emerging high-throughput approach to systems biology, but data analysis tools are lacking compared to other systems level disciplines such as transcriptomics and proteomics. Metabolomic data analysis requires a normalization step to remove systematic effects of confounding variables on metabolite measurements. Current tools may not correctly normalize every metabolite when the relationships between each metabolite quantity and fixed-effect confounding variables are different, or for the effects of random-effect confounding variables. Linear mixed models, an established methodology in the microarray literature, offer a standardized and flexible approach for removing the effects of fixed- and random-effect confounding variables from metabolomic data. Findings Here we present a simple menu-driven program, “MetabR”, designed to aid researchers with no programming background in statistical analysis of metabolomic data. Written in the open-source statistical programming language R, MetabR implements linear mixed models to normalize metabolomic data and analysis of variance (ANOVA to test treatment differences. MetabR exports normalized data, checks statistical model assumptions, identifies differentially abundant metabolites, and produces output files to help with data interpretation. Example data are provided to illustrate normalization for common confounding variables and to demonstrate the utility of the MetabR program. Conclusions We developed MetabR as a simple and user-friendly tool for implementing linear mixed model-based normalization and statistical analysis of targeted metabolomic data, which helps to fill a lack of available data analysis tools in this field. The program, user guide, example data, and any future news or updates related to the program may be found at http://metabr.r-forge.r-project.org/.

  5. A Novel Metabolomic Data Scaling Method Based on K-L Divergence%基于K-L散度的核磁共振波谱数据尺度缩放方法

    Institute of Scientific and Technical Information of China (English)

    邓伶莉; Cheng Kian-Kai; 沈桂平; 周玲; 刘新卓; 董继扬; 陈忠

    2014-01-01

    A new scaling method in the current study based on Kullback-Leibler (K-L) divergence is proposed for NMR metabo-lomic data .The proposed method (called K-L scaling) is a supervised scaling method as group information is incorporated in the scaling procedure .Notably ,K-L divergence measures the difference between two different datasets by their probability distribu-tions ,it can be used for the analysis of data that either follows Gaussian or non-Gaussian distributions .In K-L scaling ,all varia-bles were first standardized to unit variance ,then their variance was adjusted using Kullback -Leibler divergence to highlight the significant variables .K-L scaling can tell effectively the difference in spectral data points between two experimental groups ,and then enhances the weights of biological-relevant variables ,and at the same time reduces the weight of noise and uninformative variables .The developed method was applied to a 1 H-NMR metabolomic dataset acquired from human urine .Analysis results of the dataset showed that this new scaling method is efficient in suppressing the contribution of noise in the resulting multivariate model .In addition ,it can increase the weights of important variables ,and improve the interpretability and predictability of sub-sequent principal component regression (PCR) and partial least squares discriminant analysis (PLS-DA) .Furthermore ,the scal-ing method facilitated the identification of metabolic signatures .The current result suggested that the developed K-L scaling method may become a useful alternative for the preprocessing of NMR-based metabolomic data .%在基于核磁共振(NMR)的代谢组学数据分析中,尺度缩放是关键的预处理步骤之一,其主要目的是通过调整数据的方差结构,改善后续的多变量统计分析的结果。从信息熵的角度出发,利用 K ullback-Leibler (K-L)散度来度量不同实验分组的生物样品的1 H NMR波谱数据的差异程度,并结合

  6. Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants

    Directory of Open Access Journals (Sweden)

    Marie-Ève Lebel

    2015-08-01

    Full Text Available Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease.

  7. Manufactured soils for plant growth at a lunar base

    Science.gov (United States)

    Ming, Douglas W.

    1989-01-01

    Advantages and disadvantages of synthetic soils are discussed. It is pointed out that synthetic soils may provide the proper physical and chemical properties necessary to maximize plant growth, such as a toxic-free composition and cation exchange capacities. The importance of nutrient retention, aeration, moisture retention, and mechanical support as qualities for synthetic soils are stressed. Zeoponics, or the cultivation of plants in zeolite substrates that both contain essential plant-growth cations on their exchange sites and have minor amounts of mineral phases and/or anion-exchange resins that supply essential plant growth ions, is discussed. It is suggested that synthetic zeolites at lunar bases could provide adsorption media for separation of various gases, act as catalysts and as molecular sieves, and serve as cation exchangers in sewage-effluent treatment, radioactive-waste disposal, and pollution control. A flow chart of a potential zeoponics system illustrates this process.

  8. Physics-Based Prognostics for Optimizing Plant Operation

    Energy Technology Data Exchange (ETDEWEB)

    Leonard J. Bond; Don B. Jarrell

    2005-03-01

    Scientists at the Pacific Northwest National Laboratory (PNNL) have examined the necessity for optimization of energy plant operation using 'DSOM{reg_sign}'--Decision Support Operation and Maintenance and this has been deployed at several sites. This approach has been expanded to include a prognostics components and tested on a pilot scale service water system, modeled on the design employed in a nuclear power plant. A key element in plant optimization is understanding and controlling the aging process of safety-specific nuclear plant components. This paper reports the development and demonstration of a physics-based approach to prognostic analysis that combines distributed computing, RF data links, the measurement of aging precursor metrics and their correlation with degradation rate and projected machine failure.

  9. Photoprotection in Plants Optical Screening-based Mechanisms

    CERN Document Server

    Solovchenko, Alexei

    2010-01-01

    Optical screening of excessive and potentially harmful solar radiation is an important photoprotective mechanism, though it has received much less attention in comparison with other systems preventing photooxidative damage to photoautotrophic organisms. This photoprotection in the form of screening appears to be especially important for juvenile and senescing plants as well as under environmental stresses—i.e. in situations where the efficiency of enzymatic ROS elimination, DNA repair and other ‘classical’ photoprotective systems could be impaired. This book represents an attempt to develop an integral view of optical screening-based photoprotection in microalgae and higher plants. Towards this end, the key groups of pigments involved in the screening of ultraviolet and visible components of solar radiation in microalgae and higher plants, and the patterns of their accumulation and distribution within plant cells and tissues, are described. Special attention is paid to the manifestations of screening pi...

  10. Time-resolved metabolomics reveals metabolic modulation in rice foliage

    Directory of Open Access Journals (Sweden)

    Arita Masanori

    2008-06-01

    Full Text Available Abstract Background To elucidate the interaction of dynamics among modules that constitute biological systems, comprehensive datasets obtained from "omics" technologies have been used. In recent plant metabolomics approaches, the reconstruction of metabolic correlation networks has been attempted using statistical techniques. However, the results were unsatisfactory and effective data-mining techniques that apply appropriate comprehensive datasets are needed. Results Using capillary electrophoresis mass spectrometry (CE-MS and capillary electrophoresis diode-array detection (CE-DAD, we analyzed the dynamic changes in the level of 56 basic metabolites in plant foliage (Oryza sativa L. ssp. japonica at hourly intervals over a 24-hr period. Unsupervised clustering of comprehensive metabolic profiles using Kohonen's self-organizing map (SOM allowed classification of the biochemical pathways activated by the light and dark cycle. The carbon and nitrogen (C/N metabolism in both periods was also visualized as a phenotypic linkage map that connects network modules on the basis of traditional metabolic pathways rather than pairwise correlations among metabolites. The regulatory networks of C/N assimilation/dissimilation at each time point were consistent with previous works on plant metabolism. In response to environmental stress, glutathione and spermidine fluctuated synchronously with their regulatory targets. Adenine nucleosides and nicotinamide coenzymes were regulated by phosphorylation and dephosphorylation. We also demonstrated that SOM analysis was applicable to the estimation of unidentifiable metabolites in metabolome analysis. Hierarchical clustering of a correlation coefficient matrix could help identify the bottleneck enzymes that regulate metabolic networks. Conclusion Our results showed that our SOM analysis with appropriate metabolic time-courses effectively revealed the synchronous dynamics among metabolic modules and elucidated the

  11. Metabolomics investigation to shed light on cheese as a possible piece in the French paradox puzzle

    DEFF Research Database (Denmark)

    Zheng, Hong; Yde, Christian C; Clausen, Morten R;

    2015-01-01

    An NMR-based metabolomics approach was used to investigate the differentiation between subjects consuming cheese or milk and to elucidate the potential link to an effect on the blood cholesterol level. Fifteen healthy young men participated in a full cross-over study where they consumed three iso...

  12. Metabolomics Approach to Anabolic Steroid Urine Profiling of Bovines Treated with Prohormones

    NARCIS (Netherlands)

    Rijk, J.C.W.; Lommen, A.; Essers, M.L.; Groot, M.J.; Hende, van J.; Doeswijk, T.G.; Nielen, M.W.F.

    2009-01-01

    In livestock production, illegal use of natural steroids is hard to prove because metabolites are either unknown or not significantly above highly fluctuating endogenous levels. In this work we outlined for the first time a metabolomics based strategy for anabolic steroid urine profiling. Urine prof

  13. The volatile metabolome of grapevine roots: First insights into the metabolic response upon phylloxera attack

    OpenAIRE

    Nora C Lawo; Weingart, Georg J.F.; Schuhmacher, Rainer; Forneck, Astrid

    2011-01-01

    Many plant species respond to herbivore attack by an increased formation of volatile organic compounds. In this preliminary study we analysed the volatile metabolome of grapevine roots [Teleki 5C (Vitis berlandieri Planch. × Vitis riparia Michx.)] with the aim to gain insight into the interaction between phylloxera (Daktulosphaira vitifoliae Fitch; Hemiptera: Phylloxeridae) and grapevine roots. In the first part of the study, headspace solid phase microextraction (HS-SPME) coupled to gas chro...

  14. PlantGL: A Python-based geometric library for 3D plant modelling at different scales

    OpenAIRE

    Pradal, Christophe; Boudon, Frédéric; Nouguier, Christophe; Chopard, Jérôme; Godin, Christophe

    2009-01-01

    International audience In this paper, we present PlantGL, an open-source graphic toolkit for the creation, simulation and analysis of 3D virtual plants. This C++ geometric library is embedded in the Python language which makes it a powerful user-interactive platform for plant modeling in various biological application domains. PlantGL makes it possible to build and manipulate geometric models of plants or plant parts, ranging from tissues and organs to plant populations. Based on a scene g...

  15. Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction

    Institute of Scientific and Technical Information of China (English)

    Taru K Pilvi; Tuulikki Sepp(a)nen-Laakso; Helena Simolin; Piet Finckenberg; Anne Huotari; Karl-Heinz Herzig; Riitta Korpela; Matej Ore(s)i(c); Eero M Mervaala

    2008-01-01

    AIM: To characterise the effect of energy restriction (ER) on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further enhanced by modification of dietary protein source and calcium.METHODS: Liver metabolomic profile of lean and obese C57BI/6] mice (n = 10/group) were compared with two groups of weight-reduced mice. ER was performed on control diet and whey protein-based high-calcium diet (whey + Ca). The metabolomic an alyses were performed using the UPLC/MS based lipidomic platform and the HPLC/MS/MS based primary metabolite platform.RESULTS: ER on both diets significantly reduced hepatic lipid accumulation and lipid droplet size, while only whey + Ca diet significantly decreased blood glucose (P 0.05, vs lean). These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway metabolites.CONCLUSION: ER-induced changes on hepatic metabolomic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.

  16. Training in metabolomics research. I. Designing the experiment, collecting and extracting samples and generating metabolomics data

    Science.gov (United States)

    Barnes, Stephen; Benton, H. Paul; Casazza, Krista; Cooper, Sara J.; Cui, Xiangqin; Du, Xiuxia; Engler, Jeffrey; Kabarowski, Janusz H.; Li, Shuzhao; Pathmasiri, Wimal; Prasain, Jeevan K.; Renfrow, Matthew B.; Tiwari, Hemant K.

    2016-01-01

    The study of metabolism has had a long history. Metabolomics, a systems biology discipline representing analysis of known and unknown pathways of metabolism, has grown tremendously over the past 20 years. Because of its comprehensive nature, metabolomics requires careful consideration of the question(s) being asked, the scale needed to answer the question(s), collection and storage of the sample specimens, methods for extraction of the metabolites from biological matrices, the analytical method(s) to be employed and the quality control of the analyses, how collected data are correlated, the statistical methods to determine metabolites undergoing significant change, putative identification of metabolites and the use of stable isotopes to aid in verifying metabolite identity and establishing pathway connections and fluxes. The National Institutes of Health Common Fund Metabolomics Program was established in 2012 to stimulate interest in the approaches and technologies of metabolomics. To deliver one of the program’s goals, the University of Alabama at Birmingham has hosted an annual 4-day short course in metabolomics for faculty, postdoctoral fellows and graduate students from national and international institutions. This paper is the first part of a summary of the training materials presented in the course to be used as a resource for all those embarking on metabolomics research. PMID:27434804

  17. Anti-acetylcholinesterase potential and metabolome classification of 4 Ocimum species as determined via UPLC/qTOF/MS and chemometric tools.

    Science.gov (United States)

    Farag, M A; Ezzat, S M; Salama, M M; Tadros, M G

    2016-06-01

    Ocimum (sweet basil) is a plant of considerable commercial importance in traditional medicine worldwide as well as for the flavor and food industry. The goal of this study was to examine Ocimum extracts anti-acetylcholinesterase activity and to correlate the activity with their secondary metabolites profiles via a metabolome based ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) approach coupled to chemometrics. The metabolomic differences in phenolics from leaves derived from 4 Ocimum species: Ocimum basilicum, Ocimum africanum, Ocimum americanum and Ocimum minimum were assessed. Under optimized conditions, 81 metabolites were identified including 21 hydroxy cinnamic acids, 4 benzoic acid conjugates, 14C/O flavonoid conjugates, 2 alcohols, 5 acyl sugars, 4 triterpenes and 12 fatty acids. Several salviolanic acid derivatives including salviolanic acid A, B, C & I found in Salvia, were found in Ocimum herein for the first time. Unsupervised principal component analysis (PCA) and supervised orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were further used for comparing and classification of samples. A clear separation among the four investigated Ocimum species was revealed, with O. africanum samples found most enriched in hydroxy cinnamates conjugates (HC) and flavonoids. To the best of our knowledge, this is the first report for compositional differences among Ocimum leaves via a metabolomic approach revealing that among examined species O. africanum leaves present a better source of Ocimum bioactive metabolites. The anticholinesrase activity of examined species was further assessed with a potent IC50 values for O. americanum, O. africanum, O. basilicum ranging from 2.5 to 6.6mg/ml, whereas O. minimum was least active with IC50 of 31.4mg/ml. Furthermore, major HC i.e., caftaric, chlorogenic and rosmarinic acids identified in extracts via UPLC-MS analysis exhibited IC50 values of 24, 0.5 and 7.9mg/ml respectively

  18. Data analysis strategies in nutritional metabolomics

    NARCIS (Netherlands)

    J. Westerhuis; E. van Velzen; H. Hoefsloot; A. Smilde

    2009-01-01

    In the expanding field of nutritional metabolomics the use of optimized and robust strategies are essential to find meaningful and significant results. Data from nutritional studies can be extremely large, multidimensional and complex. Moreover the data may hide just a subtle biological variation du

  19. 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...

  20. 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.

  1. 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

  2. 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

  3. Plant-based fertilizers for organic vegetable production

    DEFF Research Database (Denmark)

    Sørensen, Jørn Nygaard; Thorup-Kristensen, Kristian

    2011-01-01

    fertility, the term “mobile green manures” is used for green-manure crops that are harvested in one field and then moved as a whole and used as fertilizer in other fields. To further investigate mobile-green-manure crops for use as efficient fertilizers, pot and field experiments were conducted......To ensure high yield and quality in organic vegetable production, crops often require additional fertilizer applied during the season. Due to the risk of contamination of edible plant products from slurry, plant-based fertilizers may be used as an alternative. The purpose of our work was to develop...

  4. Biomarkers of whale shark health: a metabolomic approach.

    Science.gov (United States)

    Dove, Alistair D M; Leisen, Johannes; Zhou, Manshui; Byrne, Jonathan J; Lim-Hing, Krista; Webb, Harry D; Gelbaum, Leslie; Viant, Mark R; Kubanek, Julia; Fernández, Facundo M

    2012-01-01

    In a search for biomarkers of health in whale sharks and as exploration of metabolomics as a modern tool for understanding animal physiology, the metabolite composition of serum in six whale sharks (Rhincodon typus) from an aquarium collection was explored using (1)H nuclear magnetic resonance (NMR) spectroscopy and direct analysis in real time (DART) mass spectrometry (MS). Principal components analysis (PCA) of spectral data showed that individual animals could be resolved based on the metabolite composition of their serum and that two unhealthy individuals could be discriminated from the remaining healthy animals. The major difference between healthy and unhealthy individuals was the concentration of homarine, here reported for the first time in an elasmobranch, which was present at substantially lower concentrations in unhealthy whale sharks, suggesting that this metabolite may be a useful biomarker of health status in this species. The function(s) of homarine in sharks remain uncertain but it likely plays a significant role as an osmolyte. The presence of trimethylamine oxide (TMAO), another well-known protective osmolyte of elasmobranchs, at 0.1-0.3 mol L(-1) was also confirmed using both NMR and MS. Twenty-three additional potential biomarkers were identified based on significant differences in the frequency of their occurrence between samples from healthy and unhealthy animals, as detected by DART MS. Overall, NMR and MS provided complementary data that showed that metabolomics is a useful approach for biomarker prospecting in poorly studied species like elasmobranchs.

  5. Biomarkers of whale shark health: a metabolomic approach.

    Directory of Open Access Journals (Sweden)

    Alistair D M Dove

    Full Text Available In a search for biomarkers of health in whale sharks and as exploration of metabolomics as a modern tool for understanding animal physiology, the metabolite composition of serum in six whale sharks (Rhincodon typus from an aquarium collection was explored using (1H nuclear magnetic resonance (NMR spectroscopy and direct analysis in real time (DART mass spectrometry (MS. Principal components analysis (PCA of spectral data showed that individual animals could be resolved based on the metabolite composition of their serum and that two unhealthy individuals could be discriminated from the remaining healthy animals. The major difference between healthy and unhealthy individuals was the concentration of homarine, here reported for the first time in an elasmobranch, which was present at substantially lower concentrations in unhealthy whale sharks, suggesting that this metabolite may be a useful biomarker of health status in this species. The function(s of homarine in sharks remain uncertain but it likely plays a significant role as an osmolyte. The presence of trimethylamine oxide (TMAO, another well-known protective osmolyte of elasmobranchs, at 0.1-0.3 mol L(-1 was also confirmed using both NMR and MS. Twenty-three additional potential biomarkers were identified based on significant differences in the frequency of their occurrence between samples from healthy and unhealthy animals, as detected by DART MS. Overall, NMR and MS provided complementary data that showed that metabolomics is a useful approach for biomarker prospecting in poorly studied species like elasmobranchs.

  6. Biomarkers of whale shark health: a metabolomic approach.

    Science.gov (United States)

    Dove, Alistair D M; Leisen, Johannes; Zhou, Manshui; Byrne, Jonathan J; Lim-Hing, Krista; Webb, Harry D; Gelbaum, Leslie; Viant, Mark R; Kubanek, Julia; Fernández, Facundo M

    2012-01-01

    In a search for biomarkers of health in whale sharks and as exploration of metabolomics as a modern tool for understanding animal physiology, the metabolite composition of serum in six whale sharks (Rhincodon typus) from an aquarium collection was explored using (1)H nuclear magnetic resonance (NMR) spectroscopy and direct analysis in real time (DART) mass spectrometry (MS). Principal components analysis (PCA) of spectral data showed that individual animals could be resolved based on the metabolite composition of their serum and that two unhealthy individuals could be discriminated from the remaining healthy animals. The major difference between healthy and unhealthy individuals was the concentration of homarine, here reported for the first time in an elasmobranch, which was present at substantially lower concentrations in unhealthy whale sharks, suggesting that this metabolite may be a useful biomarker of health status in this species. The function(s) of homarine in sharks remain uncertain but it likely plays a significant role as an osmolyte. The presence of trimethylamine oxide (TMAO), another well-known protective osmolyte of elasmobranchs, at 0.1-0.3 mol L(-1) was also confirmed using both NMR and MS. Twenty-three additional potential biomarkers were identified based on significant differences in the frequency of their occurrence between samples from healthy and unhealthy animals, as detected by DART MS. Overall, NMR and MS provided complementary data that showed that metabolomics is a useful approach for biomarker prospecting in poorly studied species like elasmobranchs. PMID:23166652

  7. Urinary metabolomic fingerprinting after consumption of a probiotic strain in women with mastitis.

    Science.gov (United States)

    Vázquez-Fresno, Rosa; Llorach, Rafael; Marinic, Jelena; Tulipani, Sara; Garcia-Aloy, Mar; Espinosa-Martos, Irene; Jiménez, Esther; Rodríguez, Juan Miguel; Andres-Lacueva, Cristina

    2014-09-01

    Infectious mastitis is a common condition among lactating women, with staphylococci and streptococci being the main aetiological agents. In this context, some lactobacilli strains isolated from breast milk appear to be particularly effective for treating mastitis and, therefore, constitute an attractive alternative to antibiotherapy. A (1)H NMR-based metabolomic approach was applied to detect metabolomic differences after consuming a probiotic strain (Lactobacillus salivarius PS2) in women with mastitis. 24h urine of women with lactational mastitis was collected at baseline and after 21 days of probiotic (PB) administration. Multivariate analysis (OSC-PLS-DA and hierarchical clustering) showed metabolome differences after PB treatment. The discriminant metabolites detected at baseline were lactose, and ibuprofen and acetaminophen (two pharmacological drugs commonly used for mastitis pain), while, after PB intake, creatine and the gut microbial co-metabolites hippurate and TMAO were detected. In addition, a voluntary desertion of the pharmacological drugs ibuprofen and acetaminophen was observed after probiotic administration. The application of NMR-based metabolomics enabled the identification of the overall effects of probiotic consumption among women suffering from mastitis and highlighted the potential of this approach in evaluating the outcomes of probiotics consumption. To our knowledge, this is the first time that this approach has been applied in women with mastitis during lactation.

  8. Introduction of nuclear power plant based on reliability centered maintenance

    International Nuclear Information System (INIS)

    A maintenance program based on RCM (reliability centered maintenance) is used by many countries and increased safety, reliability and economy of plants. RCM and its application conditions to the nuclear power plants in USA and introduction conditions for Japan are explained. The present situation of maintenance and change of maintenance technologies in the world is stated. RCM is the best tool for working out the maintenance program. The basic approach is selection of system and the sphere of activity, identification of accident mode and causes by the FFA (functional failure analysis) and the FMEA (failure modes and effects analysis), and selection of the effective maintenance method for accident mode by the LTA (logic tree analysis) and optimization of maintenance. The maintenance of nuclear power plants and an on-side inspection of RCM in USA are described. The system for maintenance program and construction of the system for keeping the electric power joint technologies in Japan are illustrated. (S.Y.)

  9. Multimedia-based Medicinal Plants Sustainability Management System

    Directory of Open Access Journals (Sweden)

    Zacchaeus Omogbadegun

    2011-09-01

    Full Text Available Medicinal plants are increasingly recognized worldwide as an alternative source of efficacious and inexpensive medications to synthetic chemo-therapeutic compound. Rapid declining wild stocks of medicinal plants accompanied by adulteration and species substitutions reduce their efficacy, quality and safety. Consequently, the low accessibility to and non-affordability of orthodox medicine costs by rural dwellers to be healthy and economically productive further threaten their life expectancy. Finding comprehensive information on medicinal plants of conservation concern at a global level has been difficult. This has created a gap between computing technologies' promises and expectations in the healing process under complementary and alternative medicine. This paper presents the design and implementation of a Multimedia-based Medicinal Plants Sustainability Management System addressing these concerns. Medicinal plants' details for designing the system were collected through semi-structured interviews and databases. Unified Modelling Language, Microsoft-Visual-Studio.Net, C#3.0, Microsoft-Jet-Engine4.0, MySQL, Loquendo Multilingual Text-to-Speech Software, YouTube, and VLC Media Player were used.

  10. 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

  11. Quantitative profiling of bile acids in biofluids and tissues based on accurate mass high resolution LC-FT-MS: Compound class targeting in a metabolomics workflow

    NARCIS (Netherlands)

    Bobeldijk, I.; Hekman, M.; Vries de- Weij, J.van der; Coulier, L.; Ramaker, R.; Kleemann, R.; Kooistra, T.; Rubingh, C.; Freidig, A.; Verheij, E.

    2008-01-01

    We report a sensitive, generic method for quantitative profiling of bile acids and other endogenous metabolites in small quantities of various biological fluids and tissues. The method is based on a straightforward sample preparation, separation by reversed-phase high performance liquid-chromatograp

  12. 基于核磁及质谱分析技术的代谢组学在卵巢癌中的研究%NMR and mass spectrometry techniques based metabolomics in ovarian cancer research

    Institute of Scientific and Technical Information of China (English)

    葛婷婷; 娄阁

    2013-01-01

    卵巢癌是女性生殖器官恶性肿瘤中死亡率最高的疾病,早期无明显症状,70%的患者发现时已为晚期,所以卵巢癌的早发现、早治疗及个性化诊疗方案是肿瘤治疗的发展方向.代谢组学(Metabolomics)作为一种新兴技术为卵巢癌的早期诊断、疗效评价及预后判断打开了新窗口.在卵巢癌的发生发展过程中,机体产生不同的代谢产物,代谢组学能对机体代谢变化作出整体评价,筛选出有价值的生物标志物,用于肿瘤的早期诊断、治疗及预后评估.本文就代谢组学的概念和方法,代谢组学在卵巢癌的早期诊断、病理分型及靶向治疗的应用做一综述.%Ovarian cancer is the highest mortality in the female genital malignancies. Because no obvious symptoms of early ovarian cancer,it is found 70% of patients with advanced. Therefore, early detection of ovarian cancer, early treatment and personalized treatment programs is the development direction of cancer treatment. Metabolomics as an emerging technology for the early diagnosis of ovarian cancer,the efficacy evaluation and prognosis has opened up a new window. Metabolomics can make a comprehensive e-valuation of changes in metabolism, screened valuable biomarker for early diagnosis and treatment of tumors, treatment and prognosis. In this paper,we reviewed the concepts and methods of metabolomics as well as metabolomics in the early diagnosis of ovarian cancer, pathological type and targeted therapy applications.

  13. Analysis of axial-induction-based wind plant control using an engineering and a high-order wind plant model

    Energy Technology Data Exchange (ETDEWEB)

    Annoni, Jennifer [Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Aerospace Engineering and Mechanics; Gebraad, Pieter M. O. [National Renewable Energy Laboratory, Golden CO (United States); Scholbrock, Andrew K. [National Renewable Energy Laboratory, Golden CO (United States); Fleming, Paul A. [National Renewable Energy Laboratory, Golden CO (United States); Wingerden, Jan-Willem van [Delft Center for Systems and Control, Delft University of Technology, Delft (Netherlands)

    2015-08-14

    Wind turbines are typically operated to maximize their performance without considering the impact of wake effects on nearby turbines. Wind plant control concepts aim to increase overall wind plant performance by coordinating the operation of the turbines. This paper focuses on axial-induction-based wind plant control techniques, in which the generator torque or blade pitch degrees of freedom of the wind turbines are adjusted. The paper addresses discrepancies between a high-order wind plant model and an engineering wind plant model. Changes in the engineering model are proposed to better capture the effects of axial-induction-based control shown in the high-order model.

  14. Present and foreseeable future of metabolomics in forensic analysis.

    Science.gov (United States)

    Castillo-Peinado, L S; Luque de Castro, M D

    2016-06-21

    The revulsive publications during the last years on the precariousness of forensic sciences worldwide have promoted the move of major steps towards improvement of this science. One of the steps (viz. a higher involvement of metabolomics in the new era of forensic analysis) deserves to be discussed under different angles. Thus, the characteristics of metabolomics that make it a useful tool in forensic analysis, the aspects in which this omics is so far implicit, but not mentioned in forensic analyses, and how typical forensic parameters such as the post-mortem interval or fingerprints take benefits from metabolomics are critically discussed in this review. The way in which the metabolomics-forensic binomial succeeds when either conventional or less frequent samples are used is highlighted here. Finally, the pillars that should support future developments involving metabolomics and forensic analysis, and the research required for a fruitful in-depth involvement of metabolomics in forensic analysis are critically discussed.

  15. Metabolomics and its application to studying metal toxicity.

    Science.gov (United States)

    Booth, Sean C; Workentine, Matthew L; Weljie, Aalim M; Turner, Raymond J

    2011-11-01

    Here we explain the omics approach of metabolomics and how it can be applied to study a physiological response to toxic metal exposure. This review aims to educate the metallomics field to the tool of metabolomics. Metabolomics is becoming an increasingly used tool to compare natural and challenged states of various organisms, from disease states in humans to toxin exposure to environmental systems. This approach is key to understanding and identifying the cellular or biochemical targets of metals and the underlying physiological response. Metabolomics steps are described and overviews of its application to metal toxicity to organisms are given. As this approach is very new there are yet only a small number of total studies and therefore only a brief overview of some metal metabolomics studies is described. A frank critical evaluation of the approach is given to provide newcomers to the method a clear idea of the challenges and the rewards of applying metabolomics to their research.

  16. 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.

  17. Plant operator performance evaluation based on cognitive process analysis experiment

    International Nuclear Information System (INIS)

    This paper reports on an experiment to clarify plant operators' cognitive processes that has been performed, to improve the man-machine interface which supports their diagnoses and decisions. The cognitive processes under abnormal conditions were evaluated by protocol analyses interviews, etc. in the experiment using a plant training simulator. A cognitive process model is represented by a stochastic network, based on Rasmussen's decision making model. Each node of the network corresponds to an element of the cognitive process, such as observation, interpretation, execution, etc. Some observations were obtained as follows, by comparison of Monte Carlo simulation results with the experiment results: A process to reconfirm the plant parameters after execution of a task and feedback paths from this process to the observation and the task definition of next task were observed. The feedback probability average and standard deviation should be determined for each incident type to explain correctly the individual differences in the cognitive processes. The tendency for the operator's cognitive level to change from skill-based to knowledge-based via rule-based behavior was observed during the feedback process

  18. Metabolomic unveiling of a diverse range of green tea (Camellia sinensis) metabolites dependent on geography.

    Science.gov (United States)

    Lee, Jang-Eun; Lee, Bum-Jin; Chung, Jin-Oh; Kim, Hak-Nam; Kim, Eun-Hee; Jung, Sungheuk; Lee, Hyosang; Lee, Sang-Jun; Hong, Young-Shick

    2015-05-01

    Numerous factors such as geographical origin, cultivar, climate, cultural practices, and manufacturing processes influence the chemical compositions of tea, in the same way as growing conditions and grape variety affect wine quality. However, the relationships between these factors and tea chemical compositions are not well understood. In this study, a new approach for non-targeted or global analysis, i.e., metabolomics, which is highly reproducible and statistically effective in analysing a diverse range of compounds, was used to better understand the metabolome of Camellia sinensis and determine the influence of environmental factors, including geography, climate, and cultural practices, on tea-making. We found a strong correlation between environmental factors and the metabolome of green, white, and oolong teas from China, Japan, and South Korea. In particular, multivariate statistical analysis revealed strong inter-country and inter-city relationships in the levels of theanine and catechin derivatives found in green and white teas. This information might be useful for assessing tea quality or producing distinct tea products across different locations, and highlights simultaneous identification of diverse tea metabolites through an NMR-based metabolomics approach. PMID:25529705

  19. 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.

  20. GIM3E: Condition-specific Models of Cellular Metabolism Developed from Metabolomics and Expression Data

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Brian; Ebrahim, Ali; Metz, Thomas O.; Adkins, Joshua N.; Palsson, Bernard O.; Hyduke, Daniel R.

    2013-11-15

    Motivation: Genome-scale metabolic models have been used extensively to investigate alterations in cellular metabolism. The accuracy of these models to represent cellular metabolism in specific conditions has been improved by constraining the model with omics data sources. However, few practical methods for integrating metabolomics data with other omics data sources into genome-scale models of metabolism have been reported. Results: GIMMME (Gene Inactivation Moderated by Metabolism, Metabolomics, and Expression) is an algorithm that enables the development of condition-specific models based on an objective function, transcriptomics, and intracellular metabolomics data. GIMMME establishes metabolite utilization requirements with metabolomics data, uses model-paired transcriptomics data to find experimentally supported solutions, and also provides calculations of the turnover (production / consumption) flux of metabolites. GIMMME was employed to investigate the effects of integrating additional omics datasets to create increasingly constrained solution spaces of Salmonella Typhimurium metabolism during growth in both rich and virulence media. This integration proved to be informative and resulted in a requirement of additional active reactions (12 in each case) or metabolites (26 or 29, respectively). The addition of constraints from transcriptomics also impacted the allowed solution space, and the cellular metabolites with turnover fluxes that were necessarily altered by the change in conditions increased from 118 to 271 of 1397. Availability: GIMMME has been implemented in Python and requires a COBRApy 0.2.x. The algorithm and sample data described here are freely available at: http://opencobra.sourceforge.net/

  1. Tools and Databases of the KOMICS Web Portal for Preprocessing, Mining, and Dissemination of Metabolomics Data

    Directory of Open Access Journals (Sweden)

    Nozomu Sakurai

    2014-01-01

    Full Text Available A metabolome—the collection of comprehensive quantitative data on metabolites in an organism—has been increasingly utilized for applications such as data-intensive systems biology, disease diagnostics, biomarker discovery, and assessment of food quality. A considerable number of tools and databases have been developed to date for the analysis of data generated by various combinations of chromatography and mass spectrometry. We report here a web portal named KOMICS (The Kazusa Metabolomics Portal, where the tools and databases that we developed are available for free to academic users. KOMICS includes the tools and databases for preprocessing, mining, visualization, and publication of metabolomics data. Improvements in the annotation of unknown metabolites and dissemination of comprehensive metabolomic data are the primary aims behind the development of this portal. For this purpose, PowerGet and FragmentAlign include a manual curation function for the results of metabolite feature alignments. A metadata-specific wiki-based database, Metabolonote, functions as a hub of web resources related to the submitters' work. This feature is expected to increase citation of the submitters' work, thereby promoting data publication. As an example of the practical use of KOMICS, a workflow for a study on Jatropha curcas is presented. The tools and databases available at KOMICS should contribute to enhanced production, interpretation, and utilization of metabolomic Big Data.

  2. Metabolomic unveiling of a diverse range of green tea (Camellia sinensis) metabolites dependent on geography.

    Science.gov (United States)

    Lee, Jang-Eun; Lee, Bum-Jin; Chung, Jin-Oh; Kim, Hak-Nam; Kim, Eun-Hee; Jung, Sungheuk; Lee, Hyosang; Lee, Sang-Jun; Hong, Young-Shick

    2015-05-01

    Numerous factors such as geographical origin, cultivar, climate, cultural practices, and manufacturing processes influence the chemical compositions of tea, in the same way as growing conditions and grape variety affect wine quality. However, the relationships between these factors and tea chemical compositions are not well understood. In this study, a new approach for non-targeted or global analysis, i.e., metabolomics, which is highly reproducible and statistically effective in analysing a diverse range of compounds, was used to better understand the metabolome of Camellia sinensis and determine the influence of environmental factors, including geography, climate, and cultural practices, on tea-making. We found a strong correlation between environmental factors and the metabolome of green, white, and oolong teas from China, Japan, and South Korea. In particular, multivariate statistical analysis revealed strong inter-country and inter-city relationships in the levels of theanine and catechin derivatives found in green and white teas. This information might be useful for assessing tea quality or producing distinct tea products across different locations, and highlights simultaneous identification of diverse tea metabolites through an NMR-based metabolomics approach.

  3. Review: Microfluidic Applications in Metabolomics and Metabolic Profiling

    OpenAIRE

    Kraly, James R.; Holcomb, Ryan E.; Guan, Qian; Charles S. Henry

    2009-01-01

    Metabolomics is an emerging area of research focused on measuring small molecules in biological samples. There are a number of different types of metabolomics, ranging from global profiling of all metabolites in a single sample to measurement of a selected group of analytes. Microfluidics and related technologies have been used in this research area with good success. The aim of this review article is to summarize the use of microfluidics in metabolomics. Direct application of microfluidics t...

  4. Condition Based and Risk Informed Management for Power Plant Efficiency

    International Nuclear Information System (INIS)

    The efficiency management of power plants is an obvious and tedious topic, but it is still one of the most important pending issues. Efficiency management is not a difficult discipline in terms of academic standard. However, we can realize how we are lack of knowledge from the viewpoint of field practice. Nowadays, utilities are trying to strictly manage plant efficiency because of cost competitiveness with other energy resources. Efficiency management can be widely characterized from the replacement of hardware to the optimization of operation and maintenance using the advanced IT technologies. In this paper, we will overview the advanced efficiency management strategy, which is based on the IT technologies. We named the strategy as condition-based risk-informed efficiency management. This strategy aims at the implementation of predictive as well as proactive maintenance considering the risk in terms of cost

  5. Applying computer-based procedures in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Mauro V. de; Carvalho, Paulo V.R. de; Santos, Isaac J.A.L. dos; Grecco, Claudio H.S. [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Div. de Instrumentacao e Confiabilidade Humana], e-mail: mvitor@ien.gov.br, e-mail: paulov@ien.gov.br, e-mail: luquetti@ien.gov.br, e-mail: grecco@ien.gov.br; Bruno, Diego S. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Escola Politecnica. Curso de Engenharia de Controle e Automacao], e-mail: diegosalomonebruno@gmail.com

    2009-07-01

    Plant operation procedures are used to guide operators in coping with normal, abnormal or emergency situations in a process control system. Historically, the plant procedures have been paper-based (PBP), with the digitalisation trend in these complex systems computer-based procedures (CBPs) are being developed to support procedure use. This work shows briefly the research on CBPs at the Human-System Interface Laboratory (LABIHS). The emergency operation procedure EOP-0 of the LABIHS NPP simulator was implemented in the ImPRO CBP system. The ImPRO system was chosen for test because it is available for download in the Internet. A preliminary operation test using the implemented procedure in the CBP system was realized and the results were compared to the operation through PBP use. (author)

  6. Sustainability of plant-based diets: back to the future.

    Science.gov (United States)

    Sabaté, Joan; Soret, Sam

    2014-07-01

    Plant-based diets in comparison to diets rich in animal products are more sustainable because they use many fewer natural resources and are less taxing on the environment. Given the global population explosion and increase in wealth, there is an increased demand for foods of animal origin. Environmental data are rapidly accumulating on the unsustainability of current worldwide food consumption practices that are high in meat and dairy products. Natural nonrenewable resources are becoming scarce, and environmental degradation is rapidly increasing. At the current trends of food consumption and environmental changes, food security and food sustainability are on a collision course. Changing course (to avoid the collision) will require extreme downward shifts in meat and dairy consumption by large segments of the world's population. Other approaches such as food waste reduction and precision agriculture and/or other technological advances have to be simultaneously pursued; however, they are insufficient to make the global food system sustainable. For millennia, meatless diets have been advocated on the basis of values, and large segments of the world population have thrived on plant-based diets. "Going back" to plant-based diets worldwide seems to be a reasonable alternative for a sustainable future. Policies in favor of the global adoption of plant-based diets will simultaneously optimize the food supply, health, environmental, and social justice outcomes for the world's population. Implementing such nutrition policy is perhaps one of the most rational and moral paths for a sustainable future of the human race and other living creatures of the biosphere that we share. PMID:24898222

  7. Plant based dietary supplement increases urinary pH

    Directory of Open Access Journals (Sweden)

    Rao A Venket

    2008-11-01

    Full Text Available Abstract Background Research has demonstrated that the net acid load of the typical Western diet has the potential to influence many aspects of human health, including osteoporosis risk/progression; obesity; cardiovascular disease risk/progression; and overall well-being. As urinary pH provides a reliable surrogate measure for dietary acid load, this study examined whether a plant-based dietary supplement, one marketed to increase alkalinity, impacts urinary pH as advertised. Methods Using pH test strips, the urinary pH of 34 healthy men and women (33.9 +/- 1.57 y, 79.3 +/- 3.1 kg was measured for seven days to establish a baseline urinary pH without supplementation. After this initial baseline period, urinary pH was measured for an additional 14 days while participants ingested the plant-based nutritional supplement. At the end of the investigation, pH values at baseline and during the treatment period were compared to determine the efficacy of the supplement. Results Mean urinary pH statistically increased (p = 0.03 with the plant-based dietary supplement. Mean urinary pH was 6.07 +/- 0.04 during the baseline period and increased to 6.21 +/- 0.03 during the first week of treatment and to 6.27 +/- 0.06 during the second week of treatment. Conclusion Supplementation with a plant-based dietary product for at least seven days increases urinary pH, potentially increasing the alkalinity of the body.

  8. Utilization of Low Temperature Heat in Coal based Power Plants

    OpenAIRE

    Sisic, Elmir

    2013-01-01

    Carbon Capture and Storage aims at capturing and storing carbon emissions from large point sources underground. One of three main ways of implementing CCS is in coal based power plants is the pressurized oxy-combustion, an advanced form of oxy-combustion. There are different approaches in designing the heat cycle with CCS. Included in the design is the acid condenser, a heat exchanger which utilizes the low temperature and latent heat of the flue gas for preheating purposes. The objective of ...

  9. Life management of power plant based on structural damage testing

    Energy Technology Data Exchange (ETDEWEB)

    Tallermo, H.; Klevtsov, I. [Thermal Engineering Department of Tallinn Technical University, Tallinn (Estonia); Arras, V. [Eesti Energia, Tallinn (Estonia)

    1998-12-31

    Life management system is based on the valid nowadays in Estonian power plants regulation documentation. The system allows to estimate stress distribution in components, find computational assessment of cumulated creep damage, determine when and where it is necessary to cut off the particular number of microsamples or take replicas. Finally, the real metal condition may be assessed on the basis of metallographic specimen research and reasonable 3-R decision - run, repair, replacement - made on further component use. (orig.) 6 refs.

  10. Adaptive model based control for wastewater treatment plants

    OpenAIRE

    Niet, de, A.; Vrugt, van de, Noëlle Maria; Korving, Hans; Boucherie, Richard J.; Savic, D.A.; Kapelan, Z.; Butler, D.

    2011-01-01

    In biological wastewater treatment, nitrogen and phosphorous are removed by activated sludge. The process requires oxygen input via aeration of the activated sludge tank. Aeration is responsible for about 60% of the energy consumption of a treatment plant. Hence optimization of aeration can contribute considerably to the increase of energy-efficiency in wastewater treatment. To this end, we introduce an adaptive model based control strategy for aeration called adaptive WOMBAT. The strategy is...

  11. Siplab, a spatial individual-based plant modelling system

    OpenAIRE

    Oscar Garcia

    2014-01-01

    Spatially-explicit individual-based models are important tools in forestry and plant ecology. They are commonly implemented through custom computer coding that is time-consuming, may cause compatibility and availability problems, and makes difficult the evaluation, comparison and re-use of model components. Siplab is an R package that aims at improving this situation with a flexible computing environment that can handle a variety of model forms, and without requiring advanced programming know...

  12. Metabolome of Vanilla planifolia (Orchidaceae) and related species under Cymbidium mosaic virus (CymMV) infection.

    Science.gov (United States)

    Palama, Tony Lionel; Grisoni, Michel; Fock-Bastide, Isabelle; Jade, Katia; Bartet, Laetitia; Choi, Young Hae; Verpoorte, Robert; Kodja, Hippolyte

    2012-11-01

    The genus Vanilla which belongs to the Orchidaceae family comprises more than 110 species of which two are commercially cultivated (Vanilla planifolia and Vanilla xtahitensis). The cured pods of these species are the source of natural vanilla flavor. In intensive cultivation systems the vines are threatened by viruses such as Cymbidium mosaic virus (CymMV). In order to investigate the effect of CymMV on the growth and metabolome of vanilla plants, four accessions grown in intensive cultivation systems under shadehouse, CR01 (V. planifolia), CR17 (V. xtahitensis), CR03 (V. planifolia × V. xtahitensis) and CR18 (Vanilla pompona), were challenged with an isolate of CymMV. CymMV infected plants of CR01, CR03 and CR17 had a reduced growth compared to healthy plants, while there was no significant difference in the growth of CR18 vines. Interestingly, CR18 had qualitatively more phenolic compounds in leaves and a virus titre that diminished over time. No differences in the metabolomic profiles of the shadehouse samples obtained by nuclear magnetic resonance (NMR) were observed between the virus infected vs. healthy plants. However, using in- vitro V. planifolia plants, the metabolomic profiles were affected by virus infection. Under these controlled conditions the levels of amino acids and sugars present in the leaves were increased in CymMV infected plants, compared to uninfected ones, whereas the levels of phenolic compounds and malic acid were decreased. The metabolism, growth and viral status of V. pompona accession CR18 contrasted from that of the other species suggesting the existence of partial resistance to CymMV in the vanilla germplasm.

  13. Metabolomics to Detect Response of Lettuce (Lactuca sativa) to Cu(OH)2 Nanopesticides: Oxidative Stress Response and Detoxification Mechanisms.

    Science.gov (United States)

    Zhao, Lijuan; Ortiz, Cruz; Adeleye, Adeyemi S; Hu, Qirui; Zhou, Hongjun; Huang, Yuxiong; Keller, Arturo A

    2016-09-01

    There has been an increasing influx of nanopesticides into agriculture in recent years. Understanding the interaction between nanopesticides and edible plants is crucial in evaluating the potential impact of nanotechnology on the environment and agriculture. Here we exposed lettuce plants to Cu(OH)2 nanopesticides (1050-2100 mg/L) through foliar spray for one month. Inductively coupled plasma-mass spectrometry (ICP-MS) results indicate that 97-99% (1353-2501 mg/kg) of copper was sequestered in the leaves and only a small percentage (1-3%) (17.5-56.9 mg/kg) was translocated to root tissues through phloem loading. Gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) based metabolomics combined with partial least squares-discriminant analysis (PLS-DA) multivariate analysis revealed that Cu(OH)2 nanopesticides altered metabolite levels of lettuce leaves. Tricarboxylic (TCA) cycle and a number of amino acid-related biological pathways were disturbed. Some antioxidant levels (cis-caffeic acid, chlorogenic acid, 3,4-dihydroxycinnamic acid, dehydroascorbic acid) were significantly decreased compared to the control, indicating that oxidative stress and a defense response occurred. Nicotianamine, a copper chelator, increased by 12-27 fold compared to the control, which may represent a detoxification mechanism. The up-regulation of polyamines (spermidine and putrescine) and potassium may mitigate oxidative stress and enhance tolerance. The data presented here provide a molecular-scale perspective on the response of plants to copper nanopesticides. PMID:27483188

  14. Selection of Taste Markers Related to Lactic Acid Bacteria Microflora Metabolism for Chinese Traditional Paocai: A Gas Chromatography-Mass Spectrometry-Based Metabolomics Approach.

    Science.gov (United States)

    Zhao, Nan; Zhang, Chuchu; Yang, Qin; Guo, Zhuang; Yang, Bo; Lu, Wenwei; Li, Dongyao; Tian, Fengwei; Liu, Xiaoming; Zhang, Hao; Chen, Wei

    2016-03-23

    Traditional paocai brine (PB) is continuously propagated by back-slopping and contains numerous lactic acid bacteria (LAB) strains. Although PB is important for the quality of paocai (Chinese sauerkraut), the taste features, taste-related compounds of PB-paocai and the effects of LAB communities from PB on the taste compounds remain unclear. An electronic tongue was used to evaluate the taste features of 13 PB-paocai samples. Umami, saltiness, bitterness, sweetness, and aftertaste astringency were the main taste features of PB-paocai. A total of 14 compounds were identified as discriminant taste markers for PB-paocai via gas chromatography-mass spectrometry (GC-MS)-based multimarker profiling. A LAB co-culture (Lactobacillus plantarum, Lactobacillus buchneri, and Pediococcus ethanoliduran) from PB could significantly increase glutamic acid (umami), sucrose (sweetness), glycine (sweetness), lactic acid (sourness), and γ-aminobutyric acid in PB-paocai, which would endow it with important flavor features. Such features could then facilitate starter screening and fermentation optimization to produce paocai-related foods with better nutritional and sensory qualities. PMID:26915389

  15. PeroxisomeDB 2.0: an integrative view of the global peroxisomal metabolome

    Science.gov (United States)

    Schlüter, Agatha; Real-Chicharro, Alejandro; Gabaldón, Toni; Sánchez-Jiménez, Francisca; Pujol, Aurora

    2010-01-01

    Peroxisomes are essential organelles that play a key role in redox signalling and lipid homeostasis. They contain a highly diverse enzymatic network among different species, mirroring the varied metabolic needs of the organisms. The previous PeroxisomeDB version organized the peroxisomal proteome of humans and Saccharomyces cerevisiae based on genetic and functional information into metabolic categories with a special focus on peroxisomal disease. The new release (http://www.peroxisomeDB.org) adds peroxisomal proteins from 35 newly sequenced eukaryotic genomes including fungi, yeasts, plants and lower eukaryotes. We searched these genomes for a core ensemble of 139 peroxisomal protein families and identified 2706 putative peroxisomal protein homologs. Approximately 37% of the identified homologs contained putative peroxisome targeting signals (PTS). To help develop understanding of the evolutionary relationships among peroxisomal proteins, the new database includes phylogenetic trees for 2386 of the peroxisomal proteins. Additional new features are provided, such as a tool to capture kinetic information from Brenda, CheBI and Sabio-RK databases and more than 1400 selected bibliographic references. PeroxisomeDB 2.0 is a freely available, highly interactive functional genomics platform that offers an extensive view on the peroxisomal metabolome across lineages, thus facilitating comparative genomics and systems analysis of the organelle. PMID:19892824

  16. Application of condition based maintenance to nuclear power plants

    International Nuclear Information System (INIS)

    Device Karte management system which supports application of condition based maintenance to nuclear power plants has been developed. The purpose of this system is to support maintenance personnel in device inspection scheduling based on operating condition monitoring and maintenance histories. There are four functions: field database, degradation estimation, inspection time decision and maintenance planning. The authors have been applying this system to dozens of devices of Onagawa Nuclear Power Station Unit No. 1 for one year. This paper represents the system concept and its application experiences. (author)

  17. Reinforcing loose foundation stones in trait-based plant ecology.

    Science.gov (United States)

    Shipley, Bill; De Bello, Francesco; Cornelissen, J Hans C; Laliberté, Etienne; Laughlin, Daniel C; Reich, Peter B

    2016-04-01

    The promise of "trait-based" plant ecology is one of generalized prediction across organizational and spatial scales, independent of taxonomy. This promise is a major reason for the increased popularity of this approach. Here, we argue that some important foundational assumptions of trait-based ecology have not received sufficient empirical evaluation. We identify three such assumptions and, where possible, suggest methods of improvement: (i) traits are functional to the degree that they determine individual fitness, (ii) intraspecific variation in functional traits can be largely ignored, and (iii) functional traits show general predictive relationships to measurable environmental gradients.

  18. Metabolomics analysis of shucked mussels' freshness.

    Science.gov (United States)

    Aru, Violetta; Pisano, Maria Barbara; Savorani, Francesco; Engelsen, Søren Balling; Cosentino, Sofia; Cesare Marincola, Flaminia

    2016-08-15

    In this work a NMR metabolomics approach was applied to analyze changes in the metabolic profile of the bivalve mollusk Mytilus galloprovincialis upon storage at 0°C and 4°C for 10 and 6 days, respectively. The most significant microbial groups involved in spoilage of mussels were also investigated. The time-related metabolic signature of mussels was analysed by Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) which revealed a clear discrimination between the fresh samples and those stored at 0°C and 4°C. The results evidenced a noticeable increase in acetate, lactate, succinate, alanine, branched chain amino acids, trimethylamine and a progressive decline of osmolytes like betaine, homarine and taurine during storage. Exploration of the correlations of these metabolites with microbial counts suggested their use as potential biomarkers of spoilage. The results support the use of NMR metabolomics as a valuable tool to provide information on seafood freshness.

  19. Metabolomics analysis of shucked mussels' freshness.

    Science.gov (United States)

    Aru, Violetta; Pisano, Maria Barbara; Savorani, Francesco; Engelsen, Søren Balling; Cosentino, Sofia; Cesare Marincola, Flaminia

    2016-08-15

    In this work a NMR metabolomics approach was applied to analyze changes in the metabolic profile of the bivalve mollusk Mytilus galloprovincialis upon storage at 0°C and 4°C for 10 and 6 days, respectively. The most significant microbial groups involved in spoilage of mussels were also investigated. The time-related metabolic signature of mussels was analysed by Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) which revealed a clear discrimination between the fresh samples and those stored at 0°C and 4°C. The results evidenced a noticeable increase in acetate, lactate, succinate, alanine, branched chain amino acids, trimethylamine and a progressive decline of osmolytes like betaine, homarine and taurine during storage. Exploration of the correlations of these metabolites with microbial counts suggested their use as potential biomarkers of spoilage. The results support the use of NMR metabolomics as a valuable tool to provide information on seafood freshness. PMID:27006214

  20. 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.

  1. Development of a metabolomic radiation signature in urine from patients undergoing total body irradiation.

    Science.gov (United States)

    Laiakis, Evagelia C; Mak, Tytus D; Anizan, Sebastien; Amundson, Sally A; Barker, Christopher A; Wolden, Suzanne L; Brenner, David J; Fornace, Albert J

    2014-04-01

    The emergence of the threat of radiological terrorism and other radiological incidents has led to the need for development of fast, accurate and noninvasive methods for detection of radiation exposure. The purpose of this study was to extend radiation metabolomic biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation at Memorial Sloan-Kettering Cancer Center prior to hematopoietic stem cell transplantation at 4-6 h postirradiation (a single dose of 1.25 Gy) and 24 h (three fractions of 1.25 Gy each). Global metabolomic profiling was obtained through analysis with ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (TOFMS). Prior to further analyses, each sample was normalized to its respective creatinine level. Statistical analysis was conducted by the nonparametric Kolmogorov-Smirnov test and the Fisher's exact test and markers were validated against pure standards. Seven markers showed distinct differences between pre- and post-exposure samples. Of those, trimethyl-l-lysine and the carnitine conjugates acetylcarnitine, decanoylcarnitine and octanoylcarnitine play an important role in the transportation of fatty acids across mitochondria for subsequent fatty acid β-oxidation. The remaining metabolites, hypoxanthine, xanthine and uric acid are the final products of the purine catabolism pathway, and high levels of excretion have been associated with increased oxidative stress and radiation induced DNA damage. Further analysis revealed sex differences in the patterns of excretion of the markers, demonstrating that generation of a sex-specific metabolomic signature will be informative and can provide a quick and reliable assessment of individuals in a radiological scenario. This is the first radiation metabolomics study in human urine laying the foundation for the use of metabolomics in biodosimetry and providing confidence in biomarker

  2. Application of 1H-NMR metabolomic profiling for reef-building corals.

    Directory of Open Access Journals (Sweden)

    Emilia M Sogin

    Full Text Available In light of global reef decline new methods to accurately, cheaply, and quickly evaluate coral metabolic states are needed to assess reef health. Metabolomic profiling can describe the response of individuals to disturbance (i.e., shifts in environmental conditions across biological models and is a powerful approach for characterizing and comparing coral metabolism. For the first time, we assess the utility of a proton-nuclear magnetic resonance spectroscopy (1H-NMR-based metabolomics approach in characterizing coral metabolite profiles by 1 investigating technical, intra-, and inter-sample variation, 2 evaluating the ability to recover targeted metabolite spikes, and 3 assessing the potential for this method to differentiate among coral species. Our results indicate 1H-NMR profiling of Porites compressa corals is highly reproducible and exhibits low levels of variability within and among colonies. The spiking experiments validate the sensitivity of our methods and showcase the capacity of orthogonal partial least squares discriminate analysis (OPLS-DA to distinguish between profiles spiked with varying metabolite concentrations (0 mM, 0.1 mM, and 10 mM. Finally, 1H-NMR metabolomics coupled with OPLS-DA, revealed species-specific patterns in metabolite profiles among four reef-building corals (Pocillopora damicornis, Porites lobata, Montipora aequituberculata, and Seriatopora hystrix. Collectively, these data indicate that 1H-NMR metabolomic techniques can profile reef-building coral metabolomes and have the potential to provide an integrated picture of the coral phenotype in response to environmental change.

  3. Application of 1H-NMR Metabolomic Profiling for Reef-Building Corals

    Science.gov (United States)

    Sogin, Emilia M.; Anderson, Paul; Williams, Philip; Chen, Chii-Shiarng; Gates, Ruth D.

    2014-01-01

    In light of global reef decline new methods to accurately, cheaply, and quickly evaluate coral metabolic states are needed to assess reef health. Metabolomic profiling can describe the response of individuals to disturbance (i.e., shifts in environmental conditions) across biological models and is a powerful approach for characterizing and comparing coral metabolism. For the first time, we assess the utility of a proton-nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomics approach in characterizing coral metabolite profiles by 1) investigating technical, intra-, and inter-sample variation, 2) evaluating the ability to recover targeted metabolite spikes, and 3) assessing the potential for this method to differentiate among coral species. Our results indicate 1H-NMR profiling of Porites compressa corals is highly reproducible and exhibits low levels of variability within and among colonies. The spiking experiments validate the sensitivity of our methods and showcase the capacity of orthogonal partial least squares discriminate analysis (OPLS-DA) to distinguish between profiles spiked with varying metabolite concentrations (0 mM, 0.1 mM, and 10 mM). Finally, 1H-NMR metabolomics coupled with OPLS-DA, revealed species-specific patterns in metabolite profiles among four reef-building corals (Pocillopora damicornis, Porites lobata, Montipora aequituberculata, and Seriatopora hystrix). Collectively, these data indicate that 1H-NMR metabolomic techniques can profile reef-building coral metabolomes and have the potential to provide an integrated picture of the coral phenotype in response to environmental change. PMID:25354140

  4. Plant-based raw material: Improved food quality for better nutrition via plant genomics

    NARCIS (Netherlands)

    Meer, van der I.M.; Bovy, A.G.; Bosch, H.J.

    2001-01-01

    Plants form the basis of the human food chain. Characteristics of plants are therefore crucial to the quantity and quality of human food. In this review, it is discussed how technological developments in the area of plant genomics and plant genetics help to mobilise the potential of plants to improv

  5. 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 that ...... that lay ahead, including the validation of identified biomarkers, methodological improvements for accelerating biomarker identification, and the development of sharing tools for data and resources....

  6. Metabolomics as a diagnostic tool in gastroenterology

    Institute of Scientific and Technical Information of China (English)

    Vicky; De; Preter; Kristin; Verbeke

    2013-01-01

    Metabolomics has increasingly been applied in addition to other "omic" approaches in the study of the pathophysiology of different gastrointestinal diseases.Metabolites represent molecular readouts of the cell status reflecting a physiological phenotype.In addition,changes in metabolite concentrations induced by exogenous factors such as environmental and dietary factors which do not affect the genome,are taken into account.Metabolic reactions initiated by the host or gut microbiota can lead to "marker" metabolites present in different biological fluids that allow differentiation between health and disease.Several lines of evidence implicated the involvement of intestinal microbiota in the pathogenesis of inflammatory bowel disease(IBD).Also in irritable bowel syndrome(IBS),a role of an abnormal microbiota composition,so-called dysbiosis,is supported by experimental data.These compositional alterations could play a role in the aetiology of both diseases by altering the metabolic activities of the gut bacteria.Several studies have applied a metabolomic approach to identify these metabolite signatures.However,before translating a potential metabolite biomarker into clinical use,additional validation studies are required.This review summarizes contributions that metabolomics has made in IBD and IBS and presents potential future directions within the field.

  7. Environmentally Optimal, Nutritionally Aware Beef Replacement Plant-Based Diets.

    Science.gov (United States)

    Eshel, Gidon; Shepon, Alon; Noor, Elad; Milo, Ron

    2016-08-01

    Livestock farming incurs large and varied environmental burdens, dominated by beef. Replacing beef with resource efficient alternatives is thus potentially beneficial, but may conflict with nutritional considerations. Here we show that protein-equivalent plant based alternatives to the beef portion of the mean American diet are readily devisible, and offer mostly improved nutritional profile considering the full lipid profile, key vitamins, minerals, and micronutrients. We then show that replacement diets require on average only 10% of land, 4% of greenhouse gas (GHG) emissions, and 6% of reactive nitrogen (Nr) compared to what the replaced beef diet requires. Applied to 320 million Americans, the beef-to-plant shift can save 91 million cropland acres (and 770 million rangeland acres), 278 million metric ton CO2e, and 3.7 million metric ton Nr annually. These nationwide savings are 27%, 4%, and 32% of the respective national environmental burdens. PMID:27387141

  8. Nuclear Power Plant Operator Reliability Research Based on Fuzzy Math

    International Nuclear Information System (INIS)

    This paper makes use of the concept and theory of fuzzy number in fuzzy mathematics, to research for the response time of operator in accident of Chinese nuclear power plant. Through the quantitative analysis for the performance shape factors (PSFs) which influence the response time of operators, the formula of the operator response time is obtained based on the possibilistic fuzzy linear regression model which is used for the first time in this kind of research. The research result shows that the correct research method can be achieved through the analysis of the information from a small sample. This method breaks through the traditional research method and can be used not only for the reference to the safe operation of nuclear power plant, but also in other areas.

  9. Gaharu, from the metabolomic aspect

    International Nuclear Information System (INIS)

    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)

  10. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases

    Science.gov (United States)

    Safaei, Akram; Arefi Oskouie, Afsaneh; Mohebbi, Seyed Reza; Rezaei-Tavirani, Mostafa; Mahboubi, Mohammad; Peyvandi, Maryam; Okhovatian, Farshad; Zamanian-Azodi, Mona

    2016-01-01

    Metabolome analysis is used to evaluate the characteristics and interactions of low molecular weight metabolites under a specific set of conditions. In cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH) the liver does not function thoroughly due to long-term damage. Unfortunately the early detection of cirrhosis, HCC, NAFLD and NASH is a clinical problem and determining a sensitive, specific and predictive novel method based on biomarker discovery is an important task. On the other hand, metabolomics has been reported as a new and powerful technology in biomarker discovery and dynamic field that cause global comprehension of system biology. In this review, it has been collected a heterogeneous set of metabolomics published studies to discovery of biomarkers in researches to introduce diagnostic biomarkers for early detection and the choice of patient-specific therapies. PMID:27458508

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

    Directory of Open Access Journals (Sweden)

    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

  12. A knowledge based method for nuclear plant loading pattern determination

    International Nuclear Information System (INIS)

    This paper deals with the design of a knowledge based system for solving an industrial problem which occurs in nuclear fuel management. The problem lies in determining satisfactory loading patterns for nuclear plants. Its primary feature consists in the huge search space involved. Conventional resolution processes are formally defined and analyzed: there is no general algorithm which guarantees to always provide a reasonable solution in each situation. We propose a new approach to solve this constrained search problem using domain-specific knowledge and general constraint-based heuristics. During a preprocessing step, a problem dependent search algorithm is designed. This procedure is then automatically implemented in FORTRAN. The generated routines have proved to be very efficient finding solutions which could not have been provided using logic programming. A prototype expert system has already been applied to actual reload pattern searches. While combining efficiency and flexibility, this knowledge based system enables human experts to rapidly match new constraints and requirements

  13. 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 sensiti

  14. 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…

  15. PSA based plant modifications and back-fits

    International Nuclear Information System (INIS)

    The mandate of Principal Working Group No. 5 - Risk Assessment states that 'The group should deal with the technology and methods for identifying contributors to risk and assessing their importance, and appropriate exchanges of information on current research'. Since being formulated in 1982, along with this mandate, the group has also endeavored to develop a common understanding of the different approaches taken in risk assessment. The focus of this report is to provide knowledge to experts on the role Probabilistic Safety Assessment (PSA) has had in safety decision making. PSA is a powerful tool for improving Nuclear Power Plant safety by identifying weaknesses in design or operation and setting priorities for plant modifications and back-fits. While the use is well recognised, it is also true that any safety decision is generally based on several elements, both probabilistic and deterministic. This document provides a general overview of insights gained from the representative set of examples collected from Member countries (Finland, France, Germany, Japan, Korea, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States). The report starts with basic types of plant modifications which were carried out (e.g. hardware or software, important or minor, etc.) and the characteristics of the PSAs used in the examples (e.g. level and scope, specific or generic, on-going or terminated, etc.). The insights gained from this small collection are then reviewed. The appendix gives a full text version of the Member country contributions

  16. ECOLOGICAL BASES OF SIMBIOGENIC DEVELOPMENT OF PLANT AT COMPLEX SOWINGS

    Directory of Open Access Journals (Sweden)

    Belyuchenko I. S.

    2015-03-01

    Full Text Available Development of plants in mixed or combined sowings is based on the symbiotic association in the basis of which we have decreased sexual process and its mechanism of genetic exchange among endosymbionts and stimulating of genetic exchange and expansion of the diversity of species among exosymbionts. The exception is the symbiosis of orchids and fungi - activators of orchids mycorrhiza with developed micellar system easily passing on saprophytic option. Coevolution of plant organisms with fungi indicates the specifics symbiogenic conjugate evolution, showing an example of the evolution of a small community with different contact with the external environment. The phenomenon of symbiogenesis has a long history and was manifested in a variety of different types of organisms. Today, some dependence of existence of one species from other organisms is observed at approximately 75% of higher plants and 90% of the animals in varying degrees of symbiogenic dependence from other species and taxa. Originality of symbiogenesis was analyzed by Academician A.A. Takhtadzhyan (1973 during its consideration of origin of eukaryotic cells as process of "assembly" of a complex system. Different approaches to determining the biological essence of symbiosis are known in the history of study of this phenomenon. On the whole phenomenon of symbiosis belongs to the category mutual relations of organisms of different phylogenetic groups

  17. HILIC-MS for metabolomics: An attractive and complementary approach to RPLC-MS.

    Science.gov (United States)

    Tang, Dao-Quan; Zou, Ll; Yin, Xiao-Xing; Ong, Choon Nam

    2016-09-01

    Hydrophilic interaction chromatography (HILIC) is an emerging separation mode of liquid chromatography (LC). Using highly hydrophilic stationary phases capable of retaining polar/ionic metabolites, and accompany with high organic content mobile phase that offer readily compatibility with mass spectrometry (MS) has made HILIC an attractive complementary tool to the widely used reverse-phase (RP) chromatographic separations in metabolomic studies. The combination of HILIC and RPLC coupled with an MS detector expands the number of detected analytes and provides more comprehensive metabolite coverage than use of only RP chromatography. This review describes the recent applications of HILIC-MS/MS in metabolomic studies, ranging from amino acids, lipids, nucleotides, organic acids, pharmaceuticals, and metabolites of specific nature. The biological systems investigated include microbials, cultured cell line, plants, herbal medicine, urine, and serum as well as tissues from animals and humans. Owing to its unique capability to measure more-polar biomolecules, the HILIC separation technique would no doubt enhance the comprehensiveness of metabolite detection, and add significant value for metabolomic investigations. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:574-600, 2016. PMID:25284160

  18. Functional Metabolomics Uncovers Metabolic Alterations Associated to Severe Oxidative Stress in MCF7 Breast Cancer Cells Exposed to Ascididemin

    OpenAIRE

    Daniel Morvan

    2013-01-01

    Marine natural products are a source of promising agents for cancer treatment. However, there is a need to improve the evaluation of their mechanism of action in tumors. Metabolomics of the response to anti-tumor agents is a tool to reveal candidate biomarkers and metabolic targets. We used two-dimensional high-resolution magic angle spinning proton-NMR spectroscopy-based metabolomics to investigate the response of MCF7 breast cancer cells to ascididemin, a marine alkaloid and lead molecule f...

  19. Data warehouse based decision support system in nuclear power plants

    International Nuclear Information System (INIS)

    Safety is an important element in business decision making processes in nuclear power plants. Information about component reliability, structures and systems, data recorded during the nuclear power plant's operation and outage periods, as well as experiences from other power plants are located in different database systems throughout the power plant. It would be possible to create a decision support system which would collect data, transform it into a standardized form and store it in a single location in a format more suitable for analyses and knowledge discovery. This single location where the data would be stored would be a data warehouse. Such data warehouse based decision support system could help make decision making processes more efficient by providing more information about business processes and predicting possible consequences of different decisions. Two main functionalities in this decision support system would be an OLAP (On Line Analytical Processing) and a data mining system. An OLAP system would enable the users to perform fast, simple and efficient multidimensional analysis of existing data and identify trends. Data mining techniques and algorithms would help discover new, previously unknown information from the data as well as hidden dependencies between various parameters. Data mining would also enable analysts to create relevant prediction models that could predict behaviour of different systems during operation and inspection results during outages. The basic characteristics and theoretical foundations of such decision support system are described and the reasons for choosing a data warehouse as the underlying structure are explained. The article analyzes obvious business benefits of such system as well as potential uses of OLAP and data mining technologies. Possible implementation methodologies and problems that may arise, especially in the field of data integration, are discussed and analyzed.(author)

  20. ITER Fast Plant System Controller prototype based on PXIe platform

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz, M., E-mail: mariano.ruiz@upm.es [Grupo de Investigacion en Instrumentacion y Acustica Aplicada, CAEND CSIC-UPM Universidad Politecnica de Madrid, Crta. Valencia Km-7, Madrid 28031 (Spain); Vega, J.; Castro, R. [Asociacion EURATOM/CIEMAT para Fusion, Madrid (Spain); Sanz, D.; Lopez, J.M.; Arcas, G. de; Barrera, E.; Nieto, J. [Grupo de Investigacion en Instrumentacion y Acustica Aplicada, CAEND CSIC-UPM Universidad Politecnica de Madrid, Crta. Valencia Km-7, Madrid 28031 (Spain); Goncalves, B.; Sousa, J.; Carvalho, B. [Associacao EURATOM/IST, Lisbon (Portugal); Utzel, N.; Makijarvi, P. [ITER Organization, CS 90 046, 13067 St. Paul lez Durance Cedex (France)

    2012-12-15

    Highlights: Black-Right-Pointing-Pointer Implementation of Fast Plant System Controller (FPSC) for ITER CODAC. Black-Right-Pointing-Pointer Efficient data acquisition and data movement using EPICS. Black-Right-Pointing-Pointer Performance of PCIe technologies in the implementation of FPSC. - Abstract: The ITER Fast Plant System Controller (FPSC) is based on embedded technologies. The FPSC will be devoted to both data acquisition tasks (sampling rates higher than 1 kHz) and control purposes (feedback loop actuators). Some of the essential requirements of these systems are: (a) data acquisition and data preprocessing; (b) interfacing with different networks and high speed links (Plant Operation Network, timing network based on IEEE1588, synchronous data transference and streaming/archiving networks); and (c) system setup and operation using EPICS (Experimental Physics and Industrial Control System) process variables. CIEMAT and UPM have implemented a prototype of FPSC using a PXIe (PCI eXtension for Instrumentation) form factor in a R and D project developed in two phases. The paper presents the main features of the two prototypes developed that have been named alpha and beta. The former was implemented using LabVIEW development tools as it was focused on modeling the FPSC software modules, using the graphical features of LabVIEW applications, and measuring the basic performance in the system. The alpha version prototype implements data acquisition with time-stamping, EPICS monitoring using waveform process variables (PVs), and archiving. The beta version prototype is a complete IOC implemented using EPICS with different software functional blocks. These functional blocks are integrated and managed using an ASYN driver solution and provide the basic functionalities required by ITER FPSC such as data acquisition, data archiving, data pre-processing (using both CPU and GPU) and streaming.